Sample records for paving pathways shaping
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Comparison of human exposure pathways in an urban brownfield: reduced risk from paving roads.
James, Kyle; Farrell, Richard E; Siciliano, Steven D
2012-10-01
Risk assessments often do not quantify the risk associated with soil inhalation. This pathway generally makes a negligible contribution to the cumulative risk, because soil ingestion is typically the dominant exposure pathway. Conditions in northern or rural centers in Canada characterized by large areas of exposed soil, including unpaved roads, favor the resuspension of soil particles, making soil inhalation a relevant risk pathway. The authors determined and compared human exposure to metals and polycyclic aromatic hydrocarbons (PAHs) from soil ingestion and inhalation and analyzed the carcinogenic and noncarcinogenic risks before and after roads were paved in a northern community. To determine the inhalation exposure, three size fractions of airborne particulate matter were collected (total suspended particulates [TSP], particulate matter with an aerodynamic diameter less than 10 µm [PM10], and particulate matter with an aerodynamic diameter less than 2.5 µm [PM2.5]) before and after roads were paved. Road paving reduced the concentration of many airborne contaminants by 25 to 75%, thus reducing risk. For example, before paving, the carcinogenic risk associated with inhalation of Cr was 3.4 excess cancers per 100,000 people exposed, whereas after paving, this risk was reduced to 1.6 in 100,000. Paving roads reduced the concentrations of total suspended particulates (TSP; p < 0.1) and PM10 (p < 0.05) but not PM25. Consequently, the ingestion of inhaled soil particles was substantially reduced. The authors conclude that resuspended soil is likely an important source of risk for many northern communities and that paving roads is an effective method of reducing risk from the inhalation of soil particles. Copyright © 2012 SETAC.
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The Regulation of Filamentous Growth in Yeast
Cullen, Paul J.; Sprague, George F.
2012-01-01
Filamentous growth is a nutrient-regulated growth response that occurs in many fungal species. In pathogens, filamentous growth is critical for host–cell attachment, invasion into tissues, and virulence. The budding yeast Saccharomyces cerevisiae undergoes filamentous growth, which provides a genetically tractable system to study the molecular basis of the response. Filamentous growth is regulated by evolutionarily conserved signaling pathways. One of these pathways is a mitogen activated protein kinase (MAPK) pathway. A remarkable feature of the filamentous growth MAPK pathway is that it is composed of factors that also function in other pathways. An intriguing challenge therefore has been to understand how pathways that share components establish and maintain their identity. Other canonical signaling pathways—rat sarcoma/protein kinase A (RAS/PKA), sucrose nonfermentable (SNF), and target of rapamycin (TOR)—also regulate filamentous growth, which raises the question of how signals from multiple pathways become integrated into a coordinated response. Together, these pathways regulate cell differentiation to the filamentous type, which is characterized by changes in cell adhesion, cell polarity, and cell shape. How these changes are accomplished is also discussed. High-throughput genomics approaches have recently uncovered new connections to filamentous growth regulation. These connections suggest that filamentous growth is a more complex and globally regulated behavior than is currently appreciated, which may help to pave the way for future investigations into this eukaryotic cell differentiation behavior. PMID:22219507
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Signaling Pathways Regulating Redox Balance in Cancer Metabolism
De Santis, Maria Chiara; Porporato, Paolo Ettore; Martini, Miriam; Morandi, Andrea
2018-01-01
The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells’ demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions. PMID:29740540
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Signaling Pathways Regulating Redox Balance in Cancer Metabolism.
De Santis, Maria Chiara; Porporato, Paolo Ettore; Martini, Miriam; Morandi, Andrea
2018-01-01
The interplay between rewiring tumor metabolism and oncogenic driver mutations is only beginning to be appreciated. Metabolic deregulation has been described for decades as a bystander effect of genomic aberrations. However, for the biology of malignant cells, metabolic reprogramming is essential to tackle a harsh environment, including nutrient deprivation, reactive oxygen species production, and oxygen withdrawal. Besides the well-investigated glycolytic metabolism, it is emerging that several other metabolic fluxes are relevant for tumorigenesis in supporting redox balance, most notably pentose phosphate pathway, folate, and mitochondrial metabolism. The relationship between metabolic rewiring and mutant genes is still unclear and, therefore, we will discuss how metabolic needs and oncogene mutations influence each other to satisfy cancer cells' demands. Mutations in oncogenes, i.e., PI3K/AKT/mTOR, RAS pathway, and MYC, and tumor suppressors, i.e., p53 and liver kinase B1, result in metabolic flexibility and may influence response to therapy. Since metabolic rewiring is shaped by oncogenic driver mutations, understanding how specific alterations in signaling pathways affect different metabolic fluxes will be instrumental for the development of novel targeted therapies. In the era of personalized medicine, the combination of driver mutations, metabolite levels, and tissue of origins will pave the way to innovative therapeutic interventions.
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ERIC Educational Resources Information Center
Harris, Roger; Rainey, Linda; Sumner, Robert
2006-01-01
One of the significant issues in vocational education and training is student pathways and how students use them to achieve their personal goals. These "pathways" can be within or across sectors, as well as into and out of paid work. This study focuses on the pathways--to and fro--between vocational education and training (VET) and…
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Formation and size distribution of self-assembled vesicles
Huang, Changjin; Quinn, David; Suresh, Subra
2017-01-01
When detergents and phospholipid membranes are dispersed in aqueous solutions, they tend to self-assemble into vesicles of various shapes and sizes by virtue of their hydrophobic and hydrophilic segments. A clearer understanding of such vesiculation processes holds promise for better elucidation of human physiology and disease, and paves the way to improved diagnostics, drug development, and drug delivery. Here we present a detailed analysis of the energetics and thermodynamics of vesiculation by recourse to nonlinear elasticity, taking into account large deformation that may arise during the vesiculation process. The effects of membrane size, spontaneous curvature, and membrane stiffness on vesiculation and vesicle size distribution were investigated, and the critical size for vesicle formation was determined and found to compare favorably with available experimental evidence. Our analysis also showed that the critical membrane size for spontaneous vesiculation was correlated with membrane thickness, and further illustrated how the combined effects of membrane thickness and physical properties influenced the size, shape, and distribution of vesicles. These findings shed light on the formation of physiological extracellular vesicles, such as exosomes. The findings also suggest pathways for manipulating the size, shape, distribution, and physical properties of synthetic vesicles, with potential applications in vesicle physiology, the pathobiology of cancer and other diseases, diagnostics using in vivo liquid biopsy, and drug delivery methods. PMID:28265065
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Shape memory polymer network with thermally distinct elasticity and plasticity.
Zhao, Qian; Zou, Weike; Luo, Yingwu; Xie, Tao
2016-01-01
Stimuli-responsive materials with sophisticated yet controllable shape-changing behaviors are highly desirable for real-world device applications. Among various shape-changing materials, the elastic nature of shape memory polymers allows fixation of temporary shapes that can recover on demand, whereas polymers with exchangeable bonds can undergo permanent shape change via plasticity. We integrate the elasticity and plasticity into a single polymer network. Rational molecular design allows these two opposite behaviors to be realized at different temperature ranges without any overlap. By exploring the cumulative nature of the plasticity, we demonstrate easy manipulation of highly complex shapes that is otherwise extremely challenging. The dynamic shape-changing behavior paves a new way for fabricating geometrically complex multifunctional devices.
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Shape memory polymer network with thermally distinct elasticity and plasticity
Zhao, Qian; Zou, Weike; Luo, Yingwu; Xie, Tao
2016-01-01
Stimuli-responsive materials with sophisticated yet controllable shape-changing behaviors are highly desirable for real-world device applications. Among various shape-changing materials, the elastic nature of shape memory polymers allows fixation of temporary shapes that can recover on demand, whereas polymers with exchangeable bonds can undergo permanent shape change via plasticity. We integrate the elasticity and plasticity into a single polymer network. Rational molecular design allows these two opposite behaviors to be realized at different temperature ranges without any overlap. By exploring the cumulative nature of the plasticity, we demonstrate easy manipulation of highly complex shapes that is otherwise extremely challenging. The dynamic shape-changing behavior paves a new way for fabricating geometrically complex multifunctional devices. PMID:26824077
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Design and application of low compaction energy concrete for use in slip-form concrete paving.
DOT National Transportation Integrated Search
2009-01-01
Slipform self-consolidating concrete (SFSCC) requires sufficient flowability in order to consolidate without the use of internal vibration. However, this concrete must also gain sufficient green strength in order to keep its shape immediately after s...
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Paving Pathways: shaping the Public Health workforce through tertiary education.
Bennett, Catherine M; Lilley, Kathleen; Yeatman, Heather; Parker, Elizabeth; Geelhoed, Elizabeth; Hanna, Elizabeth G; Robinson, Priscilla
2010-01-03
Public health educational pathways in Australia have traditionally been the province of Universities, with the Master of Public Health (MPH) recognised as the flagship professional entry program. Public health education also occurs within the fellowship training of the Faculty of Public Health Medicine, but within Australia this remains confined to medical graduates. In recent years, however, we have seen a proliferation of undergraduate degrees as well as an increasing public health presence in the Vocational Education and Training (VET) sector.Following the 2007 Australian Federal election, the new Labour government brought with it a refreshing commitment to a more inclusive and strategic style of government. An important example of this was the 2020 visioning process that identified key issues of public health concern, including an acknowledgment that it was unacceptable to allocate less than 2% of the health budget towards disease prevention. This led to the recommendation for the establishment of a national preventive health agency (Australia: the healthiest country by 2020 National Preventative Health Strategy, Prepared by the Preventative Health Taskforce 2009).The focus on disease prevention places a spotlight on the workforce that will be required to deliver the new investment in health prevention, and also on the role of public health education in developing and upskilling the workforce. It is therefore timely to reflect on trends, challenges and opportunities from a tertiary sector perspective. Is it more desirable to focus education efforts on selected lead issues such as the "obesity epidemic", climate change, Indigenous health and so on, or on the underlying theory and skills that build a flexible workforce capable of responding to a range of health challenges? Or should we aspire to both?This paper presents some of the key discussion points from 2008 - 2009 of the Public Health Educational Pathways workshops and working group of the Australian Network of Public Health Institutions. We highlight some of the competing tensions in public health tertiary education, their impact on public health training programs, and the educational pathways that are needed to grow, shape and prepare the public health workforce for future challenges.
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Self-shaping of bioinspired chiral composites
NASA Astrophysics Data System (ADS)
Rong, Qing-Qing; Cui, Yu-Hong; Shimada, Takahiro; Wang, Jian-Shan; Kitamura, Takayuki
2014-08-01
Self-shaping materials such as shape memory polymers have recently drawn considerable attention owing to their high shape-changing ability in response to changes in ambient conditions, and thereby have promising applications in the biomedical, biosensing, soft robotics and aerospace fields. Their design is a crucial issue of both theoretical and technological interest. Motivated by the shape-changing ability of Towel Gourd tendril helices during swelling/deswelling, we present a strategy for realizing self-shaping function through the deformation of micro/nanohelices. To guide the design and fabrication of self-shaping materials, the shape equations of bent configurations, twisted belts, and helices of slender chiral composite are developed using the variation method. Furthermore, it is numerically shown that the shape changes of a chiral composite can be tuned by the deformation of micro/nanohelices and the fabricated fiber directions. This work paves a new way to create self-shaping composites.
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Rekik, Islem; Li, Gang; Yap, Pew-Thian; Chen, Geng; Lin, Weili; Shen, Dinggang
2017-01-01
The human brain can be modeled as multiple interrelated shapes (or a multishape), each for characterizing one aspect of the brain, such as the cortex and white matter pathways. Predicting the developing multishape is a very challenging task due to the contrasting nature of the developmental trajectories of the constituent shapes: smooth for the cortical surface and non-smooth for white matter tracts due to changes such as bifurcation. We recently addressed this problem and proposed an approach for predicting the multishape developmental spatiotemporal trajectories of infant brains based only on neonatal MRI data using a set of geometric, dynamic, and fiber-to-surface connectivity features. In this paper, we propose two key innovations to further improve the prediction of multishape evolution. First, for a more accurate cortical surface prediction, instead of simply relying on one neonatal atlas to guide the prediction of the multishape, we propose to use multiple neonatal atlases to build a spatially heterogeneous atlas using the multidirectional varifold representation. This individualizes the atlas by locally maximizing its similarity to the testing baseline cortical shape for each cortical region, thereby better representing the baseline testing cortical surface, which founds the multishape prediction process. Second, for temporally consistent fiber prediction, we propose to reliably estimate spatiotemporal connectivity features using low-rank tensor completion, thereby capturing the variability and richness of the temporal development of fibers. Experimental results confirm that the proposed variants significantly improve the prediction performance of our original multishape prediction framework for both cortical surfaces and fiber tracts shape at 3, 6, and 9 months of age. Our pioneering model will pave the way for learning how to predict the evolution of anatomical shapes with abnormal changes. Ultimately, devising accurate shape evolution prediction models that can help quantify and predict the severity of a brain disorder as it progresses will be of great aid in individualized treatment planning. PMID:28284800
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Rekik, Islem; Li, Gang; Yap, Pew-Thian; Chen, Geng; Lin, Weili; Shen, Dinggang
2017-05-15
The human brain can be modeled as multiple interrelated shapes (or a multishape), each for characterizing one aspect of the brain, such as the cortex and white matter pathways. Predicting the developing multishape is a very challenging task due to the contrasting nature of the developmental trajectories of the constituent shapes: smooth for the cortical surface and non-smooth for white matter tracts due to changes such as bifurcation. We recently addressed this problem and proposed an approach for predicting the multishape developmental spatiotemporal trajectories of infant brains based only on neonatal MRI data using a set of geometric, dynamic, and fiber-to-surface connectivity features. In this paper, we propose two key innovations to further improve the prediction of multishape evolution. First, for a more accurate cortical surface prediction, instead of simply relying on one neonatal atlas to guide the prediction of the multishape, we propose to use multiple neonatal atlases to build a spatially heterogeneous atlas using the multidirectional varifold representation. This individualizes the atlas by locally maximizing its similarity to the testing baseline cortical shape for each cortical region, thereby better representing the baseline testing cortical surface, which founds the multishape prediction process. Second, for temporally consistent fiber prediction, we propose to reliably estimate spatiotemporal connectivity features using low-rank tensor completion, thereby capturing the variability and richness of the temporal development of fibers. Experimental results confirm that the proposed variants significantly improve the prediction performance of our original multishape prediction framework for both cortical surfaces and fiber tracts shape at 3, 6, and 9 months of age. Our pioneering model will pave the way for learning how to predict the evolution of anatomical shapes with abnormal changes. Ultimately, devising accurate shape evolution prediction models that can help quantify and predict the severity of a brain disorder as it progresses will be of great aid in individualized treatment planning. Copyright © 2017 Elsevier Inc. All rights reserved.
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Charter School Path Paved with Choice, Compromise, Common Sense
ERIC Educational Resources Information Center
Junge, Ember Reichgott
2014-01-01
A state legislator who played a key role in enacting the nation's first charter school law in Minnesota tells the story of shaping the ideas and the bill. She now looks for ways that charter schools can coexist with traditional public schools to deliver a better education for all children.
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Copernican Mathematics: Calculating Periods and Distances of the Planets
ERIC Educational Resources Information Center
Rosenkrantz, Kurt J.
2004-01-01
The heliocentric, or Sun-centered model, one of the most important revolutions in scientific thinking, allowed Nicholas Copernicus to calculate the periods, relative distances, and approximate orbital shapes of all the known planets, thereby paving the way for Kepler's laws and Newton's formation of gravitation. Recreating Copernicus's…
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The large-scale organization of shape processing in the ventral and dorsal pathways
Culham, Jody C; Plaut, David C; Behrmann, Marlene
2017-01-01
Although shape perception is considered a function of the ventral visual pathway, evidence suggests that the dorsal pathway also derives shape-based representations. In two psychophysics and neuroimaging experiments, we characterized the response properties, topographical organization and perceptual relevance of these representations. In both pathways, shape sensitivity increased from early visual cortex to extrastriate cortex but then decreased in anterior regions. Moreover, the lateral aspect of the ventral pathway and posterior regions of the dorsal pathway were sensitive to the availability of fundamental shape properties, even for unrecognizable images. This apparent representational similarity between the posterior-dorsal and lateral-ventral regions was corroborated by a multivariate analysis. Finally, as with ventral pathway, the activation profile of posterior dorsal regions was correlated with recognition performance, suggesting a possible contribution to perception. These findings challenge a strict functional dichotomy between the pathways and suggest a more distributed model of shape processing. PMID:28980938
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Investigation of terpene diversification across multiple sequenced plant genomes
Boutanaev, Alexander M.; Moses, Tessa; Zi, Jiachen; Nelson, David R.; Mugford, Sam T.; Peters, Reuben J.; Osbourn, Anne
2015-01-01
Plants produce an array of specialized metabolites, including chemicals that are important as medicines, flavors, fragrances, pigments and insecticides. The vast majority of this metabolic diversity is untapped. Here we take a systematic approach toward dissecting genetic components of plant specialized metabolism. Focusing on the terpenes, the largest class of plant natural products, we investigate the basis of terpene diversity through analysis of multiple sequenced plant genomes. The primary drivers of terpene diversification are terpenoid synthase (TS) “signature” enzymes (which generate scaffold diversity), and cytochromes P450 (CYPs), which modify and further diversify these scaffolds, so paving the way for further downstream modifications. Our systematic search of sequenced plant genomes for all TS and CYP genes reveals that distinct TS/CYP gene pairs are found together far more commonly than would be expected by chance, and that certain TS/CYP pairings predominate, providing signals for key events that are likely to have shaped terpene diversity. We recover TS/CYP gene pairs for previously characterized terpene metabolic gene clusters and demonstrate new functional pairing of TSs and CYPs within previously uncharacterized clusters. Unexpectedly, we find evidence for different mechanisms of pathway assembly in eudicots and monocots; in the former, microsyntenic blocks of TS/CYP gene pairs duplicate and provide templates for the evolution of new pathways, whereas in the latter, new pathways arise by mixing and matching of individual TS and CYP genes through dynamic genome rearrangements. This is, to our knowledge, the first documented observation of the unique pattern of TS and CYP assembly in eudicots and monocots. PMID:25502595
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Singh, Bhupinder; Bandopadhyay, Shantanu; Kapil, Rishi; Singh, Ramandeep; Katare, O
2009-01-01
Self-emulsifying drug delivery systems (SEDDS) possess unparalleled potential in improving oral bioavailability of poorly water-soluble drugs. Following their oral administration, these systems rapidly disperse in gastrointestinal fluids, yielding micro- or nanoemulsions containing the solubilized drug. Owing to its miniscule globule size, the micro/nanoemulsifed drug can easily be absorbed through lymphatic pathways, bypassing the hepatic first-pass effect. We present an exhaustive and updated account of numerous literature reports and patents on diverse types of self-emulsifying drug formulations, with emphasis on their formulation, characterization, and systematic optimization strategies. Recent advancements in various methodologies employed to characterize their globule size and shape, ability to encapsulate the drug, gastrointestinal and thermodynamic stability, rheological characteristics, and so forth, are discussed comprehensively to guide the formula-tor in preparing an effective and robust SEDDS formulation. Also, this exhaustive review offers an explicit discussion on vital applications of the SEDDS in bioavailability enhancement of various drugs, outlining an overview on myriad in vitro, in situ, and ex vivo techniques to assess the absorption and/ or permeation potential of drugs incorporated in the SEDDS in animal and cell line models, and the subsequent absorption pathways followed by them. In short, the current article furnishes an updated compilation of wide-ranging information on all the requisite vistas of the self-emulsifying formulations, thus paving the way for accelerated progress into the SEDDS application in pharmaceutical research.
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2015-01-01
Heterologous expression of secondary metabolic pathways is a promising approach for the discovery and characterization of bioactive natural products. Herein we report the first heterologous expression of a natural product from the model marine actinomycete genus Salinispora. Using the recently developed method of yeast-mediated transformation-associated recombination for natural product gene clusters, we captured a type II polyketide synthase pathway from Salinispora pacifica with high homology to the enterocin pathway from Streptomyces maritimus and successfully produced enterocin in two different Streptomyces host strains. This result paves the way for the systematic interrogation of Salinispora’s promising secondary metabolome. PMID:25382643
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Bonet, Bailey; Teufel, Robin; Crüsemann, Max; Ziemert, Nadine; Moore, Bradley S
2015-03-27
Heterologous expression of secondary metabolic pathways is a promising approach for the discovery and characterization of bioactive natural products. Herein we report the first heterologous expression of a natural product from the model marine actinomycete genus Salinispora. Using the recently developed method of yeast-mediated transformation-associated recombination for natural product gene clusters, we captured a type II polyketide synthase pathway from Salinispora pacifica with high homology to the enterocin pathway from Streptomyces maritimus and successfully produced enterocin in two different Streptomyces host strains. This result paves the way for the systematic interrogation of Salinispora's promising secondary metabolome.
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Roma-Rodrigues, Catarina; Raposo, Luís R.; Cabral, Rita; Paradinha, Fabiana; Baptista, Pedro V.; Fernandes, Alexandra R.
2017-01-01
Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes’ release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs’ properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs’ role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression. PMID:28098821
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Roma-Rodrigues, Catarina; Raposo, Luís R; Cabral, Rita; Paradinha, Fabiana; Baptista, Pedro V; Fernandes, Alexandra R
2017-01-14
Exosomes are nanovesicles formed in the endosomal pathway with an important role in paracrine and autocrine cell communication. Exosomes secreted by cancer cells, malicious exosomes, have important roles in tumor microenvironment maturation and cancer progression. The knowledge of the role of exosomes in tumorigenesis prompted a new era in cancer diagnostics and therapy, taking advantage of the use of circulating exosomes as tumor biomarkers due to their stability in body fluids and targeting malignant exosomes' release and/or uptake to inhibit or delay tumor development. In recent years, nanotechnology has paved the way for the development of a plethora of new diagnostic and therapeutic platforms, fostering theranostics. The unique physical and chemical properties of gold nanoparticles (AuNPs) make them suitable vehicles to pursuit this goal. AuNPs' properties such as ease of synthesis with the desired shape and size, high surface:volume ratio, and the possibility of engineering their surface as desired, potentiate AuNPs' role in nanotheranostics, allowing the use of the same formulation for exosome detection and restraining the effect of malicious exosomes in cancer progression.
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ERIC Educational Resources Information Center
Heflinger, Craig Anne; Doykos, Bernadette
2016-01-01
The breadth of doctoral education has expanded to include professional development activities in order to prepare students for academic and nonacademic careers. This mixed methods study focused on students' perceptions of professional development opportunities at a Research One university. The findings suggest that most students feel prepared in…
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Shape Memory Polymers for Body Motion Energy Harvesting and Self-Powered Mechanosensing.
Liu, Ruiyuan; Kuang, Xiao; Deng, Jianan; Wang, Yi-Cheng; Wang, Aurelia C; Ding, Wenbo; Lai, Ying-Chih; Chen, Jun; Wang, Peihong; Lin, Zhiqun; Qi, H Jerry; Sun, Baoquan; Wang, Zhong Lin
2018-02-01
Growing demand in portable electronics raises a requirement to electronic devices being stretchable, deformable, and durable, for which functional polymers are ideal choices of materials. Here, the first transformable smart energy harvester and self-powered mechanosensation sensor using shape memory polymers is demonstrated. The device is based on the mechanism of a flexible triboelectric nanogenerator using the thermally triggered shape transformation of organic materials for effectively harvesting mechanical energy. This work paves a new direction for functional polymers, especially in the field of mechanosensation for potential applications in areas such as soft robotics, biomedical devices, and wearable electronics. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Slope-area thresholds of road-induced gully erosion and consequent hillslope-channel interactions
Harry Alexander Katz; J. Michael Daniels; Sandra Ryan-Burkett
2014-01-01
Pikes Peak Highway is a partially paved road between Cascade, Colorado and the summit of Pikes Peak. Significant gully erosion is occurring on the hillslopes due to the concentration of surface runoff, the rearrangement of drainage pathways along the road surface and adjacent drainage ditches, and the high erodibility of weathered Pikes Peak granite that underlies the...
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Paving the road to maximum productivity.
Holland, C
1998-01-01
"Job security" is an oxymoron in today's environment of downsizing, mergers, and acquisitions. Workers find themselves living by new rules in the workplace that they may not understand. How do we cope? It is the leader's charge to take advantage of this chaos and create conditions under which his or her people can understand the need for change and come together with a shared purpose to effect that change. The clinical laboratory at Arkansas Children's Hospital has taken advantage of this chaos to down-size and to redesign how the work gets done to pave the road to maximum productivity. After initial hourly cutbacks, the workers accepted the cold, hard fact that they would never get their old world back. They set goals to proactively shape their new world through reorganizing, flexing staff with workload, creating a rapid response laboratory, exploiting information technology, and outsourcing. Today the laboratory is a lean, productive machine that accepts change as a way of life. We have learned to adapt, trust, and support each other as we have journeyed together over the rough roads. We are looking forward to paving a new fork in the road to the future.
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[3D structure of DKK1 indicates its involvement in both canonical and non-canonical Wnt pathways].
Khalili, S; Rasaee, M J; Bamdad, T
2017-01-01
Dikkoppf-1 (DKK1) is an antagonist of the canonical Wnt signaling pathway. The importance of DKK1 as a diagnostic and therapeutic agent in a wide range of diseases along with its significance in a variety of biological processes accentuate the necessity to decipher its 3D structure that would pave the way towards the development of relevant selective inhibitors. A DKK1 structure model predicted by the Robetta server with structural refinements including a 10 ns molecular dynamics run was subjected to functional and docking analyses. We hypothesize that the N-terminal region of the DKK1 molecule could be functionally important for both canonical and noncanonical Wnt pathways. Moreover, it seems that DKK1 could be involved in interactions with the Frizzled receptors, leading to the activation of the Planar Cell Polarity (PCP) pathway (activation of Jun N-terminal kinase (JNK) Pathway) and Wnt/Ca^(2+) pathway (activation of CamKII).
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Berrada, Salim, E-mail: s.berrada@insa.ueuromed.org; Bescond, Marc, E-mail: marc.bescond@im2np.fr; Cavassilas, Nicolas
2015-10-12
This work theoretically studies the influence of both the geometry and the discrete nature of dopants of the access regions in ultra-scaled nanowire transistors. By means of self-consistent quantum transport simulations, we show that discrete dopants induce quasi-localized states which govern carrier injection into the channel. Carrier injection can be enhanced by taking advantage of the dielectric confinement occurring in these access regions. We demonstrate that the optimization of access resistance can be obtained by a careful control of shape and dopant position. These results pave the way for contact resistance engineering in forthcoming device generations.
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Vijayan, Saptha; Mallick, Sathi; Dutta, Mouparna; Narayani, M; Ghosh, Anindya S
2014-02-01
MreB is a cytoskeletal protein, which is responsible for maintaining proper cellular morphology and is essential for cell survival. Likewise, penicillin-binding protein 5 (PBP5) helps in maintaining cell shape, though non-essential for survival. The contradicting feature of these two proteins paves the way for this study, wherein we attempt to draw a relation on the nature of distribution of MreB in PBP deletion mutants. The study revealed that the uniform MreB helices/patches were destabilized/disturbed at the zone of deformities of the PBP mutants, whereas the helical patterns were retained at the regions maintaining a rod shape. We interpret that MreB remains functional irrespective of its distribution being misguided by the aberrant shapes of PBP mutants.
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ERIC Educational Resources Information Center
O'Bryant, Camille
2015-01-01
The purpose of this lecture is to provide the voice and visibility of African American women who have upheld the tradition of excellence set by Amy Morris Homans in the development of physical education in higher education for women and set pathways to transition our field to be more inclusive and diverse and have served as transformative leaders…
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2014-06-13
supporting democracies for better or for worse such as South Vietnam, and not supporting Marxist regimes, such as Cuba . Much less was done to shape the...another small coastal nation focused on banking and tourism . The outliers on the lower end of the range are Zimbabwe, which suffers under the strict
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Sugars and plant innate immunity.
Bolouri Moghaddam, Mohammad Reza; Van den Ende, Wim
2012-06-01
Sugars are involved in many metabolic and signalling pathways in plants. Sugar signals may also contribute to immune responses against pathogens and probably function as priming molecules leading to pathogen-associated molecular patterns (PAMP)-triggered immunity and effector-triggered immunity in plants. These putative roles also depend greatly on coordinated relationships with hormones and the light status in an intricate network. Although evidence in favour of sugar-mediated plant immunity is accumulating, more in-depth fundamental research is required to unravel the sugar signalling pathways involved. This might pave the way for the use of biodegradable sugar-(like) compounds to counteract plant diseases as cheaper and safer alternatives for toxic agrochemicals.
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Biosensor-based engineering of biosynthetic pathways
Rogers, Jameson K.; Taylor, Noah D.; Church, George M.
2016-03-18
Biosynthetic pathways provide an enzymatic route from inexpensive renewable resources to valuable metabolic products such as pharmaceuticals and plastics. However, designing these pathways is challenging due to the complexities of biology. Advances in the design and construction of genetic variants has enabled billions of cells, each possessing a slightly different metabolic design, to be rapidly generated. However, our ability to measure the quality of these designs lags by several orders of magnitude. Recent research has enabled cells to report their own success in chemical production through the use of genetically encoded biosensors. A new engineering discipline is emerging around themore » creation and application of biosensors. Biosensors, implemented in selections and screens to identify productive cells, are paving the way for a new era of biotechnological progress.« less
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High-performance shape-engineerable thermoelectric painting
Park, Sung Hoon; Jo, Seungki; Kwon, Beomjin; Kim, Fredrick; Ban, Hyeong Woo; Lee, Ji Eun; Gu, Da Hwi; Lee, Se Hwa; Hwang, Younghun; Kim, Jin-Sang; Hyun, Dow-Bin; Lee, Sukbin; Choi, Kyoung Jin; Jo, Wook; Son, Jae Sung
2016-01-01
Output power of thermoelectric generators depends on device engineering minimizing heat loss as well as inherent material properties. However, the device engineering has been largely neglected due to the limited flat or angular shape of devices. Considering that the surface of most heat sources where these planar devices are attached is curved, a considerable amount of heat loss is inevitable. To address this issue, here, we present the shape-engineerable thermoelectric painting, geometrically compatible to surfaces of any shape. We prepared Bi2Te3-based inorganic paints using the molecular Sb2Te3 chalcogenidometalate as a sintering aid for thermoelectric particles, with ZT values of 0.67 for n-type and 1.21 for p-type painted materials that compete the bulk values. Devices directly brush-painted onto curved surfaces produced the high output power of 4.0 mW cm−2. This approach paves the way to designing materials and devices that can be easily transferred to other applications. PMID:27834369
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Koopman, Frank; Wierckx, Nick; de Winde, Johannes H.; Ruijssenaars, Harald J.
2010-01-01
The toxic fermentation inhibitors in lignocellulosic hydrolysates pose significant problems for the production of second-generation biofuels and biochemicals. Among these inhibitors, 5-(hydroxymethyl)furfural (HMF) and furfural are specifically notorious. In this study, we describe the complete molecular identification and characterization of the pathway by which Cupriavidus basilensis HMF14 metabolizes HMF and furfural. The identification of this pathway enabled the construction of an HMF and furfural-metabolizing Pseudomonas putida. The genetic information obtained furthermore enabled us to predict the HMF and furfural degrading capabilities of sequenced bacterial species that had not previously been connected to furanic aldehyde metabolism. These results pave the way for in situ detoxification of lignocellulosic hydrolysates, which is a major step toward improved efficiency of utilization of lignocellulosic feedstock. PMID:20194784
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Analysis of cellular signal transduction from an information theoretic approach.
Uda, Shinsuke; Kuroda, Shinya
2016-03-01
Signal transduction processes the information of various cellular functions, including cell proliferation, differentiation, and death. The information for controlling cell fate is transmitted by concentrations of cellular signaling molecules. However, how much information is transmitted in signaling pathways has thus far not been investigated. Shannon's information theory paves the way to quantitatively analyze information transmission in signaling pathways. The theory has recently been applied to signal transduction, and mutual information of signal transduction has been determined to be a measure of information transmission. We review this work and provide an overview of how signal transduction transmits informational input and exerts biological output. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Meta-q-plate for complex beam shaping
Ji, Wei; Lee, Chun-Hong; Chen, Peng; Hu, Wei; Ming, Yang; Zhang, Lijian; Lin, Tsung-Hsien; Chigrinov, Vladimir; Lu, Yan-Qing
2016-01-01
Optical beam shaping plays a key role in optics and photonics. In this work, meta-q-plate featured by arbitrarily space-variant optical axes is proposed and demonstrated via liquid crystal photoalignment based on a polarization-sensitive alignment agent and a dynamic micro-lithography system. Meta-q-plates with multiple-, azimuthally/radially variant topological charges and initial azimuthal angles are fabricated. Accordingly, complex beams with elliptical, asymmetrical, multi-ringed and hurricane transverse profiles are generated, making the manipulation of optical vortex up to an unprecedented flexibility. The evolution, handedness and Michelson interferogram of the hurricane one are theoretically analysed and experimentally verified. The design facilitates the manipulation of polarization and spatial degrees of freedom of light in a point-to-point manner. The realization of meta-q-plate drastically enhances the capability of beam shaping and may pave a bright way towards optical manipulations, OAM based informatics, quantum optics and other fields. PMID:27149897
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Meta-q-plate for complex beam shaping.
Ji, Wei; Lee, Chun-Hong; Chen, Peng; Hu, Wei; Ming, Yang; Zhang, Lijian; Lin, Tsung-Hsien; Chigrinov, Vladimir; Lu, Yan-Qing
2016-05-06
Optical beam shaping plays a key role in optics and photonics. In this work, meta-q-plate featured by arbitrarily space-variant optical axes is proposed and demonstrated via liquid crystal photoalignment based on a polarization-sensitive alignment agent and a dynamic micro-lithography system. Meta-q-plates with multiple-, azimuthally/radially variant topological charges and initial azimuthal angles are fabricated. Accordingly, complex beams with elliptical, asymmetrical, multi-ringed and hurricane transverse profiles are generated, making the manipulation of optical vortex up to an unprecedented flexibility. The evolution, handedness and Michelson interferogram of the hurricane one are theoretically analysed and experimentally verified. The design facilitates the manipulation of polarization and spatial degrees of freedom of light in a point-to-point manner. The realization of meta-q-plate drastically enhances the capability of beam shaping and may pave a bright way towards optical manipulations, OAM based informatics, quantum optics and other fields.
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A lateral signalling pathway coordinates shape volatility during cell migration
Zhang, Liang; Luga, Valbona; Armitage, Sarah K.; Musiol, Martin; Won, Amy; Yip, Christopher M.; Plotnikov, Sergey V.; Wrana, Jeffrey L.
2016-01-01
Cell migration is fundamental for both physiological and pathological processes. Migrating cells usually display high dynamics in morphology, which is orchestrated by an integrative array of signalling pathways. Here we identify a novel pathway, we term lateral signalling, comprised of the planar cell polarity (PCP) protein Pk1 and the RhoGAPs, Arhgap21/23. We show that the Pk1–Arhgap21/23 complex inhibits RhoA, is localized on the non-protrusive lateral membrane cortex and its disruption leads to the disorganization of the actomyosin network and altered focal adhesion dynamics. Pk1-mediated lateral signalling confines protrusive activity and is regulated by Smurf2, an E3 ubiquitin ligase in the PCP pathway. Furthermore, we demonstrate that dynamic interplay between lateral and protrusive signalling generates cyclical fluctuations in cell shape that we quantify here as shape volatility, which strongly correlates with migration speed. These studies uncover a previously unrecognized lateral signalling pathway that coordinates shape volatility during productive cell migration. PMID:27226243
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Personalised Medicine: Genome Maintenance Lessons Learned from Studies in Yeast as a Model Organism.
Abugable, Arwa A; Awwad, Dahlia A; Fleifel, Dalia; Ali, Mohamed M; El-Khamisy, Sherif; Elserafy, Menattallah
2017-01-01
Yeast research has been tremendously contributing to the understanding of a variety of molecular pathways due to the ease of its genetic manipulation, fast doubling time as well as being cost-effective. The understanding of these pathways did not only help scientists learn more about the cellular functions but also assisted in deciphering the genetic and cellular defects behind multiple diseases. Hence, yeast research not only opened the doors for transforming basic research into applied research, but also paved the roads for improving diagnosis and innovating personalized therapy of different diseases. In this chapter, we discuss how yeast research has contributed to understanding major genome maintenance pathways such as the S-phase checkpoint activation pathways, repair via homologous recombination and non-homologous end joining as well as topoisomerases-induced protein linked DNA breaks repair. Defects in these pathways lead to neurodegenerative diseases and cancer. Thus, the understanding of the exact genetic defects underlying these diseases allowed the development of personalized medicine, improving the diagnosis and treatment and overcoming the detriments of current conventional therapies such as the side effects, toxicity as well as drug resistance.
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A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs
Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F.; Lecuit, Marc
2016-01-01
Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents. PMID:27177310
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A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.
Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F; Lecuit, Marc
2016-05-12
Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents.
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Chen, Yun; Nielsen, Jens
2013-12-01
Bio-based production of chemical building blocks from renewable resources is an attractive alternative to petroleum-based platform chemicals. Metabolic pathway and strain engineering is the key element in constructing robust microbial chemical factories within the constraints of cost effective production. Here we discuss how the development of computational algorithms, novel modules and methods, omics-based techniques combined with modeling refinement are enabling reduction in development time and thus advance the field of industrial biotechnology. We further discuss how recent technological developments contribute to the development of novel cell factories for the production of the building block chemicals: adipic acid, succinic acid and 3-hydroxypropionic acid. Copyright © 2013 Elsevier Ltd. All rights reserved.
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Gene expression analysis of colorectal cancer by bioinformatics strategy.
Cui, Meng; Yuan, Junhua; Li, Jun; Sun, Bing; Li, Tao; Li, Yuantao; Wu, Guoliang
2014-10-01
We used bioinformatics technology to analyze gene expression profiles involved in colorectal cancer tissue samples and healthy controls. In this paper, we downloaded the gene expression profile GSE4107 from Gene Expression Omnibus (GEO) database, in which a total of 22 chips were available, including normal colonic mucosa tissue from normal healthy donors (n=10), colorectal cancer tissue samples from colorectal patients (n=33). To further understand the biological functions of the screened DGEs, the KEGG pathway enrichment analysis were conducted. Then we built a transcriptome network to study differentially co-expressed links. A total of 3151 DEGs of CRC were selected. Besides, total 164 DCGs (Differentially Coexpressed Gene, DCG) and 29279 DCLs (Differentially Co-expressed Link, DCL) were obtained. Furthermore, the significantly enriched KEGG pathways were Endocytosis, Calcium signaling pathway, Vascular smooth muscle contraction, Linoleic acid metabolism, Arginine and proline metabolism, Inositol phosphate metabolism and MAPK signaling pathway. Our results show that the generation of CRC involves multiple genes, TFs and pathways. Several signal and immune pathways are linked to CRC and give us more clues in the process of CRC. Hence, our work would pave ways for novel diagnosis of CRC, and provided theoretical guidance into cancer therapy.
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ASPHALT FOR OFF-STREET PAVING AND PLAY AREAS, 3RD EDITION.
ERIC Educational Resources Information Center
Asphalt Inst., College Park, MD.
THIS PAMPHLET DISCUSSES THE ALTERNATIVE METHODS, APPLICATIONS, AND TECHNICAL CONSIDERATIONS FOR OFF-STREET PAVING AND PLAY AREAS. OFF-STREET PAVING INCLUDES--(1) ASPHALT-PAVED PARKING AREAS, (2) ROOF DECK PARKING AREAS, (3) ASPHALT-PAVED DRIVEWAYS, (4) ASPHALT-PAVED SERVICE STATION LOTS, AND (5) SIDEWALKS. THE DISCUSSION OF PLAY AREAS…
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Programmable Extreme Chirality in the Visible by Helix-Shaped Metamaterial Platform.
Esposito, Marco; Tasco, Vittorianna; Todisco, Francesco; Cuscunà, Massimo; Benedetti, Alessio; Scuderi, Mario; Nicotra, Giuseppe; Passaseo, Adriana
2016-09-14
The capability to fully control the chiro-optical properties of metamaterials in the visible range enables a number of applications from integrated photonics to life science. To achieve this goal, a simultaneous control over complex spatial and localized structuring as well as material composition at the nanoscale is required. Here, we demonstrate how circular dichroic bands and optical rotation can be effectively and independently tailored throughout the visible regime as a function of the fundamental meta-atoms properties and of their three dimensional architecture in a the helix-shaped metamaterials. The record chiro-optical effects obtained in the visible range are accompanied by an additional control over optical efficiency, even in the plasmonic context. These achievements pave the way toward fully integrated chiral photonic devices.
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NASA Astrophysics Data System (ADS)
Karolina, R.; Syahrizal; Bahri, N.
2018-02-01
The waste of coal burning has a very negative impact on the environment if the waste is not managed as well as possible. The remaining waste of coal combustion consists of fly ash and bottom ash. FA and BA can be developed into substitution materials in the process of making paving blocks. The purpose of this study was to determine the quality of paving block in accordance with SK SNI 03-0691-1996 with optimization in the use of FA and BA. This study uses a 351 paving block sample size of 20x10x6 cm. Paving blocks are divided by 4 categories, namely normal paving block, paving block with FA substitution, BA substitution and combination of FA-BA with each variation 0%, 25%, 50%, 75% and 100%. Each variation amounted to 27 samples. Paving block quality measurement is done through 4 tests: absorption, compressive strength, sodium sulphate resistance and Los Angeles tests. The result of the test shows the absorption of normal paving block is 3,229%, paving block with 25% FA is 3,889%, paving block with 50% BA is 5,560% and paving block with 25% FA-BA combination is 5,794%. Compressive strength in normal paving block is 25,50 MPa, paving block with 25% FA is 25,28 MPa, paving block with 25% BA is equal to 27,61 MPa and paving block with 25% FA-BA is 26, 00 MPa. In testing of sodium sulfate resistance, almost all test specimens are eligible except for paving block with 50% FA and 75% FA. In the test of wear resistance, no specimen is eligible according to SK SNI 03-0691-1996. The comparison of the strength of the test specimen can be seen in substitution with 25% BA which reaches maximum strength.
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In situ 3D nanoprinting of free-form coupling elements for hybrid photonic integration
NASA Astrophysics Data System (ADS)
Dietrich, P.-I.; Blaicher, M.; Reuter, I.; Billah, M.; Hoose, T.; Hofmann, A.; Caer, C.; Dangel, R.; Offrein, B.; Troppenz, U.; Moehrle, M.; Freude, W.; Koos, C.
2018-04-01
Hybrid photonic integration combines complementary advantages of different material platforms, offering superior performance and flexibility compared with monolithic approaches. This applies in particular to multi-chip concepts, where components can be individually optimized and tested. The assembly of such systems, however, requires expensive high-precision alignment and adaptation of optical mode profiles. We show that these challenges can be overcome by in situ printing of facet-attached beam-shaping elements. Our approach allows precise adaptation of vastly dissimilar mode profiles and permits alignment tolerances compatible with cost-efficient passive assembly techniques. We demonstrate a selection of beam-shaping elements at chip and fibre facets, achieving coupling efficiencies of up to 88% between edge-emitting lasers and single-mode fibres. We also realize printed free-form mirrors that simultaneously adapt beam shape and propagation direction, and we explore multi-lens systems for beam expansion. The concept paves the way to automated assembly of photonic multi-chip systems with unprecedented performance and versatility.
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When things go pear shaped: contour variations of contacts
NASA Astrophysics Data System (ADS)
Utzny, Clemens
2013-04-01
Traditional control of critical dimensions (CD) on photolithographic masks considers the CD average and a measure for the CD variation such as the CD range or the standard deviation. Also systematic CD deviations from the mean such as CD signatures are subject to the control. These measures are valid for mask quality verification as long as patterns across a mask exhibit only size variations and no shape variation. The issue of shape variations becomes especially important in the context of contact holes on EUV masks. For EUV masks the CD error budget is much smaller than for standard optical masks. This means that small deviations from the contact shape can impact EUV waver prints in the sense that contact shape deformations induce asymmetric bridging phenomena. In this paper we present a detailed study of contact shape variations based on regular product data. Two data sets are analyzed: 1) contacts of varying target size and 2) a regularly spaced field of contacts. Here, the methods of statistical shape analysis are used to analyze CD SEM generated contour data. We demonstrate that contacts on photolithographic masks do not only show size variations but exhibit also pronounced nontrivial shape variations. In our data sets we find pronounced shape variations which can be interpreted as asymmetrical shape squeezing and contact rounding. Thus we demonstrate the limitations of classic CD measures for describing the feature variations on masks. Furthermore we show how the methods of statistical shape analysis can be used for quantifying the contour variations thus paving the way to a new understanding of mask linearity and its specification.
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Leveraging algal omics to reveal potential targets for augmenting TAG accumulation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Arora, Neha; Pienkos, Philip T.; Pruthi, Vikas
Ongoing global efforts to commercialize microalgal biofuels have expedited the use of multi-omics techniques to gain insights into lipid biosynthetic pathways. Functional genomics analyses have recently been employed to complement existing sequence-level omics studies, shedding light on the dynamics of lipid synthesis and its interplay with other cellular metabolic pathways, thus revealing possible targets for metabolic engineering. Here, we review the current status of algal omics studies to reveal potential targets to augment TAG accumulation in various microalgae. Here, this review specifically aims to examine and catalog systems level data related to stress-induced TAG accumulation in oleaginous microalgae and informmore » future metabolic engineering strategies to develop strains with enhanced bioproductivity, which could pave a path for sustainable green energy.« less
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Leveraging Algal Omics to Reveal Potential Targets for Augmenting TAG Accumulation
DOE Office of Scientific and Technical Information (OSTI.GOV)
Guarnieri, Michael T; Pienkos, Philip T; Arora, Neha
2018-04-18
Ongoing global efforts to commercialize microalgal biofuels have expedited the use of multi-omics techniques to gain insights into lipid biosynthetic pathways. Functional genomics analyses have recently been employed to complement existing sequence-level omics studies, shedding light on the dynamics of lipid synthesis and its interplay with other cellular metabolic pathways, thus revealing possible targets for metabolic engineering. Here, we review the current status of algal omics studies to reveal potential targets to augment TAG accumulation in various microalgae. This review specifically aims to examine and catalog systems level data related to stress-induced TAG accumulation in oleaginous microalgae and inform futuremore » metabolic engineering strategies to develop strains with enhanced bioproductivity, which could pave a path for sustainable green energy.« less
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Leveraging algal omics to reveal potential targets for augmenting TAG accumulation
Arora, Neha; Pienkos, Philip T.; Pruthi, Vikas; ...
2018-04-18
Ongoing global efforts to commercialize microalgal biofuels have expedited the use of multi-omics techniques to gain insights into lipid biosynthetic pathways. Functional genomics analyses have recently been employed to complement existing sequence-level omics studies, shedding light on the dynamics of lipid synthesis and its interplay with other cellular metabolic pathways, thus revealing possible targets for metabolic engineering. Here, we review the current status of algal omics studies to reveal potential targets to augment TAG accumulation in various microalgae. Here, this review specifically aims to examine and catalog systems level data related to stress-induced TAG accumulation in oleaginous microalgae and informmore » future metabolic engineering strategies to develop strains with enhanced bioproductivity, which could pave a path for sustainable green energy.« less
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Leveraging algal omics to reveal potential targets for augmenting TAG accumulation.
Arora, Neha; Pienkos, Philip T; Pruthi, Vikas; Poluri, Krishna Mohan; Guarnieri, Michael T
2018-04-18
Ongoing global efforts to commercialize microalgal biofuels have expedited the use of multi-omics techniques to gain insights into lipid biosynthetic pathways. Functional genomics analyses have recently been employed to complement existing sequence-level omics studies, shedding light on the dynamics of lipid synthesis and its interplay with other cellular metabolic pathways, thus revealing possible targets for metabolic engineering. Here, we review the current status of algal omics studies to reveal potential targets to augment TAG accumulation in various microalgae. This review specifically aims to examine and catalog systems level data related to stress-induced TAG accumulation in oleaginous microalgae and inform future metabolic engineering strategies to develop strains with enhanced bioproductivity, which could pave a path for sustainable green energy. Copyright © 2018. Published by Elsevier Inc.
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Quantum ring with the Rashba spin-orbit interaction in the regime of strong light-matter coupling
NASA Astrophysics Data System (ADS)
Kozin, V. K.; Iorsh, I. V.; Kibis, O. V.; Shelykh, I. A.
2018-04-01
We developed the theory of electronic properties of semiconductor quantum rings with the Rashba spin-orbit interaction irradiated by an off-resonant high-frequency electromagnetic field (dressing field). Within the Floquet theory of periodically driven quantum systems, it is demonstrated that the dressing field drastically modifies all electronic characteristics of the rings, including spin-orbit coupling, effective electron mass, and optical response. In particular, the present effect paves the way to controlling the spin polarization of electrons with light in prospective ring-shaped spintronic devices.
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In situ realization of particlelike scattering states in a microwave cavity
NASA Astrophysics Data System (ADS)
Böhm, Julian; Brandstötter, Andre; Ambichl, Philipp; Rotter, Stefan; Kuhl, Ulrich
2018-02-01
We realize scattering states in a lossy and chaotic two-dimensional microwave cavity which follow bundles of classical particle trajectories. To generate such particlelike scattering states, we measure the system's complex transmission matrix and apply an adapted Wigner-Smith time-delay formalism to it. The necessary shaping of the incident wave is achieved in situ using phase- and amplitude-regulated microwave antennas. Our experimental findings pave the way for establishing spatially confined communication channels that avoid possible intruders or obstacles in wave-based communication systems.
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Hartman, Nicholas D; Harper, Erin N; Leppert, Lauren M; Browning, Brittany M; Askew, Kim; Manthey, David E; Mahler, Simon A
We created and tested an educational intervention to support implementation of an institution wide QI project (the HEART Pathway) designed to improve care for patients with acute chest pain. Although online learning modules have been shown effective in imparting knowledge regarding QI projects, it is unknown whether these modules are effective across specialties and healthcare professions. Participants, including nurses, advanced practice clinicians, house staff and attending physicians (N = 486), were enrolled into an online, self-directed learning course exploring the key concepts of the HEART Pathway. The module was completed by 97% of enrollees (469/486) and 90% passed on the first attempt (422/469). Out of 469 learners, 323 completed the pretest, learning module and posttest in the correct order. Mean test scores across learners improved significantly from 74% to 89% from the pretest to the posttest. Following the intervention, the HEART Pathway was used for 88% of patients presenting to our institution with acute chest pain. Our data demonstrate that this online, self-directed learning module can improve knowledge of the HEART Pathway across specialties-paving the way for more efficient and informed care for acute chest pain patients.
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Sakai, Kaori; Taconnat, Ludivine; Borrega, Nero; Yansouni, Jennifer; Brunaud, Véronique; Paysant-Le Roux, Christine; Delannoy, Etienne; Martin Magniette, Marie-Laure; Lepiniec, Loïc; Faure, Jean Denis; Balzergue, Sandrine; Dubreucq, Bertrand
2018-01-01
Genome-wide characterization of tissue- or cell-specific gene expression is a recurrent bottleneck in biology. We have developed a sensitive approach based on ultra-low RNA sequencing coupled to laser assisted microdissection for analyzing different tissues of the small Arabidopsis embryo. We first characterized the number of genes detected according to the quantity of tissue yield and total RNA extracted. Our results revealed that as low as 0.02 mm 2 of tissue and 50 pg of total RNA can be used without compromising the number of genes detected. The optimised protocol was used to compare the epidermal versus mesophyll cell transcriptomes of cotyledons at the torpedo-shaped stage of embryo development. The approach was validated by the recovery of well-known epidermal genes such AtML1 or AtPDF2 and genes involved in flavonoid and cuticular waxes pathways. Moreover, the interest and sensitivity of this approach were highlighted by the characterization of several transcription factors preferentially expressed in epidermal cells. This technical advance unlocks some current limitations of transcriptomic analyses and allows to investigate further and efficiently new biological questions for which only a very small amounts of cells need to be isolated. For instance, it paves the way to increasing the spatial accuracy of regulatory networks in developing small embryo of Arabidopsis or other plant tissues.
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2017-01-01
Recent studies have challenged the ventral/“what” and dorsal/“where” two-visual-processing-pathway view by showing the existence of “what” and “where” information in both pathways. Is the two-pathway distinction still valid? Here, we examined how goal-directed visual information processing may differentially impact visual representations in these two pathways. Using fMRI and multivariate pattern analysis, in three experiments on human participants (57% females), by manipulating whether color or shape was task-relevant and how they were conjoined, we examined shape-based object category decoding in occipitotemporal and parietal regions. We found that object category representations in all the regions examined were influenced by whether or not object shape was task-relevant. This task effect, however, tended to decrease as task-relevant and irrelevant features were more integrated, reflecting the well-known object-based feature encoding. Interestingly, task relevance played a relatively minor role in driving the representational structures of early visual and ventral object regions. They were driven predominantly by variations in object shapes. In contrast, the effect of task was much greater in dorsal than ventral regions, with object category and task relevance both contributing significantly to the representational structures of the dorsal regions. These results showed that, whereas visual representations in the ventral pathway are more invariant and reflect “what an object is,” those in the dorsal pathway are more adaptive and reflect “what we do with it.” Thus, despite the existence of “what” and “where” information in both visual processing pathways, the two pathways may still differ fundamentally in their roles in visual information representation. SIGNIFICANCE STATEMENT Visual information is thought to be processed in two distinctive pathways: the ventral pathway that processes “what” an object is and the dorsal pathway that processes “where” it is located. This view has been challenged by recent studies revealing the existence of “what” and “where” information in both pathways. Here, we found that goal-directed visual information processing differentially modulates shape-based object category representations in the two pathways. Whereas ventral representations are more invariant to the demand of the task, reflecting what an object is, dorsal representations are more adaptive, reflecting what we do with the object. Thus, despite the existence of “what” and “where” information in both pathways, visual representations may still differ fundamentally in the two pathways. PMID:28821655
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Houdayer, Jérôme; Poitevin, Frédéric
This paper shows how small-angle scattering (SAS) curves can be decomposed in a simple sum using a set of invariant parameters calledK nwhich are related to the shape of the object of study. TheseK n, together with a radiusR, give a complete theoretical description of the SAS curve. Adding an overall constant, these parameters are easily fitted against experimental data giving a concise comprehensive description of the data. The pair distance distribution function is also entirely described by this invariant set and theD maxparameter can be measured. In addition to the understanding they bring, these invariants can be used tomore » reliably estimate structural moments beyond the radius of gyration, thereby rigorously expanding the actual set of model-free quantities one can extract from experimental SAS data, and possibly paving the way to designing new shape reconstruction strategies.« less
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Localized surface plasmons in vibrating graphene nanodisks
NASA Astrophysics Data System (ADS)
Wang, Weihua; Li, Bo-Hong; Stassen, Erik; Mortensen, N. Asger; Christensen, Johan
2016-02-01
Localized surface plasmons are confined collective oscillations of electrons in metallic nanoparticles. When driven by light, the optical response is dictated by geometrical parameters and the dielectric environment and plasmons are therefore extremely important for sensing applications. Plasmons in graphene disks have the additional benefit of being highly tunable via electrical stimulation. Mechanical vibrations create structural deformations in ways where the excitation of localized surface plasmons can be strongly modulated. We show that the spectral shift in such a scenario is determined by a complex interplay between the symmetry and shape of the modal vibrations and the plasmonic mode pattern. Tuning confined modes of light in graphene via acoustic excitations, paves new avenues in shaping the sensitivity of plasmonic detectors, and in the enhancement of the interaction with optical emitters, such as molecules, for future nanophotonic devices.
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Cabet, Eva; Batonnet-Pichon, Sabrina; Delort, Florence; Gausserès, Blandine; Vicart, Patrick; Lilienbaum, Alain
2015-01-01
Desminopathies, a subgroup of myofibrillar myopathies (MFMs), the progressive muscular diseases characterized by the accumulation of granulofilamentous desmin-positive aggregates, result from mutations in the desmin gene (DES), encoding a muscle-specific intermediate filament. Desminopathies often lead to severe disability and premature death from cardiac and/or respiratory failure; no specific treatment is currently available. To identify drug-targetable pathophysiological pathways, we performed pharmacological studies in C2C12 myoblastic cells expressing mutant DES. We found that inhibition of the Rac1 pathway (a G protein signaling pathway involved in diverse cellular processes), antioxidant treatment, and stimulation of macroautophagy reduced protein aggregation by up to 75% in this model. Further, a combination of two or three of these treatments was more effective than any of them alone. These results pave the way towards the development of the first treatments for desminopathies and are potentially applicable to other muscle or brain diseases associated with abnormal protein aggregation. PMID:26333167
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Ma, Jane Y C; Rengasamy, Apavoo; Frazer, Dave; Barger, Mark W; Hubbs, Ann F; Battelli, Lori; Tomblyn, Seith; Stone, Samuel; Castranova, Vince
2003-01-01
Asphalt fumes are complex mixtures of various organic compounds, including polycyclic aromatic hydrocarbons (PAHs). PAHs require bioactivation by the cytochrome P-450 monooxygenase system to exert toxic/carcinogenic effects. The present study was carried out to characterize the acute pulmonary inflammatory responses and the alterations of pulmonary xenobiotic pathways in rats exposed to asphalt fumes by inhalation. Rats were exposed at various doses and time periods to air or to asphalt fumes generated at paving temperatures. To assess the acute damage and inflammatory responses, differential cell counts, acellular lactate dehydrogenase (LDH) activity, and protein content of bronchoalveolar lavage fluid were determined. Alveolar macrophage (AM) function was assessed by monitoring generation of chemiluminescence and production of tumor necrosis factor-alpha and interleukin-1. Alteration of pulmonary xenobiotic pathways was determined by monitoring the protein levels and activities of P-450 isozymes (CYP1A1 and CYP2B1), glutathioneS-transferase (GST), and NADPH:quinone oxidoreductase (QR). The results show that acute asphalt fume exposure did not cause neutrophil infiltration, alter LDH activity or protein content, or affect AM function, suggesting that short-term asphalt fume exposure did not induce acute lung damage or inflammation. However, acute asphalt fume exposure significantly increased the activity and protein level of CYP1A1 whereas it markedly reduced the activity and protein level of CYP2B1 in the lung. The induction of CYP1A1 was localized in nonciliated bronchiolar epithelial (Clara) cells, alveolar septa, and endothelial cells by immunofluorescence microscopy. Cytosolic QR activity was significantly elevated after asphalt fume exposure, whereas GST activity was not affected by the exposure. This induction of CYP1A1 and QR with the concomitant down-regulation of CYP2B1 after asphalt fume exposure could alter PAH metabolism and may lead to potential toxic effects in the lung. PMID:12842776
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Mattiazzi, M.; Jambhekar, A.; Kaferle, P.; DeRisi, J. L.; Križaj, I.
2010-01-01
Modulating composition and shape of biological membranes is an emerging mode of regulation of cellular processes. We investigated the global effects that such perturbations have on a model eukaryotic cell. Phospholipases A2 (PLA2s), enzymes that cleave one fatty acid molecule from membrane phospholipids, exert their biological activities through affecting both membrane composition and shape. We have conducted a genome-wide analysis of cellular effects of a PLA2 in the yeast Saccharomyces cerevisiae as a model system. We demonstrate functional genetic and biochemical interactions between PLA2 activity and the Rim101 signaling pathway in S. cerevisiae. Our results suggest that the composition and/or the shape of the endosomal membrane affect the Rim101 pathway. We describe a genetically and functionally related network, consisting of components of the Rim101 pathway and the prefoldin, retromer and SWR1 complexes, and predict its functional relation to PLA2 activity in a model eukaryotic cell. This study provides a list of the players involved in the global response to changes in membrane composition and shape in a model eukaryotic cell, and further studies are needed to understand the precise molecular mechanisms connecting them. Electronic supplementary material The online version of this article (doi:10.1007/s00438-010-0533-8) contains supplementary material, which is available to authorized users. PMID:20379744
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Pitzer, Martin; Kastirke, Gregor; Kunitski, Maksim; Jahnke, Till; Bauer, Tobias; Goihl, Christoph; Trinter, Florian; Schober, Carl; Henrichs, Kevin; Becht, Jasper; Zeller, Stefan; Gassert, Helena; Waitz, Markus; Kuhlins, Andreas; Sann, Hendrik; Sturm, Felix; Wiegandt, Florian; Wallauer, Robert; Schmidt, Lothar Ph H; Johnson, Allan S; Mazenauer, Manuel; Spenger, Benjamin; Marquardt, Sabrina; Marquardt, Sebastian; Schmidt-Böcking, Horst; Stohner, Jürgen; Dörner, Reinhard; Schöffler, Markus; Berger, Robert
2016-08-18
The absolute configuration of individual small molecules in the gas phase can be determined directly by light-induced Coulomb explosion imaging (CEI). Herein, this approach is demonstrated for ionization with a single X-ray photon from a synchrotron light source, leading to enhanced efficiency and faster fragmentation as compared to previous experiments with a femtosecond laser. In addition, it is shown that even incomplete fragmentation pathways of individual molecules from a racemic CHBrClF sample can give access to the absolute configuration in CEI. This leads to a significant increase of the applicability of the method as compared to the previously reported complete break-up into atomic ions and can pave the way for routine stereochemical analysis of larger chiral molecules by light-induced CEI. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Statewide implementation of Pave-IR in the Texas Department of Transportation.
DOT National Transportation Integrated Search
2012-02-01
This project conducted work to complement implementation of Pave-IR into the Texas Department of : Transportations hot-mix-asphalt quality control/quality assurance specification. Pave-IR provides real-time : thermal profiling of paving operations...
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Understanding pave-IR : background, use, and advanced techniques
DOT National Transportation Integrated Search
2010-01-01
Why Has TxDOT Implemented Pave-IR? : Promote more uniform, higher quality pavements : Minimize/eliminate thermal segregation : Expand range of weather conditions for paving : Special Provision 341-024 : Contains option for contractor to use Pave-IR :...
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DOT National Transportation Integrated Search
1990-01-01
The objectives of this study were (1) to review the literature on paved shoulders, (2) to survey state departments of transportation on their use of paved shoulders on two laneroads, (3) to perform a cost analysis on paved shoulders, and (4) to draw ...
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Spin Pumping in Electrodynamically Coupled Magnon-Photon Systems.
Bai, Lihui; Harder, M; Chen, Y P; Fan, X; Xiao, J Q; Hu, C-M
2015-06-05
We use electrical detection, in combination with microwave transmission, to investigate both resonant and nonresonant magnon-photon coupling at room temperature. Spin pumping in a dynamically coupled magnon-photon system is found to be distinctly different from previous experiments. Characteristic coupling features such as modes anticrossing, linewidth evolution, peculiar line shape, and resonance broadening are systematically measured and consistently analyzed by a theoretical model set on the foundation of classical electrodynamic coupling. Our experimental and theoretical approach paves the way for pursuing microwave coherent manipulation of pure spin current via the combination of spin pumping and magnon-photon coupling.
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A class of invisible inhomogeneous media and the control of electromagnetic waves
NASA Astrophysics Data System (ADS)
Vial, B.; Liu, Y.; Horsley, S. A. R.; Philbin, T. G.; Hao, Y.
2016-12-01
We propose a general method to arbitrarily manipulate an electromagnetic wave propagating in a two-dimensional medium, without introducing any scattering. This leads to a whole class of isotropic spatially varying permittivity and permeability profiles that are invisible while shaping the field magnitude and/or phase. In addition, we propose a metamaterial structure working in the infrared that demonstrates deep subwavelength control of the electric field amplitude and strong reduction of the scattering. This work offers an alternative strategy to achieve invisibility with isotropic materials and paves the way for tailoring the propagation of light at the nanoscale.
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Abdus-Saboor, Ishmail; Stone, Craig E.; Murray, John I.; Sundaram, Meera V.
2012-01-01
Cells perform wide varieties of functions that are facilitated, in part, by adopting unique shapes. Many of the genes and pathways that promote cell fate specification have been elucidated. However, relatively few transcription factors have been identified that promote shape acquisition after fate specification. Here we show that the Nkx5/HMX homeodomain protein MLS-2 is required for cellular elongation and shape maintenance of two tubular epithelial cells in the C.elegans excretory system, the duct and pore cells. The Nkx5/HMX family is highly conserved from sea urchins to humans, with known roles in neuronal and glial development. MLS-2 is expressed in the duct and pore, and defects in mls-2 mutants first arise when the duct and pore normally adopt unique shapes. MLS-2 cooperates with the EGF-Ras-ERK pathway to turn on the LIN-48/Ovo transcription factor in the duct cell during morphogenesis. These results reveal a novel interaction between the Nkx5/HMX family and the EGF-Ras pathway and implicate a transcription factor, MLS-2, as a regulator of cell shape. PMID:22537498
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Abdus-Saboor, Ishmail; Stone, Craig E; Murray, John I; Sundaram, Meera V
2012-06-15
Cells perform wide varieties of functions that are facilitated, in part, by adopting unique shapes. Many of the genes and pathways that promote cell fate specification have been elucidated. However, relatively few transcription factors have been identified that promote shape acquisition after fate specification. Here we show that the Nkx5/HMX homeodomain protein MLS-2 is required for cellular elongation and shape maintenance of two tubular epithelial cells in the C. elegans excretory system, the duct and pore cells. The Nkx5/HMX family is highly conserved from sea urchins to humans, with known roles in neuronal and glial development. MLS-2 is expressed in the duct and pore, and defects in mls-2 mutants first arise when the duct and pore normally adopt unique shapes. MLS-2 cooperates with the EGF-Ras-ERK pathway to turn on the LIN-48/Ovo transcription factor in the duct cell during morphogenesis. These results reveal a novel interaction between the Nkx5/HMX family and the EGF-Ras pathway and implicate a transcription factor, MLS-2, as a regulator of cell shape. Copyright © 2012 Elsevier Inc. All rights reserved.
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Automated laser guidance of neuronal growth cones using a spatial light modulator.
Carnegie, David J; Cizmár, Tomás; Baumgartl, Jörg; Gunn-Moore, Frank J; Dholakia, Kishan
2009-11-01
The growth cone of a developing neuron can be guided using a focused infra-red (IR) laser beam [1]. In previous setups this process has required a significant amount of user intervention to adjust continuously the laser beam to guide the growing neuron. Previously, a system using an acousto-optical deflector (AOD) has been developed to steer the beam [2]. However, to enhance the controllability of this system, here we demonstrate the use of a computer controlled spatial light modulator (SLM) to steer and manipulate the shape of a laser beam for use in guided neuronal growth. This new experimental setup paves the way to enable a comprehensive investigation into beam shaping effects on neuronal growth and we show neuronal growth initiated by a Bessel light mode. This is a robust platform to explore the biochemistry of this novel phenomenon. (c) 2009 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
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Electrically controlled wire-channel GaN/AlGaN transistor for terahertz plasma applications
NASA Astrophysics Data System (ADS)
Cywiński, G.; Yahniuk, I.; Kruszewski, P.; Grabowski, M.; Nowakowski-Szkudlarek, K.; Prystawko, P.; Sai, P.; Knap, W.; Simin, G. S.; Rumyantsev, S. L.
2018-03-01
We report on a design of fin-shaped channel GaN/AlGaN field-effect transistors developed for studying resonant terahertz plasma oscillations. Unlike common two dimensional FinFET transistor design, the gates were deposited only to the sides of the two dimensional electron gas channel, i.e., metal layers were not deposited on the top of the AlGaN. This side gate configuration allowed us to electrically control the conductivity of the channel by changing its width while keeping the carrier density and mobility virtually unchanged. Computer simulations and analytical model describe well the general shape of the characteristics. The side gate control of the channel width of these transistors allowed us to eliminate the so-called oblique plasma wave modes and paves the way towards future terahertz detectors and emitters using high quality factor plasma wave resonances.
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NASA Astrophysics Data System (ADS)
Chen, Ming; Xiao, Xiaofei; Chang, Linzi; Wang, Congyun; Zhao, Deping
2017-07-01
In this work, a high-efficiency and tunable dual-frequency reflective polarization converter composed of graphene metasurface with twisting double L-shaped unit is firstly realized. Numerical results demonstrate that the device can convert a linearly polarized wave to its cross-polarized wave, and meantime it can also convert to a circularly polarized wave. Subsequently, one thickness of 500 nm SiO2 layer sandwiched by two graphene metasurfaces with similar pattern is stacked on the top of the two-layered structure, a four-frequency efficient reflective polarization converters is realized. Above all, those working frequencies can also be dynamically tuned within a large frequency range by adjusting the Fermi energy of the graphene, without reoptimizing and refabricating the nanostructures, which paves a novel way toward developing a controllable polarization converter for mid-infrared applications.
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DAPD: A Knowledgebase for Diabetes Associated Proteins.
Gopinath, Krishnasamy; Jayakumararaj, Ramaraj; Karthikeyan, Muthusamy
2015-01-01
Recent advancements in genomics and proteomics provide a solid foundation for understanding the pathogenesis of diabetes. Proteomics of diabetes associated pathways help to identify the most potent target for the management of diabetes. The relevant datasets are scattered in various prominent sources which takes much time to select the therapeutic target for the clinical management of diabetes. However, additional information about target proteins is needed for validation. This lacuna may be resolved by linking diabetes associated genes, pathways and proteins and it will provide a strong base for the treatment and planning management strategies of diabetes. Thus, a web source "Diabetes Associated Proteins Database (DAPD)" has been developed to link the diabetes associated genes, pathways and proteins using PHP, MySQL. The current version of DAPD has been built with proteins associated with different types of diabetes. In addition, DAPD has been linked to external sources to gain the access to more participatory proteins and their pathway network. DAPD will reduce the time and it is expected to pave the way for the discovery of novel anti-diabetic leads using computational drug designing for diabetes management. DAPD is open accessed via following url www.mkarthikeyan.bioinfoau.org/dapd.
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NASA Astrophysics Data System (ADS)
Zhang, Song; Zhang, Hong; Xu, Ting; Wang, Wenxin; Zhu, Yuhang; Li, Daimin; Zhang, Zhiyi; Yi, Juemin; Wang, Wei
2018-06-01
In this paper we investigate the strong exciton-plasmon coupling in a hybrid system consisting of an atomic thick WS2 monolayer and a gold nanogroove array. We theoretically identify the coexistence of two damping pathways: a coherent damping pathway resulting from the resonant dipole-dipole interaction and a coupling-induced incoherent damping pathway due to the spontaneous emissions of a photon by one subsystem and its subsequent reabsorption by the other. We show that the interplay between both interaction processes not only determines the optical property of the hybrid system, but also results in a pronounced modification of the radiative damping due to the formation of super- and subradiant polariton states. Importantly, we reveal that the radiative damping property of the polariton modes is determined only by the effect of coupling-induced sub- and super-radiance, which is distinctly different from that previously observed in a metal-molecular hybrid system where pure dephasing of J-aggregate excitons dominates the polariton dynamics. Our findings may pave the way towards active manipulation of polariton dynamics and offer possibilities for realizing coherent active control in novel plasmonic devices.
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Resolving the Spatial Structures of Bound Hole States in Black Phosphorus.
Qiu, Zhizhan; Fang, Hanyan; Carvalho, Alexandra; Rodin, A S; Liu, Yanpeng; Tan, Sherman J R; Telychko, Mykola; Lv, Pin; Su, Jie; Wang, Yewu; Castro Neto, A H; Lu, Jiong
2017-11-08
Understanding the local electronic properties of individual defects and dopants in black phosphorus (BP) is of great importance for both fundamental research and technological applications. Here, we employ low-temperature scanning tunnelling microscope (LT-STM) to probe the local electronic structures of single acceptors in BP. We demonstrate that the charge state of individual acceptors can be reversibly switched by controlling the tip-induced band bending. In addition, acceptor-related resonance features in the tunnelling spectra can be attributed to the formation of Rydberg-like bound hole states. The spatial mapping of the quantum bound states shows two distinct shapes evolving from an extended ellipse shape for the 1s ground state to a dumbbell shape for the 2p x excited state. The wave functions of bound hole states can be well-described using the hydrogen-like model with anisotropic effective mass, corroborated by our theoretical calculations. Our findings not only provide new insight into the many-body interactions around single dopants in this anisotropic two-dimensional material but also pave the way to the design of novel quantum devices.
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DNA repair targeted therapy: the past or future of cancer treatment?
Gavande, Navnath S.; VanderVere-Carozza, Pamela S.; Hinshaw, Hilary D.; Jalal, Shadia I.; Sears, Catherine R.; Pawelczak, Katherine S.; Turchi, John J.
2016-01-01
The repair of DNA damage is a complex process that relies on particular pathways to remedy specific types of damage to DNA. The range of insults to DNA includes small, modest changes in structure including mismatched bases and simple methylation events to oxidized bases, intra- and interstrand DNA crosslinks, DNA double strand breaks and protein-DNA adducts. Pathways required for the repair of these lesions include mismatch repair, base excision repair, nucleotide excision repair, and the homology directed repair/Fanconi anemia pathway. Each of these pathways contributes to genetic stability, and mutations in genes encoding proteins involved in these pathways have been demonstrated to promote genetic instability and cancer. In fact, it has been suggested all cancers display defects in DNA repair. It has also been demonstrated that the ability of cancer cells to repair therapeutically induced DNA damage impacts therapeutic efficacy. This has led to targeting DNA repair pathways and proteins to develop anti-cancer agents that will increase sensitivity to traditional chemotherapeutics. While initial studies languished and were plagued by a lack of specificity and a defined mechanism of action, more recent approaches to exploit synthetic lethal interaction and develop high affinity chemical inhibitors have proven considerably more effective. In this review we will highlight recent advances and discuss previous failures in targeting DNA repair to pave the way for future DNA repair targeted agents and their use in cancer therapy. PMID:26896565
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Targeting Developmental Pathways: The Achilles Heel of Cancer?
Dempke, Wolfram C M; Fenchel, Klaus; Uciechowski, Peter; Chevassut, Timothy
2017-01-01
Developmental pathways (e.g., Notch, Hippo, Hedgehog, Wnt, and TGF-β/BMP/FGF) are networks of genes that act co-ordinately to establish the body plan, and disruptions of genes in one pathway can have effects in related pathways and may result in serious dysmorphogenesis or cancer. Interestingly, all developmental pathways are highly conserved cell signalling systems present in almost all multicellular organisms. In addition, they have a crucial role in cell proliferation, apoptosis, differentiation, and finally in organ development. Of note, almost all of these pathways promote oncogenesis through synergistic associations with the Hippo signalling pathway, and several lines of evidence have also indicated that these pathways (e.g., Wnt/β-catenin) may be implicated in checkpoint inhibitor resistance (e.g., CTLA-4, PD-1, and PD-L1). Since Notch inhibition in vivo results in partial loss of its stemness features such as self-renewal, chemoresistance, invasive and migratory potential, and tumorigenesis, these highly conserved developmental pathways are regarded as being critical for regulation of self-renewal in both embryonic and adult stem cells and hence are likely to be implicated in the maintenance of cancer stem cells. Many small molecules are currently in preclinical and early clinical development, and only two compounds are approved for treatment of advanced or metastatic basal cell carcinoma (vismodegib and sonidegib). Furthermore, therapeutic targeting of cancer stem cells using drugs that disrupt activated developmental pathways may also represent an attractive strategy that is potentially relevant to many types of malignancy, notably blood cancers, where the evidence for leukaemia stem cells is well established. Future work will hopefully pave the way for the development of new strategies for targeting these pervasive oncogenic pathways. © 2017 S. Karger AG, Basel.
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Shen, Yun; Chen, Ri-Dao; Xie, Ke-Bo; Zou, Jian-Hua; Dai, Jun-Gui
2016-12-01
Secoisolariciresinol dehydrogenase (SDH) is a key enzyme involved in the biosynthetic pathway of podophyllotoxin.In this study, two SDH candidate genes,SO282 and SO1223, were cloned from callus of Dysosma versipellis by homology-based PCR and rapid amplification of cDNA end (RACE).The SDH candidate genes were expressed in Escherichia coli and the subsequent enzyme assay in vitro showed that recombinant SO282 had the SDH activity. These results pave the way to the follow-up investigation of the biosynthetic of podophyllotoxin. Copyright© by the Chinese Pharmaceutical Association.
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Sugumaran, Sathish; Jamlos, Mohd Faizal; Ahmad, Mohd Noor; Bellan, Chandar Shekar; Schreurs, Dominique
2018-02-15
Early cancer detection and treatment is an emerging and fascinating field of plasmonic nanobiosensor research. It paves to enrich a life without affecting living cells leading to a possible survival of the patient. This review describes a past and future prospect of an integrated research field on nanostructured metamaterials, microwave transmission, surface plasmonic resonance, nanoantennas, and their manifested versatile properties with nano-biosensors towards early cancer detection to preserve human health. Interestingly, (i) microwave transmission shows more advantages than other electromagnetic radiation in reacting with biological tissues, (ii) nanostructured metamaterial (Au) with special properties like size and shape can stimulate plasmonic effects, (iii) plasmonic based nanobiosensors are to explore the efficacy for early cancer tumour detection or single molecular detection and (iv) nanoantenna wireless communication by using microwave inverse scattering nanomesh (MISN) technique instead of conventional techniques can be adopted to characterize the microwave scattered signals from the biomarkers. It reveals that the nanostructured material with plasmonic nanobiosensor paves a fascinating platform towards early detection of cancer tumour and is anticipated to be exploited as a magnificent field in the future. Copyright © 2017 Elsevier B.V. All rights reserved.
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Replacement of Fine Aggregate by using Recyclable Materials in Paving Blocks
NASA Astrophysics Data System (ADS)
Koganti, Shyam Prakash; Hemanthraja, Kommineni; Sajja, Satish
2017-08-01
Cement concrete paving blocks are precast hard products complete out of cement concrete. The product is made in various sizes and shapes like square, round and rectangular blocks of different dimensions with designs for interlocking of adjacent tiles blocks. Several Research Works have been carried out in the past to study the possibility of utilizing waste materials and industrial byproducts in the manufacturing of paver blocks. Various industrial waste materials like quarry dust, glass powder, ceramic dust and coal dust are used as partial replacement of fine aggregate and assessed the strength parameters and compared the profit percentages after replacement with waste materials. Quarry dust can be replaced by 20% and beyond that the difference in strength is not much higher but considering cost we can replace upto 40% so that we can get a profit of almost 10%. Similarly we can replace glass powder and ceramic dust by 20% only beyond that there is decrement in strength and even with 20% replacement we can get 1.34 % and 2.42% of profit. Coal dust is not suitable for alternative material as fine aggregate as it reduces the strength.
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DOT National Transportation Integrated Search
2009-06-01
This product updates the prior users manual for Pave-IR to reflect changes in hardware and software made : to accommodate collection of GPS data simultaneously during the collection of thermal profiles. The current : Pave-IR system described in th...
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1983-03-01
concrete paving block ( Van der Vlist 1980). The concrete paving block was readily accepted as a substitute for the scarce paving brick and today has...seen in Figure 4, its growth.has been steady ( Van der Vlist 1980). 20 15 0< 0. n 10 1 978 960 1 62 63 64 65 66 67 68 6970 71 72 73 74 7678 7778 79...Figure 4. Concrete paving block production in the Netherlands ( Van der Vlist 1980) 8. The use of concrete paving block in the Netherlands developedI
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Frieder, Jillian; Kivelevitch, Dario; Haugh, Isabel; Watson, Ian; Menter, Alan
2018-01-01
Advancements in the immunopathogenesis of psoriasis have identified interleukin (IL)-23 and IL-17 as fundamental contributors in the immune pathways of the disease. Leveraging these promising therapeutic targets has led to the emergence of a number of anti-IL-23 and -17 biologic agents with the potential to treat multiple conditions with common underlying pathology. The unprecedented clinical efficacy of these agents in the treatment of psoriasis has paved way for their evaluation in diseases such as psoriatic arthritis, Crohn's disease, rheumatoid arthritis, in addition to other immune-mediated conditions. Here we review the IL-23/IL-17 immune pathways and discuss the key clinical and safety data of the anti-IL-23 and anti-IL-17 biologic agents in psoriasis and other immune-mediated diseases. © 2017 American Society for Clinical Pharmacology and Therapeutics.
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Imani, Saber; Panahi, Yunes; Salimian, Jafar; Fu, Junjiang; Ghanei, Mostafa
2015-01-01
Sulfur mustard (SM, bis- (2-chloroethyl) sulphide) is a chemical warfare agent that causes DNA alkylation, protein modification and membrane damage. SM can trigger several molecular pathways involved in inflammation and oxidative stress, which cause cell necrosis and apoptosis, and loss of cells integrity and function. Epigenetic regulation of gene expression is a growing research topic and is addressed by DNA methylation, histone modification, chromatin remodeling, and noncoding RNAs expression. It seems SM can induce the epigenetic modifications that are translated into change in gene expression. Classification of epigenetic modifications long after exposure to SM would clarify its mechanism and paves a better strategy for the treatment of SM-affected patients. In this study, we review the key aberrant epigenetic modifications that have important roles in chronic obstructive pulmonary disease (COPD) and compared with mustard lung. PMID:26557960
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Ventral and Dorsal Visual Stream Contributions to the Perception of Object Shape and Object Location
Zachariou, Valentinos; Klatzky, Roberta; Behrmann, Marlene
2017-01-01
Growing evidence suggests that the functional specialization of the two cortical visual pathways may not be as distinct as originally proposed. Here, we explore possible contributions of the dorsal “where/how” visual stream to shape perception and, conversely, contributions of the ventral “what” visual stream to location perception in human adults. Participants performed a shape detection task and a location detection task while undergoing fMRI. For shape detection, comparable BOLD activation in the ventral and dorsal visual streams was observed, and the magnitude of this activation was correlated with behavioral performance. For location detection, cortical activation was significantly stronger in the dorsal than ventral visual pathway and did not correlate with the behavioral outcome. This asymmetry in cortical profile across tasks is particularly noteworthy given that the visual input was identical and that the tasks were matched for difficulty in performance. We confirmed the asymmetry in a subsequent psychophysical experiment in which participants detected changes in either object location or shape, while ignoring the other, task-irrelevant dimension. Detection of a location change was slowed by an irrelevant shape change matched for difficulty, but the reverse did not hold. We conclude that both ventral and dorsal visual streams contribute to shape perception, but that location processing appears to be essentially a function of the dorsal visual pathway. PMID:24001005
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14 CFR 151.79 - Runway paving: Second runway; wind conditions.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Runway paving: Second runway; wind...: Second runway; wind conditions. (a) All airports. Paving a second runway on the basis of wind conditions... second runway is oriented with the existing paved runway to achieve the maximum wind coverage, with due...
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14 CFR 151.79 - Runway paving: Second runway; wind conditions.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Runway paving: Second runway; wind...: Second runway; wind conditions. (a) All airports. Paving a second runway on the basis of wind conditions... second runway is oriented with the existing paved runway to achieve the maximum wind coverage, with due...
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14 CFR 151.79 - Runway paving: Second runway; wind conditions.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Runway paving: Second runway; wind...: Second runway; wind conditions. (a) All airports. Paving a second runway on the basis of wind conditions... second runway is oriented with the existing paved runway to achieve the maximum wind coverage, with due...
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14 CFR 151.79 - Runway paving: Second runway; wind conditions.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Runway paving: Second runway; wind...: Second runway; wind conditions. (a) All airports. Paving a second runway on the basis of wind conditions... second runway is oriented with the existing paved runway to achieve the maximum wind coverage, with due...
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Plasticity within non-cerebellar pathways rapidly shapes motor performance in vivo
Mitchell, Diana E.; Della Santina, Charles C.; Cullen, Kathleen E.
2016-01-01
Although cerebellar mechanisms are vital to maintain accuracy during complex movements and to calibrate simple reflexes, recent in vitro studies have called into question the widely held view that synaptic changes within cerebellar pathways exclusively guide alterations in motor performance. Here we investigate the vestibulo-ocular reflex (VOR) circuitry by applying temporally precise activation of vestibular afferents in awake-behaving monkeys to link plasticity at different neural sites with changes in motor performance. Behaviourally relevant activation patterns produce rapid attenuation of direct pathway VOR neurons, but not their nerve input. Changes in the strength of this pathway are sufficient to induce a lasting decrease in the evoked VOR. In addition, indirect brainstem pathways display complementary nearly instantaneous changes, contributing to compensating for the reduced sensitivity of primary VOR neurons. Taken together, our data provide evidence that multiple sites of plasticity within VOR pathways can rapidly shape motor performance in vivo. PMID:27157829
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Plasticity within non-cerebellar pathways rapidly shapes motor performance in vivo.
Mitchell, Diana E; Della Santina, Charles C; Cullen, Kathleen E
2016-05-09
Although cerebellar mechanisms are vital to maintain accuracy during complex movements and to calibrate simple reflexes, recent in vitro studies have called into question the widely held view that synaptic changes within cerebellar pathways exclusively guide alterations in motor performance. Here we investigate the vestibulo-ocular reflex (VOR) circuitry by applying temporally precise activation of vestibular afferents in awake-behaving monkeys to link plasticity at different neural sites with changes in motor performance. Behaviourally relevant activation patterns produce rapid attenuation of direct pathway VOR neurons, but not their nerve input. Changes in the strength of this pathway are sufficient to induce a lasting decrease in the evoked VOR. In addition, indirect brainstem pathways display complementary nearly instantaneous changes, contributing to compensating for the reduced sensitivity of primary VOR neurons. Taken together, our data provide evidence that multiple sites of plasticity within VOR pathways can rapidly shape motor performance in vivo.
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Calcaterra, Andrea; Iovine, Valentina; Botta, Bruno; Quaglio, Deborah; D'Acquarica, Ilaria; Ciogli, Alessia; Iazzetti, Antonia; Alfonsi, Romina; Lospinoso Severini, Ludovica; Infante, Paola; Di Marcotullio, Lucia; Mori, Mattia; Ghirga, Francesca
2018-12-01
This work aims at elucidating the mechanism and kinetics of hydrolysis of GANT61, the first and most-widely used inhibitor of the Hedgehog (Hh) signalling pathway that targets Glioma-associated oncogene homologue (Gli) proteins, and at confirming the chemical nature of its bioactive form. GANT61 is poorly stable under physiological conditions and rapidly hydrolyses into an aldehyde species (GANT61-A), which is devoid of the biological activity against Hh signalling, and a diamine derivative (GANT61-D), which has shown inhibition of Gli-mediated transcription. Here, we combined chemical synthesis, NMR spectroscopy, analytical studies, molecular modelling and functional cell assays to characterise the GANT61 hydrolysis pathway. Our results show that GANT61-D is the bioactive form of GANT61 in NIH3T3 Shh-Light II cells and SuFu -/- mouse embryonic fibroblasts, and clarify the structural requirements for GANT61-D binding to Gli1. This study paves the way to the design of GANT61 derivatives with improved potency and chemical stability.
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Emerging therapeutic targets for treatment of leishmaniasis.
Sundar, Shyam; Singh, Bhawana
2018-06-01
Parasitic diseases that pose a threat to human life include leishmaniasis - caused by protozoan parasite Leishmania species. Existing drugs have limitations due to deleterious side effects like teratogenicity, high cost and drug resistance. This calls for the need to have an insight into therapeutic aspects of disease. Areas covered: We have identified different drug targets via. molecular, imuunological, metabolic as well as by system biology approaches. We bring these promising drug targets into light so that they can be explored to their maximum. In an effort to bridge the gaps between existing knowledge and prospects of drug discovery, we have compiled interesting studies on drug targets, thereby paving the way for establishment of better therapeutic aspects. Expert opinion: Advancements in technology shed light on many unexplored pathways. Further probing of well established pathways led to the discovery of new drug targets. This review is a comprehensive report on current and emerging drug targets, with emphasis on several metabolic targets, organellar biochemistry, salvage pathways, epigenetics, kinome and more. Identification of new targets can contribute significantly towards strengthening the pipeline for disease elimination.
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Optical detection of radon decay in air
Sand, Johan; Ihantola, Sakari; Peräjärvi, Kari; Toivonen, Harri; Toivonen, Juha
2016-01-01
An optical radon detection method is presented. Radon decay is directly measured by observing the secondary radiolumines cence light that alpha particles excite in air, and the selectivity of coincident photon detection is further enhanced with online pulse-shape analysis. The sensitivity of a demonstration device was 6.5 cps/Bq/l and the minimum detectable concentration was 12 Bq/m3 with a 1 h integration time. The presented technique paves the way for optical approaches in rapid radon detec tion, and it can be applied beyond radon to the analysis of any alpha-active sample which can be placed in the measurement chamber. PMID:26867800
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Solar energy collection system
NASA Technical Reports Server (NTRS)
Miller, C. G.; Stephens, J. B. (Inventor)
1979-01-01
A fixed, linear, ground-based primary reflector having an extended curved sawtooth-contoured surface covered with a metalized polymeric reflecting material, reflects solar energy to a movably supported collector that is kept at the concentrated line focus reflector primary. The primary reflector may be constructed by a process utilizing well known freeway paving machinery. The solar energy absorber is preferably a fluid transporting pipe. Efficient utilization leading to high temperatures from the reflected solar energy is obtained by cylindrical shaped secondary reflectors that direct off-angle energy to the absorber pipe. A seriatim arrangement of cylindrical secondary reflector stages and spot-forming reflector stages produces a high temperature solar energy collection system of greater efficiency.
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Ethylene resistance in flowering ornamental plants – improvements and future perspectives
Olsen, Andreas; Lütken, Henrik; Hegelund, Josefine Nymark; Müller, Renate
2015-01-01
Various strategies of plant breeding have been attempted in order to improve the ethylene resistance of flowering ornamental plants. These approaches span from conventional techniques such as simple cross-pollination to new breeding techniques which modify the plants genetically such as precise genome-editing. The main strategies target the ethylene pathway directly; others focus on changing the ethylene pathway indirectly via pathways that are known to be antagonistic to the ethylene pathway, e.g. increasing cytokinin levels. Many of the known elements of the ethylene pathway have been addressed experimentally with the aim of modulating the overall response of the plant to ethylene. Elements of the ethylene pathway that appear particularly promising in this respect include ethylene receptors as ETR1, and transcription factors such as EIN3. Both direct and indirect approaches seem to be successful, nevertheless, although genetic transformation using recombinant DNA has the ability to save much time in the breeding process, they are not readily used by breeders yet. This is primarily due to legislative issues, economic issues, difficulties of implementing this technology in some ornamental plants, as well as how these techniques are publically perceived, particularly in Europe. Recently, newer and more precise genome-editing techniques have become available and they are already being implemented in some crops. New breeding techniques may help change the current situation and pave the way toward a legal and public acceptance if products of these technologies are indistinguishable from plants obtained by conventional techniques. PMID:26504580
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NASA Astrophysics Data System (ADS)
Hastuty, I. P.; Sembiringand Nursyamsi, I. S.
2018-02-01
Paving block is one of the material used as the top layer of road structure besides asphalt and concrete paving block is usually made of mixed material such as Portland cement or other adhesive material, water, and aggregate. People nowadays prefer paving block compared to other pavement such as concrete or asphalt. Their interest toward the use of paving block increase because paving block is an eco-friendly construction which is very useful in helping soil water conservation, can be done faster, has easier installation and maintenance, has a variety of shades that increase the aesthetic value, also costs cheaper than the other. Preparation of the specimens with a mixture of Sinabung ash and a mixture of Sinabung ash and lime are implemented with a mixture ratio of cement : sand : stone ash is 1: 2 : 3. The mixture is used as a substitute material by reducing the percentage amount of the weight of the cement with the composition ratio variation based on the comparative volume category of the paving block aggregate, i.e. 0%, 5%, 10%, 15%, 20%, and 25%. The result of this research shows that the maximum compressive strength value is 42.27 Mpa, it was obtained from a mixture of 10% lime with curing time 28 days. The maximum compressive strength value which is obtained from the mixture of sinabung ash is 41.60 Mpa, it was obtained from a mixture of 15% sinabung ash. From the use of these two materials, paving blocks produced are classified as paving blocks quality A and B (350 - 400 Mpa) in accordance to specification from SNI 03-0691-1996.
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Assessing methanotrophy and carbon fixation for biofuel production by Methanosarcina acetivorans
Nazem-Bokaee, Hadi; Gopalakrishnan, Saratram; Ferry, James G.; ...
2016-01-17
Methanosarcina acetivorans is a model archaeon with renewed interest due to its unique reversible methane production pathways. However, the mechanism and relevant pathways implicated in (co)utilizing novel carbon substrates in this organism are still not fully understood. This paper provides a comprehensive inventory of thermodynamically feasible routes for anaerobic methane oxidation, co-reactant utilization, and maximum carbon yields of major biofuel candidates by M. acetivorans. Here, an updated genome-scale metabolic model of M. acetivorans is introduced (iMAC868 containing 868 genes, 845 reactions, and 718 metabolites) by integrating information from two previously reconstructed metabolic models (i.e., iVS941 and iMB745), modifying 17 reactions,more » adding 24 new reactions, and revising 64 gene-proteinreaction associations based on newly available information. The new model establishes improved predictions of growth yields on native substrates and is capable of correctly predicting the knockout outcomes for 27 out of 28 gene deletion mutants. By tracing a bifurcated electron flow mechanism, the iMAC868 model predicts thermodynamically feasible (co)utilization pathway of methane and bicarbonate using various terminal electron acceptors through the reversal of the aceticlastic pathway. In conclusion, this effort paves the way in informing the search for thermodynamically feasible ways of (co)utilizing novel carbon substrates in the domain Archaea.« less
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Ge, Wei; Zhang, Ying; Cheng, Zhanchao; Hou, Dan; Li, Xueping; Gao, Jian
2017-01-01
Moso bamboo is characterized by infrequent sexual reproduction and erratic flowering habit; however, the molecular biology of flower formation and development is not well studied in this species. We studied the molecular regulation mechanisms of moso bamboo development and flowering by selecting three key regulatory pathways: plant-pathogen interaction, plant hormone signal transduction and protein processing in endoplasmic reticulum at different stages of flowering in moso bamboo. We selected PheDof1, PheMADS14 and six microRNAs involved in the three pathways through KEGG pathway and cluster analysis. Subcellular localization, transcriptional activation, Western blotting, in situ hybridization and qRT-PCR were used to further investigate the expression patterns and regulatory roles of pivotal genes at different flower development stages. Differential expression patterns showed that PheDof1, PheMADS14 and six miRNAs may play vital regulatory roles in flower development and floral transition in moso bamboo. Our research paves way for further studies on metabolic regulatory networks and provides insight into the molecular regulation mechanisms of moso bamboo flowering and senescence. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.
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The Papillomavirus Episteme: a central resource for papillomavirus sequence data and analysis.
Van Doorslaer, Koenraad; Tan, Qina; Xirasagar, Sandhya; Bandaru, Sandya; Gopalan, Vivek; Mohamoud, Yasmin; Huyen, Yentram; McBride, Alison A
2013-01-01
The goal of the Papillomavirus Episteme (PaVE) is to provide an integrated resource for the analysis of papillomavirus (PV) genome sequences and related information. The PaVE is a freely accessible, web-based tool (http://pave.niaid.nih.gov) created around a relational database, which enables storage, analysis and exchange of sequence information. From a design perspective, the PaVE adopts an Open Source software approach and stresses the integration and reuse of existing tools. Reference PV genome sequences have been extracted from publicly available databases and reannotated using a custom-created tool. To date, the PaVE contains 241 annotated PV genomes, 2245 genes and regions, 2004 protein sequences and 47 protein structures, which users can explore, analyze or download. The PaVE provides scientists with the data and tools needed to accelerate scientific progress for the study and treatment of diseases caused by PVs.
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Wu, Wenming; Loan, Kieu The Loan; Lee, Nae Yoon
2012-05-07
Consistent temperature control in an on-chip flow-through polymerase chain reaction (PCR) employing two or more heaters is one of the main obstacles for device miniaturization and integration when realizing micro total analysis systems (μTAS), and also leads to operational complexity. In this study, we propose a qiandu (right triangular prism)-shaped polydimethylsiloxane (PDMS) microdevice with serpentine microchannels fabricated on its slanted plane, and apply the device for an on-chip flow-through PCR employing a single heater. The inclined nature of the qiandu-shaped microdevice enables the formation of a surface temperature gradient along the slanted plane of the microdevice in a height-dependent manner by the use of a single heater, and enables liquid to traverse over wide ranges of temperatures, including the three temperature zones--denaturation, annealing, and extension temperatures--required in a typical PCR. The feasibility of the qiandu-shaped PDMS microdevice as a versatile platform for performing a flow-through PCR was examined by employing multiple templates and varying the inclination angle of the device. In addition, the potential of performing a multiplex PCR using a single qiandu-shaped PDMS microdevice was explored. A 409 bp long gene fragment effective as a marker for diagnosing lung cancer and a 230 bp long gene fragment from a plasmid vector were simultaneously amplified in less than 25 min on a single microdevice, paving the way for a microscale, multiplex PCR on a single device employing a single heater.
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Frontiers of Theoretical Research on Shape Memory Alloys: A General Overview
NASA Astrophysics Data System (ADS)
Chowdhury, Piyas
2018-03-01
In this concise review, general aspects of modeling shape memory alloys (SMAs) are recounted. Different approaches are discussed under four general categories, namely, (a) macro-phenomenological, (b) micromechanical, (c) molecular dynamics, and (d) first principles models. Macro-phenomenological theories, stemming from empirical formulations depicting continuum elastic, plastic, and phase transformation, are primarily of engineering interest, whereby the performance of SMA-made components is investigated. Micromechanical endeavors are generally geared towards understanding microstructural phenomena within continuum mechanics such as the accommodation of straining due to phase change as well as role of precipitates. By contrast, molecular dynamics, being a more recently emerging computational technique, concerns attributes of discrete lattice structures, and thus captures SMA deformation mechanism by means of empirically reconstructing interatomic bonding forces. Finally, ab initio theories utilize quantum mechanical framework to peek into atomistic foundation of deformation, and can pave the way for studying the role of solid-sate effects. With specific examples, this paper provides concise descriptions of each category along with their relative merits and emphases.
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Performance of TenCate Paving interlayers in asphalt concrete pavements.
DOT National Transportation Integrated Search
2017-08-01
As a continued effort of a previously completed project entitled Performance of TenCate Mirafi PGM-G4 Interlayer-Reinforced Asphalt Pavements in Alaska, this project evaluated two newly modified paving interlayers (TruPave and Mirapave) through...
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An asphalt paving tool for adverse conditions
DOT National Transportation Integrated Search
1998-06-01
Poor compaction can lead to early deterioration of an asphalt pavement. It often happens when paving occurs during adverse weather conditions. Yet, in Minnesota, paving must often occur under adverse conditions. A new tool now simulates the cooling o...
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DOT National Transportation Integrated Search
2006-10-01
The Issue : Two key questions must be answered when developing a gravel : road maintenance plan: : 1. What is the best way to maintain a gravel road? : 2. When should the roadway be upgraded to a paved surface? : These are not easy questions because ...
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Relational Identities of Students, Families, and Educators: Shaping Educational Pathways
ERIC Educational Resources Information Center
March, Evangelia; Gaffney, Janet S.
2010-01-01
This retrospective study sketched the educational pathways of two seniors attending an alternative high school in an attempt to discern how relational identities of students, families, and educators are defining forces of such pathways. Cumulative school records and special education files were triangulated with interviews of the students, their…
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Shaping of Looped Miniaturized Chalcogenide Fiber Sensing Heads for Mid-Infrared Sensing
Houizot, Patrick; Anne, Marie-Laure; Boussard-Plédel, Catherine; Loréal, Olivier; Tariel, Hugues; Lucas, Jacques; Bureau, Bruno
2014-01-01
Chalcogenide glass fibers are promising photonic tools to develop Fiber Evanescent Wave Spectroscopy (FEWS) optical sensors working in the mid-infrared region. Numerous pioneering works have already been carried out showing their efficiency, especially for bio-medical applications. Nevertheless, this technology remains confined to academic studies at the laboratory scale because chalcogenide glass fibers are difficult to shape to produce reliable, sensitive and compact sensors. In this paper, a new method for designing and fabricating a compact and robust sensing head with a selenide glass fiber is described. Compact looped sensing heads with diameter equal to 2 mm were thus shaped. This represents an outstanding achievement considering the brittleness of such uncoated fibers. FEWS experiments were implemented using alcoholic solutions as target samples showing that the sensitivity is higher than with the routinely used classical fiber. It is also shown that the best compromise in term of sensitivity is to fabricate a sensing head including two full loops. From a mechanical point of view, the breaking loads of the loop shaped head are also much higher than with classical fiber. Finally, this achievement paves the way for the use of mid-infrared technology during in situ and even in vivo medical operations. Indeed, is is now possible to slide a chalcogenide glass fiber in the operating channel of a standard 2.8 mm diameter catheter. PMID:25264953
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Overview of the ARPA/WL Smart Structures and Materials Development-Smart Wing contract
NASA Astrophysics Data System (ADS)
Kudva, Jayanth N.; Jardine, A. Peter; Martin, Christopher A.; Appa, Kari
1996-05-01
While the concept of an adaptive aircraft wing, i.e., a wing whose shape parameters such as camber, wing twist, and thickness can be varied to optimize the wing shape for various flight conditions, has been extensively studied, the complexity and weight penalty of the actuation mechanisms have precluded their practical implementation. Recent development of sensors and actuators using smart materials could potentially alleviate the shortcomings of prior designs, paving the way for a practical, `smart' adaptive wing which responds to changes in flight and environmental conditions by modifying its shape to provide optimal performance. This paper presents a summary of recent work done on adaptive wing designs under an on-going ARPA/WL contract entitled `Smart Structures and Materials Development--Smart Wing.' Specifically, the design, development and planned wind tunnel testing of a 16% model representative of a fighter aircraft wing and incorporating the following features, are discussed: (1) a composite wing torque box whose span-wise twist can be varied by activating built-in shape memory alloy (SMA) torque tubes to provide increased lift and enhanced maneuverability at multiple flight conditions, (2) trailing edge control surfaces deployed using composite SMA actuators to provide smooth, hingeless aerodynamic surfaces, and (3) a suite of fiber optic sensors integrated into the wing skin which provide real-time strain and pressure data to a feedback control system.
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Ras oncogenes in oral cancer: the past 20 years.
Murugan, Avaniyapuram Kannan; Munirajan, Arasambattu Kannan; Tsuchida, Nobuo
2012-05-01
Oral squamous cell carcinoma (OSCC) of head and neck is associated with high morbidity and mortality in both Western and Asian countries. Several risk factors for the development of oral cancer are very well established, including tobacco chewing, betel quid, smoking, alcohol drinking and human papilloma virus (HPV) infection. Apart from these risk factors, many genetic factors such as oncogenes, tumor suppressor genes and regulatory genes are identified to involve in oral carcinogenesis with these risk factors dependent and independent manner. Ras is one of the most frequently genetically deregulated oncogene in oral cancer. In this review, we analyze the past 22years of literature on genetic alterations such as mutations and amplifications of the isoforms of the ras oncogene in oral cancer. Further, we addressed the isoform-specific role of the ras in oral carcinogenesis. We also discussed how targeting the Akt and MEK, downstream effectors of the PI3K/Akt and MAPK pathways, respectively, would probably pave the possible molecular therapeutic target for the ras driven tumorigenesis in oral cancer. Analysis of these ras isoforms may critically enlighten specific role of a particular ras isoform in oral carcinogenesis, enhance prognosis and pave the way for isoform-specific molecular targeted therapy in OSCC. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Pediatric Brain Tumors: Genomics and Epigenomics Pave the Way.
Fontebasso, Adam M; Jabado, Nada
2015-01-01
Primary malignant brain tumors remain a disproportionate cause of morbidity and mortality in humans. A number of studies exploring the cancer genome of brain tumors across ages using integrated genetics and epigenetics and next-generation sequencing technologies have recently emerged. This has led to considerable advances in the understanding of the basic biology and pathogenesis of brain tumors, including the most malignant and common variants in children: gliomas and medulloblastoma. Notably, studies of pediatric brain tumors have identified unexpected oncogenic pathways implicated in tumorigenesis. These range from a single pathway/molecule defect such as abnormalities of the mitogen-activated protein kinase pathway, considered to be a hallmark of pilocytic astrocytomas, to alterations in the epigenome as a critical component altered in many subgroups of high-grade brain tumors. Importantly, the type, timing, and spatial clustering of these molecular alterations provide a better understanding of the pathogenesis of the respective brain tumor they target and critical markers for therapy that will help refine pathological grading. We summarize these novel findings in pediatric brain tumors, which also are put in the context of the evolving notion of molecular pathology, now a mandated tool for proper classification and therapy assignment in the clinical setting.
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14 CFR 151.81 - Taxiway paving.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Taxiway paving. 151.81 Section 151.81 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.81 Taxiway paving. (a) The construction...
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14 CFR 151.81 - Taxiway paving.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Taxiway paving. 151.81 Section 151.81 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.81 Taxiway paving. (a) The construction...
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14 CFR 151.81 - Taxiway paving.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Taxiway paving. 151.81 Section 151.81 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.81 Taxiway paving. (a) The construction...
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14 CFR 151.81 - Taxiway paving.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Taxiway paving. 151.81 Section 151.81 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.81 Taxiway paving. (a) The construction...
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14 CFR 151.81 - Taxiway paving.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Taxiway paving. 151.81 Section 151.81 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.81 Taxiway paving. (a) The construction...
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DAMBE7: New and Improved Tools for Data Analysis in Molecular Biology and Evolution.
Xia, Xuhua
2018-06-01
DAMBE is a comprehensive software package for genomic and phylogenetic data analysis on Windows, Linux, and Macintosh computers. New functions include imputing missing distances and phylogeny simultaneously (paving the way to build large phage and transposon trees), new bootstrapping/jackknifing methods for PhyPA (phylogenetics from pairwise alignments), and an improved function for fast and accurate estimation of the shape parameter of the gamma distribution for fitting rate heterogeneity over sites. Previous method corrects multiple hits for each site independently. DAMBE's new method uses all sites simultaneously for correction. DAMBE, featuring a user-friendly graphic interface, is freely available from http://dambe.bio.uottawa.ca (last accessed, April 17, 2018).
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Health policy in Denmark: leaving the decentralized welfare path?
Vrangbaek, Karsten; Christiansen, Terkel
2005-01-01
In this article, we investigate developments in Danish health care policy. After a short presentation of its historical roots, we focus on the decades after the administrative reform of 1970, which shaped the current decentralized public health care system. Theories of path dependency and institutional inertia are used to explain the relative stability in the overall structure, and theories of policy process and reform are used to discuss gradual changes within the overall framework. Although comprehensive reforms have not taken place in Denmark, many gradual changes may pave the way for more radical changes in the future. The political climate currently seems to be more favorable toward structural reform than in the past.
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First Predictions of the Angular Power Spectrum of the Astrophysical Gravitational Wave Background
NASA Astrophysics Data System (ADS)
Cusin, Giulia; Dvorkin, Irina; Pitrou, Cyril; Uzan, Jean-Philippe
2018-06-01
We present the first predictions for the angular power spectrum of the astrophysical gravitational wave background constituted of the radiation emitted by all resolved and unresolved astrophysical sources. Its shape and amplitude depend on both the astrophysical properties on galactic scales and on cosmological properties. We show that the angular power spectrum behaves as Cℓ∝1 /ℓ on large scales and that relative fluctuations of the signal are of order 30% at 100 Hz. We also present the correlations of the astrophysical gravitational wave background with weak lensing and galaxy distribution. These numerical results pave the way to the study of a new observable at the crossroad between general relativity, astrophysics, and cosmology.
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Electroactive Polymers as Artificial Muscles: Capabilities, Potentials and Challenges
NASA Technical Reports Server (NTRS)
Bar-Cohen, Yoseph
2000-01-01
The low density and the relative ease of shaping made polymers highly attractive materials and they are increasingly being chosen for aerospace applications. Polymer matrix composite materials significantly impacted the construction of high performance aircraft components and structures. In recent years, the resilience characteristics of polymers made them attractive to the emerging field of inflatable structures. Balloons were used to cushion the deployment of the Mars Pathfinder lander on July 4, 1997, paving the way for the recent large number of related initiatives. Inflatable structures are now being used to construct a rover, aerial vehicles, telescopes, radar antennas, and others. Some of these applications have reached space flight experiments, whereas others are now at advanced stages of development.
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Li, Dong-Mei; Zhang, Hai-Sen; Tan, Qiu-Ping; Li, Ling; Yu, Qin; Gao, Dong-Sheng
2011-11-01
Taking the nectarine variety 'Shuguang' (Prunus persica var. nectariana cv. Shuguang) as test material, and by using respiration inhibitors KCN and SHAM, this paper studied the cytochrome electron transport pathway and the alternative respiration pathway in nectarine flower bud during dormancy induction under the effects of short sunlight. Both the total respiration rate (V(t)) and the cytochrome electron transport pathway respiration rate (rho' V(cyt)) presented double hump-shaped variation. Short sunlight brought the first-hump of V(t) and rho' V(cyt), forward and delayed the second-hump synchronously, inhibited the rho' V(cyt), but had no significant effects on the V(t). The capacity (V(alt)) and activity (rho V (alt)) of alternative respiration pathway also varied in double hump-shape, and the variation was basically in synchronous. Short sunlight made the first climax of V(alt) and rhoV(alt) advanced, but had little effects on the later period climax. The inhibition of cytochrome electron transport pathway and the enhancement of alternative respiration pathway were the important features of nectarine flower bud during dormancy induction, and according to the respective contributions of the two electron transport pathways to the total respiration rate, the cytochrome electron transport pathway was still the main pathway of electron transport, whereas the alternative respiration pathway played an auxiliary and branched role.
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Necroptosis: Modules and molecular switches with therapeutic implications.
Arora, Deepika; Sharma, Pradeep Kumar; Siddiqui, Mohammed Haris; Shukla, Yogeshwer
2017-06-01
Among the various programmed cell death (PCD) pathways, "Necroptosis" has gained much importance as a novel paradigm of cell death. This pathway has emerged as a backup mechanism when physiologically conserved PCD (apoptosis) is non-functional either genetically or pathogenically. The expanding spectrum of necroptosis from physiological development to diverse patho-physiological disorders, including xenobiotics-mediated toxicity has now grabbed the attention worldwide. The efficient role of necroptosis regulators in disease development and management are under constant examination. In fact, few regulators (e.g. MLKL) have already paved their way towards clinical trials and others are in queue. In this review, emphasis has been paid to the various contributing factors and molecular switches that can regulate necroptosis. Here we linked the overview of current knowledge of this enigmatic signaling with magnitude of therapeutics that may underpin the opportunities for novel therapeutic approaches to suppress the pathogenesis of necroptosis-driven disorders. Copyright © 2017 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.
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Inhibition of NHEJ repair by type II-A CRISPR-Cas systems in bacteria.
Bernheim, Aude; Calvo-Villamañán, Alicia; Basier, Clovis; Cui, Lun; Rocha, Eduardo P C; Touchon, Marie; Bikard, David
2017-12-12
Type II CRISPR-Cas systems introduce double-strand breaks into DNA of invading genetic material and use DNA fragments to acquire novel spacers during adaptation. These breaks can be the substrate of several DNA repair pathways, paving the way for interactions. We report that non-homologous end-joining (NHEJ) and type II-A CRISPR-Cas systems only co-occur once among 5563 fully sequenced prokaryotic genomes. We investigated experimentally the possible molecular interactions using the NHEJ pathway from Bacillus subtilis and the type II-A CRISPR-Cas systems from Streptococcus thermophilus and Streptococcus pyogenes. Our results suggest that the NHEJ system has no effect on CRISPR immunity. On the other hand, we provide evidence for the inhibition of NHEJ repair by the Csn2 protein. Our findings give insights on the complex interactions between CRISPR-Cas systems and repair mechanisms in bacteria, contributing to explain the scattered distribution of CRISPR-Cas systems in bacterial genome.
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NASA Astrophysics Data System (ADS)
Lipani, Luca; Dupont, Bertrand G. R.; Doungmene, Floriant; Marken, Frank; Tyrrell, Rex M.; Guy, Richard H.; Ilie, Adelina
2018-06-01
Currently, there is no available needle-free approach for diabetics to monitor glucose levels in the interstitial fluid. Here, we report a path-selective, non-invasive, transdermal glucose monitoring system based on a miniaturized pixel array platform (realized either by graphene-based thin-film technology, or screen-printing). The system samples glucose from the interstitial fluid via electroosmotic extraction through individual, privileged, follicular pathways in the skin, accessible via the pixels of the array. A proof of principle using mammalian skin ex vivo is demonstrated for specific and `quantized' glucose extraction/detection via follicular pathways, and across the hypo- to hyper-glycaemic range in humans. Furthermore, the quantification of follicular and non-follicular glucose extraction fluxes is clearly shown. In vivo continuous monitoring of interstitial fluid-borne glucose with the pixel array was able to track blood sugar in healthy human subjects. This approach paves the way to clinically relevant glucose detection in diabetics without the need for invasive, finger-stick blood sampling.
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Frontiers of Knowledge: An Interview with 2017 Edward Novitski Prize Recipient Jonathan Hodgkin.
Hodgkin, Jonathan
2017-12-01
The Genetics Society of America's Edward Novitski Prize recognizes a single experimental accomplishment or a body of work in which an exceptional level of creativity and intellectual ingenuity has been used to design and execute scientific experiments to solve a difficult problem in genetics. The 2017 winner, Jonathan Hodgkin, used elegant genetic studies to unravel the sex determination pathway in Caenorhabditis elegans He inferred the order of genes in the pathway and their modes of regulation using epistasis analyses-a powerful tool that was quickly adopted by other researchers. He expanded the number and use of informational suppressor mutants in C. elegans that are able to act on many genes. He also introduced the use of collections of wild C. elegans to study naturally occurring genetic variation, paving the way for SNP mapping and QTL analysis, as well as studies of hybrid incompatibilities between worm species. His current work focuses on nematode-bacterial interactions and innate immunity. Copyright © 2017 by the Genetics Society of America.
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Ben Yehuda Greenwald, Maya; Frušić-Zlotkin, Marina; Soroka, Yoram; Ben Sasson, Shmuel; Bitton, Ronit; Bianco-Peled, Havazelet; Kohen, Ron
2017-01-01
Curcumin was found to be beneficial in treating several skin pathologies and diseases, providing antioxidant protection due to its reducing properties and its electrophilic properties (the ability to activate the Nrf 2 pathway and induce phase II cytoprotective enzymes). Nevertheless, clinical applications of curcumin are being hampered by its insufficient solubility, chemical instability, and poor absorption, leading to low efficacy in preventing skin pathologies. These limitations can be overcome by using a nanotechnology-based delivery system. Here, we elucidated the possibility of using curcumin encapsulated in a microemulsion preserving its unique chemical structure. We also examined whether curcumin microemulsion would reduce UVB-induced toxicity in skin. A significant curcumin concentration was found in the human skin dermis following topical application of a curcumin microemulsion. Moreover, curcumin microemulsion enhanced the reduction of UV-induced cytotoxicity in epidermal cells, paving the way for other incorporated electrophiles in encapsulated form protecting skin against stress-related diseases.
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Palomero, Teresa; Ferrando, Adolfo
2008-01-01
The identification of activating mutations in NOTCH1 in the majority of T-cell acute lymphoblastic leukemias and lymphomas (T-ALL) has brought much interest in inhibiting NOTCH1 signaling as therapeutic target in this disease. Small molecule inhibitors of the γ-secretase complex, which mediates a critical proteolytic cleavage required for NOTCH1 activation, hold the promise of becoming an effective molecular therapy against relapsed and refractory T-ALL. Recent progress in the elucidation of the transcriptional regulatory networks downstream of oncogenic NOTCH1 has uncovered a central role of NOTCH1 signaling in promoting leukemic cell growth and revealed an intricate circuitry that connects NOTCH1 signaling with MYC and the PI3K-AKT signaling pathway. The identification of the downstream effector pathways controlled by NOTCH1 should pave the way for the rational design of anti-NOTCH1 therapies for the treatment of T-ALL. PMID:18765521
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The roles of ubiquitin modifying enzymes in neoplastic disease.
Kumari, Nishi; Jaynes, Patrick William; Saei, Azad; Iyengar, Prasanna Vasudevan; Richard, John Lalith Charles; Eichhorn, Pieter Johan Adam
2017-12-01
The initial experiments performed by Rose, Hershko, and Ciechanover describing the identification of a specific degradation signal in short-lived proteins paved the way to the discovery of the ubiquitin mediated regulation of numerous physiological functions required for cellular homeostasis. Since their discovery of ubiquitin and ubiquitin function over 30years ago it has become wholly apparent that ubiquitin and their respective ubiquitin modifying enzymes are key players in tumorigenesis. The human genome encodes approximately 600 putative E3 ligases and 80 deubiquitinating enzymes and in the majority of cases these enzymes exhibit specificity in sustaining either pro-tumorigenic or tumour repressive responses. In this review, we highlight the known oncogenic and tumour suppressive effects of ubiquitin modifying enzymes in cancer relevant pathways with specific focus on PI3K, MAPK, TGFβ, WNT, and YAP pathways. Moreover, we discuss the capacity of targeting DUBs as a novel anticancer therapeutic strategy. Copyright © 2017 Elsevier B.V. All rights reserved.
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Ben Yehuda Greenwald, Maya; Frušić-Zlotkin, Marina; Soroka, Yoram; Ben Sasson, Shmuel; Bitton, Ronit; Bianco-Peled, Havazelet
2017-01-01
Curcumin was found to be beneficial in treating several skin pathologies and diseases, providing antioxidant protection due to its reducing properties and its electrophilic properties (the ability to activate the Nrf2 pathway and induce phase II cytoprotective enzymes). Nevertheless, clinical applications of curcumin are being hampered by its insufficient solubility, chemical instability, and poor absorption, leading to low efficacy in preventing skin pathologies. These limitations can be overcome by using a nanotechnology-based delivery system. Here, we elucidated the possibility of using curcumin encapsulated in a microemulsion preserving its unique chemical structure. We also examined whether curcumin microemulsion would reduce UVB-induced toxicity in skin. A significant curcumin concentration was found in the human skin dermis following topical application of a curcumin microemulsion. Moreover, curcumin microemulsion enhanced the reduction of UV-induced cytotoxicity in epidermal cells, paving the way for other incorporated electrophiles in encapsulated form protecting skin against stress-related diseases. PMID:28757910
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The Papillomavirus Episteme: a major update to the papillomavirus sequence database.
Van Doorslaer, Koenraad; Li, Zhiwen; Xirasagar, Sandhya; Maes, Piet; Kaminsky, David; Liou, David; Sun, Qiang; Kaur, Ramandeep; Huyen, Yentram; McBride, Alison A
2017-01-04
The Papillomavirus Episteme (PaVE) is a database of curated papillomavirus genomic sequences, accompanied by web-based sequence analysis tools. This update describes the addition of major new features. The papillomavirus genomes within PaVE have been further annotated, and now includes the major spliced mRNA transcripts. Viral genes and transcripts can be visualized on both linear and circular genome browsers. Evolutionary relationships among PaVE reference protein sequences can be analysed using multiple sequence alignments and phylogenetic trees. To assist in viral discovery, PaVE offers a typing tool; a simplified algorithm to determine whether a newly sequenced virus is novel. PaVE also now contains an image library containing gross clinical and histopathological images of papillomavirus infected lesions. Database URL: https://pave.niaid.nih.gov/. Published by Oxford University Press on behalf of Nucleic Acids Research 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.
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CAVER 3.0: A Tool for the Analysis of Transport Pathways in Dynamic Protein Structures
Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri
2012-01-01
Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz. PMID:23093919
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CAVER 3.0: a tool for the analysis of transport pathways in dynamic protein structures.
Chovancova, Eva; Pavelka, Antonin; Benes, Petr; Strnad, Ondrej; Brezovsky, Jan; Kozlikova, Barbora; Gora, Artur; Sustr, Vilem; Klvana, Martin; Medek, Petr; Biedermannova, Lada; Sochor, Jiri; Damborsky, Jiri
2012-01-01
Tunnels and channels facilitate the transport of small molecules, ions and water solvent in a large variety of proteins. Characteristics of individual transport pathways, including their geometry, physico-chemical properties and dynamics are instrumental for understanding of structure-function relationships of these proteins, for the design of new inhibitors and construction of improved biocatalysts. CAVER is a software tool widely used for the identification and characterization of transport pathways in static macromolecular structures. Herein we present a new version of CAVER enabling automatic analysis of tunnels and channels in large ensembles of protein conformations. CAVER 3.0 implements new algorithms for the calculation and clustering of pathways. A trajectory from a molecular dynamics simulation serves as the typical input, while detailed characteristics and summary statistics of the time evolution of individual pathways are provided in the outputs. To illustrate the capabilities of CAVER 3.0, the tool was applied for the analysis of molecular dynamics simulation of the microbial enzyme haloalkane dehalogenase DhaA. CAVER 3.0 safely identified and reliably estimated the importance of all previously published DhaA tunnels, including the tunnels closed in DhaA crystal structures. Obtained results clearly demonstrate that analysis of molecular dynamics simulation is essential for the estimation of pathway characteristics and elucidation of the structural basis of the tunnel gating. CAVER 3.0 paves the way for the study of important biochemical phenomena in the area of molecular transport, molecular recognition and enzymatic catalysis. The software is freely available as a multiplatform command-line application at http://www.caver.cz.
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Shang, Fei-Fei; Zhao, Wei; Zhao, Qi; Liu, Jia; Li, Da-Wei; Zhang, Hua; Zhou, Xin-Fu; Li, Cheng-Yun; Wang, Ting-Hua
2013-10-08
It is well known that trauma is frequently accompanied by spontaneous functional recovery after spinal cord injury (SCI), but the underlying mechanisms remain elusive. In this study, BBB scores showed a gradual return of locomotor functions after SCT. Proteomics analysis revealed 16 differential protein spots in the gastrocnemius muscle between SCT and normal rats. Of these differential proteins, eukaryotic translation initiation factor 5A1 (elf-5A1), a highly conserved molecule throughout eukaryotes, exhibited marked upregulation in the gastrocnemius muscle after SCT. To study the role of eIF-5A1 in the restoration of hindlimb locomotor functions following SCT, we used siRNA to downregulate the mRNA level of eIF-5A1. Compared with untreated SCT control rats, those subjected to eIF-5A1 knockdown exhibited impaired functional recovery. Moreover, gene expression microarrays and bioinformatic analysis showed high correlation between three main signal pathways (ErbB, MAPK and neurotrophin signal pathways) and eIF-5A1. These signal pathways regulate cell proliferation, differentiation and neurocyte growth. Consequently, eIF-5A1 played a pivotal role via these signal pathways in hindlimb locomotor functional recovery after SCT, which could pave the way for the development of a new strategy for the treatment of spinal cord injury in clinical trials. Copyright © 2012. Published by Elsevier B.V.
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Analysis of heavy metal sources in storm water from urban areas
NASA Astrophysics Data System (ADS)
Scherer, U.; Fuchs, S.
2009-04-01
The input of heavy metals into surface waters is a serious impairment of the aquatic environment. The emissions of heavy metals via point and diffuse pathways into the German river basins were thus quantified for the period of 1985 through 2005. The total emission into the German river systems decreased for each metal during the observed period. This reduction is mainly caused by the decline of emissions via point sources. The measures taken by industry and implemented within the scope of a stringently water legislation have decisively contributed to an improvement of environmental conditions. Today's emissions of heavy metals into river basins of Germany are dominated by the input via diffuse pathways. One of the most important diffuse input is the storm water discharged from paved urban areas into the surface waters via storm sewers and combined sewer overflows especially for the metals copper, zinc and lead. The objective of this project was to identify the sources of these three heavy metals washed of from paved urban areas. The use of copper, zinc and lead on the outsides of buildings results in emissions to water and soil via rainwater due to weathering and runoff of soluble and insoluble metallic compounds. Copper and zinc are traditionally used materials in the building sector especially for roofs, gutters and facades. Lead, in contrast, plays only a subordinate role due to its more limited outdoor use. The corrosion rates vary widely. Climatic factors (temperature, humidity etc.), above all the presence of corrosive gases (sulphur dioxide, nitrogen oxide, ozone etc.) influence the corrosion processes. Estimates of industrial associations were referred to in order to determine the corrosion relevant metal surfaces. Heavy metal emissions caused by traffic are complex and depend on many parameters which vary by locality, time and substance. In principle, substances can be emitted by vehicles, the road surface and by maintenance. Emissions of copper, lead and zinc are mainly caused by wear and tear of tyres and brake pads. The reference figures of the environmental emissions are usually the kilometres driven per vehicle. The emissions can then be calculated based on the road performance. Furthermore atmospheric deposition on paved urban areas was considered. The heavy metal emission from each individual source and the portion discharged into surface waters via storm sewers and combined sewer overflows was quantified. The emission sum of all sources was validated using emission data of storm sewers based on measured heavy metal concentrations and the discharge volume showing a good agreement.
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Project P.A.V.E. Evaluation. Technical Report 1977-78. Publication Number: 77.49.
ERIC Educational Resources Information Center
Eglsaer, Richard; Matuszek, Paula
Project PAVE was implemented in Travis High School, Austin, Texas, to extend and coordinate services for certain high school special education students. Four components were crucial to the Project PAVE model: parental involvement, academic achievement, vocational programing, and extracurricular opportunities. The project evaluation, conducted in…
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14 CFR 151.80 - Runway paving: Additional runway; other conditions.
Code of Federal Regulations, 2012 CFR
2012-01-01
... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Runway paving: Additional runway; other conditions. 151.80 Section 151.80 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.80 Runway paving...
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14 CFR 151.80 - Runway paving: Additional runway; other conditions.
Code of Federal Regulations, 2014 CFR
2014-01-01
... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Runway paving: Additional runway; other conditions. 151.80 Section 151.80 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.80 Runway paving...
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14 CFR 151.80 - Runway paving: Additional runway; other conditions.
Code of Federal Regulations, 2013 CFR
2013-01-01
... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Runway paving: Additional runway; other conditions. 151.80 Section 151.80 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.80 Runway paving...
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14 CFR 151.79 - Runway paving: Second runway; wind conditions.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Runway paving: Second runway; wind conditions. 151.79 Section 151.79 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.79 Runway paving...
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14 CFR 151.80 - Runway paving: Additional runway; other conditions.
Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Runway paving: Additional runway; other conditions. 151.80 Section 151.80 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.80 Runway paving...
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14 CFR 151.80 - Runway paving: Additional runway; other conditions.
Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Runway paving: Additional runway; other conditions. 151.80 Section 151.80 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIRPORTS FEDERAL AID TO AIRPORTS Project Programming Standards § 151.80 Runway paving...
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The emerging roles of long non-coding RNA in gallbladder cancer tumorigenesis.
Chen, Bing; Li, Ya; He, Yuting; Xue, Chen; Xu, Feng
2018-05-04
Accumulating evidence suggests that long non-coding RNAs (lncRNAs) have important regulatory functions in gallbladder cancer (GBC) tumorigenesis and can serve as potential novel markers and/or targets for GBC. In this review, we critically discuss the emerging alteration of lncRNAs in GBC, the lncRNAs induced epigenetic regulation, the interaction of lncRNAs with microRNAs and lncRNAs effects on tumor-related signaling pathways. Additionally, contributions of lncRNAs in epithelial-mesenchymal transition process and energy metabolism reprogramming in GBC are also addressed. This may pave new ways towards the determination of GBC pathogenesis and lead to the development of new preventive and therapeutic strategies for GBC.
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Common developmental pathways link tooth shape to regeneration
Fraser, Gareth J.; Bloomquist, Ryan F.; Streelman, J. Todd
2013-01-01
In many non-mammalian vertebrates, adult dentitions result from cyclical rounds of tooth regeneration wherein simple unicuspid teeth are replaced by more complex forms. Therefore and by contrast to mammalian models, the numerical majority of vertebrate teeth develop shape during the process of replacement. Here, we exploit the dental diversity of Lake Malawi cichlid fishes to ask how vertebrates generally replace their dentition and in turn how this process acts to influence resulting tooth morphologies. First, we used immunohistochemistry to chart organogenesis of continually replacing cichlid teeth and discovered an epithelial down-growth that initiates the replacement cycle via a labial proliferation bias. Next, we identified sets of co-expressed genes from common pathways active during de novo, lifelong tooth replacement and tooth morphogenesis. Of note, we found two distinct epithelial cell populations, expressing markers of dental competence and cell potency, which may be responsible for tooth regeneration. Related gene sets were simultaneously active in putative signaling centers associated with the differentiation of replacement teeth with complex shapes. Finally, we manipulated targeted pathways (BMP, FGF, Hh, Notch, Wnt/β-catenin) in vivo with small molecules and demonstrated dose-dependent effects on both tooth replacement and tooth shape. Our data suggest that the processes of tooth regeneration and tooth shape morphogenesis are integrated via a common set of molecular signals. This linkage has subsequently been lost or decoupled in mammalian dentitions where complex tooth shapes develop in first generation dentitions that lack the capacity for lifelong replacement. Our dissection of the molecular mechanics of vertebrate tooth replacement coupled to complex shape pinpoints aspects of odontogenesis that might be re-evolved in the lab to solve problems in regenerative dentistry. PMID:23422830
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Zhang, Shian; Yao, Yunhua; Shuwu, Xu; Liu, Pei; Ding, Jingxin; Jia, Tianqing; Qiu, Jianrong; Sun, Zhenrong
2015-01-01
The ability to tune color output of nanomaterials is very important for their applications in laser, optoelectronic device, color display and multiplexed biolabeling. Here we first propose a femtosecond pulse shaping technique to realize the up-conversion fluorescence tuning in lanthanide-doped nanocrystals dispersed in the glass. The multiple subpulse formation by a square phase modulation can create different excitation pathways for various up-conversion fluorescence generations. By properly controlling these excitation pathways, the multicolor up-conversion fluorescence can be finely tuned. This color tuning by the femtosecond pulse shaping technique is realized in single material by single-color laser field, which is highly desirable for further applications of the lanthanide-doped nanocrystals. This femtosecond pulse shaping technique opens an opportunity to tune the color output in the lanthanide-doped nanocrystals, which may bring a new revolution in the control of luminescence properties of nanomaterials. PMID:26290391
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Shape-Dependent Skin Penetration of Silver Nanoparticles: Does It Really Matter?
Tak, Yu Kyung; Pal, Sukdeb; Naoghare, Pravin K.; Rangasamy, Sabarinathan; Song, Joon Myong
2015-01-01
Advancements in nano-structured materials have facilitated several applications of nanoparticles (NPs). Skin penetration of NPs is a crucial factor for designing suitable topical antibacterial agents with low systemic toxicity. Available reports focus on size-dependent skin penetration of NPs, mainly through follicular pathways. Herein, for the first time, we demonstrate a proof-of-concept study that entails variations in skin permeability and diffusion coefficients, penetration rates and depth-of-penetration of differently shaped silver NPs (AgNPs) via intercellular pathways using both in vitro and in vivo models. The antimicrobial activity of AgNPs is known. Different shapes of AgNPs may exhibit diverse antimicrobial activities and skin penetration capabilities depending upon their active metallic facets. Consideration of the shape dependency of AgNPs in antimicrobial formulations could help developing an ideal topical agent with the highest efficacy and low systemic toxicity. PMID:26584777
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Testone, Giulio; Mele, Giovanni; Di Giacomo, Elisabetta; Gonnella, Maria; Renna, Massimiliano; Tenore, Gian Carlo; Nicolodi, Chiara; Frugis, Giovanna; Iannelli, Maria Adelaide; Arnesi, Giuseppe; Schiappa, Alessandro; Giannino, Donato
2016-01-01
Stem-chicory of the “Catalogna” group is a vegetable consumed for bitter-flavored stems. Type and levels of bitter sesquiterpene lactones (STLs) participate in conferring bitterness in vegetables. The content of lactucin—and lactucopocrin-like STLs was higher in “Molfettese” than “Galatina” landrace stalks, regardless of the cultivation sites, consistently with bitterness scores and gustative differences. The “Galatina” transcriptome assembly resulted in 58,872 unigenes, 77% of which were annotated, paving the way to molecular investigation of the STL pathway. Comparative transcriptome analysis allowed the identification of 69,352 SNPs and of 1640 differentially expressed genes that maintained the pattern independently of the site. Enrichment analyses revealed that 4 out of 29 unigenes were up-regulated in “Molfettese” vs “Galatina” within the sesquiterpenoid pathway. The expression of two germacrene A -synthase (GAS) and one -oxidase (GAO) genes of the costunolide branch correlated positively with the contents of lactucin-like molecules, supporting that STL biosynthesis regulation occurs at the transcriptional level. Finally, 46 genes encoding transcription factors (TFs) maintained a differential expression pattern between the two varieties regardless of the growth site; correlation analyses among TFs, GAS, GAO gene expressions and STLs contents suggest that one MYB and one bHLH may act in the pathway. PMID:27877190
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MoCha: Molecular Characterization of Unknown Pathways.
Lobo, Daniel; Hammelman, Jennifer; Levin, Michael
2016-04-01
Automated methods for the reverse-engineering of complex regulatory networks are paving the way for the inference of mechanistic comprehensive models directly from experimental data. These novel methods can infer not only the relations and parameters of the known molecules defined in their input datasets, but also unknown components and pathways identified as necessary by the automated algorithms. Identifying the molecular nature of these unknown components is a crucial step for making testable predictions and experimentally validating the models, yet no specific and efficient tools exist to aid in this process. To this end, we present here MoCha (Molecular Characterization), a tool optimized for the search of unknown proteins and their pathways from a given set of known interacting proteins. MoCha uses the comprehensive dataset of protein-protein interactions provided by the STRING database, which currently includes more than a billion interactions from over 2,000 organisms. MoCha is highly optimized, performing typical searches within seconds. We demonstrate the use of MoCha with the characterization of unknown components from reverse-engineered models from the literature. MoCha is useful for working on network models by hand or as a downstream step of a model inference engine workflow and represents a valuable and efficient tool for the characterization of unknown pathways using known data from thousands of organisms. MoCha and its source code are freely available online under the GPLv3 license.
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Tigano, Marco; Ruotolo, Roberta; Dallabona, Cristina; Fontanesi, Flavia; Barrientos, Antoni; Donnini, Claudia; Ottonello, Simone
2015-01-01
To gain a wider view of the pathways that regulate mitochondrial function, we combined the effect of heat stress on respiratory capacity with the discovery potential of a genome-wide screen in Saccharomyces cerevisiae. We identified 105 new genes whose deletion impairs respiratory growth at 37°C by interfering with processes such as transcriptional regulation, ubiquitination and cytosolic tRNA wobble uridine modification via 5-methoxycarbonylmethyl-2-thiouridine formation. The latter process, specifically required for efficient decoding of AA-ending codons under stress conditions, was covered by multiple genes belonging to the Elongator (e.g. ELP3) and urmylation (e.g., NCS6) pathways. ELP3 or NCS6 deletants had impaired mitochondrial protein synthesis. Their respiratory deficiency was selectively rescued by overexpression of tRNALysUUU as well by overexpression of genes (BCK1 and HFM1) with a strong bias for the AAA codon read by this tRNA. These data extend the mitochondrial regulome, demonstrate that heat stress can impair respiration by disturbing cytoplasmic translation of proteins critically involved in mitochondrial function and document, for the first time, the involvement in such process of the Elongator and urmylation pathways. Given the conservation of these pathways, the present findings may pave the way to a better understanding of the human mitochondrial regulome in health and disease. PMID:26240381
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Malone, Kevin M.; McGuinness, Seamus G.; Cleary, Eimear; Jefferies, Janis; Owens, Christabel; Kelleher, Cecily C.
2017-01-01
Background: Suicide is a significant public health concern, which impacts on health outcomes. Few suicide research studies have been interdisciplinary. We combined a psychobiographical autopsy with a visual arts autopsy, in which families donated stories, images and objects associated with the lived life of a loved one lost to suicide. From this interdisciplinary research platform, a mediated exhibition was created ( Lived Lives) with artist, scientist and families, co-curated by communities, facilitating dialogue, response and public action around suicide prevention. Indigenous ethnic minorities (IEMs) bear a significant increased risk for suicide. Irish Travellers are an IEM with social and cultural parallels with IEMs internationally, experiencing racism, discrimination, and poor health outcomes including elevated suicide rates (SMR 6.6). Methods: An adjusted Lived Lives exhibition, Lived Lives: A Pavee Perspective manifested in Pavee Point, the national Traveller and Roma Centre. The project was evaluated by the Travelling Community as to how it related to suicide in their community, how it has shaped their understanding of suicide and its impacts, and its relevance to other socio-cultural contexts, nationally and internationally. The project also obtained feedback from all relevant stakeholders. Evaluation was carried out by an international visual arts research advisor and an independent observer from the field of suicide research. Results: Outputs included an arts-science mediated exhibition with reference to elevated Irish Traveller suicide rates. Digital online learning materials about suicide and its aftermath among Irish Travellers were also produced. The project reached its target audience, with a high level of engagement from members of the Travelling Community. Discussion: The Lived Lives methodology navigated the societal barriers of stigma and silence to foster communication and engagement, working with cultural values, consistent with an adapted intervention. Feedback from this project can inform awareness, health promotion, education and interventions around suicide and its aftermath in IEMs. PMID:28540367
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Malone, Kevin M; McGuinness, Seamus G; Cleary, Eimear; Jefferies, Janis; Owens, Christabel; Kelleher, Cecily C
2017-04-13
Background: Suicide is a significant public health concern, which impacts on health outcomes. Few suicide research studies have been interdisciplinary. We combined a psychobiographical autopsy with a visual arts autopsy, in which families donated stories, images and objects associated with the lived life of a loved one lost to suicide. From this interdisciplinary research platform, a mediated exhibition was created ( Lived Lives ) with artist, scientist and families, co-curated by communities, facilitating dialogue, response and public action around suicide prevention. Indigenous ethnic minorities (IEMs) bear a significant increased risk for suicide. Irish Travellers are an IEM with social and cultural parallels with IEMs internationally, experiencing racism, discrimination, and poor health outcomes including elevated suicide rates (SMR 6.6). Methods: An adjusted Lived Lives exhibition, Lived Lives: A Pavee Perspective manifested in Pavee Point, the national Traveller and Roma Centre. The project was evaluated by the Travelling Community as to how it related to suicide in their community, how it has shaped their understanding of suicide and its impacts, and its relevance to other socio-cultural contexts, nationally and internationally. The project also obtained feedback from all relevant stakeholders. Evaluation was carried out by an international visual arts research advisor and an independent observer from the field of suicide research. Results: Outputs included an arts-science mediated exhibition with reference to elevated Irish Traveller suicide rates. Digital online learning materials about suicide and its aftermath among Irish Travellers were also produced. The project reached its target audience, with a high level of engagement from members of the Travelling Community. Discussion: The Lived Lives methodology navigated the societal barriers of stigma and silence to foster communication and engagement, working with cultural values, consistent with an adapted intervention. Feedback from this project can inform awareness, health promotion, education and interventions around suicide and its aftermath in IEMs.
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Cheon, Mookyung; Hall, Carol K.; Chang, Iksoo
2015-01-01
Discovering the mechanisms by which proteins aggregate into fibrils is an essential first step in understanding the molecular level processes underlying neurodegenerative diseases such as Alzheimer’s and Parkinson's. The goal of this work is to provide insights into the structural changes that characterize the kinetic pathways by which amyloid-β peptides convert from monomers to oligomers to fibrils. By applying discontinuous molecular dynamics simulations to PRIME20, a force field designed to capture the chemical and physical aspects of protein aggregation, we have been able to trace out the entire aggregation process for a system containing 8 Aβ17–42 peptides. We uncovered two fibrillization mechanisms that govern the structural conversion of Aβ17–42 peptides from disordered oligomers into protofilaments. The first mechanism is monomeric conversion templated by a U-shape oligomeric nucleus into U-shape protofilament. The second mechanism involves a long-lived and on-pathway metastable oligomer with S-shape chains, having a C-terminal turn, en route to the final U-shape protofilament. Oligomers with this C-terminal turn have been regarded in recent experiments as a major contributing element to cell toxicity in Alzheimer’s disease. The internal structures of the U-shape protofilaments from our PRIME20/DMD simulation agree well with those from solid state NMR experiments. The approach presented here offers a simple molecular-level framework to describe protein aggregation in general and to visualize the kinetic evolution of a putative toxic element in Alzheimer’s disease in particular. PMID:25955249
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Selective involvement of superior frontal cortex during working memory for shapes.
Yee, Lydia T S; Roe, Katherine; Courtney, Susan M
2010-01-01
A spatial/nonspatial functional dissociation between the dorsal and ventral visual pathways is well established and has formed the basis of domain-specific theories of prefrontal cortex (PFC). Inconsistencies in the literature regarding prefrontal organization, however, have led to questions regarding whether the nature of the dissociations observed in PFC during working memory are equivalent to those observed in the visual pathways for perception. In particular, the dissociation between dorsal and ventral PFC during working memory for locations versus object identities has been clearly present in some studies but not in others, seemingly in part due to the type of objects used. The current study compared functional MRI activation during delayed-recognition tasks for shape or color, two object features considered to be processed by the ventral pathway for perceptual recognition. Activation for the shape-delayed recognition task was greater than that for the color task in the lateral occipital cortex, in agreement with studies of visual perception. Greater memory-delay activity was also observed, however, in the parietal and superior frontal cortices for the shape than for the color task. Activity in superior frontal cortex was associated with better performance on the shape task. Conversely, greater delay activity for color than for shape was observed in the left anterior insula and this activity was associated with better performance on the color task. These results suggest that superior frontal cortex contributes to performance on tasks requiring working memory for object identities, but it represents different information about those objects than does the ventral frontal cortex.
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There were two major areas of focus in this project: a) determination of potential water quality improvements using sustainable paving alternatives and b) determination of potential aesthetic improvement by the use of the sustainable alternatives. In order to address both obje...
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Carina Wyborn; Laurie Yung; Daniel Murphy; Daniel R. Williams
2015-01-01
Adaptation is situated within multiple, interacting social, political, and economic forces. Adaptation pathways envision adaptation as a continual pathway of change and response embedded within this broader sociopolitical context. Pathways emphasize that current decisions are both informed by past actions and shape the landscape of future options. This research...
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Feeding the Elite: The Evolution of Elite Pathways from Star High Schools to Elite Universities
ERIC Educational Resources Information Center
LeTendre, Gerald K.; Gonzalez, Roger Geertz; Nomi, Takako
2006-01-01
During the last 50 years, private "feeder" schools in Japan came to dominate entry into elite colleges. Intense organizational competition shaped the organizational environment and changed the pathways available to social elites. Compared to Japan, elite private feeders in the US have failed to dominate pathways into elite colleges. In…
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Regional analysis of the effect of paved roads on sodium and chloride in lakes.
Kelting, Daniel L; Laxson, Corey L; Yerger, Elizabeth C
2012-05-15
Salinization of surface water from sodium chloride (road salt) applied to paved roads is a widely recognized environmental concern in the northern hemisphere, yet practical information to improve winter road management to reduce the environmental impacts of this deicer is lacking. The purpose of our study was to provide such information by developing baseline concentrations for sodium and chloride for lakes in watersheds without paved roads, and then determining the relationship between these ions and density, type, and proximity of paved roads to shoreline. We used average summer (June-September) sodium and chloride data for 138 lakes combined in a watershed based analysis of paved road networks in the Adirondack Park of New York, U.S.A. The watersheds used in our study represented a broad range in paved road density and type, 56 of which had no paved roads. Median lake sodium and chloride concentrations in these 56 watersheds averaged 0.55 and 0.24 mg/L, respectively. In contrast, the median sodium and chloride concentrations for the 82 lakes in watersheds with paved roads were 3.60 and 7.22 mg/L, respectively. Paved road density (lane-km/km(2)) was positively correlated with sodium and chloride concentrations, but only state roads were significantly correlated with sodium and chloride while local roads were not. State road density alone explained 84 percent of the variation in both ions. We also successfully modeled the relationship between road proximity to shoreline and sodium and chloride concentrations in lakes, which allowed us to identify sections of road that contributed more to explaining the variation in sodium and chloride in lakes. This model and our approach could be used as part of larger efforts to identify environmentally sensitive areas where alternative winter road management treatments should be applied. Copyright © 2012 Elsevier Ltd. All rights reserved.
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NASA Astrophysics Data System (ADS)
Bucsela, E. J.; Perring, A. E.; Cohen, R. C.; Boersma, K. F.; Celarier, E. A.; Gleason, J. F.; Wenig, M. O.; Bertram, T. H.; Wooldridge, P. J.; Dirksen, R.; Veefkind, J. P.
2008-08-01
We present an analysis of in situ NO2 measurements from aircraft experiments between summer 2004 and spring 2006. The data are from the INTEX-A, PAVE, and INTEX-B campaigns and constitute the most comprehensive set of tropospheric NO2 profiles to date. Profile shapes from INTEX-A and PAVE are found to be qualitatively similar to annual mean profiles from the GEOS-Chem model. Using profiles from the INTEX-B campaign, we perform error-weighted linear regressions to compare the Ozone Monitoring Instrument (OMI) tropospheric NO2 columns from the near-real-time product (NRT) and standard product (SP) with the integrated in situ columns. Results indicate that the OMI SP algorithm yields NO2 amounts lower than the in situ columns by a factor of 0.86 (±0.2) and that NO2 amounts from the NRT algorithm are higher than the in situ data by a factor of 1.68 (±0.6). The correlation between the satellite and in situ data is good (r = 0.83) for both algorithms. Using averaging kernels, the influence of the algorithm's a priori profiles on the satellite retrieval is explored. Results imply that air mass factors from the a priori profiles are on average slightly larger (˜10%) than those from the measured profiles, but the differences are not significant.
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Posterior Inferotemporal Cortex Cells Use Multiple Input Pathways for Shape Encoding.
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.
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Posterior Inferotemporal Cortex Cells Use Multiple Input Pathways for Shape Encoding
2017-01-01
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. PMID:28416597
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NASA Technical Reports Server (NTRS)
Pena, Francisco; Martins, Benjamin L.; Richards, W. Lance
2018-01-01
Morphing wing technologies have gained research interest in recent years as technological advancements pave the way for such innovations. A key benefit of such a morphing wing concept is the ability of the wing to transition into an optimal configuration at multiple flight conditions. Such a morphing wing will have applications not only in drag reduction but also in flutter suppression and gust alleviation. By manipulating the wing geometry to match a given flight profile it is likely that the wing will yield increases in not just aerodynamic efficiency but also structural efficiency. These structurally efficient designs will likely rely on some type of structural sensing system which will ensure the wing maintains positive margins throughout its flight profile.
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Concave Pd-Ru nanocubes bounded with high active area for boosting ethylene glycol electrooxidation
NASA Astrophysics Data System (ADS)
Xiong, Zhiping; Xu, Hui; Li, Shumin; Gu, Zhulan; Yan, Bo; Guo, Jun; Du, Yukou
2018-01-01
This paper reported our extensive efforts in the design of concave PdRu nanocubes via a facile wet-chemical strategy. Different from the previously reported PdRu nanostructures, the as-prepared concave PdRu nanocubes combined the advantages of fascinating nanocube structure, synergistic and electronic effect as well as high surface area. All of these beneficial terms endow them to exhibit superior electrocatalytic activity and long-term stability towards ethylene glycol oxidation as compared with commercial Pd/C. Our work highlights the significance of shape-controlled of PdRu nanostructures over the electrocatalytic performances towards the electrooxidation of ethylene glycol (EG), which will pave up a new strategy for boosting the development of renewable and clean energy technology.
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Harnessing the bistable composite shells to design a tunable phononic band gap structure
NASA Astrophysics Data System (ADS)
Li, Yi; Xu, Yanlong
2018-02-01
By proposing a system composed of an array of bistable composite shells immersed in air, we develop a new class of periodic structure to control the propagation of sound. Through numerical investigation, we find that the acoustic band gap of this system can be switched on and off by triggering the snap through deformation of the bistable composite shells. The shape of cross section and filling fraction of unit cell can be altered by different number of bistable composite shells, and they have strong impact on the position and width of the band gap. The proposed concept paves the way of using the bistable structures to design a new class of metamaterials that can be enable to manipulate sound.
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The ecology and biogeochemistry of stream biofilms.
Battin, Tom J; Besemer, Katharina; Bengtsson, Mia M; Romani, Anna M; Packmann, Aaron I
2016-04-01
Streams and rivers form dense networks, shape the Earth's surface and, in their sediments, provide an immensely large surface area for microbial growth. Biofilms dominate microbial life in streams and rivers, drive crucial ecosystem processes and contribute substantially to global biogeochemical fluxes. In turn, water flow and related deliveries of nutrients and organic matter to biofilms constitute major constraints on microbial life. In this Review, we describe the ecology and biogeochemistry of stream biofilms and highlight the influence of physical and ecological processes on their structure and function. Recent advances in the study of biofilm ecology may pave the way towards a mechanistic understanding of the effects of climate and environmental change on stream biofilms and the biogeochemistry of stream ecosystems.
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Self-assembled thin films of Fe3O4-Ag composite nanoparticles for spintronic applications
NASA Astrophysics Data System (ADS)
Jiang, Chengpeng; Leung, Chi Wah; Pong, Philip W. T.
2017-10-01
Controlled self-assembly of multi-component magnetic nanoparticles could lead to nanomaterial-based magnetic devices with novel structures and intriguing properties. Herein, self-assembled thin films of Fe3O4-Ag composite nanoparticles (CNPs) with hetero-dimeric shapes were fabricated using interfacial assembly method. The CNP-assembled thin films were further transferred to patterned silicon substrates followed by vacuum annealing, producing CNP-based magnetoresistive (MR) devices. Due to the presence of intra-particle interfaces and inter-particle barriers, an enhanced MR ratio and a non-linear current-voltage relation were observed in the device. The results of this work can potentially pave the way to the future exploration and development of spintronic devices built from composite nanomaterials.
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Iatropoulos, Paraskevas; Daina, Erica; Curreri, Manuela; Piras, Rossella; Valoti, Elisabetta; Mele, Caterina; Bresin, Elena; Gamba, Sara; Alberti, Marta; Breno, Matteo; Perna, Annalisa; Bettoni, Serena; Sabadini, Ettore; Murer, Luisa; Vivarelli, Marina; Noris, Marina; Remuzzi, Giuseppe
2018-01-01
Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement-mediated C3 glomerulopathy (C3G) and immune complex-mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1-3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment. Copyright © 2018 by the American Society of Nephrology.
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Motor pathway convergence predicts syllable repertoire size in oscine birds
Moore, Jordan M.; Székely, Tamás; Büki, József; DeVoogd, Timothy J.
2011-01-01
Behavioral specializations are frequently associated with expansions of the brain regions controlling them. This principle of proper mass spans sensory, motor, and cognitive abilities and has been observed in a wide variety of vertebrate species. Yet, it is unknown if this concept extrapolates to entire neural pathways or how selection on a behavioral capacity might otherwise shape circuit structure. We investigate these questions by comparing the songs and neuroanatomy of 49 species from 17 families of songbirds, which vary immensely in the number of unique song components they produce and possess a conserved neural network dedicated to this behavior. We find that syllable repertoire size is strongly related to the degree of song motor pathway convergence. Repertoire size is more accurately predicted by the number of neurons in higher motor areas relative to that in their downstream targets than by the overall number of neurons in the song motor pathway. Additionally, the convergence values along serial premotor and primary motor projections account for distinct portions of the behavioral variation. These findings suggest that selection on song has independently shaped different components of this hierarchical pathway, and they elucidate how changes in pathway structure could have underlain elaborations of this learned motor behavior. PMID:21918109
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Kuang, Xiao; Chen, Kaijuan; Dunn, Conner K; Wu, Jiangtao; Li, Vincent C F; Qi, H Jerry
2018-02-28
The three-dimensional (3D) printing of flexible and stretchable materials with smart functions such as shape memory (SM) and self-healing (SH) is highly desirable for the development of future 4D printing technology for myriad applications, such as soft actuators, deployable smart medical devices, and flexible electronics. Here, we report a novel ink that can be used for the 3D printing of highly stretchable, SM, and SH elastomer via UV-light-assisted direct-ink-write printing. An ink containing urethane diacrylate and a linear semicrystalline polymer is developed for the 3D printing of a semi-interpenetrating polymer network elastomer that can be stretched by up to 600%. The 3D-printed complex structures show interesting functional properties, such as high strain SM and SM -assisted SH capability. We demonstrate that such a 3D-printed SM elastomer has the potential application for biomedical devices, such as vascular repair devices. This research paves a new way for the further development of novel 4D printing, soft robotics, and biomedical devices.
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Thermal Analysis of Fluidized Bed and Fixed Bed Latent Heat Thermal Storage System
NASA Astrophysics Data System (ADS)
Beemkumar, N.; Karthikeyan, A.; Shiva Keshava Reddy, Kota; Rajesh, Kona; Anderson, A.
2017-05-01
Thermal energy storage technology is essential because its stores available energy at low cost. Objective of the work is to store the thermal energy in a most efficient method. This work is deal with thermal analysis of fluidized bed and fixed bed latent heat thermal storage (LHTS) system with different encapsulation materials (aluminium, brass and copper). D-Mannitol has been used as phase change material (PCM). Encapsulation material which is in orbicular shape with 4 inch diameter and 2 mm thickness orbicular shaped product is used. Therminol-66 is used as a heat transfer fluid (HTF). Arrangement of encapsulation material is done in two ways namely fluidized bed and fixed bed thermal storage system. Comparison was made between the performance of fixed bed and fluidized bed with different encapsulation material. It is observed that from the economical point of view aluminium in fluidized bed LHTS System has highest efficiency than copper and brass. The thermal energy storage system can be analyzed with fixed bed by varying mass flow rate of oil paves a way to find effective heat energy transfer.
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The Active Sites of a Rod-Shaped Hollandite DeNOx Catalyst.
Hu, Pingping; Schuster, Manfred Erwin; Huang, Zhiwei; Xu, Fei; Jin, Shifeng; Chen, Yaxin; Hua, Weiming; Su, Dang Sheng; Tang, Xingfu
2015-06-26
The identification of catalytically active sites (CASs) in heterogeneous catalysis is of vital importance to design and develop improved catalysts, but remains a great challenge. The CASs have been identified in the low-temperature selective catalytic reduction of nitrogen oxides by ammonia (SCR) over a hollandite manganese oxide (HMO) catalyst with a rod-shaped morphology and one-dimensional tunnels. Electron microscopy and synchrotron X-ray diffraction determine the surface and crystal structures of the one-dimensional HMO rods closed by {100} side facets and {001} top facets. A combination of X-ray absorption spectra, molecular probes with potassium and nitric oxide, and catalytic tests reveals that the CASs are located on the {100} side facets of the HMO rods rather than on the top facets or in the tunnels, and hence semi-tunnel structural motifs on the {100} facets are evidenced to be the CASs of the SCR reaction. This work paves the way to further investigate the intrinsic mechanisms of SCR reactions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Wang, Qingrong; Wang, Xinyu; Wan, Fang; Chen, Kena; Niu, Zhiqiang; Chen, Jun
2018-06-01
The emergence of flexible and wearable electronics has raised the demand for flexible supercapacitors with accurate sizes and aesthetic shapes. Here, a strategy is developed to prepare flexible all-in-one integrated supercapacitors by combining all-freeze-casting with typography technique. The continuous seamless connection of all-in-one supercapacitor devices enhances the load and/or electron transfer capacity and avoids displacing and detaching between their neighboring components at bending status. Therefore, such a unique structure of all-in-one integrated devices is beneficial for retaining stable electrochemical performance at different bending levels. More importantly, the sizes and aesthetic shapes of integrated supercapacitors could be controlled by the designed molds, like type matrices of typography. The molds could be assembled together and typeset randomly, achieving the controllable construction and series and/or parallel connection of several supercapacitor devices. The preparation of flexible integrated supercapacitors will pave the way for assembling programmable all-in-one energy storage devices into highly flexible electronics. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Garcia, Carlos B W; Zhang, Yuanming; Mahajan, Surbhi; DiSalvo, Francis; Wiesner, Ulrich
2003-11-05
In the present study poly(isoprene-block-ethylene oxide), PI-b-PEO, block copolymers are used to structure iron oxide and silica precursors into reverse mesophases, which upon dissolution of the organic matrix lead to well-defined nanoparticles of spheres, cylinders, and plates based on the original structure of the mesophase prepared. The hybrid mesophases with sphere, cylinder, and lamellar morphologies containing the inorganic components in the minority phases are characterized through a combination of small-angle X-ray scattering (SAXS), transmission electron microscopy (TEM), scanning transmission electron microscopy (STEM), and electron energy loss spectroscopy (EELS). After heat treatments the respective nanoparticles on mica surfaces are characterized by scanning force microscopy (SFM). X-ray diffraction (XRD) and superconducting quantum interference device (SQUID) magnetometer measurements are performed to demonstrate that the heat treatment leads to the formation of a magnetic gamma-Fe2O3 crystalline phase within the amorphous aluminosilicate. The results pave the way to functional, i.e., magnetic nanoparticles where the size, shape, and iron oxide concentration can be controlled opening a range of possible applications.
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Designer Shape Anisotropy on Transition-Metal-Dichalcogenide Nanosheets.
Martella, Christian; Mennucci, Carlo; Lamperti, Alessio; Cappelluti, Emmanuele; de Mongeot, Francesco Buatier; Molle, Alessandro
2018-03-01
MoS 2 and generally speaking, the wide family of transition-metal dichalcogenides represents a solid nanotechnology platform on which to engineer a wealth of new and outperforming applications involving 2D materials. An even richer flexibility can be gained by extrinsically inducing an in-plane shape anisotropy of the nanosheets. Here, the synthesis of anisotropic MoS 2 nanosheets is proposed as a prototypical example in this respect starting from a highly conformal chemical vapor deposition on prepatterend substrates and aiming at the more general purpose of tailoring anisotropy of 2D nanosheets by design. This is envisioned to be a suitable configuration for strain engineering as far as strain can be spatially redistributed in morphologically different regions. With a similar approach, both the optical and electronic properties of the 2D transition-metal dichalcogenides can be tailored over macroscopic sample areas in a self-organized fashion, thus paving the way for new applications in the field of optical metasurfaces, light harvesting, and catalysis. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Coherent diffractive imaging of single helium nanodroplets with a high harmonic generation source.
Rupp, Daniela; Monserud, Nils; Langbehn, Bruno; Sauppe, Mario; Zimmermann, Julian; Ovcharenko, Yevheniy; Möller, Thomas; Frassetto, Fabio; Poletto, Luca; Trabattoni, Andrea; Calegari, Francesca; Nisoli, Mauro; Sander, Katharina; Peltz, Christian; J Vrakking, Marc; Fennel, Thomas; Rouzée, Arnaud
2017-09-08
Coherent diffractive imaging of individual free nanoparticles has opened routes for the in situ analysis of their transient structural, optical, and electronic properties. So far, single-shot single-particle diffraction was assumed to be feasible only at extreme ultraviolet and X-ray free-electron lasers, restricting this research field to large-scale facilities. Here we demonstrate single-shot imaging of isolated helium nanodroplets using extreme ultraviolet pulses from a femtosecond-laser-driven high harmonic source. We obtain bright wide-angle scattering patterns, that allow us to uniquely identify hitherto unresolved prolate shapes of superfluid helium droplets. Our results mark the advent of single-shot gas-phase nanoscopy with lab-based short-wavelength pulses and pave the way to ultrafast coherent diffractive imaging with phase-controlled multicolor fields and attosecond pulses.Diffraction imaging studies of free individual nanoparticles have so far been restricted to XUV and X-ray free - electron laser facilities. Here the authors demonstrate the possibility of using table-top XUV laser sources to image prolate shapes of superfluid helium droplets.
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Kakkar, Aanchal; Majumdar, Atreye; Kumar, Anupam; Tripathi, Manjari; Pathak, Pankaj; Sharma, Mehar C; Suri, Vaishali; Tandon, Vivek; Chandra, Sarat P; Sarkar, Chitra
2016-11-01
Recently, BRAF V600E mutation, and activation of mTOR and MAPK pathways have been identified in various glial/glioneuronal tumors. Dysembryoplastic neuroepithelial tumors (DNTs) are epilepsy-associated glioneuronal neoplasms which have not been analyzed extensively in this respect. Sequencing for BRAF V600E mutation, analysis of BRAF copy number by qRT-PCR, and immunohistochemistry for mTOR (p-S6, p-4EBP1) and MAPK (p-MAPK) pathways were performed. Sixty-four DNTs were identified, accounting for 15.1% of patients with drug-refractory epilepsy (mean age: 15.5 years). Duration of seizures ranged from 1 to 22 years. BRAF V600E mutation was identified in 3.7% of DNTs, while BRAF copy number gain was observed in 33.3%. mTOR-pathway activation indicated by p-S6 or p-4EBP1 immunopositivity was seen in 89.7% cases. Interestingly, p-S6 positivity was also seen in adjacent dysplastic cortex. p-MAPK immunopositivity was seen in 50% cases. MAPK and mTOR pathway activation was independent of BRAF alterations. All patients that underwent incomplete resection had Engel grade II-III outcomes (p<0.001). BRAF alterations are frequent in DNTs, particularly BRAF copy number gain which is being reported for the first time in these tumors. Evidence of activation of mTOR and MAPK pathways suggests a role for altered signalling in DNT pathogenesis, and will pave the way for development of targeted therapies, particularly relevant for patients having persistent seizures after incomplete resection. Copyright © 2016 Elsevier B.V. All rights reserved.
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ECTODERMAL WNT/β-CATENIN SIGNALING SHAPES THE MOUSE FACE
Reid, Bethany S.; Yang, Hui; Melvin, Vida Senkus; Taketo, Makoto M.; Williams, Trevor
2010-01-01
The canonical Wnt/β-catenin pathway is an essential component of multiple developmental processes. To investigate the role of this pathway in the ectoderm during facial morphogenesis, we generated conditional β-catenin mouse mutants using a novel ectoderm-specific Cre recombinase transgenic line. Our results demonstrate that ablating or stabilizing β-catenin in the embryonic ectoderm causes dramatic changes in facial morphology. There are accompanying alterations in the expression of Fgf8 and Shh, key molecules that establish a signaling center critical for facial patterning, the frontonasal ectodermal zone (FEZ). These data indicate that Wnt/β-catenin signaling within the ectoderm is critical for facial development and further suggest that this pathway is an important mechanism for generating the diverse facial shapes of vertebrates during evolution. PMID:21087601
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Qiao, Yan; Zhang, Jinjin; Zhang, Jinwen; Wang, Zhiwei; Ran, An; Guo, Haixia; Wang, Di; Zhang, Junlian
2017-02-01
Light is a major environmental factor that affects metabolic pathways and stimulates the production of secondary metabolites in potato. However, adaptive changes in potato metabolic pathways and physiological functions triggered by light are partly explained by gene expression changes. Regulation of secondary metabolic pathways in potato has been extensively studied at transcriptional level, but little is known about the mechanisms of post-transcriptional regulation by miRNAs. To identify light-responsive miRNAs/mRNAs and construct putative metabolism pathways regulated by the miRNA-mRNA pairs, an integrated omics (sRNAome and transcriptome) analysis was performed to potato under light stimulus. A total of 31 and 48 miRNAs were identified to be differentially expressed in the leaves and tubers, respectively. Among the DEGs, 1353 genes in the leaves and 1841 genes in the tubers were upregulated, while 1595 genes in the leaves and 897 genes in the tubers were downregulated by light. Mapman enrichment analyses showed that genes related to MVA pathway, alkaloids-like, phenylpropanoids, flavonoids, and carotenoids metabolism were significantly upregulated, while genes associated with major CHO metabolism were repressed in the leaves and tubers. Integrated miRNA and mRNA profiles revealed that light-responsive miRNAs are important regulators in alkaloids metabolism, UMP salvage, lipid biosynthesis, and cellulose catabolism. Moreover, several miRNAs may participate in glycoalkaloids metabolism via JA signaling pathway, UDP-glucose biosynthesis and hydroxylation reaction. This study provides a global view of miRNA and mRNA expression profiles in potato response to light, our results suggest that miRNAs might play important roles in secondary metabolic pathways, especially in glycoalkaloid biosynthesis. The findings will enlighten us on the genetic regulation of secondary metabolite pathways and pave the way for future application of genetically engineered potato.
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The process of justifying assisted reproductive technologies in Iran.
Gooshki, Ehsan Shamsi; Allahbedashti, Neda
2015-01-01
Infertility is medically defined as one year of unprotected intercourse that does not result in pregnancy. Infertility is a noticeable medical problem in Iran, and about a quarter of Iranian couples experience primary infertility at some point in their lives. Since having children is a basic social value in Iran, infertility has an adverse effect on the health of the couple and affects their well-being. The various methods of assisting infertile couples raise several ethical questions and touch upon certain sensitive points. Although the present Iranian legislative system, which is based on the Shi'a school of Islam, has legalised some aspects of assisted reproductive technologies (ARTs), given the absence of a general officially ratified act (official pathway), such medical interventions are usually justified through a fatwa system (non-official pathway). Officially registered married couples can access almost all ART methods, including third-party gamete donation, if they use such pathways. The process of justifying ART interventions generally began when in vitro fertilisation was given the nod and later, Ayatollah Khamenei (the political-religious leader of the country) issued a fatwa which permitted gamete donation by third parties. This open juristic approach paved the way for the ratification of the Embryo Donation to Infertile Spouses Act in 2003.
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Park, Young-Uk; Bai, Jianming; Wang, Liping; Yoon, Gabin; Zhang, Wei; Kim, Hyungsub; Lee, Seongsu; Kim, Sung-Wook; Looney, J Patrick; Kang, Kisuk; Wang, Feng
2017-09-13
Ion exchange is a ubiquitous phenomenon central to wide industrial applications, ranging from traditional (bio)chemical separation to the emerging chimie douce synthesis of materials with metastable structure for batteries and other energy applications. The exchange process is complex, involving substitution and transport of different ions under non-equilibrium conditions, and thus difficult to probe, leaving a gap in mechanistic understanding of kinetic exchange pathways toward final products. Herein, we report in situ tracking kinetic pathways of Li + /Na + substitution during solvothermal ion-exchange synthesis of Li x Na 1.5-x VOPO 4 F 0.5 (0 ≤ x ≤ 1.5), a promising multi-Li polyanionic cathode for batteries. The real-time observation, corroborated by first-principles calculations, reveals a selective replacement of Na + by Li + , leading to peculiar Na + /Li + /vacancy orderings in the intermediates. Contradicting the traditional belief of facile topotactic substitution via solid solution reaction, an abrupt two-phase transformation occurs and predominantly governs the kinetics of ion exchange and transport in the 1D polyanionic framework, consequently leading to significant difference of Li stoichiometry and electrochemical properties in the exchanged products. The findings may help to pave the way for rational design of ion exchange synthesis for making new materials.
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Xu, Baofu; Lei, Lei; Zhu, Xiaocen; Zhou, Yiqing; Xiao, Youli
2017-04-01
Lysine decarboxylation is the first biosynthetic step of Huperzine A (HupA). Six cDNAs encoding lysine decarboxylases (LDCs) were cloned from Huperzia serrata by degenerate PCR and rapid amplification of cDNA ends (RACE). One HsLDC isoform was functionally characterized as lysine decarboxylase. The HsLDC exhibited greatest catalytic efficiency (k cat /K m , 2.11 s -1 mM -1 ) toward L-lysine in vitro among all reported plant-LDCs. Moreover, transient expression of the HsLDC in tobacco leaves specifically increased cadaverine content from zero to 0.75 mg per gram of dry mass. Additionally, a convenient and reliable method used to detect the two catalytic products was developed. With the novel method, the enzymatic products of HsLDC and HsCAO, namely cadaverine and 5-aminopentanal, respectively, were detected simultaneously both in assay with purified enzymes and in transgenic tobacco leaves. This work not only provides direct evidence of the first two-step in biosynthetic pathway of HupA in Huperzia serrata and paves the way for further elucidation of the pathway, but also enables engineering heterologous production of HupA. Copyright © 2017 Elsevier Ltd. All rights reserved.
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Joint deep shape and appearance learning: application to optic pathway glioma segmentation
NASA Astrophysics Data System (ADS)
Mansoor, Awais; Li, Ien; Packer, Roger J.; Avery, Robert A.; Linguraru, Marius George
2017-03-01
Automated tissue characterization is one of the major applications of computer-aided diagnosis systems. Deep learning techniques have recently demonstrated impressive performance for the image patch-based tissue characterization. However, existing patch-based tissue classification techniques struggle to exploit the useful shape information. Local and global shape knowledge such as the regional boundary changes, diameter, and volumetrics can be useful in classifying the tissues especially in scenarios where the appearance signature does not provide significant classification information. In this work, we present a deep neural network-based method for the automated segmentation of the tumors referred to as optic pathway gliomas (OPG) located within the anterior visual pathway (AVP; optic nerve, chiasm or tracts) using joint shape and appearance learning. Voxel intensity values of commonly used MRI sequences are generally not indicative of OPG. To be considered an OPG, current clinical practice dictates that some portion of AVP must demonstrate shape enlargement. The method proposed in this work integrates multiple sequence magnetic resonance image (T1, T2, and FLAIR) along with local boundary changes to train a deep neural network. For training and evaluation purposes, we used a dataset of multiple sequence MRI obtained from 20 subjects (10 controls, 10 NF1+OPG). To our best knowledge, this is the first deep representation learning-based approach designed to merge shape and multi-channel appearance data for the glioma detection. In our experiments, mean misclassification errors of 2:39% and 0:48% were observed respectively for glioma and control patches extracted from the AVP. Moreover, an overall dice similarity coefficient of 0:87+/-0:13 (0:93+/-0:06 for healthy tissue, 0:78+/-0:18 for glioma tissue) demonstrates the potential of the proposed method in the accurate localization and early detection of OPG.
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Representation of Gravity-Aligned Scene Structure in Ventral Pathway Visual Cortex.
Vaziri, Siavash; Connor, Charles E
2016-03-21
The ventral visual pathway in humans and non-human primates is known to represent object information, including shape and identity [1]. Here, we show the ventral pathway also represents scene structure aligned with the gravitational reference frame in which objects move and interact. We analyzed shape tuning of recently described macaque monkey ventral pathway neurons that prefer scene-like stimuli to objects [2]. Individual neurons did not respond to a single shape class, but to a variety of scene elements that are typically aligned with gravity: large planes in the orientation range of ground surfaces under natural viewing conditions, planes in the orientation range of ceilings, and extended convex and concave edges in the orientation range of wall/floor/ceiling junctions. For a given neuron, these elements tended to share a common alignment in eye-centered coordinates. Thus, each neuron integrated information about multiple gravity-aligned structures as they would be seen from a specific eye and head orientation. This eclectic coding strategy provides only ambiguous information about individual structures but explicit information about the environmental reference frame and the orientation of gravity in egocentric coordinates. In the ventral pathway, this could support perceiving and/or predicting physical events involving objects subject to gravity, recognizing object attributes like animacy based on movement not caused by gravity, and/or stabilizing perception of the world against changes in head orientation [3-5]. Our results, like the recent discovery of object weight representation [6], imply that the ventral pathway is involved not just in recognition, but also in physical understanding of objects and scenes. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Recent Progress in the Development of Metabolome Databases for Plant Systems Biology
Fukushima, Atsushi; Kusano, Miyako
2013-01-01
Metabolomics has grown greatly as a functional genomics tool, and has become an invaluable diagnostic tool for biochemical phenotyping of biological systems. Over the past decades, a number of databases involving information related to mass spectra, compound names and structures, statistical/mathematical models and metabolic pathways, and metabolite profile data have been developed. Such databases complement each other and support efficient growth in this area, although the data resources remain scattered across the World Wide Web. Here, we review available metabolome databases and summarize the present status of development of related tools, particularly focusing on the plant metabolome. Data sharing discussed here will pave way for the robust interpretation of metabolomic data and advances in plant systems biology. PMID:23577015
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Marine drugs: A hidden wealth and a new epoch for cancer management.
Shakeel, Eram; Arora, Deepika; Jamal, Qazi Mohammad Sajid; Akhtar, Salman; Khan, Mohd Kalim Ahmad; Kamal, Mohammad A; Siddiqui, Mohd Haris; Lohani, Mohtashim; Arif, Jamal M
2017-02-20
Malignant tumors are the leading cause of death in humans. Due to tedious efforts and investigation made in the field of marine drug discovery, there is now a scientific bridge between marine and pharmaceutical sciences. However, at present only few marine drugs have been paved towards anticancer management, yet many more to be established. Marine organisms are profuse manufacturer of structurally inimitable bioactive metabolites that have unusual mechanisms of action and diverse biosynthetic pathways. Some of the compounds derived from marine organisms have antioxidant property and anticancer activities, but they are largely unexplored. The present review is summarising various source of marine chemicals and their exploration of anticancerous potential. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
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Nomura, Ken-Ichi; Kalia, Rajiv K; Nakano, Aiichiro; Vashishta, Priya; van Duin, Adri C T; Goddard, William A
2007-10-05
Mechanical stimuli in energetic materials initiate chemical reactions at shock fronts prior to detonation. Shock sensitivity measurements provide widely varying results, and quantum-mechanical calculations are unable to handle systems large enough to describe shock structure. Recent developments in reactive force-field molecular dynamics (ReaxFF-MD) combined with advances in parallel computing have paved the way to accurately simulate reaction pathways along with the structure of shock fronts. Our multimillion-atom ReaxFF-MD simulations of l,3,5-trinitro-l,3,5-triazine (RDX) reveal that detonation is preceded by a transition from a diffuse shock front with well-ordered molecular dipoles behind it to a disordered dipole distribution behind a sharp front.
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Nuclear export of RNA: Different sizes, shapes and functions.
Williams, Tobias; Ngo, Linh H; Wickramasinghe, Vihandha O
2018-03-01
Export of protein-coding and non-coding RNA molecules from the nucleus to the cytoplasm is critical for gene expression. This necessitates the continuous transport of RNA species of different size, shape and function through nuclear pore complexes via export receptors and adaptor proteins. Here, we provide an overview of the major RNA export pathways in humans, highlighting the similarities and differences between each. Its importance is underscored by the growing appreciation that deregulation of RNA export pathways is associated with human diseases like cancer. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.
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Zhang, Yan; Shi, Junling; Liu, Laping; Gao, Zhenhong; Che, Jinxin; Shao, Dongyan; Liu, Yanlin
2015-01-01
Pinoresinol diglucoside (PDG) and pinoresinol (Pin) are normally produced by plant cells via the phenylpropanoid pathway. This study reveals the existence of a related pathway in Phomopsis sp. XP-8, a PDG-producing fungal strain isolated from the bark of the Tu-chung tree (Eucommiaulmoides Oliv.). After addition of 0.15 g/L glucose to Phomopsis sp. XP-8, PDG and Pin formed when phenylalanine, tyrosine, leucine, cinnamic acid, and p-coumaric acid were used as the substrates respectively. No PDG formed in the absence of glucose, but Pin was detected after addition of all these substrates except leucine. In all systems in the presence of glucose, production of PDG and/or Pin and the accumulation of phenylalanine, cinnamic acid, or p-coumaric acid correlated directly with added substrate in a time- and substrate concentration- dependent manner. After analysis of products produced after addition of each substrate, the mass flow sequence for PDG and Pin biosynthesis was defined as: glucose to phenylalanine, phenylalanine to cinnamic acid, then to p-coumaric acid, and finally to Pin or PDG. During the bioconversion, the activities of four key enzymes in the phenylpropanoid pathway were also determined and correlated with accumulation of their corresponding products. PDG production by Phomopsis sp. exhibits greater efficiency and cost effectiveness than the currently-used plant-based system and will pave the way for large scale production of PDG and/or Pin for medical applications. PMID:26331720
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Tigano, Marco; Ruotolo, Roberta; Dallabona, Cristina; Fontanesi, Flavia; Barrientos, Antoni; Donnini, Claudia; Ottonello, Simone
2015-09-30
To gain a wider view of the pathways that regulate mitochondrial function, we combined the effect of heat stress on respiratory capacity with the discovery potential of a genome-wide screen in Saccharomyces cerevisiae. We identified 105 new genes whose deletion impairs respiratory growth at 37°C by interfering with processes such as transcriptional regulation, ubiquitination and cytosolic tRNA wobble uridine modification via 5-methoxycarbonylmethyl-2-thiouridine formation. The latter process, specifically required for efficient decoding of AA-ending codons under stress conditions, was covered by multiple genes belonging to the Elongator (e.g. ELP3) and urmylation (e.g., NCS6) pathways. ELP3 or NCS6 deletants had impaired mitochondrial protein synthesis. Their respiratory deficiency was selectively rescued by overexpression of tRNA(Lys) UUU as well by overexpression of genes (BCK1 and HFM1) with a strong bias for the AAA codon read by this tRNA. These data extend the mitochondrial regulome, demonstrate that heat stress can impair respiration by disturbing cytoplasmic translation of proteins critically involved in mitochondrial function and document, for the first time, the involvement in such process of the Elongator and urmylation pathways. Given the conservation of these pathways, the present findings may pave the way to a better understanding of the human mitochondrial regulome in health and disease. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
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Identification of senescence-associated genes in human bone marrow mesenchymal stem cells
DOE Office of Scientific and Technical Information (OSTI.GOV)
Ryu, Eunsook; Hong, Su; Kang, Jaeku
2008-07-04
Human bone marrow mesenchymal stem cells (hBMMSCs) are multipotent stem cells that can differentiate into several specialized cell types, including bone, cartilage, and fat cells. The proliferative capacity of hBMMSCs paves the way for the development of regenerative medicine and tissue engineering. However, long-term in vitro culture of hBMMSCs leads to a reduced life span of the cells due to senescence, which leads eventually to growth arrest. To investigate the molecular mechanism behind the cellular senescence of hBMMSCs, microarray analysis was used to compare the expression profiles of early passage hBMMSCs, late passage hBMMSCs and hBMMSCs ectopically expressing human telomerasemore » reverse transcriptase (hTERT). Using an intersection analysis of 3892 differentially expressed genes (DEGs) out of 27,171 total genes analyzed, we identified 338 senescence-related DEGs. GO term categorization and pathway network analysis revealed that the identified genes are strongly related to known senescence pathways and mechanisms. The genes identified using this approach will facilitate future studies of the mechanisms underlying the cellular senescence of hBMMSCs.« less
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NASA Astrophysics Data System (ADS)
Leung, Kevin; Sai, Na; Zador, Judit; Henkelman, Graeme
2014-03-01
Photo-oxidation is one of the leading chemical degradation mechanisms in polymer solar cells. In this work, using hybrid density functional theory and periodic boundary condition, we investigate reaction pathways that may lead to the sulfur oxidation in poly(3-hexylthiophene)(P3HT) as a step toward breaking the macromolecule backbone. We calculate energy barriers for reactions of P3HT backbone with oxidizing radicals suggested by infrared spectroscopy (IR) and XPS studies. Our results strongly suggest that an attack of hydroxyl radical on sulfur as proposed in the literature is unlikely to be thermodynamically favored. On the other hand, a reaction between the alkylperoxyl radical and the polymer backbone may provide low barrier reaction pathways to photo-oxidation of conjugated polymers with side chains. Our work paves way for future studies using ab-initio calculations in a condensed phase setting to model complex chemical reactions relevant to photochemical stability of novel polymers. Supported by the Energy Frontier Research Center funded by the U.S. DOE Office of Basic Energy Sciences under Award #DE-SC0001091.
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Micro-RNAs and their roles in eye disorders.
Raghunath, Azhwar; Perumal, Ekambaram
2015-01-01
Micro-RNAs (miRNAs) are members of the family of noncoding RNA molecules that regulate gene expression by translational repression and mRNA degradation. Initial identification of miRNAs revealed them only as developmental regulators; later, their radiated roles in various cellular processes have been established. They regulate several pathways, including developmental timing, hematopoiesis, organogenesis, apoptosis, cell differentiation and proliferation. Their roles in eye disorders are being explored by biologists around the world. Eye physiology requires the perfect orchestration of all the regulatory networks; any defect in any of the networks leads to eye disorders. The dysregulation of miRNA expression has been reported in many eye disorders, which paves the way for new therapeutics. This review summarizes the biogenesis of miRNAs and their role in eye disorders. miRNA studies also have implications for the understanding of various complex metabolic pathways leading to disorders of the eye. The ultimate understanding leads to potential opportunities in evaluating miRNAs as molecular biomarkers, prognostic tools, diagnostic tools and therapeutic agents for eye disorders. © 2015 S. Karger AG, Basel.
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Dunleavy, Kieron; Steidl, Christian
2015-04-01
While primary mediastinal large B-cell lymphoma (PMBCL) is considered to be a subtype of diffuse large B-cell lymphoma, it is a distinct clinicopathologic entity, with clinical and biological features closely resembling nodular sclerosing Hodgkin lymphoma. Recent studies have highlighted the shared biology of these two entities and identified novel critical pathways of lymphomagenesis, including the presence of distinct mutations. Mediastinal grey zone lymphomas with features in between PMBCL and nodular sclerosing Hodgkin lymphoma have been described as the missing link between the two parent entities. While the standard therapeutic approach to PMBCL has been immunochemotherapy followed by mediastinal radiation, strategies that obviate the need for radiation and thus eliminate its long-term toxicities have recently been developed. The identification of novel targets in PMBCL and mediastinal grey zone lymphomas have paved the way for testing of agents such as small molecule inhibitors of Janus kinase pathways and immune checkpoint inhibitors. Future directions in these diseases should focus on combining effective novel agents with immunochemotherapy platforms. Published by Elsevier Inc.
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Parkinson's: a syndrome rather than a disease?
Titova, Nataliya; Padmakumar, C; Lewis, Simon J G; Chaudhuri, K Ray
2017-08-01
Emerging concepts suggest that a multitude of pathology ranging from misfolding of alpha-synuclein to neuroinflammation, mitochondrial dysfunction, and neurotransmitter driven alteration of brain neuronal networks lead to a syndrome that is commonly known as Parkinson's disease. The complex underlying pathology which may involve degeneration of non-dopaminergic pathways leads to the expression of a range of non-motor symptoms from the prodromal stage of Parkinson's to the palliative stage. Non-motor clinical subtypes, cognitive and non-cognitive, have now been proposed paving the way for possible subtype specific and non-motor treatments, a key unmet need currently. Natural history of these subtypes remains unclear and need to be defined. In addition to in vivo biomarkers which suggest variable involvement of the cholinergic and noradrenergic patterns of the Parkinson syndrome, abnormal alpha-synuclein accumulation have now been demonstrated in the gut, pancreas, heart, salivary glands, and skin suggesting that Parkinson's is a multi-organ disorder. The Parkinson's phenotype is thus not just a dopaminergic motor syndrome, but a dysfunctional multi-neurotransmitter pathway driven central and peripheral nervous system disorder that possibly ought to be considered a syndrome and not a disease.
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Induction of cellular and molecular immunomodulatory pathways by vitamin A and Flavonoids
Patel, Sapna; Vajdy, Michael
2016-01-01
Introduction A detailed study of reports on the immunomodulatory properties of vitamin A and select flavonoids may pave the way for using these natural compounds or compounds with similar structures in novel drug and vaccine designs against infectious and autoimmune diseases and cancers. Areas Covered Intracellular transduction pathways, cellular differentiation and functional immunomodulatory responses have been reviewed. The reported studies encompass in vitro, in vivo preclinical and clinical studies that address the role of Vitamin A and select flavonoids in induction of innate and adaptive B and T cell responses, including TH1, TH2 and Treg. Expert Opinion While the immunomodulatory role of vitamin A, and related compounds, is well-established in many preclinical studies, its role in humans has begun to gain wider acceptance. In contrast, the role of flavonoids is mostly controversial in clinical trials, due to the diversity of the various classes of these compounds, and possibly due to the purity and the selected doses of the compounds. However, current preclinical and clinical studies warrant further detailed studies of these promising immuno-modulatory compounds. PMID:26185959
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Interns at an International, Humanitarian Organization: Career Pathways and Meaning Making
ERIC Educational Resources Information Center
Mather, Peter C.
2008-01-01
This qualitative study examined the career shaping experiences and related meaning making processes of 12 interns at The Carter Center, an international, humanitarian organization. Experiences shaping participants' careers were grouped into the following themes--academics and intellectual curiosity; travel abroad; religion; relationships--family,…
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Socioeconomic Status, Schooling, and the Developmental Trajectories of Adolescents
ERIC Educational Resources Information Center
Crosnoe, Robert; Huston, Aletha C.
2007-01-01
The socioeconomic stratification of American society profoundly influences how the life course unfolds by shaping various developmental pathways as well as the connections among these pathways. Drawing on a nationally representative sample of American adolescents, this study charted trajectories of personal control and parental consultation from…
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NASA Astrophysics Data System (ADS)
Nurzal; Nursyuhada, Aries
2017-12-01
This research aims based on SNI 03-0691-1996 to investigate the effect of coloring and compacting pressure with the addition of 5 wt.% fly ash (Fa) on compressive strength. Fa derived from waste material coal-fired Sijantang Sawahlunto thermal power plant. The growing production of Fa caused negative environmental impact. So, one of the solutions to overcome that effects is to use the Fa as a raw material for paving block mixture that can reduce the cost of raw material and increase its strength. Paving blocks are gray and red with 0 wt.%, 5 wt.% Fa + Pb composition. Compaction pressure variations 55, 65, 75, 85 and 95 Kg/cm2. The drying time for 35 days. Specimens were produced in the form of rectangular bar (length, L = 20 cm, width, B = 10 cm, thickness, W = 6 cm). The test results showed that the addition of 5 wt% FA has a compressive strength value higher than 0 wt%. The red color has a compressive strength lower than the gray color paving block caused the red color (Iron Oxide) is less binding at the time of mixing the material. Gray and red Paving blocks both increase in each additional compaction pressure, because the higher the compaction pressure will increase the bond between the particles so porosity is reduced increased compressive strength. The overall data, the gray paving block with the composition of 5 wt% FA at compaction pressure 95 kg/cm2 with the optimal compressive strength value of 36.1 MPa and the lowest value is found in the red color paving block at 0 wt% FA at a pressure of 55 kg/cm2 with a value of 6.5 MPa. Gray and red Color paving blocks has a compressive strength quality based on SNI 03-0691-1996.
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Changes in Visual Object Recognition Precede the Shape Bias in Early Noun Learning
Yee, Meagan; Jones, Susan S.; Smith, Linda B.
2012-01-01
Two of the most formidable skills that characterize human beings are language and our prowess in visual object recognition. They may also be developmentally intertwined. Two experiments, a large sample cross-sectional study and a smaller sample 6-month longitudinal study of 18- to 24-month-olds, tested a hypothesized developmental link between changes in visual object representation and noun learning. Previous findings in visual object recognition indicate that children’s ability to recognize common basic level categories from sparse structural shape representations of object shape emerges between the ages of 18 and 24 months, is related to noun vocabulary size, and is lacking in children with language delay. Other research shows in artificial noun learning tasks that during this same developmental period, young children systematically generalize object names by shape, that this shape bias predicts future noun learning, and is lacking in children with language delay. The two experiments examine the developmental relation between visual object recognition and the shape bias for the first time. The results show that developmental changes in visual object recognition systematically precede the emergence of the shape bias. The results suggest a developmental pathway in which early changes in visual object recognition that are themselves linked to category learning enable the discovery of higher-order regularities in category structure and thus the shape bias in novel noun learning tasks. The proposed developmental pathway has implications for understanding the role of specific experience in the development of both visual object recognition and the shape bias in early noun learning. PMID:23227015
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Epithelial tricellular junctions act as interphase cell shape sensors to orient mitosis
Bosveld, Floris; Markova, Olga; Guirao, Boris; Martin, Charlotte; Wang, Zhimin; Pierre, Anaëlle; Balakireva, Maria; Gaugue, Isabelle; Ainslie, Anna; Christophorou, Nicolas; Lubensky, David K.; Minc, Nicolas; Bellaïche, Yohanns
2017-01-01
The orientation of cell division along the interphase cell long-axis, the century old Hertwig’s rule, has profound roles in tissue proliferation, morphogenesis, architecture and mechanics1,2. In epithelial tissues, the shape of the interphase cell is influenced by cell adhesion, mechanical stress, neighbour topology, and planar polarity pathways3–12. At mitosis, epithelial cells usually round up to ensure faithful chromosome segregation and to promote morphogenesis1. The mechanisms underlying interphase cell shape sensing in tissues are therefore unknown. We found that in Drosophila epithelia, tricellular junctions (TCJ) localize microtubule force generators, orienting cell division via the Dynein associated protein Mud independently of the classical Pins/Gαi pathway. Moreover, as cells round up during mitosis, TCJs serve as spatial landmarks, encoding information about interphase cell shape anisotropy to orient division in the rounded mitotic cell. Finally, experimental and simulation data show that shape and mechanical strain sensing by the TCJ emerge from a general geometric property of TCJ distributions in epithelial tissues. Thus, in addition to their function as epithelial barrier structures, TCJs serve as polarity cues promoting geometry and mechanical sensing in epithelial tissues. PMID:26886796
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Electrophoretic assembly of organic molecules and composites for electrochemical supercapacitors.
Su, Y; Zhitomirsky, I
2013-02-15
Electrophoretic deposition (EPD) method has been developed for the fabrication of 1-pyrenebutyric acid (PBH) films from aqueous solutions. The films can be deposited at constant voltage or potentiodynamic conditions. The method allowed the formation of 0.1-2 μm thick films, containing needle-shape PBH particles. The deposition mechanism involved the electrophoresis, pH decrease at the anode surface, charge neutralization and formation of insoluble PBH films. The film morphology and shape of the PBH particles are controlled by the π-π stacking mechanism of the polyaromatic PBH molecules. The important finding was the possibility of controlled EPD of multiwalled carbon nanotubes (MWCNTs) using PBH as a charging, dispersing and film forming agent. It was found that at low voltages or low PBH concentrations the deposits contained mainly MWCNT. The increase in the deposition voltage or/and PBH concentration resulted in co-deposition of MWCNT and needle-shape PBH particles. The new approach to the deposition of MWCNT was used for the fabrication of composite MnO(2)-MWCNT films for electrodes of electrochemical supercapacitors, which showed a specific capacitance of 250 F g(-1). The EPD method developed in this investigation paves the way for the deposition of other small organic molecules and composites and their applications in new materials and devices, utilizing functional properties of the organic molecules, CNT, and other advanced materials. Copyright © 2012 Elsevier Inc. All rights reserved.
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Agricultural land use is a primary driver of environmental impacts on streams. However, the causal processes that shape these impacts operate through multiple pathways and at several spatial scales. This complexity undermines the development of more effective management approache...
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NASA Astrophysics Data System (ADS)
Wan, Danny; Manfrini, Mauricio; Vaysset, Adrien; Souriau, Laurent; Wouters, Lennaert; Thiam, Arame; Raymenants, Eline; Sayan, Safak; Jussot, Julien; Swerts, Johan; Couet, Sebastien; Rassoul, Nouredine; Babaei Gavan, Khashayar; Paredis, Kristof; Huyghebaert, Cedric; Ercken, Monique; Wilson, Christopher J.; Mocuta, Dan; Radu, Iuliana P.
2018-04-01
Magnetic tunnel junctions (MTJs) interconnected via a continuous ferromagnetic free layer were fabricated for spin torque majority gate (STMG) logic. The MTJs are biased independently and show magnetoelectric response under spin transfer torque. The electrical control of these devices paves the way to future spin logic devices based on domain wall (DW) motion. In particular, it is a significant step towards the realization of a majority gate. To our knowledge, this is the first fabrication of a cross-shaped free layer shared by several perpendicular MTJs. The fabrication process can be generalized to any geometry and any number of MTJs. Thus, this framework can be applied to other spin logic concepts based on magnetic interconnect. Moreover, it allows exploration of spin dynamics for logic applications.
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A programmable nonlinear acoustic metamaterial
NASA Astrophysics Data System (ADS)
Yang, Tianzhi; Song, Zhi-Guang; Clerkin, Eoin; Zhang, Ye-Wei; Sun, Jia-He; Su, Yi-Shu; Chen, Li-Qun; Hagedorn, Peter
2017-09-01
Acoustic metamaterials with specifically designed lattices can manipulate acoustic/elastic waves in unprecedented ways. Whereas there are many studies that focus on passive linear lattice, with non-reconfigurable structures. In this letter, we present the design, theory and experimental demonstration of an active nonlinear acoustic metamaterial, the dynamic properties of which can be modified instantaneously with reversibility. By incorporating active and nonlinear elements in a single unit cell, a real-time tunability and switchability of the band gap is achieved. In addition, we demonstrate a dynamic "editing" capability for shaping transmission spectra, which can be used to create the desired band gap and resonance. This feature is impossible to achieve in passive metamaterials. These advantages demonstrate the versatility of the proposed device, paving the way toward smart acoustic devices, such as logic elements, diode and transistor.
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2016-01-01
Cancer heterogeneity, which enables clonal survival and treatment resistance, is shaped by active immune responses. Antigen-specific T cells can control cancer, as revealed clinically by immunotherapeutics such as adoptive T–cell transfer and checkpoint blockade. The host immune system is thus a powerful tool that if better harnessed could significantly enhance the efficacy of chemotherapeutics and improve outcomes for cancer sufferers. To realize this vision, however, a number of research frontiers must be tackled. These include developing strategies for neutralizing tumor-promoting inflammation, broadening T cell repertoires (via vaccination), and elucidating the mechanisms by which immune cells organize tumor microenvironments to regulate T cell activity. Such efforts will pave the way for identifying new targets for combination therapies that overcome resistance to current treatments and promote long-term cancer control. PMID:26967289
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On the Physics of Fizziness: How Bubble Bursting Controls Droplets Ejection
NASA Astrophysics Data System (ADS)
Seon, Thomas; Ghabache, Elisabeth; Antkowiak, Arnaud; Josserand, Christophe
2014-11-01
Either in a champagne glass or at the oceanic scales, the tiny bubbles rising at the surface burst in ejecting myriads of droplets. Focusing on the bubble bursting jet, prelude for these aerosols, we propose a simple scaling for the jet velocity, we unravel experimentally the intricate roles of bubble shape, capillary waves and liquid properties, and we demonstrate that droplets ejection can be tuned by changing the liquid properties. In particular, as capillary waves are shown to always evolve into a self-similar collapsing cavity, faster and smaller droplets can be produced by sheltering this collapse from remnant ripples using damping action of viscosity. These results pave the road to the characterization and control of the bursting bubble aerosols. Applications to champagne aroma diffusion will be discussed.
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Jiang, Huaidong; Xu, Rui; Chen, Chien-Chun; Yang, Wenge; Fan, Jiadong; Tao, Xutang; Song, Changyong; Kohmura, Yoshiki; Xiao, Tiqiao; Wang, Yong; Fei, Yingwei; Ishikawa, Tetsuya; Mao, Wendy L; Miao, Jianwei
2013-05-17
We report quantitative 3D coherent x-ray diffraction imaging of a molten Fe-rich alloy and crystalline olivine sample, synthesized at 6 GPa and 1800 °C, with nanoscale resolution. The 3D mass density map is determined and the 3D distribution of the Fe-rich and Fe-S phases in the olivine-Fe-S sample is observed. Our results indicate that the Fe-rich melt exhibits varied 3D shapes and sizes in the olivine matrix. This work has potential for not only improving our understanding of the complex interactions between Fe-rich core-forming melts and mantle silicate phases but also paves the way for quantitative 3D imaging of materials at nanoscale resolution under extreme pressures and temperatures.
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Gene Transfers Shaped the Evolution of De Novo NAD+ Biosynthesis in Eukaryotes
Ternes, Chad M.; Schönknecht, Gerald
2014-01-01
NAD+ is an essential molecule for life, present in each living cell. It can function as an electron carrier or cofactor in redox biochemistry and energetics, and serves as substrate to generate the secondary messenger cyclic ADP ribose and nicotinic acid adenine dinucleotide phosphate. Although de novo NAD+ biosynthesis is essential, different metabolic pathways exist in different eukaryotic clades. The kynurenine pathway starting with tryptophan was most likely present in the last common ancestor of all eukaryotes, and is active in fungi and animals. The aspartate pathway, detected in most photosynthetic eukaryotes, was probably acquired from the cyanobacterial endosymbiont that gave rise to chloroplasts. An evolutionary analysis of enzymes catalyzing de novo NAD+ biosynthesis resulted in evolutionary trees incongruent with established organismal phylogeny, indicating numerous gene transfers. Endosymbiotic gene transfers probably introduced the aspartate pathway into eukaryotes and may have distributed it among different photosynthetic clades. In addition, several horizontal gene transfers substituted eukaryotic genes with bacterial orthologs. Although horizontal gene transfer is accepted as a key mechanism in prokaryotic evolution, it is supposed to be rare in eukaryotic evolution. The essential metabolic pathway of de novo NAD+ biosynthesis in eukaryotes was shaped by numerous gene transfers. PMID:25169983
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Unmixing techniques for better segmentation of urban zones, roads, and open pit mines
NASA Astrophysics Data System (ADS)
Nikolov, Hristo; Borisova, Denitsa; Petkov, Doyno
2010-10-01
In this paper the linear unmixing method has been applied in classification of manmade objects, namely urbanized zones, roads etc. The idea is to exploit to larger extent the possibilities offered by multispectral imagers having mid spatial resolution in this case TM/ETM+ instruments. In this research unmixing is used to find consistent regression dependencies between multispectral data and those gathered in-situ and airborne-based sensors. The correct identification of the mixed pixels is key element for the subsequent segmentation forming the shape of the artificial feature is determined much more reliable. This especially holds true for objects with relatively narrow structure for example two-lane roads for which the spatial resolution is larger that the object itself. We have combined ground spectrometry of asphalt, Landsat images of RoI, and in-situ measured asphalt in order to determine the narrow roads. The reflectance of paving stones made from granite is highest compared to another ones which is true for open and stone pits. The potential for mapping is not limited to the mid-spatial Landsat data, but also may be used if the data has higher spatial resolution (as fine as 0.5 m). In this research the spectral and directional reflection properties of asphalt and concrete surfaces compared to those of paving stone made from different rocks have been measured. The in-situ measurements, which plays key role have been obtained using the Thematically Oriented Multichannel Spectrometer (TOMS) - designed in STIL-BAS.
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Koohestani, Faezeh; Braundmeier, Andrea G; Mahdian, Arash; Seo, Jane; Bi, JiaJia; Nowak, Romana A
2013-01-01
Uterine leiomyomas (ULs) are benign tumors occurring in the majority of reproductive aged women. Despite the high prevalence of these tumors, little is known about their etiology. A hallmark of ULs is the excessive deposition of extracellular matrix (ECM), primarily collagens. Collagens are known to modulate cell behavior and function singularly or through interactions with integrins and growth factor-mediated mitogenic pathways. To better understand the pathogenesis of ULs and the role of ECM collagens in their growth, we investigated the interaction of leiomyoma smooth muscle cells (LSMCs) with two different forms of collagen, non-polymerized collagen (monomeric) and polymerized collagen (fibrillar), in the absence or presence of platelet-derived growth factor (PDGF), an abundant growth factor in ULs. Primary cultures of human LSMCS from symptomatic patients were grown on these two different collagen matrices and their morphology, cytoskeletal organization, cellular proliferation, and signaling pathways were evaluated. Our results showed that LSMCs had distinct morphologies on the different collagen matrices and their basal as well as PDGF-stimulated proliferation varied on these matrices. These differences in proliferation were accompanied by changes in cell cycle progression and p21, an inhibitory cell cycle protein. In addition we found alterations in the phosphorylation of focal adhesion kinase, cytoskeletal reorganization, and activation of the mitogen activated protein kinase (MAPK) signaling pathway. In conclusion, our results demonstrate a direct effect of ECM on the proliferation of LSMCs through interplay between the collagen matrix and the PDGF-stimulated MAPK pathway. In addition, these findings will pave the way for identifying novel therapeutic approaches for ULs that target ECM proteins and their signaling pathways in ULs.
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Koohestani, Faezeh; Braundmeier, Andrea G.; Mahdian, Arash; Seo, Jane; Bi, JiaJia; Nowak, Romana A.
2013-01-01
Uterine leiomyomas (ULs) are benign tumors occurring in the majority of reproductive aged women. Despite the high prevalence of these tumors, little is known about their etiology. A hallmark of ULs is the excessive deposition of extracellular matrix (ECM), primarily collagens. Collagens are known to modulate cell behavior and function singularly or through interactions with integrins and growth factor-mediated mitogenic pathways. To better understand the pathogenesis of ULs and the role of ECM collagens in their growth, we investigated the interaction of leiomyoma smooth muscle cells (LSMCs) with two different forms of collagen, non-polymerized collagen (monomeric) and polymerized collagen (fibrillar), in the absence or presence of platelet-derived growth factor (PDGF), an abundant growth factor in ULs. Primary cultures of human LSMCS from symptomatic patients were grown on these two different collagen matrices and their morphology, cytoskeletal organization, cellular proliferation, and signaling pathways were evaluated. Our results showed that LSMCs had distinct morphologies on the different collagen matrices and their basal as well as PDGF-stimulated proliferation varied on these matrices. These differences in proliferation were accompanied by changes in cell cycle progression and p21, an inhibitory cell cycle protein. In addition we found alterations in the phosphorylation of focal adhesion kinase, cytoskeletal reorganization, and activation of the mitogen activated protein kinase (MAPK) signaling pathway. In conclusion, our results demonstrate a direct effect of ECM on the proliferation of LSMCs through interplay between the collagen matrix and the PDGF-stimulated MAPK pathway. In addition, these findings will pave the way for identifying novel therapeutic approaches for ULs that target ECM proteins and their signaling pathways in ULs. PMID:24040420
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Bade, Geetanjali; Khan, Meraj Alam; Srivastava, Akhilesh Kumar; Khare, Parul; Solaiappan, Krishna Kumar; Guleria, Randeep; Palaniyar, Nades; Talwar, Anjana
2014-01-01
Chronic obstructive pulmonary disease (COPD) is a major global health problem. It results from chronic inflammation and causes irreversible airway damage. Levels of different serum cytokines could be surrogate biomarkers for inflammation and lung function in COPD. We aimed to determine the serum levels of different biomarkers in COPD patients, the association between cytokine levels and various prognostic parameters, and the key pathways/networks involved in stable COPD. In this study, serum levels of 48 cytokines were examined by multiplex assays in 30 subjects (control, n=9; COPD, n=21). Relationships between serum biomarkers and forced expiratory volume in 1 second, peak oxygen uptake, body mass index, dyspnea score, and smoking were assessed. Enrichment pathways and network analyses were implemented, using a list of cytokines showing differential expression between healthy controls and patients with COPD by Cytoscape and GeneGo Metacore™ software (Thomson-Reuters Corporation, New York, NY, USA). Concentrations of cutaneous T-cell attracting chemokine, eotaxin, hepatocyte growth factor, interleukin 6 (IL-6), IL-16, and stem cell factor are significantly higher in COPD patients compared with in control patients. Notably, this study identifies stem cell factor as a biomarker for COPD. Multiple regression analysis predicts that cutaneous T-cell-attracting chemokine, eotaxin, IL-6, and stem cell factor are inversely associated with forced expiratory volume in 1 second and peak oxygen uptake change, whereas smoking is related to eotaxin and hepatocyte growth factor changes. Enrichment pathways and network analyses reveal the potential involvement of specific inflammatory and immune process pathways in COPD. Identified network interaction and regulation of different cytokines would pave the way for deeper insight into mechanisms of the disease process.
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Kim, Eun Jin; Angell, Scott; Janes, Jeff; Watanabe, Coran M H
2008-06-01
Traditional approaches to natural product discovery involve cell-based screening of natural product extracts followed by compound isolation and characterization. Their importance notwithstanding, continued mining leads to depletion of natural resources and the reisolation of previously identified metabolites. Metagenomic strategies aimed at localizing the biosynthetic cluster genes and expressing them in surrogate hosts offers one possible alternative. A fundamental question that naturally arises when pursuing such a strategy is, how large must the genomic library be to effectively represent the genome of an organism(s) and the biosynthetic gene clusters they harbor? Such an issue is certainly augmented in the absence of expensive robotics to expedite colony picking and/or screening of clones. We have developed an algorism, named BPC (biosynthetic pathway coverage), supported by molecular simulations to deduce the number of BAC clones required to achieve proper coverage of the genome and their respective biosynthetic pathways. The strategy has been applied to the construction of a large-insert BAC library from a marine microorganism, Hon6 (isolated from Honokohau, Maui) thought to represent a new species. The genomic library is constructed with a BAC yeast shuttle vector pClasper lacZ paving the way for the culturing of libraries in both prokaryotic and eukaryotic hosts. Flow cytometric methods are utilized to estimate the genome size of the organism and BPC implemented to assess P-coverage or percent coverage. A genetic selection strategy is illustrated, applications of which could expedite screening efforts in the identification and localization of biosynthetic pathways from marine microbial consortia, offering a powerful complement to genome sequencing and degenerate probe strategies. Implementing this approach, we report on the biotin biosynthetic pathway from the marine microorganism Hon6.
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Fearnside, Philip M
2007-05-01
Brazil's Cuiabá-Santarém (BR-163) Highway provides a valuable example of ways in which decision-making procedures for infrastructure projects in tropical forest areas need to be reformulated in order to guarantee that environmental concerns are properly weighed. BR-163, which is slated to be paved as an export corridor for soybeans via the Amazon River, traverses an area that is largely outside of Brazilian government control. A climate of generalized lawlessness and impunity prevails, and matters related to environment and to land tenure are especially unregulated. Deforestation and illegal logging have accelerated in anticipation of highway paving. Paving would further speed forest loss in the area, as well as stimulate migration of land thieves (grileiros) to other frontiers. An argument is made that the highway should not be reconstructed and paved until after a state of law has been established and it has been independently certified that sufficient governance prevails to secure protected areas and enforce environmental legislation. A waiting period is needed after this is achieved before proceeding with the highway paving. Above all, the logical sequence of steps must be followed, whereby environmental costs are assessed, reported, and weighed prior to making de facto decisions on implementation of infrastructure projects. Deviation from this logical sequence is a common occurrence in many parts of the world, especially in tropical areas.
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Exposure to ultrafine particles in asphalt work.
Elihn, Karine; Ulvestad, Bente; Hetland, Siri; Wallen, Anna; Randem, Britt Grethe
2008-12-01
An epidemiologic study has demonstrated that asphalt workers show increased loss of lung function and an increase of biomarkers of inflammation over the asphalt paving season. The aim of this study was to investigate which possible agent(s) causes the inflammatory reaction, with emphasis on ultrafine particles. The workers' exposure to total dust, polycyclic aromatic hydrocarbons, and NO(2) was determined by personal sampling. Exposure to ultrafine particles was measured by means of particle counters and scanning mobility particle sizer mounted on a van following the paving machine. The fractions of organic and elemental carbon were determined. Asphalt paving workers were exposed to ultrafine particles with medium concentration of about 3.4 x 10(4)/cm(3). Ultrafine particles at the paving site originated mainly from asphalt paving activities and traffic exhaust; most seemed to originate from asphalt fumes. Oil mist exceeded occupational limits on some occasions. Diesel particulate matter was measured as elemental carbon, which was low, around 3 microg/m(3). NO(2) and total dust did not exceed limits. Asphalt pavers were exposed to relatively high concentrations of ultrafine particles throughout their working day, with possible adverse health effects.
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Educational Pathways through Nanoscience: Nitinol as a Paradigmatic Smart Material
ERIC Educational Resources Information Center
Lisotti, Annamaria; De Renzi, Valentina; Rozzi, Carlo Andrea; Villa, Elena; Albertini, Franca; Goldoni, Guido
2013-01-01
We developed an educational path based on nitinol, a shape memory alloy which conveniently exemplifies the smart material concept, i.e., a material that performs a predetermined, reversible action in response to a change in the environment. Nitinol recovers a given shape, changes its resistivity drastically and modifies its elastic properties if…
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Eidenschenk, Celine; Dunne, Jean; Jouanguy, Emmanuelle; Fourlinnie, Claire; Gineau, Laure; Bacq, Delphine; McMahon, Corrina; Smith, Owen; Casanova, Jean-Laurent; Abel, Laurent; Feighery, Conleth
2006-04-01
We describe four children with a novel primary immunodeficiency consisting of specific natural-killer (NK) cell deficiency and susceptibility to viral diseases. One child developed an Epstein-Barr virus-driven lymphoproliferative disorder; two others developed severe respiratory illnesses of probable viral etiology. The four patients are related and belong to a large inbred kindred of Irish nomadic descent, which suggests autosomal recessive inheritance of this defect. A genomewide scan identified a single 12-Mb region on chromosome 8p11.23-q11.21 that was linked to this immunodeficiency (maximum LOD score 4.51). The mapping of the disease-causing genomic region paves the way for the identification of a novel pathway governing NK cell differentiation in humans.
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Eidenschenk, Céline; Dunne, Jean; Jouanguy, Emmanuelle; Fourlinnie, Claire; Gineau, Laure; Bacq, Delphine; McMahon, Corrina; Smith, Owen; Casanova, Jean-Laurent; Abel, Laurent; Feighery, Conleth
2006-01-01
We describe four children with a novel primary immunodeficiency consisting of specific natural-killer (NK) cell deficiency and susceptibility to viral diseases. One child developed an Epstein-Barr virus–driven lymphoproliferative disorder; two others developed severe respiratory illnesses of probable viral etiology. The four patients are related and belong to a large inbred kindred of Irish nomadic descent, which suggests autosomal recessive inheritance of this defect. A genomewide scan identified a single 12-Mb region on chromosome 8p11.23-q11.21 that was linked to this immunodeficiency (maximum LOD score 4.51). The mapping of the disease-causing genomic region paves the way for the identification of a novel pathway governing NK cell differentiation in humans. PMID:16532402
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Rational design and evolutional fine tuning of Saccharomyces cerevisiae for biomass breakdown.
Hasunuma, Tomohisa; Ishii, Jun; Kondo, Akihiko
2015-12-01
Conferring biomass hydrolysis activity on yeast through genetic engineering has paved the way for the development of groundbreaking processes for producing liquid fuels and commodity chemicals from lignocellulosic biomass. However, the overproduction and misfolding of heterologous and endogenous proteins can trigger cellular stress, increasing the metabolic burden and retarding growth. Improving the efficiency of lignocellulosic breakdown requires engineering of yeast secretory pathway based on system-wide metabolic analysis as well as DNA constructs for enhanced cellulase gene expression with advanced molecular biology tools. Also, yeast is subjected to severe stress due to toxic compounds generated during lignocellulose pretreatment in consolidated saccharification and fermentation processes. The prospect for development of robust yeast strains makes combining evolutionary and rational engineering strategies. Copyright © 2015 Elsevier Ltd. All rights reserved.
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Neurochemical measurements in the zebrafish brain
Jones, Lauren J.; McCutcheon, James E.; Young, Andrew M. J.; Norton, William H. J.
2015-01-01
The zebrafish is an ideal model organism for behavioral genetics and neuroscience. The high conservation of genes and neurotransmitter pathways between zebrafish and other vertebrates permits the translation of research between species. Zebrafish behavior can be studied at both larval and adult stages and recent research has begun to establish zebrafish models for human disease. Fast scan cyclic voltammetry (FSCV) is an electrochemical technique that permits the detection of neurotransmitter release and reuptake. In this study we have used in vitro FSCV to measure the release of analytes in the adult zebrafish telencephalon. We compare different stimulation methods and present a characterization of neurochemical changes in the wild-type zebrafish brain. This study represents the first FSCV recordings in zebrafish, thus paving the way for neurochemical analysis of the fish brain. PMID:26441575
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Nonmonotonic dose response curves (NMDRCs) are common after Estrogen or Androgen signaling pathway disruption. Fact or Falderal? Leon Earl Gray Jr, USEPA, ORD, NHEERL, TAD, RTB. RTP, NC, USA The shape of the dose response curve in the low dose region has been debated since th...
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The non-canonical Wnt-PCP pathway shapes the mouse caudal neural plate.
López-Escobar, Beatriz; Caro-Vega, José Manuel; Vijayraghavan, Deepthi S; Plageman, Timothy F; Sanchez-Alcazar, José A; Moreno, Roberto Carlos; Savery, Dawn; Márquez-Rivas, Javier; Davidson, Lance A; Ybot-González, Patricia
2018-05-08
The last stage of neural tube (NT) formation involves closure of the caudal neural plate (NP), an embryonic structure formed by neuromesodermal progenitors and newly differentiated cells that becomes incorporated into the NT. Here, we show in mouse that, as cell specification progresses, neuromesodermal progenitors and their progeny undergo significant changes in shape prior to their incorporation into the NT. The caudo-rostral progression towards differentiation is coupled to a gradual reliance on a unique combination of complex mechanisms that drive tissue folding, involving pulses of apical actomyosin contraction and planar polarised cell rearrangements, all of which are regulated by the Wnt-PCP pathway. Indeed, when this pathway is disrupted, either chemically or genetically, the polarisation and morphology of cells within the entire caudal NP is disturbed, producing delays in NT closure. The most severe disruptions of this pathway prevent caudal NT closure and result in spina bifida. In addition, a decrease in Vangl2 gene dosage also appears to promote more rapid progression towards a neural fate, but not the specification of more neural cells. © 2018. Published by The Company of Biologists Ltd.
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Multiple Causal Links Between Magnocellular-Dorsal Pathway Deficit and Developmental Dyslexia.
Gori, Simone; Seitz, Aaron R; Ronconi, Luca; Franceschini, Sandro; Facoetti, Andrea
2016-10-17
Although impaired auditory-phonological processing is the most popular explanation of developmental dyslexia (DD), the literature shows that the combination of several causes rather than a single factor contributes to DD. Functioning of the visual magnocellular-dorsal (MD) pathway, which plays a key role in motion perception, is a much debated, but heavily suspected factor contributing to DD. Here, we employ a comprehensive approach that incorporates all the accepted methods required to test the relationship between the MD pathway dysfunction and DD. The results of 4 experiments show that (1) Motion perception is impaired in children with dyslexia in comparison both with age-match and with reading-level controls; (2) pre-reading visual motion perception-independently from auditory-phonological skill-predicts future reading development, and (3) targeted MD trainings-not involving any auditory-phonological stimulation-leads to improved reading skill in children and adults with DD. Our findings demonstrate, for the first time, a causal relationship between MD deficits and DD, virtually closing a 30-year long debate. Since MD dysfunction can be diagnosed much earlier than reading and language disorders, our findings pave the way for low resource-intensive, early prevention programs that could drastically reduce the incidence of DD. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
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"Am I Doing the Right Thing?": Pathways to Parenting a Gender Variant Child.
Gray, Sarah A O; Sweeney, Kristen K; Randazzo, Renee; Levitt, Heidi M
2016-03-01
Gender variant (GV) children have a subjective sense of gender identity and/or preferences regarding clothing, activities, and/or playmates that are different from what is culturally normative for their biological sex. Despite increases in rates of GV children and their families presenting at clinics, there is little research on how raising a GV child affects the family as a whole or how families make decisions regarding their care. This study took an ecological-transactional framework to explore the question, "what is the experience of parents who raise a GV or transgender child?" Eight mothers and three fathers of GV male and female children (ages 5-13) referred through a GV support group participated in interviews. Transcripts were analyzed using an adaptation of grounded theory analysis. These parents attempted to pave the way to a nonstigmatized childhood for their GV child, typically through two pathways: rescuing the child from fear of stigma and hurt or accepting GV and advocating for a more tolerant world. Many participants used both pathways to different degrees or shifted paths over time, and the paths selected were related to parents' own understanding of GV and their experiences and backgrounds as well as characteristics of the children they were parenting and the communities they inhabited. Limitations, clinical implications, and future directions are discussed. © 2015 Family Process Institute.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Park, Young-Uk; Bai, Jianming; Wang, Liping
Ion exchange is a ubiquitous phenomenon central to wide industrial applications, ranging from traditional (bio)chemical separation to the emerging chimie douce synthesis of materials for batteries and other energy applications. The exchange process is complex, involving substitution and transport of different ions under non-equilibrium conditions, and thus difficult to probe, leaving a gap in mechanistic understanding of kinetic exchange pathways toward final products. Herein, we report in situ tracking kinetic pathways of Li +/Na + substitution during solvothermal ion-exchange synthesis of Li xNa 1.5-xVOPO 4F 0.5 (0 ≤ x ≤ 1.5), a promising multi-Li polyanionic cathode for batteries. The real-timemore » observation, corroborated by first-principles calculations, reveals a selective replacement of Na + by Li +, leading to peculiar Na +/Li +/vacancy orderings in the intermediates. Contradicting the traditional belief of facile topotactic substitution via solid solution reaction, an abrupt two-phase transformation occurs and predominantly governs the kinetics of ion exchange and transport in the 1D polyanionic framework, consequently leading to significant difference of Li stoichiometry and electrochemical properties in the exchanged products. The findings may help to pave the way for rational design of ion exchange synthesis for making new materials.« less
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“Am I Doing the Right Thing?”: Pathways to Parenting a Gender Variant Child
GRAY, SARAH A. O.; SWEENEY, KRISTEN K.; RANDAZZO, RENEE; LEVITT, HEIDI M.
2017-01-01
Gender variant (GV) children have a subjective sense of gender identity and/or preferences regarding clothing, activities, and/or playmates that are different from what is culturally normative for their biological sex. Despite increases in rates of GV children and their families presenting at clinics, there is little research on how raising a GV child affects the family as a whole or how families make decisions regarding their care. This study took an ecological-transactional framework to explore the question, “what is the experience of parents who raise a GV or transgender child?” Eight mothers and three fathers of GV male and female children (ages 5–13) referred through a GV support group participated in interviews. Transcripts were analyzed using an adaptation of grounded theory analysis. These parents attempted to pave the way to a nonstigmatized childhood for their GV child, typically through two pathways: rescuing the child from fear of stigma and hurt or accepting GV and advocating for a more tolerant world. Many participants used both pathways to different degrees or shifted paths over time, and the paths selected were related to parents’ own understanding of GV and their experiences and backgrounds as well as characteristics of the children they were parenting and the communities they inhabited. Limitations, clinical implications, and future directions are discussed. PMID:25639568
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Park, Young-Uk; Bai, Jianming; Wang, Liping; ...
2017-08-29
Ion exchange is a ubiquitous phenomenon central to wide industrial applications, ranging from traditional (bio)chemical separation to the emerging chimie douce synthesis of materials for batteries and other energy applications. The exchange process is complex, involving substitution and transport of different ions under non-equilibrium conditions, and thus difficult to probe, leaving a gap in mechanistic understanding of kinetic exchange pathways toward final products. Herein, we report in situ tracking kinetic pathways of Li +/Na + substitution during solvothermal ion-exchange synthesis of Li xNa 1.5-xVOPO 4F 0.5 (0 ≤ x ≤ 1.5), a promising multi-Li polyanionic cathode for batteries. The real-timemore » observation, corroborated by first-principles calculations, reveals a selective replacement of Na + by Li +, leading to peculiar Na +/Li +/vacancy orderings in the intermediates. Contradicting the traditional belief of facile topotactic substitution via solid solution reaction, an abrupt two-phase transformation occurs and predominantly governs the kinetics of ion exchange and transport in the 1D polyanionic framework, consequently leading to significant difference of Li stoichiometry and electrochemical properties in the exchanged products. The findings may help to pave the way for rational design of ion exchange synthesis for making new materials.« less
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Xu, Yiyi; Lindh, Christian H; Jönsson, Bo A G; Broberg, Karin; Albin, Maria
2018-03-27
Asphalt workers are exposed to polyaromatic hydrocarbons (PAHs) from hot mix asphalt via both inhalation and dermal absorption. The use of crumb rubber modified (CRM) asphalt may result in higher exposure to PAHs and more adverse effects. Our aim is to assess occupational exposure to PAHs from conventional and CRM asphalt paving by measuring PAH metabolites in urine, and to investigate the effects on mitochondrial DNA copy number (mtDNAcn) and telomere length. We recruited 116 workers paving conventional asphalt, 51 workers paving CRM asphalt and 100 controls in Sweden, all males. A repeated-measures analysis included 31 workers paving both types of asphalt. Urine and blood samples were collected pre-working on Monday morning and post-working on Thursday afternoon after 4 days working. PAH metabolites: 1-hydroxypyrene (1-OH-PYR) and 2-hydroxyphenanthrene (2-OH-PH) were measured in urine by LC-MS/MS. Relative mtDNAcn and telomere length were measured by quantitative PCR. Conventional and CRM asphalt workers showed higher 1-OH-PYR and 2-OH-PH than controls (p < 0.001 for all). Relative mtDNAcn were 0.21 units (p < 0.001) higher in conventional asphalt workers and 0.13 units (p = 0.010) higher in CRM asphalt workers compared to controls. Relative telomere length did not differ across occupational groups, but it was positively associated with increment of 2-OH-PH (β = 0.075, p = 0.037) in asphalt workers. The repeated-measures analysis showed no difference in either increment of 1-OH-PYP, or changes in effect biomarkers (mtDNAcn or telomere length) between paving with conventional and CRM asphalt. Increment of 2-OH-PH was smaller after paving with CRM asphalt. Road asphalt paving in open areas resulted in PAHs exposure, as shown by elevation of PAH metabolites in urine. Asphalt workers may experience oxidative stress, evidenced by alternation in mtDNAcn; however the effects could not be fully explained by exposure to PAHs from the asphalt mixture.
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Implementing GPS into Pave-IR.
DOT National Transportation Integrated Search
2009-03-01
To further enhance the capabilities of the Pave-IR thermal segregation detection system developed at the Texas Transportation Institute, researchers incorporated global positioning system (GPS) data collection into the thermal profiles. This GPS capa...
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A new approach to children's footwear based on foot type classification.
Mauch, M; Grau, S; Krauss, I; Maiwald, C; Horstmann, T
2009-08-01
Current shoe designs do not allow for the comprehensive 3-D foot shape, which means they are unable to reproduce the wide variability in foot morphology. Therefore, the purpose of this study was to capture these variations of children's feet by classifying them into groups (types) and thereby provide a basis for their implementation in the design of children's shoes. The feet of 2867 German children were measured using a 3-D foot scanner. Cluster analysis was then applied to classify the feet into three different foot types. The characteristics of these foot types differ regarding their volume and forefoot shape both within and between shoe sizes. This new approach is in clear contrast to previous systems, since it captures the variability of foot morphology in a more comprehensive way by using a foot typing system and therefore paves the way for the unimpaired development of children's feet. Previous shoe systems do not allow for the wide variations in foot morphology. A new approach was developed regarding different morphological foot types based on 3-D measurements relevant in shoe construction. This can be directly applied to create specific designs for children's shoes.
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NASA Astrophysics Data System (ADS)
Wang, Wenqi; Xie, Yangbo; Popa, Bogdan-Ioan; Cummer, Steven A.
2016-11-01
Acoustic metasurfaces provide useful wavefront shaping capabilities, such as beam steering, acoustic focusing, and asymmetric transmission, in a compact structure. Most acoustic metasurfaces described in the literature are transmissive devices and focus their performance on steering sound beam of the fundamental diffractive order. In addition, the range of incident angles studied is usually below the critical incidence predicted by generalized Snell's law of reflection. In this work, we comprehensively analyze the wave interaction with a generic periodic phase-modulating structure in order to predict the behavior of all diffractive orders, especially for cases beyond critical incidence. Under the guidance of the presented analysis, a broadband reflective metasurface is designed based on an expanded library of labyrinthine acoustic metamaterials. Various local and nonlocal wavefront shaping properties are experimentally demonstrated, and enhanced absorption of higher order diffractive waves is experimentally shown for the first time. The proposed methodology provides an accurate approach for predicting practical diffracted wave behaviors and opens a new perspective for the study of acoustic periodic structures. The designed metasurface extends the functionalities of acoustic metasurfaces and paves the way for the design of thin planar reflective structures for broadband acoustic wave manipulation and extraordinary absorption.
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Editors' Introduction: Abstract Concepts: Structure, Processing, and Modeling.
Bolognesi, Marianna; Steen, Gerard
2018-06-22
Our ability to deal with abstract concepts is one of the most intriguing faculties of human cognition. Still, we know little about how such concepts are formed, processed, and represented in mind. For example, because abstract concepts do not designate referents that can be experienced through our body, the role of perceptual experiences in shaping their content remains controversial. Current theories suggest a variety of alternative explanations to the question of "how abstract concepts are represented in the human mind." These views pinpoint specific streams of semantic information that would play a prominent role in shaping the content of abstract concepts, such as situation-based information (e.g., Barsalou & Wiemer-Hastings, ), affective information (Kousta, Vigliocco, Vinson, Andrews, & Del Campo, ), and linguistic information (Louwerse, ). Rarely, these theoretical views are directly compared. In this special issue, current views are presented in their most recent and advanced form, and directly compared and discussed in a debate, which is reported at the end of each article. As a result, new exciting questions and challenges arise. These questions and challenges, reported in this introductory article, can arguably pave the way to new empirical studies and theoretical developments on the nature of abstract concepts. © 2018 Cognitive Science Society, Inc.
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Terry, Alan J; Chaplain, Mark A J
2011-12-07
The nuclear factor kappa B (NF-κB) intracellular signalling pathway is central to many stressful, inflammatory, and innate immune responses. NF-κB proteins themselves are transcription factors for hundreds of genes. Experiments have shown that the NF-κB pathway can exhibit oscillatory dynamics-a negative feedback loop causes oscillatory nuclear-cytoplasmic translocation of NF-κB. Given that cell size and shape are known to influence intracellular signal transduction, we consider a spatio-temporal model of partial differential equations for the NF-κB pathway, where we model molecular movement by diffusion and, for several key species including NF-κB, by active transport as well. Through numerical simulations we find values for model parameters such that sustained oscillatory dynamics occur. Our spatial profiles and animations bear a striking resemblance to experimental images and movie clips employing fluorescent fusion proteins. We discover that oscillations in nuclear NF-κB may occur when active transport is across the nuclear membrane only, or when no species are subject to active transport. However, when active transport is across the nuclear membrane and NF-κB is additionally actively transported through the cytoplasm, oscillations are lost. Hence transport mechanisms in a cell will influence its response to activation of its NF-κB pathway. We also demonstrate that sustained oscillations in nuclear NF-κB are somewhat robust to changes in the shape of the cell, or the shape, location, and size of its nucleus, or the location of ribosomes. Yet if the cell is particularly flat or the nucleus sufficiently small, then oscillations are lost. Thus the geometry of a cell may partly determine its response to NF-κB activation. The NF-κB pathway is known to be constitutively active in several human cancers. Our spatially explicit modelling approach will allow us, in future work, to investigate targeted drug therapy of tumours. Copyright © 2011 Elsevier Ltd. All rights reserved.
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Mardi, Mohsen; Karimi Farsad, Laleh; Gharechahi, Javad; Salekdeh, Ghasem Hosseini
2015-01-01
Witches' broom disease of acid lime greatly affects the production of Mexican lime in Iran. It is caused by a phytoplasma (Candidatus Phytoplasma aurantifolia). However, the molecular mechanisms that underlie phytoplasma pathogenicity and the mode of interactions with host plants are largely unknown. Here, high-throughput transcriptome sequencing was conducted to explore gene expression signatures associated with phytoplasma infection in Mexican lime trees. We assembled 78,185 unique transcript sequences (unigenes) with an average length of 530 nt. Of these, 41,805 (53.4%) were annotated against the NCBI non-redundant (nr) protein database using a BLASTx search (e-value ≤ 1e-5). When the abundances of unigenes in healthy and infected plants were compared, 2,805 transcripts showed significant differences (false discovery rate ≤ 0.001 and log2 ratio ≥ 1.5). These differentially expressed genes (DEGs) were significantly enriched in 43 KEGG metabolic and regulatory pathways. The up-regulated DEGs were mainly categorized into pathways with possible implication in plant-pathogen interaction, including cell wall biogenesis and degradation, sucrose metabolism, secondary metabolism, hormone biosynthesis and signalling, amino acid and lipid metabolism, while down-regulated DEGs were predominantly enriched in ubiquitin proteolysis and oxidative phosphorylation pathways. Our analysis provides novel insight into the molecular pathways that are deregulated during the host-pathogen interaction in Mexican lime trees infected by phytoplasma. The findings can be valuable for unravelling the molecular mechanisms of plant-phytoplasma interactions and can pave the way for engineering lime trees with resistance to witches' broom disease.
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Gnanasekaran, Thiyagarajan; Karcher, Daniel; Nielsen, Agnieszka Zygadlo; Martens, Helle Juel; Ruf, Stephanie; Kroop, Xenia; Olsen, Carl Erik; Motawie, Mohammed Saddik; Pribil, Mathias; Møller, Birger Lindberg; Bock, Ralph; Jensen, Poul Erik
2016-01-01
Plant chloroplasts are light-driven cell factories that have great potential to act as a chassis for metabolic engineering applications. Using plant chloroplasts, we demonstrate how photosynthetic reducing power can drive a metabolic pathway to synthesise a bio-active natural product. For this purpose, we stably engineered the dhurrin pathway from Sorghum bicolor into the chloroplasts of Nicotiana tabacum (tobacco). Dhurrin is a cyanogenic glucoside and its synthesis from the amino acid tyrosine is catalysed by two membrane-bound cytochrome P450 enzymes (CYP79A1 and CYP71E1) and a soluble glucosyltransferase (UGT85B1), and is dependent on electron transfer from a P450 oxidoreductase. The entire pathway was introduced into the chloroplast by integrating CYP79A1, CYP71E1, and UGT85B1 into a neutral site of the N. tabacum chloroplast genome. The two P450s and the UGT85B1 were functional when expressed in the chloroplasts and converted endogenous tyrosine into dhurrin using electrons derived directly from the photosynthetic electron transport chain, without the need for the presence of an NADPH-dependent P450 oxidoreductase. The dhurrin produced in the engineered plants amounted to 0.1–0.2% of leaf dry weight compared to 6% in sorghum. The results obtained pave the way for plant P450s involved in the synthesis of economically important compounds to be engineered into the thylakoid membrane of chloroplasts, and demonstrate that their full catalytic cycle can be driven directly by photosynthesis-derived electrons. PMID:26969746
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2012-01-01
Background The Azadirachta indica (neem) tree is a source of a wide number of natural products, including the potent biopesticide azadirachtin. In spite of its widespread applications in agriculture and medicine, the molecular aspects of the biosynthesis of neem terpenoids remain largely unexplored. The current report describes the draft genome and four transcriptomes of A. indica and attempts to contextualise the sequence information in terms of its molecular phylogeny, transcript expression and terpenoid biosynthesis pathways. A. indica is the first member of the family Meliaceae to be sequenced using next generation sequencing approach. Results The genome and transcriptomes of A. indica were sequenced using multiple sequencing platforms and libraries. The A. indica genome is AT-rich, bears few repetitive DNA elements and comprises about 20,000 genes. The molecular phylogenetic analyses grouped A. indica together with Citrus sinensis from the Rutaceae family validating its conventional taxonomic classification. Comparative transcript expression analysis showed either exclusive or enhanced expression of known genes involved in neem terpenoid biosynthesis pathways compared to other sequenced angiosperms. Genome and transcriptome analyses in A. indica led to the identification of repeat elements, nucleotide composition and expression profiles of genes in various organs. Conclusions This study on A. indica genome and transcriptomes will provide a model for characterization of metabolic pathways involved in synthesis of bioactive compounds, comparative evolutionary studies among various Meliaceae family members and help annotate their genomes. A better understanding of molecular pathways involved in the azadirachtin synthesis in A. indica will pave ways for bulk production of environment friendly biopesticides. PMID:22958331
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Role of DAF-21protein in Caenorhabditis elegans immunity against Proteus mirabilis infection.
JebaMercy, Gnanasekaran; Durai, Sellegounder; Prithika, Udayakumar; Marudhupandiyan, Shanmugam; Dasauni, Pushpanjali; Kundu, Suman; Balamurugan, Krishnaswamy
2016-08-11
Caenorhabditis elegans is emerging as one of the handy model for proteome related studies due to its simplest system biology. The present study, deals with changes in protein expression in C. elegans infected with Proteus mirabilis. Proteins were separated using two-dimensional differential gel electrophoresis (2D-DIGE) and identified using MALDI-TOF. Twelve distinctly regulated proteins identified in the infected worms, included heat shock proteins involved stress pathway (HSP-1 and HSP-6), proteins involved in immune response pathway (DAF-21), enzymes involved in normal cellular process (Eukaryotic translation Elongation Factor, actin family member, S-adenosyl homocysteine hydrolase ortholog, glutamate dehydrogenase and Vacuolar H ATPase family member) and few least characterized proteins (H28O16.1 and H08J11.2). The regulation of selected players at the transcriptional level during Proteus mirabilis infection was analyzed using qPCR. Physiological experiments revealed the ability of P. mirabilis to kill daf-21 mutant C. elegans significantly compared with the wild type. This is the first report studying proteome changes in C. elegans and exploring the involvement of MAP Kinase pathway during P. mirabilis infection. This is the first report studying proteome changes in C. elegans during P. mirabilis infection. The present study explores the role and contribution of MAP Kinase pathway and its regulator protein DAF-21 involvement in the immunity against opportunistic pathogen P. mirabilis infection. Manipulation of this DAF-21 protein in host, may pave the way for new drug development or disease control strategy during opportunistic pathogen infections. Copyright © 2016 Elsevier B.V. All rights reserved.
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Lichen Symbiosis: Nature's High Yielding Machines for Induced Hydrogen Production
Papazi, Aikaterini; Kastanaki, Elizabeth; Pirintsos, Stergios; Kotzabasis, Kiriakos
2015-01-01
Hydrogen is a promising future energy source. Although the ability of green algae to produce hydrogen has long been recognized (since 1939) and several biotechnological applications have been attempted, the greatest obstacle, being the O2-sensitivity of the hydrogenase enzyme, has not yet been overcome. In the present contribution, 75 years after the first report on algal hydrogen production, taking advantage of a natural mechanism of oxygen balance, we demonstrate high hydrogen yields by lichens. Lichens have been selected as the ideal organisms in nature for hydrogen production, since they consist of a mycobiont and a photobiont in symbiosis. It has been hypothesized that the mycobiont’s and photobiont’s consumption of oxygen (increase of COX and AOX proteins of mitochondrial respiratory pathways and PTOX protein of chrolorespiration) establishes the required anoxic conditions for the activation of the phycobiont’s hydrogenase in a closed system. Our results clearly supported the above hypothesis, showing that lichens have the ability to activate appropriate bioenergetic pathways depending on the specific incubation conditions. Under light conditions, they successfully use the PSII-dependent and the PSII-independent pathways (decrease of D1 protein and parallel increase of PSaA protein) to transfer electrons to hydrogenase, while under dark conditions, lichens use the PFOR enzyme and the dark fermentative pathway to supply electrons to hydrogenase. These advantages of lichen symbiosis in combination with their ability to survive in extreme environments (while in a dry state) constitute them as unique and valuable hydrogen producing natural factories and pave the way for future biotechnological applications. PMID:25826211
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Paving fabrics for reducing reflective cracking
DOT National Transportation Integrated Search
1991-11-01
This research effort was part of ADOT's New Product Evaluation Program. The objective was to evaluate the construction and field performances of three commercially available paving fabrics; Paveprep, Glassgrid, and Tapecoat. The fabrics were designed...
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Paving fabrics for reducing reflective cracking
DOT National Transportation Integrated Search
1989-12-01
This report documents the installation of three commercially available paving fabrics for the reduction of reflective cracking in asphalt overlays. The fabrics installed were Paveprep, Glassgrid, and Tapecoat. The test section is in Willcox, Arizona,...
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Denning, Gerene M; Jennissen, Charles A
2016-05-18
All-terrain vehicles (ATVs) are designed for off-highway use only, and many of their features create increased risk with roadway travel. Over half of all ATV-related fatalities occur on roadways, and nonfatal roadway crashes result in more serious injuries than those off the road. A number of jurisdictions have passed or have considered legislation allowing ATVs on public roadways, sometimes limiting them to those unpaved, arguing that they are safe for ATVs. However, no studies have determined the epidemiology of ATV-related fatalities on different road surface types. The objective of the study was to compare ATV-related deaths on paved versus unpaved roads and to contrast them with off-road fatalities. Retrospective descriptive and multivariable analyses were performed using U.S. Consumer Product Safety Commission fatality data from 1982 through 2012. After 1998, ATV-related deaths increased at twice the rate on paved versus unpaved roads. Still, 42% of all roadway deaths during the study period occurred on unpaved surfaces. States varied considerably, ranging from 18% to 79% of their ATV-related roadway deaths occurring on unpaved roads. Paved road crashes were more likely than those on unpaved surfaces to involve males, adolescents and younger adults, passengers, and collisions with other vehicles. Both the pattern of other vehicles involved in collisions and which vehicle hit the other were different for the 2 road types. Alcohol use was higher, helmet use was lower, and head injuries were more likely in paved versus unpaved roadway crashes. However, head injuries still occurred in 76% of fatalities on unpaved roads. Helmets were associated with lower proportions of head injuries among riders, regardless of road surface type. Relative to off-road crashes, both paved and unpaved roads were more likely to involve collisions with another vehicle. The vast majority of roadway crashes, however, did not involve a traffic collision on either paved or unpaved roads. Although differences were observed between paved and unpaved roads, our results show that riding on either represented significantly greater dangers than riding off the road. Many vehicle warnings specifically mention the risks of paved but not unpaved roads, yet we found 23 states with half or more of their roadway deaths on unpaved surfaces. Safety warnings should explicitly state the dangers of roadway riding regardless of surface type. These data further support laws/ordinances greatly restricting ATV riding on all types of public roadways.
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In silico profiling of Escherichia coli and Saccharomyces cerevisiae as terpenoid factories
2013-01-01
Background Heterologous microbial production of rare plant terpenoids of medicinal or industrial interest is attracting more and more attention but terpenoid yields are still low. Escherichia coli and Saccharomyces cerevisiae are the most widely used heterologous hosts; a direct comparison of both hosts based on experimental data is difficult though. Hence, the terpenoid pathways of E. coli (via 1-deoxy-D-xylulose 5-phosphate, DXP) and S. cerevisiae (via mevalonate, MVA), the impact of the respective hosts metabolism as well as the impact of different carbon sources were compared in silico by means of elementary mode analysis. The focus was set on the yield of isopentenyl diphosphate (IPP), the general terpenoid precursor, to identify new metabolic engineering strategies for an enhanced terpenoid yield. Results Starting from the respective precursor metabolites of the terpenoid pathways (pyruvate and glyceraldehyde-3-phosphate for the DXP pathway and acetyl-CoA for the MVA pathway) and considering only carbon stoichiometry, the two terpenoid pathways are identical with respect to carbon yield. However, with glucose as substrate, the MVA pathway has a lower potential to supply terpenoids in high yields than the DXP pathway if the formation of the required precursors is taken into account, due to the carbon loss in the formation of acetyl-CoA. This maximum yield is further reduced in both hosts when the required energy and reduction equivalents are considered. Moreover, the choice of carbon source (glucose, xylose, ethanol or glycerol) has an effect on terpenoid yield with non-fermentable carbon sources being more promising. Both hosts have deficiencies in energy and redox equivalents for high yield terpenoid production leading to new overexpression strategies (heterologous enzymes/pathways) for an enhanced terpenoid yield. Finally, several knockout strategies are identified using constrained minimal cut sets enforcing a coupling of growth to a terpenoid yield which is higher than any yield published in scientific literature so far. Conclusions This study provides for the first time a comprehensive and detailed in silico comparison of the most prominent heterologous hosts E. coli and S. cerevisiae as terpenoid factories giving an overview on several promising metabolic engineering strategies paving the way for an enhanced terpenoid yield. PMID:24059635
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Validity of empirical models of exposure in asphalt paving
Burstyn, I; Boffetta, P; Burr, G; Cenni, A; Knecht, U; Sciarra, G; Kromhout, H
2002-01-01
Aims: To investigate the validity of empirical models of exposure to bitumen fume and benzo(a)pyrene, developed for a historical cohort study of asphalt paving in Western Europe. Methods: Validity was evaluated using data from the USA, Italy, and Germany not used to develop the original models. Correlation between observed and predicted exposures was examined. Bias and precision were estimated. Results: Models were imprecise. Furthermore, predicted bitumen fume exposures tended to be lower (-70%) than concentrations found during paving in the USA. This apparent bias might be attributed to differences between Western European and USA paving practices. Evaluation of the validity of the benzo(a)pyrene exposure model revealed a similar to expected effect of re-paving and a larger than expected effect of tar use. Overall, benzo(a)pyrene models underestimated exposures by 51%. Conclusions: Possible bias as a result of underestimation of the impact of coal tar on benzo(a)pyrene exposure levels must be explored in sensitivity analysis of the exposure–response relation. Validation of the models, albeit limited, increased our confidence in their applicability to exposure assessment in the historical cohort study of cancer risk among asphalt workers. PMID:12205236
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Impact of nighttime paving operations on asphalt roughness behavior.
DOT National Transportation Integrated Search
2013-05-01
The relationship between nighttime construction scheduling and future road quality in terms of roughness was investigated. Research was three-phased: interviews with local leaders in paving, on-site observations, and historical data analyses. Intervi...
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DOT National Transportation Integrated Search
2018-05-01
This project implemented additional features into MnPAVE-Rigid, leading to a new version of MnDOTs rigid pavement design software. The database of American Association of State Highway Transportation Officers (AASHTO) mechanistic-empirical (M-E) p...
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VIEW LOOKING NORTH ALONG COOMBE AVENUE. NOTE FLAGSTONE PAVING MATERIAL ...
VIEW LOOKING NORTH ALONG COOMBE AVENUE. NOTE FLAGSTONE PAVING MATERIAL FOR FORMER CEREMONIAL ENTRANCE AND MATURE SOUTHERN MAGNOLIA TREE IN BACKGROUND. - Congressional Cemetery, 1801 E Street, Southeast, Washington, District of Columbia, DC
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Management of paved secondary roads.
DOT National Transportation Integrated Search
1991-01-01
This report provides the background for the development of a pavement management system for the paved roads of Virginia's secondary highway system. Included are descriptions of a study to develop an acceptable surface-condition rating system for surf...
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DOT National Transportation Integrated Search
2013-01-01
Four projects were built over two construction seasons using special devices attached to the paving machine that produces a 30 slope on the outside pavement edge instead of the near vertical drop-off common with conventional paving equipment. This ...
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Lu, Fang; Zhang, Yu; Liu, Shizhong
Four-electron oxygen reduction reaction (4e-ORR), as a key pathway in energy conversion, is preferred over the two-electron reduction pathway that falls short in dissociating dioxygen molecules. Gold (Au) surfaces exhibit high sensitivity of the ORR pathway to its atomic structures. The long-standing puzzle remains unsolved why the Au surfaces with {100} sub-facets were exceptionally capable to catalyze the 4e-ORR in alkaline solution, though limited within a narrow potential window. Herein we report the discovery of a dominant 4e-ORR over the whole potential range on {310} surface of Au nanocrystal shaped as truncated ditetragonal prism (TDP). In contrast, ORR pathways onmore » single-crystalline facets of shaped nanoparticles, including {111} on nano-octahedra and {100} on nano-cubes, are similar to their single-crystal counterparts. Combining our experimental results with density functional theory calculations, we elucidate the key role of surface proton transfers from co-adsorbed H 2O molecules in activating the facet- and potential-dependent 4e ORR on Au in alkaline solutions. These results elucidate how surface atomic structures determine the reaction pathways via bond scission and formation among weakly adsorbed water and reaction intermediates. The new insight helps in developing facet-specific nanocatalysts for various reactions.« less
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Lu, Fang; Zhang, Yu; Liu, Shizhong; ...
2017-05-11
Four-electron oxygen reduction reaction (4e-ORR), as a key pathway in energy conversion, is preferred over the two-electron reduction pathway that falls short in dissociating dioxygen molecules. Gold (Au) surfaces exhibit high sensitivity of the ORR pathway to its atomic structures. The long-standing puzzle remains unsolved why the Au surfaces with {100} sub-facets were exceptionally capable to catalyze the 4e-ORR in alkaline solution, though limited within a narrow potential window. Herein we report the discovery of a dominant 4e-ORR over the whole potential range on {310} surface of Au nanocrystal shaped as truncated ditetragonal prism (TDP). In contrast, ORR pathways onmore » single-crystalline facets of shaped nanoparticles, including {111} on nano-octahedra and {100} on nano-cubes, are similar to their single-crystal counterparts. Combining our experimental results with density functional theory calculations, we elucidate the key role of surface proton transfers from co-adsorbed H 2O molecules in activating the facet- and potential-dependent 4e ORR on Au in alkaline solutions. These results elucidate how surface atomic structures determine the reaction pathways via bond scission and formation among weakly adsorbed water and reaction intermediates. The new insight helps in developing facet-specific nanocatalysts for various reactions.« less
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ERIC Educational Resources Information Center
Swan, Amy
2015-01-01
This qualitative study explores the formation of educational and vocational goals among female first-year engineering students at two community colleges and one four-year institution, as well as contextual influences on this process. Participants' pathways to college are also explored, as well as their pathways into engineering. The findings…
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Highly stretchable carbon aerogels.
Guo, Fan; Jiang, Yanqiu; Xu, Zhen; Xiao, Youhua; Fang, Bo; Liu, Yingjun; Gao, Weiwei; Zhao, Pei; Wang, Hongtao; Gao, Chao
2018-02-28
Carbon aerogels demonstrate wide applications for their ultralow density, rich porosity, and multifunctionalities. Their compressive elasticity has been achieved by different carbons. However, reversibly high stretchability of neat carbon aerogels is still a great challenge owing to their extremely dilute brittle interconnections and poorly ductile cells. Here we report highly stretchable neat carbon aerogels with a retractable 200% elongation through hierarchical synergistic assembly. The hierarchical buckled structures and synergistic reinforcement between graphene and carbon nanotubes enable a temperature-invariable, recoverable stretching elasticity with small energy dissipation (~0.1, 100% strain) and high fatigue resistance more than 10 6 cycles. The ultralight carbon aerogels with both stretchability and compressibility were designed as strain sensors for logic identification of sophisticated shape conversions. Our methodology paves the way to highly stretchable carbon and neat inorganic materials with extensive applications in aerospace, smart robots, and wearable devices.
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Conformation-controlled binding kinetics of antibodies
NASA Astrophysics Data System (ADS)
Galanti, Marta; Fanelli, Duccio; Piazza, Francesco
2016-01-01
Antibodies are large, extremely flexible molecules, whose internal dynamics is certainly key to their astounding ability to bind antigens of all sizes, from small hormones to giant viruses. In this paper, we build a shape-based coarse-grained model of IgG molecules and show that it can be used to generate 3D conformations in agreement with single-molecule Cryo-Electron Tomography data. Furthermore, we elaborate a theoretical model that can be solved exactly to compute the binding rate constant of a small antigen to an IgG in a prescribed 3D conformation. Our model shows that the antigen binding process is tightly related to the internal dynamics of the IgG. Our findings pave the way for further investigation of the subtle connection between the dynamics and the function of large, flexible multi-valent molecular machines.
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Two-photon quantum walk in a multimode fiber
Defienne, Hugo; Barbieri, Marco; Walmsley, Ian A.; Smith, Brian J.; Gigan, Sylvain
2016-01-01
Multiphoton propagation in connected structures—a quantum walk—offers the potential of simulating complex physical systems and provides a route to universal quantum computation. Increasing the complexity of quantum photonic networks where the walk occurs is essential for many applications. We implement a quantum walk of indistinguishable photon pairs in a multimode fiber supporting 380 modes. Using wavefront shaping, we control the propagation of the two-photon state through the fiber in which all modes are coupled. Excitation of arbitrary output modes of the system is realized by controlling classical and quantum interferences. This report demonstrates a highly multimode platform for multiphoton interference experiments and provides a powerful method to program a general high-dimensional multiport optical circuit. This work paves the way for the next generation of photonic devices for quantum simulation, computing, and communication. PMID:27152325
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PAYING FOR PERFORMANCE: THE POWER OF INCENTIVES OVER HABITS
Sindelar, Jody L.
2010-01-01
New evidence suggests that individuals do not always make rational decisions, especially with regard to health habits. Smoking, misuse of alcohol, overeating and illicit drug use are leading causes of morbidity and mortality. Thus, influencing health habits is critical for improving overall health and well-being. This editorial argues that economists should take a more active role in shaping individuals’ health habits. Two recent innovations in economic theory pave the way. One change is that some economists now view rationality as bounded and willpower in short supply. Another, related to the first, is a more accepting perspective on paternalism, authorizing economists to help individuals make better choices when the neoclassical model breaks down. Findings from psychology offer incentive-based approaches; specifically, contingency management (CM). Economists could use this approach as a basis for developing public and private policies. PMID:18348117
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NASA Astrophysics Data System (ADS)
Jannasch, Anita; Demirörs, Ahmet F.; van Oostrum, Peter D. J.; van Blaaderen, Alfons; Schäffer, Erik
2012-07-01
Optical tweezers are exquisite position and force transducers and are widely used for high-resolution measurements in fields as varied as physics, biology and materials science. Typically, small dielectric particles are trapped in a tightly focused laser and are often used as handles for sensitive force measurements. Improvement to the technique has largely focused on improving the instrument and shaping the light beam, and there has been little work exploring the benefit of customizing the trapped object. Here, we describe how anti-reflection coated, high-refractive-index core-shell particles composed of titania enable single-beam optical trapping with an optical force greater than a nanonewton. The increased force range broadens the scope of feasible optical trapping experiments and will pave the way towards more efficient light-powered miniature machines, tools and applications.
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Cherenkov Radiation Control via Self-accelerating Wave-packets.
Hu, Yi; Li, Zhili; Wetzel, Benjamin; Morandotti, Roberto; Chen, Zhigang; Xu, Jingjun
2017-08-18
Cherenkov radiation is a ubiquitous phenomenon in nature. It describes electromagnetic radiation from a charged particle moving in a medium with a uniform velocity larger than the phase velocity of light in the same medium. Such a picture is typically adopted in the investigation of traditional Cherenkov radiation as well as its counterparts in different branches of physics, including nonlinear optics, spintronics and plasmonics. In these cases, the radiation emitted spreads along a "cone", making it impractical for most applications. Here, we employ a self-accelerating optical pump wave-packet to demonstrate controlled shaping of one type of generalized Cherenkov radiation - dispersive waves in optical fibers. We show that, by tuning the parameters of the wave-packet, the emitted waves can be judiciously compressed and focused at desired locations, paving the way to such control in any physical system.
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NASA Astrophysics Data System (ADS)
Shen, Xiangying; Li, Ying; Jiang, Chaoran; Ni, Yushan; Huang, Jiping
2016-07-01
For macroscopically manipulating heat flow at will, thermal metamaterials have opened a practical way, which possesses a single function, such as either cloaking or concentrating the flow of heat even though environmental temperature varies. By developing a theory of transformation heat transfer for multiple functions, here we introduce the concept of intelligent thermal metamaterials with a dual function, which is in contrast to the existing thermal metamaterials with single functions. By assembling homogeneous isotropic materials and shape-memory alloys, we experimentally fabricate a kind of intelligent thermal metamaterials, which can automatically change from a cloak (or concentrator) to a concentrator (or cloak) when the environmental temperature changes. This work paves an efficient way for a controllable gradient of heat, and also provides guidance both for arbitrarily manipulating the flow of heat and for efficiently designing similar intelligent metamaterials in other fields.
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Pathway to a Phenocopy: Heat Stress Effects in Early Embryogenesis
Crews, Sarah M.; McCleery, W. Tyler; Hutson, M. Shane
2015-01-01
Background Heat shocks applied at the onset of gastrulation in early Drosophila embryos frequently lead to phenocopies of U-shaped mutants – having characteristic failures in the late morphogenetic processes of germband retraction and dorsal closure. The pathway from non-specific heat stress to phenocopied abnormalities is unknown. Results Drosophila embryos subjected to 30-min, 38-°C heat shocks at gastrulation appear to recover and restart morphogenesis. Post-heat-shock development appears normal, albeit slower, until a large fraction of embryos develop amnioserosa holes (diameters > 100 μm). These holes are positively correlated with terminal U-shaped phenocopies. They initiate between amnioserosa cells and open over tens of minutes by evading normal wound healing responses. They are not caused by tissue-wide increases in mechanical stress or decreases in cell-cell adhesion, but instead appear to initiate from isolated apoptosis of amnioserosa cells. Conclusions The pathway from heat shock to U-shaped phenocopies involves the opening of one or more large holes in the amnioserosa that compromise its structural integrity and lead to failures in morphogenetic processes that rely on amnioserosa-generated tensile forces. The proposed mechanism by which heat shock leads to hole initiation and expansion is heterochonicity – i.e., disruption of morphogenetic coordination between embryonic and extra-embryonic cell types. PMID:26498920
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Security Paving Company, Inc.: Consent Agreement and Proposed Final Order
Consent Agreement and Proposed Final Order (“Proposed Consent Agreement”), between the U.S. Environmental Protection Agency, Region 9 (“EPA”), and Security Paving Company (“Respondent”) to resolve a civil administrative penalty proceeding.
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Evaluation of quick-dry asphalt paving seal (QDAPS).
DOT National Transportation Integrated Search
1987-10-01
Quick-Dry Asphalt Paving Seal (QDAPS) manufactured for Texas Refinery Corp. Fort Worth, Texas. : According to the manufacturer, the primary use for this product is "a moisture resistant preventative maintenance asphalt coating for coating and sealing...
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Reexamination of cold weather paving specifications for bituminous concrete.
DOT National Transportation Integrated Search
1978-01-01
The cold weather paving specification for bituminous concrete adopted in 1970 was reexamined to determine its effectiveness and any need for revisions. Density and temperature measurements were obtained on five field projects and observations were ma...
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ePave: A Self-Powered Wireless Sensor for Smart and Autonomous Pavement.
Xiao, Jian; Zou, Xiang; Xu, Wenyao
2017-09-26
"Smart Pavement" is an emerging infrastructure for various on-road applications in transportation and road engineering. However, existing road monitoring solutions demand a certain periodic maintenance effort due to battery life limits in the sensor systems. To this end, we present an end-to-end self-powered wireless sensor-ePave-to facilitate smart and autonomous pavements. The ePave system includes a self-power module, an ultra-low-power sensor system, a wireless transmission module and a built-in power management module. First, we performed an empirical study to characterize the piezoelectric module in order to optimize energy-harvesting efficiency. Second, we developed an integrated sensor system with the optimized energy harvester. An adaptive power knob is designated to adjust the power consumption according to energy budgeting. Finally, we intensively evaluated the ePave system in real-world applications to examine the system's performance and explore the trade-off.
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Altamura, Gennaro; Corteggio, Annunziata; Nasir, Lubna; Yuan, Zheng Qiang; Roperto, Franco; Borzacchiello, Giuseppe
2013-01-01
Equine sarcoids are skin tumours of fibroblastic origin affecting equids worldwide. Bovine papillomavirus type-1 (BPV-1) and, less commonly, type-2 are recognized as etiological factors of sarcoids. The transforming activity of BPV is related to the functions of its major oncoprotein E5 which binds to the platelet-derived growth factor β receptor (PDGFβR) causing its phosphorylation and activation. In this study, we demonstrate, by coimmunoprecipitation and immunoblotting, that in equine sarcoid derived cell lines PDGFβR is phosphorylated and binds downstream molecules related to Ras-mitogen-activated protein kinase-ERK pathway thus resulting in Ras activation. Imatinib mesylate is a tyrosine kinase receptors inhibitor which selectively inhibits the activation of PDGFβR in the treatment of several human and animal cancers. Here we show that imatinib inhibits receptor phosphorylation, and cell viability assays demonstrate that this drug decreases sarcoid fibroblasts viability in a dose-dependent manner. This study contributes to a better understanding of the molecular mechanisms involved in the pathology of sarcoids and paves the way to a new therapeutic approach for the treatment of this common equine skin neoplasm. PMID:23936786
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Pietra, Francesco
2017-11-01
In this work, viable models of cysteine dioxygenase (CDO) and its complex with l-cysteine dianion were built for the first time, under strict adherence to the crystal structure from X-ray diffraction studies, for all atom molecular dynamics (MD). Based on the CHARMM36 FF, the active site, featuring an octahedral dummy Fe(II) model, allowed us observing water exchange, which would have escaped attention with the more popular bonded models. Free dioxygen (O 2 ) and l-cysteine, added at the active site, could be observed being expelled toward the solvating medium under Random Accelerated Molecular Dynamics (RAMD) along major and minor pathways. Correspondingly, free dioxygen (O 2 ), added to the solvating medium, could be observed to follow the same above pathways in getting to the active site under unbiased MD. For the bulky l-cysteine, 600 ns of trajectory were insufficient for protein penetration, and the molecule was stuck at the protein borders. These models pave the way to free energy studies of ligand associations, devised to better clarify how this cardinal enzyme behaves in human metabolism. © 2017 Wiley-VHCA AG, Zurich, Switzerland.
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Gut Microbiome and Obesity: A Plausible Explanation for Obesity.
Sanmiguel, Claudia; Gupta, Arpana; Mayer, Emeran A
2015-06-01
Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest-host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host's adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review we summarize the current evidence for possible mechanisms underlying gut microbiota induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity.
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Gut Microbiome and Obesity: A Plausible Explanation for Obesity
Sanmiguel, Claudia; Gupta, Arpana; Mayer, Emeran A.
2015-01-01
Obesity is a multifactorial disorder that results in excessive accumulation of adipose tissue. Although obesity is caused by alterations in the energy consumption/expenditure balance, the factors promoting this disequilibrium are incompletely understood. The rapid development of new technologies and analysis strategies to decode the gut microbiota composition and metabolic pathways has opened a door into the complexity of the guest-host interactions between the gut microbiota and its human host in health and in disease. Pivotal studies have demonstrated that manipulation of the gut microbiota and its metabolic pathways can affect host’s adiposity and metabolism. These observations have paved the way for further assessment of the mechanisms underlying these changes. In this review we summarize the current evidence for possible mechanisms underlying gut microbiota induced obesity. The review addresses some well-known effects of the gut microbiota on energy harvesting and changes in metabolic machinery, on metabolic and immune interactions and on possible changes in brain function and behavior. Although there is limited understanding on the symbiotic relationship between us and our gut microbiome, and how disturbances of this relationship affects our health, there is compelling evidence for an important role of the gut microbiota in the development and perpetuation of obesity. PMID:26029487
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Asea, Alexzander; Rehli, Michael; Kabingu, Edith; Boch, Jason A; Bare, Olivia; Auron, Philip E; Stevenson, Mary Ann; Calderwood, Stuart K
2002-04-26
Recent studies have initiated a paradigm shift in the understanding of the function of heat shock proteins (HSP). It is now clear that HSP can and do exit mammalian cells, interact with cells of the immune system, and exert immunoregulatory effects. We recently demonstrated that exogenously added HSP70 possesses potent cytokine activity, with the ability to bind with high affinity to the plasma membrane, elicit a rapid intracellular Ca(2+) flux, activate NF-kappaB, and up-regulate the expression of pro-inflammatory cytokines in human monocytes. Here for the first time, we report that HSP70-induced proinflammatory cytokine production is mediated via the MyD88/IRAK/NF-kappaB signal transduction pathway and that HSP70 utilizes both TLR2 (receptor for Gram-positive bacteria) and TLR4 (receptor for Gram-negative bacteria) to transduce its proinflammatory signal in a CD14-dependent fashion. These studies now pave the way for the development of highly effective pharmacological or molecular tools that will either up-regulate or suppress HSP70-induced functions in conditions where HSP70 effects are desirable (cancer) or disorders where HSP70 effects are undesirable (arthritis and arteriosclerosis).
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Sharma, Mukesh; Sarma, Plaban Jyoti; Goswami, Manash Jyoti; Bania, Kusum K
2017-03-15
Metallogel of iron-carboxylates was obtained from trans-1,2-cyclohexanedicarboxylic acid in dimethylformamide (DMF) at basic condition. Spectroscopic and SEM morphology study of the iron-metallogel revealed that the iron complex with dicarboxylic acid was linked together via carboxylates and led to a supramolecular helical like architecture. The synthesized metallogel served as an excellent template for in-situ reduction of silver ion to silver particles micro to nano scale range. Variation of AgNO 3 concentration shepherd to change the morphology of the Ag-particles. AgNO 3 concentration was found to affect the shape and size of silver particles. On going from lower to higher concentration shape of silver particles changed from spherical to large agglomerated particles. Cubic shape Ag-particles were found on treatment of 0.05M AgNO 3 solution with metallogel. Cubical shape silver particles were found to be effective catalyst for nitro-arene reduction in presence of NaBH 4 . Density functional theory (DFT) calculations were performed to rationalize the role of Ag-particles in catalytic reduction of 4-nitrophenol to 4-aminophenol. Based on DFT study, we proposed that catalytic reduction occurred via Ag-hydride complex formation. Since metallogels as well as the 4-aminophenol are finding large application in pharmaceuticals industries therefore the current work can provide an alternatives path in production of 4-aminophenols. In addition to this, the synthesis of Ag-nanomaterials using metallogel as template can pave a new direction in the development of nanotechnology and might find wide applications in catalytic industrial processes. Copyright © 2016 Elsevier Inc. All rights reserved.
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NASA Astrophysics Data System (ADS)
Strambini, E.; Golovach, V. N.; De Simoni, G.; Moodera, J. S.; Bergeret, F. S.; Giazotto, F.
2017-10-01
A ferromagnetic insulator in contact with a superconductor is known to induce an exchange splitting of the singularity in the Bardeen-Cooper-Schrieffer (BCS) density of states (DoS). The magnitude of the splitting is proportional to the exchange field that penetrates into the superconductor to a depth comparable with the superconducting coherence length and which ranges in magnitude from a few to a few tens of tesla. We study this magnetic proximity effect in EuS/Al bilayers and show that the domain structure of the EuS affects the positions and the line shapes of the exchange-split BCS peaks. Remarkably, a clear exchange splitting is observed even in the unmagnetized state of the EuS layer, suggesting that the domain size of the EuS is comparable with the superconducting coherence length. Upon magnetizing the EuS layer, the splitting increases while the peaks change shape. Conductance measurements as a function of bias voltage at the lowest temperatures allowed us to relate the line shape of the split BCS DoS to the characteristic domain structure in the ultrathin EuS layer. These results pave the way to engineering triplet superconducting correlations at domain walls in EuS/Al bilayers. Furthermore, the hard gap and large splitting observed in our tunneling spectroscopy measurements make EuS/Al an excellent candidate for substituting strong magnetic fields in experiments studying Majorana bound states.
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Fuel Cell Electric Vehicles: Paving the Way to Commercial Success -
emissions. Photo by Dennis Schroeder, NREL Fuel Cell Electric Vehicles: Paving the Way to Commercial Success advanced vehicle ride-and-drive event at the NREL Education Center. Photo by Dennis Schroeder, NREL "
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Cold weather paving requirements for bituminous concrete.
DOT National Transportation Integrated Search
1973-01-01
Cold weather paving specifications were developed from work by Corlew and Dickson, who used a computer solution to predict the cooling rate of bituminous concrete. Virginia had used a minimum atmospheric temperature as a criterion; however, it was ev...
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Nitric oxide-sphingolipid interplays in plant signalling: a new enigma from the Sphinx?
Guillas, Isabelle; Puyaubert, Juliette; Baudouin, Emmanuel
2013-09-12
Nitric oxide (NO) emerged as one of the major signaling molecules operating during plant development and plant responses to its environment. Beyond the identification of the direct molecular targets of NO, a series of studies considered its interplay with other actors of signal transduction and the integration of NO into complex signaling networks. Beside the close relationships between NO and calcium or phosphatidic acid signaling pathways that are now well-established, recent reports paved the way for interplays between NO and sphingolipids (SLs). This mini-review summarizes our current knowledge of the influence NO and SLs might exert on each other in plant physiology. Based on comparisons with examples from the animal field, it further indicates that, although SL-NO interplays are common features in signaling networks of eukaryotic cells, the underlying mechanisms and molecular targets significantly differ.
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Wnt Signaling in Normal and Malignant Hematopoiesis
Lento, William; Congdon, Kendra; Voermans, Carlijn; Kritzik, Marcie; Reya, Tannishtha
2013-01-01
One of the most remarkable characteristics of stem cells is their ability to perpetuate themselves through self-renewal while concomitantly generating differentiated cells. In the hematopoietic system, stem cells balance these mechanisms to maintain steady-state hematopoiesis for the lifetime of the organism, and to effectively regenerate the system following injury. Defects in the proper control of self-renewal and differentiation can be potentially devastating and contribute to the development of malignancies. In this review, we trace the emerging role of Wnt signaling as a critical regulator of distinct aspects of self-renewal and differentiation, its contribution to the maintenance of homeostasis and regeneration, and how the pathway can be hijacked to promote leukemia development. A better understanding of these processes could pave the way to enhancing recovery after injury and to developing better therapeutic approaches for hematologic malignancies. PMID:23378582
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Sol processing of conjugated carbon nitride powders for thin-film fabrication.
Zhang, Jinshui; Zhang, Mingwen; Lin, Lihua; Wang, Xinchen
2015-05-18
The chemical protonation of graphitic carbon nitride (CN) solids with strong oxidizing acids, for example HNO3, is demonstrated as an efficient pathway for the sol processing of a stable CN colloidal suspension, which can be translated into thin films by dip/disperse-coating techniques. The unique features of CN colloids, such as the polymeric matrix and the reversible hydrogen bonding, result in the thin-film electrodes derived from the sol solution exhibiting a high mechanical stability with improved conductivity for charge transport, and thus show a remarkably enhanced photo-electrochemical performance. The polymer system can in principle be broadly tuned by hybridization with desired functionalities, thus paving the way for the application of CN for specific tasks, as exemplified here by coupling with carbon nanotubes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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The use of hypnosis in therapy to increase happiness.
Ruysschaert, Nicole
2014-01-01
In their journey through life, most people are looking for happiness. Definitions of happiness and the concepts of a pleasant, good, meaningful, and a full life are reviewed. Next, Seligman's (2002) concept of "authentic happiness" and a happiness formula, S+C+V (Set + Circumstances + Variables), are discussed. An integration of happiness, as a goal, and hypnosis, as a facilitative approach, are presented. Hypnotic techniques with case examples are given. Hypnosis is presented as an efficient companion intervention to work on these variables in a creative way and to pave the way to a happy and full life. The following results are presented: (1) hypnosis allows for increased executive attention with control of emotions, (2) focusing on positive imagery contributes to strengthening "happy pathways," and (3) emotions about the past, present, and future are subject to change.
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Thermoacoustics of solids: A pathway to solid state engines and refrigerators
NASA Astrophysics Data System (ADS)
Hao, Haitian; Scalo, Carlo; Sen, Mihir; Semperlotti, Fabio
2018-01-01
Thermoacoustic oscillations have been one of the most exciting discoveries of the physics of fluids in the 19th century. Since its inception, scientists have formulated a comprehensive theoretical explanation of the basic phenomenon which has later found several practical applications to engineering devices. To date, all studies have concentrated on the thermoacoustics of fluid media where this fascinating mechanism was exclusively believed to exist. Our study shows theoretical and numerical evidence of the existence of thermoacoustic instabilities in solid media. Although the underlying physical mechanism exhibits some interesting similarities with its counterpart in fluids, the theoretical framework highlights relevant differences that have important implications on the ability to trigger and sustain the thermoacoustic response. This mechanism could pave the way to the development of highly robust and reliable solid-state thermoacoustic engines and refrigerators.
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Rein, Theo
2016-09-01
This review portraits FK506 binding protein (FKBP) 51 as "reactivity protein" and collates recent publications to develop the concept of FKBP51 as contributor to different levels of adaptation. Adaptation is a fundamental process that enables unicellular and multicellular organisms to adjust their molecular circuits and structural conditions in reaction to environmental changes threatening their homeostasis. FKBP51 is known as chaperone and co-chaperone of heat shock protein (HSP) 90, thus involved in processes ensuring correct protein folding in response to proteotoxic stress. In mammals, FKBP51 both shapes the stress response and is calibrated by the stress levels through an ultrashort molecular feedback loop. More recently, it has been linked to several intracellular pathways related to the reactivity to drug exposure and stress. Through its role in autophagy and DNA methylation in particular it influences adaptive pathways, possibly also in a transgenerational fashion. Also see the video abstract here. © 2016 WILEY Periodicals, Inc.
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ERIC Educational Resources Information Center
Lanskey, Caroline
2015-01-01
Many young people in the youth justice system in England and Wales are educationally marginalised and systemic barriers to their engagement with education persist. This article presents an analytical framework for understanding how education and youth justice practices shape young people's educational pathways during their time in the youth…
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Laboratory testing of precast paving notch system.
DOT National Transportation Integrated Search
2008-02-01
Bridge approach pavement settlement and the resulting formation of bumps at the end : of bridges is a recurring problem on a number of Iowa bridges. One of the contributing : factors in this settlement is failure of the bridge paving notch. A p...
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Effect on asphalt quality due to nighttime construction : final report.
DOT National Transportation Integrated Search
2017-06-01
The objectives of this project were to identify and analyze the nighttime paving traffic control standards in other states and compare the effects of daytime vs. nighttime paving on quality, safety, costs, and construction time. Surveys of various De...
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Work plan for special design features and crack sealing maintenance.
DOT National Transportation Integrated Search
2013-09-01
The Alaska DOT&PF wants to construct and maintain asphalt concrete (AC) paved highways in a way that minimizes roadway lifecycle costs while preserving acceptable : performance. Thermal cracking is a natural feature of most paved Alaska roadways that...
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Phase I: Evaluation of Low Flexural Strength for Northern Nevada Concrete Paving Mixtures
DOT National Transportation Integrated Search
2017-07-01
Production paving grade concrete in Northern Nevada having acceptable strength is universally acknowledged to be difficult; however understanding why this is true remains elusive. Current practice is to meet flexural strength requirements by using mi...
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28. DOWNSTREAM VIEW OF ROCK PAVING OPERATIONS ON LEFT BANK ...
28. DOWNSTREAM VIEW OF ROCK PAVING OPERATIONS ON LEFT BANK OF OUTLET CHANNEL.... Volume XVI, No. 18, September 29, 1939. - Prado Dam, Outlet Works, Santa Ana River near junction of State Highways 71 & 91, Corona, Riverside County, CA
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Assessment of tri-dyne precast concrete panels.
DOT National Transportation Integrated Search
2008-01-01
Tri-Dyne Industries has developed precast concrete paving slabs (PCPS) that connect using tongue and groove joints and overlap joints, as shown in Figure 1 (1). This proprietary system is referred to as the Pro-Active Paving SystemTM and consis...
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Assessment of burrowing mammal impacts on paved highways in Montana.
DOT National Transportation Integrated Search
2010-12-01
The burrowing behavior of some rodents, insectivores, and mustelids has the potential to cause : damage to paved roads or exacerbate existing deterioration. The main objective of this project : was to characterize the nature and extent of burrowing m...
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Keep the Rain Where It Belongs with Porous Pavement.
ERIC Educational Resources Information Center
American School and University, 1979
1979-01-01
Paved roads and parking lots have contributed to present and projected shortages of fresh water as well as to problems of flash floods. The utilization of porous asphalt paving can help prevent decreasing the reserves of ground water. (Author/MLF)
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Novel method of extracting motion from natural movies.
Suzuki, Wataru; Ichinohe, Noritaka; Tani, Toshiki; Hayami, Taku; Miyakawa, Naohisa; Watanabe, Satoshi; Takeichi, Hiroshige
2017-11-01
The visual system in primates can be segregated into motion and shape pathways. Interaction occurs at multiple stages along these pathways. Processing of shape-from-motion and biological motion is considered to be a higher-order integration process involving motion and shape information. However, relatively limited types of stimuli have been used in previous studies on these integration processes. We propose a new algorithm to extract object motion information from natural movies and to move random dots in accordance with the information. The object motion information is extracted by estimating the dynamics of local normal vectors of the image intensity projected onto the x-y plane of the movie. An electrophysiological experiment on two adult common marmoset monkeys (Callithrix jacchus) showed that the natural and random dot movies generated with this new algorithm yielded comparable neural responses in the middle temporal visual area. In principle, this algorithm provided random dot motion stimuli containing shape information for arbitrary natural movies. This new method is expected to expand the neurophysiological and psychophysical experimental protocols to elucidate the integration processing of motion and shape information in biological systems. The novel algorithm proposed here was effective in extracting object motion information from natural movies and provided new motion stimuli to investigate higher-order motion information processing. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.
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Targeting the Hippo signalling pathway for cancer treatment.
Nakatani, Keisuke; Maehama, Tomohiko; Nishio, Miki; Goto, Hiroki; Kato, Wakako; Omori, Hirofumi; Miyachi, Yosuke; Togashi, Hideru; Shimono, Yohei; Suzuki, Akira
2017-03-01
The Hippo signalling pathway monitors cell-cell contact and external factors that shape tissue structure. In mice, tumourigenesis and developmental abnormalities are common consequences of dysregulated Hippo signalling. Expression of Hippo pathway components is also frequently altered in human tumours and correlates with poor prognosis and reduced patient survival. Thus, the Hippo pathway is an attractive anti-cancer target. Here, we provide an overview of the function and regulation of Hippo signalling components and summarize progress to date on the development of agents able to regulate Hippo signalling for cancer therapy. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.
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Infrared thermography-driven flaw detection and evaluation of hot mix asphalt pavements.
DOT National Transportation Integrated Search
2010-01-01
This research was conducted to study more realistic explanations of how variables are created and : dealt with during hot mix asphalt (HMA) paving construction. Several paving projects across the : state of Nebraska have been visited where sensory de...
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EVALUATION OF EMISSIONS FROM PAVING ASPHALTS
The report provides data from pilot-scale measurements of the emissions of specific air pollutants from paving asphalt both with and without recycled crumb rubber additives. The methods used in this work measured emissions from a static layer of asphalt maintained for several hou...
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Long-term field monitoring of paving fabric interlayer systems to reduce reflective cracking.
DOT National Transportation Integrated Search
2016-06-01
The formation of reflective cracking of pavement overlays has confronted highway engineers for many years. Stress-relieving interlayers, such as paving fabrics, have been used in an attempt to reduce or delay reflective cracking. The primary objectiv...
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Improved rice method for determining theoretical maximum density of asphalt paving mixtures
DOT National Transportation Integrated Search
1992-05-01
Rice method (ASTM D2041 ) is used for determining the theoretical maximum specific gravity of asphalt paving mixtures which is one of the main test parameters used for mix design and construction quality control. The repeatability and reproducibility...
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Evaluation of Tack Coat Materials on Longitudinal Joints in Louisiana
DOT National Transportation Integrated Search
2018-02-01
One of the advantages of asphalt pavements is that they can minimize traffic disruptions by being paved and opened to traffic quickly. Often, asphalt paving is performed while traffic is maintained in an adjacent lane. The disadvantage of this constr...
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43. CAPE COD AIR STATION PAVE PAWS FACILITY WITH ...
43. CAPE COD AIR STATION PAVE PAWS FACILITY - WITH BUILDING METAL SIDING BEING APPLIED ON "C" FACE (RIGHT) AND "B" FACE BEING PREPARED FOR INSTALLATION. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA
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Construction of a thin-bonded Portland cement concrete overlay using accelerated paving techniques.
DOT National Transportation Integrated Search
1992-01-01
The report describes the Virginia Department of Transportations' first modern experience with the construction of thin-bonded Portland cement concrete overlays of existing concrete pavements and with the fast track mode of rigid paving. The study was...
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49 CFR 571.224 - Standard No. 224; Rear impact protection.
Code of Federal Regulations, 2010 CFR
2010-10-01
... trailers, pulpwood trailers, road construction controlled horizontal discharge trailers, special purpose... latches are excluded from the determination of the rearmost point. Road construction controlled horizontal... machine or paving equipment for road construction and paving operations. Rounded corner means a guard's...
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Graziani, Valentina; Marrone, Alessandro; Re, Nazzareno; Coletti, Cecilia; Platts, James A; Casini, Angela
2017-10-04
Structural studies have paved the avenue to a deeper understanding of aquaporins (AQPs), small ancient proteins providing efficient transmembrane pathways for water, small uncharged solutes such as glycerol, and possibly gas molecules. Despite the numerous studies, their roles in health and disease remain to be fully disclosed. The recent discovery of Au III complexes as potent and selective inhibitors of aquaglyceroporin isoforms paves the way to their possible therapeutic application. The binding of the selective human AQP3 inhibitor, the cationic complex [Au(bipy)Cl 2 ] + (Aubipy), to the protein channel has been investigated here by means of a multi-level theoretical workflow that includes QM, MD and QM/MM approaches. The hydroxo complex was identified as the prevalent form of Aubipy in physiological media and its binding to AQP3 studied by MD. Both non-covalent and coordinative Aubipy-AQP3 adducts were simulated to probe their role in the modulation of water channel functionality. The electronic structures of representative Aubipy-AQP3 adducts were then analysed to unveil the role played by the metal moiety in their stabilisation. This study spotlights the overall importance of three key aspects for AQP3 inhibition: 1) water speciation of the Au III complex, 2) stability of non-covalent adducts and 3) conformational changes induced within the pore by the coordinative binding of Au III . The obtained results are expected to orient future developments in the design of isoform-selective Au III inhibitors. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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PAVE: program for assembling and viewing ESTs.
Soderlund, Carol; Johnson, Eric; Bomhoff, Matthew; Descour, Anne
2009-08-26
New sequencing technologies are rapidly emerging. Many laboratories are simultaneously working with the traditional Sanger ESTs and experimenting with ESTs generated by the 454 Life Science sequencers. Though Sanger ESTs have been used to generate contigs for many years, no program takes full advantage of the 5' and 3' mate-pair information, hence, many tentative transcripts are assembled into two separate contigs. The new 454 technology has the benefit of high-throughput expression profiling, but introduces time and space problems for assembling large contigs. The PAVE (Program for Assembling and Viewing ESTs) assembler takes advantage of the 5' and 3' mate-pair information by requiring that the mate-pairs be assembled into the same contig and joined by n's if the two sub-contigs do not overlap. It handles the depth of 454 data sets by "burying" similar ESTs during assembly, which retains the expression level information while circumventing time and space problems. PAVE uses MegaBLAST for the clustering step and CAP3 for assembly, however it assembles incrementally to enforce the mate-pair constraint, bury ESTs, and reduce incorrect joins and splits. The PAVE data management system uses a MySQL database to store multiple libraries of ESTs along with their metadata; the management system allows multiple assemblies with variations on libraries and parameters. Analysis routines provide standard annotation for the contigs including a measure of differentially expressed genes across the libraries. A Java viewer program is provided for display and analysis of the results. Our results clearly show the benefit of using the PAVE assembler to explicitly use mate-pair information and bury ESTs for large contigs. The PAVE assembler provides a software package for assembling Sanger and/or 454 ESTs. The assembly software, data management software, Java viewer and user's guide are freely available.
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Hypothalamic mTOR pathway mediates thyroid hormone-induced hyperphagia in hyperthyroidism.
Varela, Luis; Martínez-Sánchez, Noelia; Gallego, Rosalía; Vázquez, María J; Roa, Juan; Gándara, Marina; Schoenmakers, Erik; Nogueiras, Rubén; Chatterjee, Krishna; Tena-Sempere, Manuel; Diéguez, Carlos; López, Miguel
2012-06-01
Hyperthyroidism is characterized in rats by increased energy expenditure and marked hyperphagia. Alterations of thermogenesis linked to hyperthyroidism are associated with dysregulation of hypothalamic AMPK and fatty acid metabolism; however, the central mechanisms mediating hyperthyroidism-induced hyperphagia remain largely unclear. Here, we demonstrate that hyperthyroid rats exhibit marked up-regulation of the hypothalamic mammalian target of rapamycin (mTOR) signalling pathway associated with increased mRNA levels of agouti-related protein (AgRP) and neuropeptide Y (NPY), and decreased mRNA levels of pro-opiomelanocortin (POMC) in the arcuate nucleus of the hypothalamus (ARC), an area where mTOR co-localizes with thyroid hormone receptor-α (TRα). Central administration of thyroid hormone (T3) or genetic activation of thyroid hormone signalling in the ARC recapitulated hyperthyroidism effects on feeding and the mTOR pathway. In turn, central inhibition of mTOR signalling with rapamycin in hyperthyroid rats reversed hyperphagia and normalized the expression of ARC-derived neuropeptides, resulting in substantial body weight loss. The data indicate that in the hyperthyroid state, increased feeding is associated with thyroid hormone-induced up-regulation of mTOR signalling. Furthermore, our findings that different neuronal modulations influence food intake and energy expenditure in hyperthyroidism pave the way for a more rational design of specific and selective therapeutic compounds aimed at reversing the metabolic consequences of this disease. Copyright © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
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Michel, L; Reygagne, P; Benech, P; Jean-Louis, F; Scalvino, S; Ly Ka So, S; Hamidou, Z; Bianovici, S; Pouch, J; Ducos, B; Bonnet, M; Bensussan, A; Patatian, A; Lati, E; Wdzieczak-Bakala, J; Choulot, J-C; Loing, E; Hocquaux, M
2017-11-01
Male androgenetic alopecia (AGA) is the most common form of hair loss in men. It is characterized by a distinct pattern of progressive hair loss starting from the frontal area and the vertex of the scalp. Although several genetic risk loci have been identified, relevant genes for AGA remain to be defined. To identify biomarkers associated with AGA. Molecular biomarkers associated with premature AGA were identified through gene expression analysis using cDNA generated from scalp vertex biopsies of hairless or bald men with premature AGA, and healthy volunteers. This monocentric study reveals that genes encoding mast cell granule enzymes, inflammatory mediators and immunoglobulin-associated immune mediators were significantly overexpressed in AGA. In contrast, underexpressed genes appear to be associated with the Wnt/β-catenin and bone morphogenic protein/transforming growth factor-β signalling pathways. Although involvement of these pathways in hair follicle regeneration is well described, functional interpretation of the transcriptomic data highlights different events that account for their inhibition. In particular, one of these events depends on the dysregulated expression of proopiomelanocortin, as confirmed by polymerase chain reaction and immunohistochemistry. In addition, lower expression of CYP27B1 in patients with AGA supports the notion that changes in vitamin D metabolism contributes to hair loss. This study provides compelling evidence for distinct molecular events contributing to alopecia that may pave the way for new therapeutic approaches. © 2017 British Association of Dermatologists.
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Gnanasekaran, Thiyagarajan; Karcher, Daniel; Nielsen, Agnieszka Zygadlo; Martens, Helle Juel; Ruf, Stephanie; Kroop, Xenia; Olsen, Carl Erik; Motawie, Mohammed Saddik; Pribil, Mathias; Møller, Birger Lindberg; Bock, Ralph; Jensen, Poul Erik
2016-04-01
Plant chloroplasts are light-driven cell factories that have great potential to act as a chassis for metabolic engineering applications. Using plant chloroplasts, we demonstrate how photosynthetic reducing power can drive a metabolic pathway to synthesise a bio-active natural product. For this purpose, we stably engineered the dhurrin pathway from Sorghum bicolor into the chloroplasts of Nicotiana tabacum (tobacco). Dhurrin is a cyanogenic glucoside and its synthesis from the amino acid tyrosine is catalysed by two membrane-bound cytochrome P450 enzymes (CYP79A1 and CYP71E1) and a soluble glucosyltransferase (UGT85B1), and is dependent on electron transfer from a P450 oxidoreductase. The entire pathway was introduced into the chloroplast by integrating CYP79A1, CYP71E1, and UGT85B1 into a neutral site of the N. tabacum chloroplast genome. The two P450s and the UGT85B1 were functional when expressed in the chloroplasts and converted endogenous tyrosine into dhurrin using electrons derived directly from the photosynthetic electron transport chain, without the need for the presence of an NADPH-dependent P450 oxidoreductase. The dhurrin produced in the engineered plants amounted to 0.1-0.2% of leaf dry weight compared to 6% in sorghum. The results obtained pave the way for plant P450s involved in the synthesis of economically important compounds to be engineered into the thylakoid membrane of chloroplasts, and demonstrate that their full catalytic cycle can be driven directly by photosynthesis-derived electrons. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Moosavi, Mohammad Amin; Yazdanparast, Razieh
2008-07-01
Despite the depth of knowledge concerning the pathogenesis of acute myeloblastic leukemia (AML), long-term survival remains unresolved. Therefore, new agents that act more selectively and more potently are required. In that line, we have recently characterized a novel diterpene ester, called 3-hydrogenkwadaphnin (3-HK), with capability to induce both differentiation and apoptosis in various leukemia cell lines. These effects of 3-HK were mediated through inhibition of inosine 5'-monophosphate dehydrogenase, a selective up-regulated enzyme in cancerous cells, especially leukemia. However, it remains elusive to understand how cells display different fates in response to 3-HK. Here, we report the distinct molecular signaling pathwaysmore » involved in forcing of 3-HK-treated U937 cells to undergo differentiation and apoptosis. After 3-HK (15 nM) treatment, a portion of U937 cells adhered to the culture plates and showed macrophage criteria while others remained in suspension and underwent apoptosis. The differentiated cells arrested in G{sub 0}/G{sub 1} phase of cell cycle and showed early activation of ERK1/2 pathway (3 h) along with ERK-dependent p21{sup Cip/WAF1} (p21) up-regulation and expression of p27{sup Kip1} and Bcl-2. In contrast, the suspension cells underwent apoptosis through Fas/FasL and mitochondrial pathways. The occurrence of apoptosis in these cells were accompanied with caspase-8-mediated p21 cleavage and delayed activation (24 h) of JNK1/2 and p38 MAPK. Taken together, these results suggest that distinct signaling pathways play a pivotal role in fates of drug-treated leukemia cells, thus this may pave some novel therapeutical utilities.« less
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DOT National Transportation Integrated Search
2001-08-01
This report discusses the variability associated with the production, construction, and testing of structural and paving concrete. The study evaluated data from over 900 projects constructed between 1992 and 1999, representing over 25,000 lots. The d...
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Code of Federal Regulations, 2012 CFR
2012-01-01
... 14 Aeronautics and Space 3 2012-01-01 2012-01-01 false Paved areas. 139.305 Section 139.305 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... paragraph (b) of this section, mud, dirt, sand, loose aggregate, debris, foreign objects, rubber deposits...
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Code of Federal Regulations, 2010 CFR
2010-01-01
... 14 Aeronautics and Space 3 2010-01-01 2010-01-01 false Paved areas. 139.305 Section 139.305 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... paragraph (b) of this section, mud, dirt, sand, loose aggregate, debris, foreign objects, rubber deposits...
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Non-invasive imaging and assessment of active karst features in proximity to paved roadways.
DOT National Transportation Integrated Search
2014-02-01
In an effort to better understand and define the lateral and vertical extent of active karst features in immediate proximity to paved : MoDOT roadways in Springfield Missouri, MS&T will acquire electrical resistivity tomography (ERT) data. The intent...
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40 CFR 443.21 - Specialized definitions.
Code of Federal Regulations, 2012 CFR
2012-07-01
... PERFORMANCE AND PRETREATMENT STANDARDS FOR NEW SOURCES FOR THE PAVING AND ROOFING MATERIALS (TARS AND ASPHALT) POINT SOURCE CATEGORY Asphalt Concrete Subcategory § 443.21 Specialized definitions. For the purpose of... paving asphalt concrete. (c) The term “process wastewater pollutants” shall mean any pollutants present...
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40 CFR 443.21 - Specialized definitions.
Code of Federal Regulations, 2013 CFR
2013-07-01
... PERFORMANCE AND PRETREATMENT STANDARDS FOR NEW SOURCES FOR THE PAVING AND ROOFING MATERIALS (TARS AND ASPHALT) POINT SOURCE CATEGORY Asphalt Concrete Subcategory § 443.21 Specialized definitions. For the purpose of... paving asphalt concrete. (c) The term “process wastewater pollutants” shall mean any pollutants present...
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40 CFR 443.21 - Specialized definitions.
Code of Federal Regulations, 2014 CFR
2014-07-01
... PERFORMANCE AND PRETREATMENT STANDARDS FOR NEW SOURCES FOR THE PAVING AND ROOFING MATERIALS (TARS AND ASPHALT) POINT SOURCE CATEGORY Asphalt Concrete Subcategory § 443.21 Specialized definitions. For the purpose of... paving asphalt concrete. (c) The term “process wastewater pollutants” shall mean any pollutants present...
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View of the PAVE PAWS radar from approach along Spencer ...
View of the PAVE PAWS radar from approach along Spencer Paul Road, looking northwest - Beale Air Force Base, Perimeter Acquisition Vehicle Entry Phased-Array Warning System, End of Spencer Paul Road, north of Warren Shingle Road (14th Street), Marysville, Yuba County, CA
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DOT National Transportation Integrated Search
2013-03-01
Incremental increases in paved shoulder widths have been studied and are shown in the Highway Safety Manual. While : each incremental increase in shoulder width is beneficial, there is evidence that suggests the relationship between safety : improvem...
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DOT National Transportation Integrated Search
1999-11-01
Connecticut Department of Transportation personnel used an infrared camera to observe thermal segregation of hot mix asphalt during pavement construction. Several sites were selected for study from ongoing paving projects. During paving operations, t...
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Code of Federal Regulations, 2014 CFR
2014-01-01
... 14 Aeronautics and Space 3 2014-01-01 2014-01-01 false Paved areas. 139.305 Section 139.305 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... paragraph (b) of this section, mud, dirt, sand, loose aggregate, debris, foreign objects, rubber deposits...
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Code of Federal Regulations, 2011 CFR
2011-01-01
... 14 Aeronautics and Space 3 2011-01-01 2011-01-01 false Paved areas. 139.305 Section 139.305 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... paragraph (b) of this section, mud, dirt, sand, loose aggregate, debris, foreign objects, rubber deposits...
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Code of Federal Regulations, 2013 CFR
2013-01-01
... 14 Aeronautics and Space 3 2013-01-01 2013-01-01 false Paved areas. 139.305 Section 139.305 Aeronautics and Space FEDERAL AVIATION ADMINISTRATION, DEPARTMENT OF TRANSPORTATION (CONTINUED) AIR CARRIERS... paragraph (b) of this section, mud, dirt, sand, loose aggregate, debris, foreign objects, rubber deposits...
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Self-consolidating concrete, applications for slip-form paving : phase II.
DOT National Transportation Integrated Search
2011-05-01
The goal of the project was to develop a new type of self-consolidating concrete (SCC) for slip-form paving to simplify construction and make smoother pavements. Developing the new SCC involved two phases: a feasibility study (Phase I sponsored by TP...
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Geotextiles in Flexible Pavement Construction
ERIC Educational Resources Information Center
Alungbe, Gabriel D.
2004-01-01
People everywhere in the developed world regularly drive on paved roads. Learning about the construction techniques and materials used in paving benefits technology and construction students. This article discusses the use of geosynthetic textiles in pavement construction. It presents background on pavements and describes geotextiles and drainage…
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42. CAPE COD AIR STATION PAVE PAWS FACILITY SHOWING ...
42. CAPE COD AIR STATION PAVE PAWS FACILITY - SHOWING BUILDING "RED IRON" STEEL STRUCTURE AT 46T DAY OF STEEL CONSTRUCTION. "BUILDING TOPPED OFF, 7 JULY, 1974. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA
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Characterization Tests for Mineral Fillers Related to Performance of Asphalt Paving Mixtures
DOT National Transportation Integrated Search
1988-01-01
Various studies have shown that the properties of mineral filler, especially the material passing 0.075 mm (No. 200) sieve (generally called P200 material), have a significant effect on the performance of asphalt paving mixtures in terms of permanent...
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Feasibility study of two-lift concrete paving : technical report.
DOT National Transportation Integrated Search
2014-04-01
Two-lift concrete paving (2LCP) involves placing two layers of concrete (wet-on-wet) instead of a single : homogeneous layer, as is typically done in the United States. 2LCP offers the opportunity to optimize the use of local : aggregates, recycled m...
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Paving asphalt products exhibit a lack of carcinogenic and mutagenic activity.
Goyak, Katy O; McKee, Richard H; Minsavage, Gary D; McGowan, Claude; Daughtrey, Wayne C; Freeman, James J
2011-10-01
A paving asphalt and a vacuum residuum (derived from crude oil by atmospheric and subsequent vacuum distillation and used as a blend stock for asphalt) were tested in skin carcinogenesis assays in mice and in optimized Ames assays for mutagenic activity. In the skin cancer tests, each substance was applied twice weekly for 104 weeks to the clipped backs of groups of 50 male C3H mice. Neither the paving asphalt nor the vacuum residuum (30% weight/volume and 75% weight/weight in US Pharmacopeia mineral oil, respectively) produced any tumors. The positive control benzo[a]pyrene (0.05% w/v in toluene) induced tumors in 46 of 50 mice, demonstrating the effectiveness of the test method. Salmonella typhimurium tester strain TA98 was used in the optimized Ames assay to evaluate mutagenic potential. Dimethylsulfoxide (DMSO) extractions of the substances were not mutagenic when tested up to toxic limits. Thus, under the conditions of these studies, neither the paving asphalt nor the vacuum residuum was carcinogenic or mutagenic.
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Imaging and controlling plasmonic interference fields at buried interfaces
NASA Astrophysics Data System (ADS)
Lummen, Tom T. A.; Lamb, Raymond J.; Berruto, Gabriele; Lagrange, Thomas; Dal Negro, Luca; García de Abajo, F. Javier; McGrouther, Damien; Barwick, B.; Carbone, F.
2016-10-01
Capturing and controlling plasmons at buried interfaces with nanometre and femtosecond resolution has yet to be achieved and is critical for next generation plasmonic devices. Here we use light to excite plasmonic interference patterns at a buried metal-dielectric interface in a nanostructured thin film. Plasmons are launched from a photoexcited array of nanocavities and their propagation is followed via photon-induced near-field electron microscopy (PINEM). The resulting movie directly captures the plasmon dynamics, allowing quantification of their group velocity at ~0.3 times the speed of light, consistent with our theoretical predictions. Furthermore, we show that the light polarization and nanocavity design can be tailored to shape transient plasmonic gratings at the nanoscale. This work, demonstrating dynamical imaging with PINEM, paves the way for the femtosecond and nanometre visualization and control of plasmonic fields in advanced heterostructures based on novel two-dimensional materials such as graphene, MoS2, and ultrathin metal films.
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Accurate computational design of multipass transmembrane proteins.
Lu, Peilong; Min, Duyoung; DiMaio, Frank; Wei, Kathy Y; Vahey, Michael D; Boyken, Scott E; Chen, Zibo; Fallas, Jorge A; Ueda, George; Sheffler, William; Mulligan, Vikram Khipple; Xu, Wenqing; Bowie, James U; Baker, David
2018-03-02
The computational design of transmembrane proteins with more than one membrane-spanning region remains a major challenge. We report the design of transmembrane monomers, homodimers, trimers, and tetramers with 76 to 215 residue subunits containing two to four membrane-spanning regions and up to 860 total residues that adopt the target oligomerization state in detergent solution. The designed proteins localize to the plasma membrane in bacteria and in mammalian cells, and magnetic tweezer unfolding experiments in the membrane indicate that they are very stable. Crystal structures of the designed dimer and tetramer-a rocket-shaped structure with a wide cytoplasmic base that funnels into eight transmembrane helices-are very close to the design models. Our results pave the way for the design of multispan membrane proteins with new functions. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.
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Rewards and the evolution of cooperation in public good games.
Sasaki, Tatsuya; Uchida, Satoshi
2014-01-01
Properly coordinating cooperation is relevant for resolving public good problems, such as clean energy and environmental protection. However, little is known about how individuals can coordinate themselves for a certain level of cooperation in large populations of strangers. In a typical situation, a consensus-building process rarely succeeds, owing to a lack of face and standing. The evolution of cooperation in this type of situation is studied here using threshold public good games, in which cooperation prevails when it is initially sufficient, or otherwise it perishes. While punishment is a powerful tool for shaping human behaviours, institutional punishment is often too costly to start with only a few contributors, which is another coordination problem. Here, we show that whatever the initial conditions, reward funds based on voluntary contribution can evolve. The voluntary reward paves the way for effectively overcoming the coordination problem and efficiently transforms freeloaders into cooperators with a perceived small risk of collective failure.
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Paving the way for space gardens
NASA Technical Reports Server (NTRS)
Phillips, Patricia
1990-01-01
The Ecological Life Support System, a plant growth experiment now in its third year of closed chamber production at the NASA Kennedy Space Center, is discussed. Possible spin-off applications of hydrophonics experiments are noted. It is projected that long-term goals will include the integration of this garden system into the process of waste recycling for fertilization, air refreshment, and potable water recovery in a closed environment. The Biomass Production Chamber, a two-story bubble-shape steel biosphere modified from a Mercury/Gemini program attitude chamber provides a usable volume of 7.3 m x 3.6 m in diameter containing growing racks, piping for nutrient solutions, specialized lighting and sensors that provide information to the computers controlling the chamber and its functions. Computer programs provide highly sensitive monitoring and regulation of the system. Crops successfully harvested to date include dwarf wheat, lettuce, and soybeans.
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Wide modulation bandwidth terahertz detection in 130 nm CMOS technology
NASA Astrophysics Data System (ADS)
Nahar, Shamsun; Shafee, Marwah; Blin, Stéphane; Pénarier, Annick; Nouvel, Philippe; Coquillat, Dominique; Safwa, Amr M. E.; Knap, Wojciech; Hella, Mona M.
2016-11-01
Design, manufacturing and measurements results for silicon plasma wave transistors based wireless communication wideband receivers operating at 300 GHz carrier frequency are presented. We show the possibility of Si-CMOS based integrated circuits, in which by: (i) specific physics based plasma wave transistor design allowing impedance matching to the antenna and the amplifier, (ii) engineering the shape of the patch antenna through a stacked resonator approach and (iii) applying bandwidth enhancement strategies to the design of integrated broadband amplifier, we achieve an integrated circuit of the 300 GHz carrier frequency receiver for wireless wideband operation up to/over 10 GHz. This is, to the best of our knowledge, the first demonstration of low cost 130 nm Si-CMOS technology, plasma wave transistors based fast/wideband integrated receiver operating at 300 GHz atmospheric window. These results pave the way towards future large scale (cost effective) silicon technology based terahertz wireless communication receivers.
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Ren, Fang-Fang; Ang, Kah-Wee; Ye, Jiandong; Yu, Mingbin; Lo, Guo-Qiang; Kwong, Dim-Lee
2011-03-09
Bull's eye antennas are capable of efficiently collecting and concentrating optical signals into an ultrasmall area, offering an excellent solution to break the bottleneck between speed and photoresponse in subwavelength photodetectors. Here, we exploit the idea of split bull's eye antenna for a nanometer germanium photodetector operating at a standard communication wavelength of 1310 nm. The nontraditional plasmonic metal aluminum has been implemented in the resonant antenna structure fabricated by standard complementary metal-oxide-semiconductor (CMOS) processing. A significant enhancement in photoresponse could be achieved over the conventional bull's eye scheme due to an increased optical near-field in the active region. Moreover, with this novel antenna design the effective grating area could be significantly reduced without sacrificing device performance. This work paves the way for the future development of low-cost, high-density, and high-speed CMOS-compatible germanium-based optoelectronic devices.
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Controlled growth of CH3NH3PbI3 nanowires in arrays of open nanofluidic channels.
Spina, Massimo; Bonvin, Eric; Sienkiewicz, Andrzej; Náfrádi, Bálint; Forró, László; Horváth, Endre
2016-01-25
Spatial positioning of nanocrystal building blocks on a solid surface is a prerequisite for assembling individual nanoparticles into functional devices. Here, we report on the graphoepitaxial liquid-solid growth of nanowires of the photovoltaic compound CH3NH3PbI3 in open nanofluidic channels. The guided growth, visualized in real-time with a simple optical microscope, undergoes through a metastable solvatomorph formation in polar aprotic solvents. The presently discovered crystallization leads to the fabrication of mm(2)-sized surfaces composed of perovskite nanowires having controlled sizes, cross-sectional shapes, aspect ratios and orientation which have not been achieved thus far by other deposition methods. The automation of this general strategy paves the way towards fabrication of wafer-scale perovskite nanowire thin films well-suited for various optoelectronic devices, e.g. solar cells, lasers, light-emitting diodes and photodetectors.
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Potential Engineering of Fermi-Hubbard Systems using a Quantum Gas Microscope
NASA Astrophysics Data System (ADS)
Ji, Geoffrey; Mazurenko, Anton; Chiu, Christie; Parsons, Maxwell; Kanász-Nagy, Márton; Schmidt, Richard; Grusdt, Fabian; Demler, Eugene; Greif, Daniel; Greiner, Markus
2017-04-01
Arbitrary control of optical potentials has emerged as an important tool in manipulating ultracold atomic systems, especially when combined with the single-site addressing afforded by quantum gas microscopy. Already, experiments have used digital micromirror devices (DMDs) to initialize and control ultracold atomic systems in the context of studying quantum walks, quantum thermalization, and many-body localization. Here, we report on progress in using a DMD located in the image plane of a quantum gas microscope to explore static and dynamic properties of a 2D Fermi-Hubbard system. By projecting a large, ring-shaped anti-confining potential, we demonstrate entropy redistribution and controlled doping of the system. Moreover, we use the DMD to prepare localized holes, which upon release interact with and disrupt the surrounding spin environment. These techniques pave the way for controlled investigations of dynamics in the low-temperature phases of the Hubbard model.
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A changing climate of skepticism: The factors shaping climate change coverage in the US press.
Schmid-Petri, Hannah; Adam, Silke; Schmucki, Ivo; Häussler, Thomas
2017-05-01
Skepticism toward climate change has a long tradition in the United States. We focus on mass media as the conveyors of the image of climate change and ask: Is climate change skepticism still a characteristic of US print media coverage? If so, to what degree and in what form? And which factors might pave the way for skeptics entering mass media debates? We conducted a quantitative content analysis of US print media during one year (1 June 2012 to 31 May 2013). Our results show that the debate has changed: fundamental forms of climate change skepticism (such as denial of anthropogenic causes) have been abandoned in the coverage, being replaced by more subtle forms (such as the goal to avoid binding regulations). We find no evidence for the norm of journalistic balance, nor do our data support the idea that it is the conservative press that boosts skepticism.
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Superior plasmon absorption in iron-doped gold nanoparticles.
Amendola, Vincenzo; Saija, Rosalba; Maragò, Onofrio M; Iatì, Maria Antonia
2015-05-21
Although the excitation of localized surface plasmons is associated with enhanced scattering and absorption of incoming photons, only the latter is relevant for the efficient conversion of light into heat. Here we show that the absorption cross section of gold nanoparticles is sensibly increased when iron is included in the lattice as a substitutional dopant, i.e. in a gold-iron nanoalloy. Such an increase is size and shape dependent, with the best performance observed in nanoshells where a 90-190% improvement is found in a size range that is crucial for practical applications. Our findings are unexpected according to the common belief and previous experimental observations that alloys of Au with transition metals show a depressed plasmonic response. These results are promising for the design of efficient plasmonic converters of light into heat and pave the way to more in-depth investigations of the plasmonic properties in noble metal nanoalloys.
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Imaging and controlling plasmonic interference fields at buried interfaces
Lummen, Tom T. A.; Lamb, Raymond J.; Berruto, Gabriele; LaGrange, Thomas; Dal Negro, Luca; García de Abajo, F. Javier; McGrouther, Damien; Barwick, B.; Carbone, F.
2016-01-01
Capturing and controlling plasmons at buried interfaces with nanometre and femtosecond resolution has yet to be achieved and is critical for next generation plasmonic devices. Here we use light to excite plasmonic interference patterns at a buried metal–dielectric interface in a nanostructured thin film. Plasmons are launched from a photoexcited array of nanocavities and their propagation is followed via photon-induced near-field electron microscopy (PINEM). The resulting movie directly captures the plasmon dynamics, allowing quantification of their group velocity at ∼0.3 times the speed of light, consistent with our theoretical predictions. Furthermore, we show that the light polarization and nanocavity design can be tailored to shape transient plasmonic gratings at the nanoscale. This work, demonstrating dynamical imaging with PINEM, paves the way for the femtosecond and nanometre visualization and control of plasmonic fields in advanced heterostructures based on novel two-dimensional materials such as graphene, MoS2, and ultrathin metal films. PMID:27725670
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Jain, Aditya; Moitra, Parikshit; Koschny, Thomas; ...
2015-07-14
Artificially created surfaces or metasurfaces, composed of appropriately shaped subwavelength structures, namely, meta-atoms, control light at subwavelength scales. Historically, metasurfaces have used radiating metallic resonators as subwavelength inclusions. However, while resonant optical metasurfaces made from metal have been sufficiently subwavelength in the propagation direction, they are too lossy for many applications. Metasurfaces made out of radiating dielectric resonators have been proposed to solve the loss problem, but are marginally subwavelength at optical frequencies. We designed subwavelength resonators made out of nonradiating dielectrics. The resonators are decorated with appropriately placed scatterers, resulting in a meta-atom with an engineered electromagnetic response. Amore » metasurface that yields an electric response is fabricated, experimentally characterized, and a method to obtain a magnetic response at optical frequencies is theoretically demonstrated. In conclusion, this design methodology paves the way for metasurfaces that are simultaneously subwavelength and low loss.« less
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Balkrishnan, Rajesh; Chang, Jongwha; Patel, Isha; Yang, Fang; Merajver, Sofia D
2013-03-01
The need to focus healthcare expenditures on innovative and sustainable health systems that efficiently use existing effective therapies are the major drivers stimulating Comparative Effectiveness Research (CER) across the globe. Lack of adequate access and high cost of essential medicines and technologies in many countries increases morbidity and mortality and cost of care that forces people and families into poverty due to disability and out-of-pocket expenses. This review illustrates the potential of value-added global health care comparative effectiveness research in shaping health systems and health care delivery paradigms in the "global south". Enabling the development of effective CER systems globally paves the way for tangible local and regional definitions of equity in health care because CER fosters the sharing of critical assets, resources, skills, and capabilities and the development of collaborative of multi-sectorial frameworks to improve health outcomes and metrics globally.
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Ittiprasert, Wannaporn; Nene, Rahul; Miller, André; Raghavan, Nithya; Lewis, Fred; Hodgson, Jacob; Knight, Matty
2009-11-01
Schistosomes develop successfully in susceptible snails but are encapsulated and killed in resistant ones. Mechanism(s) shaping these outcomes involves the parasites ability to evade the snail's defenses. RNA analysis from resistant (BS-90), non-susceptible (LAC2) and susceptible (NMRI) juvenile Biomphalaria glabrata to Schistosoma mansoni revealed that stress-related genes, heat shock protein 70 (Hsp 70) and reverse transcriptase (RT), were dramatically co-induced early in susceptible snails, but not in resistant/non-susceptible ones. These transcripts were, however, down regulated upon exposure to irradiated parasites although penetration behavior of irradiated vs. normal parasites were the same, indicating that Hsp 70 and RT regulation was elicited by infection and not injury. Understanding molecular events involved in stress response transcriptional regulation of Hsp 70 in juvenile snails could pave a way towards the identification of genes involved in schistosome/snail interactions.
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NASA Astrophysics Data System (ADS)
Chi, X. F.
2017-10-01
This article investigated laser re-manufacturing technology application in mining industry. The research focused on green re-manufacturing of failure spur. Leave the main gear body stay intact after the dirty, rust, fatigue and injured part were removed completely before the green re-manufacturing procedure begin. The optimized laser operating parameters paved the road for excellent mechanical properties and comparatively neat shape which often means less post processing. The laser re-manufactured gear surface was systematically examined, including microstructure observation, and dry wear test at room temperature. The test results were compared with new gear surface and used but not broken gear surface. Finally, it proved that the green re-manufactured gear surface displayed best comprehensive mechanical properties, followed the new gear surface. The resistance of dry wear properties of used but not broken gear surface was the worst.
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NASA Astrophysics Data System (ADS)
Bonilla, L. L.; Carretero, M.; Terragni, F.; Birnir, B.
2016-08-01
Angiogenesis is a multiscale process by which blood vessels grow from existing ones and carry oxygen to distant organs. Angiogenesis is essential for normal organ growth and wounded tissue repair but it may also be induced by tumours to amplify their own growth. Mathematical and computational models contribute to understanding angiogenesis and developing anti-angiogenic drugs, but most work only involves numerical simulations and analysis has lagged. A recent stochastic model of tumour-induced angiogenesis including blood vessel branching, elongation, and anastomosis captures some of its intrinsic multiscale structures, yet allows one to extract a deterministic integropartial differential description of the vessel tip density. Here we find that the latter advances chemotactically towards the tumour driven by a soliton (similar to the famous Korteweg-de Vries soliton) whose shape and velocity change slowly. Analysing these collective coordinates paves the way for controlling angiogenesis through the soliton, the engine that drives this process.
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DOT National Transportation Integrated Search
2013-03-01
Incremental increases in paved shoulder widths have been studied and are shown in the Highway Safety Manual (HSM). While each incremental increase in shoulder width is beneficial, there is evidence that suggests the relationship between safety improv...
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40 CFR 443.21 - Specialized definitions.
Code of Federal Regulations, 2011 CFR
2011-07-01
... PRETREATMENT STANDARDS FOR NEW SOURCES FOR THE PAVING AND ROOFING MATERIALS (TARS AND ASPHALT) POINT SOURCE CATEGORY Asphalt Concrete Subcategory § 443.21 Specialized definitions. For the purpose of this subpart: (a..., intermediate product, by-product, or product used in or resulting from the production of paving asphalt...
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Project 0-6749 : feasibility study of two-lift concrete paving : [project summary].
DOT National Transportation Integrated Search
2013-08-01
Two-lift concrete paving (2LCP) involves placing two layers of : concrete (wet-on-wet) instead of a single homogeneous layer, as is : typically done in the United States. 2LCP offers the opportunity to optimize the use of local aggregates and : recyc...
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Best practices for the design, evaluation and quality control of high percentage RAP mixes.
DOT National Transportation Integrated Search
2015-12-01
Placing reclaimed asphalt pavement (RAP) back on the roadway is a common and popular technique in the paving industry. There are always challenges associated with this type of recycling, especially when the RAP content in the newly paved asphalt mix ...
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CHARACTERIZATION OF MUD/DIRT CARRYOUT ONTO PAVED ROADS FROM CONSTRUCTION AND DEMOLITION ACTIVITIES
The report characterizes fugitive dust generated by vehicular traffic on paved streets and highways resulting from mud/dirt carryout from unpaved areas as a primary source of PM-10 (particles = or < 10 micrometers in aerodynamic diameter), and evaluates three technologies for eff...
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Lavin, Matt; Brummer, Tyler J; Quire, Ryan; Maxwell, Bruce D; Rew, Lisa J
2013-01-01
Fire is thought to profoundly change the ecology of the sagebrush steppe. The Idaho National Laboratory provides an ideal setting to compare the effects of fire and physical disturbance on plant diversity in high-native-cover sagebrush steppe. Seventy-eight 1-hectare transects were established along paved, green-striped, gravel, and two-track roads, in overgrazed rangeland, and within sagebrush steppe involving different fire histories. Transects were sampled for the diversity and abundance of all vascular plants. Alpha, beta, and phylogenetic beta diversity were analyzed as a response to fire and physical disturbance. Postfire vegetation readily rebounds to prefire levels of alpha plant diversity. Physical disturbance, in contrast, strongly shapes patterns of alpha, beta, and especially phylogenetic beta diversity much more profoundly than fire disturbance. If fire is a concern in the sagebrush steppe then the degree of physical-disturbance should be more so. This finding is probably not specific to the study area but applicable to the northern and eastern portions of the sagebrush biome, which is characterized by a pulse of spring moisture and cold mean minimum winter temperatures. The distinction of sagebrush steppe from Great Basin sagebrush should be revised especially with regard to reseeding efforts and the control of annual grasses. PMID:23789073
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Understanding nonlinear vibration behaviours in high-power ultrasonic surgical devices
Mathieson, Andrew; Cardoni, Andrea; Cerisola, Niccolò; Lucas, Margaret
2015-01-01
Ultrasonic surgical devices are increasingly used in oral, craniofacial and maxillofacial surgery to cut mineralized tissue, offering the surgeon high accuracy with minimal risk to nerve and vessel tissue. Power ultrasonic devices operate in resonance, requiring their length to be a half-wavelength or multiple-half-wavelength. For bone surgery, devices based on a half-wavelength have seen considerable success, but longer multiple-half-wavelength endoscopic devices have recently been proposed to widen the range of surgeries. To provide context for these developments, some examples of surgical procedures and the associated designs of ultrasonic cutting tips are presented. However, multiple-half-wavelength components, typical of endoscopic devices, have greater potential to exhibit nonlinear dynamic behaviours that have a highly detrimental effect on device performance. Through experimental characterization of the dynamic behaviour of endoscopic devices, it is demonstrated how geometrical features influence nonlinear dynamic responses. Period doubling, a known route to chaotic behaviour, is shown to be significantly influenced by the cutting tip shape, whereas the cutting tip has only a limited effect on Duffing-like responses, particularly the shape of the hysteresis curve, which is important for device stability. These findings underpin design, aiming to pave the way for a new generation of ultrasonic endoscopic surgical devices. PMID:27547081
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Lavin, Matt; Brummer, Tyler J; Quire, Ryan; Maxwell, Bruce D; Rew, Lisa J
2013-06-01
Fire is thought to profoundly change the ecology of the sagebrush steppe. The Idaho National Laboratory provides an ideal setting to compare the effects of fire and physical disturbance on plant diversity in high-native-cover sagebrush steppe. Seventy-eight 1-hectare transects were established along paved, green-striped, gravel, and two-track roads, in overgrazed rangeland, and within sagebrush steppe involving different fire histories. Transects were sampled for the diversity and abundance of all vascular plants. Alpha, beta, and phylogenetic beta diversity were analyzed as a response to fire and physical disturbance. Postfire vegetation readily rebounds to prefire levels of alpha plant diversity. Physical disturbance, in contrast, strongly shapes patterns of alpha, beta, and especially phylogenetic beta diversity much more profoundly than fire disturbance. If fire is a concern in the sagebrush steppe then the degree of physical-disturbance should be more so. This finding is probably not specific to the study area but applicable to the northern and eastern portions of the sagebrush biome, which is characterized by a pulse of spring moisture and cold mean minimum winter temperatures. The distinction of sagebrush steppe from Great Basin sagebrush should be revised especially with regard to reseeding efforts and the control of annual grasses.
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Triboelectrification-Enabled Self-Powered Data Storage.
Kuang, Shuang Yang; Zhu, Guang; Wang, Zhong Lin
2018-02-01
Data storage by any means usually requires an electric driving power for writing or reading. A novel approach for self-powered, triboelectrification-enabled data storage (TEDS) is presented. Data are incorporated into a set of metal-based surface patterns. As a probe slides across the patterned surface, triboelectrification between the scanning probe and the patterns produces alternatively varying voltage signal in quasi-square wave. The trough and crest of the quasi-square wave signal are coded as binary bits of "0" and "1," respectively, while the time span of the trough and the crest is associated with the number of bits. The storage of letters and sentences is demonstrated through either square-shaped or disc-shaped surface patterns. Based on experimental data and numerical calculation, the theoretically predicted maximum data storage density could reach as high as 38.2 Gbit in -2 . Demonstration of real-time data retrieval is realized with the assistance of software interface. For the TEDS reported in this work, the measured voltage signal is self-generated as a result of triboelectrification without the reliance on an external power source. This feature brings about not only low power consumption but also a much more simplified structure. Therefore, this work paves a new path to a unique approach of high-density data storage that may have widespread applications.
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The Importance of Patient-Specific Factors for Hepatic Drug Response and Toxicity
Lauschke, Volker M.; Ingelman-Sundberg, Magnus
2016-01-01
Responses to drugs and pharmacological treatments differ considerably between individuals. Importantly, only 50%–75% of patients have been shown to react adequately to pharmacological interventions, whereas the others experience either a lack of efficacy or suffer from adverse events. The liver is of central importance in the metabolism of most drugs. Because of this exposed status, hepatotoxicity is amongst the most common adverse drug reactions and hepatic liabilities are the most prevalent reason for the termination of development programs of novel drug candidates. In recent years, more and more factors were unveiled that shape hepatic drug responses and thus underlie the observed inter-individual variability. In this review, we provide a comprehensive overview of different principle mechanisms of drug hepatotoxicity and illustrate how patient-specific factors, such as genetic, physiological and environmental factors, can shape drug responses. Furthermore, we highlight other parameters, such as concomitantly prescribed medications or liver diseases and how they modulate drug toxicity, pharmacokinetics and dynamics. Finally, we discuss recent progress in the field of in vitro toxicity models and evaluate their utility in reflecting patient-specific factors to study inter-individual differences in drug response and toxicity, as this understanding is necessary to pave the way for a patient-adjusted medicine. PMID:27754327
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Liu, W; Liu, Y; Guo, T; Hu, C; Luo, H; Zhang, L; Shi, S; Cai, T; Ding, Y; Jin, Y
2013-01-01
Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basis of the preliminary results, we observed the contrary effect of canonical Wnt signaling on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in the different culture environment. Furthermore, we found that the expression level of miR-17 was also varied with the change in the culture environment. Therefore, we hypothesized that miR-17 and canonical Wnt signaling may have potential interactions, particularly the inner regulation relationship in different microenvironments. In this paper, we observed that canonical Wnt signaling promoted osteogenesis of PDLSCs in the fully culture medium, while inhibited it in the osteogenic differentiation medium. Interestingly, alteration in the expression level of endogenous miR-17 could partially reverse the different effect of canonical Wnt signaling. Furthermore, the role of miR-17 was because of its target gene TCF3 (transcription factor 3), a key transcription factor of canonical Wnt pathway. Overexpression of TCF3 attenuated the effect of miR-17 on modulating canonical Wnt signaling. Finally, we elucidated that TCF3 enhanced osteogenesis both in vitro and in vivo. In brief, the different level of miR-17 was the main cause of the different effect of canonical Wnt signaling, and TCF3 was the crucial node of miR-17–canonial Wnt signaling regulation loop. This understanding of microRNAs regulating signaling pathways in different microenvironments may pave the way for fine-tuning the process of osteogenesis in bone-related disorders. PMID:23492770
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Liu, W; Liu, Y; Guo, T; Hu, C; Luo, H; Zhang, L; Shi, S; Cai, T; Ding, Y; Jin, Y
2013-03-14
Wnt signaling pathways are a highly conserved pathway, which plays an important role from the embryonic development to bone formation. The effect of Wnt pathway on osteogenesis relies on their cellular environment and the expression of target genes. However, the molecular mechanism of that remains unclear. On the basis of the preliminary results, we observed the contrary effect of canonical Wnt signaling on osteogenic differentiation of periodontal ligament stem cells (PDLSCs) in the different culture environment. Furthermore, we found that the expression level of miR-17 was also varied with the change in the culture environment. Therefore, we hypothesized that miR-17 and canonical Wnt signaling may have potential interactions, particularly the inner regulation relationship in different microenvironments. In this paper, we observed that canonical Wnt signaling promoted osteogenesis of PDLSCs in the fully culture medium, while inhibited it in the osteogenic differentiation medium. Interestingly, alteration in the expression level of endogenous miR-17 could partially reverse the different effect of canonical Wnt signaling. Furthermore, the role of miR-17 was because of its target gene TCF3 (transcription factor 3), a key transcription factor of canonical Wnt pathway. Overexpression of TCF3 attenuated the effect of miR-17 on modulating canonical Wnt signaling. Finally, we elucidated that TCF3 enhanced osteogenesis both in vitro and in vivo. In brief, the different level of miR-17 was the main cause of the different effect of canonical Wnt signaling, and TCF3 was the crucial node of miR-17-canonial Wnt signaling regulation loop. This understanding of microRNAs regulating signaling pathways in different microenvironments may pave the way for fine-tuning the process of osteogenesis in bone-related disorders.
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PAVES: A Presentation Strategy for Beginning Presenters in Inclusive Environments
ERIC Educational Resources Information Center
Combes, Bertina H.; Walker, Michelle; Harrell, Pamela Esprivalo; Tyler-Wood, Tandra
2008-01-01
Public speaking will continue to be an unsettling experience for some students, including those with disabilities. Experts have suggested several reasons for fearing public speaking; adequate preparation and practice can alleviate most of them. Using the PAVES (Posture, Attitude, Voice, Eye Contact, Smile) strategy described in this article can…
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17. CAPE COD AIR STATION PAVE PAWS FACILITY AERIAL VIEW ...
17. CAPE COD AIR STATION PAVE PAWS FACILITY AERIAL VIEW WITH PROJECT NEARING COMPLETION. VIEW SHOWS "A" FACE (LEFT) AND "B" FACE OF RADAR ARRAY SYSTEM. NOTE THAT NORTH IS GENERALLY TO RIGHT OF VIEW. - Cape Cod Air Station, Massachusetts Military Reservation, Sandwich, Barnstable County, MA
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47. CAPE COD AIR STATION PAVE PAWS FACILITY AERIAL VIEW ...
47. CAPE COD AIR STATION PAVE PAWS FACILITY AERIAL VIEW OF "A" FACE (LEFT) WITH CLEANING SYSTEM INSTALLED (NOW REMOVED) AND "B" FACE (RIGHT) WITH CONSTRUCTION CRANE IN USE. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA
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Distinguishing Signatures of Multipathway Conformational Transitions
NASA Astrophysics Data System (ADS)
Pierse, Christopher A.; Dudko, Olga K.
2017-02-01
The folding and binding of biomolecules into functional conformations are thought to be commonly mediated by multiple pathways rather than a unique route. Yet even in experiments where one can "see" individual conformational transitions, their stochastic nature generally precludes one from determining whether the transitions occurred through one or multiple pathways. We establish model-free, observable signatures in the response of macromolecules to force that unambiguously identify multiple pathways—even when the pathways themselves cannot be resolved. The unified analytical description reveals that, through multiple pathways, the response of molecules to external forces can be shaped in diverse ways, resulting in a rich design space for a tailored biological function already at the single-molecule level.
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Definition of RNA Polymerase II CoTC Terminator Elements in the Human Genome
Nojima, Takayuki; Dienstbier, Martin; Murphy, Shona; Proudfoot, Nicholas J.; Dye, Michael J.
2013-01-01
Summary Mammalian RNA polymerase II (Pol II) transcription termination is an essential step in protein-coding gene expression that is mediated by pre-mRNA processing activities and DNA-encoded terminator elements. Although much is known about the role of pre-mRNA processing in termination, our understanding of the characteristics and generality of terminator elements is limited. Whereas promoter databases list up to 40,000 known and potential Pol II promoter sequences, fewer than ten Pol II terminator sequences have been described. Using our knowledge of the human β-globin terminator mechanism, we have developed a selection strategy for mapping mammalian Pol II terminator elements. We report the identification of 78 cotranscriptional cleavage (CoTC)-type terminator elements at endogenous gene loci. The results of this analysis pave the way for the full understanding of Pol II termination pathways and their roles in gene expression. PMID:23562152
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What determines human body odour?
Hamada, Kaoru; Haruyama, Sanehito; Yamaguchi, Takashi; Yamamoto, Kayo; Hiromasa, Kana; Yoshioka, Manabu; Nishio, Daisuke; Nakamura, Motonobu
2014-05-01
Human body odour and earwax type are genetically dependent on a single-nucleotide polymorphism (SNP) located in the ABCC11 gene. So far, it still remains to be clear how SNP in the ABCC11 gene is associated with human malodour. In a recent issue of Experimental Dermatology, Baumann et al. propose one of the underlying molecular pathways. Although one of the amino acid conjugated of the odorants, Cys-Gly-3-methyl-3-sulfanylhexanol (3M3SH), was not taken up by the transporter ABCC11, glutathione conjugate of 3MSH (SG-3MSH) was transported by ABCC11. Moreover, SG-3MSH was processed to 3M3SH by γ-glutamyl-transferase 1 (GGT1), which was abundantly expressed in apocrine sweat glands. These findings may pave a way for the pharmacogenetics of human body odour and the development of innovative deodorant products. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
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Nitric oxide-sphingolipid interplays in plant signalling: a new enigma from the Sphinx?
Guillas, Isabelle; Puyaubert, Juliette; Baudouin, Emmanuel
2013-01-01
Nitric oxide (NO) emerged as one of the major signaling molecules operating during plant development and plant responses to its environment. Beyond the identification of the direct molecular targets of NO, a series of studies considered its interplay with other actors of signal transduction and the integration of NO into complex signaling networks. Beside the close relationships between NO and calcium or phosphatidic acid signaling pathways that are now well-established, recent reports paved the way for interplays between NO and sphingolipids (SLs). This mini-review summarizes our current knowledge of the influence NO and SLs might exert on each other in plant physiology. Based on comparisons with examples from the animal field, it further indicates that, although SL–NO interplays are common features in signaling networks of eukaryotic cells, the underlying mechanisms and molecular targets significantly differ. PMID:24062754
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Alea, Mileidys Perez; Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Fuxe, Kjell; Garriga, Pere
2011-08-15
Muscarinic acetylcholine receptors expression and signaling in the human Jurkat T cell line were investigated. Semiquantitative real-time PCR and radioligand binding studies, using a wide set of antagonist compounds, showed the co-existence of M(3), M(4), and M(5) subtypes. Stimulation of these subpopulations caused a concentration and time- dependent activation of second messengers and ERK signaling pathways, with a major contribution of the M(3) subtype in a G(q/11)-mediated response. In addition, we found that T-cell stimulation leads to increased expression of M(3) and M(5) both at transcriptional and protein levels in a PLC/PKCθ dependent manner. Our data clarifies the functional role of AChR subtypes in Jurkat cells and pave the way to future studies on the potential cross-talk among these subpopulations and their regulation of T lymphocytes immune function. Copyright © 2011 Elsevier B.V. All rights reserved.
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Organization of the Drosophila larval visual circuit
Gendre, Nanae; Neagu-Maier, G Larisa; Fetter, Richard D; Schneider-Mizell, Casey M; Truman, James W; Zlatic, Marta; Cardona, Albert
2017-01-01
Visual systems transduce, process and transmit light-dependent environmental cues. Computation of visual features depends on photoreceptor neuron types (PR) present, organization of the eye and wiring of the underlying neural circuit. Here, we describe the circuit architecture of the visual system of Drosophila larvae by mapping the synaptic wiring diagram and neurotransmitters. By contacting different targets, the two larval PR-subtypes create two converging pathways potentially underlying the computation of ambient light intensity and temporal light changes already within this first visual processing center. Locally processed visual information then signals via dedicated projection interneurons to higher brain areas including the lateral horn and mushroom body. The stratified structure of the larval optic neuropil (LON) suggests common organizational principles with the adult fly and vertebrate visual systems. The complete synaptic wiring diagram of the LON paves the way to understanding how circuits with reduced numerical complexity control wide ranges of behaviors.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Di, Jun; Chen, Chao; Yang, Shi -Ze
Photocatalytic solar energy conversion is a clean technology for producing renewable energy sources, but its efficiency is greatly hindered by the kinetically sluggish oxygen evolution reaction. Herein, confined defects in atomically-thin BiOCl nanosheets were created to serve as a remarkable platform to explore the relationship between defects and photocatalytic activity. Surface defects can be clearly observed on atomically-thin BiOCl nanosheets from scanning transmission electron microscopy images. Theoretical/experimental results suggest that defect engineering increased states of density and narrowed the band gap. With combined effects from defect induced shortened hole migratory paths and creation of coordination-unsaturated active atoms with dangling bonds,more » defect-rich BiOCl nanosheets displayed 3 and 8 times higher photocatalytic activity towards oxygen evolution compared with atomically-thin BiOCl nanosheets and bulk BiOCl, respectively. As a result, this successful application of defect engineering will pave a new pathway for improving photocatalytic oxygen evolution activity of other materials.« less
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Paving pathways: Brazil's implementation of a national human papillomavirus immunization campaign.
Baker, Misha L; Figueroa-Downing, Daniella; Chiang, Ellen Dias De Oliveira; Villa, Luisa; Baggio, Maria Luiza; Eluf-Neto, José; Bednarczyk, Robert A; Evans, Dabney P
2015-08-01
In 2014, Brazil introduced an HPV immunization program for girls 9-13 years of age as part of the Unified Health System's (SUS) National Immunization Program. The first doses were administered in March 2014; the second ones, in September 2014. In less than 3 months more than 3 million girls received the first dose of quadrivalent HPV vaccine, surpassing the target rate of 80%. This paper examines three elements that may influence the program's long-term success in Brazil: sustaining effective outreach, managing a large technology-transfer collaboration, and developing an electronic immunization registry, with a focus on the State of São Paulo. If these three factors are managed, the Government of Brazil is primed to serve as a model of success for other countries interested in implementing a national HPV vaccination program to decrease HPV-related morbidity and mortality.
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Su, Fei; Xu, Ping
2014-01-29
Microbial strains with high substrate efficiency and excellent environmental tolerance are urgently needed for the production of platform bio-chemicals. Bacillus coagulans has these merits; however, little genetic information is available about this species. Here, we determined the genome sequences of five B. coagulans strains, and used a comparative genomic approach to reconstruct the central carbon metabolism of this species to explain their fermentation features. A novel xylose isomerase in the xylose utilization pathway was identified in these strains. Based on a genome-wide positive selection scan, the selection pressure on amino acid metabolism may have played a significant role in the thermal adaptation. We also researched the immune systems of B. coagulans strains, which provide them with acquired resistance to phages and mobile genetic elements. Our genomic analysis provides comprehensive insights into the genetic characteristics of B. coagulans and paves the way for improving and extending the uses of this species.
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Su, Fei; Xu, Ping
2014-01-01
Microbial strains with high substrate efficiency and excellent environmental tolerance are urgently needed for the production of platform bio-chemicals. Bacillus coagulans has these merits; however, little genetic information is available about this species. Here, we determined the genome sequences of five B. coagulans strains, and used a comparative genomic approach to reconstruct the central carbon metabolism of this species to explain their fermentation features. A novel xylose isomerase in the xylose utilization pathway was identified in these strains. Based on a genome-wide positive selection scan, the selection pressure on amino acid metabolism may have played a significant role in the thermal adaptation. We also researched the immune systems of B. coagulans strains, which provide them with acquired resistance to phages and mobile genetic elements. Our genomic analysis provides comprehensive insights into the genetic characteristics of B. coagulans and paves the way for improving and extending the uses of this species. PMID:24473268
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Wichuk, Kristine; Brynjólfsson, Sigurður; Fu, Weiqi
2014-01-01
We recently evaluated the relationship between abiotic environmental stresses and lutein biosynthesis in the green microalga Dunaliella salina and suggested a rational design of stress-driven adaptive evolution experiments for carotenoids production in microalgae. Here, we summarize our recent findings regarding the biotechnological production of carotenoids from microalgae and outline emerging technology in this field. Carotenoid metabolic pathways are characterized in several representative algal species as they pave the way for biotechnology development. The adaptive evolution strategy is highlighted in connection with enhanced growth rate and carotenoid metabolism. In addition, available genetic modification tools are described, with emphasis on model species. A brief discussion on the role of lights as limiting factors in carotenoid production in microalgae is also included. Overall, our analysis suggests that light-driven metabolism and the photosynthetic efficiency of microalgae in photobioreactors are the main bottlenecks in enhancing biotechnological potential of carotenoid production from microalgae.
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Transcriptome analyses of the Giardia lamblia life cycle
Birkeland, Shanda R.; Preheim, Sarah P.; Davids, Barbara J.; Cipriano, Michael J.; Palm, Daniel; Reiner, David S.; Svärd, Staffan G.; Gillin, Frances D.; McArthur, Andrew G.
2010-01-01
We quantified mRNA abundance from 10 stages in the Giardia lamblia life cycle in vitro using Serial Analysis of Gene Expression (SAGE). 163 abundant transcripts were expressed constitutively. 71 transcripts were upregulated specifically during excystation and 42 during encystation. Nonetheless, the transcriptomes of cysts and trophozoites showed major differences. SAGE detected co-expressed clusters of 284 transcripts differentially expressed in cysts and excyzoites and 287 transcripts in vegetative trophozoites and encysting cells. All clusters included known genes and pathways as well as proteins unique to Giardia or diplomonads. SAGE analysis of the Giardia life cycle identified a number of kinases, phosphatases, and DNA replication proteins involved in excystation and encystation, which could be important for examining the roles of cell signaling in giardial differentiation. Overall, these data pave the way for directed gene discovery and a better understanding of the biology of Giardia lamblia. PMID:20570699
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Journet, Agnès; Klein, Gérard; Brugière, Sabine; Vandenbrouck, Yves; Chapel, Agnès; Kieffer, Sylvie; Bruley, Christophe; Masselon, Christophe; Aubry, Laurence
2012-01-01
The cellular slime mold Dictyostelium discoideum is a soil-living eukaryote, which feeds on microorganisms engulfed by phagocytosis. Axenic laboratory strains have been produced that are able to use liquid growth medium internalized by macropinocytosis as the source of food. To better define the macropinocytosis process, we established the inventory of proteins associated with this pathway using mass spectrometry-based proteomics. Using a magnetic purification procedure and high-performance LC-MS/MS proteome analysis, a list of 2108 non-redundant proteins was established, of which 24% featured membrane-spanning domains. Bioinformatics analyses indicated that the most abundant proteins were linked to signaling, vesicular trafficking and the cytoskeleton. The present repertoire validates our purification method and paves the way for a future proteomics approach to study the dynamics of macropinocytosis. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Real-life helping behaviours in North America: A genome-wide association approach
Fieder, Martin
2018-01-01
In humans, prosocial behaviour is essential for social functioning. Twin studies suggest this distinct human trait to be partly hardwired. In the last decade research on the genetics of prosocial behaviour focused on neurotransmitters and neuropeptides, such as oxytocin, dopamine, and their respective pathways. Recent trends towards large scale medical studies targeting the genetic basis of complex diseases such as Alzheimer’s disease and schizophrenia pave the way for new directions also in behavioural genetics. Based on data from 10,713 participants of the American Health and Retirement Study we estimated heritability of helping behaviour–its total variance explained by 1.2 million single nucleotide polymorphisms–to be 11%. Both, fixed models and mixed linear models identified rs11697300, an intergene variant on chromosome 20, as a candidate variant moderating this particular helping behaviour. We assume that this so far undescribed area is worth further investigation in association with human prosocial behaviour. PMID:29324852
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Ultrahigh Oxidation Resistance and High Electrical Conductivity in Copper-Silver Powder.
Li, Jiaxiang; Li, Yunping; Wang, Zhongchang; Bian, Huakang; Hou, Yuhang; Wang, Fenglin; Xu, Guofu; Liu, Bin; Liu, Yong
2016-12-22
The electrical conductivity of pure Cu powder is typically deteriorated at elevated temperatures due to the oxidation by forming non-conducting oxides on surface, while enhancing oxidation resistance via alloying is often accompanied by a drastic decline of electrical conductivity. Obtaining Cu powder with both a high electrical conductivity and a high oxidation resistance represents one of the key challenges in developing next-generation electrical transferring powder. Here, we fabricate a Cu-Ag powder with a continuous Ag network along grain boundaries of Cu particles and demonstrate that this new structure can inhibit the preferential oxidation in grain boundaries at elevated temperatures. As a result, the Cu-Ag powder displays considerably high electrical conductivity and high oxidation resistance up to approximately 300 °C, which are markedly higher than that of pure Cu powder. This study paves a new pathway for developing novel Cu powders with much enhanced electrical conductivity and oxidation resistance in service.
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Li, Xin; Lan, Shi-Ming; Zhu, Zhong-Ping; Zhang, Chang; Zeng, Guang-Ming; Liu, Yun-Guo; Cao, Wei-Cheng; Song, Biao; Yang, Hong; Wang, Sheng-Fan; Wu, Shao-Hua
2018-04-20
Sulfate-reducing bacteria (SRB), a group of anaerobic prokaryotes, can use sulfur species as a terminal electron acceptor for the oxidation of organic compounds. They not only have significant ecological functions, but also play an important role in bioremediation of contaminated sites. Although numerous studies on metabolism and applications of SRB have been conducted, they still remain incompletely understood and even controversial. Fully understanding the metabolism of SRB paves the way for allowing the microorganisms to provide more beneficial services in bioremediation. Here we review progress in bioenergetics mechanisms and application of SRB including: (1) electron acceptors and donors for SRB; (2) pathway for sulfate reduction; (3) electron transfer in sulfate reduction; (4) application of SRB for economical and concomitant treatment of heavy metal, organic contaminants and sulfates. Moreover, current knowledge gaps and further research needs are identified. Copyright © 2018 Elsevier Inc. All rights reserved.
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Built environment analysis for road traffic hotspot locations in Moshi, Tanzania.
Waldon, Meredith; Ibingira, Treasure Joelson; de Andrade, Luciano; Mmbaga, Blandina T; Vissoci, João Ricardo N; Mvungi, Mark; Staton, Catherine A
2018-02-08
Road traffic injuries (RTIs) cause significant morbidity and mortality in low- and middle-income countries. Investigation of high risk areas for RTIs is needed to guide improvements. This study provides built environmental analysis of road traffic crash hotspots within Moshi, Tanzania. Spatial analysis of police data identified 36 hotspots. Qualitative comparative analysis revealed 40% of crash sites were on local roads without night lighting and increased motorcycle density. Paved narrow roads represented 26% of hotspots and 13% were unpaved roads with uneven roadsides. Roadside unevenness was more predominate in low risk [n = 19, (90.5%)] than high risk sites [n = 7 (46.7%)]. Both low [n = 6 (28.6%)] and high risk [n = 1 (6.7%)] sites had minimal signage. All sites had informal pedestrian pathways. Little variability between risk sites suggests hazardous conditions are widespread. Findings suggest improvement in municipal infrastructure, signage and enforcement is needed to reduce RTI burden.
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The 2015 Nobel Prize in Chemistry The Discovery of Essential Mechanisms that Repair DNA Damage.
Lindahl, Tomas; Modrich, Paul; Sancar, Aziz
2016-01-01
The Royal Swedish Academy awarded the Nobel Prize in Chemistry for 2015 to Tomas Lindahl, Paul Modrich and Aziz Sancar for their discoveries in fundamental mechanisms of DNA repair. This pioneering research described three different essential pathways that correct DNA damage, safeguard the integrity of the genetic code to ensure its accurate replication through generations, and allow proper cell division. Working independently of each other, Tomas Lindahl, Paul Modrich and Aziz Sancar delineated the mechanisms of base excision repair, mismatch repair and nucleotide excision repair, respectively. These breakthroughs challenged and dismissed the early view that the DNA molecule was very stable, paving the way for the discovery of human hereditary diseases associated with distinct DNA repair deficiencies and a susceptibility to cancer. It also brought a deeper understanding of cancer as well as neurodegenerative or neurological diseases, and let to novel strategies to treat cancer.
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Alvarez, Santiago; Menjón, Babil; Falceto, Andrés; Casanova, David; Alemany, Pere
2014-11-17
To each coordination polyhedron we can associate a normalized coordination polyhedron that retains the angular orientation of the central atom-ligand bonds but has all the vertices at the same distance from the center. The use of shape measures of these normalized coordination polyhedra provides a simple and efficient way of discriminating angular and bond distance distortions from an ideal polyhedron. In this paper we explore the applications of such an approach to analyses of several stereochemical problems. Among others, we discuss how to discern the off-center displacement of the metal from metal-ligand bond shortening distortions in families of square planar biscarbene and octahedral dioxo complexes. The normalized polyhedron approach is also shown to be very useful to understand stereochemical trends with the help of shape maps, minimal distortion pathways, and ligand association/dissociation pathways, illustrated by the Berry and anti Berry distortions of triple-bonded [X≡ML4] complexes, the square pyramidal geometries of Mo coordination polyhedra in oxido-reductases, the coordination geometries of actinyl complexes, and the tetrahedricity of heavy atom-substituted carbon centers.
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Complex patchy colloids shaped from deformable seed particles through capillary interactions.
Meester, V; Kraft, D J
2018-02-14
We investigate the mechanisms underlying the reconfiguration of random aggregates of spheres through capillary interactions, the so-called "colloidal recycling" method, to fabricate a wide variety of patchy particles. We explore the influence of capillary forces on clusters of deformable seed particles by systematically varying the crosslink density of the spherical seeds. Spheres with a poorly crosslinked polymer network strongly deform due to capillary forces and merge into large spheres. With increasing crosslink density and therefore rigidity, the shape of the spheres is increasingly preserved during reconfiguration, yielding patchy particles of well-defined shape for up to five spheres. In particular, we find that the aspect ratio between the length and width of dumbbells, L/W, increases with the crosslink density (cd) as L/W = B - A·exp(-cd/C). For clusters consisting of more than five spheres, the particle deformability furthermore determines the patch arrangement of the resulting particles. The reconfiguration pathway of clusters of six densely or poorly crosslinked seeds leads to octahedral and polytetrahedral shaped patchy particles, respectively. For seven particles several geometries were obtained with a preference for pentagonal dipyramids by the rigid spheres, while the soft spheres do rarely arrive in these structures. Even larger clusters of over 15 particles form non-uniform often aspherical shapes. We discuss that the reconfiguration pathway is largely influenced by confinement and geometric constraints. The key factor which dominates during reconfiguration depends on the deformability of the spherical seed particles.
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Structural insights of a PI3K/mTOR dual inhibitor with the morpholino-triazine scaffold
NASA Astrophysics Data System (ADS)
Takeda, Takako; Wang, Yanli; Bryant, Stephen H.
2016-04-01
Stimulation of the PI3K/Akt/mTOR pathway, which controls cell proliferation and growth, is often observed in cancer cell. Inhibiting both PI3K and mTOR in this pathway can switch off Akt activation and hence, plays a powerful role for modulating this pathway. PKI-587, a drug containing the structure of morpholino-triazines, shows a dual and nano-molar inhibition activity and is currently in clinical trial. To provide an insight into the mechanism of this dual inhibition, pharmacophore and QSAR models were developed in this work using compounds based on the morpholino-triazines scaffold, followed by a docking study. Pharmacophore model suggested the mechanism of the inhibition of PI3Kα and mTOR by the compounds were mostly the same, which was supported by the docking study showing similar docking modes. The analysis also suggested the importance of the flat plane shape of the ligands, the space surrounding the ligands in the binding pocket, and the slight difference in the shape of the binding sites between PI3Kα and mTOR.
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NSCLC and HER2: between lights and shadows.
Ricciardi, Giuseppina Rosaria Rita; Russo, Alessandro; Franchina, Tindara; Ferraro, Giuseppa; Zanghì, Mariangela; Picone, Antonio; Scimone, Antonino; Adamo, Vincenzo
2014-12-01
The therapeutic landscape of non-small-cell lung cancer (NSCLC) has dramatically changed in the last few years with the introduction of molecularly targeted agents, leading to unprecedented results in lung tumors with a paradigmatic shift from a "one size fits all" approach to an histologic and molecular-based approach. The discovery of epidermal growth factor receptor (EGFR) mutations in NSCLC in 2004 and the marked response to the EGFR tyrosine kinase inhibitor gefitinib, in a small subset of patients harboring these genetic abnormalities, stimulated the study of other kinase mutants involvement in NSCLC. The incredible story of ALK rearranged tumors, with the rapid Food and Drug Administration approval of Crizotinib after only 4 years from the discovery of EML4-ALK translocation in NSCLC, has profoundly influenced the concept of drug development in NSCLC, paving the way to a novel series of molecularly selected studies with specific inhibitors. The identification of these oncogenic drivers has dramatically changed the genetic landscape of NSCLC moving away from the old concept of a large indistinct histological entity to a combination of rare clinically relevant molecular subsets. Recently, a renewed interest has been emerging on the human epidermal growth factor-2 (HER2) pathway. Genetic aberrations of this signaling pathway have been reported over time to be associated in NSCLC with different sensitivity to the EGFR tyrosine kinase inhibitors, to have a possible prognostic role and more recently HER2 amplification has been emerged as a possible mechanism in EGFR-mutated tumors of acquired resistance to the EGFR tyrosine kinase inhibitors. In addition, dysregulation of the HER2 pathway, in particular HER2 mutations (mostly, in-frame exon 20 insertions), may represent a possible novel therapeutic target in NSCLC, paving the way for a new generation of targeted agents in NSCLC. Since anecdotal case reports of clinical activity of anti-HER2 agents in NSCLC patients with HER2 mutations, several targeted agents have been evaluated in HER2-mutated patients, generating a growing interest upon this oncogenic driver, leading to the design of molecularly selected trials with anti-HER2 compounds and the rediscover of hastily thrown out drugs, such as neratinib. The aim of this article is to provide an overview of the role of HER2 dysregulation in NSCLCs, trying to throw a light not only on the strengths but also the weaknesses of the studies conducted so far. It is a long way to the clinical implementation of these biomarkers and probably the increasing use of next generation sequencing techniques, the creation of large multi-institutional molecular testing platforms and the design of rationally based trials can get closer personalized medicine in NSCLC.
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Wang, Dawei; Kou, Ronghui; Ren, Yang; Sun, Cheng-Jun; Zhao, Hu; Zhang, Ming-Jian; Li, Yan; Huq, Ashifia; Ko, J Y Peter; Pan, Feng; Sun, Yang-Kook; Yang, Yong; Amine, Khalil; Bai, Jianming; Chen, Zonghai; Wang, Feng
2017-10-01
Nickel-rich layered transition metal oxides, LiNi 1- x (MnCo) x O 2 (1-x ≥ 0.5), are appealing candidates for cathodes in next-generation lithium-ion batteries (LIBs) for electric vehicles and other large-scale applications, due to their high capacity and low cost. However, synthetic control of the structural ordering in such a complex quaternary system has been a great challenge, especially in the presence of high Ni content. Herein, synthesis reactions for preparing layered LiNi 0.7 Mn 0.15 Co 0.15 O 2 (NMC71515) by solid-state methods are investigated through a combination of time-resolved in situ high-energy X-ray diffraction and absorption spectroscopy measurements. The real-time observation reveals a strong temperature dependence of the kinetics of cationic ordering in NMC71515 as a result of thermal-driven oxidation of transition metals and lithium/oxygen loss that concomitantly occur during heat treatment. Through synthetic control of the kinetic reaction pathway, a layered NMC71515 with low cationic disordering and a high reversible capacity is prepared in air. The findings may help to pave the way for designing high-Ni layered oxide cathodes for LIBs. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Dawei; Kou, Ronghui; Ren, Yang
Nickel-rich layered transition metal oxides, LiNi1-x(MnCo)(x)O-2 (1-x >= 0.5), are appealing candidates for cathodes in next-generation lithium-ion batteries (LIBs) for electric vehicles and other large-scale applications, due to their high capacity and low cost. However, synthetic control of the structural ordering in such a complex quaternary system has been a great challenge, especially in the presence of high Ni content. Herein, synthesis reactions for preparing layered LiNi0.7Mn0.15Co0.15O2 (NMC71515) by solid-state methods are investigated through a combination of time-resolved in situ high-energy X-ray diffraction and absorption spectroscopy measurements. The real-time observation reveals a strong temperature dependence of the kinetics of cationicmore » ordering in NMC71515 as a result of thermal-driven oxidation of transition metals and lithium/oxygen loss that concomitantly occur during heat treatment. Through synthetic control of the kinetic reaction pathway, a layered NMC71515 with low cationic disordering and a high reversible capacity is prepared in air. The findings may help to pave the way for designing high-Ni layered oxide cathodes for LIBs.« less
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Wang, Dawei; Kou, Ronghui; Ren, Yang
Nickel-rich layered transition metal oxides, LiNi 1-x(MnCo) xO 2 (1-x ≥ 0.5), are appealing candidates for cathodes in next-generation lithium-ion batteries (LIBs) for electric vehicles and other large-scale applications, due to their high capacity and low cost. However, synthetic control of the structural ordering in such a complex quaternary system has been a great challenge, especially in the presence of high Ni content. Herein, synthesis reactions for preparing layered LiNi 0.7Mn 0.15Co 0.15O 2 (NMC71515) by solid-state methods are investigated through a combination of time-resolved in situ high-energy X-ray diffraction and absorption spectroscopy measurements. The real-time observation reveals a strongmore » temperature dependence of the kinetics of cationic ordering in NMC71515 as a result of thermal-driven oxidation of transition metals and lithium/oxygen loss that concomitantly occur during heat treatment. Through synthetic control of the kinetic reaction pathway, a layered NMC71515 with low cationic disordering and a high reversible capacity is prepared in air. The findings may help to pave the way for designing high-Ni layered oxide cathodes for LIBs« less
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A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone.
Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J; Lesport, Pierre; Bourinet, Emmanuel; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille
2017-07-18
Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans , is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT₂ receptors (angiotensin II type 2 receptors; AT₂R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT₂R, with this action being not affected by known ligands of AT₂R. This result points towards novel AT₂R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics.
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Aging and Immune Function: Molecular Mechanisms to Interventions
Ponnappan, Subramaniam
2011-01-01
Abstract The immune system of an organism is an essential component of the defense mechanism aimed at combating pathogenic stress. Age-associated immune dysfunction, also dubbed “immune senescence,” manifests as increased susceptibility to infections, increased onset and progression of autoimmune diseases, and onset of neoplasia. Over the years, extensive research has generated consensus in terms of the phenotypic and functional defects within the immune system in various organisms, including humans. Indeed, age-associated alterations such as thymic involution, T cell repertoire skewing, decreased ability to activate naïve T cells and to generate robust memory responses, have been shown to have a causative role in immune decline. Further, understanding the molecular mechanisms underlying the generation of proteotoxic stress, DNA damage response, modulation of ubiquitin proteasome pathway, and regulation of transcription factor NFκB activation, in immune decline, have paved the way to delineating signaling pathways that cross-talk and impact immune senescence. Given the role of the immune system in combating infections, its effectiveness with age may well be a marker of health and a predictor of longevity. It is therefore believed that a better understanding of the mechanisms underlying immune senescence will lead to an effective interventional strategy aimed at improving the health span of individuals. Antioxid. Redox Signal. 14, 1551–1585. PMID:20812785
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Prenatal treatment of Down syndrome: a reality?
Guedj, Fayçal; Bianchi, Diana W; Delabar, Jean-Maurice
2014-04-01
Down syndrome affects more than 5 million people globally. During the last 10 years, there has been a dramatic increase in the research efforts focused on therapeutic interventions to improve learning and memory in Down syndrome. This review summarizes the different functional abnormalities targeted by researchers in mouse models of Down syndrome. Three main strategies have been used: neural stem cell implantation; environmental enrichment and physical exercise; and pharmacotherapy. Pharmacological targets include the choline pathway, GABA and NMDA receptors, DYRK1A protein, oxidative stress and pathways involved in development and neurogenesis. Many strategies have improved learning and memory as well as electrophysiological and molecular alterations in affected animals. To date, eight molecules have been tested in human adult clinical trials. No studies have yet been performed on infants. However, compelling studies reveal that permanent brain alterations originate during fetal life in Down syndrome. Early prenatal diagnosis offers a 28 weeks window to positively impact brain development and improve postnatal cognitive outcome in affected individuals. Only a few approaches (Epigallocatechine gallate, NAP/SAL, fluoxetine, and apigenin) have been used to treat mice in utero; these showed therapeutic effects that persisted to adulthood. In this article, we discuss the challenges, recent progress, and lessons learned that pave the way for new therapeutic approaches in Down syndrome.
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Leverson, Joel D; Sampath, Deepak; Souers, Andrew J; Rosenberg, Saul H; Fairbrother, Wayne J; Amiot, Martine; Konopleva, Marina; Letai, Anthony
2017-12-01
Since the discovery of apoptosis as a form of programmed cell death, targeting the apoptosis pathway to induce cancer cell death has been a high-priority goal for cancer therapy. After decades of effort, drug-discovery scientists have succeeded in generating small-molecule inhibitors of antiapoptotic BCL2 family proteins. Innovative medicinal chemistry and structure-based drug design, coupled with a strong fundamental understanding of BCL2 biology, were essential to the development of BH3 mimetics such as the BCL2-selective inhibitor venetoclax. We review a number of preclinical studies that have deepened our understanding of BCL2 biology and facilitated the clinical development of venetoclax. Significance: Basic research into the pathways governing programmed cell death have paved the way for the discovery of apoptosis-inducing agents such as venetoclax, a BCL2-selective inhibitor that was recently approved by the FDA and the European Medicines Agency. Preclinical studies aimed at identifying BCL2-dependent tumor types have translated well into the clinic thus far and will likely continue to inform the clinical development of venetoclax and other BCL2 family inhibitors. Cancer Discov; 7(12); 1376-93. ©2017 AACR. ©2017 American Association for Cancer Research.
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Curcumin in combined cancer therapy.
Troselj, Koraljka Gall; Kujundzic, Renata Novak
2014-01-01
The mechanisms of beneficial preventive and therapeutic effects achieved by traditional and complementary medicine are currently being deciphered in molecular medicine. Curcumin, a yellow-colored polyphenol derived from the rhizome of turmeric (Curcuma longa), influences a wide variety of cellular processes through the reshaping of many molecular targets. One of them, nuclear factor kappa B (NF-κB), represents a strong mediator of inflammation and, in a majority of systems, supports the pro-proliferative features of cancer cells. The application of various anticancer drugs, cytostatics, triggers signals which lead to an increase in cellular NF-κB activity. As a consequence, cancer cells often reshape their survival signaling pathways and, over time, become resistant to applied therapy. Curcumin was shown to be a strong inhibitor of NF-κB activity and its inhibitory effect on NF-κB related pathways often leads to cellular apoptotic response. All these facts, tested and confirmed in many different biological systems, have paved the way for research aimed to elucidate the potential beneficial effects of combining curcumin and various anti-cancer drugs in order to establish more efficient and less toxic cancer treatment modalities. This review addresses certain aspects of NF-κB-related inflammatory response, its role in carcinogenesis and therapy benefits that may be gained through silencing NF-κB by selectively combining curcumin and various anticancer drugs.
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Wang, Dawei; Kou, Ronghui; Ren, Yang; ...
2017-08-25
Nickel-rich layered transition metal oxides, LiNi 1-x(MnCo) xO 2 (1-x ≥ 0.5), are appealing candidates for cathodes in next-generation lithium-ion batteries (LIBs) for electric vehicles and other large-scale applications, due to their high capacity and low cost. However, synthetic control of the structural ordering in such a complex quaternary system has been a great challenge, especially in the presence of high Ni content. Herein, synthesis reactions for preparing layered LiNi 0.7Mn 0.15Co 0.15O 2 (NMC71515) by solid-state methods are investigated through a combination of time-resolved in situ high-energy X-ray diffraction and absorption spectroscopy measurements. The real-time observation reveals a strongmore » temperature dependence of the kinetics of cationic ordering in NMC71515 as a result of thermal-driven oxidation of transition metals and lithium/oxygen loss that concomitantly occur during heat treatment. Through synthetic control of the kinetic reaction pathway, a layered NMC71515 with low cationic disordering and a high reversible capacity is prepared in air. The findings may help to pave the way for designing high-Ni layered oxide cathodes for LIBs« less
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The structural basis of arrestin-mediated regulation of G-protein-coupled receptors
Gurevich, Vsevolod V.; Gurevich, Eugenia V.
2008-01-01
The 4 mammalian arrestins serve as almost universal regulators of the largest known family of signaling proteins, G-protein-coupled receptors (GPCRs). Arrestins terminate receptor interactions with G proteins, redirect the signaling to a variety of alternative pathways, and orchestrate receptor internalization and subsequent intracellular trafficking. The elucidation of the structural basis and fine molecular mechanisms of the arrestin–receptor interaction paved the way to the targeted manipulation of this interaction from both sides to produce very stable or extremely transient complexes that helped to understand the regulation of many biologically important processes initiated by active GPCRs. The elucidation of the structural basis of arrestin interactions with numerous non-receptor-binding partners is long overdue. It will allow the construction of fully functional arrestins in which the ability to interact with individual partners is specifically disrupted or enhanced by targeted mutagenesis. These “custom-designed” arrestin mutants will be valuable tools in defining the role of various interactions in the intricate interplay of multiple signaling pathways in the living cell. The identification of arrestin-binding sites for various signaling molecules will also set the stage for designing molecular tools for therapeutic intervention that may prove useful in numerous disorders associated with congenital or acquired disregulation of GPCR signaling. PMID:16460808
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Applying Evolutionary Genetics to Developmental Toxicology and Risk Assessment
Leung, Maxwell C. K.; Procter, Andrew C.; Goldstone, Jared V.; Foox, Jonathan; DeSalle, Robert; Mattingly, Carolyn J.; Siddall, Mark E.; Timme-Laragy, Alicia R.
2018-01-01
Evolutionary thinking continues to challenge our views on health and disease. Yet, there is a communication gap between evolutionary biologists and toxicologists in recognizing the connections among developmental pathways, high-throughput screening, and birth defects in humans. To increase our capability in identifying potential developmental toxicants in humans, we propose to apply evolutionary genetics to improve the experimental design and data interpretation with various in vitro and whole-organism models. We review five molecular systems of stress response and update 18 consensual cell-cell signaling pathways that are the hallmark for early development, organogenesis, and differentiation; and revisit the principles of teratology in light of recent advances in high-throughput screening, big data techniques, and systems toxicology. Multiscale systems modeling plays an integral role in the evolutionary approach to cross-species extrapolation. Phylogenetic analysis and comparative bioinformatics are both valuable tools in identifying and validating the molecular initiating events that account for adverse developmental outcomes in humans. The discordance of susceptibility between test species and humans (ontogeny) reflects their differences in evolutionary history (phylogeny). This synthesis not only can lead to novel applications in developmental toxicity and risk assessment, but also can pave the way for applying an evo-devo perspective to the study of developmental origins of health and disease. PMID:28267574
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Selective Mitochondrial Targeting Exerts Anxiolytic Effects In Vivo
Nussbaumer, Markus; Asara, John M; Teplytska, Larysa; Murphy, Michael P; Logan, Angela; Turck, Christoph W; Filiou, Michaela D
2016-01-01
Current treatment strategies for anxiety disorders are predominantly symptom-based. However, a third of anxiety patients remain unresponsive to anxiolytics highlighting the need for more effective, mechanism-based therapeutic approaches. We have previously compared high vs low anxiety mice and identified changes in mitochondrial pathways, including oxidative phosphorylation and oxidative stress. In this work, we show that selective pharmacological targeting of these mitochondrial pathways exerts anxiolytic effects in vivo. We treated high anxiety-related behavior (HAB) mice with MitoQ, an antioxidant that selectively targets mitochondria. MitoQ administration resulted in decreased anxiety-related behavior in HAB mice. This anxiolytic effect was specific for high anxiety as MitoQ treatment did not affect the anxiety phenotype of C57BL/6N and DBA/2J mouse strains. We furthermore investigated the molecular underpinnings of the MitoQ-driven anxiolytic effect and found that MitoQ treatment alters the brain metabolome and that the response to MitoQ treatment is characterized by distinct molecular signatures. These results indicate that a mechanism-driven approach based on selective mitochondrial targeting has the potential to attenuate the high anxiety phenotype in vivo, thus paving the way for translational implementation as long-term MitoQ administration is well-tolerated with no reported side effects in mice and humans. PMID:26567514
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Selective Mitochondrial Targeting Exerts Anxiolytic Effects In Vivo.
Nussbaumer, Markus; Asara, John M; Teplytska, Larysa; Murphy, Michael P; Logan, Angela; Turck, Christoph W; Filiou, Michaela D
2016-06-01
Current treatment strategies for anxiety disorders are predominantly symptom-based. However, a third of anxiety patients remain unresponsive to anxiolytics highlighting the need for more effective, mechanism-based therapeutic approaches. We have previously compared high vs low anxiety mice and identified changes in mitochondrial pathways, including oxidative phosphorylation and oxidative stress. In this work, we show that selective pharmacological targeting of these mitochondrial pathways exerts anxiolytic effects in vivo. We treated high anxiety-related behavior (HAB) mice with MitoQ, an antioxidant that selectively targets mitochondria. MitoQ administration resulted in decreased anxiety-related behavior in HAB mice. This anxiolytic effect was specific for high anxiety as MitoQ treatment did not affect the anxiety phenotype of C57BL/6N and DBA/2J mouse strains. We furthermore investigated the molecular underpinnings of the MitoQ-driven anxiolytic effect and found that MitoQ treatment alters the brain metabolome and that the response to MitoQ treatment is characterized by distinct molecular signatures. These results indicate that a mechanism-driven approach based on selective mitochondrial targeting has the potential to attenuate the high anxiety phenotype in vivo, thus paving the way for translational implementation as long-term MitoQ administration is well-tolerated with no reported side effects in mice and humans.
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Emerging roles for antigen presentation in establishing host-microbiome symbiosis
Bessman, Nicholas J.; Sonnenberg, Gregory F.
2016-01-01
Trillions of beneficial bacteria inhabit the intestinal tract of healthy mammals from birth. Accordingly, mammalian hosts have evolved a series of complementary and redundant pathways to limit pathologic immune responses against these bacteria, while simultaneously protecting against enteric pathogen invasion. These pathways can be generically responsive to the presence of any commensal bacteria and innate in nature, as for IL-22-related pathways. Alternatively, specific bacterial antigens can drive a distinct set of adaptive immune cell responses, including IgA affinity maturation and secretion, and a recently described pathway of intestinal selection whereby MHCII+ ILC3 deletes commensal bacteria-reactive CD4 T cells. These pathways can either promote or inhibit colonization by specific subsets of commensal bacteria, and cooperatively maintain intestinal homeostasis. In this review, we will highlight recent developments in understanding how these diverse pathways complement each other to cooperatively shape the symbiotic relationship between commensal bacteria and mammalian hosts. PMID:27319348
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36 CFR 7.15 - Shenandoah National Park.
Code of Federal Regulations, 2010 CFR
2010-07-01
... those areas of the park which are more than 250 yards from a paved road, and more than one-half mile from any park facilities other than trails, unpaved roads and trail shelters. The Superintendent may...; (3) No person or group may backcountry camp: (i) Within 250 yards or in view from any paved park road...
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Evaluation of fly ash in water reduced paving mixtures.
DOT National Transportation Integrated Search
1985-06-01
Fly ash was used to replace 15% of the cement in C3WR and C6WR concrete : paving mixes containing ASTM C494 Type A water reducin9 admixtures. Two Class : C ashes and one Class F ash from Iowa approved sources were examined in each : mix. When Class C...
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45. CAPE COD AIR STATION PAVE PAWS FACILITY BUILDING ...
45. CAPE COD AIR STATION PAVE PAWS FACILITY - BUILDING ELEVATION VIEW WITH BUILDING METAL SIDING BEING APPLIED ON "A" FACE (LEFT) AND "B" FACE (RIGHT). NOTE THAT NORTH IS GENERALLY TO RIGHT OF VIEW. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA
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Permeability of roads to movement of scrubland lizards and small mammals.
Brehme, Cheryl S; Tracey, Jeff A; McClenaghan, Leroy R; Fisher, Robert N
2013-08-01
A primary objective of road ecology is to understand and predict how roads affect connectivity of wildlife populations. Road avoidance behavior can fragment populations, whereas lack of road avoidance can result in high mortality due to wildlife-vehicle collisions. Many small animal species focus their activities to particular microhabitats within their larger habitat. We sought to assess how different types of roads affect the movement of small vertebrates and to explore whether responses to roads may be predictable on the basis of animal life history or microhabitat preferences preferences. We tracked the movements of fluorescently marked animals at 24 sites distributed among 3 road types: low-use dirt, low-use secondary paved, and rural 2-lane highway. Most data we collected were on the San Diego pocket mouse (Chaetodipus fallax), cactus mouse (Peromyscus eremicus), western fence lizard (Sceloporus occidentalis), orange-throated whiptail (Aspidoscelis hyperythra), Dulzura kangaroo rat (Dipodomys simulans) (dirt, secondary paved), and deer mouse (Peromyscus maniculatus) (highway only). San Diego pocket mice and cactus mice moved onto dirt roads but not onto a low-use paved road of similar width or onto the highway, indicating they avoid paved road substrate. Both lizard species moved onto the dirt and secondary paved roads but avoided the rural 2-lane rural highway, indicating they may avoid noise, vibration, or visual disturbance from a steady flow of traffic. Kangaroo rats did not avoid the dirt or secondary paved roads. Overall, dirt and secondary roads were more permeable to species that prefer to forage or bask in open areas of their habitat, rather than under the cover of rocks or shrubs. However, all study species avoided the rural 2-lane highway. Our results suggest that microhabitat use preferences and road substrate help predict species responses to low-use roads, but roads with heavy traffic may deter movement of a much wider range of small animal species. © 2013 Society for Conservation Biology.
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Submicron particle monitoring of paving and related road construction operations.
Freund, Alice; Zuckerman, Norman; Baum, Lisa; Milek, Debra
2012-01-01
This study identified activities and sources that contribute to ultrafine and other submicron particle exposure that could trigger respiratory symptoms in highway repair workers. Submicron particle monitoring was conducted for paving, milling, and pothole repair operations in a major metropolitan area where several highway repair workers were identified as symptomatic for respiratory illness following exposures at the 2001 World Trade Center disaster site. Exposure assessments were conducted for eight trades involved in road construction using a TSI P-Trak portable condensation particle counter. Direct readings near the workers' breathing zones and observations of activities and potential sources were logged on 7 days on 27 workers using four different models of pavers and two types of millers. Average worker exposure levels ranged from 2 to 3 times background during paving and from 1 to 4 times background during milling. During asphalt paving, average personal exposures to submicron particulates were 25,000-60,000, 28,000-70,000, and 23,000-37,000 particles/ cm(3) for paver operators, screed operators, and rakers, respectively. Average personal exposures during milling were 19,000-111,000, 28,000-81,000, and 19,000 particles/cm(3) for the large miller operators, miller screed operators, and raker, respectively. Personal peak exposures were measured up to 467,000 and 455,000 particles/cm(3) in paving and milling, respectively. Several sources of submicron particles were identified. These included the diesel and electric fired screed heaters; engine exhaust from diesel powered construction vehicles passing by or idling; raking, dumping, and paving of asphalt; exhaust from the hotbox heater; pavement dust or fumes from milling operations, especially when the large miller started and stopped; and secondhand cigarette smoke. To reduce the potential for health effects in workers, over 40 recommendations were made to control exposures, including improved maintenance of paver ventilation systems; diesel fume engineering controls; reduced idling; provision of cabs for the operators; and improved dust suppression systems on the milling machine.
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Koyama, Takashi; Mendes, Cláudia C.; Mirth, Christen K.
2013-01-01
Nutrition, via the insulin/insulin-like growth factor (IIS)/Target of Rapamycin (TOR) signaling pathway, can provide a strong molding force for determining animal size and shape. For instance, nutrition induces a disproportionate increase in the size of male horns in dung and rhinoceros beetles, or mandibles in staghorn or horned flour beetles, relative to body size. In these species, well-fed male larvae produce adults with greatly enlarged horns or mandibles, whereas males that are starved or poorly fed as larvae bear much more modest appendages. Changes in IIS/TOR signaling plays a key role in appendage development by regulating growth in the horn and mandible primordia. In contrast, changes in the IIS/TOR pathway produce minimal effects on the size of other adult structures, such as the male genitalia in fruit flies and dung beetles. The horn, mandible and genitalia illustrate that although all tissues are exposed to the same hormonal environment within the larval body, the extent to which insulin can induce growth is organ specific. In addition, the IIS/TOR pathway affects body size and shape by controlling production of metamorphic hormones important for regulating developmental timing, like the steroid molting hormone ecdysone and sesquiterpenoid hormone juvenile hormone. In this review, we discuss recent results from Drosophila and other insects that highlight mechanisms allowing tissues to differ in their sensitivity to IIS/TOR and the potential consequences of these differences on body size and shape. PMID:24133450
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Asymmetric shape transitions of epitaxial quantum dots
2016-01-01
We construct a two-dimensional continuum model to describe the energetics of shape transitions in fully faceted epitaxial quantum dots (strained islands) via minimization of elastic energy and surface energy at fixed volume. The elastic energy of the island is based on a third-order approximation, enabling us to consider shape transitions between pyramids, domes, multifaceted domes and asymmetric intermediate states. The energetics of the shape transitions are determined by numerically calculating the facet lengths that minimize the energy of a given island type of prescribed island volume. By comparing the energy of different island types with the same volume and analysing the energy surface as a function of the island shape parameters, we determine the bifurcation diagram of equilibrium solutions and their stability, as well as the lowest barrier transition pathway for the island shape as a function of increasing volume. The main result is that the shape transition from pyramid to dome to multifaceted dome occurs through sequential nucleation of facets and involves asymmetric metastable transition shapes. We also explicitly determine the effect of corner energy (facet edge energy) on shape transitions and interpret the results in terms of the relative stability of asymmetric island shapes as observed in experiment. PMID:27436989
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Tajiri, Naoki; Kaneko, Yuji; Shinozuka, Kazutaka; Ishikawa, Hiroto; Yankee, Ernest; McGrogan, Michael; Case, Casey; Borlongan, Cesar V
2013-01-01
Here, we report that a unique mechanism of action exerted by stem cells in the repair of the traumatically injured brain involves their ability to harness a biobridge between neurogenic niche and injured brain site. This biobridge, visualized immunohistochemically and laser captured, corresponded to an area between the neurogenic subventricular zone and the injured cortex. That the biobridge expressed high levels of extracellular matrix metalloproteinases characterized initially by a stream of transplanted stem cells, but subsequently contained only few to non-detectable grafts and overgrown by newly formed host cells, implicates a novel property of stem cells. The transplanted stem cells manifest themselves as pathways for trafficking the migration of host neurogenic cells, but once this biobridge is formed between the neurogenic site and the injured brain site, the grafted cells disappear and relinquish their task to the host neurogenic cells. Our findings reveal that long-distance migration of host cells from the neurogenic niche to the injured brain site can be achieved through transplanted stem cells serving as biobridges for initiation of endogenous repair mechanisms. This is the first report of a stem cell-paved "biobridge". Indeed, to date the two major schools of discipline in stem cell repair mechanism primarily support the concept of "cell replacement" and bystander effects of "trophic factor secretion". The present novel observations of a stem cell seducing a host cell to engage in brain repair advances basic science concepts on stem cell biology and extracellular matrix, as well as provokes translational research on propagating this stem cell-paved biobridge beyond cell replacement and trophic factor secretion for the treatment of traumatic brain injury and other neurological disorders.
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Back to the biology in systems biology: what can we learn from biomolecular networks?
Huang, Sui
2004-02-01
Genome-scale molecular networks, including protein interaction and gene regulatory networks, have taken centre stage in the investigation of the burgeoning disciplines of systems biology and biocomplexity. What do networks tell us? Some see in networks simply the comprehensive, detailed description of all cellular pathways, others seek in networks simple, higher-order qualities that emerge from the collective action of the individual pathways. This paper discusses networks from an encompassing category of thinking that will hopefully help readers to bridge the gap between these polarised viewpoints. Systems biology so far has emphasised the characterisation of large pathway maps. Now one has to ask: where is the actual biology in 'systems biology'? As structures midway between genome and phenome, and by serving as an 'extended genotype' or an 'elementary phenotype', molecular networks open a new window to the study of evolution and gene function in complex living systems. For the study of evolution, features in network topology offer a novel starting point for addressing the old debate on the relative contributions of natural selection versus intrinsic constraints to a particular trait. To study the function of genes, it is necessary not only to see them in the context of gene networks, but also to reach beyond describing network topology and to embrace the global dynamics of networks that will reveal higher-order, collective behaviour of the interacting genes. This will pave the way to understanding how the complexity of genome-wide molecular networks collapses to produce a robust whole-cell behaviour that manifests as tightly-regulated switching between distinct cell fates - the basis for multicellular life.
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Adverse Outcome Pathways can drive non-animal approaches for safety assessment
Burden, Natalie; Sewell, Fiona; Andersen, Melvin E; Boobis, Alan; Chipman, J Kevin; Cronin, Mark T D; Hutchinson, Thomas H; Kimber, Ian; Whelan, Maurice
2015-01-01
Adverse Outcome Pathways (AOPs) provide an opportunity to develop new and more accurate safety assessment processes for drugs and other chemicals, and may ultimately play an important role in regulatory decision making. Not only can the development and application of AOPs pave the way for the development of improved evidence-based approaches for hazard and risk assessment, there is also the promise of a significant impact on animal welfare, with a reduced reliance on animal-based methods. The establishment of a useable and coherent knowledge framework under which AOPs will be developed and applied has been a first critical step towards realizing this opportunity. This article explores how the development of AOPs under this framework, and their application in practice, could benefit the science and practice of safety assessment, while in parallel stimulating a move away from traditional methods towards an increased acceptance of non-animal approaches. We discuss here the key areas where current, and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. © 2015 The Authors. Journal of Applied Toxicology published by John Wiley & Sons Ltd. This article explores how the development and application of Adverse Outcome Pathways (AOPs) could benefit the science and practice of chemical safety assessment, with a particular focus on how their use in practice could reduce reliance on traditional animal toxicity tests. This includes discussion of the key areas where current and future initiatives should be focused to enable the translation of AOPs into routine chemical safety assessment, and lasting 3Rs benefits. PMID:25943792
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High content cell-based assay for the inflammatory pathway
NASA Astrophysics Data System (ADS)
Mukherjee, Abhishek; Song, Joon Myong
2015-07-01
Cellular inflammation is a non-specific immune response to tissue injury that takes place via cytokine network orchestration to maintain normal tissue homeostasis. However chronic inflammation that lasts for a longer period, plays the key role in human diseases like neurodegenerative disorders and cancer development. Understanding the cellular and molecular mechanisms underlying the inflammatory pathways may be effective in targeting and modulating their outcome. Tumor necrosis factor alpha (TNF-α) is a pro-inflammatory cytokine that effectively combines the pro-inflammatory features with the pro-apoptotic potential. Increased levels of TNF-α observed during acute and chronic inflammatory conditions are believed to induce adverse phenotypes like glucose intolerance and abnormal lipid profile. Natural products e. g., amygdalin, cinnamic acid, jasmonic acid and aspirin have proven efficacy in minimizing the TNF-α induced inflammation in vitro and in vivo. Cell lysis-free quantum dot (QDot) imaging is an emerging technique to identify the cellular mediators of a signaling cascade with a single assay in one run. In comparison to organic fluorophores, the inorganic QDots are bright, resistant to photobleaching and possess tunable optical properties that make them suitable for long term and multicolor imaging of various components in a cellular crosstalk. Hence we tested some components of the mitogen activated protein kinase (MAPK) pathway during TNF-α induced inflammation and the effects of aspirin in HepG2 cells by QDot multicolor imaging technique. Results demonstrated that aspirin showed significant protective effects against TNF-α induced cellular inflammation. The developed cell based assay paves the platform for the analysis of cellular components in a smooth and reliable way.
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NREL's EVI-Pro Lite Tool Paves the Way for Future Electric Vehicle
Electric Vehicle Infrastructure Planning NREL's EVI-Pro Lite Tool Paves the Way for Future Electric Vehicle electric vehicle charging station To assist state and local governments anticipating this type of growth in simplified version of the Electric Vehicle Infrastructure Projection Tool (EVI-Pro) model. Combining a sleek
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46. CAPE COD AIR STATION PAVE PAWS FACILITY BUILDING ...
46. CAPE COD AIR STATION PAVE PAWS FACILITY - BUILDING ELEVATION VIEW WITH ALL METAL SIDING INSTALLED AND WITH EMITTER/ANTENNA ARRAY SYSTEM NEARING OCMPLETION ON "B" FACE (RIGHT). VIEW ALSO SHOWS TRAVELING "CLEANING" SYSTEM ON "B" FACE - NOW REMOVED. - Cape Cod Air Station, Technical Facility-Scanner Building & Power Plant, Massachusetts Military Reservation, Sandwich, Barnstable County, MA
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Freud, Erez; Ganel, Tzvi; Avidan, Galia; Gilaie-Dotan, Sharon
2016-03-01
According to the two visual systems model, the cortical visual system is segregated into a ventral pathway mediating object recognition, and a dorsal pathway mediating visuomotor control. In the present study we examined whether the visual control of action could develop normally even when visual perceptual abilities are compromised from early childhood onward. Using his fingers, LG, an individual with a rare developmental visual object agnosia, manually estimated (perceptual condition) the width of blocks that varied in width and length (but not in overall size), or simply picked them up across their width (grasping condition). LG's perceptual sensitivity to target width was profoundly impaired in the manual estimation task compared to matched controls. In contrast, the sensitivity to object shape during grasping, as measured by maximum grip aperture (MGA), the time to reach the MGA, the reaction time and the total movement time were all normal in LG. Further analysis, however, revealed that LG's sensitivity to object shape during grasping emerged at a later time stage during the movement compared to controls. Taken together, these results demonstrate a dissociation between action and perception of object shape, and also point to a distinction between different stages of the grasping movement, namely planning versus online control. Moreover, the present study implies that visuomotor abilities can develop normally even when perceptual abilities developed in a profoundly impaired fashion. Copyright © 2016 Elsevier Ltd. All rights reserved.
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MicroRNA and receptor mediated signaling pathways as potential therapeutic targets in heart failure.
Tuttolomondo, Antonino; Simonetta, Irene; Pinto, Antonio
2016-11-01
Cardiac remodelling is a complex pathogenetic pathway involving genome expression, molecular, cellular, and interstitial changes that cause changes in size, shape and function of the heart after cardiac injury. Areas covered: We will review recent advances in understanding the role of several receptor-mediated signaling pathways and micro-RNAs, in addition to their potential as candidate target pathways in the pathogenesis of heart failure. The myocyte is the main target cell involved in the remodelling process via ischemia, cell necrosis and apoptosis (by means of various receptor pathways), and other mechanisms mediated by micro-RNAs. We will analyze the role of some receptor mediated signaling pathways such as natriuretic peptides, mediators of glycogen synthase kinase 3 and ERK1/2 pathways, beta-adrenergic receptor subtypes and relaxin receptor signaling mechanisms, TNF/TNF receptor family and TWEAK/Fn14 axis, and some micro-RNAs as candidate target pathways in pathogenesis of heart failure. These mediators of receptor-mediated pathways and micro-RNA are the most addressed targets of emerging therapies in modern heart failure treatment strategies. Expert opinion: Future treatment strategies should address mediators involved in multiple steps within heart failure pathogenetic pathways.
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Light-Induced Indeterminacy Alters Shade-Avoiding Tomato Leaf Morphology1[OPEN
Chitwood, Daniel H.; Kumar, Ravi; Ranjan, Aashish; Pelletier, Julie M.; Townsley, Brad T.; Ichihashi, Yasunori; Martinez, Ciera C.; Zumstein, Kristina; Harada, John J.; Maloof, Julin N.; Sinha, Neelima R.
2015-01-01
Plants sense the foliar shade of competitors and alter their developmental programs through the shade-avoidance response. Internode and petiole elongation, and changes in overall leaf area and leaf mass per area, are the stereotypical architectural responses to foliar shade in the shoot. However, changes in leaf shape and complexity in response to shade remain incompletely, and qualitatively, described. Using a meta-analysis of more than 18,000 previously published leaflet outlines, we demonstrate that shade avoidance alters leaf shape in domesticated tomato (Solanum lycopersicum) and wild relatives. The effects of shade avoidance on leaf shape are subtle with respect to individual traits but are combinatorially strong. We then seek to describe the developmental origins of shade-induced changes in leaf shape by swapping plants between light treatments. Leaf size is light responsive late into development, but patterning events, such as stomatal index, are irrevocably specified earlier. Observing that shade induces increases in shoot apical meristem size, we then describe gene expression changes in early leaf primordia and the meristem using laser microdissection. We find that in leaf primordia, shade avoidance is not mediated through canonical pathways described in mature organs but rather through the expression of KNOTTED1-LIKE HOMEOBOX and other indeterminacy genes, altering known developmental pathways responsible for patterning leaf shape. We also demonstrate that shade-induced changes in leaf primordium gene expression largely do not overlap with those found in successively initiated leaf primordia, providing evidence against classic hypotheses that shaded leaf morphology results from the prolonged production of juvenile leaf types. PMID:26381315
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Zovko, Monika; Kiefer, Markus
2013-02-01
According to classical theories, automatic processes operate independently of attention. Recent evidence, however, shows that masked visuomotor priming, an example of an automatic process, depends on attention to visual form versus semantics. In a continuation of this approach, we probed feature-specific attention within the perceptual domain and tested in two event-related potential (ERP) studies whether masked visuomotor priming in a shape decision task specifically depends on attentional sensitization of visual pathways for shape in contrast to color. Prior to the masked priming procedure, a shape or a color decision task served to induce corresponding task sets. ERP analyses revealed visuomotor priming effects over the occipitoparietal scalp only after the shape, but not after the color induction task. Thus, top-down control coordinates automatic processing streams in congruency with higher-level goals even at a fine-grained level. Copyright © 2012 Society for Psychophysiological Research.
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Brain evolution by brain pathway duplication
Chakraborty, Mukta; Jarvis, Erich D.
2015-01-01
Understanding the mechanisms of evolution of brain pathways for complex behaviours is still in its infancy. Making further advances requires a deeper understanding of brain homologies, novelties and analogies. It also requires an understanding of how adaptive genetic modifications lead to restructuring of the brain. Recent advances in genomic and molecular biology techniques applied to brain research have provided exciting insights into how complex behaviours are shaped by selection of novel brain pathways and functions of the nervous system. Here, we review and further develop some insights to a new hypothesis on one mechanism that may contribute to nervous system evolution, in particular by brain pathway duplication. Like gene duplication, we propose that whole brain pathways can duplicate and the duplicated pathway diverge to take on new functions. We suggest that one mechanism of brain pathway duplication could be through gene duplication, although other mechanisms are possible. We focus on brain pathways for vocal learning and spoken language in song-learning birds and humans as example systems. This view presents a new framework for future research in our understanding of brain evolution and novel behavioural traits. PMID:26554045
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Olivier-Mason, Anique; Wojtyniak, Martin; Bowie, Rachel V; Nechipurenko, Inna V; Blacque, Oliver E; Sengupta, Piali
2013-04-01
The structure and function of primary cilia are critically dependent on intracellular trafficking pathways that transport ciliary membrane and protein components. The mechanisms by which these trafficking pathways are regulated are not fully characterized. Here we identify the transmembrane protein OSTA-1 as a new regulator of the trafficking pathways that shape the morphology and protein composition of sensory cilia in C. elegans. osta-1 encodes an organic solute transporter alpha-like protein, mammalian homologs of which have been implicated in membrane trafficking and solute transport, although a role in regulating cilia structure has not previously been demonstrated. We show that mutations in osta-1 result in altered ciliary membrane volume, branch length and complexity, as well as defects in localization of a subset of ciliary transmembrane proteins in different sensory cilia types. OSTA-1 is associated with transport vesicles, localizes to a ciliary compartment shown to house trafficking proteins, and regulates both retrograde and anterograde flux of the endosome-associated RAB-5 small GTPase. Genetic epistasis experiments with sensory signaling, exocytic and endocytic proteins further implicate OSTA-1 as a crucial regulator of ciliary architecture via regulation of cilia-destined trafficking. Our findings suggest that regulation of transport pathways in a cell type-specific manner contributes to diversity in sensory cilia structure and might allow dynamic remodeling of ciliary architecture via multiple inputs.
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Carpenter, April C.; Smith, April N.; Wagner, Heidi; Cohen-Tayar, Yamit; Rao, Sujata; Wallace, Valerie; Ashery-Padan, Ruth; Lang, Richard A.
2015-01-01
The Wnt/β-catenin response pathway is central to many developmental processes. Here, we assessed the role of Wnt signaling in early eye development using the mouse as a model system. We showed that the surface ectoderm region that includes the lens placode expressed 12 out of 19 possible Wnt ligands. When these activities were suppressed by conditional deletion of wntless (Le-cre; Wlsfl/fl) there were dramatic consequences that included a saucer-shaped optic cup, ventral coloboma, and a deficiency of periocular mesenchyme. This phenotype shared features with that produced when the Wnt/β-catenin pathway co-receptor Lrp6 is mutated or when retinoic acid (RA) signaling in the eye is compromised. Consistent with this, microarray and cell fate marker analysis identified a series of expression changes in genes known to be regulated by RA or by the Wnt/β-catenin pathway. Using pathway reporters, we showed that Wnt ligands from the surface ectoderm directly or indirectly elicit a Wnt/β-catenin response in retinal pigment epithelium (RPE) progenitors near the optic cup rim. In Le-cre; Wlsfl/fl mice, the numbers of RPE cells are reduced and this can explain, using the principle of the bimetallic strip, the curvature of the optic cup. These data thus establish a novel hypothesis to explain how differential cell numbers in a bilayered epithelium can lead to shape change. PMID:25715397
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Mkhitaryan, V. V.; Danilovic, D.; Hippola, C.
We present a comparative theoretical study of magnetic resonance within the polaron pair recombination (PPR) and the triplet exciton-polaron quenching (TPQ) models. Both models have been invoked to interpret the photoluminescence detected magnetic resonance (PLDMR) results in π-conjugated materials and devices. We show that resonance line shapes calculated within the two models differ dramatically in several regards. First, in the PPR model, the line shape exhibits unusual behavior upon increasing the microwave power: it evolves from fully positive at weak power to fully negative at strong power. In contrast, in the TPQ model, the PLDMR is completely positive, showing amore » monotonic saturation. Second, the two models predict different dependencies of the resonance signal on the photoexcitation power, PL. At low PL, the resonance amplitude Δ I/I is ∝ PL within the PPR model, while it is ∝ P2L crossing over to P3L within the TPQ model. On the physical level, the differences stem from different underlying spin dynamics. Most prominently, a negative resonance within the PPR model has its origin in the microwave-induced spin-Dicke effect, leading to the resonant quenching of photoluminescence. The spin-Dicke effect results from the spin-selective recombination, leading to a highly correlated precession of the on-resonance pair partners under the strong microwave power. This effect is not relevant for TPQ mechanism, where the strong zero-field splitting renders the majority of triplets off resonance. On the technical level, the analytical evaluation of the line shapes for the two models is enabled by the fact that these shapes can be expressed via the eigenvalues of a complex Hamiltonian. This bypasses the necessity of solving the much larger complex linear system of the stochastic Liouville equations. Lastly, our findings pave the way towards a reliable discrimination between the two mechanisms via cw PLDMR.« less
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Mkhitaryan, V. V.; Danilovic, D.; Hippola, C.; ...
2018-01-03
We present a comparative theoretical study of magnetic resonance within the polaron pair recombination (PPR) and the triplet exciton-polaron quenching (TPQ) models. Both models have been invoked to interpret the photoluminescence detected magnetic resonance (PLDMR) results in π-conjugated materials and devices. We show that resonance line shapes calculated within the two models differ dramatically in several regards. First, in the PPR model, the line shape exhibits unusual behavior upon increasing the microwave power: it evolves from fully positive at weak power to fully negative at strong power. In contrast, in the TPQ model, the PLDMR is completely positive, showing amore » monotonic saturation. Second, the two models predict different dependencies of the resonance signal on the photoexcitation power, PL. At low PL, the resonance amplitude Δ I/I is ∝ PL within the PPR model, while it is ∝ P2L crossing over to P3L within the TPQ model. On the physical level, the differences stem from different underlying spin dynamics. Most prominently, a negative resonance within the PPR model has its origin in the microwave-induced spin-Dicke effect, leading to the resonant quenching of photoluminescence. The spin-Dicke effect results from the spin-selective recombination, leading to a highly correlated precession of the on-resonance pair partners under the strong microwave power. This effect is not relevant for TPQ mechanism, where the strong zero-field splitting renders the majority of triplets off resonance. On the technical level, the analytical evaluation of the line shapes for the two models is enabled by the fact that these shapes can be expressed via the eigenvalues of a complex Hamiltonian. This bypasses the necessity of solving the much larger complex linear system of the stochastic Liouville equations. Lastly, our findings pave the way towards a reliable discrimination between the two mechanisms via cw PLDMR.« less
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NASA Astrophysics Data System (ADS)
Mkhitaryan, V. V.; Danilović, D.; Hippola, C.; Raikh, M. E.; Shinar, J.
2018-01-01
We present a comparative theoretical study of magnetic resonance within the polaron pair recombination (PPR) and the triplet exciton-polaron quenching (TPQ) models. Both models have been invoked to interpret the photoluminescence detected magnetic resonance (PLDMR) results in π -conjugated materials and devices. We show that resonance line shapes calculated within the two models differ dramatically in several regards. First, in the PPR model, the line shape exhibits unusual behavior upon increasing the microwave power: it evolves from fully positive at weak power to fully negative at strong power. In contrast, in the TPQ model, the PLDMR is completely positive, showing a monotonic saturation. Second, the two models predict different dependencies of the resonance signal on the photoexcitation power, PL. At low PL, the resonance amplitude Δ I /I is ∝PL within the PPR model, while it is ∝PL2 crossing over to PL3 within the TPQ model. On the physical level, the differences stem from different underlying spin dynamics. Most prominently, a negative resonance within the PPR model has its origin in the microwave-induced spin-Dicke effect, leading to the resonant quenching of photoluminescence. The spin-Dicke effect results from the spin-selective recombination, leading to a highly correlated precession of the on-resonance pair partners under the strong microwave power. This effect is not relevant for TPQ mechanism, where the strong zero-field splitting renders the majority of triplets off resonance. On the technical level, the analytical evaluation of the line shapes for the two models is enabled by the fact that these shapes can be expressed via the eigenvalues of a complex Hamiltonian. This bypasses the necessity of solving the much larger complex linear system of the stochastic Liouville equations. Our findings pave the way towards a reliable discrimination between the two mechanisms via cw PLDMR.
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Zhang, Qichong; Xu, Weiwei; Sun, Juan; Pan, Zhenghui; Zhao, Jingxin; Wang, Xiaona; Zhang, Jun; Man, Ping; Guo, Jiabin; Zhou, Zhenyu; He, Bing; Zhang, Zengxing; Li, Qingwen; Zhang, Yuegang; Xu, Lai; Yao, Yagang
2017-12-13
Increased efforts have recently been devoted to developing high-energy-density flexible supercapacitors for their practical applications in portable and wearable electronics. Although high operating voltages have been achieved in fiber-shaped asymmetric supercapacitors (FASCs), low specific capacitance still restricts the further enhancement of their energy density. This article specifies a facile and cost-effective method to directly grow three-dimensionally well-aligned zinc-nickel-cobalt oxide (ZNCO)@Ni(OH) 2 nanowire arrays (NWAs) on a carbon nanotube fiber (CNTF) with an ultrahigh specific capacitance of 2847.5 F/cm 3 (10.678 F/cm 2 ) at a current density of 1 mA/cm 2 , These levels are approximately five times higher than those of ZNCO NWAs/CNTF electrodes (2.10 F/cm 2 ) and four times higher than Ni(OH) 2 /CNTF electrodes (2.55 F/cm 2 ). Benefiting from their unique features, we successfully fabricated a prototype coaxial FASC (CFASC) with a maximum operating voltage of 1.6 V, which was assembled by adopting ZNCO@Ni(OH) 2 NWAs/CNTF as the core electrode and a thin layer of carbon coated vanadium nitride (VN@C) NWAs on a carbon nanotube strip (CNTS) as the outer electrode with KOH poly(vinyl alcohol) (PVA) as the gel electrolyte. A high specific capacitance of 94.67 F/cm 3 (573.75 mF/cm 2 ) and an exceptional energy density of 33.66 mWh/cm 3 (204.02 μWh/cm 2 ) were achieved for our CFASC device, which represent the highest levels of fiber-shaped supercapacitors to date. More importantly, the fiber-shaped ZnO-based photodetector is powered by the integrated CFASC, and it demonstrates excellent sensitivity in detecting UV light. Thus, this work paves the way to the construction of ultrahigh-capacity electrode materials for next-generation wearable energy-storage devices.
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Deygout, François; Auburtin, Guy
2015-03-01
Variability in occupational exposure levels to bitumen emissions has been observed during road paving operations. This is due to recurrent field factors impacting the level of exposure experienced by workers during paving. The present study was undertaken in order to quantify the impact of such factors. Pre-identified variables currently encountered in the field were monitored and recorded during paving surveys, and were conducted randomly covering current applications performed by road crews. Multivariate variance analysis and regressions were then used on computerized field data. The statistical investigations were limited due to the relatively small size of the study (36 data). Nevertheless, the particular use of the step-wise regression tool enabled the quantification of the impact of several predictors despite the existing collinearity between variables. The two bitumen organic fractions (particulates and volatiles) are associated with different field factors. The process conditions (machinery used and delivery temperature) have a significant impact on the production of airborne particulates and explain up to 44% of variability. This confirms the outcomes described by previous studies. The influence of the production factors is limited though, and should be complemented by studying factors involving the worker such as work style and the mix of tasks. The residual volatile compounds, being part of the bituminous binder and released during paving operations, control the volatile emissions; 73% of the encountered field variability is explained by the composition of the bitumen batch. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.
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ERIC Educational Resources Information Center
McGillion, Michelle; Herbert, Jane S.; Pine, Julian; Vihman, Marilyn; dePaolis, Rory; Keren-Portnoy, Tamar; Matthews, Danielle
2017-01-01
A child's first words mark the emergence of a uniquely human ability. Theories of the developmental steps that pave the way for word production have proposed that either vocal or gestural precursors are key. These accounts were tested by assessing the developmental synchrony in the onset of babbling, pointing, and word production for 46 infants…
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Dietzek, Benjamin; Brüggemann, Ben; Pascher, Torbjörn; Yartsev, Arkady
2007-10-31
Using optimal control as a spectroscopic tool we decipher the details of the molecular dynamics of the essential multidimensional excited-state photoisomerization - a fundamental chemical reaction of key importance in biology. Two distinct nuclear motions are identified in addition to the overall bond-twisting motion: Initially, the reaction is dominated by motion perpendicular to the torsion coordinate. At later times, a second optically active vibration drives the system along the reaction path to the bottom of the excited-state potential. The time scales of the wavepacket motion on a different part of the excited-state potential are detailed by pump-shaped dump optimal control. This technique offers new means to control a chemical reaction far from the Franck-Condon point of absorption and to map details of excited-state reaction pathways revealing unique insights into the underlying reaction mechanism.
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NiTi shape memory via solid-state nudge-elastic band
NASA Astrophysics Data System (ADS)
Zarkevich, Nikolai A.; Johnson, Duane D.
2014-03-01
We determine atomic mechanisms of the shape memory effect in NiTi from a generalized solid-state nudge elastic band (SSNEB) method. We consider transformation between the austenite B2 and the ground-state base-centered orthorhombic (BCO) structures. In these pathways we obtain the R-phase and discuss its structure. We confirm that BCO is the ground state, and determine the pathways to BCO martensite, which dictate transition barriers. While ideal B2 is unstable, we find a B2-like NiTi high-temperature solid phase with significant local displacement disorder, which is B2 on average. This B2-like phase appears to be entropically stabilized. This work is supported by the U.S. Department of Energy, Office of Basic Energy Science, Division of Materials Science and Engineering. Ames Laboratory is operated for the U.S. DOE by Iowa State University under contract DE-AC02-07CH11358.
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Rago, Alfredo; While, Geoffrey M; Uller, Tobias
2012-01-01
A major goal for ecology and evolution is to understand how abiotic and biotic factors shape patterns of biological diversity. Here, we show that variation in establishment success of nonnative frogs and toads is primarily explained by variation in introduction pathways and climatic similarity between the native range and introduction locality, with minor contributions from phylogeny, species ecology, and life history. This finding contrasts with recent evidence that particular species characteristics promote evolutionary range expansion and reduce the probability of extinction in native populations of amphibians, emphasizing how different mechanisms may shape species distributions on different temporal and spatial scales. We suggest that contemporary changes in the distribution of amphibians will be primarily determined by human-mediated extinctions and movement of species within climatic envelopes, and less by species-typical traits. PMID:22957152
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Cortical Actomyosin Breakage Triggers Shape Oscillations in Cells and Cell Fragments
Paluch, Ewa; Piel, Matthieu; Prost, Jacques; Bornens, Michel; Sykes, Cécile
2005-01-01
Cell shape and movements rely on complex biochemical pathways that regulate actin, microtubules, and substrate adhesions. Some of these pathways act through altering the cortex contractility. Here we examined cellular systems where contractility is enhanced by disassembly of the microtubules. We found that adherent cells, when detached from their substrate, developed a membrane bulge devoid of detectable actin and myosin. A constriction ring at the base of the bulge oscillated from one side of the cell to the other. The movement was accompanied by sequential redistribution of actin and myosin to the membrane. We observed this oscillatory behavior also in cell fragments of various sizes, providing a simplified, nucleus-free system for biophysical studies. Our observations suggest a mechanism based on active gel dynamics and inspired by symmetry breaking of actin gels growing around beads. The proposed mechanism for breakage of the actomyosin cortex may be used for cell polarization. PMID:15879479
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Tuning the anticancer activity of a novel pro-apoptotic peptide using gold nanoparticle platforms
Akrami, Mohammad; Balalaie, Saeed; Hosseinkhani, Saman; Alipour, Mohsen; Salehi, Fahimeh; Bahador, Abbas; Haririan, Ismaeil
2016-01-01
Pro-apoptotic peptides induce intrinsic apoptosis pathway in cancer cells. However, poor cellular penetration of the peptides is often associated with limited therapeutic efficacy. In this report, a series of peptide-gold nanoparticle platforms were developed to evaluate the anticancer activity of a novel alpha-lipoic acid-peptide conjugate, LA-WKRAKLAK, with respect to size and shape of nanoparticles. Gold nanoparticles (AuNPs) were found to enhance cell internalization as well as anticancer activity of the peptide conjugates. The smaller nanospheres showed a higher cytotoxicity, morphological change and cellular uptake compared to larger nanospheres and nanorods, whereas nanorods showed more hemolytic activity compared to nanospheres. The findings suggested that the anticancer and biological effects of the peptides induced by intrinsic apoptotic pathway were tuned by peptide-functionalized gold nanoparticles (P-AuNPs) as a function of their size and shape. PMID:27491007
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Tuning the anticancer activity of a novel pro-apoptotic peptide using gold nanoparticle platforms
NASA Astrophysics Data System (ADS)
Akrami, Mohammad; Balalaie, Saeed; Hosseinkhani, Saman; Alipour, Mohsen; Salehi, Fahimeh; Bahador, Abbas; Haririan, Ismaeil
2016-08-01
Pro-apoptotic peptides induce intrinsic apoptosis pathway in cancer cells. However, poor cellular penetration of the peptides is often associated with limited therapeutic efficacy. In this report, a series of peptide-gold nanoparticle platforms were developed to evaluate the anticancer activity of a novel alpha-lipoic acid-peptide conjugate, LA-WKRAKLAK, with respect to size and shape of nanoparticles. Gold nanoparticles (AuNPs) were found to enhance cell internalization as well as anticancer activity of the peptide conjugates. The smaller nanospheres showed a higher cytotoxicity, morphological change and cellular uptake compared to larger nanospheres and nanorods, whereas nanorods showed more hemolytic activity compared to nanospheres. The findings suggested that the anticancer and biological effects of the peptides induced by intrinsic apoptotic pathway were tuned by peptide-functionalized gold nanoparticles (P-AuNPs) as a function of their size and shape.
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Harris, Greg M.; Shazly, Tarek; Jabbarzadeh, Ehsan
2013-01-01
Significant effort has gone towards parsing out the effects of surrounding microenvironment on macroscopic behavior of stem cells. Many of the microenvironmental cues, however, are intertwined, and thus, further studies are warranted to identify the intricate interplay among the conflicting downstream signaling pathways that ultimately guide a cell response. In this contribution, by patterning adhesive PEG (polyethylene glycol) hydrogels using Dip Pen Nanolithography (DPN), we demonstrate that substrate elasticity, subcellular elasticity, ligand density, and topography ultimately define mesenchymal stem cells (MSCs) spreading and shape. Physical characteristics are parsed individually with 7 kilopascal (kPa) hydrogel islands leading to smaller, spindle shaped cells and 105 kPa hydrogel islands leading to larger, polygonal cell shapes. In a parallel effort, a finite element model was constructed to characterize and confirm experimental findings and aid as a predictive tool in modeling cell microenvironments. Signaling pathway inhibition studies suggested that RhoA is a key regulator of cell response to the cooperative effect of the tunable substrate variables. These results are significant for the engineering of cell-extra cellular matrix interfaces and ultimately decoupling matrix bound cues presented to cells in a tissue microenvironment for regenerative medicine. PMID:24282570
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Convergence, recurrence and diversification of complex sperm traits in diving beetles (Dytiscidae)
Higginson, Dawn M.; Miller, Kelly B.; Segraves, Kari A.; Pitnick, Scott
2013-01-01
Sperm display remarkable morphological diversity among even closely related species, a pattern that is widely attributed to postcopulatory sexual selection. Surprisingly few studies have used phylogenetic analyses to discern the details of evolutionary diversification in ornaments and armaments subject to sexual selection, and the origins of novel sperm traits and their subsequent modification are particularly poorly understood. Here we investigate sperm evolution in diving beetles (Dytiscidae), revealing dramatic diversification in flagellum length, head shape, presence of sperm heteromorphism, and the presence/type of sperm conjugation, an unusual trait where two or more sperm unite for motility or transport. Sperm conjugation was found to be the ancestral condition in diving beetles, with subsequent diversification into three forms, each exhibiting varying degrees of evolutionary loss, convergence and recurrence. Sperm head shape, but not length or heteromorphism, was found to evolve in a significantly correlated manner with conjugation, consistent with the different mechanisms of head alignment and binding required for the different forms of conjugation. Our study reveals that sperm morphological evolution is channeled along particular evolutionary pathways (i.e., conjugate form), yet subject to considerable diversification within those pathways through modification in sperm length, head shape and heteromorphism. PMID:22519797
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The potential use of tar sand bitumen as paving asphalt
DOE Office of Scientific and Technical Information (OSTI.GOV)
Petersen, J.C.
1988-01-01
In this paper several research reports describing the preparation of potential paving asphalts from tar sand bitumen are reviewed and the results of the studies compared. The tar sand asphalts described in the studies were prepared from 1) hot water-recovered bitumen from deposits near San Luis Obispo, California (Edna deposits), and deposits near Vernal and Sunnyside, Utah; and 2) bitumen recovered from the Northwest Asphalt Ridge deposits near Vernal, Utah, by both in situ steamflood and in situ combustion recovery processes. Important properties of the tar sand asphalts compare favorably with those of specification petroleum asphalts. Laboratory data suggest thatmore » some tar sand asphalts may have superior aging characteristics and produce more water-resistant paving mixtures than typical petroleum asphalts.« less
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Ojovan, Silviya M; Rabieh, Noha; Shmoel, Nava; Erez, Hadas; Maydan, Eilon; Cohen, Ariel; Spira, Micha E
2015-09-14
The development of multi-electrode array platforms for large scale recording of neurons is at the forefront of neuro-engineering research efforts. Recently we demonstrated, at the proof-of-concept level, a breakthrough neuron-microelectrode interface in which cultured Aplysia neurons tightly engulf gold mushroom-shaped microelectrodes (gMμEs). While maintaining their extracellular position, the gMμEs record synaptic- and action-potentials with characteristic features of intracellular recordings. Here we examined the feasibility of using gMμEs for intracellular recordings from mammalian neurons. To that end we experimentally examined the innate size limits of cultured rat hippocampal neurons to engulf gMμEs and measured the width of the "extracellular" cleft formed between the neurons and the gold surface. Using the experimental results we next analyzed the expected range of gMμEs-neuron electrical coupling coefficients. We estimated that sufficient electrical coupling levels to record attenuated synaptic- and action-potentials can be reached using the gMμE-neuron configuration. The definition of the engulfment limits of the gMμEs caps diameter at ≤2-2.5 μm and the estimated electrical coupling coefficients from the simulations pave the way for rational development and application of the gMμE based concept for in-cell recordings from mammalian neurons.
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Coherent control of alkali cluster fragmentation dynamics
NASA Astrophysics Data System (ADS)
Lindinger, Albrecht; Lupulescu, Cosmin; Bartelt, Andreas; Vajda, Štefan; Wöste, Ludger
2003-06-01
Metal clusters exhibit extraordinary chemical and catalytic properties, which sensitively depend upon their size. This behavior makes them interesting candidates for the real-time analysis of ultrafast photo-induced processes—ultimately leading to coherent control scenarii. We have performed transient multi-photon ionization experiments on small alkali clusters of different size in order to probe their wave packet dynamics, structural reorientations, charge transfers and dissociative events in different vibrationally excited electronic states including their ground state. The observed processes were highly dependent on the irradiated pulse parameters, like its phase, amplitude and duration; an emphasis to employ a feedback control system for generating the optimum pulse shapes. Their spectral and temporal behavior reflects interesting properties about the investigated system and the irradiated photochemical process. We present first the vibrational dynamics of bound, dissociated, and pre-dissociated electronically excited states of alkali dimers and trimers. The scheme for observing the wave packet dynamics in the electronic ground state using stimulated Raman-pumping is shown. Since the employed pulse parameters significantly influence the efficiency of the irradiated dynamic pathways photo-induced fragmentation experiments on bifurcating reaction channels were carried out. In these experiments different branching ionization and fragmentation pathways of electronically excited Na 2K were investigated. By employing an evolutionary algorithm for optimizing the phase and amplitude of the applied laser field, the yield of the resulting parent or fragment ions could significantly be influenced and interesting features could be concluded from the obtained optimum pulse shapes revealing the characteristic molecular oscillation period. Moreover, the influence on the optimal pulse shape due to fragmentation from larger clusters into NaK is obtained. The substructure of the optimal pulse shape thereby offers new insight into the fragmentation channel during the control process. Characteristic motions of the involved wave packets are proposed, in order to explain the optimized dynamic dissociation pathways.
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Guiding the folding pathway of DNA origami
NASA Astrophysics Data System (ADS)
Dunn, Katherine E.; Dannenberg, Frits; Ouldridge, Thomas E.; Kwiatkowska, Marta; Turberfield, Andrew J.; Bath, Jonathan
2015-09-01
DNA origami is a robust assembly technique that folds a single-stranded DNA template into a target structure by annealing it with hundreds of short `staple' strands. Its guiding design principle is that the target structure is the single most stable configuration. The folding transition is cooperative and, as in the case of proteins, is governed by information encoded in the polymer sequence. A typical origami folds primarily into the desired shape, but misfolded structures can kinetically trap the system and reduce the yield. Although adjusting assembly conditions or following empirical design rules can improve yield, well-folded origami often need to be separated from misfolded structures. The problem could in principle be avoided if assembly pathway and kinetics were fully understood and then rationally optimized. To this end, here we present a DNA origami system with the unusual property of being able to form a small set of distinguishable and well-folded shapes that represent discrete and approximately degenerate energy minima in a vast folding landscape, thus allowing us to probe the assembly process. The obtained high yield of well-folded origami structures confirms the existence of efficient folding pathways, while the shape distribution provides information about individual trajectories through the folding landscape. We find that, similarly to protein folding, the assembly of DNA origami is highly cooperative; that reversible bond formation is important in recovering from transient misfoldings; and that the early formation of long-range connections can very effectively enforce particular folds. We use these insights to inform the design of the system so as to steer assembly towards desired structures. Expanding the rational design process to include the assembly pathway should thus enable more reproducible synthesis, particularly when targeting more complex structures. We anticipate that this expansion will be essential if DNA origami is to continue its rapid development and become a reliable manufacturing technology.
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Guiding the folding pathway of DNA origami.
Dunn, Katherine E; Dannenberg, Frits; Ouldridge, Thomas E; Kwiatkowska, Marta; Turberfield, Andrew J; Bath, Jonathan
2015-09-03
DNA origami is a robust assembly technique that folds a single-stranded DNA template into a target structure by annealing it with hundreds of short 'staple' strands. Its guiding design principle is that the target structure is the single most stable configuration. The folding transition is cooperative and, as in the case of proteins, is governed by information encoded in the polymer sequence. A typical origami folds primarily into the desired shape, but misfolded structures can kinetically trap the system and reduce the yield. Although adjusting assembly conditions or following empirical design rules can improve yield, well-folded origami often need to be separated from misfolded structures. The problem could in principle be avoided if assembly pathway and kinetics were fully understood and then rationally optimized. To this end, here we present a DNA origami system with the unusual property of being able to form a small set of distinguishable and well-folded shapes that represent discrete and approximately degenerate energy minima in a vast folding landscape, thus allowing us to probe the assembly process. The obtained high yield of well-folded origami structures confirms the existence of efficient folding pathways, while the shape distribution provides information about individual trajectories through the folding landscape. We find that, similarly to protein folding, the assembly of DNA origami is highly cooperative; that reversible bond formation is important in recovering from transient misfoldings; and that the early formation of long-range connections can very effectively enforce particular folds. We use these insights to inform the design of the system so as to steer assembly towards desired structures. Expanding the rational design process to include the assembly pathway should thus enable more reproducible synthesis, particularly when targeting more complex structures. We anticipate that this expansion will be essential if DNA origami is to continue its rapid development and become a reliable manufacturing technology.
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The place of public inquiries in shaping New Zealand's national mental health policy 1858-1996.
Brunton, Warwick
2005-10-10
This paper discusses the role of public inquiries as an instrument of public policy-making in New Zealand, using mental health as a case study. The main part of the paper analyses the processes and outcomes of five general inquiries into the state of New Zealand's mental health services that were held between 1858 and 1996. The membership, form, style and processes used by public inquiries have all changed over time in line with constitutional and social trends. So has the extent of public participation. The records of five inquiries provide periodic snapshots of a system bedevilled by long-standing problems such as unacceptable standards, under-resourcing, and poor co-ordination. Demands for an investigation no less than the reports and recommendations of public inquiries have been the catalyst of some important policy changes, if not immediately, then by creating a climate of opinion that supported later change. Inquiries played a significant role in establishing lunatic asylums, in shaping the structure of mental health legislation, establishing and maintaining a national mental health bureaucracy within the machinery of government, and in paving the way for deinstitutionalisation. Ministers and their departmental advisers have mediated this contribution. Public inquiries have helped shape New Zealand's mental health policy, both directly and indirectly, at different stages of evolution. In both its advisory and investigative forms, the public inquiry remains an important tool of public administration. The inquiry/cause and policy/effect relationship is not necessarily immediate but may facilitate changes in public opinion with corresponding policy outcomes long after any direct causal link could be determined. When considered from that long-term perspective, the five inquiries can be linked to several significant and long-term contributions to mental health policy in New Zealand.
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The place of public inquiries in shaping New Zealand's national mental health policy 1858–1996
Brunton, Warwick
2005-01-01
Background This paper discusses the role of public inquiries as an instrument of public policy-making in New Zealand, using mental health as a case study. The main part of the paper analyses the processes and outcomes of five general inquiries into the state of New Zealand's mental health services that were held between 1858 and 1996. Results The membership, form, style and processes used by public inquiries have all changed over time in line with constitutional and social trends. So has the extent of public participation. The records of five inquiries provide periodic snapshots of a system bedevilled by long-standing problems such as unacceptable standards, under-resourcing, and poor co-ordination. Demands for an investigation no less than the reports and recommendations of public inquiries have been the catalyst of some important policy changes, if not immediately, then by creating a climate of opinion that supported later change. Inquiries played a significant role in establishing lunatic asylums, in shaping the structure of mental health legislation, establishing and maintaining a national mental health bureaucracy within the machinery of government, and in paving the way for deinstitutionalisation. Ministers and their departmental advisers have mediated this contribution. Conclusion Public inquiries have helped shape New Zealand's mental health policy, both directly and indirectly, at different stages of evolution. In both its advisory and investigative forms, the public inquiry remains an important tool of public administration. The inquiry/cause and policy/effect relationship is not necessarily immediate but may facilitate changes in public opinion with corresponding policy outcomes long after any direct causal link could be determined. When considered from that long-term perspective, the five inquiries can be linked to several significant and long-term contributions to mental health policy in New Zealand. PMID:16216131
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Optimal control of multiphoton ionization dynamics of small alkali aggregates
NASA Astrophysics Data System (ADS)
Lindinger, A.; Bartelt, A.; Lupulescu, C.; Vajda, S.; Woste, Ludger
2003-11-01
We have performed transient multi-photon ionization experiments on small alkali clusters of different size in order to probe their wave packet dynamics, structural reorientations, charge transfers and dissociative events in different vibrationally excited electronic states including their ground state. The observed processes were highly dependent on the irradiated pulse parameters like wavelength range or its phase and amplitude; an emphasis to employ a feedback control system for generating the optimum pulse shapes. Their spectral and temporal behavior reflects interesting properties about the investigated system and the irradiated photo-chemical process. First, we present the vibrational dynamics of bound electronically excited states of alkali dimers and trimers. The scheme for observing the wave packet dynamics in the electronic ground state using stimulated Raman-pumping is shown. Since the employed pulse parameters significantly influence the efficiency of the irradiated dynamic pathways photo-induced ioniziation experiments were carried out. The controllability of 3-photon ionization pathways is investigated on the model-like systems NaK and K2. A closed learning loop for adaptive feedback control is used to find the optimal fs pulse shape. Sinusoidal parameterizations of the spectral phase modulation are investigated in regard to the obtained optimal field. By reducing the number of parameters and thereby the complexity of the phase moduation, optimal pulse shapes can be generated that carry fingerprints of the molecule's dynamical properties. This enables to find "understandable" optimal pulse forms and offers the possiblity to gain insight into the photo-induced control process. Characteristic motions of the involved wave packets are proposed to explain the optimized dynamic dissociation pathways.
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Women's Work Pathways Across the Life Course.
Damaske, Sarah; Frech, Adrianne
2016-04-01
Despite numerous changes in women's employment in the latter half of the twentieth century, women's employment continues to be uneven and stalled. Drawing from data on women's weekly work hours in the National Longitudinal Survey of Youth (NLSY79), we identify significant inequality in women's labor force experiences across adulthood. We find two pathways of stable full-time work for women, three pathways of part-time employment, and a pathway of unpaid labor. A majority of women follow one of the two full-time work pathways, while fewer than 10% follow a pathway of unpaid labor. Our findings provide evidence of the lasting influence of work-family conflict and early socioeconomic advantages and disadvantages on women's work pathways. Indeed, race, poverty, educational attainment, and early family characteristics significantly shaped women's work careers. Work-family opportunities and constraints also were related to women's work hours, as were a woman's gendered beliefs and expectations. We conclude that women's employment pathways are a product of both their resources and changing social environment as well as individual agency. Significantly, we point to social stratification, gender ideologies, and work-family constraints, all working in concert, as key explanations for how women are "tracked" onto work pathways from an early age.
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NASA Astrophysics Data System (ADS)
Shirshin, Evgeny; Cherkasova, Olga; Tikhonova, Tatiana; Berlovskaya, Elena; Priezzhev, Alexander; Fadeev, Victor
2015-05-01
We present the results of a native fluorescence spectroscopy study of blood plasma of rats with experimental diabetes. It was shown that the fluorescence emission band shape at 320 nm excitation is the most indicative of hyperglycemia in the blood plasma samples. We provide the interpretation of this fact based on the changes in reduced nicotinamide adenine dinucleotide phosphate concentration due to glucose-related metabolic pathways and protein fluorescent cross-linking formation following nonenzymatic glycation.
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An Investigation of CTOL Dual-Mode PAVE Concepts
NASA Technical Reports Server (NTRS)
Marchman, James F., III; Interatep, Nanyaporn; Skelton, Eugene; Mason, William H.
2002-01-01
A study was conducted to assess the feasibility of the dual-mode concept for a personal air vehicle, to determine how constraints differ between the dual-mode concept and a Conventional Takeoff and Landing (CTOL) general aviation aircraft, to recommend a dual-mode vehicle concept, and to recommend areas where further research can contribute to the successful development of a viable PAVE vehicle design.
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A neural model of the temporal dynamics of figure-ground segregation in motion perception.
Raudies, Florian; Neumann, Heiko
2010-03-01
How does the visual system manage to segment a visual scene into surfaces and objects and manage to attend to a target object? Based on psychological and physiological investigations, it has been proposed that the perceptual organization and segmentation of a scene is achieved by the processing at different levels of the visual cortical hierarchy. According to this, motion onset detection, motion-defined shape segregation, and target selection are accomplished by processes which bind together simple features into fragments of increasingly complex configurations at different levels in the processing hierarchy. As an alternative to this hierarchical processing hypothesis, it has been proposed that the processing stages for feature detection and segregation are reflected in different temporal episodes in the response patterns of individual neurons. Such temporal epochs have been observed in the activation pattern of neurons as low as in area V1. Here, we present a neural network model of motion detection, figure-ground segregation and attentive selection which explains these response patterns in an unifying framework. Based on known principles of functional architecture of the visual cortex, we propose that initial motion and motion boundaries are detected at different and hierarchically organized stages in the dorsal pathway. Visual shapes that are defined by boundaries, which were generated from juxtaposed opponent motions, are represented at different stages in the ventral pathway. Model areas in the different pathways interact through feedforward and modulating feedback, while mutual interactions enable the communication between motion and form representations. Selective attention is devoted to shape representations by sending modulating feedback signals from higher levels (working memory) to intermediate levels to enhance their responses. Areas in the motion and form pathway are coupled through top-down feedback with V1 cells at the bottom end of the hierarchy. We propose that the different temporal episodes in the response pattern of V1 cells, as recorded in recent experiments, reflect the strength of modulating feedback signals. This feedback results from the consolidated shape representations from coherent motion patterns and the attentive modulation of responses along the cortical hierarchy. The model makes testable predictions concerning the duration and delay of the temporal episodes of V1 cell responses as well as their response variations that were caused by modulating feedback signals. Copyright 2009 Elsevier Ltd. All rights reserved.
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Sinabung Volcanic Ash Utilization As The Additive for Paving Block Quality A and B
NASA Astrophysics Data System (ADS)
Sembiring, I. S.; Hastuty, I. P.
2017-03-01
Paving block is one of the building materials used as the top layer of the road structure besides asphalt and concrete. Paving block is made of mixed materials such as portland cement or other adhesive materials, water and aggregate. In this research, the material used as the additive of cement and concrete is volcanic ash from Mount Sinabung, it is based on the results of the material testing, Sinabung ash contains 74.3% silica (SiO2). The purpose of this research aims to analyze the behavior of the paving blocks quality A and B with and without a mixture of Sinabung ash, to analyze the workability of fresh concrete using Sinabung ash as an additive in concrete, and to compare the test results of paving blocks with and without using Sinabung ash. The samples that we made consist of four variations of the concrete mix to experiment a mixture of normal sample without additive, samples which are mixed with the addition of Sinabung ash 5%, 10%, 15%, 20% and 25% of the volume of concrete/m3. Each variation consists of 10 samples of the concrete with 28 days curing time period. We will do the compressive strength and water absorption test to the samples to determine whether the samples are in accordance with the type needed. According to the test result, paving blocks with Sinabung ash and curing time reach quality A at 0%, 5% and 10% mixture with the compressive strength of each 50.14 MPa, 46.20 MPa and 1.49Mpa, and reach quality B at 15%, 20 %,25% mixture with curing time and 0%, 5%, 10%, 15%, 20% and 25% mixture without curing time. According to the absorption values we got from the test which are 6.66%, 6.73%, 6.88%, 7.03%, 7.09% and 7.16%, the entire sample have average absorption exceeding SNI standardization which is above 6% and reach quality C. Based on compressive strength and absorption data obtained Sinabung ash can’t fully replace cement as the binder because of the low CaO content.
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Salmonella Typhi genomics: envisaging the future of typhoid eradication.
Yap, Kien-Pong; Thong, Kwai Lin
2017-08-01
Next-generation whole-genome sequencing has revolutionised the study of infectious diseases in recent years. The availability of genome sequences and its understanding have transformed the field of molecular microbiology, epidemiology, infection treatments and vaccine developments. We review the key findings of the publicly accessible genomes of Salmonella enterica serovar Typhi since the first complete genome to the most recent release of thousands of Salmonella Typhi genomes, which remarkably shape the genomic research of S. Typhi and other pathogens. Important new insights acquired from the genome sequencing of S. Typhi, pertaining to genomic variations, evolution, population structure, antibiotic resistance, virulence, pathogenesis, disease surveillance/investigation and disease control are discussed. As the numbers of sequenced genomes are increasing at an unprecedented rate, fine variations in the gene pool of S. Typhi are captured in high resolution, allowing deeper understanding of the pathogen's evolutionary trends and its pathogenesis, paving the way to bringing us closer to eradication of typhoid through effective vaccine/treatment development. © 2017 John Wiley & Sons Ltd.
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NASA Astrophysics Data System (ADS)
Bagchi, A.; Sarkar, S.; Mukhopadhyay, P. K.
2018-02-01
Three different coloured focused laser beams were used to study the photo induced microactuation effect found in some ferromagnetic shape memory alloys. Besides trying to uncover the basic causes of this unique and as yet unexplained effect, these studies are to help find other conditions to further characterize the effect for practical use. In this study some mechanisms have been proposed to control the amplitude of actuation of the sample. Control of the actuation of the FSMA sample both linearly with the help of a continuously variable neutral density filter as well periodically with the help of a linear polarizer was achieved. Statistical analysis of the experimental data was also done by applying ANOVA studies on the data to conclusively provide evidence in support of the relationship between the actuation of the sample and the various controlling factors. This study is expected to pave the way to implement this property of the sample in fabricating and operating useful micro-mechanical systems in the near future.
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Recent Progress on High-Current SRF Cavities at Jlab
DOE Office of Scientific and Technical Information (OSTI.GOV)
Robert Rimmer, William Clemens, James Henry, Peter Kneisel, Kurt Macha, Frank Marhauser, Larry Turlington, Haipeng Wang, Daniel Forehand
2010-05-01
JLab has designed and fabricated several prototype SRF cavities with cell shapes optimized for high current beams and with strong damping of unwanted higher order modes. We report on the latest test results of these cavities and on developments of concepts for new variants optimized for particular applications such as light sources and high-power proton accelerators, including betas less than one. We also report on progress towards a first beam test of this design in the recirculation loop of the JLab ERL based FEL. With growing interest worldwide in applications of SRF for high-average power electron and hadron machines, amore » practical test of these concepts is highly desirable. We plan to package two prototype cavities in a de-mountable cryomodule for temporary installation into the JLab FEL for testing with RF and beam. This will allow verification of all critical design and operational parameters paving the way to a full-scale prototype cryomodule.« less
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Automated Reconstruction of Three-Dimensional Fish Motion, Forces, and Torques
Voesenek, Cees J.; Pieters, Remco P. M.; van Leeuwen, Johan L.
2016-01-01
Fish can move freely through the water column and make complex three-dimensional motions to explore their environment, escape or feed. Nevertheless, the majority of swimming studies is currently limited to two-dimensional analyses. Accurate experimental quantification of changes in body shape, position and orientation (swimming kinematics) in three dimensions is therefore essential to advance biomechanical research of fish swimming. Here, we present a validated method that automatically tracks a swimming fish in three dimensions from multi-camera high-speed video. We use an optimisation procedure to fit a parameterised, morphology-based fish model to each set of video images. This results in a time sequence of position, orientation and body curvature. We post-process this data to derive additional kinematic parameters (e.g. velocities, accelerations) and propose an inverse-dynamics method to compute the resultant forces and torques during swimming. The presented method for quantifying 3D fish motion paves the way for future analyses of swimming biomechanics. PMID:26752597
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Liang, Yufeng; Vinson, John; Pemmaraju, Sri
Constrained-occupancy delta-self-consistent-field (ΔSCF) methods and many-body perturbation theories (MBPT) are two strategies for obtaining electronic excitations from first principles. Using the two distinct approaches, we study the O 1s core excitations that have become increasingly important for characterizing transition-metal oxides and understanding strong electronic correlation. The ΔSCF approach, in its current single-particle form, systematically underestimates the pre-edge intensity for chosen oxides, despite its success in weakly correlated systems. By contrast, the Bethe-Salpeter equation within MBPT predicts much better line shapes. This motivates one to reexamine the many-electron dynamics of x-ray excitations. We find that the single-particle ΔSCF approach can bemore » rectified by explicitly calculating many-electron transition amplitudes, producing x-ray spectra in excellent agreement with experiments. This study paves the way to accurately predict x-ray near-edge spectral fingerprints for physics and materials science beyond the Bethe-Salpether equation.« less
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Hwang, Sung Hoon; Miller, Joseph B; Shahsavari, Rouzbeh
2017-10-25
Many natural materials, such as nacre and dentin, exhibit multifunctional mechanical properties via structural interplay between compliant and stiff constituents arranged in a particular architecture. Herein, we present, for the first time, the bottom-up synthesis and design of strong, tough, and self-healing composite using simple but universal spherical building blocks. Our composite system is composed of calcium silicate porous nanoparticles with unprecedented monodispersity over particle size, particle shape, and pore size, which facilitate effective loading and unloading with organic sealants, resulting in 258% and 307% increases in the indentation hardness and elastic modulus of the compacted composite. Furthermore, heating the damaged composite triggers the controlled release of the nanoconfined sealant into the surrounding area, enabling moderate recovery in strength and toughness. This work paves the path towards fabricating a novel class of biomimetic composites using low-cost spherical building blocks, potentially impacting bone-tissue engineering, insulation, refractory and constructions materials, and ceramic matrix composites.
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Synthesis and characterization of attosecond light vortices in the extreme ultraviolet
Géneaux, R.; Camper, A.; Auguste, T.; Gobert, O.; Caillat, J.; Taïeb, R.; Ruchon, T.
2016-01-01
Infrared and visible light beams carrying orbital angular momentum (OAM) are currently thoroughly studied for their extremely broad applicative prospects, among which are quantum information, micromachining and diagnostic tools. Here we extend these prospects, presenting a comprehensive study for the synthesis and full characterization of optical vortices carrying OAM in the extreme ultraviolet (XUV) domain. We confirm the upconversion rules of a femtosecond infrared helically phased beam into its high-order harmonics, showing that each harmonic order carries the total number of OAM units absorbed in the process up to very high orders (57). This allows us to synthesize and characterize helically shaped XUV trains of attosecond pulses. To demonstrate a typical use of these new XUV light beams, we show our ability to generate and control, through photoionization, attosecond electron beams carrying OAM. These breakthroughs pave the route for the study of a series of fundamental phenomena and the development of new ultrafast diagnosis tools using either photonic or electronic vortices. PMID:27573787
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Schoderboeck, Lucia; Adzemovic, Milena; Nicolussi, Eva-Maria; Crupinschi, Claudia; Hochmeister, Sonja; Fischer, Marie-Therese; Lassmann, Hans; Bradl, Monika
2013-01-01
Early in postnatal development, the immature central nervous system (CNS) is more susceptible to inflammation than its adult counterpart. We show here that this “window of susceptibility” is characterized by the presence of leaky vessels in the CNS, and by a global chemokine expression profile which is clearly distinct from the one observed in the adult CNS and has three important characteristics. First, it contains chemokines with known roles in the differentiation and maturation of glia and neurons. Secondly, these chemokines have been described before in inflammatory lesions of the CNS, where they are important for the recruitment of monocytes and T cells. And last, the chemokine profile is shaped by pathological changes like oligodendrocyte stress and attempts of myelin repair. Changes in the chemokine expression profile along with a leaky blood brain barrier pave the ground for an accelerated development of CNS inflammation. PMID:19520164
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Räupke, André; Albrecht, Fabian; Maibach, Julia; Behrendt, Andreas; Polywka, Andreas; Heiderhoff, Ralf; Helzel, Jonatan; Rabe, Torsten; Johannes, Hans-Hermann; Kowalsky, Wolfgang; Mankel, Eric; Mayer, Thomas; Görrn, Patrick; Riedl, Thomas
2014-01-22
The gas-phase molecular layer deposition (MLD) of conformal and highly luminescent monolayers of tris(8-hydroxyquinolinato)aluminum (Alq3) is reported. The controlled formation of Alq3 monolayers is achieved for the first time by functionalization of the substrate with amino groups, which serve as initial docking sites for trimethyl aluminum (TMA) molecules binding datively to the amine. Thereby, upon exposure to 8-hydroxyquinoline (8-HQ), the self-limiting formation of highly luminescent Alq3 monolayers is afforded. The growth process and monolayer formation were studied and verified by in situ quartz crystal monitoring, optical emission and absorption spectroscopy, and X-ray photoelectron spectroscopy. The nature of the MLD process provides an avenue to coat arbitrarily shaped 3D surfaces and porous structures with high surface areas, as demonstrated in this work for silica aerogels. The concept presented here paves the way to highly sensitive luminescent sensors and dye-sensitized metal oxides for future applications (e.g., in photocatalysis and solar cells).
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NASA Astrophysics Data System (ADS)
Bagchi, A.; Sarkar, S.; Mukhopadhyay, P. K.
2018-07-01
Three different coloured focused laser beams were used to study the photo induced microactuation effect found in some ferromagnetic shape memory alloys. Besides trying to uncover the basic causes of this unique and as yet unexplained effect, these studies are to help find other conditions to further characterize the effect for practical use. In this study some mechanisms have been proposed to control the amplitude of actuation of the sample. Control of the actuation of the FSMA sample both linearly with the help of a continuously variable neutral density filter as well periodically with the help of a linear polarizer was achieved. Statistical analysis of the experimental data was also done by applying ANOVA studies on the data to conclusively provide evidence in support of the relationship between the actuation of the sample and the various controlling factors. This study is expected to pave the way to implement this property of the sample in fabricating and operating useful micro-mechanical systems in the near future.
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Designing Hysteresis with Dipolar Chains
NASA Astrophysics Data System (ADS)
Concha, Andrés; Aguayo, David; Mellado, Paula
2018-04-01
Materials that have hysteretic response to an external field are essential in modern information storage and processing technologies. A myriad of magnetization curves of several natural and artificial materials have previously been measured and each has found a particular mechanism that accounts for it. However, a phenomenological model that captures all the hysteresis loops and at the same time provides a simple way to design the magnetic response of a material while remaining minimal is missing. Here, we propose and experimentally demonstrate an elementary method to engineer hysteresis loops in metamaterials built out of dipolar chains. We show that by tuning the interactions of the system and its geometry we can shape the hysteresis loop which allows for the design of the softness of a magnetic material at will. Additionally, this mechanism allows for the control of the number of loops aimed to realize multiple-valued logic technologies. Our findings pave the way for the rational design of hysteretical responses in a variety of physical systems such as dipolar cold atoms, ferroelectrics, or artificial magnetic lattices, among others.
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Synthesis and characterization of attosecond light vortices in the extreme ultraviolet
Géneaux, R.; Camper, A.; Auguste, T.; ...
2016-08-30
Infrared and visible light beams carrying orbital angular momentum (OAM) are currently thoroughly studied for their extremely broad applicative prospects, among which are quantum information, micromachining and diagnostic tools. Here we extend these prospects, presenting a comprehensive study for the synthesis and full characterization of optical vortices carrying OAM in the extreme ultraviolet (XUV) domain. We confirm the upconversion rules of a femtosecond infrared helically phased beam into its high-order harmonics, showing that each harmonic order carries the total number of OAM units absorbed in the process up to very high orders (57). This allows us to synthesize and characterizemore » helically shaped XUV trains of attosecond pulses. To demonstrate a typical use of these new XUV light beams, we show our ability to generate and control, through photoionization, attosecond electron beams carrying OAM. Furthermore, these breakthroughs pave the route for the study of a series of fundamental phenomena and the development of new ultrafast diagnosis tools using either photonic or electronic vortices.« less
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Direct mapping of local redox current density on a monolith electrode by laser scanning.
Lee, Seung-Woo; Lopez, Jeffrey; Saraf, Ravi F
2013-09-15
An optical method of mapping local redox reaction over a monolith electrode using simple laser scanning is described. As the optical signal is linearly proportional to the maximum redox current that is measured concomitantly by voltammetry, the optical signal quantitatively maps the local redox current density distribution. The method is demonstrated on two types of reactions: (1) a reversible reaction where the redox moieties are ionic, and (2) an irreversible reaction on two different types of enzymes immobilized on the electrode where the reaction moieties are nonionic. To demonstrate the scanning capability, the local redox behavior on a "V-shaped" electrode is studied where the local length scale and, hence, the local current density, is nonuniform. The ability to measure the current density distribution by this method will pave the way for multianalyte analysis on a monolith electrode using a standard three-electrode configuration. The method is called Scanning Electrometer for Electrical Double-layer (SEED). Copyright © 2013 Elsevier B.V. All rights reserved.
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Designing Hysteresis with Dipolar Chains.
Concha, Andrés; Aguayo, David; Mellado, Paula
2018-04-13
Materials that have hysteretic response to an external field are essential in modern information storage and processing technologies. A myriad of magnetization curves of several natural and artificial materials have previously been measured and each has found a particular mechanism that accounts for it. However, a phenomenological model that captures all the hysteresis loops and at the same time provides a simple way to design the magnetic response of a material while remaining minimal is missing. Here, we propose and experimentally demonstrate an elementary method to engineer hysteresis loops in metamaterials built out of dipolar chains. We show that by tuning the interactions of the system and its geometry we can shape the hysteresis loop which allows for the design of the softness of a magnetic material at will. Additionally, this mechanism allows for the control of the number of loops aimed to realize multiple-valued logic technologies. Our findings pave the way for the rational design of hysteretical responses in a variety of physical systems such as dipolar cold atoms, ferroelectrics, or artificial magnetic lattices, among others.
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Liang, Yufeng; Vinson, John; Pemmaraju, Sri; ...
2017-03-03
Constrained-occupancy delta-self-consistent-field (ΔSCF) methods and many-body perturbation theories (MBPT) are two strategies for obtaining electronic excitations from first principles. Using the two distinct approaches, we study the O 1s core excitations that have become increasingly important for characterizing transition-metal oxides and understanding strong electronic correlation. The ΔSCF approach, in its current single-particle form, systematically underestimates the pre-edge intensity for chosen oxides, despite its success in weakly correlated systems. By contrast, the Bethe-Salpeter equation within MBPT predicts much better line shapes. This motivates one to reexamine the many-electron dynamics of x-ray excitations. We find that the single-particle ΔSCF approach can bemore » rectified by explicitly calculating many-electron transition amplitudes, producing x-ray spectra in excellent agreement with experiments. This study paves the way to accurately predict x-ray near-edge spectral fingerprints for physics and materials science beyond the Bethe-Salpether equation.« less
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Caring sexual assault patients in the military: past, present, and future.
Ferguson, Cynthia T
2008-01-01
Recently instituted sexual assault prevention and response policies and programs within the Department of Defense (DoD) have paved the way for significant improvements in the medical care of sexual assault patients in the military services. Military personnel who suffer assault are now able to choose a method of reporting that either immediately triggers an investigation or allows the incident to remain confidential. This process allows for the development of an enhanced trust in the system and allows military personnel to receive medical and forensic care on the level of their choice. Military medical professionals are continually striving to provide the highest standard of care for military personnel, DoD employees, and beneficiaries. The new policies and programs are continually taking shape; however, there are barriers to education and understanding of the sexual assault prevention and response processes that require increased coordination between military and civilian personnel and their medical services in order to provide optimum care for all patients involved.
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NASA Astrophysics Data System (ADS)
Guo, Wei; Li, Junmei; Sheikhi, Moheb; Jiang, Jie’an; Yang, Zhenhai; Li, Hongwei; Guo, Shiping; Sheng, Jiang; Sun, Jie; Bo, Baoxue; Ye, Jichun
2018-06-01
Light extraction and current injection are two important considerations in the development of high efficiency light-emitting-diodes (LEDs), but usually cannot be satisfied simultaneously in nanostructure patterned devices. In this work, we investigated near-UV LEDs with nanopillar and nanohole patterns to improve light extraction efficiency. Photoluminescence (PL) intensities were enhanced by 8.0 and 4.1 times for nanopillar and nanohole LEDs compared to that of planar LED. Nanopillar LED exhibits higher PL emission than that of the nanohole LED, attributing to a convex shape sidewall for more effective outward light scattering, and reduction of quantum-confined-stark-effect owing to strain relaxation. However, nanopillar LED exhibits lower electroluminescence intensity than the nanohole sample, which calls for further optimization in carrier distributions. Experimental results were further supported by near-field electric field simulations. This work demonstrates the difference in optical and electrical behaviors between the nanopillar and nanohole LEDs, paving the way for detailed understanding on luminescence extraction mechanisms of nanostructure patterned UV emitters.
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Polarization recovery through scattering media.
de Aguiar, Hilton B; Gigan, Sylvain; Brasselet, Sophie
2017-09-01
The control and use of light polarization in optical sciences and engineering are widespread. Despite remarkable developments in polarization-resolved imaging for life sciences, their transposition to strongly scattering media is currently not possible, because of the inherent depolarization effects arising from multiple scattering. We show an unprecedented phenomenon that opens new possibilities for polarization-resolved microscopy in strongly scattering media: polarization recovery via broadband wavefront shaping. We demonstrate focusing and recovery of the original injected polarization state without using any polarizing optics at the detection. To enable molecular-level structural imaging, an arbitrary rotation of the input polarization does not degrade the quality of the focus. We further exploit the robustness of polarization recovery for structural imaging of biological tissues through scattering media. We retrieve molecular-level organization information of collagen fibers by polarization-resolved second harmonic generation, a topic of wide interest for diagnosis in biomedical optics. Ultimately, the observation of this new phenomenon paves the way for extending current polarization-based methods to strongly scattering environments.
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Jia, Yuechen; Cheng, Chen; Vázquez de Aldana, Javier R; Castillo, Gabriel R; Rabes, Blanca del Rosal; Tan, Yang; Jaque, Daniel; Chen, Feng
2014-08-07
Miniature laser sources with on-demand beam features are desirable devices for a broad range of photonic applications. Lasing based on direct-pump of miniaturized waveguiding active structures offers a low-cost but intriguing solution for compact light-emitting devices. In this work, we demonstrate a novel family of three dimensional (3D) photonic microstructures monolithically integrated in a Nd:YAG laser crystal wafer. They are produced by the femtosecond laser writing, capable of simultaneous light waveguiding and beam manipulation. In these guiding systems, tailoring of laser modes by both passive/active beam splitting and ring-shaped transformation are achieved by an appropriate design of refractive index patterns. Integration of graphene thin-layer as saturable absorber in the 3D laser structures allows for efficient passive Q-switching of tailored laser radiations which may enable miniature waveguiding lasers for broader applications. Our results pave a way to construct complex integrated passive and active laser circuits in dielectric crystals by using femtosecond laser written monolithic photonic chips.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Fang, X.; Xia, C.; Keppens, R.
We present the first multidimensional, magnetohydrodynamic simulations that capture the initial formation and long-term sustainment of the enigmatic coronal rain phenomenon. We demonstrate how thermal instability can induce a spectacular display of in situ forming blob-like condensations which then start their intimate ballet on top of initially linear force-free arcades. Our magnetic arcades host a chromospheric, transition region, and coronal plasma. Following coronal rain dynamics for over 80 minutes of physical time, we collect enough statistics to quantify blob widths, lengths, velocity distributions, and other characteristics which directly match modern observational knowledge. Our virtual coronal rain displays the deformation ofmore » blobs into V-shaped features, interactions of blobs due to mostly pressure-mediated levitations, and gives the first views of blobs that evaporate in situ or are siphoned over the apex of the background arcade. Our simulations pave the way for systematic surveys of coronal rain showers in true multidimensional settings to connect parameterized heating prescriptions with rain statistics, ultimately allowing us to quantify the coronal heating input.« less
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Liang, Yufeng; Vinson, John; Pemmaraju, Sri; Drisdell, Walter S; Shirley, Eric L; Prendergast, David
2017-03-03
Constrained-occupancy delta-self-consistent-field (ΔSCF) methods and many-body perturbation theories (MBPT) are two strategies for obtaining electronic excitations from first principles. Using the two distinct approaches, we study the O 1s core excitations that have become increasingly important for characterizing transition-metal oxides and understanding strong electronic correlation. The ΔSCF approach, in its current single-particle form, systematically underestimates the pre-edge intensity for chosen oxides, despite its success in weakly correlated systems. By contrast, the Bethe-Salpeter equation within MBPT predicts much better line shapes. This motivates one to reexamine the many-electron dynamics of x-ray excitations. We find that the single-particle ΔSCF approach can be rectified by explicitly calculating many-electron transition amplitudes, producing x-ray spectra in excellent agreement with experiments. This study paves the way to accurately predict x-ray near-edge spectral fingerprints for physics and materials science beyond the Bethe-Salpether equation.
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Multidimensional Modeling of Coronal Rain Dynamics
NASA Astrophysics Data System (ADS)
Fang, X.; Xia, C.; Keppens, R.
2013-07-01
We present the first multidimensional, magnetohydrodynamic simulations that capture the initial formation and long-term sustainment of the enigmatic coronal rain phenomenon. We demonstrate how thermal instability can induce a spectacular display of in situ forming blob-like condensations which then start their intimate ballet on top of initially linear force-free arcades. Our magnetic arcades host a chromospheric, transition region, and coronal plasma. Following coronal rain dynamics for over 80 minutes of physical time, we collect enough statistics to quantify blob widths, lengths, velocity distributions, and other characteristics which directly match modern observational knowledge. Our virtual coronal rain displays the deformation of blobs into V-shaped features, interactions of blobs due to mostly pressure-mediated levitations, and gives the first views of blobs that evaporate in situ or are siphoned over the apex of the background arcade. Our simulations pave the way for systematic surveys of coronal rain showers in true multidimensional settings to connect parameterized heating prescriptions with rain statistics, ultimately allowing us to quantify the coronal heating input.
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Anti-obesity drugs: past, present and future
Rodgers, R. John; Tschöp, Matthias H.; Wilding, John P. H.
2012-01-01
The ideal anti-obesity drug would produce sustained weight loss with minimal side effects. The mechanisms that regulate energy balance have substantial built-in redundancy, overlap considerably with other physiological functions, and are influenced by social, hedonic and psychological factors that limit the effectiveness of pharmacological interventions. It is therefore unsurprising that anti-obesity drug discovery programmes have been littered with false starts, failures in clinical development, and withdrawals due to adverse effects that were not fully appreciated at the time of launch. Drugs that target pathways in metabolic tissues, such as adipocytes, liver and skeletal muscle, have shown potential in preclinical studies but none has yet reached clinical development. Recent improvements in the understanding of peptidergic signalling of hunger and satiety from the gastrointestinal tract mediated by ghrelin, cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), and of homeostatic mechanisms related to leptin and its upstream pathways in the hypothalamus, have opened up new possibilities. Although some have now reached clinical development, it is uncertain whether they will meet the strict regulatory hurdles required for licensing of an anti-obesity drug. However, GLP-1 receptor agonists have already succeeded in diabetes treatment and, owing to their attractive body-weight-lowering effects in humans, will perhaps also pave the way for other anti-obesity agents. To succeed in developing drugs that control body weight to the extent seen following surgical intervention, it seems obvious that a new paradigm is needed. In other therapeutic arenas, such as diabetes and hypertension, lower doses of multiple agents targeting different pathways often yield better results than strategies that modify one pathway alone. Some combination approaches using peptides and small molecules have now reached clinical trials, although recent regulatory experience suggests that large challenges lie ahead. In future, this polytherapeutic strategy could possibly rival surgery in terms of efficacy, safety and sustainability of weight loss. PMID:22915024
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Chowdhury, Md Rabiul Hossain; Bhuiyan, Md IqbalKaiser; Saha, Ayan; Mosleh, Ivan MHAI; Mondol, Sobuj; Ahmed, C M Sabbir
2014-01-01
Purpose Streptococcus sanguinis is a Gram-positive, facultative aerobic bacterium that is a member of the viridans streptococcus group. It is found in human mouths in dental plaque, which accounts for both dental cavities and bacterial endocarditis, and which entails a mortality rate of 25%. Although a range of remedial mediators have been found to control this organism, the effectiveness of agents such as penicillin, amoxicillin, trimethoprim–sulfamethoxazole, and erythromycin, was observed. The emphasis of this investigation was on finding substitute and efficient remedial approaches for the total destruction of this bacterium. Materials and methods In this computational study, various databases and online software were used to ascertain some specific targets of S. sanguinis. Particularly, the Kyoto Encyclopedia of Genes and Genomes databases were applied to determine human nonhomologous proteins, as well as the metabolic pathways involved with those proteins. Different software such as Phyre2, CastP, DoGSiteScorer, the Protein Function Predictor server, and STRING were utilized to evaluate the probable active drug binding site with its known function and protein–protein interaction. Results In this study, among 218 essential proteins of this pathogenic bacterium, 81 nonhomologous proteins were accrued, and 15 proteins that are unique in several metabolic pathways of S. sanguinis were isolated through metabolic pathway analysis. Furthermore, four essentially membrane-bound unique proteins that are involved in distinct metabolic pathways were revealed by this research. Active sites and druggable pockets of these selected proteins were investigated with bioinformatic techniques. In addition, this study also mentions the activity of those proteins, as well as their interactions with the other proteins. Conclusion Our findings helped to identify the type of protein to be considered as an efficient drug target. This study will pave the way for researchers to develop and discover more effective and specific therapeutic agents against S. sanguinis. PMID:25473301
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Chowdhury, Md Rabiul Hossain; Bhuiyan, Md IqbalKaiser; Saha, Ayan; Mosleh, Ivan Mhai; Mondol, Sobuj; Ahmed, C M Sabbir
2014-01-01
Streptococcus sanguinis is a Gram-positive, facultative aerobic bacterium that is a member of the viridans streptococcus group. It is found in human mouths in dental plaque, which accounts for both dental cavities and bacterial endocarditis, and which entails a mortality rate of 25%. Although a range of remedial mediators have been found to control this organism, the effectiveness of agents such as penicillin, amoxicillin, trimethoprim-sulfamethoxazole, and erythromycin, was observed. The emphasis of this investigation was on finding substitute and efficient remedial approaches for the total destruction of this bacterium. In this computational study, various databases and online software were used to ascertain some specific targets of S. sanguinis. Particularly, the Kyoto Encyclopedia of Genes and Genomes databases were applied to determine human nonhomologous proteins, as well as the metabolic pathways involved with those proteins. Different software such as Phyre2, CastP, DoGSiteScorer, the Protein Function Predictor server, and STRING were utilized to evaluate the probable active drug binding site with its known function and protein-protein interaction. In this study, among 218 essential proteins of this pathogenic bacterium, 81 nonhomologous proteins were accrued, and 15 proteins that are unique in several metabolic pathways of S. sanguinis were isolated through metabolic pathway analysis. Furthermore, four essentially membrane-bound unique proteins that are involved in distinct metabolic pathways were revealed by this research. Active sites and druggable pockets of these selected proteins were investigated with bioinformatic techniques. In addition, this study also mentions the activity of those proteins, as well as their interactions with the other proteins. Our findings helped to identify the type of protein to be considered as an efficient drug target. This study will pave the way for researchers to develop and discover more effective and specific therapeutic agents against S. sanguinis.
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All-zigzag graphene nanoribbons for planar interconnect application
NASA Astrophysics Data System (ADS)
Chen, Po-An; Chiang, Meng-Hsueh; Hsu, Wei-Chou
2017-07-01
A feasible "lightning-shaped" zigzag graphene nanoribbon (ZGNR) structure for planar interconnects is proposed. Based on the density functional theory and non-equilibrium Green's function, the electron transport properties are evaluated. The lightning-shaped structure increases significantly the conductance of the graphene interconnect with an odd number of zigzag chains. This proposed technique can effectively utilize the linear I-V characteristic of asymmetric ZGNRs for interconnect application. Variability study accounting for width/length variation and the edge effect is also included. The transmission spectra, transmission eigenstates, and transmission pathways are analyzed to gain the physical insights. This lightning-shaped ZGNR enables all 2D material-based devices and circuits on flexible and transparent substrates.
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Diversity of bile salts in fish and amphibians: evolution of a complex biochemical pathway.
Hagey, Lee R; Møller, Peter R; Hofmann, Alan F; Krasowski, Matthew D
2010-01-01
Bile salts are the major end metabolites of cholesterol and are also important in lipid and protein digestion, as well as shaping of the gut microflora. Previous studies had demonstrated variation of bile salt structures across vertebrate species. We greatly extend prior surveys of bile salt variation in fish and amphibians, particularly in analysis of the biliary bile salts of Agnatha and Chondrichthyes. While there is significant structural variation of bile salts across all fish orders, bile salt profiles are generally stable within orders of fish and do not correlate with differences in diet. This large data set allowed us to infer evolutionary changes in the bile salt synthetic pathway. The hypothesized ancestral bile salt synthetic pathway, likely exemplified in extant hagfish, is simpler and much shorter than the pathway of most teleost fish and terrestrial vertebrates. Thus, the bile salt synthetic pathway has become longer and more complex throughout vertebrate evolution. Analysis of the evolution of bile salt synthetic pathways provides a rich model system for the molecular evolution of a complex biochemical pathway in vertebrates.
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Bosch, Carles; Masachs, Nuria; Exposito-Alonso, David; Martínez, Albert; Teixeira, Cátia M.; Fernaud, Isabel; Pujadas, Lluís; Ulloa, Fausto; Comella, Joan X.; DeFelipe, Javier; Merchán-Pérez, Angel; Soriano, Eduardo
2016-01-01
The Reelin pathway is essential for both neural migration and for the development and maturation of synaptic connections. However, its role in adult synaptic formation and remodeling is still being investigated. Here, we investigated the impact of the Reelin/Dab1 pathway on the synaptogenesis of newborn granule cells (GCs) in the young-adult mouse hippocampus. We show that neither Reelin overexpression nor the inactivation of its intracellular adapter, Dab1, substantially alters dendritic spine numbers in these neurons. In contrast, 3D-electron microscopy (focused ion beam milling/scanning electron microscope) revealed that dysregulation of the Reelin/Dab1 pathway leads to both transient and permanent changes in the types and morphology of dendritic spines, mainly altering mushroom, filopodial, and branched GC spines. We also found that the Reelin/Dab1 pathway controls synaptic configuration of presynaptic boutons in the dentate gyrus, with its dysregulation leading to a substantial decrease in multi-synaptic bouton innervation. Lastly, we show that the Reelin/Dab1 pathway controls astroglial ensheathment of synapses. Thus, the Reelin pathway is a key regulator of adult-generated GC integration, by controlling dendritic spine types and shapes, their synaptic innervation patterns, and glial ensheathment. These findings may help to better understanding of hippocampal circuit alterations in neurological disorders in which the Reelin pathway is implicated. Significance Statement The extracellular protein Reelin has an important role in neurological diseases, including epilepsy, Alzheimer's disease and psychiatric diseases, targeting hippocampal circuits. Here we address the role of Reelin in the development of synaptic contacts in adult-generated granule cells (GCs), a neuronal population that is crucial for learning and memory and implicated in neurological and psychiatric diseases. We found that the Reelin pathway controls the shapes, sizes, and types of dendritic spines, the complexity of multisynaptic innervations and the degree of the perisynaptic astroglial ensheathment that controls synaptic homeostasis. These findings show a pivotal role of Reelin in GC synaptogenesis and provide a foundation for structural circuit alterations caused by Reelin deregulation that may occur in neurological and psychiatric disorders. PMID:27624722
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Domingos, Sara; Fino, Joana; Paulo, Octávio S; Oliveira, Cristina M; Goulao, Luis F
2016-03-01
Flower-to-fruit transition depends of nutrient availability and regulation at the molecular level by sugar and hormone signalling crosstalk. However, in most species, the identities of fruit initiation regulators and their targets are largely unknown. To ascertain the main pathways involved in stenospermocarpic table grape fruit set, comprehensive transcriptional and metabolomic analyses were conducted specifically targeting the early phase of this developmental stage in 'Thompson Seedless'. The high-throughput analyses performed disclosed the involvement of 496 differentially expressed genes and 28 differently accumulated metabolites in the sampled inflorescences. Our data show broad transcriptome reprogramming of molecule transporters, globally down-regulating gene expression, and suggest that regulation of sugar- and hormone-mediated pathways determines the downstream activation of berry development. The most affected gene was the SWEET14 sugar transporter. Hormone-related transcription changes were observed associated with increased indole-3-acetic acid, stimulation of ethylene and gibberellin metabolisms and cytokinin degradation, and regulation of MADS-box and AP2-like ethylene-responsive transcription factor expression. Secondary metabolism, the most representative biological process at transcriptome level, was predominantly repressed. The results add to the knowledge of molecular events occurring in grapevine inflorescence fruit set and provide a list of candidates, paving the way for genetic manipulation aimed at model research and plant breeding. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
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Induction of immune-related gene expression by seminal exosomes in the porcine endometrium.
Bai, Rulan; Latifi, Zeinab; Kusama, Kazuya; Nakamura, Keigo; Shimada, Masayuki; Imakawa, Kazuhiko
2018-01-01
Seminal plasma (SP) is considered as a vehicle to carry sperm into female reproductive tract, of which functions have not been completely understood. This study aimed to identify the function of seminal exosomes on porcine endometrium. Exosomes were isolated from the sperm-rich fraction of boar semen and were confirmed by the expression of exosome marker HSP70 and size distribution using nano-sight tracking analysis. Porcine endometrial epithelial cells (EECs) were then treated with seminal exosomes, and RNA extracted were subjected to global expression analysis. Transcripts related to "immune response", "inflammatory response" and their associated signaling pathways were up-regulated in EECs treated with seminal exosome, whereas those associated with "steroid biosynthesis", "metabolic pathways" and "T cell differentiation" were down-regulated. The decrease in PMVK, SC5D, INSIG1, HSD17B7, NSDHL, HMGCR, SQLE and FDFT1, and increase in CCL20, TNFSF15, AMCFII, CXCL2 and CXCL8 were also found in the endometrium from the naturally mated pigs. Moreover, changes in exosome-induced CYP24A1, EBP, CCL20, AMCFII and IL1A expression were not regulated by the exosome removed SP. These observations indicated that exosomes present in SP are involved in the immune-related gene regulation in the uterus, which could pave the passage for sperm and possibly fertilized eggs. Copyright © 2017 Elsevier Inc. All rights reserved.
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The mTOR signalling cascade: paving new roads to cure neurological disease.
Crino, Peter B
2016-07-01
Defining the multiple roles of the mechanistic (formerly 'mammalian') target of rapamycin (mTOR) signalling pathway in neurological diseases has been an exciting and rapidly evolving story of bench-to-bedside translational research that has spanned gene mutation discovery, functional experimental validation of mutations, pharmacological pathway manipulation, and clinical trials. Alterations in the dual contributions of mTOR - regulation of cell growth and proliferation, as well as autophagy and cell death - have been found in developmental brain malformations, epilepsy, autism and intellectual disability, hypoxic-ischaemic and traumatic brain injuries, brain tumours, and neurodegenerative disorders. mTOR integrates a variety of cues, such as growth factor levels, oxygen levels, and nutrient and energy availability, to regulate protein synthesis and cell growth. In line with the positioning of mTOR as a pivotal cell signalling node, altered mTOR activation has been associated with a group of phenotypically diverse neurological disorders. To understand how altered mTOR signalling leads to such divergent phenotypes, we need insight into the differential effects of enhanced or diminished mTOR activation, the developmental context of these changes, and the cell type affected by altered signalling. A particularly exciting feature of the tale of mTOR discovery is that pharmacological mTOR inhibitors have shown clinical benefits in some neurological disorders, such as tuberous sclerosis complex, and are being considered for clinical trials in epilepsy, autism, dementia, traumatic brain injury, and stroke.
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A Bacterial Toxin with Analgesic Properties: Hyperpolarization of DRG Neurons by Mycolactone
Song, Ok-Ryul; Kim, Han-Byul; Jouny, Samuel; Ricard, Isabelle; Vandeputte, Alexandre; Deboosere, Nathalie; Marion, Estelle; Queval, Christophe J.; Lesport, Pierre; Henrion, Daniel; Oh, Seog Bae; Lebon, Guillaume; Sandoz, Guillaume; Yeramian, Edouard; Marsollier, Laurent; Brodin, Priscille
2017-01-01
Mycolactone, a polyketide molecule produced by Mycobacterium ulcerans, is the etiological agent of Buruli ulcer. This lipid toxin is endowed with pleiotropic effects, presents cytotoxic effects at high doses, and notably plays a pivotal role in host response upon colonization by the bacillus. Most remarkably, mycolactone displays intriguing analgesic capabilities: the toxin suppresses or alleviates the pain of the skin lesions it inflicts. We demonstrated that the analgesic capability of mycolactone was not attributable to nerve damage, but instead resulted from the triggering of a cellular pathway targeting AT2 receptors (angiotensin II type 2 receptors; AT2R), and leading to potassium-dependent hyperpolarization. This demonstration paves the way to new nature-inspired analgesic protocols. In this direction, we assess here the hyperpolarizing properties of mycolactone on nociceptive neurons. We developed a dedicated medium-throughput assay based on membrane potential changes, and visualized by confocal microscopy of bis-oxonol-loaded Dorsal Root Ganglion (DRG) neurons. We demonstrate that mycolactone at non-cytotoxic doses triggers the hyperpolarization of DRG neurons through AT2R, with this action being not affected by known ligands of AT2R. This result points towards novel AT2R-dependent signaling pathways in DRG neurons underlying the analgesic effect of mycolactone, with the perspective for the development of new types of nature-inspired analgesics. PMID:28718822
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Production of Putative Diterpene Carboxylic Acid Intermediates of Triptolide in Yeast
DOE Office of Scientific and Technical Information (OSTI.GOV)
Forman, Victor; Callari, Roberta; Folly, Christophe
The development of medical applications exploiting the broad bioactivities of the diterpene therapeutic triptolide from Tripterygium wilfordii is limited by low extraction yields from the native plant. Furthermore, the extraordinarily high structural complexity prevents an economically attractive enantioselective total synthesis. An alternative production route of triptolide through engineered Saccharomyces cerevisiae (yeast) could provide a sustainable source of triptolide. A potential intermediate in the unknown biosynthetic route to triptolide is the diterpene dehydroabietic acid. Here, we report a biosynthetic route to dehydroabietic acid by transient expression of enzymes from T. wilfordii and Sitka spruce (Picea sitchensis) in Nicotiana benthamiana. The combinationmore » of diterpene synthases TwTPS9, TwTPS27, and cytochromes P450 PsCYP720B4 yielded dehydroabietic acid and a novel analog, tentatively identified as ‘miltiradienic acid’. This biosynthetic pathway was reassembled in a yeast strain engineered for increased yields of the pathway intermediates, the diterpene olefins miltiradiene and dehydroabietadiene. Introduction in that strain of PsCYP720B4 in combination with two alternative NADPH-dependent cytochrome P450 reductases resulted in scalable in vivo production of dehydroabietic acid and its analog from glucose. Approaching future elucidation of the remaining biosynthetic steps to triptolide, our findings may provide an independent platform for testing of additional recombinant candidate genes, and ultimately pave the way to biotechnological production of the high value diterpenoid therapeutic.« less
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Xia, En-Hua; Zhang, Hai-Bin; Sheng, Jun; Li, Kui; Zhang, Qun-Jie; Kim, Changhoon; Zhang, Yun; Liu, Yuan; Zhu, Ting; Li, Wei; Huang, Hui; Tong, Yan; Nan, Hong; Shi, Cong; Shi, Chao; Jiang, Jian-Jun; Mao, Shu-Yan; Jiao, Jun-Ying; Zhang, Dan; Zhao, Yuan; Zhao, You-Jie; Zhang, Li-Ping; Liu, Yun-Long; Liu, Ben-Ying; Yu, Yue; Shao, Sheng-Fu; Ni, De-Jiang; Eichler, Evan E; Gao, Li-Zhi
2017-06-05
Tea is the world's oldest and most popular caffeine-containing beverage with immense economic, medicinal, and cultural importance. Here, we present the first high-quality nucleotide sequence of the repeat-rich (80.9%), 3.02-Gb genome of the cultivated tea tree Camellia sinensis. We show that an extraordinarily large genome size of tea tree is resulted from the slow, steady, and long-term amplification of a few LTR retrotransposon families. In addition to a recent whole-genome duplication event, lineage-specific expansions of genes associated with flavonoid metabolic biosynthesis were discovered, which enhance catechin production, terpene enzyme activation, and stress tolerance, important features for tea flavor and adaptation. We demonstrate an independent and rapid evolution of the tea caffeine synthesis pathway relative to cacao and coffee. A comparative study among 25 Camellia species revealed that higher expression levels of most flavonoid- and caffeine- but not theanine-related genes contribute to the increased production of catechins and caffeine and thus enhance tea-processing suitability and tea quality. These novel findings pave the way for further metabolomic and functional genomic refinement of characteristic biosynthesis pathways and will help develop a more diversified set of tea flavors that would eventually satisfy and attract more tea drinkers worldwide. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
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Production of Putative Diterpene Carboxylic Acid Intermediates of Triptolide in Yeast
Forman, Victor; Callari, Roberta; Folly, Christophe; ...
2017-06-13
The development of medical applications exploiting the broad bioactivities of the diterpene therapeutic triptolide from Tripterygium wilfordii is limited by low extraction yields from the native plant. Furthermore, the extraordinarily high structural complexity prevents an economically attractive enantioselective total synthesis. An alternative production route of triptolide through engineered Saccharomyces cerevisiae (yeast) could provide a sustainable source of triptolide. A potential intermediate in the unknown biosynthetic route to triptolide is the diterpene dehydroabietic acid. Here, we report a biosynthetic route to dehydroabietic acid by transient expression of enzymes from T. wilfordii and Sitka spruce (Picea sitchensis) in Nicotiana benthamiana. The combinationmore » of diterpene synthases TwTPS9, TwTPS27, and cytochromes P450 PsCYP720B4 yielded dehydroabietic acid and a novel analog, tentatively identified as ‘miltiradienic acid’. This biosynthetic pathway was reassembled in a yeast strain engineered for increased yields of the pathway intermediates, the diterpene olefins miltiradiene and dehydroabietadiene. Introduction in that strain of PsCYP720B4 in combination with two alternative NADPH-dependent cytochrome P450 reductases resulted in scalable in vivo production of dehydroabietic acid and its analog from glucose. Approaching future elucidation of the remaining biosynthetic steps to triptolide, our findings may provide an independent platform for testing of additional recombinant candidate genes, and ultimately pave the way to biotechnological production of the high value diterpenoid therapeutic.« less
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Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk.
Orozco, Carlos A; Martinez-Bosch, Neus; Guerrero, Pedro E; Vinaixa, Judith; Dalotto-Moreno, Tomás; Iglesias, Mar; Moreno, Mireia; Djurec, Magdolna; Poirier, Françoise; Gabius, Hans-Joachim; Fernandez-Zapico, Martin E; Hwang, Rosa F; Guerra, Carmen; Rabinovich, Gabriel A; Navarro, Pilar
2018-04-17
Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a Kras -driven mouse model of PDA ( Ela-Kras G12V p53 -/- ) results in a significant increase in survival through mechanisms involving decreased stroma activation, attenuated vascularization, and enhanced T cell infiltration leading to diminished metastasis rates. In a human setting, human pancreatic stellate cells (HPSCs) promote cancer proliferation, migration, and invasion via Gal1-driven pathways. Moreover, in vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted HPSCs leads to impaired tumor formation and metastasis in mice. Gene-expression analyses of pancreatic tumor cells exposed to Gal1 reveal modulation of multiple regulatory pathways involved in tumor progression. Thus, Gal1 hierarchically regulates different events implicated in PDA biology including tumor cell proliferation, invasion, angiogenesis, inflammation, and metastasis, highlighting the broad therapeutic potential of Gal1-specific inhibitors, either alone or in combination with other therapeutic modalities.
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Islam, Md. Tariqul; Ferdous, Ahlan Sabah; Najnin, Rifat Ara; Sarker, Suprovath Kumar; Khan, Haseena
2015-01-01
MicroRNAs play a pivotal role in regulating a broad range of biological processes, acting by cleaving mRNAs or by translational repression. A group of plant microRNAs are evolutionarily conserved; however, others are expressed in a species-specific manner. Jute is an agroeconomically important fibre crop; nonetheless, no practical information is available for microRNAs in jute to date. In this study, Illumina sequencing revealed a total of 227 known microRNAs and 17 potential novel microRNA candidates in jute, of which 164 belong to 23 conserved families and the remaining 63 belong to 58 nonconserved families. Among a total of 81 identified microRNA families, 116 potential target genes were predicted for 39 families and 11 targets were predicted for 4 among the 17 identified novel microRNAs. For understanding better the functions of microRNAs, target genes were analyzed by Gene Ontology and their pathways illustrated by KEGG pathway analyses. The presence of microRNAs identified in jute was validated by stem-loop RT-PCR followed by end point PCR and qPCR for randomly selected 20 known and novel microRNAs. This study exhaustively identifies microRNAs and their target genes in jute which will ultimately pave the way for understanding their role in this crop and other crops. PMID:25861616
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Shaping Future Phosphorus Management Pathways by Understanding the Past and Present
Sustainable phosphorus (P) management in agricultural and urban ecosystems is necessary to ensure global food security and healthy aquatic ecosystems. Researchers and decision-makers alike need to understand how social, economic, political, and biophysical factors interact to cre...
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3. "LAUNCH SILOS; AREA PAVING AND GRADING PLAN." Specifications No. ...
3. "LAUNCH SILOS; AREA PAVING AND GRADING PLAN." Specifications No. ENG-04-353-59-73; Drawing No. 5841C-11; D.O. SERIES AW-1525/17; Stamped: RECORD DRAWING AS CONSTRUCTED. Below stamp: Contract No. 6601, Date 18 Sep 59. - Edwards Air Force Base, Air Force Rocket Propulsion Laboratory, Missile Silo Type, Test Area 1-100, northeast end of Test Area 1-100 Road, Boron, Kern County, CA
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Installation Restoration Program (IRP). Operable Unit B1 Remedial Investigation/Feasibility Study
1993-07-01
Alternative Evaluation Criteria ......................... 8-2 8-2 Remedial Alternative Evaluation Criteria Rating System ................ 8-3 8-3...ies, various technologies and process options relative numerical rating system was developed were identified and screened on the basis of (see Table 8-2...extensive paving and PCBs were found (north/central ditch). This storm drainage system , and because of the ditch was paved with asphalt in 1981; before
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Gerards, Mike; Sallevelt, Suzanne C E H; Smeets, Hubert J M
2016-03-01
Leigh syndrome is a progressive neurodegenerative disorder, affecting 1 in 40,000 live births. Most patients present with symptoms between the ages of three and twelve months, but adult onset Leigh syndrome has also been described. The disease course is characterized by a rapid deterioration of cognitive and motor functions, in most cases resulting in death due to respiratory failure. Despite the high genetic heterogeneity of Leigh syndrome, patients present with identical, symmetrical lesions in the basal ganglia or brainstem on MRI, while additional clinical manifestations and age of onset varies from case to case. To date, mutations in over 60 genes, both nuclear and mitochondrial DNA encoded, have been shown to cause Leigh syndrome, still explaining only half of all cases. In most patients, these mutations directly or indirectly affect the activity of the mitochondrial respiratory chain or pyruvate dehydrogenase complex. Exome sequencing has accelerated the discovery of new genes and pathways involved in Leigh syndrome, providing novel insights into the pathophysiological mechanisms. This is particularly important as no general curative treatment is available for this devastating disorder, although several recent studies imply that early treatment might be beneficial for some patients depending on the gene or process affected. Timely, gene-based personalized treatment may become an important strategy in rare, genetically heterogeneous disorders like Leigh syndrome, stressing the importance of early genetic diagnosis and identification of new genes/pathways. In this review, we provide a comprehensive overview of the most important clinical manifestations and genes/pathways involved in Leigh syndrome, and discuss the current state of therapeutic interventions in patients. Copyright © 2015 Elsevier Inc. All rights reserved.
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The Hippo-YAP signaling pathway and contact inhibition of growth
Gumbiner, Barry M.; Kim, Nam-Gyun
2014-01-01
ABSTRACT The Hippo-YAP pathway mediates the control of cell proliferation by contact inhibition as well as other attributes of the physical state of cells in tissues. Several mechanisms sense the spatial and physical organization of cells, and function through distinct upstream modules to stimulate Hippo-YAP signaling: adherens junction or cadherin–catenin complexes, epithelial polarity and tight junction complexes, the FAT-Dachsous morphogen pathway, as well as cell shape, actomyosin or mechanotransduction. Soluble extracellular factors also regulate Hippo pathway signaling, often inhibiting its activity. Indeed, the Hippo pathway mediates a reciprocal relationship between contact inhibition and mitogenic signaling. As a result, cells at the edges of a colony, a wound in a tissue or a tumor are more sensitive to ambient levels of growth factors and more likely to proliferate, migrate or differentiate through a YAP and/or TAZ-dependent process. Thus, the Hippo-YAP pathway senses and responds to the physical organization of cells in tissues and coordinates these physical cues with classic growth-factor-mediated signaling pathways. This Commentary is focused on the biological significance of Hippo-YAP signaling and how upstream regulatory modules of the pathway interact to produce biological outcomes. PMID:24532814
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Mosaic Convergence of Rodent Dentitions
Lazzari, Vincent; Charles, Cyril; Tafforeau, Paul; Vianey-Liaud, Monique; Aguilar, Jean-Pierre; Jaeger, Jean-Jacques; Michaux, Jacques; Viriot, Laurent
2008-01-01
Background Understanding mechanisms responsible for changes in tooth morphology in the course of evolution is an area of investigation common to both paleontology and developmental biology. Detailed analyses of molar tooth crown shape have shown frequent homoplasia in mammalian evolution, which requires accurate investigation of the evolutionary pathways provided by the fossil record. The necessity of preservation of an effective occlusion has been hypothesized to functionally constrain crown morphological changes and to also facilitate convergent evolution. The Muroidea superfamily constitutes a relevant model for the study of molar crown diversification because it encompasses one third of the extant mammalian biodiversity. Methodology/Principal Findings Combined microwear and 3D-topographic analyses performed on fossil and extant muroid molars allow for a first quantification of the relationships between changes in crown morphology and functionality of occlusion. Based on an abundant fossil record and on a well resolved phylogeny, our results show that the most derived functional condition associates longitudinal chewing and non interlocking of cusps. This condition has been reached at least 7 times within muroids via two main types of evolutionary pathways each respecting functional continuity. In the first type, the flattening of tooth crown which induces the removal of cusp interlocking occurs before the rotation of the chewing movement. In the second type however, flattening is subsequent to rotation of the chewing movement which can be associated with certain changes in cusp morphology. Conclusion/Significance The reverse orders of the changes involved in these different pathways reveal a mosaic evolution of mammalian dentition in which direction of chewing and crown shape seem to be partly decoupled. Either can change in respect to strong functional constraints affecting occlusion which thereby limit the number of the possible pathways. Because convergent pathways imply distinct ontogenetic trajectories, new Evo/Devo comparative studies on cusp morphogenesis are necessary. PMID:18974837
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Yan, Jun-Feng; Huang, Wen-Jie; Zhao, Jian-Feng; Fu, Hui-Ying; Zhang, Gao-Yue; Huang, Xiao-Jun; Lv, Bo-Dong
2017-01-01
Erectile dysfunction (ED) is a common clinical disease that is difficult to treat. We previously found that hypoxia modulates the phenotype of primary corpus cavernosum smooth muscle cells (CCSMCs) in rats, but the underlying molecular mechanism is still unknown. Platelet-derived growth factor receptor (PDGFR)-related signaling pathways are correlated with cell phenotypic transition, but research has been focused more on vascular smooth muscle and tracheal smooth muscle and less on CCSMCs. Here, we investigated the role of PDGFR-related signaling pathways in penile CCSMCs, which were successfully isolated from rats and cultured in vitro. PDGF-BB at 5, 10, or 20 ng/ml altered CCSMC morphology from the original elongated, spindle shape to a broader shape and promoted the synthetic phenotype and expression of the related proteins vimentin and collagen-I, while inhibiting the contractile phenotype and expression of the related proteins smooth muscle (SM) α-actin (α-SMA) and desmin. Inhibition of PDGFR activity via siRNA or the PDGFR inhibitor crenolanib inhibited vimentin and collagen-I expression, increased α-SMA and desmin expression, and considerably inhibited serine-threonine protein kinase (AKT) and signal transducer and activator of transcription 3 (STAT3) phosphorylation. STAT3 knockdown promoted the contractile phenotype, inhibited vimentin and collagen-I expression, and increased α-SMA and desmin expression, whereas AKT knockdown did not affect phenotype-associated proteins. STAT3 overexpression in CCSMC cells weakened the suppressive effect of PDGFR inhibition on the morphology and phenotypic transformation induced by PDGF-BB. Through activation of the PDGFR/STAT3 signaling pathway, PDGF promoted the synthetic phenotype transition; thus, regulation of this pathway might contribute to ED therapy.
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Feature-Specific Organization of Feedback Pathways in Mouse Visual Cortex.
Huh, Carey Y L; Peach, John P; Bennett, Corbett; Vega, Roxana M; Hestrin, Shaul
2018-01-08
Higher and lower cortical areas in the visual hierarchy are reciprocally connected [1]. Although much is known about how feedforward pathways shape receptive field properties of visual neurons, relatively little is known about the role of feedback pathways in visual processing. Feedback pathways are thought to carry top-down signals, including information about context (e.g., figure-ground segmentation and surround suppression) [2-5], and feedback has been demonstrated to sharpen orientation tuning of neurons in the primary visual cortex (V1) [6, 7]. However, the response characteristics of feedback neurons themselves and how feedback shapes V1 neurons' tuning for other features, such as spatial frequency (SF), remain largely unknown. Here, using a retrograde virus, targeted electrophysiological recordings, and optogenetic manipulations, we show that putatively feedback neurons in layer 5 (hereafter "L5 feedback") in higher visual areas, AL (anterolateral area) and PM (posteromedial area), display distinct visual properties in awake head-fixed mice. AL L5 feedback neurons prefer significantly lower SF (mean: 0.04 cycles per degree [cpd]) compared to PM L5 feedback neurons (0.15 cpd). Importantly, silencing AL L5 feedback reduced visual responses of V1 neurons preferring low SF (mean change in firing rate: -8.0%), whereas silencing PM L5 feedback suppressed responses of high-SF-preferring V1 neurons (-20.4%). These findings suggest that feedback connections from higher visual areas convey distinctly tuned visual inputs to V1 that serve to boost V1 neurons' responses to SF. Such like-to-like functional organization may represent an important feature of feedback pathways in sensory systems and in the nervous system in general. Copyright © 2017 Elsevier Ltd. All rights reserved.
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GAS6/TAM Pathway Signaling in Hemostasis and Thrombosis.
Law, Luke A; Graham, Douglas K; Di Paola, Jorge; Branchford, Brian R
2018-01-01
The GAS6/TYRO3-AXL-MERTK (TAM) signaling pathway is essential for full and sustained platelet activation, as well as thrombus stabilization. Inhibition of this pathway decreases platelet aggregation, shape change, clot retraction, aggregate formation under flow conditions, and surface expression of activation markers. Transgenic mice deficient in GAS6, or any of the TAM family of receptors that engage this ligand, exhibit in vivo protection against arterial and venous thrombosis but do not demonstrate either spontaneous or prolonged bleeding compared to their wild-type counterparts. Comparable results are observed in wild-type mice treated with pharmacological inhibitors of the GAS6-TAM pathway. Thus, GAS6/TAM inhibition offers an attractive novel therapeutic option that may allow for a moderate reduction in platelet activation and decreased thrombosis while still permitting the primary hemostatic function of platelet plug formation.
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Lazim, Raudah; Mei, Ye; Zhang, Dawei
2012-03-01
Replica exchange molecular dynamics (REMD) simulation provides an efficient conformational sampling tool for the study of protein folding. In this study, we explore the mechanism directing the structure variation from α/4β-fold protein to 3α-fold protein after mutation by conducting REMD simulation on 42 replicas with temperatures ranging from 270 K to 710 K. The simulation began from a protein possessing the primary structure of GA88 but the tertiary structure of GB88, two G proteins with "high sequence identity." Albeit the large Cα-root mean square deviation (RMSD) of the folded protein (4.34 Å at 270 K and 4.75 Å at 304 K), a variation in tertiary structure was observed. Together with the analysis of secondary structure assignment, cluster analysis and principal component, it provides insights to the folding and unfolding pathway of 3α-fold protein and α/4β-fold protein respectively paving the way toward the understanding of the ongoings during conformational variation.
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Drug-Abuse Nanotechnology: Opportunities and Challenges.
Mahmoudi, Morteza; Pakpour, Sepideh; Perry, George
2018-05-31
Opioid drug abuse and dependence/addiction are complex disorders regulated by a wide range of interacting networks of genes and pathways that control a variety of phenotypes. Although the field has been extensively progressed since the birth of the National Institute on Drug Abuse in 1974, the fundamental knowledge and involved mechanisms that lead to drug dependence/addiction are poorly understood, and thus, there has been limited success in the prevention of drug addiction and development of therapeutics for definitive treatment and cure of addiction disease. The lack of success in both identification of addiction in at-risk populations and the development of efficient drugs has resulted in a serious social and economic burden from opioid drug abuse with global increasing rate of mortality from drug overdoses. This perspective aims to draw the attention of scientists to the potential role of nanotechnologies, which might pave the way for the development of more practical platforms for either drug development or identification and screening of patients who may be vulnerable to addiction after using opioid drugs.
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Rewritable ferroelectric vortex pairs in BiFeO3
NASA Astrophysics Data System (ADS)
Li, Yang; Jin, Yaming; Lu, Xiaomei; Yang, Jan-Chi; Chu, Ying-Hao; Huang, Fengzhen; Zhu, Jinsong; Cheong, Sang-Wook
2017-08-01
Ferroelectric vortex in multiferroic materials has been considered as a promising alternative to current memory cells for the merit of high storage density. However, the formation of regular natural ferroelectric vortex is difficult, restricting the achievement of vortex memory device. Here, we demonstrated the creation of ferroelectric vortex-antivortex pairs in BiFeO3 thin films by using local electric field. The evolution of the polar vortex structure is studied by piezoresponse force microscopy at nanoscale. The results reveal that the patterns and stability of vortex structures are sensitive to the poling position. Consecutive writing and erasing processes cause no influence on the original domain configuration. The Z4 proper coloring vortex-antivortex network is then analyzed by graph theory, which verifies the rationality of artificial vortex-antivortex pairs. This study paves a foundation for artificial regulation of vortex, which provides a possible pathway for the design and realization of non-volatile vortex memory devices and logical devices.
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Definition of RNA polymerase II CoTC terminator elements in the human genome.
Nojima, Takayuki; Dienstbier, Martin; Murphy, Shona; Proudfoot, Nicholas J; Dye, Michael J
2013-04-25
Mammalian RNA polymerase II (Pol II) transcription termination is an essential step in protein-coding gene expression that is mediated by pre-mRNA processing activities and DNA-encoded terminator elements. Although much is known about the role of pre-mRNA processing in termination, our understanding of the characteristics and generality of terminator elements is limited. Whereas promoter databases list up to 40,000 known and potential Pol II promoter sequences, fewer than ten Pol II terminator sequences have been described. Using our knowledge of the human β-globin terminator mechanism, we have developed a selection strategy for mapping mammalian Pol II terminator elements. We report the identification of 78 cotranscriptional cleavage (CoTC)-type terminator elements at endogenous gene loci. The results of this analysis pave the way for the full understanding of Pol II termination pathways and their roles in gene expression. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.
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Domínguez-Gil, Teresa; Molina, Rafael; Alcorlo, Martín; Hermoso, Juan A
2016-09-01
Antimicrobial resistance is one of the most serious health threats. Cell-wall remodeling processes are tightly regulated to warrant bacterial survival and in some cases are directly linked to antibiotic resistance. Remodeling produces cell-wall fragments that are recycled but can also act as messengers for bacterial communication, as effector molecules in immune response and as signaling molecules triggering antibiotic resistance. This review is intended to provide state-of-the-art information about the molecular mechanisms governing this process and gather structural information of the different macromolecular machineries involved in peptidoglycan recycling in Gram-negative bacteria. The growing body of literature on the 3D structures of the corresponding macromolecules reveals an extraordinary complexity. Considering the increasing incidence and widespread emergence of Gram-negative multidrug-resistant pathogens in clinics, structural information on the main actors of the recycling process paves the way for designing novel antibiotics disrupting cellular communication in the recycling-resistance pathway. Copyright © 2016. Published by Elsevier Ltd.
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Iron-Induced Damage in Cardiomyopathy: Oxidative-Dependent and Independent Mechanisms
Gammella, Elena; Recalcati, Stefania; Rybinska, Ilona; Buratti, Paolo; Cairo, Gaetano
2015-01-01
The high incidence of cardiomyopathy in patients with hemosiderosis, particularly in transfusional iron overload, strongly indicates that iron accumulation in the heart plays a major role in the process leading to heart failure. In this context, iron-mediated generation of noxious reactive oxygen species is believed to be the most important pathogenetic mechanism determining cardiomyocyte damage, the initiating event of a pathologic progression involving apoptosis, fibrosis, and ultimately cardiac dysfunction. However, recent findings suggest that additional mechanisms involving subcellular organelles and inflammatory mediators are important factors in the development of this disease. Moreover, excess iron can amplify the cardiotoxic effect of other agents or events. Finally, subcellular misdistribution of iron within cardiomyocytes may represent an additional pathway leading to cardiac injury. Recent advances in imaging techniques and chelators development remarkably improved cardiac iron overload detection and treatment, respectively. However, increased understanding of the pathogenic mechanisms of iron overload cardiomyopathy is needed to pave the way for the development of improved therapeutic strategies. PMID:25878762
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Metabolic Adaptations of CD4+ T Cells in Inflammatory Disease
Dumitru, Cristina; Kabat, Agnieszka M.; Maloy, Kevin J.
2018-01-01
A controlled and self-limiting inflammatory reaction generally results in removal of the injurious agent and repair of the damaged tissue. However, in chronic inflammation, immune responses become dysregulated and prolonged, leading to tissue destruction. The role of metabolic reprogramming in orchestrating appropriate immune responses has gained increasing attention in recent years. Proliferation and differentiation of the T cell subsets that are needed to address homeostatic imbalance is accompanied by a series of metabolic adaptations, as T cells traveling from nutrient-rich secondary lymphoid tissues to sites of inflammation experience a dramatic shift in microenvironment conditions. How T cells integrate information about the local environment, such as nutrient availability or oxygen levels, and transfer these signals to functional pathways remains to be fully understood. In this review, we discuss how distinct subsets of CD4+ T cells metabolically adapt to the conditions of inflammation and whether these insights may pave the way to new treatments for human inflammatory diseases. PMID:29599783
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Endothelial-specific inhibition of NF-κB enhances functional haematopoiesis.
Poulos, Michael G; Ramalingam, Pradeep; Gutkin, Michael C; Kleppe, Maria; Ginsberg, Michael; Crowley, Michael J P; Elemento, Olivier; Levine, Ross L; Rafii, Shahin; Kitajewski, Jan; Greenblatt, Matthew B; Shim, Jae-Hyuck; Butler, Jason M
2016-12-21
Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IκBα cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated recovery of haematopoiesis following myelosuppression, in part through protection of the BM microenvironment following radiation and chemotherapeutic-induced insult. Moreover, transplantation of NF-κB-inhibited BM ECs enhanced haematopoietic recovery and protected mice from pancytopenia-induced death. These findings pave the way for development of niche-specific cellular approaches for the treatment of haematological disorders requiring myelosuppressive regimens.
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Endothelial-specific inhibition of NF-κB enhances functional haematopoiesis
Poulos, Michael G.; Ramalingam, Pradeep; Gutkin, Michael C.; Kleppe, Maria; Ginsberg, Michael; Crowley, Michael J. P.; Elemento, Olivier; Levine, Ross L.; Rafii, Shahin; Kitajewski, Jan; Greenblatt, Matthew B.; Shim, Jae-Hyuck; Butler, Jason M.
2016-01-01
Haematopoietic stem cells (HSCs) reside in distinct niches within the bone marrow (BM) microenvironment, comprised of endothelial cells (ECs) and tightly associated perivascular constituents that regulate haematopoiesis through the expression of paracrine factors. Here we report that the canonical NF-κB pathway in the BM vascular niche is a critical signalling axis that regulates HSC function at steady state and following myelosuppressive insult, in which inhibition of EC NF-κB promotes improved HSC function and pan-haematopoietic recovery. Mice expressing an endothelial-specific dominant negative IκBα cassette under the Tie2 promoter display a marked increase in HSC activity and self-renewal, while promoting the accelerated recovery of haematopoiesis following myelosuppression, in part through protection of the BM microenvironment following radiation and chemotherapeutic-induced insult. Moreover, transplantation of NF-κB-inhibited BM ECs enhanced haematopoietic recovery and protected mice from pancytopenia-induced death. These findings pave the way for development of niche-specific cellular approaches for the treatment of haematological disorders requiring myelosuppressive regimens. PMID:28000664
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Gadelha, Ary; Zugman, André; Calzavara, Mariana Bendlin; de Mendonça Furtado, Remo Holanda; Scorza, Fulvio Alexandre; Bressan, Rodrigo Afonsecca
2018-01-01
Schizophrenia is associated with an increased mortality from cardiovascular disease. Relatively few studies have assessed the putative association of schizophrenia pathophysiology with sudden death. Low adenosine levels have been associated with schizophrenia. In cardiology, increased mortality among patients with congestive heart failure has been associated with genetic polymorphisms that potentially lead to lower adenosine levels. Thus, we hypothesize that adenosine could link schizophrenia and cardiovascular mortality, with decreased adenosine levels leading to increased vulnerability to hyperexcitability following hypoxic insults, increasing the odds of fatal arrhythmias. Low adenosine levels might also lead to a small increase in overall mortality rates and a major increase in the sudden death rate. This hypothesis paves the way for further investigation of the increased cardiac mortality associated with schizophrenia. Potentially, a better characterization of adenosine-related mechanisms of sudden death in schizophrenia could lead to new evidence of factors leading to sudden death in the general population. Copyright © 2017. Published by Elsevier Ltd.
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DOE Office of Scientific and Technical Information (OSTI.GOV)
Bosserman, Mary A.; Downey, Theresa; Noinaj, Nicholas
Baeyer–Villiger monooxygenases (BVMOs) have been shown to play key roles for the biosynthesis of important natural products. MtmOIV, a homodimeric FAD- and NADPH-dependent BVMO, catalyzes the key frame-modifying steps of the mithramycin biosynthetic pathway, including an oxidative C–C bond cleavage, by converting its natural substrate premithramycin B into mithramycin DK, the immediate precursor of mithramycin. The drastically improved protein structure of MtmOIV along with the high-resolution structure of MtmOIV in complex with its natural substrate premithramycin B are reported here, revealing previously undetected key residues that are important for substrate recognition and catalysis. Kinetic analyses of selected mutants allowed usmore » to probe the substrate binding pocket of MtmOIV and also to discover the putative NADPH binding site. This is the first substrate-bound structure of MtmOIV providing new insights into substrate recognition and catalysis, which paves the way for the future design of a tailored enzyme for the chemo-enzymatic preparation of novel mithramycin analogues.« less
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Xpo7 is a broad-spectrum exportin and a nuclear import receptor.
Aksu, Metin; Pleiner, Tino; Karaca, Samir; Kappert, Christin; Dehne, Heinz-Jürgen; Seibel, Katharina; Urlaub, Henning; Bohnsack, Markus T; Görlich, Dirk
2018-05-10
Exportins bind cargo molecules in a RanGTP-dependent manner inside nuclei and transport them through nuclear pores to the cytoplasm. CRM1/Xpo1 is the best-characterized exportin because specific inhibitors such as leptomycin B allow straightforward cargo validations in vivo. The analysis of other exportins lagged far behind, foremost because no such inhibitors had been available for them. In this study, we explored the cargo spectrum of exportin 7/Xpo7 in depth and identified not only ∼200 potential export cargoes but also, surprisingly, ∼30 nuclear import substrates. Moreover, we developed anti-Xpo7 nanobodies that acutely block Xpo7 function when transfected into cultured cells. The inhibition is pathway specific, mislocalizes export cargoes of Xpo7 to the nucleus and import substrates to the cytoplasm, and allowed validation of numerous tested cargo candidates. This establishes Xpo7 as a broad-spectrum bidirectional transporter and paves the way for a much deeper analysis of exportin and importin function in the future. © 2018 Aksu et al.
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Liu, Xiaoliu; Zhu, Ping; Jiang, Ruifan; Wu, Lingtian; Feng, Xiaohai; Li, Sha; Xu, Hong
2017-01-20
Welan gum is a microbial polysaccharide produced by Sphingomonas sp. Its production is limited by the dissolved oxygen levels in the highly viscous fermentation. A strategy of heterologous expression of the Vitreoscilla hemoglobin gene in Sphingomonas sp. HT-1 was investigated to alleviate oxygen limitation and improve the yield of welan gum. Ultimately, the welan gum production increased from 25.3g/L to 34.6g/L, whereas the rheological behavior of welan gum solutions remained virtually unchanged. The transcriptional levels of the key genes in the electron transfer chain, TCA cycle and welan gum synthesis pathway, as well as ATP level revealed that the VHb expression in Sphingomonas sp. HT-1 enhanced welan gum biosynthesis by improving respiration and ATP supply. This study would pave the genetic manipulation way for enhancing welan gum yield, and it's also of great importance for the industrial applications of welan gum under harsh conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.
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Cocrystals Strategy towards Materials for Near-Infrared Photothermal Conversion and Imaging.
Wang, Yu; Zhu, Weigang; Du, Wenna; Liu, Xinfeng; Zhang, Xiaotao; Dong, Huanli; Hu, Wenping
2018-04-03
A cocrystal strategy with a simple preparation process is developed to prepare novel materials for near-infrared photothermal (PT) conversion and imaging. DBTTF and TCNB are selected as electron donor (D) and electron acceptor (A) to self-assemble into new cocrystals through non-covalent interactions. The strong D-A interaction leads to a narrow band gap with NIR absorption and that both the ground state and lowest-lying excited state are charge transfer states. Under the NIR laser illumination, the temperature of the cocrystal sharply increases in a short time with high PT conversion efficiency (η=18.8 %), which is due to the active non-radiative pathways and inhibition of radiative transition process, as revealed by femtosecond transient absorption spectroscopy. This is the first PT conversion cocrystal, which not only provides insights for the development of novel PT materials, but also paves the way of designing functional materials with appealing applications. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.
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Phosphoproteomics of Primary Cells Reveals Druggable Kinase Signatures in Ovarian Cancer.
Francavilla, Chiara; Lupia, Michela; Tsafou, Kalliopi; Villa, Alessandra; Kowalczyk, Katarzyna; Rakownikow Jersie-Christensen, Rosa; Bertalot, Giovanni; Confalonieri, Stefano; Brunak, Søren; Jensen, Lars J; Cavallaro, Ugo; Olsen, Jesper V
2017-03-28
Our understanding of the molecular determinants of cancer is still inadequate because of cancer heterogeneity. Here, using epithelial ovarian cancer (EOC) as a model system, we analyzed a minute amount of patient-derived epithelial cells from either healthy or cancerous tissues by single-shot mass-spectrometry-based phosphoproteomics. Using a multi-disciplinary approach, we demonstrated that primary cells recapitulate tissue complexity and represent a valuable source of differentially expressed proteins and phosphorylation sites that discriminate cancer from healthy cells. Furthermore, we uncovered kinase signatures associated with EOC. In particular, CDK7 targets were characterized in both EOC primary cells and ovarian cancer cell lines. We showed that CDK7 controls cell proliferation and that pharmacological inhibition of CDK7 selectively represses EOC cell proliferation. Our approach defines the molecular landscape of EOC, paving the way for efficient therapeutic approaches for patients. Finally, we highlight the potential of phosphoproteomics to identify clinically relevant and druggable pathways in cancer. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.
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Defect engineering in atomically-thin bismuth oxychloride towards photocatalytic oxygen evolution
DOE Office of Scientific and Technical Information (OSTI.GOV)
Di, Jun; Chen, Chao; Yang, Shi -Ze
Photocatalytic solar energy conversion is a clean technology for producing renewable energy sources, but its efficiency is greatly hindered by the kinetically sluggish oxygen evolution reaction. Herein, confined defects in atomically-thin BiOCl nanosheets were created to serve as a remarkable platform to explore the relationship between defects and photocatalytic activity. Surface defects can be clearly observed on atomically-thin BiOCl nanosheets from scanning transmission electron microscopy images. Theoretical/experimental results suggest that defect engineering increased states of density and narrowed the band gap. With combined effects from defect induced shortened hole migratory paths and creation of coordination-unsaturated active atoms with dangling bonds,more » defect-rich BiOCl nanosheets displayed 3 and 8 times higher photocatalytic activity towards oxygen evolution compared with atomically-thin BiOCl nanosheets and bulk BiOCl, respectively. As a result, this successful application of defect engineering will pave a new pathway for improving photocatalytic oxygen evolution activity of other materials.« less
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Defect engineering in atomically-thin bismuth oxychloride towards photocatalytic oxygen evolution
Di, Jun; Chen, Chao; Yang, Shi -Ze; ...
2017-06-26
Photocatalytic solar energy conversion is a clean technology for producing renewable energy sources, but its efficiency is greatly hindered by the kinetically sluggish oxygen evolution reaction. Herein, confined defects in atomically-thin BiOCl nanosheets were created to serve as a remarkable platform to explore the relationship between defects and photocatalytic activity. Surface defects can be clearly observed on atomically-thin BiOCl nanosheets from scanning transmission electron microscopy images. Theoretical/experimental results suggest that defect engineering increased states of density and narrowed the band gap. With combined effects from defect induced shortened hole migratory paths and creation of coordination-unsaturated active atoms with dangling bonds,more » defect-rich BiOCl nanosheets displayed 3 and 8 times higher photocatalytic activity towards oxygen evolution compared with atomically-thin BiOCl nanosheets and bulk BiOCl, respectively. As a result, this successful application of defect engineering will pave a new pathway for improving photocatalytic oxygen evolution activity of other materials.« less
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Huang, Miaojun; Li, Tianjie; Pan, Ting; Zhao, Naru; Yao, Yongchang; Zhai, Zhichen; Zhou, Jiaan; Du, Chang; Wang, Yingjun
2016-10-01
Yeast cells have controllable biosorption on metallic ions during metabolism. However, few studies were dedicated to using yeast-regulated biomimetic mineralization process to control the strontium-doped positions in calcium phosphate microcapsules. In this study, the yeast cells were allowed to pre-adsorb strontium ions metabolically and then served as sacrificing template for the precipitation and calcination of mineral shell. The pre-adsorption enabled the microorganism to enrich of strontium ions into the inner part of the microcapsules, which ensured a slow-release profile of the trace element from the microcapsule. The co-culture with human marrow stromal cells showed that gene expressions of alkaline phosphatase and Collagen-I were promoted. The promotion of osteogenic differentiation was further confirmed in the 3D culture of cell-material complexes. The strategy using living microorganism as 'smart doping apparatus' to control incorporation of trace element into calcium phosphate paved a pathway to new functional materials for hard tissue regeneration.
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Sebastián, María; Velázquez-Campoy, Adrián; Medina, Milagros
2018-12-01
Emergence of multidrug-resistant bacteria forces us to explore new therapeutic strategies, and proteins involved in key metabolic pathways are promising anti-bacterial targets. Bifunctional flavin-adenine dinucleotide (FAD) synthetases (FADS) are prokaryotic enzymes that synthesise the flavin mononucleotide (FMN) and FAD cofactors. The FADS from the human pathogen Streptococcus pneumoniae (SpnFADS)-causative agent of pneumonia in humans - shows relevant catalytic dissimilarities compared to other FADSs. Here, by integrating thermodynamic and kinetic data, we present a global description of the riboflavin kinase activity of SpnFADS, as well as of the inhibition mechanisms regulating this activity. Our data shed light on biophysical determinants that modulate species-specific conformational changes leading to catalytically competent conformations, as well as binding rates and affinities of substrates versus products. This knowledge paves the way for the development of tools - that taking advantage of the regulatory dissimilarities during FMN biosynthesis in different species - might be used in the discovery of specific anti-pneumococcal drugs.