ERIC Educational Resources Information Center
Wallace, Gregory L.; Peng, Cynthia S.; Williams, David
2017-01-01
Purpose: According to Vygotskian theory, verbal thinking serves to guide our behavior and underpins critical self-regulatory functions. Indeed, numerous studies now link inner speech usage with performance on tests of executive function (EF). However, the selectivity of inner speech contributions to multifactorial executive planning performance…
Examining the use of HIT functions among physicians serving minority populations.
Tarver, Will; Menachemi, Nir
2014-02-01
The Institute of Medicine highlighted the fact that the U.S. health care system does not provide consistent, high quality medical care to all people. The routine use of health information technology (HIT) that includes certain key functions may be critical in reducing such disparities. We used logistic regression analyses to examine differences when it comes to the routine use of key HIT functions that are linked to improvements in clinical care. Physicians predominantly serving Black patients were more likely than physicians predominantly serving White patients to routinely use HIT to generate reminders for clinicians and patients about preventive services. Similarly, physicians predominantly serving Hispanic patients were more likely than physicians predominantly serving White patients to routinely use HIT to access patients' preferred language. Importantly, although minority-serving institutions have lower adoption rates overall, differences exist in the routine use of key HIT functions that have the potential to reduce health disparities.
Lysine 63-linked polyubiquitin chain may serve as a targeting signal for the 26S proteasome
Saeki, Yasushi; Kudo, Tai; Sone, Takayuki; Kikuchi, Yoshiko; Yokosawa, Hideyoshi; Toh-e, Akio; Tanaka, Keiji
2009-01-01
Recruitment of substrates to the 26S proteasome usually requires covalent attachment of the Lys48-linked polyubiquitin chain. In contrast, modifications with the Lys63-linked polyubiquitin chain and/or monomeric ubiquitin are generally thought to function in proteasome-independent cellular processes. Nevertheless, the ubiquitin chain-type specificity for the proteasomal targeting is still poorly understood, especially in vivo. Using mass spectrometry, we found that Rsp5, a ubiquitin-ligase in budding yeast, catalyzes the formation of Lys63-linked ubiquitin chains in vitro. Interestingly, the 26S proteasome degraded well the Lys63-linked ubiquitinated substrate in vitro. To examine whether Lys63-linked ubiquitination serves in degradation in vivo, we investigated the ubiquitination of Mga2-p120, a substrate of Rsp5. The polyubiquitinated p120 contained relatively high levels of Lys63-linkages, and the Lys63-linked chains were sufficient for the proteasome-binding and subsequent p120-processing. In addition, Lys63-linked chains as well as Lys48-linked chains were detected in the 26S proteasome-bound polyubiquitinated proteins. These results raise the possibility that Lys63-linked ubiquitin chain also serves as a targeting signal for the 26S proteaseome in vivo. PMID:19153599
Prodinger, Birgit; Tennant, Alan; Stucki, Gerold; Cieza, Alarcos; Üstün, Tevfik Bedirhan
2016-10-01
Our aim was to specify the requirements of an architecture to serve as the foundation for standardized reporting of health information and to provide an exemplary application of this architecture. The World Health Organization's International Classification of Functioning, Disability and Health (ICF) served as the conceptual framework. Methods to establish content comparability were the ICF Linking Rules. The Rasch measurement model, as a special case of additive conjoint measurement, which satisfies the required criteria for fundamental measurement, allowed for the development of a common metric foundation for measurement unit conversion. Secondary analysis of data from the North Yorkshire Survey was used to illustrate these methods. Patients completed three instruments and the items were linked to the ICF. The Rasch measurement model was applied, first to each scale, and then to items across scales which were linked to a common domain. Based on the linking of items to the ICF, the majority of items were grouped into two domains, Mobility and Self-care. Analysis of the individual scales and of items linked to a common domain across scales satisfied the requirements of the Rasch measurement model. The measurement unit conversion between items from the three instruments linked to the Mobility and Self-care domains, respectively, was demonstrated. The realization of an ICF-based architecture for information on patients' functioning enables harmonization of health information while allowing clinicians and researchers to continue using their existing instruments. This architecture will facilitate access to comprehensive and consistently reported health information to serve as the foundation for informed decision-making. © The Author(s) 2016.
Bannasch, Detlev; Mehrle, Alexander; Glatting, Karl-Heinz; Pepperkok, Rainer; Poustka, Annemarie; Wiemann, Stefan
2004-01-01
We have implemented LIFEdb (http://www.dkfz.de/LIFEdb) to link information regarding novel human full-length cDNAs generated and sequenced by the German cDNA Consortium with functional information on the encoded proteins produced in functional genomics and proteomics approaches. The database also serves as a sample-tracking system to manage the process from cDNA to experimental read-out and data interpretation. A web interface enables the scientific community to explore and visualize features of the annotated cDNAs and ORFs combined with experimental results, and thus helps to unravel new features of proteins with as yet unknown functions. PMID:14681468
Single proteins that serve linked functions in intracellular and extracellular microenvironments
DOE Office of Scientific and Technical Information (OSTI.GOV)
Radisky, Derek C.; Stallings-Mann, Melody; Hirai, Yohei
2009-06-03
Maintenance of organ homeostasis and control of appropriate response to environmental alterations requires intimate coordination of cellular function and tissue organization. An important component of this coordination may be provided by proteins that can serve distinct, but linked, functions on both sides of the plasma membrane. Here we present a novel hypothesis in which non-classical secretion can provide a mechanism through which single proteins can integrate complex tissue functions. Single genes can exert a complex, dynamic influence through a number of different processes that act to multiply the function of the gene product(s). Alternative splicing can create many different transcriptsmore » that encode proteins of diverse, even antagonistic, function from a single gene. Posttranslational modifications can alter the stability, activity, localization, and even basic function of proteins. A protein can exist in different subcellular localizations. More recently, it has become clear that single proteins can function both inside and outside the cell. These proteins often lack defined secretory signal sequences, and transit the plasma membrane by mechanisms separate from the classical ER/Golgi secretory process. When examples of such proteins are examined individually, the multifunctionality and lack of a signal sequence are puzzling - why should a protein with a well known function in one context function in such a distinct fashion in another? We propose that one reason for a single protein to perform intracellular and extracellular roles is to coordinate organization and maintenance of a global tissue function. Here, we describe in detail three specific examples of proteins that act in this fashion, outlining their specific functions in the extracellular space and in the intracellular space, and we discuss how these functions may be linked. We present epimorphin/syntaxin-2, which may coordinate morphogenesis of secretory organs (as epimorphin) with control of protein secretion (as syntaxin-2), amphoterin/high mobility group box-1 (HMGB1), which may link inflammation (as amphoterin) with regulation of gene expression (as HMGB1), and tissue transglutaminase, which affects delivery of and response to apoptotic signals by serving a related function on both sides of the plasma membrane. As it is notable that all three of these proteins have been reported to transit the plasma membrane through non-classical secretory mechanisms, we will also discuss why coordinated inside/outside functions may be found in some examples of proteins which transit the plasma membrane through non-classical mechanisms and how this relationship can be used to identify additional proteins that share these characteristics.« less
Shared Secrets versus Secrets Kept Private Are Linked to Better Adolescent Adjustment
ERIC Educational Resources Information Center
Frijns, Tom; Finkenauer, Catrin; Keijsers, Loes
2013-01-01
It is a household notion that secrecy is bad while sharing is good. But what about shared secrets? The present research adopts a functional analysis of sharing secrets, arguing that it should negate harmful consequences generally associated with secrecy and serves important interpersonal functions in adolescence. A survey study among 790 Dutch…
Institutionalized Hypocrisy: The Myth of Intercollegiate Athletics
ERIC Educational Resources Information Center
Flowers, Ronald D.
2009-01-01
America is unique in that participation in sports has historically been linked to colleges and universities under the premise that participation serves an educational function and supplements the mission of higher education. Yet, intercollegiate athletics is seldom discussed in institutional accreditation self-studies, mission statements, or…
Ocklenburg, Sebastian; Friedrich, Patrick; Güntürkün, Onur; Genç, Erhan
2016-07-01
Hemispheric asymmetries are a central principle of nervous system architecture and shape the functional organization of most cognitive systems. Structural gray matter asymmetries and callosal interactions have been identified as contributing neural factors but always fell short to constitute a full explanans. Meanwhile, recent advances in in vivo white matter tractography have unrevealed the asymmetrical organization of many intrahemispheric white matter pathways, which might serve as the missing link to explain the substrate of functional lateralization. By taking into account callosal interactions, gray matter asymmetries and asymmetrical interhemispheric pathways, we opt for a new triadic model that has the potential to explain many observations which cannot be elucidated within the current frameworks of lateralized cognition.
47 CFR 15.713 - TV bands database.
Code of Federal Regulations, 2014 CFR
2014-10-01
... 47 Telecommunication 1 2014-10-01 2014-10-01 false TV bands database. 15.713 Section 15.713... TV bands database. Link to an amendment published at 79 FR 48536, August 15, 2014. (a) Purpose. The TV bands database serves the following functions: (1) To determine and provide to a TVBD, upon...
The Role of Peer Relationships in Adjustment to College
ERIC Educational Resources Information Center
Swenson, Lisa A.; Nordstrom, Alicia; Hiester, Marnie
2008-01-01
According to developmental research, peer relationships serve a positive function in children's, adolescents', and adults' lives. We expected that peer relationships would also benefit emerging adults as they transition into college. Using friendship quality and attachment measures, we examined the link between the closeness of peer relationships…
College Admission: Profession or Industry?
ERIC Educational Resources Information Center
Thacker, Lloyd
1999-01-01
Discusses how the condition and fate of both the college admissions profession and liberal arts education are linked, and how they are both threatened by elements of commercialism. Argues for reasserting professionalism by looking beyond the competitive advantage of the college's interest to serve a broader function as trustees of students'…
Ma, Junfeng; Liu, Ting; Wei, An-Chi; Banerjee, Partha; O'Rourke, Brian; Hart, Gerald W.
2015-01-01
Dynamic cycling of O-linked β-N-acetylglucosamine (O-GlcNAc) on nucleocytoplasmic proteins serves as a nutrient sensor to regulate numerous biological processes. However, mitochondrial protein O-GlcNAcylation and its effects on function are largely unexplored. In this study, we performed a comparative analysis of the proteome and O-GlcNAcome of cardiac mitochondria from rats acutely (12 h) treated without or with thiamet-G (TMG), a potent and specific inhibitor of O-GlcNAcase. We then determined the functional consequences in mitochondria isolated from the two groups. O-GlcNAcomic profiling finds that over 88 mitochondrial proteins are O-GlcNAcylated, with the oxidative phosphorylation system as a major target. Moreover, in comparison with controls, cardiac mitochondria from TMG-treated rats did not exhibit altered protein abundance but showed overall elevated O-GlcNAcylation of many proteins. However, O-GlcNAc was unexpectedly down-regulated at certain sites of specific proteins. Concomitantly, TMG treatment resulted in significantly increased mitochondrial oxygen consumption rates, ATP production rates, and enhanced threshold for permeability transition pore opening by Ca2+. Our data reveal widespread and dynamic mitochondrial protein O-GlcNAcylation, serving as a regulator to their function. PMID:26446791
Immune heterogeneity in neuroinflammation: dendritic cells in the brain.
Colton, Carol A
2013-03-01
Dendritic cells (DC) are critical to an integrated immune response and serve as the key link between the innate and adaptive arms of the immune system. Under steady state conditions, brain DC's act as sentinels, continually sampling their local environment. They share this function with macrophages derived from the same basic hemopoietic (bone marrow-derived) precursor and with parenchymal microglia that arise from a unique non-hemopoietic origin. While multiple cells may serve as antigen presenting cells (APCs), dendritic cells present both foreign and self-proteins to naïve T cells that, in turn, carry out effector functions that serve to protect or destroy. The resulting activation of the adaptive response is a critical step to resolution of injury or infection and is key to survival. In this review we will explore the critical roles that DCs play in the brain's response to neuroinflammatory disease with emphasis on how the brain's microenvironment impacts these actions.
A New Reactive FMIPv6 Mechanism for Minimizing Packet Loss
NASA Astrophysics Data System (ADS)
Kim, Pyungsoo
This paper considers a new reactive fast handover MIPv6 (FMIPv6) mechanism to minimize packet loss of the existing mechanism. The primary idea of the proposed reactive FMIPv6 mechanism is that the serving access router buffers packets toward the mobile node (MN) as soon as the link layer between MN and serving base station is disconnected. To implement the proposed mechanism, the router discovery message exchanged between MN and serving access router is extended. In addition, the IEEE 802.21 Media Independent Handover Function event service message is defined newly. Through analytic performance evaluation and experiments, the proposed reactive FMIPv6 mechanism can be shown to minimize packet loss much than the existing mechanism.
Subdimensions of Adolescent Belonging in High School
ERIC Educational Resources Information Center
Wallace, Tanner LeBaron; Ye, Feifei; Chhuon, Vichet
2012-01-01
Adolescents' sense of belonging in high school may serve a protective function, linking school-based relationships to positive youth outcomes. To advance the study of sense of belonging, we conducted a mixed method, factor analytic study (Phase 1 focus groups, N = 72; Phase 2 cross-sectional survey, N = 890) to explore the multidimensionality of…
Applying Cognitive Neuroscience Research to Education: The Case of Literacy
ERIC Educational Resources Information Center
Katzir, Tami; Pare-Blagoev, Juliana
2006-01-01
Neuroscience has provided fascinating glimpses into the brain's development and function. Despite remarkable progress, brain research has not yet been successfully brought to bear in many fields of educational psychology. In this article, work on literacy serves as a test case for an examination of potential future bridges linking mind, brain, and…
Friends with benefits: the evolved psychology of same- and opposite-sex friendship.
Lewis, David M G; Conroy-Beam, Daniel; Al-Shawaf, Laith; Raja, Annia; DeKay, Todd; Buss, David M
2011-12-08
During human evolution, men and women faced distinct adaptive problems, including pregnancy, hunting, childcare, and warfare. Due to these sex-linked adaptive problems, natural selection would have favored psychological mechanisms that oriented men and women toward forming friendships with individuals possessing characteristics valuable for solving these problems. The current study explored sex-differentiated friend preferences and the psychological design features of same- and opposite-sex friendship in two tasks. In Task 1, participants (N = 121) categorized their same-sex friends (SSFs) and opposite-sex friends (OSFs) according to the functions these friends serve in their lives. In Task 2, participants designed their ideal SSFs and OSFs using limited budgets that forced them to make trade-offs between the characteristics they desire in their friends. In Task 1, men, more than women, reported maintaining SSFs for functions related to athleticism and status enhancement and OSFs for mating opportunities. In Task 2, both sexes prioritized agreeableness and dependability in their ideal SSFs, but men prioritized physical attractiveness in their OSFs, whereas women prioritized economic resources and physical prowess. These findings suggest that friend preferences may have evolved to solve ancestrally sex-linked adaptive problems, and that opposite-sex friendship may directly or indirectly serve mating functions.
Raver, C. Cybele; Blair, Clancy; Willoughby, Michael
2017-01-01
In a predominantly low-income, population-based longitudinal sample of 1,259 children followed from birth, results suggest that chronic exposure to poverty and the strains of financial hardship were each uniquely predictive of young children’s performance on measures of executive functioning. Results suggest that temperament-based vulnerability serves as a statistical moderator of the link between poverty-related risk and children’s executive functioning. Implications for models of ecology and biology in shaping the development of children’s self-regulation are discussed. PMID:22563675
Mitochondrial and ER Calcium Uptake and Release Fluxes and their Interplay in Intact Nerve Cells
NASA Astrophysics Data System (ADS)
Friel, David D.
Ionized free Ca ( Ca 2+) is a ubiquitous signaling ion that serves as the critical link between a variety of physiological stimuli and their intracellular effectors. Previous studies of reduced in vitro preparations have provided functional characterizations of various Ca 2+ channels, pumps and exchangers that regulate cellular Ca 2+ movements. However, little is known about the functional interplay between transporters that are expressed together in intact cells and orchestrate stimulus-evoked changes in [ Ca 2+]. This review summarizes recent progress in characterizing Ca 2+ transporters in sympathetic neurons, which provide an ideal model for studying Ca 2+ dynamics in neurons. Our results show how the functional interplay between Ca 2+ transport systems that are regulated by Ca 2+ in quantitatively differ-ent ways leads to emergent properties of Ca 2+ signaling that are expected to play a critical role in defining how Ca 2+ serves its role as a signaling ion.
Lyu, Ming; Wang, Yue-Fei; Fan, Guan-Wei; Wang, Xiao-Ying; Xu, Shuang-Yong; Zhu, Yan
2017-01-01
It has become apparent that gut microbiota is closely associated with cardiometabolic diseases (CMDs), and alteration in microbiome compositions is also linked to the host environment. Next generation sequencing (NGS) has facilitated in-depth studies on the effects of herbal medicine and functional food on gut microbiota. Both herbal medicine and functional food contain fiber, polyphenols and polysaccharides, exerting prebiotics-like activities in the prevention and treatment of CMDs. The administrations of herbal medicine and functional food lead to increased the abundance of phylum Bacteroidetes, and genus Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella , while reducing phylum Firmicutes and Firmicutes/Bacteroidetes ratio in gut. Both herbal medicine and functional food interact with gut microbiome and alter the microbial metabolites including short-chain fatty acids (SCFAs), bile acids (BAs) and lipopolysaccharides (LPS), which are now correlated with metabolic diseases such as type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). In addition, trimethylamine (TMA)-N-oxide (TMAO) is recently linked to atherosclerosis (AS) and cardiovascular disease (CVD) risks. Moreover, gut-organs axes may serve as the potential strategy for treating CMDs with the intervention of herbal medicine and functional food. In summary, a balance between herbal medicine and functional food rich in fiber, polyphenols and polysaccharides plays a vital role in modulating gut microbiota (phylum Bacteroidetes, Firmicutes and Firmicutes/Bacteroidetes ratio, and genus Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella ) through SCFAs, BAs, LPS and TMAO signaling regarding CMDs. Targeting gut-organs axes may serve as a new therapeutic strategy for CMDs by herbal medicine and functional food in the future. This review aims to summarize the balance between herbal medicine and functional food utilized for the prevention and treatment of CMDs through modulating gut microbiota.
Lyu, Ming; Wang, Yue-fei; Fan, Guan-wei; Wang, Xiao-ying; Xu, Shuang-yong; Zhu, Yan
2017-01-01
It has become apparent that gut microbiota is closely associated with cardiometabolic diseases (CMDs), and alteration in microbiome compositions is also linked to the host environment. Next generation sequencing (NGS) has facilitated in-depth studies on the effects of herbal medicine and functional food on gut microbiota. Both herbal medicine and functional food contain fiber, polyphenols and polysaccharides, exerting prebiotics-like activities in the prevention and treatment of CMDs. The administrations of herbal medicine and functional food lead to increased the abundance of phylum Bacteroidetes, and genus Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella, while reducing phylum Firmicutes and Firmicutes/Bacteroidetes ratio in gut. Both herbal medicine and functional food interact with gut microbiome and alter the microbial metabolites including short-chain fatty acids (SCFAs), bile acids (BAs) and lipopolysaccharides (LPS), which are now correlated with metabolic diseases such as type 2 diabetes (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). In addition, trimethylamine (TMA)-N-oxide (TMAO) is recently linked to atherosclerosis (AS) and cardiovascular disease (CVD) risks. Moreover, gut-organs axes may serve as the potential strategy for treating CMDs with the intervention of herbal medicine and functional food. In summary, a balance between herbal medicine and functional food rich in fiber, polyphenols and polysaccharides plays a vital role in modulating gut microbiota (phylum Bacteroidetes, Firmicutes and Firmicutes/Bacteroidetes ratio, and genus Akkermansia, Bifidobacteria, Lactobacillus, Bacteroides and Prevotella) through SCFAs, BAs, LPS and TMAO signaling regarding CMDs. Targeting gut-organs axes may serve as a new therapeutic strategy for CMDs by herbal medicine and functional food in the future. This review aims to summarize the balance between herbal medicine and functional food utilized for the prevention and treatment of CMDs through modulating gut microbiota. PMID:29167659
Jonker, Anna; Kuntsche, Emmanuel
2014-12-01
This study investigated whether adolescents who drink and those who are teetotal differ in the link between music motives and health-related outcomes (life satisfaction, self-rated health, school pressure, somatic complaints, depressed and aggressive mood, physical powerlessness, frequency of being bullied and bullying others and evenings spent out with friends). It also looked at whether associations between music motives and health-related outcomes remained significant when drinking motives were included among drinkers. Confirmatory factor analysis and structural equation models were estimated based on data from 4,481 adolescents from Switzerland (mean age 14.5, SD = 0.9). It was confirmed that the four music motives and the four drinking motives obtained by crossing the valence (positive–negative) and the source (internal–external) of expected change in affect form distinct dimensions (i.e. the 8-factor model best fitted the data). Drinkers and non-drinkers differed in the various links between music motives and health-related outcomes. For example, almost all the links between conformity music motives and the health-related outcomes were significant for non-drinkers but not for drinkers. Enhancement music motives, by contrast, were often significant for drinkers but not for non-drinkers. Coping music motives were significant among both drinkers and non-drinkers. These links were basically unchanged when drinking motives were taken into account. This study indicates that music serves important functions in the lives of adolescents, even among those who use alcohol for different motives. This makes listening to music a promising potential alternative to alcohol use.
Shin, Won-Kyung; Cho, Jinhyun; Kannan, Aravindaraj G.; Lee, Yoon-Sung; Kim, Dong-Won
2016-01-01
Liquid electrolytes composed of lithium salt in a mixture of organic solvents have been widely used for lithium-ion batteries. However, the high flammability of the organic solvents can lead to thermal runaway and explosions if the system is accidentally subjected to a short circuit or experiences local overheating. In this work, a cross-linked composite gel polymer electrolyte was prepared and applied to lithium-ion polymer cells as a safer and more reliable electrolyte. Mesoporous SiO2 nanoparticles containing reactive methacrylate groups as cross-linking sites were synthesized and dispersed into the fibrous polyacrylonitrile membrane. They directly reacted with gel electrolyte precursors containing tri(ethylene glycol) diacrylate, resulting in the formation of a cross-linked composite gel polymer electrolyte with high ionic conductivity and favorable interfacial characteristics. The mesoporous SiO2 particles also served as HF scavengers to reduce the HF content in the electrolyte at high temperature. As a result, the cycling performance of the lithium-ion polymer cells with cross-linked composite gel polymer electrolytes employing methacrylate-functionalized mesoporous SiO2 nanoparticles was remarkably improved at elevated temperatures. PMID:27189842
Linking mitochondrial bioenergetics to insulin resistance via redox biology
Fisher-Wellman, Kelsey H.; Neufer, P. Darrell
2012-01-01
Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H2O2) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal to ultimately decrease insulin sensitivity. H2O2 is a major input to cellular redox circuits that link to cysteine residues throughout the entire proteome to regulate cell function. Here we review the principles of mitochondrial bioenergetics and redox systems biology and offer new insight as to how H2O2 emission may be linked via redox biology to the etiology of insulin resistance. PMID:22305519
JONKER, ANNA; KUNTSCHE, EMMANUEL
2014-01-01
Background and aims: This study investigated whether adolescents who drink and those who are teetotal differ in the link between music motives and health-related outcomes (life satisfaction, self-rated health, school pressure, somatic complaints, depressed and aggressive mood, physical powerlessness, frequency of being bullied and bullying others and evenings spent out with friends). It also looked at whether associations between music motives and health-related outcomes remained significant when drinking motives were included among drinkers. Methods: Confirmatory factor analysis and structural equation models were estimated based on data from 4,481 adolescents from Switzerland (mean age 14.5, SD = 0.9). Results: It was confirmed that the four music motives and the four drinking motives obtained by crossing the valence (positive–negative) and the source (internal–external) of expected change in affect form distinct dimensions (i.e. the 8-factor model best fitted the data). Drinkers and non-drinkers differed in the various links between music motives and health-related outcomes. For example, almost all the links between conformity music motives and the health-related outcomes were significant for non-drinkers but not for drinkers. Enhancement music motives, by contrast, were often significant for drinkers but not for non-drinkers. Coping music motives were significant among both drinkers and non-drinkers. These links were basically unchanged when drinking motives were taken into account. Discussion and conclusions: This study indicates that music serves important functions in the lives of adolescents, even among those who use alcohol for different motives. This makes listening to music a promising potential alternative to alcohol use. PMID:25592307
Figure and caption for LDRD annual report
DOE Office of Scientific and Technical Information (OSTI.GOV)
Suratwala, T.
2017-10-16
Material removal rate of various optical material workpieces polished using various colloidal slurries as a function of partial charge difference. Partial charge difference is a parameter calculated from a new chemical model proposed to link the condensation reaction rate with polishing material removal rate. This chemical model can serve as a global platform to predict & design polishing processes for a wide variety of workpiece materials and slurry compositions.
The mitonuclear compatibility hypothesis of sexual selection
Hill, Geoffrey E.; Johnson, James D.
2013-01-01
Why females assess ornaments when choosing mates remains a central question in evolutionary biology. We hypothesize that the imperative for a choosing female to find a mate with nuclear oxidative phosphorylation (OXPHOS) genes that are compatible with her mitochondrial OXPHOS genes drives the evolution of ornaments. Indicator traits are proposed to signal the efficiency of OXPHOS function thus enabling females to select mates with nuclear genes that are compatible with maternal mitochondrial genes in the formation of OXPHOS complexes. Species-typical pattern of ornamentation is proposed to serve as a marker of mitochondrial type ensuring that females assess prospective mates with a shared mitochondrial background. The mitonuclear compatibility hypothesis predicts that the production of ornaments will be closely linked to OXPHOS pathways, and that sexual selection for compatible mates will be strongest when genes for nuclear components of OXPHOS complexes are Z-linked. The implications of this hypothesis are that sexual selection may serve as a driver for the evolution of more efficient cellular respiration. PMID:23945683
Multiple-Ring Digital Communication Network
NASA Technical Reports Server (NTRS)
Kirkham, Harold
1992-01-01
Optical-fiber digital communication network to support data-acquisition and control functions of electric-power-distribution networks. Optical-fiber links of communication network follow power-distribution routes. Since fiber crosses open power switches, communication network includes multiple interconnected loops with occasional spurs. At each intersection node is needed. Nodes of communication network include power-distribution substations and power-controlling units. In addition to serving data acquisition and control functions, each node acts as repeater, passing on messages to next node(s). Multiple-ring communication network operates on new AbNET protocol and features fiber-optic communication.
Kringelbach, Morten L.; Berridge, Kent C.
2017-01-01
Arguably, emotion is always valenced—either pleasant or unpleasant—and dependent on the pleasure system. This system serves adaptive evolutionary functions; relying on separable wanting, liking, and learning neural mechanisms mediated by mesocorticolimbic networks driving pleasure cycles with appetitive, consummatory, and satiation phases. Liking is generated in a small set of discrete hedonic hotspots and coldspots, while wanting is linked to dopamine and to larger distributed brain networks. Breakdown of the pleasure system can lead to anhedonia and other features of affective disorders. Eudaimonia and well-being are difficult to study empirically, yet whole-brain computational models could offer novel insights (e.g., routes to eudaimonia such as caregiving of infants or music) potentially linking eudaimonia to optimal metastability in the pleasure system. PMID:28943891
Pain, motor and gait assessment of murine osteoarthritis in a cruciate ligament transection model
Ruan, Merry ZC; Patel, Ronak M; Dawson, Brian C; Jiang, Ming-ming; Lee, Brendan HI
2013-01-01
Objective The major complaint of Osteoarthritis (OA) patients is pain. However, due to the nature of clinical studies and the limitation of animal studies, few studies have linked function impairment and behavioral changes in OA animal models to cartilage loss and histopathology. Our objective was to study surrogate markers of functional impairment in relation to cartilage loss and pathological changes in a post-traumatic mouse model of OA. Method We performed a battery of functional analyses in a mouse model of OA generated by cruciate ligament transection (CLT). The changes in functional analyses were linked to histological changes graded by OARSI standards, histological grading of synovitis, and volumetric changes of the articular cartilage and osteophytes quantified by phase contrast micro-CT. Results OA generated by CLT led to decreased time on rotarod, delayed response on hotplate analysis, and altered gait starting from 4 weeks after surgery. Activity in open field analysis did not change at 4, 8, or 12 weeks after CLT. The magnitude of behavioral changes was directly correlated with higher OARSI histological scores of OA, synovitis in the knee joints, cartilage volume loss, and osteophyte formation. Conclusion Our findings link functional analyses to histological grading, synovitis, comprehensive 3-dimensional assessment of cartilage volume and osteophyte formation. This serves as a reference for a mouse model in predicting outcomes of OA treatment. PMID:23973150
Unifying Time to Contact Estimation and Collision Avoidance across Species
Keil, Matthias S.; López-Moliner, Joan
2012-01-01
The -function and the -function are phenomenological models that are widely used in the context of timing interceptive actions and collision avoidance, respectively. Both models were previously considered to be unrelated to each other: is a decreasing function that provides an estimation of time-to-contact (ttc) in the early phase of an object approach; in contrast, has a maximum before ttc. Furthermore, it is not clear how both functions could be implemented at the neuronal level in a biophysically plausible fashion. Here we propose a new framework – the corrected modified Tau function – capable of predicting both -type (“”) and -type (“”) responses. The outstanding property of our new framework is its resilience to noise. We show that can be derived from a firing rate equation, and, as , serves to describe the response curves of collision sensitive neurons. Furthermore, we show that predicts the psychophysical performance of subjects determining ttc. Our new framework is thus validated successfully against published and novel experimental data. Within the framework, links between -type and -type neurons are established. Therefore, it could possibly serve as a model for explaining the co-occurrence of such neurons in the brain. PMID:22915999
Erazo-Oliveras, Alfredo; Fuentes, Natividad R; Wright, Rachel C; Chapkin, Robert S
2018-06-02
The cell plasma membrane serves as a nexus integrating extra- and intracellular components, which together enable many of the fundamental cellular signaling processes that sustain life. In order to perform this key function, plasma membrane components assemble into well-defined domains exhibiting distinct biochemical and biophysical properties that modulate various signaling events. Dysregulation of these highly dynamic membrane domains can promote oncogenic signaling. Recently, it has been demonstrated that select membrane-targeted dietary bioactives (MTDBs) have the ability to remodel plasma membrane domains and subsequently reduce cancer risk. In this review, we focus on the importance of plasma membrane domain structural and signaling functionalities as well as how loss of membrane homeostasis can drive aberrant signaling. Additionally, we discuss the intricacies associated with the investigation of these membrane domain features and their associations with cancer biology. Lastly, we describe the current literature focusing on MTDBs, including mechanisms of chemoprevention and therapeutics in order to establish a functional link between these membrane-altering biomolecules, tuning of plasma membrane hierarchal organization, and their implications in cancer prevention.
SINGLE NEURON ACTIVITY AND THETA MODULATION IN POSTRHINAL CORTEX DURING VISUAL OBJECT DISCRIMINATION
Furtak, Sharon C.; Ahmed, Omar J.; Burwell, Rebecca D.
2012-01-01
Postrhinal cortex, the rodent homolog of the primate parahippocampal cortex, processes spatial and contextual information. Our hypothesis of postrhinal function is that it serves to encode context, in part, by forming representations that link objects to places. We recorded postrhinal neuronal activity and local field potentials (LFPs) in rats trained on a two-choice, visual discrimination task. As predicted, a large proportion of postrhinal neurons signaled object-location conjunctions. In addition, postrhinal LFPs exhibited strong oscillatory rhythms in the theta band, and many postrhinal neurons were phase locked to theta. Although correlated with running speed, theta power was lower than predicted by speed alone immediately before and after choice. However, theta power was significantly increased following incorrect decisions, suggesting a role in signaling error. These findings provide evidence that postrhinal cortex encodes representations that link objects to places and suggest that postrhinal theta modulation extends to cognitive as well as spatial functions. PMID:23217745
Space Station communications and tracking systems modeling and RF link simulation
NASA Technical Reports Server (NTRS)
Tsang, Chit-Sang; Chie, Chak M.; Lindsey, William C.
1986-01-01
In this final report, the effort spent on Space Station Communications and Tracking System Modeling and RF Link Simulation is described in detail. The effort is mainly divided into three parts: frequency division multiple access (FDMA) system simulation modeling and software implementation; a study on design and evaluation of a functional computerized RF link simulation/analysis system for Space Station; and a study on design and evaluation of simulation system architecture. This report documents the results of these studies. In addition, a separate User's Manual on Space Communications Simulation System (SCSS) (Version 1) documents the software developed for the Space Station FDMA communications system simulation. The final report, SCSS user's manual, and the software located in the NASA JSC system analysis division's VAX 750 computer together serve as the deliverables from LinCom for this project effort.
A scale-free systems theory of motivation and addiction.
Chambers, R Andrew; Bickel, Warren K; Potenza, Marc N
2007-01-01
Scale-free organizations, characterized by uneven distributions of linkages between nodal elements, describe the structure and function of many life-based complex systems developing under evolutionary pressures. We explore motivated behavior as a scale-free map toward a comprehensive translational theory of addiction. Motivational and behavioral repertoires are reframed as link and nodal element sets, respectively, comprising a scale-free structure. These sets are generated by semi-independent information-processing streams within cortical-striatal circuits that cooperatively provide decision-making and sequential processing functions necessary for traversing maps of motivational links connecting behavioral nodes. Dopamine modulation of cortical-striatal plasticity serves a central-hierarchical mechanism for survival-adaptive sculpting and development of motivational-behavioral repertoires by guiding a scale-free design. Drug-induced dopamine activity promotes drug taking as a highly connected behavioral hub at the expense of natural-adaptive motivational links and behavioral nodes. Conceptualizing addiction as pathological alteration of scale-free motivational-behavioral repertoires unifies neurobiological, neurocomputational and behavioral research while addressing addiction vulnerability in adolescence and psychiatric illness. This model may inform integrative research in defining more effective prevention and treatment strategies for addiction.
A Scale-Free Systems Theory of Motivation and Addiction
Bickel, Warren K.; Potenza, Marc N.
2007-01-01
Scale-free organizations, characterized by uneven distributions of linkages between nodal elements, describe the structure and function of many life-based complex systems developing under evolutionary pressures. We explore motivated behavior as a scale-free map toward a comprehensive translational theory of addiction. Motivational and behavioral repertoires are reframed as link and nodal element sets, respectively, comprising a scale-free structure. These sets are generated by semi-independent information-processing streams within cortical-striatal circuits that cooperatively provide decision-making and sequential processing functions necessary for traversing maps of motivational links connecting behavioral nodes. Dopamine modulation of cortical-striatal plasticity serves a central-hierarchical mechanism for survival-adaptive sculpting and development of motivational-behavioral repertoires by guiding a scale-free design. Drug-induced dopamine activity promotes drug-taking as a highly connected behavioral hub at the expense of natural-adaptive motivational links and behavioral nodes. Conceptualizing addiction as pathological alteration of scale-free motivational-behavioral repertoires unifies neurobiological, neurocomputational and behavioral research while addressing addiction vulnerability in adolescence and psychiatric illness. This model may inform integrative research in defining more effective prevention and treatment strategies for addiction. PMID:17574673
Pal Sharma, C; Goldmann, Wolfgang H
2004-01-01
Actin-binding protein (ABP-280; filamin) is a phosphoprotein present in the periphery of the cytoplasm where it can cross-link actin filaments, associate with lipid membranes, and bind to membrane surface receptors. Given its function and localization in the cell, we decided to investigate the possibility of whether it serves as substrate for p56lck, a lymphocyte-specific member of the src family of protein tyrosine kinases associated with cell surface glycoproteins. The interaction of p56lck with membrane glycoproteins is important for cell development and functional activation. Here, we show that purified p56lck interacts and catalyzes in vitro kinase reactions. Tyrosine phosphorylation by p56lck is restricted to a single peptide of labeled ABP-280 shown by protease digest. The addition of phorbol ester to cells results in the inhibition of phosphorylation of ABP-280 by p56lck. These results show a decrease in phosphorylation suggesting conformationally induced regulation. Dynamic light scattering confirmed increased actin filament cross-linking due to phosphorylation of ABP-280 by p56lck.
Simple measurement-based admission control for DiffServ access networks
NASA Astrophysics Data System (ADS)
Lakkakorpi, Jani
2002-07-01
In order to provide good Quality of Service (QoS) in a Differentiated Services (DiffServ) network, a dynamic admission control scheme is definitely needed as an alternative to overprovisioning. In this paper, we present a simple measurement-based admission control (MBAC) mechanism for DiffServ-based access networks. Instead of using active measurements only or doing purely static bookkeeping with parameter-based admission control (PBAC), the admission control decisions are based on bandwidth reservations and periodically measured & exponentially averaged link loads. If any link load on the path between two endpoints is over the applicable threshold, access is denied. Link loads are periodically sent to Bandwidth Broker (BB) of the routing domain, which makes the admission control decisions. The information needed in calculating the link loads is retrieved from the router statistics. The proposed admission control mechanism is verified through simulations. Our results prove that it is possible to achieve very high bottleneck link utilization levels and still maintain good QoS.
Emerson, Sam R; Rosenkranz, Sara K; Rosenkranz, Richard R; Kurti, Stephanie P; Harms, Craig A
2016-09-01
The prevalence of asthma is rising, presenting serious public health challenges. Recent data suggest that sugar-sweetened beverage (SSB) consumption plays a role in asthma aetiology. The purpose of the present study was to determine whether SSB consumption is linked to post-exercise airway narrowing (predictor of asthma development) across puberty. Participants completed pulmonary function tests, physical activity and dietary habit questionnaires, and an exercise test to exhaustion. Community in Manhattan, Kansas, USA. We recruited ten boys and ten girls from an original cohort of forty participants tested in our laboratory approximately 5 years prior. Participants were aged 9·7 (sd 0·9) years at baseline and 14·7 (sd 0·9) years at follow-up. Pre-puberty, boys consumed 6·8 (sd 4·8) servings/week and girls consumed 6·9 (sd 3·7) servings/week, while post-puberty boys consumed 11·5 (sd 5·3) servings/week and girls consumed 7·7 (sd 4·3) servings/week. Using Pearson correlation, SSB consumption was not significantly related to post-exercise airway narrowing at pre-puberty (r=-0·35, P=0·130). In linear regression analyses, SSB consumption was significantly related to post-exercise airway narrowing post-puberty before (standardized β=-0·60, P=0·005) but not after (standardized β=-0·33, P=0·211) adjustment for confounders. Change in SSB consumption from pre- to post-puberty was significantly associated with post-exercise airway narrowing post-puberty (r=-0·61, P=0·010) and change in post-exercise airway narrowing from pre- to post-puberty (r=-0·45, P=0·048) when assessed via Pearson correlations. These findings suggest a possible link between SSB consumption and asthma development during maturation. Reduced SSB intake may be a possible public health avenue for blunting rising asthma prevalence.
Muscle glycogen and cell function--Location, location, location.
Ørtenblad, N; Nielsen, J
2015-12-01
The importance of glycogen, as a fuel during exercise, is a fundamental concept in exercise physiology. The use of electron microscopy has revealed that glycogen is not evenly distributed in skeletal muscle fibers, but rather localized in distinct pools. In this review, we present the available evidence regarding the subcellular localization of glycogen in skeletal muscle and discuss this from the perspective of skeletal muscle fiber function. The distribution of glycogen in the defined pools within the skeletal muscle varies depending on exercise intensity, fiber phenotype, training status, and immobilization. Furthermore, these defined pools may serve specific functions in the cell. Specifically, reduced levels of these pools of glycogen are associated with reduced SR Ca(2+) release, muscle relaxation rate, and membrane excitability. Collectively, the available literature strongly demonstrates that the subcellular localization of glycogen has to be considered to fully understand the role of glycogen metabolism and signaling in skeletal muscle function. Here, we propose that the effect of low muscle glycogen on excitation-contraction coupling may serve as a built-in mechanism, which links the energetic state of the muscle fiber to energy utilization. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Pain, motor and gait assessment of murine osteoarthritis in a cruciate ligament transection model.
Ruan, M Z C; Patel, R M; Dawson, B C; Jiang, M-M; Lee, B H L
2013-09-01
The major complaint of Osteoarthritis (OA) patients is pain. However, due to the nature of clinical studies and the limitation of animal studies, few studies have linked function impairment and behavioral changes in OA animal models to cartilage loss and histopathology. Our objective was to study surrogate markers of functional impairment in relation to cartilage loss and pathological changes in a post-traumatic mouse model of OA. We performed a battery of functional analyses in a mouse model of OA generated by cruciate ligament transection (CLT). The changes in functional analyses were linked to histological changes graded by OARSI standards, histological grading of synovitis, and volumetric changes of the articular cartilage and osteophytes quantified by phase contrast micro-computed tomography (μCT). OA generated by CLT led to decreased time on rotarod, delayed response on hotplate analysis, and altered gait starting from 4 weeks after surgery. Activity in open field analysis did not change at 4, 8, or 12 weeks after CLT. The magnitude of behavioral changes was directly correlated with higher OARSI histological scores of OA, synovitis in the knee joints, cartilage volume loss, and osteophyte formation. Our findings link functional analyses to histological grading, synovitis, comprehensive three-dimensional assessment of cartilage volume and osteophyte formation. This serves as a reference for a mouse model in predicting outcomes of OA treatment. Copyright © 2013 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.
Neoproteoglycans in tissue engineering.
Weyers, Amanda; Linhardt, Robert J
2013-05-01
Proteoglycans, comprised of a core protein to which glycosaminoglycan chains are covalently linked, are an important structural and functional family of macromolecules found in the extracellular matrix. Advances in our understanding of biological interactions have lead to a greater appreciation for the need to design tissue engineering scaffolds that incorporate mimetics of key extracellular matrix components. A variety of synthetic and semisynthetic molecules and polymers have been examined by tissue engineers that serve as structural, chemical and biological replacements for proteoglycans. These proteoglycan mimetics have been referred to as neoproteoglycans and serve as functional and therapeutic replacements for natural proteoglycans that are often unavailable for tissue engineering studies. Although neoproteoglycans have important limitations, such as limited signaling ability and biocompatibility, they have shown promise in replacing the natural activity of proteoglycans through cell and protein binding interactions. This review focuses on the recent in vivo and in vitro tissue engineering applications of three basic types of neoproteoglycan structures, protein-glycosaminoglycan conjugates, nano-glycosaminoglycan composites and polymer-glycosaminoglycan complexes. © 2013 The Authors Journal compilation © 2013 FEBS.
Neoproteoglycans in tissue engineering
Weyers, Amanda; Linhardt, Robert J.
2014-01-01
Proteoglycans, comprised of a core protein to which glycosaminoglycan chains are covalently linked, are an important structural and functional family of macromolecules found in the extracellular matrix. Advances in our understanding of biological interactions have lead to a greater appreciation for the need to design tissue engineering scaffolds that incorporate mimetics of key extracellular matrix components. A variety of synthetic and semisynthetic molecules and polymers have been examined by tissue engineers that serve as structural, chemical and biological replacements for proteoglycans. These proteoglycan mimetics have been referred to as neoproteoglycans and serve as functional and therapeutic replacements for natural proteoglycans that are often unavailable for tissue engineering studies. Although neoproteoglycans have important limitations, such as limited signaling ability and biocompatibility, they have shown promise in replacing the natural activity of proteoglycans through cell and protein binding interactions. This review focuses on the recent in vivo and in vitro tissue engineering applications of three basic types of neoproteoglycan structures, protein–glycosaminoglycan conjugates, nano-glycosaminoglycan composites and polymer–glycosaminoglycan complexes. PMID:23399318
Trecartin, Shannon M; Cummings, Sherry M
2018-07-01
Older adults with functional impairments are at risk of being excluded from participation in day-to-day life. This exclusion can have detrimental effects on psychological well-being. The physical home environment is a potential force for both enhancing and limiting participation for this population. This systematic review of literature examined relationships between the physical home environment, functional impairment, and psychological well-being among older adults who live in community settings. The Ecological Model of Aging served as the guiding framework for this review. Results suggest that knowledge of the relationships between these constructs is still in the early stages. While associational relationships are established, the nature of these relationships is clouded by the inconsistency of measurement across studies, as well as design challenges. Objective and subjective features of the physical home environment are linked to psychological well-being throughout the literature. A growing body of evidence demonstrates that personal competence serves as a moderator of those relationships.
Linking Community Health Centers with Schools Serving Low-Income Children: An Idea Book.
ERIC Educational Resources Information Center
Health Resources and Services Administration (DHHS/PHS), Rockville, MD. Bureau of Primary Health Care.
By working together, pooling resources and energy, both health centers and schools can do more to help children to be ready to learn and to reach their full potential as citizens. This book focuses on establishing links between schools serving low-income children and community or migrant health centers. The book is organized into three chapters…
Organelle communication: signaling crossroads between homeostasis and disease.
Bravo-Sagua, Roberto; Torrealba, Natalia; Paredes, Felipe; Morales, Pablo E; Pennanen, Christian; López-Crisosto, Camila; Troncoso, Rodrigo; Criollo, Alfredo; Chiong, Mario; Hill, Joseph A; Simmen, Thomas; Quest, Andrew F; Lavandero, Sergio
2014-05-01
Cellular organelles do not function as isolated or static units, but rather form dynamic contacts between one another that can be modulated according to cellular needs. The physical interfaces between organelles are important for Ca2+ and lipid homeostasis, and serve as platforms for the control of many essential functions including metabolism, signaling, organelle integrity and execution of the apoptotic program. Emerging evidence also highlights the importance of organelle communication in disorders such as Alzheimer's disease, pulmonary arterial hypertension, cancer, skeletal and cardiac muscle dysfunction. Here, we provide an overview of the current literature on organelle communication and the link to human pathologies. Copyright © 2014 Elsevier Ltd. All rights reserved.
Exploitation of peptide motif sequences and their use in nanobiotechnology.
Shiba, Kiyotaka
2010-08-01
Short amino acid sequences extracted from natural proteins or created using in vitro evolution systems are sometimes associated with particular biological functions. These peptides, called peptide motifs, can serve as functional units for the creation of various tools for nanobiotechnology. In particular, peptide motifs that have the ability to specifically recognize the surfaces of solid materials and to mineralize certain inorganic materials have been linking biological science to material science. Here, I review how these peptide motifs have been isolated from natural proteins or created using in vitro evolution systems, and how they have been used in the nanobiotechnology field. Copyright © 2010 Elsevier Ltd. All rights reserved.
Amine-Functionalized Covalent Organic Framework for Efficient SO2 Capture with High Reversibility.
Lee, Gang-Young; Lee, Joohyeon; Vo, Huyen Thanh; Kim, Sangwon; Lee, Hyunjoo; Park, Taiho
2017-04-03
Removing sulfur dioxide (SO 2 ) from exhaust flue gases of fossil fuel power plants is an important issue given the toxicity of SO 2 and subsequent environmental problems. To address this issue, we successfully developed a new series of imide-linked covalent organic frameworks (COFs) that have high mesoporosity with large surface areas to support gas flowing through channels; furthermore, we incorporated 4-[(dimethylamino)methyl]aniline (DMMA) as the modulator to the imide-linked COF. We observed that the functionalized COFs serving as SO 2 adsorbents exhibit outstanding molar SO 2 sorption capacity, i.e., PI-COF-m10 record 6.30 mmol SO 2 g -1 (40 wt%). To our knowledge, it is firstly reported COF as SO 2 sorbent to date. We also observed that the adsorbed SO 2 is completely desorbed in a short time period with remarkable reversibility. These results suggest that channel-wall functional engineering could be a facile and powerful strategy for developing mesoporous COFs for high-performance reproducible gas storage and separation.
Simon, Matthew J.; Iliff, Jeffrey J.
2015-01-01
Cerebrospinal fluid (CSF) circulation and turnover provides a sink for the elimination of solutes from the brain interstitium, serving an important homeostatic role for the function of the central nervous system. Disruption of normal CSF circulation and turnover is believed to contribute to the development of many diseases, including neurodegenerative conditions such as Alzheimer’s disease, ischemic and traumatic brain injury, and neuroinflammatory conditions such as multiple sclerosis. Recent insights into CSF biology suggesting that CSF and interstitial fluid exchange along a brain-wide network of perivascular spaces termed the ‘glymphatic’ system suggest that CSF circulation may interact intimately with glial and vascular function to regulate basic aspects of brain function. Dysfunction within this glial vascular network, which is a feature of the aging and injured brain, is a potentially critical link between brain injury, neuroinflammation and the development of chronic neurodegeneration. Ongoing research within this field may provide a powerful new framework for understanding the common links between neurodegenerative, neurovascular and neuroinflammatory disease, in addition to providing potentially novel therapeutic targets for these conditions. PMID:26499397
DOE Office of Scientific and Technical Information (OSTI.GOV)
Arbing, Mark A.; Handelman, Samuel K.; Kuzin, Alexandre P.
2010-09-27
Bacterial toxin-antitoxin (TA) systems serve a variety of physiological functions including regulation of cell growth and maintenance of foreign genetic elements. Sequence analyses suggest that TA families are linked by complex evolutionary relationships reflecting likely swapping of functional domains between different TA families. Our crystal structures of Phd-Doc from bacteriophage P1, the HigA antitoxin from Escherichia coli CFT073, and YeeU of the YeeUWV systems from E. coli K12 and Shigella flexneri confirm this inference and reveal additional, unanticipated structural relationships. The growth-regulating Doc toxin exhibits structural similarity to secreted virulence factors that are toxic for eukaryotic target cells. The Phdmore » antitoxin possesses the same fold as both the YefM and NE2111 antitoxins that inhibit structurally unrelated toxins. YeeU, which has an antitoxin-like activity that represses toxin expression, is structurally similar to the ribosome-interacting toxins YoeB and RelE. These observations suggest extensive functional exchanges have occurred between TA systems during bacterial evolution.« less
Students Serving Arizona. 1994 "Serve-America" Evaluation Report.
ERIC Educational Resources Information Center
Sandler, Linda; Vandegrift, Judith A.
Arizona's Serve-America program, administered by the Arizona Department of Education (ADE), began in fiscal year 1992-93 under the auspices of the National and Community Service Act of 1990. Serve-America links community service projects with schools and youths in grades K-12. This second annual report documents the second year of project…
LMSS communication network design
NASA Technical Reports Server (NTRS)
1982-01-01
The architecture of the telecommunication network as the first step in the design of the LMSS system is described. A set of functional requirements including the total number of users to be served by the LMSS are hypothesized. The design parameters are then defined at length and are systematically selected such that the resultant system is capable of serving the hypothesized number of users. The design of the backhaul link is presented. The number of multiple backhaul beams required for communication to the base stations is determined. A conceptual procedure for call-routing and locating a mobile subscriber within the LMSS network is presented. The various steps in placing a call are explained, and the relationship between the two sets of UHF and S-band multiple beams is developed. A summary of the design parameters is presented.
Genetics Home Reference: Arts syndrome
... its chemical cousin RNA, and molecules such as ATP and GTP that serve as energy sources in ... Syndrome ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...
Lustenberger, Nadia A; Prodinger, Birgit; Dorjbal, Delgerjargal; Rubinelli, Sara; Schmitt, Klaus; Scheel-Sailer, Anke
2017-09-23
To illustrate how routinely written narrative admission and discharge reports of a rehabilitation program for eight youths with chronic neurological health conditions can be transformed to the International Classification of Functioning, Disability and Health. First, a qualitative content analysis was conducted by building meaningful units with text segments assigned of the reports to the five elements of the Rehab-Cycle ® : goal; assessment; assignment; intervention; evaluation. Second, the meaningful units were then linked to the ICF using the refined ICF Linking Rules. With the first step of transformation, the emphasis of the narrative reports changed to a process oriented interdisciplinary layout, revealing three thematic blocks of goals: mobility, self-care, mental, and social functions. The linked 95 unique ICF codes could be grouped in clinically meaningful goal-centered ICF codes. Between the two independent linkers, the agreement rate was improved after complementing the rules with additional agreements. The ICF Linking Rules can be used to compile standardized health information from narrative reports if prior structured. The process requires time and expertise. To implement the ICF into common practice, the findings provide the starting point for reporting rehabilitation that builds upon existing practice and adheres to international standards. Implications for Rehabilitation This study provides evidence that routinely collected health information from rehabilitation practice can be transformed to the International Classification of Functioning, Disability and Health by using the "ICF Linking Rules", however, this requires time and expertise. The Rehab-Cycle ® , including assessments, assignments, goal setting, interventions and goal evaluation, serves as feasible framework for structuring this rehabilitation program and ensures that the complexity of local practice is appropriately reflected. The refined "ICF Linking Rules" lead to a standardized transformation process of narrative text and thus a higher quality with increased transparency. As a next step, the resulting format of goal codes supplemented by goal-clarifying codes could be validated to strengthen the implementation of the International Classification of Functioning, Disability and Health into rehabilitation routine by respecting the variety of clinical practice.
The Biochemistry of O-GlcNAc Transferase: Which Functions Make It Essential in Mammalian Cells?
Levine, Zebulon G; Walker, Suzanne
2016-06-02
O-linked N-acetylglucosamine transferase (OGT) is found in all metazoans and plays an important role in development but at the single-cell level is only essential in dividing mammalian cells. Postmitotic mammalian cells and cells of invertebrates such as Caenorhabditis elegans and Drosophila can survive without copies of OGT. Why OGT is required in dividing mammalian cells but not in other cells remains unknown. OGT has multiple biochemical activities. Beyond its well-known role in adding β-O-GlcNAc to serine and threonine residues of nuclear and cytoplasmic proteins, OGT also acts as a protease in the maturation of the cell cycle regulator host cell factor 1 (HCF-1) and serves as an integral member of several protein complexes, many of them linked to gene expression. In this review, we summarize current understanding of the mechanisms underlying OGT's biochemical activities and address whether known functions of OGT could be related to its essential role in dividing mammalian cells.
Karasawa, Akira; Erkens, Guus B.; Berntsson, Ronnie P.-A.; Otten, Renee; Schuurman-Wolters, Gea K.; Mulder, Frans A. A.; Poolman, Bert
2011-01-01
The cystathionine β-synthase module of OpuA in conjunction with an anionic membrane surface acts as a sensor of internal ionic strength, which allows the protein to respond to osmotic stress. We now show by chemical modification and cross-linking studies that CBS2-CBS2 interface residues are critical for transport activity and/or ionic regulation of transport, whereas CBS1 serves no functional role. We establish that Cys residues in CBS1, CBS2, and the nucleotide-binding domain are more accessible for cross-linking at high than low ionic strength, indicating that these domains undergo conformational changes when transiting between the active and inactive state. Structural analyses suggest that the cystathionine β-synthase module is largely unstructured. Moreover, we could substitute CBS1 by a linker and preserve ionic regulation of transport. These data suggest that CBS1 serves as a linker and the structured CBS2-CBS2 interface forms a hinge point for ionic strength-dependent rearrangements that are transmitted to the nucleotide-binding domain and thereby affect translocation activity. PMID:21878634
NASA Astrophysics Data System (ADS)
Wang, Chao; Durney, Krista M.; Fomovsky, Gregory; Ateshian, Gerard A.; Vukelic, Sinisa
2016-03-01
The onset of osteoarthritis (OA)in articular cartilage is characterized by degradation of extracellular matrix (ECM). Specifically, breakage of cross-links between collagen fibrils in the articular cartilage leads to loss of structural integrity of the bulk tissue. Since there are no broadly accepted, non-invasive, label-free tools for diagnosing OA at its early stage, Raman spectroscopyis therefore proposed in this work as a novel, non-destructive diagnostic tool. In this study, collagen thin films were employed to act as a simplified model system of the cartilage collagen extracellular matrix. Cross-link formation was controlled via exposure to glutaraldehyde (GA), by varying exposure time and concentration levels, and Raman spectral information was collected to quantitatively characterize the cross-link assignments imparted to the collagen thin films during treatment. A novel, quantitative method was developed to analyze the Raman signal obtained from collagen thin films. Segments of Raman signal were decomposed and modeled as the sum of individual bands, providing an optimization function for subsequent curve fitting against experimental findings. Relative changes in the concentration of the GA-induced pyridinium cross-links were extracted from the model, as a function of the exposure to GA. Spatially resolved characterization enabled construction of spectral maps of the collagen thin films, which provided detailed information about the variation of cross-link formation at various locations on the specimen. Results showed that Raman spectral data correlate with glutaraldehyde treatment and therefore may be used as a proxy by which to measure loss of collagen cross-links in vivo. This study proposes a promising system of identifying onset of OA and may enable early intervention treatments that may serve to slow or prevent osteoarthritis progression.
Fish connectivity mapping intermediate data files and outputs
RLWrankedLists.tar.gz:These lists linked to various chemical treatment conditions serve as the target collection of Cmap. Probes of the entire microarray are sorted based on their log fold changes over control conditions. RLWsignatures2015.tar.gz: These signatures linked to various chemical treatment conditions serve as queries in Cmap.This dataset is associated with the following publication:Wang , R., A. Biales , N. Garcia-Reyero, E. Perkins, D. Villeneuve, G. Ankley, and D. Bencic. Fish Connectivity Mapping: Linking Chemical Stressors by Their MOA-Driven Transcriptomic Profiles. BMC Genomics. BioMed Central Ltd, London, UK, 17(84): 1-20, (2016).
Non-Gaussian statistics and optical rogue waves in stimulated Raman scattering.
Monfared, Yashar E; Ponomarenko, Sergey A
2017-03-20
We explore theoretically and numerically optical rogue wave formation in stimulated Raman scattering inside a hydrogen filled hollow core photonic crystal fiber. We assume a weak noisy Stokes pulse input and explicitly construct the input Stokes pulse ensemble using the coherent mode representation of optical coherence theory, thereby providing a link between optical coherence and rogue wave theories. We show that the Stokes pulse peak power probability distribution function (PDF) acquires a long tail in the limit of nearly incoherent input Stokes pulses. We demonstrate a clear link between the PDF tail magnitude and the source coherence time. Thus, the latter can serve as a convenient parameter to control the former. We explain our findings qualitatively using the concepts of statistical granularity and global degree of coherence.
Polythioether Particles Armored with Modifiable Graphene Oxide Nanosheets.
Rodier, Bradley J; Mosher, Eric P; Burton, Spencer T; Matthews, Rachael; Pentzer, Emily
2016-06-01
Facile and scalable fabrication methods are attractive to prepare materials for diverse applications. Herein, a method is presented to prepare cross-linked polymeric nanoparticles with graphene oxide (GO) nanosheets covalently attached to the surface. Alkene-modified GO serves as a surfactant in a miniemulsion polymerization, and the alkene functionalities of GO exposed to the oil-phase are incorporated into the polymer particle through thiol-ene reactions, leaving the unreacted alkene functional groups of the other face of GO available for further functionalization. The surface of GO-armored polymer particles is then modified with a small molecule fluorophore or carboxylic acid functional groups that bind to Fe2 O3 and TiO2 nanoparticles. This methodology provides a facile route to preparing complex hybrid composite materials. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Ziegler, Andreas; Dohr, Gotrfried; Uchanska-Ziegler, Barbara
2002-07-01
Polymorphic genes of the human major histocompatibility complex [MHC; human leukocyte antigen (HLA)] are probably important in determining resistance to parasites and avoidance of inbreeding. We investigated whether HLA-associated sexual selection could also involve HLA-linked olfactory receptor (OR) genes, which might not only participate in olfaction-guided mate choice, but also in selection processes within the testis. The testicular expression status of HLA class I molecules (by immunohistology) and HLA-linked OR genes (by transcriptional analysis) was determined. Various HLA class I heavy chains, but not beta2-microglobulin (beta2m), were expressed, mainly at the spermatocyte I stage. Of 17 HLA-linked OR genes analyzed, eight were found to be transcribed in the testis. They exhibited varying numbers of 5'- or 3'-non-coding exons as well as differential splicing. We suggest that testis-expressed polymorphic HLA and OR proteins are functionally connected and serve the selection of spermatozoa, enabling them to distinguish 'self from 'non-self [the sperm-receptor-selection (SRS) hypothesis].
Regulatory T Cells: Differentiation and Function.
Plitas, George; Rudensky, Alexander Y
2016-09-02
The immune system of vertebrate animals has evolved to mount an effective defense against a diverse set of pathogens while minimizing transient or lasting impairment in tissue function that could result from the inflammation caused by immune responses to infectious agents. In addition, misguided immune responses to "self" and dietary antigens, as well as to commensal microorganisms, can lead to a variety of inflammatory disorders, including autoimmunity, metabolic syndrome, allergies, and cancer. Regulatory T cells expressing the X chromosome-linked transcription factor Foxp3 suppress inflammatory responses in diverse biological settings and serve as a vital mechanism of negative regulation of immune-mediated inflammation. Cancer Immunol Res; 4(9); 721-5. ©2016 AACR. ©2016 American Association for Cancer Research.
Versatile On-Resin Synthesis of High Mannose Glycosylated Asparagine with Functional Handles
Chen, Rui; Pawlicki, Mark A.; Tolbert, Thomas J.
2013-01-01
Here we present a synthetic route for solid phase synthesis of N-linked glycoconjugates containing high mannose oligosaccharides which allows the incorporation of useful functional handles on the N-terminus of asparagine. In this strategy, the C-terminus of an Fmoc protected aspartic acid residue is first attached to a solid phase support. The side chain of aspartic acid is protected by a 2-phenylisopropyl protecting group, which allows selective deprotection for the introduction of glycosylation. By using a convergent on-resin glycosylamine coupling strategy, an N-glycosidic linkage is successfully formed on the free side chain of the resin bound aspartic acid with a large high mannose oligosaccharide, Man8GlcNAc2, to yield N-linked high mannose glycosylated asparagine. The use of on-resin glycosylamine coupling provides excellent glycosylation yield, can be applied to couple other types of oligosaccharides, and also makes it possible to recover excess oligosaccharides conveniently after the on-resin coupling reaction. Useful functional handles including an alkene (p-vinylbenzoic acid), an alkyne (4-pentynoic acid), biotin, and 5-carboxyfluorescein are then conjugated onto the N-terminal amine of asparagine on-resin after the removal of the Fmoc protecting group. In this way, useful functional handles are introduced onto the glycosylated asparagine while maintaining the structural integrity of the reducing end of the oligosaccharide. The asparagine side chain also serves as a linker between the glycan and the functional group and preserves the native presentation of N-linked glycan which may aid in biochemical and structural studies. As an example of a biochemical study using functionalized high mannose glycosylated asparagine, a fluorescence polarization assay has been utilized to study the binding of the lectin Concanavalin A (ConA) using 5-carboxyfluorescein labeled high mannose glycosylated asparagine. PMID:24326091
Design Principles of Regulatory Networks: Searching for the Molecular Algorithms of the Cell
Lim, Wendell A.; Lee, Connie M.; Tang, Chao
2013-01-01
A challenge in biology is to understand how complex molecular networks in the cell execute sophisticated regulatory functions. Here we explore the idea that there are common and general principles that link network structures to biological functions, principles that constrain the design solutions that evolution can converge upon for accomplishing a given cellular task. We describe approaches for classifying networks based on abstract architectures and functions, rather than on the specific molecular components of the networks. For any common regulatory task, can we define the space of all possible molecular solutions? Such inverse approaches might ultimately allow the assembly of a design table of core molecular algorithms that could serve as a guide for building synthetic networks and modulating disease networks. PMID:23352241
Bonta, Iván L
2004-01-01
The three events, viz. schizophrenia, dissociative anaesthesia and Near-Death Experience, despite their seemingly unrelated manifestation to each other, have nevertheless similar functional basis. All three events are linked to the glutamate sensitive N-methyl-D-aspartate (NMDA) receptor complex, which serves as their common functional denominator. Arguments and speculations are presented in favor of the view that, the three events might be considered as functional models of each other. Antagonism to the recognition NMDA-site of the receptor induces dissociative anaesthesia and precipitates Near-Death Experience. Agonist reinforcement at the modulatory glycine-site of the receptor counteracts negative symptoms of schizophrenia. Both types of challenges towards the receptor are compatible with a glutamate deficiency concept which underlies the meeting of the three events at the NMDA receptor.
Queues on a Dynamically Evolving Graph
NASA Astrophysics Data System (ADS)
Mandjes, Michel; Starreveld, Nicos J.; Bekker, René
2018-04-01
This paper considers a population process on a dynamically evolving graph, which can be alternatively interpreted as a queueing network. The queues are of infinite-server type, entailing that at each node all customers present are served in parallel. The links that connect the queues have the special feature that they are unreliable, in the sense that their status alternates between `up' and `down'. If a link between two nodes is down, with a fixed probability each of the clients attempting to use that link is lost; otherwise the client remains at the origin node and reattempts using the link (and jumps to the destination node when it finds the link restored). For these networks we present the following results: (a) a system of coupled partial differential equations that describes the joint probability generating function corresponding to the queues' time-dependent behavior (and a system of ordinary differential equations for its stationary counterpart), (b) an algorithm to evaluate the (time-dependent and stationary) moments, and procedures to compute user-perceived performance measures which facilitate the quantification of the impact of the links' outages, (c) a diffusion limit for the joint queue length process. We include explicit results for a series relevant special cases, such as tandem networks and symmetric fully connected networks.
Beyond the Stone Town: Maritime Architecture at Fourteenth-Fifteenth Century Songo Mnara, Tanzania
NASA Astrophysics Data System (ADS)
Pollard, Edward; Fleisher, Jeffrey; Wynne-Jones, Stephanie
2012-10-01
The towns of the Swahili coast of East Africa are widely acknowledged as the remains of a maritime society whose relationship with the ocean was fundamental to their economy and identity. Yet research that links the terrestrial environments of the towns to their adjacent maritime landscapes is rare, and urgently required in the light of marine erosional processes unmitigated by human actions. In the Kilwa archipelago of southern Tanzania, survey of the coastal foreshore has documented maritime architecture—particularly a series of coral-built causeways—that serve to link the medieval towns of this area to coastal resources and to expand the limits of the settlements themselves. This paper reports on survey recovering these causeways on Songo Mnara Island, putting the structures into context as part of the broader spatial manifestation of the island's fourteenth-fifteenth century town. Several possible uses of the causeways are discussed, including functional explanations linked to the exploitation of oceanic resources, and more social reasons of territoriality and spatial demarcation.
Scaffolding proteins in the development and maintenance of the epidermal permeability barrier.
Crawford, Melissa; Dagnino, Lina
2017-10-02
The skin of mammals and other terrestrial vertebrates protects the organism against the external environment, preventing heat, water and electrolyte loss, as well as entry of chemicals and pathogens. Impairments in the epidermal permeability barrier function are associated with the genesis and/or progression of a variety of pathological conditions, including genetic inflammatory diseases, microbial and viral infections, and photodamage induced by UV radiation. In mammals, the outside-in epidermal permeability barrier is provided by the joint action of the outermost cornified layer, together with assembled tight junctions in granular keratinocytes found in the layers underneath. Tight junctions serve as both outside-in and inside-out barriers, and impede paracellular movements of ions, water, macromolecules and microorganisms. At the molecular level, tight junctions consist of integral membrane proteins that form an extracellular seal between adjacent cells, and associate with cytoplasmic scaffold proteins that serve as links with the actin cytoskeleton. In this review, we address the roles that scaffold proteins play specifically in the establishment and maintenance of the epidermal permeability barrier, and how various pathologies alter or impair their functions.
Another look at roles and functions: has hospital case management lost its way?
Reynolds, John J
2013-01-01
The purpose of this study was to identify the roles, functions, and types of activities that hospital case managers engage in on a day-to-day basis and that leverage the most amounts of time. Previous studies superimpose a priori categories on research tools. Hospital case management. This study analyzes 4,064 spontaneous, unstructured list serve postings from the American Case Management Association Learning Link list serve from August 15, 2011, to August 18, 2012. The study group was a cross section of 415 case management professionals. The data suggest that hospital case managers' time is inordinately leveraged by issues related to observation status/leveling of patients and the Centers for Medicare and Medicaid Services compliance. The data also suggest that hospital case management has taken a conceptual trajectory that has deviated significantly from what was initially conceived (quality, advocacy, and care coordination) and what is publicly purported. Case management education and practical orientation will need to be commensurate with this emerging emphasis. Case management leadership will need to be adept at mitigating the stresses of role confusion, role conflict, and role ambiguity.
Biomarkers in adult posthemorrhagic hydrocephalus.
Hua, Cong; Zhao, Gang
2017-08-01
Posthemorrhagic hydrocephalus is a severe complication following intracranial hemorrhage. Posthemorrhagic hydrocephalus is often associated with high morbidity and mortality and serves as an important clinical predictor of adverse outcomes after intracranial hemorrhage. Currently, no effective medical intervention exists to improve functional outcomes in posthemorrhagic hydrocephalus patients because little is still known about the mechanisms of posthemorrhagic hydrocephalus pathogenesis. Because a better understanding of the posthemorrhagic hydrocephalus pathogenesis would facilitate development of clinical treatments, this is an active research area. The purpose of this review is to describe recent progress in elucidation of molecular mechanisms that cause posthemorrhagic hydrocephalus. What we are certain of is that the entry of blood into the ventricular system and subarachnoid space results in release of lytic blood products which cause a series of physiological and pathological changes in the brain. Blood components that can be linked to pathology would serve as disease biomarkers. From studies of posthemorrhagic hydrocephalus, such biomarkers are known to mutually synergize to initiate and promote posthemorrhagic hydrocephalus progression. These findings suggest that modulation of biomarker expression or function may benefit posthemorrhagic hydrocephalus patients.
Microarray characterization of gene expression changes in blood during acute ethanol exposure
2013-01-01
Background As part of the civil aviation safety program to define the adverse effects of ethanol on flying performance, we performed a DNA microarray analysis of human whole blood samples from a five-time point study of subjects administered ethanol orally, followed by breathalyzer analysis, to monitor blood alcohol concentration (BAC) to discover significant gene expression changes in response to the ethanol exposure. Methods Subjects were administered either orange juice or orange juice with ethanol. Blood samples were taken based on BAC and total RNA was isolated from PaxGene™ blood tubes. The amplified cDNA was used in microarray and quantitative real-time polymerase chain reaction (RT-qPCR) analyses to evaluate differential gene expression. Microarray data was analyzed in a pipeline fashion to summarize and normalize and the results evaluated for relative expression across time points with multiple methods. Candidate genes showing distinctive expression patterns in response to ethanol were clustered by pattern and further analyzed for related function, pathway membership and common transcription factor binding within and across clusters. RT-qPCR was used with representative genes to confirm relative transcript levels across time to those detected in microarrays. Results Microarray analysis of samples representing 0%, 0.04%, 0.08%, return to 0.04%, and 0.02% wt/vol BAC showed that changes in gene expression could be detected across the time course. The expression changes were verified by qRT-PCR. The candidate genes of interest (GOI) identified from the microarray analysis and clustered by expression pattern across the five BAC points showed seven coordinately expressed groups. Analysis showed function-based networks, shared transcription factor binding sites and signaling pathways for members of the clusters. These include hematological functions, innate immunity and inflammation functions, metabolic functions expected of ethanol metabolism, and pancreatic and hepatic function. Five of the seven clusters showed links to the p38 MAPK pathway. Conclusions The results of this study provide a first look at changing gene expression patterns in human blood during an acute rise in blood ethanol concentration and its depletion because of metabolism and excretion, and demonstrate that it is possible to detect changes in gene expression using total RNA isolated from whole blood. The analysis approach for this study serves as a workflow to investigate the biology linked to expression changes across a time course and from these changes, to identify target genes that could serve as biomarkers linked to pilot performance. PMID:23883607
NASA Astrophysics Data System (ADS)
Zhu, Lian; Weber, Stephanie; Berry, Joel; Vaidya, Nilesh; Haataja, Mikko; Brangwynne, Clifford
2015-03-01
The nucleolus is a liquid-like membrane-less nuclear body which plays an important role in cell growth and size control. By modulating nucleolar component concentration through RNAi conditions that change C. elegans cell size, we find that nucleoli only assemble above a threshold concentration; moreover, the ripening dynamics of nucleated droplets are consistent with the hypothesis that the assembly of the nucleolus represents an intracellular liquid-liquid phase transition. A key question is how this phase-transition is linked to the primary function of the nucleolus, in transcribing and processing ribosomal RNA. To address this, we characterize the localization of RNA Polymerase I, a key transcriptional enzyme, into nucleolar foci as a function of nucleolar component concentration. Our results suggest that there are a small number of key disordered phosphoproteins that may serve as a link between transcription and assembly. Finally, we present preliminary results using a reduced model system consisting of purified nucleolar proteins to assess the ability of nucleolar proteins to drive liquid-liquid phase separation in vitro. These results lay the foundation for a quantitative understanding of intracellular phase transitions and their impact on biomedically-critical RNA-processing steps.
Simon, Matthew J; Iliff, Jeffrey J
2016-03-01
Cerebrospinal fluid (CSF) circulation and turnover provides a sink for the elimination of solutes from the brain interstitium, serving an important homeostatic role for the function of the central nervous system. Disruption of normal CSF circulation and turnover is believed to contribute to the development of many diseases, including neurodegenerative conditions such as Alzheimer's disease, ischemic and traumatic brain injury, and neuroinflammatory conditions such as multiple sclerosis. Recent insights into CSF biology suggesting that CSF and interstitial fluid exchange along a brain-wide network of perivascular spaces termed the 'glymphatic' system suggest that CSF circulation may interact intimately with glial and vascular function to regulate basic aspects of brain function. Dysfunction within this glial vascular network, which is a feature of the aging and injured brain, is a potentially critical link between brain injury, neuroinflammation and the development of chronic neurodegeneration. Ongoing research within this field may provide a powerful new framework for understanding the common links between neurodegenerative, neurovascular and neuroinflammatory disease, in addition to providing potentially novel therapeutic targets for these conditions. This article is part of a Special Issue entitled: Neuro Inflammation edited by Helga E. de Vries and Markus Schwaninger. Copyright © 2015 Elsevier B.V. All rights reserved.
Krautkrämer, Martina
2017-01-01
Subcellular compartmentalization of receptor signaling is an emerging principle in innate immunity. However, the functional integration of receptor signaling pathways into membrane trafficking routes and its physiological relevance for immune responses is still largely unclear. In this study, using Lyst-mutant beige mice, we show that lysosomal trafficking regulator Lyst links endolysosomal organization to the selective control of toll-like receptor 3 (TLR3)– and TLR4-mediated proinflammatory responses. Consequently, Lyst-mutant mice showed increased susceptibility to bacterial infection and were largely resistant to endotoxin-induced septic shock. Mechanistic analysis revealed that Lyst specifically controls TLR3- and TLR4-induced endosomal TRIF (TIR domain–containing adapter-inducing interferon β) signaling pathways. Loss of functional Lyst leads to dysregulated phagosomal maturation, resulting in a failure to form an activation-induced Rab7+ endosomal/phagosomal compartment. This specific Rab7+ compartment was further demonstrated to serve as a major site for active TRIF signaling events, thus linking phagosomal maturation to specific TLR signaling pathways. The immunoregulatory role of Lyst on TLR signaling pathways was confirmed in human cells by CRISPR/Cas9-mediated gene inactivation. As mutations in LYST cause human Chédiak-Higashi syndrome, a severe immunodeficiency, our findings also contribute to a better understanding of human disease mechanisms. PMID:27881733
Metabolically Driven Self-Restoration of Energy-Linked Functions by Avocado Mitochondria
Huang, Li-Shar; Romani, Roger J.
1991-01-01
To assess the restorative capacity of isolated avocado (Persea americana) fruit mitochondria, the organelles were first aged in the absence of an energy source at 25°C for several hours until respiratory control and oxidative phosphorylation were greatly diminished or totally lost. Energy-linked functions were then gradually restored over a period of several hours after the addition of substrate. Restoration of respiratory control resulted from both an increase in state 3 and a decrease in state 4 respiratory rates. Either α-ketoglutarate or succinate served as restorants, each with distinctive rates of recovery in state 3 and state 4 respiration. ATP also served as a restorative agent but not as effectively as metabolizable substrate. ATP synthase activity was modulated by stress and restoration but neither the extent nor the rate of change was sufficient to constrain state 3 rates. Orthophosphate was released from the mitochondria during substrate-deprived stress. Restoration of phosphorylation preceded that of RC with phosphate uptake and phosphorylation being evident immediately upon the addition of substrate. During restoration [32P]orthophosphate was incorporated into several organic fractions: phospholipid, ATP, a trichloroacetic acid-precipitable mitochondrial fraction, and an organophosphate that accumulated in the medium in relatively large amounts. The organophosphate was tentatively identified as a hexosephosphate. Incorporation into ATP and the putative hexosephosphate continued unabated beyond the point of maximum restoration. Phosphate metabolism thus appears to be a necessary but not sufficient precondition for mitochondrial restoration and maintenance. Based on the recovery kinetics of the various phosphorylated components, the mitochondrial-bound fraction appears to be most directly linked with restoration. Results are discussed with reference to specific characteristics and components of self-restoration and to possible underlying mechanisms. We suggest that a degree of self-restoration is consistent with the quasi-autonomous nature of mitochondria and that this intrinsic capacity may be pivotal to the respiratory climacteric in senescent fruit cells and to cellular homeostasis in general. PMID:16668096
Strehl ratio: a tool for optimizing optical nulls and singularities.
Hénault, François
2015-07-01
In this paper a set of radial and azimuthal phase functions are reviewed that have a null Strehl ratio, which is equivalent to generating a central extinction in the image plane of an optical system. The study is conducted in the framework of Fraunhofer scalar diffraction, and is oriented toward practical cases where optical nulls or singularities are produced by deformable mirrors or phase plates. The identified solutions reveal unexpected links with the zeros of type-J Bessel functions of integer order. They include linear azimuthal phase ramps giving birth to an optical vortex, azimuthally modulated phase functions, and circular phase gratings (CPGs). It is found in particular that the CPG radiometric efficiency could be significantly improved by the null Strehl ratio condition. Simple design rules for rescaling and combining the different phase functions are also defined. Finally, the described analytical solutions could also serve as starting points for an automated searching software tool.
Structural and Functional Assessment of APOBEC3G Macromolecular Complexes
Polevoda, Bogdan; McDougall, William M.; Bennett, Ryan P.; Salter, Jason D.; Smith, Harold C.
2016-01-01
There are eleven members in the human APOBEC family of proteins that are evolutionarily related through their zinc-dependent cytidine deaminase domains. The human APOBEC gene clusters arose on chromosome 6 and 22 through gene duplication and divergence to where current day APOBEC proteins are functionally diverse and broadly expressed in tissues. APOBEC serve enzymatic and non enzymatic functions in cells. In both cases, formation of higher-order structures driven by APOBEC protein-protein interactions and binding to RNA and/or single stranded DNA are integral to their function. In some circumstances, these interactions are regulatory and modulate APOBEC activities. We are just beginning to understand how macromolecular interactions drive processes such as APOBEC subcellular compartmentalization, formation of holoenzyme complexes, gene targeting, foreign DNA restriction, anti-retroviral activity, formation of ribonucleoprotein particles and APOBEC degradation. Protein-protein and protein-nucleic acid cross-linking methods coupled with mass spectrometry, electrophoretic mobility shift assays, glycerol gradient sedimentation, fluorescence anisotropy and APOBEC deaminase assays are enabling mapping of interacting surfaces that are essential for these functions. The goal of this methods review is through example of our research on APOBEC3G, describe the application of cross-linking methods to characterize and quantify macromolecular interactions and their functional implications. Given the homology in structure and function, it is proposed that these methods will be generally applicable to the discovery process for other APOBEC and RNA and DNA editing and modifying proteins. PMID:26988126
McLaughlin, William A; Chen, Ken; Hou, Tingjun; Wang, Wei
2007-01-01
Background Protein domains coordinate to perform multifaceted cellular functions, and domain combinations serve as the functional building blocks of the cell. The available methods to identify functional domain combinations are limited in their scope, e.g. to the identification of combinations falling within individual proteins or within specific regions in a translated genome. Further effort is needed to identify groups of domains that span across two or more proteins and are linked by a cooperative function. Such functional domain combinations can be useful for protein annotation. Results Using a new computational method, we have identified 114 groups of domains, referred to as domain assembly units (DASSEM units), in the proteome of budding yeast Saccharomyces cerevisiae. The units participate in many important cellular processes such as transcription regulation, translation initiation, and mRNA splicing. Within the units the domains were found to function in a cooperative manner; and each domain contributed to a different aspect of the unit's overall function. The member domains of DASSEM units were found to be significantly enriched among proteins contained in transcription modules, defined as genes sharing similar expression profiles and presumably similar functions. The observation further confirmed the functional coherence of DASSEM units. The functional linkages of units were found in both functionally characterized and uncharacterized proteins, which enabled the assessment of protein function based on domain composition. Conclusion A new computational method was developed to identify groups of domains that are linked by a common function in the proteome of Saccharomyces cerevisiae. These groups can either lie within individual proteins or span across different proteins. We propose that the functional linkages among the domains within the DASSEM units can be used as a non-homology based tool to annotate uncharacterized proteins. PMID:17937820
Ghoshal, Ayan; Conn, P Jeffrey
2015-01-01
The hippocampo-prefrontal (H-PFC) pathway has been linked to cognitive and emotional disturbances in several psychiatric disorders including schizophrenia. Preclinical evidence from the NMDA receptor antagonism rodent model of schizophrenia shows severe pathology selective to the H-PFC pathway. It is speculated that there is an increased excitatory drive from the hippocampus to the prefrontal cortex due to dysfunctions in the H-PFC plasticity, which may serve as the basis for the behavioral consequences observed in this rodent model. Thus, the H-PFC pathway is currently emerging as a promising therapeutic target for the negative and cognitive symptom clusters of schizophrenia. Here, we have reviewed the physiological, pharmacological and functional characteristics of the H-PFC pathway and we propose that allosteric activation of glutamatergic and cholinergic neurotransmission can serve as a plausible therapeutic approach. PMID:25825588
CD22 serves as a receptor for soluble IgM.
Adachi, Takahiro; Harumiya, Satoru; Takematsu, Hiromu; Kozutsumi, Yasunori; Wabl, Matthias; Fujimoto, Manabu; Tedder, Thomas F
2012-01-01
CD22 (Siglec-2) is a B-cell membrane-bound lectin that recognizes glycan ligands containing α2,6-linked sialic acid (α2,6Sia) and negatively regulates signaling through the B-cell Ag receptor (BCR). Although CD22 has been investigated extensively, its precise function remains unclear due to acting multiple phases. Here, we demonstrate that CD22 is efficiently activated in trans by complexes of Ag and soluble IgM (sIgM) due to the presence of glycan ligands on sIgM. This result strongly suggests sIgM as a natural trans ligand for CD22. Also, CD22 appears to serve as a receptor for sIgM, which induces a negative feedback loop for B-cell activation similar to the Fc receptor for IgG (FcγRIIB). Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Rühl, A; Nasser, Y; Sharkey, K A
2004-04-01
The enteric nervous system is composed of both enteric neurones and enteric glia. Enteric glial cells were first described by Dogiel and are now known to outnumber neurones approximately 4 : 1. In the past, these cells were assumed to subserve a largely supportive role; however, recent evidence indicates that enteric glial cells may play a more active role in the control of gut function. In transgenic mouse models, where enteric glial cells are selectively ablated, the loss of glia results in intestinal inflammation and disruption of the epithelial barrier. Enteric glia are activated specifically by inflammatory insults and may contribute actively to inflammatory pathology via antigen presentation and cytokine synthesis. Enteric glia also express receptors for neurotransmitters and so may serve as intermediaries in enteric neurotransmission. Thus, enteric glia may serve as a link between the nervous and immune systems of the gut and may also have an important role in maintaining the integrity of the mucosal barrier and in other aspects of intestinal homeostasis.
ASC filament formation serves as a signal amplification mechanism for inflammasomes
Dick, Mathias S.; Sborgi, Lorenzo; Rühl, Sebastian; Hiller, Sebastian; Broz, Petr
2016-01-01
A hallmark of inflammasome activation is the ASC speck, a micrometre-sized structure formed by the inflammasome adaptor protein ASC (apoptosis-associated speck-like protein containing a CARD), which consists of a pyrin domain (PYD) and a caspase recruitment domain (CARD). Here we show that assembly of the ASC speck involves oligomerization of ASCPYD into filaments and cross-linking of these filaments by ASCCARD. ASC mutants with a non-functional CARD only assemble filaments but not specks, and moreover disrupt endogenous specks in primary macrophages. Systematic site-directed mutagenesis of ASCPYD is used to identify oligomerization-deficient ASC mutants and demonstrate that ASC speck formation is required for efficient processing of IL-1β, but dispensable for gasdermin-D cleavage and pyroptosis induction. Our results suggest that the oligomerization of ASC creates a multitude of potential caspase-1 activation sites, thus serving as a signal amplification mechanism for inflammasome-mediated cytokine production. PMID:27329339
Zhang, Yaqing; Zhang, Xiangmei; Xu, Ling; Wei, Shicheng; Zhai, Maolin
2015-01-01
Ionizing radiation effectively cross-links collagen into network with enhanced anti-degradability and biocompatibility, while radiation-cross-linked collagen scaffold lacks flexibility, satisfactory surface appearance, and performs poor in cell penetration and ingrowth. To make the radiation-cross-linked collagen scaffold to serve as an ideal artificial dermis, dextran was incorporated into collagen. Scaffolds with the collagen/dextran (Col/Dex) ratios of 10/0, 7/3, and 5/5 were fabricated via (60)Co γ-irradiation cross-linking, followed by lyophilization. The morphology, microstructure, physicochemical, and biological properties were investigated. Compared with pure collagen, scaffolds with dextran demonstrated more porous appearance, enhanced hydrophilicity while the cross-linking density was lower with the consequence of larger pore size, higher water uptake, as well as reduced stiffness. Accelerated degradation was observed when dextran was incorporated in both the in vitro and in vivo assays, which led to earlier integration with cell and host tissue. The effect of dextran on degradation was ascribed to the decreased cross-linking density, looser microstructure, more porous and hydrophilic surface. Considering the better appearance, softness, moderate degradation rate due to controllable cross-linking degree and good biocompatibility as well, radiation-cross-linked collagen/dextran scaffolds are expected to serve as promising artificial dermal substitutes.
Computational Nuclear Physics and Post Hartree-Fock Methods
DOE Office of Scientific and Technical Information (OSTI.GOV)
Lietz, Justin; Sam, Novario; Hjorth-Jensen, M.
We present a computational approach to infinite nuclear matter employing Hartree-Fock theory, many-body perturbation theory and coupled cluster theory. These lectures are closely linked with those of chapters 9, 10 and 11 and serve as input for the correlation functions employed in Monte Carlo calculations in chapter 9, the in-medium similarity renormalization group theory of dense fermionic systems of chapter 10 and the Green's function approach in chapter 11. We provide extensive code examples and benchmark calculations, allowing thereby an eventual reader to start writing her/his own codes. We start with an object-oriented serial code and end with discussions onmore » strategies for porting the code to present and planned high-performance computing facilities.« less
On whether mirror neurons play a significant role in processing affective prosody.
Ramachandra, Vijayachandra
2009-02-01
Several behavioral and neuroimaging studies have indicated that both right and left cortical structures and a few subcortical ones are involved in processing affective prosody. Recent investigations have shown that the mirror neuron system plays a crucial role in several higher-level functions such as empathy, theory of mind, language, etc., but no studies so far link the mirror neuron system with affective prosody. In this paper is a speculation that the mirror neuron system, which serves as a common neural substrate for different higher-level functions, may play a significant role in processing affective prosody via its connections with the limbic lobe. Actual research must apply electrophysiological and neuroimaging techniques to assess whether the mirror neuron systems underly affective prosody in humans.
Dyke, Jason Christopher; Knight, Kelly Jane; Zhou, Huaxing; Chiu, Chi-Kai; Ko, Ching-Chang; You, Wei
2012-01-01
Causes of bone deficiency are numerous, but biomimetic alloplastic grafts provide an alternative to repair tissue naturally. Previously, a hydroxyapatite-gelatin modified siloxane (HAp-Gemosil) composite was prepared by cross-linking (N, N′-bis[(3-trimethoxysilyl)propyl]ethylene diamine (enTMOS) around the HAp-Gel nanocomposite particles, to mimic the natural composition and properties of bone. However, the tensile strength remained too low for many orthopedic applications. It was hypothesized that incorporating a polymer chain into the composite could help improve long range interaction. Furthermore, designing this polymer to interact with the enTMOS siloxane cross-linked matrix would provide improved adhesion between the polymer and the ceramic composite, and improve mechanical properties. To this end, copolymers of L-Lactide (LLA), and a novel alkyne derivatized trimethylene carbonate, propargyl carbonate (PC), were synthesized. Incorporation of PC during copolymerization affects properties of copolymers such as molecular weight, Tg, and % PC incorporation. More importantly, PC monomers bear a synthetic handle, allowing copolymers to undergo post-polymerization functionalization with graft monomers to specifically tailor the properties of the final composite. For our investigation, P(LLA-co-PC) copolymers were functionalized by an azido-silane (AS) via copper catalyzed azide-alkyne cycloaddition (CuAAC) through terminal alkyne on PC monomers. The new functionalized polymer, P(LLA-co-PC)(AS) was blended with HAp-Gemosil, with the azido-silane linking the copolymer to the silsesquioxane matrix within the final composite. These HAp-Gemosil/P(LLA-co-PC)(AS) composites were subjected to mechanical and biological testing, and the results were compared with those from the HAp-Gemosil composites. This study revealed that incorporating a cross-linkable polymer served to increase the flexural strength of the composite by 50%, while maintaining the biocompatibility of HAp-Gemosil ceramics. PMID:23139457
Cellular Metabolic and Autophagic Pathways: Traffic Control by Redox Signaling
Dodson, Matthew; Darley-Usmar, Victor; Zhang, Jianhua
2013-01-01
It has been established that the key metabolic pathways of glycolysis and oxidative phosphorylation are intimately related to redox biology through control of cell signaling. Under physiological conditions glucose metabolism is linked to control of the NADH/NAD redox couple, as well as providing the major reductant, NADPH, for thiol-dependent antioxidant defenses. Retrograde signaling from the mitochondrion to the nucleus or cytosol controls cell growth and differentiation. Under pathological conditions mitochondria are targets for reactive oxygen and nitrogen species and are critical in controlling apoptotic cell death. At the interface of these metabolic pathways, the autophagy-lysosomal pathway functions to maintain mitochondrial quality, and generally serves an important cytoprotective function. In this review we will discuss the autophagic response to reactive oxygen and nitrogen species that are generated from perturbations of cellular glucose metabolism and bioenergetic function. PMID:23702245
Restaurant Cooking Trends and Increased Risk for Campylobacter Infection.
Jones, Anna K; Rigby, Dan; Burton, Michael; Millman, Caroline; Williams, Nicola J; Jones, Trevor R; Wigley, Paul; O'Brien, Sarah J; Cross, Paul
2016-07-01
In the United Kingdom, outbreaks of Campylobacter infection are increasingly attributed to undercooked chicken livers, yet many recipes, including those of top chefs, advocate short cooking times and serving livers pink. During 2015, we studied preferences of chefs and the public in the United Kingdom and investigated the link between liver rareness and survival of Campylobacter. We used photographs to assess chefs' ability to identify chicken livers meeting safe cooking guidelines. To investigate the microbiological safety of livers chefs preferred to serve, we modeled Campylobacter survival in infected chicken livers cooked to various temperatures. Most chefs correctly identified safely cooked livers but overestimated the public's preference for rareness and thus preferred to serve them more rare. We estimated that 19%-52% of livers served commercially in the United Kingdom fail to reach 70°C and that predicted Campylobacter survival rates are 48%-98%. These findings indicate that cooking trends are linked to increasing Campylobacter infections.
MicroRNAs in Leukemias: Emerging Diagnostic Tools and Therapeutic Targets
Mian, Yousaf A.; Zeleznik-Le, Nancy J.
2010-01-01
MicroRNAs (miRNA) are small non-coding RNAs of ~22 nucleotides that regulate the translation and stability of mRNA to control different functions of the cell. Misexpression of miRNA has been linked to disruption of normal cellular functions, which results in various disorders including cancers such as leukemias. MicroRNA involvement in disease has been the subject of much attention and is increasing our current understanding of disease biology. Such linkages have been determined by high-throughput studies, which provide a framework for characterizing differential miRNA expression levels correlating to different cytogenetic abnormalities and their corresponding malignancies. In addition, functional studies of particular miRNAs have begun to define the effects of miRNA on predicted mRNA targets. It is clear that miRNAs can serve as molecular markers of leukemias and the hope is that they can also serve as new therapeutic targets. Studies are beginning to elucidate how to deliver therapeutic antagonists to attenuate overexpressed miRNAs and to replace underexpressed miRNAs. In this review, we: i) discuss the current understanding of miRNA function and expression in normal hematopoiesis, ii) provide examples of miRNAs that are misregulated in leukemias, and iii) evaluate the current status and potential future directions for the burgeoning field of antisense oligonucleotides and other therapeutic attempts to intervene in miRNA disregulation in leukemias. PMID:20370647
Chandra, Sadanandavalli Retnaswami; Ahamed, Safwan; Vidhya Annapoorni, Chandra Sasitharan
2018-01-01
Introduction: Creativity is a physiological need based biological function very essential for survival. However, generally in disorders of progressive cognitive dysfunction creative skills are lost. However there are situations where these potentials are temporarily enhanced. Patients and Methods: We did an observational study of children and adults, 5 adults and 2 childrens, who showed extraordinary creativity evaluated based on evidence shown by patient, peers and re produced in test situation. Discussion: Our observational study reveals spontaneous interest in new and useful creative activity in our patients with various disorders causing progressive cognitive dysfunction. This observation reveals creative gain of function does take place in the face of progressive cognitive dysfunction in the setting of several diseases and it serves as a treatment option in behaviour management. Whether it is due to disinhibition of creative areas in the brain or facilitated function in regenerating data linking circuits needs further study. Conclusion: Set goals which are survival instinct based activities are probably removed by neurodegeneration and thereby the innate creativity gets disinhibited and expressed in wonderful forms of creativity. Whether special creative circuits in the brain, which causes this extraordinary creativity also needs to be studied. These creative skills in some of our patients served as effective pharmaco sparing agents during periods of aggression and agitation by engaging them in those activities, utility of which can be considered as a therapeutic option. PMID:29403132
Zhang, Mingming; Li, Shuya; Yan, Xuzhou; Zhou, Zhixuan; Saha, Manik Lal; Wang, Yu-Cai; Stang, Peter J
2016-10-04
The covalent linkage of supramolecular monomers provides a powerful strategy for constructing dynamic polymeric materials whose properties can be readily tuned either by the selection of monomers or the choice of functional linkers. In this strategy, the stabilities of the supramolecular monomers and the reactions used to link the monomers are crucial because such monomers are normally dynamic and can disassemble during the linking process, leading to mixture of products. Therefore, although noncovalent interactions have been widely introduced into metallacycle structures to prepare metallosupramolecular polymers, metallacycle-cored polymers linked by covalent bonds have been rarely reported. Herein, we used the mild, highly efficient amidation reaction between alkylamine and N-hydroxysuccinimide-activated carboxylic acid to link the pendent amino functional groups of a rhomboidal metallacycle 10 to give metallacycle-cored polymers P1 and P2, which further yielded nanoparticles at low concentration and transformed into network structures as the concentration increased. Moreover, these polymers exhibited enhanced emission and showed better quantum yields than metallacycle 10 in methanol and methanol/water (1/9, vol/vol) due to the aggregation-induced emission properties of a tetraphenylethene-based pyridyl donor, which serves as a precursor for metallacycle 10. The fluorescence properties of these polymers were further used in cell imaging, and they showed a significant enrichment in lung cells after i.v. injection. Considering the anticancer activity of rhomboidal Pt(II) metallacycles, this type of fluorescent metallacycle-cored polymers can have potential applications toward lung cancer treatment.
Unifying the field: developing an integrative paradigm for behavior therapy.
Eifert, G H; Forsyth, J P; Schauss, S L
1993-06-01
The limitations of early conditioning models and treatments have led many behavior therapists to abandon conditioning principles and replace them with loosely defined cognitive theories and treatments. Systematic theory extensions to human behavior, using new concepts and processes derived from and built upon the basic principles, could have prevented the divisive debates over whether psychological dysfunctions are the results of conditioning or cognition and whether they should be treated with conditioning or cognitive techniques. Behavior therapy could also benefit from recent advances in experimental cognitive psychology that provide objective behavioral methods of studying dysfunctional processes. We suggest a unifying paradigm for explaining abnormal behavior that links and integrates different fields of study and processes that are frequently believed to be incompatible or antithetical such as biological vulnerability variables, learned behavioral repertoires, and that also links historical and current antecedents of the problem. An integrative paradigmatic behavioral approach may serve a unifying function in behavior therapy (a) by promoting an understanding of the dysfunctional processes involved in different disorders and (b) by helping clinicians conduct functional analyses that lead to theory-based, individualized, and effective treatments.
Macroscopic Biological Characteristics of Individualized Therapy in Chinese Mongolian Osteopathy
NASA Astrophysics Data System (ADS)
Namula, Zhao; Mei, Wang; Li, Xue-en
Objective: Chinese Mongolian osteopathy has been passed down from ancient times and includes unique practices and favorable efficacy. In this study, we investigate the macroscopic biological characteristics of individualized Chinese Mongolian osteopathy, in order to provide new principle and methods for the treatment of bone fracture. Method: With a view to provide a vital link between nature and humans, the four stages of Chinese Mongolian osteopathy focus on the unity of the mind and body, the limbs and body organs, the body and its functions, and humans and nature. Results: We discuss the merits of individualized osteopathy in terms of the underlying concepts, and evaluate the approaches and principles of traditional medicine, as well as biomechanics. Conclusions: Individualized Mongolian osteopathy targets macroscopic biological components including dynamic reduction, natural fixation, and functional healing. Chinese Mongolian osteopathy is a natural, ecological and non-invasive osteopathy that values the link between nature and humans, including the unity of mind and body. The biological components not only serve as a foundation for Chinese Mongolian osteopathy but are also important for the future development of modern osteopathy, focusing on individualization, actualization and integration.
Fervaha, Gagan; Foussias, George; Agid, Ofer; Remington, Gary
2015-08-01
Negative symptoms, in particular motivational deficits, are reported as impediments to functional recovery in patients with schizophrenia. This study examined the prevalence of motivational deficits in patients early in the illness, and the impact these deficits have on community functioning. Patients with schizophrenia between the ages of 18 and 35years, and within 5years of initiating antipsychotic treatment were included in the present investigation (N=166). The impact of motivation and cognition on concurrent and longitudinal functioning was evaluated. Motivational impairments were found in more than 75% of participants, and were not associated with receipt of social support. These deficits served as the most robust and reliable predictor of functional outcome, while neurocognition demonstrated significantly weaker associations with outcome. When considered together, motivational deficits demonstrated a reliable link with concurrent and longitudinal functioning, with cognition not offering any independent predictive value. Moreover, motivation was found to mediate the relationship between cognition and outcome. Changes in motivation were linked to changes in functioning; however, this was not the case for changes in cognitive performance. Motivation emerged as a significant predictor of functioning even after selected demographic and clinical characteristics (e.g., positive symptoms) were accounted for. These data indicate that motivational deficits are prevalent in patients with schizophrenia, even in the early stages of the illness, and these deficits stand as one of the most robust barriers to people with schizophrenia achieving functional recovery. Greater understanding of the mechanisms underlying these deficits is critical to effective treatment innovation. Copyright © 2015 Elsevier B.V. All rights reserved.
Cross-linkable liposomes stabilize a magnetic resonance contrast-enhancing polymeric fastener.
Smith, Cartney E; Kong, Hyunjoon
2014-04-08
Liposomes are commonly used to deliver drugs and contrast agents to their target site in a controlled manner. One of the greatest obstacles in the performance of such delivery vehicles is their stability in the presence of serum. Here, we demonstrate a method to stabilize a class of liposomes that load gadolinium, a magnetic resonance (MR) contrast agent, as a model cargo on their surfaces. We hypothesized that the sequential adsorption of a gadolinium-binding chitosan fastener on the liposome surface followed by covalent cross-linking of the lipid bilayer would provide enhanced stability and improved MR signal in the presence of human serum. To investigate this hypothesis, liposomes composed of diyne-containing lipids were assembled and functionalized via chitosan conjugated with a hydrophobic anchor and diethylenetriaminepentaacetic acid (DTPA). This postadsorption cross-linking strategy served to stabilize the thermodynamically favorable association between liposome and polymeric fastener. Furthermore, the chitosan-coated, cross-linked liposomes proved more effective as delivery vehicles of gadolinium than uncross-linked liposomes due to the reduced liposome degradation and chitosan desorption. Overall, this study demonstrates a useful method to stabilize a broad class of particles used for systemic delivery of various molecular payloads.
Cross-Linkable Liposomes Stabilize a Magnetic Resonance Contrast-Enhancing Polymeric Fastener
2015-01-01
Liposomes are commonly used to deliver drugs and contrast agents to their target site in a controlled manner. One of the greatest obstacles in the performance of such delivery vehicles is their stability in the presence of serum. Here, we demonstrate a method to stabilize a class of liposomes that load gadolinium, a magnetic resonance (MR) contrast agent, as a model cargo on their surfaces. We hypothesized that the sequential adsorption of a gadolinium-binding chitosan fastener on the liposome surface followed by covalent cross-linking of the lipid bilayer would provide enhanced stability and improved MR signal in the presence of human serum. To investigate this hypothesis, liposomes composed of diyne-containing lipids were assembled and functionalized via chitosan conjugated with a hydrophobic anchor and diethylenetriaminepentaacetic acid (DTPA). This postadsorption cross-linking strategy served to stabilize the thermodynamically favorable association between liposome and polymeric fastener. Furthermore, the chitosan-coated, cross-linked liposomes proved more effective as delivery vehicles of gadolinium than uncross-linked liposomes due to the reduced liposome degradation and chitosan desorption. Overall, this study demonstrates a useful method to stabilize a broad class of particles used for systemic delivery of various molecular payloads. PMID:24635565
Genetics Home Reference: adenylosuccinate lyase deficiency
... its chemical cousin RNA, and molecules such as ATP that serve as energy sources in the cell. ... For People With Intellectual and Developmental Disabilities Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...
Genetics Home Reference: histiocytosis-lymphadenopathy plus syndrome
... its chemical cousin RNA, and molecules such as ATP and GTP, which serve as energy sources in ... Skin Association Histiocytosis Association: Rosai-Dorfman Disease Scientific Articles on PubMed (1 link) PubMed OMIM (1 link) ...
Some news from the unknown soldier, the Peyer's patch macrophage.
Wagner, Camille; Bonnardel, Johnny; Da Silva, Clément; Martens, Liesbet; Gorvel, Jean-Pierre; Lelouard, Hugues
2018-01-31
In mammals, macrophages (MF) are present in virtually all tissues where they serve many different functions linked primarily to the maintenance of homeostasis, innate defense against pathogens, tissue repair and metabolism. Although some of these functions appear common to all tissues, others are specific to the homing tissue. Thus, MF become adapted to perform particular functions in a given tissue. Accordingly, MF express common markers but also sets of tissue-specific markers linked to dedicated functions. One of the largest pool of MF in the body lines up the wall of the gut. Located in the small intestine, Peyer's patches (PP) are primary antigen sampling and mucosal immune response inductive sites. Surprisingly, although markers of intestinal MF, such as F4/80, have been identified more than 30 years ago, MF of PP escaped any kind of phenotypic description and remained "unknown" for decades. In absence of MF identification, the characterization of the PP mononuclear phagocyte system (MPS) functions has been impaired. However, taking into account that PP are privileged sites of entry for pathogens, it is important to understand how the latter are handled by and/or escape the PP MPS, especially MF, which role in killing invaders is well known. This review focuses on recent advances on the PP MPS, which have allowed, through new criteria of PP phagocyte subset identification, the characterization of PP MF origin, diversity, specificity, location and functions. Copyright © 2018 Elsevier Inc. All rights reserved.
The coupling between gaze behavior and opponent kinematics during anticipation of badminton shots.
Alder, David; Ford, Paul R; Causer, Joe; Williams, A Mark
2014-10-01
We examined links between the kinematics of an opponent's actions and the visual search behaviors of badminton players responding to those actions. A kinematic analysis of international standard badminton players (n = 4) was undertaken as they completed a range of serves. Video of these players serving was used to create a life-size temporal occlusion test to measure anticipation responses. Expert (n = 8) and novice (n = 8) badminton players anticipated serve location while wearing an eye movement registration system. During the execution phase of the opponent's movement, the kinematic analysis showed between-shot differences in distance traveled and peak acceleration at the shoulder, elbow, wrist and racket. Experts were more accurate at responding to the serves compared to novice players. Expert players fixated on the kinematic locations that were most discriminating between serve types more frequently and for a longer duration compared to novice players. Moreover, players were generally more accurate at responding to serves when they fixated vision upon the discriminating arm and racket kinematics. Findings extend previous literature by providing empirical evidence that expert athletes' visual search behaviors and anticipatory responses are inextricably linked to the opponent action being observed. Copyright © 2014 Elsevier B.V. All rights reserved.
Linking the Smarter Balanced Assessments to NWEA MAP Assessments
ERIC Educational Resources Information Center
Northwest Evaluation Association, 2015
2015-01-01
Concordance tables have been used for decades to relate scores on different tests measuring similar but distinct constructs. These tables, typically derived from statistical linking procedures, provide a direct link between scores on different tests and serve various purposes. Aside from describing how a score on one test relates to performance on…
Requirements for a mobile communications satellite system. Volume 2: Technical report
NASA Technical Reports Server (NTRS)
Horstein, M.
1983-01-01
Three types of satellite aided mobile communications are considered for users in areas not served by (terrestrial) cellular radio systems. In system 1, mobile units are provided a direct satellite link to a gateway station, which serves as the interface to the terrestrial toll network. In system 2, a terrestrial radio link similar to those in cellular systems connects the mobile unit to a translator station; each translator relays the traffic from mobile units in its vicinity, via satellite, to the regional gateway. It is not feasible for system 2 to provide obiquitous coverage. Therefore, system 3 is introduced, in which the small percentage of users not within range of a translator are provided a direct satellite link as in system 1.
Childhood Maltreatment and Educational Outcomes.
Romano, Elisa; Babchishin, Lyzon; Marquis, Robyn; Fréchette, Sabrina
2015-10-01
Children (0-18 years) with maltreatment histories are vulnerable to experiencing difficulties across multiple domains of functioning, including educational outcomes that encompass not only academic achievement but also mental well-being. The current literature review adopted Slade and Wissow's model to examine (1) the link between childhood maltreatment and academic achievement, (2) the link between childhood maltreatment and mental health outcomes (i.e., emotional and behavioral difficulties), and (3) the bidirectional relationship between childhood academic achievement and mental health. In addition, we reviewed variables that might influence or help explain the link between childhood maltreatment and educational outcomes, drawing on developmental perspectives and Bronfenbrenner's ecological model. Finally, whenever possible, we presented findings specific to maltreated children in out-of-home care to highlight the unique challenges experienced by this population. Results indicated that children with maltreatment histories often experience impairments in both their academic performance (e.g., special education, grade retention, lower grades) and mental well-being (e.g., anxiety, low mood, aggression, social skills deficits, poor interpersonal relationships). These impairments appeared to be particularly pronounced among maltreated children in out-of-home care. Findings, albeit sparse, also indicated that mental health difficulties are negatively associated with children's academic achievement and, similarly, that academic achievement deficits are linked with mental health problems. The link between childhood maltreatment and educational outcomes may be partly explained through the disruption of key developmental processes in children, such as attachment, emotion regulation, and sense of agency. As well, maltreatment characteristics and the functioning of various systems in which children are embedded (e.g., family, school, child welfare) can serve to positively or negatively influence the educational outcomes of maltreated children. The theoretical, research, and applied implications stemming from the findings are considered. © The Author(s) 2014.
DefenseLink Feature: Women's History Month
, assigning 1,500 contract nurses to Army hospitals. By the end of World War II, more than 110,000 women had served as military nurses and more than 400,000 had served in noncombat jobs at home and overseas. In
Marshall, Stephen
2006-08-01
Traditionally, nutrients such as glucose and amino acids have been viewed as substrates for the generation of high-energy molecules and as precursors for the biosynthesis of macromolecules. However, it is now apparent that nutrients also function as signaling molecules in functionally diverse signal transduction pathways. Glucose and amino acids trigger signaling cascades that regulate various aspects of fuel and energy metabolism and control the growth, proliferation, and survival of cells. Here, we provide a functional and regulatory overview of three well-established nutrient signaling pathways-the hexosamine signaling pathway, the mTOR (mammalian target of rapamycin) signaling pathway, and the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Nutrient signaling pathways are interconnected, coupled to insulin signaling, and linked to the release of metabolic hormones from adipose tissue. Thus, nutrient signaling pathways do not function in isolation. Rather, they appear to serve as components of a larger "metabolic regulatory network" that controls fuel and energy metabolism (at the cell, tissue, and whole-body levels) and links nutrient availability with cell growth and proliferation. Understanding the diverse roles of nutrients and delineating nutrient signaling pathways should facilitate drug discovery research and the search for novel therapeutic compounds to prevent and treat various human diseases such as diabetes, obesity, and cancer.
Koskinen, Sanna; Hokkinen, Eeva-Maija; Wilson, Lindsay; Sarajuuri, Jaana; Von Steinbüchel, Nicole; Truelle, Jean-Luc
2011-01-01
The aim is to examine two aspects of outcome after traumatic brain injury (TBI). Functional outcome was assessed by the Glasgow Outcome Scale - Extended (GOSE) and by clinician ratings, while health-related quality of life (HRQoL) was assessed by the Quality of Life after Brain Injury (QOLIBRI). The GOSE and the QOLIBRI were linked to the International Classification of Functioning, Disability and Health (ICF) to analyse their content. Functional outcome on ICF categories was assessed by rehabilitation clinicians in 55 participants with TBI and was compared to the participants' own judgements of their HRQoL. The QOLIBRI was linked to 42 and the GOSE to 57 two-level ICF categories covering 78% of the categories on the ICF brief core set for TBI. The closest agreement in the views of the professionals and the participants was found on the Physical Problems and Cognition scales of the QOLIBRI. The problems encountered after TBI are well covered by the QOLIBRI and the GOSE. They capture important domains that are not traditionally sufficiently documented, especially in the domains of interpersonal relationships, social and leisure activities, self and the environment. The findings indicate that they are useful and complementary outcome measures for TBI. In rehabilitation, they can serve as tools in assessment, setting meaningful goals and creating therapeutic alliance.
Reineman, Julia
2011-10-01
During Argentina's 'Dirty War' (1976-83), the military regime attempted to erase an entire population; today the photographs of the dead/missing stand in defiance, contradicting that attempted erasure of the desaparecidos. In this essay, I explain the connection between photography and loss, and how photography fits within Lacan's understanding of the Imaginary, the Symbolic, the Real, and the 'gaze'. I discuss complicated mourning (circumstances which inhibit/delay mourning) and the difficulties created by political disappearances: as long as the family members maintain the belief that their loved one(s) might still be alive, they cannot begin the process of mourning the permanently lost object. Beginning with the Madres de Plaza de Mayo and, using the web-based art exhibits of Marcelo Brodsky and Inés Ulanovsky, I analyze the role of the photograph in Argentina, how it serves as a linking object, how it is used to symbolize the dead/missing, and how it can function to facilitate mourning, or to serve as proof of pathological melancholia. I argue that such artistic representations of loss function to reinscribe healthy mourning rituals within the Argentine society. Copyright © 2011 Institute of Psychoanalysis.
N-mustard analogs of S-adenosyl-L-methionine as biochemical probes of protein arginine methylation.
Hymbaugh Bergman, Sarah J; Comstock, Lindsay R
2015-08-01
Nucleosomes, the fundamental building blocks of eukaryotic chromatin, undergo post-synthetic modifications and play a major role in the regulation of transcriptional processes. Combinations of these modifications, including methylation, regulate chromatin structure, determining its different functional states and playing a central role in differentiation. The biological significance of cellular methylation, particularly on chromatin, is widely recognized, yet we know little about the mechanisms that link biological methylation events. To characterize and fully understand protein methylation, we describe here novel N-mustard analogs of S-adenosyl-l-methionine (SAM) as biochemical tools to better understand protein arginine methylation events using protein arginine methyltransferase 1 (PRMT1). Specifically, azide- and alkyne-functionalized N-mustard analogs serve as cofactor mimics of SAM and are enzymatically transferred to a model peptide substrate in a PRMT1-dependent fashion. Once incorporated, the resulting alkynes and azides can be modified through chemoselective ligations, including click chemistry and the Staudinger ligation. These results readily demonstrate the feasibility of utilizing N-mustard analogs as biochemical tools to site-specifically label substrates of PRMT1 and serve as an alternative approach to study protein methylation events. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.
Nair, Rajni L; Roche, Kathleen M; White, Rebecca M B
2018-01-01
Latino youth have higher rates of educational and mental health difficulties compared to peers from other racial/ethnic groups. To understand the factors related to such maladjustment, a mediational model linking youth report of parent-youth acculturation gaps to prospective changes (from spring to fall semester) in youth report of academic performance, depressive symptoms and alcohol use via youth report of parent-youth conflict and family cohesion, was studied in a sample of 248 U.S.-and foreign-born Latino youth (Mage = 15.21 years; 50% female; 67% U.S.-born). Parent-youth acculturation gaps were associated with changes in youth academic performance across two semesters via their negative impact on family functioning. For U.S.-born youth, parent-youth acculturation gaps were also linked to changes in alcohol use via parent-adolescent conflict. Results provide some support for the acculturative gap hypotheses while unique findings across nativity groups suggest that such individual-level characteristics may serve as important sources of variation for Latino youth.
Collioud, A; Clémence, J F; Sänger, M; Sigrist, H
1993-01-01
Light-dependent oriented and covalent immobilization of target molecules has been achieved by combining two modification procedures: light-dependent coupling of target molecules to inert surfaces and thiol-selective reactions occurring at macromolecule or substrate surfaces. For immobilization purposes the heterobifunctional reagent N-[m-[3-(trifluoromethyl)diazirin-3-yl]phenyl]-4-maleimidobutyr amide was synthesized and chemically characterized. The photosensitivity of the carbene-generating reagent and its reactivity toward thiols were ascertained. Light-induced cross-linking properties of the reagent were documented (i) by reacting first the maleimide function with a thiolated surface, followed by carbene insertion into applied target molecules, (ii) by photochemical coupling of the reagent to an inert support followed by thermochemical reactions with thiol functions, and (iii) by thermochemical modification of target molecules prior to carbene-mediated insertion into surface materials. Procedures mentioned led to light-dependent covalent immobilization of target molecules including amino acids, a synthetic peptide, and antibody-derived F(ab') fragments. Topically selective, light-dependent immobilization was attained with the bifunctional reagent by irradiation of coated surfaces through patterned masks. Glass and polystyrene served as substrates. Molecular orientation is asserted by inherently available or selectively introduced terminal thiol functions in F(ab') fragments and synthetic polypeptides, respectively.
Structural and functional analysis of 5S rRNA in Saccharomyces cerevisiae
Kiparisov, S.; Sergiev, P. V.; Dontsova, O. A.; Petrov, A.; Meskauskas, A.; Dinman, J. D.
2005-01-01
5S rRNA extends from the central protuberance of the large ribosomal subunit, through the A-site finger, and down to the GTPase-associated center. Here, we present a structure-function analysis of seven 5S rRNA alleles which are sufficient for viability in the yeast Saccharomyces cerevisiae when expressed in the absence of wild-type 5S rRNAs, and extend this analysis using a large bank of mutant alleles that show semidominant phenotypes in the presence of wild-type 5S rRNA. This analysis supports the hypothesis that 5S rRNA serves to link together several different functional centers of the ribosome. Data are also presented which suggest that in eukaryotic genomes selection has favored the maintenance of multiple alleles of 5S rRNA, and that these may provide cells with a mechanism to post-transcriptionally regulate gene expression. PMID:16047201
Salt, chloride, bleach, and innate host defense
Wang, Guoshun; Nauseef, William M.
2015-01-01
Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. PMID:26048979
Pili and flagella biology, structure, and biotechnological applications.
Van Gerven, Nani; Waksman, Gabriel; Remaut, Han
2011-01-01
Bacteria and Archaea expose on their outer surfaces a variety of thread-like proteinaceous organelles with which they interact with their environments. These structures are repetitive assemblies of covalently or non-covalently linked protein subunits, organized into filamentous polymers known as pili ("hair"), flagella ("whips") or injectisomes ("needles"). They serve different roles in cell motility, adhesion and host invasion, protein and DNA secretion and uptake, conductance, or cellular encapsulation. Here we describe the functional, morphological and genetic diversity of these bacterial filamentous protein structures. The organized, multi-copy build-up and/or the natural function of pili and flagella have lead to their biotechnological application as display and secretion tools, as therapeutic targets or as molecular motors. We review the documented and potential technological exploitation of bacterial surface filaments in light of their structural and functional traits. Copyright © 2011 Elsevier Inc. All rights reserved.
NASA Astrophysics Data System (ADS)
Kim, Minsu; Or, Dani
2017-12-01
Biological soil crusts (biocrusts) are self-organised thin assemblies of microbes, lichens, and mosses that are ubiquitous in arid regions and serve as important ecological and biogeochemical hotspots. Biocrust ecological function is intricately shaped by strong gradients of water, light, oxygen, and dynamics in the abundance and spatial organisation of the microbial community within a few millimetres of the soil surface. We report a mechanistic model that links the biophysical and chemical processes that shape the functioning of biocrust representative microbial communities that interact trophically and respond dynamically to cycles of hydration, light, and temperature. The model captures key features of carbon and nitrogen cycling within biocrusts, such as microbial activity and distribution (during early stages of biocrust establishment) under diurnal cycles and the associated dynamics of biogeochemical fluxes at different hydration conditions. The study offers new insights into the highly dynamic and localised processes performed by microbial communities within thin desert biocrusts.
Salt, chloride, bleach, and innate host defense.
Wang, Guoshun; Nauseef, William M
2015-08-01
Salt provides 2 life-essential elements: sodium and chlorine. Chloride, the ionic form of chlorine, derived exclusively from dietary absorption and constituting the most abundant anion in the human body, plays critical roles in many vital physiologic functions, from fluid retention and secretion to osmotic maintenance and pH balance. However, an often overlooked role of chloride is its function in innate host defense against infection. Chloride serves as a substrate for the generation of the potent microbicide chlorine bleach by stimulated neutrophils and also contributes to regulation of ionic homeostasis for optimal antimicrobial activity within phagosomes. An inadequate supply of chloride to phagocytes and their phagosomes, such as in CF disease and other chloride channel disorders, severely compromises host defense against infection. We provide an overview of the roles that chloride plays in normal innate immunity, highlighting specific links between defective chloride channel function and failures in host defense. © Society for Leukocyte Biology.
Ralston, Timothy E; Kanzler, Kathryn E
2016-01-01
Postural orthostatic tachycardia syndrome (POTS) is a multifaceted disorder of the autonomic nervous system that profoundly impacts physical functioning. In addition to physical consequences, many patients develop situational anxiety that causes reduced activity level, which may impede functional recovery from POTS. Despite links with anxiety, to date there have been no reports of psychological intervention for POTS. Here we report a case study of POTS in a 40-year-old female serving on active duty in the US military. Because there are no established guidelines for the psychological treatment of POTS, intervention techniques were adapted for use with the patient. Elements of cognitive behavioral therapy, including in-vivo exposure and symptom discrimination, were used to target avoidance of feared situations. Over the course of treatment, the patient learned to discriminate her POTS symptoms from anxiety and displayed a significant decrease in POTS-related functional impairment. Implications for future care are discussed.
ERIC Educational Resources Information Center
Wittman, Hannah; Beckie, Mary; Hergesheimer, Chris
2012-01-01
Often organized as grassroots, nonprofit organizations, many farmers' markets serve as strategic venues linking producers and consumers of local food while fulfilling multiple social, economic, and environmental objectives. This article examines the potential of farmers' markets to play a catalyst role in linking local food systems to the social…
Functional Analysis of HIV/AIDS Stigma: Consensus or Divergence?
ERIC Educational Resources Information Center
Hosseinzadeh, Hassan; Hossain, Syeda Zakia
2011-01-01
Functional theory proposes that attitudes may serve a variety of purposes for individuals. This study aimed to determine whether stigmatized attitudes toward HIV/AIDS serve the same function for all (consensus function) or serve different functions for different individuals (divergence function) by assessing various aspects of HIV/AIDS stigma…
Mental Health of Homeless Youth: Moderation by Peer Victimization and Teacher Support.
Armstrong, Jenna M; Owens, Caitlyn R; Haskett, Mary E
2018-02-14
The link between youth homelessness and mental health functioning was examined using state population-representative 2015 Youth Risk Behavior Survey (YRBS) data. The moderating role of victimization and perceived teacher support also was examined. Consistent with hypotheses, results indicated that homelessness was associated with greater mental health challenges, more victimization, and less teacher support. The association between homelessness and mental health was not moderated by perceived teacher support. However, victimization experiences served as a moderator such that more victimization exacerbated the effect of homelessness on mental health challenges. This study supports the utility of the YRBS for gaining understanding of the experiences and needs of youth experiencing homelessness and adds to the growing literature on predictors of individual differences in mental health functioning of these vulnerable youth.
Shi, Jiafu; Zhang, Wenyan; Wang, Xiaoli; Jiang, Zhongyi; Zhang, Shaohua; Zhang, Xiaoman; Zhang, Chunhong; Song, Xiaokai; Ai, Qinghong
2013-06-12
A facile approach to preparing mesoporous hybrid microcapsules is developed by exploring the segregating and mineralization-inducing capacities of cationic hydrophilic polymer. The preparation process contains four steps: segregation of cationic hydrophilic polymer during template formation, cross-linking of the segregated polymer, biomimetic mineralization within cross-linked polymer network, and removal of template to simultaneously generate capsule lumen and mesopores on the capsule wall. Poly(allylamine hydrochloride) (PAH) is chosen as the model polymer, its hydrophilicity renders the segregating capacity and spontaneous enrichment in the near-surface region of CaCO3 microspheres; its biopolyamine-mimic structure renders the mineralization-inducing capacity to produce titania from the water-soluble titanium(IV) precursor. Meanwhile, CaCO3 microspheres serve the dual templating functions in the formation of hollow lumen and mesoporous wall. The thickness of capsule wall can be controlled by changing the polymer segregating and cross-linking conditions, while the pore size on the capsule wall can be tuned by changing the template synthesizing conditions. The robust hybrid microcapsules exhibit desirable efficiency in enzymatic catalysis, wastewater treatment and drug delivery. This approach may open facile, generic, and efficient pathway to designing and preparing a variety of hybrid microcapsules with high and tunable permeability, good stability and multiple functionalities for a broad range of applications.
Heinzmann, Christian; Salz, Ulrich; Moszner, Norbert; Fiore, Gina L; Weder, Christoph
2015-06-24
Hydrogen-bonded, side-chain-functionalized supramolecular poly(alkyl methacrylate)s were investigated as light- and temperature-responsive reversible adhesives that are useful for bonding and debonding on demand applications. Here, 2-hydroxyethyl methacrylate (HEMA) was functionalized with 2-ureido-4[1H]pyrimidinone (UPy) via a hexamethylenediisocyanate (HMDI) linker, to create a monomer (UPy-HMDI-HEMA) that serves to form supramolecular cross-links by way of forming quadruple hydrogen bonded dimers. UPy-HMDI-HEMA was copolymerized with either hexyl methacrylate or butyl methacrylate to create copolymers comprising 2.5, 5, or 10 mol % of the cross-linker. The mechanical properties of all (co)polymers were investigated with stress-strain experiments and dynamic mechanical analysis. Furthermore, the adhesive properties were studied at temperatures between 20 and 60 °C by testing single lap joints formed with stainless steel substrates. It was found that increasing the concentration of the UPy-HMDI-HEMA cross-linker leads to improved mechanical and adhesive properties at elevated temperatures. Concurrently, the reversibility of the bond formation remained unaffected, where rebonded samples displayed the same adhesive strength as regularly bonded samples. Debonding on demand abilities were also tested exemplarily for one copolymer, which for light-induced debonding experiments was blended with a UV-absorber that served as light-heat converter. Single lap joints were subjected to a constant force and heated or irradiated with UV light until debonding occurred. The necessary debonding temperature was comparable for direct heating and UV irradiation and varied between 28 and 82 °C, depending on the applied force. The latter also influenced the debonding time, which under the chosen conditions ranged from 30 s to 12 min.
Restaurant Cooking Trends and Increased Risk for Campylobacter Infection
Jones, Anna K.; Rigby, Dan; Burton, Michael; Millman, Caroline; Williams, Nicola J.; Jones, Trevor R.; Wigley, Paul; Cross, Paul
2016-01-01
In the United Kingdom, outbreaks of Campylobacter infection are increasingly attributed to undercooked chicken livers, yet many recipes, including those of top chefs, advocate short cooking times and serving livers pink. During 2015, we studied preferences of chefs and the public in the United Kingdom and investigated the link between liver rareness and survival of Campylobacter. We used photographs to assess chefs’ ability to identify chicken livers meeting safe cooking guidelines. To investigate the microbiological safety of livers chefs preferred to serve, we modeled Campylobacter survival in infected chicken livers cooked to various temperatures. Most chefs correctly identified safely cooked livers but overestimated the public’s preference for rareness and thus preferred to serve them more rare. We estimated that 19%–52% of livers served commercially in the United Kingdom fail to reach 70°C and that predicted Campylobacter survival rates are 48%–98%. These findings indicate that cooking trends are linked to increasing Campylobacter infections. PMID:27314748
A Cellular Neural Networks Based DiffServ Switch for Satellite Communication Systems
NASA Astrophysics Data System (ADS)
Tarchi, Daniele; Fantacci, Romano; Gubellini, Roberto; Pecorella, Tommaso
2003-07-01
Recent developments of Internet services and advanced compression methods has revived interest on IP based multimedia satellite communication systems. However a main problem arising here is to guarantee specific Quality of Service (QoS) constraints in order to have good performance for each traffic class.Among various QoS approach used in Internet, recently the DiffServ technique has became the most promising so- lution, mainly for its simplicity with respect to different alternatives. Moreover, in satellite communication systems, DiffServ policy computational capabilities are placed at the edge points (end-to-end philosophy); this is very important for a network constituted by one satellite link because it allows to reduce the implementation complexity of the satellite on-board equipments.The satellite switch under consideration makes use of the Multiple Input Queuing approach. Packets arrived at a switch input are stored in a shared buffer but they are logically ordered in individual queues, one for each possible output link. According to the DiffServ policy, within a same logical queue, packets are reordered in individual sub-queues according to the priority. A suitable implementation of the DiffServ policy based on a Cellular Neural Network (CNN) is proposed in the paper in order to achieve QoS requirements.The CNNs are a set of linear and nonlinear circuits connected among them that allow parallel and asynchronous computation. CNNs are a class of neural networks similar to Hopfield Neural Networks (HNN), but more flexible and suitable for solving the output contention problem, inherent of switching systems, for VLSI implementation.In this paper a CNN has been designed in order to maximize a cost functional, related to the on-board switch through- put and QoS constraints. The initial state for each neural cell is obtained looking at the presence of at least one packet from a certain input logical queue to a specific output line. The input value for each neural cell is a function of priority and length of each input logical queue. The versatility of neural network make feasible to take the best decision for the packet to be delivered to each output satellite beam, in order to meet specific QoS constraints. Numerical results for CNN approach highlights that Neural network convergence within a time slot is guaranteed, and an optimal, or at least near-optimal, solution in terms of cost function is achieved.The proposed system is based on the IETF (Internet Engineering Task Force) recommendations; this means that traffic entering the switching fabric could be marked as Expedited Forward (EF) or Assured Forward (AF), otherwise handled as Best Effort (BE). Two Assured Forward classes with different emission priority have been implemented, taking into account time spent inside the logical queue and its length. Expedited Forward traffic is typical of services to be delivered with the maximum priority, as streaming or interactive services. The packets, belonging to services that need a certain level of priority with low packet loss, are marked as Assured Forward. Best Effort traffic is related to e-mail or file transfer, or other that have not particular QoS requirements. The CNN used to solve conflict situations act as an arbiter for all the output links. Differently from other Multiple Input Queuing approach, where one arbiter for each output line is present, in proposed approach there exist only one arbiter that make the best decision. The selected rule has been defined in order to give priority to packets, according to opportunely defined functionals characteristic of each traffic class, under the constraint that no more than one packet can be delivered to the same output line. The functionals depend on queue length and time spent inside the queue by front packet.The performance of the proposed DiffServ switch has been derived in terms of delay and jitter; buffer occupancy has been analyzed for different configuration, such as a unique common buffer, one buffer for each input line, one buffer for each input line and each priority class.The obtained results highlight an high flexibility of satellite switch with CNN, taking into account that functional used to calculate priority of each queue could be easily changed, without any complexity gain nor change in CNN structure, in order to consider different traffic characteristic. Numerical results show that proposed algorithm outperform the switches based on Multiple Input Queuing, that use strictly priority methods, in terms of delay and jitter. Different buffer size have been also considered in order to analyze packet loss for CNN switch algorithm, comparing different configuration described above.The good behavior of the proposed DiffServ switch has been verified in the case of traffic with pareto distribution for packet length and a geometrical distribution for packet interarrival time, highlighting good performance in terms of delay and jitter. Numerical results also demonstrate the stability of this method for heavy load traffic; in particular maximum permitted load is higher for higher priority classes.
Mahdi, Soheil; Viljoen, Marisa; Yee, Tamara; Selb, Melissa; Singhal, Nidhi; Almodayfer, Omar; Granlund, Mats; de Vries, Petrus J.; Zwaigenbaum, Lonnie
2017-01-01
This is the third in a series of four empirical studies designed to develop International Classification of Functioning, Disability and Health (ICF) Core Sets for Autism Spectrum Disorder (ASD). The present study aimed to describe functioning in ASD (as operationalized by the ICF) derived from the perspectives of diagnosed individuals, family members, and professionals. A qualitative study using focus groups and semi‐structured interviews were conducted with 19 stakeholder groups (N = 90) from Canada, India, Saudi Arabia, South Africa, and Sweden. Meaningful concepts from the focus groups and individual interviews were linked to ICF categories using a deductive qualitative approach with standardized linking procedures. The deductive qualitative content analysis yielded meaningful functioning concepts that were linked to 110 ICF categories across all four ICF components. Broad variation of environmental factors and activities and participation categories were identified in this study, while body functions consisted mainly of mental functions. Body structures were sparsely mentioned by the participants. Positive aspects of ASD included honesty, attention to detail, and memory. The experiences provided by international stakeholders support the need to understand individuals with ASD in a broader perspective, extending beyond diagnostic criteria into many areas of functioning and environmental domains. This study is part of a larger systematic effort that will provide the basis to define ICF Core Sets for ASD, from which assessment tools can be generated for use in clinical practice, research, and health care policy making. Autism Res 2018, 11: 463–475. © 2017 The Authors Autism Research published by International Society for Autism Research and Wiley Periodicals, Inc. Lay Summary The study findings support the need to understand the living experiences of individuals with Autism Spectrum Disorder (ASD) from a broader perspective, taking into account many areas of an individual's functioning and environment. The ICF can serve as foundation for exploring these living experiences more extensively by offering tools that enable wide variety of individual difficulties and strengths to be captured along with important environmental influences. As such, these tools can facilitate interventions that meet the needs and goals of the individual. PMID:29226604
DOT National Transportation Integrated Search
2011-01-01
Intermodal connections with other scheduled public trans- : portation modes are available at 70 percent of all stations : served by commuter rail trains. Commuter rail passengers : are able to connect to other transportation modes at 8121 of : the 1,...
Forum Guide to the Teacher-Student Data Link: A Technical Implementation Resource. NFES 2013-802
ERIC Educational Resources Information Center
National Forum on Education Statistics, 2013
2013-01-01
This document is intended to serve as a practical guide for implementing a teacher-student data link (TSDL) that supports a range of uses at the local, regional, and state levels. The guide addresses the considerations for linking teacher and student data from multiple perspectives, including governance, policies, data components, business rules,…
Le, N; Simon, M A
1998-08-01
DRK, the Drosophila homolog of the SH2-SH3 domain adaptor protein Grb2, is required during signaling by the sevenless receptor tyrosine kinase (SEV). One role of DRK is to provide a link between activated SEV and the Ras1 activator SOS. We have investigated the possibility that DRK performs other functions by identifying additional DRK-binding proteins. We show that the phosphotyrosine-binding (PTB) domain-containing protein Disabled (DAB) binds to the DRK SH3 domains. DAB is expressed in the ommatidial clusters, and loss of DAB function disrupts ommatidial development. Moreover, reduction of DAB function attenuates signaling by a constitutively activated SEV. Our biochemical analysis suggests that DAB binds SEV directly via its PTB domain, becomes tyrosine phosphorylated upon SEV activation, and then serves as an adaptor protein for SH2 domain-containing proteins. Taken together, these results indicate that DAB is a novel component of the SEV signaling pathway.
Tissue oxygen demand in regulation of the behavior of the cells in the vasculature.
Barvitenko, Nadezhda N; Aslam, Muhammad; Filosa, Jessica; Matteucci, Elena; Nikinmaa, Mikko; Pantaleo, Antonella; Saldanha, Carlota; Baskurt, Oguz K
2013-08-01
The control of arteriolar diameters in microvasculature has been in the focus of studies on mechanisms matching oxygen demand and supply at the tissue level. Functionally, important vascular elements include EC, VSMC, and RBC. Integration of these different cell types into functional units aimed at matching tissue oxygen supply with tissue oxygen demand is only achieved when all these cells can respond to the signals of tissue oxygen demand. Many vasoactive agents that serve as signals of tissue oxygen demand have their receptors on all these types of cells (VSMC, EC, and RBC) implying that there can be a coordinated regulation of their behavior by the tissue oxygen demand. Such functions of RBC as oxygen carrying by Hb, rheology, and release of vasoactive agents are considered. Several common extra- and intracellular signaling pathways that link tissue oxygen demand with control of VSMC contractility, EC permeability, and RBC functioning are discussed. © 2013 John Wiley & Sons Ltd.
Fermionic Approach to Weighted Hurwitz Numbers and Topological Recursion
NASA Astrophysics Data System (ADS)
Alexandrov, A.; Chapuy, G.; Eynard, B.; Harnad, J.
2017-12-01
A fermionic representation is given for all the quantities entering in the generating function approach to weighted Hurwitz numbers and topological recursion. This includes: KP and 2D Toda {τ} -functions of hypergeometric type, which serve as generating functions for weighted single and double Hurwitz numbers; the Baker function, which is expanded in an adapted basis obtained by applying the same dressing transformation to all vacuum basis elements; the multipair correlators and the multicurrent correlators. Multiplicative recursion relations and a linear differential system are deduced for the adapted bases and their duals, and a Christoffel-Darboux type formula is derived for the pair correlator. The quantum and classical spectral curves linking this theory with the topological recursion program are derived, as well as the generalized cut-and-join equations. The results are detailed for four special cases: the simple single and double Hurwitz numbers, the weakly monotone case, corresponding to signed enumeration of coverings, the strongly monotone case, corresponding to Belyi curves and the simplest version of quantum weighted Hurwitz numbers.
Fermionic Approach to Weighted Hurwitz Numbers and Topological Recursion
NASA Astrophysics Data System (ADS)
Alexandrov, A.; Chapuy, G.; Eynard, B.; Harnad, J.
2018-06-01
A fermionic representation is given for all the quantities entering in the generating function approach to weighted Hurwitz numbers and topological recursion. This includes: KP and 2 D Toda {τ} -functions of hypergeometric type, which serve as generating functions for weighted single and double Hurwitz numbers; the Baker function, which is expanded in an adapted basis obtained by applying the same dressing transformation to all vacuum basis elements; the multipair correlators and the multicurrent correlators. Multiplicative recursion relations and a linear differential system are deduced for the adapted bases and their duals, and a Christoffel-Darboux type formula is derived for the pair correlator. The quantum and classical spectral curves linking this theory with the topological recursion program are derived, as well as the generalized cut-and-join equations. The results are detailed for four special cases: the simple single and double Hurwitz numbers, the weakly monotone case, corresponding to signed enumeration of coverings, the strongly monotone case, corresponding to Belyi curves and the simplest version of quantum weighted Hurwitz numbers.
Walke, Jenifer B; Becker, Matthew H; Loftus, Stephen C; House, Leanna L; Teotonio, Thais L; Minbiole, Kevin P C; Belden, Lisa K
2015-01-01
The vertebrate microbiome contributes to disease resistance, but few experiments have examined the link between microbiome community structure and disease resistance functions. Chytridiomycosis, a major cause of amphibian population declines, is a skin disease caused by the fungus, Batrachochytrium dendrobatidis (Bd). In a factorial experiment, bullfrog skin microbiota was reduced with antibiotics, augmented with an anti-Bd bacterial isolate (Janthinobacterium lividum), or unmanipulated, and individuals were then either exposed or not exposed to Bd. We found that the microbial community structure of individual frogs prior to Bd exposure influenced Bd infection intensity one week following exposure, which, in turn, was negatively correlated with proportional growth during the experiment. Microbial community structure and function differed among unmanipulated, antibiotic-treated, and augmented frogs only when frogs were exposed to Bd. Bd is a selective force on microbial community structure and function, and beneficial states of microbial community structure may serve to limit the impacts of infection.
Walke, Jenifer B.; Becker, Matthew H.; Loftus, Stephen C.; House, Leanna L.; Teotonio, Thais L.; Minbiole, Kevin P. C.; Belden, Lisa K.
2015-01-01
The vertebrate microbiome contributes to disease resistance, but few experiments have examined the link between microbiome community structure and disease resistance functions. Chytridiomycosis, a major cause of amphibian population declines, is a skin disease caused by the fungus, Batrachochytrium dendrobatidis (Bd). In a factorial experiment, bullfrog skin microbiota was reduced with antibiotics, augmented with an anti-Bd bacterial isolate (Janthinobacterium lividum), or unmanipulated, and individuals were then either exposed or not exposed to Bd. We found that the microbial community structure of individual frogs prior to Bd exposure influenced Bd infection intensity one week following exposure, which, in turn, was negatively correlated with proportional growth during the experiment. Microbial community structure and function differed among unmanipulated, antibiotic-treated, and augmented frogs only when frogs were exposed to Bd. Bd is a selective force on microbial community structure and function, and beneficial states of microbial community structure may serve to limit the impacts of infection. PMID:26445500
Psychoanalysis and the brain - why did freud abandon neuroscience?
Northoff, Georg
2012-01-01
Sigmund Freud, the founder of psychoanalysis, was initially a neuroscientist but abandoned neuroscience completely after he made a last attempt to link both in his writing, "Project of a Scientific Psychology," in 1895. The reasons for his subsequent disregard of the brain remain unclear though. I here argue that one central reason may be that the approach to the brain during his time was simply not appealing to Freud. More specifically, Freud was interested in revealing the psychological predispositions of psychodynamic processes. However, he was not so much focused on the actual psychological functions themselves which though were the prime focus of the neuroscience at his time and also in current Cognitive Neuroscience. Instead, he probably would have been more interested in the brain's resting state and its constitution of a spatiotemporal structure. I here assume that the resting state activity constitutes a statistically based virtual structure extending and linking the different discrete points in time and space within the brain. That in turn may serve as template, schemata, or grid for all subsequent neural processing during stimulus-induced activity. As such the resting state' spatiotemporal structure may serve as the neural predisposition of what Freud described as "psychological structure." Hence, Freud and also current neuropsychoanalysis may want to focus more on neural predispositions, the necessary non-sufficient conditions, rather than the neural correlates, i.e., sufficient, conditions of psychodynamic processes.
Levitz, S M; Nong , S; Mansour, M K; Huang, C; Specht, C A
2001-08-28
The fungus Cryptococcus neoformans is a major cause of morbidity and mortality in patients with impaired CD4(+) T cell function, particularly those with AIDS. To identify cryptococcal antigens that could serve as vaccine candidates by stimulating T cell responses, C. neoformans-reactive CD4(+) T cell hybridomas were generated by immunization of C57BL/6 mice and fusion of splenocytes with thymoma cells. The antigen that stimulated one of the hybridomas, designated P1D6, to produce IL-2 was purified to homogeneity by sequential anion exchange chromatography, hydrophobic interaction chromatography, and SDS/PAGE. Based on its apparent molecular mass of 98 kDa and mannosylation, the antigen of interest was named MP98. MP98 was N terminal-sequenced, and the gene encoding the protein was cloned and sequenced. Recombinant MP98, expressed in Saccharomyces cerevisiae, stimulated P1D6 to produce IL-2. Analysis of the derived 458-aa sequence of MP98 reveals an N-terminal cleavable signal sequence, a polysaccharide deacetylase domain found in fungal chitin deacetylases, and a serine/threonine-rich C-terminal region. Overall, there were 103 serine/threonine residues serving as potential O-linked glycosylation sites as well as 12 possible N-linked glycosylation sites. Thus, a C. neoformans mannoprotein has been characterized that stimulates T cell responses and has molecular properties of a chitin deacetylase.
Drug Offers as a Context for Violence Perpetration and Victimization
Helm, Susana; Okamoto, Scott; Kaliades, Alexis; Giroux, Danielle
2014-01-01
Objective Drug use has been linked empirically with aggression and violence among youth in national and State of Hawai`i samples. However, the nature of this link and its implications for prevention are unclear. Therefore, this paper explores the intersection of drugs with aggression and violence by using the drug offer context as the unit of analysis. Method Native Hawaiian youth are sampled because substance use rates tend to be higher and onset tends to be earlier than their non-Hawaiian peers. Fourteen sex-specific focus group discussions were held with rural Native Hawaiian middle school students (N=64). Students discussed what they thought they would do in terms of drug refusal strategies in a variety of drug offer contexts. Results While aggression and violence were perceived to be socially inappropriate, students nonetheless felt drug use would be less socially competent. Narrative analyses indicated aggression and violence were perceived to function as potential drug refusal strategies. As proximal drug resistance, aggression and violence perpetration served as an immediate deterrent to the drug offerer, and thus drug use. As distal drug resistance, victimization served as a rationale for avoiding drug using contexts. Conclusions Implications are discussed in terms of prevention policy and practice, specifically in terms of a school-based prevention curriculum. Future research in Hawaiian epistemology and gendered approaches are warranted. PMID:24564559
ERIC Educational Resources Information Center
Andrade, Luis M.; Lundberg, Carol A.
2018-01-01
This study investigated the ways that mission statements from 70 Hispanic-serving community colleges communicated their commitment to their Hispanic-serving function. Reference specifically to the Hispanic-serving function was absent, but references to culture and access were relatively common. Findings describe the ways culture and access were…
Danecka, Marta K; Woidy, Mathias; Zschocke, Johannes; Feillet, François; Muntau, Ania C; Gersting, Søren W
2015-03-01
In phenylketonuria, genetic heterogeneity, frequent compound heterozygosity, and the lack of functional data for phenylalanine hydroxylase genotypes hamper reliable phenotype prediction and individualised treatment. A literature search revealed 690 different phenylalanine hydroxylase genotypes in 3066 phenylketonuria patients from Europe and the Middle East. We determined phenylalanine hydroxylase function of 30 frequent homozygous and compound heterozygous genotypes covering 55% of the study population, generated activity landscapes, and assessed the phenylalanine hydroxylase working range in the metabolic (phenylalanine) and therapeutic (tetrahydrobiopterin) space. Shared patterns in genotype-specific functional landscapes were linked to biochemical and pharmacological phenotypes, where (1) residual activity below 3.5% was associated with classical phenylketonuria unresponsive to pharmacological treatment; (2) lack of defined peak activity induced loss of response to tetrahydrobiopterin; (3) a higher cofactor need was linked to inconsistent clinical phenotypes and low rates of tetrahydrobiopterin response; and (4) residual activity above 5%, a defined peak of activity, and a normal cofactor need were associated with pharmacologically treatable mild phenotypes. In addition, we provide a web application for retrieving country-specific information on genotypes and genotype-specific phenylalanine hydroxylase function that warrants continuous extension, updates, and research on demand. The combination of genotype-specific functional analyses with biochemical, clinical, and therapeutic data of individual patients may serve as a powerful tool to enable phenotype prediction and to establish personalised medicine strategies for dietary regimens and pharmacological treatment in phenylketonuria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Protocol for sortase-mediated construction of DNA-protein hybrids and functional nanostructures.
Koussa, Mounir A; Sotomayor, Marcos; Wong, Wesley P
2014-05-15
Recent methods in DNA nanotechnology are enabling the creation of intricate nanostructures through the use of programmable, bottom-up self-assembly. However, structures consisting only of DNA are limited in their ability to act on other biomolecules. Proteins, on the other hand, perform a variety of functions on biological materials, but directed control of the self-assembly process remains a challenge. While DNA-protein hybrids have the potential to provide the best-of-both-worlds, they can be difficult to create as many of the conventional techniques for linking proteins to DNA render proteins dysfunctional. We present here a sortase-based protocol for covalently coupling proteins to DNA with minimal disturbance to protein function. To accomplish this we have developed a two-step process. First, a small synthetic peptide is bioorthogonally and covalently coupled to a DNA oligo using click chemistry. Next, the DNA-peptide chimera is covalently linked to a protein of interest under protein-compatible conditions using the enzyme sortase. Our protocol allows for the simple coupling and purification of a functional DNA-protein hybrid. We use this technique to form oligos bearing cadherin-23 and protocadherin-15 protein fragments. Upon incorporation into a linear M13 scaffold, these protein-DNA hybrids serve as the gate to a binary nanoswitch. The outlined protocol is reliable and modular, facilitating the construction of libraries of oligos and proteins that can be combined to form functional DNA-protein nanostructures. These structures will enable a new class of functional nanostructures, which could be used for therapeutic and industrial processes. Copyright © 2014. Published by Elsevier Inc.
Protocol for sortase-mediated construction of DNA-protein hybrids and functional nanostructures
Koussa, Mounir A.; Sotomayor, Marcos; Wong, Wesley P.
2014-01-01
Recent methods in DNA nanotechnology are enabling the creation of intricate nanostructures through the use of programmable, bottom-up self-assembly. However, structures consisting only of DNA are limited in their ability to act on other biomolecules. Proteins, on the other hand, perform a variety of functions on biological materials, but directed control of the self-assembly process remains a challenge. While DNA-protein hybrids have the potential to provide the best-of-both-worlds, they can be difficult to create as many of the conventional techniques for linking proteins to DNA render proteins dysfunctional. We present here a sortase-based protocol for covalently coupling proteins to DNA with minimal disturbance to protein function. To accomplish this we have developed a two-step process. First, a small synthetic peptide is bioorthogonally and covalently coupled to a DNA oligo using click chemistry. Next, the DNA-peptide chimera is covalently linked to a protein of interest under protein-compatible conditions using the enzyme sortase. Our protocol allows for the simple coupling and purification of a functional DNA-protein hybrid. We use this technique to form oligos bearing cadherin-23 and protocadherin-15 protein fragments. Upon incorporation into a linear M13 scaffold, these protein-DNA hybrids serve as the gate to a binary nanoswitch. The outlined protocol is reliable and modular, facilitating the construction of libraries of oligos and proteins that can be combined to form functional DNA-protein nanostructures. These structures will enable a new class of functional nanostructures, which could be used for therapeutic and industrial processes. PMID:24568941
Serving up Success! Team Nutrition Days, 1997.
ERIC Educational Resources Information Center
Food and Nutrition Service (USDA), Washington, DC.
This publication presents success stories and actual activities from Team Nutrition Days 1997 to serve as a starting point for other schools wanting to create their own nutrition education activities. Team Nutrition Days was a 1-week celebration that used innovative, interactive activities to teach children that nutrition is the link between…
Estimating Family Planning Program Effects on U.S. Fertility Rates
ERIC Educational Resources Information Center
Cutright, Phillips; Jaffe, Frederick S.
1977-01-01
Family planning enrollment statistics were linked to county-level Census data for subgroups defined by age, race, marital status, and economic status. The evidence indicates significant reductions of marital fertility among low socioeconomic status wives served by the program and no effects on groups not served. (Author/CTM)
Dalle, Stéphane; Ravier, Magalie A; Bertrand, Gyslaine
2011-03-01
Defective insulin secretion is a feature of type 2 diabetes that results from inadequate compensatory increase in β-cell mass, decreased β-cell survival and impaired glucose-dependent insulin release. Pancreatic β-cell proliferation, survival and secretion are thought to be regulated by signalling pathways linked to G-protein coupled receptors (GPCRs), such as the glucagon-like peptide-1 (GLP-1) and the pituitary adenylate cyclase-activating polypeptide (PACAP) receptors. β-arrestin-1 serves as a multifunctional adaptor protein that mediates receptor desensitization, receptor internalization, and links GPCRs to downstream pathways such as tyrosine kinase Src, ERK1/2 or Akt/PKB. Importantly, recent studies found that β-arrestin-1 mediates GLP-1 signalling to insulin secretion, GLP-1 antiapoptotic effect by phosphorylating the proapoptotic protein Bad through ERK1/2 activation, and PACAP potentiation of glucose-induced long-lasting ERK1/2 activation controlling IRS-2 expression. Together, these novel findings reveal an important functional role for β-arrestin-1 in the regulation of insulin secretion and β-cell survival by GPCRs. Copyright © 2010 Elsevier Inc. All rights reserved.
Miller-Fleming, Tyne W; Petersen, Sarah C; Manning, Laura; Matthewman, Cristina; Gornet, Megan; Beers, Allison; Hori, Sayaka; Mitani, Shohei; Bianchi, Laura; Richmond, Janet; Miller, David M
2016-01-01
Genetic programming and neural activity drive synaptic remodeling in developing neural circuits, but the molecular components that link these pathways are poorly understood. Here we show that the C. elegans Degenerin/Epithelial Sodium Channel (DEG/ENaC) protein, UNC-8, is transcriptionally controlled to function as a trigger in an activity-dependent mechanism that removes synapses in remodeling GABAergic neurons. UNC-8 cation channel activity promotes disassembly of presynaptic domains in DD type GABA neurons, but not in VD class GABA neurons where unc-8 expression is blocked by the COUP/TF transcription factor, UNC-55. We propose that the depolarizing effect of UNC-8-dependent sodium import elevates intracellular calcium in a positive feedback loop involving the voltage-gated calcium channel UNC-2 and the calcium-activated phosphatase TAX-6/calcineurin to initiate a caspase-dependent mechanism that disassembles the presynaptic apparatus. Thus, UNC-8 serves as a link between genetic and activity-dependent pathways that function together to promote the elimination of GABA synapses in remodeling neurons. DOI: http://dx.doi.org/10.7554/eLife.14599.001 PMID:27403890
Functional Nanoclay Suspension for Printing-Then-Solidification of Liquid Materials.
Jin, Yifei; Compaan, Ashley; Chai, Wenxuan; Huang, Yong
2017-06-14
Additive manufacturing (AM) enables the freeform fabrication of complex structures from various build materials. The objective of this study is to develop a novel Laponite nanoclay-enabled "printing-then-solidification" additive manufacturing approach to extrude complex three-dimensional (3D) structures made of various liquid build materials. Laponite, a member of the smectite mineral family, is investigated to serve as a yield-stress support bath material for the extrusion printing of liquid build materials. Using the printing-then-solidification approach, the printed structure remains liquid and retains its shape with the help of the Laponite support bath. Then the completed liquid structures are solidified in situ by applying suitable cross-linking mechanisms. Finally, the solidified structures are harvested from the Laponite nanoclay support bath for any further processing as needed. Due to its chemical and physical stability, liquid build materials with different solidification/curing/gelation mechanisms can be fabricated in the Laponite bath using the printing-then-solidification approach. The feasibility of the proposed Laponite-enabled printing-then-solidification approach is demonstrated by fabricating several complicated structures made of various liquid build materials, including alginate with ionic cross-linking, gelatin with thermal cross-linking, and SU-8 with photo-cross-linking. During gelatin structure printing, living cells are included and the postfabrication cell viability is above 90%.
Knovich, Mary Ann; Storey, Jonathan A.; Coffman, Lan G.; Torti, Suzy V.
2009-01-01
Ferritin, a major iron storage protein, is essential to iron homeostasis and is involved in a wide range of physiologic and pathologic processes. In clinical medicine, ferritin is predominantly utilized as a serum marker of total body iron stores. In cases of iron deficiency and overload, serum ferritin serves a critical role in both diagnosis and management. Elevated serum and tissue ferritin are linked to coronary artery disease, malignancy, and poor outcomes following stem cell transplantation. Ferritin is directly implicated in less common but potentially devastating human diseases including sideroblastic anemias, neurodegenerative disorders, and hemophagocytic syndrome. Additionally, recent research describes novel functions of ferritin independent of iron storage. PMID:18835072
Joswig, Holger; Hildebrandt, Gerhard
2017-07-01
In between Carl Wernicke's locationist aphasia concept from 1874 and Norman Geschwind's new connectionist model of human brain functions in 1965, little notice was taken of the historical debate on aphasia and brain plasticity. Interestingly, Kurt Goldstein made long-forgotten, but highly relevant remarks on the connectionist model and thereby served as an important connecting link between Wernicke and Geschwind. With the original contributions of Goldstein and contemporary authors, we analyzed the historical background of the aphasia debate in the time period between Wernicke and Geschwind, which still influences current aphasia concepts and neurosurgical practice of today.
Endocannabinoid signalling and the deteriorating brain
Di Marzo, Vincenzo; Stella, Nephi; Zimmer, Andreas
2015-01-01
Ageing is characterized by the progressive impairment of physiological functions and increased risk of developing debilitating disorders, including chronic inflammation and neurodegenerative diseases. These disorders have common molecular mechanisms that can be targeted therapeutically. In the wake of the approval of the first cannabinoid-based drug for the symptomatic treatment of multiple sclerosis, we examine how endocannabinoid (eCB) signalling controls — and is affected by — normal ageing and neuroinflammatory and neurodegenerative disorders. We propose a conceptual framework linking eCB signalling to the control of the cellular and molecular hallmarks of these processes, and categorize the key components of endocannabinoid signalling that may serve as targets for novel therapeutics. PMID:25524120
1994-06-17
LINK? .......... .. 19 The People ...... ............... .. 19 The Impact .......... ............ .. 21 V WHAT DOES IT ALL MEAN ? ... ......... .. 23...people who will serve as the key link in the chain needed to pull the system together. 22 CHAPTER V WHAT DOES IT ALL MEAN ? Conclusions. As the military
Polymer-silica hybrids for separation of CO2 and catalysis of organic reactions
NASA Astrophysics Data System (ADS)
Silva Mojica, Ernesto
Porous materials comprising polymeric and inorganic segments have attracted interest from the scientific community due to their unique properties and functionalities. The physical and chemical characteristics of these materials can be effectively exploited for adsorption applications. This dissertation covers the experimental techniques for fabrication of poly(vinyl alcohol) (PVA) and silica (SiO2) porous supports, and their functionalization with polyamines for developing adsorbents with potential applications in separation of CO2 and catalysis of organic reactions. The supports were synthesized by processes involving (i) covalent cross-linking of PVA, (ii) hydrolysis and poly-condensation of silica precursors (i,e,. sol-gel synthesis), and formation of porous structures via (iii) direct templating and (iv) phase inversion techniques. Their physical structure was controlled by the proper combination of the preparation procedures, which resulted in micro-structured porous materials in the form of micro-particles, membranes, and pellets. Their adsorption characteristics were tailored by functionalization with polyethyleneimine (PEI), and their physicochemical properties were characterized by vibrational spectroscopy (FTIR, UV-vis), microscopy (SEM), calorimetry (TGA, DSC), and adsorption techniques (BET, step-switch adsorption). Spectroscopic investigations of the interfacial cross-linking reactions of PEI and PVA with glutaraldehyde (GA) revealed that PEI catalyzes the cross-linking reactions of PVA in absence of external acid catalysts. In-situ IR spectroscopy coupled with a focal plane array (FPA) image detector allowed the characterization of a gradient interface on a PEI/PVA composite membrane and the investigation of the cross-linking reactions as a function of time and position. The results served as a basis to postulate possible intermediates, and propose the reaction mechanisms. The formulation of amine-functionalized CO2 capture sorbents was based on the spectroscopic investigation of the interactions of CO 2 with amine molecules under simulated CO2 capture conditions. Industrial CO2 capture processes involve fluidization and require degradation-resistant sorbents in the form of pellets. Agglomeration of silica-based CO2 capture sorbents involved the formulation of a polymer binder solution and the design of a scalable pelletization process. The characterization of these pellets revealed the formation of a CO 2-permeable polymer-silica network, which is resistant to attrition, and exhibits similar CO2 capture and degradation performance as the non-pelletized sorbents. The performance of these sorbents and pellets was tested in lab-scale and bench-scale adsorption units, using in-house fabricated fixed-bed and fluidized-bed reactors. A compartmental modeling technique was used to simulate the CO2 adsorption process and to elucidate the kinetic and thermodynamic parameters that impact the commercial viability of emerging CO2 capture technologies. The fundamental concepts and experimental techniques developed for the preparation of CO2 capture sorbents served as a basis for fabricating amine-functionalized polymer-silica hybrids for applications in catalysis of organic reactions. (i) Basic catalysts for carbon-carbon addition reactions were prepared by immobilization of amine molecules on silica supports. The activity of these catalysts and the mechanisms of base-catalyzed organic condensation reactions were investigated by an in-situ FTIR micro-scale reactor. (ii) Particle-loaded PVA composite membranes were selected for immobilization of glucose oxidase (GOx). GOx was immobilized by adsorption at pH values between 3.5 and 7.1. The results showed that adsorption was primarily achieved via hydrophobic interactions, and that PVA membranes loaded with amine-functionalized particles could help retain the activity of immobilized GOx by providing a proper hydrophilic/hydrophobic balance to the immobilized enzymes micro-environment.
The Electron Microscopy Outreach Program: A Web-based resource for research and education.
Sosinsky, G E; Baker, T S; Hand, G; Ellisman, M H
1999-01-01
We have developed a centralized World Wide Web (WWW)-based environment that serves as a resource of software tools and expertise for biological electron microscopy. A major focus is molecular electron microscopy, but the site also includes information and links on structural biology at all levels of resolution. This site serves to help integrate or link structural biology techniques in accordance with user needs. The WWW site, called the Electron Microscopy (EM) Outreach Program (URL: http://emoutreach.sdsc.edu), provides scientists with computational and educational tools for their research and edification. In particular, we have set up a centralized resource containing course notes, references, and links to image analysis and three-dimensional reconstruction software for investigators wanting to learn about EM techniques either within or outside of their fields of expertise. Copyright 1999 Academic Press.
Compositional dynamics of the human intestinal microbiota with aging: implications for health.
Lakshminarayanan, B; Stanton, C; O'Toole, P W; Ross, R P
2014-11-01
The human gut contains trillions of microbes which form an essential part of the complex ecosystem of the host. This microbiota is relatively stable throughout adult life, but may fluctuate over time with aging and disease. The gut microbiota serves a number of functions including roles in energy provision, nutrition and also in the maintenance of host health such as protection against pathogens. This review summarizes the age-related changes in the microbiota of the gastrointestinal tract (GIT) and the link between the gut microbiota in health and disease. Understanding the composition and function of the gut microbiota along with the changes it undergoes overtime should aid the design of novel therapeutic strategies to counteract such alterations. These strategies include probiotic and prebiotic preparations as well as targeted nutrients, designed to enrich the gut microbiota of the aging population.
Surface Sites for Engineering Allosteric Control in Proteins
Lee, Jeeyeon; Natarajan, Madhusudan; Nashine, Vishal C.; Socolich, Michael; Vo, Tina; Russ, William P.; Benkovic, Stephen J.; Ranganathan, Rama
2010-01-01
Statistical analyses of protein families reveal networks of coevolving amino acids that functionally link distantly positioned functional surfaces. Such linkages suggest a concept for engineering allosteric control into proteins: The intramolecular networks of two proteins could be joined across their surface sites such that the activity of one protein might control the activity of the other. We tested this idea by creating PAS-DHFR, a designed chimeric protein that connects a light-sensing signaling domain from a plant member of the Per/Arnt/Sim (PAS) family of proteins with Escherichia coli dihydrofolate reductase (DHFR). With no optimization, PAS-DHFR exhibited light-dependent catalytic activity that depended on the site of connection and on known signaling mechanisms in both proteins. PAS-DHFR serves as a proof of concept for engineering regulatory activities into proteins through interface design at conserved allosteric sites. PMID:18927392
Thriving on Stress for Success. Principals Taking Action Series.
ERIC Educational Resources Information Center
Gmelch, Walter H.; Chan, Wilbert
When properly managed, stress can serve as a key to successful job performance. This book explores the link between pressure and performance in schools. It shows how to recognize stress as both a facilitator and debilitator of effective performance. Chapter 1 serves as a personal stress checkup. Chapter 2 explores the myths of administrative…
ERIC Educational Resources Information Center
Powers, Stefanie
2012-01-01
Fostering healthy social and emotional development provides the foundation for school readiness in programs serving infants, toddlers, and their families. In this article, the author explores four key concepts that make the link between social and emotional development and early learning: 1) Cognitive and social-emotional development are…
Preventing Student Expulsions through Policies, and Procedures for At-Risk Students
ERIC Educational Resources Information Center
Smith, Michael Dale
2012-01-01
Staff members working at alternative schools must use best practices to effectively serve at-risk students and reduce expulsion rates. Expulsion is directly linked to high school dropout rates, with subsequent social costs. Today's alternative schools serve at-risk students who exhibit problematic behaviors, providing them an opportunity to…
Communication: A Plan for Small School Districts.
ERIC Educational Resources Information Center
Council of Communicators, Austin, TX.
Since communication is the working link between the school district and the community it serves, public school administrators serving small towns or rural areas are developing a planned program of two-way communication based on a clear policy statement adopted by the board of trustees which basically upholds the public's right to know. In order to…
El Hajj, Elia C; El Hajj, Milad C; Ninh, Van K; Gardner, Jason D
2018-05-18
The cardiac extracellular matrix is a complex architectural network that serves many functions including providing structural and biochemical support to surrounding cells, and regulating intercellular signaling pathways. Cardiac function is directly affected by extracellular matrix (ECM) composition, and alterations of the ECM contribute to progression of heart failure. Initially, collagen deposition is an adaptive response that aims to preserve tissue integrity and maintain normal ventricular function. However, the synergistic effects of the pro-inflammatory and pro-fibrotic responses induce a vicious cycle which causes excess activation of myofibroblasts, significantly increasing collagen deposition and accumulation in the matrix. Further, excess synthesis and activation of the enzyme lysyl oxidase (LOX) during disease increases collagen cross-linking, which significantly increases collagen resistance to degradation by matrix metalloproteinases (MMPs). In this study, the aortocaval fistula model of volume overload (VO) was used to determine whether LOX inhibition could prevent adverse changes in the ECM and subsequent cardiac dysfunction. The major findings from this study are that LOX inhibition: (a) prevented VO-induced increases in LV wall stress, (b) partially attenuated VO-induced ventricular hypertrophy, (c) completely blocked the increases in fibrotic proteins, including collagens, MMPs, and their tissue inhibitors (TIMPs), and (d) prevented the VO-induced decline in cardiac function. It remains unclear whether a direct interaction between LOX and MMPs exists; however our studies suggest a potential link between the two since LOX inhibition completely attenuated the VO-induced increases in MMPs. Overall, our studies demonstrate key cardioprotective effects of LOX inhibition against adverse cardiac remodeling due to chronic VO.
A top-down perspective on dopamine, motivation and memory.
Phillips, Anthony G; Vacca, Giada; Ahn, Soyon
2008-08-01
Dopamine (DA) activity, in the form of increased neural firing or enhanced release of transmitter from nerve terminals and varicosities, is linked to a number of important psychological processes including: movement; hedonic reactions to positive reward; provision of an error detection signal during the acquisition of new learning; response to novel stimuli; provision of reinforcement signals essential for acquisition of new action patterns; and incentive motivation. This review focuses primarily on our research linking dynamic changes in DA efflux on the timescale of minutes, with incentive motivation, as revealed by brain dialysis experiments in behaving animals. Recent experiments on sensory-specific satiety and successive positive and negative contrast are discussed along with the distinction between preparatory behaviors that precede contact with biologically significant stimuli and subsequent consummatory behaviors. The relationship between DA efflux in the medial prefrontal cortex (mPFC) and foraging for food based on working memory is also discussed in support of the conjecture that DA may serve as a link between motivation and memory functions. Evidence in support of 'top-down' regulation of dopaminergic activity in the mesocorticolimbic DA pathways is reviewed briefly to introduce a mechanism by which activation of ascending DA projections in this manner might optimize dopaminergic modulation of executive function within regions such as the mPFC. Collectively, these processes could ensure coordination between cognitive processes that assess current opportunities and the motivational systems that select and engage patterns of approach behavior that bring organisms into contact with the essentials for survival.
Grow-ING, Age-ING and Die-ING: ING proteins link cancer, senescence and apoptosis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Russell, Michael; Berardi, Philip; Gong Wei
The INhibitor of Growth (ING) family of plant homeodomain (PHD) proteins induce apoptosis and regulate gene expression through stress-inducible binding of phospholipids with subsequent nuclear and nucleolar localization. Relocalization occurs concomitantly with interaction with a subset of nuclear proteins, including PCNA, p53 and several regulators of acetylation such as the p300/CBP and PCAF histone acetyltransferases (HATs), as well as the histone deacetylases HDAC1 and hSir2. These interactions alter the localized state of chromatin compaction, subsequently affecting the expression of subsets of genes, including those associated with the stress response (Hsp70), apoptosis (Bax, MDM2) and cell cycle regulation (p21{sup WAF1}, cyclinmore » B) in a cell- and tissue-specific manner. The expression levels and subcellular localization of ING proteins are altered in a significant number of human cancer types, while the expression of ING isoforms changes during cellular aging, suggesting that ING proteins may play a role in linking cellular transformation and replicative senescence. The variety of functions attributed to ING proteins suggest that this tumor suppressor serves to link the disparate processes of cell cycle regulation, cell suicide and cellular aging through epigenetic regulation of gene expression. This review examines recent findings in the ING field with a focus on the functions of protein-protein interactions involving ING family members and the mechanisms by which these interactions facilitate the various roles that ING proteins play in tumorigenesis, apoptosis and senescence.« less
DOT National Transportation Integrated Search
2010-10-01
Re-Os isotope measurements of sulfide minerals from 10 occurrences that span a radial distance of over 200 Km : serve to geochemically link epithermal mineralization in Pennsylvania to an Eocene event. The most likely geologic : event that could have...
New Perspectives on the Technical Communication Internship: Professionalism in the Workplace
ERIC Educational Resources Information Center
Bourelle, Tiffany
2014-01-01
This article argues for developing linked courses in technical communication where the instructor facilitates a service-learning curriculum and then serves as faculty advisor within subsequent internships. In these linked courses, students write technical documents before moving into internships where they write similar documents. Specifically,…
Malone, Andrew F; Funk, Steven D; Alhamad, Tarek; Miner, Jeffrey H
2017-06-01
Many COL4A5 splice region variants have been described in patients with X-linked Alport syndrome, but few have been confirmed by functional analysis to actually cause defective splicing. We sought to demonstrate that a novel COL4A5 splice region variant in a family with Alport syndrome is pathogenic using functional studies. We also describe an alternative method of diagnosis. Targeted next-generation sequencing results of an individual with Alport syndrome were analyzed and the results confirmed by Sanger sequencing in family members. A splicing reporter minigene assay was used to examine the variant's effect on splicing in transfected cells. Plucked hair follicles from patients and controls were examined for collagen IV proteins using immunofluorescence microscopy. A novel splice region mutation in COL4A5, c.1780-6T>G, was identified and segregated with disease in this family. This variant caused frequent skipping of exon 25, resulting in a frameshift and truncation of collagen α5(IV) protein. We also developed and validated a new approach to characterize the expression of collagen α5(IV) protein in the basement membranes of plucked hair follicles. Using this approach we demonstrated reduced collagen α5(IV) protein in affected male and female individuals in this family, supporting frequent failure of normal splicing. Differing normal to abnormal transcript ratios in affected individuals carrying splice region variants may contribute to variable disease severity observed in Alport families. Examination of plucked hair follicles in suspected X-linked Alport syndrome patients may offer a less invasive alternative method of diagnosis and serve as a pathogenicity test for COL4A5 variants of uncertain significance.
Malone, Andrew F.; Funk, Steven D.; Alhamad, Tarek; Miner, Jeffrey H.
2016-01-01
Introduction Many COL4A5 splice region variants have been described in patients with X-linked Alport syndrome, but few have been confirmed by functional analysis to actually cause defective splicing. We sought to demonstrate that a novel COL4A5 splice region variant in a family with Alport syndrome is pathogenic using functional studies. We also describe an alternative method of diagnosis. Methods We analyzed targeted next-generation sequencing results of an individual with Alport syndrome and confirmed results by Sanger sequencing in family members. A splicing reporter minigene assay was used to examine the variant’s effect on splicing in transfected cells. Plucked hair follicles from patients and controls were examined for collagen IV proteins using immunofluorescence microscopy. Results A novel splice region mutation in COL4A5, c.1780-6T>G, was identified and segregated with disease in this family. This variant caused frequent skipping of exon 25, resulting in a frameshift and truncation of collagen α5(IV) protein. We also developed and validated a new approach to characterize the expression of collagen α5(IV) protein in the basement membranes of plucked hair follicles. We demonstrated reduced collagen α5(IV) protein in affected male and female individuals in this family, supporting frequent failure of normal splicing. Conclusions Differing normal to abnormal transcript ratios in affected individuals carrying splice region variants may contribute to variable disease severity observed in Alport families. Examination of plucked hair follicles in suspected X-linked Alport syndrome patients may offer a less invasive alternative method of diagnosis and serve as a pathogenicity test for COL4A5 variants of uncertain significance. PMID:28013382
MSD-MAP: A Network-Based Systems Biology Platform for Predicting Disease-Metabolite Links.
Wathieu, Henri; Issa, Naiem T; Mohandoss, Manisha; Byers, Stephen W; Dakshanamurthy, Sivanesan
2017-01-01
Cancer-associated metabolites result from cell-wide mechanisms of dysregulation. The field of metabolomics has sought to identify these aberrant metabolites as disease biomarkers, clues to understanding disease mechanisms, or even as therapeutic agents. This study was undertaken to reliably predict metabolites associated with colorectal, esophageal, and prostate cancers. Metabolite and disease biological action networks were compared in a computational platform called MSD-MAP (Multi Scale Disease-Metabolite Association Platform). Using differential gene expression analysis with patient-based RNAseq data from The Cancer Genome Atlas, genes up- or down-regulated in cancer compared to normal tissue were identified. Relational databases were used to map biological entities including pathways, functions, and interacting proteins, to those differential disease genes. Similar relational maps were built for metabolites, stemming from known and in silico predicted metabolite-protein associations. The hypergeometric test was used to find statistically significant relationships between disease and metabolite biological signatures at each tier, and metabolites were assessed for multi-scale association with each cancer. Metabolite networks were also directly associated with various other diseases using a disease functional perturbation database. Our platform recapitulated metabolite-disease links that have been empirically verified in the scientific literature, with network-based mapping of jointly-associated biological activity also matching known disease mechanisms. This was true for colorectal, esophageal, and prostate cancers, using metabolite action networks stemming from both predicted and known functional protein associations. By employing systems biology concepts, MSD-MAP reliably predicted known cancermetabolite links, and may serve as a predictive tool to streamline conventional metabolomic profiling methodologies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.
A web-based system architecture for ontology-based data integration in the domain of IT benchmarking
NASA Astrophysics Data System (ADS)
Pfaff, Matthias; Krcmar, Helmut
2018-03-01
In the domain of IT benchmarking (ITBM), a variety of data and information are collected. Although these data serve as the basis for business analyses, no unified semantic representation of such data yet exists. Consequently, data analysis across different distributed data sets and different benchmarks is almost impossible. This paper presents a system architecture and prototypical implementation for an integrated data management of distributed databases based on a domain-specific ontology. To preserve the semantic meaning of the data, the ITBM ontology is linked to data sources and functions as the central concept for database access. Thus, additional databases can be integrated by linking them to this domain-specific ontology and are directly available for further business analyses. Moreover, the web-based system supports the process of mapping ontology concepts to external databases by introducing a semi-automatic mapping recommender and by visualizing possible mapping candidates. The system also provides a natural language interface to easily query linked databases. The expected result of this ontology-based approach of knowledge representation and data access is an increase in knowledge and data sharing in this domain, which will enhance existing business analysis methods.
Living with disability: patterns of health problems and symptom mediation of health consequences.
Patterson, Brandon J; Doucette, William R; Lindgren, Scott D; Chrischilles, Elizabeth A
2012-07-01
People with disability experience a range of symptoms that may serve as an important linkage between disability and other health consequences. The aims of this study were to describe and compare symptom experiences of people with and without disability using a population-based sample and to test direct relationships between disability and health status and indirect effects of disability mediated through symptom experience. A Midwestern sample of 12,249 adults aged 40 and older responded to a cross-sectional survey. Data collected included symptom prevalence and frequencies for 21 commonly reported symptoms, self-perceived health status and physical functioning, number of medications, and demographic variables. Two mediation analyses were conducted using cumulative symptom frequency as the mediator between disability status and both self-rated health and physical functioning. Adults with disability reported significantly greater prevalence and frequencies for all 21 symptoms, with pain and fatigue being the most common. The indirect effect through cumulative symptom frequency explained roughly half of the total effect of disability on general health status, and about one third of the total effect of disability on physical functioning. This study found evidence supporting the diverse and significant symptom experience of people living with disability, especially for symptoms of pain and fatigue. Moreover, symptom experience was found to partially mediate the effects of disability on self-reported general health status and physical functioning. This provides support for symptoms serving as an important link to health outcomes in patients with disability. Copyright © 2012 Elsevier Inc. All rights reserved.
NMR Guided Design of Endcaps With Improved Oxidation Resistance
NASA Technical Reports Server (NTRS)
Meador, Mary Ann B.; Frimer, Aryeh A.
2002-01-01
A polyimide is a polymer composed of alternating units of diamine and dianhydride, linked to each other via an imide bond. PMR polyimides, commonly used in the aerospace industry, are generally capped at each end by a norbornene endcap which serves a double function: (1) It limits the number of repeating units and, hence, the average molecular weight of the various polymer chains (oligomers), thereby improving processibility; (2) Upon further treatment (curing), the endcap crosslinks the various oligomer strands into a tough heat-resistant piece. Norbornenyl-end capped PMR polyimide resins' are widely used as polymer matrix composite materials for aircraft engine applications,2 since they combine ease of processing with good oxidative stability up to 300 C. PMR resins are prepared by a twestep approach involving the initial formation of oligomeric pre-polymers capped at both ends by a latent reactive end cap. The end cap undergoes cross-linking during higher temperature processing, producing the desired low density, high specific strength materials, as shown for PMR-15.
Polymer physics of chromosome large-scale 3D organisation
NASA Astrophysics Data System (ADS)
Chiariello, Andrea M.; Annunziatella, Carlo; Bianco, Simona; Esposito, Andrea; Nicodemi, Mario
2016-07-01
Chromosomes have a complex architecture in the cell nucleus, which serves vital functional purposes, yet its structure and folding mechanisms remain still incompletely understood. Here we show that genome-wide chromatin architecture data, as mapped by Hi-C methods across mammalian cell types and chromosomes, are well described by classical scaling concepts of polymer physics, from the sub-Mb to chromosomal scales. Chromatin is a complex mixture of different regions, folded in the conformational classes predicted by polymer thermodynamics. The contact matrix of the Sox9 locus, a region linked to severe human congenital diseases, is derived with high accuracy in mESCs and its molecular determinants identified by the theory; Sox9 self-assembles hierarchically in higher-order domains, involving abundant many-body contacts. Our approach is also applied to the Bmp7 locus. Finally, the model predictions on the effects of mutations on folding are tested against available data on a deletion in the Xist locus. Our results can help progressing new diagnostic tools for diseases linked to chromatin misfolding.
Crawshaw, Marilyn A; Blyth, Eric D; Feast, Julia
2017-06-01
Current birth registration systems fail to serve adequately the interests of those born as a result of gamete and embryo donation and surrogacy. In the UK, changes to the birth registration system have been piecemeal, reactive and situation-specific and no information is recorded about gamete donors. Birth registration has thereby become a statement of legal parentage and citizenship only, without debate as to whether it should serve any wider functions. This sits uneasily with the increasingly accepted human right to know one's genetic and gestational as well as legal parents, and the duty of the State to facilitate that right. This commentary sets out one possible model for reform to better ensure that those affected become aware of, and/or have access to, knowledge about their origins and that such information is stored and released effectively without compromising individual privacy. Among other features, our proposal links the birth registration system and the information stored in the Human Fertilization and Embryology Authority's Register of Information, although further work than we have been able to undertake here is necessary to ensure a better fit where cross-border treatment services or informal arrangements have been involved. The time for debate and reform is well overdue.
A simple method for serving Web hypermaps with dynamic database drill-down
Boulos, Maged N Kamel; Roudsari, Abdul V; Carson, Ewart R
2002-01-01
Background HealthCyberMap aims at mapping parts of health information cyberspace in novel ways to deliver a semantically superior user experience. This is achieved through "intelligent" categorisation and interactive hypermedia visualisation of health resources using metadata, clinical codes and GIS. HealthCyberMap is an ArcView 3.1 project. WebView, the Internet extension to ArcView, publishes HealthCyberMap ArcView Views as Web client-side imagemaps. The basic WebView set-up does not support any GIS database connection, and published Web maps become disconnected from the original project. A dedicated Internet map server would be the best way to serve HealthCyberMap database-driven interactive Web maps, but is an expensive and complex solution to acquire, run and maintain. This paper describes HealthCyberMap simple, low-cost method for "patching" WebView to serve hypermaps with dynamic database drill-down functionality on the Web. Results The proposed solution is currently used for publishing HealthCyberMap GIS-generated navigational information maps on the Web while maintaining their links with the underlying resource metadata base. Conclusion The authors believe their map serving approach as adopted in HealthCyberMap has been very successful, especially in cases when only map attribute data change without a corresponding effect on map appearance. It should be also possible to use the same solution to publish other interactive GIS-driven maps on the Web, e.g., maps of real world health problems. PMID:12437788
ERIC Educational Resources Information Center
Tran, Natalie A.; Jean-Marie, Gaetane; Powers, Katherine; Bell, Sean; Sanders, Kimberly
2016-01-01
There is a growing body of evidence that links increased social capital to minority student success in college. This paper seeks to expand specifically on the graduate experience of underrepresented minorities (URM) at a Hispanic Serving Institution (HSI) using the social capital framework. In a cross-sectional survey, 198 graduate students…
Schwieterman, Alicia A.; Steves, Alyse N.; Yee, Vivian; Donelson, Cory J.; Bentley, Melissa R.; Santorella, Elise M.; Mehlenbacher, Taylor V.; Pital, Aaron; Howard, Austin M.; Wilson, Melissa R.; Ereddia, Danielle E.; Effrein, Kelsie S.; McMurry, Jonathan L.; Ackley, Brian D.; Chisholm, Andrew D.; Hudson, Martin L.
2016-01-01
The Eph receptors and their cognate ephrin ligands play key roles in many aspects of nervous system development. These interactions typically occur within an individual tissue type, serving either to guide axons to their terminal targets or to define boundaries between the rhombomeres of the hindbrain. We have identified a novel role for the Caenorhabditis elegans ephrin EFN-4 in promoting primary neurite outgrowth in AIY interneurons and D-class motor neurons. Rescue experiments reveal that EFN-4 functions non-cell autonomously in the epidermis to promote primary neurite outgrowth. We also find that EFN-4 plays a role in promoting ectopic axon branching in a C. elegans model of X-linked Kallmann syndrome. In this context, EFN-4 functions non-cell autonomously in the body-wall muscle and in parallel with HS modification genes and HSPG core proteins. This is the first report of an epidermal ephrin providing a developmental cue to the nervous system. PMID:26645816
Psychoanalysis and the Brain – Why Did Freud Abandon Neuroscience?
Northoff, Georg
2012-01-01
Sigmund Freud, the founder of psychoanalysis, was initially a neuroscientist but abandoned neuroscience completely after he made a last attempt to link both in his writing, “Project of a Scientific Psychology,” in 1895. The reasons for his subsequent disregard of the brain remain unclear though. I here argue that one central reason may be that the approach to the brain during his time was simply not appealing to Freud. More specifically, Freud was interested in revealing the psychological predispositions of psychodynamic processes. However, he was not so much focused on the actual psychological functions themselves which though were the prime focus of the neuroscience at his time and also in current Cognitive Neuroscience. Instead, he probably would have been more interested in the brain’s resting state and its constitution of a spatiotemporal structure. I here assume that the resting state activity constitutes a statistically based virtual structure extending and linking the different discrete points in time and space within the brain. That in turn may serve as template, schemata, or grid for all subsequent neural processing during stimulus-induced activity. As such the resting state’ spatiotemporal structure may serve as the neural predisposition of what Freud described as “psychological structure.” Hence, Freud and also current neuropsychoanalysis may want to focus more on neural predispositions, the necessary non-sufficient conditions, rather than the neural correlates, i.e., sufficient, conditions of psychodynamic processes. PMID:22485098
Molecular Cogs: Interplay between Circadian Clock and Cell Cycle.
Gaucher, Jonathan; Montellier, Emilie; Sassone-Corsi, Paolo
2018-05-01
The cell cycle and the circadian clock operate as biological oscillators whose timed functions are tightly regulated. Accumulating evidence illustrates the presence of molecular links between these two oscillators. This mutual interplay utilizes various coupling mechanisms, such as the use of common regulators. The connection between these two cyclic systems has unique interest in the context of aberrant cell proliferation since both of these oscillators are frequently misregulated in cancer cells. Further studies will provide deeper understanding of the detailed molecular connections between the cell cycle and the circadian clock and may also serve as a basis for the design of innovative therapeutic strategies. Copyright © 2018 Elsevier Ltd. All rights reserved.
Novel CuS-based nanoprobes for photoacoustic molecular imaging in the second near-infrared region
NASA Astrophysics Data System (ADS)
Yuan, Zhen; Gao, Duyang
2018-02-01
In this work, protein-modified hydrophilic copper sufide (CuS) nanotriangles with tunable absorption in the second near-infrared (NIR-II) region are developed, which can be served as contrast agents for enhanced in vivo photoacoustic imaging. In vitro and in vivo toxicity analysis are also performed, which show that the nanoprobes are biocompatible for most of the test cases. As a result, the nanoprones is able to pave a new avenue for improving the photoacoustic imaigng contrast and penetration depth in cancer detection. It should be pointed out that other functional blocks may also be linked on it, which makes it a general method to design multifunctional nanoprobes.
A Review of Membrane-Based Biosensors for Pathogen Detection
van den Hurk, Remko; Evoy, Stephane
2015-01-01
Biosensors are of increasing interest for the detection of bacterial pathogens in many applications such as human, animal and plant health, as well as food and water safety. Membranes and membrane-like structures have been integral part of several pathogen detection platforms. Such structures may serve as simple mechanical support, function as a part of the transduction mechanism, may be used to filter out or concentrate pathogens, and may be engineered to specifically house active proteins. This review focuses on membrane materials, their associated biosensing applications, chemical linking procedures, and transduction mechanisms. The sensitivity of membrane biosensors is discussed, and the state of the field is evaluated and summarized. PMID:26083229
Ronchi, Virginia P; Kim, Elizabeth D; Summa, Christopher M; Klein, Jennifer M; Haas, Arthur L
2017-11-03
To understand the mechanism for assembly of Lys 48 -linked polyubiquitin degradation signals, we previously demonstrated that the E6AP/UBE3A ligase harbors two functionally distinct E2∼ubiquitin-binding sites: a high-affinity Site 1 required for E6AP Cys 820 ∼ubiquitin thioester formation and a canonical Site 2 responsible for subsequent chain elongation. Ordered binding to Sites 1 and 2 is here revealed by observation of UbcH7∼ubiquitin-dependent substrate inhibition of chain formation at micromolar concentrations. To understand substrate inhibition, we exploited the PatchDock algorithm to model in silico UbcH7∼ubiquitin bound to Site 1, validated by chain assembly kinetics of selected point mutants. The predicted structure buries an extensive solvent-excluded surface bringing the UbcH7∼ubiquitin thioester bond within 6 Å of the Cys 820 nucleophile. Modeling onto the active E6AP trimer suggests that substrate inhibition arises from steric hindrance between Sites 1 and 2 of adjacent subunits. Confirmation that Sites 1 and 2 function in trans was demonstrated by examining the effect of E6APC820A on wild-type activity and single-turnover pulse-chase kinetics. A cyclic proximal indexation model proposes that Sites 1 and 2 function in tandem to assemble thioester-linked polyubiquitin chains from the proximal end attached to Cys 820 before stochastic en bloc transfer to the target protein. Non-reducing SDS-PAGE confirms assembly of the predicted Cys 820 -linked 125 I-polyubiquitin thioester intermediate. Other studies suggest that Glu 550 serves as a general base to generate the Cys 820 thiolate within the low dielectric binding interface and Arg 506 functions to orient Glu 550 and to stabilize the incipient anionic transition state during thioester exchange. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.
NASA Astrophysics Data System (ADS)
Xing, Ling-Bao; Hou, Shu-Fen; Zhou, Jin; Zhang, Jing-Li; Si, Weijiang; Dong, Yunhui; Zhuo, Shuping
2015-10-01
In present work, we demonstrate an efficient and facile strategy to fabricate three-dimensional (3D) nitrogen-doped graphene aerogels (NGAs) based on melamine, which serves as reducing and functionalizing agent of graphene oxide (GO) in an aqueous medium with ammonia. Benefiting from well-defined and cross-linked 3D porous network architectures, the supercapacitor based on the NGAs exhibited a high specific capacitance of 170.5 F g-1 at 0.2 A g-1, and this capacitance also showed good electrochemical stability and a high degree of reversibility in the repetitive charge/discharge cycling test. More interestingly, the prepared NGAs further exhibited high adsorption capacities and high recycling performance toward several metal ions such as Pb2+, Cu2+ and Cd2+. Moreover, the hydrophobic carbonized nitrogen-doped graphene aerogels (CNGAs) showed outstanding adsorption and recycling performance for the removal of various oils and organic solvents.
Abandon or embrace: Functionalism perspective of photojournalists on Syrian refugees
NASA Astrophysics Data System (ADS)
Tsuroyya; Tandyonomanu, D.; Dharmawan, A.
2018-01-01
This research examines photojournalist’ perspectives of Syrian refugees in Europe, encoding, and dissemination processes. It employs a qualitative approach and functionalism perspective of mass media by sending questionnaires to voluntary respondents. The findings show sharing similar background and/or having experiences in the Middle Eastern countries highly influence the perspective of photojournalists on Syrian refugees. The encoding process covers through research of priority issues, target audience, trustworthiness of photos, and audience interpretation. The distribution method includes taking advantages of personal social media to promote the links of photos. As part of mass media industry, photojournalists play a crucial role to contribute to social integration, particularly, in creating a shared understanding between European community and Syrian refugees. The current research serves as a basis to future investigations on the perspective of European community towards Syrian refugees, whether or not their perspective is influenced by such photos.
Tilsner, Jens; Nicolas, William; Rosado, Abel; Bayer, Emmanuelle M
2016-04-29
Multicellularity differs in plants and animals in that the cytoplasm, plasma membrane, and endomembrane of plants are connected between cells through plasmodesmal pores. Plasmodesmata (PDs) are essential for plant life and serve as conduits for the transport of proteins, small RNAs, hormones, and metabolites during developmental and defense signaling. They are also the only pathways available for viruses to spread within plant hosts. The membrane organization of PDs is unique, characterized by the close apposition of the endoplasmic reticulum and the plasma membrane and spoke-like filamentous structures linking the two membranes, which define PDs as membrane contact sites (MCSs). This specialized membrane arrangement is likely critical for PD function. Here, we review how PDs govern developmental and defensive signaling in plants, compare them with other types of MCSs, and discuss in detail the potential functional significance of the MCS nature of PDs.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Harstad, E. N.; Harlow, Francis Harvey,; Schreyer, H. L.
Our goal is to develop constitutive relations for the behavior of a solid polymer during high-strain-rate deformations. In contrast to the classic thermodynamic techniques for deriving stress-strain response in static (equilibrium) circumstances, we employ a statistical-mechanics approach, in which we evolve a probability distribution function (PDF) for the velocity fluctuations of the repeating units of the chain. We use a Langevin description for the dynamics of a single repeating unit and a Lioville equation to describe the variations of the PDF. Moments of the PDF give the conservation equations for a single polymer chain embedded in other similar chains. Tomore » extract single-chain analytical constitutive relations these equations have been solved for representative loading paths. By this process we discover that a measure of nonuniform chain link displacement serves this purpose very well. We then derive an evolution equation for the descriptor function, with the result being a history-dependent constitutive relation.« less
[The function of analogies in natural sciences, also in contrast to metaphors and models].
Hentschel, Klaus
2010-01-01
This introduction surveys the various functions of analogies in science, medicine and technology. The focus is on their heuristic importance. The productiveness of analogies is linked to the systematic depth and breadth of the established connections. Various examples are presented from different periods in the history of science, most notably Galileo; such late-Victorian Maxwellians as George Francis FitzGerald and Oliver Lodge; and Heinrich HERTZ and Niels BOHR. These examples are examined in terms of the specific differing temporal ranges of their claimed validities. They serve as evidence or counterevidence for various systematic analyses of analogies as put forward by various philosophers of science, most notably Francis Bacon, John Stuart Mill, Ernst Mach, Harald Høffding, Ernest Nagel, Mary Hesse and Peter Achinstein. The analytic framework for analogies supported here is what the cognitive scientist Dedre Gentner has termed structure-mapping.
What is the role of impression management in adolescent cigarette smoking?
O'Callaghan, F; Doyle, J
2001-01-01
This study examined the role of impression management in cigarette smoking by linking the constructs of self-monitoring, perceived success in impression management, self-esteem and social anxiety among nonsmokers (NS), occasional smokers (OS), and frequent smokers (FS). High school students (N=243) in years 8-12 completed a questionnaire assessing the above-mentioned variables. Multivariate discriminant function analysis and a priori contrasts were used to analyze the data. In comparison to OS, FS and NS had the lowest levels of self-monitoring, perceived success in impression management and self-esteem, while having the highest levels of social anxiety. Cigarette use may serve an impression management function during adolescence and subsequently influences OS' level of smoking. Intervention programs need to give greater consideration to providing adolescents with alternative strategies for both social acceptance and the acquisition and maintenance of self-esteem.
Human factors evaluation of remote afterloading brachytherapy. Volume 2, Function and task analysis
DOE Office of Scientific and Technical Information (OSTI.GOV)
Callan, J.R.; Gwynne, J.W. III; Kelly, T.T.
1995-05-01
A human factors project on the use of nuclear by-product material to treat cancer using remotely operated afterloaders was undertaken by the Nuclear Regulatory Commission. The purpose of the project was to identify factors that contribute to human error in the system for remote afterloading brachytherapy (RAB). This report documents the findings from the first phase of the project, which involved an extensive function and task analysis of RAB. This analysis identified the functions and tasks in RAB, made preliminary estimates of the likelihood of human error in each task, and determined the skills needed to perform each RAB task.more » The findings of the function and task analysis served as the foundation for the remainder of the project, which evaluated four major aspects of the RAB system linked to human error: human-system interfaces; procedures and practices; training and qualifications of RAB staff; and organizational practices and policies. At its completion, the project identified and prioritized areas for recommended NRC and industry attention based on all of the evaluations and analyses.« less
Kullmann, Stephanie; Heni, Martin; Veit, Ralf; Scheffler, Klaus; Machann, Jürgen; Häring, Hans-Ulrich; Fritsche, Andreas; Preissl, Hubert
2017-05-09
Brain insulin sensitivity is an important link between metabolism and cognitive dysfunction. Intranasal insulin is a promising tool to investigate central insulin action in humans. We evaluated the acute effects of 160 U intranasal insulin on resting-state brain functional connectivity in healthy young adults. Twenty-five lean and twenty-two overweight and obese participants underwent functional magnetic resonance imaging, on two separate days, before and after intranasal insulin or placebo application. Insulin compared to placebo administration resulted in increased functional connectivity between the prefrontal regions of the default-mode network and the hippocampus as well as the hypothalamus. The change in hippocampal functional connectivity significantly correlated with visceral adipose tissue and the change in subjective feeling of hunger after intranasal insulin. Mediation analysis revealed that the intranasal insulin induced hippocampal functional connectivity increase served as a mediator, suppressing the relationship between visceral adipose tissue and hunger. The insulin-induced hypothalamic functional connectivity change showed a significant interaction with peripheral insulin sensitivity. Only participants with high peripheral insulin sensitivity showed a boost in hypothalamic functional connectivity. Hence, brain insulin action may regulate eating behavior and facilitate weight loss by modifying brain functional connectivity within and between cognitive and homeostatic brain regions.
Route to Success: A Leader School's Youth Consultant Program. Linking Learning with Life.
ERIC Educational Resources Information Center
Kelley, Jennifer; Specter, Joanna; Young, Jamaal
This booklet explains how high schools can replicate the service learning youth consultant program that was originally formed at Spring Valley High School (SVHS) in Columbia, South Carolina, in 1996 to assume governance of SVHS's service learning program, which is called VikingServe. The booklet begins with an overview of VikingServe and a listing…
ERIC Educational Resources Information Center
Winfree, Terri L.
2012-01-01
Community college trustees are officials entrusted by the public to oversee the resources and property of community colleges; the board of trustees is seen as the link between the institution and the community they serve. Trustees make decisions that affect every aspect of an institution; therefore the accountability of these individuals at the…
Access and Use of MMS Data through SPDF Services
NASA Astrophysics Data System (ADS)
McGuire, R. E.; Bilitza, D.; Boardsen, S. A.; Candey, R. M.; Chimiak, R.; Cooper, J. F.; Garcia, L. N.; Harris, B. T.; Johnson, R. C.; Kovalick, T. J.; Lal, N.; Leckner, H. A.; Liu, M. H.; Papitashvili, N. E.; Rao, U. R.; Roberts, D. A.; Yurow, R. E.
2016-12-01
In its role as a Heliophysics Active Final Archive and in close cooperation with the MMS project and its Science Data Center, the Space Physics Data Facility (SPDF) now serves a full set of public MMS data and QuickLook plots. All SPDF services for this data and all data are available via links from the SPDF home page (http://spdf.gsfc.nasa.gov). SPDF's CDAWeb features MMS Level-2 survey and burst mode data with graphics, listing and data superset/subset functions. These capabilities are available (1) through our html user interface, (2) through calls to our CDAS web services API, and (3) through other interfaces and libraries using the CDAS web services or that otherwise access our holdings including SPDF's Heliophysics Data Portal and several external systems. As context in use of the MMS data, CDAWeb also serves current data from many other current missions. These include the Van Allen Probes 1/2 and the five THEMIS/ARTEMIS spacecraft, as well as e.g. ACE, Cluster 1/2/3/4, DMSP 16/17/18, Geotail, GOES 13/14/15, NOAA/POES 15/16/18/19, MetOP POES 1/2, Stereo A/B, TWINS 1/2, Wind and >120 Ground-Based investigations). This full set of public MMS Level-2 science data and QuickLook plots, and all other public data held by SPDF, are also available for direct file download by HTTP or FTP links from the SPDF home page above. As a reminder, MMS Level-2 data are publicly available about 30 days after data is taken, and QuickLook survey plots are available about a day after data is taken). MMS orbits (current and predictive) are served through SPDF's SSCWeb service and our Java-based interactive 4D Orbit Viewer, also with orbits of many other current missions). Our presentation will discuss recent enhancements to CDAWeb and other services and our plans to support new MMS data products and upcoming heliophysics missions including ICON, GOLD and Solar Probe Plus.
"Only Connect": Professors and Teachers with a Common Mission.
ERIC Educational Resources Information Center
Feldman, Sandra
1999-01-01
Higher education consistently fails to see that K-12 education and higher education, although discrete, are linked by a responsibility to the students served, that the sectors face similar threats, and that ultimately they are linked in success and failure. The good news is that collaborations between K-12 and higher education have begun and are…
Schoof, Heiko; Ernst, Rebecca; Nazarov, Vladimir; Pfeifer, Lukas; Mewes, Hans-Werner; Mayer, Klaus F. X.
2004-01-01
Arabidopsis thaliana is the most widely studied model plant. Functional genomics is intensively underway in many laboratories worldwide. Beyond the basic annotation of the primary sequence data, the annotated genetic elements of Arabidopsis must be linked to diverse biological data and higher order information such as metabolic or regulatory pathways. The MIPS Arabidopsis thaliana database MAtDB aims to provide a comprehensive resource for Arabidopsis as a genome model that serves as a primary reference for research in plants and is suitable for transfer of knowledge to other plants, especially crops. The genome sequence as a common backbone serves as a scaffold for the integration of data, while, in a complementary effort, these data are enhanced through the application of state-of-the-art bioinformatics tools. This information is visualized on a genome-wide and a gene-by-gene basis with access both for web users and applications. This report updates the information given in a previous report and provides an outlook on further developments. The MAtDB web interface can be accessed at http://mips.gsf.de/proj/thal/db. PMID:14681437
The Tale of the Storyteller and the Painter: The Paradoxes in Nature.
Chandra, Sadanandavalli Retnaswami; Viswanathan, Lakshminarayanapuram Gopal; Wahatule, Rahul; Shetty, Safal
2017-01-01
Brain as the seat of behavior is acknowledged from the times of Charaka, however where neurology ends and philosophy begins remains an enigma. It is certainly every neurologist's observation that there is loss of function either region based or domain based in progressive diseases of the nervous system making it the seat of all useful activities. However, there are references to occurrence of new skills seen during various illnesses causing progressive cognitive dysfunction. This serves as a pharmaco-sparing agent in behavior management and therefore serves as a rehabilitatory tool. However, its pathomechanism is not clear. Two patients comprising one male and one female who were being evaluated for progressive cognitive dysfunction and were found to have interesting creative skills and are being described. The first patient is a case of young onset behavioral variant frontotemporal dementia and the second patient is a case of neurosarcoidosis. The emergence of these skills could be due to disinhibition of some of the innate skills of the patients during degeneration or establishment of new data linking circuits with creative potential during attempted repair.
Gap junctional coupling in the vertebrate retina: variations on one theme?
Völgyi, Béla; Kovács-Oller, Tamás; Atlasz, Tamás; Wilhelm, Márta; Gábriel, Róbert
2013-05-01
Gap junctions connect cells in the bodies of all multicellular organisms, forming either homologous or heterologous (i.e. established between identical or different cell types, respectively) cell-to-cell contacts by utilizing identical (homotypic) or different (heterotypic) connexin protein subunits. Gap junctions in the nervous system serve electrical signaling between neurons, thus they are also called electrical synapses. Such electrical synapses are particularly abundant in the vertebrate retina where they are specialized to form links between neurons as well as glial cells. In this article, we summarize recent findings on retinal cell-to-cell coupling in different vertebrates and identify general features in the light of the evergrowing body of data. In particular, we describe and discuss tracer coupling patterns, connexin proteins, junctional conductances and modulatory processes. This multispecies comparison serves to point out that most features are remarkably conserved across the vertebrate classes, including (i) the cell types connected via electrical synapses; (ii) the connexin makeup and the conductance of each cell-to-cell contact; (iii) the probable function of each gap junction in retinal circuitry; (iv) the fact that gap junctions underlie both electrical and/or tracer coupling between glial cells. These pan-vertebrate features thus demonstrate that retinal gap junctions have changed little during the over 500 million years of vertebrate evolution. Therefore, the fundamental architecture of electrically coupled retinal circuits seems as old as the retina itself, indicating that gap junctions deeply incorporated in retinal wiring from the very beginning of the eye formation of vertebrates. In addition to hard wiring provided by fast synaptic transmitter-releasing neurons and soft wiring contributed by peptidergic, aminergic and purinergic systems, electrical coupling may serve as the 'skeleton' of lateral processing, enabling important functions such as signal averaging and synchronization. 2013 Elsevier Ltd. All rights reserved.
Dynamic Remodeling of Microbial Biofilms by Functionally Distinct Exopolysaccharides
Chew, Su Chuen; Kundukad, Binu; Seviour, Thomas; van der Maarel, Johan R. C.; Yang, Liang; Rice, Scott A.; Doyle, Patrick
2014-01-01
ABSTRACT Biofilms are densely populated communities of microbial cells protected and held together by a matrix of extracellular polymeric substances. The structure and rheological properties of the matrix at the microscale influence the retention and transport of molecules and cells in the biofilm, thereby dictating population and community behavior. Despite its importance, quantitative descriptions of the matrix microstructure and microrheology are limited. Here, particle-tracking microrheology in combination with genetic approaches was used to spatially and temporally study the rheological contributions of the major exopolysaccharides Pel and Psl in Pseudomonas aeruginosa biofilms. Psl increased the elasticity and effective cross-linking within the matrix, which strengthened its scaffold and appeared to facilitate the formation of microcolonies. Conversely, Pel reduced effective cross-linking within the matrix. Without Psl, the matrix becomes more viscous, which facilitates biofilm spreading. The wild-type biofilm decreased in effective cross-linking over time, which would be advantageous for the spreading and colonization of new surfaces. This suggests that there are regulatory mechanisms to control production of the exopolysaccharides that serve to remodel the matrix of developing biofilms. The exopolysaccharides were also found to have profound effects on the spatial organization and integration of P. aeruginosa in a mixed-species biofilm model of P. aeruginosa-Staphylococcus aureus. Pel was required for close association of the two species in mixed-species microcolonies. In contrast, Psl was important for P. aeruginosa to form single-species biofilms on top of S. aureus biofilms. Our results demonstrate that Pel and Psl have distinct physical properties and functional roles during biofilm formation. PMID:25096883
Williams, DeWayne P; Thayer, Julian F; Koenig, Julian
2016-12-01
Intraindividual reaction time variability (IIV), defined as the variability in trial-to-trial response times, is thought to serve as an index of central nervous system function. As such, greater IIV reflects both poorer executive brain function and cognitive control, in addition to lapses in attention. Resting-state vagally mediated heart rate variability (vmHRV), a psychophysiological index of self-regulatory abilities, has been linked with executive brain function and cognitive control such that those with greater resting-state vmHRV often perform better on cognitive tasks. However, research has yet to investigate the direct relationship between resting vmHRV and task IIV. The present study sought to examine this relationship in a sample of 104 young and healthy participants who first completed a 5-min resting-baseline period during which resting-state vmHRV was assessed. Participants then completed an attentional (target detection) task, where reaction time, accuracy, and trial-to-trial IIV were obtained. Results showed resting vmHRV to be significantly related to IIV, such that lower resting vmHRV predicted higher IIV on the task, even when controlling for several covariates (including mean reaction time and accuracy). Overall, our results provide further evidence for the link between resting vmHRV and cognitive control, and extend these notions to the domain of lapses in attention, as indexed by IIV. Implications and recommendations for future research on resting vmHRV and cognition are discussed. © 2016 Society for Psychophysiological Research.
Lo, Te-Wen; Bennett, Daniel C; Goodman, S Jay; Stern, Michael J
2010-06-01
The components of receptor tyrosine kinase signaling complexes help to define the specificity of the effects of their activation. The Caenorhabditis elegans fibroblast growth factor receptor (FGFR), EGL-15, regulates a number of processes, including sex myoblast (SM) migration guidance and fluid homeostasis, both of which require a Grb2/Sos/Ras cassette of signaling components. Here we show that SEM-5/Grb2 can bind directly to EGL-15 to mediate SM chemoattraction. A yeast two-hybrid screen identified SEM-5 as able to interact with the carboxy-terminal domain (CTD) of EGL-15, a domain that is specifically required for SM chemoattraction. This interaction requires the SEM-5 SH2-binding motifs present in the CTD (Y(1009) and Y(1087)), and these sites are required for the CTD role of EGL-15 in SM chemoattraction. SEM-5, but not the SEM-5 binding sites located in the CTD, is required for the fluid homeostasis function of EGL-15, indicating that SEM-5 can link to EGL-15 through an alternative mechanism. The multi-substrate adaptor protein FRS2 serves to link vertebrate FGFRs to Grb2. In C. elegans, an FRS2-like gene, rog-1, functions upstream of a Ras/MAPK pathway for oocyte maturation but is not required for EGL-15 function. Thus, unlike the vertebrate FGFRs, which require the multi-substrate adaptor FRS2 to recruit Grb2, EGL-15 can recruit SEM-5/Grb2 directly.
Facile Synthesis of Boron-Doped rGO as Cathode Material for High Energy Li–O 2 Batteries
DOE Office of Scientific and Technical Information (OSTI.GOV)
Wu, Feng; Xing, Yi; Li, Li
To improve the electrochemical performance of the high energy Li–O2 batteries, it is important to design and construct a suitable and effective oxygen-breathing cathode. Herein, a three-dimensional (3D) porous boron-doped reduction graphite oxide (B-rGO) material with a hierarchical structure has been prepared by a facile freeze-drying method. In this design, boric acid as the boron source helps to form the 3D porous structure, owing to its cross-linking and pore-forming function. This architecture facilitates the rapid oxygen diffusion and electrolyte penetration in the electrode. Meanwhile, the boron–oxygen functional groups linking to the carbon surface or edge serve as additional reaction sitesmore » to activate the ORR process. It is vital that boron atoms have been doped into the carbon lattices to greatly activate the electrons in the carbon π system, which is beneficial for fast charge under large current densities. Density functional theory calculation demonstrates that B-rGO exhibits much stronger interactions with Li5O6 clusters, so that B-rGO more effectively activates Li–O bonds to decompose Li2O2 during charge than rGO does. With B-rGO as a catalytic substrate, the Li–O2 battery achieves a high discharge capacity and excellent rate capability. Moreover, catalysts could be added into the B-rGO substrate to further lower the overpotential and enhance the cycling performance in future.« less
The functional cancer map: a systems-level synopsis of genetic deregulation in cancer.
Krupp, Markus; Maass, Thorsten; Marquardt, Jens U; Staib, Frank; Bauer, Tobias; König, Rainer; Biesterfeld, Stefan; Galle, Peter R; Tresch, Achim; Teufel, Andreas
2011-06-30
Cancer cells are characterized by massive dysegulation of physiological cell functions with considerable disruption of transcriptional regulation. Genome-wide transcriptome profiling can be utilized for early detection and molecular classification of cancers. Accurate discrimination of functionally different tumor types may help to guide selection of targeted therapy in translational research. Concise grouping of tumor types in cancer maps according to their molecular profile may further be helpful for the development of new therapeutic modalities or open new avenues for already established therapies. Complete available human tumor data of the Stanford Microarray Database was downloaded and filtered for relevance, adequacy and reliability. A total of 649 tumor samples from more than 1400 experiments and 58 different tissues were analyzed. Next, a method to score deregulation of KEGG pathway maps in different tumor entities was established, which was then used to convert hundreds of gene expression profiles into corresponding tumor-specific pathway activity profiles. Based on the latter, we defined a measure for functional similarity between tumor entities, which yielded to phylogeny of tumors. We provide a comprehensive, easy-to-interpret functional cancer map that characterizes tumor types with respect to their biological and functional behavior. Consistently, multiple pathways commonly associated with tumor progression were revealed as common features in the majority of the tumors. However, several pathways previously not linked to carcinogenesis were identified in multiple cancers suggesting an essential role of these pathways in cancer biology. Among these pathways were 'ECM-receptor interaction', 'Complement and Coagulation cascades', and 'PPAR signaling pathway'. The functional cancer map provides a systematic view on molecular similarities across different cancers by comparing tumors on the level of pathway activity. This work resulted in identification of novel superimposed functional pathways potentially linked to cancer biology. Therefore, our work may serve as a starting point for rationalizing combination of tumor therapeutics as well as for expanding the application of well-established targeted tumor therapies.
He, Hao; Sui, Jing; Du, Yuhui; Yu, Qingbao; Lin, Dongdong; Drevets, Wayne C; Savitz, Jonathan B; Yang, Jian; Victor, Teresa A; Calhoun, Vince D
2017-12-01
Bipolar disorder (BD) and major depressive disorder (MDD) share similar clinical characteristics that often obscure the diagnostic distinctions between their depressive conditions. Both functional and structural brain abnormalities have been reported in these two disorders. However, the direct link between altered functioning and structure in these two diseases is unknown. To elucidate this relationship, we conducted a multimodal fusion analysis on the functional network connectivity (FNC) and gray matter density from MRI data from 13 BD, 40 MDD, and 33 matched healthy controls (HC). A data-driven fusion method called mCCA+jICA was used to identify the co-altered FNC and gray matter components. Comparing to HC, BD exhibited reduced gray matter density in the parietal and occipital cortices, which correlated with attenuated functional connectivity within sensory and motor networks, as well as hyper-connectivity in regions that are putatively engaged in cognitive control. In addition, lower gray matter density was found in MDD in the amygdala and cerebellum. High accuracy in discriminating across groups was also achieved by trained classification models, implying that features extracted from the fusion analysis hold the potential to ultimately serve as diagnostic biomarkers for mood disorders.
Exposing the structure of an Arctic food web.
Wirta, Helena K; Vesterinen, Eero J; Hambäck, Peter A; Weingartner, Elisabeth; Rasmussen, Claus; Reneerkens, Jeroen; Schmidt, Niels M; Gilg, Olivier; Roslin, Tomas
2015-09-01
How food webs are structured has major implications for their stability and dynamics. While poorly studied to date, arctic food webs are commonly assumed to be simple in structure, with few links per species. If this is the case, then different parts of the web may be weakly connected to each other, with populations and species united by only a low number of links. We provide the first highly resolved description of trophic link structure for a large part of a high-arctic food web. For this purpose, we apply a combination of recent techniques to describing the links between three predator guilds (insectivorous birds, spiders, and lepidopteran parasitoids) and their two dominant prey orders (Diptera and Lepidoptera). The resultant web shows a dense link structure and no compartmentalization or modularity across the three predator guilds. Thus, both individual predators and predator guilds tap heavily into the prey community of each other, offering versatile scope for indirect interactions across different parts of the web. The current description of a first but single arctic web may serve as a benchmark toward which to gauge future webs resolved by similar techniques. Targeting an unusual breadth of predator guilds, and relying on techniques with a high resolution, it suggests that species in this web are closely connected. Thus, our findings call for similar explorations of link structure across multiple guilds in both arctic and other webs. From an applied perspective, our description of an arctic web suggests new avenues for understanding how arctic food webs are built and function and of how they respond to current climate change. It suggests that to comprehend the community-level consequences of rapid arctic warming, we should turn from analyses of populations, population pairs, and isolated predator-prey interactions to considering the full set of interacting species.
Thomas, Laura; Richards, Mark; Mort, Matthew; Dunlop, Elaine; Cooper, David N; Upadhyaya, Meena
2012-12-01
Neurofibromatosis type-1 (NF1) is caused by constitutional mutations of the NF1 tumor-suppressor gene. Although ∼85% of inherited NF1 microlesions constitute truncating mutations, the remaining ∼15% are missense mutations whose pathological relevance is often unclear. The GTPase-activating protein-related domain (GRD) of the NF1-encoded protein, neurofibromin, serves to define its major function as a negative regulator of the Ras-MAPK (mitogen-activated protein kinase) signaling pathway. We have established a functional assay to assess the potential pathogenicity of 15 constitutional nonsynonymous NF1 missense mutations (11 novel and 4 previously reported but not functionally characterized) identified in the NF1-GRD (p.R1204G, p.R1204W, p.R1276Q, p.L1301R, p.I1307V, p.T1324N, p.E1327G, p.Q1336R, p.E1356G, p.R1391G, p.V1398D, p.K1409E, p.P1412R, p.K1436Q, p.S1463F). Individual mutations were introduced into an NF1-GRD expression vector and activated Ras was assayed by an enzyme-linked immunosorbent assay (ELISA). Ten NF1-GRD variants were deemed to be potentially pathogenic by virtue of significantly elevated levels of activated GTP-bound Ras in comparison to wild-type NF1 protein. The remaining five NF1-GRD variants were deemed less likely to be of pathological significance as they exhibited similar levels of activated Ras to the wild-type protein. These conclusions received broad support from both bioinformatic analysis and molecular modeling and serve to improve our understanding of NF1-GRD structure and function. © 2012 Wiley Periodicals, Inc.
Soni, Vijay; Suryadevara, Priyanka; Sriram, Dharmarajan; Kumar, Santhosh; Nandicoori, Vinay Kumar; Yogeeswari, Perumal
2015-07-01
Persistent nature of Mycobacterium tuberculosis is one of the major factors which make the drug development process monotonous against this organism. The highly lipophilic cell wall, which constituting outer mycolic acid and inner peptidoglycan layers, acts as a barrier for the drugs to enter the bacteria. The rigidity of the cell wall is imparted by the peptidoglycan layer, which is covalently linked to mycolic acid by arabinogalactan. Uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc) serves as the starting material in the biosynthesis of this peptidoglycan layers. This UDP-GlcNAc is synthesized by N-acetylglucosamine-1-phosphate uridyltransferase (GlmU(Mtb)), a bi-functional enzyme with two functional sites, acetyltransferase site and uridyltransferase site. Here, we report design and screening of nine inhibitors against UTP and NAcGlc-1-P of uridyltransferase active site of glmU(Mtb). Compound 4 was showing good inhibition and was selected for further analysis. The isothermal titration calorimetry (ITC) experiments showed the binding energy pattern of compound 4 to the uridyltransferase active site is similar to that of substrate UTP. In silico molecular dynamics (MD) simulation studies, for compound 4, carried out for 10 ns showed the protein-compound complex to be stable throughout the simulation with relative rmsd in acceptable range. Hence, these compounds can serve as a starting point in the drug discovery processes against Mycobacterium tuberculosis.
Metabolically programmed quality control system for dolichol-linked oligosaccharides
Harada, Yoichiro; Nakajima, Kazuki; Masahara-Negishi, Yuki; Freeze, Hudson H.; Angata, Takashi; Taniguchi, Naoyuki; Suzuki, Tadashi
2013-01-01
The glycolipid Glc3Man9GlcNAc2-pyrophosphate-dolichol serves as the precursor for asparagine (N)-linked protein glycosylation in mammals. The biosynthesis of dolichol-linked oligosaccharides (DLOs) is arrested in low-glucose environments via unknown mechanisms, resulting in abnormal N-glycosylation. Here, we show that under glucose deprivation, DLOs are prematurely degraded during the early stages of DLO biosynthesis by pyrophosphatase, leading to the release of singly phosphorylated oligosaccharides into the cytosol. We identified that the level of GDP-mannose (Man), which serves as a donor substrate for DLO biosynthesis, is substantially reduced under glucose deprivation. We provide evidence that the selective shutdown of the GDP-Man biosynthetic pathway is sufficient to induce the release of phosphorylated oligosaccharides. These results indicate that glucose-regulated metabolic changes in the GDP-Man biosynthetic pathway cause the biosynthetic arrest of DLOs and facilitate their premature degradation by pyrophosphatase. We propose that this degradation system may avoid abnormal N-glycosylation with premature oligosaccharides under conditions that impair efficient DLO biosynthesis. PMID:24218558
Drilling Deep Into STEM Education with JOIDES Resolution Education and Outreach Officers
NASA Astrophysics Data System (ADS)
Christiansen, E. A.
2015-12-01
During International Ocean Discovery Program (IODP) expeditions, IODP scientists and Education/Outreach (E/O) Officers enter classrooms and informal science venues via live Internet video links between the JOIDES Resolution (JR) and land-based learning centers. Post-expedition, E/O Officers, serving as JR Ambassadors, deepen and broaden the learning experience by bringing STEM from the JR to the general public through targeted outreach events at those land-based sites. Youth and adult learners participate in scientific inquiry through interactive activities linked directly to the video broadcast experience. Outreach venues include museums, summer camps, and after-school programs; classroom visits from E/O Officers encompass kindergarten to undergraduate school groups and often include professional development for educators. Events are hands-on with simulations, expedition samples, core models, and equipment available for interaction. This program can serve as a model for linking virtual and real experiences; deepening the educational value of virtual field trip events; and bringing cutting edge science into both classrooms and informal science venues.
LRP8-Reelin-regulated Neuronal (LRN) Enhancer Signature Underlying Learning and Memory Formation
Telese, Francesca; Ma, Qi; Perez, Patricia Montilla; Notani, Dimple; Oh, Soohwan; Li, Wenbo; Comoletti, Davide; Ohgi, Kenneth A.; Taylor, Havilah; Rosenfeld, Michael G.
2015-01-01
Summary One of the exceptional properties of the brain is its ability to acquire new knowledge through learning and to store that information through memory. The epigenetic mechanisms linking changes in neuronal transcriptional programs to behavioral plasticity remain largely unknown. Here, we identify the epigenetic signature of the neuronal enhancers required for transcriptional regulation of synaptic plasticity genes during memory formation, linking this to Reelin signaling. The binding of Reelin to its receptor, LRP8, triggers activation of this cohort of LRP8-Reelin-regulated-Neuronal (LRN) enhancers that serve as the ultimate convergence point of a novel synapse-to-nucleus pathway. Reelin simultaneously regulates NMDA-receptor transmission, which reciprocally permits the required, γ-secretase-dependent cleavage of LRP8, revealing an unprecedented role for its intracellular domain in the regulation of synaptically generated signals. These results uncover an in vivo enhancer code serving as a critical molecular component of cognition and relevant to psychiatric disorders linked to defects in Reelin signaling. PMID:25892301
Sugar Lego: gene composition of bacterial carbohydrate metabolism genomic loci.
Kaznadzey, Anna; Shelyakin, Pavel; Gelfand, Mikhail S
2017-11-25
Bacterial carbohydrate metabolism is extremely diverse, since carbohydrates serve as a major energy source and are involved in a variety of cellular processes. Bacterial genes belonging to same metabolic pathway are often co-localized in the chromosome, but it is not a strict rule. Gene co-localization in linked to co-evolution and co-regulation. This study focuses on a large-scale analysis of bacterial genomic loci related to the carbohydrate metabolism. We demonstrate that only 53% of 148,000 studied genes from over six hundred bacterial genomes are co-localized in bacterial genomes with other carbohydrate metabolism genes, which points to a significant role of singleton genes. Co-localized genes form cassettes, ranging in size from two to fifteen genes. Two major factors influencing the cassette-forming tendency are gene function and bacterial phylogeny. We have obtained a comprehensive picture of co-localization preferences of genes for nineteen major carbohydrate metabolism functional classes, over two hundred gene orthologous clusters, and thirty bacterial classes, and characterized the cassette variety in size and content among different species, highlighting a significant role of short cassettes. The preference towards co-localization of carbohydrate metabolism genes varies between 40 and 76% for bacterial taxa. Analysis of frequently co-localized genes yielded forty-five significant pairwise links between genes belonging to different functional classes. The number of such links per class range from zero to eight, demonstrating varying preferences of respective genes towards a specific chromosomal neighborhood. Genes from eleven functional classes tend to co-localize with genes from the same class, indicating an important role of clustering of genes with similar functions. At that, in most cases such co-localization does not originate from local duplication events. Overall, we describe a complex web formed by evolutionary relationships of bacterial carbohydrate metabolism genes, manifested as co-localization patterns. This article was reviewed by Daria V. Dibrova (A.N. Belozersky Institute of Physico-Chemical Biology, Lomonosov Moscow State University, Moscow, Russia), nominated by Armen Mulkidjanian (University of Osnabrück, Germany), Igor Rogozin (NCBI, NLM, NIH, USA) and Yuri Wolf (NCBI, NLM, NIH, USA).
NADPH oxidases of the brain: distribution, regulation, and function.
Infanger, David W; Sharma, Ram V; Davisson, Robin L
2006-01-01
The NADPH oxidase is a multi-subunit enzyme that catalyzes the reduction of molecular oxygen to form superoxide (O(2)(-)). While classically linked to the respiratory burst in neutrophils, recent evidence now shows that O(2)(-) (and associated reactive oxygen species, ROS) generated by NADPH oxidase in nonphagocytic cells serves myriad functions in health and disease. An entire new family of NADPH Oxidase (Nox) homologues has emerged, which vary widely in cell and tissue distribution, as well as in function and regulation. A major concept in redox signaling is that while NADPH oxidase-derived ROS are necessary for normal cellular function, excessive oxidative stress can contribute to pathological disease. This certainly is true in the central nervous system (CNS), where normal NADPH oxidase function appears to be required for processes such as neuronal signaling, memory, and central cardiovascular homeostasis, but overproduction of ROS contributes to neurotoxicity, neurodegeneration, and cardiovascular diseases. Despite implications of NADPH oxidase in normal and pathological CNS processes, still relatively little is known about the mechanisms involved. This paper summarizes the evidence for NADPH oxidase distribution, regulation, and function in the CNS, emphasizing the diversity of Nox isoforms and their new and emerging role in neuro-cardiovascular function. In addition, perspectives for future research and novel therapeutic targets are offered.
Karav, Sercan; Le Parc, Annabelle; Leite Nobrega de Moura Bell, Juliana Maria; Frese, Steven A.; Kirmiz, Nina; Block, David E.; Barile, Daniela
2016-01-01
ABSTRACT Milk, in addition to nourishing the neonate, provides a range of complex glycans whose construction ensures a specific enrichment of key members of the gut microbiota in the nursing infant, a consortium known as the milk-oriented microbiome. Milk glycoproteins are thought to function similarly, as specific growth substrates for bifidobacteria common to the breast-fed infant gut. Recently, a cell wall-associated endo-β-N-acetylglucosaminidase (EndoBI-1) found in various infant-borne bifidobacteria was shown to remove a range of intact N-linked glycans. We hypothesized that these released oligosaccharide structures can serve as a sole source for the selective growth of bifidobacteria. We demonstrated that EndoBI-1 released N-glycans from concentrated bovine colostrum at the pilot scale. EndoBI-1-released N-glycans supported the rapid growth of Bifidobacterium longum subsp. infantis (B. infantis), a species that grows well on human milk oligosaccharides, but did not support growth of Bifidobacterium animalis subsp. lactis (B. lactis), a species which does not. Conversely, B. infantis ATCC 15697 did not grow on the deglycosylated milk protein fraction, clearly demonstrating that the glycan portion of milk glycoproteins provided the key substrate for growth. Mass spectrometry-based profiling revealed that B. infantis consumed 73% of neutral and 92% of sialylated N-glycans, while B. lactis degraded only 11% of neutral and virtually no (<1%) sialylated N-glycans. These results provide mechanistic support that N-linked glycoproteins from milk serve as selective substrates for the enrichment of infant-associated bifidobacteria capable of carrying out the initial deglycosylation. Moreover, released N-glycans were better growth substrates than the intact milk glycoproteins, suggesting that EndoBI-1 cleavage is a key initial step in consumption of glycoproteins. Finally, the variety of N-glycans released from bovine milk glycoproteins suggests that they may serve as novel prebiotic substrates with selective properties similar to those of human milk oligosaccharides. IMPORTANCE It has been previously shown that glycoproteins serve as growth substrates for bifidobacteria. However, which part of a glycoprotein (glycans or polypeptides) is responsible for this function was not known. In this study, we used a novel enzyme to cleave conjugated N-glycans from milk glycoproteins and tested their consumption by various bifidobacteria. The results showed that the glycans selectively stimulated the growth of B. infantis, which is a key infant gut microbe. The selectivity of consumption of individual N-glycans was determined using advanced mass spectrometry (nano-liquid chromatography chip–quadrupole time of flight mass spectrometry [nano-LC-Chip-Q-TOF MS]) to reveal that B. infantis can consume the range of glycan structures released from whey protein concentrate. PMID:27084007
Serving the Needs of Gifted Learners around the Globe: An Interview with Julia Link Roberts
ERIC Educational Resources Information Center
Henshon, Suzanna E.
2018-01-01
Julia Link Roberts is the Mahurin Professor of Gifted Studies at Western Kentucky University (WKU) and the executive director of The Center for Gifted Studies and The Gatton Academy of Mathematics and Science in Kentucky. Dr. Roberts is the president of the World Council for Gifted and Talented Children; current past-president of The Association…
ERIC Educational Resources Information Center
Buehler, Bruce
This 34-minute videotape on meeting the special medical needs of children is intended for use in staff development with special educators, regular educators, and school nurses serving children with special health care needs in inclusive school settings. Emphasis is on linking "what we know" in the field of medicine to "how we…
Rietberg, K; Lloyd, J; Melius, B; Wyman, P; Treadwell, R; Olson, G; Kang, M-G; Duchin, J S
2016-10-01
Two cases of hospital-acquired listeriosis were linked to a commercially produced, pasteurized ice cream mix. Manufacturers should implement safety measures from the Food Safety Modernization Act to minimize the risk of Listeria contamination. Dietary guidelines for persons at high risk of listeriosis may need revision to recognize the potential risk from pasteurized products.
Pericentrin in cellular function and disease
Delaval, Benedicte
2010-01-01
Pericentrin is an integral component of the centrosome that serves as a multifunctional scaffold for anchoring numerous proteins and protein complexes. Through these interactions, pericentrin contributes to a diversity of fundamental cellular processes. Recent studies link pericentrin to a growing list of human disorders. Studies on pericentrin at the cellular, molecular, and, more recently, organismal level, provide a platform for generating models to elucidate the etiology of these disorders. Although the complexity of phenotypes associated with pericentrin-mediated disorders is somewhat daunting, insights into the cellular basis of disease are beginning to come into focus. In this review, we focus on human conditions associated with loss or elevation of pericentrin and propose cellular and molecular models that might explain them. PMID:19951897
Wu, Baolin; Woodward, Robert; Wen, Liuqing; Wang, Xuan; Zhao, Guohui; Wang, Peng George
2013-12-01
Polyprenols, a type of universal glycan lipid carrier, play important roles for glycan bio-assembly in wide variety of living systems. Chemical synthesis of natural polyisoprenols such as undecaprenol and dolichols, but especially their homologs, could serves as a powerful molecular tool to dissect and define the functions of enzymes involved in glycan biosynthesis. In this paper, we report an efficient and reliable method to construct this type of hydrophoic molecule through a base-mediated iterative coupling approach using a key bifunctional ( Z , Z )-diisoprenyl building block. The ligation with N -acetyl-D-glactosamine (GalNAc) with a set of the synthesized lipid analogs forming polyprenol pyrophosphate linked GalNAc (GalNAc-PP-lipid) conjugates is also demonstrated.
Time code dissemination experiment via the SIRIO-1 VHF transponder
NASA Technical Reports Server (NTRS)
Detoma, E.; Gobbo, G.; Leschiutta, S.; Pettiti, V.
1982-01-01
An experiment to evaluate the possibility of disseminating a time code via the SIRIO-1 satellite, by using the onboard VHF repeater is described. The precision in the synchronization of remote clocks was expected to be of the order of 0.1 to 1 ms. The RF carrier was in the VHF band, so that low cost receivers could be used and then a broader class of users could be served. An already existing repeater, even if not designed specifically for communications could be utilized; the operation of this repeater was not intended to affect any other function of the spacecraft (both the SHF repeater and the VHF telemetry link were active during the time code dissemination via the VHF transponder).
Tool for use in lifting pin supported objects
NASA Technical Reports Server (NTRS)
Marzek, R. A.; Read, W. S. (Inventor)
1974-01-01
A tool for use in lifting a pin-supported, electronic package mounted in juxtaposition with the surface of an electronic circuit board is described. The tool is configured to be received beneath a pin-supported package and is characterized by a manually operable linkage, including an elongated, rigid link is supported for axial reciprocation and a pivotal link pinned to the body and supported for oscillation induced in response to axial motion imparted to the rigid link. A lifting plate is pivotally coupled to the distal end of the pivotal link so that oscillatory motion imparted to the pivotal link serves to move the plate vertically for elevating the plate into lifting engagement with the electronic package positioned thereabove.
Bartels, Emil D.; Nielsen, Jan M.; Hellgren, Lars I.; Ploug, Thorkil; Nielsen, Lars B.
2009-01-01
Obesity causes lipid accumulation in the heart and may lead to lipotoxic heart disease. Traditionally, the size of the cardiac triglyceride pool is thought to reflect the balance between uptake and β-oxidation of fatty acids. However, triglycerides can also be exported from cardiomyocytes via secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism remain unknown, we investigated how cardiac lipoprotein synthesis affects cardiac expression of triglyceride metabolism-controlling genes, insulin sensitivity, and function in obese mice. Heart-specific ablation of MTP-A in mice using Cre-loxP technology impaired upregulation of MTP expression in response to increased fatty acid availability during fasting and fat feeding. This resulted in cardiac triglyceride accumulation but unaffected cardiac insulin-stimulated glucose uptake. Long-term fat-feeding of male C57Bl/6 mice increased cardiac triglycerides, induced cardiac expression of triglyceride metabolism-controlling genes and attenuated heart function. Abolishing cardiac triglyceride accumulation in fat-fed mice by overexpression of an apoB transgene in the heart prevented the induction of triglyceride metabolism-controlling genes and improved heart function. The results suggest that in obesity, the physiological increase of cardiac MTP expression serves to attenuate cardiac triglyceride accumulation albeit without major effects on cardiac insulin sensitivity. Nevertheless, the data suggest that genetically increased lipoprotein secretion prevents development of obesity-induced lipotoxic heart disease. PMID:19390571
Discovery of a nucleocytoplasmic O-mannose glycoproteome in yeast
Halim, Adnan; Larsen, Ida Signe Bohse; Neubert, Patrick; Joshi, Hiren Jitendra; Petersen, Bent Larsen; Vakhrushev, Sergey Y.; Strahl, Sabine; Clausen, Henrik
2015-01-01
Dynamic cycling of N-Acetylglucosamine (GlcNAc) on serine and threonine residues (O-GlcNAcylation) is an essential process in all eukaryotic cells except yeast, including Saccharomyces cerevisiae and Schizosaccharomyces pombe. O-GlcNAcylation modulates signaling and cellular processes in an intricate interplay with protein phosphorylation and serves as a key sensor of nutrients by linking the hexosamine biosynthetic pathway to cellular signaling. A longstanding conundrum has been how yeast survives without O-GlcNAcylation in light of its similar phosphorylation signaling system. We previously developed a sensitive lectin enrichment and mass spectrometry workflow for identification of the human O-linked mannose (O-Man) glycoproteome and used this to identify a pleothora of O-Man glycoproteins in human cell lines including the large family of cadherins and protocadherins. Here, we applied the workflow to yeast with the aim to characterize the yeast O-Man glycoproteome, and in doing so, we discovered hitherto unknown O-Man glycosites on nuclear, cytoplasmic, and mitochondrial proteins in S. cerevisiae and S. pombe. Such O-Man glycoproteins were not found in our analysis of human cell lines. However, the type of yeast O-Man nucleocytoplasmic proteins and the localization of identified O-Man residues mirror that of the O-GlcNAc glycoproteome found in other eukaryotic cells, indicating that the two different types of O-glycosylations serve the same important biological functions. The discovery opens for exploration of the enzymatic machinery that is predicted to regulate the nucleocytoplasmic O-Man glycosylations. It is likely that manipulation of this type of O-Man glycosylation will have wide applications for yeast bioprocessing. PMID:26644575
Introducing glycomics data into the Semantic Web
2013-01-01
Background Glycoscience is a research field focusing on complex carbohydrates (otherwise known as glycans)a, which can, for example, serve as “switches” that toggle between different functions of a glycoprotein or glycolipid. Due to the advancement of glycomics technologies that are used to characterize glycan structures, many glycomics databases are now publicly available and provide useful information for glycoscience research. However, these databases have almost no link to other life science databases. Results In order to implement support for the Semantic Web most efficiently for glycomics research, the developers of major glycomics databases agreed on a minimal standard for representing glycan structure and annotation information using RDF (Resource Description Framework). Moreover, all of the participants implemented this standard prototype and generated preliminary RDF versions of their data. To test the utility of the converted data, all of the data sets were uploaded into a Virtuoso triple store, and several SPARQL queries were tested as “proofs-of-concept” to illustrate the utility of the Semantic Web in querying across databases which were originally difficult to implement. Conclusions We were able to successfully retrieve information by linking UniCarbKB, GlycomeDB and JCGGDB in a single SPARQL query to obtain our target information. We also tested queries linking UniProt with GlycoEpitope as well as lectin data with GlycomeDB through PDB. As a result, we have been able to link proteomics data with glycomics data through the implementation of Semantic Web technologies, allowing for more flexible queries across these domains. PMID:24280648
Introducing glycomics data into the Semantic Web.
Aoki-Kinoshita, Kiyoko F; Bolleman, Jerven; Campbell, Matthew P; Kawano, Shin; Kim, Jin-Dong; Lütteke, Thomas; Matsubara, Masaaki; Okuda, Shujiro; Ranzinger, Rene; Sawaki, Hiromichi; Shikanai, Toshihide; Shinmachi, Daisuke; Suzuki, Yoshinori; Toukach, Philip; Yamada, Issaku; Packer, Nicolle H; Narimatsu, Hisashi
2013-11-26
Glycoscience is a research field focusing on complex carbohydrates (otherwise known as glycans)a, which can, for example, serve as "switches" that toggle between different functions of a glycoprotein or glycolipid. Due to the advancement of glycomics technologies that are used to characterize glycan structures, many glycomics databases are now publicly available and provide useful information for glycoscience research. However, these databases have almost no link to other life science databases. In order to implement support for the Semantic Web most efficiently for glycomics research, the developers of major glycomics databases agreed on a minimal standard for representing glycan structure and annotation information using RDF (Resource Description Framework). Moreover, all of the participants implemented this standard prototype and generated preliminary RDF versions of their data. To test the utility of the converted data, all of the data sets were uploaded into a Virtuoso triple store, and several SPARQL queries were tested as "proofs-of-concept" to illustrate the utility of the Semantic Web in querying across databases which were originally difficult to implement. We were able to successfully retrieve information by linking UniCarbKB, GlycomeDB and JCGGDB in a single SPARQL query to obtain our target information. We also tested queries linking UniProt with GlycoEpitope as well as lectin data with GlycomeDB through PDB. As a result, we have been able to link proteomics data with glycomics data through the implementation of Semantic Web technologies, allowing for more flexible queries across these domains.
Chen, Ke; Ding, Jin; Zhang, Shuhao; Tang, Xuke; Yue, Yonghai; Guo, Lin
2017-03-28
Creating lightweight engineering materials combining high strength and great toughness remains a significant challenge. Despite possessing-enhanced strength and stiffness, bioinspired/polymeric materials usually suffer from clearly reduced extensibility and toughness when compared to corresponding bulk polymer materials. Herein, inspired by tiny amounts of various inorganic impurities for mechanical improvement in natural materials, we present a versatile and effective metal ion (M n+ )-based synergic cross-linking (MSC) strategy incorporating eight types of metal ions into material bulks that can drastically enhance the tensile strength (∼24.1-70.8%), toughness (∼18.6-110.1%), modulus (∼21.6-66.7%), and hardness (∼6.4-176.5%) of multiple types of pristine materials (from hydrophilic to hydrophobic and from unary to binary). More importantly, we also explore the primarily elastic-plastic deformation mechanism and brittle fracture behavior (indentation strain of >5%) of the synergic cross-linked graphene oxide (Syn-GO) paper by means of in situ nanoindentation SEM. The MSC strategy for mechanically enhanced integration can be readily attributed to the formation of the complicated metals-based cross-linking/complex networks in the interfaces and intermolecules between functional groups of materials and various metal ions that give rise to efficient energy dissipation. This work suggests a promising MSC strategy for designing advanced materials with outstanding mechanical properties by adding low amounts (<1.0 wt %) of synergic metal ions serving as synergic ion-bonding cross-linkers.
Colacurcio, Daniel J.; Nixon, Ralph A.
2016-01-01
Autophagy and endocytosis deliver unneeded cellular materials to lysosomes for degradation. Beyond processing cellular waste, lysosomes release metabolites and ions that serve signaling and nutrient sensing roles, linking the functions of the lysosome to various pathways for intracellular metabolism and nutrient homeostasis. Each of these lysosomal behaviors is influenced by the intraluminal pH of the lysosome, which is maintained in the low acidic range by a proton pump, the vacuolar ATPase (v-ATPase). New reports implicate altered v-ATPase activity and lysosomal pH dysregulation in cellular aging, longevity, and adult-onset neurodegenerative diseases, including forms of Parkinson Disease and Alzheimer Disease. Genetic defects of subunits composing the v-ATPase or v-ATPase-related proteins occur in an increasingly recognized group of familial neurodegenerative diseases. Here, we review the expanding roles of the v-ATPase complex as a platform regulating lysosomal proteolysis and cellular homeostasis. We discuss the unique vulnerability of neurons to persistent low level lysosomal dysfunction and review recent clinical and experimental studies that link dysfunction of the v-ATPase complex to neurodegenerative diseases across the age spectrum. PMID:27197071
Toma, Ildikó; Kang, Jung Julie; Sipos, Arnold; Vargas, Sarah; Bansal, Eric; Hanner, Fiona; Meer, Elliott; Peti-Peterdi, János
2008-01-01
Diabetes mellitus is the most common and rapidly growing cause of end-stage renal disease in developed countries. A classic hallmark of early diabetes mellitus includes activation of the renin-angiotensin system (RAS), which may lead to hypertension and renal tissue injury, but the mechanism of RAS activation is elusive. Here we identified a paracrine signaling pathway in the kidney in which high levels of glucose directly triggered the release of the prohypertensive hormone renin. The signaling cascade involved the local accumulation of succinate and activation of the kidney-specific G protein–coupled metabolic receptor, GPR91, in the glomerular endothelium as observed in rat, mouse, and rabbit kidney sections. Elements of signal transduction included endothelial Ca2+, the production of NO and prostaglandin (PGE2), and their paracrine actions on adjacent renin-producing cells. This GPR91 signaling cascade may serve to modulate kidney function and help remove metabolic waste products through renal hyperfiltration, and it could also link metabolic diseases, such as diabetes, or metabolic syndrome with RAS overactivation, systemic hypertension, and organ injury. PMID:18535668
FANCJ/BRIP1 recruitment and regulation of FANCD2 in DNA damage responses
Zhang, Fan; Fan, Qiang; Ren, Keqin; Auerbach, Arleen D.; Andreassen, Paul R.
2016-01-01
FANCJ/BRIP1 encodes a helicase that has been implicated in the maintenance of genomic stability. Here, to better understand FANCJ function in DNA damage responses, we have examined the regulation of its cellular localization. FANCJ nuclear foci assemble spontaneously during S phase and are induced by various stresses. FANCJ foci colocalize with the replication fork following treatment with hydroxyurea, but not spontaneously. Using FANCJ mutants, we find that FANCJ helicase activity and the capacity to bind BRCA1 are both involved in FANCJ recruitment. Given similarities to the recruitment of another Fanconi anemia protein, FANCD2, we tested for colocalization of FANCJ and FANCD2. Importantly, these proteins show substantial colocalization, and FANCJ promotes the assembly of FANCD2 nuclear foci. This process is linked to the proper localization of FANCJ itself since both FANCJ and FANCD2 nuclear foci are compromised by FANCJ mutants that abrogate its helicase activity or interaction with BRCA1. Our results suggest that FANCJ is recruited in response to replication stress and that FANCJ/BRIP1 may serve to link FANCD2 to BRCA1. PMID:20676667
MICOS and phospholipid transfer by Ups2-Mdm35 organize membrane lipid synthesis in mitochondria.
Aaltonen, Mari J; Friedman, Jonathan R; Osman, Christof; Salin, Bénédicte; di Rago, Jean-Paul; Nunnari, Jodi; Langer, Thomas; Tatsuta, Takashi
2016-06-06
Mitochondria exert critical functions in cellular lipid metabolism and promote the synthesis of major constituents of cellular membranes, such as phosphatidylethanolamine (PE) and phosphatidylcholine. Here, we demonstrate that the phosphatidylserine decarboxylase Psd1, located in the inner mitochondrial membrane, promotes mitochondrial PE synthesis via two pathways. First, Ups2-Mdm35 complexes (SLMO2-TRIAP1 in humans) serve as phosphatidylserine (PS)-specific lipid transfer proteins in the mitochondrial intermembrane space, allowing formation of PE by Psd1 in the inner membrane. Second, Psd1 decarboxylates PS in the outer membrane in trans, independently of PS transfer by Ups2-Mdm35. This latter pathway requires close apposition between both mitochondrial membranes and the mitochondrial contact site and cristae organizing system (MICOS). In MICOS-deficient cells, limiting PS transfer by Ups2-Mdm35 and reducing mitochondrial PE accumulation preserves mitochondrial respiration and cristae formation. These results link mitochondrial PE metabolism to MICOS, combining functions in protein and lipid homeostasis to preserve mitochondrial structure and function. © 2016 Aaltonen et al.
Muraleedharan, Simi; Sam, Aksah; Skaer, Helen; Inamdar, Maneesha S
2018-03-15
Insect nephrocytes provide a valuable model for kidney disease, as they are structurally and functionally homologous to mammalian kidney podocytes. They possess an exceptional macromolecular assembly, the nephrocyte diaphragm (ND), which serves as a filtration barrier and helps maintain tissue homeostasis by filtering out wastes and toxic products. However, the elements that maintain nephrocyte architecture and the ND are not understood. We show that Drosophila nephrocytes have a unique cytoplasmic cluster of F-actin, which is maintained by the microtubule cytoskeleton and Rho-GTPases. A balance of Rac1 and Cdc42 activity as well as proper microtubule organization and endoplasmic reticulum structure, are required to position the actin cluster. Further, ND proteins Sns and Duf also localize to this cluster and regulate organization of the actin and microtubule cytoskeleton. Perturbation of any of these inter-dependent components impairs nephrocyte ultrafiltration. Thus cytoskeletal components, Rho-GTPases and ND proteins work in concert to maintain the specialized nephrocyte architecture and function. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.
Impact Mediated Loading Cytoplasmic Loading of Macromolecules into Adherent Cells
NASA Technical Reports Server (NTRS)
Clarke, Mark S. F.; Feeback, Daniel L.; Vanderburg, Charles R.
2003-01-01
The advent of modern molecular biology, including the development of gene array technologies, has resulted in an explosion of information concerning the specific genes activated during normal cellular development, as well as those associated with a variety of pathological conditions. These techniques have served as a highly efficient, broacI.-based screening approach for those specific genes involved. in regulating normal cellular physiology and identifying candidate genes directly associated with the etiology of specific disease states. However, this approach provides information at the transcriptional' level only and does not necessarily indicate . that the gene in question is in fact translated ito a protein, or whether or not post-translational modification of the protein occurs. The critical importance of post-translational modification (i.e. phosphorylation, glycosylation, sialyation, etc.) to protein function has been recognized with regard to a number of proteins involved in a variety of important disease states. For example, altered glycosylation of beta-amyloid precursor protein results in an increase in the amount of beta-amyloid peptide generated and hence secreted as insoluble extracellular amyloid deposits (Georgopoulou, McLaughlin et al. 2001; Walter, Fluhrer et al. 2001), a pathological hal1nark of Alzheimer's disease. Abnormal phosphorylaion of synapsin I has been linked to alterations in synaptic vesicle trafficking leading to defective neurotransmission in Huntington's disease (Lievens, Woodman et al. 2002). Altered phosphorylation of the TAU protein involved in microtubule function has been linked to a number of neurodegenative diseases such as Alzheimer's disease (Billingsley and Kincaid 1997; Sanchez, Alvarez-Tllada et a1. 2001). Aberrant siaIyation of cell/I surface antigens has been detected in a number of different tumor cell types and has been linked to the acquisition of a neoplastic phenotype (Sell 1990), while improper' sia1yation of sodium channels in cardiac tissue has been linked to heart failure (Ufret-Vincenty, Baro et al. 2001; Fozzard and Kyle 2002).
Mimetic discretization of the Abelian Chern-Simons theory and link invariants
DOE Office of Scientific and Technical Information (OSTI.GOV)
Di Bartolo, Cayetano; Grau, Javier; Leal, Lorenzo
A mimetic discretization of the Abelian Chern-Simons theory is presented. The study relies on the formulation of a theory of differential forms in the lattice, including a consistent definition of the Hodge duality operation. Explicit expressions for the Gauss Linking Number in the lattice, which correspond to their continuum counterparts are given. A discussion of the discretization of metric structures in the space of transverse vector densities is presented. The study of these metrics could serve to obtain explicit formulae for knot an link invariants in the lattice.
Mimetic discretization of the Abelian Chern-Simons theory and link invariants
NASA Astrophysics Data System (ADS)
Di Bartolo, Cayetano; Grau, Javier; Leal, Lorenzo
2013-12-01
A mimetic discretization of the Abelian Chern-Simons theory is presented. The study relies on the formulation of a theory of differential forms in the lattice, including a consistent definition of the Hodge duality operation. Explicit expressions for the Gauss Linking Number in the lattice, which correspond to their continuum counterparts are given. A discussion of the discretization of metric structures in the space of transverse vector densities is presented. The study of these metrics could serve to obtain explicit formulae for knot an link invariants in the lattice.
A link representation for gravity amplitudes
NASA Astrophysics Data System (ADS)
He, Song
2013-10-01
We derive a link representation for all tree amplitudes in supergravity, from a recent conjecture by Cachazo and Skinner. The new formula explicitly writes amplitudes as contour integrals over constrained link variables, with an integrand naturally expressed in terms of determinants, or equivalently tree diagrams. Important symmetries of the amplitude, such as supersymmetry, parity and (partial) permutation invariance, are kept manifest in the formulation. We also comment on rewriting the formula in a GL( k)-invariant manner, which may serve as a starting point for the generalization to possible Grassmannian contour integrals.
Cho, Jin-Gun; Witting, Paul K.; Verma, Manisha; Wu, Ben J.; Shanu, Anu; Kairaitis, Kristina; Amis, Terence C.; Wheatley, John R.
2011-01-01
Study Objectives: We have previously identified heavy snoring as an independent risk factor for carotid atherosclerosis. In order to explore the hypothesis that snoring-associated vibration of the carotid artery induces endothelial dysfunction (an established atherogenic precursor), we utilized an animal model to examine direct effects of peri-carotid tissue vibration on carotid artery endothelial function and structure. Design: In supine anesthetized, ventilated rabbits, the right carotid artery (RCA) was directly exposed to vibrations for 6 h (peak frequency 60 Hz, energy matched to that of induced snoring in rabbits). Similarly instrumented unvibrated rabbits served as controls. Features of OSA such as hypoxemia, large intra-pleural swings and blood pressure volatility were prevented. Carotid endothelial function was then examined: (1) biochemically by measurement of tissue cyclic guanosine monophosphate (cGMP) to acetylcholine (ACh) and sodium nitroprusside (SNP); and (2) functionally by monitoring vessel relaxation with acetylcholine in a myobath. Measurement and Results: Vessel cGMP after stimulation with ACh was reduced in vibrated RCA compared with unvibrated (control) arteries in a vibration energy dose-dependent manner. Vibrated RCA also showed decreased vasorelaxation to ACh compared with control arteries. Notably, after addition of SNP (nitric oxide donor), cGMP levels did not differ between vibrated and control arteries, thereby isolating vibration-induced dysfunction to the endothelium alone. This dysfunction occurred in the presence of a morphologically intact endothelium without increased apoptosis. Conclusions: Carotid arteries subjected to 6 h of continuous peri-carotid tissue vibration displayed endothelial dysfunction, suggesting a direct plausible mechanism linking heavy snoring to the development of carotid atherosclerosis. Citation: Cho JG; Witting PK; Verma M; Wu BJ; Shanu A; Kairaitis K; Amis TC; Wheatley JR. Tissue vibration induces carotid artery endothelial dysfunction: a mechanism linking snoring and carotid atherosclerosis?. SLEEP 2011;34(6):751-757. PMID:21629363
Expressive suppression and neural responsiveness to nonverbal affective cues.
Petrican, Raluca; Rosenbaum, R Shayna; Grady, Cheryl
2015-10-01
Optimal social functioning occasionally requires concealment of one's emotions in order to meet one's immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors' restricted affective displays reportedly inhibit their interlocutors' emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors' restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target's affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to nonverbal affective cues, while also suggesting one explanation for the suppressors' poorer cognitive performance in social situations. Moreover, our results point to a potential neural mechanism supporting the development and perpetuation of expressive suppression as an emotion regulation strategy. Copyright © 2015 Elsevier Ltd. All rights reserved.
Expressive suppression and neural responsiveness to nonverbal affective cues
Petrican, Raluca; Rosenbaum, R. Shayna; Grady, Cheryl
2016-01-01
Optimal social functioning occasionally requires concealment of one’s emotions in order to meet one’s immediate goals and environmental demands. However, because emotions serve an important communicative function, their habitual suppression disrupts the flow of social exchanges and, thus, incurs significant interpersonal costs. Evidence is accruing that the disruption in social interactions, linked to habitual expressive suppression use, stems not only from intrapersonal, but also from interpersonal causes, since the suppressors’ restricted affective displays reportedly inhibit their interlocutors’ emotionally expressive behaviors. However, expressive suppression use is not known to lead to clinically significant social impairments. One explanation may be that over the lifespan, individuals who habitually suppress their emotions come to compensate for their interlocutors’ restrained expressive behaviors by developing an increased sensitivity to nonverbal affective cues. To probe this issue, the present study used functional magnetic resonance imaging (fMRI) to scan healthy older women while they viewed silent videos of a male social target displaying nonverbal emotional behavior, together with a brief verbal description of the accompanying context, and then judged the target’s affect. As predicted, perceivers who reported greater habitual use of expressive suppression showed increased neural processing of nonverbal affective cues. This effect appeared to be coordinated in a top-down manner via cognitive control. Greater neural processing of nonverbal cues among perceivers who habitually suppress their emotions was linked to increased ventral striatum activity, suggestive of increased reward value/personal relevance ascribed to emotionally expressive nonverbal behaviors. These findings thus provide neural evidence broadly consistent with the hypothesized link between habitual use of expressive suppression and compensatory development of increased responsiveness to nonverbal affective cues, while also suggesting one explanation for the suppressors’ poorer cognitive performance in social situations. Moreover, our results point to a potential neural mechanism supporting the development and perpetuation of expressive suppression as an emotion regulation strategy. PMID:26365712
Brdicka, Tomás; Imrich, Martin; Angelisová, Pavla; Brdicková, Nadezda; Horváth, Ondrej; Spicka, Jirí; Hilgert, Ivan; Lusková, Petra; Dráber, Petr; Novák, Petr; Engels, Niklas; Wienands, Jürgen; Simeoni, Luca; Osterreicher, Jan; Aguado, Enrique; Malissen, Marie; Schraven, Burkhart; Horejsí, Václav
2002-12-16
A key molecule necessary for activation of T lymphocytes through their antigen-specific T cell receptor (TCR) is the transmembrane adaptor protein LAT (linker for activation of T cells). Upon TCR engagement, LAT becomes rapidly tyrosine phosphorylated and then serves as a scaffold organizing a multicomponent complex that is indispensable for induction of further downstream steps of the signaling cascade. Here we describe the identification and preliminary characterization of a novel transmembrane adaptor protein that is structurally and evolutionarily related to LAT and is expressed in B lymphocytes, natural killer (NK) cells, monocytes, and mast cells but not in resting T lymphocytes. This novel transmembrane adaptor protein, termed NTAL (non-T cell activation linker) is the product of a previously identified WBSCR5 gene of so far unknown function. NTAL becomes rapidly tyrosine-phosphorylated upon cross-linking of the B cell receptor (BCR) or of high-affinity Fcgamma- and Fc epsilon -receptors of myeloid cells and then associates with the cytoplasmic signaling molecules Grb2, Sos1, Gab1, and c-Cbl. NTAL expressed in the LAT-deficient T cell line J.CaM2.5 becomes tyrosine phosphorylated and rescues activation of Erk1/2 and minimal transient elevation of cytoplasmic calcium level upon TCR/CD3 cross-linking. Thus, NTAL appears to be a structural and possibly also functional homologue of LAT in non-T cells.
UAV field demonstration of social media enabled tactical data link
NASA Astrophysics Data System (ADS)
Olson, Christopher C.; Xu, Da; Martin, Sean R.; Castelli, Jonathan C.; Newman, Andrew J.
2015-05-01
This paper addresses the problem of enabling Command and Control (C2) and data exfiltration functions for missions using small, unmanned, airborne surveillance and reconnaissance platforms. The authors demonstrated the feasibility of using existing commercial wireless networks as the data transmission infrastructure to support Unmanned Aerial Vehicle (UAV) autonomy functions such as transmission of commands, imagery, metadata, and multi-vehicle coordination messages. The authors developed and integrated a C2 Android application for ground users with a common smart phone, a C2 and data exfiltration Android application deployed on-board the UAVs, and a web server with database to disseminate the collected data to distributed users using standard web browsers. The authors performed a mission-relevant field test and demonstration in which operators commanded a UAV from an Android device to search and loiter; and remote users viewed imagery, video, and metadata via web server to identify and track a vehicle on the ground. Social media served as the tactical data link for all command messages, images, videos, and metadata during the field demonstration. Imagery, video, and metadata were transmitted from the UAV to the web server via multiple Twitter, Flickr, Facebook, YouTube, and similar media accounts. The web server reassembled images and video with corresponding metadata for distributed users. The UAV autopilot communicated with the on-board Android device via on-board Bluetooth network.
ObsPy: A Python Toolbox for Seismology
NASA Astrophysics Data System (ADS)
Krischer, Lion; Megies, Tobias; Sales de Andrade, Elliott; Barsch, Robert; MacCarthy, Jonathan
2017-04-01
In recent years the Python ecosystem evolved into one of the most powerful and productive scientific environments across disciplines. ObsPy (https://www.obspy.org) is a fully community-driven, open-source project dedicated to providing a bridge for seismology into that ecosystem. It does so by offering Read and write support for essentially every commonly used data format in seismology with a unified interface and automatic format detection. This includes waveform data (MiniSEED, SAC, SEG-Y, Reftek, …) as well as station (SEED, StationXML, …) and event meta information (QuakeML, ZMAP, …). Integrated access to the largest data centers, web services, and real-time data streams (FDSNWS, ArcLink, SeedLink, ...). A powerful signal processing toolbox tuned to the specific needs of seismologists. Utility functionality like travel time calculations with the TauP method, geodetic functions, and data visualizations. ObsPy has been in constant development for more than seven years and is developed and used by scientists around the world with successful applications in all branches of seismology. Additionally it nowadays serves as the foundation for a large number of more specialized packages. This presentation will give a short overview of the capabilities of ObsPy and point out several representative or new use cases. Additionally we will discuss the road ahead as well as the long-term sustainability of open-source scientific software.
Hypothesizing dopaminergic genetic antecedents in schizophrenia and substance seeking behavior.
Blum, Kenneth; Oscar-Berman, Marlene; Badgaiyan, Rajendra D; Palomo, Tomas; Gold, Mark S
2014-05-01
The dopamine system has been implicated in both substance use disorder (SUD) and schizophrenia. A recent meta-analysis suggests that A1 allele of the DRD2 gene imposes genetic risk for SUD, especially alcoholism and has been implicated in Reward Deficiency Syndrome (RDS). We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non-SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse. Schizophrenics with SUD may be carriers of the DRD2 Taq1 A1 allele, and/or other RDS reward polymorphisms and have hypodopaminergic reward function. One plausible mechanism for alcohol seeking in schizophrenics with SUD, based on previous research, may be a deficiency of gamma type endorphins that has been linked to schizophrenic type psychosis. We also propose that alcohol seeking behavior in schizophrenics, may serve as a physiological self-healing process linked to the increased function of the gamma endorphins, thereby reducing abnormal dopaminergic activity at the nucleus accumbens (NAc). These hypotheses warrant further investigation and cautious interpretation. We, therefore, encourage research involving neuroimaging, genome wide association studies (GWAS), and epigenetic investigation into the relationship between neurogenetics and systems biology to unravel the role of dopamine in psychiatric illness and SUD. Copyright © 2014 Elsevier Ltd. All rights reserved.
Epigenetic modification of OXT and human sociability.
Haas, Brian W; Filkowski, Megan M; Cochran, R Nick; Denison, Lydia; Ishak, Alexandra; Nishitani, Shota; Smith, Alicia K
2016-07-05
Across many mammalian species there exist genetic and biological systems that facilitate the tendency to be social. Oxytocin is a neuropeptide involved in social-approach behaviors in humans and others mammals. Although there exists a large, mounting body of evidence showing that oxytocin signaling genes are associated with human sociability, very little is currently known regarding the way the structural gene for oxytocin (OXT) confers individual differences in human sociability. In this study, we undertook a comprehensive approach to investigate the association between epigenetic modification of OXT via DNA methylation, and overt measures of social processing, including self-report, behavior, and brain function and structure. Genetic data were collected via saliva samples and analyzed to target and quantify DNA methylation across the promoter region of OXT We observed a consistent pattern of results across sociability measures. People that exhibit lower OXT DNA methylation (presumably linked to higher OXT expression) display more secure attachment styles, improved ability to recognize emotional facial expressions, greater superior temporal sulcus activity during two social-cognitive functional MRI tasks, and larger fusiform gyrus gray matter volume than people that exhibit higher OXT DNA methylation. These findings provide empirical evidence that epigenetic modification of OXT is linked to several overt measures of sociability in humans and serve to advance progress in translational social neuroscience research toward a better understanding of the evolutionary and genetic basis of normal and abnormal human sociability.
Hypothesizing Dopaminergic Genetic Antecedents in Schizophrenia and Substance Seeking Behavior
Blum, Kenneth; Oscar-Berman, Marlene; Badgaiyan, Rajendra; Palomo, Tomas; Gold, Mark S.
2014-01-01
The dopamine system has been implicated in both substance use disorder (SUD) and schizophrenia. A recent meta- analysis suggests that A1 allele of the DRD2 gene imposes genetic risk for SUD, especially alcoholism and has been implicated in Reward Deficiency Syndrome (RDS). We hypothesize that dopamine D2 receptor (DRD2) gene Taq1 A2 allele is associated with a subtype of non- SUD schizophrenics and as such may act as a putative protective agent against the development of addiction to alcohol or other drugs of abuse. Schizophrenics with SUD may be carriers of the DRD2 Taq1 A1 allele, and/or other RDS reward polymorphisms and have hypodopaminergic reward function. One plausible mechanism for alcohol seeking in schizophrenics with SUD, based on previous research, may be a deficiency of gamma type endorphins that has been linked to schizophrenic type psychosis.. We also propose that alcohol seeking behavior in schizophrenics, may serve as a physiological self-healing process linked to the increased function of the gamma endorphins, thereby reducing abnormal dopaminergic activity at the nucleus accumbens (NAc). These hypotheses warrant further investigation and cautious interpretation. We, therefore, encourage research involving neuroimaging, genome wide association studies (GWAS), and epigenetic investigation into the relationship between neurogenetics and systems biology to unravel the role of dopamine in psychiatric illness and SUD. PMID:24636783
Rahim, S M; Mazlan, A G; Simon, K D; Delaunoy, J P; Laurent, P
2014-02-01
Pseudobranch function has long interested scientists, but its role has yet to be elucidated. Several studies have suggested that pseudobranchs serve respiratory, osmoregulatory, and sensory functions. This work investigated the immunolocalization of pseudobranch carbonic anhydrase (CA) in the teleost fish species rainbow trout (Oncorhynchus mykiss) to clarify its physiological function. CA was purified from rainbow trout gills O. mykiss and specific antibodies were raised. Immunoblotting between tissue homogenates of pseudobranch and gill CA antibodies showed specific immunostaining with only one band corresponding to CA in the pseudobranch homogenate. Results of immunohistochemical technique revealed that CA was distributed within pseudobranch cells and more precisely in the apical parts (anti-vascular) of cells. The basal (vascular) parts of cells, tubular system, blood capillaries, and pillar cells were not immunostained. Immunocytochemistry confirmed these results and showed that some CA enzyme was cytoplasmic and the remainder was linked to membranous structures. The results also showed that the lacunar tissue layers did not display immunoperoxidase activity. Our results indicated that pseudobranch CA may have a function related to the extracellular medium wherein CA intervenes with the mechanism of stimulation of afferent nerve fibers.
NASA Astrophysics Data System (ADS)
Meyer, Nele Kristin; Schwanghart, Wolfgang; Korup, Oliver
2014-05-01
Norwegian's road network is frequently affected by debris flows. Both damage repair and traffic interruption generate high economic losses and necessitate a rigorous assessment of where losses are expected to be high and where preventive measures should be focused on. In recent studies, we have developed susceptibility and trigger probability maps that serve as input into a hazard calculation at the scale of first-order watersheds. Here we combine these results with graph theory to assess the impact of debris flows on the road network of southern Norway. Susceptibility and trigger probability are aggregated for individual road sections to form a reliability index that relates to the failure probability of a link that connects two network vertices, e.g., road junctions. We define link vulnerability as a function of traffic volume and additional link failure distance. Additional link failure distance is the extra length of the alternative path connecting the two associated link vertices in case the network link fails and is calculated by a shortest-path algorithm. The product of network reliability and vulnerability indices represent the risk index. High risk indices identify critical links for the Norwegian road network and are investigated in more detail. Scenarios demonstrating the impact of single or multiple debris flow events are run for the most important routes between seven large cities in southern Norway. First results show that the reliability of the road network is lowest in the central and north-western part of the study area. Road network vulnerability is highest in the mountainous regions in central southern Norway where the road density is low and in the vicinity of cities where the traffic volume is large. The scenarios indicate that city connections that have their shortest path via routes crossing the central part of the study area have the highest risk of route failure.
NASA Astrophysics Data System (ADS)
Spiegel, J. Dominik; Lyskov, Igor; Kleinschmidt, Martin; Marian, Christel M.
2017-01-01
BODIPY-based dyads serve as model systems for the investigation of excitation energy transfer (EET). Through-space EET is brought about by direct and exchange interactions between the transition densities of donor and acceptor localized states. The presence of a molecular linker gives rise to additional charge transfer (CT) contributions. Here, we present a novel approach for the calculation of the excitonic coupling matrix element (ECME) including CT contributions which is based on supermolecular one-electron transition density matrices (STD). The validity of the approach is assessed for a model system of two π -stacked ethylene molecules at varying intermolecular separation. Wave functions and electronic excitation energies of five EET cassettes comprising anthracene as exciton donor and BODIPY as exciton acceptor are obtained by the redesigned combined density functional theory and multireference configuration interaction (DFT/MRCI-R) method. CT contributions to the ECME are shown to be important in the covalently linked EET cassettes.
Chronic Methamphetamine Abuse and Corticostriatal Deficits Revealed by Neuroimaging
London, Edythe D.; Kohno, Milky; Morales, Angelica; Ballard, Michael E.
2014-01-01
Despite aggressive efforts to contain it, methamphetamine use disorder continues to be major public health problem; and with generic behavioral therapies still the mainstay of treatment for methamphetamine abuse, rates of attrition and relapse remain high. This review summarizes the findings of structural, molecular, and functional neuroimaging studies of methamphetamine abusers, focusing on cortical and striatal abnormalities and their potential contributions to cognitive and behavioral phenotypes that can serve to promote compulsive drug use. These studies indicate that individuals with a history of chronic methamphetamine abuse often display several signs of corticostriatal dysfunction, including abnormal gray- and white-matter integrity, monoamine neurotransmitter system deficiencies, neuroinflammation, poor neuronal integrity, and aberrant patterns of brain connectivity and function, both when engaged in cognitive tasks and at rest. More importantly, many of these neural abnormalities were found to be linked with certain addiction-related phenotypes that may influence treatment response (e.g., poor self-control, cognitive inflexibility, maladaptive decision-making), raising the possibility that they may represent novel therapeutic targets. PMID:25451127
Melanin, Radiation, and Energy Transduction in Fungi.
Casadevall, Arturo; Cordero, Radames J B; Bryan, Ruth; Nosanchuk, Joshua; Dadachova, Ekaterina
2017-03-01
Melanin pigments are found in many diverse fungal species, where they serve a variety of functions that promote fitness and cell survival. Melanotic fungi inhabit some of the most extreme habitats on earth such as the damaged nuclear reactor at Chernobyl and the highlands of Antarctica, both of which are high-radiation environments. Melanotic fungi migrate toward radioactive sources, which appear to enhance their growth. This phenomenon, combined with the known capacities of melanin to absorb a broad spectrum of electromagnetic radiation and transduce this radiation into other forms of energy, raises the possibility that melanin also functions in harvesting such energy for biological usage. The ability of melanotic fungi to harness electromagnetic radiation for physiological processes has enormous implications for biological energy flows in the biosphere and for exobiology, since it provides new mechanisms for survival in extraterrestrial conditions. Whereas some features of the way melanin-related energy transduction works can be discerned by linking various observations and circumstantial data, the mechanistic details remain to be discovered.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sills, Robert C.; Harry, G. Jean; Valentine, William M.
2005-09-01
Inhalation studies were conducted on the hazardous air pollutants, carbon disulfide, which targets the central nervous system (spinal cord) and peripheral nervous system (distal portions of long myelinated axons), and carbonyl sulfide, which targets the central nervous system (brain). The objectives were to investigate the neurotoxicity of these compounds by a comprehensive evaluation of function, structure, and mechanisms of disease. Through interdisciplinary research, the major finding in the carbon disulfide inhalation studies was that carbon disulfide produced intra- and intermolecular protein cross-linking in vivo. The observation of dose-dependent covalent cross-linking in neurofilament proteins prior to the onset of lesions ismore » consistent with this process contributing to the development of the neurofilamentous axonal swellings characteristic of carbon disulfide neurotoxicity. Of significance is that valine-lysine thiourea cross-linking on rat globin and lysine-lysine thiourea cross-linking on erythrocyte spectrin reflect cross-linking events occurring within the axon and could potentially serve as biomarkers of carbon disulfide exposure and effect. In the carbonyl sulfide studies, using magnetic resonance microscopy (MRM), we determined that carbonyl sulfide targets the auditory pathway in the brain. MRM allowed the examination of 200 brain slices and made it possible to identify the most vulnerable sites of neurotoxicity, which would have been missed in our traditional neuropathology evaluations. Electrophysiological studies were focused on the auditory system and demonstrated decreases in auditory brain stem evoked responses. Similarly, mechanistic studies focused on evaluating cytochrome oxidase activity in the posterior colliculus and parietal cortex. A decrease in cytochrome oxidase activity was considered to be a contributing factor to the pathogenesis of carbonyl sulfide neurotoxicity.« less
Williamson, Rebecca; Meacham, Lillian; Cherven, Brooke; Hassen-Schilling, Leann; Edwards, Paula; Palgon, Michael; Espinoza, Sofia; Mertens, Ann
2014-09-01
Cancer SurvivorLink™, www.cancersurvivorlink.org , is a patient-controlled communication tool where survivors can electronically store and share documents with healthcare providers. Functionally, SurvivorLink serves as an electronic personal health record-a record of health-related information managed and controlled by the survivor. Recruitment methods to increase registration and the characteristics of registrants who completed each step of using SurvivorLink are described. Pediatric cancer survivors were recruited via mailings, survivor clinic, and community events. Recruitment method and Aflac Survivor Clinic attendance was determined for each registrant. Registration date, registrant type (parent vs. survivor), zip code, creation of a personal health record in SurvivorLink, storage of documents, and document sharing were measured. Logistic regression was used to determine the characteristics that predicted creation of a health record and storage of documents. To date, 275 survivors/parents have completed registration: 63 were recruited via mailing, 99 from clinic, 56 from community events, and 57 via other methods. Overall, 66.9 % registrants created a personal health record and 45.7 % of those stored a health document. There were no significant predictors for creating a personal health record. Attending a survivor clinic was the strongest predictor of document storage (p < 0.01). Of those with a document stored, 21.4 % shared with a provider. Having attended survivor clinic is the biggest predictor of registering and using SurvivorLink. Many survivors must advocate for their survivorship care. Survivor Link provides educational material and supports the dissemination of survivor-specific follow-up recommendations to facilitate shared clinical care decision making.
Politi, Yael; Pippel, Eckhard; Licuco-Massouh, Ana C J; Bertinetti, Luca; Blumtritt, Horst; Barth, Friedrich G; Fratzl, Peter
2017-01-01
We identify the presence of multiple vascular channels within the spider fang. These channels seem to serve the transport of zinc to the tip of the fang to cross-link the protein matrix by binding to histidine residues. According to amino acid and elemental analysis of fangs extracted shortly after ecdysis, His-rich proteins are deposited before Zn is incorporated into the cuticle. Microscopic and spectroscopic investigations in the electron microscope and synchrotron radiation experiments suggest that Zn ions are transported through these channels in a liable (yet unidentified) form, and then form stable complexes upon His binding. The resulting cross-linking through the Zn-His complexes is conferring hardness to the fang. Our observations of nano-channels serving the Zn-transport within the His-rich protein matrix of the fibre reinforced spider fang may also support recent bio-inspired attempts to design artificial polymeric vascular materials for self-healing and in-situ curing. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Shahidullah, Jeffrey D; Azad, Gazi; Mezher, Katherine R; McClain, Maryellen Brunson; McIntyre, Laura Lee
2018-05-01
Children with autism spectrum disorder (ASD) present with complex medical problems that are often exacerbated by a range of other intellectual and psychiatric comorbidities. These children receive care for their physical and mental health from a range of providers within numerous child-serving systems, including their primary care clinic, school, and the home and community. Given the longitudinal nature in which care is provided for this chronic disorder, it is particularly necessary for services and providers to coordinate their care to ensure optimal efficiency and effectiveness. There are 2 primary venues that serve as a "home" for coordination of service provision for children with ASD and their families-the "medical home" and the "educational home." Unfortunately, these venues often function independently from the other. Furthermore, there are limited guidelines demonstrating methods through which pediatricians and other primary care providers (PCPs) can coordinate care with schools and school-based providers. The purpose of this article is 2-fold: (1) we highlight the provision of evidence-based care within the medical home and educational home and (2) we offer practice recommendations for PCPs in integrating these systems to optimally address the complex medical, intellectual, and psychiatric symptomology affected by autism.
The Tale of the Storyteller and the Painter: The Paradoxes in Nature
Chandra, Sadanandavalli Retnaswami; Viswanathan, Lakshminarayanapuram Gopal; Wahatule, Rahul; Shetty, Safal
2017-01-01
Introduction: Brain as the seat of behavior is acknowledged from the times of Charaka, however where neurology ends and philosophy begins remains an enigma. It is certainly every neurologist's observation that there is loss of function either region based or domain based in progressive diseases of the nervous system making it the seat of all useful activities. However, there are references to occurrence of new skills seen during various illnesses causing progressive cognitive dysfunction. This serves as a pharmaco-sparing agent in behavior management and therefore serves as a rehabilitatory tool. However, its pathomechanism is not clear. Patient and Methods: Two patients comprising one male and one female who were being evaluated for progressive cognitive dysfunction and were found to have interesting creative skills and are being described. Results: The first patient is a case of young onset behavioral variant frontotemporal dementia and the second patient is a case of neurosarcoidosis. Conclusion: The emergence of these skills could be due to disinhibition of some of the innate skills of the patients during degeneration or establishment of new data linking circuits with creative potential during attempted repair. PMID:29284821
Structural and Functional Components of the Skate Sensory Organ Ampullae of Lorenzini.
Zhang, Xing; Xia, Ke; Lin, Lei; Zhang, Fuming; Yu, Yanlei; St Ange, Kalib; Han, Xiaorui; Edsinger, Eric; Sohn, Joel; Linhardt, Robert J
2018-05-09
The skate, a cartilaginous fish related to sharks and rays, possesses a unique electrosensitive sensory organ known as the ampullae of Lorenzini (AoL). This organ is responsible for the detection of weak electric field changes caused by the muscle contractions of their prey. While keratan sulfate (KS) is believed to be a component of a jelly that fills this sensory organ and has been credited with its high proton conductivity, modern analytical methods have not been applied to its characterization. Surprisingly, total glycosaminoglycan (GAG) analysis demonstrates that the KS from skate jelly is extraordinarily pure, containing no other GAGs. This KS had a molecular weight of 20 to 30 kDa, consisting primarily of N-linked KS comprised mostly of a monosulfated disaccharide repeating unit, →3) Gal (1→4) GlcNAc6S (1→. Proteomic analysis of AoL jelly suggests that transferrin, keratin, and mucin serve as KS core proteins. Actin and tropomyosin are responsible for assembling the macrostructure of the jelly, and parvalbumin α-like protein and calreticulin regulate calcium and potassium channels involved in the transduction of the electrical signal, once conducted down the AoL by the jelly, serving as the molecular basis for electroreception.
Microbial megacities fueled by methane oxidation in a mineral spring cave
Karwautz, Clemens; Kus, Günter; Stöckl, Michael; Neu, Thomas R; Lueders, Tillmann
2018-01-01
Massive biofilms have been discovered in the cave of an iodine-rich former medicinal spring in southern Germany. The biofilms completely cover the walls and ceilings of the cave, giving rise to speculations about their metabolism. Here we report on first insights into the structure and function of the biofilm microbiota, combining geochemical, imaging and molecular analytics. Stable isotope analysis indicated that thermogenic methane emerging into the cave served as an important driver of biofilm formation. The undisturbed cavern atmosphere contained up to 3000 p.p.m. methane and was microoxic. A high abundance and diversity of aerobic methanotrophs primarily within the Methylococcales (Gammaproteobacteria) and methylotrophic Methylophilaceae (Betaproteobacteria) were found in the biofilms, along with a surprising diversity of associated heterotrophic bacteria. The highest methane oxidation potentials were measured for submerged biofilms on the cavern wall. Highly organized globular structures of the biofilm matrix were revealed by fluorescent lectin staining. We propose that the extracellular matrix served not only as an electron sink for nutrient-limited biofilm methylotrophs but potentially also as a diffusive barrier against volatilized iodine species. Possible links between carbon and iodine cycling in this peculiar habitat are discussed. PMID:28949325
Light-induced cross-linking and post-cross-linking modification of polyglycidol.
Marquardt, F; Bruns, M; Keul, H; Yagci, Y; Möller, M
2018-02-08
The photoinduced radical generation process has received renewed interest due to its economic and ecological appeal. Herein the light-induced cross-linking of functional polyglycidol and its post-cross-linking modification are presented. Linear polyglycidol was first functionalized with a tertiary amine in a two-step reaction. Dimethylaminopropyl functional polyglycidol was cross-linked in a UV-light mediated reaction with camphorquinone as a type II photoinitiator. The cross-linked polyglycidol was further functionalized by quaternization with various organoiodine compounds. Aqueous dispersions of the cross-linked polymers were investigated by means of DLS and zeta potential measurements. Polymer films were evaluated by DSC and XPS.
Thermal feedback in virtual reality and telerobotic systems
NASA Technical Reports Server (NTRS)
Zerkus, Mike; Becker, Bill; Ward, Jon; Halvorsen, Lars
1994-01-01
A new concept has been developed that allows temperature to be part of the virtual world. The Displaced Temperature Sensing System (DTSS) can 'display' temperature in a virtual reality system.The DTSS can also serve as a feedback device for telerobotics. For virtual reality applications the virtual world software would be required to have a temperature map of its world. By whatever means (magnetic tracker, ultrasound tracker, etc.) the hand and fingers, which have been instrumented with thermodes, would be tracked. The temperature associated with the current position would be transmitted to the DRSS via a serial data link. The DTSS would provide that temperature to the fingers. For telerobotic operation the function of the DTSS is to transmit a temperature from a remote location to the fingers where the temperature can be felt.
Stuewig, Jeffrey; Tangney, June P.; Heigel, Caron; Harty, Laura; McCloskey, Laura
2010-01-01
Theory suggests that shame should be positively related to aggression while guilt may serve as a protective factor. Little research has examined mediators between the moral emotions and aggression. Results using path analyses in four diverse samples were consistent with a model of no direct relationship between shame-proneness and aggression. There was, however, a significant indirect relationship through externalization of blame, but mostly when aggression was measured using self-report. Guilt-proneness, on the other hand, showed a direct negative relationship to aggression whether using self-report or other reports of aggression. Guilt was also inversely related to aggression indirectly through externalization of blame and empathy. Identifying these differing mechanisms may be useful in developing more effective interventions for aggressive individuals. PMID:20369025
Identification and functional validation of novel autoantigens in equine uveitis.
Deeg, Cornelia A; Pompetzki, Dirk; Raith, Albert J; Hauck, Stefanie M; Amann, Barbara; Suppmann, Sabine; Goebel, Thomas W F; Olazabal, Ursula; Gerhards, Hartmut; Reese, Sven; Stangassinger, Manfred; Kaspers, Bernd; Ueffing, Marius
2006-08-01
The development, progression, and recurrence of autoimmune diseases are frequently driven by a group of participatory autoantigens. We identified and characterized novel autoantigens by analyzing the autoantibody binding pattern from horses affected by spontaneous equine recurrent uveitis to the retinal proteome. Cellular retinaldehyde-binding protein (cRALBP) had not been described previously as autoantigen, but subsequent characterization in equine recurrent uveitis horses revealed B and T cell autoreactivity to this protein and established a link to epitope spreading. We further immunized healthy rats and horses with cRALBP and observed uveitis in both species with typical tissue lesions at cRALBP expression sites. The autoantibody profiling outlined here could be used in various autoimmune diseases to detect autoantigens involved in the dynamic spreading cascade or serve as predictive markers.
Ren, Xuezhu; Schweizer, Karl; Wang, Tengfei; Chu, Pei; Gong, Qin
2017-10-01
The aim of the current study is to provide new insights into the relationship between executive functions and intelligence measures in considering the item-position effect observed in intelligence items. Raven's Advanced Progressive Matrices (APM) and Horn's LPS reasoning test were used to assess fluid intelligence which served as criterion in investigating the relationship between intelligence and executive functions. A battery of six experimental tasks measured the updating, shifting, and inhibition processes of executive functions. Data were collected from 205 university students. Fluid intelligence showed substantial correlations with the updating and inhibition processes and no correlation with the shifting process without considering the item-position effect. Next, the fixed-link model was applied to APM and LPS data separately to decompose them into an ability component and an item-position component. The results of relating the components to executive functions showed that the updating and shifting processes mainly contributed to the item-position component whereas the inhibition process was mainly associated with the ability component of each fluid intelligence test. These findings suggest that improvements in the efficiency of updating and shifting processes are likely to occur during the course of completing intelligence measures and inhibition is important for intelligence in general. Copyright © 2017 Elsevier B.V. All rights reserved.
Motor Control of Human Spinal Cord Disconnected from the Brain and Under External Movement.
Mayr, Winfried; Krenn, Matthias; Dimitrijevic, Milan R
2016-01-01
Motor control after spinal cord injury is strongly depending on residual ascending and descending pathways across the lesion. The individually altered neurophysiology is in general based on still intact sublesional control loops with afferent sensory inputs linked via interneuron networks to efferent motor outputs. Partial or total loss of translesional control inputs reduces and alters the ability to perform voluntary movements and results in motor incomplete (residual voluntary control of movement functions) or motor complete (no residual voluntary control) spinal cord injury classification. Of particular importance are intact functionally silent neural structures with residual brain influence but reduced state of excitability that inhibits execution of voluntary movements. The condition is described by the term discomplete spinal cord injury. There are strong evidences that artificial afferent input, e.g., by epidural or noninvasive electrical stimulation of the lumbar posterior roots, can elevate the state of excitability and thus re-enable or augment voluntary movement functions. This modality can serve as a powerful assessment technique for monitoring details of the residual function profile after spinal cord injury, as a therapeutic tool for support of restoration of movement programs and as a neuroprosthesis component augmenting and restoring movement functions, per se or in synergy with classical neuromuscular or muscular electrical stimulation.
Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins.
Larsen, Ida Signe Bohse; Narimatsu, Yoshiki; Joshi, Hiren Jitendra; Siukstaite, Lina; Harrison, Oliver J; Brasch, Julia; Goodman, Kerry M; Hansen, Lars; Shapiro, Lawrence; Honig, Barry; Vakhrushev, Sergey Y; Clausen, Henrik; Halim, Adnan
2017-10-17
The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1-4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3.
Silva, Martina Rios; Moser, Doris; Pflüger, Melanie; Pusswald, Gisela; Stögmann, Elisabeth; Dal-Bianco, Peter; Auff, Eduard; Lehrner, Johann
2016-06-01
Awareness of subjective memory is an important factor for adequate treatment of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). This study served to find out whether awareness of subjective memory complies with objective performance, if differences in awareness are observed longitudinally and whether decrease of awareness can serve as a predictor of AD in MCI patients. Thirty-four patients with MCI seeking help in a memory outpatient clinic were included. All participants underwent thorough neuropsychological examination. Awareness of subjective memory was obtained by calculating difference scores between patient and informant ratings on a 16-item questionnaire concerning complaints about loss of memory in every-day life. Retesting was performed after a mean follow-up period of 24 months. Whole group analyses showed that awareness remained relatively stable across time. Self-reported memory complaints correlated with episodic memory at baseline and with performance on a language task at follow-up. Retests displayed decrease of awareness. At group level differences in awareness between both times of assessment were not significant for MCI and MCI patients converting to mild AD at follow-up. The predictive value of awareness was low. Awareness of subjective memory deficit is linked to episodic memory function and decreases with decline of cognitive ability. Further studies evaluating predictive power of awareness of subjective memory should include a larger patient sample.
Parenting Stress as a Mediator Between Childhood ADHD and Early Adult Female Outcomes.
Gordon, Chanelle T; Hinshaw, Stephen P
2017-01-01
The purpose of this study is to examine the mediating role of parenting stress (both parental distress and stress due to dysfunctional interactions in the mother-daughter relationship [PSDI]) in the link between childhood attention-deficit/hyperactivity disorder (ADHD) status and several important young adult outcomes. The diverse sample comprised 140 girls with ADHD and 88 age- and ethnicity-matched comparisons, evaluated at ages 6-12 years and followed prospectively for five years (M age = 14.2) and 10 years (M age = 19.6). The PSDI experienced by a mother during her daughter's adolescence mediated the link between her daughter's childhood ADHD status and adult externalizing and internalizing symptoms. PSDI also mediated the link between ADHD status and young adult nonsuicidal self-injury and had an indirect effect in the relation between childhood ADHD and young adult depressive symptoms. The mediating role of PSDI with respect to internalizing symptoms and depressive symptoms remained in place even when covarying adolescent internalizing/depressive symptoms. Parenting stress, particularly related to maternal perceptions of dysfunctional interactions with adolescent daughters, serves as a key mediator in the association between childhood ADHD status and important domains of young adult functioning. Minimizing parenting stress and dysfunctional mother-daughter interactions during adolescence might reduce the risk of adverse adult outcomes for girls with ADHD.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Green, E.D.; Baenziger, J.U.
1988-01-05
The asparagine-linked oligosaccharides on the pituitary glycoprotein hormones lutropin (LH), follitropin (FSH), and thyrotropin (TSH) consist of a heterogeneous array of neutral, sulfated, sialylated, and sulfated/sialylated structures. In this study, the authors determined the relative quantities of the various asparagine-linked oligosaccharides on LH, FSH, and TSH from these three animal species. The proportions of sulfated versus sialylated oligosaccharides varied markedly among the different hormones. Both hormone- and animal species-specific differences in the types and distributions of sulfated, sialylated, and sulfated/sialylated structures were evident. In particular, LH and FSH, which are synthesized in the same pituitary cell and bear ..cap alpha..-subunitsmore » with the identical amino acid sequence, contained significantly different distributions of sulfated and sialylated oligosaccharides. For all three animal species, the ratio of sialylated to sulfated oligosaccharides differed by >10-fold for LH and FSH, with sulfated structures dominating on LH and sialylated structures on FSH. Sialylated oligosaccharides were also heterogeneous with respect to sialic acid linkage (..cap alpha..2,3 versus ..cap alpha..2,6). The differences in oligosaccharide structures among the various pituitary glycoprotein hormones as well as among the various glycosylation sites within a single hormone support the hypothesis that glycosylation may serve important functional roles in the expression and/or regulation of hormone bioactivity.« less
Cognitive Neuroscience of Sleep
Poe, Gina R.; Walsh, Christine M.; Bjorness, Theresa E.
2014-01-01
Mechanism is at the heart of understanding, and this chapter addresses underlying brain mechanisms and pathways of cognition and the impact of sleep on these processes, especially those serving learning and memory. This chapter reviews the current understanding of the relationship between sleep/waking states and cognition from the perspective afforded by basic neurophysiological investigations. The extensive overlap between sleep mechanisms and the neurophysiology of learning and memory processes provide a foundation for theories of a functional link between the sleep and learning systems. Each of the sleep states, with its attendant alterations in neurophysiology, is associated with facilitation of important functional learning and memory processes. For rapid eye movement (REM) sleep, salient features such as PGO waves, theta synchrony, increased acetylcholine, reduced levels of monoamines and, within the neuron, increased transcription of plasticity-related genes, cumulatively allow for freely occurring bidirectional plasticity (long-term potentiation (LTP) and its reversal, depotentiation). Thus, REM sleep provides a novel neural environment in which the synaptic remodeling essential to learning and cognition can occur, at least within the hippocampal complex. During nonREM sleep Stage 2 spindles, the cessation and subsequent strong bursting of noradrenergic cells and coincident reactivation of hippocampal and cortical targets would also increase synaptic plasticity, allowing targeted bidirectional plasticity in the neocortex as well. In delta nonREM sleep, orderly neuronal reactivation events in phase with slow wave delta activity, together with high protein synthesis levels, would facilitate the events that convert early LTP to long lasting LTP. Conversely, delta sleep does not activate immediate early genes associated with de novo LTP. This nonREM sleep-unique genetic environment combined with low acetylcholine levels may serve to reduce the strength of cortical circuits that activate in the ~50% of delta-coincident reactivation events that do not appear in their waking firing sequence. The chapter reviews the results of manipulation studies, typically total sleep or REM sleep deprivation, that serve to underscore the functional significance of the phenomenological associations. Finally, the implications of sleep neurophysiology for learning and memory will be considered from a larger perspective in which the association of specific sleep states with both potentiation or depotentiation is integrated into mechanistic models of cognition. PMID:21075230
Role of Nitric Oxide in Stress-Induced Anxiety: From Pathophysiology to Therapeutic Target.
Kumar, A; Chanana, P
2017-01-01
Stress is often marked by a state of hyperarousal to aid the initiation of necessary stress response for the successful management of stressful stimuli. It can be manifested as a challenge (stimulus) that requires behavioral, psychological, and physiological adaptations for the maintenance of a state of homeostasis in response to stressful stimuli. In an organism, miscellaneous stressors trigger a wide spectrum of alterations in hormonal and neuronal physiologies, resulting in behavioral (anxiety and depression disorders, diminished food intake and gastrointestinal dysfunctions, decline in sexual behavior, diabetes, and loss of cognitive function) and other physiological responses. Stress serves as a potent etiological link to development of several neuropsychiatric diseases such as depression, anxiety, and cognitive impairments. Exposure to stressful stimuli has been found to be associated with activation of nitric oxide synthase and generation of NO which reacts with spontaneous oxygen species to aid formation of active nitrogen radicals. High concentrations of reactive nitrogen radicals may cause damage to intracellular proteins, in addition to causing impairment to components of the mitochondrial transport chain, leading to cellular energy deficiency. This may further serve as an etiological link to the development of secondary neurological diseases associated with chronic stress. Also, during stress exposure, pharmacological inhibition of nitric oxide production displays reduction in indicators of anxiety- and depressive-like behavior in animal models. Therefore, the purpose of this chapter is to present an overview on the role of NO in stress-evoked emergence of secondary neurological disorders like anxiety as well as citing examples where NO has been used as a therapeutic target for the management of stress-induced anxiety-like behavior. © 2017 Elsevier Inc. All rights reserved.
Hidden wholesale: The drug diffusing capacity of online drug cryptomarkets.
Aldridge, Judith; Décary-Hétu, David
2016-09-01
In spite of globalizing processes 'offline' retail drug markets remain localized and - in recent decades - typically 'closed', in which dealers sell primarily to known customers. We characterize drug cryptomarkets as 'anonymous open' marketplaces that allow the diffusion of drugs across locales. Where cryptomarket customers make stock-sourcing purchases for offline distribution, the cryptomarket may indirectly serve drug users who are not themselves cryptomarket customers, thereby increasing the drug diffusing capacity of these marketplaces. Our research aimed to identify wholesale activity on the first major cryptomarket, Silk Road 1. Data were collected 13-15 September 2013. A bespoke web crawler downloaded content from the first major drug cryptomarket, Silk Road 1. This generated data on 1031 vendors and 10,927 drug listings. We estimated monthly revenues to ascertain the relative importance of wholesale priced listings. Wholesale-level revenue generation (sales for listings priced over USD $1000.00) accounted for about a quarter of the revenue generation on SR1 overall. Ecstasy-type drugs dominated wholesale activity on this marketplace, but we also identified substantial wholesale transactions for benzodiazepines and prescription stimulants. Less important, but still generating wholesale revenue, were cocaine, methamphetamine and heroin. Although vendors on the marketplace were located in 41 countries, wholesale activity was confined to only a quarter of these, with China, the Netherlands, Canada and Belgium prominent. The cryptomarket may function in part as a virtual broker, linking wholesalers with offline retail-level distributors. For drugs like ecstasy, these marketplaces may link vendors in producer countries directly with retail level suppliers. Wholesale activity on cryptomarkets may serve to increase the diffusion of new drugs - and wider range of drugs - in offline drug markets, thereby indirectly serving drug users who are not cryptomarket customers themselves. Cryptomarkets provide researchers and policy makers with a rich source of drug monitoring information. Further research should ascertain whether their virtual location may reduce the violence associated with middle market drug activity. We caution that conflict may instead manifest in other ways, including threats, fraud, and blackmail. Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.
Configurable Multi-Purpose Processor
NASA Technical Reports Server (NTRS)
Valencia, J. Emilio; Forney, Chirstopher; Morrison, Robert; Birr, Richard
2010-01-01
Advancements in technology have allowed the miniaturization of systems used in aerospace vehicles. This technology is driven by the need for next-generation systems that provide reliable, responsive, and cost-effective range operations while providing increased capabilities such as simultaneous mission support, increased launch trajectories, improved launch, and landing opportunities, etc. Leveraging the newest technologies, the command and telemetry processor (CTP) concept provides for a compact, flexible, and integrated solution for flight command and telemetry systems and range systems. The CTP is a relatively small circuit board that serves as a processing platform for high dynamic, high vibration environments. The CTP can be reconfigured and reprogrammed, allowing it to be adapted for many different applications. The design is centered around a configurable field-programmable gate array (FPGA) device that contains numerous logic cells that can be used to implement traditional integrated circuits. The FPGA contains two PowerPC processors running the Vx-Works real-time operating system and are used to execute software programs specific to each application. The CTP was designed and developed specifically to provide telemetry functions; namely, the command processing, telemetry processing, and GPS metric tracking of a flight vehicle. However, it can be used as a general-purpose processor board to perform numerous functions implemented in either hardware or software using the FPGA s processors and/or logic cells. Functionally, the CTP was designed for range safety applications where it would ultimately become part of a vehicle s flight termination system. Consequently, the major functions of the CTP are to perform the forward link command processing, GPS metric tracking, return link telemetry data processing, error detection and correction, data encryption/ decryption, and initiate flight termination action commands. Also, the CTP had to be designed to survive and operate in a launch environment. Additionally, the CTP was designed to interface with the WFF (Wallops Flight Facility) custom-designed transceiver board which is used in the Low Cost TDRSS Transceiver (LCT2) also developed by WFF. The LCT2 s transceiver board demodulates commands received from the ground via the forward link and sends them to the CTP, where they are processed. The CTP inputs and processes data from the inertial measurement unit (IMU) and the GPS receiver board, generates status data, and then sends the data to the transceiver board where it is modulated and sent to the ground via the return link. Overall, the CTP has combined processing with the ability to interface to a GPS receiver, an IMU, and a pulse code modulation (PCM) communication link, while providing the capability to support common interfaces including Ethernet and serial interfaces boarding a relatively small-sized, lightweight package.
The collaborative edge: patient empowerment for vulnerable populations.
Safran, Charles
2003-03-01
The problems with access to care and the special needs for educational outreach for disadvantage or vulnerable populations of patients require innovation. This paper describes Baby CareLink use of information technology to support communication, consultation, and collaboration among colleagues as well as with patients, their families, and community resources. In response to the educational, emotional and communication needs of parents of premature infants and the clinicians who care for the infants and support the families, we developed Baby CareLink, a secure collaborative environment. Baby CareLink provides a nurturing environment where parents, even though remote from the Neonatal Intensive Care Unit, can actively participate in decisions surrounding their baby's care. In a southeastern hospital serving a mostly Medicaid population in a rural setting, more than 300 parents have used Baby CareLink more than 11000 times during the past year. Despite the common wisdom that Medicaid families do not have access to the Internet, approximately 85% of the parents access Baby CareLink from home, at work, from the library or other public access point. The median use of Baby CareLinks from outside the hospital by parents is 17 separate sessions. In a city hospital in the midwestern US which exclusively serves a Medicaid population, experience has been equally encouraging. More than 70 parents have initiated more than 600 secure sessions with Baby CareLink. In contrast to the rural hospital, only 35% of sessions have been initiated outside the hospital. Experience with Baby CareLink suggests that families from all walks of life will use and benefit from collaborative tools that keep them informed and involved in the care of their children. The most significant barrier to wider deployment is bandwidth limitations into the homes of most families. The care of premature infants is a great example of an area where medical knowledge and ability has grown dramatically, and where information and communication technology holds enormous potential.
Uneke, Chigozie Jesse; Ndukwe, Chinwendu Daniel; Ezeoha, Abel Abeh; Uro-Chukwu, Henry Chukwuemeka; Ezeonu, Chinonyelum Thecla
2015-01-01
Background: In recent times, there has been a growing demand internationally for health policies to be based on reliable research evidence. Consequently, there is a need to strengthen institutions and mechanisms that can promote interactions among researchers, policy-makers and other stakeholders who can influence the uptake of research findings. The Health Policy Advisory Committee (HPAC) is one of such mechanisms that can serve as an excellent forum for the interaction of policy-makers and researchers. Therefore, the need to have a long term mechanism that allows for periodic interactions between researchers and policy-makers within the existing government system necessitated our implementation of a newly established HPAC in Ebonyi State Nigeria, as a Knowledge Translation (KT) platform. The key study objective was to enhance the capacity of the HPAC and equip its members with the skills/competence required for the committee to effectively promote evidence informed policy-making and function as a KT platform. Methods: A series of capacity building programmes and KT activities were undertaken including: i) Capacity building of the HPAC using Evidence-to-Policy Network (EVIPNet) SUPPORT tools; ii) Capacity enhancement mentorship programme of the HPAC through a three-month executive training programme on health policy/health systems and KT in Ebonyi State University Abakaliki; iii) Production of a policy brief on strategies to improve the performance of the Government’s Free Maternal and Child Health Care Programme in Ebonyi State Nigeria; and iv) Hosting of a multi-stakeholders policy dialogue based on the produced policy brief on the Government’s Free Maternal and Child Health Care Programme. Results: The study findings indicated a noteworthy improvement in knowledge of evidence-to-policy link among the HPAC members; the elimination of mutual mistrust between policy-makers and researchers; and an increase in the awareness of importance of HPAC in the Ministry of Health (MoH). Conclusion: Findings from this study suggest that a HPAC can function as a KT platform and can introduce a new dimension towards facilitating evidence-to-policy link into the operation of the MoH, and can serve as an excellent platform to bridge the gap between research and policy. PMID:25774373
DOE Office of Scientific and Technical Information (OSTI.GOV)
Corbin, Cyrielle; Drouet, Samantha; Markulin, Lucija
Identification of DIR encoding genes in flax genome. Analysis of phylogeny, gene/protein structures and evolution. Identification of new conserved motifs linked to biochemical functions. Investigation of spatio-temporal gene expression and response to stress. Dirigent proteins (DIRs) were discovered during 8-8' lignan biosynthesis studies, through identification of stereoselective coupling to afford either (+)- or (-)-pinoresinols from E-coniferyl alcohol. DIRs are also involved or potentially involved in terpenoid, allyl/propenyl phenol lignan, pterocarpan and lignin biosynthesis. DIRs have very large multigene families in different vascular plants including flax, with most still of unknown function. DIR studies typically focus on a small subset ofmore » genes and identification of biochemical/physiological functions. Herein, a genome-wide analysis and characterization of the predicted flax DIR 44-membered multigene family was performed, this species being a rich natural grain source of 8-8' linked secoisolariciresinol-derived lignan oligomers. All predicted DIR sequences, including their promoters, were analyzed together with their public gene expression datasets. Expression patterns of selected DIRs were examined using qPCR, as well as through clustering analysis of DIR gene expression. These analyses further implicated roles for specific DIRs in (-)-pinoresinol formation in seed-coats, as well as (+)-pinoresinol in vegetative organs and/or specific responses to stress. Phylogeny and gene expression analysis segregated flax DIRs into six distinct clusters with new cluster-specific motifs identified. We propose that these findings can serve as a foundation to further systematically determine functions of DIRs, i.e. other than those already known in lignan biosynthesis in flax and other species. Given the differential expression profiles and inducibility of the flax DIR family, we provisionally propose that some DIR genes of unknown function could be involved in different aspects of secondary cell wall biosynthesis and plant defense.« less
Protein S-glutathionlyation links energy metabolism to redox signaling in mitochondria
Mailloux, Ryan J.; Treberg, Jason R.
2015-01-01
At its core mitochondrial function relies on redox reactions. Electrons stripped from nutrients are used to form NADH and NADPH, electron carriers that are similar in structure but support different functions. NADH supports ATP production but also generates reactive oxygen species (ROS), superoxide (O2·-) and hydrogen peroxide (H2O2). NADH-driven ROS production is counterbalanced by NADPH which maintains antioxidants in an active state. Mitochondria rely on a redox buffering network composed of reduced glutathione (GSH) and peroxiredoxins (Prx) to quench ROS generated by nutrient metabolism. As H2O2 is quenched, NADPH is expended to reactivate antioxidant networks and reset the redox environment. Thus, the mitochondrial redox environment is in a constant state of flux reflecting changes in nutrient and ROS metabolism. Changes in redox environment can modulate protein function through oxidation of protein cysteine thiols. Typically cysteine oxidation is considered to be mediated by H2O2 which oxidizes protein thiols (SH) forming sulfenic acid (SOH). However, problems begin to emerge when one critically evaluates the regulatory function of SOH. Indeed SOH formation is slow, non-specific, and once formed SOH reacts rapidly with a variety of molecules. By contrast, protein S-glutathionylation (PGlu) reactions involve the conjugation and removal of glutathione moieties from modifiable cysteine residues. PGlu reactions are driven by fluctuations in the availability of GSH and oxidized glutathione (GSSG) and thus should be exquisitely sensitive to changes ROS flux due to shifts in the glutathione pool in response to varying H2O2 availability. Here, we propose that energy metabolism-linked redox signals originating from mitochondria are mediated indirectly by H2O2 through the GSH redox buffering network in and outside mitochondria. This proposal is based on several observations that have shown that unlike other redox modifications PGlu reactions fulfill the requisite criteria to serve as an effective posttranslational modification that controls protein function. PMID:26773874
Corbin, Cyrielle; Drouet, Samantha; Markulin, Lucija; Auguin, Daniel; Lainé, Éric; Davin, Laurence B; Cort, John R; Lewis, Norman G; Hano, Christophe
2018-05-01
Identification of DIR encoding genes in flax genome. Analysis of phylogeny, gene/protein structures and evolution. Identification of new conserved motifs linked to biochemical functions. Investigation of spatio-temporal gene expression and response to stress. Dirigent proteins (DIRs) were discovered during 8-8' lignan biosynthesis studies, through identification of stereoselective coupling to afford either (+)- or (-)-pinoresinols from E-coniferyl alcohol. DIRs are also involved or potentially involved in terpenoid, allyl/propenyl phenol lignan, pterocarpan and lignin biosynthesis. DIRs have very large multigene families in different vascular plants including flax, with most still of unknown function. DIR studies typically focus on a small subset of genes and identification of biochemical/physiological functions. Herein, a genome-wide analysis and characterization of the predicted flax DIR 44-membered multigene family was performed, this species being a rich natural grain source of 8-8' linked secoisolariciresinol-derived lignan oligomers. All predicted DIR sequences, including their promoters, were analyzed together with their public gene expression datasets. Expression patterns of selected DIRs were examined using qPCR, as well as through clustering analysis of DIR gene expression. These analyses further implicated roles for specific DIRs in (-)-pinoresinol formation in seed-coats, as well as (+)-pinoresinol in vegetative organs and/or specific responses to stress. Phylogeny and gene expression analysis segregated flax DIRs into six distinct clusters with new cluster-specific motifs identified. We propose that these findings can serve as a foundation to further systematically determine functions of DIRs, i.e. other than those already known in lignan biosynthesis in flax and other species. Given the differential expression profiles and inducibility of the flax DIR family, we provisionally propose that some DIR genes of unknown function could be involved in different aspects of secondary cell wall biosynthesis and plant defense.
Protein S-glutathionlyation links energy metabolism to redox signaling in mitochondria.
Mailloux, Ryan J; Treberg, Jason R
2016-08-01
At its core mitochondrial function relies on redox reactions. Electrons stripped from nutrients are used to form NADH and NADPH, electron carriers that are similar in structure but support different functions. NADH supports ATP production but also generates reactive oxygen species (ROS), superoxide (O2(·-)) and hydrogen peroxide (H2O2). NADH-driven ROS production is counterbalanced by NADPH which maintains antioxidants in an active state. Mitochondria rely on a redox buffering network composed of reduced glutathione (GSH) and peroxiredoxins (Prx) to quench ROS generated by nutrient metabolism. As H2O2 is quenched, NADPH is expended to reactivate antioxidant networks and reset the redox environment. Thus, the mitochondrial redox environment is in a constant state of flux reflecting changes in nutrient and ROS metabolism. Changes in redox environment can modulate protein function through oxidation of protein cysteine thiols. Typically cysteine oxidation is considered to be mediated by H2O2 which oxidizes protein thiols (SH) forming sulfenic acid (SOH). However, problems begin to emerge when one critically evaluates the regulatory function of SOH. Indeed SOH formation is slow, non-specific, and once formed SOH reacts rapidly with a variety of molecules. By contrast, protein S-glutathionylation (PGlu) reactions involve the conjugation and removal of glutathione moieties from modifiable cysteine residues. PGlu reactions are driven by fluctuations in the availability of GSH and oxidized glutathione (GSSG) and thus should be exquisitely sensitive to changes ROS flux due to shifts in the glutathione pool in response to varying H2O2 availability. Here, we propose that energy metabolism-linked redox signals originating from mitochondria are mediated indirectly by H2O2 through the GSH redox buffering network in and outside mitochondria. This proposal is based on several observations that have shown that unlike other redox modifications PGlu reactions fulfill the requisite criteria to serve as an effective posttranslational modification that controls protein function. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
The strength of friendship ties in proximity sensor data.
Sekara, Vedran; Lehmann, Sune
2014-01-01
Understanding how people interact and socialize is important in many contexts from disease control to urban planning. Datasets that capture this specific aspect of human life have increased in size and availability over the last few years. We have yet to understand, however, to what extent such electronic datasets may serve as a valid proxy for real life social interactions. For an observational dataset, gathered using mobile phones, we analyze the problem of identifying transient and non-important links, as well as how to highlight important social interactions. Applying the Bluetooth signal strength parameter to distinguish between observations, we demonstrate that weak links, compared to strong links, have a lower probability of being observed at later times, while such links-on average-also have lower link-weights and probability of sharing an online friendship. Further, the role of link-strength is investigated in relation to social network properties.
Frossard, Aline; Gerull, Linda; Mutz, Michael; Gessner, Mark O
2012-03-01
A fundamental issue in microbial and general ecology is the question to what extent environmental conditions dictate the structure of communities and the linkages with functional properties of ecosystems (that is, ecosystem function). We approached this question by taking advantage of environmental gradients established in soil and sediments of small stream corridors in a recently created, early successional catchment. Specifically, we determined spatial and temporal patterns of bacterial community structure and their linkages with potential microbial enzyme activities along the hydrological flow paths of the catchment. Soil and sediments were sampled in a total of 15 sites on four occasions spread throughout a year. Denaturing gradient gel electrophoresis (DGGE) was used to characterize bacterial communities, and substrate analogs linked to fluorescent molecules served to track 10 different enzymes as specific measures of ecosystem function. Potential enzyme activities varied little among sites, despite contrasting environmental conditions, especially in terms of water availability. Temporal changes, in contrast, were pronounced and remarkably variable among the enzymes tested. This suggests much greater importance of temporal dynamics than spatial heterogeneity in affecting specific ecosystem functions. Most strikingly, bacterial community structure revealed neither temporal nor spatial patterns. The resulting disconnect between bacterial community structure and potential enzyme activities indicates high functional redundancy within microbial communities even in the physically and biologically simplified stream corridors of early successional landscapes.
The GM2 Glycan Serves as a Functional Coreceptor for Serotype 1 Reovirus
Liu, Yan; Blaum, Bärbel S.; Reiter, Dirk M.; Feizi, Ten; Dermody, Terence S.; Stehle, Thilo
2012-01-01
Viral attachment to target cells is the first step in infection and also serves as a determinant of tropism. Like many viruses, mammalian reoviruses bind with low affinity to cell-surface carbohydrate receptors to initiate the infectious process. Reoviruses disseminate with serotype-specific tropism in the host, which may be explained by differential glycan utilization. Although α2,3-linked sialylated oligosaccharides serve as carbohydrate receptors for type 3 reoviruses, neither a specific glycan bound by any reovirus serotype nor the function of glycan binding in type 1 reovirus infection was known. We have identified the oligosaccharide portion of ganglioside GM2 (the GM2 glycan) as a receptor for the attachment protein σ1 of reovirus strain type 1 Lang (T1L) using glycan array screening. The interaction of T1L σ1 with GM2 in solution was confirmed using NMR spectroscopy. We established that GM2 glycan engagement is required for optimal infection of mouse embryonic fibroblasts (MEFs) by T1L. Preincubation with GM2 specifically inhibited type 1 but not type 3 reovirus infection of MEFs. To provide a structural basis for these observations, we defined the mode of receptor recognition by determining the crystal structure of T1L σ1 in complex with the GM2 glycan. GM2 binds in a shallow groove in the globular head domain of T1L σ1. Both terminal sugar moieties of the GM2 glycan, N-acetylneuraminic acid and N-acetylgalactosamine, form contacts with the protein, providing an explanation for the observed specificity for GM2. Viruses with mutations in the glycan-binding domain display diminished hemagglutination capacity, a property dependent on glycan binding, and reduced capacity to infect MEFs. Our results define a novel mode of virus-glycan engagement and provide a mechanistic explanation for the serotype-dependent differences in glycan utilization by reovirus. PMID:23236285
The GM2 glycan serves as a functional coreceptor for serotype 1 reovirus.
Reiss, Kerstin; Stencel, Jennifer E; Liu, Yan; Blaum, Bärbel S; Reiter, Dirk M; Feizi, Ten; Dermody, Terence S; Stehle, Thilo
2012-01-01
Viral attachment to target cells is the first step in infection and also serves as a determinant of tropism. Like many viruses, mammalian reoviruses bind with low affinity to cell-surface carbohydrate receptors to initiate the infectious process. Reoviruses disseminate with serotype-specific tropism in the host, which may be explained by differential glycan utilization. Although α2,3-linked sialylated oligosaccharides serve as carbohydrate receptors for type 3 reoviruses, neither a specific glycan bound by any reovirus serotype nor the function of glycan binding in type 1 reovirus infection was known. We have identified the oligosaccharide portion of ganglioside GM2 (the GM2 glycan) as a receptor for the attachment protein σ1 of reovirus strain type 1 Lang (T1L) using glycan array screening. The interaction of T1L σ1 with GM2 in solution was confirmed using NMR spectroscopy. We established that GM2 glycan engagement is required for optimal infection of mouse embryonic fibroblasts (MEFs) by T1L. Preincubation with GM2 specifically inhibited type 1 but not type 3 reovirus infection of MEFs. To provide a structural basis for these observations, we defined the mode of receptor recognition by determining the crystal structure of T1L σ1 in complex with the GM2 glycan. GM2 binds in a shallow groove in the globular head domain of T1L σ1. Both terminal sugar moieties of the GM2 glycan, N-acetylneuraminic acid and N-acetylgalactosamine, form contacts with the protein, providing an explanation for the observed specificity for GM2. Viruses with mutations in the glycan-binding domain display diminished hemagglutination capacity, a property dependent on glycan binding, and reduced capacity to infect MEFs. Our results define a novel mode of virus-glycan engagement and provide a mechanistic explanation for the serotype-dependent differences in glycan utilization by reovirus.
DefenseLink.mil - Special Report: Travels with Gates
, leaving the field to Boeing, but said the process was balanced. Story >> Gates Shares Insights From served eight presidents, and he shared some of his insights into that experience with U.S. servicemembers
The Role of Nearshore Ecosystems as Fish and Shellfish Nurseries
The module provides a link to an article that is part of a series of articles in Issues in Ecology. This article provides information on the necessity to protect nearshore habitats that serve as nurseries.
Neuronal RNA granules: a link between RNA localization and stimulation-dependent translation
NASA Technical Reports Server (NTRS)
Krichevsky, A. M.; Kosik, K. S.
2001-01-01
RNA granules are a macromolecular structure observed in neurons, where they serve as motile units that translocate mRNAs. Isolated RNA granules are highly enriched in Staufen protein and ultrastructurally contain densely packed clusters of ribosomes. With depolarization, many mRNAs, including those involved in plasticity, rapidly shift from the RNA granule fraction to polysomes. Depolarization reorganizes granules and induces a less compact organization of their ribosomes. RNA granules are not translationally competent, as indicated by the failure to incorporate radioactive amino acids and the absence of eIF4E, 4G, and tRNAs. We concluded that RNA granules are a local storage compartment for mRNAs under translational arrest but are poised for release to actively translated pools. Local release of mRNAs and ribosomes from granules may serve as a macromolecular mechanism linking RNA localization to translation and synaptic plasticity.
Pracht, Etienne E; Bass, Elizabeth
2011-01-01
This paper explores the link between utilization of ambulatory care and the likelihood of rehospitalization for an avoidable reason in veterans served by the Veteran Health Administration (VA). The analysis used administrative data containing healthcare utilization and patient characteristics stored at the national VA data warehouse, the Corporate Franchise Data Center. The study sample consisted of 284 veterans residing in Florida who had been hospitalized at least once for an avoidable reason. A bivariate probit model with instrumental variables was used to estimate the probability of rehospitalization. Veterans who had at least 1 ambulatory care visit per month experienced a significant reduction in the probability of rehospitalization for the same avoidable hospitalization condition. The findings suggest that ambulatory care can serve as an important substitute for more expensive hospitalization for the conditions characterized as avoidable. © 2011 National Association for Healthcare Quality.
Cordonnier, M M; Greppin, H; Pratt, L H
1984-01-01
Nine monoclonal antibodies to pea (Pisum sativum L.) and 16 to oat (Avena sativa L.) phytochrome are characterized by enzyme-linked immunosorbent assay against phytochrome from six different sources: pea, zucchini (Cucurbita pepo L.), lettuce (Lactuca sativa L.), oat, rye (Secale cereale L.), and barley (Hordeum vulgare L.). All antibodies were raised against phytochrome with a monomer size near 120,000 daltons. Nevertheless, none of them discriminated qualitatively between 118/114-kilodalton oat phytochrome and a photoreversible, 60-kilodalton proteolytic degradation product derived from it. In addition, none of the 23 antibodies tested discriminated substantially between phytochrome-red-absorbing form and phytochrome-far red-absorbing form. Two antibodies to pea and six to oat phytochrome also bound strongly to phytochrome from the other species, even though these two plants are evolutionarily widely divergent. Of these eight antibodies, two bound significantly to all of the six phytochrome preparations tested, indicating that these two may recognize highly conserved regions of the chromoprotein. Since the molecular function of phytochrome is unknown, these two antibodies may serve as unique probes for regions of this pigment that are important to its mode of action.
Kirensky, L V; Terskov, I A; Gitelson, I I; Lisovsky, G M; Kovrov, B G; Okladnikov, Y N
1968-01-01
According to the opinion of many researchers, a culture of microalgae may serve as a regenerator of atmosphere in the cabin of a spaceship. To use microalgae for these objectives, it was necessary to have an automatic unit possessing a high productivity of the cultivation process. This unit, containing a minimum of equipment, enables carrying on for an unlimited time the cultivation of algae without a drop in their productivity. The unit meeting these requirements (the cultivator) was developed by the authors and will be described in the presentation. The stability of the microalga photosynthetic system is characterized by the fact that after 70% biosynthesis repression by the ultraviolet radiation, a full regeneration of the productivity level takes place within 24 hours. In our experiments the system was functioning with the stable estimated productivity for many days (up to two months without interruption). During the process, no biological inhibitions to permanent performance and further prolongation of its life were found. As to the productivity, stability and control, the described biotechnological method may appear to be useful as a link of the closed ecosystem.
The Role of the Lateral Intraparietal Area in (the Study of) Decision Making.
Huk, Alexander C; Katz, Leor N; Yates, Jacob L
2017-07-25
Over the past two decades, neurophysiological responses in the lateral intraparietal area (LIP) have received extensive study for insight into decision making. In a parallel manner, inferred cognitive processes have enriched interpretations of LIP activity. Because of this bidirectional interplay between physiology and cognition, LIP has served as fertile ground for developing quantitative models that link neural activity with decision making. These models stand as some of the most important frameworks for linking brain and mind, and they are now mature enough to be evaluated in finer detail and integrated with other lines of investigation of LIP function. Here, we focus on the relationship between LIP responses and known sensory and motor events in perceptual decision-making tasks, as assessed by correlative and causal methods. The resulting sensorimotor-focused approach offers an account of LIP activity as a multiplexed amalgam of sensory, cognitive, and motor-related activity, with a complex and often indirect relationship to decision processes. Our data-driven focus on multiplexing (and de-multiplexing) of various response components can complement decision-focused models and provides more detailed insight into how neural signals might relate to cognitive processes such as decision making.
Woody, Mary L; Kudinova, Anastacia Y; McGeary, John E; Knopik, Valerie S; Palmer, Rohan H C; Gibb, Brandon E
2016-01-01
There is growing evidence that brooding rumination plays a key role in the intergenerational transmission of major depressive disorder (MDD) and may be an endophenotype for depression risk. However, less is known about the mechanisms underlying this role. Therefore, the goal of the current study was to examine levels of brooding in children of mothers with a history of MDD (n = 129) compared to children of never depressed mothers (n = 126) and to determine whether the variation in a gene known to influence hypothalamic-pituitary-adrenal axis functioning--corticotropin-releasing hormone receptor 1 (CRHR1)--would moderate the link between maternal MDD and children's levels of brooding. We predicted children of mothers with a history of MDD would exhibit higher levels of brooding than children of mothers with no lifetime depression history but that this link would be stronger among children carrying no copies of the protective CRHR1 TAT haplotype. Our results supported these hypotheses and suggest that the development of brooding among children of depressed mothers, particularly children without the protective CRHR1 haplotype, may serve as an important mechanism of risk for the intergenerational transmission of depression.
Macrophages: An Inflammatory Link between Angiogenesis and Lymphangiogenesis
Corliss, Bruce A.; Azimi, Mohammad S.; Munson, Jenny; Peirce, Shayn M.; Murfee, Walter Lee
2015-01-01
Angiogenesis and lymphangiogenesis often occur in response to tissue injury or in the presence of pathology (e.g. cancer), and it is these types of environments in which macrophages are activated and increased in number. Moreover, the blood vascular microcirculation and the lymphatic circulation serve as the conduits for entry and exit for monocyte-derived macrophages in nearly every tissue and organ. Macrophages both affect and are affected by the vessels through which they travel. Therefore, it is not surprising that examination of macrophage behaviors in both angiogenesis and lymphangiogenesis has yielded interesting observations that suggest macrophages may be key regulators of these complex growth and remodeling processes. In this review, we will take a closer look at macrophages through the lens of angiogenesis and lymphangiogenesis, examining how their dynamic behaviors may regulate vessel sprouting and function. We present macrophages as a cellular link that spatially and temporally connects angiogenesis with lymphangiogenesis, in both physiological growth and in pathological adaptations, such as tumorigenesis. As such, attempts to therapeutically target macrophages in order to affect these processes may be particularly effective, and studying macrophages in both settings will accelerate the field’s understanding of this important cell type in health and disease. PMID:26614117
Choi, Sung E; Kwon, Sanghoon; Seok, Sunmi; Xiao, Zhen; Lee, Kwan-Woo; Kang, Yup; Li, Xiaoling; Shinoda, Kosaku; Kajimura, Shingo; Kemper, Byron; Kemper, Jongsook Kim
2017-08-01
Sirtuin1 (SIRT1) deacetylase delays and improves many obesity-related diseases, including nonalcoholic fatty liver disease (NAFLD) and diabetes, and has received great attention as a drug target. SIRT1 function is aberrantly low in obesity, so understanding the underlying mechanisms is important for drug development. Here, we show that obesity-linked phosphorylation of SIRT1 inhibits its function and promotes pathological symptoms of NAFLD. In proteomic analysis, Ser-164 was identified as a major serine phosphorylation site in SIRT1 in obese, but not lean, mice, and this phosphorylation was catalyzed by casein kinase 2 (CK2), the levels of which were dramatically elevated in obesity. Mechanistically, phosphorylation of SIRT1 at Ser-164 substantially inhibited its nuclear localization and modestly affected its deacetylase activity. Adenovirus-mediated liver-specific expression of SIRT1 or a phosphor-defective S164A-SIRT1 mutant promoted fatty acid oxidation and ameliorated liver steatosis and glucose intolerance in diet-induced obese mice, but these beneficial effects were not observed in mice expressing a phosphor-mimic S164D-SIRT1 mutant. Remarkably, phosphorylated S164-SIRT1 and CK2 levels were also highly elevated in liver samples of NAFLD patients and correlated with disease severity. Thus, inhibition of phosphorylation of SIRT1 by CK2 may serve as a new therapeutic approach for treatment of NAFLD and other obesity-related diseases. Copyright © 2017 American Society for Microbiology.
Choi, Sung E.; Kwon, Sanghoon; Seok, Sunmi; Xiao, Zhen; Lee, Kwan-Woo; Kang, Yup; Li, Xiaoling; Shinoda, Kosaku; Kajimura, Shingo; Kemper, Byron
2017-01-01
ABSTRACT Sirtuin1 (SIRT1) deacetylase delays and improves many obesity-related diseases, including nonalcoholic fatty liver disease (NAFLD) and diabetes, and has received great attention as a drug target. SIRT1 function is aberrantly low in obesity, so understanding the underlying mechanisms is important for drug development. Here, we show that obesity-linked phosphorylation of SIRT1 inhibits its function and promotes pathological symptoms of NAFLD. In proteomic analysis, Ser-164 was identified as a major serine phosphorylation site in SIRT1 in obese, but not lean, mice, and this phosphorylation was catalyzed by casein kinase 2 (CK2), the levels of which were dramatically elevated in obesity. Mechanistically, phosphorylation of SIRT1 at Ser-164 substantially inhibited its nuclear localization and modestly affected its deacetylase activity. Adenovirus-mediated liver-specific expression of SIRT1 or a phosphor-defective S164A-SIRT1 mutant promoted fatty acid oxidation and ameliorated liver steatosis and glucose intolerance in diet-induced obese mice, but these beneficial effects were not observed in mice expressing a phosphor-mimic S164D-SIRT1 mutant. Remarkably, phosphorylated S164-SIRT1 and CK2 levels were also highly elevated in liver samples of NAFLD patients and correlated with disease severity. Thus, inhibition of phosphorylation of SIRT1 by CK2 may serve as a new therapeutic approach for treatment of NAFLD and other obesity-related diseases. PMID:28533219
Bypass of a psoralen DNA interstrand cross-link by DNA polymerases beta, iota, and kappa in vitro
Smith, Leigh A.; Makarova, Alena V.; Samson, Laura; Thiesen, Katherine E.; Dhar, Alok; Bessho, Tadayoshi
2012-01-01
Repair of DNA inter-strand cross-links in mammalian cells involves several biochemically distinctive processes, including the release of one of the cross-linked strands and translesion DNA synthesis (TLS). In this report, we investigated in vitro TLS activity of psoralen DNA inter-strand cross-link by three DNA repair polymerases, DNA polymerase beta, kappa and iota. DNA polymerase beta is capable of bypassing a psoralen cross-link with a low efficiency. Cell extracts prepared from DNA polymerase beta knockout mouse embryonic fibroblast showed a reduced bypass activity of the psoralen cross-link and purified DNA polymerase beta restored the bypass activity. In addition, DNA polymerase iota mis-incorporated thymine across the psoralen cross-link and DNA polymerase kappa extended these mis-paired primer ends, suggesting that DNA polymerase iota may serve as an inserter and DNA polymerase kappa may play a role as an extender in the repair of psoralen DNA inter-strand cross-links. The results demonstrated here indicate that multiple DNA polymerases could participate in TLS steps in mammalian DNA inter-strand cross-link repair. PMID:23106263
[Autism, epilepsy and tuberous sclerosis complex: a functional model linked to mTOR pathway].
García-Peñas, Juan José; Carreras-Sááez, Inmaculada
2013-02-22
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that results from mutations in the TSC1 or TSC2 genes and is associated with hamartoma formation in multiple organ systems. Brain disorders are the origin of more frequent and severe problems and include infantile spasms, intractable epilepsy, brain tumors, cognitive disabilities, and autism. TSC1 or TSC2 encoded proteins modulate cell function via the mTOR signaling cascade and serve as keystones in regulating cell growth and proliferation. AIM. To review the etiopathogenic mechanisms and the natural course of the association of autism and epilepsy in TSC. Both the clinical and the neuroimaging findings of TSC, including early onset epilepsy and the localization of cortical tubers in the temporal lobes, and the molecular understanding of the mTOR signaling pathway, not only involved in cell growth, but also in synaptogenesis, synaptic plasticity and neuronal functioning, have suggested a multimodal origin of autism in these patients. A greater understanding of the pathogenetic mechanisms underlying autism in TSC could help in devising targeted and potentially more effective treatment strategies. Antagonism of the mTOR pathway with rapamycin and everolimus may provide new therapeutic options for these TSC patients.
Raz, Gal; Shpigelman, Lavi; Jacob, Yael; Gonen, Tal; Benjamini, Yoav; Hendler, Talma
2016-12-01
We introduce a novel method for delineating context-dependent functional brain networks whose connectivity dynamics are synchronized with the occurrence of a specific psychophysiological process of interest. In this method of context-related network dynamics analysis (CRNDA), a continuous psychophysiological index serves as a reference for clustering the whole-brain into functional networks. We applied CRNDA to fMRI data recorded during the viewing of a sadness-inducing film clip. The method reliably demarcated networks in which temporal patterns of connectivity related to the time series of reported emotional intensity. Our work successfully replicated the link between network connectivity and emotion rating in an independent sample group for seven of the networks. The demarcated networks have clear common functional denominators. Three of these networks overlap with distinct empathy-related networks, previously identified in distinct sets of studies. The other networks are related to sensorimotor processing, language, attention, and working memory. The results indicate that CRNDA, a data-driven method for network clustering that is sensitive to transient connectivity patterns, can productively and reliably demarcate networks that follow psychologically meaningful processes. Hum Brain Mapp 37:4654-4672, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.
Budak, Erdal; Fernández Sánchez, Manuel; Bellver, José; Cerveró, Ana; Simón, Carlos; Pellicer, Antonio
2006-06-01
To summarize the effects of novel hormones (leptin, ghrelin, adiponectin, resistin, and PYY3-36) secreted from adipose tissue and the gastrointestinal tract that have been discovered to exert different effects on several reproductive functions, such as the hypothalamic-pituitary-gonadal axis, embryo development, implantation physiology, and clinically relevant conditions. A MEDLINE computer search was performed to identify relevant articles. Leptin and ghrelin exert important roles on body weight regulation, eating behavior, and reproduction, acting on the central nervous system and target reproductive organs. As a marker of adequate nutritional stores, these hormones may act on the central nervous system to initiate the complex process of puberty and maintain normal reproductive function. In addition, leptin and ghrelin and their receptors are involved in reproductive events such as gonadal function, embryo development, and embryo-endometrial interaction. Leptin and ghrelin and other adipose tissue-secreted hormones have significant effects on reproduction. Acting through the brain, these hormones may serve as links between adipose tissue and the reproductive system to supply and regulate energy needs for normal reproduction and pregnancy. Future studies are needed to further clarify the role of these hormones in reproductive events and other related gynecological conditions.
Structural Features of Antiviral APOBEC3 Proteins are Linked to Their Functional Activities
Kitamura, Shingo; Ode, Hirotaka; Iwatani, Yasumasa
2011-01-01
Human APOBEC3 (A3) proteins are cellular cytidine deaminases that potently restrict the replication of retroviruses by hypermutating viral cDNA and/or inhibiting reverse transcription. There are seven members of this family including A3A, B, C, DE, F, G, and H, all encoded in a tandem array on human chromosome 22. A3F and A3G are the most potent inhibitors of HIV-1, but only in the absence of the virus-encoded protein, Vif. HIV-1 utilizes Vif to abrogate A3 functions in the producer cells. More specifically, Vif, serving as a substrate receptor, facilitates ubiquitination of A3 proteins by forming a Cullin5 (Cul5)-based E3 ubiquitin ligase complex, which targets A3 proteins for rapid proteasomal degradation. The specificity of A3 degradation is determined by the ability of Vif to bind to the target. Several lines of evidence have suggested that three distinct regions of A3 proteins are involved in the interaction with Vif. Here, we review the biological functions of A3 family members with special focus on A3G and base our analysis on the available structural information. PMID:22203821
Wu, Sheng; Tian, Li
2017-09-25
Having served as a symbolic fruit since ancient times, pomegranate ( Punica granatum ) has also gained considerable recognition as a functional food in the modern era. A large body of literature has linked pomegranate polyphenols, particularly anthocyanins (ATs) and hydrolyzable tannins (HTs), to the health-promoting activities of pomegranate juice and fruit extracts. However, it remains unclear as to how, and to what extent, the numerous phytochemicals in pomegranate may interact and exert cooperative activities in humans. In this review, we examine the structural and analytical information of the diverse phytochemicals that have been identified in different pomegranate tissues, to establish a knowledge base for characterization of metabolite profiles, discovery of novel phytochemicals, and investigation of phytochemical interactions in pomegranate. We also assess recent findings on the function and molecular mechanism of ATs as well as urolithins, the intestinal microbial derivatives of pomegranate HTs, on human nutrition and health. A better understanding of the structural diversity of pomegranate phytochemicals as well as their bioconversions and bioactivities in humans will facilitate the interrogation of their synergistic/antagonistic interactions and accelerate their applications in dietary-based cancer chemoprevention and treatment in the future.
Managing daily life with age-related sensory loss: cognitive resources gain in importance.
Heyl, Vera; Wahl, Hans-Werner
2012-06-01
This paper investigates the role of cognitive resources in everyday functioning, comparing visually impaired, hearing impaired, and sensory unimpaired older adults. According to arguments that cognitive resources are of increased importance and a greater awareness of cognitive restrictions exists among sensory impaired individuals, in particular among visually impaired individuals, we hypothesized differential relationships between resources and outcomes when comparing sensory impaired and sensory unimpaired older adults. Findings are based on samples of 121 visually impaired, 116 hearing impaired, and 150 sensory unimpaired older adults (M = 82 years). Results from a sample of 43 dual sensory impaired older adults are reported for comparison. Assessment relied on established instruments (e.g., WAIS-R, ADL/IADL). Structural equation modeling showed that cognitive resources and behavior-related everyday functioning were more strongly related in the sensory impaired groups as compared to the sensory unimpaired group. Cognitive resources and evaluation of everyday functioning were significantly linked only among the sensory impaired groups. When medical condition was controlled for, these effects persisted. It is concluded that both cognitive training as well as psychosocial support may serve as important additions to classic vision and hearing loss rehabilitation. PsycINFO Database Record (c) 2012 APA, all rights reserved
McCrickerd, Keri; Leong, Claudia; Forde, Ciaran G
2017-07-01
A strong predictor of children's food intake at a meal is the amount they are served, and with a high percentage children attending preschool, there is a need to consider the relationship between portion size and intake in this context. In a two-part repeated measures study we investigated whether the portions teachers serve to children i) differ from those children would serve themselves and ii) impact food intake at a local preschool in Singapore. Part 1 (n = 37, 20 boys, 3.0-6.8 years) compared the quantity of food served, consumed and leftover across three serving methods: 'regular' teacher-serving; child self-served portions; and a deliberately large portion served by the teacher (150% of each child's average previous gram intake). Part 2 (n = 44, 23 boys, 2.4-6.2 years old) consisted of three additional observations of school-based servings outside of the experimental manipulation and enhance external validity of the study findings. Results indicated that serving size and intake was similar when the children and teachers served their 'regular' portions, but children consumed most overall when the teacher served the larger 150% portion. This was dependent on the child's age, with the oldest children being most responsive to the large portions while the youngest children tended to serve and consume a similar weight of food, regardless of the serving method. Though the younger children were generally served less than the older children, they consistently had more leftovers across all of the study observations. These data suggest that younger preschool children moderated food intake by leaving food in their bowl, and emphasise the unique influence of caregivers over children's eating behaviours outside of the home environment. Copyright © 2017 Elsevier Ltd. All rights reserved.
Shippee, Nathan D; Shah, Nilay D; May, Carl R; Mair, Frances S; Montori, Victor M
2012-10-01
To design a functional, patient-centered model of patient complexity with practical applicability to analytic design and clinical practice. Existing literature on patient complexity has mainly identified its components descriptively and in isolation, lacking clarity as to their combined functions in disrupting care or to how complexity changes over time. The authors developed a cumulative complexity model, which integrates existing literature and emphasizes how clinical and social factors accumulate and interact to complicate patient care. A narrative literature review is used to explicate the model. The model emphasizes a core, patient-level mechanism whereby complicating factors impact care and outcomes: the balance between patient workload of demands and patient capacity to address demands. Workload encompasses the demands on the patient's time and energy, including demands of treatment, self-care, and life in general. Capacity concerns ability to handle work (e.g., functional morbidity, financial/social resources, literacy). Workload-capacity imbalances comprise the mechanism driving patient complexity. Treatment and illness burdens serve as feedback loops, linking negative outcomes to further imbalances, such that complexity may accumulate over time. With its components largely supported by existing literature, the model has implications for analytic design, clinical epidemiology, and clinical practice. Copyright © 2012 Elsevier Inc. All rights reserved.
Moza, Monica; Mologni, Luca; Trokovic, Ras; Faulkner, Georgine; Partanen, Juha; Carpén, Olli
2007-01-01
Myotilin, palladin, and myopalladin form a novel small subfamily of cytoskeletal proteins that contain immunoglobulin-like domains. Myotilin is a thin filament-associated protein localized at the Z-disk of skeletal and cardiac muscle cells. The direct binding to F-actin, efficient cross-linking of actin filaments, and prevention of induced disassembly of filaments are key roles of myotilin that are thought to be involved in structural maintenance and function of the sarcomere. Missense mutations in the myotilin-encoding gene cause dominant limb girdle muscular dystrophy type 1A and spheroid body myopathy and are the molecular defect that can cause myofibrillar myopathy. Here we describe the generation and analysis of mice that lack myotilin, myo−/− mice. Surprisingly, myo−/− mice maintain normal muscle sarcomeric and sarcolemmal integrity. Also, loss of myotilin does not cause alterations in the heart or other organs of newborn or adult myo−/− mice. The mice develop normally and have a normal life span, and their muscle capacity does not significantly differ from wild-type mice even after prolonged physical stress. The results suggest that either myotilin does not participate in muscle development and basal function maintenance or other proteins serve as structural and functional compensatory molecules when myotilin is absent. PMID:17074808
Analysis of Aspergillus nidulans metabolism at the genome-scale
David, Helga; Özçelik, İlknur Ş; Hofmann, Gerald; Nielsen, Jens
2008-01-01
Background Aspergillus nidulans is a member of a diverse group of filamentous fungi, sharing many of the properties of its close relatives with significance in the fields of medicine, agriculture and industry. Furthermore, A. nidulans has been a classical model organism for studies of development biology and gene regulation, and thus it has become one of the best-characterized filamentous fungi. It was the first Aspergillus species to have its genome sequenced, and automated gene prediction tools predicted 9,451 open reading frames (ORFs) in the genome, of which less than 10% were assigned a function. Results In this work, we have manually assigned functions to 472 orphan genes in the metabolism of A. nidulans, by using a pathway-driven approach and by employing comparative genomics tools based on sequence similarity. The central metabolism of A. nidulans, as well as biosynthetic pathways of relevant secondary metabolites, was reconstructed based on detailed metabolic reconstructions available for A. niger and Saccharomyces cerevisiae, and information on the genetics, biochemistry and physiology of A. nidulans. Thereby, it was possible to identify metabolic functions without a gene associated, and to look for candidate ORFs in the genome of A. nidulans by comparing its sequence to sequences of well-characterized genes in other species encoding the function of interest. A classification system, based on defined criteria, was developed for evaluating and selecting the ORFs among the candidates, in an objective and systematic manner. The functional assignments served as a basis to develop a mathematical model, linking 666 genes (both previously and newly annotated) to metabolic roles. The model was used to simulate metabolic behavior and additionally to integrate, analyze and interpret large-scale gene expression data concerning a study on glucose repression, thereby providing a means of upgrading the information content of experimental data and getting further insight into this phenomenon in A. nidulans. Conclusion We demonstrate how pathway modeling of A. nidulans can be used as an approach to improve the functional annotation of the genome of this organism. Furthermore we show how the metabolic model establishes functional links between genes, enabling the upgrade of the information content of transcriptome data. PMID:18405346
Targeted Delivery of Ubiquitin-Conjugated BH3 Peptide-Based Mcl-1 Inhibitors into Cancer Cells
2015-01-01
BH3 peptides are key mediators of apoptosis and have served as the lead structures for the development of anticancer therapeutics. Previously, we reported the application of a simple cysteine-based side chain cross-linking chemistry to NoxaBH3 peptides that led to the generation of the cross-linked NoxaBH3 peptides with increased cell permeability and higher inhibitory activity against Mcl-1 (Muppidi, A., Doi, K., Edwardraja, S., Drake, E. J., Gulick, A. M., Wang, H.-G., Lin, Q. (2012) J. Am. Chem. Soc.134, 1473422920569). To deliver cross-linked NoxaBH3 peptides selectively into cancer cells for enhanced efficacy and reduced systemic toxicity, here we report the conjugation of the NoxaBH3 peptides with the extracellular ubiquitin, a recently identified endogenous ligand for CXCR4, a chemokine receptor overexpressed in cancer cells. The resulting ubiquitin-NoxaBH3 peptide conjugates showed increased inhibitory activity against Mcl-1 and selective killing of the CXCR4-expressing cancer cells. The successful delivery of the NoxaBH3 peptides by ubiquitin into cancer cells suggests that the ubiquitin/CXCR4 axis may serve as a general route for the targeted delivery of anticancer agents. PMID:24410055
Harper, Stephen; Gratton, Hayley E; Cornaciu, Irina; Oberer, Monika; Scott, David J; Emsley, Jonas; Dreveny, Ingrid
2014-05-13
The ubiquitin specific protease 11 (USP11) is implicated in DNA repair, viral RNA replication, and TGFβ signaling. We report the first characterization of the USP11 domain architecture and its role in regulating the enzymatic activity. USP11 consists of an N-terminal "domain present in USPs" (DUSP) and "ubiquitin-like" (UBL) domain, together referred to as DU domains, and the catalytic domain harboring a second UBL domain. Crystal structures of the DU domains show a tandem arrangement with a shortened β-hairpin at the two-domain interface and altered surface characteristics compared to the homologues USP4 and USP15. A conserved VEVY motif is a signature feature at the two-domain interface that shapes a potential protein interaction site. Small angle X-ray scattering and gel filtration experiments are consistent with the USP11DU domains and full-length USP11 being monomeric. Unexpectedly, we reveal, through kinetic assays of a series of deletion mutants, that the catalytic activity of USP11 is not regulated through intramolecular autoinhibition or activation by the N-terminal DU or UBL domains. Moreover, ubiquitin chain cleavage assays with all eight linkages reveal a preference for Lys(63)-, Lys(6)-, Lys(33)-, and Lys(11)-linked chains over Lys(27)-, Lys(29)-, and Lys(48)-linked and linear chains consistent with USP11's function in DNA repair pathways that is mediated by the protease domain. Our data support a model whereby USP11 domains outside the catalytic core domain serve as protein interaction or trafficking modules rather than a direct regulatory function of the proteolytic activity. This highlights the diversity of USPs in substrate recognition and regulation of ubiquitin deconjugation.
O'Connor, Eoin C; Bariselli, Sebastiano; Bellone, Camilla
2014-04-01
Most of us engage in social interactions on a daily basis and the repertoire of social behaviors we acquire during development and later in life are incredibly varied. However, in many neurodevelopmental disorders, including autism spectrum disorders (ASDs), social behavior is severely compromised and indeed this represents a key diagnostic component for such conditions. From genetic association studies, it is increasingly apparent that genes identified as altered in individuals with ASDs often encode synaptic proteins. Moreover, these synaptic proteins typically serve to scaffold group-I metabotropic glutamate receptors (group-I mGluRs) and ionotropic glutamate receptors (iGluRs; AMPARs and NMDARs), or to enable group-I mGluR to iGluR crosstalk via protein synthesis. Here we aim to explore the possibility of a causal link between altered function of such synaptic proteins and impaired social behaviors that feature in neurodevelopmental disorders, such as ASDs. We review the known synaptic function and role in social behaviors of selected post-synaptic structural proteins (Shank, SAPAP and neuroligin) and regulators of protein synthesis (TSC1/2, FMRP and PTEN). While manipulations of proteins involved in group-I mGluR and iGluR scaffolding or crosstalk frequently lead to profound alterations in synaptic function and one or more components of social behavior, the neuronal circuits responsible for impairments in specific social behaviors are often poorly defined. We argue for an improved understanding of the neuronal circuits underlying specific social behaviors to aid the development of new ASD therapies. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.
Business establishment survival and transportation level of service.
DOT National Transportation Integrated Search
2016-06-15
In this project we seek to fill a gap in empirically supported knowledge linking the survival and : economic success of business establishments to local land use and access to the transportation : system that serves these establishments. We investiga...
What are the effects of sleep deprivation and fatigue in surgical practice?
Sugden, Colin; Athanasiou, Thanos; Darzi, Ara
2012-01-01
Sleep deprivation and fatigue have long been linked with accidents in high-risk industries and serious errors in the medical profession, but their effects on surgical performance are less well understood. This article outlines the important functions that human sleep serves and describes the neurobehavioral effects of wakefulness extension and mental fatigue that are relevant to surgical performance, including attentional failure, risk taking, and decision-making bias. Methods used to explore the effects of sleep deprivation and fatigue on surgical performance, from laboratory studies to outcomes data, are discussed; the findings are summarized; and important deficiencies in the literature are highlighted. Future strategies to mitigate performance decline, such as novel assessment tools and countermeasures with proven efficacy, are presented, and their deployment is discussed in the context of key ethical principles. Copyright © 2012 Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bounoua, Lahouari; Kahime, Kholoud; Houti, Leila
Shifts in surface climate may have changed the dynamic of zoonotic cutaneous leishmaniasis (ZCL) in the pre-Saharan zones of North Africa. Caused by Leishmania major, this form multiplies in the body of rodents serving as reservoirs of the disease. The parasite is then transmitted to human hosts by the bite of a Phlebotomine sand fly (Diptera: Psychodidae) that was previously fed by biting an infected reservoir. We examine the seasonal and interannual dynamics of the incidence of this ZCL as a function of surface climate indicators in two regions covering a large area of the semi-arid Pre-Saharan North Africa. Resultsmore » suggest that in this area, changes in climate may have initiated a trophic cascade that resulted in an increase in ZCL incidence.« less
Dual-radiolabeled nanoparticle probes for depth-independent in vivo imaging of enzyme activation
NASA Astrophysics Data System (ADS)
Black, Kvar C. L.; Zhou, Mingzhou; Sarder, Pinaki; Kuchuk, Maryna; Al-Yasiri, Amal Y.; Gunsten, Sean P.; Liang, Kexian; Hennkens, Heather M.; Akers, Walter J.; Laforest, Richard; Brody, Steven L.; Cutler, Cathy S.; Achilefu, Samuel
2018-02-01
Quantitative and noninvasive measurement of protease activities has remained an imaging challenge in deep tissues such as the lungs. Here, we designed a dual-radiolabeled probe for reporting the activities of proteases such as matrix metalloproteinases (MMPs) with multispectral single photon emission computed tomography (SPECT) imaging. A gold nanoparticle (NP) was radiolabeled with 125I and 111In and functionalized with an MMP9-cleavable peptide to form a multispectral SPECT imaging contrast agent. In another design, incorporation of 199Au radionuclide into the metal crystal structure of gold NPs provided a superior and stable reference signal in lungs, and 111In was linked to the NP surface via a protease-cleavable substrate, which can serve as an enzyme activity reporter. This work reveals strategies to correlate protease activities with diverse pathologies in a tissue-depth independent manner.
Alternate pathways of thyroid hormone metabolism.
Wu, Sing-Yung; Green, William L; Huang, Wen-Sheng; Hays, Marguerite T; Chopra, Inder J
2005-08-01
The major thyroid hormone (TH) secreted by the thyroid gland is thyroxine (T(4)). Triiodothyronine (T(3)), formed chiefly by deiodination of T(4), is the active hormone at the nuclear receptor, and it is generally accepted that deiodination is the major pathway regulating T(3) bioavailability in mammalian tissues. The alternate pathways, sulfation and glucuronidation of the phenolic hydroxyl group of iodothyronines, the oxidative deamination and decarboxylation of the alanine side chain to form iodothyroacetic acids, and ether link cleavage provide additional mechanisms for regulating the supply of active hormone. Sulfation may play a general role in regulation of iodothyronine metabolism, since sulfation of T(4) and T(3) markedly accelerates deiodination to the inactive metabolites, reverse triiodothyronine (rT(3)) and T(2). Sulfoconjugation is prominent during intrauterine development, particularly in the precocial species in the last trimester including humans and sheep, where it may serve both to regulate the supply of T(3), via sulfation followed by deiodination, and to facilitate maternal-fetal exchange of sulfated iodothyronines (e.g., 3,3'-diiodothyronine sulfate [T(2)S]). The resulting low serum T(3) may be important for normal fetal development in the late gestation. The possibility that T(2)S or its derivative, transferred from the fetus and appearing in maternal serum or urine, can serve as a marker of fetal thyroid function is being studied. Glucuronidation of TH often precedes biliary-fecal excretion of hormone. In rats, stimulation of glucuronidation by various drugs and toxins may lead to lower T(4) and T(3) levels, provocation of thyrotropin (TSH) secretion, and goiter. In man, drug induced stimulation of glucuronidation is limited to T(4), and does not usually compromise normal thyroid function. However, in hypothyroid subjects, higher doses of TH may be required to maintain euthyroidism when these drugs are given. In addition, glucuronidates and sulfated iodothyronines can be hydrolyzed to their precursors in gastrointestinal tract and various tissues. Thus, these conjugates can serve as a reservoir for biologically active iodothyronines (e.g., T(4), T(3), or T(2)). The acetic acid derivatives of T(4), tetrac and triac, are minor products in normal thyroid physiology. However, triac has a different pattern of receptor affinity than T(3), binding preferentially to the beta receptor. This makes it useful in the treatment of the syndrome of resistance to thyroid hormone action, where the typical mutation affects only the beta receptor. Thus, adequate binding to certain mutated beta receptors can be achieved without excessive stimulation of alpha receptors, which predominate in the heart. Ether link cleavage of TH is also a minor pathway in normal subjects. However, this pathway may become important during infections, when augmented TH breakdown by ether-link cleavage (ELC) may assist in bactericidal activity. There is a recent claim that decarboxylated derivates of thyronines, that is, monoiodothyronamine (T(1)am) and thyronamine (T(0)am), may be biologically important and have actions different from those of TH. Further information on these interesting derivatives is awaited.
Sanaa, Moez; Coroller, Louis; Cerf, Olivier
2004-04-01
This article reports a quantitative risk assessment of human listeriosis linked to the consumption of soft cheeses made from raw milk. Risk assessment was based on data purposefully acquired inclusively over the period 2000-2001 for two French cheeses, namely: Camembert of Normandy and Brie of Meaux. Estimated Listeria monocytogenes concentration in raw milk was on average 0.8 and 0.3 cells/L, respectively, in Normandy and Brie regions. A Monte Carlo simulation was used to account for the time-temperature history of the milk and cheeses from farm to table. It was assumed that cell progeny did not spread within the solid cheese matrix (as they would be free to do in liquid broth). Interaction between pH and temperature was accounted for in the growth model. The simulated proportion of servings with no L. monocytogenes cell was 88% for Brie and 82% for Camembert. The 99th percentile of L. monocytogenes cell numbers in servings of 27 g of cheese was 131 for Brie and 77 for Camembert at the time of consumption, corresponding respectively to three and five cells of L. monocytogenes per gram. The expected number of severe listeriosis cases would be < or =10(-3) and < or =2.5 x 10(-3) per year for 17 million servings of Brie of Meaux and 480 million servings of Camembert of Normandy, respectively.
Heitmar, R; Varma, C; De, P; Lau, Y C; Blann, A D
2016-11-01
To test the hypothesis of a significant relationship between systemic markers of renal and vascular function (processes linked to cardiovascular disease and its development) and retinal microvascular function in diabetes and/or cardiovascular disease. Ocular microcirculatory function was measured in 116 patients with diabetes and/or cardiovascular disease using static and continuous retinal vessel responses to three cycles of flickering light. Endothelial function was evaluated by von Willebrand factor (vWf), endothelial microparticles and soluble E selectin, renal function by serum creatinine, creatinine clearance and estimated glomerular filtration rate (eGFR). HbA1c was used as a control index. Central retinal vein equivalence and venous maximum dilation to flicker were linked to HbA1c (both p < 0.05). Arterial reaction time was linked to serum creatinine (p = 0.036) and eGFR (p = 0.039); venous reaction time was linked to creatinine clearance (p = 0.018). Creatinine clearance and eGFR were linked to arterial maximum dilatation (p < 0.001 and p = 0.003, respectively) and the dilatation amplitude (p = 0.038 and p = 0.048, respectively) responses in the third flicker cycle. Of venous responses to the first flicker cycle, HbA1c was linked to the maximum dilation response (p = 0.004) and dilatation amplitude (p = 0.017), vWf was linked to the maximum constriction response (p = 0.016), and creatinine clearance to the baseline diameter fluctuation (p = 0.029). In the second flicker cycle, dilatation amplitude was linked to serum creatinine (p = 0.022). Several retinal blood vessel responses to flickering light are linked to glycaemia and renal function, but only one index is linked to endothelial function. Renal function must be considered when interpreting retinal vessel responses.
NASA Astrophysics Data System (ADS)
Khan, Akhtar Nawaz
2017-11-01
Currently, analytical models are used to compute approximate blocking probabilities in opaque and all-optical WDM networks with the homogeneous link capacities. Existing analytical models can also be extended to opaque WDM networking with heterogeneous link capacities due to the wavelength conversion at each switch node. However, existing analytical models cannot be utilized for all-optical WDM networking with heterogeneous structure of link capacities due to the wavelength continuity constraint and unequal numbers of wavelength channels on different links. In this work, a mathematical model is extended for computing approximate network blocking probabilities in heterogeneous all-optical WDM networks in which the path blocking is dominated by the link along the path with fewer number of wavelength channels. A wavelength assignment scheme is also proposed for dynamic traffic, termed as last-fit-first wavelength assignment, in which a wavelength channel with maximum index is assigned first to a lightpath request. Due to heterogeneous structure of link capacities and the wavelength continuity constraint, the wavelength channels with maximum indexes are utilized for minimum hop routes. Similarly, the wavelength channels with minimum indexes are utilized for multi-hop routes between source and destination pairs. The proposed scheme has lower blocking probability values compared to the existing heuristic for wavelength assignments. Finally, numerical results are computed in different network scenarios which are approximately equal to values obtained from simulations. Since January 2016, he is serving as Head of Department and an Assistant Professor in the Department of Electrical Engineering at UET, Peshawar-Jalozai Campus, Pakistan. From May 2013 to June 2015, he served Department of Telecommunication Engineering as an Assistant Professor at UET, Peshawar-Mardan Campus, Pakistan. He also worked as an International Internship scholar in the Fukuda Laboratory, National Institute of Informatics, Tokyo, Japan on the topic large-scale simulation for internet topology analysis. His research interests include design and analysis of optical WDM networks, network algorithms, network routing, and network resource optimization problems.
Aizawa, Naoya; Fuentes-Hernandez, Canek; Kolesov, Vladimir A; Khan, Talha M; Kido, Junji; Kippelen, Bernard
2016-03-07
Poly[N-9'-heptadecanyl-2,7-carbazole-alt-5,5-(4',7'-di-2-thienyl-2',1',3'-benzothiadiazole)] (PCDTBT) is shown to be simultaneously cross-linked and p-doped when immersed into a phosphomolybdic acid solution, yielding conductive films with low solubility that can withstand the solution processing of subsequent photoactive layers. Such a modified PCDTBT film serves to improve hole collection and limit carrier recombination in organic solar cells.
Performance evaluation of multiple (32 channels) sub-nanosecond TDC implemented in low-cost FPGA
NASA Astrophysics Data System (ADS)
Lichard, P.; Konstantinou, G.; Villar Vilanueva, A.; Palladino, V.
2014-03-01
NA62 experiment Straw tracker frontend board serves as a gas-tight detector cover and integrates two CARIOCA chips, a low cost FPGA (Cyclon III, Altera) and a set of 400Mbit/s links to the backend. The FPGA houses 16 pairs of sub-nanosecond resolution TDCs with derandomizers and an output link serializer. Evaluation methods, including simulations, and performance results of the system in the lab and on a detector prototype are presented.
Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins
Larsen, Ida Signe Bohse; Narimatsu, Yoshiki; Siukstaite, Lina; Harrison, Oliver J.; Brasch, Julia; Goodman, Kerry M.; Hansen, Lars; Shapiro, Lawrence; Honig, Barry; Vakhrushev, Sergey Y.; Clausen, Henrik
2017-01-01
The cadherin (cdh) superfamily of adhesion molecules carry O-linked mannose (O-Man) glycans at highly conserved sites localized to specific β-strands of their extracellular cdh (EC) domains. These O-Man glycans do not appear to be elongated like O-Man glycans found on α-dystroglycan (α-DG), and we recently demonstrated that initiation of cdh/protocadherin (pcdh) O-Man glycosylation is not dependent on the evolutionary conserved POMT1/POMT2 enzymes that initiate O-Man glycosylation on α-DG. Here, we used a CRISPR/Cas9 genetic dissection strategy combined with sensitive and quantitative O-Man glycoproteomics to identify a homologous family of four putative protein O-mannosyltransferases encoded by the TMTC1–4 genes, which were found to be imperative for cdh and pcdh O-Man glycosylation. KO of all four TMTC genes in HEK293 cells resulted in specific loss of cdh and pcdh O-Man glycosylation, whereas combined KO of TMTC1 and TMTC3 resulted in selective loss of O-Man glycans on specific β-strands of EC domains, suggesting that each isoenzyme serves a different function. In addition, O-Man glycosylation of IPT/TIG domains of plexins and hepatocyte growth factor receptor was not affected in TMTC KO cells, suggesting the existence of yet another O-Man glycosylation machinery. Our study demonstrates that regulation of O-mannosylation in higher eukaryotes is more complex than envisioned, and the discovery of the functions of TMTCs provide insight into cobblestone lissencephaly caused by deficiency in TMTC3. PMID:28973932
The biogenesis pathway of tRNA-derived piRNAs in Bombyx germ cells
Honda, Shozo; Kawamura, Takuya; Loher, Phillipe; Morichika, Keisuke; Rigoutsos, Isidore
2017-01-01
Abstract Transfer RNAs (tRNAs) function in translational machinery and further serves as a source of short non-coding RNAs (ncRNAs). tRNA-derived ncRNAs show differential expression profiles and play roles in many biological processes beyond translation. Molecular mechanisms that shape and regulate their expression profiles are largely unknown. Here, we report the mechanism of biogenesis for tRNA-derived Piwi-interacting RNAs (td-piRNAs) expressed in Bombyx BmN4 cells. In the cells, two cytoplasmic tRNA species, tRNAAspGUC and tRNAHisGUG, served as major sources for td-piRNAs, which were derived from the 5′-part of the respective tRNAs. cP-RNA-seq identified the two tRNAs as major substrates for the 5′-tRNA halves as well, suggesting a previously uncharacterized link between 5′-tRNA halves and td-piRNAs. An increase in levels of the 5′-tRNA halves, induced by BmNSun2 knockdown, enhanced the td-piRNA expression levels without quantitative change in mature tRNAs, indicating that 5′-tRNA halves, not mature tRNAs, are the direct precursors for td-piRNAs. For the generation of tRNAHisGUG-derived piRNAs, BmThg1l-mediated nucleotide addition to −1 position of tRNAHisGUG was required, revealing an important function of BmThg1l in piRNA biogenesis. Our study advances the understanding of biogenesis mechanisms and the genesis of specific expression profiles for tRNA-derived ncRNAs. PMID:28645172
Linking Transportation System Improvements To New Business Development In Eastern Washington
DOT National Transportation Integrated Search
1994-02-01
An extensive highway, rail, barge and air system serves the transportation needs of eastern Washington's businesses and industries. Future public investment in this system will be guided by multiple criteria ranging from improved public safety to enh...
Guide to Managing Pasture Water: Streamside Buffers
USDA-ARS?s Scientific Manuscript database
Properly managed pasture water not only provides high-quality water which promotes healthy and productive livestock, but also contributes to maintaining water quality downstream. Riparian (streamside) areas serve as a transition between upland pastures and waterways. In other words, they link pastur...
Highlights of Ferry Operators in the United States
DOT National Transportation Integrated Search
2014-09-01
Ferries provide links for commuters in major metropolitan areas and offer a means of transportation across bodies of water not easily served by bridges or tunnels. Ferries are also used for emergency evacuations in times of disaster, natural or other...
Why are you telling me that? A conceptual model of the social function of autobiographical memory.
Alea, Nicole; Bluck, Susan
2003-03-01
In an effort to stimulate and guide empirical work within a functional framework, this paper provides a conceptual model of the social functions of autobiographical memory (AM) across the lifespan. The model delineates the processes and variables involved when AMs are shared to serve social functions. Components of the model include: lifespan contextual influences, the qualitative characteristics of memory (emotionality and level of detail recalled), the speaker's characteristics (age, gender, and personality), the familiarity and similarity of the listener to the speaker, the level of responsiveness during the memory-sharing process, and the nature of the social relationship in which the memory sharing occurs (valence and length of the relationship). These components are shown to influence the type of social function served and/or, the extent to which social functions are served. Directions for future empirical work to substantiate the model and hypotheses derived from the model are provided.
Development of photopolymerizable clay nanocomposites utilizing reactive dispersants
NASA Astrophysics Data System (ADS)
Owusu-Adom, Kwame
Nanocomposites hold tremendous promise for expanding the utility of polymeric materials. However, accessing particulate sizes in the nanoscale domain continues to be a scientific challenge, especially in highly cross-linked photopolymerizable systems. In this study, photopolymerizable nanocomposites utilizing clay nanoparticles and reactive dispersants have been developed. The influence of particle size, dispersant-clay interactions, and surfactant concentration on photopolymerization behavior and nanoparticle dispersion has been elucidated. Clay particles serve as templates upon which surfactants aggregate during photopolymerization. This results in higher photopolymerization rates with addition of increasing concentrations of polymerizable surfactants. Furthermore, polymerizable surfactants induce faster photopolymerization rates compared to non-polymerizable analogues in systems that have ionically-bound dispersants on the particle surface. Utilizing reactive organoclays induces significant changes to the photopolymerization behavior depending on the choice of reactive functionality employed. Faster acrylate photopolymerization rates occur in photopolymer systems containing thiol-modified clays, while much slower rates occur for nonpolymerizable organoclay systems. In addition, chemical compatibility between monomer and clay dispersant (based on chemical similarity or polarity) allows enhancement of exfoliation in photopolymerizable formulations. With polymerizable dispersants, exfoliation is readily achieved in various multifunctional acrylate systems. The degree of exfoliation depends on the position of the reactive group relative to the surfactant's cationic site and the type of functionality. Thiolated organoclays exfoliate during polymerization, while methacrylated clays show substantially less dependence on polymerization behavior. Interestingly, changes in the physical properties of the resulting nanocomposite are independent of the degree of exfoliation in polymerizable organoclay systems. The polymer cross-link density dictates the magnitude of change in both modulus and glass transition temperature of the nanocomposite. Substantial increases in modulus and Tg occur in elastomeric and low cross-link density polymers, while decreases occur in the modulus and Tg of highly cross-linked polymer networks. Finally, these parameters have formed a basis for developing nanocomposites with higher moduli and lower volumetric shrinkage. The photopolymerization rates of these systems are controllable and increase substantially with addition of polymerizable organoclays. Such properties occur in traditional multifunctional acrylate photopolymer systems as well as new binary thiol-(meth)acrylate and ternary thiol-ene-(meth)acrylate photopolymers.
Practical choices for infobutton customization: experience from four sites.
Cimino, James J; Overby, Casey L; Devine, Emily B; Hulse, Nathan C; Jing, Xia; Maviglia, Saverio M; Del Fiol, Guilherme
2013-01-01
Context-aware links between electronic health records (EHRs) and online knowledge resources, commonly called "infobuttons" are being used increasingly as part of EHR "meaningful use" requirements. While an HL7 standard exists for specifying how the links should be constructed, there is no guidance on what links to construct. Collectively, the authors manage four infobutton systems that serve 16 institutions. The purpose of this paper is to publish our experience with linking various resources and specifying particular criteria that can be used by infobutton managers to select resources that are most relevant for a given situation. This experience can be used directly by those wishing to customize their own EHRs, for example by using the OpenInfobutton infobutton manager and its configuration tool, the Librarian Infobutton Tailoring Environment.
Broadcasting satellite feeder links - Characteristics and planning
NASA Technical Reports Server (NTRS)
Kiebler, J. W.
1982-01-01
The paper presents the results of recent studies by the Feeder Link Sub-Working Group of the FCC Advisory Committee for the 1983 Regional Administrative Radio Conference (RARC). These studies conclude that specification of a few key parameters will make feeder link planning relatively straightforward. Feeder links can be located anywhere within a country if satellite orbit locations are separated by 10 deg for adjacent service areas and key parameter values presented in the paper are adopted. Colocated satellites serving a common service area need special attention to attain sufficient isolation between a desired channel and its adjacent cross-polarized channels and alternate co-polarized channels. In addition to presenting planning conclusions by the Advisory Committee, the paper presents and analyzes actions of the International Radio Consultative Committee's Conference Planning Meeting (CPM) concerning feeder links. The CPM reached conclusions similar to, and compatible with, those of the Advisory Committee.
Fallon, Justin R; McNally, Elizabeth M
2018-08-01
The extracellular matrix (ECM) plays key roles in normal and diseased skeletal and cardiac muscle. In healthy muscle the ECM is essential for transmitting contractile force, maintaining myofiber integrity and orchestrating cellular signaling. Duchenne Muscular Dystrophy (DMD) is caused by loss of dystrophin, a cytosolic protein that anchors a transmembrane complex and serves as a vital link between the actin cytoskeleton and the basal lamina. Loss of dystrophin leads to membrane fragility and impaired signaling, resulting in myofiber death and cycles of inflammation and regeneration. Fibrosis is also a cardinal feature of DMD. In this review, we will focus on two cases where understanding the normal function and regulation of ECM in muscle has led to the discovery of candidate therapeutics for DMD. Biglycan is a small leucine rich repeat ECM protein present as two glycoforms in muscle that have dramatically different functions. One widely expressed form is biglycan proteoglycan (PG) that bears two chondroitin sulfate GAG chains (typically chondroitin sulfate) and two N-linked carbohydrates. The second glycoform, referred to as 'NG' (non-glycanated) biglycan, lacks the GAG side chains. NG, but not PG biglycan recruits utrophin, an autosomal paralog of dystrophin, and an NOS-containing signaling complex to the muscle cell membrane. Recombinant NG biglycan can be systemically delivered to dystrophic mice where it upregulates utrophin at the membrane and improves muscle health and function. An optimized version of NG biglycan, 'TVN-102', is under development as a candidate therapeutic for DMD. A second matrix-embedded protein being evaluated for therapeutic potential is latent TGFβ binding protein 4 (LTBP4). Identified in a genomic screen for modifiers of muscular dystrophy, LTBP4 binds both TGFβ and myostatin. Genetic studies identified the hinge region of LTBP4 as linked to TGFβ release and contributing to the "hyper-TGFβ" signaling state that promotes fibrosis in muscular dystrophy. This hinge region can be stabilized by antibodies directed towards this domain. Stabilizing the hinge region of LTBP4 is expected to reduce latent TGFβ release and thus reduce fibrosis. Copyright © 2018 Elsevier B.V. All rights reserved.
NASA Astrophysics Data System (ADS)
Laudon, Hjalmar; Tetzlaff, Doerthe; Seibert, Jan; Soulsby, Chris; Carey, Sean; Buttle, Jim; McDonnell, Jeff; McGuire, Kevin; Caissie, Daniel; Shanley, Jamie
2010-05-01
There has been an increasing interest in understanding the regulating mechanisms of surface water dissolved organic carbon (DOC) the last decade. A majority of this recent work has been based on individual well characterized research catchments or on regional synoptic datasets combined with readily available landscape and climatic variables. However, as the production and transport of DOC primarily is a function of hydro-climatic conditions a better description of catchment hydrological functioning across large geographic regions would be favorable for moving the mechanistic understanding forward. To do this we report from a first assessment of catchment DOC within the international inter-catchment comparison program North-Watch (http://www.abdn.ac.uk/northwatch/). North-Watch includes long-term research catchments ranging from northern temperate regions to the boreal and sub-arctic biomes with the aim to better understand the variable hydrological and biogeochemical responses in Northern catchments to climate change. The North-Watch catchments are located in Sweden (Krycklan), Scotland (Mharcaidh, Girnock and Strontian), the US (Sleepers River and HJ Andrews) and Canada (Catamaran, Dorset and Wolf Creek). The annual average DOC concentration in the nine catchments investigated were directly linked to hydro-climatic influences (e.g. temperature, water storage) and landscape configuration. In general, the DOC concentration followed a parabolic shape with temperature, where the highest concentrations were found in the boreal and near boreal sites and with the lowest concentrations in the temperate and sub-arctic catchments. The between catchment variability in DOC concentration could also be explained by catchment water storage and amount of wetlands in the catchment. Whereas there is a mechanistic link between long-term climatic conditions and the areal coverage of wetlands, the total catchment storage of water is more strongly linked to topography, parent material and soil depth. The result from this analysis will serve as a conceptual framework for understanding biogeochemical response to environmental change across northern catchments. The next step in this work will be to include more detailed comparisons of the role catchment hydrological functioning for explaining the patterns and dynamics of catchment DOC of these northern watersheds.
Mechanical Properties of the Upper Airway
Strohl, Kingman P.; Butler, James P.; Malhotra, Atul
2013-01-01
The importance of the upper airway (nose, pharynx, and larynx) in health and in the pathogenesis of sleep apnea, asthma, and other airway diseases, discussed elsewhere in the Comprehensive Physiology series, prompts this review of the biomechanical properties and functional aspects of the upper airway. There is a literature based on anatomic or structural descriptions in static circumstances, albeit studied in limited numbers of individuals in both health and disease. As for dynamic features, the literature is limited to studies of pressure and flow through all or parts of the upper airway and to the effects of muscle activation on such features; however, the links between structure and function through airway size, shape, and compliance remain a topic that is completely open for investigation, particularly through analyses using concepts of fluid and structural mechanics. Throughout are included both historically seminal references, as well as those serving as signposts or updated reviews. This article should be considered a resource for concepts needed for the application of biomechanical models of upper airway physiology, applicable to understanding the pathophysiology of disease and anticipated results of treatment interventions. PMID:23723026
[The Role and Function of Informatics Nurses in Information Technology Decision-Making].
Lee, Tso-Ying
2017-08-01
The medical environment has changed greatly with the coming of the information age, and, increasingly, the operating procedures for medical services have been altered in keeping with the trend toward mobile, paperless services. Informatization has the potential to improve the working efficiency of medical personnel, enhance patient care safety, and give medical organizations a positive image. Informatics nurses play an important role in the decision-making processes that accompany informatization. As one of the decision-making links in the information technology lifecycle, this role affects the success of the development and operation of information systems. The present paper examines the functions and professional knowledge that informatics nurses must possess during the technology lifecycle, the four stages of which include: planning, analysis, design/development/revision, and implementation/assessment/support/maintenance. The present paper further examines the decision-making shortcomings and errors that an informatics nurses may make during the decision-making process. We hope that this paper will serve as an effective and useful reference for informatics nurses during the informatization decision-making process.
Effects of diabetes on brain metabolism--is brain glycogen a significant player?
Sickmann, Helle M; Waagepetersen, Helle S
2015-02-01
Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may be associated with brain impairments e.g. cognitive decline and dementia. It is however, not clear how these impairments on brain function are linked to alterations in brain energy and neurotransmitter metabolism. In this review, we will illuminate how rodent diabetes models have contributed to a better understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes.
Rebels with a cause: molecular features and physiological consequences of yeast prions.
Garcia, David M; Jarosz, Daniel F
2014-02-01
Prions are proteins that convert between structurally and functionally distinct states, at least one of which is self-perpetuating. The prion fold templates the conversion of native protein, altering its structure and function, and thus serves as a protein-based element of inheritance. Molecular chaperones ensure that these prion aggregates are divided and faithfully passed from mother cells to their daughters. Prions were originally identified as the cause of several rare neurodegenerative diseases in mammals, but the last decade has brought great progress in understanding their broad importance in biology and evolution. Most prion proteins regulate information flow in signaling networks, or otherwise affect gene expression. Consequently, switching into and out of prion states creates diverse new traits – heritable changes based on protein structure rather than nucleic acid. Despite intense study of the molecular mechanisms of this paradigm-shifting, epigenetic mode of inheritance, many key questions remain. Recent studies in yeast that support the view that prions are common, often beneficial elements of inheritance that link environmental stress to the appearance of new traits.
Covalent Organic Frameworks: From Materials Design to Biomedical Application
Zhao, Fuli; Liu, Huiming; Mathe, Salva D. R.; Dong, Anjie
2017-01-01
Covalent organic frameworks (COFs) are newly emerged crystalline porous polymers with well-defined skeletons and nanopores mainly consisted of light-weight elements (H, B, C, N and O) linked by dynamic covalent bonds. Compared with conventional materials, COFs possess some unique and attractive features, such as large surface area, pre-designable pore geometry, excellent crystallinity, inherent adaptability and high flexibility in structural and functional design, thus exhibiting great potential for various applications. Especially, their large surface area and tunable porosity and π conjugation with unique photoelectric properties will enable COFs to serve as a promising platform for drug delivery, bioimaging, biosensing and theranostic applications. In this review, we trace the evolution of COFs in terms of linkages and highlight the important issues on synthetic method, structural design, morphological control and functionalization. And then we summarize the recent advances of COFs in the biomedical and pharmaceutical sectors and conclude with a discussion of the challenges and opportunities of COFs for biomedical purposes. Although currently still at its infancy stage, COFs as an innovative source have paved a new way to meet future challenges in human healthcare and disease theranostic. PMID:29283423
A novel Phex mutation with defective glycosylation causes hypophosphatemia and rickets in mice.
Xiong, Xiwen; Qi, Xin; Ge, Xiaomei; Gu, Pengyu; Zhao, Jing; Zhao, Qingshun; Gao, Xiang
2008-01-01
N-ethyl-N-nitrosourea (ENU) mutagenesis is a phenotype-driven approach with potential to assign function to every locus in the mouse genome. In this article, we describe a new mutation, Pug, as a mouse model for X-linked hypophosphatemic rickets (XLH) in human. Mice carrying the Pug mutation exhibit abnormal phenotypes including growth retardation, hypophosphatemia and decreased bone mineral density (BMD). The new mutation was mapped to X-chromosome between 65.4 cM and 66.6 cM, where Phex gene resides. Sequence analysis revealed a unique T-to-C transition mutation resulting in Phe-to-Ser substitution at amino acid 80 of PHEX protein. In vitro studies of Pug mutation demonstrated that PHEX(pug) was incompletely glycosylated and sequestrated in the endoplasmic reticulum region of cell, whereas wild-type PHEX could be fully glycosylated and transported to the plasma membrane to exert its function as an endopeptidase. Taken together, the Pug mutant directly confirms the role of Phex in phosphate homeostasis and normal skeletal development and may serves as a new disease model of human hypophosphatemic rickets.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Holman, Holly A.; Nguyen, Lynn Y.; Tran, Vy M.
Glycosaminoglycans (GAGs) are ubiquitous in the inner ear, and disorders altering their structure or production often result in debilitating hearing and balance deficits. The specific mechanisms responsible for loss of hair-cell function are not well understood. We recently reported that introduction of a novel BODIPY conjugated xyloside (BX) into the endolymph primes fluorescent GAGs in vivo [6, 15]. Confocal and two-photon fluorescence imaging revealed rapid turnover and assembly of a glycocalyx enveloping the kinocilia and extending into the cupula, a structure that presumably serves as a mechanical link between the hair bundle and the cupula. Extracellular fluorescence was also observedmore » around the basolateral surface of hair cells and surrounding afferent nerve projections into the crista. Single unit afferent recordings during mechanical hair bundle stimulation revealed temporary interruption of synaptic transmission following BX administration followed by recovery, demonstrating an essential role for GAGs in function of the hair cell synapse. In the present work we present a pharmacokinetic model to quantify the time course of BX primed GAG production and turnover in the ear.« less
Inorganic polyphosphate in the microbial world. Emerging roles for a multifaceted biopolymer.
Albi, Tomás; Serrano, Aurelio
2016-02-01
Inorganic polyphosphates (polyP) are linear polymers of tens to hundreds orthophosphate residues linked by phosphoanhydride bonds. These fairly abundant biopolymers occur in all extant forms of life, from prokaryotes to mammals, and could have played a relevant role in prebiotic evolution. Since the first identification of polyP deposits as metachromatic or volutin granules in yeasts in the nineteenth century, an increasing number of varied physiological functions have been reported. Due to their "high energy" bonds analogous to those in ATP and their properties as polyanions, polyP serve as microbial phosphagens for a variety of biochemical reactions, as a buffer against alkalis, as a storage of Ca(2+) and as a metal-chelating agent. In addition, recent studies have revealed polyP importance in signaling and regulatory processes, cell viability and proliferation, pathogen virulence, as a structural component and chemical chaperone, and as modulator of microbial stress response. This review summarizes the current status of knowledge and future perspectives of polyP functions and their related enzymes in the microbial world.
NASA Astrophysics Data System (ADS)
Holman, Holly A.; Tran, Vy M.; Nguyen, Lynn Y.; Arungundram, Sailaja; Kalita, Mausam; Kuberan, Balagurunathan; Rabbitt, Richard D.
2015-12-01
Glycosaminoglycans (GAGs) are ubiquitous in the inner ear, and disorders altering their structure or production often result in debilitating hearing and balance deficits. The specific mechanisms responsible for loss of hair-cell function are not well understood. We recently reported that introduction of a novel BODIPY conjugated xyloside (BX) into the endolymph primes fluorescent GAGs in vivo [6, 15]. Confocal and two-photon fluorescence imaging revealed rapid turnover and assembly of a glycocalyx enveloping the kinocilia and extending into the cupula, a structure that presumably serves as a mechanical link between the hair bundle and the cupula. Extracellular fluorescence was also observed around the basolateral surface of hair cells and surrounding afferent nerve projections into the crista. Single unit afferent recordings during mechanical hair bundle stimulation revealed temporary interruption of synaptic transmission following BX administration followed by recovery, demonstrating an essential role for GAGs in function of the hair cell synapse. In the present work we present a pharmacokinetic model to quantify the time course of BX primed GAG production and turnover in the ear.
Ketone bodies as epigenetic modifiers.
Ruan, Hai-Bin; Crawford, Peter A
2018-07-01
Ketone body metabolism is a dynamic and integrated metabolic node in human physiology, whose roles include but extend beyond alternative fuel provision during carbohydrate restriction. Here we discuss the most recent observations suggesting that ketosis coordinates cellular function via epigenomic regulation. Ketosis has been linked to covalent modifications, including lysine acetylation, methylation, and hydroxybutyrylation, to key histones that serve as dynamic regulators of chromatin architecture and gene transcription. Although it remains to be fully established whether these changes to the epigenome are attributable to ketone bodies themselves or other aspects of ketotic states, the regulated genes mediate classical responses to carbohydrate restriction. Direct regulation of gene expression may occur in-vivo via through ketone body-mediated histone modifications during adherence to low-carbohydrate diets, fasting ketosis, exogenous ketone body therapy, and diabetic ketoacidosis. Additional convergent functional genomics, metabolomics, and proteomics studies are required in both animal models and in humans to identify the molecular mechanisms through which ketosis regulates nuclear signaling events in a myriad of conditions relevant to disease, and the contexts in which the benefits of ketosis might outweigh the risks.
Miao, Yi-Liang; Williams, Carmen J.
2012-01-01
Calcium (Ca2+) signals drive the fundamental events surrounding fertilization and the activation of development in all species examined to date. Initial studies of Ca2+ signaling at fertilization in marine animals were tightly linked to new discoveries of bioluminescent proteins and their use as fluorescent Ca2+ sensors. Since that time, there has been rapid progress in our understanding of the key functions for Ca2+ in many cell types and the impact of cellular localization on Ca2+ signaling pathways. In this review, which focuses on mammalian egg activation, we consider how Ca2+ is regulated and stored at different stages of oocyte development and examine the functions of molecules that serve as both regulators of Ca2+ release and effectors of Ca2+ signals. We then summarize studies exploring how Ca2+ directs downstream effectors mediating both egg activation and later signaling events required for successful preimplantation embryo development. Throughout this review, we focus attention on how localization of Ca2+ signals influences downstream signaling events, and attempt to highlight gaps in our knowledge that are ripe areas for future research. PMID:22888043
HDDTOOLS: an R package serving Hydrological Data Discovery Tools
NASA Astrophysics Data System (ADS)
Vitolo, C.; Buytaert, W.
2014-12-01
Many governmental bodies and institutions are currently committed to publish open data as the result of a trend of increasing transparency, based on which a wide variety of information produced at public expense is now becoming open and freely available to improve public involvement in the process of decision and policy making. Discovery, access and retrieval of information is, however, not always a simple task. Especially when programmatic access to data resources is not allowed, downloading metadata catalogue, select the information needed, request datasets, de-compression, conversion, manual filtering and parsing can become rather tedious. The R package "hddtools" is an open source project, designed to make all the above operations more efficient by means of re-usable functions. The package facilitate non programmatic access to various online data sources such as the Global Runoff Data Centre, NASA's TRMM mission, the Data60UK database amongst others. This package complements R's growing functionality in environmental web technologies to bridge the gap between data providers and data consumers and it is designed to be the starting building block of scientific workflows for linking data and models in a seamless fashion.
Determination of Optimal Portion Size for Hot Combat Rations
1986-07-12
Gravy 20 3 slices 18 027 Stuffed Peppers 8 2 peppers NA 006 Swedish Meatballs 15 2 meatballs 12 106 Chicken/Noodles 12 1 cup 12 107 Chicken Cacciatore...1/2 cups NA 005 Lasagna 12 cut 3x4 12 016 Spaghetti/ Meatballs 8 1-1/2 cups incl 2 meatballs NA 036 Beef Swiss Steak/Gravy 14 1 slice 12 112... Meatballs /Rice/Cabbag e 15 2 meatballs 12 a Prepared by Ration Design and Evaluation Branch, FED. D When used as an entree, servs 5 links (18 servings
Kaplan, Zeev; Weiser, Mark; Reichenberg, Abraham; Rabinowitz, Jonathan; Caspi, Asaf; Bodner, Ehud; Zohar, Joseph
2002-01-31
High motivation and belief in a cause have been reported to be protective against posttraumatic stress disorder (PTSD), while below-average intellectual functioning and poor educational achievements have been reported to increase vulnerability to PTSD. The main goal of this study was to assess the effect of education, and intellectual and behavioral functioning on the risk for future PTSD. Data collected before exposure to trauma, on intellectual and behavioral functioning, and educational achievements of 901 male Israeli adolescents who had performed pre-induction screening tests by the Israeli Draft Board, and were later diagnosed with PTSD, were compared with a control group of adolescents who were not later diagnosed with PTSD. Future PTSD patients had significantly lower intelligence, fewer years of formal education and lower scores on a scale assessing motivation to serve in the military, in comparison with the control group, with effect sizes (ES) ranging from 0.14-0.34. In contrast, future PTSD patients scored significantly higher on a scale assessing social functioning, ES=0.13. However, when controlling for the differences in motivation to serve, all of these differences disappeared. In this cohort, although slightly below average intellectual functioning and formal education, and better social functioning, independently increased vulnerability to suffer from PTSD, these associations disappeared when the future PTSD patients' lower motivation to serve in the military was included in the analysis. This suggests that low motivation to serve in the military might increase vulnerability for PTSD.
Evaluation of Hierarchical Clustering Algorithms for Document Datasets
2002-06-03
link, complete-link, and group average ( UPGMA )) and a new set of merging criteria derived from the six partitional criterion functions. Overall, we...used the single-link, complete-link, and UPGMA schemes, as well as, the various partitional criterion functions described in Section 3.1. The single-link...other (complete-link approach). The UPGMA scheme [16] (also known as group average) overcomes these problems by measuring the similarity of two clusters
Cognition and procedure representational requirements for predictive human performance models
NASA Technical Reports Server (NTRS)
Corker, K.
1992-01-01
Models and modeling environments for human performance are becoming significant contributors to early system design and analysis procedures. Issues of levels of automation, physical environment, informational environment, and manning requirements are being addressed by such man/machine analysis systems. The research reported here investigates the close interaction between models of human cognition and models that described procedural performance. We describe a methodology for the decomposition of aircrew procedures that supports interaction with models of cognition on the basis of procedures observed; that serves to identify cockpit/avionics information sources and crew information requirements; and that provides the structure to support methods for function allocation among crew and aiding systems. Our approach is to develop an object-oriented, modular, executable software representation of the aircrew, the aircraft, and the procedures necessary to satisfy flight-phase goals. We then encode in a time-based language, taxonomies of the conceptual, relational, and procedural constraints among the cockpit avionics and control system and the aircrew. We have designed and implemented a goals/procedures hierarchic representation sufficient to describe procedural flow in the cockpit. We then execute the procedural representation in simulation software and calculate the values of the flight instruments, aircraft state variables and crew resources using the constraints available from the relationship taxonomies. The system provides a flexible, extensible, manipulative and executable representation of aircrew and procedures that is generally applicable to crew/procedure task-analysis. The representation supports developed methods of intent inference, and is extensible to include issues of information requirements and functional allocation. We are attempting to link the procedural representation to models of cognitive functions to establish several intent inference methods including procedural backtracking with concurrent search, temporal reasoning, and constraint checking for partial ordering of procedures. Finally, the representation is being linked to models of human decision making processes that include heuristic, propositional and prescriptive judgement models that are sensitive to the procedural content in which the valuative functions are being performed.
Influence of cross-linked arabinoxylans on the postprandial blood glucose response in rats.
Vogel, Barbara; Gallaher, Daniel D; Bunzel, Mirko
2012-04-18
Viscous dietary fibers are well established to reduce the blood glucose response to a meal. In this study, arabinoxylans, the most abundant dietary fiber in most cereals, were extracted under alkaline conditions and cross-linked by using laccase. Cross-linking of the arabinoxylans led to gel formation and increased in vitro viscosity almost 100-fold after drying and rehydration. To determine the ability of these cross-linked arabinoxylans to blunt the postprandial blood glucose curve of a meal, arabinoxylans, either native or cross-linked, and either prehydrated or not, were fed to rats as part of a meal, and blood glucose was monitored at intervals after the meal. Cellulose, a nonviscous fiber, served as a control. Cross-linked, but not native, arabinoxylans significantly reduced the area under the blood glucose time curve 5-9% relative to cellulose, indicating that they remained viscous within the gastrointestinal tract, and thus likely provide the health benefits found with other viscous fibers.
ERIC Educational Resources Information Center
Yang, Hongfei; Li, Juan
2016-01-01
The present study examined the associations between linking, response to positive affect, and psychological functioning in Chinese college students. The results of conducting multiple mediation analyses indicated that emotion- and self-focused positive rumination mediated the relationship between linking and psychological functioning, whereas…
Thieltges, David W.; Amundsen, Per-Arne; Hechinger, Ryan F.; Johnson, Pieter T.J.; Lafferty, Levin D.; Mouritsen, Kim N.; Preston, Daniel L.; Reise, Karsten; Zander, C. Dieter; Poulin, Robert
2013-01-01
While the recent inclusion of parasites into food-web studies has highlighted the role of parasites as consumers, there is accumulating evidence that parasites can also serve as prey for predators. Here we investigated empirical patterns of predation on parasites and their relationships with parasite transmission in eight topological food webs representing marine and freshwater ecosystems. Within each food web, we examined links in the typical predator–prey sub web as well as the predator–parasite sub web, i.e. the quadrant of the food web indicating which predators eat parasites. Most predator– parasite links represented ‘concomitant predation’ (consumption and death of a parasite along with the prey/host; 58–72%), followed by ‘trophic transmission’ (predator feeds on infected prey and becomes infected; 8–32%) and predation on free-living parasite life-cycle stages (4–30%). Parasite life-cycle stages had, on average, between 4.2 and 14.2 predators. Among the food webs, as predator richness increased, the number of links exploited by trophically transmitted parasites increased at about the same rate as did the number of links where these stages serve as prey. On the whole, our analyses suggest that predation on parasites has important consequences for both predators and parasites, and food web structure. Because our analysis is solely based on topological webs, determining the strength of these interactions is a promising avenue for future research.
Teachers, Curriculum and the Community.
ERIC Educational Resources Information Center
Molnar, Alex
In this essay teachers, school curriculum and their relationship to the society they serve and the community in which they function are discussed. Since educational institutions serve a regulatory function, what goes on in schools mirrors the interests of the status quo in the society. Therefore the question facing educators and community people…
Lodge Programs Serving Family Functions for People with Psychiatric Disabilities.
ERIC Educational Resources Information Center
Onaga, Esther E.; McKinney, Kathleen G.; Pfaff, Judy
2000-01-01
Interviews were conducted with people affiliated with lodges, a community program for people with psychiatric disabilities, about their perceptions of promising practices. Responses validated the notion that the lodge serves many of the functions of a family. Provides excerpts from interviews to supplement this theme. Discusses implications for…
77 FR 25168 - Appraisal Subcommittee (ASC); ASC Rules of Operation; Amended
Federal Register 2010, 2011, 2012, 2013, 2014
2012-04-27
... heads of the Bureau of Consumer Financial Protection and the Federal Housing Finance Agency. The ASC Rules of Operation serve as corporate bylaws outlining the ASC's purpose, functions, authority... Title XI. The ASC Rules of Operation serve as corporate bylaws outlining the ASC's purpose, functions...
Identification of Prostate Cancer-Specific Circular RNAs
2016-12-01
they often have regulatory functions. For example, circRNAs can serve as endogenous microRNA sponges to neutralize the microRNA function. However, it...circRNAs is the capability to serve as sponges to neutralize the endogenous microRNAs. In this regard, all of these circRNAs had the potential to
Pulse-chase Analysis of N-linked Sugar Chains from Glycoproteins in Mammalian Cells
Avezov, Edward; Ron, Efrat; Izenshtein, Yana; Adan, Yosef; Lederkremer, Gerardo Z.
2010-01-01
Attachment of the Glc3Man9GlcNAc2 precursor oligosaccharide to nascent polypeptides in the ER is a common modification for secretory proteins. Although this modification was implicated in several biological processes, additional aspects of its function are emerging, with recent evidence of its role in the production of signals for glycoprotein quality control and trafficking. Thus, phenomena related to N-linked glycans and their processing are being intensively investigated. Methods that have been recently developed for proteomic analysis have greatly improved the characterization of glycoprotein N-linked glycans. Nevertheless, they do not provide insight into the dynamics of the sugar chain processing involved. For this, labeling and pulse-chase analysis protocols are used that are usually complex and give very low yields. We describe here a simple method for the isolation and analysis of metabolically labeled N-linked oligosaccharides. The protocol is based on labeling of cells with [2-3H] mannose, denaturing lysis and enzymatic release of the oligosaccharides from either a specifically immunoprecipitated protein of interest or from the general glycoprotein pool by sequential treatments with endo H and N-glycosidase F, followed by molecular filtration (Amicon). In this method the isolated oligosaccharides serve as an input for HPLC analysis, which allows discrimination between various glycan structures according to the number of monosaccharide units comprising them, with a resolution of a single monosaccharide. Using this method we were able to study high mannose N-linked oligosaccharide profiles of total cell glycoproteins after pulse-chase in normal conditions and under proteasome inhibition. These profiles were compared to those obtained from an immunoprecipitated ER-associated degradation (ERAD) substrate. Our results suggest that most NIH 3T3 cellular glycoproteins are relatively stable and that most of their oligosaccharides are trimmed to Man9-8GlcNAc2. In contrast, unstable ERAD substrates are trimmed to Man6-5GlcNAc2 and glycoproteins bearing these species accumulate upon inhibition of proteasomal degradation. PMID:20424595
Pulse-chase analysis of N-linked sugar chains from glycoproteins in mammalian cells.
Avezov, Edward; Ron, Efrat; Izenshtein, Yana; Adan, Yosef; Lederkremer, Gerardo Z
2010-04-27
Attachment of the Glc3Man9GlcNAc2 precursor oligosaccharide to nascent polypeptides in the ER is a common modification for secretory proteins. Although this modification was implicated in several biological processes, additional aspects of its function are emerging, with recent evidence of its role in the production of signals for glycoprotein quality control and trafficking. Thus, phenomena related to N-linked glycans and their processing are being intensively investigated. Methods that have been recently developed for proteomic analysis have greatly improved the characterization of glycoprotein N-linked glycans. Nevertheless, they do not provide insight into the dynamics of the sugar chain processing involved. For this, labeling and pulse-chase analysis protocols are used that are usually complex and give very low yields. We describe here a simple method for the isolation and analysis of metabolically labeled N-linked oligosaccharides. The protocol is based on labeling of cells with [2-(3)H] mannose, denaturing lysis and enzymatic release of the oligosaccharides from either a specifically immunoprecipitated protein of interest or from the general glycoprotein pool by sequential treatments with endo H and N-glycosidase F, followed by molecular filtration (Amicon). In this method the isolated oligosaccharides serve as an input for HPLC analysis, which allows discrimination between various glycan structures according to the number of monosaccharide units comprising them, with a resolution of a single monosaccharide. Using this method we were able to study high mannose N-linked oligosaccharide profiles of total cell glycoproteins after pulse-chase in normal conditions and under proteasome inhibition. These profiles were compared to those obtained from an immunoprecipitated ER-associated degradation (ERAD) substrate. Our results suggest that most NIH 3T3 cellular glycoproteins are relatively stable and that most of their oligosaccharides are trimmed to Man9-8GlcNAc2. In contrast, unstable ERAD substrates are trimmed to Man6-5GlcNAc2 and glycoproteins bearing these species accumulate upon inhibition of proteasomal degradation.
On-Demand Dissolution of Chemically Cross-Linked Hydrogels.
Konieczynska, Marlena D; Grinstaff, Mark W
2017-02-21
The formation and subsequent on-demand dissolution of chemically cross-linked hydrogels is of keen interest to chemists, engineers, and clinicians. In this Account, we summarize our recent advances in the area of dissolvable chemically cross-linked hydrogels and provide a comparative discussion of other recent hydrogel systems. Using biocompatible macromonomers, we developed a library of cross-linked dendritic hydrogels that possess favorable properties, including biocompatibility, tissue adhesion, and swelling. Additionally, these hydrogels possess the unique ability to dissolve on-demand via application of a biocompatible aqueous solution. Each of the three hydrogel systems described employs a thiol-thioester exchange reaction as the mechanism of dissolution. These new materials successfully decrease bleeding in in vivo models of hepatic and aortic hemorrhage and dissolve on-demand, providing easy removal. In addition, we evaluated these hydrogels as dressings for second-degree burn wounds and performed proof-of-concept in vivo studies. These hydrogel wound dressings provide a means of repeatedly changing the dressing in a minimally invasive and atraumatic manner while also serving as a protective barrier against bacterial infection. Finally, we highlight the seminal work of other researchers in the field of dissolvable chemically cross-linked hydrogels using thiol-disulfide exchange, retro-Michael-type, and retro-Diels-Alder reactions. These chemistries provide a versatile synthetic toolbox to dissolve hydrogels in a controlled manner on time scales from minutes to weeks. Continued investigation of these dissolution approaches as well as the development of new chemical reactions will open doors to other avenues of on-demand dissolution and expand the application space for these materials. In summary, the management and closure of wounds after traumatic injury or surgical intervention are of significant clinical importance. Stimuli-responsive hydrogels that function as sealants, adhesives, or dressings are emerging as vital alternatives to current standards of care that rely upon conventional sutures, staples, or dressings.
ObsPy - A Python Toolbox for Seismology - and Applications
NASA Astrophysics Data System (ADS)
Krischer, L.; Megies, T.; Barsch, R.; MacCarthy, J.; Lecocq, T.; Koymans, M. R.; Carothers, L.; Eulenfeld, T.; Reyes, C. G.; Falco, N.; Sales de Andrade, E.
2017-12-01
Recent years witnessed the evolution of Python's ecosystem into one of the most powerful and productive scientific environments across disciplines. ObsPy (https://www.obspy.org) is a fully community driven, open-source project dedicated to provide a bridge for seismology into that ecosystem. It is a Python toolbox offering: Read and write support for essentially every commonly used data format in seismology with a unified interface and automatic format detection. This includes waveform data (MiniSEED, SAC, SEG-Y, Reftek, …) as well as station (SEED, StationXML, SC3ML, …) and event meta information (QuakeML, ZMAP, …). Integrated access to the largest data centers, web services, and real-time data streams (FDSNWS, ArcLink, SeedLink, ...). A powerful signal processing toolbox tuned to the specific needs of seismologists. Utility functionality like travel time calculations with the TauP method, geodetic functions, and data visualizations. ObsPy has been in constant development for more than eight years and is developed and used by scientists around the world with successful applications in all branches of seismology. Additionally it nowadays serves as the foundation for a large number of more specialized packages. Newest features include: Full interoperability of SEED and StationXML/Inventory objects Access to the Nominal Response Library (NRL) for easy and quick creation of station metadata from scratch Support for the IRIS Federated Catalog Service Improved performance of the EarthWorm client Several improvements to MiniSEED read/write module Improved plotting capabilities for PPSD (spectrograms, PSD of discrete frequencies over time, ..) Support for.. Reading ArcLink Inventory XML Reading Reftek data format Writing SeisComp3 ML (SC3ML) Writing StationTXT format This presentation will give a short overview of the capabilities of ObsPy and point out several representative or new use cases and show-case some projects that are based on ObsPy, e.g.: seismo-live.org Seedlink-plotter MSNoise, and others..
Jäger, Marcus; van Wasen, Andrea; Warwas, Sebastian; Landgraeber, Stefan; Haversath, Marcel; Group, VITAS
2014-01-01
Since polyethylene is one of the most frequently used biomaterials as a liner in total hip arthroplasty, strong efforts have been made to improve design and material properties over the last 50 years. Antioxidants seems to be a promising alternative to further increase durability and reduce polyethylene wear in long term. As of yet, only in vitro results are available. While they are promising, there is yet no clinical evidence that the new material shows these advantages in vivo. To answer the question if vitamin-E enhanced ultra-high molecular weight polyethylene (UHMWPE) is able to improve long-term survivorship of cementless total hip arthroplasty we initiated a randomized long-term multicenter trial. Designed as a superiority study, the oxidation index assessed in retrieval analyses of explanted liners was chosen as primary parameter. Radiographic results (wear rate, osteolysis, radiolucency) and functional outcome (Harris Hip Scores, University of California-Los Angeles, Hip Disability and Osteoarthritis Outcome Score, Visual Analogue Scale) will serve as secondary parameters. Patients with the indication for a cementless total hip arthroplasty will be asked to participate in the study and will be randomized to either receive a standard hip replacement with a highly cross-linked UHMWPE-X liner or a highly cross-linked vitamin-E supplemented UHMWPE-XE liner. The follow-up will be 15 years, with evaluation after 5, 10 and 15 years. The controlled randomized study has been designed to determine if Vitamin-E supplemented highly cross-linked polyethylene liners are superior to standard XLPE liners in cementless total hip arthroplasty. While several studies have been started to evaluate the influence of vitamin-E, most of them evaluate wear rates and functional results. The approach used for this multicenter study, to analyze the oxidation status of retrieved implants, should make it possible to directly evaluate the ageing process and development of the implant material itself over a time period of 15 years. PMID:25002933
Technology Candidates for Air-to-Air and Air-to-Ground Data Exchange
NASA Technical Reports Server (NTRS)
Haynes, Brian D.
2015-01-01
Technology Candidates for Air-to-Air and Air-to-Ground Data Exchange is a two-year research effort to visualize the U. S. aviation industry at a point 50 years in the future, and to define potential communication solutions to meet those future data exchange needs. The research team, led by XCELAR, was tasked with identifying future National Airspace System (NAS) scenarios, determining requirements and functions (including gaps), investigating technical and business issues for air, ground, & air-to-ground interactions, and reporting on the results. The project was conducted under technical direction from NASA and in collaboration with XCELAR's partner, National Institute of Aerospace, and NASA technical representatives. Parallel efforts were initiated to define the information exchange functional needs of the future NAS, and specific communication link technologies to potentially serve those needs. Those efforts converged with the mapping of each identified future NAS function to potential enabling communication solutions; those solutions were then compared with, and ranked relative to, each other on a technical basis in a structured analysis process. The technical solutions emerging from that process were then assessed from a business case perspective to determine their viability from a real-world adoption and deployment standpoint. The results of that analysis produced a proposed set of future solutions and most promising candidate technologies. Gap analyses were conducted at two points in the process, the first examining technical factors, and the second as part of the business case analysis. In each case, no gaps or unmet needs were identified in applying the solutions evaluated to the requirements identified. The future communication solutions identified in the research comprise both specific link technologies and two enabling technologies that apply to most or all specific links. As a result, the research resulted in a new analysis approach, viewing the underlying architecture of ground-air and air-air communications as a whole, rather than as simple "link to function" paired solutions. For the business case analysis, a number of "reference architectures" were developed for both the future technologies and the current systems, based on three typical configurations of current aircraft. Current and future costs were assigned, and various comparisons made between the current and future architectures. In general, it was assumed that if a future architecture offers lower cost than the current typical architecture, while delivering equivalent or better performance, it is likely that the future solution will gain industry acceptance. Conversely, future architectures presenting higher costs than their current counterparts must present a compelling benefit case in other areas or risk a lack of industry acceptance. The business case analysis consistently indicated lower costs for the proposed future architectures, and in most cases, significantly so. The proposed future solutions were found to offer significantly greater functionality, flexibility, and growth potential over time, at lower cost, than current systems. This was true for overall, fleet-wide equipage for domestic and oceanic air carriers, as well as for single, General Aviation (GA) aircraft. The overall research results indicate that all identified requirements can be met by the proposed solutions with significant capacity for future growth. Results also illustrate that the majority of the future communication needs can be met using currently allocated aviation RF spectrum, if used in more effective ways than it is today. A combination of such optimized aviation-specific links and commercial communication systems meets all identified needs for the 50-year future and beyond, with the caveat that a new, overall function will be needed to manage all information exchange, individual links, security, cost, and other factors. This function was labeled "Delivery Manager" (DM) within this research. DM employs a distributed client/server architecture, for both airborne and ground communications architectures. Final research results included identifying the most promising candidate technologies for the future system, conclusions and recommendations, and identifying areas where further research should be considered.
Linking the Central Office and Its Schools for Reform
ERIC Educational Resources Information Center
Johnson, Peggy E.; Chrispeels, Janet H.
2010-01-01
Purpose: This study investigates how linkages between a central office and its schools served as administrative controls while fostering professional accountability and organizational learning. Method: Using qualitative data sources (interviews, focus groups, observations, field notes, and document reviews), the study examines how resource,…
Code of Federal Regulations, 2010 CFR
2010-01-01
... identity when filing documents and serving participants electronically through the E-Filing system, and... transmitted electronically from the E-Filing system to the submitter confirming receipt of electronic filing... presentation of the docket and a link to its files. E-Filing System means an electronic system that receives...
CERF Launches CESN En Espanol in 2012
CERF launched Coastal and Estuarine Science News (CESN) in 2003 as an electronic companion to the journal Estuaries and Coasts. CESN serves to strengthen the link between science and management of coastal systems by reaching out to a wider audience with accessible summaries of 4...
Escaping the Tyranny of Belief
ERIC Educational Resources Information Center
Wiswell, Albert K.; Wells, C. Leanne
2004-01-01
This study describes an action research case study through which the dynamics of identifying and changing strongly held assumptions illustrate the differences between experiences that serve to strengthen beliefs from those that lead to learning. Theoretical considerations are presented linking cognitive schema, action science, attribution theory,…
NASA Technical Reports Server (NTRS)
Ertem, G.; Ferris, J. P.
1997-01-01
The synthesis of oligoguanylates [oligo(G)s] is catalyzed by a template of oligocytidylates [oligo(C)s] containing 2',5'- and 3',5'-linked phosphodiester bonds with and without incorporated C5'ppC groupings. An oligo(C) template containing exclusively 2',5'-phosphodiester bonds also serves as a template for the synthesis of complementary oligo(G)s. The oligo(C) template was prepared by the condensation of the 5'-phosphorimidazolide of cytidine on montmorillonite clay. These studies establish that RNA oligomers prepared by mineral catalysis, or other routes on the primitive earth, did not have to be exclusively 3',5'-linked to catalyze template-directed synthesis, since oligo(C)s containing a variety of linkage isomers serve as templates for the formation of complementary oligo(G)s. These findings support the postulate that origin of the RNA world was initiated by the RNA oligomers produced by polymerization of activated monomers formed by prebiotic processes.
Zheng, Lai; Ismail, Karim
2017-05-01
Traffic conflict indicators measure the temporal and spatial proximity of conflict-involved road users. These indicators can reflect the severity of traffic conflicts to a reliable extent. Instead of using the indicator value directly as a severity index, many link functions have been developed to map the conflict indicator to a severity index. However, little information is available about the choice of a particular link function. To guard against link misspecification or subjectivity, a generalized exponential link function was developed. The severity index generated by this link was introduced to a parametric safety continuum model which objectively models the centre and tail regions. An empirical method, together with full Bayesian estimation method was adopted to estimate model parameters. The safety implication of return level was calculated based on the model parameters. The proposed approach was applied to the conflict and crash data collected from 21 segments from three freeways located in Guangdong province, China. The Pearson's correlation test between return levels and observed crashes showed that a θ value of 1.2 was the best choice of the generalized parameter for current data set. This provides statistical support for using the generalized exponential link function. With the determined generalized exponential link function, the visualization of parametric safety continuum was found to be a gyroscope-shaped hierarchy. Copyright © 2017 Elsevier Ltd. All rights reserved.
Hu, Xiangen; Graesser, Arthur C
2004-05-01
The Human Use Regulatory Affairs Advisor (HURAA) is a Web-based facility that provides help and training on the ethical use of human subjects in research, based on documents and regulations in United States federal agencies. HURAA has a number of standard features of conventional Web facilities and computer-based training, such as hypertext, multimedia, help modules, glossaries, archives, links to other sites, and page-turning didactic instruction. HURAA also has these intelligent features: (1) an animated conversational agent that serves as a navigational guide for the Web facility, (2) lessons with case-based and explanation-based reasoning, (3) document retrieval through natural language queries, and (4) a context-sensitive Frequently Asked Questions segment, called Point & Query. This article describes the functional learning components of HURAA, specifies its computational architecture, and summarizes empirical tests of the facility on learners.
Zhou, Li; Collins, Sarah; Morgan, Stephen J.; Zafar, Neelam; Gesner, Emily J.; Fehrenbach, Martin; Rocha, Roberto A.
2016-01-01
Structured clinical documentation is an important component of electronic health records (EHRs) and plays an important role in clinical care, administrative functions, and research activities. Clinical data elements serve as basic building blocks for composing the templates used for generating clinical documents (such as notes and forms). We present our experience in creating and maintaining data elements for three different EHRs (one home-grown and two commercial systems) across different clinical settings, using flowsheet data elements as examples in our case studies. We identified basic but important challenges (including naming convention, links to standard terminologies, and versioning and change management) and possible solutions to address them. We also discussed more complicated challenges regarding governance, documentation vs. structured data capture, pre-coordination vs. post-coordination, reference information models, as well as monitoring, communication and training. PMID:28269927
Mood disorders: A potential link between ghrelin and leptin on human body?
Zarouna, Stalo; Wozniak, Greta; Papachristou, Anastasia Ioannis
2015-05-20
Leptin and ghrelin are two hormones associated with multiple physiological functions, especially energy balance. Leptin is an adipocyte-secreted hormone discovered in 1950 and ghrelin which was found in 1999, is a peptide hormone produced and secreted in the stomach. A number of previous studies showed that these hormones could be associated with different types of mood disorders. The results of previous studies, nevertheless, are confounded by diverse sample selection and different methodologies. A search for related articles in the PubMed database was attempted. The search covered studies, reports, reviews and editorials published in the last ten years. Older references served as auxiliary sources for comparison purposes. However, due to the different results of the studies, there is a need for more investigation in order to establish the exact biochemical mechanisms that are responsible for these diseases and ghrelin's and leptin's effects on mood.
Food-web stability signals critical transitions in temperate shallow lakes
Kuiper, Jan J.; van Altena, Cassandra; de Ruiter, Peter C.; van Gerven, Luuk P. A.; Janse, Jan H.; Mooij, Wolf M.
2015-01-01
A principal aim of ecologists is to identify critical levels of environmental change beyond which ecosystems undergo radical shifts in their functioning. Both food-web theory and alternative stable states theory provide fundamental clues to mechanisms conferring stability to natural systems. Yet, it is unclear how the concept of food-web stability is associated with the resilience of ecosystems susceptible to regime change. Here, we use a combination of food web and ecosystem modelling to show that impending catastrophic shifts in shallow lakes are preceded by a destabilizing reorganization of interaction strengths in the aquatic food web. Analysis of the intricate web of trophic interactions reveals that only few key interactions, involving zooplankton, diatoms and detritus, dictate the deterioration of food-web stability. Our study exposes a tight link between food-web dynamics and the dynamics of the whole ecosystem, implying that trophic organization may serve as an empirical indicator of ecosystem resilience. PMID:26173798
Chromatin landscape and circadian dynamics: Spatial and temporal organization of clock transcription
Aguilar-Arnal, Lorena; Sassone-Corsi, Paolo
2015-01-01
Circadian rhythms drive the temporal organization of a wide variety of physiological and behavioral functions in ∼24-h cycles. This control is achieved through a complex program of gene expression. In mammals, the molecular clock machinery consists of interconnected transcriptional–translational feedback loops that ultimately ensure the proper oscillation of thousands of genes in a tissue-specific manner. To achieve circadian transcriptional control, chromatin remodelers serve the clock machinery by providing appropriate oscillations to the epigenome. Recent findings have revealed the presence of circadian interactomes, nuclear “hubs” of genome topology where coordinately expressed circadian genes physically interact in a spatial and temporal-specific manner. Thus, a circadian nuclear landscape seems to exist, whose interplay with metabolic pathways and clock regulators translates into specific transcriptional programs. Deciphering the molecular mechanisms that connect the circadian clock machinery with the nuclear landscape will reveal yet unexplored pathways that link cellular metabolism to epigenetic control. PMID:25378702
Search without Boundaries Using Simple APIs
Tong, Qi
2009-01-01
The U.S. Geological Survey (USGS) Library, where the author serves as the digital services librarian, is increasingly challenged to make it easier for users to find information from many heterogeneous information sources. Information is scattered throughout different software applications (i.e., library catalog, federated search engine, link resolver, and vendor websites), and each specializes in one thing. How could the library integrate the functionalities of one application with another and provide a single point of entry for users to search across? To improve the user experience, the library launched an effort to integrate the federated search engine into the library's intranet website. The result is a simple search box that leverages the federated search engine's built-in application programming interfaces (APIs). In this article, the author describes how this project demonstrated the power of APIs and their potential to be used by other enterprise search portals inside or outside of the library.
Everything Is Permitted? People Intuitively Judge Immorality as Representative of Atheists
Gervais, Will M.
2014-01-01
Scientific research yields inconsistent and contradictory evidence relating religion to moral judgments and outcomes, yet most people on earth nonetheless view belief in God (or gods) as central to morality, and many view atheists with suspicion and scorn. To evaluate intuitions regarding a causal link between religion and morality, this paper tested intuitive moral judgments of atheists and other groups. Across five experiments (N = 1,152), American participants intuitively judged a wide variety of immoral acts (e.g., serial murder, consensual incest, necrobestiality, cannibalism) as representative of atheists, but not of eleven other religious, ethnic, and cultural groups. Even atheist participants judged immoral acts as more representative of atheists than of other groups. These findings demonstrate a prevalent intuition that belief in God serves a necessary function in inhibiting immoral conduct, and may help explain persistent negative perceptions of atheists. PMID:24717972
Milk Glycans and Their Interaction with the Infant-Gut Microbiota
Kirmiz, Nina; Robinson, Randall C.; Shah, Ishita M.; Barile, Daniela; Mills, David A.
2018-01-01
Human milk is a unique and complex fluid that provides infant nutrition and delivers an array of bioactive molecules that serve various functions. Glycans, abundant in milk, can be found as free oligosaccharides or as glycoconjugates. Milk glycans are increasingly linked to beneficial outcomes in neonates through protection from pathogens and modulation of the immune system. Indeed, these glycans influence the development of the infant and the infant-gut microbiota. Bifidobacterium species commonly are enriched in breastfed infants and are among a limited group of bacteria that readily consume human milk oligosaccharides (HMOs) and milk glycoconjugates. Given the importance of bifidobacteria in infant health, numerous studies have examined the molecular mechanisms they employ to consume HMOs and milk glycans, thus providing insight into this unique enrichment and shedding light on a range of translational opportunities to benefit at-risk infants. PMID:29580136
Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates
Vohs, Jenifer L.; Hummer, Tom A.; Yung, Matthew G.; Francis, Michael M.; Lysaker, Paul H.; Breier, Alan
2015-01-01
Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis. PMID:26132568
Manufacturing Technology Information Analysis Center: Knowledge Is Strength
NASA Technical Reports Server (NTRS)
Safar, Michal
1992-01-01
The Center's primary function is to facilitate technology transfer within DoD, other government agencies and industry. The DoD has recognized the importance of technology transfer, not only to support specific weapon system manufacture, but to strengthen the industrial base that sustains DoD. MTIAC uses an experienced technical staff of engineers and information specialists to acquire, analyze, and disseminate technical information. Besides ManTech project data, MTIAC collects manufacturing technology from other government agencies, commercial publications, proceedings, and various international sources. MTIAC has various means of disseminating this information. Much of the technical data is on user accessible data bases. The Center researches and writes a number of technical reports each year and publishes a newsletter monthly. Customized research is performed in response to specific inquiries from government and industry. MTIAC serves as a link between Government and Industry to strengthen the manufacturing technology base through the dissemination of advanced manufacturing information.
Microscopic insights into the NMR relaxation based protein conformational entropy meter
Kasinath, Vignesh; Sharp, Kim A.; Wand, A. Joshua
2013-01-01
Conformational entropy is a potentially important thermodynamic parameter contributing to protein function. Quantitative measures of conformational entropy are necessary for an understanding of its role but have been difficult to obtain. An empirical method that utilizes changes in conformational dynamics as a proxy for changes in conformational entropy has recently been introduced. Here we probe the microscopic origins of the link between conformational dynamics and conformational entropy using molecular dynamics simulations. Simulation of seven pro! teins gave an excellent correlation with measures of side-chain motion derived from NMR relaxation. The simulations show that the motion of methyl-bearing side-chains are sufficiently coupled to that of other side chains to serve as excellent reporters of the overall side-chain conformational entropy. These results tend to validate the use of experimentally accessible measures of methyl motion - the NMR-derived generalized order parameters - as a proxy from which to derive changes in protein conformational entropy. PMID:24007504
Development of Postural Muscles and Their Innervation
IJkema-Paassen, J.; Gramsbergen, A.
2005-01-01
Control of posture is a prerequisite for efficient motor performance. Posture depends on muscles capable of enduring contractions, whereas movements often require quick, forceful muscle actions. To serve these different goals, muscles contain fibers that meet these different tasks. Muscles with strong postural functions mainly consist of slow muscle fibers with a great resistance against fatigue. Flexor muscles in the leg and arm muscles are mainly composed of fast muscle fibers producing relatively large forces that are rapidly fatigable. Development of the neuromuscular system continues after birth. We discuss in the human baby and in animal experiments changes in muscle fiber properties, regression from polyneural into mononeural innervation, and developmental changes in the motoneurons of postural muscles during that period. The regression of poly-neural innervation in postural muscles and the development of dendrite bundles of their motoneurons seem to be linked to the transition from the immature into the adult-like patterns of moving and postural control. PMID:16097482
Calcium dynamics and signaling in vascular regulation: computational models
Tsoukias, Nikolaos Michael
2013-01-01
Calcium is a universal signaling molecule with a central role in a number of vascular functions including in the regulation of tone and blood flow. Experimentation has provided insights into signaling pathways that lead to or affected by Ca2+ mobilization in the vasculature. Mathematical modeling offers a systematic approach to the analysis of these mechanisms and can serve as a tool for data interpretation and for guiding new experimental studies. Comprehensive models of calcium dynamics are well advanced for some systems such as the heart. This review summarizes the progress that has been made in modeling Ca2+ dynamics and signaling in vascular cells. Model simulations show how Ca2+ signaling emerges as a result of complex, nonlinear interactions that cannot be properly analyzed using only a reductionist's approach. A strategy of integrative modeling in the vasculature is outlined that will allow linking macroscale pathophysiological responses to the underlying cellular mechanisms. PMID:21061306
Enterprise-wide worklist management.
Locko, Roberta C; Blume, Hartwig; Goble, John C
2002-01-01
Radiologists in multi-facility health care delivery networks must serve not only their own departments but also departments of associated clinical facilities. We describe our experience with a picture archiving and communication system (PACS) implementation that provides a dynamic view of relevant radiological workload across multiple facilities. We implemented a distributed query system that permits management of enterprise worklists based on modality, body part, exam status, and other criteria that span multiple compatible PACSs. Dynamic worklists, with lesser flexibility, can be constructed if the incompatible PACSs support specific DICOM functionality. Enterprise-wide worklists were implemented across Generations Plus/Northern Manhattan Health Network, linking radiology departments of three hospitals (Harlem, Lincoln, and Metropolitan) with 1465 beds and 4260 ambulatory patients per day. Enterprise-wide, dynamic worklist management improves utilization of radiologists and enhances the quality of care across large multi-facility health care delivery organizations. Integration of other workflow-related components remain a significant challenge.
Everything is permitted? People intuitively judge immorality as representative of atheists.
Gervais, Will M
2014-01-01
Scientific research yields inconsistent and contradictory evidence relating religion to moral judgments and outcomes, yet most people on earth nonetheless view belief in God (or gods) as central to morality, and many view atheists with suspicion and scorn. To evaluate intuitions regarding a causal link between religion and morality, this paper tested intuitive moral judgments of atheists and other groups. Across five experiments (N = 1,152), American participants intuitively judged a wide variety of immoral acts (e.g., serial murder, consensual incest, necrobestiality, cannibalism) as representative of atheists, but not of eleven other religious, ethnic, and cultural groups. Even atheist participants judged immoral acts as more representative of atheists than of other groups. These findings demonstrate a prevalent intuition that belief in God serves a necessary function in inhibiting immoral conduct, and may help explain persistent negative perceptions of atheists.
Current advances in the cognitive neuroscience of music.
Levitin, Daniel J; Tirovolas, Anna K
2009-03-01
The study of music perception and cognition is one of the oldest topics in experimental psychology. The last 20 years have seen an increased interest in understanding the functional neuroanatomy of music processing in humans, using a variety of technologies including fMRI, PET, ERP, MEG, and lesion studies. We review current findings in the context of a rich intellectual history of research, organized by the cognitive systems underlying different aspects of human musical behavior. We pay special attention to the perception of components of musical processing, musical structure, laterality effects, cultural issues, links between music and movement, emotional processing, expertise, and the amusias. Current trends are noted, such as the increased interest in evolutionary origins of music and comparisons of music and language. The review serves to demonstrate the important role that music can play in informing broad theories of higher order cognitive processes such as music in humans.
Mars Telecommunications Orbiter, Artist's Concept
NASA Technical Reports Server (NTRS)
2005-01-01
This illustration depicts a concept for NASA's Mars Telecommunications Orbiter in flight around Mars. The orbiter is in development to be the first spacecraft with a primary function of providing communication links while orbiting a foreign planet. The project's plans call for launch in September 2009, arrival at Mars in August 2010 and a mission of six to 10 years while in orbit. Mars Telecommunication Orbiter would serve as the Mars hub for an interplanetery Internet, greatly increasing the information payoff from other future Mars missions. The mission is designed to orbit Mars more than 10 times farther from the planet than orbiters dedicated primarily to science. The high-orbit design minimizes the time that Mars itself blocks the orbiter from communicating with Earth and maximizes the time that the orbiter is above the horizon -- thus capable of communications relay -- for rovers and stationary landers on Mars' surface.Potential communicative acts in children with autism spectrum disorders.
Braddock, Barbara A; Pickett, Colleen; Ezzelgot, Jamie; Sheth, Shivani; Korte-Stroff, Emily; Loncke, Filip; Bock, Lynn
2015-01-01
To describe potential communicative acts in a sample of 17 children with autism spectrum disorders who produced few to no intelligible words (mean age = 32.82 months). Parents reported on children's potential communicative acts for 10 different communicative functions. A potential communicative act was defined as any behavior produced by an individual that may be interpreted by others to serve a communicative purpose. Significant associations were found between higher number of gesture types and increased scores on language comprehension, language expression, and non-verbal thinking measures. Relative to other types of potential communicative acts, parents reported that children used higher proportions of body movement. Number of body movement types was not related to child ability, while number of gesture types was related to receptive and expressive language. Findings underscore the link between language and gesture, and offer support for an ecological systems perspective of language learning.
Hericium erinaceus extracts alter behavioral rhythm in mice.
Furuta, Shoko; Kuwahara, Rika; Hiraki, Eri; Ohnuki, Koichiro; Yasuo, Shinobu; Shimizu, Kuniyoshi
2016-01-01
Hericium erinaceus (HE), an edible mushroom, has been used as a herbal medicine in several Asian countries since ancient times. HE has potential as a medicine for the treatment and prevention of dementia, a disorder closely linked with circadian rhythm. This study investigated the effects of the intake of HE extracts on behavioral rhythm, photosensitivity of the circadian clock, and clock gene mRNA expression in the suprachiasmatic nucleus (SCN), a central clock, in mice. Although the HE ethanol extract only affected the offset time of activity, the HE water extract advanced the sleep-wake cycle without affecting the free-running period, photosensitivity, or the clock gene mRNA expression in SCN. In addition, both extracts decreased wakefulness around end of active phase. The findings of the present study suggest that HE may serve as a functional food in the prevention and treatment of Alzheimer's disease and delayed sleep phase syndrome.
Trögl, Josef; Chauhan, Archana; Ripp, Steven; Layton, Alice C.; Kuncová, Gabriela; Sayler, Gary S.
2012-01-01
Initially described in 1990, Pseudomonas fluorescens HK44 served as the first whole-cell bioreporter genetically endowed with a bioluminescent (luxCDABE) phenotype directly linked to a catabolic (naphthalene degradative) pathway. HK44 was the first genetically engineered microorganism to be released in the field to monitor bioremediation potential. Subsequent to that release, strain HK44 had been introduced into other solids (soils, sands), liquid (water, wastewater), and volatile environments. In these matrices, it has functioned as one of the best characterized chemically-responsive environmental bioreporters and as a model organism for understanding bacterial colonization and transport, cell immobilization strategies, and the kinetics of cellular bioluminescent emission. This review summarizes the characteristics of P. fluorescens HK44 and the extensive range of its applications with special focus on the monitoring of bioremediation processes and biosensing of environmental pollution. PMID:22438725
NASA Astrophysics Data System (ADS)
Blakely, R. J.; Sherrod, B. L.; Glen, J. M. G.; Ritzinger, B. T.; Staisch, L.
2017-12-01
High-resolution aeromagnetic surveys of Washington and Oregon, acquired over the past two decades by the U.S. Geological Survey, serve as proxies for geologic mapping in a terrain modified by glacial and catastrophic flood processes and covered by vegetation and urban development. In concert with geologic mapping and ancillary geophysical measurements, these data show possible kinematic links between forearc and backarc regions and have improved understanding of Cascadia crustal framework. Here we investigate a possible link between the NW-striking Wallula fault zone (WFZ), a segment of the Olympic-Wallowa lineament (OWL), and the N-striking Hite fault in Cascadia's backarc. Strike-slip displacement on the WFZ is indicated by offset of NW-striking Ice Harbor dikes (8.5 Ma), as displayed in magnetic anomalies. An exposed dike immediately south of the Walla Walla River has been used by others to argue against strike-slip displacement; i.e., the exposure lies south of one strand of the WFZ but is not displaced with respect to its linear magnetic anomaly north of the fault. However, high-resolution magnetic anomalies and a recently discovered, 25-km-long LiDAR scarp show that the dike exposure actually lies north of the fault and thus is irrelevant in determining strike-slip displacement on the fault. Our most recent magnetic survey illuminates with unprecedented detail strands of the N-striking Hite fault system and structural links to the WFZ. The survey lies over an area underlain by strongly magnetic Miocene Columbia River flood basalts (CRB) and older intrusive and volcanic rocks. NW-striking magnetic anomalies associated with the WFZ do not extend eastward beyond the Hite fault, suggesting that this is the region at which strain is transferred from the OWL. Magnetic anomalies originating from CRB across the Hite fault serve as piercing points and indicate 1.5 to 2 km of sinistral slip since middle Miocene. Vertical offsets in depth to magnetic basement across the fault suggest that vertical displacement also was important. We conclude that the WFZ and Hite fault are kinematically linked and that both exhibit oblique-slip displacement. Faults north and south of the WFZ are dominantly compressional and extensional, respectively, suggesting that the Hite fault serves as a backstop to dextral slip on the OWL.
Anand, Deepti; Agrawal, Smriti A; Slavotinek, Anne; Lachke, Salil A
2018-04-01
Mutations in the transcription factor genes FOXE3, HSF4, MAF, and PITX3 cause congenital lens defects including cataracts that may be accompanied by defects in other components of the eye or in nonocular tissues. We comprehensively describe here all the variants in FOXE3, HSF4, MAF, and PITX3 genes linked to human developmental defects. A total of 52 variants for FOXE3, 18 variants for HSF4, 20 variants for MAF, and 19 variants for PITX3 identified so far in isolated cases or within families are documented. This effort reveals FOXE3, HSF4, MAF, and PITX3 to have 33, 16, 18, and 7 unique causal mutations, respectively. Loss-of-function mutant animals for these genes have served to model the pathobiology of the associated human defects, and we discuss the currently known molecular function of these genes, particularly with emphasis on their role in ocular development. Finally, we make the detailed FOXE3, HSF4, MAF, and PITX3 variant information available in the Leiden Online Variation Database (LOVD) platform at https://www.LOVD.nl/FOXE3, https://www.LOVD.nl/HSF4, https://www.LOVD.nl/MAF, and https://www.LOVD.nl/PITX3. Thus, this article informs on key variants in transcription factor genes linked to cataract, aphakia, corneal opacity, glaucoma, microcornea, microphthalmia, anterior segment mesenchymal dysgenesis, and Ayme-Gripp syndrome, and facilitates their access through Web-based databases. © 2018 Wiley Periodicals, Inc.
Metagenomic Insights into the Fibrolytic Microbiome in Yak Rumen
Song, Lei; Liu, Di; Liu, Li; Chen, Furong; Wang, Min; Li, Jiabao; Zeng, Xiaowei; Dong, Zhiyang; Hu, Songnian; Li, Lingyan; Xu, Jian; Huang, Li; Dong, Xiuzhu
2012-01-01
The rumen hosts one of the most efficient microbial systems for degrading plant cell walls, yet the predominant cellulolytic proteins and fibrolytic mechanism(s) remain elusive. Here we investigated the cellulolytic microbiome of the yak rumen by using a combination of metagenome-based and bacterial artificial chromosome (BAC)-based functional screening approaches. Totally 223 fibrolytic BAC clones were pyrosequenced and 10,070 ORFs were identified. Among them 150 were annotated as the glycoside hydrolase (GH) genes for fibrolytic proteins, and the majority (69%) of them were clustered or linked with genes encoding related functions. Among the 35 fibrolytic contigs of >10 Kb in length, 25 were derived from Bacteroidetes and four from Firmicutes. Coverage analysis indicated that the fibrolytic genes on most Bacteroidetes-contigs were abundantly represented in the metagenomic sequences, and they were frequently linked with genes encoding SusC/SusD-type outer-membrane proteins. GH5, GH9, and GH10 cellulase/hemicellulase genes were predominant, but no GH48 exocellulase gene was found. Most (85%) of the cellulase and hemicellulase proteins possessed a signal peptide; only a few carried carbohydrate-binding modules, and no cellulosomal domains were detected. These findings suggest that the SucC/SucD-involving mechanism, instead of one based on cellulosomes or the free-enzyme system, serves a major role in lignocellulose degradation in yak rumen. Genes encoding an endoglucanase of a novel GH5 subfamily occurred frequently in the metagenome, and the recombinant proteins encoded by the genes displayed moderate Avicelase in addition to endoglucanase activities, suggesting their important contribution to lignocellulose degradation in the exocellulase-scarce rumen. PMID:22808161
PEM public key certificate cache server
NASA Astrophysics Data System (ADS)
Cheung, T.
1993-12-01
Privacy Enhanced Mail (PEM) provides privacy enhancement services to users of Internet electronic mail. Confidentiality, authentication, message integrity, and non-repudiation of origin are provided by applying cryptographic measures to messages transferred between end systems by the Message Transfer System. PEM supports both symmetric and asymmetric key distribution. However, the prevalent implementation uses a public key certificate-based strategy, modeled after the X.509 directory authentication framework. This scheme provides an infrastructure compatible with X.509. According to RFC 1422, public key certificates can be stored in directory servers, transmitted via non-secure message exchanges, or distributed via other means. Directory services provide a specialized distributed database for OSI applications. The directory contains information about objects and then provides structured mechanisms for accessing that information. Since directory services are not widely available now, a good approach is to manage certificates in a centralized certificate server. This document describes the detailed design of a centralized certificate cache serve. This server manages a cache of certificates and a cache of Certificate Revocation Lists (CRL's) for PEM applications. PEMapplications contact the server to obtain/store certificates and CRL's. The server software is programmed in C and ELROS. To use this server, ISODE has to be configured and installed properly. The ISODE library 'libisode.a' has to be linked together with this library because ELROS uses the transport layer functions provided by 'libisode.a.' The X.500 DAP library that is included with the ELROS distribution has to be linked in also, since the server uses the DAP library functions to communicate with directory servers.
Bielczyk, Natalia Z.; Buitelaar, Jan K.; Glennon, Jeffrey C.; Tiesinga, Paul H. E.
2015-01-01
Major depressive disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% worldwide. MDD is a heterogeneous disorder that involves multiple behavioral symptoms on the one hand and multiple neuronal circuits on the other hand. In this review, we integrate the literature on cognitive and physiological biomarkers of MDD with the insights derived from mathematical models of brain networks, especially models that can be used for fMRI datasets. We refer to the recent NIH research domain criteria initiative, in which a concept of “constructs” as functional units of mental disorders is introduced. Constructs are biomarkers present at multiple levels of brain functioning – cognition, genetics, brain anatomy, and neurophysiology. In this review, we propose a new approach which we called circuit to construct mapping (CCM), which aims to characterize causal relations between the underlying network dynamics (as the cause) and the constructs referring to the clinical symptoms of MDD (as the effect). CCM involves extracting diagnostic categories from behavioral data, linking circuits that are causal to these categories with use of clinical neuroimaging data, and modeling the dynamics of the emerging circuits with attractor dynamics in order to provide new, neuroimaging-related biomarkers for MDD. The CCM approach optimizes the clinical diagnosis and patient stratification. It also addresses the recent demand for linking circuits to behavior, and provides a new insight into clinical treatment by investigating the dynamics of neuronal circuits underneath cognitive dimensions of MDD. CCM can serve as a new regime toward personalized medicine, assisting the diagnosis and treatment of MDD. PMID:25767450
Jadid, Nurul; Mialoundama, Alexis Samba; Heintz, Dimitri; Ayoub, Daniel; Erhardt, Mathieu; Mutterer, Jérôme; Meyer, Denise; Alioua, Abdelmalek; Van Dorsselaer, Alain; Rahier, Alain; Camara, Bilal; Bouvier, Florence
2011-01-01
The most abundant posttranslational modification in nature is the attachment of preassembled high-mannose-type glycans, which determines the fate and localization of the modified protein and modulates the biological functions of glycosylphosphatidylinositol-anchored and N-glycosylated proteins. In eukaryotes, all mannose residues attached to glycoproteins from the luminal side of the endoplasmic reticulum (ER) derive from the polyprenyl monosaccharide carrier, dolichol P-mannose (Dol-P-Man), which is flipped across the ER membrane to the lumen. We show that in plants, Dol-P-Man is synthesized when Dol-P-Man synthase1 (DPMS1), the catalytic core, interacts with two binding proteins, DPMS2 and DPMS3, that may serve as membrane anchors for DPMS1 or provide catalytic assistance. This configuration is reminiscent of that observed in mammals but is distinct from the single DPMS protein catalyzing Dol-P-Man biosynthesis in bakers’ yeast and protozoan parasites. Overexpression of DPMS1 in Arabidopsis thaliana results in disorganized stem morphology and vascular bundle arrangements, wrinkled seed coat, and constitutive ER stress response. Loss-of-function mutations and RNA interference–mediated reduction of DPMS1 expression in Arabidopsis also caused a wrinkled seed coat phenotype and most remarkably enhanced hypersensitivity to ammonium that was manifested by extensive chlorosis and a strong reduction of root growth. Collectively, these data reveal a previously unsuspected role of the prenyl-linked carrier pathway for plant development and physiology that may help integrate several aspects of candidate susceptibility genes to ammonium stress. PMID:21558543
Hung, Wei-Ting; Wu, Fang-Ju; Wang, Chun-Jen; Luo, Ching-Wei
2012-05-01
Although differential screening-selected gene aberrative in neuroblastoma (DAN, official symbol NBL1) is the founding member of the DAN subfamily of bone morphogenetic protein (BMP) antagonists, its antagonizing targets, gene regulation, and physiological functions remain unclear. Using diverse cell expression systems, we found that the generation of bioactive DAN is likely to be cell type specific. Unlike other phylogenetically close members, which are covalently linked homodimers, DAN forms a noncovalently linked homodimer during folding. Purified recombinant DAN specifically blocked signaling of BMP2 and BMP4 but not that of other ovarian-expressed transforming growth factor-beta members. Although widely distributed in many organs, DAN transcript level was periodically regulated by gonadotropins. Ovarian microdissection indicated that NBL1 (DAN) mRNA is mainly expressed in granulosa cells, where its transcript level is up-regulated by the gonadotropin-driven cAMP cascade. We further investigated the local regulation and ovarian functions of DAN. NBL1 (DAN) mRNA expression in granulosa cells was up-regulated by oocyte-derived growth differentiation factor 9 (GDF9), whereas treatment with DAN significantly reversed the inhibitory effect of BMP4 on follicle-stimulating hormone-induced progesterone production in cultured granulosa cells. Our findings suggest the DAN gradient in granulosa cells, established by oocyte-derived GDF9, may serve as an antagonist barrier that modulates the actions of theca-derived BMP4 and granulosa/theca-derived BMP2 during folliculogenesis both spatially and temporally.
Mackness, Brian C.; Tran, Meme T.; McClain, Shannan P.; Matthews, C. Robert; Zitzewitz, Jill A.
2014-01-01
Pathological alteration of TDP-43 (TAR DNA-binding protein-43), a protein involved in various RNA-mediated processes, is a hallmark feature of the neurodegenerative diseases amyotrophic lateral sclerosis and frontotemporal lobar degeneration. Fragments of TDP-43, composed of the second RNA recognition motif (RRM2) and the disordered C terminus, have been observed in cytoplasmic inclusions in sporadic amyotrophic lateral sclerosis cases, suggesting that conformational changes involving RRM2 together with the disordered C terminus play a role in aggregation and toxicity. The biophysical data collected by CD and fluorescence spectroscopies reveal a three-state equilibrium unfolding model for RRM2, with a partially folded intermediate state that is not observed in RRM1. Strikingly, a portion of RRM2 beginning at position 208, which mimics a cleavage site observed in patient tissues, increases the population of this intermediate state. Mutually stabilizing interactions between the domains in the tethered RRM1 and RRM2 construct reduce the population of the intermediate state and enhance DNA/RNA binding. Despite the high sequence homology of the two domains, a network of large hydrophobic residues in RRM2 provides a possible explanation for the increased stability of RRM2 compared with RRM1. The cluster analysis suggests that the intermediate state may play a functional role by enhancing access to the nuclear export signal contained within its sequence. The intermediate state may also serve as a molecular hazard linking productive folding and function with pathological misfolding and aggregation that may contribute to disease. PMID:24497641
Functions of autobiographical memory in Taiwanese and American emerging adults.
Liao, Hsiao-Wen; Bluck, Susan; Alea, Nicole; Cheng, Ching-Ling
2016-01-01
The study addresses cultural and person-level factors contributing to emerging adult's use of memory to serve adaptive functions. The focus is on three functions: self-continuity, social-bonding and directing-behaviour. Taiwanese (N = 85, 52 women) and American (N = 95, 51 women) emerging adults completed the Thinking about Life Experiences scale, and measures of trait personality, self-concept clarity and future time perspective. Findings show that individuals from both cultures use memory to serve these three functions, but Taiwanese individuals use memory more frequently than Americans to maintain self-continuity. Culture also interacted with person-level factors: in Taiwan, but not America, memory is more frequently used to create self-continuity in individuals high in conscientiousness. Across cultures, having lower self-concept clarity was related to greater use of memory to create self-continuity. Findings are discussed in terms of how memory serves functions in context and specific aspects of the Taiwanese and American cultural context that may predict the functional use of memory in emerging adulthood.
Caring, Conversing, and Realizing Values: New Directions in Language Studies
ERIC Educational Resources Information Center
Hodges, Bert H.; Steffensen, Sune V.; Martin, James E.
2012-01-01
Language serves many functions for humans, but three of the most important are coordination, learning, and friendship. All of those functions were well served by the conversations from which this special issue emerged, a conference, "Grounding language in perception and (inter) action", held at Gordon College in June 2009. The conference brought…
Unidirectional Transition Waves in Bistable Lattices
NASA Astrophysics Data System (ADS)
Nadkarni, Neel; Arrieta, Andres F.; Chong, Christopher; Kochmann, Dennis M.; Daraio, Chiara
2016-06-01
We present a model system for strongly nonlinear transition waves generated in a periodic lattice of bistable members connected by magnetic links. The asymmetry of the on-site energy wells created by the bistable members produces a mechanical diode that supports only unidirectional transition wave propagation with constant wave velocity. We theoretically justify the cause of the unidirectionality of the transition wave and confirm these predictions by experiments and simulations. We further identify how the wave velocity and profile are uniquely linked to the double-well energy landscape, which serves as a blueprint for transition wave control.
CCP interoperability and system stability
NASA Astrophysics Data System (ADS)
Feng, Xiaobing; Hu, Haibo
2016-09-01
To control counterparty risk, financial regulations such as the Dodd-Frank Act are increasingly requiring standardized derivatives trades to be cleared by central counterparties (CCPs). It is anticipated that in the near term future, CCPs across the world will be linked through interoperability agreements that facilitate risk sharing but also serve as a conduit for transmitting shocks. This paper theoretically studies a networked network with CCPs that are linked through interoperability arrangements. The major finding is that the different configurations of networked network CCPs contribute to the different properties of the cascading failures.
Valenzuela, Edgardo I.; Prieto-Davó, Alejandra; López-Lozano, Nguyen E.; Hernández-Eligio, Alberto; Vega-Alvarado, Leticia; Juárez, Katy; García-González, Ana Sarahí; López, Mercedes G.
2017-01-01
ABSTRACT Wetlands constitute the main natural source of methane on Earth due to their high content of natural organic matter (NOM), but key drivers, such as electron acceptors, supporting methanotrophic activities in these habitats are poorly understood. We performed anoxic incubations using freshly collected sediment, along with water samples harvested from a tropical wetland, amended with 13C-methane (0.67 atm) to test the capacity of its microbial community to perform anaerobic oxidation of methane (AOM) linked to the reduction of the humic fraction of its NOM. Collected evidence demonstrates that electron-accepting functional groups (e.g., quinones) present in NOM fueled AOM by serving as a terminal electron acceptor. Indeed, while sulfate reduction was the predominant process, accounting for up to 42.5% of the AOM activities, the microbial reduction of NOM concomitantly occurred. Furthermore, enrichment of wetland sediment with external NOM provided a complementary electron-accepting capacity, of which reduction accounted for ∼100 nmol 13CH4 oxidized · cm−3 · day−1. Spectroscopic evidence showed that quinone moieties were heterogeneously distributed in the wetland sediment, and their reduction occurred during the course of AOM. Moreover, an enrichment derived from wetland sediments performing AOM linked to NOM reduction stoichiometrically oxidized methane coupled to the reduction of the humic analogue anthraquinone-2,6-disulfonate. Microbial populations potentially involved in AOM coupled to microbial reduction of NOM were dominated by divergent biota from putative AOM-associated archaea. We estimate that this microbial process potentially contributes to the suppression of up to 114 teragrams (Tg) of CH4 · year−1 in coastal wetlands and more than 1,300 Tg · year−1, considering the global wetland area. IMPORTANCE The identification of key processes governing methane emissions from natural systems is of major importance considering the global warming effects triggered by this greenhouse gas. Anaerobic oxidation of methane (AOM) coupled to the microbial reduction of distinct electron acceptors plays a pivotal role in mitigating methane emissions from ecosystems. Given their high organic content, wetlands constitute the largest natural source of atmospheric methane. Nevertheless, processes controlling methane emissions in these environments are poorly understood. Here, we provide tracer analysis with 13CH4 and spectroscopic evidence revealing that AOM linked to the microbial reduction of redox functional groups in natural organic matter (NOM) prevails in a tropical wetland. We suggest that microbial reduction of NOM may largely contribute to the suppression of methane emissions from tropical wetlands. This is a novel avenue within the carbon cycle in which slowly decaying NOM (e.g., humic fraction) in organotrophic environments fuels AOM by serving as a terminal electron acceptor. PMID:28341676
Valenzuela, Edgardo I; Prieto-Davó, Alejandra; López-Lozano, Nguyen E; Hernández-Eligio, Alberto; Vega-Alvarado, Leticia; Juárez, Katy; García-González, Ana Sarahí; López, Mercedes G; Cervantes, Francisco J
2017-06-01
Wetlands constitute the main natural source of methane on Earth due to their high content of natural organic matter (NOM), but key drivers, such as electron acceptors, supporting methanotrophic activities in these habitats are poorly understood. We performed anoxic incubations using freshly collected sediment, along with water samples harvested from a tropical wetland, amended with 13 C-methane (0.67 atm) to test the capacity of its microbial community to perform anaerobic oxidation of methane (AOM) linked to the reduction of the humic fraction of its NOM. Collected evidence demonstrates that electron-accepting functional groups (e.g., quinones) present in NOM fueled AOM by serving as a terminal electron acceptor. Indeed, while sulfate reduction was the predominant process, accounting for up to 42.5% of the AOM activities, the microbial reduction of NOM concomitantly occurred. Furthermore, enrichment of wetland sediment with external NOM provided a complementary electron-accepting capacity, of which reduction accounted for ∼100 nmol 13 CH 4 oxidized · cm -3 · day -1 Spectroscopic evidence showed that quinone moieties were heterogeneously distributed in the wetland sediment, and their reduction occurred during the course of AOM. Moreover, an enrichment derived from wetland sediments performing AOM linked to NOM reduction stoichiometrically oxidized methane coupled to the reduction of the humic analogue anthraquinone-2,6-disulfonate. Microbial populations potentially involved in AOM coupled to microbial reduction of NOM were dominated by divergent biota from putative AOM-associated archaea. We estimate that this microbial process potentially contributes to the suppression of up to 114 teragrams (Tg) of CH 4 · year -1 in coastal wetlands and more than 1,300 Tg · year -1 , considering the global wetland area. IMPORTANCE The identification of key processes governing methane emissions from natural systems is of major importance considering the global warming effects triggered by this greenhouse gas. Anaerobic oxidation of methane (AOM) coupled to the microbial reduction of distinct electron acceptors plays a pivotal role in mitigating methane emissions from ecosystems. Given their high organic content, wetlands constitute the largest natural source of atmospheric methane. Nevertheless, processes controlling methane emissions in these environments are poorly understood. Here, we provide tracer analysis with 13 CH 4 and spectroscopic evidence revealing that AOM linked to the microbial reduction of redox functional groups in natural organic matter (NOM) prevails in a tropical wetland. We suggest that microbial reduction of NOM may largely contribute to the suppression of methane emissions from tropical wetlands. This is a novel avenue within the carbon cycle in which slowly decaying NOM (e.g., humic fraction) in organotrophic environments fuels AOM by serving as a terminal electron acceptor. Copyright © 2017 American Society for Microbiology.
Zhang, Guo-Qiang; Tao, Shiqiang; Xing, Guangming; Mozes, Jeno; Zonjy, Bilal; Lhatoo, Samden D; Cui, Licong
2015-11-10
A unique study identifier serves as a key for linking research data about a study subject without revealing protected health information in the identifier. While sufficient for single-site and limited-scale studies, the use of common unique study identifiers has several drawbacks for large multicenter studies, where thousands of research participants may be recruited from multiple sites. An important property of study identifiers is error tolerance (or validatable), in that inadvertent editing mistakes during their transmission and use will most likely result in invalid study identifiers. This paper introduces a novel method called "Randomized N-gram Hashing (NHash)," for generating unique study identifiers in a distributed and validatable fashion, in multicenter research. NHash has a unique set of properties: (1) it is a pseudonym serving the purpose of linking research data about a study participant for research purposes; (2) it can be generated automatically in a completely distributed fashion with virtually no risk for identifier collision; (3) it incorporates a set of cryptographic hash functions based on N-grams, with a combination of additional encryption techniques such as a shift cipher; (d) it is validatable (error tolerant) in the sense that inadvertent edit errors will mostly result in invalid identifiers. NHash consists of 2 phases. First, an intermediate string using randomized N-gram hashing is generated. This string consists of a collection of N-gram hashes f1, f2, ..., fk. The input for each function fi has 3 components: a random number r, an integer n, and input data m. The result, fi(r, n, m), is an n-gram of m with a starting position s, which is computed as (r mod |m|), where |m| represents the length of m. The output for Step 1 is the concatenation of the sequence f1(r1, n1, m1), f2(r2, n2, m2), ..., fk(rk, nk, mk). In the second phase, the intermediate string generated in Phase 1 is encrypted using techniques such as shift cipher. The result of the encryption, concatenated with the random number r, is the final NHash study identifier. We performed experiments using a large synthesized dataset comparing NHash with random strings, and demonstrated neglegible probability for collision. We implemented NHash for the Center for SUDEP Research (CSR), a National Institute for Neurological Disorders and Stroke-funded Center Without Walls for Collaborative Research in the Epilepsies. This multicenter collaboration involves 14 institutions across the United States and Europe, bringing together extensive and diverse expertise to understand sudden unexpected death in epilepsy patients (SUDEP). The CSR Data Repository has successfully used NHash to link deidentified multimodal clinical data collected in participating CSR institutions, meeting all desired objectives of NHash.
Generation of comprehensive thoracic oncology database--tool for translational research.
Surati, Mosmi; Robinson, Matthew; Nandi, Suvobroto; Faoro, Leonardo; Demchuk, Carley; Kanteti, Rajani; Ferguson, Benjamin; Gangadhar, Tara; Hensing, Thomas; Hasina, Rifat; Husain, Aliya; Ferguson, Mark; Karrison, Theodore; Salgia, Ravi
2011-01-22
The Thoracic Oncology Program Database Project was created to serve as a comprehensive, verified, and accessible repository for well-annotated cancer specimens and clinical data to be available to researchers within the Thoracic Oncology Research Program. This database also captures a large volume of genomic and proteomic data obtained from various tumor tissue studies. A team of clinical and basic science researchers, a biostatistician, and a bioinformatics expert was convened to design the database. Variables of interest were clearly defined and their descriptions were written within a standard operating manual to ensure consistency of data annotation. Using a protocol for prospective tissue banking and another protocol for retrospective banking, tumor and normal tissue samples from patients consented to these protocols were collected. Clinical information such as demographics, cancer characterization, and treatment plans for these patients were abstracted and entered into an Access database. Proteomic and genomic data have been included in the database and have been linked to clinical information for patients described within the database. The data from each table were linked using the relationships function in Microsoft Access to allow the database manager to connect clinical and laboratory information during a query. The queried data can then be exported for statistical analysis and hypothesis generation.
An evolutionary metabolic engineering approach for enhancing lipogenesis in Yarrowia lipolytica.
Liu, Leqian; Pan, Anny; Spofford, Caitlin; Zhou, Nijia; Alper, Hal S
2015-05-01
Lipogenic organisms provide an ideal platform for biodiesel and oleochemical production. Through our previous rational metabolic engineering efforts, lipogenesis titers in Yarrowia lipolytica were significantly enhanced. However, the resulting strain still suffered from decreased biomass generation rates. Here, we employ a rapid evolutionary metabolic engineering approach linked with a floating cell enrichment process to improve lipogenesis rates, titers, and yields. Through this iterative process, we were able to ultimately improve yields from our prior strain by 55% to achieve production titers of 39.1g/L with upwards of 76% of the theoretical maximum yield of conversation. Isolated cells were saturated with up to 87% lipid content. An average specific productivity of 0.56g/L/h was achieved with a maximum instantaneous specific productivity of 0.89g/L/h during the lipid production phase in fermentation. Genomic sequencing of the evolved strains revealed a link between a decrease/loss of function mutation of succinate semialdehyde dehydrogenase, uga2, suggesting the importance of gamma-aminobutyric acid assimilation in lipogenesis. This linkage was validated through gene deletion experiments. This work presents an improved host strain that can serve as a platform for efficient oleochemical production. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.
Adult Attachment Interview Discourse Patterns Predict Metabolic Syndrome in Midlife
Davis, Cynthia R.; Usher, Nicole; Dearing, Eric; Barkai, Ayelet R.; Crowell-Doom, Cindy; Mantzoros, Christos S.; Crowell, Judith A.
2017-01-01
Objective Adult attachment discourse patterns and current family relationship quality were examined as predictors of health behaviors and number of Metabolic Syndrome (MetS) criteria met. Methods A sample of 215 White/European American and Black/African American adults, aged 35 to 55, were examined cross-sectionally. Discourse was assessed with the Adult Attachment Interview (AAI), specifically: 1) coherence, a marker of attachment security, 2) unresolved trauma/loss, a marker of disorganized and distorted cognition related to trauma, and 3) idealization, the tendency to minimize the impact of stressful experiences. Health behaviors of diet, exercise, smoking and alcohol use were also assessed, as were adverse childhood experiences, current depressive symptoms and relationship functioning. MetS includes hypertension, hyperglycemia, high triglycerides, low HDL cholesterol, and obesity. Results Using path analysis and accounting for childhood adversity and depressive symptoms, AAI coherence and unresolved trauma or loss were directly linked to number of MetS criteria met (β = −.22 and .21 respectively). Idealization was indirectly linked to MetS through poor diet (β = −.26 and −.36 respectively), predicting 21% of the variance in number of MetS criteria met. Conclusions Attachment representations related to stress appraisal and care-seeking behaviors appear to serve as cognitive mechanisms increasing risk of MetS. PMID:25264975
Chloroplast two-component systems: evolution of the link between photosynthesis and gene expression
Puthiyaveetil, Sujith; Allen, John F.
2009-01-01
Two-component signal transduction, consisting of sensor kinases and response regulators, is the predominant signalling mechanism in bacteria. This signalling system originated in prokaryotes and has spread throughout the eukaryotic domain of life through endosymbiotic, lateral gene transfer from the bacterial ancestors and early evolutionary precursors of eukaryotic, cytoplasmic, bioenergetic organelles—chloroplasts and mitochondria. Until recently, it was thought that two-component systems inherited from an ancestral cyanobacterial symbiont are no longer present in chloroplasts. Recent research now shows that two-component systems have survived in chloroplasts as products of both chloroplast and nuclear genes. Comparative genomic analysis of photosynthetic eukaryotes shows a lineage-specific distribution of chloroplast two-component systems. The components and the systems they comprise have homologues in extant cyanobacterial lineages, indicating their ancient cyanobacterial origin. Sequence and functional characteristics of chloroplast two-component systems point to their fundamental role in linking photosynthesis with gene expression. We propose that two-component systems provide a coupling between photosynthesis and gene expression that serves to retain genes in chloroplasts, thus providing the basis of cytoplasmic, non-Mendelian inheritance of plastid-associated characters. We discuss the role of this coupling in the chronobiology of cells and in the dialogue between nuclear and cytoplasmic genetic systems. PMID:19324807
Measuring the regulation of keratin filament network dynamics
Moch, Marcin; Herberich, Gerlind; Aach, Til; Leube, Rudolf E.; Windoffer, Reinhard
2013-01-01
The organization of the keratin intermediate filament cytoskeleton is closely linked to epithelial function. To study keratin network plasticity and its regulation at different levels, tools are needed to localize and measure local network dynamics. In this paper, we present image analysis methods designed to determine the speed and direction of keratin filament motion and to identify locations of keratin filament polymerization and depolymerization at subcellular resolution. Using these methods, we have analyzed time-lapse fluorescence recordings of fluorescent keratin 13 in human vulva carcinoma-derived A431 cells. The fluorescent keratins integrated into the endogenous keratin cytoskeleton, and thereby served as reliable markers of keratin dynamics. We found that increased times after seeding correlated with down-regulation of inward-directed keratin filament movement. Bulk flow analyses further revealed that keratin filament polymerization in the cell periphery and keratin depolymerization in the more central cytoplasm were both reduced. Treating these cells and other human keratinocyte-derived cells with EGF reversed all these processes within a few minutes, coinciding with increased keratin phosphorylation. These results highlight the value of the newly developed tools for identifying modulators of keratin filament network dynamics and characterizing their mode of action, which, in turn, contributes to understanding the close link between keratin filament network plasticity and epithelial physiology. PMID:23757496
COMPASS time synchronization and dissemination—Toward centimetre positioning accuracy
NASA Astrophysics Data System (ADS)
Wang, ZhengBo; Zhao, Lu; Wang, ShiGuang; Zhang, JianWei; Wang, Bo; Wang, LiJun
2014-09-01
In this paper we investigate methods to achieve highly accurate time synchronization among the satellites of the COMPASS global navigation satellite system (GNSS). Owing to the special design of COMPASS which implements several geo-stationary satellites (GEO), time synchronization can be highly accurate via microwave links between ground stations to the GEO satellites. Serving as space-borne relay stations, the GEO satellites can further disseminate time and frequency signals to other satellites such as the inclined geo-synchronous (IGSO) and mid-earth orbit (MEO) satellites within the system. It is shown that, because of the accuracy in clock synchronization, the theoretical accuracy of COMPASS positioning and navigation will surpass that of the GPS. In addition, the COMPASS system can function with its entire positioning, navigation, and time-dissemination services even without the ground link, thus making it much more robust and secure. We further show that time dissemination using the COMPASS-GEO satellites to earth-fixed stations can achieve very high accuracy, to reach 100 ps in time dissemination and 3 cm in positioning accuracy, respectively. In this paper, we also analyze two feasible synchronization plans. All special and general relativistic effects related to COMPASS clocks frequency and time shifts are given. We conclude that COMPASS can reach centimeter-level positioning accuracy and discuss potential applications.
Mesoporous Polymer Frameworks from End-Reactive Bottlebrush Copolymers
Altay, Esra; Nykypanchuk, Dmytro; Rzayev, Javid
2017-08-07
Reticulated nanoporous materials generated by versatile molecular framework approaches are limited to pore dimensions on the scale of the utilized rigid molecular building blocks (<5 nm). The inherent flexibility of linear polymers precludes their utilization as long framework connectors for the extension of this strategy to larger length scales. We report a method for the fabrication of mesoporous frameworks by using bottlebrush copolymers with reactive end blocks serving as rigid macromolecular interconnectors with directional reactivity. End-reactive bottlebrush copolymers with pendant alkene functionalities were synthesized by a combination of controlled radical polymerization and polymer modification protocols. Ru-catalyzed cross-metathesis cross-linking of bottlebrushmore » copolymers with two reactive end blocks resulted in the formation of polymer frameworks where isolated cross-linked domains were interconnected with bottlebrush copolymer bridges. The resulting materials were characterized by a continuous network pore structure with average pore sizes of 9–50 nm, conveniently tunable by the length of the utilized bottlebrush copolymer building blocks. As a result, the materials fabrication strategy described in this work expands the length scale of molecular framework materials and provides access to mesoporous polymers with a molecularly tunable reticulated pore structure without the need for templating, sacrificial component etching, or supercritical fluid drying.« less
Chloroplast two-component systems: evolution of the link between photosynthesis and gene expression.
Puthiyaveetil, Sujith; Allen, John F
2009-06-22
Two-component signal transduction, consisting of sensor kinases and response regulators, is the predominant signalling mechanism in bacteria. This signalling system originated in prokaryotes and has spread throughout the eukaryotic domain of life through endosymbiotic, lateral gene transfer from the bacterial ancestors and early evolutionary precursors of eukaryotic, cytoplasmic, bioenergetic organelles-chloroplasts and mitochondria. Until recently, it was thought that two-component systems inherited from an ancestral cyanobacterial symbiont are no longer present in chloroplasts. Recent research now shows that two-component systems have survived in chloroplasts as products of both chloroplast and nuclear genes. Comparative genomic analysis of photosynthetic eukaryotes shows a lineage-specific distribution of chloroplast two-component systems. The components and the systems they comprise have homologues in extant cyanobacterial lineages, indicating their ancient cyanobacterial origin. Sequence and functional characteristics of chloroplast two-component systems point to their fundamental role in linking photosynthesis with gene expression. We propose that two-component systems provide a coupling between photosynthesis and gene expression that serves to retain genes in chloroplasts, thus providing the basis of cytoplasmic, non-Mendelian inheritance of plastid-associated characters. We discuss the role of this coupling in the chronobiology of cells and in the dialogue between nuclear and cytoplasmic genetic systems.
Linking Cognition and Literacy in Students with Autism Spectrum Disorder
ERIC Educational Resources Information Center
Carnahan, Christina R.; Williamson, Pamela S.; Christman, Jennifer
2011-01-01
Literacy skills, especially silent reading comprehension, serve as the foundation for learning, independence, and quality of life for all individuals. It is well documented that students on the autism spectrum have difficulties with reading comprehension even though they demonstrate adequate decoding skills. Unfortunately, communication…
Linking Employee Development Activity, Social Exchange and Organizational Citizenship Behavior
ERIC Educational Resources Information Center
Pierce, Heather R.; Maurer, Todd J.
2009-01-01
The authors examined "perceived beneficiary" of employee development (self, organization) for relationships with employee development activity. Perceived organizational support served as a moderator. The authors conclude that employees may engage in development activities to partly benefit their organization to the extent that a positive exchange…
Linking Stereotype Threat and Anxiety
ERIC Educational Resources Information Center
Osborne, Jason W.
2007-01-01
Claude Steele's stereotype threat hypothesis has attracted significant attention in recent years. This study tested one of the main tenets of his theory--that stereotype threat serves to increase individual anxiety levels, thus hurting performance--using real-time measures of physiological arousal. Subjects were randomly assigned to either high or…
"Who ate our corn?" We want to know and so should you!
USDA-ARS?s Scientific Manuscript database
The Future Scientists Program is designed to assist USDA/Hispanic Serving Institutions National Program reach out to communities, schools (grades K-12) and undergraduates with hands-on, inquiry-based activities that link them with United States Department of Agriculture (USDA)/Agricultural Research ...
Individual Differences in Dynamic Functional Brain Connectivity across the Human Lifespan.
Davison, Elizabeth N; Turner, Benjamin O; Schlesinger, Kimberly J; Miller, Michael B; Grafton, Scott T; Bassett, Danielle S; Carlson, Jean M
2016-11-01
Individual differences in brain functional networks may be related to complex personal identifiers, including health, age, and ability. Dynamic network theory has been used to identify properties of dynamic brain function from fMRI data, but the majority of analyses and findings remain at the level of the group. Here, we apply hypergraph analysis, a method from dynamic network theory, to quantify individual differences in brain functional dynamics. Using a summary metric derived from the hypergraph formalism-hypergraph cardinality-we investigate individual variations in two separate, complementary data sets. The first data set ("multi-task") consists of 77 individuals engaging in four consecutive cognitive tasks. We observe that hypergraph cardinality exhibits variation across individuals while remaining consistent within individuals between tasks; moreover, the analysis of one of the memory tasks revealed a marginally significant correspondence between hypergraph cardinality and age. This finding motivated a similar analysis of the second data set ("age-memory"), in which 95 individuals, aged 18-75, performed a memory task with a similar structure to the multi-task memory task. With the increased age range in the age-memory data set, the correlation between hypergraph cardinality and age correspondence becomes significant. We discuss these results in the context of the well-known finding linking age with network structure, and suggest that hypergraph analysis should serve as a useful tool in furthering our understanding of the dynamic network structure of the brain.
Neural Conflict–Control Mechanisms Improve Memory for Target Stimuli
Krebs, Ruth M.; Boehler, Carsten N.; De Belder, Maya; Egner, Tobias
2015-01-01
According to conflict-monitoring models, conflict serves as an internal signal for reinforcing top-down attention to task-relevant information. While evidence based on measures of ongoing task performance supports this idea, implications for long-term consequences, that is, memory, have not been tested yet. Here, we evaluated the prediction that conflict-triggered attentional enhancement of target-stimulus processing should be associated with superior subsequent memory for those stimuli. By combining functional magnetic resonance imaging (fMRI) with a novel variant of a face-word Stroop task that employed trial-unique face stimuli as targets, we were able to assess subsequent (incidental) memory for target faces as a function of whether a given face had previously been accompanied by congruent, neutral, or incongruent (conflicting) distracters. In line with our predictions, incongruent distracters not only induced behavioral conflict, but also gave rise to enhanced memory for target faces. Moreover, conflict-triggered neural activity in prefrontal and parietal regions was predictive of subsequent retrieval success, and displayed conflict-enhanced functional coupling with medial-temporal lobe regions. These data provide support for the proposal that conflict evokes enhanced top-down attention to task-relevant stimuli, thereby promoting their encoding into long-term memory. Our findings thus delineate the neural mechanisms of a novel link between cognitive control and memory. PMID:24108799
Disrupted resting brain graph measures in individuals at high risk for alcoholism.
Holla, Bharath; Panda, Rajanikant; Venkatasubramanian, Ganesan; Biswal, Bharat; Bharath, Rose Dawn; Benegal, Vivek
2017-07-30
Familial susceptibility to alcoholism is likely to be linked to the externalizing diathesis seen in high-risk offspring from high-density alcohol use disorder (AUD) families. The present study aimed at comparing resting brain functional connectivity and their association with externalizing symptoms and alcoholism familial density in 40 substance-naive high-risk (HR) male offspring from high-density AUD families and 30 matched healthy low-risk (LR) males without a family history of substance dependence using graph theory-based network analysis. The HR subjects from high-density AUD families compared with LR, showed significantly reduced clustering, small-worldness, and local network efficiency. The frontoparietal, cingulo-opercular, sensorimotor and cerebellar networks exhibited significantly reduced functional segregation. These disruptions exhibited independent incremental value in predicting the externalizing symptoms over and above the demographic variables. The reduction of functional segregation in HR subjects was significant across both the younger and older age groups and was proportional to the family loading of AUDs. Detection and estimation of these developmentally relevant disruptions in small-world architecture at critical brain regions sub-serving cognitive, affective, and sensorimotor processes are vital for understanding the familial risk for early onset alcoholism as well as for understanding the pathophysiological mechanism of externalizing behaviors. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.
Redox-linked Conformational Dynamics in Apoptosis Inducing Factor
Sevrioukova, Irina F.
2009-01-01
Apoptosis inducing factor (AIF) is a bifunctional mitochondrial flavoprotein critical for energy metabolism and induction of caspase-independent apoptosis, whose exact role in normal mitochondria remains unknown. Upon reduction with NADH, AIF undergoes dimerization and forms tight, long-lived FADH2-NAD charge-transfer complexes (CTC) proposed to be functionally important. To get a deeper insight into structure/function relations and redox mechanism of this vitally important protein, we determined the x-ray structures of oxidized and NADH-reduced forms of naturally folded recombinant murine AIF. Our structures reveal that CTC with the pyridine nucleotide is stabilized by (i) π-stacking interactions between coplanar nicotinamide, isoalloxazine and Phe309 rings, (ii) rearrangement of multiple aromatic residues in the C-terminal domain, likely serving as an electron delocalization site, and (iii) an extensive hydrogen-bonding network involving His453, a key residue undergoing a conformational switch to directly interact and orient the nicotinamide in position optimal for charge transfer. Via the His453-containing peptide, redox changes in the active site are transmitted to the surface, promoting AIF dimerization and restricting access to a primary nuclear localization signal through which the apoptogenic form is transported to the nucleus. Structural findings agree with the biochemical data and support the hypothesis that both normal and apoptogenic functions of AIF are controlled by NADH. PMID:19447115
Brain plasticity and sensorimotor deterioration as a function of 70 days head down tilt bed rest
Bloomberg, Jacob J.; De Dios, Yiri E.; Wood, Scott J.; Reuter-Lorenz, Patricia A.; Kofman, Igor S.; Riascos, Roy; Mulavara, Ajitkumar P.; Seidler, Rachael D.
2017-01-01
Background Adverse effects of spaceflight on sensorimotor function have been linked to altered somatosensory and vestibular inputs in the microgravity environment. Whether these spaceflight sequelae have a central nervous system component is unknown. However, experimental studies have shown spaceflight-induced brain structural changes in rodents’ sensorimotor brain regions. Understanding the neural correlates of spaceflight-related motor performance changes is important to ultimately develop tailored countermeasures that ensure mission success and astronauts’ health. Method Head down-tilt bed rest (HDBR) can serve as a microgravity analog because it mimics body unloading and headward fluid shifts of microgravity. We conducted a 70-day 6° HDBR study with 18 right-handed males to investigate how microgravity affects focal gray matter (GM) brain volume. MRI data were collected at 7 time points before, during and post-HDBR. Standing balance and functional mobility were measured pre and post-HDBR. The same metrics were obtained at 4 time points over ~90 days from 12 control subjects, serving as reference data. Results HDBR resulted in widespread increases GM in posterior parietal regions and decreases in frontal areas; recovery was not yet complete by 12 days post-HDBR. Additionally, HDBR led to balance and locomotor performance declines. Increases in a cluster comprising the precuneus, precentral and postcentral gyrus GM correlated with less deterioration or even improvement in standing balance. This association did not survive Bonferroni correction and should therefore be interpreted with caution. No brain or behavior changes were observed in control subjects. Conclusions Our results parallel the sensorimotor deficits that astronauts experience post-flight. The widespread GM changes could reflect fluid redistribution. Additionally, the association between focal GM increase and balance changes suggests that HDBR also may result in neuroplastic adaptation. Future studies are warranted to determine causality and underlying mechanisms. PMID:28767698
Maynard, Daniel S; Covey, Kristofer R; Crowther, Thomas W; Sokol, Noah W; Morrison, Eric W; Frey, Serita D; van Diepen, Linda T A; Bradford, Mark A
2018-04-01
Environmental conditions exert strong controls on the activity of saprotrophic microbes, yet abiotic factors often fail to adequately predict wood decomposition rates across broad spatial scales. Given that species interactions can have significant positive and negative effects on wood-decay fungal activity, one possibility is that biotic processes serve as the primary controls on community function, with abiotic controls emerging only after species associations are accounted for. Here we explore this hypothesis in a factorial field warming- and nitrogen-addition experiment by examining relationships among wood decomposition rates, fungal activity, and fungal community structure. We show that functional outcomes and community structure are largely unrelated to abiotic conditions, with microsite and plot-level abiotic variables explaining at most 19% of the total variability in decomposition and fungal activity, and 2% of the variability in richness and evenness. In contrast, taxonomic richness, evenness, and species associations (i.e., co-occurrence patterns) exhibited strong relationships with community function, accounting for 52% of the variation in decomposition rates and 73% in fungal activity. A greater proportion of positive vs. negative species associations in a community was linked to strong declines in decomposition rates and richness. Evenness emerged as a key mediator between richness and function, with highly even communities exhibiting a positive richness-function relationship and uneven communities exhibiting a negative or null response. These results suggest that community-assembly processes and species interactions are important controls on the function of wood-decay fungal communities, ultimately overwhelming substantial differences in abiotic conditions. © 2018 by the Ecological Society of America.
Chronic obstructive pulmonary disease readmissions at minority-serving institutions.
Prieto-Centurion, Valentin; Gussin, Hélène A; Rolle, Andrew J; Krishnan, Jerry A
2013-12-01
About 20% of patients hospitalized for chronic obstructive pulmonary disease (COPD) exacerbations are readmitted within 30 days. High 30-day risk-standardized readmission rates after COPD exacerbations will likely place hospitals at risk for financial penalties from the Centers for Medicare and Medicaid Services starting in fiscal year 2015. Factors contributing to hospital readmissions include healthcare quality, access to care, coordination of care between hospital and ambulatory settings, and factors linked to socioeconomic resources (e.g., social support, stable housing, transportation, and food). These concerns are exacerbated at minority-serving institutions, which provide a disproportionate share of care to patients with low socioeconomic resources. Solutions tailored to the needs of minority-serving institutions are urgently needed. We recommend research that will provide the evidence base for strategies to reduce readmissions at minority-serving institutions. Promising innovative approaches include using a nontraditional healthcare workforce, such as community health workers and peer-coaches, and telemedicine. These strategies have been successfully used in other conditions and need to be studied in patients with COPD.
NASA Astrophysics Data System (ADS)
Sun, Lining; Wei, Zuwu; Chen, Haige; Liu, Jinliang; Guo, Jianjian; Cao, Ming; Wen, Tieqiao; Shi, Liyi
2014-07-01
Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents.Folate receptors (FRs) are overexpressed on a variety of human cancer cells and tissues, including cancers of the breast, ovaries, endometrium, and brain. This over-expression of FRs can be used to target folate-linked imaging specifically to FR-expressing tumors. Fluorescence is emerging as a powerful new modality for molecular imaging in both the diagnosis and treatment of disease. Combining innovative molecular biology and chemistry, we prepared three kinds of folate-targeted up-conversion nanoparticles as imaging agents (UCNC-FA: UCNC-Er-FA, UCNC-Tm-FA, and UCNC-Er,Tm-FA). In vivo and in vitro toxicity studies showed that these nanoparticles have both good biocompatibility and low toxicity. Moreover, the up-conversion luminescence imaging indicated that they have good targeting to HeLa cells and can therefore serve as potential fluorescent contrast agents. Electronic supplementary information (ESI) available: Up-conversion luminescence spectra of UCNC-Er and UCNC-Er-FA, UCNC-Tm and UCNC-Tm-FA. Confocal luminescence imaging data collected as a series along the Z optical axis. See DOI: 10.1039/c4nr02312a
Multifunction Data Link for an Advanced Air-Traffic Management System
DOT National Transportation Integrated Search
1972-11-01
This report evaluates the requirements relating to a multi-function data link for an advanced Air Traffic Management System. A two-way time ordered data link is postulated to accomplish the communication and control function. Several candidate modula...
The hitchhiker’s guide to the voltage-gated sodium channel galaxy
2016-01-01
Eukaryotic voltage-gated sodium (Nav) channels contribute to the rising phase of action potentials and served as an early muse for biophysicists laying the foundation for our current understanding of electrical signaling. Given their central role in electrical excitability, it is not surprising that (a) inherited mutations in genes encoding for Nav channels and their accessory subunits have been linked to excitability disorders in brain, muscle, and heart; and (b) Nav channels are targeted by various drugs and naturally occurring toxins. Although the overall architecture and behavior of these channels are likely to be similar to the more well-studied voltage-gated potassium channels, eukaryotic Nav channels lack structural and functional symmetry, a notable difference that has implications for gating and selectivity. Activation of voltage-sensing modules of the first three domains in Nav channels is sufficient to open the channel pore, whereas movement of the domain IV voltage sensor is correlated with inactivation. Also, structure–function studies of eukaryotic Nav channels show that a set of amino acids in the selectivity filter, referred to as DEKA locus, is essential for Na+ selectivity. Structures of prokaryotic Nav channels have also shed new light on mechanisms of drug block. These structures exhibit lateral fenestrations that are large enough to allow drugs or lipophilic molecules to gain access into the inner vestibule, suggesting that this might be the passage for drug entry into a closed channel. In this Review, we will synthesize our current understanding of Nav channel gating mechanisms, ion selectivity and permeation, and modulation by therapeutics and toxins in light of the new structures of the prokaryotic Nav channels that, for the time being, serve as structural models of their eukaryotic counterparts. PMID:26712848
Feld, Charlie S; Stoddard, Donna B
2004-02-01
Modern information technology started four decades ago, yet in most major corporations, IT remains an expensive mess. This is partly because the relatively young and rapidly evolving practice of IT continues to be either grossly misunderstood or blindly ignored by top management. Senior managers know how to talk about finances because they all speak or understand the language of profit and loss and balance sheets. But when they allow themselves to be befuddled by IT discussions or bedazzled by three-letter acronyms, they shirk a critical responsibility. In this article, the authors say a systematic approach to understanding and executing IT can and should be implemented, and it should be organized along three interconnected principles: A Long-Term IT Renewal Plan Linked to Corporate Strategy. Such a plan focuses the entire IT group on the company's over-arching goals during a multiyear period, makes appropriate investments directed toward cutting costs in the near term, and generates a detailed blueprint for long-term systems rejuvenation and value creation. A Simplified, Unifying Corporate Technology Platform. Instead of relying on vertically oriented data silos that serve individual corporate units (HR, accounting, and so on), companies adopt a clean, horizontally oriented architecture designed to serve the whole organization. A Highly Functional, Performance-Oriented IT Organization. Instead of functioning as if it were different from the rest of the firm or as a loose confederation of tribes, the IT department works as a team and operates according to corporate performance standards. Getting IT right demands the same inspired leadership and superb execution that other parts of the business require. By sticking to the three central principles outlined in this article, companies can turn IT from a quagmire into a powerful weapon.
2018-01-01
ABSTRACT The alphaproteobacterial general stress response is governed by a conserved partner-switching mechanism that is triggered by phosphorylation of the response regulator PhyR. In the model organism Caulobacter crescentus, PhyR was proposed to be phosphorylated by the histidine kinase PhyK, but biochemical evidence in support of such a role of PhyK is missing. Here, we identify a single-domain response regulator, MrrA, that is essential for general stress response activation in C. crescentus. We demonstrate that PhyK does not function as a kinase but accepts phosphoryl groups from MrrA and passes them on to PhyR, adopting the role of a histidine phosphotransferase. MrrA is phosphorylated by at least six histidine kinases that likely serve as stress sensors. MrrA also transfers phosphate to LovK, a histidine kinase involved in C. crescentus holdfast production and attachment, which also negatively regulates the general stress response. We show that LovK together with the response regulator LovR acts as a phosphate sink to redirect phosphate flux away from the PhyKR branch. In agreement with the biochemical data, an mrrA mutant is unable to activate the general stress response and shows a hyperattachment phenotype, which is linked to decreased expression of the major holdfast inhibitory protein HfiA. We propose that MrrA serves as a central phosphorylation hub that coordinates the general stress response with C. crescentus development and other adaptive behaviors. The characteristic bow-tie architecture of this phosphorylation network with MrrA as the central knot may expedite the evolvability and species-specific niche adaptation of this group of bacteria. PMID:29789370
Wang, Yong-Tang; Lu, Xiu-Min; Zhu, Feng; Zhao, Min
2014-01-01
As a new type of biomaterials, gold nanoparticles (GNPs), also known as colloidal gold (CG), have a wide biomedical application. In this study, GNPs with diameters of 10, 15, and 25 nm were prepared by sodium citrate reduction, and detected by common optical property, ultraviolet-visible (UV-vis) absorbance spectroscopy, and scanning electron microscope (SEM), separately for identification of the particle size and uniformity. In order to observe the effects of GNPs on immune function, adult Sprague Dawley (SD) rats were immunized with the above three GNPs, each having three doses of 0.2, 0.4, and 0.6 ml, and rats without immunization served as negative control. After immunization, proliferation activity of blood and spleen lymphocyte and the levels of interleukin-2 (IL-2) in serum and supernatant of spleen lymphocyte were detected by thiazoleblue (MTT) assay and enzyme linked immunosorbent assay (ELISA), respectively. The results indicated that different size of GNPs was prepared, and the uniformity increased with the decrease of the size of particles. Different diameters and doses of GNPs have different effects on proliferation of blood and spleen lymphocyte, as well as the levels of IL-2 in serum and supernatant of spleen lymphocyte. The 15 nm CG in 0.6 ml dose group could most significantly promote blood and spleen lymphocyte proliferation, and enhance IL-2 levels in serum and supernatant of spleen lymphocyte. Taken together, the findings revealed that application of CG prepared by sodium citrate reduction could enhance specific and nonspecific immune responses, and the 0.6 ml dose of 15 nm CG might be the best immunizing dose in rats. This fact may serve as a further evidence for using CG as a novel immunoadjuvant in the future.
Tsui, Tiffany Y L; Lahat, Ayelet; Schmidt, Louis A
2017-10-01
Although childhood shyness has been linked to social anxiety problems, the factors playing a role in this association have gone largely unexplored. Here we examined the potential moderating roles of sex and age on this relation in a sample of 119 (75 girls) children (10-12 years) and adolescents (14-16 years). As predicted, shyness was positively associated with social anxiety symptoms. Sex, but not age, served as a moderating factor in linking shyness and social anxiety. Specifically, shyness was more strongly associated with social anxiety symptoms among girls than boys. These results suggest the importance of considering sex differences when examining the relation between shyness and social anxiety in childhood and adolescence.
A Unique Role of Endogenous Visual-Spatial Attention in Rapid Processing of Multiple Targets
ERIC Educational Resources Information Center
Guzman-Martinez, Emmanuel; Grabowecky, Marcia; Palafox, German; Suzuki, Satoru
2011-01-01
Visual spatial attention can be exogenously captured by a salient stimulus or can be endogenously allocated by voluntary effort. Whether these two attention modes serve distinctive functions is debated, but for processing of single targets the literature suggests superiority of exogenous attention (it is faster acting and serves more functions).…
Structure and Function of Wood
Alex C. Wiedenhoeft
2012-01-01
Wood is a complex biological structure, a composite of many cell types and chemistries acting together to serve the needs of living plant. Attempting to understand wood inthe context of wood technology, we have often overlooked the basic fact that wood evolved over the course of millions of years to serve three main functions in plants-conduction of water from the...
Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions☆
Mailloux, Ryan J.; Jin, Xiaolei; Willmore, William G.
2013-01-01
Mitochondria have a myriad of essential functions including metabolism and apoptosis. These chief functions are reliant on electron transfer reactions and the production of ATP and reactive oxygen species (ROS). The production of ATP and ROS are intimately linked to the electron transport chain (ETC). Electrons from nutrients are passed through the ETC via a series of acceptor and donor molecules to the terminal electron acceptor molecular oxygen (O2) which ultimately drives the synthesis of ATP. Electron transfer through the respiratory chain and nutrient oxidation also produces ROS. At high enough concentrations ROS can activate mitochondrial apoptotic machinery which ultimately leads to cell death. However, if maintained at low enough concentrations ROS can serve as important signaling molecules. Various regulatory mechanisms converge upon mitochondria to modulate ATP synthesis and ROS production. Given that mitochondrial function depends on redox reactions, it is important to consider how redox signals modulate mitochondrial processes. Here, we provide the first comprehensive review on how redox signals mediated through cysteine oxidation, namely S-oxidation (sulfenylation, sulfinylation), S-glutathionylation, and S-nitrosylation, regulate key mitochondrial functions including nutrient oxidation, oxidative phosphorylation, ROS production, mitochondrial permeability transition (MPT), apoptosis, and mitochondrial fission and fusion. We also consider the chemistry behind these reactions and how they are modulated in mitochondria. In addition, we also discuss emerging knowledge on disorders and disease states that are associated with deregulated redox signaling in mitochondria and how mitochondria-targeted medicines can be utilized to restore mitochondrial redox signaling. PMID:24455476
Redox regulation of mitochondrial function with emphasis on cysteine oxidation reactions.
Mailloux, Ryan J; Jin, Xiaolei; Willmore, William G
2014-01-01
Mitochondria have a myriad of essential functions including metabolism and apoptosis. These chief functions are reliant on electron transfer reactions and the production of ATP and reactive oxygen species (ROS). The production of ATP and ROS are intimately linked to the electron transport chain (ETC). Electrons from nutrients are passed through the ETC via a series of acceptor and donor molecules to the terminal electron acceptor molecular oxygen (O2) which ultimately drives the synthesis of ATP. Electron transfer through the respiratory chain and nutrient oxidation also produces ROS. At high enough concentrations ROS can activate mitochondrial apoptotic machinery which ultimately leads to cell death. However, if maintained at low enough concentrations ROS can serve as important signaling molecules. Various regulatory mechanisms converge upon mitochondria to modulate ATP synthesis and ROS production. Given that mitochondrial function depends on redox reactions, it is important to consider how redox signals modulate mitochondrial processes. Here, we provide the first comprehensive review on how redox signals mediated through cysteine oxidation, namely S-oxidation (sulfenylation, sulfinylation), S-glutathionylation, and S-nitrosylation, regulate key mitochondrial functions including nutrient oxidation, oxidative phosphorylation, ROS production, mitochondrial permeability transition (MPT), apoptosis, and mitochondrial fission and fusion. We also consider the chemistry behind these reactions and how they are modulated in mitochondria. In addition, we also discuss emerging knowledge on disorders and disease states that are associated with deregulated redox signaling in mitochondria and how mitochondria-targeted medicines can be utilized to restore mitochondrial redox signaling.
Using computational fluid dynamics to test functional and ecological hypotheses in fossil taxa
NASA Astrophysics Data System (ADS)
Rahman, Imran
2016-04-01
Reconstructing how ancient organisms moved and fed is a major focus of study in palaeontology. Traditionally, this has been hampered by a lack of objective data on the functional morphology of extinct species, especially those without a clear modern analogue. However, cutting-edge techniques for characterizing specimens digitally and in three dimensions, coupled with state-of-the-art computer models, now provide a robust framework for testing functional and ecological hypotheses even in problematic fossil taxa. One such approach is computational fluid dynamics (CFD), a method for simulating fluid flows around objects that has primarily been applied to complex engineering-design problems. Here, I will present three case studies of CFD applied to fossil taxa, spanning a range of specimen sizes, taxonomic groups and geological ages. First, I will show how CFD enabled a rigorous test of hypothesized feeding modes in an enigmatic Ediacaran organism with three-fold symmetry, revealing previously unappreciated complexity of pre-Cambrian ecosystems. Second, I will show how CFD was used to evaluate hydrodynamic performance and feeding in Cambrian stem-group echinoderms, shedding light on the probable feeding strategy of the latest common ancestor of all deuterostomes. Third, I will show how CFD allowed us to explore the link between form and function in Mesozoic ichthyosaurs. These case studies serve to demonstrate the enormous potential of CFD for addressing long-standing hypotheses for a variety of fossil taxa, opening up an exciting new avenue in palaeontological studies of functional morphology.
Why Do the Children (Pretend) Play?
Lillard, Angeline S
2017-11-01
Pretend play appears to be an evolved behavior because it is universal and appears on a set schedule. However, no specific functions have been determined for pretend play and empirical tests for its functions in humans are elusive. Yet animal play fighting can serve as an analog, as both activities involve as-if, metacommunicative signaling and symbolism. In the rat and some other animals, adaptive functions of play fighting include assisting social behavior and emotion regulation. Research is presented suggesting that pretend play might serve similar functions for humans. Copyright © 2017 Elsevier Ltd. All rights reserved.
Proving relations between modular graph functions
NASA Astrophysics Data System (ADS)
Basu, Anirban
2016-12-01
We consider modular graph functions that arise in the low energy expansion of the four graviton amplitude in type II string theory. The vertices of these graphs are the positions of insertions of vertex operators on the toroidal worldsheet, while the links are the scalar Green functions connecting the vertices. Graphs with four and five links satisfy several non-trivial relations, which have been proved recently. We prove these relations by using elementary properties of Green functions and the details of the graphs. We also prove a relation between modular graph functions with six links.
Wikidata as a semantic framework for the Gene Wiki initiative.
Burgstaller-Muehlbacher, Sebastian; Waagmeester, Andra; Mitraka, Elvira; Turner, Julia; Putman, Tim; Leong, Justin; Naik, Chinmay; Pavlidis, Paul; Schriml, Lynn; Good, Benjamin M; Su, Andrew I
2016-01-01
Open biological data are distributed over many resources making them challenging to integrate, to update and to disseminate quickly. Wikidata is a growing, open community database which can serve this purpose and also provides tight integration with Wikipedia. In order to improve the state of biological data, facilitate data management and dissemination, we imported all human and mouse genes, and all human and mouse proteins into Wikidata. In total, 59,721 human genes and 73,355 mouse genes have been imported from NCBI and 27,306 human proteins and 16,728 mouse proteins have been imported from the Swissprot subset of UniProt. As Wikidata is open and can be edited by anybody, our corpus of imported data serves as the starting point for integration of further data by scientists, the Wikidata community and citizen scientists alike. The first use case for these data is to populate Wikipedia Gene Wiki infoboxes directly from Wikidata with the data integrated above. This enables immediate updates of the Gene Wiki infoboxes as soon as the data in Wikidata are modified. Although Gene Wiki pages are currently only on the English language version of Wikipedia, the multilingual nature of Wikidata allows for usage of the data we imported in all 280 different language Wikipedias. Apart from the Gene Wiki infobox use case, a SPARQL endpoint and exporting functionality to several standard formats (e.g. JSON, XML) enable use of the data by scientists. In summary, we created a fully open and extensible data resource for human and mouse molecular biology and biochemistry data. This resource enriches all the Wikipedias with structured information and serves as a new linking hub for the biological semantic web. Database URL: https://www.wikidata.org/. © The Author(s) 2016. Published by Oxford University Press.
A Statewide Service Learning Network Ignites Teachers and Students.
ERIC Educational Resources Information Center
Monsour, Florence
Service learning, curriculum-linked community service, has proved remarkably effective in igniting students' desire to learn. In 1997, the Wisconsin Partnership in Service Learning was initiated as a cross-disciplinary, cross-institutional endeavor. Supported by a grant from Learn and Serve America, the partnership created a network throughout…
Writing Useful Instructional Objectives in Physical Education
ERIC Educational Resources Information Center
Young, Shawna
2016-01-01
Within a physical education curriculum, and presented in individual lesson plans, instructional objectives serve several important purposes: they provide a direct link between the curriculum content and procedures for students to master that content; they provide a clear path for assessment--a way to determine whether students have indeed learned…
Advisory Boards: Academic Partnerships That Work.
ERIC Educational Resources Information Center
Silver, Gerald
An academic advisory board of volunteers drawn from college alumni and the general community can serve institutions of higher education at the college, school and even departmental level. Board members link the academic community to the external community by sharing expertise gained through practical experience. Such a board exists solely to give…
ERIC Educational Resources Information Center
Zemsky, Robert, Ed.
1996-01-01
This article grew out of a roundtable of national leaders in higher education which explored the role of the academic department in serving as both a force for institutional change and a link to the scholarly world of disciplinary knowledge and practice. The essay argues that the principal threat to the academy is its own fragmentation, with…
47 CFR 90.361 - Interference from part 15 and Amateur operations.
Code of Federal Regulations, 2010 CFR
2010-10-01
... communications of entities eligible under subpart B or C of this part, or is providing the final link for communications of health care providers that serve rural areas, elementary schools, secondary schools or... operations. 90.361 Section 90.361 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND...
Dose-Response Analysis of Early MicroRNA Alterations Linked to PPAR-alpha Activation
MicroRNAs (miRNAs) are short non-coding RNA species that play a critical role in post-transcriptional regulation of gene expression. MiRNAs also serve as a promising source of early predictive biomarkers for different types of health outcomes, although there is limited informatio...
Student Participation in Academic Advising: Propensity, Behavior, Attribution and Satisfaction
ERIC Educational Resources Information Center
Braun, Jakob; Zolfagharian, Mohammadali
2016-01-01
While there is general consensus that students are more or less participants in their educational experiences, the relationship between student participation and satisfaction has not been extensively examined in higher education literature. Looking to participation research in other literatures serves as a starting point for exploring this link.…
ERIC Educational Resources Information Center
Bukoski, Beth E.; Lewis, Tiffanie C.; Carpenter, Bradley W.; Berry, Matthew S.; Sanders, Kimberly N.
2015-01-01
Meaningful community involvement has been linked to enhancements in student achievement and quality of educational experiences. Assistant principals are positioned to build effective partnerships yet remain understudied in the leadership preparation field. This qualitative study investigated how assistant principals (N = 9) serving historically…
Design and implementation of an intranet dashboard.
Wolpin, S E
2005-01-01
Healthcare organizations are complex systems and well served by efficient feedback mechanisms. Many organizations have invested in data warehouses; however there are few tools for automatically extracting and delivering relevant measures to decision makers. This research study resulted in the design and implementation of an intranet dashboard linked to a data warehouse.
ERIC Educational Resources Information Center
Neuhauser, Claudia; Weber, Kendra
2011-01-01
An innovative position, a Student Success Coach, was created in response to a newly developed undergraduate-degree program on the recently established University of Minnesota Rochester campus. Student Success Coaches serve as the link between the academic and student affairs sides of the campus. They interact closely with students and faculty to…
Social Networking Sites as Virtual Communities of Practice: A Mixed Method Study
ERIC Educational Resources Information Center
Davis, Lorretta J.
2010-01-01
Membership in social networking sites is increasing rapidly. Social networking sites serve many purposes including networking, communication, recruitment, and sharing knowledge. Social networking sites, public or private, may be hosted on applications such as Facebook and LinkedIn. As individuals begin to follow and participate in social…
Linking Schools with Human Service Agencies. ERIC/CUE Digest No. 62.
ERIC Educational Resources Information Center
Ascher, Carol
A number of factors put pressure on schools to work more closely with health, social service, and other youth-serving institutions but poor communications, program redundancies, fear for job security, and concerns about parent and community support for controversial services inhibit close collaboration. Recent successful collaborative school,…
Technology-Oriented Job Preparation. Final Report.
ERIC Educational Resources Information Center
One America, Inc., Washington, DC.
An extensive review of literature dealing with 263 technology-oriented vocational training programs was conducted to gather current information on the state of such training. Particular emphasis was placed on links between programs and government bodies or private sector entities and programs that could serve as models for those wishing to…
From Capacity to Success: HSIs and Latino Student Success through Title V
ERIC Educational Resources Information Center
Villarreal, Rebecca C.; Santiago, Deborah A.
2012-01-01
Latinos are the second largest student population enrolled in higher education and the majority are concentrated in a small number of institutions--Hispanic-Serving Institutions (HSIs). Given the concentrated enrollment of Latinos at HSIs and the opportunity to increase Latinos' educational achievement, reviewing the link between capacity…
Infrared microspectroscopic determination of collagen cross-links in articular cartilage
NASA Astrophysics Data System (ADS)
Rieppo, Lassi; Kokkonen, Harri T.; Kulmala, Katariina A. M.; Kovanen, Vuokko; Lammi, Mikko J.; Töyräs, Juha; Saarakkala, Simo
2017-03-01
Collagen forms an organized network in articular cartilage to give tensile stiffness to the tissue. Due to its long half-life, collagen is susceptible to cross-links caused by advanced glycation end-products. The current standard method for determination of cross-link concentrations in tissues is the destructive high-performance liquid chromatography (HPLC). The aim of this study was to analyze the cross-link concentrations nondestructively from standard unstained histological articular cartilage sections by using Fourier transform infrared (FTIR) microspectroscopy. Half of the bovine articular cartilage samples (n=27) were treated with threose to increase the collagen cross-linking while the other half (n=27) served as a control group. Partial least squares (PLS) regression with variable selection algorithms was used to predict the cross-link concentrations from the measured average FTIR spectra of the samples, and HPLC was used as the reference method for cross-link concentrations. The correlation coefficients between the PLS regression models and the biochemical reference values were r=0.84 (p<0.001), r=0.87 (p<0.001) and r=0.92 (p<0.001) for hydroxylysyl pyridinoline (HP), lysyl pyridinoline (LP), and pentosidine (Pent) cross-links, respectively. The study demonstrated that FTIR microspectroscopy is a feasible method for investigating cross-link concentrations in articular cartilage.
Creating a Linked Data Hub in the Geosciences
NASA Astrophysics Data System (ADS)
Narock, T. W.; Rozell, E. A.; Robinson, E. M.
2012-12-01
Linked data is a paradigm for publishing data on the Web by using, among other things, non-proprietary data formats and resolvable identifiers for things in your dataset. One linked data initiative, DBPedia, is widely used as a "crystallization point" for linked data on the Web. It serves as a hub for links from external datasets covering a broad variety of domains. Within the Earth Science Information Partnership (ESIP) efforts have begun to create a similar crystallization point for linked data in the geosciences. The initial project was created by converting more than 100,000 abstracts from the American Geophysical Union (AGU) into linked data using the Resource Description Framework. Like the Wikipedia data DBPedia is derived from, AGU publications have extremely broad coverage of topics in the geosciences. To better characterize the network, we have linked this AGU data to ESIP meeting and membership data, as well as to National Science Foundation-funded research projects. In doing so, we can visualize connections between different collaborative clusters like the ESIP Community or NSF grantees within the broader Geosciences communities that attend AGU conferences. Efforts to extend this project include - the ability to annotate abstracts, provide links to referenced tools or datasets, and the enabling of a crowd-sourcing approach to co-reference resolution.
The Effect of Error in Item Parameter Estimates on the Test Response Function Method of Linking.
ERIC Educational Resources Information Center
Kaskowitz, Gary S.; De Ayala, R. J.
2001-01-01
Studied the effect of item parameter estimation for computation of linking coefficients for the test response function (TRF) linking/equating method. Simulation results showed that linking was more accurate when there was less error in the parameter estimates, and that 15 or 25 common items provided better results than 5 common items under both…
NASA Technical Reports Server (NTRS)
Roth, Don J.; Whalen, Mike F.; Hendricks, J. Lynne; Bodis, James R.
2001-01-01
To interface with other solids, many surfaces are engineered via methods such as plating, coating, and machining to produce a functional surface ensuring successful end products. In addition, subsurface properties such as hardness, residual stress, deformation, chemical composition, and microstructure are often linked to surface characteristics. Surface topography, therefore, contains the signatures of the surface and possibly links to volumetric properties, and as a result serves as a vital link between surface design, manufacturing, and performance. Hence, surface topography can be used to diagnose, monitor, and control fabrication methods. At the NASA Glenn Research Center, the measurement of surface topography is important in developing high-temperature structural materials and for profiling the surface changes of materials during microgravity combustion experiments. A prior study demonstrated that focused air-coupled ultrasound at 1 MHz could profile surfaces with a 25-m depth resolution and a 400-m lateral resolution over a 1.4-mm depth range. In this work, we address the question of whether higher frequency focused water-coupled ultrasound can improve on these specifications. To this end, we employed 10- and 25-MHz focused ultrasonic transducers in the water-coupled mode. The surface profile results seen in this investigation for 25-MHz water-coupled ultrasound, in comparison to those for 1-MHz air-coupled ultrasound, represent an 8 times improvement in depth resolution (3 vs. 25 m seen in practice), an improvement of at least 2 times in lateral resolution (180 vs. 400 m calculated and observed in practice), and an improvement in vertical depth range of 4 times (calculated).
Roads at risk - traffic detours from debris flows in southern Norway
NASA Astrophysics Data System (ADS)
Meyer, N. K.; Schwanghart, W.; Korup, O.; Nadim, F.
2014-10-01
Globalization and interregional exchange of people, goods, and services has boosted the importance of and reliance on all kinds of transport networks. The linear structure of road networks is especially sensitive to natural hazards. In southern Norway, steep topography and extreme weather events promote frequent traffic disruption caused by debris flows. Topographic susceptibility and trigger frequency maps serve as input into a hazard appraisal at the scale of first-order catchments to quantify the impact of debris flows on the road network in terms of a failure likelihood of each link connecting two network vertices, e.g., road junctions. We compute total additional traffic loads as a function of traffic volume and excess distance, i.e. the extra length of an alternative path connecting two previously disrupted network vertices using a shortest-path algorithm. Our risk metric of link failure is the total additional annual traffic load expressed as vehicle kilometers because of debris-flow related road closures. We present two scenarios demonstrating the impact of debris flows on the road network, and quantify the associated path failure likelihood between major cities in southern Norway. The scenarios indicate that major routes crossing the central and northwestern part of the study area are associated with high link failure risk. Yet options for detours on major routes are manifold, and incur only little additional costs provided that drivers are sufficiently well informed about road closures. Our risk estimates may be of importance to road network managers and transport companies relying of speedy delivery of services and goods.
The antibiotic resistance "mobilome": searching for the link between environment and clinic.
Perry, Julie A; Wright, Gerard D
2013-01-01
Antibiotic resistance is an ancient problem, owing to the co-evolution of antibiotic-producing and target organisms in the soil and other environments over millennia. The environmental "resistome" is the collection of all genes that directly or indirectly contribute to antibiotic resistance. Many of these resistance determinants originate in antibiotic-producing organisms (where they serve to mediate self-immunity), while others become resistance determinants only when mobilized and over-expressed in non-native hosts (like plasmid-encoded β-lactamases). The modern environmental resistome is under selective pressure from human activities such as agriculture, which may influence the composition of the local resistome and lead to gene transfer events. Beyond the environment, we are challenged in the clinic by the rise in both frequency and diversity of antibiotic resistant pathogens. We assume that clinical resistance originated in the environment, but few examples of direct gene exchange between the environmental resistome and the clinical resistome have been documented. Strong evidence exists to suggest that clinical aminoglycoside and vancomycin resistance enzymes, the extended-spectrum β-lactamase CTX-M and the quinolone resistance gene qnr have direct links to the environmental resistome. In this review, we highlight recent advances in our understanding of horizontal gene transfer of antibiotic resistance genes from the environment to the clinic. Improvements in sequencing technologies coupled with functional metagenomic studies have revealed previously underappreciated diversity in the environmental resistome, and also established novel genetic links to the clinic. Understanding mechanisms of gene exchange becomes vital in controlling the future dissemination of antibiotic resistance.
The antibiotic resistance “mobilome”: searching for the link between environment and clinic
Perry, Julie A.; Wright, Gerard D.
2013-01-01
Antibiotic resistance is an ancient problem, owing to the co-evolution of antibiotic-producing and target organisms in the soil and other environments over millennia. The environmental “resistome” is the collection of all genes that directly or indirectly contribute to antibiotic resistance. Many of these resistance determinants originate in antibiotic-producing organisms (where they serve to mediate self-immunity), while others become resistance determinants only when mobilized and over-expressed in non-native hosts (like plasmid-encoded β-lactamases). The modern environmental resistome is under selective pressure from human activities such as agriculture, which may influence the composition of the local resistome and lead to gene transfer events. Beyond the environment, we are challenged in the clinic by the rise in both frequency and diversity of antibiotic resistant pathogens. We assume that clinical resistance originated in the environment, but few examples of direct gene exchange between the environmental resistome and the clinical resistome have been documented. Strong evidence exists to suggest that clinical aminoglycoside and vancomycin resistance enzymes, the extended-spectrum β-lactamase CTX-M and the quinolone resistance gene qnr have direct links to the environmental resistome. In this review, we highlight recent advances in our understanding of horizontal gene transfer of antibiotic resistance genes from the environment to the clinic. Improvements in sequencing technologies coupled with functional metagenomic studies have revealed previously underappreciated diversity in the environmental resistome, and also established novel genetic links to the clinic. Understanding mechanisms of gene exchange becomes vital in controlling the future dissemination of antibiotic resistance. PMID:23755047
Roads at risk: traffic detours from debris flows in southern Norway
NASA Astrophysics Data System (ADS)
Meyer, N. K.; Schwanghart, W.; Korup, O.; Nadim, F.
2015-05-01
Globalisation and interregional exchange of people, goods, and services has boosted the importance of and reliance on all kinds of transport networks. The linear structure of road networks is especially sensitive to natural hazards. In southern Norway, steep topography and extreme weather events promote frequent traffic disruption caused by debris flows. Topographic susceptibility and trigger frequency maps serve as input into a hazard appraisal at the scale of first-order catchments to quantify the impact of debris flows on the road network in terms of a failure likelihood of each link connecting two network vertices, e.g. road junctions. We compute total additional traffic loads as a function of traffic volume and excess distance, i.e. the extra length of an alternative path connecting two previously disrupted network vertices using a shortest-path algorithm. Our risk metric of link failure is the total additional annual traffic load, expressed as vehicle kilometres, because of debris-flow-related road closures. We present two scenarios demonstrating the impact of debris flows on the road network and quantify the associated path-failure likelihood between major cities in southern Norway. The scenarios indicate that major routes crossing the central and north-western part of the study area are associated with high link-failure risk. Yet options for detours on major routes are manifold and incur only little additional costs provided that drivers are sufficiently well informed about road closures. Our risk estimates may be of importance to road network managers and transport companies relying on speedy delivery of services and goods.
Basic Science Evidence for the Link Between Erectile Dysfunction and Cardiometabolic Dysfunction
Musicki, Biljana; Bella, Anthony J.; Bivalacqua, Trinity J.; Davies, Kelvin P.; DiSanto, Michael E.; Gonzalez-Cadavid, Nestor F.; Hannan, Johanna L.; Kim, Noel N.; Podlasek, Carol A.; Wingard, Christopher J.; Burnett, Arthur L.
2016-01-01
Introduction Although clinical evidence supports an association between cardiovascular/metabolic diseases (CVMD) and erectile dysfunction (ED), scientific evidence for this link is incompletely elucidated. Aim This study aims to provide scientific evidence for the link between CVMD and ED. Methods In this White Paper, the Basic Science Committee of the Sexual Medicine Society of North America assessed the current literature on basic scientific support for a mechanistic link between ED and CVMD, and deficiencies in this regard with a critical assessment of current preclinical models of disease. Results A link exists between ED and CVMD on several grounds: the endothelium (endothelium-derived nitric oxide and oxidative stress imbalance); smooth muscle (SM) (SM abundance and altered molecular regulation of SM contractility); autonomic innervation (autonomic neuropathy and decreased neuronal-derived nitric oxide); hormones (impaired testosterone release and actions); and metabolics (hyperlipidemia, advanced glycation end product formation). Conclusion Basic science evidence supports the link between ED and CVMD. The Committee also highlighted gaps in knowledge and provided recommendations for guiding further scientific study defining this risk relationship. This endeavor serves to develop novel strategic directions for therapeutic interventions. PMID:26646025
Software for Experimental Air-Ground Data Link Volume I : Functional Description and Flowcharts.
DOT National Transportation Integrated Search
1975-10-01
Experimental Data Link System which was implemented for flight test during the Air-Ground Data Link Development Program (FAA-TSC Project Number FA-13). : The software development is presented in three volumes as follows: : Volume I: -- Functional Des...
Law, Ben M. F.; Shek, Daniel T. L.
2009-01-01
The relationships among beliefs about volunteerism, volunteering intention, volunteering behavior, and purpose in life were examined in this study. A total of 5,946 participants completed a series of scales, including the Revised Personal Functions of Volunteerism Scale, Volunteering Intention Scale, and Purpose in Life Scale. The results showed that participants whose purpose in life had different levels also had varied prosocial beliefs about volunteerism, volunteering intention, and volunteering behavior. Purpose in life was associated more strongly with prosocial value function than with other types of beliefs (except understanding function). When different beliefs are grouped, the correlation between purpose in life and other-serving beliefs was higher than that between purpose in life and self-serving beliefs. Purpose in life was also associated with volunteering intention and behavior. Path analyses showed that purpose in life predicted volunteering behavior via beliefs and intention. While other-serving beliefs predicted volunteering behavior directly, self-serving beliefs did not have such direct effect. PMID:19734959
Law, Ben M F; Shek, Daniel T L
2009-09-01
The relationships among beliefs about volunteerism, volunteering intention, volunteering behavior, and purpose in life were examined in this study. A total of 5,946 participants completed a series of scales, including the Revised Personal Functions of Volunteerism Scale, Volunteering Intention Scale, and Purpose in Life Scale. The results showed that participants whose purpose in life had different levels also had varied prosocial beliefs about volunteerism, volunteering intention, and volunteering behavior. Purpose in life was associated more strongly with prosocial value function than with other types of beliefs (except understanding function). When different beliefs are grouped, the correlation between purpose in life and other-serving beliefs was higher than that between purpose in life and self-serving beliefs. Purpose in life was also associated with volunteering intention and behavior. Path analyses showed that purpose in life predicted volunteering behavior via beliefs and intention. While other-serving beliefs predicted volunteering behavior directly, self-serving beliefs did not have such direct effect.
The Kinematic Analysis of Flat Leverage Mechanism of the Third Class
NASA Astrophysics Data System (ADS)
Zhauyt, A.; Mamatova, G.; Abdugaliyeva, G.; Alipov, K.; Sakenova, A.; Alimbetov, A.
2017-10-01
It is necessary to make link mechanisms calculation to the strength at designing of flat link mechanisms of high class after definition of block diagrams and link linear sizes i.e. it is rationally to choose their forms and to determine the section sizes. The algorithm of the definition of dimension of link mechanism lengths of high classes (MHC) and their metric parameters at successive approach is offered in this work. It this paper educational and research software named GIM is presented. This software has been developed with the aim of approaching the difficulties students usually encounter when facing up to kinematic analysis of mechanisms. A deep understanding of the kinematic analysis is necessary to go a step further into design and synthesis of mechanisms. In order to support and complement the theoretical lectures, GIM software is used during the practical exercises, serving as an educational complementary tool reinforcing the knowledge acquired by the students.
Too Much or Too Little? Eco-hydrology in Arid and Semi-arid Regions
NASA Astrophysics Data System (ADS)
Toch, S. L.
2009-04-01
Around the world, disastrous effects of floods and droughts are painful evidence of our continuing struggle between human resource demands and the sustainability of our hydrologic ecosystems. Too much or too little rainfall is often deemed the culprit in these water crises, focusing on water "lacks and needs" instead of exploring the diverse mechanisms of the hydrologic functions and processes that sustain us. Applicable to regions around the world, this unified approach focuses on the connections between our human and ecological qualities, with user friendly concepts and how-to guides backed up by real life experiences. From the poorest parts of Africa to Urban France to the wealthiest state in the USA, examples from surface to groundwater to marine environments demonstrate how the links between vulnerable natural areas, and the basins that they support are integral to the availability, adequacy and accessibility of our drinking water. The interactions of watersheds within our diverse communities can link our resource practices with our human needs, serving as a basis for our ecological health and human well-being. Hydrologic ecosystems provide links to geographic and cultural information traversing physical and social boundaries. This international, community-based project demonstrates how our human resource demands can be managed within ecological constraints. An inter-disciplinary process is used that specifically explores the connections between ecological integrity and the preservation of potable supplies. A monitoring strategy is developed that assesses risk to human health from resource use practices, and explores the similarities and interactions between our human needs and those of the ecosystems in which we all must live together. This work is geared as a reference for groups, individuals and agencies concerned with land use and watershed management, a supplement for interdisciplinary high school through University curriculum, for professional development in technical and field assistance, and for community awareness in the trade-offs and consequences of resource decisions that affect our shared hydrologic eco-systems. Disastrous conditions worldwide have triggered reactions in crisis relief rather than crisis prevention. Through a unified management approach geared towards traversing boundaries in professional disciplines, geographic areas and cultural interests, the flows of water that connect all water users can serve as a basis for the maintenance and protection our valuable watersheds.
Mortality Among Very Low-Birthweight Infants in Hospitals Serving Minority Populations
Morales, Leo S.; Staiger, Douglas; Horbar, Jeffrey D.; Carpenter, Joseph; Kenny, Michael; Geppert, Jeffrey; Rogowski, Jeannette
2005-01-01
Objective. We investigated whether the proportion of Black very low-birth-weight (VLBW) infants treated by hospitals is associated with neonatal mortality for Black and White VLBW infants. Methods. We analyzed medical records linked to secondary data sources for 74050 Black and White VLBW infants (501 g to 1500 g) treated by 332 hospitals participating in the Vermont Oxford Network from 1995 to 2000. Hospitals where more than 35% of VLBW infants treated were Black were defined as “minority-serving.” Results. Compared with hospitals where less than 15% of the VLBW infants were Black, minority-serving hospitals had significantly higher risk-adjusted neonatal mortality rates (White infants: odds ratio [OR]=1.30, 95% confidence interval [CI] = 1.09, 1.56; Black infants: OR = 1.29, 95% CI = 1.01, 1.64; Pooled: OR = 1.28, 95% CI=1.10, 1.50). Higher neonatal mortality in minority-serving hospitals was not explained by either hospital or treatment variables. Conclusions. Minority-serving hospitals may provide lower quality of care to VLBW infants compared with other hospitals. Because VLBW Black infants are disproportionately treated by minority-serving hospitals, higher neonatal mortality rates at these hospitals may contribute to racial disparities in infant mortality in the United States. PMID:16304133
Yang, Yimu; Schmidt, Eric P.
2013-01-01
Once thought to be a structure of small size and uncertain significance, the endothelial glycocalyx is now known to be an important regulator of endothelial function. Studies of the systemic vasculature have demonstrated that the glycocalyx forms a substantial in vivo endothelial surface layer (ESL) critical to inflammation, barrier function and mechanotransduction. The pulmonary ESL is significantly thicker than the systemic ESL, suggesting unique physiologic function. We have recently demonstrated that the pulmonary ESL regulates exposure of endothelial surface adhesion molecules, thereby serving as a barrier to neutrophil adhesion and extravasation. While the pulmonary ESL is not a critical structural component of the endothelial barrier to fluid and protein, it serves a major role in the mechanotransduction of vascular pressure, with impact on the active regulation of endothelial permeability. It is likely that the ESL serves numerous additional functions in vascular physiology, representing a fertile area for future investigation. PMID:24073386
Optimal Linking Design for Response Model Parameters
ERIC Educational Resources Information Center
Barrett, Michelle D.; van der Linden, Wim J.
2017-01-01
Linking functions adjust for differences between identifiability restrictions used in different instances of the estimation of item response model parameters. These adjustments are necessary when results from those instances are to be compared. As linking functions are derived from estimated item response model parameters, parameter estimation…
Synthesis of chiral alpha-amino aldehydes linked by their amine function to solid support.
Cantel, Sonia; Heitz, Annie; Martinez, Jean; Fehrentz, Jean-Alain
2004-09-01
The anchoring of an alpha-amino-acid derivative by its amine function on to a solid support allows some chemical reactions starting from the carboxylic acid function. This paper describes the preparation of alpha-amino aldehydes linked to the support by their amine function. This was performed by reduction with LiAlH4 of the corresponding Weinreb amide linked to the resin. The aldehydes obtained were then involved in Wittig or reductive amination reactions. In addition, the linked Weinreb amide was reacted with methylmagnesium bromide to yield the corresponding ketone. After cleavage from the support, the compounds were obtained in good to excellent yields and characterized.
Analyzing Radio-Frequency Coverage for the ISS
NASA Technical Reports Server (NTRS)
Bolen, Steven M.; Sham, Catherine C.
2007-01-01
The Interactive Coverage Analysis Tool (iCAT) is an interactive desktop computer program serving to (1) support planning of coverage, and management of usage of frequencies, of current and proposed radio communication systems on and near the International Space Station (ISS) and (2) enable definition of requirements for development of future such systems. The iCAT can also be used in design trade studies for other (both outer-space and terrestrial) communication systems. A user can enter the parameters of a communication-system link budget in a table in a worksheet. The nominal (onaxis) link values for the bit-to-noise-energy ratio, received isotropic power (RIP), carrier-to-noise ratio (C/N), power flux density (PFD), and link margin of the system are calculated and displayed in the table. Plots of field gradients for the RIP, C/N, PFD, and link margin are constructed in an ISS coordinate system, at a specified link range, for both the forward and return link parameters, and are displayed in worksheets. The forward and reverse link antenna gain patterns are also constructed and displayed. Line-of-sight (LOS) obstructions can be both incorporated into the gradient plots and displayed on separate plots.
Freas, Nicholas; Newton, Peter; Perozich, John
2016-01-01
UDP-glucose dehydrogenase (UDPGDH), UDP-N-acetyl-mannosamine dehydrogenase (UDPNAMDH) and GDP-mannose dehydrogenase (GDPMDH) belong to a family of NAD (+)-linked 4-electron-transfering oxidoreductases called nucleotide diphosphate sugar dehydrogenases (NDP-SDHs). UDPGDH is an enzyme responsible for converting UDP-d-glucose to UDP-d-glucuronic acid, a product that has different roles depending on the organism in which it is found. UDPNAMDH and GDPMDH convert UDP-N-acetyl-mannosamine to UDP-N-acetyl-mannosaminuronic acid and GDP-mannose to GDP-mannuronic acid, respectively, by a similar mechanism to UDPGDH. Their products are used as essential building blocks for the exopolysaccharides found in organisms like Pseudomonas aeruginosa and Staphylococcus aureus. Few studies have investigated the relationships between these enzymes. This study reveals the relationships between the three enzymes by analysing 229 amino acid sequences. Eighteen invariant and several other highly conserved residues were identified, each serving critical roles in maintaining enzyme structure, coenzyme binding or catalytic function. Also, 10 conserved motifs that included most of the conserved residues were identified and their roles proposed. A phylogenetic tree demonstrated relationships between each group and verified group assignment. Finally, group entropy analysis identified novel conservations unique to each NDP-SDH group, including residue positions critical to NDP-sugar substrate interaction, enzyme structure and intersubunit contact. These positions may serve as targets for future research. UDP-glucose dehydrogenase (UDPGDH, EC 1.1.1.22).
Kim, Juyoung; Lee, Seung Mi; Bae, In Young; Park, Hyuk-Gu; Gyu Lee, Hyeon; Lee, Suyong
2011-08-15
Extensive physiological and biological emphasis has been placed on pharmaceutical and medicinal uses of mushrooms containing β-glucans, but their incorporation into processed functional foods is quite limited. Thus, low-grade Lentinus edodes mushrooms were utilised to produce β-glucan-enriched materials (BGEMs), which were evaluated as a high-fibre and low-calorie substitute for wheat flour. The fractions obtained from Lentinus edodes mushrooms contained 514 g kg⁻¹ of (1-3)-β-glucans with (1-6)-β-linked side chains and the chemical structure was confirmed by ¹³C NMR and FTIR spectroscopy. Replacement of a portion of the wheat flour with BGEMs resulted in the solutions with lower values of pasting parameters and also caused significant changes in starch gelatinisation. When BGEMs were incorporated into cake formulations, batter viscosity increased with more shear-thinning behaviours and elastic properties improved. Overall, the cakes containing more BGEMs showed decreased volume and increased hardness while no significant differences were observed between the control and BGEM cakes containing 1 g of β-glucan per serving. As a wheat flour substitute, the BGEMs that were prepared from low-grade Lentinus edodes mushrooms, could be successfully used to produce cakes containing 1 g of β-glucan per serving with quality attributes similar to those of the control. Copyright © 2011 Society of Chemical Industry.
Using FlyBase, a Database of Drosophila Genes and Genomes.
Marygold, Steven J; Crosby, Madeline A; Goodman, Joshua L
2016-01-01
For nearly 25 years, FlyBase (flybase.org) has provided a freely available online database of biological information about Drosophila species, focusing on the model organism D. melanogaster. The need for a centralized, integrated view of Drosophila research has never been greater as advances in genomic, proteomic, and high-throughput technologies add to the quantity and diversity of available data and resources.FlyBase has taken several approaches to respond to these changes in the research landscape. Novel report pages have been generated for new reagent types and physical interaction data; Drosophila models of human disease are now represented and showcased in dedicated Human Disease Model Reports; other integrated reports have been established that bring together related genes, datasets, or reagents; Gene Reports have been revised to improve access to new data types and to highlight functional data; links to external sites have been organized and expanded; and new tools have been developed to display and interrogate all these data, including improved batch processing and bulk file availability. In addition, several new community initiatives have served to enhance interactions between researchers and FlyBase, resulting in direct user contributions and improved feedback.This chapter provides an overview of the data content, organization, and available tools within FlyBase, focusing on recent improvements. We hope it serves as a guide for our diverse user base, enabling efficient and effective exploration of the database and thereby accelerating research discoveries.
Oxytocin promotes group-serving dishonesty
Shalvi, Shaul; De Dreu, Carsten K. W.
2014-01-01
To protect and promote the well-being of others, humans may bend the truth and behave unethically. Here we link such tendencies to oxytocin, a neuropeptide known to promote affiliation and cooperation with others. Using a simple coin-toss prediction task in which participants could dishonestly report their performance levels to benefit their group’s outcome, we tested the prediction that oxytocin increases group-serving dishonesty. A double-blind, placebo-controlled experiment allowing individuals to lie privately and anonymously to benefit themselves and fellow group members showed that healthy males (n = 60) receiving intranasal oxytocin, rather than placebo, lied more to benefit their group, and did so faster, yet did not necessarily do so because they expected reciprocal dishonesty from fellow group members. Treatment effects emerged when lying had financial consequences and money could be gained; when losses were at stake, individuals in placebo and oxytocin conditions lied to similar degrees. In a control condition (n = 60) in which dishonesty only benefited participants themselves, but not fellow group members, oxytocin did not influence lying. Together, these findings fit a functional perspective on morality revealing dishonesty to be plastic and rooted in evolved neurobiological circuitries, and align with work showing that oxytocin shifts the decision-maker’s focus from self to group interests. These findings highlight the role of bonding and cooperation in shaping dishonesty, providing insight into when and why collaboration turns into corruption. PMID:24706799
Oxytocin promotes group-serving dishonesty.
Shalvi, Shaul; De Dreu, Carsten K W
2014-04-15
To protect and promote the well-being of others, humans may bend the truth and behave unethically. Here we link such tendencies to oxytocin, a neuropeptide known to promote affiliation and cooperation with others. Using a simple coin-toss prediction task in which participants could dishonestly report their performance levels to benefit their group's outcome, we tested the prediction that oxytocin increases group-serving dishonesty. A double-blind, placebo-controlled experiment allowing individuals to lie privately and anonymously to benefit themselves and fellow group members showed that healthy males (n = 60) receiving intranasal oxytocin, rather than placebo, lied more to benefit their group, and did so faster, yet did not necessarily do so because they expected reciprocal dishonesty from fellow group members. Treatment effects emerged when lying had financial consequences and money could be gained; when losses were at stake, individuals in placebo and oxytocin conditions lied to similar degrees. In a control condition (n = 60) in which dishonesty only benefited participants themselves, but not fellow group members, oxytocin did not influence lying. Together, these findings fit a functional perspective on morality revealing dishonesty to be plastic and rooted in evolved neurobiological circuitries, and align with work showing that oxytocin shifts the decision-maker's focus from self to group interests. These findings highlight the role of bonding and cooperation in shaping dishonesty, providing insight into when and why collaboration turns into corruption.
Goldman, L Elizabeth; Walker, Rod; Hubbard, Rebecca; Kerlikowske, Karla
2013-04-01
Whether timeliness of follow-up after abnormal mammography differs at facilities serving vulnerable populations, such as women with limited education or income, in rural areas, and racial/ethnic minorities is unknown. We examined receipt of diagnostic evaluation after abnormal mammography using 1998-2006 Breast Cancer Surveillance Consortium-linked Medicare claims. We compared whether time to recommended breast imaging or biopsy depended on whether women attended facilities serving vulnerable populations. We characterized a facility by the proportion of mammograms performed on women with limited education or income, in rural areas, or racial/ethnic minorities. We analyzed 30,874 abnormal screening examinations recommended for follow-up imaging across 142 facilities and 10,049 abnormal diagnostic examinations recommended for biopsy across 114 facilities. Women at facilities serving populations with less education or more racial/ethnic minorities had lower rates of follow-up imaging (4%-5% difference, P<0.05), and women at facilities serving more rural and low-income populations had lower rates of biopsy (4%-5% difference, P<0.05). Women undergoing biopsy at facilities serving vulnerable populations had longer times until biopsy than those at facilities serving nonvulnerable populations (21.6 vs. 15.6 d; 95% confidence interval for mean difference 4.1-7.7). The proportion of women receiving recommended imaging within 11 months and biopsy within 3 months varied across facilities (interquartile range, 85.5%-96.5% for imaging and 79.4%-87.3% for biopsy). Among Medicare recipients, follow-up rates were slightly lower at facilities serving vulnerable populations, and among those women who returned for diagnostic evaluation, time to follow-up was slightly longer at facilities that served vulnerable population. Interventions should target variability in follow-up rates across facilities, and evaluate effectiveness particularly at facilities serving vulnerable populations.
Structure and function of wood
Alex Wiedenhoeft
2010-01-01
Wood is a complex biological structure, a composite of many chemistries and cell types acting together to serve the needs of a living plant. Attempting to understand wood in the context of wood technology, we have often overlooked the key and basic fact that wood evolved over the course of millions of years to serve three main functions in plantsâ conduction of water...
Function in context: why American and Trinidadian young and older adults remember the personal past.
Alea, Nicole; Bluck, Susan; Ali, Sideeka
2015-01-01
Multiple and interacting contextual (culture, life phase) and person-specific predictors (i.e., personality, tendency to think-talk about the past) of the functions of autobiographical memory were examined using the Thinking about Life Experiences Scale. American (N = 174) and Trinidadian (N = 182) young and older adults self-reported how frequently they remembered the personal past to serve self, social and directive functions, how often they thought and talked about their past overall, and completed a measure of trait personality. Independent contextual and person-specific predictors were found for using memory to serve a social-bonding function: Americans, young adults, those higher in extraversion, lower in conscientiousness and individuals who frequently think and talk about the past more often use autobiographical memory for social bonding. Across cultures, younger adults report more frequently using memory to serve all three functions, whereas Trinidadians who think more often about the past compared with those who reflect less often are more likely to use it for self and directive functions. Findings are discussed in terms of the individual's embeddedness in cultural and life phase contexts when remembering.
Flexible link functions in nonparametric binary regression with Gaussian process priors.
Li, Dan; Wang, Xia; Lin, Lizhen; Dey, Dipak K
2016-09-01
In many scientific fields, it is a common practice to collect a sequence of 0-1 binary responses from a subject across time, space, or a collection of covariates. Researchers are interested in finding out how the expected binary outcome is related to covariates, and aim at better prediction in the future 0-1 outcomes. Gaussian processes have been widely used to model nonlinear systems; in particular to model the latent structure in a binary regression model allowing nonlinear functional relationship between covariates and the expectation of binary outcomes. A critical issue in modeling binary response data is the appropriate choice of link functions. Commonly adopted link functions such as probit or logit links have fixed skewness and lack the flexibility to allow the data to determine the degree of the skewness. To address this limitation, we propose a flexible binary regression model which combines a generalized extreme value link function with a Gaussian process prior on the latent structure. Bayesian computation is employed in model estimation. Posterior consistency of the resulting posterior distribution is demonstrated. The flexibility and gains of the proposed model are illustrated through detailed simulation studies and two real data examples. Empirical results show that the proposed model outperforms a set of alternative models, which only have either a Gaussian process prior on the latent regression function or a Dirichlet prior on the link function. © 2015, The International Biometric Society.
Flexible Link Functions in Nonparametric Binary Regression with Gaussian Process Priors
Li, Dan; Lin, Lizhen; Dey, Dipak K.
2015-01-01
Summary In many scientific fields, it is a common practice to collect a sequence of 0-1 binary responses from a subject across time, space, or a collection of covariates. Researchers are interested in finding out how the expected binary outcome is related to covariates, and aim at better prediction in the future 0-1 outcomes. Gaussian processes have been widely used to model nonlinear systems; in particular to model the latent structure in a binary regression model allowing nonlinear functional relationship between covariates and the expectation of binary outcomes. A critical issue in modeling binary response data is the appropriate choice of link functions. Commonly adopted link functions such as probit or logit links have fixed skewness and lack the flexibility to allow the data to determine the degree of the skewness. To address this limitation, we propose a flexible binary regression model which combines a generalized extreme value link function with a Gaussian process prior on the latent structure. Bayesian computation is employed in model estimation. Posterior consistency of the resulting posterior distribution is demonstrated. The flexibility and gains of the proposed model are illustrated through detailed simulation studies and two real data examples. Empirical results show that the proposed model outperforms a set of alternative models, which only have either a Gaussian process prior on the latent regression function or a Dirichlet prior on the link function. PMID:26686333
Real-time interactive tractography analysis for multimodal brain visualization tool: MultiXplore
NASA Astrophysics Data System (ADS)
Bakhshmand, Saeed M.; de Ribaupierre, Sandrine; Eagleson, Roy
2017-03-01
Most debilitating neurological disorders can have anatomical origins. Yet unlike other body organs, the anatomy alone cannot easily provide an understanding of brain functionality. In fact, addressing the challenge of linking structural and functional connectivity remains in the frontiers of neuroscience. Aggregating multimodal neuroimaging datasets may be critical for developing theories that span brain functionality, global neuroanatomy and internal microstructures. Functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) are main such techniques that are employed to investigate the brain under normal and pathological conditions. FMRI records blood oxygenation level of the grey matter (GM), whereas DTI is able to reveal the underlying structure of the white matter (WM). Brain global activity is assumed to be an integration of GM functional hubs and WM neural pathways that serve to connect them. In this study we developed and evaluated a two-phase algorithm. This algorithm is employed in a 3D interactive connectivity visualization framework and helps to accelerate clustering of virtual neural pathways. In this paper, we will detail an algorithm that makes use of an index-based membership array formed for a whole brain tractography file and corresponding parcellated brain atlas. Next, we demonstrate efficiency of the algorithm by measuring required times for extracting a variety of fiber clusters, which are chosen in such a way to resemble all sizes probable output data files that algorithm will generate. The proposed algorithm facilitates real-time visual inspection of neuroimaging data to further the discovery in structure-function relationship of the brain networks.
Barotto, Antonio José; Fernandez, María Elena; Gyenge, Javier; Meyra, Ariel; Martinez-Meier, Alejandro; Monteoliva, Silvia
2016-12-01
The relationship between hydraulic specific conductivity (k s ) and vulnerability to cavitation (VC) with size and number of vessels has been studied in many angiosperms. However, few of the studies link other cell types (vasicentric tracheids (VT), fibre-tracheids, parenchyma) with these hydraulic functions. Eucalyptus is one of the most important genera in forestry worldwide. It exhibits a complex wood anatomy, with solitary vessels surrounded by VT and parenchyma, which could serve as a good model to investigate the functional role of the different cell types in xylem functioning. Wood anatomy (several traits of vessels, VT, fibres and parenchyma) in conjunction with maximum k s and VC was studied in adult trees of commercial species with medium-to-high wood density (Eucalyptus globulus Labill., Eucalyptus viminalis Labill. and Eucalyptus camaldulensis Dehnh.). Traits of cells accompanying vessels presented correlations with functional variables suggesting that they contribute to both increasing connectivity between adjacent vessels-and, therefore, to xylem conduction efficiency-and decreasing the probability of embolism propagation into the tissue, i.e., xylem safety. All three species presented moderate-to-high resistance to cavitation (mean P 50 values = -2.4 to -4.2 MPa) with no general trade-off between efficiency and safety at the interspecific level. The results in these species do not support some well-established hypotheses of the functional meaning of wood anatomy. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
RAId_aPS: MS/MS Analysis with Multiple Scoring Functions and Spectrum-Specific Statistics
Alves, Gelio; Ogurtsov, Aleksey Y.; Yu, Yi-Kuo
2010-01-01
Statistically meaningful comparison/combination of peptide identification results from various search methods is impeded by the lack of a universal statistical standard. Providing an -value calibration protocol, we demonstrated earlier the feasibility of translating either the score or heuristic -value reported by any method into the textbook-defined -value, which may serve as the universal statistical standard. This protocol, although robust, may lose spectrum-specific statistics and might require a new calibration when changes in experimental setup occur. To mitigate these issues, we developed a new MS/MS search tool, RAId_aPS, that is able to provide spectrum-specific -values for additive scoring functions. Given a selection of scoring functions out of RAId score, K-score, Hyperscore and XCorr, RAId_aPS generates the corresponding score histograms of all possible peptides using dynamic programming. Using these score histograms to assign -values enables a calibration-free protocol for accurate significance assignment for each scoring function. RAId_aPS features four different modes: (i) compute the total number of possible peptides for a given molecular mass range, (ii) generate the score histogram given a MS/MS spectrum and a scoring function, (iii) reassign -values for a list of candidate peptides given a MS/MS spectrum and the scoring functions chosen, and (iv) perform database searches using selected scoring functions. In modes (iii) and (iv), RAId_aPS is also capable of combining results from different scoring functions using spectrum-specific statistics. The web link is http://www.ncbi.nlm.nih.gov/CBBresearch/Yu/raid_aps/index.html. Relevant binaries for Linux, Windows, and Mac OS X are available from the same page. PMID:21103371
Biological factors of natural and artificial ecosystems stable (unstable) functioning
NASA Astrophysics Data System (ADS)
Pechurkin, Nikolai S.
The problem of sustainable development of humanity on Earth and the problem of supporting human life in space have the same scientific and methodological bases. The key to solve both problems is a long term maintenance of balanced material cycle. As a whole, natural or artificial ecosystems are to be more closed than open, but their elements (links of systems) are to be substantially open in interactions with each other. Prolonged stable interactions of different links have to have unique joint results - closed material cycling or biotic turnover. It is necessary to include, at least, three types of main links into any system to support real material cycling: producers, consumers, reducers. Producer links are now under studies in many laboratories. It is evident that the higher productivity of link, the lower link stability. Especially, it concerns with parasite impact to plants. As usual, artificial ecosystems are more simple (incomplete) than natural ecosystems, sometimes, they have not enough links for prolonged stable functioning. For example, life support system for space flight can be incomplete in consumer link, having only some crew persons, instead of interacting populations of consumers. As for reducer link, it is necessary to "organize" a special coordinated work of microbial biocenoses to fulfill proper cycling. Possible evolution of links, their self development is a matter of special attention for the maintenance of prolonged stable functioning. It's the most danger for systems with populations of quickly reproducing, so-called, R - strategists, according to symbols of logistic equation. From another side, quick reproduction of R - strategists is able to increase artificial ecosystems and their links functioning. After some damages of system, R - strategist's link can be quickly "self repaired" up to level of normal functioning. Some experimental data of this kind and mathematical models are to be discussed in the paper. This work is supported by grant, Yenissey, 07-04-96806
Adolescent Overweight and Obesity: Links to Socioeconomic Status and Fruit and Vegetable Intakes
You, Jihyun; Choo, Jina
2016-01-01
Whether adolescent overweight/obesity is linked to socioeconomic status (SES) and fruit and vegetable (F/V) intakes has not been confirmed. We aimed to determine whether there is an association between SES and adolescent overweight/obesity and to test the mediating effect of F/V intakes. This cross-sectional study included the data of 63,111 adolescents extracted from the 2013 Korea Youth Risk Behavior Web-based Survey. Overweight/obesity was defined as a body mass index ≥ 85th percentile, while F/V intakes were categorized as high (recommended levels: ≥1 fruit serving and ≥3 vegetable servings per day) versus low. Among girls, low SES (beta = 0.50, p < 0.001) and F/V intakes (beta = −0.17, p = 0.038) were both significantly associated with overweight/obesity; the former association was significantly mediated by F/V intakes (Sobel test: z = 2.00, p = 0.046). Among boys, neither SES nor F/V intakes was significantly associated with overweight/obesity. Adolescent overweight/obesity was significantly linked to low SES and F/V intakes among girls only; low SES indirectly increased the risk of overweight/obesity via low F/V intakes. Therefore, promoting F/V intakes for socially disadvantaged girls should be prioritized as a population-based strategy for preventing adolescent overweight/obesity in South Korea. PMID:27005654
Data Acquisition Backbone Core DABC release v1.0
NASA Astrophysics Data System (ADS)
Adamczewski-Musch, J.; Essel, H. G.; Kurz, N.; Linev, S.
2010-04-01
The Data Acquisition Backbone Core (DABC) is a general purpose software framework designed for the implementation of a wide-range of data acquisition systems - from various small detector test beds to high performance systems. DABC consists of a compact data-flow kernel and a number of plug-ins for various functional components like data inputs, device drivers, user functional modules and applications. DABC provides configurable components for implementing event building over fast networks like InfiniBand or Gigabit Ethernet. A generic Java GUI provides the dynamic control and visualization of control parameters and commands, provided by DIM servers. A first set of application plug-ins has been implemented to use DABC as event builder for the front-end components of the GSI standard DAQ system MBS (Multi Branch System). Another application covers the connection to DAQ readout chains from detector front-end boards (N-XYTER) linked to read-out controller boards (ROC) over UDP into DABC for event building, archiving and data serving. This was applied for data taking in the September 2008 test beamtime for the CBM experiment at GSI. DABC version 1.0 is released and available from the website.
The specific features of methionine biosynthesis and metabolism in plants
Ravanel, Stéphane; Gakière, Bertrand; Job, Dominique; Douce, Roland
1998-01-01
Plants, unlike other higher eukaryotes, possess all the necessary enzymatic equipment for de novo synthesis of methionine, an amino acid that supports additional roles than simply serving as a building block for protein synthesis. This is because methionine is the immediate precursor of S-adenosylmethionine (AdoMet), which plays numerous roles of being the major methyl-group donor in transmethylation reactions and an intermediate in the biosynthesis of polyamines and of the phytohormone ethylene. In addition, AdoMet has regulatory function in plants behaving as an allosteric activator of threonine synthase. Among the AdoMet-dependent reactions occurring in plants, methylation of cytosine residues in DNA has raised recent interest because impediment of this function alters plant morphology and induces homeotic alterations in flower organs. Also, AdoMet metabolism seems somehow implicated in plant growth via an as yet fully understood link with plant-growth hormones such as cytokinins and auxin and in plant pathogen interactions. Because of this central role in cellular metabolism, a precise knowledge of the biosynthetic pathways that are responsible for homeostatic regulation of methionine and AdoMet in plants has practical implications, particularly in herbicide design. PMID:9636232
Comparison of sea turtle thrombocyte aggregation to human platelet aggregation in whole blood.
Soslau, Gerald; Prest, Phillip J; Class, Reiner; George, Robert; Paladino, Frank; Violetta, Gary
2005-11-01
The endangered sea turtles are living "fossils" that afford us an opportunity to study the hemostatic process as it likely existed millions of years ago. There are essentially no data about turtle thrombocyte aggregation prior to our studies. Thrombocytes are nucleated cells that serve the same hemostatic functions as the anucleated mammalian platelet. Sea turtle thrombocytes aggregate in response to collagen and beta-thrombin. Ristocetin induces an agglutination/aggregation response indicating the presence of a von Willebrand-like receptor, GPIb, found in all mammalian platelets. Samples treated with alpha-thrombin plus gamma-thrombin followed by ristocetin results in a rapid, stronger response than ristocetin alone. These responses are inhibited by the RGDS peptide that blocks fibrinogen cross-linking of mammalian platelets via the fibrinogen receptor, GPIIb/IIIa. Three platelet-like proteins, GPIb, GPIIb/IIIa and P-selection are detected in sea turtle thrombocytes by fluorescence activated cell sorting. Turtle thrombocytes do not respond to ADP, epinephrine, serotonin, thromboxane A2 mimetic, U46619, trypsin, or alpha-thrombin and gamma-thrombin added alone. Comparison of hemostasis in sea turtles to other vertebrates could provide a framework for understanding the structure/function and evolution of these pathways and their individual components.
Live imaging of rat embryos with Doppler swept-source optical coherence tomography
NASA Astrophysics Data System (ADS)
Larina, Irina V.; Furushima, Kenryo; Dickinson, Mary E.; Behringer, Richard R.; Larin, Kirill V.
2009-09-01
The rat has long been considered an excellent system to study mammalian embryonic cardiovascular physiology, but has lacked the extensive genetic tools available in the mouse to be able to create single gene mutations. However, the recent establishment of rat embryonic stem cell lines facilitates the generation of new models in the rat embryo to link changes in physiology with altered gene function to define the underlying mechanisms behind congenital cardiovascular birth defects. Along with the ability to create new rat genotypes there is a strong need for tools to analyze phenotypes with high spatial and temporal resolution. Doppler OCT has been previously used for 3-D structural analysis and blood flow imaging in other model species. We use Doppler swept-source OCT for live imaging of early postimplantation rat embryos. Structural imaging is used for 3-D reconstruction of embryo morphology and dynamic imaging of the beating heart and vessels, while Doppler-mode imaging is used to visualize blood flow. We demonstrate that Doppler swept-source OCT can provide essential information about the dynamics of early rat embryos and serve as a basis for a wide range of studies on functional evaluation of rat embryo physiology.
Live imaging of rat embryos with Doppler swept-source optical coherence tomography
Larina, Irina V.; Furushima, Kenryo; Dickinson, Mary E.; Behringer, Richard R.; Larin, Kirill V.
2009-01-01
The rat has long been considered an excellent system to study mammalian embryonic cardiovascular physiology, but has lacked the extensive genetic tools available in the mouse to be able to create single gene mutations. However, the recent establishment of rat embryonic stem cell lines facilitates the generation of new models in the rat embryo to link changes in physiology with altered gene function to define the underlying mechanisms behind congenital cardiovascular birth defects. Along with the ability to create new rat genotypes there is a strong need for tools to analyze phenotypes with high spatial and temporal resolution. Doppler OCT has been previously used for 3-D structural analysis and blood flow imaging in other model species. We use Doppler swept-source OCT for live imaging of early postimplantation rat embryos. Structural imaging is used for 3-D reconstruction of embryo morphology and dynamic imaging of the beating heart and vessels, while Doppler-mode imaging is used to visualize blood flow. We demonstrate that Doppler swept-source OCT can provide essential information about the dynamics of early rat embryos and serve as a basis for a wide range of studies on functional evaluation of rat embryo physiology. PMID:19895102
NASA Technical Reports Server (NTRS)
Adams, Catherine A.; Murdoch, Jennifer L.; Consiglio, Maria C.; WIlliams, Daniel M.
2005-01-01
One objective of the Small Aircraft Transportation System (SATS) Higher Volume Operations (HVO) project is to increase the capacity and utilization of small non-towered, non-radar equipped airports by transferring traffic management activities to an automated Airport Management Module (AMM) and separation responsibilities to general aviation (GA) pilots. Implementation of this concept required the development of a research Multi-Function Display (MFD) to support the interactive communications between pilots and the AMM. The interface also had to accommodate traffic awareness, self-separation, and spacing tasks through dynamic messaging and symbology for flight path conformance and conflict detection and alerting (CDA). The display served as the mechanism to support the examination of the viability of executing instrument operations designed for SATS designated airports. Results of simulation and flight experiments conducted at the National Aeronautics and Space Administration's (NASA) Langley Research Center indicate that the concept, as facilitated by the research MFD, did not increase pilots subjective workload levels or reduce their situation awareness (SA). Post-test usability assessments revealed that pilots preferred using the enhanced MFD to execute flight procedures, reporting improved SA over conventional instrument flight rules (IFR) procedures.
A robust neuromuscular system protects rat and human skeletal muscle from sarcopenia.
Pannérec, Alice; Springer, Margherita; Migliavacca, Eugenia; Ireland, Alex; Piasecki, Mathew; Karaz, Sonia; Jacot, Guillaume; Métairon, Sylviane; Danenberg, Esther; Raymond, Frédéric; Descombes, Patrick; McPhee, Jamie S; Feige, Jerome N
2016-04-01
Declining muscle mass and function is one of the main drivers of loss of independence in the elderly. Sarcopenia is associated with numerous cellular and endocrine perturbations, and it remains challenging to identify those changes that play a causal role and could serve as targets for therapeutic intervention. In this study, we uncovered a remarkable differential susceptibility of certain muscles to age-related decline. Aging rats specifically lose muscle mass and function in the hindlimbs, but not in the forelimbs. By performing a comprehensive comparative analysis of these muscles, we demonstrate that regional susceptibility to sarcopenia is dependent on neuromuscular junction fragmentation, loss of motoneuron innervation, and reduced excitability. Remarkably, muscle loss in elderly humans also differs in vastus lateralis and tibialis anterior muscles in direct relation to neuromuscular dysfunction. By comparing gene expression in susceptible and non-susceptible muscles, we identified a specific transcriptomic signature of neuromuscular impairment. Importantly, differential molecular profiling of the associated peripheral nerves revealed fundamental changes in cholesterol biosynthetic pathways. Altogether our results provide compelling evidence that susceptibility to sarcopenia is tightly linked to neuromuscular decline in rats and humans, and identify dysregulation of sterol metabolism in the peripheral nervous system as an early event in this process.
DaMab-2: Anti-Human DGKα Monoclonal Antibody for Immunocytochemistry.
Nakano, Tomoyuki; Ogasawara, Satoshi; Tanaka, Toshiaki; Hozumi, Yasukazu; Mizuno, Satoru; Satoh, Eri; Sakane, Fumio; Okada, Naoki; Taketomi, Akinobu; Honma, Ryusuke; Nakamura, Takuro; Saidoh, Noriko; Yanaka, Miyuki; Itai, Shunsuke; Handa, Saori; Chang, Yao-Wen; Yamada, Shinji; Kaneko, Mika K; Kato, Yukinari; Goto, Kaoru
2017-08-01
Diacylglycerol kinase (DGK) is responsible for the enzymatic conversion of diacylglycerol to phosphatidic acid. Since both diacylglycerol and phosphatidic acid serve as signaling molecules, DGK is regarded as a hub between diacylglycerol-mediated and phosphatidic acid-mediated signaling. One of the 10 DGK isozymes, DGKα, is shown to be involved in T cell function. Transfection studies using tagged expression vectors revealed that DGKα localizes to the cytoplasm and nucleus and translocates to the plasma membrane in response to T cell receptor stimulation. However, a limited number of studies reported the localization of native protein of DGKα in tissues and cells. In this study, we immunized mice with recombinant DGKα and developed several anti-DGKα monoclonal antibodies (mAbs). One of the established anti-DGKα mAbs is a clone DaMab-2 (mouse IgG 1 , kappa). In enzyme-linked immunosorbent assay, DaMab-2 recognized only DGKα, and did not react with the other isozymes, such as DGKγ, DGKζ, DGKη, and DGKδ. Importantly, DaMab-2 is very useful in immunocytochemical analysis of human cultured cells, indicating that DaMab-2 is advantageous to analyze the localization and function of DGKα.
NF-κB, inflammation, immunity and cancer: coming of age.
Taniguchi, Koji; Karin, Michael
2018-05-01
Fourteen years have passed since nuclear factor-κB (NF-κB) was first shown to serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. The young field of inflammation and cancer has now come of age, and inflammation has been recognized by the broad cancer research community as a hallmark and cause of cancer. Here, we discuss how the initial discovery of a role for NF-κB in linking inflammation and cancer led to an improved understanding of tumour-elicited inflammation and its effects on anticancer immunity.
Information technology and behavioral medicine: impact on autism treatment & research.
Oberleitner, Ron; Laxminarayan, Swamy
2004-01-01
Families, clinicians and researchers involved with varying neurological disorders face amazing challenges to understand, treat, and assist the people they are serving. Autism brings unique challenges and serves as an important model for the application of important concepts in information technology and telemedicine. The rising incidence of autism with limited professional resources has led to more consideration for using information technology and related specialties to link families and professionals, and to implement strategies which implement information technology to improve the outcomes for individuals with autism and their families. These are reviewed in context of the unique health, education, and the research issues facing those dealing with autism.
Zhong, Chunmei; Xu, Hao; Ye, Siting; Wang, Shiyi; Li, Lingfei; Zhang, Shengchun; Wang, Xiaojing
2015-11-01
The DELLA protein REPRESSOR OF ga1-3-LIKE2 (RGL2) plays an important role in seed germination under different conditions through a number of transcription factors. However, the functions of the structural genes associated with RGL2-regulated germination are less defined. Here, we report the role of an Arabidopsis (Arabidopsis thaliana) cell wall-localized protein, Gibberellic Acid-Stimulated Arabidopsis6 (AtGASA6), in functionally linking RGL2 and a cell wall loosening expansin protein (Arabidopsis expansin A1 [AtEXPA1]), resulting in the control of embryonic axis elongation and seed germination. AtGASA6-overexpressing seeds showed precocious germination, whereas transfer DNA and RNA interference mutant seeds displayed delayed seed germination under abscisic acid, paclobutrazol, and glucose (Glc) stress conditions. The differences in germination rates resulted from corresponding variation in cell elongation in the hypocotyl-radicle transition region of the embryonic axis. AtGASA6 was down-regulated by RGL2, GLUCOSE INSENSITIVE2, and ABSCISIC ACID-INSENSITIVE5 genes, and loss of AtGASA6 expression in the gasa6 mutant reversed the insensitivity shown by the rgl2 mutant to paclobutrazol and the gin2 mutant to Glc-induced stress, suggesting that it is involved in regulating both the gibberellin and Glc signaling pathways. Furthermore, it was found that the promotion of seed germination and length of embryonic axis by AtGASA6 resulted from a promotion of cell elongation at the embryonic axis mediated by AtEXPA1. Taken together, the data indicate that AtGASA6 links RGL2 and AtEXPA1 functions and plays a role as an integrator of gibberellin, abscisic acid, and Glc signaling, resulting in the regulation of seed germination through a promotion of cell elongation. © 2015 American Society of Plant Biologists. All Rights Reserved.
Ferris, Laura J; Jetten, Jolanda; Johnstone, Melissa; Girdham, Elise; Parsell, Cameron; Walter, Zoe C
2016-01-01
Frontline employees in the helping professions often perform their duties against a difficult backdrop, including a complex client base and ongoing themes of crisis, suffering, and distress. These factors combine to create an environment in which workers are vulnerable to workplace stress and burnout. The present study tested two models to understand how frontline workers in the homelessness sector deal with the suffering of their clients. First, we examined whether relationships between suffering and workplace functioning (job satisfaction and burnout) would be mediated by organizational identification. Second, we examined whether emotional distance from clients (i.e., infrahumanization, measured as reduced attribution of secondary emotions) would predict improved workplace functioning (less burnout and greater job satisfaction), particularly when client contact is high. The study involved a mixed-methods design comprising interview (N = 26) and cross-sectional survey data (N = 60) with a sample of frontline staff working in the homelessness sector. Participants were asked to rate the level of client suffering and attribute emotions in a hypothetical client task, and to complete questionnaire measures of burnout, job satisfaction, and organizational identification. We found no relationships between secondary emotion attribution and burnout or satisfaction. Instead, we found that perceiving higher client suffering was linked with higher job satisfaction and lower burnout. Mediation analyses revealed a mediating role for identification, such that recognizing suffering predicted greater identification with the organization, which fully mediated the relationship between suffering and job satisfaction, and also between suffering and burnout. Qualitative analysis of interview data also resonated with this conceptualization. We introduce this novel finding as the 'Florence Nightingale effect'. With this sample drawn from the homelessness sector, we provide preliminary evidence for the proposition that recognizing others' suffering may serve to increase job satisfaction and reduce burnout - by galvanizing organizational identification.
Sequence-Specific Targeting of Dosage Compensation in Drosophila Favors an Active Chromatin Context
Gelbart, Marnie; Tolstorukov, Michael Y.; Plachetka, Annette; Kharchenko, Peter V.; Jung, Youngsook L.; Gorchakov, Andrey A.; Larschan, Erica; Gu, Tingting; Minoda, Aki; Riddle, Nicole C.; Schwartz, Yuri B.; Elgin, Sarah C. R.; Karpen, Gary H.; Pirrotta, Vincenzo; Kuroda, Mitzi I.; Park, Peter J.
2012-01-01
The Drosophila MSL complex mediates dosage compensation by increasing transcription of the single X chromosome in males approximately two-fold. This is accomplished through recognition of the X chromosome and subsequent acetylation of histone H4K16 on X-linked genes. Initial binding to the X is thought to occur at “entry sites” that contain a consensus sequence motif (“MSL recognition element” or MRE). However, this motif is only ∼2 fold enriched on X, and only a fraction of the motifs on X are initially targeted. Here we ask whether chromatin context could distinguish between utilized and non-utilized copies of the motif, by comparing their relative enrichment for histone modifications and chromosomal proteins mapped in the modENCODE project. Through a comparative analysis of the chromatin features in male S2 cells (which contain MSL complex) and female Kc cells (which lack the complex), we find that the presence of active chromatin modifications, together with an elevated local GC content in the surrounding sequences, has strong predictive value for functional MSL entry sites, independent of MSL binding. We tested these sites for function in Kc cells by RNAi knockdown of Sxl, resulting in induction of MSL complex. We show that ectopic MSL expression in Kc cells leads to H4K16 acetylation around these sites and a relative increase in X chromosome transcription. Collectively, our results support a model in which a pre-existing active chromatin environment, coincident with H3K36me3, contributes to MSL entry site selection. The consequences of MSL targeting of the male X chromosome include increase in nucleosome lability, enrichment for H4K16 acetylation and JIL-1 kinase, and depletion of linker histone H1 on active X-linked genes. Our analysis can serve as a model for identifying chromatin and local sequence features that may contribute to selection of functional protein binding sites in the genome. PMID:22570616
Ferris, Laura J.; Jetten, Jolanda; Johnstone, Melissa; Girdham, Elise; Parsell, Cameron; Walter, Zoe C.
2016-01-01
Frontline employees in the helping professions often perform their duties against a difficult backdrop, including a complex client base and ongoing themes of crisis, suffering, and distress. These factors combine to create an environment in which workers are vulnerable to workplace stress and burnout. The present study tested two models to understand how frontline workers in the homelessness sector deal with the suffering of their clients. First, we examined whether relationships between suffering and workplace functioning (job satisfaction and burnout) would be mediated by organizational identification. Second, we examined whether emotional distance from clients (i.e., infrahumanization, measured as reduced attribution of secondary emotions) would predict improved workplace functioning (less burnout and greater job satisfaction), particularly when client contact is high. The study involved a mixed-methods design comprising interview (N = 26) and cross-sectional survey data (N = 60) with a sample of frontline staff working in the homelessness sector. Participants were asked to rate the level of client suffering and attribute emotions in a hypothetical client task, and to complete questionnaire measures of burnout, job satisfaction, and organizational identification. We found no relationships between secondary emotion attribution and burnout or satisfaction. Instead, we found that perceiving higher client suffering was linked with higher job satisfaction and lower burnout. Mediation analyses revealed a mediating role for identification, such that recognizing suffering predicted greater identification with the organization, which fully mediated the relationship between suffering and job satisfaction, and also between suffering and burnout. Qualitative analysis of interview data also resonated with this conceptualization. We introduce this novel finding as the ‘Florence Nightingale effect’. With this sample drawn from the homelessness sector, we provide preliminary evidence for the proposition that recognizing others’ suffering may serve to increase job satisfaction and reduce burnout – by galvanizing organizational identification. PMID:26858670
Zhong, Chunmei; Xu, Hao; Ye, Siting; Wang, Shiyi; Li, Lingfei; Zhang, Shengchun; Wang, Xiaojing
2015-01-01
The DELLA protein REPRESSOR OF ga1-3-LIKE2 (RGL2) plays an important role in seed germination under different conditions through a number of transcription factors. However, the functions of the structural genes associated with RGL2-regulated germination are less defined. Here, we report the role of an Arabidopsis (Arabidopsis thaliana) cell wall-localized protein, Gibberellic Acid-Stimulated Arabidopsis6 (AtGASA6), in functionally linking RGL2 and a cell wall loosening expansin protein (Arabidopsis expansin A1 [AtEXPA1]), resulting in the control of embryonic axis elongation and seed germination. AtGASA6-overexpressing seeds showed precocious germination, whereas transfer DNA and RNA interference mutant seeds displayed delayed seed germination under abscisic acid, paclobutrazol, and glucose (Glc) stress conditions. The differences in germination rates resulted from corresponding variation in cell elongation in the hypocotyl-radicle transition region of the embryonic axis. AtGASA6 was down-regulated by RGL2, GLUCOSE INSENSITIVE2, and ABSCISIC ACID-INSENSITIVE5 genes, and loss of AtGASA6 expression in the gasa6 mutant reversed the insensitivity shown by the rgl2 mutant to paclobutrazol and the gin2 mutant to Glc-induced stress, suggesting that it is involved in regulating both the gibberellin and Glc signaling pathways. Furthermore, it was found that the promotion of seed germination and length of embryonic axis by AtGASA6 resulted from a promotion of cell elongation at the embryonic axis mediated by AtEXPA1. Taken together, the data indicate that AtGASA6 links RGL2 and AtEXPA1 functions and plays a role as an integrator of gibberellin, abscisic acid, and Glc signaling, resulting in the regulation of seed germination through a promotion of cell elongation. PMID:26400990
Cytoplasmic RNA Granules in Somatic Maintenance.
Moujaber, Ossama; Stochaj, Ursula
2018-05-30
Cytoplasmic RNA granules represent subcellular compartments that are enriched in protein-bound RNA species. RNA granules are produced by evolutionary divergent eukaryotes, including yeast, mammals, and plants. The functions of cytoplasmic RNA granules differ widely. They are dictated by the cell type and physiological state, which in turn is determined by intrinsic cell properties and environmental factors. RNA granules provide diverse cellular functions. However, all of the granules contribute to aspects of RNA metabolism. This is exemplified by transcription, RNA storage, silencing, and degradation, as well as mRNP remodeling and regulated translation. Several forms of cytoplasmic mRNA granules are linked to normal physiological processes. For instance, they may coordinate protein synthesis and thereby serve as posttranscriptional "operons". RNA granules also participate in cytoplasmic mRNA trafficking, a process particularly well understood for neurons. Many forms of RNA granules support the preservation of somatic cell performance under normal and stress conditions. On the other hand, severe insults or disease can cause the formation and persistence of RNA granules that contribute to cellular dysfunction, especially in the nervous system. Neurodegeneration and many other diseases linked to RNA granules are associated with aging. Nevertheless, information related to the impact of aging on the various types of RNA granules is presently very limited. This review concentrates on cytoplasmic RNA granules and their role in somatic cell maintenance. We summarize the current knowledge on different types of RNA granules in the cytoplasm, their assembly and function under normal, stress, or disease conditions. Specifically, we discuss processing bodies, neuronal granules, stress granules, and other less characterized cytoplasmic RNA granules. Our focus is primarily on mammalian and yeast models, because they have been critical to unravel the physiological role of various RNA granules. RNA granules in plants and pathogens are briefly described. We conclude our viewpoint by summarizing the emerging concepts for RNA granule biology and the open questions that need to be addressed in future studies. © 2018 S. Karger AG, Basel.
Patently Obvious: The Place for Patents in Information Literacy in the Sciences
ERIC Educational Resources Information Center
MacMillan, Don
2005-01-01
Patents are an underutilized source of scientific information, particularly in the life and health sciences. Patents and patent applications usually contain the first disclosure of new technologies and processes and serve to link theory with practice, providing "real world" examples of the application of scientific research. Increasingly,…
ERIC Educational Resources Information Center
Lawrence, Heather J.; Mullin, Christopher M.; Horton, David, Jr.
2009-01-01
Collegiate athletic programs have often been referred to as the "front porch" of an institution. Coaches, athletic teams, student athletes, and athletic department staff serve as a "link between the immediate campus family and the larger community. It is this front-porch principle that makes managing intercollegiate athletics a unique and…
Geotagging Digital Collections: BeaverTracks Mobile Project
ERIC Educational Resources Information Center
Griggs, Kim
2011-01-01
BeaverTracks Historical Locations and Walking Tour is a mobile project at Oregon State University (OSU), where the author serves as programmer/analyst. It connects the past to the present by linking historic images to current campus locations. The goal of BeaverTracks is to showcase and bring attention to OSU Libraries' digital collections as well…
ERIC Educational Resources Information Center
Marriott, Pru
2009-01-01
According to the Quality Assurance Agency, "Assessment describes any processes that appraise an individual's knowledge, understanding, abilities or skills", and is inextricably linked to a course or programme's intended learning outcomes. It also has a fundamental effect on students' learning where it serves a variety of purposes including…
Materials for Serving Homeless Adult Learners. A Resource Guide.
ERIC Educational Resources Information Center
Office of Vocational and Adult Education (ED), Washington, DC. Div. of Adult Education and Literacy.
This guide is intended to assist in linking service providers to existing resources and models and to build awareness of the body of innovative work that has been developed to respond to needs of homeless adult learners. It describes materials for instruction, outreach, and program management that were primarily developed in projects funded under…
Linking Two Worlds: Serving Resource Students at the Secondary Level.
ERIC Educational Resources Information Center
Adamson, David R.
1983-01-01
The Granite School District (Salt Lake City, Utah) tracking program provides a practical framework for incorporating many of the recent developments in secondary special education into a single program. The approach has a dual focus--providing direct instruction in the resource room and indirect consultative and backup services for the regular…
Rubric for Linked Learning Pathway Certification
ERIC Educational Resources Information Center
LaPlante, Arlene; Stearns, Roman
2010-01-01
This rubric was created to help pathway teams as they work together to develop and improve a comprehensive program of study. Specifically, the rubric can serve as a tool for: (1) Visioning; (2) Self-assessment; (3) Planning; and (4) Quality review. ConnectEd designed this rubric to be used in coordination with the Certification Criteria for Linked…
ERIC Educational Resources Information Center
Missouri Department of Elementary and Secondary Education, 2005
2005-01-01
The Outstanding Schools Act (1993) called upon Missouri's educational community to strengthen expectations and opportunities for students served by Missouri public schools to ensure that graduates of Missouri's public schools have the knowledge, skills, and competencies essential to lead productive, fulfilling, and successful lives. Four major…
Coming Together for Children: Six Community Partnerships Make a Big Difference
ERIC Educational Resources Information Center
Friedman, Susan
2007-01-01
Community partnerships serving young children and families take many forms. This article presents six community partnerships that are engaged in innovative and creative approaches to learning. These programs have varied goals, but they share a common focus on linking community resources to enhance learning opportunities for the children and…
Linking the Occupational Pressures of College Presidents to Presidential Turnover
ERIC Educational Resources Information Center
Tekniepe, Robert J.
2014-01-01
Community colleges are expected to serve the needs of their local communities. Hence, college presidents are called on to lead this collaboration between the college and the community. Presidents, however, are affected by a multitude of factors that contribute to abridged tenures, a scenario that can have harmful effects on the educational…
Character Development among Youth: Linking Lives in Time and Place
ERIC Educational Resources Information Center
Lerner, Richard M.
2018-01-01
This article embeds the study of character development within the two-decades-long research program framed by the Lerner and Lerner model of positive youth development. Character development involves attaining the feelings, thoughts, and skills needed to act coherently across time and place to serve self and others in mutually beneficial, positive…
Online Search Services in the Public Library: Project Dialib.
ERIC Educational Resources Information Center
Ahlgren, Alice E.
Lockheed has undertaken Project DIALIB to determine whether online retrieval services could be useful to the general public, and if the public library could serve as the linking agent for these services. As part of the study, DIALOG, Lockheed's online reference retrieval system, has been made available to the public through four public libraries…