WorldWideScience

Sample records for requires distinct contributions

  1. Amygdala and ventral striatum make distinct contributions to reinforcement learning

    Science.gov (United States)

    Costa, Vincent D.; Monte, Olga Dal; Lucas, Daniel R.; Murray, Elisabeth A.; Averbeck, Bruno B.

    2016-01-01

    Summary Reinforcement learning (RL) theories posit that dopaminergic signals are integrated within the striatum to associate choices with outcomes. Often overlooked is that the amygdala also receives dopaminergic input and is involved in Pavlovian processes that influence choice behavior. To determine the relative contributions of the ventral striatum (VS) and amygdala to appetitive RL we tested rhesus macaques with VS or amygdala lesions on deterministic and stochastic versions of a two-arm bandit reversal learning task. When learning was characterized with a RL model relative to controls, amygdala lesions caused general decreases in learning from positive feedback and choice consistency. By comparison, VS lesions only affected learning in the stochastic task. Moreover, the VS lesions hastened the monkeys’ choice reaction times, which emphasized a speed-accuracy tradeoff that accounted for errors in deterministic learning. These results update standard accounts of RL by emphasizing distinct contributions of the amygdala and VS to RL. PMID:27720488

  2. Managing today's complex healthcare business enterprise: reflections on distinctive requirements of healthcare management education.

    Science.gov (United States)

    Welton, William E

    2004-01-01

    In early 2001, the community of educational programs offering master's-level education in healthcare management began an odyssey to modernize its approach to the organization and delivery of healthcare management education. The community recognized that cumulative long-term changes within healthcare management practice required a careful examination of healthcare management context and manpower requirements. This article suggests an evidence-based rationale for defining the distinctive elements of healthcare management, thus suggesting a basis for review and transformation of master's-level healthcare management curricula. It also suggests ways to modernize these curricula in a manner that recognizes the distinctiveness of the healthcare business enterprise as well as the changing management roles and careers within these complex organizations and systems. Through such efforts, the healthcare management master's-level education community would be better prepared to meet current and future challenges, to increase its relevance to the management practice community, and to allocate scarce faculty and program resources more effectively.

  3. The urban explosion of black majority churches : their origin, growth, distinctives and contribution to British Christianity / by Babatunde Aderemi Adedibu

    OpenAIRE

    Adedibu, Babatunde Aderemi

    2010-01-01

    British church history in the last sixty years is best described as a “coat of many colours”. This image is appropriate because of the growth and proliferation of Black Majority Churches in urban areas of the British Isles. The advent of these churches has contributed to the prevailing pluralistic theological landscape. This thesis aims to evaluate the current status of Black Majority Churches with respect to their origin, growth, distinctives and contributions to British Ch...

  4. Distinct contributions of the dorsolateral prefrontal and orbitofrontal cortex during emotion regulation.

    Directory of Open Access Journals (Sweden)

    Armita Golkar

    Full Text Available The lateral prefrontal and orbitofrontal cortices have both been implicated in emotion regulation, but their distinct roles in regulation of negative emotion remain poorly understood. To address this issue we enrolled 58 participants in an fMRI study in which participants were instructed to reappraise both negative and neutral stimuli. This design allowed us to separately study activations reflecting cognitive processes associated with reappraisal in general and activations specifically related to reappraisal of negative emotion. Our results confirmed that both the dorsolateral prefrontal cortex (DLPFC and the lateral orbitofrontal cortex (OFC contribute to emotion regulation through reappraisal. However, activity in the DLPFC was related to reappraisal independently of whether negative or neutral stimuli were reappraised, whereas the lateral OFC was uniquely related to reappraisal of negative stimuli. We suggest that relative to the lateral OFC, the DLPFC serves a more general role in emotion regulation, perhaps by reflecting the cognitive demand that is inherent to the regulation task.

  5. Indigenous Foods and Their Contribution to Nutrient Requirements

    African Journals Online (AJOL)

    indigenous foods and dietary diversity within an ecosystem can be powerful ... income generation, food culture and can contribute to nutrient requirements. ... species in 12 Asian countries and 10 countries in Africa in 36 studies, and reported 90 .... Taruvinga and. Nengovhela32 investigated the consumers' perception and.

  6. 24 CFR 92.222 - Reduction of matching contribution requirement.

    Science.gov (United States)

    2010-04-01

    ... major disaster pursuant to the Robert T. Stafford Disaster Relief and Emergency Assistance Act is made... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Reduction of matching contribution requirement. 92.222 Section 92.222 Housing and Urban Development Office of the Secretary, Department of...

  7. Pseudomonas chlororaphis Produces Two Distinct R-Tailocins That Contribute to Bacterial Competition in Biofilms and on Roots.

    Science.gov (United States)

    Dorosky, Robert J; Yu, Jun Myoung; Pierson, Leland S; Pierson, Elizabeth A

    2017-08-01

    R-type tailocins are high-molecular-weight bacteriocins that resemble bacteriophage tails and are encoded within the genomes of many Pseudomonas species. In this study, analysis of the P. chlororaphis 30-84 R-tailocin gene cluster revealed that it contains the structural components to produce two R-tailocins of different ancestral origins. Two distinct R-tailocin populations differing in length were observed in UV-induced lysates of P. chlororaphis 30-84 via transmission electron microscopy. Mutants defective in the production of one or both R-tailocins demonstrated that the killing spectrum of each tailocin is limited to Pseudomonas species. The spectra of pseudomonads killed by the two R-tailocins differed, although a few Pseudomonas species were either killed by or insusceptible to both tailocins. Tailocin release was disrupted by deletion of the holin gene within the tailocin gene cluster, demonstrating that the lysis cassette is required for the release of both R-tailocins. The loss of functional tailocin production reduced the ability of P. chlororaphis 30-84 to compete with an R-tailocin-sensitive strain within biofilms and rhizosphere communities. Our study demonstrates that Pseudomonas species can produce more than one functional R-tailocin particle sharing the same lysis cassette but differing in their killing spectra. This study provides evidence for the role of R-tailocins as determinants of bacterial competition among plant-associated Pseudomonas in biofilms and the rhizosphere. IMPORTANCE Recent studies have identified R-tailocin gene clusters potentially encoding more than one R-tailocin within the genomes of plant-associated Pseudomonas but have not demonstrated that more than one particle is produced or the ecological significance of the production of multiple R-tailocins. This study demonstrates for the first time that Pseudomonas strains can produce two distinct R-tailocins with different killing spectra, both of which contribute to bacterial

  8. Salmonella Persistence in Tomatoes Requires a Distinct Set of Metabolic Functions Identified by Transposon Insertion Sequencing

    Science.gov (United States)

    Desai, Prerak; Porwollik, Steffen; Canals, Rocio; Perez, Daniel R.; Chu, Weiping; McClelland, Michael; Teplitski, Max

    2016-01-01

    ABSTRACT Human enteric pathogens, such as Salmonella spp. and verotoxigenic Escherichia coli, are increasingly recognized as causes of gastroenteritis outbreaks associated with the consumption of fruits and vegetables. Persistence in plants represents an important part of the life cycle of these pathogens. The identification of the full complement of Salmonella genes involved in the colonization of the model plant (tomato) was carried out using transposon insertion sequencing analysis. With this approach, 230,000 transposon insertions were screened in tomato pericarps to identify loci with reduction in fitness, followed by validation of the screen results using competition assays of the isogenic mutants against the wild type. A comparison with studies in animals revealed a distinct plant-associated set of genes, which only partially overlaps with the genes required to elicit disease in animals. De novo biosynthesis of amino acids was critical to persistence within tomatoes, while amino acid scavenging was prevalent in animal infections. Fitness reduction of the Salmonella amino acid synthesis mutants was generally more severe in the tomato rin mutant, which hyperaccumulates certain amino acids, suggesting that these nutrients remain unavailable to Salmonella spp. within plants. Salmonella lipopolysaccharide (LPS) was required for persistence in both animals and plants, exemplifying some shared pathogenesis-related mechanisms in animal and plant hosts. Similarly to phytopathogens, Salmonella spp. required biosynthesis of amino acids, LPS, and nucleotides to colonize tomatoes. Overall, however, it appears that while Salmonella shares some strategies with phytopathogens and taps into its animal virulence-related functions, colonization of tomatoes represents a distinct strategy, highlighting this pathogen's flexible metabolism. IMPORTANCE Outbreaks of gastroenteritis caused by human pathogens have been increasingly associated with foods of plant origin, with tomatoes

  9. Understanding the addiction cycle: a complex biology with distinct contributions of genotype vs. sex at each stage.

    Science.gov (United States)

    Wilhelm, C J; Hashimoto, J G; Roberts, M L; Sonmez, M K; Wiren, K M

    2014-10-24

    Ethanol abuse can lead to addiction, brain damage and premature death. The cycle of alcohol addiction has been described as a composite consisting of three stages: intoxication, withdrawal and craving/abstinence. There is evidence for contributions of both genotype and sex to alcoholism, but an understanding of the biological underpinnings is limited. Utilizing both sexes of genetic animal models with highly divergent alcohol withdrawal severity, Withdrawal Seizure-Resistant (WSR) and Withdrawal Seizure-Prone (WSP) mice, the distinct contributions of genotype/phenotype and of sex during addiction stages on neuroadaptation were characterized. Transcriptional profiling was performed to identify expression changes as a consequence of chronic intoxication in the medial prefrontal cortex. Significant expression differences were identified on a single platform and tracked over a behaviorally relevant time course that covered each stage of alcohol addiction; i.e., after chronic intoxication, during peak withdrawal, and after a defined period of abstinence. Females were more sensitive to ethanol with higher fold expression differences. Bioinformatics showed a strong effect of sex on the data structure of expression profiles during chronic intoxication and at peak withdrawal irrespective of genetic background. However, during abstinence, differences were observed instead between the lines/phenotypes irrespective of sex. Confirmation of identified pathways showed distinct inflammatory signaling following intoxication at peak withdrawal, with a pro-inflammatory phenotype in females but overall suppression of immune signaling in males. Combined, these results suggest that each stage of the addiction cycle is influenced differentially by sex vs. genetic background and support the development of stage- and sex-specific therapies for alcohol withdrawal and the maintenance of sobriety. Published by Elsevier Ltd.

  10. Feline immunodeficiency virus envelope glycoproteins antagonize tetherin through a distinctive mechanism that requires virion incorporation.

    Science.gov (United States)

    Morrison, James H; Guevara, Rebekah B; Marcano, Adriana C; Saenz, Dyana T; Fadel, Hind J; Rogstad, Daniel K; Poeschla, Eric M

    2014-03-01

    BST2/tetherin inhibits the release of enveloped viruses from cells. Primate lentiviruses have evolved specific antagonists (Vpu, Nef, and Env). Here we characterized tetherin proteins of species representing both branches of the order Carnivora. Comparison of tiger and cat (Feliformia) to dog and ferret (Caniformia) genes demonstrated that the tiger and cat share a start codon mutation that truncated most of the tetherin cytoplasmic tail early in the Feliformia lineage (19 of 27 amino acids, including the dual tyrosine motif). Alpha interferon (IFN-α) induced tetherin and blocked feline immunodeficiency virus (FIV) replication in lymphoid and nonlymphoid feline cells. Budding of bald FIV and HIV particles was blocked by carnivore tetherins. However, infectious FIV particles were resistant, and spreading FIV replication was uninhibited. Antagonism mapped to the envelope glycoprotein (Env), which rescued FIV from carnivore tetherin restriction when expressed in trans but, in contrast to known antagonists, did not rescue noncognate particles. Also unlike the primate lentiviral antagonists, but similar to the Ebola virus glycoprotein, FIV Env did not reduce intracellular or cell surface tetherin levels. Furthermore, FIV-enveloped FIV particles actually required tetherin for optimal release from cells. The results show that FIV Envs mediate a distinctive tetherin evasion. Well adapted to a phylogenetically ancient tetherin tail truncation in the Felidae, it requires functional virion incorporation of Env, and it shields the budding particle without downregulating plasma membrane tetherin. Moreover, FIV has evolved dependence on this protein: particles containing FIV Env need tetherin for optimal release from the cell, while Env(-) particles do not. HIV-1 antagonizes the restriction factor tetherin with the accessory protein Vpu, while HIV-2 and the filovirus Ebola use their envelope (Env) glycoproteins for this purpose. It turns out that the FIV tetherin antagonist is

  11. Functional diversification of hsp40: distinct j-protein functional requirements for two prions allow for chaperone-dependent prion selection.

    Science.gov (United States)

    Harris, Julia M; Nguyen, Phil P; Patel, Milan J; Sporn, Zachary A; Hines, Justin K

    2014-07-01

    Yeast prions are heritable amyloid aggregates of functional yeast proteins; their propagation to subsequent cell generations is dependent upon fragmentation of prion protein aggregates by molecular chaperone proteins. Mounting evidence indicates the J-protein Sis1 may act as an amyloid specificity factor, recognizing prion and other amyloid aggregates and enabling Ssa and Hsp104 to act in prion fragmentation. Chaperone interactions with prions, however, can be affected by variations in amyloid-core structure resulting in distinct prion variants or 'strains'. Our genetic analysis revealed that Sis1 domain requirements by distinct variants of [PSI+] are strongly dependent upon overall variant stability. Notably, multiple strong [PSI+] variants can be maintained by a minimal construct of Sis1 consisting of only the J-domain and glycine/phenylalanine-rich (G/F) region that was previously shown to be sufficient for cell viability and [RNQ+] prion propagation. In contrast, weak [PSI+] variants are lost under the same conditions but maintained by the expression of an Sis1 construct that lacks only the G/F region and cannot support [RNQ+] propagation, revealing mutually exclusive requirements for Sis1 function between these two prions. Prion loss is not due to [PSI+]-dependent toxicity or dependent upon a particular yeast genetic background. These observations necessitate that Sis1 must have at least two distinct functional roles that individual prions differentially require for propagation and which are localized to the glycine-rich domains of the Sis1. Based on these distinctions, Sis1 plasmid-shuffling in a [PSI+]/[RNQ+] strain permitted J-protein-dependent prion selection for either prion. We also found that, despite an initial report to the contrary, the human homolog of Sis1, Hdj1, is capable of [PSI+] prion propagation in place of Sis1. This conservation of function is also prion-variant dependent, indicating that only one of the two Sis1-prion functions may have

  12. Revitalizing the “civic” and “ethnic” distinction

    DEFF Research Database (Denmark)

    Larsen, Christian Albrekt

    2017-01-01

    This article describes how contemporary publics think about the nation along Kohn’s classic distinction between “civic” and “ethnic” nationalism. The article makes three contributes to the existing literature. Firstly, it introduces a new statistical tool, multi-classification-analysis, to establ......This article describes how contemporary publics think about the nation along Kohn’s classic distinction between “civic” and “ethnic” nationalism. The article makes three contributes to the existing literature. Firstly, it introduces a new statistical tool, multi...

  13. 34 CFR 636.5 - What are the matching contribution and planning consortium requirements?

    Science.gov (United States)

    2010-07-01

    ... 34 Education 3 2010-07-01 2010-07-01 false What are the matching contribution and planning... PROGRAM General § 636.5 What are the matching contribution and planning consortium requirements? (a) The... agreed to by the members of a planning consortium. (Authority: 20 U.S.C. 1136b, 1136e) ...

  14. Three distinct domains contribute to nuclear transport of murine Foxp3.

    Directory of Open Access Journals (Sweden)

    Wayne W Hancock

    2009-11-01

    Full Text Available Foxp3, a 47-kDa transcription factor, is necessary for the function of CD4+CD25+ regulatory T cells (Tregs, with an essential role in the control of self-reactive T cells and in preventing autoimmunity. Activation of Tregs by TCR engagement results in upregulation of Foxp3 expression, followed by its rapid nuclear transport and binding to chromatin. Here, we identify three distinct Foxp3 domains that contribute to nuclear transport. The first domain (Domain 1 comprises the C-terminal 12 amino acids. The second domain (Domain 2 is located immediately N-terminal to the forkhead domain (FHD, recently reported to be a binding site for the runt-related transcription factor 1/acute myeloid leukemia 1 (Runx1/AML1. The third domain (Domain 3 is located within the N-terminal first 51 amino acids. Unlike the known nuclear localization signals (NLSs, none of these three regions are rich in basic residues and do not bear any similarity to known monopartite or bipartite NLSs that have one or more clusters of basic amino acids. The basic arginine-lysine-lysine-arginine (RKKR sequence, located 12-aa from the C-terminal end of Foxp3 was previously reported to be a nuclear localization signal (NLS for several proteins, including for a GFP-Foxp3 hybrid. Evidence is provided here that in the full-length native Foxp3 RKKR does not function as an NLS. The data reported in this study indicates that Foxp3 achieves nuclear transport by binding to other nuclear factors and co-transporting with them to the nucleus.

  15. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Directory of Open Access Journals (Sweden)

    Myron S Ignatius

    Full Text Available The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382 mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382 mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382 mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382 defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  16. Distinct functional and temporal requirements for zebrafish Hdac1 during neural crest-derived craniofacial and peripheral neuron development.

    Science.gov (United States)

    Ignatius, Myron S; Unal Eroglu, Arife; Malireddy, Smitha; Gallagher, Glen; Nambiar, Roopa M; Henion, Paul D

    2013-01-01

    The regulation of gene expression is accomplished by both genetic and epigenetic means and is required for the precise control of the development of the neural crest. In hdac1(b382) mutants, craniofacial cartilage development is defective in two distinct ways. First, fewer hoxb3a, dlx2 and dlx3-expressing posterior branchial arch precursors are specified and many of those that are consequently undergo apoptosis. Second, in contrast, normal numbers of progenitors are present in the anterior mandibular and hyoid arches, but chondrocyte precursors fail to terminally differentiate. In the peripheral nervous system, there is a disruption of enteric, DRG and sympathetic neuron differentiation in hdac1(b382) mutants compared to wildtype embryos. Specifically, enteric and DRG-precursors differentiate into neurons in the anterior gut and trunk respectively, while enteric and DRG neurons are rarely present in the posterior gut and tail. Sympathetic neuron precursors are specified in hdac1(b382) mutants and they undergo generic neuronal differentiation but fail to undergo noradrenergic differentiation. Using the HDAC inhibitor TSA, we isolated enzyme activity and temporal requirements for HDAC function that reproduce hdac1(b382) defects in craniofacial and sympathetic neuron development. Our study reveals distinct functional and temporal requirements for zebrafish hdac1 during neural crest-derived craniofacial and peripheral neuron development.

  17. Distinct regions in the C-Terminus required for GLP-1R cell surface expression, activity and internalisation.

    Science.gov (United States)

    Thompson, Aiysha; Kanamarlapudi, Venkateswarlu

    2015-09-15

    The glucagon-like peptide-1 (GLP-1) receptor (GLP-1R), an important drug target in the treatment of type 2 diabetes, is a G-protein coupled receptor (GPCR) that mediates insulin secretion by GLP-1. The N-terminus controls GLP-1R biosynthetic trafficking to the cell surface but the C-terminus involvement in that trafficking is unknown. The aim of this study was to identify distinct regions within the C-terminal domain required for human GLP-1R (hGLP-1R) cell surface expression, activity and internalisation using a number of C-terminal deletions and site-directed mutations. The results of this study revealed that the residues 411-418 within the C-terminal domain of the hGLP-1R are critical in targeting the newly synthesised receptor to the plasma membrane. The residues 419-430 are important for cAMP producing activity of the receptor, most likely by coupling to Gαs. However, the residues 431-450 within the C-terminus are essential for agonist-induced hGLP-1R internalisation. In conclusion, these findings demonstrate the hGLP-1R has distinct regions within the C-terminal domain required for its cell surface expression, activity and agonist-induced internalisation. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  18. Review of selected contributions of the conference 'Suppliers and requirements for quality provision'

    International Nuclear Information System (INIS)

    2007-03-01

    There were 12 contributions presented at the conference focused on the requirements of the standard ISO 9001:2000 for supplies of services and products, especially from the point of view of supplies for nuclear power plants. Two contributions were focused in the issue of quality assurance of finishing of the building of 3. and 4. block of the Nuclear Power Plant Mochovce

  19. Sepsis Induces Hematopoietic Stem Cell Exhaustion and Myelosuppression through Distinct Contributions of TRIF and MYD88

    Directory of Open Access Journals (Sweden)

    Huajia Zhang

    2016-06-01

    Full Text Available Toll-like receptor 4 (TLR4 plays a central role in host responses to bacterial infection, but the precise mechanism(s by which its downstream signaling components coordinate the bone marrow response to sepsis is poorly understood. Using mice deficient in TLR4 downstream adapters MYD88 or TRIF, we demonstrate that both cell-autonomous and non-cell-autonomous MYD88 activation are major causes of myelosuppression during sepsis, while having a modest impact on hematopoietic stem cell (HSC functions. In contrast, cell-intrinsic TRIF activation severely compromises HSC self-renewal without directly affecting myeloid cells. Lipopolysaccharide-induced activation of MYD88 or TRIF contributes to cell-cycle activation of HSC and induces rapid and permanent changes in transcriptional programs, as indicated by persistent downregulation of Spi1 and CebpA expression after transplantation. Thus, distinct mechanisms downstream of TLR4 signaling mediate myelosuppression and HSC exhaustion during sepsis through unique effects of MyD88 and TRIF.

  20. Genome-Wide Requirements for Resistance to Functionally Distinct DNA-Damaging Agents.

    Directory of Open Access Journals (Sweden)

    2005-08-01

    Full Text Available The mechanistic and therapeutic differences in the cellular response to DNA-damaging compounds are not completely understood, despite intense study. To expand our knowledge of DNA damage, we assayed the effects of 12 closely related DNA-damaging agents on the complete pool of ~4,700 barcoded homozygous deletion strains of Saccharomyces cerevisiae. In our protocol, deletion strains are pooled together and grown competitively in the presence of compound. Relative strain sensitivity is determined by hybridization of PCR-amplified barcodes to an oligonucleotide array carrying the barcode complements. These screens identified genes in well-characterized DNA-damage-response pathways as well as genes whose role in the DNA-damage response had not been previously established. High-throughput individual growth analysis was used to independently confirm microarray results. Each compound produced a unique genome-wide profile. Analysis of these data allowed us to determine the relative importance of DNA-repair modules for resistance to each of the 12 profiled compounds. Clustering the data for 12 distinct compounds uncovered both known and novel functional interactions that comprise the DNA-damage response and allowed us to define the genetic determinants required for repair of interstrand cross-links. Further genetic analysis allowed determination of epistasis for one of these functional groups.

  1. Temporomandibular joint formation requires two distinct hedgehog-dependent steps.

    Science.gov (United States)

    Purcell, Patricia; Joo, Brian W; Hu, Jimmy K; Tran, Pamela V; Calicchio, Monica L; O'Connell, Daniel J; Maas, Richard L; Tabin, Clifford J

    2009-10-27

    We conducted a genetic analysis of the developing temporo-mandibular or temporomandi-bular joint (TMJ), a highly specialized synovial joint that permits movement and function of the mammalian jaw. First, we used laser capture microdissection to perform a genome-wide expression analysis of each of its developing components. The expression patterns of genes identified in this screen were examined in the TMJ and compared with those of other synovial joints, including the shoulder and the hip joints. Striking differences were noted, indicating that the TMJ forms via a distinct molecular program. Several components of the hedgehog (Hh) signaling pathway are among the genes identified in the screen, including Gli2, which is expressed specifically in the condyle and in the disk of the developing TMJ. We found that mice deficient in Gli2 display aberrant TMJ development such that the condyle loses its growth-plate-like cellular organization and no disk is formed. In addition, we used a conditional strategy to remove Smo, a positive effector of the Hh signaling pathway, from chondrocyte progenitors. This cell autonomous loss of Hh signaling allows for disk formation, but the resulting structure fails to separate from the condyle. Thus, these experiments establish that Hh signaling acts at two distinct steps in disk morphogenesis, condyle initiation, and disk-condyle separation and provide a molecular framework for future studies of the TMJ.

  2. Social conformity despite individual preferences for distinctiveness.

    Science.gov (United States)

    Smaldino, Paul E; Epstein, Joshua M

    2015-03-01

    We demonstrate that individual behaviours directed at the attainment of distinctiveness can in fact produce complete social conformity. We thus offer an unexpected generative mechanism for this central social phenomenon. Specifically, we establish that agents who have fixed needs to be distinct and adapt their positions to achieve distinctiveness goals, can nevertheless self-organize to a limiting state of absolute conformity. This seemingly paradoxical result is deduced formally from a small number of natural assumptions and is then explored at length computationally. Interesting departures from this conformity equilibrium are also possible, including divergence in positions. The effect of extremist minorities on these dynamics is discussed. A simple extension is then introduced, which allows the model to generate and maintain social diversity, including multimodal distinctiveness distributions. The paper contributes formal definitions, analytical deductions and counterintuitive findings to the literature on individual distinctiveness and social conformity.

  3. 26 CFR 1.6115-1 - Disclosure requirements for quid pro quo contributions.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 13 2010-04-01 2010-04-01 false Disclosure requirements for quid pro quo contributions. 1.6115-1 Section 1.6115-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY... unique qualities of the goods or services that are being valued. (3) Examples. The following examples...

  4. Distinct contribution of the parietal and temporal cortex to hand configuration and contextual judgements about tools.

    Science.gov (United States)

    Andres, Michael; Pelgrims, Barbara; Olivier, Etienne

    2013-09-01

    Neuropsychological studies showed that manipulatory and semantic knowledge can be independently impaired in patients with upper-limb apraxia, leading to different tool use disorders. The present study aimed to dissociate the brain regions involved in judging the hand configuration or the context associated to tool use. We focussed on the left supramarginalis gyrus (SMG) and left middle temporal gyrus (MTG), whose activation, as evidenced by functional magnetic resonance imaging (fMRI) studies, suggests that they may play a critical role in tool use. The distinctive location of SMG in the dorsal visual stream led us to postulate that this parietal region could play a role in processing incoming information about tools to shape hand posture. In contrast, we hypothesized that MTG, because of its interconnections with several cortical areas involved in semantic memory, could contribute to retrieving semantic information necessary to create a contextual representation of tool use. To test these hypotheses, we used neuronavigated transcranial magnetic stimulation (TMS) to interfere transiently with the function of either left SMG or left MTG in healthy participants performing judgement tasks about either hand configuration or context of tool use. We found that SMG virtual lesions impaired hand configuration but not contextual judgements, whereas MTG lesions selectively interfered with judgements about the context of tool use while leaving hand configuration judgements unaffected. This double dissociation demonstrates that the ability to infer a context of use or a hand posture from tool perception relies on distinct processes, performed in the temporal and parietal regions. The present findings suggest that tool use disorders caused by SMG lesions will be characterized by difficulties in selecting the appropriate hand posture for tool use, whereas MTG lesions will yield difficulties in using tools in the appropriate context. Copyright © 2012. Published by Elsevier Ltd.

  5. Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans.

    Directory of Open Access Journals (Sweden)

    Maria C Ow

    2018-02-01

    Full Text Available Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite ("seesaw" transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome.

  6. Early experiences mediate distinct adult gene expression and reproductive programs in Caenorhabditis elegans

    Science.gov (United States)

    Ow, Maria C.; Nichitean, Alexandra M.; Dorus, Steve; Hall, Sarah E.

    2018-01-01

    Environmental stress during early development in animals can have profound effects on adult phenotypes via programmed changes in gene expression. Using the nematode C. elegans, we demonstrated previously that adults retain a cellular memory of their developmental experience that is manifested by differences in gene expression and life history traits; however, the sophistication of this system in response to different environmental stresses, and how it dictates phenotypic plasticity in adults that contribute to increased fitness in response to distinct environmental challenges, was unknown. Using transcriptional profiling, we show here that C. elegans adults indeed retain distinct cellular memories of different environmental conditions. We identified approximately 500 genes in adults that entered dauer due to starvation that exhibit significant opposite (“seesaw”) transcriptional phenotypes compared to adults that entered dauer due to crowding, and are distinct from animals that bypassed dauer. Moreover, we show that two-thirds of the genes in the genome experience a 2-fold or greater seesaw trend in gene expression, and based upon the direction of change, are enriched in large, tightly linked regions on different chromosomes. Importantly, these transcriptional programs correspond to significant changes in brood size depending on the experienced stress. In addition, we demonstrate that while the observed seesaw gene expression changes occur in both somatic and germline tissue, only starvation-induced changes require a functional GLP-4 protein necessary for germline development, and both programs require the Argonaute CSR-1. Thus, our results suggest that signaling between the soma and the germ line can generate phenotypic plasticity as a result of early environmental experience, and likely contribute to increased fitness in adverse conditions and the evolution of the C. elegans genome. PMID:29447162

  7. Distinct requirements for activation of NKT and NK cells during viral infection.

    Science.gov (United States)

    Tyznik, Aaron J; Verma, Shilpi; Wang, Qiao; Kronenberg, Mitchell; Benedict, Chris A

    2014-04-15

    NK cells are key regulators of innate defense against mouse CMV (MCMV). Like NK cells, NKT cells also produce high levels of IFN-γ rapidly after MCMV infection. However, whether similar mechanisms govern activation of these two cell types, as well as the significance of NKT cells for host resistance, remain unknown. In this article, we show that, although both NKT and NK cells are activated via cytokines, their particular cytokine requirements differ significantly in vitro and in vivo. IL-12 is required for NKT cell activation in vitro but is not sufficient, whereas NK cells have the capacity to be activated more promiscuously in response to individual cytokines from innate cells. In line with these results, GM-CSF-derived dendritic cells activated only NK cells upon MCMV infection, consistent with their virtual lack of IL-12 production, whereas Flt3 ligand-derived dendritic cells produced IL-12 and activated both NK and NKT cells. In vivo, NKT cell activation was abolished in IL-12(-/-) mice infected with MCMV, whereas NK cells were still activated. In turn, splenic NK cell activation was more IL-18 dependent. The differential requirements for IL-12 and IL-18 correlated with the levels of cytokine receptor expression by NK and NKT cells. Finally, mice lacking NKT cells showed reduced control of MCMV, and depleting NK cells further enhanced viral replication. Taken together, our results show that NKT and NK cells have differing requirements for cytokine-mediated activation, and both can contribute nonredundantly to MCMV defense, revealing that these two innate lymphocyte subsets function together to fine-tune antiviral responses.

  8. A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation

    Directory of Open Access Journals (Sweden)

    Shokat Kevan M

    2008-09-01

    Full Text Available Abstract Background Neurons assemble into a functional network through a sequence of developmental processes including neuronal polarization and synapse formation. In Caenorhabditis elegans, the serine/threonine SAD-1 kinase is essential for proper neuronal polarity and synaptic organization. To determine if SAD-1 activity regulates the establishment or maintenance of these neuronal structures, we examined its temporal requirements using a chemical-genetic method that allows for selective and reversible inactivation of its kinase activity in vivo. Results We generated a PP1 analog-sensitive variant of SAD-1. Through temporal inhibition of SAD-1 kinase activity we show that its activity is required for the establishment of both neuronal polarity and synaptic organization. However, while SAD-1 activity is needed strictly when neurons are polarizing, the temporal requirement for SAD-1 is less stringent in synaptic organization, which can also be re-established during maintenance. Conclusion This study reports the first temporal analysis of a neural kinase activity using the chemical-genetic system. It reveals that neuronal polarity and synaptic organization have distinct temporal requirements for SAD-1.

  9. Calculating the Contribution of Zooxanthellae to Giant Clams Respiration Energy Requirements

    OpenAIRE

    Ambariyanto

    2002-01-01

    Giant clams (Tridacnidae) are known to live in association with photosynthetic single cell dinoflagellate algae commonly called zooxanthellae. These algae which can be found in the mantle of the clams are capable of transferring part of their photosynthates which become an important source of energy to the host ( apart from filter feeding activity). In order to understand the basic biological processes of the giant clams , the contribution of zooxanthellae to the clam's energy requirement nee...

  10. Distinctive Dynamic Capabilities for New Business Creation

    DEFF Research Database (Denmark)

    Rosenø, Axel; Enkel, Ellen; Mezger, Florian

    2013-01-01

    This study examines the distinctive dynamic capabilities for new business creation in established companies. We argue that these are very different from those for managing incremental innovation within a company's core business. We also propose that such capabilities are needed in both slow...... and fast-paced industries, and that similarities exist across industries. Hence, the study contributes to dynamic capabilities literature by: 1) identifying the distinctive dynamic capabilities for new business creation; 2) shifting focus away from dynamic capabilities in environments characterised by high...... clock-speed and uncertainty towards considering dynamic capabilities for the purpose of developing new businesses, which also implies a high degree of uncertainty. Based on interviews with 33 companies, we identify distinctive dynamic capabilities for new business creation, find that dynamic...

  11. Fermionic bound states in distinct kinklike backgrounds

    Energy Technology Data Exchange (ETDEWEB)

    Bazeia, D. [Universidade Federal da Paraiba, Departamento de Fisica, Joao Pessoa, Paraiba (Brazil); Mohammadi, A. [Universidade Federal de Campina Grande, Departamento de Fisica, Caixa Postal 10071, Campina Grande, Paraiba (Brazil)

    2017-04-15

    This work deals with fermions in the background of distinct localized structures in the two-dimensional spacetime. Although the structures have a similar topological character, which is responsible for the appearance of fractionally charged excitations, we want to investigate how the geometric deformations that appear in the localized structures contribute to the change in the physical properties of the fermionic bound states. We investigate the two-kink and compact kinklike backgrounds, and we consider two distinct boson-fermion interactions, one motivated by supersymmetry and the other described by the standard Yukawa coupling. (orig.)

  12. Figure-ground segregation requires two distinct periods of activity in V1: a transcranial magnetic stimulation study.

    Science.gov (United States)

    Heinen, Klaartje; Jolij, Jacob; Lamme, Victor A F

    2005-09-08

    Discriminating objects from their surroundings by the visual system is known as figure-ground segregation. This process entails two different subprocesses: boundary detection and subsequent surface segregation or 'filling in'. In this study, we used transcranial magnetic stimulation to test the hypothesis that temporally distinct processes in V1 and related early visual areas such as V2 or V3 are causally related to the process of figure-ground segregation. Our results indicate that correct discrimination between two visual stimuli, which relies on figure-ground segregation, requires two separate periods of information processing in the early visual cortex: one around 130-160 ms and the other around 250-280 ms.

  13. Linking new information to a reactivated memory requires consolidation and not reconsolidation mechanisms.

    Directory of Open Access Journals (Sweden)

    2005-09-01

    Full Text Available A new memory is initially labile and becomes stabilized through a process of consolidation, which depends on gene expression. Stable memories, however, can again become labile if reactivated by recall and require another phase of protein synthesis in order to be maintained. This process is known as reconsolidation. The functional significance of the labile phase of reconsolidation is unknown; one hypothesis proposes that it is required to link new information with reactivated memories. Reconsolidation is distinct from the initial consolidation, and one distinction is that the requirement for specific proteins or general protein synthesis during the two processes occurs in different brain areas. Here, we identified an anatomically distinctive molecular requirement that doubly dissociates consolidation from reconsolidation of an inhibitory avoidance memory. We then used this requirement to investigate whether reconsolidation and consolidation are involved in linking new information with reactivated memories. In contrast to what the hypothesis predicted, we found that reconsolidation does not contribute to the formation of an association between new and reactivated information. Instead, it recruits mechanisms similar to those underlying consolidation of a new memory. Thus, linking new information to a reactivated memory is mediated by consolidation and not reconsolidation mechanisms.

  14. Distinct populations of GABAergic neurons in mouse rhombomere 1 express but do not require the homeodomain transcription factor PITX2.

    Science.gov (United States)

    Waite, Mindy R; Skaggs, Kaia; Kaviany, Parisa; Skidmore, Jennifer M; Causeret, Frédéric; Martin, James F; Martin, Donna M

    2012-01-01

    Hindbrain rhombomere 1 (r1) is located caudal to the isthmus, a critical organizer region, and rostral to rhombomere 2 in the developing mouse brain. Dorsal r1 gives rise to the cerebellum, locus coeruleus, and several brainstem nuclei, whereas cells from ventral r1 contribute to the trochlear and trigeminal nuclei as well as serotonergic and GABAergic neurons of the dorsal raphe. Recent studies have identified several molecular events controlling dorsal r1 development. In contrast, very little is known about ventral r1 gene expression and the genetic mechanisms regulating its formation. Neurons with distinct neurotransmitter phenotypes have been identified in ventral r1 including GABAergic, serotonergic, and cholinergic neurons. Here we show that PITX2 marks a distinct population of GABAergic neurons in mouse embryonic ventral r1. This population appears to retain its GABAergic identity even in the absence of PITX2. We provide a comprehensive map of markers that places these PITX2-positive GABAergic neurons in a region of r1 that intersects and is potentially in communication with the dorsal raphe. Copyright © 2011 Elsevier Inc. All rights reserved.

  15. NSAID gastropathy and enteropathy: distinct pathogenesis likely necessitates distinct prevention strategies.

    Science.gov (United States)

    Wallace, John L

    2012-01-01

    The mechanisms underlying the ability of nonsteroidal anti-inflammatory drugs (NSAIDs) to cause ulceration in the stomach and proximal duodenum are well understood, and this injury can largely be prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors). In contrast, the pathogenesis of small intestinal injury induced by NSAIDs is less well understood, involving more complex mechanisms than those in the stomach and proximal duodenum. There is clear evidence for important contributions to NSAID enteropathy of enteric bacteria, bile and enterohepatic recirculation of the NSAID. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. Indeed, clinical data suggest little, if any, benefit. Animal studies suggest a significant exacerbation of NSAID enteropathy when proton pump inhibitors are co-administered with the NSAID. This worsening of damage appears to be linked to changes in the number and types of bacteria in the small intestine during proton pump inhibitor therapy. The distinct mechanisms of NSAID-induced injury in the stomach/proximal duodenum versus the more distal small intestine likely dictate distinct strategies for prevention. © 2011 The Author. British Journal of Pharmacology © 2011 The British Pharmacological Society.

  16. Human Nav1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons

    Science.gov (United States)

    Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D.

    2015-01-01

    Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Nav1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Nav1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Nav1.8 channels. We also show that native human DRG neurons recapitulate these properties of Nav1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Nav1.8, which contribute to the firing properties of human DRG neurons. PMID:25787950

  17. Distinct functional domains within the acidic cluster of tegument protein pp28 required for trafficking and cytoplasmic envelopment of human cytomegalovirus.

    Science.gov (United States)

    Seo, Jun-Young; Jeon, Hyejin; Hong, Sookyung; Britt, William J

    2016-10-01

    Human cytomegalovirus UL99-encoded tegument protein pp28 contains a 16 aa acidic cluster that is required for pp28 trafficking to the assembly compartment (AC) and the virus assembly. However, functional signals within the acidic cluster of pp28 remain undefined. Here, we demonstrated that an acidic cluster rather than specific sorting signals was required for trafficking to the AC. Recombinant viruses with chimeric pp28 proteins expressing non-native acidic clusters exhibited delayed viral growth kinetics and decreased production of infectious virus, indicating that the native acidic cluster of pp28 was essential for wild-type virus assembly. These results suggested that the acidic cluster of pp28 has distinct functional domains required for trafficking and for efficient virus assembly. The first half (aa 44-50) of the acidic cluster was sufficient for pp28 trafficking, whereas the native acidic cluster consisting of aa 51-59 was required for the assembly of wild-type levels of infectious virus.

  18. Some feminist contributions to community social psychology

    Directory of Open Access Journals (Sweden)

    Claudia Mayorga

    2014-02-01

    Full Text Available This article analyzes the contributions of feminist debate about intersectionality of social categories for Community Social Psychology in Brazil. This was set up as dedicated to theoretical analyze the social inequalities that characterize contemporary societies and propose methodological processes of intervention for questioning and processing of these realities. We discuss how the emergence of new actors and demands on public space, as distinct from the 60/70, is required to understand the oppression from various power systems such as gender, race and sexuality. We conclude that intersectional analysis should consider different levels of relationships between categories, the history of the same differential and common aspects of different systems of power as naturalization of inequality, the relationship between public and private relationship between equality and difference. Analyses based on intersectionality can contribute to processes of social intervention that considers the complexity of contemporary societies.

  19. Distinctiveness of Saudi Arabian EFL Learners

    Directory of Open Access Journals (Sweden)

    Manssour Habbash

    2016-04-01

    Full Text Available In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs (Preparatory Year Programs in Saudi Arabia. This study examines the distinctiveness with regard to the learning attitudes of Saudi students that are often cultivated by the culture and academic environment in their homeland. Employing an emic approach for collecting the required data an analysis was carried out in light of the other studies on ‘education’ in Saudi Arabia that have particular reference to the factors that can positively influence student motivation, student success and the academic environment. The findings were used in constructing the rationale behind such distinctiveness. Assuming that the outcome of the discussion on the findings of this exploration can be helpful for teachers in adapting their teaching methodology and improving their teacher efficacy in dealing with students both from the kingdom and in the kingdom, some recommendations are made. Keywords: China Distinctiveness, Saudi Arabian University context, Expatriate teachers’ perspective, Distinctiveness Theory

  20. Human Na(v)1.8: enhanced persistent and ramp currents contribute to distinct firing properties of human DRG neurons.

    Science.gov (United States)

    Han, Chongyang; Estacion, Mark; Huang, Jianying; Vasylyev, Dymtro; Zhao, Peng; Dib-Hajj, Sulayman D; Waxman, Stephen G

    2015-05-01

    Although species-specific differences in ion channel properties are well-documented, little has been known about the properties of the human Nav1.8 channel, an important contributor to pain signaling. Here we show, using techniques that include voltage clamp, current clamp, and dynamic clamp in dorsal root ganglion (DRG) neurons, that human Na(v)1.8 channels display slower inactivation kinetics and produce larger persistent current and ramp current than previously reported in other species. DRG neurons expressing human Na(v)1.8 channels unexpectedly produce significantly longer-lasting action potentials, including action potentials with half-widths in some cells >10 ms, and increased firing frequency compared with the narrower and usually single action potentials generated by DRG neurons expressing rat Na(v)1.8 channels. We also show that native human DRG neurons recapitulate these properties of Na(v)1.8 current and the long-lasting action potentials. Together, our results demonstrate strikingly distinct properties of human Na(v)1.8, which contribute to the firing properties of human DRG neurons.

  1. Automatic and Controlled Semantic Retrieval: TMS Reveals Distinct Contributions of Posterior Middle Temporal Gyrus and Angular Gyrus.

    Science.gov (United States)

    Davey, James; Cornelissen, Piers L; Thompson, Hannah E; Sonkusare, Saurabh; Hallam, Glyn; Smallwood, Jonathan; Jefferies, Elizabeth

    2015-11-18

    Semantic retrieval involves both (1) automatic spreading activation between highly related concepts and (2) executive control processes that tailor this activation to suit the current context or goals. Two structures in left temporoparietal cortex, angular gyrus (AG) and posterior middle temporal gyrus (pMTG), are thought to be crucial to semantic retrieval and are often recruited together during semantic tasks; however, they show strikingly different patterns of functional connectivity at rest (coupling with the "default mode network" and "frontoparietal control system," respectively). Here, transcranial magnetic stimulation (TMS) was used to establish a causal yet dissociable role for these sites in semantic cognition in human volunteers. TMS to AG disrupted thematic judgments particularly when the link between probe and target was strong (e.g., a picture of an Alsatian with a bone), and impaired the identification of objects at a specific but not a superordinate level (for the verbal label "Alsatian" not "animal"). In contrast, TMS to pMTG disrupted thematic judgments for weak but not strong associations (e.g., a picture of an Alsatian with razor wire), and impaired identity matching for both superordinate and specific-level labels. Thus, stimulation to AG interfered with the automatic retrieval of specific concepts from the semantic store while stimulation of pMTG impaired semantic cognition when there was a requirement to flexibly shape conceptual activation in line with the task requirements. These results demonstrate that AG and pMTG make a dissociable contribution to automatic and controlled aspects of semantic retrieval. We demonstrate a novel functional dissociation between the angular gyrus (AG) and posterior middle temporal gyrus (pMTG) in conceptual processing. These sites are often coactivated during neuroimaging studies using semantic tasks, but their individual contributions are unclear. Using transcranial magnetic stimulation and tasks designed to

  2. 29 CFR 549.3 - Distinction between plan and trust.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Distinction between plan and trust. 549.3 Section 549.3 Labor Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS REQUIREMENTS OF A âBONA FIDE PROFIT-SHARING PLAN OR TRUSTâ § 549.3 Distinction between plan and trust. As used in this part: (a) Profit-sharing plan...

  3. Two distinct modes of RecA action are required for DNA polymerase V-catalyzed translesion synthesis.

    Science.gov (United States)

    Pham, Phuong; Seitz, Erica M; Saveliev, Sergei; Shen, Xuan; Woodgate, Roger; Cox, Michael M; Goodman, Myron F

    2002-08-20

    SOS mutagenesis in Escherichia coli requires DNA polymerase V (pol V) and RecA protein to copy damaged DNA templates. Here we show that two distinct biochemical modes for RecA protein are necessary for pol V-catalyzed translesion synthesis. One RecA mode is characterized by a strong stimulation in nucleotide incorporation either directly opposite a lesion or at undamaged template sites, but by the absence of lesion bypass. A separate RecA mode is necessary for translesion synthesis. The RecA1730 mutant protein, which was identified on the basis of its inability to promote pol V (UmuD'(2)C)-dependent UV-mutagenesis, appears proficient for the first mode of RecA action but is deficient in the second mode. Data are presented suggesting that the two RecA modes are "nonfilamentous". That is, contrary to current models for SOS mutagenesis, formation of a RecA nucleoprotein filament may not be required for copying damaged DNA templates. Instead, SOS mutagenesis occurs when pol V interacts with two RecA molecules, first at a 3' primer end, upstream of a template lesion, where RecA mode 1 stimulates pol V activity, and subsequently at a site immediately downstream of the lesion, where RecA mode 2 cocatalyzes lesion bypass. We posit that in vivo assembly of a RecA nucleoprotein filament may be required principally to target pol V to a site of DNA damage and to stabilize the pol V-RecA interaction at the lesion. However, it is only a RecA molecule located at the 3' filament tip, proximal to a damaged template base, that is directly responsible for translesion synthesis.

  4. Distinctions, Affiliations, and Professional Knowledge in Financial Reform Expert Groups

    DEFF Research Database (Denmark)

    Seabrooke, Leonard; Tsingou, Eleni

    2014-01-01

    to understand the different stresses in reports with and without clear mandates, and the role of important members of the policy community in promoting particular reform ideas. The contribution finds that differences in ideas emerging from the financial reform expert groups reflect nested power relationships...... the reports. Fractal distinctions, such as between ‘behaviour’ or ‘system’ as a reform focus, allow us to locate the object of regulation within expert groups, the experts' professional context and the politics behind the commissioning of work. Analysing fractal distinctions provides a useful way...... in the commissioning of work, constituent audiences and reform priorities among governing institutions, rather than distinct ‘European’ and ‘American’ ideas....

  5. Identification of RNA Binding Proteins Associated with Dengue Virus RNA in Infected Cells Reveals Temporally Distinct Host Factor Requirements.

    Directory of Open Access Journals (Sweden)

    Olga V Viktorovskaya

    2016-08-01

    Full Text Available There are currently no vaccines or antivirals available for dengue virus infection, which can cause dengue hemorrhagic fever and death. A better understanding of the host pathogen interaction is required to develop effective therapies to treat DENV. In particular, very little is known about how cellular RNA binding proteins interact with viral RNAs. RNAs within cells are not naked; rather they are coated with proteins that affect localization, stability, translation and (for viruses replication.Seventy-nine novel RNA binding proteins for dengue virus (DENV were identified by cross-linking proteins to dengue viral RNA during a live infection in human cells. These cellular proteins were specific and distinct from those previously identified for poliovirus, suggesting a specialized role for these factors in DENV amplification. Knockdown of these proteins demonstrated their function as viral host factors, with evidence for some factors acting early, while others late in infection. Their requirement by DENV for efficient amplification is likely specific, since protein knockdown did not impair the cell fitness for viral amplification of an unrelated virus. The protein abundances of these host factors were not significantly altered during DENV infection, suggesting their interaction with DENV RNA was due to specific recruitment mechanisms. However, at the global proteome level, DENV altered the abundances of proteins in particular classes, including transporter proteins, which were down regulated, and proteins in the ubiquitin proteasome pathway, which were up regulated.The method for identification of host factors described here is robust and broadly applicable to all RNA viruses, providing an avenue to determine the conserved or distinct mechanisms through which diverse viruses manage the viral RNA within cells. This study significantly increases the number of cellular factors known to interact with DENV and reveals how DENV modulates and usurps

  6. Mycobacteria exploit three genetically distinct DNA double-strand break repair pathways.

    Science.gov (United States)

    Gupta, Richa; Barkan, Daniel; Redelman-Sidi, Gil; Shuman, Stewart; Glickman, Michael S

    2011-01-01

    Bacterial pathogens rely on their DNA repair pathways to resist genomic damage inflicted by the host. DNA double-strand breaks (DSBs) are especially threatening to bacterial viability. DSB repair by homologous recombination (HR) requires nucleases that resect DSB ends and a strand exchange protein that facilitates homology search. RecBCD and RecA perform these functions in Escherichia coli and constitute the major pathway of error-free DSB repair. Mycobacteria, including the human pathogen M. tuberculosis, elaborate an additional error-prone pathway of DSB repair via non-homologous end-joining (NHEJ) catalysed by Ku and DNA ligase D (LigD). Little is known about the relative contributions of HR and NHEJ to mycobacterial chromosome repair, the factors that dictate pathway choice, or the existence of additional DSB repair pathways. Here we demonstrate that Mycobacterium smegmatis has three DSB repair pathway options: HR, NHEJ and a novel mechanism of single-strand annealing (SSA). Inactivation of NHEJ or SSA is compensated by elevated HR. We find that mycobacterial RecBCD does not participate in HR or confer resistance to ionizing radiation (IR), but is required for the RecA-independent SSA pathway. In contrast, the mycobacterial helicase-nuclease AdnAB participates in the RecA-dependent HR pathway, and is a major determinant of resistance to IR and oxidative DNA damage. These findings reveal distinctive features of mycobacterial DSB repair, most notably the dedication of the RecBCD and AdnAB helicase-nuclease machines to distinct repair pathways. © 2010 Blackwell Publishing Ltd.

  7. Short- and long-term memory in Drosophila require cAMP signaling in distinct neuron types.

    Science.gov (United States)

    Blum, Allison L; Li, Wanhe; Cressy, Mike; Dubnau, Josh

    2009-08-25

    A common feature of memory and its underlying synaptic plasticity is that each can be dissected into short-lived forms involving modification or trafficking of existing proteins and long-term forms that require new gene expression. An underlying assumption of this cellular view of memory consolidation is that these different mechanisms occur within a single neuron. At the neuroanatomical level, however, different temporal stages of memory can engage distinct neural circuits, a notion that has not been conceptually integrated with the cellular view. Here, we investigated this issue in the context of aversive Pavlovian olfactory memory in Drosophila. Previous studies have demonstrated a central role for cAMP signaling in the mushroom body (MB). The Ca(2+)-responsive adenylyl cyclase RUTABAGA is believed to be a coincidence detector in gamma neurons, one of the three principle classes of MB Kenyon cells. We were able to separately restore short-term or long-term memory to a rutabaga mutant with expression of rutabaga in different subsets of MB neurons. Our findings suggest a model in which the learning experience initiates two parallel associations: a short-lived trace in MB gamma neurons, and a long-lived trace in alpha/beta neurons.

  8. The physician-administrator as patient: distinctive aspects of medical care.

    Science.gov (United States)

    Cappell, Mitchell S

    2011-01-01

    This article examines distinctive aspects of medical care experienced by a 55-year-old hospitalized for quintuple coronary artery bypass surgery who was also a senior physician-administrator (chief of gastroenterology) at the same hospital. The article describes eight distinctive aspects of administrator-physicians as patients, including special patient treatment; exalted patient expectations by hospital personnel; patient suppression of emotions; patient denial; self-doctoring; job stress contributing to disease; self-sacrifice to achieve better health; and rational medical decisions when not under stress. Health-care workers should recognize how these distinctive aspects of medical care and behavior affect administrator-physicians as patients, in order to mitigate their negative effects, potentiate their positive effects, and optimize the care of these patients.

  9. Pax7 lineage contributions to the mammalian neural crest.

    Directory of Open Access Journals (Sweden)

    Barbara Murdoch

    Full Text Available Neural crest cells are vertebrate-specific multipotent cells that contribute to a variety of tissues including the peripheral nervous system, melanocytes, and craniofacial bones and cartilage. Abnormal development of the neural crest is associated with several human maladies including cleft/lip palate, aggressive cancers such as melanoma and neuroblastoma, and rare syndromes, like Waardenburg syndrome, a complex disorder involving hearing loss and pigment defects. We previously identified the transcription factor Pax7 as an early marker, and required component for neural crest development in chick embryos. In mammals, Pax7 is also thought to play a role in neural crest development, yet the precise contribution of Pax7 progenitors to the neural crest lineage has not been determined.Here we use Cre/loxP technology in double transgenic mice to fate map the Pax7 lineage in neural crest derivates. We find that Pax7 descendants contribute to multiple tissues including the cranial, cardiac and trunk neural crest, which in the cranial cartilage form a distinct regional pattern. The Pax7 lineage, like the Pax3 lineage, is additionally detected in some non-neural crest tissues, including a subset of the epithelial cells in specific organs.These results demonstrate a previously unappreciated widespread distribution of Pax7 descendants within and beyond the neural crest. They shed light regarding the regionally distinct phenotypes observed in Pax3 and Pax7 mutants, and provide a unique perspective into the potential roles of Pax7 during disease and development.

  10. Alcohol-related biases in selective attention and action tendency make distinct contributions to dysregulated drinking behaviour.

    Science.gov (United States)

    Sharbanee, Jason M; Stritzke, Werner G K; Wiers, Reinout W; MacLeod, Colin

    2013-10-01

    To assess whether alcohol-related biases in selective-attention and action tendency uniquely or concurrently predict the ability to regulate alcohol consumption. Two groups of undergraduate social drinkers (total n = 55) who differed in their ability to regulate their alcohol consumption completed a novel Selective-Attention/Action-Tendency Task (SA/ATT), which assessed separately alcohol-related biases in selective attention and action tendency. University of Western Australia, Australia. Dysregulated drinking was operationalized as a self-reported high level of alcohol consumption on the Alcohol Consumption Questionnaire, and a high desire to reduce consumption on the Brief Readiness to Change Algorithm. Selective attention and action tendency were assessed using the SA/ATT, working memory was assessed using the operation-span task and participant characteristics were assessed using the Alcohol Use Disorders Identification Test (AUDIT) and Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Results indicated that (i) there was no significant association between alcohol-related biases in selective attention and action tendency, r = 0.16, P = 0.274, and (ii) biases towards alcohol, in both selective attention, β = 1.01, odds ratio = 2.74, P = 0.022, and action tendency, β = 1.24, odds ratio = 3.45, P = 0.015, predicted independent variance in dysregulated-drinker status. Biases in selective attention and action tendency appear to be distinct mechanisms that contribute independently to difficulty regulating alcohol consumption. Treatment components that could be combined to target both mechanisms could enhance treatment outcomes for alcohol-use disorders. © 2013 Society for the Study of Addiction.

  11. On the roles of distinctiveness and semantic expectancies in episodic encoding of emotional words.

    Science.gov (United States)

    Kamp, Siri-Maria; Potts, Geoffrey F; Donchin, Emanuel

    2015-12-01

    We examined the factors that contribute to enhanced recall for emotionally arousing words by analyzing behavioral performance, the P300 as an index of distinctiveness, and the N400 as an index of semantic expectancy violation in a modified Von Restorff paradigm. While their EEG was recorded, participants studied three list types (1) neutral words including one emotionally arousing isolate (either positive or negative), (2) arousing, negative words including one neutral isolate, or (3) arousing, positive words including one neutral isolate. Immediately after each list, free recall was tested. Negative, but not positive, words exhibited enhanced recall when presented as isolates in lists of neutral words and elicited a larger P300 for subsequently recalled than not-recalled words. This suggests that arousing, negative words stand out and that their distinctiveness contributes to their superior recall. Positive valence had an enhancing effect on recall only when the list contained mostly other positive words. Neutral isolates placed in either positive or negative lists elicited an N400, suggesting that semantic expectations developed in emotional word lists regardless of valence. However, semantic relatedness appeared to more strongly contribute to recall for positive than negative words. Our results suggest that distinctiveness and semantic relatedness contribute to episodic encoding of arousing words, but the impact of each factor depends on both a word's valence and its context. © 2015 Society for Psychophysiological Research.

  12. Ethical distinctions between different kinds of plant breeding

    DEFF Research Database (Denmark)

    Myskja, B.K.; Schouten, H.J.; Gjerris, Mickey

    2015-01-01

    The article discusses whether there are ethically significant distinctions between different forms of plant breeding. We distinguish different forms of plant breeding according to the kind of technology and degree of human intervention compared to plant reproduction occurring in nature. According...... differences between plant breeding methods. The framework can contribute to an improved dialogue between the scientific community and the wider public by making the scepticism towards GM-technology more intelligible....

  13. 20 CFR 404.1536 - Treatment required for individuals whose drug addiction or alcoholism is a contributing factor...

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Treatment required for individuals whose drug addiction or alcoholism is a contributing factor material to the determination of disability. 404.1536 Section 404.1536 Employees' Benefits SOCIAL SECURITY ADMINISTRATION FEDERAL OLD-AGE, SURVIVORS AND DISABILITY INSURANCE (1950- ) Determining...

  14. Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens.

    Science.gov (United States)

    Glinsky, Gennadi V

    2016-09-19

    Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8-10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P sapiens is driven by the evolution of human-specific genomic regulatory networks via at least two mechanistically distinct pathways of creation of

  15. 20 CFR 416.936 - Treatment required for individuals whose drug addiction or alcoholism is a contributing factor...

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 2 2010-04-01 2010-04-01 false Treatment required for individuals whose drug addiction or alcoholism is a contributing factor material to the determination of disability. 416.936 Section 416.936 Employees' Benefits SOCIAL SECURITY ADMINISTRATION SUPPLEMENTAL SECURITY INCOME FOR THE AGED, BLIND, AND DISABLED Determining...

  16. Consistency requirements on Δ contributions to the NN potential

    International Nuclear Information System (INIS)

    Rinat, A.S.

    1982-04-01

    We discuss theories leading to intermediate state NΔ and ΔΔ contributions to Vsub(NN). We focus on the customary addition of Lsub(ΔNπ)' to Lsub(πNN)' in a conventional field theory and argue that overcounting of contributions to tsub(πN) and Vsub(NN) will be the rule. We then discuss the cloudy bag model where a similar interaction naturally arises and which leads to a consistent theory. (author)

  17. Entrepreneurship research in Spain: developments and distinctiveness.

    Science.gov (United States)

    Sánchez, José C; Gutiérrez, Andrea

    2011-08-01

    This article presents a review of research on entrepreneurship in Spain, paying particular attention to its beginnings, nature and main focus of interest. We have developed a database based on the review of 471 works produced between 1977 and 2009, including articles published in national and international journals and dissertations (read in Spain) that allowed us to extract the following results. There is a preference for qualitative methods, conceptual contributions and the entrepreneurial process as the privileged research theme. There is also a strong focus of interest on micro and small enterprises. These characteristics of Spanish research in areas of entrepreneurship can make a distinctive contribution to international research. However, the dissemination of knowledge and inadequate strategies for international publication limit the diffusion of Spanish research in entrepreneurship. Lastly, we discuss the implications for future research.

  18. The N- and C-terminal carbohydrate recognition domains of Haemonchus contortus galectin bind to distinct receptors of goat PBMC and contribute differently to its immunomodulatory functions in host-parasite interactions.

    Science.gov (United States)

    Lu, MingMin; Tian, XiaoWei; Yang, XinChao; Yuan, Cheng; Ehsan, Muhammad; Liu, XinChao; Yan, RuoFeng; Xu, LiXin; Song, XiaoKai; Li, XiangRui

    2017-09-05

    Hco-gal-m is a tandem-repeat galectin isolated from the adult worm of Haemonchus contortus. A growing body of studies have demonstrated that Hco-gal-m could exert its immunomodulatory effects on host peripheral blood mononuclear cells (PBMC) to facilitate the immune evasion. Our previous work revealed that C-terminal and N-terminal carbohydrate recognition domains (CRD) of Hco-gal-m had different sugar binding abilities. However, whether different domains of Hco-gal-m account differently for its multiple immunomodulatory functions in the host-parasite interaction remains to be elucidated. We found that the N-terminal CRD of Hco-gal-m (MNh) and the C-terminal CRD (MCh) could bind to goat peripheral blood mononuclear cells by distinct receptors: transmembrane protein 63A (TMEM63A) was a binding receptor of MNh, while transmembrane protein 147 (TMEM147) was a binding receptor of MCh. In addition, MCh was much more potent than MNh in inhibiting cell proliferation and inducing apoptosis, while MNh was much more effective in inhibiting NO production. Moreover, MNh could suppress the transcription of interferon-γ (IFN-γ), but MCh not. Our data suggested that these two CRDs of Hco-gal-m bind to distinct receptors and contributed differently to its ability to downregulate host immune response. These results will improve our understanding of galectins from parasitic nematodes contributing to the mechanism of parasitic immune evasion and continue to illustrate the diverse range of biological activities attributable to the galectin family.

  19. Student Teachers' Distinctive Contributions to Research on Primary School Children's Beliefs about Knowledge and Knowing

    Science.gov (United States)

    Kershner, Ruth; Hargreaves, Linda

    2012-01-01

    Student teachers' research is usually valued more for its contribution to their professional learning than for its contribution to the research topic itself. This paper reports on a research collaboration with eight student primary teachers in England, intended to build on a previously established project investigating young children's…

  20. Ultrasound Microbubble Treatment Enhances Clathrin-Mediated Endocytosis and Fluid-Phase Uptake through Distinct Mechanisms.

    Directory of Open Access Journals (Sweden)

    Farnaz Fekri

    Full Text Available Drug delivery to tumors is limited by several factors, including drug permeability of the target cell plasma membrane. Ultrasound in combination with microbubbles (USMB is a promising strategy to overcome these limitations. USMB treatment elicits enhanced cellular uptake of materials such as drugs, in part as a result of sheer stress and formation of transient membrane pores. Pores formed upon USMB treatment are rapidly resealed, suggesting that other processes such as enhanced endocytosis may contribute to the enhanced material uptake by cells upon USMB treatment. How USMB regulates endocytic processes remains incompletely understood. Cells constitutively utilize several distinct mechanisms of endocytosis, including clathrin-mediated endocytosis (CME for the internalization of receptor-bound macromolecules such as Transferrin Receptor (TfR, and distinct mechanism(s that mediate the majority of fluid-phase endocytosis. Tracking the abundance of TfR on the cell surface and the internalization of its ligand transferrin revealed that USMB acutely enhances the rate of CME. Total internal reflection fluorescence microscopy experiments revealed that USMB treatment altered the assembly of clathrin-coated pits, the basic structural units of CME. In addition, the rate of fluid-phase endocytosis was enhanced, but with delayed onset upon USMB treatment relative to the enhancement of CME, suggesting that the two processes are distinctly regulated by USMB. Indeed, vacuolin-1 or desipramine treatment prevented the enhancement of CME but not of fluid phase endocytosis upon USMB, suggesting that lysosome exocytosis and acid sphingomyelinase, respectively, are required for the regulation of CME but not fluid phase endocytosis upon USMB treatment. These results indicate that USMB enhances both CME and fluid phase endocytosis through distinct signaling mechanisms, and suggest that strategies for potentiating the enhancement of endocytosis upon USMB treatment may

  1. Differential Contribution of RNA Interference Components in Response to Distinct Fusarium graminearum Virus Infections.

    Science.gov (United States)

    Yu, Jisuk; Lee, Kyung-Mi; Cho, Won Kyong; Park, Ju Yeon; Kim, Kook-Hyung

    2018-05-01

    The mechanisms of RNA interference (RNAi) as a defense response against viruses remain unclear in many plant-pathogenic fungi. In this study, we used reverse genetics and virus-derived small RNA profiling to investigate the contributions of RNAi components to the antiviral response against Fusarium graminearum viruses 1 to 3 (FgV1, -2, and -3). Real-time reverse transcription-quantitative PCR (qRT-PCR) indicated that infection of Fusarium graminearum by FgV1, -2, or -3 differentially induces the gene expression of RNAi components in F. graminearum Transcripts of the DICER-2 and AGO-1 genes of F. graminearum ( FgDICER-2 and FgAGO-1 ) accumulated at lower levels following FgV1 infection than following FgV2 or FgV3 infection. We constructed gene disruption and overexpression mutants for each of the Argonaute and dicer genes and for two RNA-dependent RNA polymerase (RdRP) genes and generated virus-infected strains of each mutant. Interestingly, mycelial growth was significantly faster for the FgV1-infected FgAGO-1 overexpression mutant than for the FgV1-infected wild type, while neither FgV2 nor FgV3 infection altered the colony morphology of the gene deletion and overexpression mutants. FgV1 RNA accumulation was significantly decreased in the FgAGO-1 overexpression mutant. Furthermore, the levels of induction of FgAGO-1 , FgDICER-2 , and some of the FgRdRP genes caused by FgV2 and FgV3 infection were similar to those caused by hairpin RNA-induced gene silencing. Using small RNA sequencing analysis, we documented different patterns of virus-derived small interfering RNA (vsiRNA) production in strains infected with FgV1, -2, and -3. Our results suggest that the Argonaute protein encoded by FgAGO-1 is required for RNAi in F. graminearum , that FgAGO-1 induction differs in response to FgV1, -2, and -3, and that FgAGO-1 might contribute to the accumulation of vsiRNAs in FgV1-infected F. graminearum IMPORTANCE To increase our understanding of how RNAi components in Fusarium

  2. Distinct Circuits for Recovery of Eye Dominance and Acuity in Murine Amblyopia.

    Science.gov (United States)

    Stephany, Céleste-Élise; Ma, Xiaokuang; Dorton, Hilary M; Wu, Jie; Solomon, Alexander M; Frantz, Michael G; Qiu, Shenfeng; McGee, Aaron W

    2018-05-24

    Degrading vision by one eye during a developmental critical period yields enduring deficits in both eye dominance and visual acuity. A predominant model is that "reactivating" ocular dominance (OD) plasticity after the critical period is required to improve acuity in amblyopic adults. However, here we demonstrate that plasticity of eye dominance and acuity are independent and restricted by the nogo-66 receptor (ngr1) in distinct neuronal populations. Ngr1 mutant mice display greater excitatory synaptic input onto both inhibitory and excitatory neurons with restoration of normal vision. Deleting ngr1 in excitatory cortical neurons permits recovery of eye dominance but not acuity. Reciprocally, deleting ngr1 in thalamus is insufficient to rectify eye dominance but yields improvement of acuity to normal. Abolishing ngr1 expression in adult mice also promotes recovery of acuity. Together, these findings challenge the notion that mechanisms for OD plasticity contribute to the alterations in circuitry that restore acuity in amblyopia. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. Distinct Contributions of Autophagy Receptors in Measles Virus Replication.

    Science.gov (United States)

    Petkova, Denitsa S; Verlhac, Pauline; Rozières, Aurore; Baguet, Joël; Claviere, Mathieu; Kretz-Remy, Carole; Mahieux, Renaud; Viret, Christophe; Faure, Mathias

    2017-05-22

    Autophagy is a potent cell autonomous defense mechanism that engages the lysosomal pathway to fight intracellular pathogens. Several autophagy receptors can recognize invading pathogens in order to target them towards autophagy for their degradation after the fusion of pathogen-containing autophagosomes with lysosomes. However, numerous intracellular pathogens can avoid or exploit autophagy, among which is measles virus (MeV). This virus induces a complete autophagy flux, which is required to improve viral replication. We therefore asked how measles virus interferes with autophagy receptors during the course of infection. We report that in addition to NDP52/CALCOCO₂ and OPTINEURIN/OPTN, another autophagy receptor, namely T6BP/TAXIBP1, also regulates the maturation of autophagosomes by promoting their fusion with lysosomes, independently of any infection. Surprisingly, only two of these receptors, NDP52 and T6BP, impacted measles virus replication, although independently, and possibly through physical interaction with MeV proteins. Thus, our results suggest that a restricted set of autophagosomes is selectively exploited by measles virus to replicate in the course of infection.

  4. Quantum Distinction: Quantum Distinctiones!

    OpenAIRE

    Zeps, Dainis

    2009-01-01

    10 pages; How many distinctions, in Latin, quantum distinctiones. We suggest approach of anthropic principle based on anthropic reference system which should be applied equally both in theoretical physics and in mathematics. We come to principle that within reference system of life subject of mathematics (that of thinking) should be equated with subject of physics (that of nature). For this reason we enter notions of series of distinctions, quantum distinction, and argue that quantum distinct...

  5. Distinct hydrophobic “patches” in the N- and C-tails of beta-catenin contribute to nuclear transport

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Manisha; Jamieson, Cara; Lui, Christina [Center for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145 (Australia); Henderson, Beric R., E-mail: beric.henderson@sydney.edu.au [Center for Cancer Research, The Westmead Institute for Medical Research, The University of Sydney, Westmead, NSW 2145 (Australia)

    2016-11-01

    β-catenin is a key mediator of Wnt signaling and its deregulated nuclear accumulation can drive cancer progression. While the central armadillo (Arm) repeats of β-catenin stimulate nuclear entry, the N- and C-terminal “tail” sequences are thought to regulate turnover and transactivation. We show here that the N- and C-tails are also potent transport sequences. The unstructured tails of β-catenin, when individually fused to a GFP-reporter, could enter and exit the nucleus rapidly in live cells. Proximity ligation assays and pull-down assays identified a weak interaction between the tail sequences and the FG-repeats of nucleoporins, consistent with a possible direct translocation of β-catenin through the nuclear pore complex. Extensive alanine mutagenesis of the tail sequences revealed that nuclear translocation of β-catenin was dependent on specific uniformly distributed patches of hydrophobic residues, whereas the mutagenesis of acidic amino acids had no effect. Moreover, the mutation of hydrophobic patches within the N-tail and C-tail of full length β-catenin reduced nuclear transport rate and diminished its ability to activate transcription. We propose that the tail sequences can contribute to β-catenin transport and suggest a possible similar role for hydrophobic unstructured regions in other proteins. - Highlights: • We show that the N- and C-tails of beta-catenin possess nuclear transport activity. • Nuclear transport of the N- or C-tails requires specific hydrophobic amino acids. • Mutagenesis of the N-terminus diminished nuclear entry of full-length beta-catenin. • We propose the N-tail contributes to beta-catenin nuclear entry and transactivation.

  6. Contribution of wind energy to future electricity requirements of Pakistan

    International Nuclear Information System (INIS)

    Harijan, K.; Uqaili, M. A.; Memon, M.

    2007-01-01

    Pakistan is an energy deficit country. About half of the country's population has no access to electricity and per capita supply is only 520 kWh. About 67% of the conventional electricity is generated from fossil fuels with 51% and 16% share of gas and oil respectively. It has been projected that electricity demand in Pakistan would increase at an average annual growth rate of 5% to 12% under different scenarios. The indigenous reserves of oil and gas are limited and the country heavily depends on imported oil. The oil import bill is a serious strain on the country's economy and has been deteriorating the balance of payment situation. Pakistan is becoming increasingly more dependent on a few sources of supply and its energy security often hangs on the fragile threat of imported oil that is subject to supply disruptions and price volatility. The production and consumption of fossil fuels also adversely affects the quality of the environment due to indiscriminate release of toxic substances. Pakistan spends huge amount on the degradation of the environment. This shows that Pakistan must develop alternate, indigenous and environment friendly energy resources such as wind energy to meet its future electricity requirements. This paper presents an overview of wind power generation potential and assessment of its contribution to future electricity requirements of Pakistan under different policy scenarios. The country has about 1050 km long coastline. The technical potential of centralized grid connected wind power and wind home systems in the coastal area of the country has been estimated as about 484 TWh and 0.135 TWh per year respectively. The study concludes that wind power could meet about 20% to 50% of the electricity demand in Pakistan by the year 2030. The development and utilization of wind power would reduce the pressure on oil imports, protect the environment from pollution and improve the socio-economic conditions of the people

  7. Shared and distinct contributions of rostrolateral prefrontal cortex to analogical reasoning and episodic memory retrieval.

    Science.gov (United States)

    Westphal, Andrew J; Reggente, Nicco; Ito, Kaori L; Rissman, Jesse

    2016-03-01

    Rostrolateral prefrontal cortex (RLPFC) is widely appreciated to support higher cognitive functions, including analogical reasoning and episodic memory retrieval. However, these tasks have typically been studied in isolation, and thus it is unclear whether they involve common or distinct RLPFC mechanisms. Here, we introduce a novel functional magnetic resonance imaging (fMRI) task paradigm to compare brain activity during reasoning and memory tasks while holding bottom-up perceptual stimulation and response demands constant. Univariate analyses on fMRI data from twenty participants identified a large swath of left lateral prefrontal cortex, including RLPFC, that showed common engagement on reasoning trials with valid analogies and memory trials with accurately retrieved source details. Despite broadly overlapping recruitment, multi-voxel activity patterns within left RLPFC reliably differentiated these two trial types, highlighting the presence of at least partially distinct information processing modes. Functional connectivity analyses demonstrated that while left RLPFC showed consistent coupling with the fronto-parietal control network across tasks, its coupling with other cortical areas varied in a task-dependent manner. During the memory task, this region strengthened its connectivity with the default mode and memory retrieval networks, whereas during the reasoning task it coupled more strongly with a nearby left prefrontal region (BA 45) associated with semantic processing, as well as with a superior parietal region associated with visuospatial processing. Taken together, these data suggest a domain-general role for left RLPFC in monitoring and/or integrating task-relevant knowledge representations and showcase how its function cannot solely be attributed to episodic memory or analogical reasoning computations. © 2015 Wiley Periodicals, Inc.

  8. Education and Training: Is There Any Longer a Useful Distinction?

    Science.gov (United States)

    Hager, Paul; Laurent, John

    1990-01-01

    Although education and training were distinct concepts when Taylorism dominated the workplace, it is no longer appropriate to separate them. Today's highly competitive environment requires the education of a flexible, multiskilled workforce, not training for narrowly defined employment tasks. (SK)

  9. Touch communicates distinct emotions.

    Science.gov (United States)

    Hertenstein, Matthew J; Keltner, Dacher; App, Betsy; Bulleit, Brittany A; Jaskolka, Ariane R

    2006-08-01

    The study of emotional signaling has focused almost exclusively on the face and voice. In 2 studies, the authors investigated whether people can identify emotions from the experience of being touched by a stranger on the arm (without seeing the touch). In the 3rd study, they investigated whether observers can identify emotions from watching someone being touched on the arm. Two kinds of evidence suggest that humans can communicate numerous emotions with touch. First, participants in the United States (Study 1) and Spain (Study 2) could decode anger, fear, disgust, love, gratitude, and sympathy via touch at much-better-than-chance levels. Second, fine-grained coding documented specific touch behaviors associated with different emotions. In Study 3, the authors provide evidence that participants can accurately decode distinct emotions by merely watching others communicate via touch. The findings are discussed in terms of their contributions to affective science and the evolution of altruism and cooperation. (c) 2006 APA, all rights reserved

  10. The contribution of material control to meeting performance requirements

    International Nuclear Information System (INIS)

    Rivers, J.D.

    1989-01-01

    The U.S. Dept. of Energy (DOE) is in the process of implementing a set of performance requirements for material control and accountability (MC ampersand A). These graded requirements set a uniform level of performance for similar materials at various facilities with respect to the threat of an insider adversary stealing special nuclear material (SNM). These requirements are phrased in terms of detecting the theft of a goal quantity of SNM within a specified time period and with a probability greater than or equal to a specified value and include defense in-depth requirements

  11. Distinct Hippocampal versus Frontoparietal Network Contributions to Retrieval and Memory-guided Exploration.

    Science.gov (United States)

    Bridge, Donna J; Cohen, Neal J; Voss, Joel L

    2017-08-01

    Memory can profoundly influence new learning, presumably because memory optimizes exploration of to-be-learned material. Although hippocampus and frontoparietal networks have been implicated in memory-guided exploration, their specific and interactive roles have not been identified. We examined eye movements during fMRI scanning to identify neural correlates of the influences of memory retrieval on exploration and learning. After retrieval of one object in a multiobject array, viewing was strategically directed away from the retrieved object toward nonretrieved objects, such that exploration was directed toward to-be-learned content. Retrieved objects later served as optimal reminder cues, indicating that exploration caused memory to become structured around the retrieved content. Hippocampal activity was associated with memory retrieval, whereas frontoparietal activity varied with strategic viewing patterns deployed after retrieval, thus providing spatiotemporal dissociation of memory retrieval from memory-guided learning strategies. Time-lagged fMRI connectivity analyses indicated that hippocampal activity predicted frontoparietal activity to a greater extent for a condition in which retrieval guided exploration occurred than for a passive control condition in which exploration was not influenced by retrieval. This demonstrates network-level interaction effects specific to influences of memory on strategic exploration. These findings show how memory guides behavior during learning and demonstrate distinct yet interactive hippocampal-frontoparietal roles in implementing strategic exploration behaviors that determine the fate of evolving memory representations.

  12. Distinct hippocampal versus frontoparietal-network contributions to retrieval and memory-guided exploration

    Science.gov (United States)

    Bridge, Donna J.; Cohen, Neal J.; Voss, Joel L.

    2017-01-01

    Memory can profoundly influence new learning, presumably because memory optimizes exploration of to-be-learned material. Although hippocampus and frontoparietal networks have been implicated in memory-guided exploration, their specific and interactive roles have not been identified. We examined eye movements during fMRI scanning to identify neural correlates of the influences of memory retrieval on exploration and learning. Following retrieval of one object in a multi-object array, viewing was strategically directed away from the retrieved object toward non-retrieved objects, such that exploration was directed towards to-be-learned content. Retrieved objects later served as optimal reminder cues, indicating that exploration caused memory to become structured around the retrieved content. Hippocampal activity was associated with memory retrieval whereas frontoparietal activity varied with strategic viewing patterns deployed following retrieval, thus providing spatiotemporal dissociation of memory retrieval from memory-guided learning strategies. Time-lagged fMRI connectivity analyses indicated that hippocampal activity predicted frontoparietal activity to a greater extent for a condition in which retrieval guided exploration than for a passive control condition in which exploration was not influenced by retrieval. This demonstrates network-level interaction effects specific to influences of memory on strategic exploration. These findings show how memory guides behavior during learning and demonstrate distinct yet interactive hippocampal-frontoparietal roles in implementing strategic exploration behaviors that determine the fate of evolving memory representations. PMID:28471729

  13. Molecular polymorphism of a cell surface proteoglycan: distinct structures on simple and stratified epithelia.

    Science.gov (United States)

    Sanderson, R D; Bernfield, M

    1988-12-01

    Epithelial cells are organized into either a single layer (simple epithelia) or multiple layers (stratified epithelia). Maintenance of these cellular organizations requires distinct adhesive mechanisms involving many cell surface molecules. One such molecule is a cell surface proteoglycan, named syndecan, that contains both heparan sulfate and chondroitin sulfate chains. This proteoglycan binds cells to fibrillar collagens and fibronectin and thus acts as a receptor for interstitial matrix. The proteoglycan is restricted to the basolateral surface of simple epithelial cells, but is located over the entire surface of stratified epithelial cells, even those surfaces not contacting matrix. We now show that the distinct localization in simple and stratified epithelia correlates with a distinct proteoglycan structure. The proteoglycan from simple epithelia (modal molecular size, 160 kDa) is larger than that from stratified epithelia (modal molecular size, 92 kDa), but their core proteins are identical in size and immunoreactivity. The proteoglycan from simple epithelia has more and larger heparan sulfate and chondroitin sulfate chains than the proteoglycan from stratified epithelia. Thus, the cell surface proteoglycan shows a tissue-specific structural polymorphism due to distinct posttranslational modifications. This polymorphism likely reflects distinct proteoglycan functions in simple and stratified epithelia, potentially meeting the different adhesive requirements of the cells in these different organizations.

  14. Color-octet contributions to J/ψ photoproduction

    International Nuclear Information System (INIS)

    Cacciari, M.; Kraemer, M.

    1996-01-01

    We have calculated the leading color-octet contributions to the production of J/ψ particles in photon-proton collisions. Using the values for the color-octet matrix elements extracted from fits to prompt J/ψ data at the Tevatron, we demonstrate that distinctive color-octet signatures should be visible in J/ψ photoproduction. However, these predictions appear at variance with recent experimental data obtained at HERA, indicating that the phenomenological importance of the color-octet contributions is smaller than expected from theoretical considerations and suggested by the Tevatron fits. (orig.)

  15. The contribution of distinct subregions of the ventromedial frontal cortex to emotion, social behavior, and decision making.

    Science.gov (United States)

    Rudebeck, P H; Bannerman, D M; Rushworth, M F S

    2008-12-01

    Damage to the ventromedial frontal cortex (VMFC) in humans is associated with deficits in decision making. Decision making, however, often happens while people are interacting with others, where it is important to take the social consequences of a course of action into account. It is well known that VMFC lesions also lead to marked alterations in patients' emotions and ability to interact socially; however, it has not been clear which parts of the VMFC are critical for these changes. Recently, there has been considerable interest in the role of the VMFC in choice behavior during interpersonal exchanges. Here, we highlight recent research that suggests that two areas within or adjacent to the VMFC, the orbitofrontal cortex (OFC) and the anterior cingulate cortex (ACC), may play distinct but complementary roles in mediating normal patterns of emotion and social behavior. Converging lines of evidence from human, macaque, and rat studies now suggest that the OFC may be more specialized for simple emotional responses, such as fear and aggression, through its role in representing primary reinforcement or punishment. By contrast, the ACC may play a distinct role in more complex aspects of emotion, such as social interaction, by virtue of its connections with the discrete parts of the temporal lobe and subcortical structures that control autonomic responses.

  16. Both differences in encoding processes and monitoring at retrieval reduce false alarms when distinctive information is studied.

    Science.gov (United States)

    Hanczakowski, Maciej; Mazzoni, Giuliana

    2011-04-01

    A reduction in false alarms to critical lures is observed in the DRM paradigm (Roediger & McDermott, 1995) when distinctive information is presented at encoding. Two mechanisms have been proposed to account for this reduction. According to the monitoring theory (e.g., the distinctiveness heuristic), lack of diagnostic recollection serves as a basis for discarding non-presented lures. According to the encoding theory, presenting distinctive information at study leads to impoverished relational processing, which results in a reduction in memorial information elicited by critical lures. In the present study a condition was created in which the use of the distinctiveness heuristic was precluded by associating, within the same study, lures with distinctive information in a context different from the study session. Under that condition reduction in false alarms to distinctive critical lures was still observed. This result supports the predictions of the encoding theory. However, when in the same study the use of the distinctiveness heuristic was not precluded, reductions in false alarms to unrelated lures were also observed when distinctive information was presented at study, indicating that both mechanisms are likely to contribute to the rejection of false memories.

  17. Ontological Distinctions between Means-End and Contribution Links in the i* Framework

    NARCIS (Netherlands)

    Guizzardi-Silva Souza, R.; Franch, Xavier; Guizzardi, G.; Wieringa, Roelf J.; Ng, Wilfred; Storey, Veda C.; Trujillo, Juan C.

    2013-01-01

    The i* framework is a renowned Requirements Engineering approach. This work is part of an ongoing effort to provide ontological interpretations for the i* core concepts. With this, we aim at proposing a more uniform use of the language, in a way that it can be more easily learned by newcomers and

  18. Suppressor of Cytokine Signaling (SOCS 5 utilises distinct domains for regulation of JAK1 and interaction with the adaptor protein Shc-1.

    Directory of Open Access Journals (Sweden)

    Edmond M Linossi

    Full Text Available Suppressor of Cytokine Signaling (SOCS5 is thought to act as a tumour suppressor through negative regulation of JAK/STAT and epidermal growth factor (EGF signaling. However, the mechanism/s by which SOCS5 acts on these two distinct pathways is unclear. We show for the first time that SOCS5 can interact directly with JAK via a unique, conserved region in its N-terminus, which we have termed the JAK interaction region (JIR. Co-expression of SOCS5 was able to specifically reduce JAK1 and JAK2 (but not JAK3 or TYK2 autophosphorylation and this function required both the conserved JIR and additional sequences within the long SOCS5 N-terminal region. We further demonstrate that SOCS5 can directly inhibit JAK1 kinase activity, although its mechanism of action appears distinct from that of SOCS1 and SOCS3. In addition, we identify phosphoTyr317 in Shc-1 as a high-affinity substrate for the SOCS5-SH2 domain and suggest that SOCS5 may negatively regulate EGF and growth factor-driven Shc-1 signaling by binding to this site. These findings suggest that different domains in SOCS5 contribute to two distinct mechanisms for regulation of cytokine and growth factor signaling.

  19. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

    Science.gov (United States)

    Le Billan, Florian; Amazit, Larbi; Bleakley, Kevin; Xue, Qiong-Yao; Pussard, Eric; Lhadj, Christophe; Kolkhof, Peter; Viengchareun, Say; Fagart, Jérôme; Lombès, Marc

    2018-05-07

    Mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) are two closely related hormone-activated transcription factors that regulate major pathophysiologic functions. High homology between these receptors accounts for the crossbinding of their corresponding ligands, MR being activated by both aldosterone and cortisol and GR essentially activated by cortisol. Their coexpression and ability to bind similar DNA motifs highlight the need to investigate their respective contributions to overall corticosteroid signaling. Here, we decipher the transcriptional regulatory mechanisms that underlie selective effects of MRs and GRs on shared genomic targets in a human renal cellular model. Kinetic, serial, and sequential chromatin immunoprecipitation approaches were performed on the period circadian protein 1 ( PER1) target gene, providing evidence that both receptors dynamically and cyclically interact at the same target promoter in a specific and distinct transcriptional signature. During this process, both receptors regulate PER1 gene by binding as homo- or heterodimers to the same promoter region. Our results suggest a novel level of MR-GR target gene regulation, which should be considered for a better and integrated understanding of corticosteroid-related pathophysiology.-Le Billan, F., Amazit, L., Bleakley, K., Xue, Q.-Y., Pussard, E., Lhadj, C., Kolkhof, P., Viengchareun, S., Fagart, J., Lombès, M. Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

  20. 20 CFR 1002.262 - When is the employer required to make the plan contribution that is attributable to the employee...

    Science.gov (United States)

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false When is the employer required to make the plan contribution that is attributable to the employee's period of uniformed service? 1002.262 Section 1002.262 Employees' Benefits OFFICE OF THE ASSISTANT SECRETARY FOR VETERANS' EMPLOYMENT AND TRAINING SERVICE, DEPARTMENT OF LABOR REGULATIONS UNDER...

  1. 75 FR 39034 - Public Housing Annual Contributions Contract

    Science.gov (United States)

    2010-07-07

    ... Contributions Contract AGENCY: Office of the Chief Information Officer, HUD. ACTION: Notice. SUMMARY: The... Contributions Contract (ACC) with certain requirements applicable to all project and other requirements... Contributions Contract. OMB Approval Number: 2577-New. Form Numbers: Certain information collections do not have...

  2. An Experimental Study of the Use of Design Thinking as a Requirements Elicitation Approach for Mobile Learning Environments

    Directory of Open Access Journals (Sweden)

    Carla Silva

    2015-04-01

    Full Text Available Mobile learning (m-learning is a research field that aims to analyze how mobile devices can contribute to learning. The development of software for mobile devices to support learning is essential for an effective implementation of m-learning or mobile learning environments (MLE. Requirements Engineering processes need to include activities that provoke creativity in the stakeholders to conceive MLEs that actually modify and improve the teaching and learning process. In this context, this paper presents a process for requirements elicitation and documentation of mobile learning environments. This process is based on the concepts of the Design Thinking process that provides a methodology to elicit customer needs, producing simple prototypes that eventually converge to innovative solutions. An experiment was conducted to evaluate if the proposed process contributes to create MLEs that present distinctive and interesting characteristics when compared to existing solutions for a specific problem.

  3. Contributions of early Arab scholars to color science

    Science.gov (United States)

    Lakshminarayanan, Vasudevan

    2017-09-01

    The Islamic world made important discoveries in the field of color science during the medieval era. These included many fundamental ideas on the nature of color. Some of the first hue scales, though partial were developed by these scholars. They also showed that color was a percept and light and color were ontologically distinct. Other contributions by these scholars include descriptions of the color mixtures, color tops, color theory, etc. A few of these contributions will be discussed in this paper with particular attention to the work of Ibn al-Haytham on color.

  4. Distinction between even and odd steps in the magnetization of a Mn_12-acetate crystal.

    Science.gov (United States)

    Suzuki, Yoko; Mertes, K. M.; Sarachik, M. P.; Paltiel, Y.; Shtrikman, H.; Zeldov, E.; Rumberger, E. M.; Hendrickson, D. N.; Christou, G.

    2002-03-01

    Data for the magnetization of a Mn_12-acetate crystal obtained for different sweep rates of a magnetic field applied along the anisotropy axis have been shown(K. M. Mertes, Y. Suzuki, M. P. Sarachik, Y. Paltiel, H. Shtrikman, E . Zeldov, E. M. Rumberger, D. N. Hendrickson, and G. Christou, Phys. Rev. Lett. 87), 227205 (2001). to collapse onto the single scaled curve predicted by Chudnovsky and Garanin(E. M. Chudnovsky and D. A. Garanin, Phys. Rev. Lett. 87, 187203 (2001).) for the case when the dominant symmetry-breaking term that drives tunneling is a second order transverse anisotropy. A detailed analysis of the data indicates there is a clear distinction between even resonances, driven by transverse anisotropy, and odd resonances which require a contribution due to a transverse internal magnetic field. It will also be shown that scaling is not obtained if one assumes that the tunneling is driven solely by transverse fields.

  5. Contribution of pitcher fragrance and fluid viscosity to high prey ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR G

    [Di Giusto B, Grosbois V, Fargeas E, Marshall D J and Gaume L 2008 Contribution of pitcher fragrance and fluid ... but does not permit distinction between the attractive and .... sweet scent between pitchers of the lower and upper forms.

  6. Distinct lipid a moieties contribute to pathogen-induced site-specific vascular inflammation.

    Directory of Open Access Journals (Sweden)

    Connie Slocum

    2014-07-01

    Full Text Available Several successful pathogens have evolved mechanisms to evade host defense, resulting in the establishment of persistent and chronic infections. One such pathogen, Porphyromonas gingivalis, induces chronic low-grade inflammation associated with local inflammatory bone loss and systemic inflammation manifested as atherosclerosis. P. gingivalis expresses an atypical lipopolysaccharide (LPS structure containing heterogeneous lipid A species, that exhibit Toll-like receptor-4 (TLR4 agonist or antagonist activity, or are non-activating at TLR4. In this study, we utilized a series of P. gingivalis lipid A mutants to demonstrate that antagonistic lipid A structures enable the pathogen to evade TLR4-mediated bactericidal activity in macrophages resulting in systemic inflammation. Production of antagonistic lipid A was associated with the induction of low levels of TLR4-dependent proinflammatory mediators, failed activation of the inflammasome and increased bacterial survival in macrophages. Oral infection of ApoE(-/- mice with the P. gingivalis strain expressing antagonistic lipid A resulted in vascular inflammation, macrophage accumulation and atherosclerosis progression. In contrast, a P. gingivalis strain producing exclusively agonistic lipid A augmented levels of proinflammatory mediators and activated the inflammasome in a caspase-11-dependent manner, resulting in host cell lysis and decreased bacterial survival. ApoE(-/- mice infected with this strain exhibited diminished vascular inflammation, macrophage accumulation, and atherosclerosis progression. Notably, the ability of P. gingivalis to induce local inflammatory bone loss was independent of lipid A expression, indicative of distinct mechanisms for induction of local versus systemic inflammation by this pathogen. Collectively, our results point to a pivotal role for activation of the non-canonical inflammasome in P. gingivalis infection and demonstrate that P. gingivalis evades immune

  7. 7 CFR 1484.53 - What are the requirements for documenting and reporting contributions?

    Science.gov (United States)

    2010-01-01

    ... contribution must be documented by the Cooperator, showing the method of computing non-cash contributions, salaries, and travel expenses. (b) Each Cooperator must keep records of the methods used to compute the value of non-cash contributions, and (1) Copies of invoices or receipts for expenses paid by the U.S...

  8. Experts' conference on the Climate and Energy Contribution

    International Nuclear Information System (INIS)

    2009-06-01

    This document first proposes the White Paper prepared for the experts' conference. After a presentation of the Emission Trading System (ETS), this paper highlights the benefit of the introduction of economical instruments rather than regulatory instruments to promote the reduction of greenhouse gas emissions. It underlines the distinction between the proposed 'climate-energy contribution' (or carbon tax) and the Cambridge tax. Then, it describes how to implement such a contribution, i.e. how to define its base, and how to relate it with existing taxes. Some graphs compare the tax rates on fuels, gas and domestic oil in European countries. The paper then defines what the field of application of the contribution could be, how to make this contribution more efficient, and what could be its economical consequences. Then, the document proposes the text of Michel Rocard's intervention on the stakes of conference on this climate-energy contribution

  9. Swedish contribution to the greenhouse effect and required reductions to meet the 550 ppmv target

    International Nuclear Information System (INIS)

    Lindell, Lina; Nilsson, Kristina

    2002-11-01

    According to the Swedish Parliament, the Swedish international climate strategy should focus on a stabilisation of the concentration of greenhouse gases in the atmosphere. An equilibrium concentration lower than 550 ppmv CO 2 -equivalents should be achieved by the end of this century. As an interim target, the yearly emissions should not exceed 4.5 tonnes CO 2 -equivalents per capita by 2050. In this study an inventory of Swedish emissions from 1834 until 2000, for the six greenhouse gases regulated by the Kyoto Protocol, is carried out. Future emission scenarios for carbon dioxide during the time period 2000-2050 are also defined. This data is used for estimating the contribution to the greenhouse effect both today and in the future. Further it is investigated if the 2050-target is sufficient for not exceeding an atmospheric concentration of 550 ppmv. The required reduction for 2100 to reach an equilibrium concentration below this level is also estimated. The Swedish contribution to the greenhouse effect today is about 30 % larger than it should be according to the fairness factor used in this study. The Swedish emission target set for 2050 is sufficient for not exceeding 550 ppmv by that year. However, to reach a stabilisation of the concentration below this level the emissions have to be reduced to 1.0-1.5 tonnes CO 2 -equivalents per capita by 2100

  10. Swedish contribution to the greenhouse effect and required reductions to meet the 550 ppmv target

    Energy Technology Data Exchange (ETDEWEB)

    Lindell, Lina; Nilsson, Kristina [Uppsala Univ. (Sweden). School of Engineering

    2002-11-01

    According to the Swedish Parliament, the Swedish international climate strategy should focus on a stabilisation of the concentration of greenhouse gases in the atmosphere. An equilibrium concentration lower than 550 ppmv CO{sub 2}-equivalents should be achieved by the end of this century. As an interim target, the yearly emissions should not exceed 4.5 tonnes CO{sub 2}-equivalents per capita by 2050. In this study an inventory of Swedish emissions from 1834 until 2000, for the six greenhouse gases regulated by the Kyoto Protocol, is carried out. Future emission scenarios for carbon dioxide during the time period 2000-2050 are also defined. This data is used for estimating the contribution to the greenhouse effect both today and in the future. Further it is investigated if the 2050-target is sufficient for not exceeding an atmospheric concentration of 550 ppmv. The required reduction for 2100 to reach an equilibrium concentration below this level is also estimated. The Swedish contribution to the greenhouse effect today is about 30 % larger than it should be according to the fairness factor used in this study. The Swedish emission target set for 2050 is sufficient for not exceeding 550 ppmv by that year. However, to reach a stabilisation of the concentration below this level the emissions have to be reduced to 1.0-1.5 tonnes CO{sub 2}-equivalents per capita by 2100.

  11. Different AMPA receptor subtypes mediate the distinct kinetic components of a biphasic EPSC in hippocampal interneurons

    Directory of Open Access Journals (Sweden)

    Todd eStincic

    2015-05-01

    Full Text Available CA1 hippocampal interneurons at the border between stratum radiatum and stratum lacunosum-moleculare have AMPA receptor (AMPAR-mediated excitatory postsynaptic currents (EPSCs that consist of two distinct phases: a typical fast component (FC, and a highly unusual slow component (SC that persists for hundreds of milliseconds. To determine whether these kinetically distinct components of the EPSC are mediated by distinct AMPAR subpopulations, we examined the relative contributions of GluA2-containing and –lacking AMPARs to the SC. GluA2-containing AMPARs mediated the majority of the FC whereas GluA2-lacking AMPARs preferentially generated the SC. When glutamate uptake through the glial glutamate transporter EAAT1 was inhibited, spill over-mediated AMPAR activation recruited an even slower third kinetic component that persisted for several seconds; however, this spillover-mediated current was mediated predominantly by GluA2-containing AMPARs and therefore was clearly distinct from the SC when uptake is intact. Thus, different AMPAR subpopulations that vary in GluA2 content mediate the distinct components of the AMPAR EPSC. The SC is developmentally downregulated in mice, declining after the second postnatal week. This downregulation affects both GluA2-containing and GluA2-lacking AMPARs mediating the SC, and is not accompanied by developmental changes in the GluA2 content of AMPARs underlying the FC. Thus, the downregulation of the SC appears to be independent of synaptic GluA2 expression, suggesting the involvement of another AMPAR subunit or an auxiliary protein. Our results therefore identify GluA2-dependent and GluA2-independent determinants of the SC: GluA2-lacking AMPARs preferentially contribute to the SC, while the developmental downregulation of the SC is independent of GluA2 content.

  12. Bourdieu's Distinction between Rules and Strategies and Secondary Principal Practice: A Review of Selected Literature

    Science.gov (United States)

    Anderson, Karen

    2016-01-01

    This paper reviews a selection of literature on secondary principal practice from which to propose an approach for further research. The review demonstrates that applications of Bourdieu's theory of practice have contributed to understandings about secondary principal practice, and that the distinction he made between rules and strategies has the…

  13. POLITICS, JUSTICE AND THE VULNERABLE SUBJECT: THE CONTRIBUTION OF FEMINIST THOUGHT

    OpenAIRE

    Casalini, Brunella

    2016-01-01

    The present article argues that the main contribution of contemporary feminist theory on vulnerability stems from the distinction of two possible kinds of vulnerability: an ontological vulnerability and a vulnerability linked to various processes (social, cultural, economic and juridical) of vulnerabilisation. This contribution is not limited to the critical and deconstructive level. As a positive proposal, it advances in the direction of an individual which, recovering its own relational, em...

  14. Distinct Siderophores Contribute to Iron Cycling in the Mesopelagic at Station ALOHA

    Directory of Open Access Journals (Sweden)

    Randelle M. Bundy

    2018-03-01

    Full Text Available The distribution of dissolved iron (Fe, total organic Fe-binding ligands, and siderophores were measured between the surface and 400 m at Station ALOHA, a long term ecological study site in the North Pacific Subtropical Gyre. Dissolved Fe concentrations were low throughout the water column and strong organic Fe-binding ligands exceeded dissolved Fe at all depths; varying from 0.9 nmol L−1 in the surface to 1.6 nmol L−1 below 150 m. Although Fe does not appear to limit microbial production, we nevertheless found siderophores at nearly all depths, indicating some populations of microbes were responding to Fe stress. Ferrioxamine siderophores were most abundant in the upper water column, with concentrations between 0.1 and 2 pmol L−1, while a suite of amphibactins were found below 200 m with concentrations between 0.8 and 11 pmol L−1. The distinct vertical distribution of ferrioxamines and amphibactins may indicate disparate strategies for acquiring Fe from dust in the upper water column and recycled organic matter in the lower water column. Amphibactins were found to have conditional stability constants (log KFeL1,Fe′cond ranging from 12.0 to 12.5, while ferrioxamines had much stronger conditional stability constants ranging from 14.0 to 14.4, within the range of observed L1 ligands by voltammetry. We used our data to calculate equilibrium Fe speciation at Station ALOHA to compare the relative concentration of inorganic and siderophore complexed Fe. The results indicate that the concentration of Fe bound to siderophores was up to two orders of magnitude higher than inorganic Fe, suggesting that even if less bioavailable, siderophores were nevertheless a viable pathway for Fe acquisition by microbes at our study site. Finally, we observed rapid production of ferrioxamine E by particle-associated bacteria during incubation of freshly collected sinking organic matter. Fe-limitation may therefore be a factor in regulating carbon metabolism

  15. 75 FR 27927 - Diversification Requirements for Certain Defined Contribution Plans

    Science.gov (United States)

    2010-05-19

    ... section 414(l) with respect to any other defined benefit plan or defined contribution plan maintained by... disclosure of the fund's portfolio holdings (for example, Form N-CSR, ``Certified Shareholder Report of... securities, as well as a direct or indirect benefit that is conditioned on investment in employer securities...

  16. Nutrient Intake and Contribution of Home Enteral Nutrition to Meeting Nutritional Requirements after Oesophagectomy and Total Gastrectomy

    Science.gov (United States)

    Baker, Melanie L; Halliday, Vanessa; Robinson, Pauline; Smith, Karen; Bowrey, David J

    2017-01-01

    Background/Objectives This study evaluated nutrition after oesophago-gastric resection and the influence of home jejunostomy feeding in the six months after surgery. Subjects/Methods Data on nutritional intake and physiologic measures were collected as part of a randomised trial with measurements taken before and up to six months after surgery. Results 41 participants (32 oesophagectomy, 9 total gastrectomy) received home jejunostomy feeding (n=18) or usual care without feeding (n=23). At hospital discharge, oral intakes were adequate for energy and protein in 9% and 6% respectively. By three and six months, these values had increased to 61% & 55%, 94% & 77% respectively. Six participants (26%) who received usual care required rescue feeding. Six weeks after hospital discharge, energy intakes were met in those who received jejunal feeding due to the contribution of enteral nutrition. Jejunal feeding did not affect oral intake, being similar in both groups (fed: 77% estimated need, usual care: 79%). At three months, inadequate micronutrient intakes were seen in over one third. Compared to baseline values, six weeks after surgery, weight loss exceeding 5% was seen in 5/18 (28%) who received feeding, 14/17 (82%) who received usual care and 5/6 (83%) of those who required rescue feeding, p=0.002. Weight loss averaged 4.1% (fed), 10.4% (usual care) and 9.2% (rescue fed), p=0.004. These trends persisted out to six months. Conclusions Supplementary jejunostomy feeding made an important contribution to meeting nutrition after oesophago-gastric resection. Importantly, oral nutritional intake was not compromised dispelling the assertion that jejunal feeding deincentivises patients from eating. PMID:28656968

  17. Distinct contributions of functional and deep neural network features to representational similarity of scenes in human brain and behavior.

    Science.gov (United States)

    Groen, Iris Ia; Greene, Michelle R; Baldassano, Christopher; Fei-Fei, Li; Beck, Diane M; Baker, Chris I

    2018-03-07

    Inherent correlations between visual and semantic features in real-world scenes make it difficult to determine how different scene properties contribute to neural representations. Here, we assessed the contributions of multiple properties to scene representation by partitioning the variance explained in human behavioral and brain measurements by three feature models whose inter-correlations were minimized a priori through stimulus preselection. Behavioral assessments of scene similarity reflected unique contributions from a functional feature model indicating potential actions in scenes as well as high-level visual features from a deep neural network (DNN). In contrast, similarity of cortical responses in scene-selective areas was uniquely explained by mid- and high-level DNN features only, while an object label model did not contribute uniquely to either domain. The striking dissociation between functional and DNN features in their contribution to behavioral and brain representations of scenes indicates that scene-selective cortex represents only a subset of behaviorally relevant scene information.

  18. Distinctive Citizenship

    DEFF Research Database (Denmark)

    Kaur, Ravinder

    2009-01-01

    The refugee, in India's Partition history, appears as an enigmatic construct - part pitiful, part heroic, though mostly shorn of agency - representing the surface of the human tragedy of Partition. Yet this archetype masks the undercurrent of social distinctions that produced hierarchies of post...

  19. Complete identification of E-selectin ligands on neutrophils reveals distinct functions of PSGL-1, ESL-1, and CD44.

    Science.gov (United States)

    Hidalgo, Andrés; Peired, Anna J; Wild, Martin; Vestweber, Dietmar; Frenette, Paul S

    2007-04-01

    The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro, but the complete identification of its physiological ligands has remained elusive. Here, we showed that E-selectin ligand-1 (ESL-1), P-selectin glycoprotein ligand-1 (PSGL-1), and CD44 encompassed all endothelial-selectin ligand activity on neutrophils by using gene- and RNA-targeted loss of function. PSGL-1 played a major role in the initial leukocyte capture, whereas ESL-1 was critical for converting initial tethers into steady slow rolling. CD44 controlled rolling velocity and mediated E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling.

  20. Concurrent topological design of composite structures and materials containing multiple phases of distinct Poisson's ratios

    Science.gov (United States)

    Long, Kai; Yuan, Philip F.; Xu, Shanqing; Xie, Yi Min

    2018-04-01

    Most studies on composites assume that the constituent phases have different values of stiffness. Little attention has been paid to the effect of constituent phases having distinct Poisson's ratios. This research focuses on a concurrent optimization method for simultaneously designing composite structures and materials with distinct Poisson's ratios. The proposed method aims to minimize the mean compliance of the macrostructure with a given mass of base materials. In contrast to the traditional interpolation of the stiffness matrix through numerical results, an interpolation scheme of the Young's modulus and Poisson's ratio using different parameters is adopted. The numerical results demonstrate that the Poisson effect plays a key role in reducing the mean compliance of the final design. An important contribution of the present study is that the proposed concurrent optimization method can automatically distribute base materials with distinct Poisson's ratios between the macrostructural and microstructural levels under a single constraint of the total mass.

  1. Differential contributions of dorsolateral and frontopolar cortices to working memory processes in the primate

    Directory of Open Access Journals (Sweden)

    Erica A. Boschin

    2015-10-01

    Full Text Available The ability to maintain and manipulate information across temporal delays is a fundamental requirement to bridge the gap between perception and action. In the case of higher-order behavior, the maintenance of rules and strategies is particularly helpful in bridging this gap. The prefrontal cortex (PFC has long been considered critical for such processes, and research has focused on different subdivisions of PFC to gain an insight into their diverse contributions to these mechanisms. Substantial evidence indicates that dorsolateral PFC (dlPFC is an important structure for maintaining information across delays, with cells actively firing across delays and lesions to this region causing deficits in tasks involving delayed responses and maintenance of rules online. Frontopolar cortex (FP, on the other hand, appears to show the opposite pattern of results, with cells not firing across delays and lesions to this region not affecting the same rule-based, delayed response tasks that are impaired following dlPFC lesions. The body of evidence therefore suggests that dlPFC and FP’s contributions to working memory differ. In this article, we will provide a perspective on how these regions might implement distinct but complementary and interactive functions that contribute to more general temporally-extended processes and support flexible, dynamic behavior.

  2. Phosphorylation and nuclear accumulation are distinct events contributing to the activation of p53

    International Nuclear Information System (INIS)

    O'Hagan, Heather M.; Ljungman, Mats

    2004-01-01

    It has been recently shown that ionizing radiation (IR) and the mRNA synthesis inhibitor 5,6-dichloro-1-b-D-ribofuranosylbenzimidazole (DRB) act in synergy to induce p53-mediated transactivation of reporter plasmids in human cells [Oncogene 19 (2000) 3829]. We have extended these studies and show that ionizing radiation and DRB also act in synergy to induce ATM-mediated phosphorylation of the ser15 site of p53 and enhance the expression of endogenous p21 protein. Examination of the localization of p53 revealed that while DRB did not induce phosphorylation of the ser15 site of p53 but efficiently accumulated p53 in the nucleus, ionizing radiation induced phosphorylation of the ser15 site of p53 without prolonged nuclear accumulation. Importantly, the combination of DRB and IR resulted in a strong accumulation of phosphorylated p53 in the nucleus that was more persistent then p53 accumulation after IR alone. Furthermore, the nuclear export inhibitor leptomycin B showed a similar synergy with IR as did DRB regarding ser15 phosphorylation of p53 and p21 induction. These results suggest that the synergistic activation of the p53 response by the combination treatment is due to the activation of two distinct pathways where DRB causes the prolonged nuclear accumulation of p53 while ionizing radiation activates p53 by ATM-mediated phosphorylation

  3. Distinct Functions of Specialized Dendritic Cell Subsets in Atherosclerosis and the Road Ahead

    Directory of Open Access Journals (Sweden)

    Alma Zernecke

    2014-01-01

    Full Text Available Atherosclerotic vascular disease is modulated by immune mechanisms. Dendritic cells (DCs and T cells are present within atherosclerotic lesions and function as central players in the initiation and modulation of adaptive immune responses. In previous years, we have studied the functional contribution of distinct DC subsets in disease development, namely, that of CCL17-expressing DCs as well as that of plasmacytoid DCs that play specialized roles in disease development. This review focuses on important findings gathered in these studies and dissects the multifaceted contribution of CCL17-expressing DCs and pDCs to the pathogenesis of atherosclerosis. Furthermore, an outlook on future challenges faced when studying DCs in this detrimental disease are provided, and hurdles that will need to be overcome in order to enable a better understanding of the contribution of DCs to atherogenesis are discussed, a prerequisite for their therapeutic targeting in atherosclerosis.

  4. The enduring scientific contributions of Sigmund Freud.

    Science.gov (United States)

    Gedo, John E

    2002-01-01

    Through the development of a novel observational method, Sigmund Freud made possible the collection of reliable data about man's inner life. The scientific hypotheses he formulated about these formed the initial version of psychoanalysis. Many of these first thoughts have had to be revised in the light of subsequent scientific findings about the operations of the central nervous system, but even these refuted propositions often had much heuristic value. Despite the passage of a whole century, many Freudian hypotheses have retained their scientific standing. Most important among these was Freud's realization that human thought is usually unconscious. His understanding of the role of the automatic repetition of basic patterns of behavior, of the fateful consequences of early childhood emotional vicissitudes in structuring enduring mental dispositions, and of the distinction between two distinct modes of thinking are the most significant among his many contributions.

  5. Counselor Identity: Conformity or Distinction?

    Science.gov (United States)

    McLaughlin, Jerry E.; Boettcher, Kathryn

    2009-01-01

    The authors explore 3 debates in other disciplines similar to counseling's identity debate in order to learn about common themes and outcomes. Conformity, distinction, and cohesion emerged as common themes. They conclude that counselors should retain their distinctive, humanistic approach rather than conforming to the dominant, medical approach.

  6. Motor cortex is required for learning but not executing a motor skill

    Science.gov (United States)

    Kawai, Risa; Markman, Timothy; Poddar, Rajesh; Ko, Raymond; Fantana, Antoniu; Dhawale, Ashesh; Kampff, Adam R.; Ölveczky, Bence P.

    2018-01-01

    Motor cortex is widely believed to underlie the acquisition and execution of motor skills, yet its contributions to these processes are not fully understood. One reason is that studies on motor skills often conflate motor cortex’s established role in dexterous control with roles in learning and producing task-specific motor sequences. To dissociate these aspects, we developed a motor task for rats that trains spatiotemporally precise movement patterns without requirements for dexterity. Remarkably, motor cortex lesions had no discernible effect on the acquired skills, which were expressed in their distinct pre-lesion forms on the very first day of post-lesion training. Motor cortex lesions prior to training, however, rendered rats unable to acquire the stereotyped motor sequences required for the task. These results suggest a remarkable capacity of subcortical motor circuits to execute learned skills and a previously unappreciated role for motor cortex in ‘tutoring’ these circuits during learning. PMID:25892304

  7. Towards a distinction between technology incubators and non-technology incubators: can they contribute to economic growth?

    NARCIS (Netherlands)

    Ratinho, Tiago; Harms, Rainer; Groen, Arend J.; Fink, M.; Hatak, I.

    2010-01-01

    Business incubators are an increasingly popular tool for promoting job and wealth creation. Yet given the heterogeneity of incubation models, it is not always clear how incubators operate, what their main characteristics are and how can they best contribute to job and wealth creation. If technology

  8. Distinct contributions of the fornix and inferior longitudinal fasciculus to episodic and semantic autobiographical memory.

    Science.gov (United States)

    Hodgetts, Carl J; Postans, Mark; Warne, Naomi; Varnava, Alice; Lawrence, Andrew D; Graham, Kim S

    2017-09-01

    Autobiographical memory (AM) is multifaceted, incorporating the vivid retrieval of contextual detail (episodic AM), together with semantic knowledge that infuses meaning and coherence into past events (semantic AM). While neuropsychological evidence highlights a role for the hippocampus and anterior temporal lobe (ATL) in episodic and semantic AM, respectively, it is unclear whether these constitute dissociable large-scale AM networks. We used high angular resolution diffusion-weighted imaging and constrained spherical deconvolution-based tractography to assess white matter microstructure in 27 healthy young adult participants who were asked to recall past experiences using word cues. Inter-individual variation in the microstructure of the fornix (the main hippocampal input/output pathway) related to the amount of episodic, but not semantic, detail in AMs - independent of memory age. Conversely, microstructure of the inferior longitudinal fasciculus, linking occipitotemporal regions with ATL, correlated with semantic, but not episodic, AMs. Further, these significant correlations remained when controlling for hippocampal and ATL grey matter volume, respectively. This striking correlational double dissociation supports the view that distinct, large-scale distributed brain circuits underpin context and concepts in AM. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Laboratory-Cultured Strains of the Sea Anemone Exaiptasia Reveal Distinct Bacterial Communities

    KAUST Repository

    Herrera Sarrias, Marcela; Ziegler, Maren; Voolstra, Christian R.; Aranda, Manuel

    2017-01-01

    Exaiptasia is a laboratory sea anemone model system for stony corals. Two clonal strains are commonly used, referred to as H2 and CC7, that originate from two genetically distinct lineages and that differ in their Symbiodinium specificity. However, little is known about their other microbial associations. Here, we examined and compared the taxonomic composition of the bacterial assemblages of these two symbiotic Exaiptasia strains, both of which have been cultured in the laboratory long-term under identical conditions. We found distinct bacterial microbiota for each strain, indicating the presence of host-specific microbial consortia. Putative differences in the bacterial functional profiles (i.e., enrichment and depletion of various metabolic processes) based on taxonomic inference were also detected, further suggesting functional differences of the microbiomes associated with these lineages. Our study contributes to the current knowledge of the Exaiptasia holobiont by comparing the bacterial diversity of two commonly used strains as models for coral research.

  10. Laboratory-Cultured Strains of the Sea Anemone Exaiptasia Reveal Distinct Bacterial Communities

    KAUST Repository

    Herrera Sarrias, Marcela

    2017-05-02

    Exaiptasia is a laboratory sea anemone model system for stony corals. Two clonal strains are commonly used, referred to as H2 and CC7, that originate from two genetically distinct lineages and that differ in their Symbiodinium specificity. However, little is known about their other microbial associations. Here, we examined and compared the taxonomic composition of the bacterial assemblages of these two symbiotic Exaiptasia strains, both of which have been cultured in the laboratory long-term under identical conditions. We found distinct bacterial microbiota for each strain, indicating the presence of host-specific microbial consortia. Putative differences in the bacterial functional profiles (i.e., enrichment and depletion of various metabolic processes) based on taxonomic inference were also detected, further suggesting functional differences of the microbiomes associated with these lineages. Our study contributes to the current knowledge of the Exaiptasia holobiont by comparing the bacterial diversity of two commonly used strains as models for coral research.

  11. Gain and loss learning differentially contribute to life financial outcomes.

    Directory of Open Access Journals (Sweden)

    Brian Knutson

    Full Text Available Emerging findings imply that distinct neurobehavioral systems process gains and losses. This study investigated whether individual differences in gain learning and loss learning might contribute to different life financial outcomes (i.e., assets versus debt. In a community sample of healthy adults (n = 75, rapid learners had smaller debt-to-asset ratios overall. More specific analyses, however, revealed that those who learned rapidly about gains had more assets, while those who learned rapidly about losses had less debt. These distinct associations remained strong even after controlling for potential cognitive (e.g., intelligence, memory, and risk preferences and socioeconomic (e.g., age, sex, ethnicity, income, education confounds. Self-reported measures of assets and debt were additionally validated with credit report data in a subset of subjects. These findings support the notion that different gain and loss learning systems may exert a cumulative influence on distinct life financial outcomes.

  12. Amygdalar auditory neurons contribute to self-other distinction during ultrasonic social vocalization in rats

    Directory of Open Access Journals (Sweden)

    Jumpei Matsumoto

    2016-09-01

    Full Text Available Although clinical studies reported hyperactivation of the auditory system and amygdala in patients with auditory hallucinations (hearing others’ but not one’s own voice, independent of any external stimulus, neural mechanisms of self/other attribution is not well understood. We recorded neuronal responses in the dorsal amygdala including the lateral amygdaloid nucleus to ultrasonic vocalization (USVs emitted by subjects and conspecifics during free social interaction in 16 adult male rats. The animals emitting the USVs were identified by EMG recordings. One-quarter of the amygdalar neurons (15/60 responded to 50 kHz calls by the subject and/or conspecifics. Among the responsive neurons, most neurons (Type-Other neurons (73%, 11/15 responded only to calls by conspecifics but not subjects. Two Type-Self neurons (13%, 2/15 responded to calls by the subject but not those by conspecifics, although their response selectivity to subjects vs. conspecifics was lower than that of Type-Other neurons. The remaining two neurons (13% responded to calls by both the subject and conspecifics. Furthermore, population coding of the amygdalar neurons represented distinction of subject vs. conspecific calls. The present results provide the first neurophysiological evidence that the amygdala discriminately represents affective social calls by subject and conspecifics. These findings suggest that the amygdala is an important brain region for self/other attribution. Furthermore, pathological activation of the amygdala, where Type-Other neurons predominate, could induce external misattribution of percepts of vocalization.

  13. Attachment and entry of Chlamydia have distinct requirements for host protein disulfide isomerase.

    Directory of Open Access Journals (Sweden)

    Stephanie Abromaitis

    2009-04-01

    Full Text Available Chlamydia is an obligate intracellular pathogen that causes a wide range of diseases in humans. Attachment and entry are key processes in infectivity and subsequent pathogenesis of Chlamydia, yet the mechanisms governing these interactions are unknown. It was recently shown that a cell line, CHO6, that is resistant to attachment, and thus infectivity, of multiple Chlamydia species has a defect in protein disulfide isomerase (PDI N-terminal signal sequence processing. Ectopic expression of PDI in CHO6 cells led to restoration of Chlamydia attachment and infectivity; however, the mechanism leading to this recovery was not ascertained. To advance our understanding of the role of PDI in Chlamydia infection, we used RNA interference to establish that cellular PDI is essential for bacterial attachment to cells, making PDI the only host protein identified as necessary for attachment of multiple species of Chlamydia. Genetic complementation and PDI-specific inhibitors were used to determine that cell surface PDI enzymatic activity is required for bacterial entry into cells, but enzymatic function was not required for bacterial attachment. We further determined that it is a PDI-mediated reduction at the cell surface that triggers bacterial uptake. While PDI is necessary for Chlamydia attachment to cells, the bacteria do not appear to utilize plasma membrane-associated PDI as a receptor, suggesting that Chlamydia binds a cell surface protein that requires structural association with PDI. Our findings demonstrate that PDI has two essential and independent roles in the process of chlamydial infectivity: it is structurally required for chlamydial attachment, and the thiol-mediated oxido-reductive function of PDI is necessary for entry.

  14. Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses.

    Science.gov (United States)

    Thwe, Phyu M; Pelgrom, Leonard; Cooper, Rachel; Beauchamp, Saritha; Reisz, Julie A; D'Alessandro, Angelo; Everts, Bart; Amiel, Eyal

    2017-09-05

    Dendritic cell (DC) activation by Toll-like receptor (TLR) agonists causes rapid glycolytic reprogramming that is required to meet the metabolic demands of their immune activation. Recent efforts in the field have identified an important role for extracellular glucose sourcing to support DC activation. However, the contributions of intracellular glucose stores to these processes have not been well characterized. We demonstrate that DCs possess intracellular glycogen stores and that cell-intrinsic glycogen metabolism supports the early effector functions of TLR-activated DCs. Inhibition of glycogenolysis significantly attenuates TLR-mediated DC maturation and impairs their ability to initiate lymphocyte activation. We further report that DCs exhibit functional compartmentalization of glucose- and glycogen-derived carbons, where these substrates preferentially contribute to distinct metabolic pathways. This work provides novel insights into nutrient homeostasis in DCs, demonstrating that differential utilization of glycogen and glucose metabolism regulates their optimal immune function. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Italy’s contribution to global health: the need for a paradigm shift

    Science.gov (United States)

    2014-01-01

    This paper reviews Italian Development Assistance for Health and overall contribution to Global Health from 2001 to 2012. It analyses strategies and roles of central and decentralized authorities as well as those of private non-profit and corporate actors. The research illustrates a very low and unstable official contribution that lags far behind internationally agreed upon objectives, a highly fragmented institutional scenario, and controversial political choices favouring “vertical” global initiatives undermining national health systems, and in contrast with Italian deep-rooted principles, traditional approaches and official guidelines. Italy’s contribution to global health goes beyond official development aid, however. The raising movement toward Universal Health Coverage may offer an extraordinary opportunity for a leading role to a country whose National Health System is founded on the principles of universal and equitable access to care. At the same time, the distinctive experience of Italian decentralized cooperation, with the involvement of a multiplicity actors in a coordinated effort for cooperation in health with homologous partners in developing countries, may offer – if adequately harnessed - new opportunities for an Italian “system” of development cooperation. Nevertheless, the indispensable prerequisite of a substantial increase in public funding is challenged by the current economic crisis and domestic political situation. For a renewed Italian role in development and global health, a paradigm shift is needed, requiring both conceptual revision and deep institutional and managerial reforms to ensure an appropriate strategic direction and an efficient and effective use of resources. PMID:24708890

  16. The two different isoforms of the RSC chromatin remodeling complex play distinct roles in DNA damage responses.

    Directory of Open Access Journals (Sweden)

    Anna L Chambers

    Full Text Available The RSC chromatin remodeling complex has been implicated in contributing to DNA double-strand break (DSB repair in a number of studies. Both survival and levels of H2A phosphorylation in response to damage are reduced in the absence of RSC. Importantly, there is evidence for two isoforms of this complex, defined by the presence of either Rsc1 or Rsc2. Here, we investigated whether the two isoforms of RSC provide distinct contributions to DNA damage responses. First, we established that the two isoforms of RSC differ in the presence of Rsc1 or Rsc2 but otherwise have the same subunit composition. We found that both rsc1 and rsc2 mutant strains have intact DNA damage-induced checkpoint activity and transcriptional induction. In addition, both strains show reduced non-homologous end joining activity and have a similar spectrum of DSB repair junctions, suggesting perhaps that the two complexes provide the same functions. However, the hypersensitivity of a rsc1 strain cannot be complemented with an extra copy of RSC2, and likewise, the hypersensitivity of the rsc2 strain remains unchanged when an additional copy of RSC1 is present, indicating that the two proteins are unable to functionally compensate for one another in DNA damage responses. Rsc1, but not Rsc2, is required for nucleosome sliding flanking a DNA DSB. Interestingly, while swapping the domains from Rsc1 into the Rsc2 protein does not compromise hypersensitivity to DNA damage suggesting they are functionally interchangeable, the BAH domain from Rsc1 confers upon Rsc2 the ability to remodel chromatin at a DNA break. These data demonstrate that, despite the similarity between Rsc1 and Rsc2, the two different isoforms of RSC provide distinct functions in DNA damage responses, and that at least part of the functional specificity is dictated by the BAH domains.

  17. The pursuit of optimal distinctiveness and consumer preferences.

    Science.gov (United States)

    He, Lingnan; Cong, Feng; Liu, Yanping; Zhou, Xinyue

    2010-10-01

    This article investigates the effect of optimal distinctiveness on consumer product consumption. The authors argue that consumers acquire and display material possessions to restore their optimal levels of distinctiveness. Results showed that placing consumers in a state of low distinctiveness increased desire to acquire distinctive products, whereas perceptions of high distinctiveness reduced desire to acquire such products. Consumers' desire for distinctiveness-related products held true for various consumer choices, including willingness to pay more for limited-edition products and preference for unpopular gifts. This finding has implications for understanding consumer choice in expressing identity. © 2010 The Authors. Scandinavian Journal of Psychology © 2010 The Scandinavian Psychological Associations.

  18. Distinct structural alterations independently contributing to working memory deficits and symptomatology in paranoid schizophrenia.

    Science.gov (United States)

    Zierhut, Kathrin C; Schulte-Kemna, Anna; Kaufmann, Jörn; Steiner, Johann; Bogerts, Bernhard; Schiltz, Kolja

    2013-04-01

    Schizophrenia is considered a brain disease with a quite heterogeneous clinical presentation. Studies in schizophrenia have yielded a wide array of correlations between structural and functional brain changes and clinical and cognitive symptoms. Reductions of grey matter volume (GMV) in the prefrontal and temporal cortex have been described which are crucial for the development of positive and negative symptoms and impaired working memory (WM). Associations between GMV reduction and positive and negative symptoms as well as WM impairment were assessed in schizophrenia patients (symptomatology in 34, WM in 26) and compared to healthy controls (36 total, WM in 26). GMV was determined by voxel-based morphometry and its relation to positive and negative symptoms as well as WM performance was assessed. In schizophrenia patients, reductions of GMV were evident in anterior cingulate cortex, ventrolateral prefrontal cortex (VLPFC), superior temporal cortex, and insula. GMV reductions in the superior temporal gyrus (STG) were associated with positive symptom severity as well as WM impairment. Furthermore, the absolute GMV of VLPFC was strongly related to negative symptoms. These predicted WM performance as well as processing speed. The present results support the assumption of two distinct pathomechanisms responsible for impaired WM in schizophrenia: (1) GMV reductions in the VLPFC predict the severity of negative symptoms. Increased negative symptoms in turn are associated with a slowing down of processing speed and predict an impaired WM. (2) GMV reductions in the temporal and mediofrontal cortex are involved in the development of positive symptoms and impair WM performance, too. Copyright © 2012 Elsevier Ltd. All rights reserved.

  19. Motor cortex is required for learning but not for executing a motor skill.

    Science.gov (United States)

    Kawai, Risa; Markman, Timothy; Poddar, Rajesh; Ko, Raymond; Fantana, Antoniu L; Dhawale, Ashesh K; Kampff, Adam R; Ölveczky, Bence P

    2015-05-06

    Motor cortex is widely believed to underlie the acquisition and execution of motor skills, but its contributions to these processes are not fully understood. One reason is that studies on motor skills often conflate motor cortex's established role in dexterous control with roles in learning and producing task-specific motor sequences. To dissociate these aspects, we developed a motor task for rats that trains spatiotemporally precise movement patterns without requirements for dexterity. Remarkably, motor cortex lesions had no discernible effect on the acquired skills, which were expressed in their distinct pre-lesion forms on the very first day of post-lesion training. Motor cortex lesions prior to training, however, rendered rats unable to acquire the stereotyped motor sequences required for the task. These results suggest a remarkable capacity of subcortical motor circuits to execute learned skills and a previously unappreciated role for motor cortex in "tutoring" these circuits during learning. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

    KAUST Repository

    Cui, Peng; Ding, Feng; Lin, Qiang; Zhang, Lingfang; Li, Ang; Zhang, Zhang; Hu, Songnian; Yu, Jun

    2012-01-01

    Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

  1. Distinct Contributions of Replication and Transcription to Mutation Rate Variation of Human Genomes

    KAUST Repository

    Cui, Peng

    2012-03-23

    Here, we evaluate the contribution of two major biological processes—DNA replication and transcription—to mutation rate variation in human genomes. Based on analysis of the public human tissue transcriptomics data, high-resolution replicating map of Hela cells and dbSNP data, we present significant correlations between expression breadth, replication time in local regions and SNP density. SNP density of tissue-specific (TS) genes is significantly higher than that of housekeeping (HK) genes. TS genes tend to locate in late-replicating genomic regions and genes in such regions have a higher SNP density compared to those in early-replication regions. In addition, SNP density is found to be positively correlated with expression level among HK genes. We conclude that the process of DNA replication generates stronger mutational pressure than transcription-associated biological processes do, resulting in an increase of mutation rate in TS genes while having weaker effects on HK genes. In contrast, transcription-associated processes are mainly responsible for the accumulation of mutations in highly-expressed HK genes.

  2. Francis Bacon and the Art-Nature Distinction.

    Science.gov (United States)

    Weeks, Sophie

    2007-07-01

    Commentators generally expound Bacon's position on the art-nature relationship in terms of how much it retained or departed from traditional conceptions. This paper argues that an appreciation of the Baconian meaning of the terms "art" and "nature" requires a close examination of his wider cosmogonical speculations. Bacon's cosmogonical account moves from a state of unbridled chaos to the relatively stable system for which the term "nature" is normally used. The fundamental principle lying at the heart of Baconian cosmogony is an enriched and appetitive matter: eternal, unchanging, and the plenipotentiary source of all things. Successive limitations of matter's absolute power produced a lazy and habitual nature, which Bacon labelled "nature free." To shift nature from this otiose condition, the Baconian operator recapitulates the original binding of matter. Bacon designated the systematic procedures of binding nature the science of magic. Magic is Bacon's human counterpart to the original cosmogonical process that gave rise to the current system of nature. In Bacon's cosmogony, all possible worlds unfold out of matter: the function of art is to shake out nature's hidden folds. Hence, the distinction between naturalia and artificialia maps on to the distinction between actual and potential. Nature free is without purpose, but art - nature bound - knowingly brings into being an alternative nature designed for human utility.

  3. Uniform and Complementary Social Interaction: Distinct Pathways to Solidarity.

    Science.gov (United States)

    Koudenburg, Namkje; Postmes, Tom; Gordijn, Ernestine H; van Mourik Broekman, Aafke

    2015-01-01

    We examine how different forms of co-action give rise to feelings of solidarity. We propose that (a) coordinated action elicits a sense of solidarity, and (b) the process through which such solidarity emerges differs for different forms of co-action. We suggest that whether solidarity within groups emerges from uniform action (e.g. synchronizing, as when people speak in unison) or from more complementary forms of action (e.g. alternating, when speaking in turns) has important consequences for the emergent position of individuals within the group. Uniform action relies on commonality, leaving little scope for individuality. In complementary action each individual makes a distinctive contribution to the group, thereby increasing a sense of personal value to the group, which should contribute to the emergence of solidarity. The predictions receive support from five studies, in which we study groups in laboratory and field settings. Results show that both complementary and uniform co-action increase a sense of solidarity compared to control conditions. However, in the complementary action condition, but not in the uniform action (or synchrony) condition, the effect on feelings of solidarity is mediated by a sense of personal value to the group.

  4. Overexpressed Genes/ESTs and Characterization of Distinct Amplicons on 17823 in Breast Cancer Cells

    Directory of Open Access Journals (Sweden)

    Ayse E. Erson

    2001-01-01

    Full Text Available 17823 is a frequent site of gene amplification in breast cancer. Several lines of evidence suggest the presence of multiple amplicons on 17823. To characterize distinct amplicons on 17823 and localize putative oncogenes, we screened genes and expressed sequence tags (ESTs in existing physical and radiation hybrid maps for amplification and overexpression in breast cancer cell lines by semiquantitative duplex PCR, semiquantitative duplex RT-PCR, Southern blot, Northern blot analyses. We identified two distinct amplicons on 17823, one including TBX2 and another proximal region including RPS6KB1 (PS6K and MUL. In addition to these previously reported overexpressed genes, we also identified amplification and overexpression of additional uncharacterized genes and ESTs, some of which suggest potential oncogenic activity. In conclusion, we have further defined two distinct regions of gene amplification and overexpression on 17823 with identification of new potential oncogene candidates. Based on the amplification and overexpression patterns of known and as of yet unrecognized genes on 17823, it is likely that some of these genes mapping to the discrete amplicons function as oncogenes and contribute to tumor progression in breast cancer cells.

  5. Krox20 defines a subpopulation of cardiac neural crest cells contributing to arterial valves and bicuspid aortic valve.

    Science.gov (United States)

    Odelin, Gaëlle; Faure, Emilie; Coulpier, Fanny; Di Bonito, Maria; Bajolle, Fanny; Studer, Michèle; Avierinos, Jean-François; Charnay, Patrick; Topilko, Piotr; Zaffran, Stéphane

    2018-01-03

    Although cardiac neural crest cells are required at early stages of arterial valve development, their contribution during valvular leaflet maturation remains poorly understood. Here, we show in mouse that neural crest cells from pre-otic and post-otic regions make distinct contributions to the arterial valve leaflets. Genetic fate-mapping analysis of Krox20-expressing neural crest cells shows a large contribution to the borders and the interleaflet triangles of the arterial valves. Loss of Krox20 function results in hyperplastic aortic valve and partially penetrant bicuspid aortic valve formation. Similar defects are observed in neural crest Krox20 -deficient embryos. Genetic lineage tracing in Krox20 -/- mutant mice shows that endothelial-derived cells are normal, whereas neural crest-derived cells are abnormally increased in number and misplaced in the valve leaflets. In contrast, genetic ablation of Krox20 -expressing cells is not sufficient to cause an aortic valve defect, suggesting that adjacent cells can compensate this depletion. Our findings demonstrate a crucial role for Krox20 in arterial valve development and reveal that an excess of neural crest cells may be associated with bicuspid aortic valve. © 2018. Published by The Company of Biologists Ltd.

  6. 'Faceness' and affectivity: evidence for genetic contributions to distinct components of electrocortical response to human faces.

    Science.gov (United States)

    Shannon, Robert W; Patrick, Christopher J; Venables, Noah C; He, Sheng

    2013-12-01

    The ability to recognize a variety of different human faces is undoubtedly one of the most important and impressive functions of the human perceptual system. Neuroimaging studies have revealed multiple brain regions (including the FFA, STS, OFA) and electrophysiological studies have identified differing brain event-related potential (ERP) components (e.g., N170, P200) possibly related to distinct types of face information processing. To evaluate the heritability of ERP components associated with face processing, including N170, P200, and LPP, we examined ERP responses to fearful and neutral face stimuli in monozygotic (MZ) and dizygotic (DZ) twins. Concordance levels for early brain response indices of face processing (N170, P200) were found to be stronger for MZ than DZ twins, providing evidence of a heritable basis to each. These findings support the idea that certain key neural mechanisms for face processing are genetically coded. Implications for understanding individual differences in recognition of facial identity and the emotional content of faces are discussed. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation

    KAUST Repository

    Abdallah, Abdallah

    2011-09-28

    During infection of humans and animals, pathogenic mycobacteria manipulate the host cell causing severe diseases such as tuberculosis and leprosy. To understand the basis of mycobacterial pathogenicity, it is crucial to identify the molecular virulence mechanisms. In this study, we address the contribution of ESX-1 and ESX-5 - two homologous type VII secretion systems of mycobacteria that secrete distinct sets of immune modulators - during the macrophage infection cycle. Using wild-type, ESX-1- and ESX-5-deficient mycobacterial strains, we demonstrate that these secretion systems differentially affect subcellular localization and macrophage cell responses. We show that in contrast to ESX-1, the effector proteins secreted by ESX-5 are not required for the translocation of Mycobacterium tuberculosis or Mycobacterium marinum to the cytosol of host cells. However, the M. marinum ESX-5 mutant does not induce inflammasome activation and IL-1b activation. The ESX-5 system also induces a caspase-independent cell death after translocation has taken place. Importantly, by means of inhibitory agents and small interfering RNA experiments, we reveal that cathepsin B is involved in both the induction of cell death and inflammasome activation upon infection with wild-type mycobacteria. These results reveal distinct roles for two different type VII secretion systems during infection and shed light on how virulent mycobacteria manipulate the host cell in various ways to replicate and spread. Copyright © 2011 by The American Association of Immunologists, Inc.

  8. The Shared Goals and Distinct Strengths of the Medical Humanities: Can the Sum of the Parts Be Greater Than the Whole?

    Science.gov (United States)

    Greene, Jeremy A; Jones, David S

    2017-12-01

    Since the 1960s, faculty from diverse fields have banded together under the banner of the medical humanities, a term which unites art, literature, history, anthropology, religious studies, philosophy, and other disciplines. Arguments for the relevance of medical humanities often emphasize contributions that any of these disciplines can make to medical education, whether those involve empathy, professionalism, critical reasoning, or tolerating ambiguity. The authors argue that the constituent disciplines of the medical humanities are not interchangeable parts, but represent different perspectives and methodologies that offer their own distinct contributions to medical training. Efforts to define a role for medical humanities in medical education should pursue two strategies in parallel. On the one hand, advocates of the medical humanities should continue to make the case for the shared contributions that all of the disciplines can make to medical education. But advocates for the medical humanities should also emphasize the valuable contributions of each specific discipline, in terms that medical educators can understand. The authors illustrate this point by delineating contributions of their own discipline, medical history. Historical analysis contributes essential insights to the understanding of disease, therapeutics, and institutions-things that all physicians must know in order to be effective as clinicians, just as they must learn anatomy or pathophysiology. Analogous but different arguments can be made for literature, philosophy, and the other disciplines that constitute the medical humanities. The field of medical humanities will be most successful if it builds on both the shared and the distinct contributions of its disciplines.

  9. A novel and lethal de novo LQT-3 mutation in a newborn with distinct molecular pharmacology and therapeutic response.

    Directory of Open Access Journals (Sweden)

    John R Bankston

    2007-12-01

    Full Text Available SCN5A encodes the alpha-subunit (Na(v1.5 of the principle Na(+ channel in the human heart. Genetic lesions in SCN5A can cause congenital long QT syndrome (LQTS variant 3 (LQT-3 in adults by disrupting inactivation of the Na(v1.5 channel. Pharmacological targeting of mutation-altered Na(+ channels has proven promising in developing a gene-specific therapeutic strategy to manage specifically this LQTS variant. SCN5A mutations that cause similar channel dysfunction may also contribute to sudden infant death syndrome (SIDS and other arrhythmias in newborns, but the prevalence, impact, and therapeutic management of SCN5A mutations may be distinct in infants compared with adults.Here, in a multidisciplinary approach, we report a de novo SCN5A mutation (F1473C discovered in a newborn presenting with extreme QT prolongation and differential responses to the Na(+ channel blockers flecainide and mexiletine. Our goal was to determine the Na(+ channel phenotype caused by this severe mutation and to determine whether distinct effects of different Na(+ channel blockers on mutant channel activity provide a mechanistic understanding of the distinct therapeutic responsiveness of the mutation carrier. Sequence analysis of the proband revealed the novel missense SCN5A mutation (F1473C and a common variant in KCNH2 (K897T. Patch clamp analysis of HEK 293 cells transiently transfected with wild-type or mutant Na(+ channels revealed significant changes in channel biophysics, all contributing to the proband's phenotype as predicted by in silico modeling. Furthermore, subtle differences in drug action were detected in correcting mutant channel activity that, together with both the known genetic background and age of the patient, contribute to the distinct therapeutic responses observed clinically.The results of our study provide further evidence of the grave vulnerability of newborns to Na(+ channel defects and suggest that both genetic background and age are

  10. Towards the Development of a Second-Order Approximation in Activity Coefficient Models Based on Group Contributions

    DEFF Research Database (Denmark)

    Abildskov, Jens; Constantinou, Leonidas; Gani, Rafiqul

    1996-01-01

    A simple modification of group contribution based models for estimation of liquid phase activity coefficients is proposed. The main feature of this modification is that contributions estimated from the present first-order groups in many instances are found insufficient since the first-order groups...... correlation/prediction capabilities, distinction between isomers and ability to overcome proximity effects....

  11. Employees as Individually and Collectively Acting Subjects—Key Contributions from Nordic Working Life Research

    Directory of Open Access Journals (Sweden)

    Peter Hasle

    2013-09-01

    Full Text Available The Nordic countries—Denmark, Finland, Iceland, Norway, and Sweden—are societies that share many features among themselves that also distinguish them from other industrialized countries. The paper poses the question whether the distinct character of the Nordic societies has generated working life research that is clearly distinguishable from similar research in other countries in terms of distinctness in topics, methods, empirical findings, or theoretical concepts. The aim of this paper is to answer this question by identifying, analyzing, and discussing selected key contributions from Nordic working life research to understand how they research and construe the conditions of humans at work with a special focus on the psychosocial well-being of industrial workers. The paper concludes that the key contributions to Nordic working life research have a distinctive emphasis on collective employee voice and autonomy and an extensive use of empirical and actionoriented research methods. Employees are construed not only as workers resisting exploitations from management or as workers pursuing individual careers, but also as members of collectives who share ideas and aspirations and who legitimately influence the management (and research using cooperation and pressure.

  12. Distinctive striatal dopamine signaling after dieting and gastric bypass.

    Science.gov (United States)

    Hankir, Mohammed K; Ashrafian, Hutan; Hesse, Swen; Horstmann, Annette; Fenske, Wiebke K

    2015-05-01

    Highly palatable and/or calorically dense foods, such as those rich in fat, engage the striatum to govern and set complex behaviors. Striatal dopamine signaling has been implicated in hedonic feeding and the development of obesity. Dieting and bariatric surgery have markedly different outcomes on weight loss, yet how these interventions affect central homeostatic and food reward processing remains poorly understood. Here, we propose that dieting and gastric bypass produce distinct changes in peripheral factors with known roles in regulating energy homeostasis, resulting in differential modulation of nigrostriatal and mesolimbic dopaminergic reward circuits. Enhancement of intestinal fat metabolism after gastric bypass may also modify striatal dopamine signaling contributing to its unique long-term effects on feeding behavior and body weight in obese individuals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Commonalities and distinctions among mechanisms of addiction to alcohol and other drugs

    Science.gov (United States)

    Ozburn, Angela R.; Janowsky, Aaron J.; Crabbe, John C.

    2015-01-01

    Alcohol abuse is comorbid with abuse of many other drugs, some with similar pharmacology and others quite different. This leads to the hypothesis of an underlying, unitary dysfunctional neurobiological basis for substance abuse risk and consequences. In this review, we discuss commonalities and distinctions of addiction to alcohol and other drugs. We focus on recent advances in pre-clinical studies using rodent models of drug self-administration. While there are specific behavioral and molecular manifestations common to alcohol, psychostimulant, opioid, and nicotine dependence, attempts to propose a unifying theory of the addictions inevitably face details where distinctions are found among classes of drugs. For alcohol, versus other drugs of abuse, we discuss and compare advances in: 1) neurocircuitry important for the different stages of drug dependence; 2) transcriptomics and genetical genomics; and 3) enduring effects. We note in particular the contributions of behavioral genetics and animal models: discussions of progress specifically relevant to treatment development can be found in the accompanying review (Karoly et al, this issue). PMID:26431116

  14. Tentonin 3/TMEM150c Confers Distinct Mechanosensitive Currents in Dorsal-Root Ganglion Neurons with Proprioceptive Function.

    Science.gov (United States)

    Hong, Gyu-Sang; Lee, Byeongjun; Wee, Jungwon; Chun, Hyeyeon; Kim, Hyungsup; Jung, Jooyoung; Cha, Joo Young; Riew, Tae-Ryong; Kim, Gyu Hyun; Kim, In-Beom; Oh, Uhtaek

    2016-07-06

    Touch sensation or proprioception requires the transduction of mechanical stimuli into electrical signals by mechanoreceptors in the periphery. These mechanoreceptors are equipped with various transducer channels. Although Piezo1 and 2 are mechanically activated (MA) channels with rapid inactivation, MA molecules with other inactivation kinetics have not been identified. Here we report that heterologously expressed Tentonin3 (TTN3)/TMEM150C is activated by mechanical stimuli with distinctly slow inactivation kinetics. Genetic ablation of Ttn3/Tmem150c markedly reduced slowly adapting neurons in dorsal-root ganglion neurons. The MA TTN3 currents were inhibited by known blockers of mechanosensitive ion channels. Moreover, TTN3 was localized in muscle spindle afferents. Ttn3-deficient mice exhibited the loss of coordinated movements and abnormal gait. Thus, TTN3 appears to be a component of a mechanosensitive channel with a slow inactivation rate and contributes to motor coordination. Identification of this gene advances our understanding of the various types of mechanosensations, including proprioception. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. Distinct requirements for signal peptidase processing and function in the stable signal peptide subunit of the Junin virus envelope glycoprotein

    International Nuclear Information System (INIS)

    York, Joanne; Nunberg, Jack H.

    2007-01-01

    The arenavirus envelope glycoprotein (GP-C) retains a cleaved and stable signal peptide (SSP) as an essential subunit of the mature complex. This 58-amino-acid residue peptide serves as a signal sequence and is additionally required to enable transit of the assembled GP-C complex to the Golgi, and for pH-dependent membrane fusion activity. We have investigated the C-terminal region of the Junin virus SSP to study the role of the cellular signal peptidase (SPase) in generating SSP. Site-directed mutagenesis at the cleavage site (positions - 1 and - 3) reveals a pattern of side-chain preferences consistent with those of SPase. Although position - 2 is degenerate for SPase cleavage, this residue in the arenavirus SSP is invariably a cysteine. In the Junin virus, this cysteine is not involved in disulfide bonding. We show that replacement with alanine or serine is tolerated for SPase cleavage but prevents the mutant SSP from associating with GP-C and enabling transport to the cell surface. Conversely, an arginine mutation at position - 1 that prevents SPase cleavage is fully compatible with GP-C-mediated membrane fusion activity when the mutant SSP is provided in trans. These results point to distinct roles of SSP sequences in SPase cleavage and GP-C biogenesis. Further studies of the unique structural organization of the GP-C complex will be important in identifying novel opportunities for antiviral intervention against arenaviral hemorrhagic disease

  16. Visual distinctiveness can enhance recency effects.

    Science.gov (United States)

    Bornstein, B H; Neely, C B; LeCompte, D C

    1995-05-01

    Experimental efforts to meliorate the modality effect have included attempts to make the visual stimulus more distinctive. McDowd and Madigan (1991) failed to find an enhanced recency effect in serial recall when the last item was made more distinct in terms of its color. In an attempt to extend this finding, three experiments were conducted in which visual distinctiveness was manipulated in a different manner, by combining the dimensions of physical size and coloration (i.e., whether the stimuli were solid or outlined in relief). Contrary to previous findings, recency was enhanced when the size and coloration of the last item differed from the other items in the list, regardless of whether the "distinctive" item was larger or smaller than the remaining items. The findings are considered in light of other research that has failed to obtain a similar enhanced recency effect, and their implications for current theories of the modality effect are discussed.

  17. Nordic Internationalists' Contribution to the Field of Comparative and International Education

    Science.gov (United States)

    Genova, Teodora

    2016-01-01

    This paper stems from a PhD dissertation research focusing on the Nordic representatives' contribution to the field of comparative and international education (CIE) since the middle of the 20th century to the present days. Following the idea of the clear-cut distinction between the two component parts of the field in the region in question, the…

  18. On Hobbes’s distinction of accidents

    Directory of Open Access Journals (Sweden)

    Lupoli Agostino

    2012-06-01

    Full Text Available An interpolation introduced by K. Schuhmann in his critical edition of "De corpore" (chap. VI, § 13 diametrically overturns the meaning of Hobbes’s doctrine of distinction of accidents in comparison with all previous editions. The article focuses on the complexity of this crucial juncture in "De corpore" argument on which depends the interpretation of Hobbes’s whole conception of science. It discusses the reasons pro and contra Schuhmann’s interpolation and concludes against it, because it is not compatible with the rationale underlying the complex architecture of "De corpore", which involves a symmetry between the ‘logical’ distinction of accidents and the ‘metaphysical’ distinction of phantasms.

  19. Rethinking the distinction between black and brown carbon

    Science.gov (United States)

    Adler, G. A.; Franchin, A.; Lamb, K. D.; Manfred, K.; Middlebrook, A. M.; Schwarz, J. P.; Wagner, N.; Washenfelder, R. A.; Womack, C.; Murphy, D. M.

    2017-12-01

    Aerosol radiative properties contribute large uncertainty to modeling of the earth's radiative budget. Black carbon (BC) aerosols originate from combustion processes and substantially contribute to warming and uncertainty - ongoing efforts are focused on reducing their anthropogenic emissions even as their emissions from biomass burning sources, such as wildfire, may increase in the future. Quantifying the radiative effect of BC is challenging, in part due to its association with other light absorbing materials including Brown carbon organic aerosol (BrC) that absorbs primarily blue and ultraviolet light while BC absorbs broadly across the visible. Conventionally BrC is thought of a low volatility spherical particles, distinguishing it from BC, which has a distinctive agglomerate morphology and is refractory at high temperatures. However, the separation of BC and BrC is often operationally defined and dependent on the measurement method. Using measurements of aerosol morphology, mass, absorption, and refractory BC mass content we were able to identify a light absorbing contribution from biomass burning aerosol that does not correspond to either BC or BrC as conventionally defined. Our measurements were collected from realistic biomass burning fires at the Missoula Fire Sciences Laboratory as part of the NOAA FIREX project (2016) and from extensive natural wildfire sampled aloft during NASA SEAC4RS field study (2013). We coin the term Dark Brown Carbon (DBrC) to describe this material, which absorbs broadly across the visible and survives thermal denuding at 250°C but does not incandesce in laser induced incandesce (LII) measurements. DBrC may be an intermediate burning stage product between polycyclic aromatic hydrocarbons (PAHs) and the mature soot. DBrC deserves further study to quantify its abundance and aging in ambient biomass burning plumes, and its relationship to tar balls. Our findings show that more than half of the light absorption in biomass burning

  20. The Clean Coal Program's contributions to addressing the requirements of the Clean Air Act Amendments of 1990

    International Nuclear Information System (INIS)

    Miller, R.L.

    1992-01-01

    The purpose of this paper is to examine the potential contributions of the US Department of Energy's Clean Coal Program (CCP) to addressing the requirements of the Clean Air Act (CAA) Amendments of 1990 (CAA90). Initially funded by Congress in 1985, the CCP is a government and industry co-funded effort to demonstrate a new generation of more efficient, economically feasible, and environmentally acceptable coal technologies in a series of full- scale ''showcase'' facilities built across the country. The CCP is expected to provide funding for more than $5 billion of projects during five rounds of competition, with at least half of the funding coming from the private sector. To date, 42 projects have been selected in the first 4 rounds of the CCP. The CAA and amendments form the basis for regulating emissions of air pollutants to protect health and the environment throughout the United States. Although the origin of the CAA can be traced back to 1955, many amendments passed since that time are testimony to the iterative process involved in the regulation of air pollution. Three key components of CAA90, the first major amendments to the CAA since 1977, include mitigation measures to reduce levels of (1) acid deposition, (2) toxic air pollutants, and (3) ambient concentrations of air pollutants. This paper focuses on the timeliness of clean coal technologies in contributing to these provisions of CAA90

  1. Contribution to and Use of Online Knowledge Repositories: The Role of Governance Mechanisms

    Science.gov (United States)

    Kayhan, Varol O.

    2010-01-01

    Drawing upon the concept of governance, this dissertation refers to the two most commonly employed mechanisms that ensure high quality knowledge in electronic repositories as expert-governance and community-governance. In three related but distinct essays, the dissertation examines the governance concept, and investigates contributing knowledge to…

  2. Distinct roles of prelimbic and infralimbic proBDNF in extinction of conditioned fear.

    Science.gov (United States)

    Sun, Wei; Li, Xiaoliang; An, Lei

    2018-03-15

    Brain-derived neurotrophic factor (BDNF) has been investigated for its positive role in regulation of fear acquisition and memory. The precursor of BDNF, proBDNF, has been identified as different protein from its mature form. The prelimbic (PL) and infralimbic (IL) sub-regions of the medial prefrontal cortex (mPFC) are functionally distinct in fear behavior. However, the role of PL and IL proBDNF in fear memory is unclear. Here, through the infusion of cleavage-resistant proBDNF and its antibody, we identified the dissociable roles of PL and IL proBDNF in fear expression and extinction memory as well as explored proBDNF's potential mechanism of action. The results suggest that the infusion of proBDNF in the IL facilitates induction of fear extinction, while infusion in the PL depresses fear expression. Blocking proBDNF by using its antibody disrupted the acquisition of fear extinction in the IL, but not the PL. Furthermore, proBDNF-induced extinction was sufficient for extinguishing new and older memories, and required NR2B, but not NR2A, -containing NMDA receptors. We also observed extinction-related proBDNF expression increased in the PL and IL during successful fear expression and extinction, respectively. Importantly, enhanced proBDNF was required for maintaining an extinguished behavior. The extinction effects of proBDNF did not involve degrading the original fear memory. Therefore, proBDNF in the IL and PL differentially contribute to the inhibitory control of fear extinction behavior. Our findings provide a strong link between proBDNF activity and deficits in fear extinction, a hallmark of several psychiatric disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. The Cell Cycle Timing of Centromeric Chromatin Assembly in Drosophila Meiosis Is Distinct from Mitosis Yet Requires CAL1 and CENP-C

    Science.gov (United States)

    Gorgescu, Walter; Tang, Jonathan; Costes, Sylvain V.; Karpen, Gary H.

    2012-01-01

    CENP-A (CID in flies) is the histone H3 variant essential for centromere specification, kinetochore formation, and chromosome segregation during cell division. Recent studies have elucidated major cell cycle mechanisms and factors critical for CENP-A incorporation in mitosis, predominantly in cultured cells. However, we do not understand the roles, regulation, and cell cycle timing of CENP-A assembly in somatic tissues in multicellular organisms and in meiosis, the specialized cell division cycle that gives rise to haploid gametes. Here we investigate the timing and requirements for CID assembly in mitotic tissues and male and female meiosis in Drosophila melanogaster, using fixed and live imaging combined with genetic approaches. We find that CID assembly initiates at late telophase and continues during G1 phase in somatic tissues in the organism, later than the metaphase assembly observed in cultured cells. Furthermore, CID assembly occurs at two distinct cell cycle phases during male meiosis: prophase of meiosis I and after exit from meiosis II, in spermatids. CID assembly in prophase I is also conserved in female meiosis. Interestingly, we observe a novel decrease in CID levels after the end of meiosis I and before meiosis II, which correlates temporally with changes in kinetochore organization and orientation. We also demonstrate that CID is retained on mature sperm despite the gross chromatin remodeling that occurs during protamine exchange. Finally, we show that the centromere proteins CAL1 and CENP-C are both required for CID assembly in meiosis and normal progression through spermatogenesis. We conclude that the cell cycle timing of CID assembly in meiosis is different from mitosis and that the efficient propagation of CID through meiotic divisions and on sperm is likely to be important for centromere specification in the developing zygote. PMID:23300382

  4. The Role of Cognitive Content and Cognitive Processes in Chronic Pain: An Important Distinction?

    Science.gov (United States)

    Jensen, Mark P; Thorn, Beverly E; Carmody, James; Keefe, Francis J; Burns, John W

    2018-05-01

    Pain-related cognitive content (what people think about pain) and cognitive processes (how people think about pain; what they do with their pain-related thoughts) and their interaction are hypothesized to play distinct roles in patient function. However, questions have been raised regarding whether it is possible or practical to assess cognitive content and cognitive process as distinct domains. The aim of this study was to determine the extent to which measures that seem to assess mostly pain-related cognitive content, cognitive processes, and content and process, are relatively independent from each other and contribute unique variance to the prediction of patient function. Individuals with chronic low back pain (N=165) participating in an ongoing RCT were administered measures of cognitions, pain, and function (depressive symptoms and pain interference) pretreatment. Analyses provided support for the hypothesis that cognitive content and cognitive process, while related, can be assessed as distinct components. However, the measure assessing a cognitive process-mindfulness-evidenced relatively weak associations with function, especially compared with the stronger and more consistent findings for the measures of content (catastrophizing and self-efficacy). The results provide preliminary evidence for the possibility that mindfulness could have both benefits and costs. Research to evaluate this possibility is warranted.

  5. Mesenchymal stem cells generate distinct functional hybrids in vitro via cell fusion or entosis.

    Science.gov (United States)

    Sottile, Francesco; Aulicino, Francesco; Theka, Ilda; Cosma, Maria Pia

    2016-11-09

    Homotypic and heterotypic cell-to-cell fusion are key processes during development and tissue regeneration. Nevertheless, aberrant cell fusion can contribute to tumour initiation and metastasis. Additionally, a form of cell-in-cell structure called entosis has been observed in several human tumours. Here we investigate cell-to-cell interaction between mouse mesenchymal stem cells (MSCs) and embryonic stem cells (ESCs). MSCs represent an important source of adult stem cells since they have great potential for regenerative medicine, even though they are also involved in cancer progression. We report that MSCs can either fuse forming heterokaryons, or be invaded by ESCs through entosis. While entosis-derived hybrids never share their genomes and induce degradation of the target cell, fusion-derived hybrids can convert into synkaryons. Importantly we show that hetero-to-synkaryon transition occurs through cell division and not by nuclear membrane fusion. Additionally, we also observe that the ROCK-actin/myosin pathway is required for both fusion and entosis in ESCs but only for entosis in MSCs. Overall, we show that MSCs can undergo fusion or entosis in culture by generating distinct functional cellular entities. These two processes are profoundly different and their outcomes should be considered given the beneficial or possible detrimental effects of MSC-based therapeutic applications.

  6. Distinct Developmental Origins Manifest in the Specialized Encoding of Movement by Adult Neurons of the External Globus Pallidus

    Science.gov (United States)

    Dodson, Paul D.; Larvin, Joseph T.; Duffell, James M.; Garas, Farid N.; Doig, Natalie M.; Kessaris, Nicoletta; Duguid, Ian C.; Bogacz, Rafal; Butt, Simon J.B.; Magill, Peter J.

    2015-01-01

    Summary Transcriptional codes initiated during brain development are ultimately realized in adulthood as distinct cell types performing specialized roles in behavior. Focusing on the mouse external globus pallidus (GPe), we demonstrate that the potential contributions of two GABAergic GPe cell types to voluntary action are fated from early life to be distinct. Prototypic GPe neurons derive from the medial ganglionic eminence of the embryonic subpallium and express the transcription factor Nkx2-1. These neurons fire at high rates during alert rest, and encode movements through heterogeneous firing rate changes, with many neurons decreasing their activity. In contrast, arkypallidal GPe neurons originate from lateral/caudal ganglionic eminences, express the transcription factor FoxP2, fire at low rates during rest, and encode movements with robust increases in firing. We conclude that developmental diversity positions prototypic and arkypallidal neurons to fulfil distinct roles in behavior via their disparate regulation of GABA release onto different basal ganglia targets. PMID:25843402

  7. Contribution of Legume Rotations to the Nitrogen Requirements of a ...

    African Journals Online (AJOL)

    Cereal crop yield improvements following legume rotations ... effects of legumes rotation in meeting the N fertilizer requirements of maize. ... The effects of the rotations on increasing the maize yields were equivalent to application of 25, 19 and.

  8. Dissociable contributions of anterior cingulate cortex and basolateral amygdala on a rodent cost/benefit decision-making task of cognitive effort.

    Science.gov (United States)

    Hosking, Jay G; Cocker, Paul J; Winstanley, Catharine A

    2014-06-01

    Personal success often requires the choice to expend greater effort for larger rewards, and deficits in such effortful decision making accompany a number of illnesses including depression, schizophrenia, and attention-deficit/hyperactivity disorder. Animal models have implicated brain regions such as the basolateral amygdala (BLA) and anterior cingulate cortex (ACC) in physical effort-based choice, but disentangling the unique contributions of these two regions has proven difficult, and effort demands in industrialized society are predominantly cognitive in nature. Here we utilize the rodent cognitive effort task (rCET), a modification of the five-choice serial reaction-time task, wherein animals can choose to expend greater visuospatial attention to obtain larger sucrose rewards. Temporary inactivation (via baclofen-muscimol) of BLA and ACC showed dissociable effects: BLA inactivation caused hard-working rats to 'slack off' and 'slacker' rats to work harder, whereas ACC inactivation caused all animals to reduce willingness to expend mental effort. Furthermore, BLA inactivation increased the time needed to make choices, whereas ACC inactivation increased motor impulsivity. These data illuminate unique contributions of BLA and ACC to effort-based decision making, and imply overlapping yet distinct circuitry for cognitive vs physical effort. Our understanding of effortful decision making may therefore require expanding our models beyond purely physical costs.

  9. Occupational Therapy Contributions in Early Intervention: Implications for Personnel Preparation and Interprofessional Practice

    Science.gov (United States)

    Muhlenhaupt, Mary; Pizur-Barnekow, Kris; Schefkind, Sandra; Chandler, Barbara; Harvison, Neil

    2015-01-01

    Occupational therapy provides a unique contribution in early intervention programs for families and their children from birth to 3 years old who are at risk for, or who have, identified disabilities. This article describes occupational therapy's distinct value and presents the profession's perspective on services to enhance families' caregiving…

  10. A retrospective appreciation of Willard Day's contributions to radical behaviorism and the analysis of verbal behavior

    Science.gov (United States)

    Moore, Jay

    1991-01-01

    Willard Day's contributions to radical behaviorism are grouped under three headings: (a) an emphasis on the distinction between radical and methodological behaviorism; (b) an emphasis on the interpretation, rather than the prediction and control, of behavior; and (c) an emphasis on the analysis of verbal behavior as a natural, ongoing phenomenon. The paper suggests that the contributions above are listed in ascending order of significance. PMID:22477632

  11. Shared versus distinct genetic contributions of mental wellbeing with depression and anxiety symptoms in healthy twins.

    Science.gov (United States)

    Routledge, Kylie M; Burton, Karen L O; Williams, Leanne M; Harris, Anthony; Schofield, Peter R; Clark, C Richard; Gatt, Justine M

    2016-10-30

    Mental wellbeing and mental illness symptoms are typically conceptualized as opposite ends of a continuum, despite only sharing about a quarter in common variance. We investigated the normative variation in measures of wellbeing and of depression and anxiety in 1486 twins who did not meet clinical criteria for an overt diagnosis. We quantified the shared versus distinct genetic and environmental variance between wellbeing and depression and anxiety symptoms. The majority of participants (93%) reported levels of depression and anxiety symptoms within the healthy range, yet only 23% reported a wellbeing score within the "flourishing" range: the remainder were within the ranges of "moderate" (67%) or "languishing" (10%). In twin models, measures of wellbeing and of depression and anxiety shared 50.09% of variance due to genetic factors and 18.27% due to environmental factors; the rest of the variance was due to unique variation impacting wellbeing or depression and anxiety symptoms. These findings suggest that an absence of clinically-significant symptoms of depression and anxiety does not necessarily indicate that an individual is flourishing. Both unique and shared genetic and environmental factors may determine why some individuals flourish in the absence of symptoms while others do not. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  12. What makes health promotion research distinct?

    Science.gov (United States)

    Woodall, James; Warwick-Booth, Louise; South, Jane; Cross, Ruth

    2018-02-01

    There have been concerns about the decline of health promotion as a practice and discipline and, alongside this, calls for a clearer articulation of health promotion research and what, if anything, makes it distinct. This discussion paper, based on a review of the literature, the authors' own experiences in the field, and a workshop delivered by two of the authors at the 8th Nordic Health Promotion Conference, seeks to state the reasons why health promotion research is distinctive. While by no means exhaustive, the paper suggests four distinctive features. The paper hopes to be a catalyst to enable health promotion researchers to be explicit in their practice and to begin the process of developing an agreed set of research principles.

  13. Quantitative image analysis reveals distinct structural transitions during aging in Caenorhabditis elegans tissues.

    Directory of Open Access Journals (Sweden)

    Josiah Johnston

    2008-07-01

    Full Text Available Aging is associated with functional and structural declines in many body systems, even in the absence of underlying disease. In particular, skeletal muscles experience severe declines during aging, a phenomenon termed sarcopenia. Despite the high incidence and severity of sarcopenia, little is known about contributing factors and development. Many studies focus on functional aspects of aging-related tissue decline, while structural details remain understudied. Traditional approaches for quantifying structural changes have assessed individual markers at discrete intervals. Such approaches are inadequate for the complex changes associated with aging. An alternative is to consider changes in overall morphology rather than in specific markers. We have used this approach to quantitatively track tissue architecture during adulthood and aging in the C. elegans pharynx, the neuromuscular feeding organ. Using pattern recognition to analyze aged-grouped pharynx images, we identified discrete step-wise transitions between distinct morphologies. The morphology state transitions were maintained in mutants with pharynx neurotransmission defects, although the pace of the transitions was altered. Longitudinal measurements of pharynx function identified a predictive relationship between mid-life pharynx morphology and function at later ages. These studies demonstrate for the first time that adult tissues undergo distinct structural transitions reflecting postdevelopmental events. The processes that underlie these architectural changes may contribute to increased disease risk during aging, and may be targets for factors that alter the aging rate. This work further demonstrates that pattern analysis of an image series offers a novel and generally accessible approach for quantifying morphological changes and identifying structural biomarkers.

  14. Quantitative image analysis reveals distinct structural transitions during aging in Caenorhabditis elegans tissues.

    Science.gov (United States)

    Johnston, Josiah; Iser, Wendy B; Chow, David K; Goldberg, Ilya G; Wolkow, Catherine A

    2008-07-30

    Aging is associated with functional and structural declines in many body systems, even in the absence of underlying disease. In particular, skeletal muscles experience severe declines during aging, a phenomenon termed sarcopenia. Despite the high incidence and severity of sarcopenia, little is known about contributing factors and development. Many studies focus on functional aspects of aging-related tissue decline, while structural details remain understudied. Traditional approaches for quantifying structural changes have assessed individual markers at discrete intervals. Such approaches are inadequate for the complex changes associated with aging. An alternative is to consider changes in overall morphology rather than in specific markers. We have used this approach to quantitatively track tissue architecture during adulthood and aging in the C. elegans pharynx, the neuromuscular feeding organ. Using pattern recognition to analyze aged-grouped pharynx images, we identified discrete step-wise transitions between distinct morphologies. The morphology state transitions were maintained in mutants with pharynx neurotransmission defects, although the pace of the transitions was altered. Longitudinal measurements of pharynx function identified a predictive relationship between mid-life pharynx morphology and function at later ages. These studies demonstrate for the first time that adult tissues undergo distinct structural transitions reflecting postdevelopmental events. The processes that underlie these architectural changes may contribute to increased disease risk during aging, and may be targets for factors that alter the aging rate. This work further demonstrates that pattern analysis of an image series offers a novel and generally accessible approach for quantifying morphological changes and identifying structural biomarkers.

  15. Weighting of Acoustic Cues to a Manner Distinction by Children with and without Hearing Loss

    Science.gov (United States)

    Nittrouer, Susan; Lowenstein, Joanna H.

    2015-01-01

    Purpose: Children must develop optimal perceptual weighting strategies for processing speech in their first language. Hearing loss can interfere with that development, especially if cochlear implants are required. The three goals of this study were to measure, for children with and without hearing loss: (a) cue weighting for a manner distinction,…

  16. Complete identification of E-selectin ligand activity on neutrophils reveals a dynamic interplay and distinct functions of PSGL-1, ESL-1 and CD44

    Science.gov (United States)

    Wild, Martin; Vestweber, Dietmar; Frenette, Paul S.

    2014-01-01

    SUMMARY The selectins and their ligands are required for leukocyte extravasation during inflammation. Several glycoproteins have been suggested to bind to E-selectin in vitro but the complete identification of its physiological ligands has remained elusive. Here, we show using gene- and RNA-targeted loss-of-function that E-selectin ligand-1 (ESL-1), PSGL-1 and CD44 encompass all endothelial selectin ligand activity on neutrophils. PSGL-1 plays a major role in the initial leukocyte capture, while ESL-1 is critical to convert initial tethers into steady slow rolling. CD44 controls rolling velocity and mediates E-selectin-dependent redistribution of PSGL-1 and L-selectin to a major pole on slowly rolling leukocytes through p38 signaling. These results suggest distinct and dynamic contributions of these three glycoproteins in selectin-mediated neutrophil adhesion and signaling. PMID:17442598

  17. Hanna Arendt and the distinction between knowing and thinking: reflections for science teaching

    Directory of Open Access Journals (Sweden)

    José Francisco Flores

    2017-03-01

    Full Text Available Theoretical contributions are proposed for the formation of science teachers from the distinction between knowledge and thought presented by Hanna Arendt. For the author, the action of knowing, accomplished by science, seeks truths, while the thought, as a action of spirit, seeks meanings. The concept of creative potential is used, suggested by the plastic artist Fayga Ostrower, as a motivational factor of thinking for production of meanings. It can be concluded that science teaching must aim at the development of the ability of not only knowing, but also thinking, promoting the expansion of the creative potential of students and teachers.

  18. Adaptation of irrigation networks to climate change: Linking robust design and stakeholder contribution

    Energy Technology Data Exchange (ETDEWEB)

    Granados, A.; Martín-Carrasco, F.J.; García de Jalón, S.; Iglesias, A.

    2015-07-01

    Agriculture is a particularly sensitive sector to the potential impacts of climate change. Thus, irrigation infrastructure is required to be robust to cope with these potential threats. The objective of this research is designing more robust irrigation networks, considering cost and stakeholder contribution. To that end, the investigation was addressed in three phases: a sensitivity analysis to understand the effectiveness of the distinct variables, a cost-effectiveness analysis assessing their efficiency, and a global study of the most efficient variables to provide an insight into their function. The sensitivity analysis indicates that the networks oversized by means of the coefficient of utilisation or the factor of safety, behave better than those oversized via the continuous specific discharge; moreover, the degree of freedom has been shown ineffective. The cost-effectiveness analysis shows that the coefficient of utilisation and the factor of safety are the most efficient variables, as they introduced safety margin oversizing fewer network elements and to a lesser extent than the continuous specific discharge. It also shows that stakeholder contribution, conveyed as a reduction of the degree of freedom, plays an important role in the network’s adaptive capacity to change. The global study of these variables reveals the subtlety of the coefficient of utilisation, which is the variable that better reproduces the farmer behaviour during demand increase scenarios. In conclusion, the results identify the coefficient of utilisation as the variable which provides the safest margins and reveal the importance of stakeholder contribution in absorb the demand increase in a better manner. (Author)

  19. Adaptation of irrigation networks to climate change: Linking robust design and stakeholder contribution

    Directory of Open Access Journals (Sweden)

    Alfredo Granados

    2015-12-01

    Full Text Available Agriculture is a particularly sensitive sector to the potential impacts of climate change. Thus, irrigation infrastructure is required to be robust to cope with these potential threats. The objective of this research is designing more robust irrigation networks, considering cost and stakeholder contribution. To that end, the investigation was addressed in three phases: a sensitivity analysis to understand the effectiveness of the distinct variables, a cost-effectiveness analysis assessing their efficiency, and a global study of the most efficient variables to provide an insight into their function. The sensitivity analysis indicates that the networks oversized by means of the coefficient of utilisation or the factor of safety, behave better than those oversized via the continuous specific discharge; moreover, the degree of freedom has been shown ineffective. The cost-effectiveness analysis shows that the coefficient of utilisation and the factor of safety are the most efficient variables, as they introduced safety margin oversizing fewer network elements and to a lesser extent than the continuous specific discharge. It also shows that stakeholder contribution, conveyed as a reduction of the degree of freedom, plays an important role in the network’s adaptive capacity to change. The global study of these variables reveals the subtlety of the coefficient of utilisation, which is the variable that better reproduces the farmer behaviour during demand increase scenarios. In conclusion, the results identify the coefficient of utilisation as the variable which provides the safest margins and reveal the importance of stakeholder contribution in absorb the demand increase in a better manner.

  20. Keeping conceptual boundaries distinct between decision making and learning is necessary to understand social influence.

    Science.gov (United States)

    Le Mens, Gaël

    2014-02-01

    Bentley et al. make the deliberate choice to blur the distinction between learning and decision making. This obscures the social influence mechanisms that operate in the various empirical settings that their map aims to categorize. Useful policy prescriptions, however, require an accurate understanding of the social influence mechanisms that underlie the dynamics of popularity.

  1. Two distinct E3 ubiquitin ligases have complementary functions in the regulation of delta and serrate signaling in Drosophila.

    Directory of Open Access Journals (Sweden)

    Roland Le Borgne

    2005-04-01

    Full Text Available Signaling by the Notch ligands Delta (Dl and Serrate (Ser regulates a wide variety of essential cell-fate decisions during animal development. Two distinct E3 ubiquitin ligases, Neuralized (Neur and Mind bomb (Mib, have been shown to regulate Dl signaling in Drosophila melanogaster and Danio rerio, respectively. While the neur and mib genes are evolutionarily conserved, their respective roles in the context of a single organism have not yet been examined. We show here that the Drosophila mind bomb (D-mib gene regulates a subset of Notch signaling events, including wing margin specification, leg segmentation, and vein determination, that are distinct from those events requiring neur activity. D-mib also modulates lateral inhibition, a neur- and Dl-dependent signaling event, suggesting that D-mib regulates Dl signaling. During wing development, expression of D-mib in dorsal cells appears to be necessary and sufficient for wing margin specification, indicating that D-mib also regulates Ser signaling. Moreover, the activity of the D-mib gene is required for the endocytosis of Ser in wing imaginal disc cells. Finally, ectopic expression of neur in D-mib mutant larvae rescues the wing D-mib phenotype, indicating that Neur can compensate for the lack of D-mib activity. We conclude that D-mib and Neur are two structurally distinct proteins that have similar molecular activities but distinct developmental functions in Drosophila.

  2. Precision Radiology Residency Training: Special Distinction Tracks for Noninterpretative Professional Development.

    Science.gov (United States)

    Snyder, Elizabeth; Solnes, Lilja; Horton, Karen M; Johnson, Pamela T

    2018-06-01

    The role of a radiologist has expanded beyond the tripartite mission of patient care, education, and research to include cross-specialty consultation for patient management, innovative solutions to improve health-care quality and safety, device design, and policy advocacy. As such, radiology residency programs should incorporate formalized training to prepare residents for these various professional roles. Since the 2015-2016 academic year, five training tracks focused on noninterpretative skills have been integrated into our residency training program: Clinician Educator, Quality Improvement, Entrepreneurship/Innovation, Health Policy Advocacy, and High-Value Care. Each track is longitudinal, with a set of requirements throughout the residents' training necessary to achieve certification at graduation. To date nine residents have participated in the programs, including two who received distinction in two separate tracks. Residents in each of the tracks have implemented successful initiatives related to the focus area. As such, these tracks enrich training by ensuring that residents make meaningful contributions to the department and institution during their training and disseminate successful initiatives through presentation at national meetings and publications. The duration of a radiology residency and resources available in an academic center provide opportunities for residency program directors to advance residents' skills in important noninterpretative components of radiology practice. Regardless of whether residents pursue academic medicine or private practice, these skills are necessary for graduates to become valuable members of a radiology practice and serve as national leaders in the field of radiology. Copyright © 2018 The Association of University Radiologists. Published by Elsevier Inc. All rights reserved.

  3. EGL-13/SoxD Specifies Distinct O2 and CO2 Sensory Neuron Fates in Caenorhabditis elegans

    DEFF Research Database (Denmark)

    Gramstrup Petersen, Jakob; Rojo Romanos, Teresa; Juozaityte, Vaida

    2013-01-01

    that EGL-13 is sufficient to induce O2- and CO2-sensing cell fates in some cellular contexts. Thus, the same core regulatory factor, egl-13, is required and sufficient to specify the distinct fates of O2- and CO2-sensing neurons in C. elegans. These findings extend our understanding of mechanisms......Animals harbor specialized neuronal systems that are used for sensing and coordinating responses to changes in oxygen (O2) and carbon dioxide (CO2). In Caenorhabditis elegans, the O2/CO2 sensory system comprises functionally and morphologically distinct sensory neurons that mediate rapid behavioral...

  4. Distinct transcriptional networks in quiescent myoblasts: a role for Wnt signaling in reversible vs. irreversible arrest.

    Directory of Open Access Journals (Sweden)

    Sindhu Subramaniam

    Full Text Available Most cells in adult mammals are non-dividing: differentiated cells exit the cell cycle permanently, but stem cells exist in a state of reversible arrest called quiescence. In damaged skeletal muscle, quiescent satellite stem cells re-enter the cell cycle, proliferate and subsequently execute divergent programs to regenerate both post-mitotic myofibers and quiescent stem cells. The molecular basis for these alternative programs of arrest is poorly understood. In this study, we used an established myogenic culture model (C2C12 myoblasts to generate cells in alternative states of arrest and investigate their global transcriptional profiles. Using cDNA microarrays, we compared G0 myoblasts with post-mitotic myotubes. Our findings define the transcriptional program of quiescent myoblasts in culture and establish that distinct gene expression profiles, especially of tumour suppressor genes and inhibitors of differentiation characterize reversible arrest, distinguishing this state from irreversibly arrested myotubes. We also reveal the existence of a tissue-specific quiescence program by comparing G0 C2C12 myoblasts to isogenic G0 fibroblasts (10T1/2. Intriguingly, in myoblasts but not fibroblasts, quiescence is associated with a signature of Wnt pathway genes. We provide evidence that different levels of signaling via the canonical Wnt pathway characterize distinct cellular states (proliferation vs. quiescence vs. differentiation. Moderate induction of Wnt signaling in quiescence is associated with critical properties such as clonogenic self-renewal. Exogenous Wnt treatment subverts the quiescence program and negatively affects clonogenicity. Finally, we identify two new quiescence-induced regulators of canonical Wnt signaling, Rgs2 and Dkk3, whose induction in G0 is required for clonogenic self-renewal. These results support the concept that active signal-mediated regulation of quiescence contributes to stem cell properties, and have implications for

  5. Distinct transcriptional networks in quiescent myoblasts: a role for Wnt signaling in reversible vs. irreversible arrest.

    Science.gov (United States)

    Subramaniam, Sindhu; Sreenivas, Prethish; Cheedipudi, Sirisha; Reddy, Vatrapu Rami; Shashidhara, Lingadahalli Subrahmanya; Chilukoti, Ravi Kumar; Mylavarapu, Madhavi; Dhawan, Jyotsna

    2014-01-01

    Most cells in adult mammals are non-dividing: differentiated cells exit the cell cycle permanently, but stem cells exist in a state of reversible arrest called quiescence. In damaged skeletal muscle, quiescent satellite stem cells re-enter the cell cycle, proliferate and subsequently execute divergent programs to regenerate both post-mitotic myofibers and quiescent stem cells. The molecular basis for these alternative programs of arrest is poorly understood. In this study, we used an established myogenic culture model (C2C12 myoblasts) to generate cells in alternative states of arrest and investigate their global transcriptional profiles. Using cDNA microarrays, we compared G0 myoblasts with post-mitotic myotubes. Our findings define the transcriptional program of quiescent myoblasts in culture and establish that distinct gene expression profiles, especially of tumour suppressor genes and inhibitors of differentiation characterize reversible arrest, distinguishing this state from irreversibly arrested myotubes. We also reveal the existence of a tissue-specific quiescence program by comparing G0 C2C12 myoblasts to isogenic G0 fibroblasts (10T1/2). Intriguingly, in myoblasts but not fibroblasts, quiescence is associated with a signature of Wnt pathway genes. We provide evidence that different levels of signaling via the canonical Wnt pathway characterize distinct cellular states (proliferation vs. quiescence vs. differentiation). Moderate induction of Wnt signaling in quiescence is associated with critical properties such as clonogenic self-renewal. Exogenous Wnt treatment subverts the quiescence program and negatively affects clonogenicity. Finally, we identify two new quiescence-induced regulators of canonical Wnt signaling, Rgs2 and Dkk3, whose induction in G0 is required for clonogenic self-renewal. These results support the concept that active signal-mediated regulation of quiescence contributes to stem cell properties, and have implications for pathological

  6. Tagging like Humans: Diverse and Distinct Image Annotation

    KAUST Repository

    Wu, Baoyuan

    2018-03-31

    In this work we propose a new automatic image annotation model, dubbed {\\\\bf diverse and distinct image annotation} (D2IA). The generative model D2IA is inspired by the ensemble of human annotations, which create semantically relevant, yet distinct and diverse tags. In D2IA, we generate a relevant and distinct tag subset, in which the tags are relevant to the image contents and semantically distinct to each other, using sequential sampling from a determinantal point process (DPP) model. Multiple such tag subsets that cover diverse semantic aspects or diverse semantic levels of the image contents are generated by randomly perturbing the DPP sampling process. We leverage a generative adversarial network (GAN) model to train D2IA. Extensive experiments including quantitative and qualitative comparisons, as well as human subject studies, on two benchmark datasets demonstrate that the proposed model can produce more diverse and distinct tags than the state-of-the-arts.

  7. Creating fair lineups for suspects with distinctive features

    OpenAIRE

    Zarkadi, Theodora; Wade, Kimberley A.; Stewart, Neil

    2009-01-01

    In their descriptions, eyewitnesses often refer to a culprit's distinctive facial features. However, in a police lineup, selecting the only member with the described distinctive feature is unfair to the suspect and provides the police with little further information. For fair and informative lineups, the distinctive feature should be either replicated across foils or concealed on the target. In the present experiments, replication produced more correct identifications in target-present lineup...

  8. Development of distinction method of production area of ginsengs by using a neutron activation analysis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Youngjin; Chung, Yongsam; Sim, Chulmuu; Sun, Gwangmin; Lee, Yuna; Yoo, Sangho

    2011-01-15

    During the last 2 years of the project, we have tried to develop the technology to make a distinction of the production areas for Korean ginsengs cultivated in the various provinces in Korea and foreign countries. It will contribute to secure the health food safety for public and stability of its market. In this year, we collected ginseng samples cultivated in the northeastern province in Chinese mainland such as Liaoning province, Jilin province and Baekdu mountain within Jilin province. 10 ginseng samples were collected at each province. The elemental concentrations in the ginseng were analyzed by using a neutron activation analysis technique at the HANARO research reactor. The distinction of production area was made by using a statistical software. As a result, the Chinese Korean ginsengs were certainly differentiated from those cultivated in the famous province in Korea though there was a limitation that the number of our sample we analyzed is very small.

  9. Development of distinction method of production area of ginsengs by using a neutron activation analysis

    International Nuclear Information System (INIS)

    Kim, Youngjin; Chung, Yongsam; Sim, Chulmuu; Sun, Gwangmin; Lee, Yuna; Yoo, Sangho

    2011-01-01

    During the last 2 years of the project, we have tried to develop the technology to make a distinction of the production areas for Korean ginsengs cultivated in the various provinces in Korea and foreign countries. It will contribute to secure the health food safety for public and stability of its market. In this year, we collected ginseng samples cultivated in the northeastern province in Chinese mainland such as Liaoning province, Jilin province and Baekdu mountain within Jilin province. 10 ginseng samples were collected at each province. The elemental concentrations in the ginseng were analyzed by using a neutron activation analysis technique at the HANARO research reactor. The distinction of production area was made by using a statistical software. As a result, the Chinese Korean ginsengs were certainly differentiated from those cultivated in the famous province in Korea though there was a limitation that the number of our sample we analyzed is very small

  10. Taxonomic distinctness and richness of helminth parasite assemblages of freshwater fishes in Mexican hydrological basins.

    Science.gov (United States)

    Quiroz-Martínez, Benjamín; Salgado-Maldonado, Guillermo

    2013-01-01

    In this paper, we analyse the distributional patterns of adult helminth parasites of freshwater fishes with respect to the main hydrological basins of Mexico. We use the taxonomic distinctness and the variation in taxonomic distinctness to explore patterns of parasite diversity and how these patterns change between zoogeographical regions. We address questions about the factors that determine the variation of observed diversity of helminths between basins. We also investigate patterns of richness, taxonomic distinctness and distance decay of similarity amongst basins. Our analyses suggest that the evolution of the fauna of helminth parasites in Mexico is mostly dominated by independent host colonization events and that intra--host speciation could be a minor factor explaining the origin of this diversity. This paper points out a clear separation between the helminth faunas of northern--nearctic and southern--neotropical components in Mexican continental waters, suggesting the availability of two distinct taxonomic pools of parasites in Mexican drainage basins. Data identifies Mexican drainage basins as unities inhabited by freshwater fishes, hosting a mixture of neotropical and nearctic species, in addition, data confirms neotropical and neartic basins/helminth faunas. The neotropical basins of Mexico are host to a richest and more diversified helminth fauna, including more families, genera and species, compared to the less rich and less diverse helminth fauna in the nearctic basins. The present analysis confirms distance--decay as one of the important factors contributing to the patterns of diversity observed. The hypothesis that helminth diversity could be explained by the ichthyological diversity of the basin received no support from present analysis.

  11. Taxonomic distinctness and richness of helminth parasite assemblages of freshwater fishes in Mexican hydrological basins.

    Directory of Open Access Journals (Sweden)

    Benjamín Quiroz-Martínez

    Full Text Available In this paper, we analyse the distributional patterns of adult helminth parasites of freshwater fishes with respect to the main hydrological basins of Mexico. We use the taxonomic distinctness and the variation in taxonomic distinctness to explore patterns of parasite diversity and how these patterns change between zoogeographical regions. We address questions about the factors that determine the variation of observed diversity of helminths between basins. We also investigate patterns of richness, taxonomic distinctness and distance decay of similarity amongst basins. Our analyses suggest that the evolution of the fauna of helminth parasites in Mexico is mostly dominated by independent host colonization events and that intra--host speciation could be a minor factor explaining the origin of this diversity. This paper points out a clear separation between the helminth faunas of northern--nearctic and southern--neotropical components in Mexican continental waters, suggesting the availability of two distinct taxonomic pools of parasites in Mexican drainage basins. Data identifies Mexican drainage basins as unities inhabited by freshwater fishes, hosting a mixture of neotropical and nearctic species, in addition, data confirms neotropical and neartic basins/helminth faunas. The neotropical basins of Mexico are host to a richest and more diversified helminth fauna, including more families, genera and species, compared to the less rich and less diverse helminth fauna in the nearctic basins. The present analysis confirms distance--decay as one of the important factors contributing to the patterns of diversity observed. The hypothesis that helminth diversity could be explained by the ichthyological diversity of the basin received no support from present analysis.

  12. Defining poverty as distinctively human

    Directory of Open Access Journals (Sweden)

    H.P.P. Lötter

    2007-05-01

    Full Text Available While it is relatively easy for most people to identify human beings suffering from poverty, it is rather more difficult to come to a proper understanding of poverty. In this article the author wants to deepen our understanding of poverty by interpreting the conventional definitions of poverty in a new light. The article starts with a defence of a claim that poverty is a concept uniquely applicable to humans. It then present a critical discussion of the distinction between absolute and relative poverty and it is then argued that a revision of this distinction can provide general standards applicable to humans everywhere.

  13. Assessment of Cultivar Distinctness in Alfalfa: A Comparison of Genotyping-by-Sequencing, Simple-Sequence Repeat Marker, and Morphophysiological Observations

    Directory of Open Access Journals (Sweden)

    Paolo Annicchiarico

    2016-07-01

    Full Text Available Cultivar registration agencies typically require morphophysiological trait-based distinctness of candidate cultivars. This requirement is difficult to achieve for cultivars of major perennial forages because of their genetic structure and ever-increasing number of registered material, leading to possible rejection of agronomically valuable cultivars. This study aimed to explore the value of molecular markers applied to replicated bulked plants (three bulks of 100 independent plants each per cultivar to assess alfalfa ( L. subsp. cultivar distinctness. We compared genotyping-by-sequencing information based on 2902 polymorphic single-nucleotide polymorphism (SNP markers (>30 reads per DNA sample with morphophysiological information based on 11 traits and with simple-sequence repeat (SSR marker information from 41 polymorphic markers for their ability to distinguish 11 alfalfa landraces representative of the germplasm from northern Italy. Three molecular criteria, one based on cultivar differences for individual SSR bands and two based on overall SNP marker variation assessed either by statistically significant cultivar differences on principal component axes or discriminant analysis, distinctly outperformed the morphophysiological criterion. Combining the morphophysiological criterion with either molecular marker method increased discrimination among cultivars, since morphophysiological diversity was unrelated to SSR marker-based diversity ( = 0.04 and poorly related to SNP marker-based diversity ( = 0.23, < 0.15. The criterion based on statistically significant SNP allele frequency differences was less discriminating than morphophysiological variation. Marker-based distinctness, which can be assessed at low cost and without interactions with testing conditions, could validly substitute for (or complement morphophysiological distinctness in alfalfa cultivar registration schemes. It also has interest in sui generis registration systems aimed at

  14. Cognitive, cultural, and linguistic sources of a handshape distinction expressing agentivity.

    Science.gov (United States)

    Brentari, Diane; Di Renzo, Alessio; Keane, Jonathan; Volterra, Virginia

    2015-01-01

    In this paper the cognitive, cultural, and linguistic bases for a pattern of conventionalization of two types of iconic handshapes are described. Work on sign languages has shown that handling handshapes (H-HSs: those that represent how objects are handled or manipulated) and object handshapes (O-HSs: those that represent the class, size, or shape of objects) express an agentive/non-agentive semantic distinction in many sign languages. H-HSs are used in agentive event descriptions and O-HSs are used in non-agentive event descriptions. In this work, American Sign Language (ASL) and Italian Sign Language (LIS) productions are compared (adults and children) as well as the corresponding groups of gesturers in each country using "silent gesture." While the gesture groups, in general, did not employ an H-HS/O-HS distinction, all participants (signers and gesturers) used iconic handshapes (H-HSs and O-HSs together) more often in agentive than in no-agent event descriptions; moreover, none of the subjects produced an opposite pattern than the expected one (i.e., H-HSs associated with no-agent descriptions and O-HSs associated with agentive ones). These effects are argued to be grounded in cognition. In addition, some individual gesturers were observed to produce the H-HS/O-HS opposition for agentive and non-agentive event descriptions-that is, more Italian than American adult gesturers. This effect is argued to be grounded in culture. Finally, the agentive/non-agentive handshape opposition is confirmed for signers of ASL and LIS, but previously unreported cross-linguistic differences were also found across both adult and child sign groups. It is, therefore, concluded that cognitive, cultural, and linguistic factors contribute to the conventionalization of this distinction of handshape type. Copyright © 2014 Cognitive Science Society, Inc.

  15. Requirement of argininosuccinate lyase for systemic nitric oxide production.

    Science.gov (United States)

    Erez, Ayelet; Nagamani, Sandesh C S; Shchelochkov, Oleg A; Premkumar, Muralidhar H; Campeau, Philippe M; Chen, Yuqing; Garg, Harsha K; Li, Li; Mian, Asad; Bertin, Terry K; Black, Jennifer O; Zeng, Heng; Tang, Yaoping; Reddy, Anilkumar K; Summar, Marshall; O'Brien, William E; Harrison, David G; Mitch, William E; Marini, Juan C; Aschner, Judy L; Bryan, Nathan S; Lee, Brendan

    2011-11-13

    Nitric oxide (NO) is crucial in diverse physiological and pathological processes. We show that a hypomorphic mouse model of argininosuccinate lyase (encoded by Asl) deficiency has a distinct phenotype of multiorgan dysfunction and NO deficiency. Loss of Asl in both humans and mice leads to reduced NO synthesis, owing to both decreased endogenous arginine synthesis and an impaired ability to use extracellular arginine for NO production. Administration of nitrite, which can be converted into NO in vivo, rescued the manifestations of NO deficiency in hypomorphic Asl mice, and a nitric oxide synthase (NOS)-independent NO donor restored NO-dependent vascular reactivity in humans with ASL deficiency. Mechanistic studies showed that ASL has a structural function in addition to its catalytic activity, by which it contributes to the formation of a multiprotein complex required for NO production. Our data demonstrate a previously unappreciated role for ASL in NOS function and NO homeostasis. Hence, ASL may serve as a target for manipulating NO production in experimental models, as well as for the treatment of NO-related diseases.

  16. The Striatal Balancing Act in Drug Addiction: Distinct Roles of Direct and Indirect Pathway Medium Spiny Neurons

    Directory of Open Access Journals (Sweden)

    Mary Kay eLobo

    2011-07-01

    Full Text Available The striatum plays a key role in mediating the acute and chronic effects of addictive drugs, with drugs of abuse causing long-lasting molecular and cellular alterations in both dorsal striatum and nucleus accumbens (ventral striatum. Despite the wealth of research on the biological actions of abused drugs in striatum, until recently, the distinct roles of the striatum’s two major subtypes of medium spiny neuron (MSN in drug addiction remained elusive. Recent advances in cell-type specific technologies, including fluorescent reporter mice, transgenic or knockout mice, and viral-mediated gene transfer, have advanced the field toward a more comprehensive understanding of the two MSN subtypes in the long-term actions of drugs of abuse. Here we review progress in defining the distinct molecular and functional contributions of the two MSN subtypes in mediating addiction.

  17. Mavericks versus team players: the trade-off between shared glory and making a personal contribution.

    Science.gov (United States)

    Charlton, Bruce G

    2008-08-01

    The modern world is characterized by progressive specialization of function and ever-larger-scale coordination of these ever-more-specialized functions. More and more of science is done by increasing-sized teams of specialists, and the ability to engage in 'teamwork' is regarded as an almost essential attribute for most scientists. But teamwork does not suit all personality types. Some 'maverick' individuals would rather have personal credit for a relatively modest scientific contribution which they achieved (mostly) by themselves, than a share of credit in a much larger scientific contribution generated by a large team. The present system of medical science is organized to discourage mavericks and, on the whole, this is probably justifiable on the basis that scientists are not natural team players. Extra inducements are necessary to get people to adopt the relatively self-effacing behaviours necessary for building the large organizations of complementary specialists that are necessary for tackling many of the most intractable modern scientific problems. However, an ethos of teamwork does carry substantial disadvantages. Although most scientists are dispensable, and do not make a significant personal contribution, the very best scientists do make a difference to the rate of progress of science. And top notch scientists are wasted as team players. The very best scientists can function only as mavericks because they are doing science for vocational reasons. The highest intensity of personal commitment requires individual rewards from distinctive contributions. In conclusion, the current incentive system that encourages teamwork involves a trade-off. The majority of modestly talented scientists can probably achieve more when working as members of a team. But the very best scientists probably need to work as mavericks.

  18. Attention and Implicit Memory: Priming-Induced Benefits and Costs Have Distinct Attentional Requirements

    OpenAIRE

    Keane, Margaret M.; Cruz, Matt E.; Verfaellie, Mieke

    2015-01-01

    Attention at encoding plays a critical and ubiquitous role in explicit memory performance, but its role in implicit memory performance (i.e., priming) is more variable: Some, but not all, priming effects are reduced by division of attention at encoding. A wealth of empirical and theoretical work has aimed to define the critical features of priming effects that do or do not require attention at encoding. This work, however, has focused exclusively on priming effects that are beneficial in natu...

  19. Growth Conditions Regulate the Requirements for Caulobacter Chromosome Segregation

    DEFF Research Database (Denmark)

    Shebelut, Conrad W.; Jensen, Rasmus Bugge; Gitai, Zemer

    2009-01-01

    Growth environments are important metabolic and developmental regulators. Here we demonstrate a growth environment-dependent effect on Caulobacter chromosome segregation of a small-molecule inhibitor of the MreB bacterial actin cytoskeleton. Our results also implicate ParAB as important segregation...... determinants, suggesting that multiple distinct mechanisms can mediate Caulobacter chromosome segregation and that their relative contributions can be environmentally regulated....

  20. Human brain basis of musical rhythm perception: common and distinct neural substrates for meter, tempo, and pattern.

    Science.gov (United States)

    Thaut, Michael H; Trimarchi, Pietro Davide; Parsons, Lawrence M

    2014-06-17

    Rhythm as the time structure of music is composed of distinct temporal components such as pattern, meter, and tempo. Each feature requires different computational processes: meter involves representing repeating cycles of strong and weak beats; pattern involves representing intervals at each local time point which vary in length across segments and are linked hierarchically; and tempo requires representing frequency rates of underlying pulse structures. We explored whether distinct rhythmic elements engage different neural mechanisms by recording brain activity of adult musicians and non-musicians with positron emission tomography (PET) as they made covert same-different discriminations of (a) pairs of rhythmic, monotonic tone sequences representing changes in pattern, tempo, and meter, and (b) pairs of isochronous melodies. Common to pattern, meter, and tempo tasks were focal activities in right, or bilateral, areas of frontal, cingulate, parietal, prefrontal, temporal, and cerebellar cortices. Meter processing alone activated areas in right prefrontal and inferior frontal cortex associated with more cognitive and abstract representations. Pattern processing alone recruited right cortical areas involved in different kinds of auditory processing. Tempo processing alone engaged mechanisms subserving somatosensory and premotor information (e.g., posterior insula, postcentral gyrus). Melody produced activity different from the rhythm conditions (e.g., right anterior insula and various cerebellar areas). These exploratory findings suggest the outlines of some distinct neural components underlying the components of rhythmic structure.

  1. The Ste20 kinase misshapen regulates both photoreceptor axon targeting and dorsal closure, acting downstream of distinct signals.

    Science.gov (United States)

    Su, Y C; Maurel-Zaffran, C; Treisman, J E; Skolnik, E Y

    2000-07-01

    We have previously shown that the Ste20 kinase encoded by misshapen (msn) functions upstream of the c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase module in Drosophila. msn is required to activate the Drosophila JNK, Basket (Bsk), to promote dorsal closure of the embryo. A mammalian homolog of Msn, Nck interacting kinase, interacts with the SH3 domains of the SH2-SH3 adapter protein Nck. We now show that Msn likewise interacts with Dreadlocks (Dock), the Drosophila homolog of Nck. dock is required for the correct targeting of photoreceptor axons. We have performed a structure-function analysis of Msn in vivo in Drosophila in order to elucidate the mechanism whereby Msn regulates JNK and to determine whether msn, like dock, is required for the correct targeting of photoreceptor axons. We show that Msn requires both a functional kinase and a C-terminal regulatory domain to activate JNK in vivo in Drosophila. A mutation in a PXXP motif on Msn that prevents it from binding to the SH3 domains of Dock does not affect its ability to rescue the dorsal closure defect in msn embryos, suggesting that Dock is not an upstream regulator of msn in dorsal closure. Larvae with only this mutated form of Msn show a marked disruption in photoreceptor axon targeting, implicating an SH3 domain protein in this process; however, an activated form of Msn is not sufficient to rescue the dock mutant phenotype. Mosaic analysis reveals that msn expression is required in photoreceptors in order for their axons to project correctly. The data presented here genetically link msn to two distinct biological events, dorsal closure and photoreceptor axon pathfinding, and thus provide the first evidence that Ste20 kinases of the germinal center kinase family play a role in axonal pathfinding. The ability of Msn to interact with distinct classes of adapter molecules in dorsal closure and photoreceptor axon pathfinding may provide the flexibility that allows it to link to distinct

  2. 37 CFR 1.142 - Requirement for restriction.

    Science.gov (United States)

    2010-07-01

    ... at any time before final action. (b) Claims to the invention or inventions not elected, if not... Inventions in One Application; Restriction § 1.142 Requirement for restriction. (a) If two or more independent and distinct inventions are claimed in a single application, the examiner in an Office action will...

  3. Reservoir floodplains support distinct fish assemblages

    Science.gov (United States)

    Miranda, Leandro E.; Wigen, S. L.; Dagel, Jonah D.

    2014-01-01

    Reservoirs constructed on floodplain rivers are unique because the upper reaches of the impoundment may include extensive floodplain environments. Moreover, reservoirs that experience large periodic water level fluctuations as part of their operational objectives seasonally inundate and dewater floodplains in their upper reaches, partly mimicking natural inundations of river floodplains. In four flood control reservoirs in Mississippi, USA, we explored the dynamics of connectivity between reservoirs and adjacent floodplains and the characteristics of fish assemblages that develop in reservoir floodplains relative to those that develop in reservoir bays. Although fish species richness in floodplains and bays were similar, species composition differed. Floodplains emphasized fish species largely associated with backwater shallow environments, often resistant to harsh environmental conditions. Conversely, dominant species in bays represented mainly generalists that benefit from the continuous connectivity between the bay and the main reservoir. Floodplains in the study reservoirs provided desirable vegetated habitats at lower water level elevations, earlier in the year, and more frequently than in bays. Inundating dense vegetation in bays requires raising reservoir water levels above the levels required to reach floodplains. Therefore, aside from promoting distinct fish assemblages within reservoirs and helping promote diversity in regulated rivers, reservoir floodplains are valued because they can provide suitable vegetated habitats for fish species at elevations below the normal pool, precluding the need to annually flood upland vegetation that would inevitably be impaired by regular flooding. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

  4. Distinct signaling mechanisms in multiple developmental pathways by the SCRAMBLED receptor of Arabidopsis.

    Science.gov (United States)

    Kwak, Su-Hwan; Woo, Sooah; Lee, Myeong Min; Schiefelbein, John

    2014-10-01

    SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase in Arabidopsis (Arabidopsis thaliana), is required for positional signaling in the root epidermis and for tissue/organ development in the shoot. To further understand SCM action, we generated a series of kinase domain variants and analyzed their ability to complement scm mutant defects. We found that the SCM kinase domain, but not kinase activity, is required for its role in root epidermal patterning, supporting the view that SCM is an atypical receptor kinase. We also describe a previously uncharacterized role for SCM in fruit dehiscence, because mature siliques from scm mutants fail to open properly. Interestingly, the kinase domain of SCM appears to be dispensable for this developmental process. Furthermore, we found that most of the SCM kinase domain mutations dramatically inhibit inflorescence development. Because this process is not affected in scm null mutants, it is likely that SCM acts redundantly to regulate inflorescence size. The importance of distinct kinase residues for these three developmental processes provides an explanation for the maintenance of the conserved kinase domain in the SCM protein, and it may generally explain its conservation in other atypical kinases. Furthermore, these results indicate that individual leucine-rich repeat receptor-like kinases may participate in multiple pathways using distinct signaling mechanisms to mediate diverse cellular communication events. © 2014 American Society of Plant Biologists. All Rights Reserved.

  5. Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality

    Directory of Open Access Journals (Sweden)

    Rebecca I. Clark

    2015-09-01

    Full Text Available Alterations in the composition of the intestinal microbiota have been correlated with aging and measures of frailty in the elderly. However, the relationships between microbial dynamics, age-related changes in intestinal physiology, and organismal health remain poorly understood. Here, we show that dysbiosis of the intestinal microbiota, characterized by an expansion of the Gammaproteobacteria, is tightly linked to age-onset intestinal barrier dysfunction in Drosophila. Indeed, alterations in the microbiota precede and predict the onset of intestinal barrier dysfunction in aged flies. Changes in microbial composition occurring prior to intestinal barrier dysfunction contribute to changes in excretory function and immune gene activation in the aging intestine. In addition, we show that a distinct shift in microbiota composition follows intestinal barrier dysfunction, leading to systemic immune activation and organismal death. Our results indicate that alterations in microbiota dynamics could contribute to and also predict varying rates of health decline during aging in mammals.

  6. Self-other integration and distinction in schizophrenia: A theoretical analysis and a review of the evidence.

    Science.gov (United States)

    van der Weiden, Anouk; Prikken, Merel; van Haren, Neeltje E M

    2015-10-01

    Difficulties in self-other processing lie at the core of schizophrenia and pose a problem for patients' daily social functioning. In the present selective review, we provide a framework for understanding self-other integration and distinction, and impairments herein in schizophrenia. For this purpose, we discuss classic motor prediction models in relation to mirror neuron functioning, theory of mind, mimicry, self-awareness, and self-agency phenomena. Importantly, we also discuss the role of more recent cognitive expectation models in these phenomena, and argue that these cognitive models form an essential contribution to our understanding of self-other integration and distinction. In doing so, we bring together different lines of research and connect findings from social psychology, affective neuropsychology, and psychiatry to further our understanding of when and how people integrate versus distinguish self and other, and how this goes wrong in schizophrenia patients. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  7. Many-Objective Distinct Candidates Optimization using Differential Evolution

    DEFF Research Database (Denmark)

    Justesen, Peter; Ursem, Rasmus Kjær

    2010-01-01

    for each objective. The Many-Objective Distinct Candidates Optimization using Differential Evolution (MODCODE) algorithm takes a novel approach by focusing search using a user-defined number of subpopulations each returning a distinct optimal solution within the preferred region of interest. In this paper......, we present the novel MODCODE algorithm incorporating the ROD measure to measure and control candidate distinctiveness. MODCODE is tested against GDE3 on three real world centrifugal pump design problems supplied by Grundfos. Our algorithm outperforms GDE3 on all problems with respect to all...

  8. Metal transport across biomembranes: emerging models for a distinct chemistry.

    Science.gov (United States)

    Argüello, José M; Raimunda, Daniel; González-Guerrero, Manuel

    2012-04-20

    Transition metals are essential components of important biomolecules, and their homeostasis is central to many life processes. Transmembrane transporters are key elements controlling the distribution of metals in various compartments. However, due to their chemical properties, transition elements require transporters with different structural-functional characteristics from those of alkali and alkali earth ions. Emerging structural information and functional studies have revealed distinctive features of metal transport. Among these are the relevance of multifaceted events involving metal transfer among participating proteins, the importance of coordination geometry at transmembrane transport sites, and the presence of the largely irreversible steps associated with vectorial transport. Here, we discuss how these characteristics shape novel transition metal ion transport models.

  9. Data Crosscutting Requirements Review

    Energy Technology Data Exchange (ETDEWEB)

    Kleese van Dam, Kerstin [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Shoshani, Arie [Pacific Northwest National Lab. (PNNL), Richland, WA (United States); Plata, Charity [Pacific Northwest National Lab. (PNNL), Richland, WA (United States)

    2013-04-01

    In April 2013, a diverse group of researchers from the U.S. Department of Energy (DOE) scientific community assembled to assess data requirements associated with DOE-sponsored scientific facilities and large-scale experiments. Participants in the review included facilities staff, program managers, and scientific experts from the offices of Basic Energy Sciences, Biological and Environmental Research, High Energy Physics, and Advanced Scientific Computing Research. As part of the meeting, review participants discussed key issues associated with three distinct aspects of the data challenge: 1) processing, 2) management, and 3) analysis. These discussions identified commonalities and differences among the needs of varied scientific communities. They also helped to articulate gaps between current approaches and future needs, as well as the research advances that will be required to close these gaps. Moreover, the review provided a rare opportunity for experts from across the Office of Science to learn about their collective expertise, challenges, and opportunities. The "Data Crosscutting Requirements Review" generated specific findings and recommendations for addressing large-scale data crosscutting requirements.

  10. Distinct Effects of Estrogen on Mouse Maternal Behavior: The Contribution of Estrogen Synthesis in the Brain

    Science.gov (United States)

    Murakami, Gen

    2016-01-01

    Estrogen surge following progesterone withdrawal at parturition plays an important role in initiating maternal behavior in various rodent species. Systemic estrogen treatment shortens the latency to onset of maternal behavior in nulliparous female rats that have not experienced parturition. In contrast, nulliparous laboratory mice show rapid onset of maternal behavior without estrogen treatment, and the role of estrogen still remains unclear. Here the effect of systemic estrogen treatment (for 2 h, 1 day, 3 days, and 7 days) after progesterone withdrawal was examined on maternal behavior of C57BL/6 mice. This estrogen regimen led to different effects on nursing, pup retrieval, and nest building behaviors. Latency to nursing was shortened by estrogen treatment within 2 h. Moreover, pup retrieval and nest building were decreased. mRNA expression was also investigated for estrogen receptor α (ERα) and for genes involved in regulating maternal behavior, specifically, the oxytocin receptor (OTR) and vasopressin receptor in the medial amygdala (MeA) and medial preoptic area (MPOA). Estrogen treatment led to decreased ERα mRNA in both regions. Although OTR mRNA was increased in the MeA, OTR and vasopressin receptor mRNA were reduced in the MPOA, showing region-dependent transcription regulation. To determine the mechanisms for the actions of estrogen treatment, the contribution of estrogen synthesis in the brain was examined. Blockade of estrogen synthesis in the brain by systemic letrozole treatment in ovariectomized mice interfered with pup retrieval and nest building but not nursing behavior, indicating different contributions of estrogen synthesis to maternal behavior. Furthermore, letrozole treatment led to an increase in ERα mRNA in the MeA but not in the MPOA, suggesting that involvement of estrogen synthesis is brain region dependent. Altogether, these results suggest that region-dependent estrogen synthesis leads to differential transcriptional activation due

  11. Mutations within Four Distinct Gag Proteins Are Required To Restore Replication of Human Immunodeficiency Virus Type 1 after Deletion Mutagenesis within the Dimerization Initiation Site

    Science.gov (United States)

    Liang, Chen; Rong, Liwei; Quan, Yudong; Laughrea, Michael; Kleiman, Lawrence; Wainberg, Mark A.

    1999-01-01

    Human immunodeficiency virus type 1 (HIV-1) genomic RNA segments at nucleotide (nt) positions +240 to +274 are thought to form a stem-loop secondary structure, termed SL1, that serves as a dimerization initiation site for viral genomic RNA. We have generated two distinct deletion mutations within this region, termed BH10-LD3 and BH10-LD4, involving nt positions +238 to +253 and +261 to +274, respectively, and have shown that each of these resulted in significant diminutions in levels of viral infectiousness. However, long-term culture of each of these viruses in MT-2 cells resulted in a restoration of infectiousness, due to a series of compensatory point mutations within four distinct proteins that are normally cleaved from the Gag precursor. In the case of BH10-LD3, these four mutations were MA1, CA1, MP2, and MNC, and they involved changes of amino acid Val-35 to Ile within the matrix protein (MA), Ile-91 to Thr within the capsid (CA), Thr-12 to Ile within p2, and Thr-24 to Ile within the nucleocapsid (NC). The order in which these mutations were acquired by the mutated BH10-LD3 was MNC > CA1 > MP2 > MA1. The results of site-directed mutagenesis studies confirmed that each of these four substitutions contributed to the increased viability of the mutated BH10-LD3 viruses and that the MNC substitution, which was acquired first, played the most important role in this regard. Three point mutations, MP2, MNC, and MA2, were also shown to be sequentially acquired by viruses that had emerged in culture from the BH10-LD4 deletion. The first two of these were identical to those described above, while the last involved a change of Val-35 to Leu. All three of these substitutions were necessary to restore the infectiousness of mutated BH10-LD4 viruses to wild-type levels, although the MP2 mutation alone, but neither of the other two substitutions, was able to confer some viability on BH10-LD4 viruses. Studies of viral RNA packaging showed that the BH10-LD4 deletion only

  12. Creating fair lineups for suspects with distinctive features.

    Science.gov (United States)

    Zarkadi, Theodora; Wade, Kimberley A; Stewart, Neil

    2009-12-01

    In their descriptions, eyewitnesses often refer to a culprit's distinctive facial features. However, in a police lineup, selecting the only member with the described distinctive feature is unfair to the suspect and provides the police with little further information. For fair and informative lineups, the distinctive feature should be either replicated across foils or concealed on the target. In the present experiments, replication produced more correct identifications in target-present lineups--without increasing the incorrect identification of foils in target-absent lineups--than did concealment. This pattern, and only this pattern, is predicted by the hybrid-similarity model of recognition.

  13. Common and distinct genetic properties of ESCRT-II components in Drosophila.

    Directory of Open Access Journals (Sweden)

    Hans-Martin Herz

    Full Text Available BACKGROUND: Genetic studies in yeast have identified class E vps genes that form the ESCRT complexes required for protein sorting at the early endosome. In Drosophila, mutations of the ESCRT-II component vps25 cause endosomal defects leading to accumulation of Notch protein and increased Notch pathway activity. These endosomal and signaling defects are thought to account for several phenotypes. Depending on the developmental context, two different types of overgrowth can be detected. Tissue predominantly mutant for vps25 displays neoplastic tumor characteristics. In contrast, vps25 mutant clones in a wild-type background trigger hyperplastic overgrowth in a non-autonomous manner. In addition, vps25 mutant clones also promote apoptotic resistance in a non-autonomous manner. PRINCIPAL FINDINGS: Here, we genetically characterize the remaining ESCRT-II components vps22 and vps36. Like vps25, mutants of vps22 and vps36 display endosomal defects, accumulate Notch protein and--when the tissue is predominantly mutant--show neoplastic tumor characteristics. However, despite these common phenotypes, they have distinct non-autonomous phenotypes. While vps22 mutations cause strong non-autonomous overgrowth, they do not affect apoptotic resistance. In contrast, vps36 mutations increase apoptotic resistance, but have little effect on non-autonomous proliferation. Further characterization reveals that although all ESCRT-II mutants accumulate Notch protein, only vps22 and vps25 mutations trigger Notch activity. CONCLUSIONS/SIGNIFICANCE: The ESCRT-II components vps22, vps25 and vps36 display common and distinct genetic properties. Our data redefine the role of Notch for hyperplastic and neoplastic overgrowth in these mutants. While Notch is required for hyperplastic growth, it appears to be dispensable for neoplastic transformation.

  14. Distinct prion-like strains of amyloid beta implicated in phenotypic diversity of Alzheimer's disease.

    Science.gov (United States)

    Cohen, Mark; Appleby, Brian; Safar, Jiri G

    2016-01-01

    Vast evidence on human prions demonstrates that variable disease phenotypes, rates of propagation, and targeting of distinct brain structures are determined by unique conformers (strains) of pathogenic prion protein (PrP(Sc)). Recent progress in the development of advanced biophysical tools that inventory structural characteristics of amyloid beta (Aβ) in the brain cortex of phenotypically diverse Alzheimer's disease (AD) patients, revealed unique spectrum of oligomeric particles in the cortex of rapidly progressive cases, implicating these structures in variable rates of propagation in the brain, and in distict disease manifestation. Since only ∼30% of phenotypic diversity of AD can be explained by polymorphisms in risk genes, these and transgenic bioassay data argue that structurally distinct Aβ particles play a major role in the diverse pathogenesis of AD, and may behave as distinct prion-like strains encoding diverse phenotypes. From these observations and our growing understanding of prions, there is a critical need for new strain-specific diagnostic strategies for misfolded proteins causing these elusive disorders. Since targeted drug therapy can induce mutation and evolution of prions into new strains, effective treatments of AD will require drugs that enhance clearance of pathogenic conformers, reduce the precursor protein, or inhibit the conversion of precursors into prion-like states.

  15. Precision of Discrete and Rhythmic Forelimb Movements Requires a Distinct Neuronal Subpopulation in the Interposed Anterior Nucleus

    Directory of Open Access Journals (Sweden)

    Aloysius Y.T. Low

    2018-02-01

    Full Text Available The deep cerebellar nuclei (DCN represent output channels of the cerebellum, and they transmit integrated sensorimotor signals to modulate limb movements. But the functional relevance of identifiable neuronal subpopulations within the DCN remains unclear. Here, we examine a genetically tractable population of neurons in the mouse interposed anterior nucleus (IntA. We show that these neurons represent a subset of glutamatergic neurons in the IntA and constitute a specific element of an internal feedback circuit within the cerebellar cortex and cerebello-thalamo-cortical pathway associated with limb control. Ablation and optogenetic stimulation of these neurons disrupt efficacy of skilled reach and locomotor movement and reveal that they control positioning and timing of the forelimb and hindlimb. Together, our findings uncover the function of a distinct neuronal subpopulation in the deep cerebellum and delineate the anatomical substrates and kinematic parameters through which it modulates precision of discrete and rhythmic limb movements.

  16. Precision of Discrete and Rhythmic Forelimb Movements Requires a Distinct Neuronal Subpopulation in the Interposed Anterior Nucleus.

    Science.gov (United States)

    Low, Aloysius Y T; Thanawalla, Ayesha R; Yip, Alaric K K; Kim, Jinsook; Wong, Kelly L L; Tantra, Martesa; Augustine, George J; Chen, Albert I

    2018-02-27

    The deep cerebellar nuclei (DCN) represent output channels of the cerebellum, and they transmit integrated sensorimotor signals to modulate limb movements. But the functional relevance of identifiable neuronal subpopulations within the DCN remains unclear. Here, we examine a genetically tractable population of neurons in the mouse interposed anterior nucleus (IntA). We show that these neurons represent a subset of glutamatergic neurons in the IntA and constitute a specific element of an internal feedback circuit within the cerebellar cortex and cerebello-thalamo-cortical pathway associated with limb control. Ablation and optogenetic stimulation of these neurons disrupt efficacy of skilled reach and locomotor movement and reveal that they control positioning and timing of the forelimb and hindlimb. Together, our findings uncover the function of a distinct neuronal subpopulation in the deep cerebellum and delineate the anatomical substrates and kinematic parameters through which it modulates precision of discrete and rhythmic limb movements. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  17. Amnesia, rehearsal, and temporal distinctiveness models of recall.

    Science.gov (United States)

    Brown, Gordon D A; Della Sala, Sergio; Foster, Jonathan K; Vousden, Janet I

    2007-04-01

    Classical amnesia involves selective memory impairment for temporally distant items in free recall (impaired primacy) together with relative preservation of memory for recency items. This abnormal serial position curve is traditionally taken as evidence for a distinction between different memory processes, with amnesia being associated with selectively impaired long-term memory. However recent accounts of normal serial position curves have emphasized the importance of rehearsal processes in giving rise to primacy effects and have suggested that a single temporal distinctiveness mechanism can account for both primacy and recency effects when rehearsal is considered. Here we explore the pattern of strategic rehearsal in a patient with very severe amnesia. When the patient's rehearsal pattern is taken into account, a temporal distinctiveness model can account for the serial position curve in both amnesic and control free recall. The results are taken as consistent with temporal distinctiveness models of free recall, and they motivate an emphasis on rehearsal patterns in understanding amnesic deficits in free recall.

  18. Cognitive Effort Requirements in Recall, Recognition, and Lexical Decision

    Science.gov (United States)

    1985-05-01

    that the amount of integrative processing required for an item is a function of its preexisting or baseline familiarity level . Low frequency words... Lockhart , Craik , & Jacoby, 1976). In the present study, increased effort, and possibly increased distinctiveness, does not influence hit rates, which are...ing of items. Second, a lexical decision task, which does not require elabo- rative processing , leads to an overall poor level of recall. Furthermore

  19. Effects of monitoring for visual events on distinct components of attention

    Directory of Open Access Journals (Sweden)

    Christian H. Poth

    2014-08-01

    Full Text Available Monitoring the environment for visual events while performing a concurrent task requires adjustment of visual processing priorities. By use of Bundesen's (1990 Theory of Visual Attention (TVA, we investigated how monitoring for an object-based brief event affected distinct components of visual attention in a concurrent task. The perceptual salience of the event was varied. Monitoring reduced the processing speed in the concurrent task, and the reduction was stronger when the event was less salient. The monitoring task neither affected the temporal threshold of conscious perception nor the storage capacity of visual short-term memory nor the efficiency of top-down controlled attentional selection.

  20. Distinct accessory cell requirements define two types of rat T cell hybridomas specific for unique determinants in the encephalitogenic 68-86 region of myelin basic protein

    International Nuclear Information System (INIS)

    Mannie, M.D.; Paterson, P.Y.; Thomas, D.W.; Nairn, R.

    1990-01-01

    Six clonotypically unique T cell hybridomas from Lewis rats were used to study accessory cell activities required for class II MHC restricted T cell responses to the 68-86 encephalitogenic sequence of myelin basic protein (MBP). T cell hybrids which were cultured with GP68-86 68-86 sequence of guinea pig MBP (GPMBP) and naive splenocytes (SPL) were induced to produce IL-2 as measured by the CTLL indicator cell line. The hybrids were categorized into two subsets (designated THYB-1 and THYB-2), because two distinct subset-specific pathways of communication between accessory cells and T cells were involved in GPMBP-induced IL-2 production. These pathways were distinguished by the following six observations. First, when the duration of a pulse of SPL with GPMBP was lengthened from 1 to 4 h, these SPL lost their ability to induce IL-2 production by THYB-2 hybrids yet nevertheless retained full stimulatory activity for THYB-1 hybrids. Second, paraformaldehyde fixation of GPMBP-pulsed SPL abrogated an activity necessary for Ag-induced IL-2 production by THYB-2 hybrids. These fixed SPL were nevertheless able to stimulate THYB-1 hybrids, albeit to a lesser extent than viable unfixed SPL. Third, the addition of either cycloheximide, cytochalasin B, or 2-deoxyglucose to an Ag pulse of SPL with GPMBP dramatically inhibited the subsequent responses of THYB-2 hybrids yet had little or no effect upon the reactivity of THYB-1 hybrids. Fourth, thymocytes lacked necessary activities for GPMBP evoked IL-2 production by THYB-2 hybrids yet strongly promoted THYB-1 hybrid responses. Fifth, exposure of SPL to as little as 500 rad of gamma-irradiation markedly attenuated THYB-2 hybrid response to GPMBP but did not affect THYB-1 responses. Sixth, anti-GPMBP responses by THYB-2 hybrids were observed only in the presence of both radioresistant adherent SPL and a distinct population of radiosensitive nonadherent SPL

  1. Blending of heritable recognition cues among ant nestmates creates distinct colony gestalt odours but prevents within-colony nepotism

    DEFF Research Database (Denmark)

    van Zweden, Jelle Stijn; Brask, Josefine B.; Christensen, Jan H.

    2010-01-01

    members to create a Gestalt odour. Although earlier studies have established that hydrocarbon profiles are influenced by heritable factors, transfer among nestmates and additional environmental factors, no studies have quantified these relative contributions for separate compounds. Here, we use the ant...... discrimination or as nestmate recognition cues. These results indicate that heritable compounds are suitable for establishing a genetic Gestalt for efficient nestmate recognition, but that recognition cues within colonies are insufficiently distinct to allow nepotistic kin discrimination....

  2. Regional transport of a chemically distinctive dust: Gypsum from White Sands, New Mexico (USA)

    Science.gov (United States)

    White, Warren H.; Hyslop, Nicole P.; Trzepla, Krystyna; Yatkin, Sinan; Rarig, Randy S.; Gill, Thomas E.; Jin, Lixin

    2015-03-01

    The White Sands complex, a National Monument and adjoining Missile Range in southern New Mexico, occupies the dry bed of an ice-age lake where an active gypsum dunefield abuts erodible playa sediments. Aerosols entrained from White Sands are sometimes visible on satellite images as distinct, light-colored plumes crossing the Sacramento Mountains to the east and northeast. The IMPROVE network (Interagency Monitoring of PROtected Visual Environments) operates long-term aerosol samplers at two sites east of the Sacramento range. In recent years a spring pulse of sulfate aerosol has appeared at these sites, eclipsing the regional summer peak resulting from atmospheric reactions of sulfur dioxide emissions. A significant fraction of this spring sulfate is contributed by gypsum and other salts from White Sands, with much of the sulfur in coarse particles and concentrations of calcium and strontium above regional levels. The increase in these gypsiferous species coincides with a drought following a period of above-average precipitation. White Sands and the IMPROVE samplers together provide a natural laboratory: a climatically sensitive dust source that is both well characterized and chemically distinct from its surroundings, with a signature that remains identifiable at long-term observatories 100-200 km downwind.

  3. MR contribution in surgery of epilepsy

    International Nuclear Information System (INIS)

    Meiners, L.C.; Valk, J.; Jansen, G.H.; Veelen, C.W.M. van

    1999-01-01

    The contribution of MR imaging in patients with drug-resistant epilepsy considered for surgical therapy is discussed. In this review we focus on: (a) focal abnormalities (mesial temporal sclerosis, focal migration disorders, hamartomatous lesions and low-grade tumours, phakomatosis and vascular malformations) associated with therapy-resistant partial epilepsy, requiring resective surgery; (b) abnormalities leading to generalized seizures that require more drastic surgical procedures, such as callosotomy and functional hemispherectomy; and (c) localisation of implanted depth-electrodes. (orig.)

  4. Distinct Contributions of Median Raphe Nucleus to Contextual Fear Conditioning and Fear-Potentiated Startle

    Science.gov (United States)

    Silva, R. C. B.; Cruz, A. P. M.; Avanzi, V.; Landeira-Fernandez, J.; Brandão, M. L.

    2002-01-01

    reduced the amount of freezing and the fear-potentiated startle. Freezing is a prominent response of contextual fear conditioning, but does not seem to be crucial for the enhancement of the startle reflex by explicit aversive cues. As fear-potentiated startle may be produced in posttraining lesioned rats that are unable to freeze to fear contextual stimuli, dissociable systems seem to be recruited in each condition. Thus, contextual fear and fear-potentiated startle are conveyed by distinct 5-HT-mediated circuits of the MRN. PMID:12959153

  5. The nursing contribution to chronic disease management: a discussion paper.

    Science.gov (United States)

    Forbes, Angus; While, Alison

    2009-01-01

    This paper explores the nature of the nursing contribution to chronic disease management (CDM) and identifies a number of key nursing activities within CDM both at the individual patient and care system levels. The activities were identified following a detailed review of the literature (160 reports and studies of nursing practice) relating to three tracer disorders: diabetes, chronic obstructive pulmonary disease and multiple sclerosis. The paper examines these activities collectively to generate models expressing some of the core functions of nursing within CDM. The paper illustrates some of the changing characteristics of nursing roles within CDM. More fundamentally, the paper questions the position of nursing in relation to the technologies that define CDM systems and proposes four levels of contribution: the nurse as technology; the nurse as technologist; the nurse as system engineer; and the nurse as architect. These different levels reflect distinctions in the nature of the nursing gaze and power relations within the health care workforce. The paper also highlights how nurses are failing to develop the evidence for their practice in CDM. The paper concludes that there is a need for some clear principles to guide clinical practice and encourage innovation in CDM. It is argued that the principles should not be rule-bound but define a distinctive nursing gaze that will position the nursing profession within the health care system and in relation to other professions. The gaze should incorporate the needs of the individual patient and the care system that they inhabit.

  6. Distinct eye movement patterns enhance dynamic visual acuity

    Science.gov (United States)

    Palidis, Dimitrios J.; Wyder-Hodge, Pearson A.; Fooken, Jolande; Spering, Miriam

    2017-01-01

    Dynamic visual acuity (DVA) is the ability to resolve fine spatial detail in dynamic objects during head fixation, or in static objects during head or body rotation. This ability is important for many activities such as ball sports, and a close relation has been shown between DVA and sports expertise. DVA tasks involve eye movements, yet, it is unclear which aspects of eye movements contribute to successful performance. Here we examined the relation between DVA and the kinematics of smooth pursuit and saccadic eye movements in a cohort of 23 varsity baseball players. In a computerized dynamic-object DVA test, observers reported the location of the gap in a small Landolt-C ring moving at various speeds while eye movements were recorded. Smooth pursuit kinematics—eye latency, acceleration, velocity gain, position error—and the direction and amplitude of saccadic eye movements were linked to perceptual performance. Results reveal that distinct eye movement patterns—minimizing eye position error, tracking smoothly, and inhibiting reverse saccades—were related to dynamic visual acuity. The close link between eye movement quality and DVA performance has important implications for the development of perceptual training programs to improve DVA. PMID:28187157

  7. Distinct Reward Properties are Encoded via Corticostriatal Interactions.

    Science.gov (United States)

    Smith, David V; Rigney, Anastasia E; Delgado, Mauricio R

    2016-02-02

    The striatum serves as a critical brain region for reward processing. Yet, understanding the link between striatum and reward presents a challenge because rewards are composed of multiple properties. Notably, affective properties modulate emotion while informative properties help obtain future rewards. We approached this problem by emphasizing affective and informative reward properties within two independent guessing games. We found that both reward properties evoked activation within the nucleus accumbens, a subregion of the striatum. Striatal responses to informative, but not affective, reward properties predicted subsequent utilization of information for obtaining monetary reward. We hypothesized that activation of the striatum may be necessary but not sufficient to encode distinct reward properties. To investigate this possibility, we examined whether affective and informative reward properties were differentially encoded in corticostriatal interactions. Strikingly, we found that the striatum exhibited dissociable connectivity patterns with the ventrolateral prefrontal cortex, with increasing connectivity for affective reward properties and decreasing connectivity for informative reward properties. Our results demonstrate that affective and informative reward properties are encoded via corticostriatal interactions. These findings highlight how corticostriatal systems contribute to reward processing, potentially advancing models linking striatal activation to behavior.

  8. Distinct eye movement patterns enhance dynamic visual acuity.

    Science.gov (United States)

    Palidis, Dimitrios J; Wyder-Hodge, Pearson A; Fooken, Jolande; Spering, Miriam

    2017-01-01

    Dynamic visual acuity (DVA) is the ability to resolve fine spatial detail in dynamic objects during head fixation, or in static objects during head or body rotation. This ability is important for many activities such as ball sports, and a close relation has been shown between DVA and sports expertise. DVA tasks involve eye movements, yet, it is unclear which aspects of eye movements contribute to successful performance. Here we examined the relation between DVA and the kinematics of smooth pursuit and saccadic eye movements in a cohort of 23 varsity baseball players. In a computerized dynamic-object DVA test, observers reported the location of the gap in a small Landolt-C ring moving at various speeds while eye movements were recorded. Smooth pursuit kinematics-eye latency, acceleration, velocity gain, position error-and the direction and amplitude of saccadic eye movements were linked to perceptual performance. Results reveal that distinct eye movement patterns-minimizing eye position error, tracking smoothly, and inhibiting reverse saccades-were related to dynamic visual acuity. The close link between eye movement quality and DVA performance has important implications for the development of perceptual training programs to improve DVA.

  9. Differential Influence of Distinct Components of Increased Blood Pressure on Cardiovascular OutcomesR3

    Science.gov (United States)

    Cheng, Susan; Gupta, Deepak K.; Claggett, Brian; Sharrett, A. Richey; Shah, Amil M.; Skali, Hicham; Takeuchi, Madoka; Ni, Hanyu; Solomon, Scott D.

    2013-01-01

    Elevation in blood pressure (BP) increases risk for all cardiovascular events. Nevertheless, the extent to which different indices of BP elevation may be associated to varying degrees with different cardiovascular outcomes remains unclear. We studied 13,340 participants (aged 54±6 years, 56% women, 27% black) of the Atherosclerosis Risk in Communities Study who were free of baseline cardiovascular disease. We used Cox proportional hazards models to compare the relative contributions of systolic (SBP), diastolic (DBP), pulse pressure (PP), and mean arterial pressure (MAP) to risk for coronary heart disease (CHD), heart failure (HF), stroke, and all-cause mortality. For each multivariable-adjusted model, the largest area under the receiver-operating curve (AUC) and smallest -2 log likelihood values were used to identify BP measures with the greatest contribution to risk prediction for each outcome. A total of 2095 CHD events, 1669 HF events, 771 stroke events, and 3016 deaths occurred during up to 18±5 years of follow up. In multivariable analyses adjusting for traditional cardiovascular risk factors, the BP measures with the greatest risk contributions were: SBP for CHD (AUC=0.74); PP for HF (AUC=0.79), SBP for stroke (AUC=0.74), and PP for all-cause mortality (AUC=0.74). With few exceptions, results were similar in analyses stratified by age, sex, and race. Our data indicate that distinct BP components contribute variably to risk for different cardiovascular outcomes. PMID:23876475

  10. Functional requirements of AID's higher order structures and their interaction with RNA-binding proteins.

    Science.gov (United States)

    Mondal, Samiran; Begum, Nasim A; Hu, Wenjun; Honjo, Tasuku

    2016-03-15

    Activation-induced cytidine deaminase (AID) is essential for the somatic hypermutation (SHM) and class-switch recombination (CSR) of Ig genes. Although both the N and C termini of AID have unique functions in DNA cleavage and recombination, respectively, during SHM and CSR, their molecular mechanisms are poorly understood. Using a bimolecular fluorescence complementation (BiFC) assay combined with glycerol gradient fractionation, we revealed that the AID C terminus is required for a stable dimer formation. Furthermore, AID monomers and dimers form complexes with distinct heterogeneous nuclear ribonucleoproteins (hnRNPs). AID monomers associate with DNA cleavage cofactor hnRNP K whereas AID dimers associate with recombination cofactors hnRNP L, hnRNP U, and Serpine mRNA-binding protein 1. All of these AID/ribonucleoprotein associations are RNA-dependent. We propose that AID's structure-specific cofactor complex formations differentially contribute to its DNA-cleavage and recombination functions.

  11. Dissociable contributions of MRI volume reductions of superior temporal and fusiform gyri to symptoms and neuropsychology in schizophrenia.

    Science.gov (United States)

    Nestor, Paul G; Onitsuka, Toshiaki; Gurrera, Ronald J; Niznikiewicz, Margaret; Frumin, Melissa; Shenton, Martha E; McCarley, Robert W

    2007-03-01

    We sought to identify the functional correlates of reduced magnetic resonance imaging (MRI) volumes of the superior temporal gyrus (STG) and the fusiform gyrus (FG) in patients with chronic schizophrenia. MRI volumes, positive/negative symptoms, and neuropsychological tests of facial memory and executive functioning were examined within the same subjects. The results indicated two distinct, dissociable brain structure-function relationships: (1) reduced left STG volume-positive symptoms-executive deficits; (2) reduced left FG-negative symptoms-facial memory deficits. STG and FG volume reductions may each make distinct contributions to symptoms and cognitive deficits of schizophrenia.

  12. The distinctive "Igualdad en la Empresa": A new certification governing equal opportunities The distinctive "Igualdad en la Empresa": A new certification on equal opportunities El distintivo “Igualdad en la Empresa”: Una nueva certificación en igualdad de oportunidades

    Directory of Open Access Journals (Sweden)

    Rosa Melero-Bolaños

    2011-11-01

    Full Text Available Purpose: Analyse the existence of equal opportunities in rules and standards related to business management and typify the "Corporate Equality" distinction as a new equal opportunities certification.Design/methodology: The existing equal opportunities principles established in different standards and rules have been studied and the "Corporate Equality" distinction has been typified according to different criteria.Findings: Having analysed the existing equal opportunities principles established in different rules and standards concerning business management, it is obvious that these principles are not put into practice. Therefore, the distinction of “Corporate Equality" would indeed stand for a new certification that specifically controls how equal opportunities principles within the company are implemented. However, the lack of information about what these companies have actually achieved up to now limits the knowledge, awareness and appreciation of the different interest groups which deal with aforesaid firms on such matter.Originality/value: The article makes a theoretical contribution to typify the "Corporate Equality" distinction as a new equal opportunities certification. Purpose: Analyse the existence of equal opportunities in rules and standards related to business management and typify the "Corporate Equality" distinction as a new equal opportunities certification.Design/methodology: The existing equal opportunities principles established in different standards and rules have been studied and the "Corporate Equality" distinction has been typified according to different criteria.Findings: Having analysed the existing equal opportunities principles established in different rules and standards concerning business management, it is obvious that these principles are not put into practice. Therefore, the distinction of “Corporate Equality" would indeed stand for a new certification that specifically controls how equal opportunities

  13. Transport of the photodynamic therapy agent 5-aminolevulinic acid by distinct H+-coupled nutrient carriers coexpressed in the small intestine.

    Science.gov (United States)

    Anderson, Catriona M H; Jevons, Mark; Thangaraju, Muthusamy; Edwards, Noel; Conlon, Nichola J; Woods, Steven; Ganapathy, Vadivel; Thwaites, David T

    2010-01-01

    5-Aminolevulinic acid (ALA) is a prodrug used in photodynamic therapy, fluorescent diagnosis, and fluorescent-guided resection because it leads to accumulation of the photosensitizer protoporphyrin IX (PpIX) in tumor tissues. ALA has good oral bioavailability, but high oral doses are required to obtain selective PpIX accumulation in colonic tumors because accumulation is also observed in normal gut mucosa. Structural similarities between ALA and GABA led us to test the hypothesis that the H(+)-coupled amino acid transporter PAT1 (SLC36A1) will contribute to luminal ALA uptake. Radiolabel uptake and electrophysiological measurements identified PAT1-mediated H(+)-coupled ALA symport after heterologous expression in Xenopus oocytes. The selectivity of the nontransported inhibitors 5-hydroxytryptophan and 4-aminomethylbenzoic acid for, respectively, PAT1 and the H(+)-coupled di/tripeptide transporter PepT1 (SLC15A1) were examined. 5-Hydroxytryptophan selectively inhibited PAT1-mediated amino acid uptake across the brush-border membrane of the human intestinal (Caco-2) epithelium whereas 4-aminomethylbenzoic acid selectively inhibited PepT1-mediated dipeptide uptake. The inhibitory effects of 5-hydroxytryptophan and 4-aminomethylbenzoic acid were additive, demonstrating that both PAT1 and PepT1 contribute to intestinal transport of ALA. This is the first demonstration of overlap in substrate specificity between these distinct transporters for amino acids and dipeptides. PAT1 and PepT1 expression was monitored by reverse transcriptase-polymerase chain reaction using paired samples of normal and cancer tissue from human colon. mRNA for both transporters was detected. PepT1 mRNA was increased 2.3-fold in cancer tissues. Thus, increased PepT1 expression in colonic cancer could contribute to the increased PpIX accumulation observed. Selective inhibition of PAT1 could enhance PpIX loading in tumor tissue relative to that in normal tissue.

  14. Estimate of the crud contribution to shipping cask containment requirements

    International Nuclear Information System (INIS)

    Sandoval, R.P.; Einziger, R.E.; Jordan, H.; Malinauskas, A.P.; Mings, W.J.

    1992-01-01

    This paper reports that a methodology is developed to relate U.S. Code of Federal Regulations, Title 10, Part 71 (10CFR71) containment requirements to leak rates for the special case in which the only radioactive species having a potential for escape form the cask is that associated with debris (crud) contained on the fuel assemblies being transported. The methodology accounts for the characteristics of the crud and for attenuation of the gas-borne crud particulates once they become suspended within the cask. Calculations are performed for typical spent-fuel transport cask geometries and the normal and accident conditions prescribed in 10CFR71. The most current published data are used for crud composition and structure, specific activity, spallation mechanics and fractions, and crud particle size. The containment criteria leak rates are calculated assuming 5-yr-old spent fuel. In each accident case, the containment leak rate criteria are well in excess of 10 cm 3 /s. Under normal conditions of transport, the regulatory containment requirements are met by leak rates ranging from 1.5 x 10 -3 cm 3 /s to 1.5 x 10 -4 cm 3 /s for the transport of boiling water reactor fuel assemblies and form 1.8 x 10 -2 cm 3 /s to 1.3 x 10 -3 cm 3 /s for pressurized water reactor fuel assemblies. The calculated leak rates are most sensitive to the cask design, type of fuel, and particle size distribution. Conservatism of the limiting leak rates is discussed

  15. Distinctiveness of Encoding and Memory for Learning Tasks.

    Science.gov (United States)

    Glover, John A.; And Others

    1982-01-01

    A distinctiveness of encoding hypothesis, as applied to the facilitative effects that higher order objectives have on readers' prose recall, was evaluated in three experiments. Results suggest that distinctiveness of encoding may offer a theoretical basis for the effects of adjunct aids as well as a guide to their construction. (Author/GK)

  16. Intergroup Leadership Across Distinct Subgroups and Identities.

    Science.gov (United States)

    Rast, David E; Hogg, Michael A; van Knippenberg, Daan

    2018-03-01

    Resolving intergroup conflict is a significant and often arduous leadership challenge, yet existing theory and research rarely, if ever, discuss or examine this situation. Leaders confront a significant challenge when they provide leadership across deep divisions between distinct subgroups defined by self-contained identities-The challenge is to avoid provoking subgroup identity distinctiveness threat. Drawing on intergroup leadership theory, three studies were conducted to test the core hypothesis that, where identity threat exists, leaders promoting an intergroup relational identity will be better evaluated and are more effective than leaders promoting a collective identity; in the absence of threat, leaders promoting a collective identity will prevail. Studies 1 and 2 ( N = 170; N = 120) supported this general proposition. Study 3 ( N = 136) extended these findings, showing that leaders promoting an intergroup relational identity, but not a collective identity, improved intergroup attitudes when participants experienced an identity distinctiveness threat.

  17. HIV-1 Env trimer opens through an asymmetric intermediate in which individual protomers adopt distinct conformations.

    Science.gov (United States)

    Ma, Xiaochu; Lu, Maolin; Gorman, Jason; Terry, Daniel S; Hong, Xinyu; Zhou, Zhou; Zhao, Hong; Altman, Roger B; Arthos, James; Blanchard, Scott C; Kwong, Peter D; Munro, James B; Mothes, Walther

    2018-03-21

    HIV-1 entry into cells requires binding of the viral envelope glycoprotein (Env) to receptor CD4 and coreceptor. Imaging of individual Env molecules on native virions shows Env trimers to be dynamic, spontaneously transitioning between three distinct well-populated conformational states: a pre-triggered Env (State 1), a default intermediate (State 2) and a three-CD4-bound conformation (State 3), which can be stabilized by binding of CD4 and coreceptor-surrogate antibody 17b. Here, using single-molecule Fluorescence Resonance Energy Transfer (smFRET), we show the default intermediate configuration to be asymmetric, with individual protomers adopting distinct conformations. During entry, this asymmetric intermediate forms when a single CD4 molecule engages the trimer. The trimer can then transition to State 3 by binding additional CD4 molecules and coreceptor.

  18. The effects of distinctiveness on memory and metamemory for face-name associations.

    Science.gov (United States)

    Watier, Nicholas; Collin, Charles

    2012-01-01

    We examined the influence of face and name distinctiveness on memory and metamemory for face-name associations. Four types of monitoring judgements were solicited during encoding and retrieval of face-name pairs that contained distinct or typical faces (Experiment 1) or names (Experiment 2). The beneficial effects of distinctiveness on associative memory were symmetrical between faces and names, such that relative to their typical counterparts, distinct faces enhanced memory for names, and distinct names enhanced memory for faces. These effects were also apparent in metamemory. Estimates of prospective and retrospective memory performance were greater for face-name associations that contained a distinct face or name compared with a typical face or name, regardless of whether the distinct item was a cue or target. Moreover, the predictive validity of prospective monitoring improved with name distinctiveness, whereas the predictive validity of retrospective monitoring improved with facial distinctiveness. Our results indicate that distinctiveness affects not only the strength of the association between a face and a name, but also the ability to monitor that association.

  19. Abstract and Effector-Selective Decision Signals Exhibit Qualitatively Distinct Dynamics before Delayed Perceptual Reports.

    Science.gov (United States)

    Twomey, Deirdre M; Kelly, Simon P; O'Connell, Redmond G

    2016-07-13

    isolated abstract neural signatures of decision formation that are independent of specific sensory and motor requirements. Here, we examine the functional distinctions between the two distinct classes of decision variable signal during decisions with deferred actions with and without foreknowledge of stimulus-effector mapping. We find salient distinctions in the dynamics of abstract versus effector-selective decision signals in the human brain, in terms of sustainment through response delays and contingency on foreknowledge of stimulus-response mapping. Copyright © 2016 Twomey et al.

  20. LPA, HGF, and EGF utilize distinct combinations of signaling pathways to promote migration and invasion of MDA-MB-231 breast carcinoma cells

    International Nuclear Information System (INIS)

    Harrison, Susan MW; Knifley, Teresa; Chen, Min; O’Connor, Kathleen L

    2013-01-01

    Various pathways impinge on the actin-myosin pathway to facilitate cell migration and invasion including members of the Rho family of small GTPases and MAPK. However, the signaling components that are considered important for these processes vary substantially within the literature with certain pathways being favored. These distinctions in signaling pathways utilized are often attributed to differences in cell type or physiological conditions; however, these attributes have not been systematically assessed. To address this question, we analyzed the migration and invasion of MDA-MB-231 breast carcinoma cell line in response to various stimuli including lysophosphatidic acid (LPA), hepatocyte growth factor (HGF) and epidermal growth factor (EGF) and determined the involvement of select signaling pathways that impact myosin light chain phosphorylation. LPA, a potent stimulator of the Rho-ROCK pathway, surprisingly did not require the Rho-ROCK pathway to stimulate migration but instead utilized Rac and MAPK. In contrast, LPA-stimulated invasion required Rho, Rac, and MAPK. Of these three major pathways, EGF-stimulated MDA-MB-231 migration and invasion required Rho; however, Rac was essential only for invasion and MAPK was dispensable for migration. HGF signaling, interestingly, utilized the same pathways for migration and invasion, requiring Rho but not Rac signaling. Notably, the dependency of HGF-stimulated migration and invasion as well as EGF-stimulated invasion on MAPK was subject to the inhibitors used. As expected, myosin light chain kinase (MLCK), a convergence point for MAPK and Rho family GTPase signaling, was required for all six conditions. These observations suggest that, while multiple signaling pathways contribute to cancer cell motility, not all pathways operate under all conditions. Thus, our study highlights the plasticity of cancer cells to adapt to multiple migratory cues

  1. The contribution of stored malate and citrate to the substrate requirements of metabolism of ripening peach (Prunus persica L. Batsch) flesh is negligible. Implications for the occurrence of phosphoenolpyruvate carboxykinase and gluconeogenesis.

    Science.gov (United States)

    Famiani, Franco; Farinelli, Daniela; Moscatello, Stefano; Battistelli, Alberto; Leegood, Richard C; Walker, Robert P

    2016-04-01

    The first aim of this study was to determine the contribution of stored malate and citrate to the substrate requirements of metabolism in the ripening flesh of the peach (Prunus persica L. Batsch) cultivar Adriatica. In the flesh, stored malate accumulated before ripening could contribute little or nothing to the net substrate requirements of metabolism. This was because there was synthesis and not dissimilation of malate throughout ripening. Stored citrate could potentially contribute a very small amount (about 5.8%) of the substrate required by metabolism when the whole ripening period was considered, and a maximum of about 7.5% over the latter part of ripening. The second aim of this study was to investigate why phosphoenolpyruvate carboxykinase (PEPCK) an enzyme utilised in gluconeogenesis from malate and citrate is present in peach flesh. The occurrence and localisation of enzymes utilised in the metabolism of malate, citrate and amino acids were determined in peach flesh throughout its development. Phosphoenolpyruvate carboxylase (essential for the synthesis of malate and citrate) was present in the same cells and at the same time as PEPCK and NADP-malic enzyme (both utilised in the dissimilation of malate and citrate). A hypothesis is presented to explain the presence of these enzymes and to account for the likely occurrence of gluconeogenesis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  2. Distinct Mechanisms of Recognizing Endosomal Sorting Complex Required for Transport III (ESCRT-III) Protein IST1 by Different Microtubule Interacting and Trafficking (MIT) Domains*

    Science.gov (United States)

    Guo, Emily Z.; Xu, Zhaohui

    2015-01-01

    The endosomal sorting complex required for transport (ESCRT) machinery is responsible for membrane remodeling in a number of biological processes including multivesicular body biogenesis, cytokinesis, and enveloped virus budding. In mammalian cells, efficient abscission during cytokinesis requires proper function of the ESCRT-III protein IST1, which binds to the microtubule interacting and trafficking (MIT) domains of VPS4, LIP5, and Spartin via its C-terminal MIT-interacting motif (MIM). Here, we studied the molecular interactions between IST1 and the three MIT domain-containing proteins to understand the structural basis that governs pairwise MIT-MIM interaction. Crystal structures of the three molecular complexes revealed that IST1 binds to the MIT domains of VPS4, LIP5, and Spartin using two different mechanisms (MIM1 mode versus MIM3 mode). Structural comparison revealed that structural features in both MIT and MIM contribute to determine the specific binding mechanism. Within the IST1 MIM sequence, two phenylalanine residues were shown to be important in discriminating MIM1 versus MIM3 binding. These observations enabled us to deduce a preliminary binding code, which we applied to provide CHMP2A, a protein that normally only binds the MIT domain in the MIM1 mode, the additional ability to bind the MIT domain of Spartin in the MIM3 mode. PMID:25657007

  3. Distinct mechanisms of recognizing endosomal sorting complex required for transport III (ESCRT-III) protein IST1 by different microtubule interacting and trafficking (MIT) domains.

    Science.gov (United States)

    Guo, Emily Z; Xu, Zhaohui

    2015-03-27

    The endosomal sorting complex required for transport (ESCRT) machinery is responsible for membrane remodeling in a number of biological processes including multivesicular body biogenesis, cytokinesis, and enveloped virus budding. In mammalian cells, efficient abscission during cytokinesis requires proper function of the ESCRT-III protein IST1, which binds to the microtubule interacting and trafficking (MIT) domains of VPS4, LIP5, and Spartin via its C-terminal MIT-interacting motif (MIM). Here, we studied the molecular interactions between IST1 and the three MIT domain-containing proteins to understand the structural basis that governs pairwise MIT-MIM interaction. Crystal structures of the three molecular complexes revealed that IST1 binds to the MIT domains of VPS4, LIP5, and Spartin using two different mechanisms (MIM1 mode versus MIM3 mode). Structural comparison revealed that structural features in both MIT and MIM contribute to determine the specific binding mechanism. Within the IST1 MIM sequence, two phenylalanine residues were shown to be important in discriminating MIM1 versus MIM3 binding. These observations enabled us to deduce a preliminary binding code, which we applied to provide CHMP2A, a protein that normally only binds the MIT domain in the MIM1 mode, the additional ability to bind the MIT domain of Spartin in the MIM3 mode. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  4. Contribution of Urease to Colonization by Shiga Toxin-Producing Escherichia coli

    Science.gov (United States)

    Steyert, Susan R.

    2012-01-01

    Shiga toxin-producing Escherichia coli (STEC) is a food-borne pathogen with a low infectious dose that colonizes the colon in humans and can cause severe clinical manifestations such as hemolytic-uremic syndrome. The urease enzyme, encoded in the STEC chromosome, has been demonstrated to act as a virulence factor in other bacterial pathogens. The NH3 produced as urease hydrolyzes urea can aid in buffering bacteria in acidic environments as well as provide an easily assimilated source of nitrogen that bacteria can use to gain a metabolic advantage over intact microflora. Here, we explore the role of urease in STEC pathogenicity. The STEC urease enzyme exhibited maximum activity near neutral pH and during the stationary-growth phase. Experiments altering growth conditions performed with three phylogenetically distinct urease-positive strains demonstrated that the STEC ure gene cluster is inducible by neither urea nor pH but does respond to nitrogen availability. Quantitative reverse transcription-PCR (qRT-PCR) data indicate that nitrogen inhibits the transcriptional response. The deletion of the ure gene locus was constructed in STEC strain 88-0643, and the ure mutant was used with the wild-type strain in competition experiments in mouse models to examine the contribution of urease. The wild-type strain was twice as likely to survive passage through the acidic stomach and demonstrated an enhanced ability to colonize the intestinal tract compared to the ure mutant strain. These in vivo experiments reveal that, although the benefit STEC gains from urease expression is modest and not absolutely required for colonization, urease can contribute to the pathogenicity of STEC. PMID:22665380

  5. Genes contribute to the switching dynamics of bistable perception.

    Science.gov (United States)

    Shannon, Robert W; Patrick, Christopher J; Jiang, Yi; Bernat, Edward; He, Sheng

    2011-03-09

    Ordinarily, the visual system provides an unambiguous representation of the world. However, at times alternative plausible interpretations of a given stimulus arise, resulting in a dynamic perceptual alternation of the differing interpretations, commonly referred to as bistable or rivalrous perception. Recent research suggests that common neural mechanisms may be involved in the dynamics of very different types of bistable phenomena. Further, evidence has emerged that genetic factors may be involved in determining the rate of switch for at least one form of bistable perception, known as binocular rivalry. The current study evaluated whether genetic factors contribute to the switching dynamics for distinctly different variants of bistable perception in the same participant sample. Switching rates were recorded for MZ and DZ twin participants in two different bistable perception tasks, binocular rivalry and the Necker Cube. Strong concordance in switching rates across both tasks was evident for MZ but not DZ twins, indicating that genetic factors indeed contribute to the dynamics of multiple forms of bistable perception.

  6. Transcription factor Tbx3 is required for the specification of the atrioventricular conduction system

    NARCIS (Netherlands)

    Bakker, Martijn L.; Boukens, Bastiaan J.; Mommersteeg, Mathilda T. M.; Brons, Janynke F.; Wakker, Vincent; Moorman, Antoon F. M.; Christoffels, Vincent M.

    2008-01-01

    The cardiac conduction system consists of distinctive heart muscle cells that initiate and propagate the electric impulse required for coordinated contraction. The conduction system expresses the transcriptional repressor Tbx3, which is required for vertebrate development and controls the formation

  7. Distinct Bacterial Communities Associated with the Coral Model Aiptasia in Aposymbiotic and Symbiotic States with Symbiodinium

    KAUST Repository

    Röthig, Till

    2016-11-18

    Coral reefs are in decline. The basic functional unit of coral reefs is the coral metaorganism or holobiont consisting of the cnidarian host animal, symbiotic algae of the genus Symbiodinium, and a specific consortium of bacteria (among others), but research is slow due to the difficulty of working with corals. Aiptasia has proven to be a tractable model system to elucidate the intricacies of cnidarian-dinoflagellate symbioses, but characterization of the associated bacterial microbiome is required to provide a complete and integrated understanding of holobiont function. In this work, we characterize and analyze the microbiome of aposymbiotic and symbiotic Aiptasia and show that bacterial associates are distinct in both conditions. We further show that key microbial associates can be cultured without their cnidarian host. Our results suggest that bacteria play an important role in the symbiosis of Aiptasia with Symbiodinium, a finding that underlines the power of the Aiptasia model system where cnidarian hosts can be analyzed in aposymbiotic and symbiotic states. The characterization of the native microbiome and the ability to retrieve culturable isolates contributes to the resources available for the Aiptasia model system. This provides an opportunity to comparatively analyze cnidarian metaorganisms as collective functional holobionts and as separated member species. We hope that this will accelerate research into understanding the intricacies of coral biology, which is urgently needed to develop strategies to mitigate the effects of environmental change.

  8. A Novel Algorithm for the Generation of Distinct Kinematic Chain

    Science.gov (United States)

    Medapati, Sreenivasa Reddy; Kuchibhotla, Mallikarjuna Rao; Annambhotla, Balaji Srinivasa Rao

    2016-07-01

    Generation of distinct kinematic chains is an important topic in the design of mechanisms for various industrial applications i.e., robotic manipulator, tractor, crane etc. Many researchers have intently focused on this area and explained various processes of generating distinct kinematic chains which are laborious and complex. It is desirable to enumerate the kinematic chains systematically to know the inherent characteristics of a chain related to its structure so that all the distinct chains can be analyzed in depth, prior to the selection of a chain for a purpose. This paper proposes a novel and simple method with set of rules defined to eliminate isomorphic kinematic chains generating distinct kinematic chains. Also, this method simplifies the process of generating distinct kinematic chains even at higher levels i.e., 10-link, 11-link with single and multiple degree of freedom.

  9. The Contributions of the Amino and Carboxy Terminal Domains of Flightin to the Biomechanical Properties of Drosophila Flight Muscle Thick Filaments.

    Science.gov (United States)

    Gasek, Nathan S; Nyland, Lori R; Vigoreaux, Jim O

    2016-04-27

    Flightin is a myosin binding protein present in Pancrustacea. In Drosophila, flightin is expressed in the indirect flight muscles (IFM), where it is required for the flexural rigidity, structural integrity, and length determination of thick filaments. Comparison of flightin sequences from multiple Drosophila species revealed a tripartite organization indicative of three functional domains subject to different evolutionary constraints. We use atomic force microscopy to investigate the functional roles of the N-terminal domain and the C-terminal domain that show different patterns of sequence conservation. Thick filaments containing a C-terminal domain truncated flightin (fln(ΔC44)) are significantly shorter (2.68 ± 0.06 μm; p thick filaments containing a full length flightin (fln⁺; 3.21 ± 0.05 μm) and thick filaments containing an N-terminal domain truncated flightin (fln(ΔN62); 3.21 ± 0.06 μm). Persistence length was significantly reduced in fln(ΔN62) (418 ± 72 μm; p thick filament bending propensity. Our results indicate that the flightin amino and carboxy terminal domains make distinct contributions to thick filament biomechanics. We propose these distinct roles arise from the interplay between natural selection and sexual selection given IFM's dual role in flight and courtship behaviors.

  10. Common and distinct brain networks underlying verbal and visual creativity.

    Science.gov (United States)

    Zhu, Wenfeng; Chen, Qunlin; Xia, Lingxiang; Beaty, Roger E; Yang, Wenjing; Tian, Fang; Sun, Jiangzhou; Cao, Guikang; Zhang, Qinglin; Chen, Xu; Qiu, Jiang

    2017-04-01

    Creativity is imperative to the progression of human civilization, prosperity, and well-being. Past creative researches tends to emphasize the default mode network (DMN) or the frontoparietal network (FPN) somewhat exclusively. However, little is known about how these networks interact to contribute to creativity and whether common or distinct brain networks are responsible for visual and verbal creativity. Here, we use functional connectivity analysis of resting-state functional magnetic resonance imaging data to investigate visual and verbal creativity-related regions and networks in 282 healthy subjects. We found that functional connectivity within the bilateral superior parietal cortex of the FPN was negatively associated with visual and verbal creativity. The strength of connectivity between the DMN and FPN was positively related to both creative domains. Visual creativity was negatively correlated with functional connectivity within the precuneus of the pDMN and right middle frontal gyrus of the FPN, and verbal creativity was negatively correlated with functional connectivity within the medial prefrontal cortex of the aDMN. Critically, the FPN mediated the relationship between the aDMN and verbal creativity, and it also mediated the relationship between the pDMN and visual creativity. Taken together, decreased within-network connectivity of the FPN and DMN may allow for flexible between-network coupling in the highly creative brain. These findings provide indirect evidence for the cooperative role of the default and executive control networks in creativity, extending past research by revealing common and distinct brain systems underlying verbal and visual creative cognition. Hum Brain Mapp 38:2094-2111, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. Latent memory facilitates relearning through molecular signaling mechanisms that are distinct from original learning.

    Science.gov (United States)

    Menges, Steven A; Riepe, Joshua R; Philips, Gary T

    2015-09-01

    A highly conserved feature of memory is that it can exist in a latent, non-expressed state which is revealed during subsequent learning by its ability to significantly facilitate (savings) or inhibit (latent inhibition) subsequent memory formation. Despite the ubiquitous nature of latent memory, the mechanistic nature of the latent memory trace and its ability to influence subsequent learning remains unclear. The model organism Aplysia californica provides the unique opportunity to make strong links between behavior and underlying cellular and molecular mechanisms. Using Aplysia, we have studied the mechanisms of savings due to latent memory for a prior, forgotten experience. We previously reported savings in the induction of three distinct temporal domains of memory: short-term (10min), intermediate-term (2h) and long-term (24h). Here we report that savings memory formation utilizes molecular signaling pathways that are distinct from original learning: whereas the induction of both original intermediate- and long-term memory in naïve animals requires mitogen activated protein kinase (MAPK) activation and ongoing protein synthesis, 2h savings memory is not disrupted by inhibitors of MAPK or protein synthesis, and 24h savings memory is not dependent on MAPK activation. Collectively, these findings reveal that during forgetting, latent memory for the original experience can facilitate relearning through molecular signaling mechanisms that are distinct from original learning. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Population-specific life histories contribute to metapopulation viability

    Science.gov (United States)

    Halsey, Samniqueka J.; Bell, Timothy J.; McEachern, A. Kathryn; Pavlovic, Noel B.

    2016-01-01

    Restoration efforts can be improved by understanding how variations in life-history traits occur within populations of the same species living in different environments. This can be done by first understanding the demographic responses of natural occurring populations. Population viability analysis continues to be useful to species management and conservation with sensitivity analysis aiding in the understanding of population dynamics. In this study, using life-table response experiments and elasticity analyses, we investigated how population-specific life-history demographic responses contributed to the metapopulation viability of the Federally threatened Pitcher's thistle (Cirsium pitcheri). Specifically, we tested the following hypotheses: (1) Subpopulations occupying different environments within a metapopulation have independent demographic responses and (2) advancing succession results in a shift from a demographic response focused on growth and fecundity to one dominated by stasis. Our results showed that reintroductions had a positive contribution to the metapopulation growth rate as compared to native populations which had a negative contribution. We found no difference in succession on the contribution to metapopulation viability. In addition, we identified distinct population-specific contributions to metapopulation viability and were able to associate specific life-history demographic responses. For example, the positive impact of Miller High Dunes population on the metapopulation growth rate resulted from high growth contributions, whereas increased time of plant in stasis for the State Park Big Blowout population resulted in negative contributions. A greater understanding of how separate populations respond in their corresponding environment may ultimately lead to more effective management strategies aimed at reducing extinction risk. We propose the continued use of sensitivity analyses to evaluate population-specific demographic influences on

  13. Distinctive signatures for new particles in e/sup +/e/sup -/ annihilation and Z-decay

    International Nuclear Information System (INIS)

    Tung, W.K.; Kitazawa, Y.

    1986-01-01

    New particles and new interactions reveal themselves most clearly where standard model contributions are negligibly small. A prominent example with this advantage is the one-lepton inclusive longitudinal structure function (W/sub L/) in e/sup +/e/sup -/ annihilation and Z-decay. The authors discuss general features of this approach and present structure functions for four types of new particles (heavy charged fermion (e.g., new sequential lepton or top quark); heavy neutral lepton; and supersymmetric scalar lepton, i.e. slepton), along with the (small) standard model 'background'. The x-dependence of W/sub L/ provides a distinct signature of the identity of the new particle. Extensions of this approach are discussed

  14. arXiv Hadronic and New Physics Contributions to B -> K* l+ l-

    CERN Document Server

    Arbey, A.; Mahmoudi, F.; Neshatpour, S.

    The significance of the observed tensions in the angular observables in $B \\to K^* \\mu^+ \\mu^-$ are dependent on the theory estimation of the hadronic contributions to these decays. Therefore, we discuss in detail the various available approaches for taking into account the long-distance hadronic effects and examine how the different estimations of these contributions result in distinct significance of the new physics interpretation of the observed anomalies. Furthermore, besides the various theory estimations of the non-factorisable contributions we consider a general parameterisation which is fully consistent with the analyticity structure of the amplitudes. We make a statistical comparison to find whether the most favoured explanation of the anomalies is new physics or underestimated hadronic effects within this general parametrisation. Moreover, assuming the source of the anomalies to be new physics, there is a priori no reason to believe that - in the effective field theory language - only one type of op...

  15. Distinction between epigenic and hypogenic maze caves

    Science.gov (United States)

    Palmer, Arthur N.

    2011-11-01

    Certain caves formed by dissolution of bedrock have maze patterns composed of closed loops in which many intersecting fractures or pores have enlarged simultaneously. Their origin can be epigenic (by shallow circulation of meteoric groundwater) or hypogenic (by rising groundwater or production of deep-seated solutional aggressiveness). Epigenic mazes form by diffuse infiltration through a permeable insoluble caprock or by floodwater supplied by sinking streams. Most hypogenic caves involve deep sources of aggressiveness. Transverse hypogenic cave origin is a recently proposed concept in which groundwater of mainly meteoric origin rises across strata in the distal portions of large flow systems, to form mazes in soluble rock sandwiched between permeable but insoluble strata. The distinction between maze types is debated and is usually based on examination of diagnostic cave features and relation of caves to their regional setting. In this paper, the principles of mass transfer are applied to clarify the limits of each model, to show how cave origin is related to groundwater discharge, dissolution rate, and time. The results show that diffuse infiltration and floodwater can each form maze caves at geologically feasible rates (typically within 500 ka). Transverse hypogenic mazes in limestone, to enlarge significantly within 1 Ma, require an unusually high permeability of the non-carbonate beds (generally ≥ 10-4 cm/s), large discharge, and calcite saturation no greater than 90%, which is rare in deep diffuse flow in sedimentary rocks. Deep sources of aggressiveness are usually required. The origin of caves by transverse hypogenic flow is much more favorable in evaporite rocks than in carbonate rocks.

  16. NMR metabolomics of human lung tumours reveals distinct metabolic signatures for adenocarcinoma and squamous cell carcinoma

    OpenAIRE

    Rocha, CM; Barros, AS; Goodfellow, BJ; Carreira, IM; Gomes, AA; Sousa, V; Bernardo, J; Carvalho, L; Gil, AM; Duarte, IF

    2015-01-01

    Lung tumour subtyping, particularly the distinction between adenocarcinoma (AdC) and squamous cell carcinoma (SqCC), is a critical diagnostic requirement. In this work, the metabolic signatures of lung carcinomas were investigated through (1)H NMR metabolomics, with a view to provide additional criteria for improved diagnosis and treatment planning. High Resolution Magic Angle Spinning Nuclear Magnetic Resonance (NMR) spectroscopy was used to analyse matched tumour and adjacent control tissue...

  17. Active Mirror Predictive and Requirements Verification Software (AMP-ReVS)

    Science.gov (United States)

    Basinger, Scott A.

    2012-01-01

    This software is designed to predict large active mirror performance at various stages in the fabrication lifecycle of the mirror. It was developed for 1-meter class powered mirrors for astronomical purposes, but is extensible to other geometries. The package accepts finite element model (FEM) inputs and laboratory measured data for large optical-quality mirrors with active figure control. It computes phenomenological contributions to the surface figure error using several built-in optimization techniques. These phenomena include stresses induced in the mirror by the manufacturing process and the support structure, the test procedure, high spatial frequency errors introduced by the polishing process, and other process-dependent deleterious effects due to light-weighting of the mirror. Then, depending on the maturity of the mirror, it either predicts the best surface figure error that the mirror will attain, or it verifies that the requirements for the error sources have been met once the best surface figure error has been measured. The unique feature of this software is that it ties together physical phenomenology with wavefront sensing and control techniques and various optimization methods including convex optimization, Kalman filtering, and quadratic programming to both generate predictive models and to do requirements verification. This software combines three distinct disciplines: wavefront control, predictive models based on FEM, and requirements verification using measured data in a robust, reusable code that is applicable to any large optics for ground and space telescopes. The software also includes state-of-the-art wavefront control algorithms that allow closed-loop performance to be computed. It allows for quantitative trade studies to be performed for optical systems engineering, including computing the best surface figure error under various testing and operating conditions. After the mirror manufacturing process and testing have been completed, the

  18. Contribution of the ''safeguarded'' to the development of safeguards

    International Nuclear Information System (INIS)

    Anderson, A.R.

    1977-01-01

    The development of an efficient system of international safeguards requires close and detailed interaction between the safeguarding authority and those being safeguarded, i.e. the plant operator and the State System to which he belongs. Such interaction is found in other control systems but the degree of international collaboration involved in Safeguards is perhaps unique and it is valuable to review and analyse the contributions which have arisen from prudent management considerations. Management has many reasons to exercise stringent control of nuclear materials stemming from the value and hazardous nature of the materials being used, and the requirements of relevant national legislation. Because systems at a plant and within a State are generally designed to control quantities of nuclear materials within limits smaller than those specified in the I.A.E.A.'s Safeguards objectives, experience at the plant level has contributed significantly to the development of International Safeguards procedures. In making such contributions, plant management and the national authorities have a common objective with that of the I.A.E.A. in developing a Safeguards system which is both technically-effective and cost-effective. The pursuit of this objective requires that implementation of the Safeguards system can be modified in the light of relevant practical experience of plant operators and of the I.A.E.A. The familiar Blue Book (INFCIRC 153) recognises clearly the need for an effective State's System of accounting for and control of nuclear materials as a necessary pre-requisite for the development and implementation of an effective I.A.E.A. system of Safeguards. It is therefore helpful to review the relevant contributions from the 'Safeguarded' in terms of the components of the State's System specified in paragraph 32 of the Blue Book. This paper reviews the continuing contributions stemming from plant and national experience, with particular emphasis on the development of

  19. The radiographic distinction of degenerative slippage (spondylolisthesis and retrolisthesis) from traumatic slippage of the cervical spine

    International Nuclear Information System (INIS)

    Lee, C.; Woodring, J.H.; Rogers, L.F.; Kim, K.S.

    1986-01-01

    In a review of 42 cases of degenerative arthritis of the cervical spine and 22 cases of cervical spine trauma with an observed anterior slip-page (spondylolisthesis) or posterior slippage (retrolisthesis) of the vertebral bodies of 2 mm or more, characteristic features were observed which allowed distinction between degenerative and traumatic slippage of the cervical spine. In degenerative slippage the shape of the articular facets and width of the facet joint space may remain normal; however, in most cases the articular facets become 'ground-down' with narrowing of the facet joint space and the articular facets themselves becoming thinned or ribbon-like. In traumatic slippage the articular facets will either be normally shaped or fractured and the facet joint space will be abnormally widened. Plain radiographs will usually allow this distinction to be made; however, in difficult cases polytomography may be required. (orig.)

  20. Contribution of the 'safeguarded' to the development of safeguards

    International Nuclear Information System (INIS)

    Anderson, A.R.

    1977-01-01

    The development of an efficient system of international safeguards requires close and detailed interaction between the safeguarding authority and those being safeguarded, i.e. the plant operator and the State System to which he belongs. Such interaction is found in other control systems but the degree of international collaboration involved in safeguards is perhaps unique and it is valuable to review and analyse the contributions which have arisen from prudent management considerations. The familiar ''Blue Book'' (INFCIRC 153) recognizes clearly the need for an effective State's System of accounting for and control of nuclear materials as a necessary pre-requisite for the development and implementation of an effective IAEA system of safeguards. It is therefore helpful to summarize the relevant contributions from the 'safeguarded' in terms of the components of the State's System specified in paragraph 32 of the Blue Book. This paper reviews the continuing contributions stemming from plant and national experience, with particular emphasis on the development of measurement systems and physical inventory procedures relevant to safeguards. Attention is also drawn to those areas where the specific objectives of IAEA Safeguards lead to requirements additional to those required for management purposes. (author)

  1. CONTRIBUTIONS OF HISTORICAL CRITICAL PEDAGOGY TO GEOGRAPHY TEACHING

    Directory of Open Access Journals (Sweden)

    Lucas André Teixeira

    2015-06-01

    Full Text Available This paper aims to show some contributions of historical critical pedagogy to Geography teaching. Such thoughts aim to discuss how this teaching enters school education in the context of neoliberalism. Assuming that the emptiness in Geography teaching in school education is a result of Brazilian educational policies in neoliberalism, we intend to characterize the impairment of the critical perspective on this area of knowledge and present some contributions of historical critical pedagogy to face and overcome the current order. Besides, we seek to highlight the required knowledge to achieve an education that contributes to build a different society.

  2. Distinct Circuits for the Formation and Retrieval of an Imprinted Olfactory Memory.

    Science.gov (United States)

    Jin, Xin; Pokala, Navin; Bargmann, Cornelia I

    2016-02-11

    Memories formed early in life are particularly stable and influential, representing privileged experiences that shape enduring behaviors. We show that exposing newly hatched C. elegans to pathogenic bacteria results in persistent aversion to those bacterial odors, whereas adult exposure generates only transient aversive memory. Long-lasting imprinted aversion has a critical period in the first larval stage and is specific to the experienced pathogen. Distinct groups of neurons are required during formation (AIB, RIM) and retrieval (AIY, RIA) of the imprinted memory. RIM synthesizes the neuromodulator tyramine, which is required in the L1 stage for learning. AIY memory retrieval neurons sense tyramine via the SER-2 receptor, which is essential for imprinted, but not for adult-learned, aversion. Odor responses in several neurons, most notably RIA, are altered in imprinted animals. These findings provide insight into neuronal substrates of different forms of memory, and lay a foundation for further understanding of early learning. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Distinct Biological Potential of Streptococcus gordonii and Streptococcus sanguinis Revealed by Comparative Genome Analysis.

    Science.gov (United States)

    Zheng, Wenning; Tan, Mui Fern; Old, Lesley A; Paterson, Ian C; Jakubovics, Nicholas S; Choo, Siew Woh

    2017-06-07

    Streptococcus gordonii and Streptococcus sanguinis are pioneer colonizers of dental plaque and important agents of bacterial infective endocarditis (IE). To gain a greater understanding of these two closely related species, we performed comparative analyses on 14 new S. gordonii and 5 S. sanguinis strains using various bioinformatics approaches. We revealed S. gordonii and S. sanguinis harbor open pan-genomes and share generally high sequence homology and number of core genes including virulence genes. However, we observed subtle differences in genomic islands and prophages between the species. Comparative pathogenomics analysis identified S. sanguinis strains have genes encoding IgA proteases, mitogenic factor deoxyribonucleases, nickel/cobalt uptake and cobalamin biosynthesis. On the contrary, genomic islands of S. gordonii strains contain additional copies of comCDE quorum-sensing system components involved in genetic competence. Two distinct polysaccharide locus architectures were identified, one of which was exclusively present in S. gordonii strains. The first evidence of genes encoding the CylA and CylB system by the α-haemolytic S. gordonii is presented. This study provides new insights into the genetic distinctions between S. gordonii and S. sanguinis, which yields understanding of tooth surfaces colonization and contributions to dental plaque formation, as well as their potential roles in the pathogenesis of IE.

  4. Distinct Residues Contribute to Motility Repression and Autoregulation in the Proteus mirabilis Fimbria-Associated Transcriptional Regulator AtfJ.

    Science.gov (United States)

    Bode, Nadine J; Chan, Kun-Wei; Kong, Xiang-Peng; Pearson, Melanie M

    2016-08-01

    Proteus mirabilis contributes to a significant number of catheter-associated urinary tract infections, where coordinated regulation of adherence and motility is critical for ascending disease progression. Previously, the mannose-resistant Proteus-like (MR/P) fimbria-associated transcriptional regulator MrpJ has been shown to both repress motility and directly induce the transcription of its own operon; in addition, it affects the expression of a wide range of cellular processes. Interestingly, 14 additional mrpJ paralogs are included in the P. mirabilis genome. Looking at a selection of MrpJ paralogs, we discovered that these proteins, which consistently repress motility, also have nonidentical functions that include cross-regulation of fimbrial operons. A subset of paralogs, including AtfJ (encoded by the ambient temperature fimbrial operon), Fim8J, and MrpJ, are capable of autoinduction. We identified an element of the atf promoter extending from 487 to 655 nucleotides upstream of the transcriptional start site that is responsive to AtfJ, and we found that AtfJ directly binds this fragment. Mutational analysis of AtfJ revealed that its two identified functions, autoregulation and motility repression, are not invariably linked. Residues within the DNA-binding helix-turn-helix domain are required for motility repression but not necessarily autoregulation. Likewise, the C-terminal domain is dispensable for motility repression but is essential for autoregulation. Supported by a three-dimensional (3D) structural model, we hypothesize that the C-terminal domain confers unique regulatory capacities on the AtfJ family of regulators. Balancing adherence with motility is essential for uropathogens to successfully establish a foothold in their host. Proteus mirabilis uses a fimbria-associated transcriptional regulator to switch between these antagonistic processes by increasing fimbrial adherence while simultaneously downregulating flagella. The discovery of multiple

  5. Deconstruction of O-glycosylation-GalNAc-T isoforms direct distinct subsets of the O-glycoproteome

    DEFF Research Database (Denmark)

    Schjoldager, Katrine T; Joshi, Hiren J; Kong, Yun

    2015-01-01

    GalNAc-type O-glycosylation is found on most proteins trafficking through the secretory pathway in metazoan cells. The O-glycoproteome is regulated by up to 20 polypeptide GalNAc-Ts and the contributions and biological functions of individual GalNAc-Ts are poorly understood. Here, we used a zinc......-finger nuclease (ZFN)-directed knockout strategy to probe the contributions of the major GalNAc-Ts (GalNAc-T1 and GalNAc-T2) in liver cells and explore how the GalNAc-T repertoire quantitatively affects the O-glycoproteome. We demonstrate that the majority of the O-glycoproteome is covered by redundancy, whereas...... distinct subsets of substrates are modified by non-redundant functions of GalNAc-T1 and GalNAc-T2. The non-redundant O-glycoproteome subsets and specific transcriptional responses for each isoform are related to different cellular processes; for the GalNAc-T2 isoform, these support a role in lipid...

  6. Bioethicists Can and Should Contribute to Addressing Racism

    Science.gov (United States)

    Danis, Marion; Wilson, Yolonda; White, Amina

    2016-01-01

    The problems of racism and racially-motivated violence in predominantly African American communities in the US are complex, multifactorial and historically rooted. While these problems are also deeply morally troubling, bioethicists have not contributed substantially to addressing them. Concern for justice has been one of the core commitments of bioethics. For this and other reasons, bioethicists should contribute to addressing these problems. We consider how bioethicists can offer meaningful contributions to the public discourse, research, teaching, training, policy development and academic scholarship in response to the alarming and persistent patterns of racism and implicit biases associated with it. To make any useful contribution, bioethicists will require preparation and should expect to play a significant role through collaborative action with others. PMID:26982911

  7. Bioethicists Can and Should Contribute to Addressing Racism.

    Science.gov (United States)

    Danis, Marion; Wilson, Yolonda; White, Amina

    2016-01-01

    The problems of racism and racially motivated violence in predominantly African American communities in the United States are complex, multifactorial, and historically rooted. While these problems are also deeply morally troubling, bioethicists have not contributed substantially to addressing them. Concern for justice has been one of the core commitments of bioethics. For this and other reasons, bioethicists should contribute to addressing these problems. We consider how bioethicists can offer meaningful contributions to the public discourse, research, teaching, training, policy development, and academic scholarship in response to the alarming and persistent patterns of racism and implicit biases associated with it. To make any useful contribution, bioethicists will require preparation and should expect to play a significant role through collaborative action with others.

  8. Distinct Signaling Mechanisms in Multiple Developmental Pathways by the SCRAMBLED Receptor of Arabidopsis1[OPEN

    Science.gov (United States)

    Kwak, Su-Hwan; Woo, Sooah; Lee, Myeong Min; Schiefelbein, John

    2014-01-01

    SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase in Arabidopsis (Arabidopsis thaliana), is required for positional signaling in the root epidermis and for tissue/organ development in the shoot. To further understand SCM action, we generated a series of kinase domain variants and analyzed their ability to complement scm mutant defects. We found that the SCM kinase domain, but not kinase activity, is required for its role in root epidermal patterning, supporting the view that SCM is an atypical receptor kinase. We also describe a previously uncharacterized role for SCM in fruit dehiscence, because mature siliques from scm mutants fail to open properly. Interestingly, the kinase domain of SCM appears to be dispensable for this developmental process. Furthermore, we found that most of the SCM kinase domain mutations dramatically inhibit inflorescence development. Because this process is not affected in scm null mutants, it is likely that SCM acts redundantly to regulate inflorescence size. The importance of distinct kinase residues for these three developmental processes provides an explanation for the maintenance of the conserved kinase domain in the SCM protein, and it may generally explain its conservation in other atypical kinases. Furthermore, these results indicate that individual leucine-rich repeat receptor-like kinases may participate in multiple pathways using distinct signaling mechanisms to mediate diverse cellular communication events. PMID:25136062

  9. Changing author counts in five major general medicine journals: effect of author contribution forms.

    Science.gov (United States)

    Baerlocher, Mark Otto; Gautam, Tina; Newton, Marshall; Tomlinson, George

    2009-08-01

    Objective and indirect evidence was used to determine whether required author contribution forms were associated with a decrease in author counts in four major general medicine journals (British Medical Journal [BMJ], Journal of the American Medical Association [JAMA], Canadian Medical Association Journal [CMAJ], and the Lancet). The number of authors listed per article before and after the introduction of explicit author contribution requirements were counted and compared with that found for the New England Journal of Medicine (NEJM) that did not require such disclosure. The primary hypothesis was that author counts decreased more in the BMJ, CMAJ, JAMA, and the Lancet after introduction of the rules than they did in the NEJM. The number of authors listed per original research article published in the five general medical journals with the greatest 2004 Impact Factors in the first issue of each month in the years before and after introduction of required author contribution forms was compared. Introduction of the required author contribution forms by the four leading general medical journals did not result in a drop in the rate of increasing authors per article per year, or in the number of authors per article compared with the control. Overall, there was a trend of an increasing number of authors listed per article. Based on the presented objective and indirect evidence, required author contribution forms were not associated with a decrease in author counts.

  10. Contribution of cellular autolysis to tissular functions during plant development

    OpenAIRE

    Escamez, Sacha; Tuominen, Hannele

    2017-01-01

    Plant development requires specific cells to be eliminated in a predictable and genetically regulated manner referred to as programmed cell death (PCD). However, the target cells do not merely die but they also undergo autolysis to degrade their cellular corpses. Recent progress in understanding developmental cell elimination suggests that distinct proteins execute PCD sensu stricto and autolysis. In addition, cell death alone and cell dismantlement can fulfill different functions. Hence, it ...

  11. Grammar-Lexicon Distinction in a Neurocognitive Context

    DEFF Research Database (Denmark)

    Ishkhanyan, Byurakn

    hypotheses and testing them through using various methods. The grammar-lexicon distinction and working memory are thus central topics of this thesis. The results suggest a potential for a successful integration of the two theories. The findings further provide evidence for Boye & Harder’s (2012......) understanding of the grammar-lexicon distinction, and for the involvement of working memory in language production, as the REF-model would predict. As a starting point for integrating the two theories, the present thesis gives directions for future research on the neurocognitive underpinning of language and its...... relation to working memory....

  12. Distinct roles of extracellular polymeric substances in Pseudomonas aeruginosa biofilm development

    DEFF Research Database (Denmark)

    Yang, Liang; Hu, Yifan; Liu, Yang

    2011-01-01

    Bacteria form surface attached biofilm communities as one of the most important survival strategies in nature. Biofilms consist of water, bacterial cells and a wide range of self‐generated extracellular polymeric substances (EPS). Biofilm formation is a dynamic self‐assembly process and several d...... polysaccharide is more important than Pel polysaccharide in P. aeruginosa PAO1 biofilm formation and antibiotic resistance. Our study thus suggests that different EPS materials play distinct roles during bacterial biofilm formation.......Bacteria form surface attached biofilm communities as one of the most important survival strategies in nature. Biofilms consist of water, bacterial cells and a wide range of self‐generated extracellular polymeric substances (EPS). Biofilm formation is a dynamic self‐assembly process and several...... distinguishable stages are observed during bacterial biofilm development. Biofilm formation is shown to be coordinated by EPS production, cell migration, subpopulation differentiation and interactions. However, the ways these different factors affect each other and contribute to community structural...

  13. Ethnocultural Groups--The Making of Canada: Economic Contributions to Canadian Life. Report 2: Seven Successful Small Business Entrepreneurs.

    Science.gov (United States)

    Dutt, S.; And Others

    Immigrants and refugees come to Canada for many reasons and are often risk-takers. Some ethnic groups follow identifiable patterns of distinctive economic development, while others meld and blend into Canadian society so that no discernible pattern can be identified. This publication provides an overview of the contributions made by seven…

  14. 26 CFR 1.170A-6 - Charitable contributions in trust.

    Science.gov (United States)

    2010-04-01

    ... governing instrument of the trust or from local law that the trustee would be required to apportion the... 26 Internal Revenue 3 2010-04-01 2010-04-01 false Charitable contributions in trust. 1.170A-6...-6 Charitable contributions in trust. (a) In general. (1) No deduction is allowed under section 170...

  15. 29 CFR 4.173 - Meeting requirements for vacation fringe benefits.

    Science.gov (United States)

    2010-07-01

    ... vacation benefits, it would place the incumbent contractor at a distinct competitive disadvantage as well... service. Rather, as illustrated below, the reason(s) for an employee's absence from work is the primary... the full amount of the employee's vacation benefit. (2) The requirements for furnishing data relative...

  16. Application of distinct element method of toppling failure of slope

    International Nuclear Information System (INIS)

    Ishida, Tsuyoshi; Hibino, Satoshi; Kitahara, Yoshihiro; Ito, Hiroshi

    1984-01-01

    The authors have pointed out, in the latest report, that DEM (Distinct Element Method) seems to be a very helpful numerical method to examine the stability of fissured rock slopes, in which toppling failure would occur during earthquakes. In this report, the applicability of DEM for such rock slopes is examined through the following comparisons between theoretical results and DEM results, referring Voegele's works (1982): (1) Stability of one block on a slope. (2) Failure of a rock block column composed of 10 same size rectangular blocks. (3) Cable force required to make a slope stable. Through above 3 comparisons, it seems that DEM give the reasonable results. Considering that these problems may not be treated by the other numerical methods such as FEM and so on, so DEM seems to be a very useful method for fissured rock slope analysis. (author)

  17. Social Media Blurred the Distinction Between Author and Reader

    Science.gov (United States)

    Lambiotte, Renaud

    The last few years have seen the emergence of the sharing economy. As social media blurred the distinction between author and reader, everyone can now offer or receive services thanks to the networking tools provided by new technological companies. Take Uber, and its billion of journeys in 2015 alone, with tens of thousands of vehicles crawling every moment in the globe's biggest cities. As often, when confronted with a technological change, we observe a polarization of society, and the search for an equilibrium characterized by new norms, rights, and obligations. Understanding the mechanisms behind this re-organization requires an integrated, interdisciplinary approach, covering an intricate web of legal, societal, economical, and computational issues which, we believe, could benefit from a complex systems perspective. As a first step, we are currently studying the dynamics of pricing in Uber. In this new de-regulated world, journey prices fluctuate in time depending on traffic but also on the service's perceived balance of passenger demand and driver supply...

  18. Distinctions, Affiliations, and Professional Knowledge in Financial Reform Commissions

    DEFF Research Database (Denmark)

    Seabrooke, Leonard; Tsingou, Eleni

    the different stresses in reports with and without clear mandates, and the role of important members of the policy community in promoting particular reform ideas. The article finds that differences in ideas emerging from the financial reform expert groups reflect nested power relationships in the commissioning...... the reports. Fractal distinctions, such as between ‘behavior’ or ‘system’ as a reform focus, allow us to locate the object of regulation within expert groups, experts’ professional context, and the politics behind the commissioning of work. Analyzing fractal distinctions provides a useful way to understand...... of work, constituent audiences, and reform priorities among governing institutions, rather than distinct ‘European’ and ‘American’ ideas....

  19. Tortuous Microvessels Contribute to Wound Healing via Sprouting Angiogenesis.

    Science.gov (United States)

    Chong, Diana C; Yu, Zhixian; Brighton, Hailey E; Bear, James E; Bautch, Victoria L

    2017-10-01

    Wound healing is accompanied by neoangiogenesis, and new vessels are thought to originate primarily from the microcirculation; however, how these vessels form and resolve during wound healing is poorly understood. Here, we investigated properties of the smallest capillaries during wound healing to determine their spatial organization and the kinetics of formation and resolution. We used intravital imaging and high-resolution microscopy to identify a new type of vessel in wounds, called tortuous microvessels. Longitudinal studies showed that tortuous microvessels increased in frequency after injury, normalized as the wound healed, and were closely associated with the wound site. Tortuous microvessels had aberrant cell shapes, increased permeability, and distinct interactions with circulating microspheres, suggesting altered flow dynamics. Moreover, tortuous microvessels disproportionately contributed to wound angiogenesis by sprouting exuberantly and significantly more frequently than nearby normal capillaries. A new type of transient wound vessel, tortuous microvessels, sprout dynamically and disproportionately contribute to wound-healing neoangiogenesis, likely as a result of altered properties downstream of flow disturbances. These new findings suggest entry points for therapeutic intervention. © 2017 The Authors.

  20. Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight

    Directory of Open Access Journals (Sweden)

    Natalia Zamorano Cuervo

    2018-01-01

    Full Text Available The mitochondrial antiviral signaling (MAVS adaptor protein is a central signaling hub required for cells to mount an antiviral response following virus sensing by retinoic acid-inducible gene I (RIG-I-like receptors. MAVS localizes in the membrane of mitochondria and peroxisomes and in mitochondrial-associated endoplasmic reticulum membranes. Structural and functional studies have revealed that MAVS activity relies on the formation of functional high molecular weight prion-like aggregates. The formation of protein aggregates typically relies on a dynamic transition between oligomerization and aggregation states. The existence of intermediate state(s of MAVS polymers, other than aggregates, has not yet been documented. Here, we used a combination of non-reducing SDS-PAGE and semi-denaturing detergent agarose gel electrophoresis (SDD-AGE to resolve whole cell extract preparations to distinguish MAVS polymerization states. While SDD-AGE analysis of whole cell extracts revealed the formation of previously described high molecular weight prion-like aggregates upon constitutively active RIG-I ectopic expression and virus infection, non-reducing SDS-PAGE allowed us to demonstrate the induction of lower molecular weight oligomers. Cleavage of MAVS using the NS3/4A protease revealed that anchoring to intracellular membranes is required for the appropriate polymerization into active high molecular weight aggregates. Altogether, our data suggest that RIG-I-dependent MAVS activation involves the coexistence of MAVS polymers with distinct molecular weights.

  1. Identifying and Managing Engineering Design Requirements for Emerging Markets

    DEFF Research Database (Denmark)

    Li, Xuemeng

    , especially for those companies originally from developed markets, to acquire an in-depth understanding of particular design requirements in emerging markets in order to adapt both company products and approaches in such contexts. Prior studies on the identification and management of design requirements have...... predominantly been conducted in the context of developed countries and relatively affluent markets. Emerging markets are distinct from developed markets in terms of numerous contextual factors, e.g., regulatory environments and competitive landscapes. These factors influence the requirement identification...... attention. There is a need for an overview of different perspectives in requirement identification for manufacturing companies and their corresponding assessments in the context of emerging markets. Therefore, this research project is motivated to 1) investigate the process of identifying and managing...

  2. Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication

    International Nuclear Information System (INIS)

    Gabet, Anne-Sophie; Moules, Vincent; Sibon, David; Nass, Catharie C.; Mortreux, Franck; Mauclere, Philippe; Gessain, Antoine; Murphy, Edward L.; Wattel, Eric

    2006-01-01

    As the replication pattern of leukemogenic PTLVs possesses a strong pathogenic impact, we investigated HTLV-2 replication in vivo in asymptomatic carriers belonging into 2 distinct populations infected by the same HTLV-2b subtype. They include epidemically infected American blood donors, in whom HTLV-2b has been present for only 30 years, and endemically infected Bakola Pygmies from Cameroon, characterized by a long viral endemicity (at least few generations). In blood donors, both the circulating proviral loads and the degree of infected cell proliferation were largely lower than those characterizing asymptomatic carriers infected with leukemogenic PTLVs (HTLV-1, STLV-1). This might contribute to explain the lack of known link between HTLV-2b infection and the development of malignancies in this population. In contrast, endemically infected individuals displayed high proviral loads resulting from the extensive proliferation of infected cells. The route and/or the duration of infection, viral genetic drift, host immune response, genetic background, co-infections or a combination thereof might have contributed to these differences between endemically and epidemically infected subjects. As the clonality pattern observed in endemically infected individuals is very reminiscent of that of leukemogenic PTLVs at the pre-leukemic stage, our results highlight the possible oncogenic effect of HTLV-2b infection in such population

  3. Regional inactivations of primate ventral prefrontal cortex reveal two distinct mechanisms underlying negative bias in decision making.

    Science.gov (United States)

    Clarke, Hannah F; Horst, Nicole K; Roberts, Angela C

    2015-03-31

    Dysregulation of the orbitofrontal and ventrolateral prefrontal cortices is implicated in anxiety and mood disorders, but the specific contributions of each region are unknown, including how they gate the impact of threat on decision making. To address this, the effects of GABAergic inactivation of these regions were studied in marmoset monkeys performing an instrumental approach-avoidance decision-making task that is sensitive to changes in anxiety. Inactivation of either region induced a negative bias away from punishment that could be ameliorated with anxiolytic treatment. However, whereas the effects of ventrolateral prefrontal cortex inactivation on punishment avoidance were seen immediately, those of orbitofrontal cortex inactivation were delayed and their expression was dependent upon an amygdala-anterior hippocampal circuit. We propose that these negative biases result from deficits in attentional control and punishment prediction, respectively, and that they provide the basis for understanding how distinct regional prefrontal dysregulation contributes to the heterogeneity of anxiety disorders with implications for cognitive-behavioral treatment strategies.

  4. When does State Interference with Property (now Amount to Expropriation? An Analysis of the Agri SA Court's State Acquisition Requirement (Part II

    Directory of Open Access Journals (Sweden)

    Ernst Jacobus Marais

    2015-04-01

    Full Text Available Section 25 of the Constitution provides two ways in which the state may interfere with property rights, namely deprivation (section 25(1 and expropriation (section 25(2. As only the latter requires compensation, there is an incentive for property holders to label any infringement with their property as expropriation in the hope of being compensated for their losses. It is therefore essential to have a principled distinction between deprivation and expropriation, especially given the danger that uncertainty in this regard can hold for legitimate land reform initiatives, which often entail severe limitations on property. This contribution attends to Agri South Africa v Minister for Minerals and Energy 2013 4 SA 1 (CC, where the Constitutional Court recently revisited this distinction and held that the distinguishing feature of expropriation is that it entails state acquisition of property. Without state acquisition the interference can (at most amount to deprivation. Unfortunately, viewing state acquisition as the "key requirement" for expropriation is problematic. Firstly, it ignores the true nature of this feature in that it is only a consequence of a valid expropriation rather than a pre-requisite for it – at least in terms of pre-constitutional law. It is therefore inaccurate, concerning both pre- and post-constitutional expropriation case law, to regard acquisition as an indispensable requirement for expropriation. Secondly, limiting the constitutional property inquiry to whether or not the state acquired property appears inadequate as a means of solving difficult cases where the state acquires property pursuant to infringements like taxation and criminal forfeiture. As both these examples result in state acquisition, there must be another explanation of why they do not amount to expropriation.

  5. Diverse Kir expression contributes to distinct bimodal distribution of resting potentials and vasotone responses of arterioles.

    Directory of Open Access Journals (Sweden)

    Yuqin Yang

    Full Text Available The resting membrane potential (RP of vascular smooth muscle cells (VSMCs is a major determinant of cytosolic calcium concentration and vascular tone. The heterogeneity of RPs and its underlying mechanism among different vascular beds remain poorly understood. We compared the RPs and vasomotion properties between the guinea pig spiral modiolar artery (SMA, brain arterioles (BA and mesenteric arteries (MA. We found: 1 RPs showed a robust bimodal distribution peaked at -76 and -40 mV evenly in the SMA, unevenly at -77 and -51 mV in the BA and ~-71 and -52 mV in the MA. Ba(2+ 0.1 mM eliminated their high RP peaks ~-75 mV. 2 Cells with low RP (~-45 mV hyperpolarized in response to 10 mM extracellular K(+, while cells with a high RP depolarized, and cells with intermediate RP (~-58 mV displayed an initial hyperpolarization followed by prolonged depolarization. Moderate high K(+ typically induced dilation, constriction and a dilation followed by constriction in the SMA, MA and BA, respectively. 3 Boltzmann-fit analysis of the Ba(2+-sensitive inward rectifier K(+ (Kir whole-cell current showed that the maximum Kir conductance density significantly differed among the vessels, and the half-activation voltage was significantly more negative in the MA. 4 Corresponding to the whole-cell data, computational modeling simulated the three RP distribution patterns and the dynamics of RP changes obtained experimentally, including the regenerative swift shifts between the two RP levels after reaching a threshold. 5 Molecular works revealed strong Kir2.1 and Kir2.2 transcripts and Kir2.1 immunolabeling in all 3 vessels, while Kir2.3 and Kir2.4 transcript levels varied. We conclude that a dense expression of functional Kir2.X channels underlies the more negative RPs in endothelial cells and a subset of VSMC in these arterioles, and the heterogeneous Kir function is primarily responsible for the distinct bimodal RPs among these arterioles. The fast Kir

  6. Timing the Generation of Distinct Retinal Cells by Homeobox Proteins

    Science.gov (United States)

    Decembrini, Sarah; Andreazzoli, Massimiliano; Vignali, Robert; Barsacchi, Giuseppina; Cremisi, Federico

    2006-01-01

    The reason why different types of vertebrate nerve cells are generated in a particular sequence is still poorly understood. In the vertebrate retina, homeobox genes play a crucial role in establishing different cell identities. Here we provide evidence of a cellular clock that sequentially activates distinct homeobox genes in embryonic retinal cells, linking the identity of a retinal cell to its time of generation. By in situ expression analysis, we found that the three Xenopus homeobox genes Xotx5b, Xvsx1, and Xotx2 are initially transcribed but not translated in early retinal progenitors. Their translation requires cell cycle progression and is sequentially activated in photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). Furthermore, by in vivo lipofection of “sensors” in which green fluorescent protein translation is under control of the 3′ untranslated region (UTR), we found that the 3′ UTRs of Xotx5b, Xvsx1, and Xotx2 are sufficient to drive a spatiotemporal pattern of translation matching that of the corresponding proteins and consistent with the time of generation of photoreceptors (Xotx5b) and bipolar cells (Xvsx1 and Xotx2). The block of cell cycle progression of single early retinal progenitors impairs their differentiation as photoreceptors and bipolar cells, but is rescued by the lipofection of Xotx5b and Xvsx1 coding sequences, respectively. This is the first evidence to our knowledge that vertebrate homeobox proteins can work as effectors of a cellular clock to establish distinct cell identities. PMID:16903786

  7. Timing the generation of distinct retinal cells by homeobox proteins.

    Directory of Open Access Journals (Sweden)

    Sarah Decembrini

    2006-09-01

    Full Text Available The reason why different types of vertebrate nerve cells are generated in a particular sequence is still poorly understood. In the vertebrate retina, homeobox genes play a crucial role in establishing different cell identities. Here we provide evidence of a cellular clock that sequentially activates distinct homeobox genes in embryonic retinal cells, linking the identity of a retinal cell to its time of generation. By in situ expression analysis, we found that the three Xenopus homeobox genes Xotx5b, Xvsx1, and Xotx2 are initially transcribed but not translated in early retinal progenitors. Their translation requires cell cycle progression and is sequentially activated in photoreceptors (Xotx5b and bipolar cells (Xvsx1 and Xotx2. Furthermore, by in vivo lipofection of "sensors" in which green fluorescent protein translation is under control of the 3' untranslated region (UTR, we found that the 3' UTRs of Xotx5b, Xvsx1, and Xotx2 are sufficient to drive a spatiotemporal pattern of translation matching that of the corresponding proteins and consistent with the time of generation of photoreceptors (Xotx5b and bipolar cells (Xvsx1 and Xotx2. The block of cell cycle progression of single early retinal progenitors impairs their differentiation as photoreceptors and bipolar cells, but is rescued by the lipofection of Xotx5b and Xvsx1 coding sequences, respectively. This is the first evidence to our knowledge that vertebrate homeobox proteins can work as effectors of a cellular clock to establish distinct cell identities.

  8. Research in Library and Information Science and the Contribution of Ranganathan.

    Science.gov (United States)

    Mangla, P. B.

    1984-01-01

    Traces historical developments and recent trends in library and information science research in United States, Great Britain, and India; discusses factors contributing to developments in United States and United Kingdom; and reviews Ranganathan's contributions in detail. Some factors hindering research in India and areas which require research are…

  9. Serpins of oat (Avena sativa) grain with distinct reactive centres and inhibitory specificity

    DEFF Research Database (Denmark)

    Hejgaard, Jørn; Hauge, S.

    2002-01-01

    Most proteinase inhibitors from plant seeds are assumed to contribute to broad-spectrum protection against pests and pathogens. In oat (Avena sativa L.) grain the main serine proteinase inhibitors were found to be serpins, which utilize a unique mechanism of irreversible inhibition. Four distinct...... inhibitors of the serpin superfamily were detected by native PAGE as major seed albumins and purified by thiophilic adsorption and anion exchange chromatography. The four serpins OSZa-d are the first proteinase inhibitors characterized from this cereal. An amino acid sequence close to the blocked N...... by chymotrypsin at the putative reactive centre bond P-1 -P-1 ' Tyrdown arrowSer, and no inhibition was detected. Together the oat grain serpins have a broader inhibitory specificity against digestive serine proteinases than represented by the major serpins of wheat, rye or barley grain. Presumably the serpins...

  10. 6 The Contribution of bank and furface.cdr

    African Journals Online (AJOL)

    user

    2005-03-17

    Mar 17, 2005 ... using a single tracer Pb to determine the relative contribution of surface and bank sediments to the fluvial .... required to design effective sediment and ... The dry season spans from November to .... Bridge (n = 8) (n = 8).

  11. Identification of factors contributing to successful self-directed weight loss: a qualitative study.

    Science.gov (United States)

    Rafiei, N; Gill, T

    2017-11-21

    Despite the number of weight management programmes and their wide promotion, most overweight and obese individuals tend to lose weight on their own. The present study aimed to understand the characteristics and strategies of those who successfully engage in self-directed weight loss, which could empower other overweight and obese individuals with information and strategies to manage their weight on their own. Men and women who had lost at least 5% of their body weight without direct interaction with professionals or weight management programmes were recruited. Demographic data were collected by questionnaire and participants' weight-loss experiences were explored using semi- structured interviews to elicit in-depth individual experiences and perspectives. Iterative thematic method data analysis was used to generate themes describing contributing factors to the success of self-directed weight loss identified by participants. Most characteristics of those who successfully self-managed their weight loss were in line with those reported by successful weight losers participating in professional-led projects. However, strategies such as early embedding of new lifestyle behaviours into daily routine, the ability to learn from previous weight-loss experiences, and not requiring social support were identified as distinctive factors that contributed to the success of self-directed weight loss by participants of the present study. Overweight or obese individuals with strong internal motivation, problem-solving skills and self-reliance are more likely to be successful at achieving self-directed weight loss. The patients identified with these characteristics could be encouraged to self-manage their weight-loss process, leaving the places available in more resource-intensive professional-led programmes to those individuals unlikely to succeed on their own. © 2017 The British Dietetic Association Ltd.

  12. Genetic Determinism and the Innate-Acquired Distinction in Medicine

    Science.gov (United States)

    2009-01-01

    This article illustrates in which sense genetic determinism is still part of the contemporary interactionist consensus in medicine. Three dimensions of this consensus are discussed: kinds of causes, a continuum of traits ranging from monogenetic diseases to car accidents, and different kinds of determination due to different norms of reaction. On this basis, this article explicates in which sense the interactionist consensus presupposes the innate–acquired distinction. After a descriptive Part 1, Part 2 reviews why the innate–acquired distinction is under attack in contemporary philosophy of biology. Three arguments are then presented to provide a limited and pragmatic defense of the distinction: an epistemic, a conceptual, and a historical argument. If interpreted in a certain manner, and if the pragmatic goals of prevention and treatment (ideally specifying what medicine and health care is all about) are taken into account, then the innate–acquired distinction can be a useful epistemic tool. It can help, first, to understand that genetic determination does not mean fatalism, and, second, to maintain a system of checks and balances in the continuing nature–nurture debates. PMID:20234831

  13. The epidermis comprises autonomous compartments maintained by distinct stem cell populations

    DEFF Research Database (Denmark)

    Page, Mahalia E; Lombard, Patrick; Ng, Felicia

    2013-01-01

    populations. In contrast, upon wounding, stem cell progeny from multiple compartments acquire lineage plasticity and make permanent contributions to regenerating tissue. We further show that oncogene activation in Lrig1(+ve) cells drives hyperplasia but requires auxiliary stimuli for tumor formation....... In summary, our data demonstrate that epidermal stem cells are lineage restricted during homeostasis and suggest that compartmentalization may constitute a conserved mechanism underlying epithelial tissue maintenance....

  14. Distinct contributions of reactive oxygen species in amygdala to bee venom-induced spontaneous pain-related behaviors.

    Science.gov (United States)

    Lu, Yun-Fei; Neugebauer, Volker; Chen, Jun; Li, Zhen

    2016-04-21

    Reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, play essential roles in physiological plasticity and are also involved in the pathogenesis of persistent pain. Roles of peripheral and spinal ROS in pain have been well established, but much less is known about ROS in the amygdala, a brain region that plays an important role in pain modulation. The present study explored the contribution of ROS in the amygdala to bee venom (BV)-induced pain behaviors. Our data show that the amygdala is activated following subcutaneous BV injection into the left hindpaw, which is reflected in the increased number of c-Fos positive cells in the central and basolateral amygdala nuclei in the right hemisphere. Stereotaxic administration of a ROS scavenger (tempol, 10mM), NADPH oxidase inhibitor (baicalein, 5mM) or lipoxygenase inhibitor (apocynin, 10mM) into the right amygdala attenuated the BV-induced spontaneous licking and lifting behaviors, but had no effect on BV-induced paw flinch reflexes. Our study provides further evidence for the involvement of the amygdala in nociceptive processing and pain behaviors, and that ROS in amygdala may be a potential target for treatment strategies to inhibit pain. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  15. Controlling the gain contribution of background emitters in few-quantum-dot microlasers

    Science.gov (United States)

    Gericke, F.; Segnon, M.; von Helversen, M.; Hopfmann, C.; Heindel, T.; Schneider, C.; Höfling, S.; Kamp, M.; Musiał, A.; Porte, X.; Gies, C.; Reitzenstein, S.

    2018-02-01

    We provide experimental and theoretical insight into single-emitter lasing effects in a quantum dot (QD)-microlaser under controlled variation of background gain provided by off-resonant discrete gain centers. For that purpose, we apply an advanced two-color excitation concept where the background gain contribution of off-resonant QDs can be continuously tuned by precisely balancing the relative excitation power of two lasers emitting at different wavelengths. In this way, by selectively exciting a single resonant QD and off-resonant QDs, we identify distinct single-QD signatures in the lasing characteristics and distinguish between gain contributions of a single resonant emitter and a countable number of off-resonant background emitters to the optical output of the microlaser. Our work addresses the important question whether single-QD lasing is feasible in experimentally accessible systems and shows that, for the investigated microlaser, the single-QD gain needs to be supported by the background gain contribution of off-resonant QDs to reach the transition to lasing. Interestingly, while a single QD cannot drive the investigated micropillar into lasing, its relative contribution to the emission can be as high as 70% and it dominates the statistics of emitted photons in the intermediate excitation regime below threshold.

  16. Clinical characteristics and distinctiveness of DSM-5 eating disorder diagnoses: findings from a large naturalistic clinical database

    Science.gov (United States)

    2013-01-01

    Background DSM-IV eating disorder (ED) diagnoses have been criticized for lack of clinical utility, diagnostic instability, and over-inclusiveness of the residual category “ED not otherwise specified” (EDNOS). Revisions made in DSM-5 attempt to generate a more scientifically valid and clinically relevant system of ED classification. The aim with the present study was to examine clinical characteristics and distinctiveness of the new DSM-5 ED diagnoses, especially concerning purging disorder (PD). Methods Using a large naturalistic Swedish ED database, 2233 adult women were diagnosed using DSM-5. Initial and 1-year follow-up psychopathology data were analyzed. Measures included the Eating Disorder Examination Questionnaire, Structural Eating Disorder Interview, Clinical Impairment Assessment, Structural Analysis of Social Behavior, Comprehensive Psychiatric Rating Scale, and Structured Clinical Interview for DSM-IV Axis I Disorders. Results Few meaningful differences emerged between anorexia nervosa binge/purge subtype (ANB/P), PD, and bulimia nervosa (BN). Unspecified Feeding and Eating Disorders (UFED) showed significantly less severity compared to other groups. Conclusions PD does not appear to constitute a distinct diagnosis, the distinction between atypical AN and PD requires clarification, and minimum inclusion criteria for UFED are needed. Further sub-classification is unlikely to improve clinical utility. Instead, better delineation of commonalities is important. PMID:24999410

  17. Identification of chilling and heat requirements of cherry trees--a statistical approach.

    Science.gov (United States)

    Luedeling, Eike; Kunz, Achim; Blanke, Michael M

    2013-09-01

    Most trees from temperate climates require the accumulation of winter chill and subsequent heat during their dormant phase to resume growth and initiate flowering in the following spring. Global warming could reduce chill and hence hamper the cultivation of high-chill species such as cherries. Yet determining chilling and heat requirements requires large-scale controlled-forcing experiments, and estimates are thus often unavailable. Where long-term phenology datasets exist, partial least squares (PLS) regression can be used as an alternative, to determine climatic requirements statistically. Bloom dates of cherry cv. 'Schneiders späte Knorpelkirsche' trees in Klein-Altendorf, Germany, from 24 growing seasons were correlated with 11-day running means of daily mean temperature. Based on the output of the PLS regression, five candidate chilling periods ranging in length from 17 to 102 days, and one forcing phase of 66 days were delineated. Among three common chill models used to quantify chill, the Dynamic Model showed the lowest variation in chill, indicating that it may be more accurate than the Utah and Chilling Hours Models. Based on the longest candidate chilling phase with the earliest starting date, cv. 'Schneiders späte Knorpelkirsche' cherries at Bonn exhibited a chilling requirement of 68.6 ± 5.7 chill portions (or 1,375 ± 178 chilling hours or 1,410 ± 238 Utah chill units) and a heat requirement of 3,473 ± 1,236 growing degree hours. Closer investigation of the distinct chilling phases detected by PLS regression could contribute to our understanding of dormancy processes and thus help fruit and nut growers identify suitable tree cultivars for a future in which static climatic conditions can no longer be assumed. All procedures used in this study were bundled in an R package ('chillR') and are provided as Supplementary materials. The procedure was also applied to leaf emergence dates of walnut (cv. 'Payne') at Davis, California.

  18. Monoclonal Antibodies Specific for STAT3β Reveal Its Contribution to Constitutive STAT3 Phosphorylation in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Uddalak Bharadwaj

    2014-09-01

    Full Text Available Since its discovery in mice and humans 19 years ago, the contribution of alternatively spliced Stat3, Stat3β, to the overall functions of Stat3 has been controversial. Tyrosine-phosphorylated (p Stat3β homodimers are more stable, bind DNA more avidly, are less susceptible to dephosphorylation, and exhibit distinct intracellular dynamics, most notably markedly prolonged nuclear retention, compared to pStat3α homodimers. Overexpression of one or the other isoform in cell lines demonstrated that Stat3β acted as a dominant-negative of Stat3α in transformation assays; however, studies with mouse strains deficient in one or the other isoform indicated distinct contributions of Stat3 isoforms to inflammation. Current immunological reagents cannot differentiate Stat3β proteins derived from alternative splicing vs. proteolytic cleavage of Stat3α. We developed monoclonal antibodies that recognize the 7 C-terminal amino acids unique to Stat3β (CT7 and do not cross-react with Stat3α. Immunoblotting studies revealed that levels of Stat3β protein, but not Stat3α, in breast cancer cell lines positively correlated with overall pStat3 levels, suggesting that Stat3β may contribute to constitutive Stat3 activation in this tumor system. The ability to unambiguously discriminate splice alternative Stat3β from proteolytic Stat3β and Stat3α will provide new insights into the contribution of Stat3β vs. Stat3α to oncogenesis, as well as other biological and pathological processes.

  19. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome

    DEFF Research Database (Denmark)

    Morselli, Eugenia; Mariño, Guillermo; Bennetzen, Martin V

    2011-01-01

    Autophagy protects organelles, cells, and organisms against several stress conditions. Induction of autophagy by resveratrol requires the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 (SIRT1). In this paper, we show that the acetylase inhibitor spermidine stimulates autophagy...... independent of SIRT1 in human and yeast cells as well as in nematodes. Although resveratrol and spermidine ignite autophagy through distinct mechanisms, these compounds stimulate convergent pathways that culminate in concordant modifications of the acetylproteome. Both agents favor convergent deacetylation...... and acetylation reactions in the cytosol and in the nucleus, respectively. Both resveratrol and spermidine were able to induce autophagy in cytoplasts (enucleated cells). Moreover, a cytoplasm-restricted mutant of SIRT1 could stimulate autophagy, suggesting that cytoplasmic deacetylation reactions dictate...

  20. Convergent Metabolic Specialization through Distinct Evolutionary Paths in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    La Rosa, Ruggero; Johansen, Helle Krogh; Molin, Søren

    2018-01-01

    fibrosis (CF) infection. In this work, we investigated how and through which trajectories evolution of Pseudomonas aeruginosa occurs when migrating from the environment to the airways of CF patients, and specifically, we determined reduction of growth rate and metabolic specialization as signatures...... of adaptive evolution. We show that central metabolic pathways of three distinct Pseudomonas aeruginosa lineages coevolving within the same environment become restructured at the cost of versatility during long-term colonization. Cell physiology changes from naive to adapted phenotypes resulted in (i......) alteration of growth potential that particularly converged to a slow-growth phenotype, (ii) alteration of nutritional requirements due to auxotrophy, (iii) tailored preference for carbon source assimilation from CF sputum, (iv) reduced arginine and pyruvate fermentation processes, and (v) increased oxygen...

  1. Contesting the science/ethics distinction in the review of clinical research

    Science.gov (United States)

    Dawson, Angus J; Yentis, Steve M

    2007-01-01

    Recent policy in relation to clinical research proposals in the UK has distinguished between two types of review: scientific and ethical. This distinction has been formally enshrined in the recent changes to research ethics committee (REC) structure and operating procedures, introduced as the UK response to the EU Directive on clinical trials. Recent reviews and recommendations have confirmed the place of the distinction and the separate review processes. However, serious reservations can be mounted about the science/ethics distinction and the policy of separate review that has been built upon it. We argue here that, first, the science/ethics distinction is incoherent, and, second, that RECs should not only be permitted to consider a study's science, but that they have anobligation do so. PMID:17329389

  2. Validity of Sensory Systems as Distinct Constructs

    OpenAIRE

    Su, Chia-Ting; Parham, L. Diane

    2014-01-01

    Confirmatory factor analysis testing whether sensory questionnaire items represented distinct sensory system constructs found, using data from two age groups, that such constructs can be measured validly using questionnaire data.

  3. Identity-specific motivation: How distinct identities direct self-regulation across distinct situations.

    Science.gov (United States)

    Browman, Alexander S; Destin, Mesmin; Molden, Daniel C

    2017-12-01

    Research on self-regulation has traditionally emphasized that people's thoughts and actions are guided by either (a) domain-general motivations that emerge from a cumulative history of life experiences, or (b) situation-specific motivations that emerge in immediate response to the incentives present in a particular context. However, more recent studies have illustrated the importance of understanding the interplay between such domain-general and situation-specific motivations across the types of contexts people regularly encounter. The present research, therefore, expands existing perspectives on self-regulation by investigating how people's identities -the internalized roles, relationships, and social group memberships that define who they are-systemically guide when and how different domain-general motivations are activated within specific types of situations. Using the motivational framework described by regulatory focus theory (Higgins, 1997), Studies 1 and 2 demonstrate that people indeed have distinct, identity-specific motivations that uniquely influence their current self-regulation when such identities are active. Studies 3-5 then begin to explore how identity-specific motivations are situated within people's larger self-concept. Studies 3a and 3b demonstrate that the less compatible people's specific identities, the more distinct are the motivations connected to those identities. Studies 4-5 then provide some initial, suggestive evidence that identity-specific motivations are not a separate, superordinate feature of people's identities that then alter how they pursue any subordinate, identity-relevant traits, but instead that such motivations emerge from the cumulative motivational significance of the subordinate traits to which the identities themselves become attached. Implications for understanding the role of the self-concept in self-regulation are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  4. Agent-specific learning signals for self-other distinction during mentalising.

    Directory of Open Access Journals (Sweden)

    Sam Ereira

    2018-04-01

    Full Text Available Humans have a remarkable ability to simulate the minds of others. How the brain distinguishes between mental states attributed to self and mental states attributed to someone else is unknown. Here, we investigated how fundamental neural learning signals are selectively attributed to different agents. Specifically, we asked whether learning signals are encoded in agent-specific neural patterns or whether a self-other distinction depends on encoding agent identity separately from this learning signal. To examine this, we tasked subjects to learn continuously 2 models of the same environment, such that one was selectively attributed to self and the other was selectively attributed to another agent. Combining computational modelling with magnetoencephalography (MEG enabled us to track neural representations of prediction errors (PEs and beliefs attributed to self, and of simulated PEs and beliefs attributed to another agent. We found that the representational pattern of a PE reliably predicts the identity of the agent to whom the signal is attributed, consistent with a neural self-other distinction implemented via agent-specific learning signals. Strikingly, subjects exhibiting a weaker neural self-other distinction also had a reduced behavioural capacity for self-other distinction and displayed more marked subclinical psychopathological traits. The neural self-other distinction was also modulated by social context, evidenced in a significantly reduced decoding of agent identity in a nonsocial control task. Thus, we show that self-other distinction is realised through an encoding of agent identity intrinsic to fundamental learning signals. The observation that the fidelity of this encoding predicts psychopathological traits is of interest as a potential neurocomputational psychiatric biomarker.

  5. Embarrassment: its distinct form and appeasement functions.

    Science.gov (United States)

    Keltner, D; Buswell, B N

    1997-11-01

    The authors address 2 questions about embarrassment. First, Is embarrassment a distinct emotion? The evidence indicates that the antecedents, experience, and display of embarrassment, and to a limited extent its autonomic physiology, are distinct from shame, guilt, and amusement and share the dynamic, temporal characteristics of emotion. Second, What are the theoretical accounts of embarrassment? Three accounts focus on the causes of embarrassment, positioning that it follows the loss of self-esteem, concern for others' evaluations, or absence of scripts to guide interactions. A fourth account focuses on the effects of the remedial actions of embarrassment, which correct preceding transgressions. A fifth account focuses on the functional parallels between embarrassment and nonhuman appeasement. The discussion focuses on unanswered questions about embarrassment.

  6. Plasma neuropeptide Y levels differ in distinct diabetic conditions.

    Science.gov (United States)

    Ilhan, Aysegül; Rasul, Sazan; Dimitrov, Alexander; Handisurya, Ammon; Gartner, Wolfgang; Baumgartner-Parzer, Sabina; Wagner, Ludwig; Kautzky-Willer, Alexandra; Base, Wolfgang

    2010-12-01

    Neuropeptide Y (NPY) is an important hormone in appetite regulation. Although the contribution of NPY to metabolic disease has been previously demonstrated, there are only a few reports addressing NPY plasma levels under distinct diabetic conditions. In this study we evaluated NPY plasma levels in diabetes mellitus type 2 (DM2) patients with (n=34) and without (n=34) diabetic polyneuropathy (PNP) and compared these with age and gender matched healthy controls (n=34). We also analyzed NPY plasma levels in gestational diabetes mellitus (GDM) patients with age and pregnancy-week matched controls with normal glucose tolerance (NGT). NPY concentration was determined using a commercially available radioimmunoassay kit. In addition, metabolic parameters of DM2 and GDM patients were recorded. One-way ANOVA tests with appropriate post hoc corrections showed elevated levels of NPY in DM2 patients with and without PNP when compared with those of healthy controls (122.32±40.86 and 117.33±29.92 vs. 84.65±52.17 pmol/L; pwomen with NGT (74.87±14.36 vs. 84.82±51.13 pmol/L, respectively). Notably, the NPY concentration correlated positively with insulin levels in DM2 patients (R=0.35, pDM2 pathology. Copyright © 2010 Elsevier Ltd. All rights reserved.

  7. Distinct growth of the nasomaxillary complex in Au. sediba.

    Science.gov (United States)

    Lacruz, Rodrigo S; Bromage, Timothy G; O'Higgins, Paul; Toro-Ibacache, Viviana; Warshaw, Johanna; Berger, Lee R

    2015-10-15

    Studies of facial ontogeny in immature hominins have contributed significantly to understanding the evolution of human growth and development. The recently discovered hominin species Autralopithecus sediba is represented by a well-preserved and nearly complete facial skeleton of a juvenile (MH1) which shows a derived facial anatomy. We examined MH1 using high radiation synchrotron to interpret features of the oronasal complex pertinent to facial growth. We also analyzed bone surface microanatomy to identify and map fields of bone deposition and bone resorption, which affect the development of the facial skeleton. The oronasal anatomy (premaxilla-palate-vomer architecture) is similar to other Australopithecus species. However surface growth remodeling of the midface (nasomaxillary complex) differs markedly from Australopithecus, Paranthropus, early Homo and from KNM-WT 15000 (H. erectus/ergaster) showing a distinct distribution of vertically disposed alternating depository and resorptive fields in relation to anterior dental roots and the subnasal region. The ontogeny of the MH1 midface superficially resembles some H. sapiens in the distribution of remodeling fields. The facial growth of MH1 appears unique among early hominins representing an evolutionary modification in facial ontogeny at 1.9 my, or to changes in masticatory system loading associated with diet.

  8. Distinct subsets of Eve-positive pericardial cells stabilise cardiac outflow and contribute to Hox gene-triggered heart morphogenesis in Drosophila.

    Science.gov (United States)

    Zmojdzian, Monika; de Joussineau, Svetlana; Da Ponte, Jean Philippe; Jagla, Krzysztof

    2018-01-17

    The Drosophila heart, composed of discrete subsets of cardioblasts and pericardial cells, undergoes Hox-triggered anterior-posterior morphogenesis, leading to a functional subdivision into heart proper and aorta, with its most anterior part forming a funnel-shaped cardiac outflow. Cardioblasts differentiate into Tin-positive 'working myocytes' and Svp-expressing ostial cells. However, developmental fates and functions of heart-associated pericardial cells remain elusive. Here, we show that the pericardial cells that express the transcription factor Even Skipped adopt distinct fates along the anterior-posterior axis. Among them, the most anterior Antp-Ubx-AbdA - negative cells form a novel cardiac outflow component we call the outflow hanging structure, whereas the Antp-expressing cells differentiate into wing heart precursors. Interestingly, Hox gene expression in the Even Skipped-positive cells not only underlies their antero-posterior diversification, but also influences heart morphogenesis in a non-cell-autonomous way. In brief, we identify a new cardiac outflow component derived from a subset of Even Skipped-expressing cells that stabilises the anterior heart tip, and demonstrate non-cell-autonomous effects of Hox gene expression in the Even Skipped-positive cells on heart morphogenesis. © 2018. Published by The Company of Biologists Ltd.

  9. Culture and the distinctiveness motive: constructing identity in individualistic and collectivistic contexts.

    Science.gov (United States)

    Becker, Maja; Vignoles, Vivian L; Owe, Ellinor; Brown, Rupert; Smith, Peter B; Easterbrook, Matt; Herman, Ginette; de Sauvage, Isabelle; Bourguignon, David; Torres, Ana; Camino, Leoncio; Lemos, Flávia Cristina Silveira; Ferreira, M Cristina; Koller, Silvia H; González, Roberto; Carrasco, Diego; Cadena, Maria Paz; Lay, Siugmin; Wang, Qian; Bond, Michael Harris; Trujillo, Elvia Vargas; Balanta, Paola; Valk, Aune; Mekonnen, Kassahun Habtamu; Nizharadze, George; Fülöp, Marta; Regalia, Camillo; Manzi, Claudia; Brambilla, Maria; Harb, Charles; Aldhafri, Said; Martin, Mariana; Macapagal, Ma Elizabeth J; Chybicka, Aneta; Gavreliuc, Alin; Buitendach, Johanna; Gallo, Inge Schweiger; Ozgen, Emre; Güner, Ulkü E; Yamakoğlu, Nil

    2012-04-01

    The motive to attain a distinctive identity is sometimes thought to be stronger in, or even specific to, those socialized into individualistic cultures. Using data from 4,751 participants in 21 cultural groups (18 nations and 3 regions), we tested this prediction against our alternative view that culture would moderate the ways in which people achieve feelings of distinctiveness, rather than influence the strength of their motivation to do so. We measured the distinctiveness motive using an indirect technique to avoid cultural response biases. Analyses showed that the distinctiveness motive was not weaker-and, if anything, was stronger-in more collectivistic nations. However, individualism-collectivism was found to moderate the ways in which feelings of distinctiveness were constructed: Distinctiveness was associated more closely with difference and separateness in more individualistic cultures and was associated more closely with social position in more collectivistic cultures. Multilevel analysis confirmed that it is the prevailing beliefs and values in an individual's context, rather than the individual's own beliefs and values, that account for these differences. (c) 2012 APA, all rights reserved.

  10. Separate elements of episodic memory subserved by distinct hippocampal-prefrontal connections.

    Science.gov (United States)

    Barker, Gareth R I; Banks, Paul J; Scott, Hannah; Ralph, G Scott; Mitrophanous, Kyriacos A; Wong, Liang-Fong; Bashir, Zafar I; Uney, James B; Warburton, E Clea

    2017-02-01

    Episodic memory formation depends on information about a stimulus being integrated within a precise spatial and temporal context, a process dependent on the hippocampus and prefrontal cortex. Investigations of putative functional interactions between these regions are complicated by multiple direct and indirect hippocampal-prefrontal connections. Here application of a pharmacogenetic deactivation technique enabled us to investigate the mnemonic contributions of two direct hippocampal-medial prefrontal cortex (mPFC) pathways, one arising in the dorsal CA1 (dCA1) and the other in the intermediate CA1 (iCA1). While deactivation of either pathway impaired episodic memory, the resulting pattern of mnemonic deficits was different: deactivation of the dCA1→mPFC pathway selectively disrupted temporal order judgments while iCA1→mPFC pathway deactivation disrupted spatial memory. These findings reveal a previously unsuspected division of function among CA1 neurons that project directly to the mPFC. Such subnetworks may enable the distinctiveness of contextual information to be maintained in an episodic memory circuit.

  11. Distinct timing mechanisms produce discrete and continuous movements.

    Directory of Open Access Journals (Sweden)

    Raoul Huys

    2008-04-01

    Full Text Available The differentiation of discrete and continuous movement is one of the pillars of motor behavior classification. Discrete movements have a definite beginning and end, whereas continuous movements do not have such discriminable end points. In the past decade there has been vigorous debate whether this classification implies different control processes. This debate up until the present has been empirically based. Here, we present an unambiguous non-empirical classification based on theorems in dynamical system theory that sets discrete and continuous movements apart. Through computational simulations of representative modes of each class and topological analysis of the flow in state space, we show that distinct control mechanisms underwrite discrete and fast rhythmic movements. In particular, we demonstrate that discrete movements require a time keeper while fast rhythmic movements do not. We validate our computational findings experimentally using a behavioral paradigm in which human participants performed finger flexion-extension movements at various movement paces and under different instructions. Our results demonstrate that the human motor system employs different timing control mechanisms (presumably via differential recruitment of neural subsystems to accomplish varying behavioral functions such as speed constraints.

  12. Soft and hard pomerons: Is there a distinction?

    International Nuclear Information System (INIS)

    Bjorken, J.D.

    1991-07-01

    One of the big unsolved problems of QCD remains the problem of the Pomeron: what is the relation of high energy elastic and diffractive phenomena to the underlying theory? This is not a subject in which I have actively worked. But my interest in it has in this year increased greatly. The reason has to do with ideas for experimentation at SSC/LHC which either directly address the problem or which require the understanding of strong-interaction diffractive phenomena as backgrounds for discovery-physics processes involving electroweak boson exchanges. I will in this talk omit these motivations, which can be found elsewhere, and instead concentrate on some personal veiwpoints regarding the Pomeron which may or may not be conventional. The main question has to do with the distinction between the original, old-fashioned ''soft'' Pomeron of the 1960s, built out of multiperipheral hadron-exchanges, and the more modern perturbative-QCD ''hard'' Pomeron, built out of multiperipheral gluon exchanges. The perspective I offer comes mainly from two sources: one is heavy-flavor physics, and the other is the Manohar-Georgi view of constituent quark physics. 27 refs., 5 figs

  13. Interaction of the amyloid precursor protein-like protein 1 (APLP1) E2 domain with heparan sulfate involves two distinct binding modes

    Energy Technology Data Exchange (ETDEWEB)

    Dahms, Sven O., E-mail: sdahms@fli-leibniz.de [Leibniz Institute for Age Research (FLI), Beutenbergstrasse 11, 07745 Jena (Germany); Mayer, Magnus C. [Freie Universität Berlin, Thielallee 63, 14195 Berlin (Germany); Miltenyi Biotec GmbH, Robert-Koch-Strasse 1, 17166 Teterow (Germany); Roeser, Dirk [Leibniz Institute for Age Research (FLI), Beutenbergstrasse 11, 07745 Jena (Germany); Multhaup, Gerd [McGill University Montreal, Montreal, Quebec H3G 1Y6 (Canada); Than, Manuel E., E-mail: sdahms@fli-leibniz.de [Leibniz Institute for Age Research (FLI), Beutenbergstrasse 11, 07745 Jena (Germany)

    2015-03-01

    Two X-ray structures of APLP1 E2 with and without a heparin dodecasaccharide are presented, revealing two distinct binding modes of the protein to heparan sulfate. The data provide a mechanistic explanation of how APP-like proteins bind to heparan sulfates and how they specifically recognize nonreducing structures of heparan sulfates. Beyond the pathology of Alzheimer’s disease, the members of the amyloid precursor protein (APP) family are essential for neuronal development and cell homeostasis in mammals. APP and its paralogues APP-like protein 1 (APLP1) and APP-like protein 2 (APLP2) contain the highly conserved heparan sulfate (HS) binding domain E2, which effects various (patho)physiological functions. Here, two crystal structures of the E2 domain of APLP1 are presented in the apo form and in complex with a heparin dodecasaccharide at 2.5 Å resolution. The apo structure of APLP1 E2 revealed an unfolded and hence flexible N-terminal helix αA. The (APLP1 E2){sub 2}–(heparin){sub 2} complex structure revealed two distinct binding modes, with APLP1 E2 explicitly recognizing the heparin terminus but also interacting with a continuous heparin chain. The latter only requires a certain register of the sugar moieties that fits to a positively charged surface patch and contributes to the general heparin-binding capability of APP-family proteins. Terminal binding of APLP1 E2 to heparin specifically involves a structure of the nonreducing end that is very similar to heparanase-processed HS chains. These data reveal a conserved mechanism for the binding of APP-family proteins to HS and imply a specific regulatory role of HS modifications in the biology of APP and APP-like proteins.

  14. B7h-expressing dendritic cells and plasma B cells mediate distinct outcomes of ICOS costimulation in T cell-dependent antibody responses

    Directory of Open Access Journals (Sweden)

    Larimore Kevin

    2012-06-01

    Full Text Available Abstract Background The ICOS-B7h costimulatory receptor-ligand pair is required for germinal center formation, the production of isotype-switched antibodies, and antibody affinity maturation in response to T cell-dependent antigens. However, the potentially distinct roles of regulated B7h expression on B cells and dendritic cells in T cell-dependent antibody responses have not been defined. Results We generated transgenic mice with lineage-restricted B7h expression to assess the cell-type specific roles of B7h expression on B cells and dendritic cells in regulating T cell-dependent antibody responses. Our results show that endogenous B7h expression is reduced on B cells after activation in vitro and is also reduced in vivo on antibody-secreting plasma B cells in comparison to both naïve and germinal center B cells from which they are derived. Increasing the level of B7h expression on activated and plasma B cells in B-B7hTg mice led to an increase in the number of antibody-secreting plasma cells generated after immunization and a corresponding increase in the concentration of antigen-specific high affinity serum IgG antibodies of all isotypes, without affecting the number of responding germinal center B cells. In contrast, ICOS costimulation mediated by dendritic cells in DC-B7hTg mice contributed to germinal center formation and selectively increased IgG2a production without affecting the overall magnitude of antibody responses. Conclusions Using transgenic mice with lineage-restricted B7h expression, we have revealed distinct roles of ICOS costimulation mediated by dendritic cells and B cells in the regulation of T cell-dependent antibody responses.

  15. Molecular Dynamics Simulation of Barnase: Contribution of Noncovalent Intramolecular Interaction to Thermostability

    Directory of Open Access Journals (Sweden)

    Zhiguo Chen

    2013-01-01

    Full Text Available Bacillus amyloliquefaciens ribonuclease Barnase (RNase Ba is a 12 kD (kilodalton small extracellular ribonuclease. It has broad application prospects in agriculture, clinical medicine, pharmaceutical, and so forth. In this work, the thermal stability of Barnase has been studied using molecular dynamics simulation at different temperatures. The present study focuses on the contribution of noncovalent intramolecular interaction to protein stability and how they affect the thermal stability of the enzyme. Profiles of root mean square deviation and root mean square fluctuation identify thermostable and thermosensitive regions of Barnase. Analyses of trajectories in terms of secondary structure content, intramolecular hydrogen bonds and salt bridge interactions indicate distinct differences in different temperature simulations. In the simulations, Four three-member salt bridge networks (Asp8-Arg110-Asp12, Arg83-Asp75-Arg87, Lys66-Asp93-Arg69, and Asp54-Lys27-Glu73 have been identified as critical salt bridges for thermostability which are maintained stably at higher temperature enhancing stability of three hydrophobic cores. The study may help enlighten our knowledge of protein structural properties, noncovalent interactions which can stabilize secondary peptide structures or promote folding, and also help understand their actions better. Such an understanding is required for designing efficient enzymes with characteristics for particular applications at desired working temperatures.

  16. Contribution of organic farming to public goods in Denmark

    DEFF Research Database (Denmark)

    Jespersen, Lizzie Melby; Baggesen, Dorte Lau; Fog, Erik

    2017-01-01

    €”in particular in relation to the public goods Energy and Climate, which at present are not addressed in the EU Organic Regulation. Moreover, some organic farming requirements and practices cause dilemmas; e.g. more space per animal and outdoor access improves Animal Health and Welfare but at the same time has......The potential contribution of organic farming to the public goods, ‘Nature and Biodiversity’, ‘Environment’, ‘Energy and Climate’, ‘Human Health and Welfare’ and ‘Animal Health and Welfare’ in Denmark is guided and partly secured by the principles and specific requirements...... of the EU Organic Regulation. However, other factors, such as the production type, farm size, geographical location and—not the least—the management of the farm, also influence the contribution. Using the ban on synthetic pesticides and restricted use of antibiotics, including the requirements...

  17. Knowledge Affords Distinctive Processing in Memory

    Science.gov (United States)

    Hunt, R. Reed; Rawson, Katherine A.

    2011-01-01

    The effect of knowledge on memory generally is processing. However, both conceptual and empirical reasons exist to suspect that the organizational account is incomplete. Recently a revised version of that account has been proposed under the rubric of distinctiveness theory (Rawson & Van Overschelde, 2008). The goal of the experiments reported…

  18. Anomalous brain functional connectivity contributing to poor adaptive behavior in Down syndrome.

    Science.gov (United States)

    Pujol, Jesus; del Hoyo, Laura; Blanco-Hinojo, Laura; de Sola, Susana; Macià, Dídac; Martínez-Vilavella, Gerard; Amor, Marta; Deus, Joan; Rodríguez, Joan; Farré, Magí; Dierssen, Mara; de la Torre, Rafael

    2015-03-01

    Research in Down syndrome has substantially progressed in the understanding of the effect of gene overexpression at the molecular level, but there is a paucity of information on the ultimate consequences on overall brain functional organization. We have assessed the brain functional status in Down syndrome using functional connectivity MRI. Resting-state whole-brain connectivity degree maps were generated in 20 Down syndrome individuals and 20 control subjects to identify sites showing anomalous synchrony with other areas. A subsequent region-of-interest mapping served to detail the anomalies and to assess their potential contribution to poor adaptive behavior. Down syndrome individuals showed higher regional connectivity in a ventral brain system involving the amygdala/anterior temporal region and the ventral aspect of both the anterior cingulate and frontal cortices. By contrast, lower functional connectivity was identified in dorsal executive networks involving dorsal prefrontal and anterior cingulate cortices and posterior insula. Both functional connectivity increases and decreases contributed to account for patient scoring on adaptive behavior related to communication skills. The data overall suggest a distinctive functional organization with system-specific anomalies associated with reduced adaptive efficiency. Opposite effects were identified on distinct frontal and anterior temporal structures and relative sparing of posterior brain areas, which is generally consistent with Down syndrome cognitive profile. Relevantly, measurable connectivity changes, as a marker of the brain functional anomaly, could have a role in the development of therapeutic strategies addressed to improve the quality of life in Down syndrome individuals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. California Considers Adding Gays' Contributions to Textbooks

    Science.gov (United States)

    Manzo, Kathleen Kennedy

    2006-01-01

    A bill that has been sent to the floor of the California Senate would require textbooks used in public schools to include information on the roles and contributions of gay people throughout history, a move that could affect the content of instructional materials throughout much of the country. The measure would help build tolerance of diverse…

  20. Dual Diathesis-Stressor Model of Emotional and Linguistic Contributions to Developmental Stuttering

    Science.gov (United States)

    Walden, Tedra A.; Frankel, Carl B.; Buhr, Anthony P.; Johnson, Kia N.; Conture, Edward G.; Karrass, Jan M.

    2012-01-01

    This study assessed emotional and speech-language contributions to childhood stuttering. A dual diathesis-stressor framework guided this study, in which both linguistic requirements and skills, and emotion and its regulation, are hypothesized to contribute to stuttering. The language diathesis consists of expressive and receptive language skills.…

  1. Five Conditions Commonly Used to Down-regulate Tor Complex 1 Generate Different Physiological Situations Exhibiting Distinct Requirements and Outcomes*

    Science.gov (United States)

    Tate, Jennifer J.; Cooper, Terrance G.

    2013-01-01

    Five different physiological conditions have been used interchangeably to establish the sequence of molecular events needed to achieve nitrogen-responsive down-regulation of TorC1 and its subsequent regulation of downstream reporters: nitrogen starvation, methionine sulfoximine (Msx) addition, nitrogen limitation, rapamycin addition, and leucine starvation. Therefore, we tested a specific underlying assumption upon which the interpretation of data generated by these five experimental perturbations is premised. It is that they generate physiologically equivalent outcomes with respect to TorC1, i.e. its down-regulation as reflected by TorC1 reporter responses. We tested this assumption by performing head-to-head comparisons of the requirements for each condition to achieve a common outcome for a downstream proxy of TorC1 inactivation, nuclear Gln3 localization. We demonstrate that the five conditions for down-regulating TorC1 do not elicit physiologically equivalent outcomes. Four of the methods exhibit hierarchical Sit4 and PP2A phosphatase requirements to elicit nuclear Gln3-Myc13 localization. Rapamycin treatment required Sit4 and PP2A. Nitrogen limitation and short-term nitrogen starvation required only Sit4. G1 arrest-correlated, long-term nitrogen starvation and Msx treatment required neither PP2A nor Sit4. Starving cells of leucine or treating them with leucyl-tRNA synthetase inhibitors did not elicit nuclear Gln3-Myc13 localization. These data indicate that the five commonly used nitrogen-related conditions of down-regulating TorC1 are not physiologically equivalent and minimally involve partially differing regulatory mechanisms. Further, identical requirements for Msx treatment and long-term nitrogen starvation raise the possibility that their effects are achieved through a common regulatory pathway with glutamine, a glutamate or glutamine metabolite level as the sensed metabolic signal. PMID:23935103

  2. Liquidity spillover in international stock markets through distinct time scales.

    Science.gov (United States)

    Righi, Marcelo Brutti; Vieira, Kelmara Mendes

    2014-01-01

    This paper identifies liquidity spillovers through different time scales based on a wavelet multiscaling method. We decompose daily data from U.S., British, Brazilian and Hong Kong stock markets indices in order to calculate the scale correlation between their illiquidities. The sample is divided in order to consider non-crisis, sub-prime crisis and Eurozone crisis. We find that there are changes in correlations of distinct scales and different periods. Association in finest scales is smaller than in coarse scales. There is a rise on associations in periods of crisis. In frequencies, there is predominance for significant distinctions involving the coarsest scale, while for crises periods there is predominance for distinctions on the finest scale.

  3. Distinctiveness of Saudi Arabian EFL Learners

    Science.gov (United States)

    Habbash, Manssour; Idapalapati, Srinivasa Rao

    2016-01-01

    In view of the increasing concern among English language teachers dealing with students from Saudi Arabia, as it manifests in TESOL community discussions, about the uniqueness of Saudi Arabian EFL learners, this paper attempts to document the outcome of a study of their distinctiveness from the perspective of expatriate teachers working for PYPs…

  4. Determining the Contribution of the Energy Systems During Exercise

    OpenAIRE

    Artioli, Guilherme G.; Bertuzzi, Rômulo C.; Roschel, Hamilton; Mendes, Sandro H.; Lancha, Antonio H.; Franchini, Emerson

    2012-01-01

    One of the most important aspects of the metabolic demand is the relative contribution of the energy systems to the total energy required for a given physical activity. Although some sports are relatively easy to be reproduced in a laboratory (e.g., running and cycling), a number of sports are much more difficult to be reproduced and studied in controlled situations. This method presents how to assess the differential contribution of the energy systems in sports that are difficult to mimic in...

  5. Genome-wide screen for salmonella genes required for long-term systemic infection of the mouse.

    Directory of Open Access Journals (Sweden)

    2006-02-01

    Full Text Available A microarray-based negative selection screen was performed to identify Salmonella enterica serovar Typhimurium (serovar Typhimurium genes that contribute to long-term systemic infection in 129X1/SvJ (Nramp1(r mice. A high-complexity transposon-mutagenized library was used to infect mice intraperitoneally, and the selective disappearance of mutants was monitored after 7, 14, 21, and 28 d postinfection. One hundred and eighteen genes were identified to contribute to serovar Typhimurium infection of the spleens of mice by 28 d postinfection. The negatively selected mutants represent many known aspects of Salmonella physiology and pathogenesis, although the majority of the identified genes are of putative or unknown function. Approximately 30% of the negatively selected genes correspond to horizontally acquired regions such as those within Salmonella pathogenicity islands (SPI 1-5, prophages (Gifsy-1 and -2 and remnant, and the pSLT virulence plasmid. In addition, mutations in genes responsible for outer membrane structure and remodeling, such as LPS- and PhoP-regulated and fimbrial genes, were also selected against. Competitive index experiments demonstrated that the secreted SPI2 effectors SseK2 and SseJ as well as the SPI4 locus are attenuated relative to wild-type bacteria during systemic infection. Interestingly, several SPI1-encoded type III secretion system effectors/translocases are required by serovar Typhimurium to establish and, unexpectedly, to persist systemically, challenging the present description of Salmonella pathogenesis. Moreover, we observed a progressive selection against serovar Typhimurium mutants based upon the duration of the infection, suggesting that different classes of genes may be required at distinct stages of infection. Overall, these data indicate that Salmonella long-term systemic infection in the mouse requires a diverse repertoire of virulence factors. This diversity of genes presumably reflects the fact that

  6. Species contributions to single biodiversity values under-estimate whole community contribution to a wider range of values to society.

    Science.gov (United States)

    Hiron, Matthew; Pärt, Tomas; Siriwardena, Gavin M; Whittingham, Mark J

    2018-05-03

    A major task for decision makers is deciding how to consider monetary, cultural and conservation values of biodiversity explicitly when planning sustainable land use. Thus, there is a great need to understand just what "valuing" biodiversity or species really means, e.g. regarding how many and which species are important in providing ecosystem services or other values. Constructing ecosystem-level indices, however, requires weighting the relative contribution of species to the different values. Using farmland birds, we illustrate how species contribute to different biodiversity values, namely utilitarian (pest seed predation potential), cultural (species occurrence in poetry), conservational (declines and rarity) and inherent (all species equal) value. Major contributions to each value are often made by a subset of the community and different species are important for different values, leading to no correlations or, in some cases, negative correlations between species' relative contributions to different values. Our results and methods using relative contributions of species to biodiversity values can aid decisions when weighing different values in policies and strategies for natural resource management. We conclude that acknowledging the importance of the range of biodiversity values that are apparent from different perspectives is critical if the full value of biodiversity to society is to be realised.

  7. A method for determining the spent-fuel contribution to transport cask containment requirements

    International Nuclear Information System (INIS)

    Sanders, T.L.; Seager, K.D.; Rashid, Y.R.; Barrett, P.R.; Malinauskas, A.P.; Einziger, R.E.; Jordan, H.; Reardon, P.C.

    1992-11-01

    This report examines containment requirements for spent-fuel transport containers that are transported under normal and hypothetical accident conditions. A methodology is described that estimates the probability of rod failure and the quantity of radioactive material released from breached rods. This methodology characterizes the dynamic environment of the cask and its contents and deterministically models the peak stresses that are induced in spent-fuel cladding by the mechanical and thermal dynamic environments. The peak stresses are evaluated in relation to probabilistic failure criteria for generated or preexisting ductile tearing and material fractures at cracks partially through the wall in fuel rods. Activity concentrations in the cask cavity are predicted from estimates of the fraction of gases, volatiles, and fuel fines that are released when the rod cladding is breached. Containment requirements based on the source term are calculated in terms of maximum permissible volumetric leak rates from the cask. Calculations are included for representative cask designs

  8. Neural correlates of the food/non-food visual distinction.

    Science.gov (United States)

    Tsourides, Kleovoulos; Shariat, Shahriar; Nejati, Hossein; Gandhi, Tapan K; Cardinaux, Annie; Simons, Christopher T; Cheung, Ngai-Man; Pavlovic, Vladimir; Sinha, Pawan

    2016-03-01

    An evolutionarily ancient skill we possess is the ability to distinguish between food and non-food. Our goal here is to identify the neural correlates of visually driven 'edible-inedible' perceptual distinction. We also investigate correlates of the finer-grained likability assessment. Our stimuli depicted food or non-food items with sub-classes of appealing or unappealing exemplars. Using data-classification techniques drawn from machine-learning, as well as evoked-response analyses, we sought to determine whether these four classes of stimuli could be distinguished based on the patterns of brain activity they elicited. Subjects viewed 200 images while in a MEG scanner. Our analyses yielded two successes and a surprising failure. The food/non-food distinction had a robust neural counterpart and emerged as early as 85 ms post-stimulus onset. The likable/non-likable distinction too was evident in the neural signals when food and non-food stimuli were grouped together, or when only the non-food stimuli were included in the analyses. However, we were unable to identify any neural correlates of this distinction when limiting the analyses only to food stimuli. Taken together, these positive and negative results further our understanding of the substrates of a set of ecologically important judgments and have clinical implications for conditions like eating-disorders and anhedonia. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. MAGDM linear-programming models with distinct uncertain preference structures.

    Science.gov (United States)

    Xu, Zeshui S; Chen, Jian

    2008-10-01

    Group decision making with preference information on alternatives is an interesting and important research topic which has been receiving more and more attention in recent years. The purpose of this paper is to investigate multiple-attribute group decision-making (MAGDM) problems with distinct uncertain preference structures. We develop some linear-programming models for dealing with the MAGDM problems, where the information about attribute weights is incomplete, and the decision makers have their preferences on alternatives. The provided preference information can be represented in the following three distinct uncertain preference structures: 1) interval utility values; 2) interval fuzzy preference relations; and 3) interval multiplicative preference relations. We first establish some linear-programming models based on decision matrix and each of the distinct uncertain preference structures and, then, develop some linear-programming models to integrate all three structures of subjective uncertain preference information provided by the decision makers and the objective information depicted in the decision matrix. Furthermore, we propose a simple and straightforward approach in ranking and selecting the given alternatives. It is worth pointing out that the developed models can also be used to deal with the situations where the three distinct uncertain preference structures are reduced to the traditional ones, i.e., utility values, fuzzy preference relations, and multiplicative preference relations. Finally, we use a practical example to illustrate in detail the calculation process of the developed approach.

  10. Dectin-1 isoforms contribute to distinct Th1/Th17 cell activation in mucosal candidiasis

    Science.gov (United States)

    Carvalho, Agostinho; Giovannini, Gloria; De Luca, Antonella; D'Angelo, Carmen; Casagrande, Andrea; Iannitti, Rossana G; Ricci, Giovanni; Cunha, Cristina; Romani, Luigina

    2012-01-01

    The recognition of β-glucans by dectin-1 has been shown to mediate cell activation, cytokine production and a variety of antifungal responses. Here, we report that the functional activity of dectin-1 in mucosal immunity to Candida albicans is influenced by the genetic background of the host. Dectin-1 was required for the proper control of gastrointestinal and vaginal candidiasis in C57BL/6, but not BALB/c mice; in fact, the latter showed increased resistance in the absence of dectin-1. The susceptibility of dectin-1-deficient C57BL/6 mice to infection was associated with defects in IL-17A and aryl hydrocarbon receptor-dependent IL-22 production and in adaptive Th1 responses. In contrast, the resistance of dectin-1-deficient BALB/c mice was associated with increased IL-17A and IL-22 production and the skewing towards Th1/Treg immune responses that provide immunological memory. Disparate canonical/noncanonical NF-κB signaling pathways downstream of dectin-1 were activated in the two different mouse strains. Thus, the net activity of dectin-1 in antifungal mucosal immunity is dependent on the host's genetic background, which affects both the innate cytokine production and the adaptive Th1/Th17 cell activation upon dectin-1 signaling. PMID:22543832

  11. The Contribution of Transactivation Subdomains 1 and 2 to p53-Induced Gene Expression Is Heterogeneous But Not Subdomain-Specific

    Directory of Open Access Journals (Sweden)

    Jennifer M. Smith

    2007-12-01

    Full Text Available Two adjacent regions within the transactivation domain of p53 are sufficient to support sequence-specific transactivation when fused to a heterologous DNA binding domain. It has been hypothesized that these two subdomains of p53 may contribute to the expression of distinct p53-responsive genes. Here we have used oligonucleotide microarrays to identify transcripts induced by variants of p53 with point mutations within subdomains 1, 2, or 1 and 2 (QS1, QS2, QS1/QS2, respectively. The expression of 254 transcripts was increased in response to wild-type p53 expression but most of these transcripts were poorly induced by these variants of p53. Strikingly, a number of known p53regulated transcripts including TNFRSF10B, BAX, BTG2, POLH were increased to wild-type levels by p53QS1 and p53QS2 but not p53QS1/QS2, indicating that either sub domain 1 or 2 is sufficient for p53-dependent expression of a small subset of p53-responsive genes. Unexpectedly, there was no evidence for p53QS1- or p53QS2-specific gene expression. Taken together, we found heterogeneity in the requirement for transactivation subdomains 1 and 2 of p53 without any subdomain-specific contribution to p53-induced gene expression.

  12. A dual resistance gene system prevents infection by three distinct pathogens.

    Science.gov (United States)

    Narusaka, Mari; Kubo, Yasuyuki; Shiraishi, Tomonori; Iwabuchi, Masaki; Narusaka, Yoshihiro

    2009-10-01

    Colletotrichum higginsianum causes typical anthracnose lesions on the leaves, petioles, and stems of cruciferous plants. Inoculation of Arabidopsis thaliana ecotype Columbia leaves with C. higginsianum results in fungal growth and disease symptoms reminiscent of those induced in other cruciferous plants. We performed map-based cloning and natural variation analysis of 19 A. thaliana ecotypes to identify a dominant resistance locus against C. higginsianum. We found that the A. thaliana RCH2 (for recognition of C. higginsianum) locus encodes two NB-LRR proteins, both of which are required for resistance to C. higginsianum in the A. thaliana ecotype Ws-0. Both proteins are well-characterized R proteins involved in resistance against bacterial pathogens; RRS1 (resistance to Ralstonia solanacearum 1) confers resistance to strain Rs1000 of R. solanacearum and RPS4 to Pseudomonas syringae pv. tomato strain DC3000 expressing avrRps4 (Pst-avrRps4). Furthermore, we found that both RRS1-Ws and RPS4-Ws genes are required for resistance to Pst-avrRps4 and to Rs1002 R. solanacearum. We therefore demonstrate that a pair of neighboring genes, RRS1-Ws and RPS4-Ws, function cooperatively as a dual R-gene system against at least three distinct pathogens.

  13. MyoD undergoes a distinct G2/M-specific regulation in muscle cells

    International Nuclear Information System (INIS)

    Batonnet-Pichon, Sabrina; Tintignac, Lionel J.; Castro, Anna; Sirri, Valentina; Leibovitch, Marie Pierre; Lorca, Thierry; Leibovitch, Serge A.

    2006-01-01

    The transcription factors MyoD and Myf5 present distinct patterns of expression during cell cycle progression and development. In contrast to the mitosis-specific disappearance of Myf5, which requires a D-box-like motif overlapping the basic domain, here we describe a stable and inactive mitotic form of MyoD phosphorylated on its serine 5 and serine 200 residues by cyclin B-cdc2. In mitosis, these modifications are required for releasing MyoD from condensed chromosomes and inhibiting its DNA-binding and transcriptional activation ability. Then, nuclear MyoD regains instability in the beginning of G1 phase due to rapid dephosphorylation events. Moreover, a non-phosphorylable MyoD S5A/S200A is not excluded from condensed chromatin and alters mitotic progression with apparent abnormalities. Thus, the drop of MyoD below a threshold level and its displacement from the mitotic chromatin could present another window in the cell cycle for resetting the myogenic transcriptional program and to maintain the myogenic determination of the proliferating cells

  14. MyoD undergoes a distinct G2/M-specific regulation in muscle cells.

    Science.gov (United States)

    Batonnet-Pichon, Sabrina; Tintignac, Lionel J; Castro, Anna; Sirri, Valentina; Leibovitch, Marie Pierre; Lorca, Thierry; Leibovitch, Serge A

    2006-12-10

    The transcription factors MyoD and Myf5 present distinct patterns of expression during cell cycle progression and development. In contrast to the mitosis-specific disappearance of Myf5, which requires a D-box-like motif overlapping the basic domain, here we describe a stable and inactive mitotic form of MyoD phosphorylated on its serine 5 and serine 200 residues by cyclin B-cdc2. In mitosis, these modifications are required for releasing MyoD from condensed chromosomes and inhibiting its DNA-binding and transcriptional activation ability. Then, nuclear MyoD regains instability in the beginning of G1 phase due to rapid dephosphorylation events. Moreover, a non-phosphorylable MyoD S5A/S200A is not excluded from condensed chromatin and alters mitotic progression with apparent abnormalities. Thus, the drop of MyoD below a threshold level and its displacement from the mitotic chromatin could present another window in the cell cycle for resetting the myogenic transcriptional program and to maintain the myogenic determination of the proliferating cells.

  15. Pseudo three-dimensional modeling of particle-fuel packing using distinct element method

    International Nuclear Information System (INIS)

    Yuki, Daisuke; Takata, Takashi; Yamaguchi, Akira

    2007-01-01

    Vibration-based packing of sphere-pac fuel is a key technology in a nuclear fuel manufacturing. In the production process of sphere-pac fuel, a Mixed Oxide (MOX) fuel is formed to spherical form and is packed in a cladding tube by adding a vibration force. In the present study, we have developed a numerical simulation method to investigate the behavior of the particles in a vibrated tube using the Distinct Element Method (DEM). In general, the DEM requires a significant computational cost. Therefore we propose a new approach in which a small particle can move through the space between three larger particles even in the two-dimensional simulation. We take into account an equivalent three-dimensional effect in the equations of motion. Thus it is named pseudo three-dimensional modeling. (author)

  16. The death of distinctions: From 9/11 to Abu Ghraib.

    Science.gov (United States)

    Moon, John Ellis van Courtland

    2004-09-01

    War, the great simplifier, is the inevitable enemy of distinctions, especially when conflicts evoke survival fears, sounding echoes from humanity's environment of evolutionary adaptation. Throughout the twentieth century, attackers and targets grew more distant, weaponry grew more destructive, and distinctions -- between combatants and civilians, between legitimate and protected targets, between defensive and offensive strategies, between the innocent and the guilty -- faded. In the twenty-first century's first major conflict, "the war against terror," distinctions have faded still further, making nearly indistinguishable the frontier between preemption and prevention and between interrogation and torture. Proclaimed a "new type of war" in which old rules and customary safeguards would often be inapplicable, this conflict quickly came to be characterized by political embarrassment and operational scandal.

  17. Differential Contributions of Selective Attention and Sensory Integration to Driving Performance in Healthy Aging and Alzheimer's Disease.

    Science.gov (United States)

    Venkatesan, Umesh M; Festa, Elena K; Ott, Brian R; Heindel, William C

    2018-05-01

    Patients with Alzheimer's disease (AD) demonstrate deficits in cross-cortical feature binding distinct from age-related changes in selective attention. This may have consequences for driving performance given its demands on multisensory integration. We examined the relationship of visuospatial search and binding to driving in patients with early AD and elderly controls (EC). Participants (42 AD; 37 EC) completed search tasks requiring either luminance-motion (L-M) or color-motion (C-M) binding, analogs of within and across visual processing stream binding, respectively. Standardized road test (RIRT) and naturalistic driving data (CDAS) were collected alongside clinical screening measures. Patients performed worse than controls on most cognitive and driving indices. Visual search and clinical measures were differentially related to driving behavior across groups. L-M search and Trail Making Test (TMT-B) were associated with RIRT performance in controls, while C-M binding, TMT-B errors, and Clock Drawing correlated with CDAS performance in patients. After controlling for demographic and clinical predictors, L-M reaction time significantly predicted RIRT performance in controls. In patients, C-M binding made significant contributions to CDAS above and beyond demographic and clinical predictors. RIRT and C-M binding measures accounted for 51% of variance in CDAS performance in patients. Whereas selective attention is associated with driving behavior in EC, cross-cortical binding appears most sensitive to driving in AD. This latter relationship may emerge only in naturalistic settings, which better reflect patients' driving behavior. Visual integration may offer distinct insights into driving behavior, and thus has important implications for assessing driving competency in early AD. (JINS, 2018, 24, 486-497).

  18. Place preference and vocal learning rely on distinct reinforcers in songbirds.

    Science.gov (United States)

    Murdoch, Don; Chen, Ruidong; Goldberg, Jesse H

    2018-04-30

    In reinforcement learning (RL) agents are typically tasked with maximizing a single objective function such as reward. But it remains poorly understood how agents might pursue distinct objectives at once. In machines, multiobjective RL can be achieved by dividing a single agent into multiple sub-agents, each of which is shaped by agent-specific reinforcement, but it remains unknown if animals adopt this strategy. Here we use songbirds to test if navigation and singing, two behaviors with distinct objectives, can be differentially reinforced. We demonstrate that strobe flashes aversively condition place preference but not song syllables. Brief noise bursts aversively condition song syllables but positively reinforce place preference. Thus distinct behavior-generating systems, or agencies, within a single animal can be shaped by correspondingly distinct reinforcement signals. Our findings suggest that spatially segregated vocal circuits can solve a credit assignment problem associated with multiobjective learning.

  19. False memories in children and adults: age, distinctiveness, and subjective experience.

    Science.gov (United States)

    Ghetti, Simona; Qin, Jianjian; Goodman, Gail S

    2002-09-01

    This study investigated developmental trends associated with the Deese/Roediger-McDermott false-memory effect, the role of distinctive information in false-memory formation, and participants' subjective experience of true and false memories. Children (5- and 7-year-olds) and adults studied lists of semantically associated words. Half of the participants studied words alone, and half studied words accompanied by pictures. There were significant age differences in recall (5-year-olds evinced more false memories than did adults) but not in recognition of critical lures. Distinctive information reduced false memory for all age groups. Younger children provided with distinctive information, and older children and adults regardless of whether they viewed distinctive information, expressed higher levels of confidence in true than in false memories. Source attributions did not significantly differ between true and false memories. Implications for theories of false memory and memory development are discussed.

  20. The picture superiority effect in conceptual implicit memory: a conceptual distinctiveness hypothesis.

    Science.gov (United States)

    Hamilton, Maryellen; Geraci, Lisa

    2006-01-01

    According to leading theories, the picture superiority effect is driven by conceptual processing, yet this effect has been difficult to obtain using conceptual implicit memory tests. We hypothesized that the picture superiority effect results from conceptual processing of a picture's distinctive features rather than a picture's semantic features. To test this hypothesis, we used 2 conceptual implicit general knowledge tests; one cued conceptually distinctive features (e.g., "What animal has large eyes?") and the other cued semantic features (e.g., "What animal is the figurehead of Tootsie Roll?"). Results showed a picture superiority effect only on the conceptual test using distinctive cues, supporting our hypothesis that this effect is mediated by conceptual processing of a picture's distinctive features.

  1. Incentives to Encourage Scientific Web Contribution (Invited)

    Science.gov (United States)

    Antunes, A. K.

    2010-12-01

    We suggest improvements to citation standards and creation of remuneration opportunities to encourage career scientist contributions to Web2.0 and social media science channels. At present, agencies want to accomplish better outreach and engagement with no funding, while scientists sacrifice their personal time to contribute to web and social media sites. Securing active participation by scientists requires career recognition of the value scientists provide to web knowledge bases and to the general public. One primary mechanism to encourage participation is citation standards, which let a contributor improve their reputation in a quantifiable way. But such standards must be recognized by their scientific and workplace communities. Using case studies such as the acceptance of web in the workplace and the growth of open access journals, we examine what agencies and individual can do as well as the time scales needed to secure increased active contribution by scientists. We also discuss ways to jumpstart this process.

  2. Distinct medial temporal networks encode surprise during motivation by reward versus punishment

    Science.gov (United States)

    Murty, Vishnu P.; LaBar, Kevin S.; Adcock, R. Alison

    2016-01-01

    Adaptive motivated behavior requires predictive internal representations of the environment, and surprising events are indications for encoding new representations of the environment. The medial temporal lobe memory system, including the hippocampus and surrounding cortex, encodes surprising events and is influenced by motivational state. Because behavior reflects the goals of an individual, we investigated whether motivational valence (i.e., pursuing rewards versus avoiding punishments) also impacts neural and mnemonic encoding of surprising events. During functional magnetic resonance imaging (fMRI), participants encountered perceptually unexpected events either during the pursuit of rewards or avoidance of punishments. Despite similar levels of motivation across groups, reward and punishment facilitated the processing of surprising events in different medial temporal lobe regions. Whereas during reward motivation, perceptual surprises enhanced activation in the hippocampus, during punishment motivation surprises instead enhanced activation in parahippocampal cortex. Further, we found that reward motivation facilitated hippocampal coupling with ventromedial PFC, whereas punishment motivation facilitated parahippocampal cortical coupling with orbitofrontal cortex. Behaviorally, post-scan testing revealed that reward, but not punishment, motivation resulted in greater memory selectivity for surprising events encountered during goal pursuit. Together these findings demonstrate that neuromodulatory systems engaged by anticipation of reward and punishment target separate components of the medial temporal lobe, modulating medial temporal lobe sensitivity and connectivity. Thus, reward and punishment motivation yield distinct neural contexts for learning, with distinct consequences for how surprises are incorporated into predictive mnemonic models of the environment. PMID:26854903

  3. Distinct medial temporal networks encode surprise during motivation by reward versus punishment.

    Science.gov (United States)

    Murty, Vishnu P; LaBar, Kevin S; Adcock, R Alison

    2016-10-01

    Adaptive motivated behavior requires predictive internal representations of the environment, and surprising events are indications for encoding new representations of the environment. The medial temporal lobe memory system, including the hippocampus and surrounding cortex, encodes surprising events and is influenced by motivational state. Because behavior reflects the goals of an individual, we investigated whether motivational valence (i.e., pursuing rewards versus avoiding punishments) also impacts neural and mnemonic encoding of surprising events. During functional magnetic resonance imaging (fMRI), participants encountered perceptually unexpected events either during the pursuit of rewards or avoidance of punishments. Despite similar levels of motivation across groups, reward and punishment facilitated the processing of surprising events in different medial temporal lobe regions. Whereas during reward motivation, perceptual surprises enhanced activation in the hippocampus, during punishment motivation surprises instead enhanced activation in parahippocampal cortex. Further, we found that reward motivation facilitated hippocampal coupling with ventromedial PFC, whereas punishment motivation facilitated parahippocampal cortical coupling with orbitofrontal cortex. Behaviorally, post-scan testing revealed that reward, but not punishment, motivation resulted in greater memory selectivity for surprising events encountered during goal pursuit. Together these findings demonstrate that neuromodulatory systems engaged by anticipation of reward and punishment target separate components of the medial temporal lobe, modulating medial temporal lobe sensitivity and connectivity. Thus, reward and punishment motivation yield distinct neural contexts for learning, with distinct consequences for how surprises are incorporated into predictive mnemonic models of the environment. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Nuclear power manpower and training requirements

    International Nuclear Information System (INIS)

    Whan, G.A.

    1984-01-01

    A broad spectrum of technical personnel is required to conduct a national nuclear power program, predominantly electrical, mechanical, and nuclear engineers and health physicists. The need for nuclear education and training, even in the early planning states, is the topic of this paper. Experience gained in the United States can provide useful information to Asia-Pacific countries developing nuclear power programs. Including both on-site and off-site personnel, U.S. plants average about 570 workers for BWRs and 700 for PWRs. The need for an additional 57,000 technical employees over the next decade is projected. The technical backgrounds of the manpower required to operate and support a nuclear power plant are distinctly different from those used by non-nuclear utilities. Manpower cannot be transferred from fossil fuel plants without extensive training. Meeting the demand for nuclear education and training must be a friendly partnership among universities, government, and industry. The long-term supply of nuclear-educated personnel requires strong, government-supported universities. Most specific training, however, must be provided by industry. (author)

  5. Convergent Metabolic Specialization through Distinct Evolutionary Paths in Pseudomonas aeruginosa.

    Science.gov (United States)

    La Rosa, Ruggero; Johansen, Helle Krogh; Molin, Søren

    2018-04-10

    Evolution by natural selection under complex and dynamic environmental conditions occurs through intricate and often counterintuitive trajectories affecting many genes and metabolic solutions. To study short- and long-term evolution of bacteria in vivo , we used the natural model system of cystic fibrosis (CF) infection. In this work, we investigated how and through which trajectories evolution of Pseudomonas aeruginosa occurs when migrating from the environment to the airways of CF patients, and specifically, we determined reduction of growth rate and metabolic specialization as signatures of adaptive evolution. We show that central metabolic pathways of three distinct Pseudomonas aeruginosa lineages coevolving within the same environment become restructured at the cost of versatility during long-term colonization. Cell physiology changes from naive to adapted phenotypes resulted in (i) alteration of growth potential that particularly converged to a slow-growth phenotype, (ii) alteration of nutritional requirements due to auxotrophy, (iii) tailored preference for carbon source assimilation from CF sputum, (iv) reduced arginine and pyruvate fermentation processes, and (v) increased oxygen requirements. Interestingly, although convergence was evidenced at the phenotypic level of metabolic specialization, comparative genomics disclosed diverse mutational patterns underlying the different evolutionary trajectories. Therefore, distinct combinations of genetic and regulatory changes converge to common metabolic adaptive trajectories leading to within-host metabolic specialization. This study gives new insight into bacterial metabolic evolution during long-term colonization of a new environmental niche. IMPORTANCE Only a few examples of real-time evolutionary investigations in environments outside the laboratory are described in the scientific literature. Remembering that biological evolution, as it has progressed in nature, has not taken place in test tubes, it is not

  6. An Adult Developmental Approach to Perceived Facial Attractiveness and Distinctiveness

    Directory of Open Access Journals (Sweden)

    Natalie C. Ebner

    2018-05-01

    Full Text Available Attractiveness and distinctiveness constitute facial features with high biological and social relevance. Bringing a developmental perspective to research on social-cognitive face perception, we used a large set of faces taken from the FACES Lifespan Database to examine effects of face and perceiver characteristics on subjective evaluations of attractiveness and distinctiveness in young (20–31 years, middle-aged (44–55 years, and older (70–81 years men and women. We report novel findings supporting variations by face and perceiver age, in interaction with gender and emotion: although older and middle-aged compared to young perceivers generally rated faces of all ages as more attractive, young perceivers gave relatively higher attractiveness ratings to young compared to middle-aged and older faces. Controlling for variations in attractiveness, older compared to young faces were viewed as more distinctive by young and middle-aged perceivers. Age affected attractiveness more negatively for female than male faces. Furthermore, happy faces were rated as most attractive, while disgusted faces were rated as least attractive, particularly so by middle-aged and older perceivers and for young and female faces. Perceivers largely agreed on distinctiveness ratings for neutral and happy emotions, but older and middle-aged compared to young perceivers rated faces displaying negative emotions as more distinctive. These findings underscore the importance of a lifespan perspective on perception of facial characteristics and suggest possible effects of age on goal-directed perception, social motivation, and in-group bias. This publication makes available picture-specific normative data for experimental stimulus selection.

  7. JAK/STAT-1 Signaling Is Required for Reserve Intestinal Stem Cell Activation during Intestinal Regeneration Following Acute Inflammation

    Directory of Open Access Journals (Sweden)

    Camilla A. Richmond

    2018-01-01

    Full Text Available The intestinal epithelium serves as an essential barrier to the outside world and is maintained by functionally distinct populations of rapidly cycling intestinal stem cells (CBC ISCs and slowly cycling, reserve ISCs (r-ISCs. Because disruptions in the epithelial barrier can result from pathological activation of the immune system, we sought to investigate the impact of inflammation on ISC behavior during the regenerative response. In a murine model of αCD3 antibody-induced small-intestinal inflammation, r-ISCs proved highly resistant to injury, while CBC ISCs underwent apoptosis. Moreover, r-ISCs were induced to proliferate and functionally contribute to intestinal regeneration. Further analysis revealed that the inflammatory cytokines interferon gamma and tumor necrosis factor alpha led to r-ISC activation in enteroid culture, which could be blocked by the JAK/STAT inhibitor, tofacitinib. These results highlight an important role for r-ISCs in response to acute intestinal inflammation and show that JAK/STAT-1 signaling is required for the r-ISC regenerative response.

  8. Cellular requirements for cutaneous sensitivity elicitation.

    Science.gov (United States)

    Aoki, I

    1985-01-01

    The role of glass-adherent cells in cutaneous sensitivity (CS) elicitation has been analyzed in this study. CS responses have been revealed to be mediated by at least two distinct subsets of genetically restricted T cells: I-restricted 'DTH-like' T cells and K/D-restricted 'CTL-like' T cells. Both T-cell responses require I-A-positive glass-adherent cell populations, which lack T-cell markers, to manifest their activities. The role of the adherent cells is different in the 'DTH-like' responses and the 'CTL-like' responses. The disparities between the present results and previous contentions are discussed in this paper.

  9. Distinct cytoskeleton populations and extensive crosstalk control Ciona notochord tubulogenesis.

    Science.gov (United States)

    Dong, Bo; Deng, Wei; Jiang, Di

    2011-04-01

    Cell elongation is a fundamental process that allows cells and tissues to adopt new shapes and functions. During notochord tubulogenesis in the ascidian Ciona intestinalis, a dramatic elongation of individual cells takes place that lengthens the notochord and, consequently, the entire embryo. We find a novel dynamic actin- and non-muscle myosin II-containing constriction midway along the anteroposterior aspect of each notochord cell during this process. Both actin polymerization and myosin II activity are required for the constriction and cell elongation. Discontinuous localization of myosin II in the constriction indicates that the actomyosin network produces local contractions along the circumference. This reveals basal constriction by the actomyosin network as a novel mechanism for cell elongation. Following elongation, the notochord cells undergo a mesenchymal-epithelial transition and form two apical domains at opposite ends. Extracellular lumens then form at the apical surfaces. We show that cortical actin and Ciona ezrin/radixin/moesin (ERM) are essential for lumen formation and that a polarized network of microtubules, which contributes to lumen development, forms in an actin-dependent manner at the apical cortex. Later in notochord tubulogenesis, when notochord cells initiate a bi-directional crawling movement on the notochordal sheath, the microtubule network rotates 90° and becomes organized as parallel bundles extending towards the leading edges of tractive lamellipodia. This process is required for the correct organization of actin-based protrusions and subsequent lumen coalescence. In summary, we establish the contribution of the actomyosin and microtubule networks to notochord tubulogenesis and reveal extensive crosstalk and regulation between these two cytoskeleton components.

  10. Stability of β-carotene during baking of orange-fleshed sweet potato-wheat composite bread and estimated contribution to vitamin A requirements.

    Science.gov (United States)

    Nzamwita, Madjaliwa; Duodu, Kwaku Gyebi; Minnaar, Amanda

    2017-08-01

    Orange-fleshed sweet potato (OFSP) is known to be a rich source of β-carotene, a precursor of vitamin A and a potential tool for fighting vitamin A deficiency (VAD) in developing countries. OFSP flour was incorporated into wheat flour at 10, 20 and 30% (w/w) substitution levels. The stability of β-carotene during baking and the contribution of OFSP-wheat composite breads to vitamin A requirements were evaluated. The retention of all-trans-β-carotene in breads containing 10, 20 and 30% OFSP flour was 62.7, 71.4 and 83% respectively, after baking. Breads containing 20% and 30% OFSP flour could be used for the eradication of vitamin A deficiency as they were found to meet 29 and 89.2% (100g portion) respectively, of the recommended dietary allowance (RDA) of vitamin A amongst children aged 3-10years. The latter would meet nearly a half of the RDA of vitamin A for pregnant and lactating women. Copyright © 2017 Elsevier Ltd. All rights reserved.

  11. Beauty hinders attention switch in change detection: the role of facial attractiveness and distinctiveness.

    Directory of Open Access Journals (Sweden)

    Wenfeng Chen

    Full Text Available BACKGROUND: Recent research has shown that the presence of a task-irrelevant attractive face can induce a transient diversion of attention from a perceptual task that requires covert deployment of attention to one of the two locations. However, it is not known whether this spontaneous appraisal for facial beauty also modulates attention in change detection among multiple locations, where a slower, and more controlled search process is simultaneously affected by the magnitude of a change and the facial distinctiveness. Using the flicker paradigm, this study examines how spontaneous appraisal for facial beauty affects the detection of identity change among multiple faces. METHODOLOGY/PRINCIPAL FINDINGS: Participants viewed a display consisting of two alternating frames of four faces separated by a blank frame. In half of the trials, one of the faces (target face changed to a different person. The task of the participant was to indicate whether a change of face identity had occurred. The results showed that (1 observers were less efficient at detecting identity change among multiple attractive faces relative to unattractive faces when the target and distractor faces were not highly distinctive from one another; and (2 it is difficult to detect a change if the new face is similar to the old. CONCLUSIONS/SIGNIFICANCE: The findings suggest that attractive faces may interfere with the attention-switch process in change detection. The results also show that attention in change detection was strongly modulated by physical similarity between the alternating faces. Although facial beauty is a powerful stimulus that has well-demonstrated priority, its influence on change detection is easily superseded by low-level image similarity. The visual system appears to take a different approach to facial beauty when a task requires resource-demanding feature comparisons.

  12. Beauty hinders attention switch in change detection: the role of facial attractiveness and distinctiveness.

    Science.gov (United States)

    Chen, Wenfeng; Liu, Chang Hong; Nakabayashi, Kazuyo

    2012-01-01

    Recent research has shown that the presence of a task-irrelevant attractive face can induce a transient diversion of attention from a perceptual task that requires covert deployment of attention to one of the two locations. However, it is not known whether this spontaneous appraisal for facial beauty also modulates attention in change detection among multiple locations, where a slower, and more controlled search process is simultaneously affected by the magnitude of a change and the facial distinctiveness. Using the flicker paradigm, this study examines how spontaneous appraisal for facial beauty affects the detection of identity change among multiple faces. Participants viewed a display consisting of two alternating frames of four faces separated by a blank frame. In half of the trials, one of the faces (target face) changed to a different person. The task of the participant was to indicate whether a change of face identity had occurred. The results showed that (1) observers were less efficient at detecting identity change among multiple attractive faces relative to unattractive faces when the target and distractor faces were not highly distinctive from one another; and (2) it is difficult to detect a change if the new face is similar to the old. The findings suggest that attractive faces may interfere with the attention-switch process in change detection. The results also show that attention in change detection was strongly modulated by physical similarity between the alternating faces. Although facial beauty is a powerful stimulus that has well-demonstrated priority, its influence on change detection is easily superseded by low-level image similarity. The visual system appears to take a different approach to facial beauty when a task requires resource-demanding feature comparisons.

  13. False Memories in Children and Adults: Age, Distinctiveness, and Subjective Experience.

    Science.gov (United States)

    Ghetti, Simona; Qin, Jianjian; Goodman, Gail S.

    2002-01-01

    Investigated developmental trends associated with the Deese/Roediger-McDermott false-memory effect, the role of distinctive information, and subjective experience of true/false memories. Found that 5-year-olds recalled more false memories than adults but no age differences in recognition of critical lures. Distinctive information reduced false…

  14. Attention and implicit memory: priming-induced benefits and costs have distinct attentional requirements.

    Science.gov (United States)

    Keane, Margaret M; Cruz, Matt E; Verfaellie, Mieke

    2015-02-01

    Attention at encoding plays a critical and ubiquitous role in explicit memory performance, but its role in implicit memory performance (i.e., priming) is more variable: some, but not all, priming effects are reduced by division of attention at encoding. A wealth of empirical and theoretical work has aimed to define the critical features of priming effects that do or do not require attention at encoding. This work, however, has focused exclusively on priming effects that are beneficial in nature (wherein performance is enhanced by prior exposure to task stimuli), and has overlooked priming effects that are costly in nature (wherein performance is harmed by prior exposure to task stimuli). The present study takes up this question by examining the effect of divided attention on priming-induced costs and benefits in a speeded picture-naming task. Experiment 1 shows that the costs, but not the benefits, are eliminated by division of attention at encoding. Experiment 2 shows that the costs (as well as the benefits) in this task are intact in amnesic participants, demonstrating that the elimination of the cost in the divided attention condition in Experiment 1 was not an artifact of the reduced availability of explicit memory in that condition. We suggest that the differential role of attention in priming-induced performance costs and benefits is linked to differences in response competition associated with these effects. This interpretation situates the present findings within a theoretical framework that has been applied to a broad range of facilitatory priming effects.

  15. Attention and Implicit Memory: Priming-Induced Benefits and Costs Have Distinct Attentional Requirements

    Science.gov (United States)

    Keane, Margaret M.; Cruz, Matt E.; Verfaellie, Mieke

    2014-01-01

    Attention at encoding plays a critical and ubiquitous role in explicit memory performance, but its role in implicit memory performance (i.e., priming) is more variable: Some, but not all, priming effects are reduced by division of attention at encoding. A wealth of empirical and theoretical work has aimed to define the critical features of priming effects that do or do not require attention at encoding. This work, however, has focused exclusively on priming effects that are beneficial in nature (wherein performance is enhanced by prior exposure to task stimuli), and has overlooked priming effects that are costly in nature (wherein performance is harmed by prior exposure to task stimuli). The present study takes up this question by examining the effect of divided attention on priming-induced costs and benefits in a speeded picture-naming task. Experiment 1 shows that the costs, but not the benefits, are eliminated by division of attention at encoding. Experiment 2 shows that the costs (as well as the benefits) in this task are intact in amnesic participants, demonstrating that the elimination of the cost in the divided attention condition in Experiment 1 was not an artifact of the reduced availability of explicit memory in that condition. We suggest that the differential role of attention in priming-induced performance costs and benefits is linked to differences in response competition associated with these effects. This interpretation situates the present findings within a theoretical framework that has been applied to a broad range of facilitatory priming effects. PMID:25257650

  16. Natural Microbial Assemblages Reflect Distinct Organismal and Functional Partitioning

    Science.gov (United States)

    Wilmes, P.; Andersson, A.; Kalnejais, L. H.; Verberkmoes, N. C.; Lefsrud, M. G.; Wexler, M.; Singer, S. W.; Shah, M.; Bond, P. L.; Thelen, M. P.; Hettich, R. L.; Banfield, J. F.

    2007-12-01

    The ability to link microbial community structure to function has long been a primary focus of environmental microbiology. With the advent of community genomic and proteomic techniques, along with advances in microscopic imaging techniques, it is now possible to gain insights into the organismal and functional makeup of microbial communities. Biofilms growing within highly acidic solutions inside the Richmond Mine (Iron Mountain, Redding, California) exhibit distinct macro- and microscopic morphologies. They are composed of microorganisms belonging to the three domains of life, including archaea, bacteria and eukarya. The proportion of each organismal type depends on sampling location and developmental stage. For example, mature biofilms floating on top of acid mine drainage (AMD) pools exhibit layers consisting of a densely packed bottom layer of the chemoautolithotroph Leptospirillum group II, a less dense top layer composed mainly of archaea, and fungal filaments spanning across the entire biofilm. The expression of cytochrome 579 (the most highly abundant protein in the biofilm, believed to be central to iron oxidation and encoded by Leptospirillum group II) is localized at the interface of the biofilm with the AMD solution, highlighting that biofilm architecture is reflected at the functional gene expression level. Distinct functional partitioning is also apparent in a biological wastewater treatment system that selects for distinct polyphosphate accumulating organisms. Community genomic data from " Candidatus Accumulibacter phosphatis" dominated activated sludge has enabled high mass-accuracy shotgun proteomics for identification of key metabolic pathways. Comprehensive genome-wide alignment of orthologous proteins suggests distinct partitioning of protein variants involved in both core-metabolism and specific metabolic pathways among the dominant population and closely related species. In addition, strain- resolved proteogenomic analysis of the AMD biofilms

  17. Lineage Reprogramming of Astroglial Cells from Different Origins into Distinct Neuronal Subtypes

    Directory of Open Access Journals (Sweden)

    Malek Chouchane

    2017-07-01

    Full Text Available Astroglial cells isolated from the rodent postnatal cerebral cortex are particularly susceptible to lineage reprogramming into neurons. However, it remains unknown whether other astroglial populations retain the same potential. Likewise, little is known about the fate of induced neurons (iNs in vivo. In this study we addressed these questions using two different astroglial populations isolated from the postnatal brain reprogrammed either with Neurogenin-2 (Neurog2 or Achaete scute homolog-1 (Ascl1. We show that cerebellum (CerebAstro and cerebral cortex astroglia (CtxAstro generates iNs with distinctive neurochemical and morphological properties. Both astroglial populations contribute iNs to the olfactory bulb following transplantation in the postnatal and adult mouse subventricular zone. However, only CtxAstro transfected with Neurog2 differentiate into pyramidal-like iNs after transplantation in the postnatal cerebral cortex. Altogether, our data indicate that the origin of the astroglial population and transcription factors used for reprogramming, as well as the region of integration, affect the fate of iNs.

  18. Moderate Load Eccentric Exercise; A Distinct Novel Training Modality

    Science.gov (United States)

    Hoppeler, Hans

    2016-01-01

    Over the last 20 years a number of studies have been published using progressive eccentric exercise protocols on motorized ergometers or similar devices that allow for controlled application of eccentric loads. Exercise protocols ramp eccentric loads over an initial 3 weeks period in order to prevent muscle damage and delayed onset muscle soreness. Final training loads reach 400–500 W in rehabilitative settings and over 1200 W in elite athletes. Training is typically carried out three times per week for durations of 20–30 min. This type of training has been characterizes as moderate load eccentric exercise. It has also been denoted RENEW (Resistance Exercise via Negative Eccentric Work by LaStayo et al., 2014). It is distinct from plyometric exercises (i.e., drop jumps) that impose muscle loads of several thousand Watts on muscles and tendons. It is also distinct from eccentric overload training whereby loads in a conventional strength training setting are increased in the eccentric phase of the movement to match concentric loads. Moderate load eccentric exercise (or RENEW) has been shown to be similarly effective as conventional strength training in increasing muscle strength and muscle volume. However, as carried out at higher angular velocities of joint movement, it reduces joint loads. A hallmark of moderate load eccentric exercise is the fact that the energy requirements are typically 4-fold smaller than in concentric exercise of the same load. This makes moderate load eccentric exercise training the tool of choice in medical conditions with limitations in muscle energy supply. The use and effectiveness of moderate load eccentric exercise has been demonstrated mostly in small scale studies for cardiorespiratory conditions, sarcopenia of old age, cancer, diabetes type 2, and neurological conditions. It has also been used effectively in the prevention and rehabilitation of injuries of the locomotor system in particular the rehabilitation after anterior

  19. Announcement, observation and honesty in the voluntary contributions game

    NARCIS (Netherlands)

    Denant-Boemont, L.; Masclet, D.; Noussair, C.N.

    2011-01-01

    In this paper, we study the effect of pre-play announcements and ex-post observation of decisions on voluntary public good provision. We find that requiring announcements, in conjunction with making contribution decisions public, has a significantly positive effect on the average level of

  20. Transcriptome signature identifies distinct cervical pathways induced in lipopolysaccharide-mediated preterm birth.

    Science.gov (United States)

    Willcockson, Alexandra R; Nandu, Tulip; Liu, Cheuk-Lun; Nallasamy, Shanmugasundaram; Kraus, W Lee; Mahendroo, Mala

    2018-03-01

    With half a million babies born preterm each year in the USA and about 15 million worldwide, preterm birth (PTB) remains a global health issue. Preterm birth is a primary cause of infant morbidity and mortality and can impact lives long past infancy. The fact that there are numerous, and many currently unidentified, etiologies of PTB has hindered development of tools for risk evaluation and preventative therapies. Infection is estimated to be involved in nearly 40% of PTBs of known etiology; therefore, understanding how infection-mediated inflammation alters the cervical milieu and leads to preterm tissue biomechanical changes are questions of interest. Using RNA-seq, we identified enrichment of components involved in inflammasome activation and unique proteases in the mouse cervix during lipopolysaccharide (LPS)-mediated PTB and not physiologically at term before labor. Despite transcriptional induction of inflammasome components, there was no evidence of functional activation based on assessment of mature IL1B and IL18 proteins. The increased transcription of proteases that target both elastic fibers and collagen and concentration of myeloid-derived cells capable of protease synthesis in the cervical stroma support the structural disruption of elastic fibers as a functional output of protease activity. The recent demonstration that elastic fibers contribute to the biomechanical function of the pregnant cervix suggests their protease-induced disruption in the infection model of LPS-mediated PTB and may contribute to premature loss of mechanical competency and preterm delivery. Collectively, the transcriptomics and ultrastructural data provide new insights into the distinct mechanisms of premature cervical remodeling in response to infection.

  1. Minerals in soil select distinct bacterial communities in their microhabitats.

    Science.gov (United States)

    Carson, Jennifer K; Campbell, Louise; Rooney, Deirdre; Clipson, Nicholas; Gleeson, Deirdre B

    2009-03-01

    We tested the hypothesis that different minerals in soil select distinct bacterial communities in their microhabitats. Mica (M), basalt (B) and rock phosphate (RP) were incubated separately in soil planted with Trifolium subterraneum, Lolium rigidum or left unplanted. After 70 days, the mineral and soil fractions were separated by sieving. Automated ribosomal intergenic spacer analysis was used to determine whether the bacterial community structure was affected by the mineral, fraction and plant treatments. Principal coordinate plots showed clustering of bacterial communities from different fraction and mineral treatments, but not from different plant treatments. Permutational multivariate anova (permanova) showed that the microhabitats of M, B and RP selected bacterial communities different from each other in unplanted and L. rigidum, and in T. subterraneum, bacterial communities from M and B differed (Ppermanova also showed that each mineral fraction selected bacterial communities different from the surrounding soil fraction (P<0.05). This study shows that the structure of bacterial communities in soil is influenced by the mineral substrates in their microhabitat and that minerals in soil play a greater role in bacterial ecology than simply providing an inert matrix for bacterial growth. This study suggests that mineral heterogeneity in soil contributes to the spatial variation in bacterial communities.

  2. Topic Modeling Reveals Distinct Interests within an Online Conspiracy Forum

    Directory of Open Access Journals (Sweden)

    Colin Klein

    2018-02-01

    Full Text Available Conspiracy theories play a troubling role in political discourse. Online forums provide a valuable window into everyday conspiracy theorizing, and can give a clue to the motivations and interests of those who post in such forums. Yet this online activity can be difficult to quantify and study. We describe a unique approach to studying online conspiracy theorists which used non-negative matrix factorization to create a topic model of authors' contributions to the main conspiracy forum on Reddit.com. This subreddit provides a large corpus of comments which spans many years and numerous authors. We show that within the forum, there are multiple sub-populations distinguishable by their loadings on different topics in the model. Further, we argue, these differences are interpretable as differences in background beliefs and motivations. The diversity of the distinct subgroups places constraints on theories of what generates conspiracy theorizing. We argue that traditional “monological” believers are only the tip of an iceberg of commenters. Neither simple irrationality nor common preoccupations can account for the observed diversity. Instead, we suggest, those who endorse conspiracies seem to be primarily brought together by epistemological concerns, and that these central concerns link an otherwise heterogenous group of individuals.

  3. Analysis of surface contributions to external doses in a radioactively contaminated urban environment designed by the EMRAS-2 Urban Areas Working Group

    International Nuclear Information System (INIS)

    Hwang, Won Tae; Jeong, Hae Sun; Jeong, Hyo Joon; Kim, Eun Han; Han, Moon Hee; Kim, In Gyu

    2013-01-01

    Highlights: ► External dose and contribution from radio-activated surface were evaluated for EMRAS-2 Urban Areas Working Group scenarios. ► The external doses showed a distinctive difference with the locations and precipitation. ► The contribution of contaminated surfaces for external dose depends on locations and precipitation. ► These results provide the essential information for decision-making support of countermeasures. - Abstract: The EMRAS-2 Urban Areas Working Group, which is supported by the IAEA, has designed a variety of accidental scenarios to test and improve the capabilities of the models used for an evaluation of radioactive contamination in an urban environment. A variety of models including a Korean model, METRO-K, are used for predictive results on the hypothetical scenarios. This paper describes the predictive results of METRO-K for the hypothetical scenarios designed in the Working Group. The external dose resulting from the air contamination of Co-60 was evaluated, and its contribution was analyzed with time as a function of the location of a receptor and precipitation conditions at the time of the contamination event. As a result, the external doses showed a distinctive difference with the locations to be evaluated and the precipitation conditions. Moreover, the contribution of contaminated surfaces for external doses was strongly dependent on the locations to be evaluated and the precipitation conditions. These results will provide essential information to assist the decision-making of appropriate countermeasures in an emergency situation of a radioactively contaminated urban environment

  4. The IFN Response in Bats Displays Distinctive IFN-Stimulated Gene Expression Kinetics with Atypical RNASEL Induction.

    Science.gov (United States)

    De La Cruz-Rivera, Pamela C; Kanchwala, Mohammed; Liang, Hanquan; Kumar, Ashwani; Wang, Lin-Fa; Xing, Chao; Schoggins, John W

    2018-01-01

    Bats host a large number of zoonotic viruses, including several viruses that are highly pathogenic to other mammals. The mechanisms underlying this rich viral diversity are unknown, but they may be linked to unique immunological features that allow bats to act as asymptomatic viral reservoirs. Vertebrates respond to viral infection by inducing IFNs, which trigger antiviral defenses through IFN-stimulated gene (ISG) expression. Although the IFN system of several bats is characterized at the genomic level, less is known about bat IFN-mediated transcriptional responses. In this article, we show that IFN signaling in bat cells from the black flying fox ( Pteropus alecto ) consists of conserved and unique ISG expression profiles. In IFN-stimulated cells, bat ISGs comprise two unique temporal subclusters with similar early induction kinetics but distinct late-phase declines. In contrast, human ISGs lack this decline phase and remained elevated for longer periods. Notably, in unstimulated cells, bat ISGs were expressed more highly than their human counterparts. We also found that the antiviral effector 2-5A-dependent endoribonuclease, which is not an ISG in humans, is highly IFN inducible in black flying fox cells and contributes to cell-intrinsic control of viral infection. These studies reveal distinctive innate immune features that may underlie a unique virus-host relationship in bats. Copyright © 2017 by The American Association of Immunologists, Inc.

  5. Distinct patterns in the gut microbiota after surgical or medical therapy in obese patients

    Directory of Open Access Journals (Sweden)

    Daniel A. Medina

    2017-06-01

    Full Text Available Bariatric surgery is highly successful in improving health compared to conventional dietary treatments. It has been suggested that the gut microbiota is a relevant factor in weight loss after bariatric surgery. Considering that bariatric procedures cause different rearrangements of the digestive tract, they probably have different effects on the gut microbiota. In this study, we compared the impact of medical treatment, sleeve gastrectomy and Roux-en-Y gastric bypass on the gut microbiota from obese subjects. Anthropometric and clinical parameters were registered before, 6 and 12 months after treatment. Fecal samples were collected and microbiota composition was studied before and six months post treatment using 16S rRNA gene sequencing and qPCR. In comparison to dietary treatment, changes in intestinal microbiota were more pronounced in patients subjected to surgery, observing a bloom in Proteobacteria. Interestingly, Bacteroidetes abundance was largely different after six months of each surgical procedure. Furthermore, changes in weight and BMI, or glucose metabolism, correlated positively with changes in these two phyla in these surgical procedures. These results indicate that distinct surgical procedures alter the gut microbiota differently, and changes in gut microbiota might contribute to health improvement. This study contributes to our understanding of the impact of weight loss surgery on the gut microbiota, and could be used to replicate this effect using targeted therapies.

  6. An Objective Approach to Identify Spectral Distinctiveness for Hearing Impairment

    Directory of Open Access Journals (Sweden)

    Yeou-Jiunn Chen

    2013-01-01

    Full Text Available To facilitate the process of developing speech perception, speech-language pathologists have to teach a subject with hearing loss the differences between two syllables by manually enhancing acoustic cues of speech. However, this process is time consuming and difficult. Thus, this study proposes an objective approach to automatically identify the regions of spectral distinctiveness between two syllables, which is used for speech-perception training. To accurately represent the characteristics of speech, mel-frequency cepstrum coefficients are selected as analytical parameters. The mismatch between two syllables in time domain is handled by dynamic time warping. Further, a filter bank is adopted to estimate the components in different frequency bands, which are also represented as mel-frequency cepstrum coefficients. The spectral distinctiveness in different frequency bands is then easily estimated by using Euclidean metrics. Finally, a morphological gradient operator is applied to automatically identify the regions of spectral distinctiveness. To evaluate the proposed approach, the identified regions are manipulated and then the manipulated syllables are measured by a close-set based speech-perception test. The experimental results demonstrated that the identified regions of spectral distinctiveness are very useful in speech perception, which indeed can help speech-language pathologists in speech-perception training.

  7. INTENDED NATIONALLY DETERMINED CONTRIBUTIONS FROM THE MIDDLE EAST AND NORTH AFRICA

    OpenAIRE

    Syed Mahbubur Rahman; Mohammad Dulal Miah

    2016-01-01

    All Parties to the United Nations Framework Convention on Climate Change (UNFCCC) were requested to communicate intended nationally determined contributions (INDCs) in a clear, transparent and understandable way before the Conference of the Parties (known as COP21) held in Paris in 2015. The Contributions were supposed to be balanced and comprehensive to ensure sustainable development and expected to include finance, technology requires, technology transfer and capacity building aiming at mit...

  8. Familiar ethical issues amplified: how members of research ethics committees describe ethical distinctions between disaster and non-disaster research.

    Science.gov (United States)

    Tansey, Catherine M; Anderson, James; Boulanger, Renaud F; Eckenwiler, Lisa; Pringle, John; Schwartz, Lisa; Hunt, Matthew

    2017-06-28

    The conduct of research in settings affected by disasters such as hurricanes, floods and earthquakes is challenging, particularly when infrastructures and resources were already limited pre-disaster. However, since post-disaster research is essential to the improvement of the humanitarian response, it is important that adequate research ethics oversight be available. We aim to answer the following questions: 1) what do research ethics committee (REC) members who have reviewed research protocols to be conducted following disasters in low- and middle-income countries (LMICs) perceive as the key ethical concerns associated with disaster research?, and 2) in what ways do REC members understand these concerns to be distinct from those arising in research conducted in non-crisis situations? This qualitative study was developed using interpretative description methodology; 15 interviews were conducted with REC members. Four key ethical issues were identified as presenting distinctive considerations for disaster research to be implemented in LMICs, and were described by participants as familiar research ethics issues that were amplified in these contexts. First, REC members viewed disaster research as having strong social value due to its potential for improving disaster response, but also as requiring a higher level of justification compared to other research settings. Second, they identified vulnerability as an overarching concern for disaster research ethics, and a feature that required careful and critical appraisal when assessing protocols. They noted that research participants' vulnerabilities frequently change in the aftermath of a disaster and often in unpredictable ways. Third, they identified concerns related to promoting and maintaining safety, confidentiality and data security in insecure or austere environments. Lastly, though REC members endorsed the need and usefulness of community engagement, they noted that there are significant challenges in a disaster

  9. Distinct cytoplasmic domains of the growth hormone receptor are required for glucocorticoid- and phorbol ester-induced decreases in growth hormone (GH) binding. These domains are different from that reported for GH-induced receptor internalization

    DEFF Research Database (Denmark)

    King, A P; Tseng, M J; Logsdon, C D

    1996-01-01

    Glucocorticoids inhibit growth in children and antagonize the growth-promoting action of GH in peripheral tissues. Recently, they have been shown to decrease GH binding. In this study we examine the molecular mechanisms by which the glucocorticoid dexamethasone (DEX) and the phorbol ester phorbol...... of GH binding are also observed in a Chinese hamster ovary (CHO) cell line stably transfected with a rat liver GHR cDNA, further arguing that DEX and PMA act post-translationally on GHR. Using mutant GHRs stably expressed in CHO cells, amino acids 455-506 and tyrosines 333 and/or 338 of GHR were shown...... to be required for maximal DEX-induced inhibition of GH binding. DEX decreased GH binding to a GHR mutant F346A, which is reported to be deficient in ligand-induced internalization, suggesting that DEX decreases GH binding by a mechanism distinct from that of ligand-induced GHR internalization. PMA reduced GH...

  10. Spasticity and Its Contribution to Hypertonia in Cerebral Palsy

    Directory of Open Access Journals (Sweden)

    Lynn Bar-On

    2015-01-01

    Full Text Available Spasticity is considered an important neural contributor to muscle hypertonia in children with cerebral palsy (CP. It is most often treated with antispasticity medication, such as Botulinum Toxin-A. However, treatment response is highly variable. Part of this variability may be due to the inability of clinical tests to differentiate between the neural (e.g., spasticity and nonneural (e.g., soft tissue properties contributions to hypertonia, leading to the terms “spasticity” and “hypertonia” often being used interchangeably. Recent advancements in instrumented spasticity assessments offer objective measurement methods for distinction and quantification of hypertonia components. These methods can be applied in clinical settings and their results used to fine-tune and improve treatment. We reviewed current advancements and new insights with respect to quantifying spasticity and its contribution to muscle hypertonia in children with CP. First, we revisit what is known about spasticity in children with CP, including the various definitions and its pathophysiology. Second, we summarize the state of the art on instrumented spasticity assessment in CP and review the parameters developed to quantify the neural and nonneural components of hypertonia. Lastly, the impact these quantitative parameters have on clinical decision-making is considered and recommendations for future clinical and research investigations are discussed.

  11. Parallel prefrontal pathways reach distinct excitatory and inhibitory systems in memory-related rhinal cortices.

    Science.gov (United States)

    Bunce, Jamie G; Zikopoulos, Basilis; Feinberg, Marcia; Barbas, Helen

    2013-12-15

    To investigate how prefrontal cortices impinge on medial temporal cortices we labeled pathways from the anterior cingulate cortex (ACC) and posterior orbitofrontal cortex (pOFC) in rhesus monkeys to compare their relationship with excitatory and inhibitory systems in rhinal cortices. The ACC pathway terminated mostly in areas 28 and 35 with a high proportion of large terminals, whereas the pOFC pathway terminated mostly through small terminals in area 36 and sparsely in areas 28 and 35. Both pathways terminated in all layers. Simultaneous labeling of pathways and distinct neurochemical classes of inhibitory neurons, followed by analyses of appositions of presynaptic and postsynaptic fluorescent signal, or synapses, showed overall predominant association with spines of putative excitatory neurons, but also significant interactions with presumed inhibitory neurons labeled for calretinin, calbindin, or parvalbumin. In the upper layers of areas 28 and 35 the ACC pathway was associated with dendrites of neurons labeled with calretinin, which are thought to disinhibit neighboring excitatory neurons, suggesting facilitated hippocampal access. In contrast, in area 36 pOFC axons were associated with dendrites of calbindin neurons, which are poised to reduce noise and enhance signal. In the deep layers, both pathways innervated mostly dendrites of parvalbumin neurons, which strongly inhibit neighboring excitatory neurons, suggesting gating of hippocampal output to other cortices. These findings suggest that the ACC, associated with attention and context, and the pOFC, associated with emotional valuation, have distinct contributions to memory in rhinal cortices, in processes that are disrupted in psychiatric diseases. Copyright © 2013 Wiley Periodicals, Inc.

  12. Common and distinct components in data fusion

    DEFF Research Database (Denmark)

    Smilde, Age Klaas; Mage, Ingrid; Næs, Tormod

    2016-01-01

    and understanding their relative merits. This paper provides a unifying framework for this subfield of data fusion by using rigorous arguments from linear algebra. The most frequently used methods for distinguishing common and distinct components are explained in this framework and some practical examples are given...

  13. [Nusing-sensitive indicadors: an opportunity for measuring the nurse contribution].

    Science.gov (United States)

    Planas-Campmany, Carme; Icart-Isern, M Teresa

    2014-01-01

    The measures directed at improving the management and funding of health services that justify the measurement of performance and the purchase of services based on results, have a direct influence on nursing. In this context, concerns about the value and contribution of nursing have been demonstrated worldwide over the last decades. Therefore efforts are being made to ensure that nurses contribute to promote the transformation of health systems. This requires identifying their contribution to the health system and, specifically, in relation to health outcomes. In recent decades, there has been a growing demand to achieve measures which allow nurses to demonstrate and assume responsibility for their contribution. The research and development of nursing-sensitive indicators and results, and its application, provide an opportunity to measure the contribution and professional performance in achieving these set objectives, in order to improve population health. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  14. Distinctiveness enhances long-term event memory in non-human primates, irrespective of reinforcement.

    Science.gov (United States)

    Lewis, Amy; Call, Josep; Berntsen, Dorthe

    2017-08-01

    Non-human primates are capable of recalling events that occurred as long as 3 years ago, and are able to distinguish between similar events; akin to human memory. In humans, distinctiveness enhances memory for events, however, it is unknown whether the same occurs in non-human primates. As such, we tested three great ape species on their ability to remember an event that varied in distinctiveness. Across three experiments, apes witnessed a baiting event in which one of three identical containers was baited with food. After a delay of 2 weeks, we tested their memory for the location of the baited container. Apes failed to recall the baited container when the event was undistinctive (Experiment 1), but were successful when it was distinctive (Experiment 2), although performance was equally good in a less-distinctive condition. A third experiment (Experiment 3) confirmed that distinctiveness, independent of reinforcement, was a consistent predictor of performance. These findings suggest that distinctiveness may enhance memory for events in non-human primates in the same way as in humans, and provides further evidence of basic similarities between the ways apes and humans remember past events. © 2017 Wiley Periodicals, Inc.

  15. Distinct types of eigenvector localization in networks

    Science.gov (United States)

    Pastor-Satorras, Romualdo; Castellano, Claudio

    2016-01-01

    The spectral properties of the adjacency matrix provide a trove of information about the structure and function of complex networks. In particular, the largest eigenvalue and its associated principal eigenvector are crucial in the understanding of nodes’ centrality and the unfolding of dynamical processes. Here we show that two distinct types of localization of the principal eigenvector may occur in heterogeneous networks. For synthetic networks with degree distribution P(q) ~ q-γ, localization occurs on the largest hub if γ > 5/2 for γ < 5/2 a new type of localization arises on a mesoscopic subgraph associated with the shell with the largest index in the K-core decomposition. Similar evidence for the existence of distinct localization modes is found in the analysis of real-world networks. Our results open a new perspective on dynamical processes on networks and on a recently proposed alternative measure of node centrality based on the non-backtracking matrix.

  16. Are functional foods redefining nutritional requirements?

    Science.gov (United States)

    Jones, Peter J; Varady, Krista A

    2008-02-01

    Functional foods are increasing in popularity owing to their ability to confer health and physiological benefits. Nevertheless, the notion that functional foods improve health when providing nutrients at levels above and beyond existing recommended intakes is inconsistent with the definition of requirement. This disparity highlights the need for an alternative definition of nutrient requirement. The present objective is to examine distinctions between optimization of health, as defined by what we currently deem as required intakes, versus adding physiological benefit using bioactive agents found in functional foods. Presently, requirement is defined as the lowest amount of intake of a nutrient that will maintain a defined level of nourishment for a specific indicator of adequacy. In contrast, functional foods are described as ingredients that are not necessary for body function, yet provide added physiological benefit that confer better overall health. Plant sterols are one example of such an ingredient. Plant sterols lower plasma cholesterol concentrations, and may thus be considered essential nutrients in physiological situations where circulating cholesterol concentrations are high. Similarly, intakes of omega-3 fats beyond existing requirement may confer additional health benefits such as hypolipidemic and anti-diabetic effects. These examples underscore the inconsistencies between what is defined as a nutrient requirement versus what is identified as a health benefit of a functional food. Such discrepancies emphasize the need for a more all-encompassing definition of a nutrient requirement; that is, one that moves beyond the prevention of overt deficiency to encompass improved health and disease risk reduction.

  17. Presidential address: distinction or extinction.

    Science.gov (United States)

    Pressman, Barry D

    2008-10-01

    Despite its continuing scientific successes in imaging, radiology as a specialty is faced with a very difficult and competitive environment. Nonradiologists are more and more interested in vertically integrating imaging into their practices, while teleradiology and picture archiving and communication systems are resulting in the greater isolation of radiologists. Commoditization is a realistic and devastating threat to the survival and professionalism of the specialty. To remain viable as a specialty, radiologists must elevate their practice by subspecializing, becoming more involved with clinical care, and actively interacting with patients and referring clinicians. Distinction will prevent extinction.

  18. The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Tong; Yu, Rong [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden); Jin, Shao-Bo [Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Han, Liwei [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden); Lendahl, Urban [Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm (Sweden); Zhao, Jian, E-mail: Jian.Zhao@ki.se [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden); Nistér, Monica [Department of Oncology–Pathology, Karolinska Institutet, CCK R8:05, Karolinska University Hospital Solna, SE-171 76 Stockholm (Sweden)

    2013-11-01

    Mitochondria are dynamic organelles whose morphology is regulated by a complex balance of fission and fusion processes, and we still know relatively little about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has recently been characterized as a key regulator of mitochondrial dynamics and in this report we explore the functions of its paralog MIEF2 (also called MiD49), to learn to what extent MIEF2 is functionally distinct from MIEF1. We show that MIEF1 and MIEF2 have many functions in common. Both are anchored in the mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the mitochondrial surface and cause mitochondrial fusion, and MIEF2, like MIEF1, can interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect than MIEF1, and in line with this, hFis1 and Mff can only partially revert the MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers, while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use distinct domains for oligomerization: in MIEF1, the region from amino acid residues 109–154 is required, whereas oligomerization of MIEF2 depends on amino acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization of MIEF1 is not required for its mitochondrial localization and interaction with Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. - Highlights: • MIEF1 and MIEF2 recruit Drp1 to mitochondria and cause mitochondrial fusion. • MIEF2, like MIEF1, can interact with Drp1 and hFis1. • MIEF1 and MIEF2 are differentially expressed in human tissues during development. • MIEF2 exerts a stronger fusion

  19. The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

    International Nuclear Information System (INIS)

    Liu, Tong; Yu, Rong; Jin, Shao-Bo; Han, Liwei; Lendahl, Urban; Zhao, Jian; Nistér, Monica

    2013-01-01

    Mitochondria are dynamic organelles whose morphology is regulated by a complex balance of fission and fusion processes, and we still know relatively little about how mitochondrial dynamics is regulated. MIEF1 (also called MiD51) has recently been characterized as a key regulator of mitochondrial dynamics and in this report we explore the functions of its paralog MIEF2 (also called MiD49), to learn to what extent MIEF2 is functionally distinct from MIEF1. We show that MIEF1 and MIEF2 have many functions in common. Both are anchored in the mitochondrial outer membrane, recruit Drp1 from the cytoplasm to the mitochondrial surface and cause mitochondrial fusion, and MIEF2, like MIEF1, can interact with Drp1 and hFis1. MIEF1 and MIEF2, however, also differ in certain aspects. MIEF1 and MIEF2 are differentially expressed in human tissues during development. When overexpressed, MIEF2 exerts a stronger fusion-promoting effect than MIEF1, and in line with this, hFis1 and Mff can only partially revert the MIEF2-induced fusion phenotype, whereas MIEF1-induced fusion is reverted to a larger extent by hFis1 and Mff. MIEF2 forms high molecular weight oligomers, while MIEF1 is largely present as a dimer. Furthermore, MIEF1 and MIEF2 use distinct domains for oligomerization: in MIEF1, the region from amino acid residues 109–154 is required, whereas oligomerization of MIEF2 depends on amino acid residues 1 to 49, i.e. the N-terminal end. We also show that oligomerization of MIEF1 is not required for its mitochondrial localization and interaction with Drp1. In conclusion, our data suggest that the mitochondrial regulators MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics. - Highlights: • MIEF1 and MIEF2 recruit Drp1 to mitochondria and cause mitochondrial fusion. • MIEF2, like MIEF1, can interact with Drp1 and hFis1. • MIEF1 and MIEF2 are differentially expressed in human tissues during development. • MIEF2 exerts a stronger fusion

  20. Clarifying relations between dispositional aggression and brain potential response: overlapping and distinct contributions of impulsivity and stress reactivity.

    Science.gov (United States)

    Venables, Noah C; Patrick, Christopher J; Hall, Jason R; Bernat, Edward M

    2011-03-01

    Impulsive-aggressive individuals exhibit deficits in amplitude of the P3 brain potential response, however, it remains unclear how separable dispositional traits account for this association. The current study sought to clarify the basis of this association by examining contributions of trait impulsiveness and stress reactivity to the observed relationship between dispositional aggression and amplitude of the P3 brain potential response in a visual novelty-oddball procedure. A significant negative association was found between aggressiveness and amplitude of P3 response to both target and novel stimuli over frontal-central scalp sites. Impulsivity showed a parallel inverse relationship with P3 amplitude, attributable to its overlap with dispositional aggression. In contrast, stress reactivity did not exhibit a zero-order association with P3 amplitude, but modestly predicted P3 in a positive direction after accounting for its overlap with aggression. Results are discussed in terms of their implications for individual difference variables and brain processes underlying impulsive-aggressive behavior. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Moral fiction or moral fact? The distinction between doing and allowing in medical ethics.

    Science.gov (United States)

    Huddle, Thomas S

    2013-06-01

    Opponents of physician-assisted suicide (PAS) maintain that physician withdrawal-of-life-sustaining-treatment cannot be morally equated to voluntary active euthanasia. PAS opponents generally distinguish these two kinds of act by positing a possible moral distinction between killing and allowing-to-die, ceteris paribus. While that distinction continues to be widely accepted in the public discourse, it has been more controversial among philosophers. Some ethicist PAS advocates are so certain that the distinction is invalid that they describe PAS opponents who hold to the distinction as in the grip of 'moral fictions'. The author contends that such a diagnosis is too hasty. The possibility of a moral distinction between active euthanasia and allowing-to-die has not been closed off by the argumentative strategies employed by these PAS advocates, including the contrasting cases strategy and the assimilation of doing and allowing to a common sense notion of causation. The philosophical debate over the doing/allowing distinction remains inconclusive, but physicians and others who rely upon that distinction in thinking about the ethics of end-of-life care need not give up on it in response to these arguments. © 2012 John Wiley & Sons Ltd.

  2. Directed networks' different link formation mechanisms causing degree distribution distinction

    Science.gov (United States)

    Behfar, Stefan Kambiz; Turkina, Ekaterina; Cohendet, Patrick; Burger-Helmchen, Thierry

    2016-11-01

    Within undirected networks, scientists have shown much interest in presenting power-law features. For instance, Barabási and Albert (1999) claimed that a common property of many large networks is that vertex connectivity follows scale-free power-law distribution, and in another study Barabási et al. (2002) showed power law evolution in the social network of scientific collaboration. At the same time, Jiang et al. (2011) discussed deviation from power-law distribution; others indicated that size effect (Bagrow et al., 2008), information filtering mechanism (Mossa et al., 2002), and birth and death process (Shi et al., 2005) could account for this deviation. Within directed networks, many authors have considered that outlinks follow a similar mechanism of creation as inlinks' (Faloutsos et al., 1999; Krapivsky et al., 2001; Tanimoto, 2009) with link creation rate being the linear function of node degree, resulting in a power-law shape for both indegree and outdegree distribution. Some other authors have made an assumption that directed networks, such as scientific collaboration or citation, behave as undirected, resulting in a power-law degree distribution accordingly (Barabási et al., 2002). At the same time, we claim (1) Outlinks feature different degree distributions than inlinks; where different link formation mechanisms cause the distribution distinctions, (2) in/outdegree distribution distinction holds for different levels of system decomposition; therefore this distribution distinction is a property of directed networks. First, we emphasize in/outlink formation mechanisms as causal factors for distinction between indegree and outdegree distributions (where this distinction has already been noticed in Barker et al. (2010) and Baxter et al. (2006)) within a sample network of OSS projects as well as Java software corpus as a network. Second, we analyze whether this distribution distinction holds for different levels of system decomposition: open

  3. On the nature of in vivo requirements for rde-4 in RNAi and developmental pathways in C. elegans.

    Science.gov (United States)

    Blanchard, Daniel; Parameswaran, Poornima; Lopez-Molina, Javier; Gent, Jonathan; Saynuk, Jamie Fleenor; Fire, Andrew

    2011-01-01

    C. elegans RDE-4 is a double-stranded RNA binding protein that has been shown to play a key role in response to foreign double-stranded RNA (dsRNA). We have used diverse tools for analysis of gene function to characterize the domain and organismal foci of RDE-4 action in C. elegans. First, we examined the focus of activity within the RDE-4 protein, by testing a series of RDE-4 deletion constructs for their ability to support dsRNA-triggered gene silencing. These assays indicated a molecular requirement for a linker region and the second dsRNA-binding domain of RDE-4, with ancillary contributions to function from the C and N terminal domains. Second, we used mosaic analysis to explore the cellular focus of action of RDE-4. These experiments indicated an ability of RDE-4 to function non-autonomously in foreign RNA responses. Third, we used growth under stressful conditions to search for evidence of an organismal focus of action for RDE-4 distinct from its role in response to foreign dsRNA. Propagation at high temperatures exposed a conditional requirement for RDE-4 for optimal growth and fertility, indicating at least under these conditions that RDE-4 can serve an essential role in C. elegans. © 2011 Landes Bioscience

  4. Short interspersed element (SINE) depletion and long interspersed element (LINE) abundance are not features universally required for imprinting.

    Science.gov (United States)

    Cowley, Michael; de Burca, Anna; McCole, Ruth B; Chahal, Mandeep; Saadat, Ghazal; Oakey, Rebecca J; Schulz, Reiner

    2011-04-20

    Genomic imprinting is a form of gene dosage regulation in which a gene is expressed from only one of the alleles, in a manner dependent on the parent of origin. The mechanisms governing imprinted gene expression have been investigated in detail and have greatly contributed to our understanding of genome regulation in general. Both DNA sequence features, such as CpG islands, and epigenetic features, such as DNA methylation and non-coding RNAs, play important roles in achieving imprinted expression. However, the relative importance of these factors varies depending on the locus in question. Defining the minimal features that are absolutely required for imprinting would help us to understand how imprinting has evolved mechanistically. Imprinted retrogenes are a subset of imprinted loci that are relatively simple in their genomic organisation, being distinct from large imprinting clusters, and have the potential to be used as tools to address this question. Here, we compare the repeat element content of imprinted retrogene loci with non-imprinted controls that have a similar locus organisation. We observe no significant differences that are conserved between mouse and human, suggesting that the paucity of SINEs and relative abundance of LINEs at imprinted loci reported by others is not a sequence feature universally required for imprinting.

  5. Short interspersed element (SINE depletion and long interspersed element (LINE abundance are not features universally required for imprinting.

    Directory of Open Access Journals (Sweden)

    Michael Cowley

    2011-04-01

    Full Text Available Genomic imprinting is a form of gene dosage regulation in which a gene is expressed from only one of the alleles, in a manner dependent on the parent of origin. The mechanisms governing imprinted gene expression have been investigated in detail and have greatly contributed to our understanding of genome regulation in general. Both DNA sequence features, such as CpG islands, and epigenetic features, such as DNA methylation and non-coding RNAs, play important roles in achieving imprinted expression. However, the relative importance of these factors varies depending on the locus in question. Defining the minimal features that are absolutely required for imprinting would help us to understand how imprinting has evolved mechanistically. Imprinted retrogenes are a subset of imprinted loci that are relatively simple in their genomic organisation, being distinct from large imprinting clusters, and have the potential to be used as tools to address this question. Here, we compare the repeat element content of imprinted retrogene loci with non-imprinted controls that have a similar locus organisation. We observe no significant differences that are conserved between mouse and human, suggesting that the paucity of SINEs and relative abundance of LINEs at imprinted loci reported by others is not a sequence feature universally required for imprinting.

  6. Viking lander tracking contributions to Mars mapping

    International Nuclear Information System (INIS)

    Michael, W.H. Jr.

    1979-01-01

    The major recent advances in planetary mapping have been accomplished through use of photography from orbiting satellites, as is the case for Mars with Mariner and Viking photographs. The requirement for greater precision demands that inputs to the photogrammatic process be more precisely defined. This paper describes how analyses of Doppler and ranging data from the Viking landers are contributing to more precise mapping of Mars in several specific areas. (Auth.)

  7. An Adult Developmental Approach to Perceived Facial Attractiveness and Distinctiveness

    OpenAIRE

    Natalie C. Ebner; Natalie C. Ebner; Natalie C. Ebner; Joerg Luedicke; Manuel C. Voelkle; Manuel C. Voelkle; Michaela Riediger; Michaela Riediger; Tian Lin; Ulman Lindenberger; Ulman Lindenberger

    2018-01-01

    Attractiveness and distinctiveness constitute facial features with high biological and social relevance. Bringing a developmental perspective to research on social-cognitive face perception, we used a large set of faces taken from the FACES Lifespan Database to examine effects of face and perceiver characteristics on subjective evaluations of attractiveness and distinctiveness in young (20–31 years), middle-aged (44–55 years), and older (70–81 years) men and women. We report novel findings su...

  8. Differential influence of distinct components of increased blood pressure on cardiovascular outcomes: from the atherosclerosis risk in communities study.

    Science.gov (United States)

    Cheng, Susan; Gupta, Deepak K; Claggett, Brian; Sharrett, A Richey; Shah, Amil M; Skali, Hicham; Takeuchi, Madoka; Ni, Hanyu; Solomon, Scott D

    2013-09-01

    Elevation in blood pressure (BP) increases risk for all cardiovascular events. Nevertheless, the extent to which different indices of BP elevation may be associated to varying degrees with different cardiovascular outcomes remains unclear. We studied 13340 participants (aged 54 ± 6 years, 56% women and 27% black) of the Atherosclerosis Risk in Communities Study who were free of baseline cardiovascular disease. We used Cox proportional hazards models to compare the relative contributions of systolic BP, diastolic BP, pulse pressure, and mean arterial pressure to risk for coronary heart disease, heart failure, stroke, and all-cause mortality. For each multivariable-adjusted model, the largest area under the receiver-operating curve (AUC) and smallest -2 log-likelihood values were used to identify BP measures with the greatest contribution to risk prediction for each outcome. A total of 2095 coronary heart disease events, 1669 heart failure events, 771 stroke events, and 3016 deaths occurred during 18 ± 5 years of follow-up. In multivariable analyses adjusting for traditional cardiovascular risk factors, the BP measures with the greatest risk contributions were the following: systolic BP for coronary heart disease (AUC=0.74); pulse pressure for heart failure (AUC=0.79); systolic BP for stroke (AUC=0.74); and pulse pressure for all-cause mortality (AUC=0.74). With few exceptions, results were similar in analyses stratified by age, sex, and race. Our data indicate that distinct BP components contribute variably to risk for different cardiovascular outcomes.

  9. Tagging like Humans: Diverse and Distinct Image Annotation

    KAUST Repository

    Wu, Baoyuan; Chen, Weidong; Sun, Peng; Liu, Wei; Ghanem, Bernard; Lyu, Siwei

    2018-01-01

    including quantitative and qualitative comparisons, as well as human subject studies, on two benchmark datasets demonstrate that the proposed model can produce more diverse and distinct tags than the state-of-the-arts.

  10. Evidence and characterization of a glide-vowel distinction in American English

    Directory of Open Access Journals (Sweden)

    Zachary Scott Jaggers

    2018-02-01

    Full Text Available This study tests whether native speakers of American English exhibit a glide-vowel distinction ([j]-[i] in a speech elicitation experiment. When reading sentences out loud, participants’ pronunciations of 4 near-minimal pairs of pre-existing lexical items (e.g., 'Eston'[iə] vs. 'pneumon'[jə] exhibit significant differences when acoustically measured, confirming the presence of a [j]-[i] distinction. This distinction is also found to be productively extended to the production of 20 near-minimal pairs of nonce words (e.g., 'Súmia '→ [sumiə] vs. 'Fímya '→ [fimjə], diversified and balanced along different phonologically relevant factors of the surrounding environment. Multiple acoustic measurements are compared to test what aspects most consistently convey the distinction: F2 (frontness, F1 (height, intensity, vocalic sequence duration, transition earliness, and transition speed. This serves the purpose of documenting the distinction’s acoustic phonetic realization. It also serves in the comparison of phonological representations. Multiple types of previously proposed phonological representations are considered along with the competing predictions they generate regarding the acoustic measurements performed. Results suggest that the primary and most consistent characteristic of the distinction is earliness of transition into the following vowel, with results also suggesting that the [j] glide has a greater degree of constriction. The [j] glide is found to have a significantly 'less 'anterior articulation, challenging the application of a representation based on place or articulator differences that would predict [j] to be 'more 'anterior.

  11. Distinctive skeletal dysplasia in Cockayne syndrome

    International Nuclear Information System (INIS)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-01-01

    Cockayne syndrom is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvment of the spine. (orig.)

  12. Distinctive skeletal dysplasia in Cockayne syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Silengo, M.C.; Franceschini, P.; Bianco, R.; Biagioli, M.; Pastorin, L.; Vista, N.; Baldassar, A.; Benso, L.

    1986-03-01

    Cockayne syndrome is a well-known autosomal recessive form of dwarfism with senile-like appearance. Skeletal changes such as flattening of vertebral bodies, ivory epiphyses and thickening of cranial vault, have been observed in some patients with this condition. We describe here a 5.5-year-old girl with the typical clinical signs of Cockayne syndrome and a distinctive form of bone dysplasia with major involvement of the spine.

  13. Decree of 16 October 1969, Stb. 475, concerning the implementation of Section 74 of the Nuclear Energy Act (Contributions)

    International Nuclear Information System (INIS)

    1969-01-01

    In accordance with the Nuclear Energy Act, this Decree determines the amount of contributions required towards the costs incurred by the State in implementation of the Act. Contributions are required when licences are granted, when packaging must be approved and when materials are transported. (NEA) [fr

  14. Contribution of cellular autolysis to tissular functions during plant development.

    Science.gov (United States)

    Escamez, Sacha; Tuominen, Hannele

    2017-02-01

    Plant development requires specific cells to be eliminated in a predictable and genetically regulated manner referred to as programmed cell death (PCD). However, the target cells do not merely die but they also undergo autolysis to degrade their cellular corpses. Recent progress in understanding developmental cell elimination suggests that distinct proteins execute PCD sensu stricto and autolysis. In addition, cell death alone and cell dismantlement can fulfill different functions. Hence, it appears biologically meaningful to distinguish between the modules of PCD and autolysis during plant development. Copyright © 2016 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  15. The usefulness of the grammaticality-acceptability distinction in functional approaches to language

    DEFF Research Database (Denmark)

    Poulsen, Mads

    2013-01-01

    between competence and performance, rather than on a distinction between syntax and meaning. The basic rationale for having such a distinction is that much of linguistics is concerned with describing relatively stable grammatical knowledge, rather than the psycholinguistic dynamics of language use...

  16. Asymmetric functional contributions of acidic and aromatic side chains in sodium channel voltage-sensor domains

    DEFF Research Database (Denmark)

    Pless, Stephan Alexander; Elstone, Fisal D; Niciforovic, Ana P

    2014-01-01

    largely enigmatic. To this end, natural and unnatural side chain substitutions were made in the S2 hydrophobic core (HC), the extracellular negative charge cluster (ENC), and the intracellular negative charge cluster (INC) of the four VSDs of the skeletal muscle sodium channel isoform (NaV1......Voltage-gated sodium (NaV) channels mediate electrical excitability in animals. Despite strong sequence conservation among the voltage-sensor domains (VSDs) of closely related voltage-gated potassium (KV) and NaV channels, the functional contributions of individual side chains in Nav VSDs remain.......4). The results show that the highly conserved aromatic side chain constituting the S2 HC makes distinct functional contributions in each of the four NaV domains. No obvious cation-pi interaction exists with nearby S4 charges in any domain, and natural and unnatural mutations at these aromatic sites produce...

  17. ORNL implementation of new health and safety requirements (DOE Order 5480.11)

    International Nuclear Information System (INIS)

    Abercrombie, J.S.

    1988-01-01

    New mandates in radiological protection outlined in DOE Order 5480. 11, include changes in the methodology for determining total radiation dose, ALARA program accountability, monitoring requirements, and standards for public entrance into controlled areas. The new order places distinct requirements concerning training at all DOE facilities. Radiation protection training requirements are addressed, including the effective communication of operations changes to all employees. This paper details the endeavors underway at ORNL in designing, developing, and delivering the training required by the new mandates. Strategies taken to reach the intended goals are explained. Efforts involve the design and implementation of the above mentioned radiation protection programs, a job-specific ALARA instructional package, and a Risk-Based Philosophy program matched to operational changes. 4 refs., 5 tabs

  18. Regenerant arabidopsis lineages display a distinct genome-wide spectrum of mutations conferring variant phenotypes

    KAUST Repository

    Jiang, Caifu

    2011-07-28

    Multicellular organisms can be regenerated from totipotent differentiated somatic cell or nuclear founders [1-3]. Organisms regenerated from clonally related isogenic founders might a priori have been expected to be phenotypically invariant. However, clonal regenerant animals display variant phenotypes caused by defective epigenetic reprogramming of gene expression [2], and clonal regenerant plants exhibit poorly understood heritable phenotypic ("somaclonal") variation [4-7]. Here we show that somaclonal variation in regenerant Arabidopsis lineages is associated with genome-wide elevation in DNA sequence mutation rate. We also show that regenerant mutations comprise a distinctive molecular spectrum of base substitutions, insertions, and deletions that probably results from decreased DNA repair fidelity. Finally, we show that while regenerant base substitutions are a likely major genetic cause of the somaclonal variation of regenerant Arabidopsis lineages, transposon movement is unlikely to contribute substantially to that variation. We conclude that the phenotypic variation of regenerant plants, unlike that of regenerant animals, is substantially due to DNA sequence mutation. 2011 Elsevier Ltd. All rights reserved.

  19. Regenerant arabidopsis lineages display a distinct genome-wide spectrum of mutations conferring variant phenotypes

    KAUST Repository

    Jiang, Caifu; Mithani, Aziz; Gan, Xiangchao; Belfield, Eric J.; Klingler, John  P.; Zhu, Jian-Kang; Ragoussis, Jiannis; Mott, Richard; Harberd, Nicholas  P.

    2011-01-01

    Multicellular organisms can be regenerated from totipotent differentiated somatic cell or nuclear founders [1-3]. Organisms regenerated from clonally related isogenic founders might a priori have been expected to be phenotypically invariant. However, clonal regenerant animals display variant phenotypes caused by defective epigenetic reprogramming of gene expression [2], and clonal regenerant plants exhibit poorly understood heritable phenotypic ("somaclonal") variation [4-7]. Here we show that somaclonal variation in regenerant Arabidopsis lineages is associated with genome-wide elevation in DNA sequence mutation rate. We also show that regenerant mutations comprise a distinctive molecular spectrum of base substitutions, insertions, and deletions that probably results from decreased DNA repair fidelity. Finally, we show that while regenerant base substitutions are a likely major genetic cause of the somaclonal variation of regenerant Arabidopsis lineages, transposon movement is unlikely to contribute substantially to that variation. We conclude that the phenotypic variation of regenerant plants, unlike that of regenerant animals, is substantially due to DNA sequence mutation. 2011 Elsevier Ltd. All rights reserved.

  20. Distinct population structure for co-occurring Anopheles goeldii and Anopheles triannulatus in Amazonian Brazil

    Directory of Open Access Journals (Sweden)

    Sascha Naomi McKeon

    2013-08-01

    Full Text Available To evaluate whether environmental heterogeneity contributes to the genetic heterogeneity in Anopheles triannulatus, larval habitat characteristics across the Brazilian states of Roraima and Pará and genetic sequences were examined. A comparison with Anopheles goeldii was utilised to determine whether high genetic diversity was unique to An. triannulatus. Student t test and analysis of variance found no differences in habitat characteristics between the species. Analysis of population structure of An. triannulatus and An. goeldii revealed distinct demographic histories in a largely overlapping geographic range. Cytochrome oxidase I sequence parsimony networks found geographic clustering for both species; however nuclear marker networks depicted An. triannulatus with a more complex history of fragmentation, secondary contact and recent divergence. Evidence of Pleistocene expansions suggests both species are more likely to be genetically structured by geographic and ecological barriers than demography. We hypothesise that niche partitioning is a driving force for diversity, particularly in An. triannulatus.

  1. An overexpression screen of Toxoplasma gondii Rab-GTPases reveals distinct transport routes to the micronemes.

    Directory of Open Access Journals (Sweden)

    Katrin Kremer

    2013-03-01

    Full Text Available The basic organisation of the endomembrane system is conserved in all eukaryotes and comparative genome analyses provides compelling evidence that the endomembrane system of the last common eukaryotic ancestor (LCEA is complex with many genes required for regulated traffic being present. Although apicomplexan parasites, causative agents of severe human and animal diseases, appear to have only a basic set of trafficking factors such as Rab-GTPases, they evolved unique secretory organelles (micronemes, rhoptries and dense granules that are sequentially secreted during invasion of the host cell. In order to define the secretory pathway of apicomplexans, we performed an overexpression screen of Rabs in Toxoplasma gondii and identified Rab5A and Rab5C as important regulators of traffic to micronemes and rhoptries. Intriguingly, we found that not all microneme proteins traffic depends on functional Rab5A and Rab5C, indicating the existence of redundant microneme targeting pathways. Using two-colour super-resolution stimulated emission depletion (STED we verified distinct localisations of independent microneme proteins and demonstrate that micronemal organelles are organised in distinct subsets or subcompartments. Our results suggest that apicomplexan parasites modify classical regulators of the endocytic system to carryout essential parasite-specific roles in the biogenesis of their unique secretory organelles.

  2. Sources, classification, and disposal of radioactive wastes: History and legal and regulatory requirements

    International Nuclear Information System (INIS)

    Kocher, D.C.

    1991-01-01

    This report discusses the following topics: (1) early definitions of different types (classes) of radioactive waste developed prior to definitions in laws and regulations; (2) sources of different classes of radioactive waste; (3) current laws and regulations addressing classification of radioactive wastes; and requirements for disposal of different waste classes. Relationship between waste classification and requirements for permanent disposal is emphasized; (4) federal and state responsibilities for radioactive wastes; and (5) distinctions between radioactive wastes produced in civilian and defense sectors

  3. Structuring Formal Requirements Specifications for Reuse and Product Families

    Science.gov (United States)

    Heimdahl, Mats P. E.

    2001-01-01

    In this project we have investigated how formal specifications should be structured to allow for requirements reuse, product family engineering, and ease of requirements change, The contributions of this work include (1) a requirements specification methodology specifically targeted for critical avionics applications, (2) guidelines for how to structure state-based specifications to facilitate ease of change and reuse, and (3) examples from the avionics domain demonstrating the proposed approach.

  4. Hf Isotope Evidence for Subducted Basalt and Sediment Contributions to the Eastern Trans-Mexican Volcanic Belt

    Science.gov (United States)

    Cai, Y.; Tuena, A. G.; Capra, L.; Straub, S. M.; Goldstein, S. L.; Langmuir, C. H.

    2005-12-01

    Magmas generated at thick crust continental arcs often have enriched continental crust-like trace element patterns and Pb-Sr-Nd isotope ratios that are intermediate to both upper mantle and crustal compositions. Thus it is difficult to distinguish between contributions from (a) the subducted basalt and the upper mantle wedge, and (b) subducted sediment and the continental crust. These issues have been the focus of major controversy. Here we show evidence for subduction contributions to lavas in a classic thick crust environment. In Eastern Trans-Mexican Volcanic Belt, the upper continental crust is 30 km to 45 km thick. However, primitive mafic lavas erupt on many sites across the arc. We have analyzed the subducting sediments as represented by DSDP 487, located seaward of the trench, where the lower third of the sediment column has strongly hydrothermal pelagic features and the upper two-thirds is composed of terrigenous sediments. The pelagic sediments have distinctive features that could be used to identify a subduction component in the volcanics, including high REE/Hf, negative Ce anomalies, and Nd-Hf isotopes that lie on the "seawater array" and offset from the "mantle-crust" array. We have focused on a unique series of lavas from volcano Nevado de Toluca, located southwest of Mexico City. These lavas show negative Ce anomalies coupled with low REE/Hf and Zr/Nd ratios. Hf-Nd isotope ratios show a shallow trend compared to the mantle-crust array, consistent with a pelagic component. In addition, Hf isotopes show a striking positive correlation with Ce anomalies that trend toward the pelagic sediment compositions. These and other observations provide clear evidence for a component from subducted sediment in the lavas. In addition, there is a negative correlation of Lu/Hf and Hf isotopes that requires a mixing endmember with MORB-like Hf isotope ratios but with lower than MORB Lu/Hf. This indicates a melt from eclogitic subducted basalt. Compared to other

  5. Business Process Modelling is an Essential Part of a Requirements Analysis. Contribution of EFMI Primary Care Working Group.

    Science.gov (United States)

    de Lusignan, S; Krause, P; Michalakidis, G; Vicente, M Tristan; Thompson, S; McGilchrist, M; Sullivan, F; van Royen, P; Agreus, L; Desombre, T; Taweel, A; Delaney, B

    2012-01-01

    To perform a requirements analysis of the barriers to conducting research linking of primary care, genetic and cancer data. We extended our initial data-centric approach to include socio-cultural and business requirements. We created reference models of core data requirements common to most studies using unified modelling language (UML), dataflow diagrams (DFD) and business process modelling notation (BPMN). We conducted a stakeholder analysis and constructed DFD and UML diagrams for use cases based on simulated research studies. We used research output as a sensitivity analysis. Differences between the reference model and use cases identified study specific data requirements. The stakeholder analysis identified: tensions, changes in specification, some indifference from data providers and enthusiastic informaticians urging inclusion of socio-cultural context. We identified requirements to collect information at three levels: micro- data items, which need to be semantically interoperable, meso- the medical record and data extraction, and macro- the health system and socio-cultural issues. BPMN clarified complex business requirements among data providers and vendors; and additional geographical requirements for patients to be represented in both linked datasets. High quality research output was the norm for most repositories. Reference models provide high-level schemata of the core data requirements. However, business requirements' modelling identifies stakeholder issues and identifies what needs to be addressed to enable participation.

  6. Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma.

    Directory of Open Access Journals (Sweden)

    Francesco Abate

    2015-10-01

    Full Text Available Endemic Burkitt lymphoma (eBL is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40%, in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL, we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20% of tumors: RHOA and cyclin F (CCNF. We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively.

  7. Distinctive fingerprints of erosional regimes in terrestrial channel networks

    Science.gov (United States)

    Grau Galofre, A.; Jellinek, M.

    2017-12-01

    Satellite imagery and digital elevation maps capture the large scale morphology of channel networks attributed to long term erosional processes, such as fluvial, glacial, groundwater sapping and subglacial erosion. Characteristic morphologies associated with each of these styles of erosion have been studied in detail, but there exists a knowledge gap related to their parameterization and quantification. This knowledge gap prevents a rigorous analysis of the dominant processes that shaped a particular landscape, and a comparison across styles of erosion. To address this gap, we use previous morphological descriptions of glaciers, rivers, sapping valleys and tunnel valleys to identify and measure quantitative metrics diagnostic of these distinctive styles of erosion. From digital elevation models, we identify four geometric metrics: The minimum channel width, channel aspect ratio (longest length to channel width at the outlet), presence of undulating longitudinal profiles, and tributary junction angle. We also parameterize channel network complexity in terms of its stream order and fractal dimension. We then perform a statistical classification of the channel networks using a Principal Component Analysis on measurements of these six metrics on a dataset of 70 channelized systems. We show that rivers, glaciers, groundwater seepage and subglacial meltwater erode the landscape in rigorously distinguishable ways. Our methodology can more generally be applied to identify the contributions of different processes involved in carving a channel network. In particular, we are able to identify transitions from fluvial to glaciated landscapes or vice-versa.

  8. Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma.

    Science.gov (United States)

    Abate, Francesco; Ambrosio, Maria Raffaella; Mundo, Lucia; Laginestra, Maria Antonella; Fuligni, Fabio; Rossi, Maura; Zairis, Sakellarios; Gazaneo, Sara; De Falco, Giulia; Lazzi, Stefano; Bellan, Cristiana; Rocca, Bruno Jim; Amato, Teresa; Marasco, Elena; Etebari, Maryam; Ogwang, Martin; Calbi, Valeria; Ndede, Isaac; Patel, Kirtika; Chumba, David; Piccaluga, Pier Paolo; Pileri, Stefano; Leoncini, Lorenzo; Rabadan, Raul

    2015-10-01

    Endemic Burkitt lymphoma (eBL) is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV) infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40%), in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL), we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20% of tumors: RHOA and cyclin F (CCNF). We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively.

  9. Human Resource Development's Contribution to Continuous Improvement

    DEFF Research Database (Denmark)

    Jørgensen, Frances; Hyland, Paul

    2007-01-01

    Continuous Improvement (CI) is an approach to organizational change that requires active involvement of skilled and motivated employees, which implies an important role for HRD practitioners. The findings from a literature review and a survey of 168 Danish manufacturing companies indicate however...... that HRD is rarely integrated with CI. The paper contributes by offering a model that depicts how HR and HRD functions could be exploited to support successful CI development and implementation....

  10. Lithospheric Contributions to Arc Magmatism: Isotope Variations Along Strike in Volcanoes of Honshu, Japan

    Science.gov (United States)

    Kersting; Arculus; Gust

    1996-06-07

    Major chemical exchange between the crust and mantle occurs in subduction zone environments, profoundly affecting the chemical evolution of Earth. The relative contributions of the subducting slab, mantle wedge, and arc lithosphere to the generation of island arc magmas, and ultimately new continental crust, are controversial. Isotopic data for lavas from a transect of volcanoes in a single arc segment of northern Honshu, Japan, have distinct variations coincident with changes in crustal lithology. These data imply that the relatively thin crustal lithosphere is an active geochemical filter for all traversing magmas and is responsible for significant modification of primary mantle melts.

  11. Fine motor skills and executive function both contribute to kindergarten achievement

    Science.gov (United States)

    Cameron, Claire E.; Brock, Laura L.; Murrah, William M.; Bell, Lindsay H.; Worzalla, Samantha L.; Grissmer, David; Morrison, Frederick J.

    2012-01-01

    This study examined the contribution of executive function (EF) and multiple aspects of fine motor skills to achievement on six standardized assessments in a sample of middle-SES kindergarteners. 3- and 4-year-olds’ (N=213) fine and gross motor skills were assessed in a home visit before kindergarten; EF was measured at fall of kindergarten; and Woodcock-Johnson III (WJ III) Tests of Academic Achievement were administered at fall and spring. Correlations indicated that EF and fine motor skills appeared distinct. Further, controlling for background variables, higher levels of both EF and fine motor skills, specifically design copy, predicted higher achievement on multiple subtests at kindergarten entry, as well as improvement from fall to spring. Implications for research on school readiness are discussed. PMID:22537276

  12. Genetically Distinct Subsets within ANCA-Associated Vasculitis

    Science.gov (United States)

    Lyons, Paul A.; Rayner, Tim F.; Trivedi, Sapna; Holle, Julia U.; Watts, Richard A.; Jayne, David R.W.; Baslund, Bo; Brenchley, Paul; Bruchfeld, Annette; Chaudhry, Afzal N.; Tervaert, Jan Willem Cohen; Deloukas, Panos; Feighery, Conleth; Gross, Wolfgang L.; Guillevin, Loic; Gunnarsson, Iva; P, Lorraine Harper M.R.C; Hrušková, Zdenka; Little, Mark A.; Martorana, Davide; Neumann, Thomas; Ohlsson, Sophie; Padmanabhan, Sandosh; Pusey, Charles D.; Salama, Alan D.; Sanders, Jan-Stephan F.; Savage, Caroline O.; Segelmark, Mårten; Stegeman, Coen A.; Tesař, Vladimir; Vaglio, Augusto; Wieczorek, Stefan; Wilde, Benjamin; Zwerina, Jochen; Rees, Andrew J.; Clayton, David G.; Smith, Kenneth G.C.

    2013-01-01

    BACKGROUND Antineutrophil cytoplasmic antibody (ANCA)–associated vasculitis is a severe condition encompassing two major syndromes: granulomatosis with polyangiitis (formerly known as Wegener’s granulomatosis) and microscopic polyangiitis. Its cause is unknown, and there is debate about whether it is a single disease entity and what role ANCA plays in its pathogenesis. We investigated its genetic basis. METHODS A genomewide association study was performed in a discovery cohort of 1233 U.K. patients with ANCA-associated vasculitis and 5884 controls and was replicated in 1454 Northern European case patients and 1666 controls. Quality control, population stratification, and statistical analyses were performed according to standard criteria. RESULTS We found both major-histocompatibility-complex (MHC) and non-MHC associations with ANCA-associated vasculitis and also that granulomatosis with polyangiitis and microscopic polyangiitis were genetically distinct. The strongest genetic associations were with the antigenic specificity of ANCA, not with the clinical syndrome. Anti–proteinase 3 ANCA was associated with HLA-DP and the genes encoding α1-antitrypsin (SERPINA1) and proteinase 3 (PRTN3) (P = 6.2×10−89, P = 5.6×10−12, and P = 2.6×10−7, respectively). Anti–myeloperoxidase ANCA was associated with HLA-DQ (P = 2.1×10−8). CONCLUSIONS This study confirms that the pathogenesis of ANCA-associated vasculitis has a genetic component, shows genetic distinctions between granulomatosis with polyangiitis and microscopic polyangiitis that are associated with ANCA specificity, and suggests that the response against the autoantigen proteinase 3 is a central pathogenic feature of proteinase 3 ANCA–associated vasculitis. These data provide preliminary support for the concept that proteinase 3 ANCA–associated vasculitis and myeloperoxidase ANCA–associated vasculitis are distinct autoimmune syndromes. (Funded by the British Heart Foundation and others.) PMID

  13. Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine fear responsiveness to unpredictable threat.

    Science.gov (United States)

    Lange, M D; Daldrup, T; Remmers, F; Szkudlarek, H J; Lesting, J; Guggenhuber, S; Ruehle, S; Jüngling, K; Seidenbecher, T; Lutz, B; Pape, H C

    2017-10-01

    The brain circuits underlying behavioral fear have been extensively studied over the last decades. Although the vast majority of experimental studies assess fear as a transient state of apprehension in response to a discrete threat, such phasic states of fear can shift to a sustained anxious apprehension, particularly in face of diffuse cues with unpredictable environmental contingencies. Unpredictability, in turn, is considered an important variable contributing to anxiety disorders. The networks of the extended amygdala have been suggested keys to the control of phasic and sustained states of fear, although the underlying synaptic pathways and mechanisms remain poorly understood. Here, we show that the endocannabinoid system acting in synaptic circuits of the extended amygdala can explain the fear response profile during exposure to unpredictable threat. Using fear training with predictable or unpredictable cues in mice, combined with local and cell-type-specific deficiency and rescue of cannabinoid type 1 (CB1) receptors, we found that presynaptic CB1 receptors on distinct amygdala projections to bed nucleus of the stria terminalis (BNST) are both necessary and sufficient for the shift from phasic to sustained fear in response to an unpredictable threat. These results thereby identify the causal role of a defined protein in a distinct brain pathway for the temporal development of a sustained state of anxious apprehension during unpredictability of environmental influences, reminiscent of anxiety symptoms in humans.

  14. Participation and social participation: are they distinct concepts?

    Science.gov (United States)

    Piškur, Barbara; Daniëls, Ramon; Jongmans, Marian J; Ketelaar, Marjolijn; Smeets, Rob J E M; Norton, Meghan; Beurskens, Anna J H M

    2014-03-01

    The concept of participation has been extensively used in health and social care literature since the World Health Organization introduced its description in the International Classification of Functioning, Disability and Health (ICF) in 2001. More recently, the concept of social participation is frequently used in research articles and policy reports. However, in the ICF, no specific definition exists for social participation, and an explanation of differences between the concepts is not available. The central question in this discussion article is whether participation, as defined by the ICF, and social participation are distinct concepts. This article illustrates the concepts of participation and social participation, presents a critical discussion of their definitions, followed by implications for rehabilitation and possible future directions. A clear definition for participation or social participation does not yet exist. Definitions for social participation differ from each other and are not sufficiently distinct from the ICF definition of participation. Although the ICF is regarded an important conceptual framework, it is criticised for not being comprehensive. The relevance of societal involvement of clients is evident for rehabilitation, but the current ICF definition of participation does not sufficiently capture societal involvement. Changing the ICF's definition of participation towards social roles would overcome a number of its shortcomings. Societal involvement would then be understood in the light of social roles. Consequently, there would be no need to make a distinction between social participation and participation.

  15. Processing vertical size disparities in distinct depth planes.

    Science.gov (United States)

    Duke, Philip A; Howard, Ian P

    2012-08-17

    A textured surface appears slanted about a vertical axis when the image in one eye is horizontally enlarged relative to the image in the other eye. The surface appears slanted in the opposite direction when the same image is vertically enlarged. Two superimposed textured surfaces with different horizontal size disparities appear as two surfaces that differ in slant. Superimposed textured surfaces with equal and opposite vertical size disparities appear as a single frontal surface. The vertical disparities are averaged. We investigated whether vertical size disparities are averaged across two superimposed textured surfaces in different depth planes or whether they induce distinct slants in the two depth planes. In Experiment 1, two superimposed textured surfaces with different vertical size disparities were presented in two depth planes defined by horizontal disparity. The surfaces induced distinct slants when the horizontal disparity was more than ±5 arcmin. Thus, vertical size disparities are not averaged over surfaces with different horizontal disparities. In Experiment 2 we confirmed that vertical size disparities are processed in surfaces away from the horopter, so the results of Experiment 1 cannot be explained by the processing of vertical size disparities in a fixated surface only. Together, these results show that vertical size disparities are processed separately in distinct depth planes. The results also suggest that vertical size disparities are not used to register slant globally by their effect on the registration of binocular direction of gaze.

  16. Contribution to the alien flora of Montenegro and Supplementum to the Preliminary list of plant invaders

    OpenAIRE

    Stešević, D.; Caković, D.

    2013-01-01

    This contribution is based on the field observations from 2011 to 2013. Besides new data about distribution of some known plant invaders, one new alien species for the flora of Montenegro is reported- Solidago gigantea. This plant was recorded in 2011, on two distinct localities near the road side in peri-urban area of Nikšić and Mojkovac, in the vicinity of gardens, were it has been grown as ornamental. In 2012 survey, species was again reported for Mojkovac, but it disappeared f...

  17. Pseudomonas aeruginosa diversity in distinct paediatric patient groups

    DEFF Research Database (Denmark)

    Tramper-Stranders, G.A.; Ent, C.K. van der; Wolfs, T.F.

    2008-01-01

    the other groups. A group of clonal isolates was observed among patients from the CF-chronic and CF-1 groups. These or different clonal isolates were not encountered among the three other patient groups. No characteristic resistance pattern could be identified among isolates from the distinct patient groups......Pseudomonas aeruginosa is a pathogen that often infects patients who are either immunocompromised or have local defects in host defences. It is known that cystic fibrosis (CF) patients are sometimes infected with certain clonal isolates. It is not clear whether these clonal isolates also infect non......-CF patients and whether clonality of isolates occurs in other patient groups. The aim of this study was to investigate P. aeruginosa diversity and the occurrence of clones within five distinct paediatric patient groups susceptible to P. aeruginosa infection. P. aeruginosa isolates were cultured from 157...

  18. A linguistic representation of the regulation of transcription initiation. I. An ordered array of complex symbols with distinctive features.

    Science.gov (United States)

    Collado-Vides, J

    1993-01-01

    The inadequacy of context-free grammars in the description of regulatory information contained in DNA gave the formal justification for a linguistic approach to the study of gene regulation. Based on that result, we have initiated a linguistic formalization of the regulatory arrays of 107 sigma 70 E. coli promoters. The complete sequences of promoter (Pr), operator (Op) and activator binding sites (I) have previously been identified as the smallest elements, or categories, for a combinatorial analysis of the range of transcription initiation of sigma 70 promoters. These categories are conceptually equivalent to phonemes of natural language. Several features associated with these categories are required in a complete description of regulatory arrays of promoters. We have to select the best way to describe the properties that are pertinent for the description of such regulatory regions. In this paper we define distinctive features of regulatory regions based on the following criteria: identification of subclasses of substitutable elements, simplicity, selection of the most directly related information, and distinction of one array among the whole set of promoters. Alternative ways to represent distances in between regulatory sites are discussed, permitting, together with a principle of precedence, the identification of an ordered set of complex symbols as a unique representation for a promoter and its associated regulatory sites. In the accompanying paper additional distinctive features of promoters and regulatory sites are identified.

  19. European freshwater VHSV genotype Ia isolates divide into two distinct subpopulations

    DEFF Research Database (Denmark)

    Kahns, Søren; Skall, Helle Frank; Kaas, Rolf Sommer

    2012-01-01

    Viral haemorrhagic septicaemia (VHS), caused by the novirhabdovirus VHSV, often leads to significant economic losses to European rainbow trout production. The virus isolates are divided into 4 distinct genotypes with additional subgroups including sublineage Ia, isolates of which are the main...... detected in Denmark since January 2009. Full-length G-genes of all Danish VHSV isolates that were submitted for diagnostic analyses in the period 2004−2009 were sequenced and analysed. All 58 Danish isolates from rainbow trout grouped with sublineage Ia isolates. Furthermore, VHSV isolates from infected...... Danish freshwater catchments appear to have evolved into a distinct clade within sublineage Ia, herein designated clade Ia-1, whereas trout isolates originating from other continental European countries cluster in another distinct clade, designated clade Ia-2. In addition, phylogenetic analyses indicate...

  20. Confluence for classical logic through the distinction between values and computations

    Directory of Open Access Journals (Sweden)

    José Espírito Santo

    2014-09-01

    Full Text Available We apply an idea originated in the theory of programming languages - monadic meta-language with a distinction between values and computations - in the design of a calculus of cut-elimination for classical logic. The cut-elimination calculus we obtain comprehends the call-by-name and call-by-value fragments of Curien-Herbelin's lambda-bar-mu-mu-tilde-calculus without losing confluence, and is based on a distinction of "modes" in the proof expressions and "mode" annotations in types. Modes resemble colors and polarities, but are quite different: we give meaning to them in terms of a monadic meta-language where the distinction between values and computations is fully explored. This meta-language is a refinement of the classical monadic language previously introduced by the authors, and is also developed in the paper.

  1. Functional Connectivity with Distinct Neural Networks Tracks Fluctuations in Gain/Loss Framing Susceptibility

    Science.gov (United States)

    Smith, David V.; Sip, Kamila E.; Delgado, Mauricio R.

    2016-01-01

    Multiple large-scale neural networks orchestrate a wide range of cognitive processes. For example, interoceptive processes related to self-referential thinking have been linked to the default-mode network (DMN); whereas exteroceptive processes related to cognitive control have been linked to the executive-control network (ECN). Although the DMN and ECN have been postulated to exert opposing effects on cognition, it remains unclear how connectivity with these spatially overlapping networks contribute to fluctuations in behavior. While previous work has suggested the medial prefrontal cortex (MPFC) is involved in behavioral change following feedback, these observations could be linked to interoceptive processes tied to DMN or exteroceptive processes tied to ECN because MPFC is positioned in both networks. To address this problem, we employed independent component analysis combined with dual-regression functional connectivity analysis. Participants made a series of financial decisions framed as monetary gains or losses. In some sessions, participants received feedback from a peer observing their choices; in other sessions, feedback was not provided. Following feedback, framing susceptibility—indexed as the increase in gambling behavior in loss frames compared to gain frames—was heightened in some participants and diminished in others. We examined whether these individual differences were linked to differences in connectivity by contrasting sessions containing feedback against those that did not contain feedback. We found two key results. As framing susceptibility increased, the MPFC increased connectivity with DMN; in contrast, temporal-parietal junction decreased connectivity with the ECN. Our results highlight how functional connectivity patterns with distinct neural networks contribute to idiosyncratic behavioral changes. PMID:25858445

  2. [Characteristics of Cannabis sativa L.: seed morphology, germination and growth characteristics, and distinction from Hibiscus cannabinus L].

    Science.gov (United States)

    Yoshimatsu, Kayo; Kitazawa, Takashi; Kawano, Noriaki; Iida, Osamu; Kawahara, Nobuo

    2010-02-01

    Illegal cannabis (Cannabis sativa L.) cultivation is still a social problem worldwide. Fifty inquiries on cannabis that Research Center for Medicinal Plant Resources (Tsukuba Division) received between January 1, 2000 and March 31, 2009 were itemized in to 8 categories; 1: seed identification, 2: plant identification, 3: indoor cultivation, 4: outdoor cultivation, 5: germination and growth characteristics, 6: expected amount of cannabis products derived from illegal cannabis plant, 7: non-narcotic cannabis and 8: usage of medicinal cannabis. Top three inquiries were 1: seed identification (16 cases), 3: indoor cultivation (10 cases) and 4: outdoor cultivation (6 cases). Characteristics of cannabis, namely seed morphology, germination and growth characteristics, and distinction from kenaf (Hibiscus cannabinus L.) that is frequently misjudged as cannabis, were studied to contribute for prevention of illegal cannabis cultivation.

  3. Unsentimental Ethics: Towards a Content-Specific Account of the Moral-Conventional Distinction

    Science.gov (United States)

    Royzman, Edward B.; Leeman, Robert F.; Baron, Jonathan

    2009-01-01

    In this paper, we offer an overview and a critique of the existing theories of the moral-conventional distinction, with emphasis on Nichols's [Nichols, S. (2002). Norms with feeling: Towards a psychological account of moral judgment. "Cognition, 84", 221-236] neo-sentimentalist approach. After discussing some distinctive features of Nichols's…

  4. Mechanical branch constraints contribute to life-history variation across tree species in a Bolivian forest.

    NARCIS (Netherlands)

    Sterck, F.J.; Gelder, van H.A.; Poorter, L.

    2006-01-01

    1 Trade-offs among plant traits may contribute to specialization for different environments and coexistence of plant species. This may be the first study that shows how trade-offs among branch traits contribute to variation in crown size, light requirements and maximum height across multiple

  5. Evidence for two distinct defects contributing to the H4 deep-level transient spectroscopy peak in electron-irradiated InP

    International Nuclear Information System (INIS)

    Darwich, R.; Massarani, B.; Kaaka, M.; Awad, F.

    2000-01-01

    Deep-level transient spectroscopy (DLTS) has been used to study the dominant deep-level H4 produced in InP by electron irradiation. The characteristics of the H4 peak in Zn-doped Inp has been studied as a function of pulse duration (t p ) before and after annealing. The results show that at least two traps contribute to the H4 peak: one is a fast trap (labeled H4 f ) and the other is a show trap (labeled H4 s ). This is show through several results concerning the activation energy, the capture cross section, the full width at half-maximum, and the peak temperature shift. It is shown that both traps are irradiation defects created in P sublattice. (authors)

  6. MDEP VICWG-02 Technical Report - Survey on quality assurance program requirements

    International Nuclear Information System (INIS)

    2011-01-01

    The survey was prepared using the requirements of Appendix B to 10 CFR Part 50, 'Quality Assurance Criteria for Nuclear Power Plants and Fuel Reprocessing Plants'. These requirements form the basis upon which the U.S. NRC oversees the activities of vendors providing parts and services to the commercial U.S. nuclear power industry. As discussed and agreed to at the October 2008 Vendor Inspection Cooperation Working Group meeting in Dijon, France, the survey that follows was developed using these requirements. The survey is divided into the 18 basic criteria of Appendix B to 10 CFR Part 50. Within each criteria there are individual requirements that have been identified as separate and distinct elements that are covered during the inspection of vendor activities. In addition to the requirements of Appendix B to 10 CFR Part 50, the requirements of 10 CFR Part 21, 'Reporting of Defects and Non-compliance', have been listed at the end of the survey as an example of 'Other Requirements Related To Vendor Inspections', for the NRC. (authors)

  7. Distinct adiponectin profiles might contribute to differences in susceptibility to type 2 diabetes in dogs and humans.

    Science.gov (United States)

    Verkest, K R; Rand, J S; Fleeman, L M; Morton, J M; Richards, A A; Rose, F J; Whitehead, J P

    2011-08-01

    Dogs develop obesity-associated insulin resistance but not type 2 diabetes mellitus. Low adiponectin is associated with progression to type 2 diabetes in obese humans. The aims of this study were to compare total and high molecular weight (HMW) adiponectin and the ratio of HMW to total adiponectin (S(A)) between dogs and humans and to examine whether total or HMW adiponectin or both are associated with insulin resistance in naturally occurring obese dogs. We compared adiponectin profiles between 10 lean dogs and 10 lean humans and between 6 lean dogs and 6 age- and sex-matched, client-owned obese dogs. Total adiponectin was measured with assays validated in each species. We measured S(A) with velocity centrifugation on sucrose gradients. The effect of total and HMW adiponectin concentrations on MINMOD-estimated insulin sensitivity was assessed with linear regression. Lean dogs had total and HMW adiponectin concentrations three to four times higher than lean humans (total: dogs 32 ± 5.6 mg/L, humans 10 ± 1.3 mg/L, Pobese dogs (0.76 ± 0.05 in both groups; P=1). Total adiponectin, HMW adiponectin, and S(A) were not associated with insulin sensitivity in dogs. We propose that differences in adiponectin profiles between humans and dogs might contribute to the propensity of humans but not dogs to develop type 2 diabetes. Dogs with chronic, naturally occurring obesity do not have selectively reduced HMW adiponectin, and adiponectin does not appear to be important in the development of canine obesity-associated insulin resistance. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Reconstructing dynamic mental models of facial expressions in prosopagnosia reveals distinct representations for identity and expression.

    Science.gov (United States)

    Richoz, Anne-Raphaëlle; Jack, Rachael E; Garrod, Oliver G B; Schyns, Philippe G; Caldara, Roberto

    2015-04-01

    The human face transmits a wealth of signals that readily provide crucial information for social interactions, such as facial identity and emotional expression. Yet, a fundamental question remains unresolved: does the face information for identity and emotional expression categorization tap into common or distinct representational systems? To address this question we tested PS, a pure case of acquired prosopagnosia with bilateral occipitotemporal lesions anatomically sparing the regions that are assumed to contribute to facial expression (de)coding (i.e., the amygdala, the insula and the posterior superior temporal sulcus--pSTS). We previously demonstrated that PS does not use information from the eye region to identify faces, but relies on the suboptimal mouth region. PS's abnormal information use for identity, coupled with her neural dissociation, provides a unique opportunity to probe the existence of a dichotomy in the face representational system. To reconstruct the mental models of the six basic facial expressions of emotion in PS and age-matched healthy observers, we used a novel reverse correlation technique tracking information use on dynamic faces. PS was comparable to controls, using all facial features to (de)code facial expressions with the exception of fear. PS's normal (de)coding of dynamic facial expressions suggests that the face system relies either on distinct representational systems for identity and expression, or dissociable cortical pathways to access them. Interestingly, PS showed a selective impairment for categorizing many static facial expressions, which could be accounted for by her lesion in the right inferior occipital gyrus. PS's advantage for dynamic facial expressions might instead relate to a functionally distinct and sufficient cortical pathway directly connecting the early visual cortex to the spared pSTS. Altogether, our data provide critical insights on the healthy and impaired face systems, question evidence of deficits

  9. Number of perceptually distinct surface colors in natural scenes.

    Science.gov (United States)

    Marín-Franch, Iván; Foster, David H

    2010-09-30

    The ability to perceptually identify distinct surfaces in natural scenes by virtue of their color depends not only on the relative frequency of surface colors but also on the probabilistic nature of observer judgments. Previous methods of estimating the number of discriminable surface colors, whether based on theoretical color gamuts or recorded from real scenes, have taken a deterministic approach. Thus, a three-dimensional representation of the gamut of colors is divided into elementary cells or points which are spaced at one discrimination-threshold unit intervals and which are then counted. In this study, information-theoretic methods were used to take into account both differing surface-color frequencies and observer response uncertainty. Spectral radiances were calculated from 50 hyperspectral images of natural scenes and were represented in a perceptually almost uniform color space. The average number of perceptually distinct surface colors was estimated as 7.3 × 10(3), much smaller than that based on counting methods. This number is also much smaller than the number of distinct points in a scene that are, in principle, available for reliable identification under illuminant changes, suggesting that color constancy, or the lack of it, does not generally determine the limit on the use of color for surface identification.

  10. Distinct Evening Fatigue Profiles in Oncology Outpatients Receiving Chemotherapy

    Science.gov (United States)

    Wright, Fay; Cooper, Bruce A.; Conley, Yvette P.; Hammer, Marilyn J.; Chen, Lee-May; Paul, Steven M.; Levine, Jon D.; Miaskowski, Christine; Kober, Kord M.

    2018-01-01

    Background Fatigue is the most common and debilitating symptom experienced by oncology patients during chemotherapy (CTX). Fatigue severity demonstrates a large amount of inter-individual and diurnal variability. Purpose Study purposes were to evaluate for subgroups of patients with distinct evening fatigue profiles and evaluate how these subgroups differed on demographic, clinical, and symptom characteristics. Methods Outpatients with breast, gastrointestinal, gynecological, or lung cancer (n=1332) completed questionnaires six times over two cycles of CTX. Lee Fatigue Scale (LFS) evaluated evening fatigue severity. Latent profile analysis was used to identify distinct evening fatigue profiles. Results Four distinct evening fatigue classes (i.e., Low (14.0%), Moderate (17.2%), High (36.0%), Very High (32.8%)) were identified. Compared to the Low class, patients in the Very High evening fatigue class were: younger, female, had childcare responsibilities, had more years of education, had a lower functional status, had a higher comorbidity burden, and were diagnosed with breast cancer. Patients in the Very High class reported higher levels of depressive symptoms, sleep disturbance, and evening fatigue at enrollment. Conclusions Findings provide new insights into modifiable risk factors for higher levels of evening fatigue. Clinicians can use this information to identify higher risk patients and plan appropriate interventions. PMID:29725554

  11. Organism versus mechanism: Losing our grip on the distinction

    Directory of Open Access Journals (Sweden)

    Henk Reitsema

    2013-11-01

    Full Text Available The distinction between organism and mechanism is often subtle or unclear and yet can prove to be fundamental to our understanding of the world. It has been tempting for many thinkers to seek to ‘understand’ all of reality through the lens of either the one or the other of these concepts rather than by giving both a place. This article sets out to argue that there is a substantial loss of understanding when either of these metaphors is absolutised to explain all causal processes and patterns in reality. Clarifying the distinction between the two may provide one more tool to grasp what is reductionist in many of the perspectives that have come to dominate public life and science today. This contention is tested on the quest for the design of self-replicating systems (i.e. synthetic organisms in the nanotech industry. It is common that the concepts of organic functioning and mechanism are used imprecisely and in an overlapping way. This is also true of much scientific debate, especially in the fields of biology, micro-biology and nano-science. This imprecise use signals a reductionist tendency both in the way that the organic is perceived and in terms of the distinctive nature of mechanisms.

  12. Dissociative effects of orthographic distinctiveness in pure and mixed lists: an item-order account.

    Science.gov (United States)

    McDaniel, Mark A; Cahill, Michael; Bugg, Julie M; Meadow, Nathaniel G

    2011-10-01

    We apply the item-order theory of list composition effects in free recall to the orthographic distinctiveness effect. The item-order account assumes that orthographically distinct items advantage item-specific encoding in both mixed and pure lists, but at the expense of exploiting relational information present in the list. Experiment 1 replicated the typical free recall advantage of orthographically distinct items in mixed lists and the elimination of that advantage in pure lists. Supporting the item-order account, recognition performances indicated that orthographically distinct items received greater item-specific encoding than did orthographically common items in mixed and pure lists (Experiments 1 and 2). Furthermore, order memory (input-output correspondence and sequential contiguity effects) was evident in recall of pure unstructured common lists, but not in recall of unstructured distinct lists (Experiment 1). These combined patterns, although not anticipated by prevailing views, are consistent with an item-order account.

  13. Heavy water: a distinctive and essential component of CANDU

    International Nuclear Information System (INIS)

    Miller, A.I.; van Alstyne, H.M.

    1994-06-01

    The exceptional properties of heavy water as a neutron moderator provide one of the distinctive features of CANDU reactors. Although most of the chemical and physical properties of deuterium and protium (mass 1 hydrogen) are appreciably different, the low terrestrial abundance of deuterium makes the separation of heavy water a relatively costly process, and so of considerable importance to the CANDU system. World heavy-water supplies are currently provided by the Girdler-Sulphide process or processes based on ammonia-hydrogen exchange. Due to cost and hazard considerations, new processes will be required for the production of heavy water in and beyond the next decade. Through AECL's development and refinement of wetproofed catalysts for the exchange of hydrogen isotopes between water and hydrogen, a family of new processes is expected to be deployed. Two monothermal processes, CECE (Combined Electrolysis and Catalytic Exchange, using water-to-hydrogen conversion by electrolysis) and CIRCE (Combined Industrially Reformed hydrogen and Catalytic Exchange, based on steam reforming of hydrocarbons), are furthest advanced. Besides its use for heavy-water production, the CECE process is a highly effective technology for heavy-water upgrading and for tritium separation from heavy (or light) water. (author). 10 refs., 1 tab., 7 figs

  14. The Yin and Yang of SagS: Distinct Residues in the HmsP Domain of SagS Independently Regulate Biofilm Formation and Biofilm Drug Tolerance

    Science.gov (United States)

    Dingemans, Jozef; Poudyal, Bandita

    2018-01-01

    ABSTRACT The formation of inherently drug-tolerant biofilms by the opportunistic pathogen Pseudomonas aeruginosa requires the sensor-regulator hybrid SagS, with ΔsagS biofilms being unstructured and exhibiting increased antimicrobial susceptibility. Recent findings indicated SagS to function as a switch to control biofilm formation and drug tolerance independently. Moreover, findings suggested the periplasmic sensory HmsP domain of SagS is likely to be the control point in the regulation of biofilm formation and biofilm cells transitioning to a drug-tolerant state. We thus asked whether specific amino acid residues present in the HmsP domain contribute to the switch function of SagS. HmsP domain residues were therefore subjected to alanine replacement mutagenesis to identify substitutions that block the sensory function(s) of SagS, which is apparent by attached cells being unable to develop mature biofilms and/or prevent transition to an antimicrobial-resistant state. Mutant analyses revealed 32 residues that only contribute to blocking one sensory function. Moreover, amino acid residues affecting attachment and subsequent biofilm formation but not biofilm tolerance also impaired histidine kinase signaling via BfiS. In contrast, residues affecting biofilm drug tolerance but not attachment and subsequent biofilm formation negatively impacted BrlR transcription factor levels. Structure prediction suggested the two sets of residues affecting sensory functions are located in distinct areas that were previously described as being involved in ligand binding interactions. Taken together, these studies identify the molecular basis for the dual regulatory function of SagS. IMPORTANCE The membrane-bound sensory protein SagS plays a pivotal role in P. aeruginosa biofilm formation and biofilm cells gaining their heightened resistance to antimicrobial agents, with SagS being the control point at which both pathways diverge. Here, we demonstrate for the first time that the two

  15. Responses to Novelty and Vulnerability to Cocaine Addiction: Contribution of a Multi-Symptomatic Animal Model

    Science.gov (United States)

    Belin, David; Deroche-Gamonet, Véronique

    2012-01-01

    Epidemiological studies have revealed striking associations between several distinct behavioral/personality traits and drug addiction, with a large emphasis on the sensation-seeking trait and the associated impulsive dimension of personality. However, in human studies, it is difficult to identify whether personality/behavioral traits actually contribute to increased vulnerability to drug addiction or reflect psychobiological adaptations to chronic drug exposure. Here we show how animal models, including the first multi-symptomatic model of addiction in the rat, have contributed to a better understanding of the relationships between different subdimensions of the sensation-seeking trait and different stages of the development of cocaine addiction, from vulnerability to initiation of cocaine self-administration to the transition to compulsive drug intake. We argue that sensation seeking predicts vulnerability to use cocaine, whereas novelty seeking, akin to high impulsivity, predicts instead vulnerability to shift from controlled to compulsive cocaine use, that is, addiction. PMID:23125204

  16. 76 FR 14883 - Endangered and Threatened Species; Proposed Threatened Status for Distinct Population Segments of...

    Science.gov (United States)

    2011-03-18

    ...-XZ58 Endangered and Threatened Species; Proposed Threatened Status for Distinct Population Segments of..., published a proposed rule to list the Beringia and Okhotsk Distinct Population Segments (DPSs) of the... published a proposed rule to list the Beringia and Okhotsk Distinct Population Segments (DPSs) of the...

  17. The theory–practice distinction and the complexity of practical knowledge

    Directory of Open Access Journals (Sweden)

    Bonnie Miller-McLemore

    2016-08-01

    Full Text Available Over the past few decades, theologians have recognised the value of practice but have been optimistic about the ease with which practice is incorporated into theology. People use all sorts of adjectives to characterise the complex relationship – ‘integrally related’, a ‘deeper reciprocity’, ‘bound up in thickly intertwined ways’ – but connecting the two is not as easy as these words suggest. This article returns to the age-old question about the relationship between theory and practice. But it studies this question from the angle of practice. Although many scholars have analysed the distinction between theory and practice as it functions conceptually, few have examined challenges in relating the two as they emerge in practice. The article argues that there is an inevitable distinction between theory and practice that receives considerably less attention and needs more understanding and even respect. It also argues that the discipline of practical theology adds a distinctive angle on this discussion because it considers how the concepts function practically.

  18. Contributions of a Science Museum for the Initial Training

    Directory of Open Access Journals (Sweden)

    Azizi Manuel Tempesta

    2017-04-01

    Full Text Available In this paper we present some results obtained in a master’s research which aimed to evaluate what are the contributions that the acting as Physical monitor in a Science Museum has for the initial training and the beginning of the teaching career. Basing our analysis, we have adopted as theoretical assumptions the Teachers Knowledge and the Training Needs. We interviewed a group of ten teachers who played the function of Physics mediator in the Interdisciplinary Dynamic Museum (MUDI of the State University of Maringá, and submit to the Textual Analysis Discursive process. The results allowed us to realize that the contributions go beyond the expected, revealing the great potential of the Science museums of as an aid to initial training, contributing to the development of competencies and abilities that today is required of the teacher, and them providing experiences load which otherwise would not be reached.

  19. Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.

    Science.gov (United States)

    Morselli, Eugenia; Mariño, Guillermo; Bennetzen, Martin V; Eisenberg, Tobias; Megalou, Evgenia; Schroeder, Sabrina; Cabrera, Sandra; Bénit, Paule; Rustin, Pierre; Criollo, Alfredo; Kepp, Oliver; Galluzzi, Lorenzo; Shen, Shensi; Malik, Shoaib Ahmad; Maiuri, Maria Chiara; Horio, Yoshiyuki; López-Otín, Carlos; Andersen, Jens S; Tavernarakis, Nektarios; Madeo, Frank; Kroemer, Guido

    2011-02-21

    Autophagy protects organelles, cells, and organisms against several stress conditions. Induction of autophagy by resveratrol requires the nicotinamide adenine dinucleotide-dependent deacetylase sirtuin 1 (SIRT1). In this paper, we show that the acetylase inhibitor spermidine stimulates autophagy independent of SIRT1 in human and yeast cells as well as in nematodes. Although resveratrol and spermidine ignite autophagy through distinct mechanisms, these compounds stimulate convergent pathways that culminate in concordant modifications of the acetylproteome. Both agents favor convergent deacetylation and acetylation reactions in the cytosol and in the nucleus, respectively. Both resveratrol and spermidine were able to induce autophagy in cytoplasts (enucleated cells). Moreover, a cytoplasm-restricted mutant of SIRT1 could stimulate autophagy, suggesting that cytoplasmic deacetylation reactions dictate the autophagic cascade. At doses at which neither resveratrol nor spermidine stimulated autophagy alone, these agents synergistically induced autophagy. Altogether, these data underscore the importance of an autophagy regulatory network of antagonistic deacetylases and acetylases that can be pharmacologically manipulated.

  20. Distinct mechanisms of a phosphotyrosyl peptide binding to two SH2 domains.

    Science.gov (United States)

    Pang, Xiaodong; Zhou, Huan-Xiang

    2014-05-01

    Protein phosphorylation is very common post-translational modification, catalyzed by kinases, for signaling and regulation. Phosphotyrosines frequently target SH2 domains. The spleen tyrosine kinase (Syk) is critical for tyrosine phosphorylation of multiple proteins and for regulation of important pathways. Phosphorylation of both Y342 and Y346 in Syk linker B is required for optimal signaling. The SH2 domains of Vav1 and PLC-γ both bind this doubly phosphorylated motif. Here we used a recently developed method to calculate the effects of Y342 and Y346 phosphorylation on the rate constants of a peptide from Syk linker B binding to the SH2 domains of Vav1 and PLC-γ. The predicted effects agree well with experimental observations. Moreover, we found that the same doubly phosphorylated peptide binds the two SH2 domains via distinct mechanisms, with apparent rigid docking for Vav1 SH2 and dock-and-coalesce for PLC-γ SH2.

  1. Japan-U. S. seminar on magmatic contributions to hydrothermal systems

    Energy Technology Data Exchange (ETDEWEB)

    Muffler, L. (U. S. Geological Survey, CA (United States)); Hedenquist, J. (Geological Survey of Japan, Tsukuba (Japan)); Kesler, S. (University of Michigan, MI (United States)); Izawa, E. (Kyushu University, Fukuoka (Japan). Faculty of Engineering)

    1992-08-31

    A multidisciplinary Seminar on Magmatic Contributions to Hydrothermal Systems'' was held at Ebino and Kagoshima at Kyushu, November, 1991. The principal purpose of the Ebino/Kagoshima Seminar was to bring together a small group of individuals which have been conducting active research on magmatic contributions to hydrothermal systems. The Seminar focussed on the porphyry and epithermal ore environments because of the potential to relate these environments to active volcanic and geothermal systems. Disciplines included valcanology, volcanic gas geochemistry, water geochemistry, isotope geochemistry, geochemical modeling, experimental geochemistry, igneous petrology, geothermal geology, economic geology, fluid-inclusion study, geophysics, and physical modeling. This paper summarizes the outline and significance of the Seminar. It was pointed out that understanding magmatic contributions to hydrothermal systems would require augmented experimental investigations, numerical modeling, field studies, and drilling.

  2. The fission yeast heterochromatin protein Rik1 is required for telomere clustering during meiosis

    DEFF Research Database (Denmark)

    Tuzon, Creighton T; Borgstrøm, Britta; Weilguny, Dietmar

    2004-01-01

    Telomeres share the ability to silence nearby transcription with heterochromatin, but the requirement of heterochromatin proteins for most telomere functions is unknown. The fission yeast Rik1 protein is required for heterochromatin formation at centromeres and the mating-type locus, as it recrui...... meiosis. However, Rik1 is dispensable for the protective roles of telomeres in preventing chromosome end-fusion. Thus, a Swi6-independent heterochromatin function distinct from that at centromeres and the mating-type locus operates at telomeres during sexual differentiation....

  3. The Skin Bacterium Propionibacterium acnes Employs Two Variants of Hyaluronate Lyase with Distinct Properties

    DEFF Research Database (Denmark)

    Nazipi, Seven; Stødkilde-Jørgensen, Kristian; Scavenius, Carsten

    2017-01-01

    Hyaluronic acid (HA) and other glycosaminoglycans are extracellular matrix components in the human epidermis and dermis. One of the most prevalent skin microorganisms, Propionibacterium acnes, possesses HA-degrading activity, possibly conferred by the enzyme hyaluronate lyase (HYL). In this study......, we identified the HYL of P. acnes and investigated the genotypic and phenotypic characteristics. Investigations include the generation of a P. acneshyl knockout mutant and HYL activity assays to determine the substrate range and formed products. We found that P. acnes employs two distinct variants...... of the observed differences between P. acnes phylotype IA and IB/II strains. Whereas type IA strains are primarily found on the skin surface and associated with acne vulgaris, type IB/II strains are more often associated with soft and deep tissue infections, which would require elaborate tissue invasion...

  4. Enhancing Critical Infrastructure and Key Resources (CIKR) Level-0 Physical Process Security Using Field Device Distinct Native Attribute Features

    Energy Technology Data Exchange (ETDEWEB)

    Lopez, Juan [Oak Ridge National Lab. (ORNL), Oak Ridge, TN (United States); Liefer, Nathan C. [Wright-Patterson AFB, Dayton, OH (United States); Busho, Colin R. [Wright-Patterson AFB, Dayton, OH (United States); Temple, Michael A. [Wright-Patterson AFB, Dayton, OH (United States)

    2017-12-04

    Here, the need for improved Critical Infrastructure and Key Resource (CIKR) security is unquestioned and there has been minimal emphasis on Level-0 (PHY Process) improvements. Wired Signal Distinct Native Attribute (WS-DNA) Fingerprinting is investigated here as a non-intrusive PHY-based security augmentation to support an envisioned layered security strategy. Results are based on experimental response collections from Highway Addressable Remote Transducer (HART) Differential Pressure Transmitter (DPT) devices from three manufacturers (Yokogawa, Honeywell, Endress+Hauer) installed in an automated process control system. Device discrimination is assessed using Time Domain (TD) and Slope-Based FSK (SB-FSK) fingerprints input to Multiple Discriminant Analysis, Maximum Likelihood (MDA/ML) and Random Forest (RndF) classifiers. For 12 different classes (two devices per manufacturer at two distinct set points), both classifiers performed reliably and achieved an arbitrary performance benchmark of average cross-class percent correct of %C > 90%. The least challenging cross-manufacturer results included near-perfect %C ≈ 100%, while the more challenging like-model (serial number) discrimination results included 90%< %C < 100%, with TD Fingerprinting marginally outperforming SB-FSK Fingerprinting; SB-FSK benefits from having less stringent response alignment and registration requirements. The RndF classifier was most beneficial and enabled reliable selection of dimensionally reduced fingerprint subsets that minimize data storage and computational requirements. The RndF selected feature sets contained 15% of the full-dimensional feature sets and only suffered a worst case %CΔ = 3% to 4% performance degradation.

  5. Magnetic mirror fusion systems: Characteristics and distinctive features

    International Nuclear Information System (INIS)

    Post, R.F.

    1987-01-01

    A tutorial account is given of the main characteristics and distinctive features of conceptual magnetic fusion systems employing the magnetic mirror principle. These features are related to the potential advantages that mirror-based fusion systems may exhibit for the generation of economic fusion power

  6. Distinct roles of synaptic and extrasynaptic GABAA receptors in striatal inhibition dynamics

    Directory of Open Access Journals (Sweden)

    Ruixi eLuo

    2013-11-01

    Full Text Available Striatonigral and striatopallidal projecting medium spiny neurons (MSNs express dopamine D1 (D1+ and D2 receptors (D2+, respectively. Both classes receive extensive GABAergic input via expression of synaptic, perisynaptic and extrasynaptic GABAA receptors. The activation patterns of different presynaptic GABAergic neurons produce transient and sustained GABAA receptor-mediated conductance that fulfill distinct physiological roles. We performed single and dual whole cell recordings from striatal neurons in mice expressing fluorescent proteins in interneurons and MSNs. We report specific inhibitory dynamics produced by distinct activation patterns of presynaptic GABAergic neurons as source of synaptic, perisynaptic and extrasynaptic inhibition. Synaptic GABAA receptors in MSNs contain the α2, γ2 and a β subunit. In addition, there is evidence for the developmental increase of the α1 subunit that contributes to faster inhibitory postsynaptic current (IPSC. Tonic GABAergic currents in MSNs from adult mice are carried by extrasynaptic receptors containing the α4 and δ subunit, while in younger mice this current is mediated by receptors that contain the α5 subunit. Both forms of tonic currents are differentially expressed in D1+ and D2+ MSNs. This study extends these findings by relating presynaptic activation with pharmacological analysis of inhibitory conductance in mice where the β3 subunit is conditionally removed in fluorescently labeled D2+ MSNs and in mice with global deletion of the δ subunit. Our results show that responses to low doses of gaboxadol (2μM, a GABAA receptor agonist with preference to δ subunit, are abolished in the δ but not the β3 subunit knock out mice. This suggests that the β3 subunit is not a component of the adult extrasynaptic receptor pool, in contrast to what has been shown for tonic current in young mice. Deletion of the β3 subunit from D2+ MSNs however, removed slow spontaneous IPSCs, implicating its

  7. 7 CFR 1484.50 - What cost share contributions are eligible?

    Science.gov (United States)

    2010-01-01

    ... FAS to ensure compliance with program requirements; (14) The cost of giveaways, awards, prizes and... development activity; (22) Payment of employee's or contractor's share of personal taxes; (23) The cost... 7 Agriculture 10 2010-01-01 2010-01-01 false What cost share contributions are eligible? 1484.50...

  8. RABA Members Act in Distinct Steps of Subcellular Trafficking of the FLAGELLIN SENSING2 Receptor[W

    Science.gov (United States)

    Choi, Seung-won; Tamaki, Takayuki; Ebine, Kazuo; Uemura, Tomohiro; Ueda, Takashi; Nakano, Akihiko

    2013-01-01

    Cell surface proteins play critical roles in the perception of environmental stimuli at the plasma membrane (PM) and ensuing signal transduction. Intracellular localization of such proteins must be strictly regulated, which requires elaborate integration of exocytic and endocytic trafficking pathways. Subcellular localization of Arabidopsis thaliana FLAGELLIN SENSING2 (FLS2), a receptor that recognizes bacterial flagellin, also depends on membrane trafficking. However, our understanding about the mechanisms involved is still limited. In this study, we visualized ligand-induced endocytosis of FLS2 using green fluorescent protein (GFP)-tagged FLS2 expressed in Nicotiana benthamiana. Upon treatment with the flg22 peptide, internalized FLS2-GFP from the PM was transported to a compartment with properties intermediate between the trans-Golgi network (TGN) and the multivesicular endosome. This compartment gradually discarded the TGN characteristics as it continued along the trafficking pathway. We further found that FLS2 endocytosis involves distinct RABA/RAB11 subgroups at different steps. Moreover, we demonstrated that transport of de novo–synthesized FLS2 to the PM also involves a distinct RABA/RAB11 subgroup. Our results demonstrate the complex regulatory system for properly localizing FLS2 and functional differentiation in RABA members in endo- and exocytosis. PMID:23532067

  9. Sensitive detection of chromosomal segments of distinct ancestry in admixed populations.

    Directory of Open Access Journals (Sweden)

    Alkes L Price

    2009-06-01

    Full Text Available Identifying the ancestry of chromosomal segments of distinct ancestry has a wide range of applications from disease mapping to learning about history. Most methods require the use of unlinked markers; but, using all markers from genome-wide scanning arrays, it should in principle be possible to infer the ancestry of even very small segments with exquisite accuracy. We describe a method, HAPMIX, which employs an explicit population genetic model to perform such local ancestry inference based on fine-scale variation data. We show that HAPMIX outperforms other methods, and we explore its utility for inferring ancestry, learning about ancestral populations, and inferring dates of admixture. We validate the method empirically by applying it to populations that have experienced recent and ancient admixture: 935 African Americans from the United States and 29 Mozabites from North Africa. HAPMIX will be of particular utility for mapping disease genes in recently admixed populations, as its accurate estimates of local ancestry permit admixture and case-control association signals to be combined, enabling more powerful tests of association than with either signal alone.

  10. Mapping Phylogenetic Trees to Reveal Distinct Patterns of Evolution.

    Science.gov (United States)

    Kendall, Michelle; Colijn, Caroline

    2016-10-01

    Evolutionary relationships are frequently described by phylogenetic trees, but a central barrier in many fields is the difficulty of interpreting data containing conflicting phylogenetic signals. We present a metric-based method for comparing trees which extracts distinct alternative evolutionary relationships embedded in data. We demonstrate detection and resolution of phylogenetic uncertainty in a recent study of anole lizards, leading to alternate hypotheses about their evolutionary relationships. We use our approach to compare trees derived from different genes of Ebolavirus and find that the VP30 gene has a distinct phylogenetic signature composed of three alternatives that differ in the deep branching structure. phylogenetics, evolution, tree metrics, genetics, sequencing. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  11. Elastin Degradation by Cathepsin V Requires Two Exosites*

    Science.gov (United States)

    Du, Xin; Chen, Nelson L. H.; Wong, Andre; Craik, Charles S.; Brömme, Dieter

    2013-01-01

    Cathepsin V is a highly effective elastase and has been implicated in physiological and pathological extracellular matrix degradation. However, its mechanism of action remains elusive. Whereas human cathepsin V exhibits a potent elastolytic activity, the structurally homologous cathepsin L, which shares a 78% amino acid sequence, has only a minimal proteolytic activity toward insoluble elastin. This suggests that there are distinct structural domains that play an important role in elastinolysis. In this study, a total of 11 chimeras of cathepsins V and L were generated to identify elastin-binding domains in cathepsin V. Evaluation of these chimeras revealed two exosites contributing to the elastolytic activity of cathepsin V that are distant from the active cleft of the protease and are located in surface loop regions. Replacement of exosite 1 or 2 with analogous residues from cathepsin L led to a 75 and 43% loss in the elastolytic activity, respectively. Replacement of both exosites yielded a non-elastase variant similar to that of cathepsin L. Identification of these exosites may contribute to the design of inhibitors that will only affect the elastolytic activity of cysteine cathepsins without interfering with other physiological protease functions. PMID:24121514

  12. Trading Robustness Requirements in Mars Entry Trajectory Design

    Science.gov (United States)

    Lafleur, Jarret M.

    2009-01-01

    One of the most important metrics characterizing an atmospheric entry trajectory in preliminary design is the size of its predicted landing ellipse. Often, requirements for this ellipse are set early in design and significantly influence both the expected scientific return from a particular mission and the cost of development. Requirements typically specify a certain probability level (6-level) for the prescribed ellipse, and frequently this latter requirement is taken at 36. However, searches for the justification of 36 as a robustness requirement suggest it is an empirical rule of thumb borrowed from non-aerospace fields. This paper presents an investigation into the sensitivity of trajectory performance to varying robustness (6-level) requirements. The treatment of robustness as a distinct objective is discussed, and an analysis framework is presented involving the manipulation of design variables to effect trades between performance and robustness objectives. The scenario for which this method is illustrated is the ballistic entry of an MSL-class Mars entry vehicle. Here, the design variable is entry flight path angle, and objectives are parachute deploy altitude performance and error ellipse robustness. Resulting plots show the sensitivities between these objectives and trends in the entry flight path angles required to design to these objectives. Relevance to the trajectory designer is discussed, as are potential steps for further development and use of this type of analysis.

  13. Distinct protease pathways control cell shape and apoptosis in v-src-transformed quail neuroretina cells

    International Nuclear Information System (INIS)

    Neel, Benjamin D.; Aouacheria, Abdel; Nouvion, Anne-Laure; Ronot, Xavier; Gillet, Germain

    2005-01-01

    Intracellular proteases play key roles in cell differentiation, proliferation and apoptosis. In nerve cells, little is known about their relative contribution to the pathways which control cell physiology, including cell death. Neoplastic transformation of avian neuroretina cells by p60 v-src tyrosine kinase results in dramatic morphological changes and deregulation of apoptosis. To identify the proteases involved in the cellular response to p60 v-src , we evaluated the effect of specific inhibitors of caspases, calpains and the proteasome on cell shape changes and apoptosis induced by p60 v-src inactivation in quail neuroretina cells transformed by tsNY68, a thermosensitive strain of Rous sarcoma virus. We found that the ubiquitin-proteasome pathway is recruited early after p60 v-src inactivation and is critical for morphological changes, whereas caspases are essential for cell death. This study provides evidence that distinct intracellular proteases are involved in the control of the morphology and fate of v-src-transformed cells

  14. Substantial Union or Substantial Distinction of Mind and Body in Descartes' Metaphysics

    Directory of Open Access Journals (Sweden)

    Fahime Jamei

    2009-01-01

    Full Text Available According to Descartes’ metaphysics there are two different kinds of substances in the world of creatures: “thinking substance” and “extended substance” or soul and matter. In Descartes’ philosophy the soul is equal to the mind and considered as a “thinking substance”. This immaterial substance is the essence of the human being. Body, being considered as a “matter“, is an “extended substance” and entirely distinct from the soul. The soul, therefore, exists and may be known prior to body and, not being corporeal, can exist after human death. Hence, Descartes can prove the immortality of human soul in the framework of the principle of substantial distinction. On the other hand, as a physiologist and psychologist, Descartes indeed believes in mind-body union, so that some causal interactions between mind and body show their substantial union. In this essay, the authors show that Descartes faces a serious problem in combining substantial union of mind and body with their substantial distinction; despite of his efforts in introducing the idea of pineal gland, the problem remains unsolved. Therefore it seems that as he cannot dispense with his only reason for proving the immortality of human soul, he has to hold the mind-body distinction theory in his metaphysics. Indeed, Descartes prefers to support the distinction theory rather than union theory in confronting a thesis and an antithesis stating one of two theories

  15. Substantial :union: or Substantial Distinction of Mind and Body in Descartes\\' Metaphysics

    Directory of Open Access Journals (Sweden)

    f Jamei

    2009-06-01

    Full Text Available According to Descartes’ metaphysics there are two different kinds of substances in the world of creatures: “thinking substance” and “extended substance” or soul and matter. In Descartes’ philosophy the soul is equal to the mind and considered as a “thinking substance”. This immaterial substance is the essence of the human being. Body, being considered as a “matter“, is an “extended substance” and entirely distinct from the soul. The soul, therefore, exists and may be known prior to body and, not being corporeal, can exist after human death. Hence, Descartes can prove the immortality of human soul in the framework of the principle of substantial distinction. On the other hand, as a physiologist and psychologist, Descartes indeed believes in mind-body :union:, so that some causal interactions between mind and body show their substantial :union:. In this essay, the authors show that Descartes faces a serious problem in combining substantial :union: of mind and body with their substantial distinction despite of his efforts in introducing the idea of pineal gland, the problem remains unsolved. Therefore it seems that as he cannot dispense with his only reason for proving the immortality of human soul, he has to hold the mind-body distinction theory in his metaphysics. Indeed, Descartes prefers to support the distinction theory rather than :union: theory in confronting a thesis and an antithesis stating one of two theories.

  16. Executive Functions Contribute Uniquely to Reading Competence in Minority Youth

    Science.gov (United States)

    Jacobson, Lisa A.; Koriakin, Taylor; Lipkin, Paul; Boada, Richard; Frijters, Jan; Lovett, Maureen; Hill, Dina; Willcutt, Erik; Gottwald, Stephanie; Wolf, Maryanne; Bosson-Heenan, Joan; Gruen, Jeffrey R.; Mahone, E. Mark

    2018-01-01

    Competent reading requires various skills beyond those for basic word reading (i.e., core language skills, rapid naming, phonological processing). Contributing “higher-level” or domain-general processes include information processing speed and executive functions (working memory, strategic problem solving, attentional switching). Research in this area has relied on largely Caucasian samples, with limited representation of children from racial or ethnic minority groups. This study examined contributions of executive skills to reading competence in 761 children of minority backgrounds. Hierarchical linear regressions examined unique contributions of executive functions (EF) to word reading, fluency, and comprehension. EF contributed uniquely to reading performance, over and above reading-related language skills; working memory contributed uniquely to all components of reading; while attentional switching, but not problem solving, contributed to isolated and contextual word reading and reading fluency. Problem solving uniquely predicted comprehension, suggesting that this skill may be especially important for reading comprehension in minority youth. Attentional switching may play a unique role in development of reading fluency in minority youth, perhaps as a result of the increased demand for switching between spoken versus written dialects. Findings have implications for educational and clinical practice with regard to reading instruction, remedial reading intervention, and assessment of individuals with reading difficulty. PMID:26755569

  17. The contribution of Qumran to historical Hebrew linguistics: Evidence from the syntax of participial negation

    Directory of Open Access Journals (Sweden)

    Jacobus A. Naudé

    2016-06-01

    Full Text Available In this article we examine how Qumran Hebrew can contribute to our knowledge of historical Hebrew linguistics. The premise of this paper is that Qumran Hebrew reflects a distinct stage in the development of Hebrew which sets it apart from Biblical Hebrew. It is further assumed that these unique features are able to assist us to understand the nature of the development of Biblical Hebrew in a more precise way. Evidence from the syntax of participial negation at Qumran as opposed to Biblical Hebrew provides evidence for this claim. Keywords: Qumran Hebrew; Biblical Hebrew; historical linguistics;l Dead Sea Scrolls

  18. Assembly of the Arp5 (Actin-related Protein) Subunit Involved in Distinct INO80 Chromatin Remodeling Activities*

    Science.gov (United States)

    Yao, Wei; Beckwith, Sean L.; Zheng, Tina; Young, Thomas; Dinh, Van T.; Ranjan, Anand; Morrison, Ashby J.

    2015-01-01

    ATP-dependent chromatin remodeling, which repositions and restructures nucleosomes, is essential to all DNA-templated processes. The INO80 chromatin remodeling complex is an evolutionarily conserved complex involved in diverse cellular processes, including transcription, DNA repair, and replication. The functional diversity of the INO80 complex can, in part, be attributed to specialized activities of distinct subunits that compose the complex. Furthermore, structural analyses have identified biochemically discrete subunit modules that assemble along the Ino80 ATPase scaffold. Of particular interest is the Saccharomyces cerevisiae Arp5-Ies6 module located proximal to the Ino80 ATPase and the Rvb1-Rvb2 helicase module needed for INO80-mediated in vitro activity. In this study we demonstrate that the previously uncharacterized Ies2 subunit is required for Arp5-Ies6 association with the catalytic components of the INO80 complex. In addition, Arp5-Ies6 module assembly with the INO80 complex is dependent on distinct conserved domains within Arp5, Ies6, and Ino80, including the spacer region within the Ino80 ATPase domain. Arp5-Ies6 interacts with chromatin via assembly with the INO80 complex, as IES2 and INO80 deletion results in loss of Arp5-Ies6 chromatin association. Interestingly, ectopic addition of the wild-type Arp5-Ies6 module stimulates INO80-mediated ATP hydrolysis and nucleosome sliding in vitro. However, the addition of mutant Arp5 lacking unique insertion domains facilitates ATP hydrolysis in the absence of nucleosome sliding. Collectively, these results define the requirements of Arp5-Ies6 assembly, which are needed to couple ATP hydrolysis to productive nucleosome movement. PMID:26306040

  19. Confronting data requirements and data provision in Space Weather: The Contribution of Long Term Archives. Part 2.

    Science.gov (United States)

    Glover, Alexi; Heynderickx, Daniel

    Operational space weather services rely heavily on reliable data streams from spacecraft and ground-based facilities, as well as from services providing processed data products. This event focuses on an unusual solar maximum viewed from several different perspectives, and as such highlights the important contribution of long term archives in supporting space weather studies and services. We invite the space weather community to contribute to a discussion on the key topics listed below, with the aim of formulating recommendations and guidelines for policy makers, stakeholders, data and service providers: - facilitating access to and awareness of existing data resources - establishing clear guidelines for space weather data archives including data quality, interoperability and metadata standards - ensuring data ownership and terms of (re)use are clearly identified such that this information can be taken into account when (potentially commercial) services are developed based on data provided without charge for scientific purposes only All participants are invited to submit input for the discussion to the authors ahead of the Assembly. The outcome of the session will be formulated as a set of proposed panel recommendations.

  20. Confronting data requirements and data provision in Space Weather: The Contribution of Long Term Archives. Part 1.

    Science.gov (United States)

    Heynderickx, Daniel; Glover, Alexi

    Operational space weather services rely heavily on reliable data streams from spacecraft and ground-based facilities, as well as from services providing processed data products. This event focuses on an unusual solar maximum viewed from several different perspectives, and as such highlights the important contribution of long term archives in supporting space weather studies and services. We invite the space weather community to contribute to a discussion on the key topics listed below, with the aim of formulating recommendations and guidelines for policy makers, stakeholders, data and service providers: - facilitating access to and awareness of existing data resources - establishing clear guidelines for space weather data archives including data quality, interoperability and metadata standards - ensuring data ownership and terms of (re)use are clearly identified such that this information can be taken into account when (potentially commercial) services are developed based on data provided without charge for scientific purposes only All participants are invited to submit input for the discussion to the authors ahead of the Assembly. The outcome of the session will be formulated as a set of proposed panel recommendations.

  1. Employee contributions: a primer on their use, historical trends and overall fit within benefits strategy.

    Science.gov (United States)

    Peters, Hudson A

    2007-01-01

    This article focuses on the use of employee contributions as a strategic tool within employee health plans. While most employers require some form of employee contributions for health care, there is no clear "one-size-fits-all" solution. A myriad of strategies are in place, some active and some passive. This article reviews both common and emerging strategies and how they differ based on industry, employer size and region; discusses how employee contribution strategy fits within overall benefits strategy; and provides a strategic framework for approaching employee contributions in the future.

  2. Soya bean Gα proteins with distinct biochemical properties exhibit differential ability to complement Saccharomyces cerevisiae gpa1 mutant.

    Science.gov (United States)

    Roy Choudhury, Swarup; Wang, Yuqi; Pandey, Sona

    2014-07-01

    Signalling pathways mediated by heterotrimeric G-proteins are common to all eukaryotes. Plants have a limited number of each of the G-protein subunits, with the most elaborate G-protein network discovered so far in soya bean (Glycine max, also known as soybean) which has four Gα, four Gβ and ten Gγ proteins. Biochemical characterization of Gα proteins from plants suggests significant variation in their properties compared with the well-characterized non-plant proteins. Furthermore, the four soya bean Gα (GmGα) proteins exhibit distinct biochemical activities among themselves, but the extent to which such biochemical differences contribute to their in vivo function is also not known. We used the yeast gpa1 mutant which displays constitutive signalling and growth arrest in the pheromone-response pathway as an in vivo model to evaluate the effect of distinct biochemical activities of GmGα proteins. We showed that specific GmGα proteins can be activated during pheromone-dependent receptor-mediated signalling in yeast and they display different strengths towards complementation of yeast gpa1 phenotypes. We also identified amino acids that are responsible for differential complementation abilities of specific Gα proteins. These data establish that specific plant Gα proteins are functional in the receptor-mediated pheromone-response pathway in yeast and that the subtle biochemical differences in their activity are physiologically relevant.

  3. Environmental requirements for oil and gas operations in Saskatchewan

    International Nuclear Information System (INIS)

    Nystuen, L.J.

    1997-01-01

    The administration and regulation of environmental issues regarding the oil and gas industry in Saskatchewan were discussed. The political and cultural differences in Saskatchewan that make environmental processes distinct from its neighbouring jurisdictions were described. The following Saskatchewan legislation deals with environmental requirements: Environmental Management and Protection Act, Environmental Assessment Act, Oil and Gas Conservation Act, Wildlife Habitat Protection Act, Clean Air Act, Planning and Development Act, Forest Act, Water Corporation Act, Heritage Property Act, and Parks Act. The Saskatchewan Department of Energy and Mines (SEM) is the primary regulator of the upstream oil and gas industry. It regulates the construction, operation, reporting and abandonment requirements for oilfield operations. SEM also manages crude oil prior to refining and manages the wastes contaminated with crude oil. Provisions of the relevant Acts regarding drilling in environmentally sensitive areas, flaring requirements, transporting and disposing of oilfield wastes, road-building, operating restrictions, emergency response plans, spill clean-up responsibilities, well abandonment and site reclamation responsibilities were discussed. 8 refs., 2 tabs

  4. Morphological distinctiveness of Javan Tupaia hypochrysa (Scandentia, Tupaiidae)

    Science.gov (United States)

    Sargis, Eric J.; Woodman, Neal; Morningstar, Natalie C.; Reese, Aspen T.; Olson, Link E.

    2013-01-01

    The common treeshrew, Tupaia glis, represents a species complex with a complicated taxonomic history. It is distributed mostly south of the Isthmus of Kra on the Malay Peninsula and surrounding islands. In our recent revision of a portion of this species complex, we did not fully assess the population from Java (T. “glis” hypochrysa) because of our limited sample. Herein, we revisit this taxon using multivariate analyses in comparisons with T. glis, T. chrysogaster of the Mentawai Islands, and T. ferruginea from Sumatra. Analyses of both the manus and skull of Javan T. “glis” hypochrysa show it to be most similar to T. chrysogaster and distinct from both T. glis and T. ferruginea. Yet, the Javan population and T. chrysogaster have different mammae counts, supporting recognition of T. hypochrysa as a distinct species. The change in taxonomic status of T. hypochrysa has conservation implications for both T. glis and this Javan endemic.

  5. African Trypanosomiasis-Associated Anemia: The Contribution of the Interplay between Parasites and the Mononuclear Phagocyte System

    Directory of Open Access Journals (Sweden)

    Benoit Stijlemans

    2018-02-01

    Full Text Available African trypanosomosis (AT is a chronically debilitating parasitic disease of medical and economic importance for the development of sub-Saharan Africa. The trypanosomes that cause this disease are extracellular protozoan parasites that have developed efficient immune escape mechanisms to manipulate the entire host immune response to allow parasite survival and transmission. During the early stage of infection, a profound pro-inflammatory type 1 activation of the mononuclear phagocyte system (MPS, involving classically activated macrophages (i.e., M1, is required for initial parasite control. Yet, the persistence of this M1-type MPS activation in trypanosusceptible animals causes immunopathology with anemia as the most prominent pathological feature. By contrast, in trypanotolerant animals, there is an induction of IL-10 that promotes the induction of alternatively activated macrophages (M2 and collectively dampens tissue damage. A comparative gene expression analysis between M1 and M2 cells identified galectin-3 (Gal-3 and macrophage migration inhibitory factor (MIF as novel M1-promoting factors, possibly acting synergistically and in concert with TNF-α during anemia development. While Gal-3 enhances erythrophagocytosis, MIF promotes both myeloid cell recruitment and iron retention within the MPS, thereby depriving iron for erythropoiesis. Hence, the enhanced erythrophagocytosis and suppressed erythropoiesis lead to anemia. Moreover, a thorough investigation using MIF-deficient mice revealed that the underlying mechanisms in AT-associated anemia development in trypanosusceptible and tolerant animals are quite distinct. In trypanosusceptible animals, anemia resembles anemia of inflammation, while in trypanotolerant animals’ hemodilution, mainly caused by hepatosplenomegaly, is an additional factor contributing to anemia. In this review, we give an overview of how trypanosome- and host-derived factors can contribute to trypanosomosis

  6. Mistakes To Avoid In Attacking The Moral/Conventional Distinction

    Directory of Open Access Journals (Sweden)

    Alejandro Rosas

    2012-11-01

    Full Text Available In an experimental critique of the moral/conventional (M/C distinction, Kelly et al. (2007 present new experimental data about responses to transgressions involving harm, where the novelty is that transgressors are grown-ups, rather than children. Their data do not support the moral/conventional distinction. The contrast between grown-up and schoolyard transgressions does not seem, however, to explain their results: they also use two schoolyard transgressions with similar negative results for the M/C distinction.I here attempt to explain away their results by calling attention to two mistakes in their experimental design. One refers to the use of questionnaire-items of the type that Turiel and collaborators have called mixed-domain situations, which extend over both a moral and a conventional domain. Participants respond to these cases differently than to prototypical moral situations, because some allow the authority rule to override the moral rule. The second mistake emerges in the grown-up transgressions labeled as Whipping/temporal, Whipping/Authority, Spanking/Authority, Prisoner abuse/Authority. These are not the typical transgressions unambiguously “involving a victim who has been harmed, whose rights have been violated, or who has been subject to an injustice”. The victims are also transgressors and harm is inflicted on them as punishment. Plausibly, rules about corporal punishment depend on authority in a way that rules about harming the innocent do not.

  7. Binding of the cSH3 domain of Grb2 adaptor to two distinct RXXK motifs within Gab1 docker employs differential mechanisms.

    Science.gov (United States)

    McDonald, Caleb B; Seldeen, Kenneth L; Deegan, Brian J; Bhat, Vikas; Farooq, Amjad

    2011-01-01

    A ubiquitous component of cellular signaling machinery, Gab1 docker plays a pivotal role in routing extracellular information in the form of growth factors and cytokines to downstream targets such as transcription factors within the nucleus. Here, using isothermal titration calorimetry (ITC) in combination with macromolecular modeling (MM), we show that although Gab1 contains four distinct RXXK motifs, designated G1, G2, G3, and G4, only G1 and G2 motifs bind to the cSH3 domain of Grb2 adaptor and do so with distinct mechanisms. Thus, while the G1 motif strictly requires the PPRPPKP consensus sequence for high-affinity binding to the cSH3 domain, the G2 motif displays preference for the PXVXRXLKPXR consensus. Such sequential differences in the binding of G1 and G2 motifs arise from their ability to adopt distinct polyproline type II (PPII)- and 3(10) -helical conformations upon binding to the cSH3 domain, respectively. Collectively, our study provides detailed biophysical insights into a key protein-protein interaction involved in a diverse array of signaling cascades central to health and disease. Copyright © 2010 John Wiley & Sons, Ltd.

  8. No contribution of GSTM1 and GSTT1 null genotypes to the risk of neutropenia due to benzene exposure in Southeastern Brazil

    Directory of Open Access Journals (Sweden)

    Carmen Silvia Passos Lima

    2009-01-01

    Full Text Available Exposure to benzene has been associated with haematological diseases such as neutropenia (NEB and acute myeloid leukaemia (AML. We tested whether the null genotypes of the GSTM1 and GSTT1 genes, involved in benzene inactivation, altered the risk for NEB in southeastern Brazil. Genomic DNA from 55 NEB patients and 330 controls was analysed by multiplex-polymerase chain reaction. The frequency of the GSTM1, GSTT1 and combined null genotypes was similar in patients and controls (GSTM1, 27.3% vs. 38.8%, p = 0.16; GSTT1, 25.5% vs. 19.7%, p = 0.24; GSTM1/GSTT1, 12.7% vs. 6.7%, p = 0.26; respectively. The distribution of genotype classes in NEB patients was similar to normal controls, suggesting that GSTM1 and GSTT1 null genotypes make no specific contribution to the risk of NEB. As the GSTM1 and GSTT1 null genotypes were previously associated with increased risk for AML in Brazil and elsewhere, we hypothesise that different thresholds of chemical exposure relative to distinct GSTM1 and GSTT1 genotypes may determine whether AML or NEB manifests in benzene exposed individuals from southeastern Brazil. Although indicative, our results still require support by prospective and large scale epidemiological studies, with rigorous assessment of daily chemical exposures and control of the possible contribution of other polymorphic genes involved in benzene metabolism.

  9. Unified thalamic model generates multiple distinct oscillations with state-dependent entrainment by stimulation.

    Directory of Open Access Journals (Sweden)

    Guoshi Li

    2017-10-01

    Full Text Available The thalamus plays a critical role in the genesis of thalamocortical oscillations, yet the underlying mechanisms remain elusive. To understand whether the isolated thalamus can generate multiple distinct oscillations, we developed a biophysical thalamic model to test the hypothesis that generation of and transition between distinct thalamic oscillations can be explained as a function of neuromodulation by acetylcholine (ACh and norepinephrine (NE and afferent synaptic excitation. Indeed, the model exhibited four distinct thalamic rhythms (delta, sleep spindle, alpha and gamma oscillations that span the physiological states corresponding to different arousal levels from deep sleep to focused attention. Our simulation results indicate that generation of these distinct thalamic oscillations is a result of both intrinsic oscillatory cellular properties and specific network connectivity patterns. We then systematically varied the ACh/NE and input levels to generate a complete map of the different oscillatory states and their transitions. Lastly, we applied periodic stimulation to the thalamic network and found that entrainment of thalamic oscillations is highly state-dependent. Our results support the hypothesis that ACh/NE modulation and afferent excitation define thalamic oscillatory states and their response to brain stimulation. Our model proposes a broader and more central role of the thalamus in the genesis of multiple distinct thalamo-cortical rhythms than previously assumed.

  10. Degree of handedness and priming: Further evidence for a distinction between production and identification priming mechanisms.

    Directory of Open Access Journals (Sweden)

    Donna J. LaVoie

    2015-02-01

    Full Text Available The distinction between implicit and explicit forms of memory retrieval is long-standing, and important to the extent it reveals how different neural architecture supports different aspects of memory function. Similarly, distinctions have been made between kinds of repetition priming, a form of implicit memory retrieval. This study focuses on the production-identification priming distinction, which delineates priming tasks involving verification of stimulus features as compared to priming tasks that require use of a cue to guide response retrieval. Studies investigating this dissociation in dementia or similar patient populations indicate that these forms of priming may differ in their neural bases. The current study looks at degree of handedness as a way of investigating inferred neural architecture supporting these two forms of priming. A growing body of research indicates that degree of handedness (consistent, or CH, versus inconsistent, or ICH is associated with greater interhemispheric interaction and functional access to right hemisphere processing in ICH, with superior performance seen in ICH on memory tasks reliant on this processing. Arguments about the theoretical mechanisms underlying identification and production forms of perceptual priming tasks suggest that performance on these tasks will differ as a function of degree of handedness. We tested this question in a group of CH and ICH young adults, who were asked to study lists of words prior to performing a production priming task (word stem completion, a perceptual word identification task, and a word stem cued recall task. While both handedness groups exhibited reliable priming across tasks, word stem completion priming was greater in ICH than CH participants, with identification priming not differing between groups. This dissociation supports the argument that production and identification forms of priming have different underlying neural bases.

  11. Differential cytokine contributions of perivascular haematopoietic stem cell niches.

    Science.gov (United States)

    Asada, Noboru; Kunisaki, Yuya; Pierce, Halley; Wang, Zichen; Fernandez, Nicolas F; Birbrair, Alexander; Ma'ayan, Avi; Frenette, Paul S

    2017-03-01

    Arterioles and sinusoids of the bone marrow (BM) are accompanied by stromal cells that express nerve/glial antigen 2 (NG2) and leptin receptor (LepR), and constitute specialized niches that regulate quiescence and proliferation of haematopoietic stem cells (HSCs). However, how niche cells differentially regulate HSC functions remains unknown. Here, we show that the effects of cytokines regulating HSC functions are dependent on the producing cell sources. Deletion of chemokine C-X-C motif ligand 12 (Cxcl12) or stem cell factor (Scf) from all perivascular cells marked by nestin-GFP dramatically depleted BM HSCs. Selective Cxcl12 deletion from arteriolar NG2 + cells, but not from sinusoidal LepR + cells, caused HSC reductions and altered HSC localization in BM. By contrast, deletion of Scf in LepR + cells, but not NG2 + cells, led to reductions in BM HSC numbers. These results uncover distinct contributions of cytokines derived from perivascular cells in separate vascular niches to HSC maintenance.

  12. Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites

    Science.gov (United States)

    Brautigam, Chad A; Xing, Wenmin; Yang, Sheng; Henry, Lisa; Doolittle, Lynda K; Walz, Thomas

    2017-01-01

    The Rho GTPase Rac1 activates the WAVE regulatory complex (WRC) to drive Arp2/3 complex-mediated actin polymerization, which underpins diverse cellular processes. Here we report the structure of a WRC-Rac1 complex determined by cryo-electron microscopy. Surprisingly, Rac1 is not located at the binding site on the Sra1 subunit of the WRC previously identified by mutagenesis and biochemical data. Rather, it binds to a distinct, conserved site on the opposite end of Sra1. Biophysical and biochemical data on WRC mutants confirm that Rac1 binds to both sites, with the newly identified site having higher affinity and both sites required for WRC activation. Our data reveal that the WRC is activated by simultaneous engagement of two Rac1 molecules, suggesting a mechanism by which cells may sense the density of active Rac1 at membranes to precisely control actin assembly. PMID:28949297

  13. SIFT-CCH: Increasing the SIFT distinctness by color co-occurrence histograms

    OpenAIRE

    ANCUTI, Cosmin; BEKAERT, Philippe

    2007-01-01

    Describing regions in a distinctive way, in order to find correct correspondences in images of two separated views, represents a complex and essential task of computer vision. Until now, SIFT (Scale Invariant Feature Transform) has been proven to be the most reliable descriptor among the others. One of the main drawbacks of SIFT is its vulnerability to color images, being designed mainly for the gray images. To overcome this problem and also to increase the overall distinctness of the SIFT ...

  14. Distinct types of glial cells populate the Drosophila antenna

    Directory of Open Access Journals (Sweden)

    Jhaveri Dhanisha

    2005-11-01

    Full Text Available Abstract Background The development of nervous systems involves reciprocal interactions between neurons and glia. In the Drosophila olfactory system, peripheral glial cells arise from sensory lineages specified by the basic helix-loop-helix transcription factor, Atonal. These glia wrap around the developing olfactory axons early during development and pattern the three distinct fascicles as they exit the antenna. In the moth Manduca sexta, an additional set of central glia migrate to the base of the antennal nerve where axons sort to their glomerular targets. In this work, we have investigated whether similar types of cells exist in the Drosophila antenna. Results We have used different P(Gal4 lines to drive Green Fluorescent Protein (GFP in distinct populations of cells within the Drosophila antenna. Mz317::GFP, a marker for cell body and perineural glia, labels the majority of peripheral glia. An additional ~30 glial cells detected by GH146::GFP do not derive from any of the sensory lineages and appear to migrate into the antenna from the brain. Their appearance in the third antennal segment is regulated by normal function of the Epidermal Growth Factor receptor and small GTPases. We denote these distinct populations of cells as Mz317-glia and GH146-glia respectively. In the adult, processes of GH146-glial cells ensheath the olfactory receptor neurons directly, while those of the Mz317-glia form a peripheral layer. Ablation of GH146-glia does not result in any significant effects on the patterning of the olfactory receptor axons. Conclusion We have demonstrated the presence of at least two distinct populations of glial cells within the Drosophila antenna. GH146-glial cells originate in the brain and migrate to the antenna along the newly formed olfactory axons. The number of cells populating the third segment of the antenna is regulated by signaling through the Epidermal Growth Factor receptor. These glia share several features of the sorting

  15. The rhetorician's craft, distinctions in science, and political morality

    OpenAIRE

    Sadler, John Z

    2006-01-01

    Abstract In his response to Szasz' Secular Humanism and Scientific Psychiatry, the author considers the use of rhetorical devices in Szasz' work, Szasz' avoidance of acknowledging psychiatry's scientific distinctions, and Szaszian libertarianism versus liberalism.

  16. Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia induce distinct host responses.

    Science.gov (United States)

    McConnell, Kevin W; McDunn, Jonathan E; Clark, Andrew T; Dunne, W Michael; Dixon, David J; Turnbull, Isaiah R; Dipasco, Peter J; Osberghaus, William F; Sherman, Benjamin; Martin, James R; Walter, Michael J; Cobb, J Perren; Buchman, Timothy G; Hotchkiss, Richard S; Coopersmith, Craig M

    2010-01-01

    Pathogens that cause pneumonia may be treated in a targeted fashion by antibiotics, but if this therapy fails, then treatment involves only nonspecific supportive measures, independent of the inciting infection. The purpose of this study was to determine whether host response is similar after disparate infections with similar mortalities. Prospective, randomized controlled study. Animal laboratory in a university medical center. Pneumonia was induced in FVB/N mice by either Streptococcus pneumoniae or two different concentrations of Pseudomonas aeruginosa. Plasma and bronchoalveolar lavage fluid from septic animals was assayed by a microarray immunoassay measuring 18 inflammatory mediators at multiple time points. The host response was dependent on the causative organism as well as kinetics of mortality, but the pro-inflammatory and anti-inflammatory responses were independent of inoculum concentration or degree of bacteremia. Pneumonia caused by different concentrations of the same bacteria, Pseudomonas aeruginosa, also yielded distinct inflammatory responses; however, inflammatory mediator expression did not directly track the severity of infection. For all infections, the host response was compartmentalized, with markedly different concentrations of inflammatory mediators in the systemic circulation and the lungs. Hierarchical clustering analysis resulted in the identification of five distinct clusters of the host response to bacterial infection. Principal components analysis correlated pulmonary macrophage inflammatory peptide-2 and interleukin-10 with progression of infection, whereas elevated plasma tumor necrosis factor sr2 and macrophage chemotactic peptide-1 were indicative of fulminant disease with >90% mortality within 48 hrs. Septic mice have distinct local and systemic responses to Streptococcus pneumoniae and Pseudomonas aeruginosa pneumonia. Targeting specific host inflammatory responses induced by distinct bacterial infections could represent a

  17. Distinct collective states due to trade-off between attractive and repulsive couplings

    Science.gov (United States)

    Sathiyadevi, K.; Chandrasekar, V. K.; Senthilkumar, D. V.; Lakshmanan, M.

    2018-03-01

    We investigate the effect of repulsive coupling together with an attractive coupling in a network of nonlocally coupled oscillators. To understand the complex interaction between these two couplings we introduce a control parameter in the repulsive coupling which plays a crucial role in inducing distinct complex collective patterns. In particular, we show the emergence of various cluster chimera death states through a dynamically distinct transition route, namely the oscillatory cluster state and coherent oscillation death state as a function of the repulsive coupling in the presence of the attractive coupling. In the oscillatory cluster state, the oscillators in the network are grouped into two distinct dynamical states of homogeneous and inhomogeneous oscillatory states. Further, the network of coupled oscillators follow the same transition route in the entire coupling range. Depending upon distinct coupling ranges, the system displays different number of clusters in the death state and oscillatory state. We also observe that the number of coherent domains in the oscillatory cluster state exponentially decreases with increase in coupling range and obeys a power-law decay. Additionally, we show analytical stability for observed solitary state, synchronized state, and incoherent oscillation death state.

  18. Adaptation of flower and fruit colours to multiple, distinct mutualists.

    Science.gov (United States)

    Renoult, Julien P; Valido, Alfredo; Jordano, Pedro; Schaefer, H Martin

    2014-01-01

    Communication in plant-animal mutualisms frequently involves multiple perceivers. A fundamental uncertainty is whether and how species adapt to communicate with groups of mutualists having distinct sensory abilities. We quantified the colour conspicuousness of flowers and fruits originating from one European and two South American plant communities, using visual models of pollinators (bee and fly) and seed dispersers (bird, primate and marten). We show that flowers are more conspicuous than fruits to pollinators, and the reverse to seed dispersers. In addition, flowers are more conspicuous to pollinators than to seed dispersers and the reverse for fruits. Thus, despite marked differences in the visual systems of mutualists, flower and fruit colours have evolved to attract multiple, distinct mutualists but not unintended perceivers. We show that this adaptation is facilitated by a limited correlation between flower and fruit colours, and by the fact that colour signals as coded at the photoreceptor level are more similar within than between functional groups (pollinators and seed dispersers). Overall, these results provide the first quantitative demonstration that flower and fruit colours are adaptations allowing plants to communicate simultaneously with distinct groups of mutualists. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

  19. Differential autoshaping to common and distinctive elements of positive and negative discriminative stimuli.

    Science.gov (United States)

    Wasserman, E A; Anderson, P A

    1974-11-01

    The learning by hungry pigeons of a discrimination between two successively presented compound visual stimuli was investigated using a two-key autoshaping procedure. Common and distinctive stimulus elements were simultaneously presented on separate keys and either followed by food delivery, S+, or not, S-. The subjects acquired both between-trial and within-trial discriminations. On S+ trials, pigeons pecked the distinctive stimulus more than the common stimulus; before responding ceased on S- trials, they pecked the common stimulus more than the distinctive one. Mastery of the within-display discrimination during S+ trials preceded mastery of the between-trials discrimination. These findings extend the Jenkins-Sainsbury analysis of discriminations based upon a single distinguishing feature to discriminations in which common and distinctive elements are associated with both the positive and negative discriminative stimuli. The similarity of these findings to other effects found in autoshaping-approach to signals that forecast reinforcement and withdrawal from signals that forecast nonreinforcement-is also discussed.

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

    Science.gov (United States)

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

    2016-11-03

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

  1. Crafty Entanglements: Knitting and Hard Distinctions in Aesthetics and Political Theory

    Directory of Open Access Journals (Sweden)

    Kate M. Daley

    2013-01-01

    Full Text Available Many theoretical writings on aesthetics and politics rely on hard distinctions between what is and is not art, and what is and is not political. In this article, I draw on the work of theorists, knitters, and fiber artists to argue that hand knitting provides a lens through which to unsettle some of these distinctions. I illustrate some of the ways in which aesthetic theory relies on hard distinctions between art and not-art and politics and not-politics, with particular focus on the work of Kant, Hegel, Heidegger, and Rancière. I explain how knitting is often seen as falling clearly outside the definitions of art and politics, and explore the surprising ways in which knitting shows the instability of these categories and expectations. I show that common social traditions and practices that often go unanalyzed can provide insight into the limitations and complexities of prevalent theoretical assumptions.

  2. Does the reading of different orthographies produce distinct brain activity patterns? An ERP study.

    Science.gov (United States)

    Bar-Kochva, Irit; Breznitz, Zvia

    2012-01-01

    Orthographies vary in the degree of transparency of spelling-sound correspondence. These range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Only a few studies have examined whether orthographic depth is reflected in brain activity. In these studies a between-language design was applied, making it difficult to isolate the aspect of orthographic depth. In the present work this question was examined using a within-subject-and-language investigation. The participants were speakers of Hebrew, as they are skilled in reading two forms of script transcribing the same oral language. One form is the shallow pointed script (with diacritics), and the other is the deep unpointed script (without diacritics). Event-related potentials (ERPs) were recorded while skilled readers carried out a lexical decision task in the two forms of script. A visual non-orthographic task controlled for the visual difference between the scripts (resulting from the addition of diacritics to the pointed script only). At an early visual-perceptual stage of processing (~165 ms after target onset), the pointed script evoked larger amplitudes with longer latencies than the unpointed script at occipital-temporal sites. However, these effects were not restricted to orthographic processing, and may therefore have reflected, at least in part, the visual load imposed by the diacritics. Nevertheless, the results implied that distinct orthographic processing may have also contributed to these effects. At later stages (~340 ms after target onset) the unpointed script elicited larger amplitudes than the pointed one with earlier latencies. As this latency has been linked to orthographic-linguistic processing and to the classification of stimuli, it is suggested that these differences are associated with distinct lexical processing of a shallow and a deep orthography.

  3. Does the reading of different orthographies produce distinct brain activity patterns? An ERP study.

    Directory of Open Access Journals (Sweden)

    Irit Bar-Kochva

    Full Text Available Orthographies vary in the degree of transparency of spelling-sound correspondence. These range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Only a few studies have examined whether orthographic depth is reflected in brain activity. In these studies a between-language design was applied, making it difficult to isolate the aspect of orthographic depth. In the present work this question was examined using a within-subject-and-language investigation. The participants were speakers of Hebrew, as they are skilled in reading two forms of script transcribing the same oral language. One form is the shallow pointed script (with diacritics, and the other is the deep unpointed script (without diacritics. Event-related potentials (ERPs were recorded while skilled readers carried out a lexical decision task in the two forms of script. A visual non-orthographic task controlled for the visual difference between the scripts (resulting from the addition of diacritics to the pointed script only. At an early visual-perceptual stage of processing (~165 ms after target onset, the pointed script evoked larger amplitudes with longer latencies than the unpointed script at occipital-temporal sites. However, these effects were not restricted to orthographic processing, and may therefore have reflected, at least in part, the visual load imposed by the diacritics. Nevertheless, the results implied that distinct orthographic processing may have also contributed to these effects. At later stages (~340 ms after target onset the unpointed script elicited larger amplitudes than the pointed one with earlier latencies. As this latency has been linked to orthographic-linguistic processing and to the classification of stimuli, it is suggested that these differences are associated with distinct lexical processing of a shallow and a deep orthography.

  4. Multi-stakeholder taskforces in Bangladesh--a distinctive approach to build sustainable tobacco control implementation.

    Science.gov (United States)

    Jackson-Morris, Angela M; Chowdhury, Ishrat; Warner, Valerie; Bleymann, Kayleigh

    2015-01-07

    The MPOWER policy package enables countries to implement effective, evidence-based strategies to address the threat posed to their population by tobacco. All countries have challenges to overcome when implementing tobacco control policy. Some are generic such as tobacco industry efforts to undermine and circumvent legislation; others are specific to national or local context. Various factors influence how successfully challenges are addressed, including the legal-political framework for enforcement, public and administrative attitudes towards the law, and whether policy implementation measures are undertaken. This paper examines District Tobacco Control Taskforces, a flexible policy mechanism developed in Bangladesh to support the implementation of the Smoking and Tobacco Products Usage (Control) Act 2005 and its 2013 Amendment. At the time of this study published research and/or data was not available and understanding about these structures, their role, contribution, limitations and potential, was limited. We consider Taskforce characteristics and suggest that the "package" comprises a distinctive tobacco control implementation model. Qualitative data is presented from interviews with key informants in ten districts with activated taskforces (n = 70) to provide insight from the perspectives of taskforce members and non-members. In all ten districts taskforces were seen as a crucial tool for tobacco control implementation. Where taskforces were perceived to be functioning well, current positive impacts were perceived, including reduced smoking in public places and tobacco advertising, and increased public awareness and political profile. In districts with less well established taskforces, interviewees believed in their taskforce's 'potential' to deliver similar benefits once their functioning was improved. Recommendations to improve functioning and enhance impact were made. The distinctive taskforce concept and lessons from their development may provide other

  5. What History Tells Us about the Distinct Nature of Chemistry.

    Science.gov (United States)

    Chang, Hasok

    2017-11-01

    Attention to the history of chemistry can help us recognise the characteristics of chemistry that have helped to maintain it as a separate scientific discipline with a unique identity. Three such features are highlighted in this paper. First, chemistry has maintained a distinct type of theoretical thinking, independent from that of physics even in the era of quantum chemistry. Second, chemical research has always been shaped by its ineliminable practical relevance and usefulness. Third, the lived experience of chemistry, spanning the laboratory, the classroom and everyday life, is distinctive in its multidimensional sensuousness. Furthermore, I argue that the combination of these three features makes chemistry an exemplary science.

  6. The rhetorician's craft, distinctions in science, and political morality

    Science.gov (United States)

    Sadler, John Z

    2006-01-01

    In his response to Szasz' Secular Humanism and Scientific Psychiatry, the author considers the use of rhetorical devices in Szasz' work, Szasz' avoidance of acknowledging psychiatry's scientific distinctions, and Szaszian libertarianism versus liberalism. PMID:16759356

  7. Fetterman-House: A Process Use Distinction and a Theory.

    Science.gov (United States)

    Fetterman, David

    2003-01-01

    Discusses the concept of process use as an important distinction between the evaluation theories of E. House and D. Fetterman, thus helping to explain the discordant results of C. Christie for these two theories. (SLD)

  8. Distinct phases of eustatic and tectonic forcing for late Quaternary landscape evolution in southwest Crete, Greece

    Directory of Open Access Journals (Sweden)

    V. Mouslopoulou

    2017-09-01

    Full Text Available The extent to which climate, eustasy and tectonics interact to shape the late Quaternary landscape is poorly known. Alluvial fans often provide useful indexes that allow the decoding of information recorded on complex coastal landscapes, such as those of the eastern Mediterranean. In this paper we analyse and date (using infrared stimulated luminescence (IRSL dating a double alluvial fan system on southwest Crete, an island straddling the forearc of the Hellenic subduction margin, in order to constrain the timing and magnitude of its vertical deformation and discuss the factors contributing to its landscape evolution. The studied alluvial system is exceptional because each of its two juxtaposed fans records individual phases of alluvial and marine incision, thus providing unprecedented resolution in the formation and evolution of its landscape. Specifically, our analysis shows that the fan sequence at Domata developed during Marine Isotope Stage (MIS 3 due to five distinct stages of marine transgressions and regressions and associated river incision, in response to sea-level fluctuations and tectonic uplift at averaged rates of  ∼ 2.2 mm yr−1. Interestingly, comparison of our results with published tectonic uplift rates from western Crete shows that uplift during 20–50 kyr BP was minimal (or even negative. Thus, most of the uplift recorded at Domata must have occurred in the last 20 kyr. This implies that eustasy and tectonism impacted the landscape at Domata over mainly distinct time intervals (e.g. sequentially and not synchronously, with eustasy forming and tectonism preserving the coastal landforms.

  9. Gene expression profiling in the striatum of inbred mouse strains with distinct opioid-related phenotypes

    Directory of Open Access Journals (Sweden)

    Piechota Marcin

    2006-06-01

    Full Text Available Abstract Background Mouse strains with a contrasting response to morphine provide a unique model for studying the genetically determined diversity of sensitivity to opioid reward, tolerance and dependence. Four inbred strains selected for this study exhibit the most distinct opioid-related phenotypes. C57BL/6J and DBA/2J mice show remarkable differences in morphine-induced antinociception, self-administration and locomotor activity. 129P3/J mice display low morphine tolerance and dependence in contrast to high sensitivity to precipitated withdrawal observed in SWR/J and C57BL/6J strains. In this study, we attempted to investigate the relationships between genetic background and basal gene expression profile in the striatum, a brain region involved in the mechanism of opioid action. Results Gene expression was studied by Affymetrix Mouse Genome 430v2.0 arrays with probes for over 39.000 transcripts. Analysis of variance with the control for false discovery rate (q Khdrbs1 and ATPase Na+/K+ alpha2 subunit (Atp1a2 with morphine self-administration and analgesic effects, respectively. Finally, the examination of transcript structure demonstrated a possible inter-strain variability of expressed mRNA forms as for example the catechol-O-methyltransferase (Comt gene. Conclusion The presented study led to the recognition of differences in the gene expression that may account for distinct phenotypes. Moreover, results indicate strong contribution of genetic background to differences in gene transcription in the mouse striatum. The genes identified in this work constitute promising candidates for further animal studies and for translational genetic studies in the field of addictive and analgesic properties of opioids.

  10. Factors contributing to outcome following traumatic brain injury.

    Science.gov (United States)

    Ponsford, Jennie

    2013-01-01

    Traumatic brain injury results in some distinctive patterns of cognitive, behavioural and physical impairment which impact significantly on independent living skills and participation in work or study, social and leisure activities and interpersonal relationships. There is, however, still considerable variability in outcome across individuals in each of the reported domains. This has led to a significant body of research examining factors associated with outcome. A range of injury-related, personal and social factors have been shown to influence survival, as well as cognitive, functional and employment outcome. This paper reviews the factors associated with each of these aspects of outcome specifically injury-related factors, including neuroimaging findings, GCS and PTA, other injuries, and cognitive and behavioural impairments; demographic factors, including age, gender, genetic status, education, pre-injury IQ and employment status; and social factors including family and other social support, cultural factors, pre-injury psychiatric history and coping style. The paper identifies contributions and complex interrelationships of all of these factors to outcome following TBI. It concludes with a brief discussion of the implications of these factors for the rehabilitation process.

  11. Three Fusarium oxysporum mitogen-activated protein kinases (MAPKs) have distinct and complementary roles in stress adaptation and cross-kingdom pathogenicity.

    Science.gov (United States)

    Segorbe, David; Di Pietro, Antonio; Pérez-Nadales, Elena; Turrà, David

    2017-09-01

    Mitogen-activated protein kinase (MAPK) cascades mediate cellular responses to environmental signals. Previous studies in the fungal pathogen Fusarium oxysporum have revealed a crucial role of Fmk1, the MAPK orthologous to Saccharomyces cerevisiae Fus3/Kss1, in vegetative hyphal fusion and plant infection. Here, we genetically dissected the individual and combined contributions of the three MAPKs Fmk1, Mpk1 and Hog1 in the regulation of development, stress response and virulence of F. oxysporum on plant and animal hosts. Mutants lacking Fmk1 or Mpk1 were affected in reactive oxygen species (ROS) homeostasis and impaired in hyphal fusion and aggregation. Loss of Mpk1 also led to increased sensitivity to cell wall and heat stress, which was exacerbated by simultaneous inactivation of Fmk1, suggesting that both MAPKs contribute to cellular adaptation to high temperature, a prerequisite for mammalian pathogens. Deletion of Hog1 caused increased sensitivity to hyperosmotic stress and resulted in partial rescue of the restricted colony growth phenotype of the mpk1Δ mutant. Infection assays on tomato plants and the invertebrate animal host Galleria mellonella revealed distinct and additive contributions of the different MAPKs to virulence. Our results indicate that positive and negative cross-talk between the three MAPK pathways regulates stress adaptation, development and virulence in the cross-kingdom pathogen F. oxysporum. © 2016 BSPP AND JOHN WILEY & SONS LTD.

  12. Paralogs hnRNP L and hnRNP LL exhibit overlapping but distinct RNA binding constraints.

    Directory of Open Access Journals (Sweden)

    Sarah A Smith

    Full Text Available HnRNP (heterogeneous nuclear ribonucleoprotein proteins are a large family of RNA-binding proteins that regulate numerous aspects of RNA processing. Interestingly, several paralogous pairs of hnRNPs exist that exhibit similar RNA-binding specificity to one another, yet have non-redundant functional targets in vivo. In this study we systematically investigate the possibility that the paralogs hnRNP L and hnRNP LL have distinct RNA binding determinants that may underlie their lack of functional redundancy. Using a combination of RNAcompete and native gel analysis we find that while both hnRNP L and hnRNP LL preferentially bind sequences that contain repeated CA dinucleotides, these proteins differ in their requirement for the spacing of the CAs. Specifically, hnRNP LL has a more stringent requirement for a two nucleotide space between CA repeats than does hnRNP L, resulting in hnRNP L binding more promiscuously than does hnRNP LL. Importantly, this differential requirement for the spacing of CA dinucleotides explains the previously observed differences in the sensitivity of hnRNP L and LL to mutations within the CD45 gene. We suggest that overlapping but divergent RNA-binding preferences, as we show here for hnRNP L and hnRNP LL, may be commonplace among other hnRNP paralogs.

  13. Calculating the capital contribution required for regulation of incentives in the energy sector; Bestimmung des Eigenkapitalzinssatzes fuer eine Anreizregulierung des Energiesektors

    Energy Technology Data Exchange (ETDEWEB)

    Schaeffner, D. [WIK GmbH, Wissenschaftliches Inst. fuer Infrastruktur und Kommunikationsdienste, Bad Honnef (Germany)

    2006-12-15

    On 30 June 2006, the Federal Regulatory Agency (BNetzA) published its final report on the introduction of regulation by incentives according to Section 21a EnWG. The new regulation regime is to start on 1 January 2008. By this date, a starting value must be defined for the initial cost level and grid use reimbursements. Further, the interest rate for the capital contribution must be redefined (currently: 6.5 percent for the electricity sector and 7.8 percent for the gas sector). The contribution presents a regulation-economic method which takes account of individual parameteres in defining the capital contribution interest rate and of tax parameters and links these to current legal boundary conditions. As an example, the well-known CAPM is presented. (orig.)

  14. Contribution of the Staphylococcus aureus Atl AM and GL murein hydrolase activities in cell division, autolysis, and biofilm formation.

    Directory of Open Access Journals (Sweden)

    Jeffrey L Bose

    Full Text Available The most prominent murein hydrolase of Staphylococcus aureus, AtlA, is a bifunctional enzyme that undergoes proteolytic cleavage to yield two catalytically active proteins, an amidase (AM and a glucosaminidase (GL. Although the bifunctional nature of AtlA has long been recognized, most studies have focused on the combined functions of this protein in cell wall metabolism and biofilm development. In this study, we generated mutant derivatives of the clinical S. aureus isolate, UAMS-1, in which one or both of the AM and GL domains of AtlA have been deleted. Examination of these strains revealed that each mutant exhibited growth rates comparable to the parental strain, but showed clumping phenotypes and lysis profiles that were distinct from the parental strain and each other, suggesting distinct roles in cell wall metabolism. Given the known function of autolysis in the release of genomic DNA for use as a biofilm matrix molecule, we also tested the mutants in biofilm assays and found both AM and GL necessary for biofilm development. Furthermore, the use of enzymatically inactive point mutations revealed that both AM and GL must be catalytically active for S. aureus to form a biofilm. The results of this study provide insight into the relative contributions of AM and GL in S. aureus and demonstrate the contribution of Atl-mediated lysis in biofilm development.

  15. Contribution of the Staphylococcus aureus Atl AM and GL murein hydrolase activities in cell division, autolysis, and biofilm formation.

    Science.gov (United States)

    Bose, Jeffrey L; Lehman, McKenzie K; Fey, Paul D; Bayles, Kenneth W

    2012-01-01

    The most prominent murein hydrolase of Staphylococcus aureus, AtlA, is a bifunctional enzyme that undergoes proteolytic cleavage to yield two catalytically active proteins, an amidase (AM) and a glucosaminidase (GL). Although the bifunctional nature of AtlA has long been recognized, most studies have focused on the combined functions of this protein in cell wall metabolism and biofilm development. In this study, we generated mutant derivatives of the clinical S. aureus isolate, UAMS-1, in which one or both of the AM and GL domains of AtlA have been deleted. Examination of these strains revealed that each mutant exhibited growth rates comparable to the parental strain, but showed clumping phenotypes and lysis profiles that were distinct from the parental strain and each other, suggesting distinct roles in cell wall metabolism. Given the known function of autolysis in the release of genomic DNA for use as a biofilm matrix molecule, we also tested the mutants in biofilm assays and found both AM and GL necessary for biofilm development. Furthermore, the use of enzymatically inactive point mutations revealed that both AM and GL must be catalytically active for S. aureus to form a biofilm. The results of this study provide insight into the relative contributions of AM and GL in S. aureus and demonstrate the contribution of Atl-mediated lysis in biofilm development.

  16. The rhetorician's craft, distinctions in science, and political morality

    Directory of Open Access Journals (Sweden)

    Sadler John Z

    2006-05-01

    Full Text Available Abstract In his response to Szasz' Secular Humanism and Scientific Psychiatry, the author considers the use of rhetorical devices in Szasz' work, Szasz' avoidance of acknowledging psychiatry's scientific distinctions, and Szaszian libertarianism versus liberalism.

  17. Identification of distinct phenotypes of locally advanced pancreatic adenocarcinoma.

    LENUS (Irish Health Repository)

    Teo, Minyuen

    2013-03-01

    A significant number of pancreatic ductal adenocarcinoma present as locally advanced disease. Optimal treatment remains controversial. We sought to analyze the clinical course of locally advanced pancreatic adenocarcinoma (LAPC) in order to identify potential distinct clinical phenotypes.

  18. The Impact of Debt Limitations and Referenda Requirements on the Cost of School District Bond Issues

    Science.gov (United States)

    Harris, Mary H.; Munley, Vincent G.

    2011-01-01

    One distinction between the markets for corporate and municipal bonds involves institutional constraints that apply to some municipal bond issues. This research focuses on how public finance institutions, in particular explicit debt limits and referenda requirements, affect the borrowing cost of individual school district bond issues. The…

  19. The Distinction Between Curative and Assistive Technology.

    Science.gov (United States)

    Stramondo, Joseph A

    2018-05-01

    Disability activists have sometimes claimed their disability has actually increased their well-being. Some even say they would reject a cure to keep these gains. Yet, these same activists often simultaneously propose improvements to the quality and accessibility of assistive technology. However, for any argument favoring assistive over curative technology (or vice versa) to work, there must be a coherent distinction between the two. This line is already vague and will become even less clear with the emergence of novel technologies. This paper asks and tries to answer the question: what is it about the paradigmatic examples of curative and assistive technologies that make them paradigmatic and how can these defining features help us clarify the hard cases? This analysis will begin with an argument that, while the common views of this distinction adequately explain the paradigmatic cases, they fail to accurately pick out the relevant features of those technologies that make them paradigmatic and to provide adequate guidance for parsing the hard cases. Instead, it will be claimed that these categories of curative or assistive technologies are defined by the role the technologies play in establishing a person's relational narrative identity as a member of one of two social groups: disabled people or non-disabled people.

  20. Ice Sheet Model Intercomparison Project (ISMIP6) contribution to CMIP6

    NARCIS (Netherlands)

    Nowicki, Sophie M J; Payne, Anthony; Larour, Eric; Seroussi, Helene; Goelzer, Heiko|info:eu-repo/dai/nl/412549123; Lipscomb, William; Gregory, Jonathan; Abe-Ouchi, Ayako; Shepherd, Andrew

    2016-01-01

    Reducing the uncertainty in the past, present, and future contribution of ice sheets to sea-level change requires a coordinated effort between the climate and glaciology communities. The Ice Sheet Model Intercomparison Project for CMIP6 (ISMIP6) is the primary activity within the Coupled Model

  1. Tributyltin Differentially Promotes Development of a Phenotypically Distinct Adipocyte

    Science.gov (United States)

    Regnier, Shane M.; El-Hashani, Essam; Kamau, Wakanene; Zhang, Xiaojie; Massad, Nicole L.; Sargis, Robert M.

    2015-01-01

    Objective Environmental endocrine disrupting chemicals (EDCs) are increasingly implicated in the pathogenesis of obesity. Evidence implicates various EDCs as being pro-adipogenic, including tributyltin (TBT), which activates the peroxisome proliferator activated receptor-γ (PPARγ). However, the conditions required for TBT-induced adipogenesis and its functional consequences are incompletely known. Methods The co-stimulatory conditions necessary for preadipocyte-to-adipocyte differentiation were compared between TBT and the pharmacological PPARγ agonist troglitazone (Trog) in the 3T3-L1 cell line; basal and insulin-stimulated glucose uptake were assessed using radiolabeled 2-deoxyglucose. Results TBT enhanced expression of the adipocyte marker C/EBPα with co-exposure to either isobutylmethylxanthine or insulin in the absence of other adipogenic stimuli. Examination of several adipocyte-specific proteins revealed that TBT and Trog differentially affected protein expression despite comparable PPARγ stimulation. In particular, TBT reduced adiponectin expression upon maximal adipogenic stimulation. Under submaximal stimulation, TBT and Trog differentially promoted adipocyte-specific gene expression despite similar lipid accumulation. Moreover, TBT attenuated Trog-induced adipocyte gene expression under conditions of co-treatment. Finally, TBT-induced adipocytes exhibited altered glucose metabolism, with increased basal glucose uptake. Conclusions TBT-induced adipocytes are functionally distinct from those generated by a pharmacological PPARγ agonist, suggesting that obesogen-induced adipogenesis may generate dysfunctional adipocytes with the capacity to deleteriously affect global energy homeostasis. PMID:26243053

  2. Tributyltin differentially promotes development of a phenotypically distinct adipocyte.

    Science.gov (United States)

    Regnier, Shane M; El-Hashani, Essam; Kamau, Wakanene; Zhang, Xiaojie; Massad, Nicole L; Sargis, Robert M

    2015-09-01

    Environmental endocrine disrupting chemicals (EDCs) are increasingly implicated in the pathogenesis of obesity. Evidence implicates various EDCs as being proadipogenic, including tributyltin (TBT), which activates the peroxisome proliferator activated receptor-γ (PPARγ). However, the conditions required for TBT-induced adipogenesis and its functional consequences are incompletely known. The costimulatory conditions necessary for preadipocyte-to-adipocyte differentiation were compared between TBT and the pharmacological PPARγ agonist troglitazone (Trog) in the 3T3-L1 cell line; basal and insulin-stimulated glucose uptake were assessed using radiolabeled 2-deoxyglucose. TBT enhanced expression of the adipocyte marker C/EBPα with coexposure to either isobutylmethylxanthine or insulin in the absence of other adipogenic stimuli. Examination of several adipocyte-specific proteins revealed that TBT and Trog differentially affected protein expression despite comparable PPARγ stimulation. In particular, TBT reduced adiponectin expression upon maximal adipogenic stimulation. Under submaximal stimulation, TBT and Trog differentially promoted adipocyte-specific gene expression despite similar lipid accumulation. Moreover, TBT attenuated Trog-induced adipocyte gene expression under conditions of cotreatment. Finally, TBT-induced adipocytes exhibited altered glucose metabolism, with increased basal glucose uptake. TBT-induced adipocytes are functionally distinct from those generated by a pharmacological PPARγ agonist, suggesting that obesogen-induced adipogenesis may generate dysfunctional adipocytes with the capacity to deleteriously affect global energy homeostasis. © 2015 The Obesity Society.

  3. STRUCTURAL IDENTIFICATION OF DISTINCT INVERSIONS OF PLANAR KINEMATIC CHAINS

    Directory of Open Access Journals (Sweden)

    Dr. Shubhashis Sanyal

    2011-12-01

    Full Text Available 0 0 1 171 979 International Islamic University 8 2 1148 14.0 Normal 0 false false false EN-US JA X-NONE /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Times New Roman";} Inversions are various structural possibilities of a kinematic chain. The number of inversions depends on the number of links of a kinematic chain. At the stage of structural synthesis, identification of distinct structural inversions of a particular type of kinematic chain is necessary. Various researchers have proposed methods for identification of distinct inversions. Present method based on Link joint connectivity is proposed to identify the distinct inversions of a planar kinematic chain. Method is tested successfully on single degree and multiple degree of freedom planar kinematic chains. ABSTRAK: Penyonsangan merupakan kebarangkalian pelbagai struktur suatu rangkaian kinematik. Jumlah songsangan bergantung kepada jumlah hubungan suatu rangkaian kinematik. Pada peringkat sintesis struktur, pengenalan songsangan struktur yang berbeza untuk suatu jenis rangkaian kinematik adalah perlu. Ramai penyelidik telah mencadangkan pelbagai kaedah pengenalan songsangan yang berbeza. Kaedah terkini berdasarkan hubungan kesambungan bersama telah dicadangkan untuk mengenalpasti songsangan yang berbeza dalam suatu satah rangkaian kinematik.

  4. Autism spectrum disorders and drug addiction: Common pathways, common molecules, distinct disorders?

    Directory of Open Access Journals (Sweden)

    Patrick E. Rothwell

    2016-02-01

    Full Text Available Autism spectrum disorders (ASDs and drug addiction do not share substantial comorbidity or obvious similarities in etiology or symptomatology. It is thus surprising that a number of recent studies implicate overlapping neural circuits and molecular signaling pathways in both disorders. The purpose of this review is to highlight this emerging intersection and consider implications for understanding the pathophysiology of these seemingly distinct disorders. One area of overlap involves neural circuits and neuromodulatory systems in the striatum and basal ganglia, which play an established role in addiction and reward but are increasingly implicated in clinical and preclinical studies of ASDs. A second area of overlap relates to molecules like Fragile X mental retardation protein (FMRP and methyl CpG-binding protein-2 (MECP2, which are best known for their contribution to the pathogenesis of syndromic ASDs, but have recently been shown to regulate behavioral and neurobiological responses to addictive drug exposure. These shared pathways and molecules point to common dimensions of behavioral dysfunction, including the repetition of behavioral patterns and aberrant reward processing. The synthesis of knowledge gained through parallel investigations of ASDs and addiction may inspire the design of new therapeutic interventions to correct common elements of striatal dysfunction.

  5. Autism Spectrum Disorders and Drug Addiction: Common Pathways, Common Molecules, Distinct Disorders?

    Science.gov (United States)

    Rothwell, Patrick E

    2016-01-01

    Autism spectrum disorders (ASDs) and drug addiction do not share substantial comorbidity or obvious similarities in etiology or symptomatology. It is thus surprising that a number of recent studies implicate overlapping neural circuits and molecular signaling pathways in both disorders. The purpose of this review is to highlight this emerging intersection and consider implications for understanding the pathophysiology of these seemingly distinct disorders. One area of overlap involves neural circuits and neuromodulatory systems in the striatum and basal ganglia, which play an established role in addiction and reward but are increasingly implicated in clinical and preclinical studies of ASDs. A second area of overlap relates to molecules like Fragile X mental retardation protein (FMRP) and methyl CpG-binding protein-2 (MECP2), which are best known for their contribution to the pathogenesis of syndromic ASDs, but have recently been shown to regulate behavioral and neurobiological responses to addictive drug exposure. These shared pathways and molecules point to common dimensions of behavioral dysfunction, including the repetition of behavioral patterns and aberrant reward processing. The synthesis of knowledge gained through parallel investigations of ASDs and addiction may inspire the design of new therapeutic interventions to correct common elements of striatal dysfunction.

  6. Distinctive safety aspects of the CANDU-PHW reactor design

    International Nuclear Information System (INIS)

    Kugler, G.

    1980-01-01

    Two lectures are presented in this report. They were prepared in response to a request from IAEA to provide information on the 'Special characteristics of the safety analysis of heavy water reactors' to delegates from member states attending the Interregional Training Course on Safety Analysis Review, held at Karlsruhe, November 19 to December 20, 1979. The CANDU-PHW reactor is used as a model for discussion. The first lecture describes the distinctive features of the CANDU reactor and how they impact on reactor safety. In the second lecture the Canadian safety philosophy, the safety design objective, and other selected topics on reactor safety analysis are discussed. The material in this report was selected with a view to assisting those not familiar with the CANDU heavy water reactor design in evaluating the distinctive safety aspects of these reactors. (auth)

  7. Key requirements for future control room functionality

    DEFF Research Database (Denmark)

    Tornelli, Carlo; Zuelli, Roberto; Marinelli, Mattia

    2016-01-01

    ) and the observability needs highlighted within WP5 led to the definition of the requirements with a Web of Cell (WoC) point of view. The main European Distribution System Operators (DSOs) provided a valuable contribution in the definition of the evolvDSO Use Cases. Their analysis lead to the definition of further...

  8. Mammalian target of rapamycin is required for phrenic long-term facilitation following severe but not moderate acute intermittent hypoxia.

    Science.gov (United States)

    Dougherty, Brendan J; Fields, Daryl P; Mitchell, Gordon S

    2015-09-01

    Phrenic long-term facilitation (pLTF) is a persistent increase in phrenic nerve activity after acute intermittent hypoxia (AIH). Distinct cell-signaling cascades give rise to pLTF depending on the severity of hypoxemia within hypoxic episodes. Moderate AIH (mAIH; three 5-min episodes, PaO2 ∼35-55 mmHG) elicits pLTF by a serotonin (5-HT)-dependent mechanism that requires new synthesis of brain-derived neurotrophic factor (BDNF), activation of its high-affinity receptor (TrkB), and ERK MAPK signaling. In contrast, severe AIH (sAIH; three 5-min episodes, PaO2 ∼25-30 mmHG) elicits pLTF by an adenosine-dependent mechanism that requires new TrkB synthesis and Akt signaling. Although both mechanisms require spinal protein synthesis, the newly synthesized proteins are distinct, as are the neurochemicals inducing plasticity (serotonin vs. adenosine). In many forms of neuroplasticity, new protein synthesis requires translational regulation via mammalian target of rapamycin (mTOR) signaling. Since Akt regulates mTOR activity, we hypothesized that mTOR activity is necessary for sAIH- but not mAIH-induced pLTF. Phrenic nerve activity in anesthetized, paralyzed, and ventilated rats was recorded before, during, and 60 min after mAIH or sAIH. Rats were pretreated with intrathecal injections of 20% DMSO (vehicle controls) or rapamycin (0.1 mM, 12 μl), a selective mTOR complex 1 inhibitor. Consistent with our hypothesis, rapamycin blocked sAIH- but not mAIH-induced pLTF. Thus spinal mTOR activity is required for adenosine-dependent (sAIH) but not serotonin-dependent (mAIH) pLTF, suggesting that distinct mechanisms regulate new protein synthesis in these forms of spinal neuroplasticity. Copyright © 2015 the American Physiological Society.

  9. UNDERSTANDING THAI CULTURE AND ITS IMPACT ON REQUIREMENTS ENGINEERING PROCESS MANAGEMENT DURING INFORMATION SYSTEMS DEVELOPMENT

    Directory of Open Access Journals (Sweden)

    Theerasak Thanasankit

    2002-01-01

    Full Text Available This paper explores the impact of Thai culture on managing the decision making process in requirements engineering and contribution a better understand of its influence on the management of requirements engineering process. The paper illustrates the interaction of technology and culture and shows that rather than technology changing culture, culture can change the way technology is used. Thai culture is naturally inherent in Thai daily life and Thais bring that into their work practices. The concepts of power and uncertainty in Thai culture contribute toward hierarchical forms of communication and decision making process in Thailand, especially during requirements engineering, where information systems requirements need to be established for further development. The research shows that the decision making process in Thailand tends to take a much longer time, as every stage during requirements engineering needs to be reported to management for final decisions. The tall structure of Thai organisations also contributes to a bureaucratic, elongated decision-making process during information systems development. Understanding the influence of Thai culture on requirements engineering and information systems development will assist multinational information systems consulting organisations to select, adapt, better manage, or change requirements engineering process and information systems developments methodologies to work best with Thai organisations.

  10. Army nurses in wartime: distinction and pride.

    Science.gov (United States)

    Higgins, L P

    1996-08-01

    Nurses have served with distinction in wartime since Florence Nightingale went to the Crimea. Women often accompanied their husbands to battle during the Revolutionary and Civil Wars, caring for the sick and wounded. Although not officially given officer status until 1920, Army nurses served in the Spanish-American War and World War I. As officers, thousands of nurses served in subsequent wars, distinguishing themselves by their heroism, devotion to duty, and sheer tenacity of spirit.

  11. Climate change - the contribution from air travel

    International Nuclear Information System (INIS)

    Beesley, Colin

    2000-01-01

    The paper discusses the Intergovernment Panel on Climate Change (IPCC) report on Aviation and the Global Atmosphere (published in 1999). It was considered necessary to treat air transport on its own since aircraft are unique in delivering emissions into the upper atmosphere rather than at ground level. The study was commissioned at the request of the International Civil Aviation Organisation and the Montreal Protocol. More than 300 experts contributed and the report has quantified the effect of aviation on the atmosphere on a world wide basis and highlighted areas where improved data are required. (UK)

  12. Dissecting the Photoprotective Mechanism Encoded by the flv4-2 Operon: a Distinct Contribution of Sll0218 in Photosystem II Stabilization.

    Science.gov (United States)

    Bersanini, Luca; Allahverdiyeva, Yagut; Battchikova, Natalia; Heinz, Steffen; Lespinasse, Maija; Ruohisto, Essi; Mustila, Henna; Nickelsen, Jörg; Vass, Imre; Aro, Eva-Mari

    2017-03-01

    In Synechocystis sp. PCC 6803, the flv4-2 operon encodes the flavodiiron proteins Flv2 and Flv4 together with a small protein, Sll0218, providing photoprotection for Photosystem II (PSII). Here, the distinct roles of Flv2/Flv4 and Sll0218 were addressed, using a number of flv4-2 operon mutants. In the ∆sll0218 mutant, the presence of Flv2/Flv4 rescued PSII functionality as compared with ∆sll0218-flv2, where neither Sll0218 nor the Flv2/Flv4 heterodimer are expressed. Nevertheless, both the ∆sll0218 and ∆sll0218-flv2 mutants demonstrated deficiency in accumulation of PSII proteins suggesting a role for Sll0218 in PSII stabilization, which was further supported by photoinhibition experiments. Moreover, the accumulation of PSII assembly intermediates occurred in Sll0218-lacking mutants. The YFP-tagged Sll0218 protein localized in a few spots per cell at the external side of the thylakoid membrane, and biochemical membrane fractionation revealed clear enrichment of Sll0218 in the PratA-defined membranes, where the early biogenesis steps of PSII occur. Further, the characteristic antenna uncoupling feature of the ∆flv4-2 operon mutants is shown to be related to PSII destabilization in the absence of Sll0218. It is concluded that the Flv2/Flv4 heterodimer supports PSII functionality, while the Sll0218 protein assists PSII assembly and stabilization, including optimization of light harvesting. © 2016 The Authors. Plant, Cell & Enviroment Published by John Wiley & Sons Ltd.

  13. Distinct contributions of explicit and implicit memory processes to weight prediction when lifting objects and judging their weights: an aging study.

    Science.gov (United States)

    Trewartha, Kevin M; Flanagan, J Randall

    2016-09-01

    Weight predictions used to scale lifting forces adapt quickly when repeatedly lifting unusually weighted objects and are readily updated by explicit information provided about weight. In contrast, weight predictions used when making perceptual judgments about weight are more resistant to change and are largely unaffected by explicit information about weight. These observations suggest that distinct memory systems underlie weight prediction when lifting objects and judging their weights. Here we examined whether these weight predictions differ in their reliance on declarative and nondeclarative memory resources by comparing the adaptability of these predictions in older adults, who exhibit relatively impaired declarative memory processes, to those in younger adults. In the size condition, we measured lift forces as participants repeatedly lifted a pair of size-weight inverted objects in alternation. To assess weight judgments, we measured the size-weight illusion every 10 lifts. The material condition was similar, except that we used material-weight inverted objects and measured the material-weight illusion. The strengths of these illusions prior to lifting, and the attenuation of the illusions that arise when lifting inverted objects, were similar for both groups. The magnitude of the change in the illusions was positively correlated with implicit memory performance in both groups, suggesting that predictions used when judging weight rely on nondeclarative memory resources. Updating of lifting forces also did not differ between groups. However, within the older group the success with which lifting forces were updated was positively correlated with working memory performance, suggesting that weight predictions used when lifting rely on declarative memory resources. Copyright © 2016 the American Physiological Society.

  14. Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

    Energy Technology Data Exchange (ETDEWEB)

    Rosendahl, K.; Maurseth, K.; Olsen, Oe.E. [Dept. of Paediatric Radiology, Haukeland University Hospital, Bergen (Norway); Halvorsen, O.J. [Dept. of Pathology, Haukeland University Hospital, Bergen (Norway); Gjelland, K. [Dept. of Gynaecology, Haukeland University Hospital, Bergen (Norway); Engebretsen, L. [Dept. of Genetics, Haukeland University Hospital, Bergen (Norway)

    2001-09-01

    We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

  15. Neonatal lethal dwarfism with distinct skeletal malformations - a separate entity?

    International Nuclear Information System (INIS)

    Rosendahl, K.; Maurseth, K.; Olsen, Oe.E.; Halvorsen, O.J.; Gjelland, K.; Engebretsen, L.

    2001-01-01

    We describe a case of neonatal lethal dwarfism characterised by short trunk, short, stick-like tubular bones, deficient ossification of the axial skeleton and broad, sclerotic horizontal ribs. Two similar cases have previously been reported as examples of the Neu-Laxova syndrome. However, the radiological findings of the Neu-Laxova syndrome, as reported in 16 out of 40 documented cases, show a heterogeneous pattern of minor features, which differ distinctively from those found in the previous two cases and by us. A literature research did not reveal similar cases, and we therefore suggest that our case, together with the two previous cases, may represent a new distinctive form of neonatal lethal dwarfism. (orig.)

  16. Utilizing Storytelling to Promote Emotional Well-Being of Children With a Distinct Physical Appearance: The Case of Children Who Wear Eyeglasses

    Directory of Open Access Journals (Sweden)

    Andreas Brouzos

    2016-03-01

    Full Text Available This study explored the effectiveness of storytelling in supporting children with unusual physical traits. Participants were forty-eight children, aged 9 – 12 who, due to various eye diseases, wear eyeglasses. They completed various standardized self-report measures, both before and after participation, in one of the six intervention groups. The measures assessed shyness and social anxiety symptoms, loneliness and social dissatisfaction, perception of negative evaluation, satisfaction with one’s appearance, and anxiety regarding physical appearance. The intervention consisted of six 90-min group sessions and included both individual and group activities. The results lend support to the hypothesis that storytelling can significantly contribute to the emotional well-being of children, with a distinct physical appearance.

  17. Narrative Refiguration of Social Events: Paul Ricoeur's Contribution to Rethinking the Social

    Directory of Open Access Journals (Sweden)

    Anna Borisenkova

    2010-12-01

    Full Text Available The analysis of events has been a central issue for social sciences for a long time. The problem of an event's definition and distinction is still at stake in sociological debates. The purpose of this paper is to demonstrate the contribution of Paul Ricoeur's narrative theory to social events studies. First, this is done through the explication of the concept in the framework of narrative approach. Secondly, the paper highlights the narrative's capacity of 'refiguring' the social by re-describing social events, subordinating their succession to the logic of story-telling and transforming temporal characteristics as well. Apart from some insights, interpretative explanations and illustrations the paper provides critical arguments concerning the limitations of Paul Ricoeur's narrative approach with respect to sociological event-analysis.     L'analyse des événements a toujours été une question centrale pour l'histoire et les sciences sociales. Le problème de la définition et de la distinction des événements est encore en jeu dans les débats sociologiques contemporains. L'objectif de cet article est de s'attarder sur la contribution de la théorie de Paul Ricœur aux études des événements sociaux.  Après avoir montré les limites d'une conception impersonnelle de l'événement, l'auteur se penche sur la solution narrative proposée par Ricœur, à savoir la capacité du récit à “refigurer” du Social par la re-description des événements sociaux. Il s'agit de soumettre la logique de la succession temporelle à la logique de la narration. Tout en rendant justice à la valeur heuristique de telles analyses (à travers une série d'explicitations et d'illustrations, l'article pointe les limites de l'approche narrative de Paul Ricœur au regard des analyses sociologique des événements.  

  18. Genomic profiling of rice sperm cell transcripts reveals conserved and distinct elements in the flowering plant male germ lineage.

    Science.gov (United States)

    Russell, Scott D; Gou, Xiaoping; Wong, Chui E; Wang, Xinkun; Yuan, Tong; Wei, Xiaoping; Bhalla, Prem L; Singh, Mohan B

    2012-08-01

    Genomic assay of sperm cell RNA provides insight into functional control, modes of regulation, and contributions of male gametes to double fertilization. Sperm cells of rice (Oryza sativa) were isolated from field-grown, disease-free plants and RNA was processed for use with the full-genome Affymetrix microarray. Comparison with Gene Expression Omnibus (GEO) reference arrays confirmed expressionally distinct gene profiles. A total of 10,732 distinct gene sequences were detected in sperm cells, of which 1668 were not expressed in pollen or seedlings. Pathways enriched in male germ cells included ubiquitin-mediated pathways, pathways involved in chromatin modeling including histones, histone modification and nonhistone epigenetic modification, and pathways related to RNAi and gene silencing. Genome-wide expression patterns in angiosperm sperm cells indicate common and divergent themes in the male germline that appear to be largely self-regulating through highly up-regulated chromatin modification pathways. A core of highly conserved genes appear common to all sperm cells, but evidence is still emerging that another class of genes have diverged in expression between monocots and dicots since their divergence. Sperm cell transcripts present at fusion may be transmitted through plasmogamy during double fertilization to effect immediate post-fertilization expression of early embryo and (or) endosperm development. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

  19. The Satellite Cell in Male and Female, Developing and Adult Mouse Muscle: Distinct Stem Cells for Growth and Regeneration

    Science.gov (United States)

    Neal, Alice; Boldrin, Luisa; Morgan, Jennifer Elizabeth

    2012-01-01

    Satellite cells are myogenic cells found between the basal lamina and the sarcolemma of the muscle fibre. Satellite cells are the source of new myofibres; as such, satellite cell transplantation holds promise as a treatment for muscular dystrophies. We have investigated age and sex differences between mouse satellite cells in vitro and assessed the importance of these factors as mediators of donor cell engraftment in an in vivo model of satellite cell transplantation. We found that satellite cell numbers are increased in growing compared to adult and in male compared to female adult mice. We saw no difference in the expression of the myogenic regulatory factors between male and female mice, but distinct profiles were observed according to developmental stage. We show that, in contrast to adult mice, the majority of satellite cells from two week old mice are proliferating to facilitate myofibre growth; however a small proportion of these cells are quiescent and not contributing to this growth programme. Despite observed changes in satellite cell populations, there is no difference in engraftment efficiency either between satellite cells derived from adult or pre-weaned donor mice, male or female donor cells, or between male and female host muscle environments. We suggest there exist two distinct satellite cell populations: one for muscle growth and maintenance and one for muscle regeneration. PMID:22662253

  20. Remembering to learn: independent place and journey coding mechanisms contribute to memory transfer.

    Science.gov (United States)

    Bahar, Amir S; Shapiro, Matthew L

    2012-02-08

    The neural mechanisms that integrate new episodes with established memories are unknown. When rats explore an environment, CA1 cells fire in place fields that indicate locations. In goal-directed spatial memory tasks, some place fields differentiate behavioral histories ("journey-dependent" place fields) while others do not ("journey-independent" place fields). To investigate how these signals inform learning and memory for new and familiar episodes, we recorded CA1 and CA3 activity in rats trained to perform a "standard" spatial memory task in a plus maze and in two new task variants. A "switch" task exchanged the start and goal locations in the same environment; an "altered environment" task contained unfamiliar local and distal cues. In the switch task, performance was mildly impaired, new firing maps were stable, but the proportion and stability of journey-dependent place fields declined. In the altered environment, overall performance was strongly impaired, new firing maps were unstable, and stable proportions of journey-dependent place fields were maintained. In both tasks, memory errors were accompanied by a decline in journey codes. The different dynamics of place and journey coding suggest that they reflect separate mechanisms and contribute to distinct memory computations. Stable place fields may represent familiar relationships among environmental features that are required for consistent memory performance. Journey-dependent activity may correspond with goal-directed behavioral sequences that reflect expectancies that generalize across environments. The complementary signals could help link current events with established memories, so that familiarity with either a behavioral strategy or an environment can inform goal-directed learning.