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Nuclear localization of DMP1 proteins suggests a role in intracellular signaling

International Nuclear Information System (INIS)

Siyam, Arwa; Wang, Suzhen; Qin, Chunlin; Mues, Gabriele; Stevens, Roy; D’Souza, Rena N.; Lu, Yongbo

2012-01-01

Highlights: ► Nuclear localization of DMP1 in various cell lines. ► Non-synchronized cells show either nuclear or cytoplasmic localization of DMP1. ► Nuclear DMP1 is restricted to the nucleoplasm but absent in the nucleolus. -- Abstract: Dentin matrix protein 1 (DMP1) is highly expressed in odontoblasts and osteoblasts/osteocytes and plays an essential role in tooth and bone mineralization and phosphate homeostasis. It is debatable whether DMP1, in addition to its function in the extracellular matrix, can enter the nucleus and function as a transcription factor. To better understand its function, we examined the nuclear localization of endogenous and exogenous DMP1 in C3H10T1/2 mesenchymal cells, MC3T3-E1 preosteoblast cells and 17IIA11 odontoblast-like cells. RT-PCR analyses showed the expression of endogenous Dmp1 in all three cell lines, while Western-blot analysis detected a major DMP1 protein band corresponding to the 57 kDa C-terminal fragment generated by proteolytic processing of the secreted full-length DMP1. Immunofluorescent staining demonstrated that non-synchronized cells presented two subpopulations with either nuclear or cytoplasmic localization of endogenous DMP1. In addition, cells transfected with a construct expressing HA-tagged full-length DMP1 also showed either nuclear or cytoplasmic localization of the exogenous DMP1 when examined with an antibody against the HA tag. Furthermore, nuclear DMP1 was restricted to the nucleoplasm but was absent in the nucleolus. In conclusion, these findings suggest that, apart from its role as a constituent of dentin and bone matrix, DMP1 might play a regulatory role in the nucleus.
Nuclear localization of DMP1 proteins suggests a role in intracellular signaling

Energy Technology Data Exchange (ETDEWEB)

Siyam, Arwa [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, 3302 Gaston Ave., Dallas, TX 75246-2013 (United States); Department of Endodontology, Kornberg School of Dentistry, Temple University, 3223 North Broad Street, Philadelphia, PA 19140-5007 (United States); Wang, Suzhen; Qin, Chunlin; Mues, Gabriele [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, 3302 Gaston Ave., Dallas, TX 75246-2013 (United States); Stevens, Roy [Department of Endodontology, Kornberg School of Dentistry, Temple University, 3223 North Broad Street, Philadelphia, PA 19140-5007 (United States); D' Souza, Rena N. [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, 3302 Gaston Ave., Dallas, TX 75246-2013 (United States); Lu, Yongbo, E-mail: ylu@bcd.tamhsc.edu [Department of Biomedical Sciences, Baylor College of Dentistry, Texas A and M Health Science Center, 3302 Gaston Ave., Dallas, TX 75246-2013 (United States)

2012-08-03

Highlights: Black-Right-Pointing-Pointer Nuclear localization of DMP1 in various cell lines. Black-Right-Pointing-Pointer Non-synchronized cells show either nuclear or cytoplasmic localization of DMP1. Black-Right-Pointing-Pointer Nuclear DMP1 is restricted to the nucleoplasm but absent in the nucleolus. -- Abstract: Dentin matrix protein 1 (DMP1) is highly expressed in odontoblasts and osteoblasts/osteocytes and plays an essential role in tooth and bone mineralization and phosphate homeostasis. It is debatable whether DMP1, in addition to its function in the extracellular matrix, can enter the nucleus and function as a transcription factor. To better understand its function, we examined the nuclear localization of endogenous and exogenous DMP1 in C3H10T1/2 mesenchymal cells, MC3T3-E1 preosteoblast cells and 17IIA11 odontoblast-like cells. RT-PCR analyses showed the expression of endogenous Dmp1 in all three cell lines, while Western-blot analysis detected a major DMP1 protein band corresponding to the 57 kDa C-terminal fragment generated by proteolytic processing of the secreted full-length DMP1. Immunofluorescent staining demonstrated that non-synchronized cells presented two subpopulations with either nuclear or cytoplasmic localization of endogenous DMP1. In addition, cells transfected with a construct expressing HA-tagged full-length DMP1 also showed either nuclear or cytoplasmic localization of the exogenous DMP1 when examined with an antibody against the HA tag. Furthermore, nuclear DMP1 was restricted to the nucleoplasm but was absent in the nucleolus. In conclusion, these findings suggest that, apart from its role as a constituent of dentin and bone matrix, DMP1 might play a regulatory role in the nucleus.
Glycosylation of DMP1 Is Essential for Chondrogenesis of Condylar Cartilage.

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Weng, Y; Liu, Y; Du, H; Li, L; Jing, B; Zhang, Q; Wang, X; Wang, Z; Sun, Y

2017-12-01

The mandibular condylar cartilage (MCC) shoulders force for the subchondral bone during mastication. The cartilage matrix contains various large molecules, such as type I, II, and X collagens and proteoglycans (PGs), which jointly play essential roles in maintaining cartilage characteristics. PGs play key roles in maintaining the elasticity of cartilage and providing a cushion against mastication forces. In addition to the well-known PGs, DMP1-PG, which is the PG form of dentin matrix protein 1 (DMP1), is a newly identified PG. DMP1 is proteolytically processed in vivo, and the N-terminus is glycosylated into its PG form-that is, DMP1-PG, which is highly expressed not only in tooth and bone but also in the matrix of the MCC. However, the specific functions of DMP1-PG in the MCC remain unclear. In human temporomandibular joint osteoarthritis and hyperocclusion model rat specimens, PGs are significantly downregulated, and DMP1-PG is the most prominently affected PG. To further investigate the role of DMP1-PG in condylar chondrogenesis, a glycosylation site mutant (S 89 -G 89 ) mouse model was established with knock-in methods. In the MCC of the S89G-DMP1 mice, the glycosylation level of DMP1 was significantly downregulated, and a series of abnormal developmental and pathologic changes could be observed. The morphologic changes included thinner cartilage layers, deformations of the MCC, and disordered arrangements of the chondrocytes, and an earlier onset of temporomandibular joint osteoarthritis-like changes was observed. In addition, markers of chondrogenesis were downregulated, and the matrix of the MCC displayed OA phenotypes in the S89G-DMP1 mice. Further investigations showed that the transforming growth factor β signaling molecules were affected in the MCC after the loss of DMP1-PG. In addition, the loss of DMP1-PG significantly accelerated the progression of cartilage injuries in the hyperocclusion models. Given these findings, we investigated the significant
The Dmp1-SOST Transgene Interacts With and Downregulates the Dmp1-Cre Transgene and the Rosa(Notch) Allele.

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Zanotti, Stefano; Canalis, Ernesto

2016-05-01

Activation of Notch1 in osteocytes of Rosa(Notch) mice, where a loxP-flanked STOP cassette and the Nicd coding sequence were targeted to the reverse orientation splice acceptor (Rosa)26 locus, causes osteopetrosis associated with suppressed Sost expression and enhanced Wnt signaling. To determine whether Sost downregulation mediates the effects of Notch activation in osteocytes, Rosa(Notch) mice were crossed with transgenics expressing Cre recombinase or SOST under the control of the dentin matrix protein (Dmp)1 promoter. Dmp1-SOST transgenics displayed vertebral osteopenia and a modest femoral cancellous and cortical bone phenotype, whereas hemizygous Dmp1-Cre transgenics heterozygous for the Rosa(Notch) allele (Dmp1-Cre;Rosa(Notch)) exhibited osteopetrosis. The phenotype of Notch activation in osteocytes was prevented in Dmp1-Cre;Rosa(Notch) mice hemizygous for the Dmp1-SOST transgene. The effect was associated with downregulated Notch signaling and suppressed Dmp1 and Rosa26 expression. To test whether SOST regulates Notch expression in osteocytes, cortical bone cultures from Dmp1-Cre;Rosa(Notch) mice or from Rosa(Notch) control littermates were exposed to recombinant human SOST. The addition of SOST had only modest effects on Notch target gene mRNA levels and suppressed Dmp1, but not Cre or Rosa26, expression. These findings suggest that prevention of the Dmp1-Cre;Rosa(Notch) skeletal phenotype by Dmp1-SOST is not secondary to SOST expression but to interactions among the Dmp1-SOST and Dmp1-Cre transgenes and the Rosa26 locus. In conclusion, the Dmp1-SOST transgene suppresses the expression of the Dmp1-Cre transgene and of Rosa26. © 2015 Wiley Periodicals, Inc.
Protective roles of DMP1 in high phosphate homeostasis.

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Afsaneh Rangiani

Full Text Available Dmp1 (dentin matrix protein1 null mice (Dmp1(-/- display hypophosphatemic rickets with a sharp increase in fibroblast growth factor 23 (FGF23. Disruption of Klotho (the obligatory co-receptor of FGF23 results in hyperphosphatemia with ectopic calcifications formed in blood vessels and kidneys. To determine the role of DMP1 in both a hyperphosphatemic environment and within the ectopic calcifications, we created Dmp1/Klotho compound deficient (Dmp1(-/-kl/kl mice.A combination of TUNEL, immunohistochemistry, TRAP, von Kossa, micro CT, bone histomorphometry, serum biochemistry and Scanning Electron Microscopy techniques were used to analyze the changes in blood vessels, kidney and bone for wild type control, Dmp1(-/-, Klotho deficient (kl/kl and Dmp1(-/-kl/kl animals.Interestingly, Dmp1(-/-kl/kl mice show a dramatic improvement of rickets and an identical serum biochemical phenotype to kl/kl mice (extremely high FGF23, hyperphosphatemia and reduced parathyroid hormone (PTH levels. Unexpectedly, Dmp1(-/-kl/kl mice presented elevated levels of apoptosis in osteocytes, endothelial and vascular smooth muscle cells in small and large blood vessels, and within the kidney as well as dramatic increase in ectopic calcification in all these tissues, as compared to kl/kl.These findings suggest that DMP1 has an anti-apoptotic role in hyperphosphatemia. Discovering this novel protective role of DMP1 may have clinical relevance in protecting the cells from apoptosis in high-phosphate environments as observed in chronic kidney disease (CKD.
Identification of Secretory Odontoblasts Using DMP1-GFP Transgenic Mice

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Balic, Anamaria; Mina, Mina

2011-01-01

Terminal differentiation of odontoblasts from dental papilla is a long process involving several intermediate steps and changes in the transcriptional profile and expression of proteins secreted by cells in the odontoblast lineage. Transgenic mouse lines in which GFP expression is under the control of tissue-and stage specific promoters have provided powerful experimental tools for identification and isolation of cells at specific stages of differentiation along a lineage. Our previous studies showed utilization of pOBCol3.6GFP and pOBCol2.3GFP animals for identification of odontoblasts at early and late stages of polarization respectively. In the present study we used the DMP1-GFP transgenic animal as an experimental model to examine its expression during the differentiation of odontoblasts from progenitor cells in vivo and in vitro. Our observations showed that DMP1-GFP transgene is first activated in secretory/functional odontoblasts engaged in secretion of predentin and then transiently expressed at high levels in newly differentiated odontoblasts. Expression of DMP1-GFP was down-regulated in highly differentiated odontoblasts. The temporal and spatial pattern of expression of DMP1-GFP transgene closely mimics the expression of endogenous DMP1. This transgenic animal will facilitate studies of gene expression and biological functions in secretory/functional odontoblasts. PMID:21172466
Transgenic Expression of Dspp Partially Rescued the Long Bone Defects of Dmp1-null Mice

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Jani, Priyam H.; Gibson, Monica P.; Liu, Chao; Zhang, Hua; Wang, Xiaofang; Lu, Yongbo; Qin, Chunlin

2016-01-01

Dentin matrix protein 1 (DMP1) and dentin sialophosphoprotein (DSPP) belong to the Small Integrin-Binding Ligand N-linked Glycoprotein (SIBLING) family. In addition to the features common to all SIBLING members, DMP1 and DSPP share several unique similarities in chemical structure, proteolytic activation and tissue localization. Mutations in, or deletion of DMP1, cause autosomal recessive hypophosphatemic rickets along with dental defects; DSPP mutations or its ablation are associated with dentinogenesis imperfecta. While the roles and functional mechanisms of DMP1 in osteogenesis have been extensively studied, those of DSPP in long bones have been studied only to a limited extent. Previous studies by our group revealed that transgenic expression of Dspp completely rescued the dentin defects of Dmp1-null (Dmp1−/−) mice. In this investigation, we assessed the effects of transgenic Dspp on osteogenesis by analyzing the formation and mineralization of the long bones in Dmp1−/− mice that expresses a transgene encoding full-length DSPP driven by a 3.6-kb rat Col1a1 promoter (referred as “Dmp1−/−;Dspp-Tg mice”). We characterized the long bones of the Dmp1−/−;Dspp-Tg mice at different ages and compared them with those from Dmp1−/− and Dmp1+/− (normal control) mice. Our analyses showed that the long bones of Dmp1−/−;Dspp-Tg mice had a significant increase in cortical bone thickness, bone volume and mineral density along with a remarkable restoration of trabecular thickness compared to those of the Dmp1−/− mice. The long bones of Dmp1−/−;Dspp-Tg mice underwent a dramatic reduction in the amount of osteoid, significant improvement of the collagen fibrillar network, and better organization of the lacunocanalicular system, compared to the Dmp1−/− mice. The elevated levels of biglycan, bone sialoprotein and osteopontin in Dmp1−/− mice were also noticeably corrected by the transgenic expression of Dspp. These findings suggest that
A Mutation in the Dmp1 Gene Alters Phosphate Responsiveness in Mice

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Gerard-O'Riley, Rita L.; Acton, Dena; McQueen, Amie K.; Strobel, Isabel E.; Witcher, Phillip C.; Feng, Jian Q.; Econs, Michael J.

2017-01-01

Mutations in the dentin matrix protein 1 (DMP1) gene cause autosomal recessive hypophosphatemic rickets (ARHR). Hypophosphatemia in ARHR results from increased circulating levels of the phosphaturic hormone, fibroblast growth factor 23 (FGF23). Similarly, elevated FGF23, caused by mutations in the PHEX gene, is responsible for the hypophosphatemia in X-linked hypophosphatemic rickets (XLH). Previously, we demonstrated that a Phex mutation in mice creates a lower set point for extracellular phosphate, where an increment in phosphorus further stimulates Fgf23 production to maintain low serum phosphorus levels. To test the presence of the similar set point defect in ARHR, we generated 4- and 12-week-old Dmp1/Galnt3 double knockout mice and controls, including Dmp1 knockout mice (a murine model of ARHR), Galnt3 knockout mice (a murine model of familial tumoral calcinosis), and phenotypically normal double heterozygous mice. Galnt3 knockout mice had increased proteolytic cleavage of Fgf23, leading to low circulating intact Fgf23 levels with consequent hyperphosphatemia. In contrast, Dmp1 knockout mice had little Fgf23 cleavage and increased femoral Fgf23 expression, resulting in hypophosphatemia and low femoral bone mineral density (BMD). However, introduction of the Galnt3 null allele to Dmp1 knockout mice resulted in a significant increase in serum phosphorus and normalization of BMD. This increased serum phosphorus was accompanied by markedly elevated Fgf23 expression and circulating Fgf23 levels, an attempt to reduce serum phosphorus in the face of improving phosphorus levels. These data indicate that a Dmp1 mutation creates a lower set point for extracellular phosphate and maintains it through the regulation of Fgf23 cleavage and expression. PMID:28005411
Blocking of proteolytic processing and deletion of glycosaminoglycan side chain of mouse DMP1 by substituting critical amino acid residues.

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Peng, Tao; Huang, Bingzhen; Sun, Yao; Lu, Yongbo; Bonewald, Lynda; Chen, Shuo; Butler, William T; Feng, Jerry Q; D'Souza, Rena N; Qin, Chunlin

2009-01-01

Dentin matrix protein 1 (DMP1) is present in the extracellular matrix (ECM) of dentin and bone as processed NH(2)- and COOH-terminal fragments, resulting from proteolytic cleavage at the NH(2) termini of 4 aspartic acid residues during rat DMP1 processing. One cleavage site residue, Asp(181) (corresponding to Asp(197) of mouse DMP1), and its flanking region are highly conserved across species. We speculate that cleavage at the NH(2) terminus of Asp(197) of mouse DMP1 represents an initial, first-step scission in the whole cascade of proteolytic processing. To test if Asp(197) is critical for initiating the proteolytic processing of mouse DMP1, we substituted Asp(197) with Ala(197) by mutating the corresponding nucleotides of mouse cDNA that encode this amino acid residue. This mutant DMP1 cDNA was cloned into a pcDNA3.1 vector. Data from transfection experiments indicated that this single substitution blocked the proteolytic processing of mouse DMP1 in HEK-293 cells, indicating that cleavage at the NH(2) terminus of Asp(197) is essential for exposing other cleavage sites for the conversion of DMP1 to its fragments. The NH(2)-terminal fragment of DMP1 occurs as a proteoglycan form (DMP1-PG) that contains a glycosaminoglycan (GAG) chain. Previously, we showed that a GAG chain is linked to Ser(74) in rat DMP1 (Ser(89) in mouse DMP1). To confirm that mouse DMP1-PG possesses a single GAG chain attached to Ser(89), we substituted Ser(89) by Gly(89). Data from transfection analysis indicated that this substitution completely prevented formation of the GAG-containing form, confirming that DMP1-PG contains a single GAG chain attached to Ser(89) in mouse DMP1. Copyright 2008 S. Karger AG, Basel.
Arabidopsis senescence-associated protein DMP1 is involved in membrane remodeling of the ER and tonoplast

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Kasaras Alexis

2012-04-01

Full Text Available Abstract Background Arabidopsis DMP1 was discovered in a genome-wide screen for senescence-associated membrane proteins. DMP1 is a member of a novel plant-specific membrane protein family of unknown function. In rosette leaves DMP1 expression increases from very low background level several 100fold during senescence progression. Results Expression of AtDMP1 fused to eGFP in Nicotiana benthamiana triggers a complex process of succeeding membrane remodeling events affecting the structure of the endoplasmic reticulum (ER and the vacuole. Induction of spherical structures (“bulbs”, changes in the architecture of the ER from tubular to cisternal elements, expansion of smooth ER, formation of crystalloid ER, and emergence of vacuolar membrane sheets and foamy membrane structures inside the vacuole are proceeding in this order. In some cells it can be observed that the process culminates in cell death after breakdown of the entire ER network and the vacuole. The integrity of the plasma membrane, nucleus and Golgi vesicles are retained until this stage. In Arabidopsis thaliana plants expressing AtDMP1-eGFP by the 35S promoter massive ER and vacuole vesiculation is observed during the latest steps of leaf senescence, whereas earlier in development ER and vacuole morphology are not perturbed. Expression by the native DMP1 promoter visualizes formation of aggregates termed “boluses” in the ER membranes and vesiculation of the entire ER network, which precedes disintegration of the central vacuole during the latest stage of senescence in siliques, rosette and cauline leaves and in darkened rosette leaves. In roots tips, DMP1 is strongly expressed in the cortex undergoing vacuole biogenesis. Conclusions Our data suggest that DMP1 is directly or indirectly involved in membrane fission during breakdown of the ER and the tonoplast during leaf senescence and in membrane fusion during vacuole biogenesis in roots. We propose that these properties of DMP1
Loss of DMP1 causes rickets and osteomalacia and identifies a role for osteocytes in mineral metabolism

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Feng, Jian Q; Ward, Leanne M; Liu, Shiguang; Lu, Yongbo; Xie, Yixia; Yuan, Baozhi; Yu, Xijie; Rauch, Frank; Davis, Siobhan I; Zhang, Shubin; Rios, Hector; Drezner, Marc K; Quarles, L Darryl; Bonewald, Lynda F; White, Kenneth E

2007-01-01

The osteocyte, a terminally differentiated cell comprising 90%–95% of all bone cells1,2, may have multiple functions, including acting as a mechanosensor in bone (re)modeling3. Dentin matrix protein 1 (encoded by DMP1) is highly expressed in osteocytes4 and, when deleted in mice, results in a hypomineralized bone phenotype5. We investigated the potential for this gene not only to direct skeletal mineralization but also to regulate phosphate (Pi) homeostasis. Both Dmp1- null mice and individuals with a newly identified disorder, autosomal recessive hypophosphatemic rickets, manifest rickets and osteomalacia with isolated renal phosphate-wasting associated with elevated fibroblast growth factor 23 (FGF23) levels and normocalciuria. Mutational analyses showed that autosomal recessive hypophosphatemic rickets family carried a mutation affecting the DMP1 start codon, and a second family carried a 7-bp deletion disrupting the highly conserved DMP1 C terminus. Mechanistic studies using Dmp1-null mice demonstrated that absence of DMP1 results in defective osteocyte maturation and increased FGF23 expression, leading to pathological changes in bone mineralization. Our findings suggest a bone-renal axis that is central to guiding proper mineral metabolism. PMID:17033621
Identification of a Novel Dentin Matrix Protein-1 (DMP-1) Mutation and Dental Anomalies in a Kindred with Autosomal Recessive Hypophosphatemia

OpenAIRE

Turan, Serap; Aydin, Cumhur; Bereket, Abdullah; Akcay, Teoman; Güran, Tülay; Yaralioglu, Betul Akmen; Bastepe, Murat; Jüppner, Harald

2009-01-01

An autosomal recessive form of hypophosphatemia (ARHP) was recently shown to be caused by homozygous mutations in DMP1, the gene encoding dentin matrix protein-1 (DMP-1), a non-collagenous bone matrix protein with an important role in the development and mineralization of bone and teeth. Here, we report a previously not reported consanguineous ARHP kindred in which the three affected individuals carry a novel homozygous DMP-1 mutation. The index case presented at the age of 3 years with bowin...
Unintended targeting of Dmp1-Cre reveals a critical role for Bmpr1a signaling in the gastrointestinal mesenchyme of adult mice.

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Lim, Joohyun; Burclaff, Joseph; He, Guangxu; Mills, Jason C; Long, Fanxin

2017-01-01

Cre/loxP technology has been widely used to study cell type-specific functions of genes. Proper interpretation of such data critically depends on a clear understanding of the tissue specificity of Cre expression. The Dmp1-Cre mouse, expressing Cre from a 14-kb DNA fragment of the mouse Dmp1 gene, has become a common tool for studying gene function in osteocytes, but the presumed cell specificity is yet to be fully established. By using the Ai9 reporter line that expresses a red fluorescent protein upon Cre recombination, we find that in 2-month-old mice, Dmp1-Cre targets not only osteocytes within the bone matrix but also osteoblasts on the bone surface and preosteoblasts at the metaphyseal chondro-osseous junction. In the bone marrow, Cre activity is evident in certain stromal cells adjacent to the blood vessels, but not in adipocytes. Outside the skeleton, Dmp1-Cre marks not only the skeletal muscle fibers, certain cells in the cerebellum and the hindbrain but also gastric and intestinal mesenchymal cells that express Pdgfra . Confirming the utility of Dmp1-Cre in the gastrointestinal mesenchyme, deletion of Bmpr1a with Dmp1-Cre causes numerous large polyps along the gastrointestinal tract, consistent with prior work involving inhibition of BMP signaling. Thus, caution needs to be exercised when using Dmp1-Cre because it targets not only the osteoblast lineage at an earlier stage than previously appreciated, but also a number of non-skeletal cell types.
A novel auditory ossicles membrane and the development of conductive hearing loss in Dmp1-null mice.

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Lv, Kun; Huang, Haiyang; Yi, Xing; Chertoff, Mark E; Li, Chaoyuan; Yuan, Baozhi; Hinton, Robert J; Feng, Jian Q

2017-10-01

Genetic mouse models are widely used for understanding human diseases but we know much less about the anatomical structure of the auditory ossicles in the mouse than we do about human ossicles. Furthermore, current studies have mainly focused on disease conditions such as osteomalacia and rickets in patients with hypophosphatemia rickets, although the reason that these patients develop late-onset hearing loss is unknown. In this study, we first analyzed Dmp1 lac Z knock-in auditory ossicles (in which the blue reporter is used to trace DMP1 expression in osteocytes) using X-gal staining and discovered a novel bony membrane surrounding the mouse malleus. This finding was further confirmed by 3-D micro-CT, X-ray, and alizarin red stained images. We speculate that this unique structure amplifies and facilitates sound wave transmissions in two ways: increasing the contact surface between the eardrum and malleus and accelerating the sound transmission due to its mineral content. Next, we documented a progressive deterioration in the Dmp1-null auditory ossicle structures using multiple imaging techniques. The auditory brainstem response test demonstrated a conductive hearing loss in the adult Dmp1-null mice. This finding may help to explain in part why patients with DMP1 mutations develop late-onset hearing loss, and supports the critical role of DMP1 in maintaining the integrity of the auditory ossicles and its bony membrane. Copyright © 2017 Elsevier Inc. All rights reserved.
Expression of DMP-1 in the human pulp tissue using low level laser therapy

International Nuclear Information System (INIS)

Neto, Natalino Lourenço; Teixeira Marques, Nádia Carolina; Fernandes, Ana Paula; Silva, Thiago Cruvinel; Andrade Moreira Machado, Maria Aparecida; Oliveira, Thais Marchini; Rodini, Camila Oliveira

2015-01-01

This study aimed to evaluate the effects of low-level laser therapy (LLLT) on DMP-1 expression in pulp tissue repair of human primary teeth. Twenty mandibular primary molars were randomly assigned into the following groups: Group I—Buckley’s Formocresol (FC); Group II—Calcium Hydroxide (CH); Group III—LLLT + CH and Group IV—LLLT + Zinc oxide/Eugenol. The teeth at the regular exfoliation period were extracted for histological analysis and immunolocalization of DMP-1. Descriptive analysis was performed on the dentin pulp complex. Histopathological assessment showed internal resorption in group FC. Groups CH and LLLT + CH provided better pulpal repair due to the absence of inflammation and the formation of hard tissue barrier. These two groups presented odontoblastic layer expressing DMP-1. According to this study, low level laser therapy preceding the use of calcium hydroxide exhibited satisfactory bio-inductive activity on pulp tissue repair of human primary teeth. However, other histological and cellular studies are needed to confirm the laser tissue action and efficacy. (paper)
Chemical changes in DMP1-null murine bone & silica based pecvd coatings for titanium implant osseoapplications

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Maginot, Megen

In order to improve clinical outcomes in bone-implant systems, a thorough understanding of both local bone chemistry and implant surface chemistry is necessary. This study consists, therefore, of two main parts: one focused on determining the nature of the changes in bone chemistry in a DMP1-null transgenic disease model and the other on the development of amorphous silica-based coatings for potential use as titanium bone implant coatings. For the study of bone mineral in the DMP1 transgenic model, which is known to have low serum phosphate levels, transgenic DMP1-null and wild type mice were fed a high phosphate diet, sacrificed, and had their long bone harvested. This bone was characterized using SEM, FTIR, microCT and XANES and compared to DMP1-null and wild type control groups to assess the therapeutic effect of high Pi levels on the phenotype and the role of DMP1 in mineralization in vivo. Findings suggest that though the high phosphate diet results in restoring serum phosphate levels, it does not completely rescue the bone mineral phenotype at an ultrastructural level and implicates DMP1 in phosphate nucleation. Since plasma enhanced chemical vapor deposition (PECVD) silica like coatings have not previously been fabricated for use in oessoapplications, the second part of this study initially focused on the characterization of novel SiOx chemistries fabricated via a chemical vapor deposition process that were designed specifically to act as bioactive coatings with a loose, hydrogenated structure. These coatings were then investigated for their potential initial stage response to bone tissue through immersion in a simulated body fluid and through the culture of MC3T3 cells on the coating surfaces. Coating surfaces were characterized by SEM, FTIR, contact angle measurements, and XANES. Coating dissolution and ionic release were also investigated by ICP-OES. Findings suggest that some SiOx chemistries may form a bioactive coating while more highly substituted
The removal of dimethyl phthalate (DMP) from contaminated water by advanced oxidation processes in the presence of methanol

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Al-Tawabini, B.S. [Research Inst., King Fahd Univ. of Petroleum and Minerals, Dhahran (Saudi Arabia)

2003-07-01

A bench-scale laboratory study was conducted to investigate the effect of alcohol (i.e. methanol) presence on the removal efficiency of phthalates from water using Fenton's reagent and UV/H{sub 2}O{sub 2} process. Dimethyl phthalate (DMP) was selected as a target compound. In one batch of experiments, only DMP was spiked into pure water, while in the other batch, DMP was initially dissolved in methanol prior to spiking into water samples. A UV lamp of 100 m Watt emitting at a wavelength of approximately 254 nm was used to provide the radiation. Temperature and pH conditions were kept constant at 25 C and 3, respectively. The results showed that Fenton's reagent was effective in reducing the concentration of DMP in water in the absence of the methanol. More than 90% of DMP was removed within 45 minutes at hydrogen peroxide (H{sub 2}O{sub 2}) and ferrous ion (Fe{sup 2+}) concentrations of 1.0 and 0.4 mM respectively. However, Fenton's reagent failed to do so in the presence of methanol. On the other hand, results showed that UV/H{sub 2}O{sub 2} system was effective in removing DMP from both pure, as well as methanol-spiked water. The results clearly indicated that UV radiation plays a fundamental role in the degradation of the target compound. (orig.)
DMP: Simple, Scalable, and Submerged; FINAL TECHNICAL REPORT (REDACTED VERSION)

Energy Technology Data Exchange (ETDEWEB)

Morrow, Mike; Delos-Reyes, Michael; McNatt, Cameron; Ozkan-Haller, Tuba; Klure, Justin; Kopf, Steven; Ai, Zhuan; Cleary, Casey; Goold, Caitlin; Vanithbuncha, Phattharawan

2012-02-08

At the start of work by M3 Wave under the current DOE funding, the DMP technology was nominally at TRL2 with some physical model testing completed. With DOE and OWET funding, much progress was made on several fronts including: cost of energy modeling, 1:50 scale model testing, numerical modeling, site evaluation, cost of mooring, construction, operations and maintenance, regulatory, and power take off. Since the technology is stationary on the ocean floor, arrays can be very dense. Even though overall efficiency is lower than buoys, the total power per acre of the technology looks to be at least twice the output per acre of known buoy WEC technologies. If the assumptions and inputs are correct, then DMP ocean power devices could be commercially competitive with other offshore renewable energy resources, such as off-shore wind power. Leveraging the data, analysis, and engineering conducted on this project, larger 1:6 scale testing was recently completed under separate funding. All aspects tested at 1:6 suggest that the DMP is a viable and disruptive technology, leading M3 Wave to continue development of the DMP.
Absolute vibrational excitation cross sections for 1-18 eV electron scattering from condensed dimethyl phosphate (DMP)

Science.gov (United States)

Lemelin, V.; Bass, A. D.; Wagner, J. R.; Sanche, L.

2017-12-01

Absolute cross sections (CSs) for vibrational excitation by 1-18 eV electrons incident on condensed dimethyl phosphate (DMP) were measured with a high-resolution electron energy loss (EEL) spectrometer. Absolute CSs were extracted from EEL spectra of DMP condensed on multilayer film of Ar held at about 20 K under ultra-high vacuum (˜1 × 10-11 Torr). Structures observed in the energy dependence of the CSs around 2, 4, 7, and 12 eV were compared with previous results of gas- and solid-phase experiments and with theoretical studies on dimethyl phosphate and related molecules. These structures were attributed to the formation of shape resonances.
Regulation of bone-renal mineral and energy metabolism: the PHEX, FGF23, DMP1, MEPE ASARM pathway.

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Rowe, Peter S N

2012-01-01

More than 300 million years ago, vertebrates emerged from the vast oceans to conquer gravity and the dry land. With this transition, new adaptations occurred that included ingenious changes in reproduction, waste secretion, and bone physiology. One new innovation, the egg shell, contained an ancestral protein (ovocleidin-116) that likely first appeared with the dinosaurs and was preserved through the theropod lineage in modern birds and reptiles. Ovocleidin-116 is an avian homolog of matrix extracellular phosphoglycoprotein (MEPE) and belongs to a group of proteins called short integrin-binding ligand-interacting glycoproteins (SIBLINGs). These proteins are all localized to a defined region on chromosome 5q in mice and chromosome 4q in humans. A unifying feature of SIBLING proteins is an acidic serine aspartate-rich MEPE-associated motif (ASARM). Recent research has shown that the ASARM motif and the released ASARM peptide have regulatory roles in mineralization (bone and teeth), phosphate regulation, vascularization, soft-tissue calcification, osteoclastogenesis, mechanotransduction, and fat energy metabolism. The MEPE ASARM motif and peptide are physiological substrates for PHEX, a zinc metalloendopeptidase. Defects in PHEX are responsible for X-linked hypophosphatemic rickets (HYP). There is evidence that PHEX interacts with another ASARM motif containing SIBLING protein, dentin matrix protein-1 (DMP1). DMP1 mutations cause bone and renal defects that are identical with the defects caused by a loss of PHEX function. This results in autosomal recessive hypophosphatemic rickets (ARHR). In both HYP and ARHR, increased FGF23 expression plays a major role in the disease and in autosomal dominant hypophosphatemic rickets (ADHR), FGF23 half-life is increased by activating mutations. ASARM peptide administration in vitro and in vivo also induces increased FGF23 expression. FGF23 is a member of the fibroblast growth factor (FGF) family of cytokines, which surfaced 500

Search for the decay $B_s^0 \\to D^{*\\mp} \\pi^\\pm$

CERN Document Server

INSPIRE-00258707; Abellan Beteta, C; Adeva, B; Adinolfi, M; Adrover, C; Affolder, A; Ajaltouni, Z; Albrecht, J; Alessio, F; Alexander, M; Ali, S; Alkhazov, G; Alvarez Cartelle, P; Alves Jr, A A; Amato, S; Amerio, S; Amhis, Y; Anderlini, L; Anderson, J; Andreassen, R; Appleby, R B; Aquines Gutierrez, O; Archilli, F; Artamonov, A; Artuso, M; Aslanides, E; Auriemma, G; Bachmann, S; Back, J J; Baesso, C; Balagura, V; Baldini, W; Barlow, R J; Barschel, C; Barsuk, S; Barter, W; Bauer, Th; Bay, A; Beddow, J; Bedeschi, F; Bediaga, I; Belogurov, S; Belous, K; Belyaev, I; Ben-Haim, E; Benayoun, M; Bencivenni, G; Benson, S; Benton, J; Berezhnoy, A; Bernet, R; Bettler, M -O; van Beuzekom, M; Bien, A; Bifani, S; Bird, T; Bizzeti, A; Bjørnstad, P M; Blake, T; Blanc, F; Blouw, J; Blusk, S; Bocci, V; Bondar, A; Bondar, N; Bonivento, W; Borghi, S; Borgia, A; Bowcock, T J V; Bowen, E; Bozzi, C; Brambach, T; van den Brand, J; Bressieux, J; Brett, D; Britsch, M; Britton, T; Brook, N H; Brown, H; Burducea, I; Bursche, A; Busetto, G; Buytaert, J; Cadeddu, S; Callot, O; Calvi, M; Calvo Gomez, M; Camboni, A; Campana, P; Carbone, A; Carboni, G; Cardinale, R; Cardini, A; Carranza-Mejia, H; Carson, L; Carvalho Akiba, K; Casse, G; Cattaneo, M; Cauet, Ch; Charles, M; Charpentier, Ph; Chen, P; Chiapolini, N; Chrzaszcz, M; Ciba, K; Cid Vidal, X; Ciezarek, G; Clarke, P E L; Clemencic, M; Cliff, H V; Closier, J; Coca, C; Coco, V; Cogan, J; Cogneras, E; Collins, P; Comerma-Montells, A; Contu, A; Cook, A; Coombes, M; Coquereau, S; Corti, G; Couturier, B; Cowan, G A; Craik, D; Cunliffe, S; Currie, R; D'Ambrosio, C; David, P; David, P N Y; De Bonis, I; De Bruyn, K; De Capua, S; De Cian, M; De Miranda, J M; De Oyanguren Campos, M; De Paula, L; De Silva, W; De Simone, P; Decamp, D; Deckenhoff, M; Del Buono, L; Derkach, D; Deschamps, O; Dettori, F; Di Canto, A; Dijkstra, H; Dogaru, M; Donleavy, S; Dordei, F; Dosil Suárez, A; Dossett, D; Dovbnya, A; Dupertuis, F; Dzhelyadin, R; Dziurda, A; Dzyuba, A; Easo, S; Egede, U; Egorychev, V; Eidelman, S; van Eijk, D; Eisenhardt, S; Eitschberger, U; Ekelhof, R; Eklund, L; El Rifai, I; Elsasser, Ch; Elsby, D; Falabella, A; Färber, C; Fardell, G; Farinelli, C; Farry, S; Fave, V; Ferguson, D; Fernandez Albor, V; Ferreira Rodrigues, F; Ferro-Luzzi, M; Filippov, S; Fitzpatrick, C; Fontana, M; Fontanelli, F; Forty, R; Francisco, O; Frank, M; Frei, C; Frosini, M; Furcas, S; Furfaro, E; Gallas Torreira, A; Galli, D; Gandelman, M; Gandini, P; Gao, Y; Garofoli, J; Garosi, P; Garra Tico, J; Garrido, L; Gaspar, C; Gauld, R; Gersabeck, E; Gersabeck, M; Gershon, T; Ghez, Ph; Gibson, V; Gligorov, V V; Göbel, C; Golubkov, D; Golutvin, A; Gomes, A; Gordon, H; Grabalosa Gándara, M; Graciani Diaz, R; Granado Cardoso, L A; Graugés, E; Graziani, G; Grecu, A; Greening, E; Gregson, S; Grünberg, O; Gui, B; Gushchin, E; Guz, Yu; Gys, T; Hadjivasiliou, C; Haefeli, G; Haen, C; Haines, S C; Hall, S; Hampson, T; Hansmann-Menzemer, S; Harnew, N; Harnew, S T; Harrison, J; Hartmann, T; He, J; Heijne, V; Hennessy, K; Henrard, P; Hernando Morata, J A; van Herwijnen, E; Hicks, E; Hill, D; Hoballah, M; Hombach, C; Hopchev, P; Hulsbergen, W; Hunt, P; Huse, T; Hussain, N; Hutchcroft, D; Hynds, D; Iakovenko, V; Idzik, M; Ilten, P; Jacobsson, R; Jaeger, A; Jans, E; Jaton, P; Jing, F; John, M; Johnson, D; Jones, C R; Jost, B; Kaballo, M; Kandybei, S; Karacson, M; Karbach, T M; Kenyon, I R; Kerzel, U; Ketel, T; Keune, A; Khanji, B; Kochebina, O; Komarov, I; Koopman, R F; Koppenburg, P; Korolev, M; Kozlinskiy, A; Kravchuk, L; Kreplin, K; Kreps, M; Krocker, G; Krokovny, P; Kruse, F; Kucharczyk, M; Kudryavtsev, V; Kvaratskheliya, T; La Thi, V N; Lacarrere, D; Lafferty, G; Lai, A; Lambert, D; Lambert, R W; Lanciotti, E; Lanfranchi, G; Langenbruch, C; Latham, T; Lazzeroni, C; Le Gac, R; van Leerdam, J; Lees, J -P; Lefèvre, R; Leflat, A; Lefrançois, J; Leo, S; Leroy, O; Leverington, B; Li, Y; Li Gioi, L; Liles, M; Lindner, R; Linn, C; Liu, B; Liu, G; von Loeben, J; Lohn, S; Lopes, J H; Lopez Asamar, E; Lopez-March, N; Lu, H; Lucchesi, D; Luisier, J; Luo, H; Machefert, F; Machikhiliyan, I V; Maciuc, F; Maev, O; Malde, S; Manca, G; Mancinelli, G; Marconi, U; Märki, R; Marks, J; Martellotti, G; Martens, A; Martin, L; Martín Sánchez, A; Martinelli, M; Martinez Santos, D; Martins Tostes, D; Massafferri, A; Matev, R; Mathe, Z; Matteuzzi, C; Maurice, E; Mazurov, A; McCarthy, J; McNulty, R; Mcnab, A; Meadows, B; Meier, F; Meissner, M; Merk, M; Milanes, D A; Minard, M -N; Molina Rodriguez, J; Monteil, S; Moran, D; Morawski, P; Morello, M J; Mountain, R; Mous, I; Muheim, F; Müller, K; Muresan, R; Muryn, B; Muster, B; Naik, P; Nakada, T; Nandakumar, R; Nasteva, I; Needham, M; Neufeld, N; Nguyen, A D; Nguyen, T D; Nguyen-Mau, C; Nicol, M; Niess, V; Niet, R; Nikitin, N; Nikodem, T; Nomerotski, A; Novoselov, A; Oblakowska-Mucha, A; Obraztsov, V; Oggero, S; Ogilvy, S; Okhrimenko, O; Oldeman, R; Orlandea, M; Otalora Goicochea, J M; Owen, P; Pal, B K; Palano, A; Palutan, M; Panman, J; Papanestis, A; Pappagallo, M; Parkes, C; Parkinson, C J; Passaleva, G; Patel, G D; Patel, M; Patrick, G N; Patrignani, C; Pavel-Nicorescu, C; Pazos Alvarez, A; Pellegrino, A; Penso, G; Pepe Altarelli, M; Perazzini, S; Perego, D L; Perez Trigo, E; Pérez-Calero Yzquierdo, A; Perret, P; Perrin-Terrin, M; Pessina, G; Petridis, K; Petrolini, A; Phan, A; Picatoste Olloqui, E; Pietrzyk, B; Pilař, T; Pinci, D; Playfer, S; Plo Casasus, M; Polci, F; Polok, G; Poluektov, A; Polycarpo, E; Popov, D; Popovici, B; Potterat, C; Powell, A; Prisciandaro, J; Pugatch, V; Puig Navarro, A; Punzi, G; Qian, W; Rademacker, J H; Rakotomiaramanana, B; Rangel, M S; Raniuk, I; Rauschmayr, N; Raven, G; Redford, S; Reid, M M; dos Reis, A C; Ricciardi, S; Richards, A; Rinnert, K; Rives Molina, V; Roa Romero, D A; Robbe, P; Rodrigues, E; Rodriguez Perez, P; Roiser, S; Romanovsky, V; Romero Vidal, A; Rouvinet, J; Ruf, T; Ruffini, F; Ruiz, H; Ruiz Valls, P; Sabatino, G; Saborido Silva, J J; Sagidova, N; Sail, P; Saitta, B; Salzmann, C; Sanmartin Sedes, B; Sannino, M; Santacesaria, R; Santamarina Rios, C; Santovetti, E; Sapunov, M; Sarti, A; Satriano, C; Satta, A; Savrie, M; Savrina, D; Schaack, P; Schiller, M; Schindler, H; Schlupp, M; Schmelling, M; Schmidt, B; Schneider, O; Schopper, A; Schune, M -H; Schwemmer, R; Sciascia, B; Sciubba, A; Seco, M; Semennikov, A; Senderowska, K; Sepp, I; Serra, N; Serrano, J; Seyfert, P; Shapkin, M; Shapoval, I; Shatalov, P; Shcheglov, Y; Shears, T; Shekhtman, L; Shevchenko, O; Shevchenko, V; Shires, A; Silva Coutinho, R; Skwarnicki, T; Smith, N A; Smith, E; Smith, M; Sokoloff, M D; Soler, F J P; Soomro, F; Souza, D; Souza De Paula, B; Spaan, B; Sparkes, A; Spradlin, P; Stagni, F; Stahl, S; Steinkamp, O; Stoica, S; Stone, S; Storaci, B; Straticiuc, M; Straumann, U; Subbiah, V K; Swientek, S; Syropoulos, V; Szczekowski, M; Szczypka, P; Szumlak, T; T'Jampens, S; Teklishyn, M; Teodorescu, E; Teubert, F; Thomas, C; Thomas, E; van Tilburg, J; Tisserand, V; Tobin, M; Tolk, S; Tonelli, D; Topp-Joergensen, S; Torr, N; Tournefier, E; Tourneur, S; Tran, M T; Tresch, M; Tsaregorodtsev, A; Tsopelas, P; Tuning, N; Ubeda Garcia, M; Ukleja, A; Urner, D; Uwer, U; Vagnoni, V; Valenti, G; Vazquez Gomez, R; Vazquez Regueiro, P; Vecchi, S; Velthuis, J J; Veltri, M; Veneziano, G; Vesterinen, M; Viaud, B; Vieira, D; Vilasis-Cardona, X; Vollhardt, A; Volyanskyy, D; Voong, D; Vorobyev, A; Vorobyev, V; Voß, C; Voss, H; Waldi, R; Wallace, R; Wandernoth, S; Wang, J; Ward, D R; Watson, N K; Webber, A D; Websdale, D; Whitehead, M; Wicht, J; Wiechczynski, J; Wiedner, D; Wiggers, L; Wilkinson, G; Williams, M P; Williams, M; Wilson, F F; Wishahi, J; Witek, M; Wotton, S A; Wright, S; Wu, S; Wyllie, K; Xie, Y; Xing, F; Xing, Z; Yang, Z; Young, R; Yuan, X; Yushchenko, O; Zangoli, M; Zavertyaev, M; Zhang, F; Zhang, L; Zhang, W C; Zhang, Y; Zhelezov, A; Zhokhov, A; Zhong, L; Zvyagin, A

2013-01-01

A search for the decay $B_s^0 \\to D^{*\\mp} \\pi^\\pm$ is presented using a data sample corresponding to an integrated luminosity of $1.0 \\ {\\rm fb}^{-1}$ of $pp$ collisions collected by LHCb. This decay is expected to be mediated by a $W$-exchange diagram, with little contribution from rescattering processes, and therefore a measurement of the branching fraction will help to understand the mechanism behind related decays such as $B_s^0 \\to \\pi^+\\pi^-$ and $B_s^0 \\to D \\overline{D}$. Systematic uncertainties are minimised by using $B^0 \\to D^{*\\mp} \\pi^\\pm$ as a normalisation channel. We find no evidence for a signal, and set an upper limit on the branching fraction of ${\\cal B}(B_s^0 \\to D^{*\\mp} \\pi^\\pm) < 6.1\\,\\left(7.8\\right) \\times 10^{-6}$ at 90% (95%) confidence level.
Influences of DMP on the fertilization process and subsequent embryogenesis of abalone (Haliotis diversicolor supertexta by gametes exposure.

Directory of Open Access Journals (Sweden)

Jin Zhou

Full Text Available Di-methyl phthalate (DMP, a typical endocrine disrupting chemical (EDC, is ubiquitously distributed in aquatic environments; yet studies regarding its impact on gametes and the resulting effects on embryogenesis in marine gastropods are relatively scarce. In this study, the influences of DMP on the gametes and subsequent developmental process of abalone (Haliotis diversicolor supertexta, a representative marine benthic gastropod were assessed. Newborn abalone eggs and sperm were exposed separately to different DMP concentrations (1, 10 or 100 ppb for 60 min. At the end-point of exposure, the DMP-treated eggs and sperm were collected for analysis of their ultra-structures, ATPase activities and total lipid levels, and the fertilized gametes (embryos were collected to monitor related reproductive parameters (fertilization rate, abnormal development rate and hatching success rate. Treatment with DMP did not significantly alter the structure or total lipid content of eggs at any of the doses tested. Hatching failures and morphological abnormalities were only observed with the highest dose of DMP (100 ppb. However, DMP exposure did suppress sperm ATPase activities and affect the morphological character of their mitochondria. DMP-treated sperm exhibited dose-dependent decreases in fertilization efficiency, morphogenesis and hatchability. Relatively obvious toxicological effects were observed when both sperm and eggs were exposed to DMP. Furthermore, RT-PCR results indicate that treatment of gametes with DMP changed the expression patterns of physiologically-regulated genes (cyp3a, 17β-HSD-11 and 17β-HSD-12 in subsequent embryogenesis. Taken together, this study proofed that pre-fertilization exposure of abalone eggs, sperm or both to DMP adversely affects the fertilization process and subsequent embryogenesis.
Evaluating cis-2,6-Dimethylpiperidide (cis-DMP) as a Base Component in Lithium-Mediated Zincation Chemistry

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Armstrong, David R; Garden, Jennifer A; Kennedy, Alan R; Leenhouts, Sarah M; Mulvey, Robert E; O'Keefe, Philip; O'Hara, Charles T; Steven, Alan

2013-01-01

Most recent advances in metallation chemistry have centred on the bulky secondary amide 2,2,6,6-tetramethylpiperidide (TMP) within mixed metal, often ate, compositions. However, the precursor amine TMP(H) is rather expensive so a cheaper substitute would be welcome. Thus this study was aimed towards developing cheaper non-TMP based mixed-metal bases and, as cis-2,6-dimethylpiperidide (cis-DMP) was chosen as the alternative amide, developing cis-DMP zincate chemistry which has received meagre attention compared to that of its methyl-rich counterpart TMP. A new lithium diethylzincate, [(TMEDA)LiZn(cis-DMP)Et2] (TMEDA=N,N,N′,N′-tetramethylethylenediamine) has been synthesised by co-complexation of Li(cis-DMP), Et2Zn and TMEDA, and characterised by NMR (including DOSY) spectroscopy and X-ray crystallography, which revealed a dinuclear contact ion pair arrangement. By using N,N-diisopropylbenzamide as a test aromatic substrate, the deprotonative reactivity of [(TMEDA)LiZn(cis-DMP)Et2] has been probed and contrasted with that of the known but previously uninvestigated di-tert-butylzincate, [(TMEDA)LiZn(cis-DMP)tBu2]. The former was found to be the superior base (for example, producing the ortho-deuteriated product in respective yields of 78 % and 48 % following D2O quenching of zincated benzamide intermediates). An 88 % yield of 2-iodo-N,N-diisopropylbenzamide was obtained on reaction of two equivalents of the diethylzincate with the benzamide followed by iodination. Comparisons are also drawn using 1,1,1,3,3,3-hexamethyldisilazide (HMDS), diisopropylamide and TMP as the amide component in the lithium amide, Et2Zn and TMEDA system. Under certain conditions, the cis-DMP base system was found to give improved results in comparison to HMDS and diisopropylamide (DA), and comparable results to a TMP system. Two novel complexes isolated from reactions of the di-tert-butylzincate and crystallographically characterised, namely the pre-metallation complex [{(iPr)2N(Ph)C=O}LiZn(cis-DMP
A novel nonsense mutation in the DMP1 gene identified by a genome-wide association study is responsible for inherited rickets in Corriedale sheep.

Directory of Open Access Journals (Sweden)

Xia Zhao

Full Text Available Inherited rickets of Corriedale sheep is characterized by decreased growth rate, thoracic lordosis and angular limb deformities. Previous outcross and backcross studies implicate inheritance as a simple autosomal recessive disorder. A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep comprising 17 affected and 3 carriers. A homozygous region of 125 consecutive single-nucleotide polymorphism (SNP loci was identified in all affected sheep, covering a region of 6 Mb on ovine chromosome 6. Among 35 candidate genes in this region, the dentin matrix protein 1 gene (DMP1 was sequenced to reveal a nonsense mutation 250C/T on exon 6. This mutation introduced a stop codon (R145X and could truncate C-terminal amino acids. Genotyping by PCR-RFLP for this mutation showed all 17 affected sheep were "T T" genotypes; the 3 carriers were "C T"; 24 phenotypically normal related sheep were either "C T" or "C C"; and 46 unrelated normal control sheep from other breeds were all "C C". The other SNPs in DMP1 were not concordant with the disease and can all be ruled out as candidates. Previous research has shown that mutations in the DMP1 gene are responsible for autosomal recessive hypophosphatemic rickets in humans. Dmp1_knockout mice exhibit rickets phenotypes. We believe the R145X mutation to be responsible for the inherited rickets found in Corriedale sheep. A simple diagnostic test can be designed to identify carriers with the defective "T" allele. Affected sheep could be used as animal models for this form of human rickets, and for further investigation of the role of DMP1 in phosphate homeostasis.
A Novel Nonsense Mutation in the DMP1 Gene Identified by a Genome-Wide Association Study Is Responsible for Inherited Rickets in Corriedale Sheep

Science.gov (United States)

Blair, Hugh T.; Thompson, Keith G.; Rothschild, Max F.; Garrick, Dorian J.

2011-01-01

Inherited rickets of Corriedale sheep is characterized by decreased growth rate, thoracic lordosis and angular limb deformities. Previous outcross and backcross studies implicate inheritance as a simple autosomal recessive disorder. A genome wide association study was conducted using the Illumina OvineSNP50 BeadChip on 20 related sheep comprising 17 affected and 3 carriers. A homozygous region of 125 consecutive single-nucleotide polymorphism (SNP) loci was identified in all affected sheep, covering a region of 6 Mb on ovine chromosome 6. Among 35 candidate genes in this region, the dentin matrix protein 1 gene (DMP1) was sequenced to reveal a nonsense mutation 250C/T on exon 6. This mutation introduced a stop codon (R145X) and could truncate C-terminal amino acids. Genotyping by PCR-RFLP for this mutation showed all 17 affected sheep were “T T” genotypes; the 3 carriers were “C T”; 24 phenotypically normal related sheep were either “C T” or “C C”; and 46 unrelated normal control sheep from other breeds were all “C C”. The other SNPs in DMP1 were not concordant with the disease and can all be ruled out as candidates. Previous research has shown that mutations in the DMP1 gene are responsible for autosomal recessive hypophosphatemic rickets in humans. Dmp1_knockout mice exhibit rickets phenotypes. We believe the R145X mutation to be responsible for the inherited rickets found in Corriedale sheep. A simple diagnostic test can be designed to identify carriers with the defective “T” allele. Affected sheep could be used as animal models for this form of human rickets, and for further investigation of the role of DMP1 in phosphate homeostasis. PMID:21747952
[Management of chronic heart failure - a systematic review of guidelines in the context of the DMP revision].

Science.gov (United States)

Kötter, Thomas; Bartel, Carmen; Schramm, Susanne; Lange, Petra; Höfer, Eva; Hänsel, Michaela; Waffenschmidt, Siw; Waldt, Susanne Ein; Hoffmann-Eßer, Wiebke; Rüther, Alric; Lühmann, Dagmar; Scherer, Martin

2013-01-01

Disease Management Programmes (DMPs) are structured treatment programmes for chronic diseases. The DMP requirements are primarily derived from evidence-based guidelines. DMPs are regularly revised to ensure that they reflect current best practice and medical knowledge. The aim of this study was to assess the need for updating the German DMP module on heart failure by comparing it to relevant guidelines and identifying recommendations that should be revised. We systematically searched for clinical guidelines on heart failure published in German, English or French, and extracted relevant guideline recommendations. All included guidelines were assessed for methodological quality. To identify revision needs in the DMP, we performed a synoptic analysis of the extracted guideline recommendations and DMP requirements. 27 guidelines were included. The extracted recommendations covered all aspects of the management of heart failure. The comparison of guideline recommendations with DMP requirements showed that, overall, guideline recommendations were more detailed than DMP requirements, and that the guidelines covered topics not included in the DMP module. The DMP module is largely consistent with current guidelines on heart failure. We did not identify any need for significant revision of the DMP requirements. However, some specific recommendations of the DMP module could benefit from revision. Copyright © 2013. Published by Elsevier GmbH.
MEKK1 is a Novel Regulator of the Dmp1-Arf-p53 Pathway and Prognostic Indicator in Breast Cancer

Science.gov (United States)

2012-12-01

hDMP1, INK4a/ARF, p53 or Hdm2 amplification. Kaplan -Meier analyses have been conducted to study the impact for the impact of loss or gain of each locus on...Palma P, Pellegrini S, Fina P et al. Mdm2 gene alterations and mdm2 protein expression in breast carcinomas. J Pathol 1995; 175: 31–38. 21 Turbin DA
PET Imaging of CRF1 with [11C]R121920 and [11C]DMP696: is the target of sufficient density?

International Nuclear Information System (INIS)

Sullivan, Gregory M.; Parsey, Ramin V.; Kumar, J.S. Dileep; Arango, Victoria; Kassir, Suham A.; Huang, Yung-yu; Simpson, Norman R.; Van Heertum, Ronald L.; Mann, J. John

2007-01-01

Aim: Overstimulation of the CRF type 1 receptor (CRF1) is implicated in anxiety and depressive disorders. The aim of this study was to investigate the in vivo binding characteristics of [ 11 C]R121920 and [ 11 C]DMP696 in the nonhuman primate for application in positron emission tomography (PET) studies of CRF1. Methods: PET imaging with the two novel CRF1 radioligands was performed in baboon. In vitro binding studies for CRF1 were performed in postmortem brain tissue of baboon and human to assess sufficiency of receptor density for PET. Results: Both [ 11 C]R121920 and [ 11 C]DMP696 distributed rapidly and uniformly throughout the brain. Washout was comparable across brain regions, without differences in volume of distribution between regions reported to have high and low in vitro CRF1 binding. Membrane-enriched tissue homogenate assay using [ 125 I]Tyr 0 -sauvagine and specific CRF1 antagonists CP154,526 and SN003 in human occipital cortex yielded maximal binding (B max ) of 63.3 and 147.3 fmol/mg protein, respectively, and in human cerebellar cortex yielded B max of 103.6 and 64.6 fmol/mg protein, respectively. Dissociation constants (K D ) were subnanomolar. In baboon, specific binding was not detectable in the same regions; therefore, B max and K D were not measurable. Autoradiographic results were consistent except there was also detectable CRF1-specific binding in baboon cerebellum. Conclusion: Neither [ 11 C]R121920 nor [ 11 C]DMP696 demonstrated quantifiable regional binding in vivo in baboon. In vitro results suggest CRF1 density in baboon may be insufficient for PET. Studies in man may generate more promising results due to the higher CRF1 density compared with baboon in cerebral cortex and cerebellum
Role of the DmpR-mediated regulatory circuit in bacterial biodegradation properties in methylphenol-amended soils.

Science.gov (United States)

Sarand, I; Skärfstad, E; Forsman, M; Romantschuk, M; Shingler, V

2001-01-01

Pathway substrates and some structural analogues directly activate the regulatory protein DmpR to promote transcription of the dmp operon genes encoding the (methyl)phenol degradative pathway of Pseudomonas sp. strain CF600. While a wide range of phenols can activate DmpR, the location and nature of substituents on the basic phenolic ring can limit the level of activation and thus utilization of some compounds as assessed by growth on plates. Here we address the role of the aromatic effector response of DmpR in determining degradative properties in two soil matrices that provide different nutritional conditions. Using the wild-type system and an isogenic counterpart containing a DmpR mutant with enhanced ability to respond to para-substituted phenols, we demonstrate (i) that the enhanced in vitro biodegradative capacity of the regulator mutant strain is manifested in the two different soil types and (ii) that exposure of the wild-type strain to 4-methylphenol-contaminated soil led to rapid selection of a subpopulation exhibiting enhanced capacities to degrade the compound. Genetic and functional analyses of 10 of these derivatives demonstrated that all harbored a single mutation in the sensory domain of DmpR that mediated the phenotype in each case. These findings establish a dominating role for the aromatic effector response of DmpR in determining degradation properties. Moreover, the results indicate that the ability to rapidly adapt regulator properties to different profiles of polluting compounds may underlie the evolutionary success of DmpR-like regulators in controlling aromatic catabolic pathways.
Gamma sterilization of disposable medical products (DMP's)

International Nuclear Information System (INIS)

Brinston, R.M.

1990-01-01

Ten million cubic meters (361 million cubic feet) of disposable medical products (DMP) and related health care items are estimated to be sterilized in the world. In this paper, current conditions and perspectives of gamma sterilization is discussed in comparison with ethylene oxide gas and electron beams. Of the total sterilization estimates for DMP, 2.8 million cubic meters (99 million cubic feet) are sterilized with gamma radiation, with a market share of 27%. Gamma radiation is becoming increased from both general market growth and the introduction of new products, as well as the conversion of product from ethylene oxide gas to cobalt-60. Regulatory pressures, legal considerations, and increasing publicity surrounding ethylene oxide usage are encouraging manufactures to switch to gamma radiation. Gamma's performance features include: no temperature change during the sterilization, high penetration, even through hermetically sealed packages, no residues, and no post-sterilization treatment or quarantine period. Gamma sterilization is economically beneficial in large volumes of product. Cost saving to the end user of gamma sterilization has meant lower minimum dose levels than 25 KGy. Despite of an increasingly accepted gamma radiation, there are still four factors to be considered, including cobalt-60 availability, price, transportation, and disposal. The price of cobalt-60 is based on neutron cost. In the future, cobalt-60 price is expected to be flat and enables gamma processing to become even more competitive with other sterilization methods. Gamma radiation using cobalt-60 has been proven as a safe, effective, and cost-competitive sterilization method for treating DMP and related health care items. It's wide use and many processing advantages will continue to make it a preferred sterilization method. (N.K.)
The (Re)-Relaunching of the DMP, the French Shared Medical Record: New Features to Improve Uptake and Use.

Science.gov (United States)

Séroussi, Brigitte; Bouaud, Jacques

2018-01-01

Health care delivery for patients with chronic conditions is complex and confusing. Care is often fragmented, less effective, and sometimes harmful. Given the potential for EHRs and other health IT systems to facilitate information flow between providers, patients, and settings, health IT-based measures are of particular interest for care coordination. Health information exchange (HIE) has the potential to improve the quality of healthcare by enabling providers with better access to patient information from multiple sources at the point of care. However, many barriers to HIE use have been reported. Another solution relies on the implementation of a nationwide centralized framework of clinical information sharing with "new" secure online care records stored in specifically created platforms. The French DMP follows this model but the adoption of the tool has been historically poor. In 2016, a renovation of the DMP program was launched in nine pilot French departments and new features have been implemented: the DMP content has been fully specified, patients can create their DMP by themselves, DMPs are automatically filled in by data claims, a mobile app has been developed, and technical issues about DMP and EHRs interoperability have been resolved. In October 2017, over 900,000 people have a DMP with an average new DMP being created every minute. These results have to be confirmed in 2018 when the new DMP will be deployed on the whole French territory.
The monomeric form of Neisseria DNA mimic protein DMP19 prevents DNA from binding to the histone-like HU protein

Science.gov (United States)

Ko, Tzu-Ping; Liao, Yi-Ting; Hsu, Kai-Cheng

2017-01-01

DNA mimicry is a direct and effective strategy by which the mimic competes with DNA for the DNA binding sites on other proteins. Until now, only about a dozen proteins have been shown to function via this strategy, including the DNA mimic protein DMP19 from Neisseria meningitides. We have shown previously that DMP19 dimer prevents the operator DNA from binding to the transcription factor NHTF. Here, we provide new evidence that DMP19 monomer can also interact with the Neisseria nucleoid-associated protein HU. Using BS3 crosslinking, gel filtration and isothermal titration calorimetry assays, we found that DMP19 uses its monomeric form to interact with the Neisseria HU dimer. Crosslinking conjugated mass spectrometry was used to investigate the binding mode of DMP19 monomer and HU dimer. Finally, an electrophoretic mobility shift assay (EMSA) confirmed that the DNA binding affinity of HU is affected by DMP19. These results showed that DMP19 is bifunctional in the gene regulation of Neisseria through its variable oligomeric forms. PMID:29220372
Mutational analysis of the PHEX, FGF23, DMP1, SLC34A3, and CLCN5 genes in patients with Hypophosphatemic Rickets

DEFF Research Database (Denmark)

Beck-Nielsen, Signe; Brixen, Kim; Gram, Jeppe

The aim of this study was to identify the underlying genetic mutation in patients with hypophosphatemic rickets (HR). The HR patients studied were recruited from a cross-sectional study of 59 HR patients living in Denmark. Genomic DNA was analysed for mutations in PHEX, FGF23, DMP1, SCL34A3...
Increasing specialty care access through use of an innovative home telehealth-based spinal cord injury disease management protocol (SCI DMP).

Science.gov (United States)

Woo, Christine; Seton, Jacinta M; Washington, Monique; Tomlinson, Suk C; Phrasavath, Douangmala; Farrell, Karen R; Goldstein, Barry

2016-01-01

A spinal cord injury disease management protocol (SCI DMP) was developed to address the unique medical, physical, functional, and psychosocial needs of those living with spinal cord injuries and disorders (SCI/D). The SCI DMP was piloted to evaluate DMP clinical content and to identify issues for broader implementation across the Veterans Affairs (VA) SCI System of Care. Thirty-three patients with SCI/D from four VA SCI centers participated in a 6-month pilot. Patients received customized SCI DMP questions through a data messaging device (DMD). Nurse home telehealth care coordinators (HTCC) monitored responses and addressed clinical alerts daily. One site administered the Duke Severity of Illness (DUSOI) Checklist and Short Form-8 (SF-8™) to evaluate the changes in comorbidity severity and health-related quality of life while on the SCI DMP. Patients remained enrolled an average of 116 days, with a mean response rate of 56%. The average distance between patient's home and their VA SCI center was 59 miles. Feedback on SCI DMP content and the DMD included requests for additional clinical topics, changes in administration frequency, and adapting the DMD for functional impairments. Improvement in clinical outcomes was seen in a subset of patients enrolled on the SCI DMP. SCI HTCCs and patients reported that the program was most beneficial for newly injured patients recently discharged from acute rehabilitation that live far from specialty SCI care facilities. SCI DMP content changes and broader implementation strategies are currently being evaluated based on lessons learned from the pilot.
Mutational analysis of PHEX, FGF23, DMP1, SLC34A3 and CLCN5 in patients with hypophosphatemic rickets

DEFF Research Database (Denmark)

Beck-Nielsen, Signe; Brixen, Kim; Gram, Jeppe

2012-01-01

This study aimed to identify the underlying genetic mutation in patients with hypophosphatemic rickets (HR). Genomic DNA was analysed for mutations in PHEX, FGF23 and CLCN5 by polymerase chain reaction (PCR) followed by denaturing high-performance liquid chromatography (dHPLC). Bi-directional seq...... identification rate of gene mutations causing HR, including 12 novel PHEX and one novel DMP1 mutation.Journal of Human Genetics advance online publication, 14 June 2012; doi:10.1038/jhg.2012.56....
Costs and outcomes of the German disease management programme (DMP) for chronic obstructive pulmonary disease (COPD)-A large population-based cohort study.

Science.gov (United States)

Achelrod, Dmitrij; Welte, Tobias; Schreyögg, Jonas; Stargardt, Tom

2016-09-01

To curb costs and improve health outcomes in chronic obstructive pulmonary disease (COPD), a nationwide disease management programme (DMP) was introduced in Germany in 2005. Yet, its effectiveness has not been comprehensively evaluated. To examine the effects of the German COPD DMP over three years on costs and health resource utilisation from the payer perspective, process quality, morbidity and mortality. A retrospective, population-based cohort study design is applied, using administrative data. After eliminating differences in observable characteristics between the DMP and the control group with entropy balancing, difference-in-difference estimators were computed to account for time-invariant unobservable heterogeneity. 215,104 individuals were included into the analysis of whom 25,269 were enrolled in the DMP. DMP patients had a reduced mortality hazard ratio (0.89, 95%CI: 0.84-0.94) but incurred excess costs of €553 per year. DMP enrolees reveal higher healthcare utilisation with larger shares of individuals being hospitalised (3.14%), consulting an outpatient clinic due to exacerbations (11.13%) and pharmaceutical prescriptions (2.78). However, average length of hospitalisation due to COPD fell by 0.49 days, adherence to medication guidelines as well as indicators for morbidity improved. The German COPD DMP achieved significant improvements in mortality, morbidity and process quality, but at higher costs. Given the low ICER per life year gained, DMP COPD may constitute a cost-effective option to promote COPD population health. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Use of a Nationwide Personally Controlled Electronic Health Record by Healthcare Professionals and Patients: A Case Study with the French DMP.

Science.gov (United States)

Seroussi, Brigitte; Bouaud, Jacques

2017-01-01

If the wide adoption of electronic health records (EHRs) is necessary to address health information sharing and care coordination issues, it is not sufficient. In order to address health information sharing, some countries, among which, France, have implemented a centralized framework with "new" nationwide care records. The French DMP is a centralized, nationally shared, electronic medical record, created according to the opt-in model. More than five years after the launching of the DMP project, DMPs have been created for 1.5% of the target population, which demonstrates the poor adoption of the tool by healthcare professionals. Among the 583,997 existing DMPs in June 2016, 41% were empty, and 24% of non-empty DMPs were actually accessed. If these "active" DMPs were equally accessed by both healthcare professionals and patients, patients accessed DMP documents four times more than healthcare professionals.
Scintigraphic detection of acute experimental endocarditis with the technetium-99m labelled glycoprotein IIb/IIIa receptor antagonist DMP444

Energy Technology Data Exchange (ETDEWEB)

Oyen, W.J.G.; Boerman, O.C.; Corstens, F.H.M. [Department of Nuclear Medicine, University Hospital Nijmegen, Nijmegen (Netherlands); Brouwers, F.M. [Department of Nuclear Medicine, University Hospital Nijmegen, Nijmegen (Netherlands); Department of Internal Medicine, University Hospital Nijmegen, Nijmegen (Netherlands); Barrett, J.A. [DuPont Pharmaceutical Company, Radiopharmaceutical Division, North Billerica, MA (United States); Verheugt, F.W.A. [Department of Cardiology, University Hospital Nijmegen, Nijmegen (Netherlands); Ruiter, D.J. [Department of Pathology, University Hospital Nijmegen, Nijmegen (Netherlands); Meer, J.W.M. van der [Department of Internal Medicine, University Hospital Nijmegen, Nijmegen (Netherlands)

2000-04-01

Bacterial endocarditis is an important clinical problem that may result in persistent bacteraemia and irreversible cardiac damage. Since endocarditis is characterized by aggregation of activated platelets, fibrin and bacteria, we studied DMP444, a technetium-99m labelled high-affinity antagonist of the GP IIb/IIIa receptor that is expressed on activated platelets. In seven Beagle dogs (11-15 kg), the left ventricle was catheterized via the right carotid artery. One hour later, 5 x 10{sup 7} colony forming units of Staphylococcus aureus were injected intracardially. Half an hour later, the catheter was removed. Two extra dogs underwent a complete sham procedure. One day after the intervention, five infected and the two non-infected dogs were injected with 37 MBq/kg {sup 99m}Tc-DMP444 and two infected dogs with 37 MBq/kg {sup 99m}Tc-IgG (used as a non-specific control agent) and imaged up to 4 h after injection. Samples were obtained for tissue counting, microbiology and histology. From 1 to 2 h post injection onward, there was clear focal accumulation of DMP444 in the aortic valve region when endocarditis was present, and this accumulation increased with time. The non-infected and the {sup 99m}Tc-IgG injected dogs showed only persisting blood pool activity without any focal abnormality. At 4 h post injection, the in vivo valve-to-blood pool ratios were 1.87{+-}0.18 in endocarditis, 1.01{+-}0.05 in non-infected controls and 1.09{+-}0.02 in {sup 99m}Tc-IgG injected dogs (P<0.05). It is concluded that targeting activated platelets with the {sup 99m}Tc-labelled GP IIb/IIIa antagonist DMP444 allows a final diagnosis of experimental bacterial endocarditis within 4 h owing to high, specific and fast in vivo uptake. (orig.)
Scintigraphic detection of acute experimental endocarditis with the technetium-99m labelled glycoprotein IIb/IIIa receptor antagonist DMP444

International Nuclear Information System (INIS)

Oyen, W.J.G.; Boerman, O.C.; Corstens, F.H.M.; Brouwers, F.M.; Barrett, J.A.; Verheugt, F.W.A.; Ruiter, D.J.; Meer, J.W.M. van der

2000-01-01

Bacterial endocarditis is an important clinical problem that may result in persistent bacteraemia and irreversible cardiac damage. Since endocarditis is characterized by aggregation of activated platelets, fibrin and bacteria, we studied DMP444, a technetium-99m labelled high-affinity antagonist of the GP IIb/IIIa receptor that is expressed on activated platelets. In seven Beagle dogs (11-15 kg), the left ventricle was catheterized via the right carotid artery. One hour later, 5 x 10 7 colony forming units of Staphylococcus aureus were injected intracardially. Half an hour later, the catheter was removed. Two extra dogs underwent a complete sham procedure. One day after the intervention, five infected and the two non-infected dogs were injected with 37 MBq/kg 99m Tc-DMP444 and two infected dogs with 37 MBq/kg 99m Tc-IgG (used as a non-specific control agent) and imaged up to 4 h after injection. Samples were obtained for tissue counting, microbiology and histology. From 1 to 2 h post injection onward, there was clear focal accumulation of DMP444 in the aortic valve region when endocarditis was present, and this accumulation increased with time. The non-infected and the 99m Tc-IgG injected dogs showed only persisting blood pool activity without any focal abnormality. At 4 h post injection, the in vivo valve-to-blood pool ratios were 1.87±0.18 in endocarditis, 1.01±0.05 in non-infected controls and 1.09±0.02 in 99m Tc-IgG injected dogs (P 99m Tc-labelled GP IIb/IIIa antagonist DMP444 allows a final diagnosis of experimental bacterial endocarditis within 4 h owing to high, specific and fast in vivo uptake. (orig.)
[Gender-specific differences in quality of life of patients with type 2 diabetes with or without participating in DMP

NARCIS (Netherlands)

Miksch, A.; Hermann, K.; Trieschmann, J.; Roelz, A.; Heiderhoff, M.; Laux, G.; Rosemann, T.J.; Szecsenyi, J.

2008-01-01

OBJECTIVE: Disease management programmes (DMP) are supposed to improve the care of patients with type 2 diabetes or other chronic conditions. One stated aim is the improvement of the health-related quality of life. Within the ELSID study (controlled study for the evaluation of the DMP for patients

Molecular level biodegradation of phenol and its derivatives through dmp operon of Pseudomonas putida: A bio-molecular modeling and docking analysis.

Science.gov (United States)

Ray, Sujay; Banerjee, Arundhati

2015-10-01

Participation of Pseudomonas putida-derived methyl phenol (dmp) operon and DmpR protein in the biodegradation of phenol or other harmful, organic, toxic pollutants was investigated at a molecular level. Documentation documents that P. putida has DmpR protein which positively regulates dmp operon in the presence of inducers; like phenols. From the operon, phenol hydroxylase encoded by dmpN gene, participates in degrading phenols after dmp operon is expressed. For the purpose, the 3-D models of the four domains from DmpR protein and of the DNA sequences from the two Upstream Activation Sequences (UAS) present at the promoter region of the operon were demonstrated using discrete molecular modeling techniques. The best modeled structures satisfying their stereo-chemical properties were selected in each of the cases. To stabilize the individual structures, energy optimization was performed. In the presence of inducers, probable interactions among domains and then the two independent DNA structures with the fourth domain were perused by manifold molecular docking simulations. The complex structures were made to be stable by minimizing their overall energy. Responsible amino acid residues, nucleotide bases and binding patterns for the biodegradation, were examined. In the presence of the inducers, the biodegradation process is initiated by the interaction of phe50 from the first protein domain with the inducers. Only after the interaction of the last domain with the DNA sequences individually, the operon is expressed. This novel residue level study is paramount for initiating transcription in the operon; thereby leading to expression of phenol hydroxylase followed by phenol biodegradation. Copyright © 2015. Published by Elsevier B.V.
METHODOLOGY OF THE HYBRID PROPULSION SYSTEM (DMP & DEP FOR TRIMARAN TYPE FAST PATROL BOAT

Directory of Open Access Journals (Sweden)

Aulia Widyandari

2012-04-01

Full Text Available There are lot of research done to develop a patrol boat, from the modification of hull model until propulsion system equipment. For example the model ship type AMV (Advanced Marine Vehicle was developed starting from the Catamaran, Trimaran and Pentamaran model. Everything is aimed at obtaining the ship design that has the speed and stability. In addition to achieving high-speed vessel must be equipped with propulsion (Main Power is great, that means the main engine dimensions, auxiliary equipments and fuel tanks is too large. Many Limitations of space on the ship's engine room trimaran vessel is the main obstacle in designing propulsion system. Beside that Patrol boat should have many missions speed, so propulsion system should be designed at that conditions. Hybrid propulsion is a combination of Diesel Mechanical Propulsion (DMP with Diesel Electric Propulsion (DEP. DMP system is connected directly to the propeller shaft (or through a reduction-gear. DMP has provide more efficiency rate of 95%. While DEP is only able to provide efficiency by 85% - 89% is slightly lower than DMP, but the DEP offers many advantages such as simplicity and suitability in the rotational speed settings, control systems, engine power production Redundancy, Flexibility in the design of equipments layout in engine rooms, noise, vibration and fuel consumption efficiency which affects the lower pollution. Design of Hybrid Propulsion system can be satisfied and achieved the Power requirements and optimally at all speed condition of patrol boat. Therefore the author made using modeling Maxsurf-11.12 software and carried out various optimization of the choice of main engine, propeller and system conditions for fast patrol boat cruise.
Sclerostin antibody (Scl-Ab) improves osteomalacia phenotype in dentin matrix protein 1(Dmp1) knockout mice with little impact on serum levels of phosphorus and FGF23.

Science.gov (United States)

Ren, Yinshi; Han, Xianglong; Jing, Yan; Yuan, Baozhi; Ke, Huazhu; Liu, Min; Feng, Jian Q

2016-01-01

Unlike treatments for most rickets, the treatment using 1,25-(OH)2 vitamin D3 has little efficacy on patients with hypophosphatemic rickets, a set of rare genetic diseases. Thus, understanding the local cause for osteomalacia in hypophosphatemic rickets and developing an effective treatment to restore mineralization in this rare disease has been a longstanding goal in medicine. Here, we used Dmp1 knockout (KO) mice (whose mutations led to the same type of autosomal recessive hypophosphatemic rickets in humans) as the model in which the monoclonal antibody of sclerostin (Scl-Ab) was tested in two age groups for 8weeks: the prevention group (starting at age 4weeks) and the treatment group (starting at age 12weeks). Applications of Scl-Ab greatly improved the osteomalacia phenotype (>15%) and the biomechanical properties (3-point bending, ~60%) in the treated long-bone group. Our studies not only showed improvement of the osteomalacia in the alveolar bone, which has the highest bone metabolism rate, as well as the long bone phenotypes in treated mice. All these improvements attributed to the use of Scl-Ab are independent of the change in serum levels of phosphorus and FGF23, since Scl-Ab had little efficacy on those parameters. Finally, we propose a model to explain how Scl-Ab can improve the Dmp1 KO osteomalacia phenotype, in which the sclerostin level is already low. Copyright © 2016 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.
On the Determinants and Outcomes of Passion for Playing Pokémon Go.

Science.gov (United States)

Orosz, Gábor; Zsila, Ágnes; Vallerand, Robert J; Böthe, Beáta

2018-01-01

In 2016, Pokémon Go became the most popular smartphone game. Despite the increasing popularity of this augmented reality game, to date, no studies have investigated passion for playing Pokémon Go. On the theoretical basis of the Dualistic Model of Passion (DMP), our goal was to investigate the associations between Pokémon Go playing motives, passion, and impulsivity. A total of 621 Pokémon Go players participated in the study (54.9% female; M age = 22.6 years, SD age = 4.4). It was found that impulsivity was more strongly associated with obsessive passion (OP) than with harmonious passion (HP). HP was associated with adaptive motives (i.e., outdoor activity, social, recreation, and nostalgia), while OP was associated with less adaptive motives (i.e., fantasy, escape, boredom, competition, and coping). Therefore, in line with the DMP, HP and OP for playing Pokémon Go can predict an almost perfectly distinguished set of adaptive or maladaptive playing motives, and OP has a noteworthy relationship with impulsivity as a determinant.
On the Determinants and Outcomes of Passion for Playing Pokémon Go

Science.gov (United States)

Orosz, Gábor; Zsila, Ágnes; Vallerand, Robert J.; Böthe, Beáta

2018-01-01

In 2016, Pokémon Go became the most popular smartphone game. Despite the increasing popularity of this augmented reality game, to date, no studies have investigated passion for playing Pokémon Go. On the theoretical basis of the Dualistic Model of Passion (DMP), our goal was to investigate the associations between Pokémon Go playing motives, passion, and impulsivity. A total of 621 Pokémon Go players participated in the study (54.9% female; Mage = 22.6 years, SDage = 4.4). It was found that impulsivity was more strongly associated with obsessive passion (OP) than with harmonious passion (HP). HP was associated with adaptive motives (i.e., outdoor activity, social, recreation, and nostalgia), while OP was associated with less adaptive motives (i.e., fantasy, escape, boredom, competition, and coping). Therefore, in line with the DMP, HP and OP for playing Pokémon Go can predict an almost perfectly distinguished set of adaptive or maladaptive playing motives, and OP has a noteworthy relationship with impulsivity as a determinant. PMID:29599735
Dmp1 Promoter-Driven Diphtheria Toxin Receptor Transgene Expression Directs Unforeseen Effects in Multiple Tissues

Directory of Open Access Journals (Sweden)

Ahmed Al-Jazzar

2016-12-01

Full Text Available Mice harbouring a dentin matrix protein 1 (Dmp1 promoter-driven human diphtheria toxin (DT receptor (HDTR transgene (Tg have recently been used to attain targeted ablation of osteocytes by diphtheria toxin (DT treatment in order to define osteocyte function. Use of these Tg mice has asserted mechano- and novel paracrine regulatory osteocyte functions. To explore osteocyte roles fully, we sought to confirm the selectivity of DT effects in these transgenic mice. However, our findings revealed incomplete DT-induced osteocyte ablation, prevalent HDTR misexpression, as well as more prominent histopathological DT-induced changes in multiple organs in Tg than in wild-type (WT littermate mice. Mechanistic evidence for DT action, via prominent regulation of phosphorylation status of elongation factor-2 (EF-2, was also found in many non-skeletal tissues in Tg mice; indicative of direct “off-target” DT action. Finally, very rapid deterioration in health and welfare status in response to DT treatment was observed in these Tg when compared to WT control mice. Together, these data lead us to conclude that alternative models for osteocyte ablation should be sought and caution be exercised when drawing conclusions from experiments using these Tg mice alone.
A novel process for the synthesis of 'Designed Molecular Precursor' (DMP) of thorium useful for broad application spectrum

International Nuclear Information System (INIS)

Sarika Verma; Amritphalae, S.S.

2016-01-01

For the first time (Patent application filed in India vide N/F No-0018NF2015) a novel process for the synthesis of 'Designed Molecular Precursor' (DMP) of thorium has been developed, which involves the unique combination of two different (dual) capping agents, one is biomolecule: Cytosine and other is non biomolecule: cetyl trimethyl ammonium bromide. The DMP essentially consists of hybrid nanosized thorium oxalate and alkaline thorate whose application lies in the area of making thorium metal, densified thorium oxide, carbide and nitride, anhydrous thorium complexes and thorium boron silicates glasses. (author)
Amphetamine and cocaine suppress social play behavior in rats through distinct mechanisms.

Science.gov (United States)

Achterberg, E J Marijke; Trezza, Viviana; Siviy, Stephen M; Schrama, Laurens; Schoffelmeer, Anton N M; Vanderschuren, Louk J M J

2014-04-01

Social play behavior is a characteristic form of social behavior displayed by juvenile and adolescent mammals. This social play behavior is highly rewarding and of major importance for social and cognitive development. Social play is known to be modulated by neurotransmitter systems involved in reward and motivation. Interestingly, psychostimulant drugs, such as amphetamine and cocaine, profoundly suppress social play, but the neural mechanisms underlying these effects remain to be elucidated. In this study, we investigated the pharmacological underpinnings of amphetamine- and cocaine-induced suppression of social play behavior in rats. The play-suppressant effects of amphetamine were antagonized by the alpha-2 adrenoreceptor antagonist RX821002 but not by the dopamine receptor antagonist alpha-flupenthixol. Remarkably, the effects of cocaine on social play were not antagonized by alpha-2 noradrenergic, dopaminergic, or serotonergic receptor antagonists, administered either alone or in combination. The effects of a subeffective dose of cocaine were enhanced by a combination of subeffective doses of the serotonin reuptake inhibitor fluoxetine, the dopamine reuptake inhibitor GBR12909, and the noradrenaline reuptake inhibitor atomoxetine. Amphetamine, like methylphenidate, exerts its play-suppressant effect through alpha-2 noradrenergic receptors. On the other hand, cocaine reduces social play by simultaneous increases in dopamine, noradrenaline, and serotonin neurotransmission. In conclusion, psychostimulant drugs with different pharmacological profiles suppress social play behavior through distinct mechanisms. These data contribute to our understanding of the neural mechanisms of social behavior during an important developmental period, and of the deleterious effects of psychostimulant exposure thereon.
Dpb11/TopBP1 plays distinct roles in DNA replication, checkpoint response and homologous recombination

DEFF Research Database (Denmark)

Germann, Susanne Manuela; Østergaard, Vibe Hallundbæk; Haas, Caroline

2011-01-01

DPB11/TopBP1 is an essential evolutionarily conserved gene involved in initiation of DNA replication and checkpoint signaling. Here, we show that Saccharomyces cerevisiae Dpb11 forms nuclear foci that localize to sites of DNA damage in G1, S and G2 phase, a recruitment that is conserved for its...... and Tel1, and of the checkpoint mediator Rad9. In a site-directed mutagenesis screen, we identify a separation-of-function mutant, dpb11-PF, that is sensitive to DSB-inducing agents yet remains proficient for DNA replication and the S-phase checkpoint at the permissive temperature. The dpb11-PF mutant...... homologue TopBP1 in Gallus gallus. Damage-induced Dpb11 foci are distinct from Sld3 replication initiation foci. Further, Dpb11 foci are dependent on the checkpoint proteins Mec3 (9-1-1 complex) and Rad24, and require the C-terminal domain of Dpb11. Dpb11 foci are independent of the checkpoint kinases Mec1...
Properties Of Reflection Holograms Recorded In Polaroid's DMP-128 Photopolymer

Science.gov (United States)

Ingwall, R. T.; Troll, M.; Vetterling, W. T.

1987-06-01

Optical and microstructural properties of reflection holograms recorded in DMP-128 are reported. The optical properties are determined from transmission spectra of the holograms by ignoring the relatively small effects of light scattering and absorption. Microstructure is revealed by light and electron microscopic examination of hologram sections prepared either by diamond grit abrasion or by freeze fracture. Fringe planes are clearly seen with both sectioning procedures. The spacing between adjacent planes is strongly affected by processing conditions. Standard processing produces reflection holograms with fringe plane spacing that decreases continuously from the film:substrate interface to the film:air interface. These holograms have wide spectral bandwidths (100-200nm) and irregular band shapes. Narrow bandwidth holograms are produced from slightly more complicated processing steps. The optical properties of both types of holograms are compared to a theoretical model developed to account for nonuniform fringe plane spacing. Important experimental features such as spectral bandwidth and diffraction efficiency are readily explained by the theory and the observed microstructure.
Resistance of holograms made in Polaroid DMP128 photopolymer to ionizing radiation damage

International Nuclear Information System (INIS)

Golden, J.P.; Summers, G.P.; Carter, W.H.

1988-01-01

Because of their light weight and general wave-front-transforming ability, holograms appear potentially useful as beam correctors and collimators for diode-laser arrays in intersatellite optical data links. However, to survive in space a hologram must withstand damage from electrons and protons trapped in the Van Allen belts. We have found that holograms made with Polaroid DMP128 photopolymer on Suprasil-2 can withstand 63-MeV protons up to a total dose of 2 Mrad in (Si) and withstand /sup 60/Co gamma rays up to a total dose of 2 Mrad in (Si) without loss of diffraction efficiency. It appears that these holograms are sufficiently radiation hard for space application
UF's Lone Cabbage Oyster Reef Restoration Project: a use case in implementing a data management plan (DMP)

OpenAIRE

Aufmuth, Joe

2018-01-01

Data management plans are created to satisfy funding agency proposal requirements related to the data life cycle. Once an award is made researchers must implement the plan they described. But how is this best accomplished? The presentation UF’s Lone Cabbage Oyster Reef Restoration Project: a use case in implementing a data management plan (DMP) describes how PI's for this grant funded research project are achieving its data management plan goals using an academic library's consulting team.
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.
Dopamine receptors play distinct roles in sexual behavior expression of rats with a different sexual motivational tone.

Science.gov (United States)

Guadarrama-Bazante, Irma L; Canseco-Alba, Ana; Rodríguez-Manzo, Gabriela

2014-10-01

Dopamine (DA) plays a central role in the expression of male sexual behavior. The effects of DA-enhancing drugs on copulation seem to vary depending on the dose of the agonist used, the type of DA receptor activated, and the sexual condition of the animals. The aim of the present study was to carry out a systematic analysis of the effects of dopaminergic agonists on the expression of male sexual behavior by sexually competent rats in different sexual motivational states, that is when sexually active (sexually experienced) and when temporarily inhibited (sexually exhausted). To this end, the same doses of the nonselective DA receptor agonist apomorphine, the selective D2-like DA receptor agonist quinpirole, and the selective D1-like DA receptor agonist SKF38393 were injected intraperitoneally to sexually experienced or sexually exhausted male rats and their sexual behavior was recorded. Low apomorphine doses induced expression of sexual behavior in sexually satiated rats, but only reduced the intromission latency of sexually experienced rats. SKF38393 facilitated the expression of sexual behavior by sexually exhausted rats, but not that of sexually experienced males and quinpirole did not exert an effect in both types of animal. In line with these results, the apomorphine-induced reversal of sexual exhaustion was blocked by the D1-like receptor antagonist SCH23390. The data suggest that DA receptors play distinct roles in the expression of sexual behavior by male rats depending on their motivational state and that activation of D1-like receptors promotes the expression of sexual behavior in satiated rats.
Bone Mass and Strength are Significantly Improved in Mice Overexpressing Human WNT16 in Osteocytes.

Science.gov (United States)

Alam, Imranul; Reilly, Austin M; Alkhouli, Mohammed; Gerard-O'Riley, Rita L; Kasipathi, Charishma; Oakes, Dana K; Wright, Weston B; Acton, Dena; McQueen, Amie K; Patel, Bhavmik; Lim, Kyung-Eun; Robling, Alexander G; Econs, Michael J

2017-04-01

Recently, we demonstrated that osteoblast-specific overexpression of human WNT16 increased both cortical and trabecular bone mass and structure in mice. To further identify the cell-specific role of Wnt16 in bone homeostasis, we created transgenic (TG) mice overexpressing human WNT16 in osteocytes using Dmp1 promoter (Dmp1-hWNT16 TG) on C57BL/6 (B6) background. We analyzed bone phenotypes and serum bone biomarkers, performed gene expression analysis and measured dynamic bone histomorphometry in Dmp1-hWNT16 TG and wild-type (WT) mice. Compared to WT mice, Dmp1-hWNT16 TG mice exhibited significantly higher whole-body, spine and femoral aBMD, BMC and trabecular (BV/TV, Tb.N, and Tb.Th) and cortical (bone area and thickness) parameters in both male and female at 12 weeks of age. Femur stiffness and ultimate force were also significantly improved in the Dmp1-hWNT16 TG female mice, compared to sex-matched WT littermates. In addition, female Dmp1-hWNT16 TG mice displayed significantly higher MS/BS, MAR and BFR/BS compared to the WT mice. Gene expression analysis demonstrated significantly higher mRNA level of Alp in both male and female Dmp1-hWNT16 TG mice and significantly higher levels of Osteocalcin, Opg and Rankl in the male Dmp1-hWNT16 TG mice in bone tissue compared to sex-matched WT mice. These results indicate that WNT16 plays a critical role for acquisition of both cortical and trabecular bone mass and strength. Strategies designed to use WNT16 as a target for therapeutic interventions will be valuable to treat osteoporosis and other low bone mass conditions.
Physical Activity Play and Preschool Children's Peer Acceptance: Distinctions between Rough-and-Tumble and Exercise Play

Science.gov (United States)

Lindsey, Eric W.

2014-01-01

Research Findings: Two forms of exercise play (toy mediated and non-mediated) and 2 forms of rough-and-tumble (R&T) play (chase and fighting) were examined in relation to preschoolers' peer competence. A total of 148 preschoolers (78 boys, 89 Euro-Americans) were observed during free play at their university-sponsored child care center. The…
[Effect of the Disease Management Program on HbA1c Value in Type 2 Diabetes Mellitus Patients: A Retrospective Comparison between Disease Management Programs and Standard Care].

Science.gov (United States)

Wiefarn, Stefan; Kostev, Karel; Heumann, Christian; Rettelbach, Anja

2017-10-01

Background This retrospective study aims to measure the effect of the disease management program (DMP) for type 2 diabetes mellitus (T2DM) patients on HbA 1c value within Germany. Methods This study is based on patient data from the Disease Analyzer panel (IMS Health). An adequate control group was created using 2:1 propensity score matching. After matching, the analysis included 14 759 patients. Of these, 5875 participated in a DMP while 8884 received standard care. The DMP effect was estimated on the basis of the matched data, using an unpaired t-test. In addition, subgroups were considered from the perspective of personalized medicine. Results The reduction in HbA 1c values in the DMP group amounted to an average of 1.0 percentage point (baseline HbA 1c = 8.1 vs. final HbA 1c = 7.1), while the SC group was able to achieve an average reduction in HbA 1c values of 0.9 percentage point (baseline HbA 1c = 8.1 vs. final HbA 1c = 7.2). The DMP group thus achieved an average reduction in HbA 1c values that exceeded that of the SC group by only 0.1 percentage point (95 % CI: 0.04 - 0.16). Descriptively, it also became apparent that patients from the DMP group received a greater average number of annual prescriptions and had more HbA 1c measurements. The subgroup analysis identified groups of patients who benefit more from DMPs than others. Thus, young patients or patients who are being treated by diabetologists are able to benefit most from a DMP. Furthermore, the baseline HbA 1c value has an influence on the DMP effect. Conclusion T2DM patients in the DMP exhibit a significantly higher reduction in HbA 1c value. However, it is questionable whether this effect is clinically relevant. Certain groups of patients benefit more from DMPs than others. Nevertheless, further studies are needed in order to better understand the impact of the DMP on HbA 1c value and the reasons for the subgroup effects. Such studies should be carried
[General practitioners' opinion and attitude towards DMPs and the change in practice routines to implement the DMP "diabetes mellitus type 2"].

Science.gov (United States)

Miksch, Antje; Trieschmann, Johanna; Ose, Dominik; Rölz, Andreas; Heiderhoff, Marc; Szecsenyi, Joachim

2011-01-01

Effective implementation of disease management programmes (DMPs) in primary care practices often requires changes in practice workflows and responsibilities and acceptance by the parties involved. Within the ELSID study (evaluation study of the DMP diabetes mellitus type 2) the physicians' attitudes toward DMPs were obtained and an optimised implementation of DMPs was developed by conducting a quality management cycle with primary care practice teams. The aim was to investigate which practice workflows will have to be changed and what kind of barriers to implement these changes are perceived. In 78 primary care practices of the two German federal states of Rheinland-Pfalz and Sachsen-Anhalt a quality management cycle was conducted using a structured analysis of the current state of DMP workflows and the need for improvement identified. Subsequently, an optimised workflow was developed and targets were agreed upon. After 6 months, the study team called to inquire about the current state of implementation and, if appropriate, actual barriers to change. After 6 months, 71 practices had been interviewed by phone. 64 of them (90.1%) had agreed on at least one target (e.g., to purchase new instrumentation, to regularly discuss feedback reports, to set up a patient registry). On average three targets had been formulated, and 2 out of 3 had been implemented in the meantime. In most cases lack of time was given as the reason for non-implementation. The majority of surveyed practices perceived some need for improvement. But sufficient resources (time, staff and money) are required to ensure efficient implementation of DMPs in primary care practices and their integration with routine processes. A redefinition of responsibilities for DMPs will strengthen the role of medical assistants and promote high-quality implementation of these programmes. Copyright © 2010. Published by Elsevier GmbH.
Active zone proteins are transported via distinct mechanisms regulated by Par-1 kinase.

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Kara R Barber

2017-02-01

Full Text Available Disruption of synapses underlies a plethora of neurodevelopmental and neurodegenerative disease. Presynaptic specialization called the active zone plays a critical role in the communication with postsynaptic neuron. While the role of many proteins at the active zones in synaptic communication is relatively well studied, very little is known about how these proteins are transported to the synapses. For example, are there distinct mechanisms for the transport of active zone components or are they all transported in the same transport vesicle? Is active zone protein transport regulated? In this report we show that overexpression of Par-1/MARK kinase, a protein whose misregulation has been implicated in Autism spectrum disorders (ASDs and neurodegenerative disorders, lead to a specific block in the transport of an active zone protein component- Bruchpilot at Drosophila neuromuscular junctions. Consistent with a block in axonal transport, we find a decrease in number of active zones and reduced neurotransmission in flies overexpressing Par-1 kinase. Interestingly, we find that Par-1 acts independently of Tau-one of the most well studied substrates of Par-1, revealing a presynaptic function for Par-1 that is independent of Tau. Thus, our study strongly suggests that there are distinct mechanisms that transport components of active zones and that they are tightly regulated.
[Health locus of control of patients in disease management programmes].

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Schnee, M; Grikscheit, F

2013-06-01

Health locus of control beliefs plays a major role in improving self-management skills of the chronically ill - a main goal in disease management programmes (DMP). This study aims at characterising participants in disease management regarding their health locus of control. Data are based on 4 cross-sectional postal surveys between spring and autumn of 2006 and 2007 within the Health Care Monitor of the Bertelsmann Foundation. Among the 6 285 respondents, 1 266 are chronically ill and not enrolled in a DMP and 327 are participating in a DMP. A high internal locus of control (HLC) occurs significantly less often in DMP patients than in normal chronically ill patients (and healthy people) controlling for age, gender and social class. With increasing age, a high internal locus of control is also significantly less likely. When comparing healthy people, the chronically ill and the DMP participants a social gradient of a high internal locus of control belief can be observed. The weaker internal and higher doctor-related external locus of control of DMP participants should be carefully observed by the physician when trying to strengthen the patients' self-management skills. Evaluators of DMP should take into account the different baselines of DMP patients and relevant control groups and incorporate these differences into the evaluation. © Georg Thieme Verlag KG Stuttgart · New York.

Preparation of Reducing Sugar Hydrolyzed from High-Lignin Coconut Coir Dust Pretreated by the Recycled Ionic Liquid [mmim][dmp] and Combination with Alkaline

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Hanny Frans Sangian

2015-03-01

Full Text Available This study aims to produce reducing sugar hydrolyzed from substrate, coconut coir dust pretreated by recycled ionic liquid and its combination with alkaline. The 1H NMR and FTIR were performed to ver-ify the synthesized ionic liquid methylmethylimidazolium dimethyl phosphate ([mmim][dmp]. The structure of pretreated substrates was analyzed by XRD measurement. The used ionic liquid was recy-cled twice to re-employ for substrate pretreatment. The treated- and untreated-coconut coir dust were hydrolyzed into sugars using pure cellulase. The reaction, which called an enzymatic hydrolysis, was conducted at 60 °C, pH 3, for 48 h. The yields of sugar hydrolyzed from fresh IL-pretreated, 1R*IL-pretreated and 2R*IL-pretreated substrates were of 0.19, 0.15 and 0.15 g sugar / g cellu-lose+hemicellulose, respectively. Pretreatment with NaOH or the combination of NaOH+IL resulted in yields of reducing sugars of 0.25, 0.28 g/g, respectively. When alkaline combined with the recycled ionic liquids, NaOH+1R*IL, NaOH+2R*IL in the pretreatment, the yields of sugar were relatively similar to those obtained using alkaline followed by fresh ionic liquid. If the mixture enzymes, cellu-lase+xylanase, used to liberate sugars from fresh IL-pretreated, or recycled IL-pretreated substrates, the amount of sugar (concentration or yield increased slightly compared to that employing a single cel-lulase. These findings showed that recycled IL pretreatment of the high-lignin lignocellulose, coconut coir dust, is a new prospect for the economical manufacture of fermentable sugars and biofuel in the coming years. © 2015 BCREC UNDIP. All rights reservedReceived: 1st July 2014; Revised: 5th September 2014; Accepted: 5th September 2014 How to Cite: Sangian, H.F., Kristian, J., Rahma, S., Dewi, H., Puspasari, D., Agnesty, S., Gunawan, S., Widjaja, A. (2015. Preparation of Reducing Sugar Hydrolyzed from High-Lignin Coconut Coir Dust Pretreated by the Recycled Ionic Liquid [mmim][dmp
Embriões liofilizados e flocos de Artemia no cultivo pós-larval de Litopenaeus vannamei (Boone, 1931 - DOI: 10.4025/actascibiolsci.v30i1.1424 Use of freeze-dried embryos and Artemia flakes in the post-larval culture of Litopenaeus vannamei (Boone, 1931 - DOI: 10.4025/actascibiolsci.v30i1.1424

Directory of Open Access Journals (Sweden)

Pedro Hercílio de Oliveira Cavalcante

2008-03-01

Full Text Available O objetivo do estudo foi avaliar o crescimento e sobrevivência de pós-larvas de Litopenaeus vannamei que receberam embriões liofilizados (EMB e flocos (FLO de Artemia como suplementos alimentares a uma dieta microparticulada (DMP. Nos tratamentos T1, T2 e T3, os camarões receberam DMP e após 2h, acréscimos de FLO (T1; de EMB (T2; e da mesma DMP, anteriormente, ofertada (T3. No T4, as pós-larvas foram alimentadas com DMP, mas sem suplementações posteriores. Não houve diferença significativa (p > 0,05 na sobrevivência dos camarões após o período experimental de 21 dias. Por outro lado, o ganho de peso absoluto (mg peso seco das pós-larvas, cuja dieta foi suplementada com BEM, foi significativamente superior (p Artemia e recomendam sua inclusão na dieta pós-larval de Litopenaeus vannameiThe objective of the study was to evaluate the growth and survival of Litopenaeus vannamei post-larvae fed with freeze-dried embryos and Artemia flakes as feeding supplements to a microparticulate diet (DMP. In treatments T1, T2 and T3, the shrimp were fed with DMP and after 2 hours, received supplements of FLO (T1; EMB (T2; and the same DMP previously offered (T3. In T4, post-larvae were fed with DMP but without additional supplementation. There was no significant difference (p > 0.05 in shrimp survival after the experimental period of 21 days. On the other hand, the absolute weight gain (mg of dry weight of post-larvae whose diet was supplemented with EMB (T2 was significantly higher (p Artemia embryos and recommend their inclusion in the post-larval diet of Litopenaeus vannamei
The MAP kinase ERK and its scaffold protein MP1 interact with the chromatin regulator Corto during Drosophila wing tissue development

Science.gov (United States)

2011-01-01

Background Mitogen-activated protein kinase (MAPK) cascades (p38, JNK, ERK pathways) are involved in cell fate acquisition during development. These kinase modules are associated with scaffold proteins that control their activity. In Drosophila, dMP1, that encodes an ERK scaffold protein, regulates ERK signaling during wing development and contributes to intervein and vein cell differentiation. Functional relationships during wing development between a chromatin regulator, the Enhancer of Trithorax and Polycomb Corto, ERK and its scaffold protein dMP1, are examined here. Results Genetic interactions show that corto and dMP1 act together to antagonize rolled (which encodes ERK) in the future intervein cells, thus promoting intervein fate. Although Corto, ERK and dMP1 are present in both cytoplasmic and nucleus compartments, they interact exclusively in nucleus extracts. Furthermore, Corto, ERK and dMP1 co-localize on several sites on polytene chromosomes, suggesting that they regulate gene expression directly on chromatin. Finally, Corto is phosphorylated. Interestingly, its phosphorylation pattern differs between cytoplasm and nucleus and changes upon ERK activation. Conclusions Our data therefore suggest that the Enhancer of Trithorax and Polycomb Corto could participate in regulating vein and intervein genes during wing tissue development in response to ERK signaling. PMID:21401930
The MAP kinase ERK and its scaffold protein MP1 interact with the chromatin regulator Corto during Drosophila wing tissue development.

Science.gov (United States)

Mouchel-Vielh, Emmanuèle; Rougeot, Julien; Decoville, Martine; Peronnet, Frédérique

2011-03-14

Mitogen-activated protein kinase (MAPK) cascades (p38, JNK, ERK pathways) are involved in cell fate acquisition during development. These kinase modules are associated with scaffold proteins that control their activity. In Drosophila, dMP1, that encodes an ERK scaffold protein, regulates ERK signaling during wing development and contributes to intervein and vein cell differentiation. Functional relationships during wing development between a chromatin regulator, the Enhancer of Trithorax and Polycomb Corto, ERK and its scaffold protein dMP1, are examined here. Genetic interactions show that corto and dMP1 act together to antagonize rolled (which encodes ERK) in the future intervein cells, thus promoting intervein fate. Although Corto, ERK and dMP1 are present in both cytoplasmic and nucleus compartments, they interact exclusively in nucleus extracts. Furthermore, Corto, ERK and dMP1 co-localize on several sites on polytene chromosomes, suggesting that they regulate gene expression directly on chromatin. Finally, Corto is phosphorylated. Interestingly, its phosphorylation pattern differs between cytoplasm and nucleus and changes upon ERK activation. Our data therefore suggest that the Enhancer of Trithorax and Polycomb Corto could participate in regulating vein and intervein genes during wing tissue development in response to ERK signaling.
The MAP kinase ERK and its scaffold protein MP1 interact with the chromatin regulator Corto during Drosophila wing tissue development

Directory of Open Access Journals (Sweden)

Peronnet Frédérique

2011-03-01

Full Text Available Abstract Background Mitogen-activated protein kinase (MAPK cascades (p38, JNK, ERK pathways are involved in cell fate acquisition during development. These kinase modules are associated with scaffold proteins that control their activity. In Drosophila, dMP1, that encodes an ERK scaffold protein, regulates ERK signaling during wing development and contributes to intervein and vein cell differentiation. Functional relationships during wing development between a chromatin regulator, the Enhancer of Trithorax and Polycomb Corto, ERK and its scaffold protein dMP1, are examined here. Results Genetic interactions show that corto and dMP1 act together to antagonize rolled (which encodes ERK in the future intervein cells, thus promoting intervein fate. Although Corto, ERK and dMP1 are present in both cytoplasmic and nucleus compartments, they interact exclusively in nucleus extracts. Furthermore, Corto, ERK and dMP1 co-localize on several sites on polytene chromosomes, suggesting that they regulate gene expression directly on chromatin. Finally, Corto is phosphorylated. Interestingly, its phosphorylation pattern differs between cytoplasm and nucleus and changes upon ERK activation. Conclusions Our data therefore suggest that the Enhancer of Trithorax and Polycomb Corto could participate in regulating vein and intervein genes during wing tissue development in response to ERK signaling.
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.
Structural and kinetic characterization of two 4-oxalocrotonate tautomerases in Methylibium petroleiphilum strain PM1.

Science.gov (United States)

Terrell, Cassidy R; Burks, Elizabeth A; Whitman, Christian P; Hoffman, David W

2013-09-01

Methylibium petroleiphilum strain PM1 uses various petroleum products including the fuel additive methyl tert-butyl ether and straight chain and aromatic hydrocarbons as sole carbon and energy sources. It has two operons, dmpI and dmpII, that code for the enzymes in a pair of parallel meta-fission pathways. In order to understand the roles of the pathways, the 4-oxalocrotonate tautomerase (4-OT) isozyme from each pathway was characterized. Tautomerase I and tautomerase II have the lowest pairwise sequence identity (35%) among the isozyme pairs in the parallel pathways, and could offer insight into substrate preferences and pathway functions. The kinetic parameters of tautomerase I and tautomerase II were determined using 2-hydroxymuconate and 5-(methyl)-2-hydroxymuconate. Both tautomerase I and tautomerase II process the substrates, but with different efficiencies. Crystal structures were determined for both tautomerase I and tautomerase II, at 1.57 and 1.64Å resolution, respectively. The backbones of tautomerase I and tautomerase II are highly similar, but have distinct active site environments. The results, in combination with those for other structurally and kinetically characterized 4-OT isozymes, suggest that tautomerase I catalyzes the tautomerization of both 2-hydroxymuconate and alkyl derivatives, whereas tautomerase II might specialize in other aromatic hydrocarbon metabolites. Copyright © 2013 Elsevier Inc. All rights reserved.
The Convergence of Heat, Groundwater & Fracture Permeability. Innovative Play Fairway Modelling Applied to the Tularosa Basin Phase 1 Project Report

Energy Technology Data Exchange (ETDEWEB)

Bennett, Carlon R. [Ruby Mountain Inc., Salt Lake City, UT (United States); Nash, Gregory D. [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Sorkhabi, Rasoul [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Moore, Joseph [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Simmons, Stuart [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Brandt, Adam [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Barker, Benjamin [Univ. of Utah, Salt Lake City, UT (United States). Energy & Geoscience Institute; Swanson, Brigitte [Ruby Mountain Inc., Salt Lake City, UT (United States)

2015-10-16

This report summarizes the activities and key findings of the project team occurring during Phase 1 (August 2014-October 2015) of the Tularosa Basin Geothermal Play Fairway Analysis Project. The Tularosa Basin Play Fairway Analysis (PFA) project tested two distinct geothermal exploration methodologies covering the entire basin within South Central New Mexico and Far West Texas. Throughout the initial phase of the project, the underexplored basin proved to be a challenging, yet ideal test bed to evaluate effectiveness of the team’s data collection techniques as well as the effectiveness of our innovative PFA. Phase 1 of the effort employed a low-cost, pragmatic approach using two methods to identify potential geothermal plays within the study area and then compared and contrasted the results of each method to rank and evaluate potential plays. Both methods appear to be very effective and highly transferable to other areas.
Impact of Disease Management Programs on HbA1c Values in Type 2 Diabetes Patients in Germany.

Science.gov (United States)

Kostev, Karel; Rockel, Timo; Jacob, Louis

2017-01-01

The aim was to analyze the impact of disease management programs on HbA1c values in type 2 diabetes mellitus (T2DM) patients in Germany. This study included 9017 patients followed in disease management programs (DMPs) who started an antihyperglycemic treatment upon inclusion in a DMP. Standard care (SC) patients were included after individual matching (1:1) to DMP cases based on age, gender, physician (diabetologist versus nondiabetologist care), HbA1c values at baseline, and index year. The main outcome was the share of patients with HbA1c HbA1c level as a dependent variable and the potential predictor (DMP versus SC). The mean age was 64.3 years and 54.7% of the patients were men. The mean HbA1c level at baseline was equal to 8.7%. In diabetologist practices, 64.7% of DMP patients and 55.1% of SC patients had HbA1c levels HbA1c levels HbA1c levels HbA1c levels HbA1c levels lower than 7.5% or 6.5% after 6 months of therapy in both diabetologist and general care practices. The present study indicates that the enrollment of T2DM patients in DMPs has a positive impact on HbA1c values in Germany.
IGF-1/IGF-1R/hsa-let-7c axis regulates the committed differentiation of stem cells from apical papilla

Science.gov (United States)

Ma, Shu; Liu, Genxia; Jin, Lin; Pang, Xiyao; Wang, Yanqiu; Wang, Zilu; Yu, Yan; Yu, Jinhua

2016-01-01

Insulin-like growth factor-1 (IGF-1) and its receptor IGF-1R play a paramount role in tooth/bone formation while hsa-let-7c actively participates in the osteogenic differentiation of mesenchymal stem cells. However, the interaction between IGF-1/IGF-1R and hsa-let-7c on the committed differentiation of stem cells from apical papilla (SCAPs) remains unclear. In this study, human SCAPs were isolated and treated with IGF-1 and hsa-let-7c over/low-expression viruses. The odonto/osteogenic differentiation of these stem cells and the involvement of mitogen-activated protein kinase (MAPK) pathway were subsequently investigated. Alizarin red staining showed that hsa-let-7c low-expression can significantly promote the mineralization of IGF-1 treated SCAPs, while hsa-let-7c over-expression can decrease the calcium deposition of IGF-1 treated SCAPs. Western blot assay and real-time reverse transcription polymerase chain reaction further demonstrated that the expression of odonto/osteogenic markers (ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, COL-I/COL-I, DSPP/DSP, and DMP-1/DMP-1) in IGF-1 treated SCAPs were significantly upregulated in Let-7c-low group. On the contrary, hsa-let-7c over-expression could downregulate the expression of these odonto/osteogenic markers. Moreover, western blot assay showed that the JNK and p38 MAPK signaling pathways were activated in Let-7c-low SCAPs but inhibited in Let-7c-over SCAPs. Together, the IGF-1/IGF-1R/hsa-let-7c axis can control the odonto/osteogenic differentiation of IGF-1-treated SCAPs via the regulation of JNK and p38 MAPK signaling pathways. PMID:27833148
Data management plan for the Oak Ridge Environmental Information System, Version 1. 1

Energy Technology Data Exchange (ETDEWEB)

1992-08-04

The Data Management Plan (DMP) describes the data management objectives, system components, data base structure and contents, system maintenance, data processing, and user interface for the prototype phase of the Oak Ridge Environmental Information System (OREIS). The major goals of OREIS data management are to compile data of known quality, to maintain the integrity of the data base, and to provide data to users. The DMP defines the requirements, describes the responsibilities, and references the procedures for meeting the data management objectives. Emphasis is on management of measurement data and the associated metadata used to support its proper interpretation and legal defensibility. The DMP covers transmittal, processing, storage, and data access activities associated with OREIS. The OREIS data dictionary is provided as an appendix.
Data management plan for the Oak Ridge Environmental Information System, Version 1.1

International Nuclear Information System (INIS)

1992-01-01

The Data Management Plan (DMP) describes the data management objectives, system components, data base structure and contents, system maintenance, data processing, and user interface for the prototype phase of the Oak Ridge Environmental Information System (OREIS). The major goals of OREIS data management are to compile data of known quality, to maintain the integrity of the data base, and to provide data to users. The DMP defines the requirements, describes the responsibilities, and references the procedures for meeting the data management objectives. Emphasis is on management of measurement data and the associated metadata used to support its proper interpretation and legal defensibility. The DMP covers transmittal, processing, storage, and data access activities associated with OREIS. The OREIS data dictionary is provided as an appendix
Why do adult dogs 'play'?

Science.gov (United States)

Bradshaw, John W S; Pullen, Anne J; Rooney, Nicola J

2015-01-01

Among the Carnivora, play behaviour is usually made up of motor patterns characteristic of predatory, agonistic and courtship behaviour. Domestic dogs are unusual in that play is routinely performed by adults, both socially, with conspecifics and with humans, and also asocially, with objects. This enhanced playfulness is commonly thought to be a side effect of paedomorphosis, the perpetuation of juvenile traits into adulthood, but here we suggest that the functions of the different types of play are sufficiently distinct that they are unlikely to have arisen through a single evolutionary mechanism. Solitary play with objects appears to be derived from predatory behaviour: preferred toys are those that can be dismembered, and a complex habituation-like feedback system inhibits play with objects that are resistant to alteration. Intraspecific social play is structurally different from interspecific play and may therefore be motivationally distinct and serve different goals; for example, dogs often compete over objects when playing with other dogs, but are usually more cooperative when the play partner is human. The majority of dogs do not seem to regard competitive games played with a human partner as "dominance" contests: rather, winning possession of objects during games appears to be simply rewarding. Play may be an important factor in sociality, since dogs are capable of extracting social information not only from games in which they participate, but also from games that they observe between third parties. We suggest that the domestic dog's characteristic playfulness in social contexts is an adaptive trait, selected during domestication to facilitate both training for specific purposes, and the formation of emotionally-based bonds between dog and owner. Play frequency and form may therefore be an indicator of the quality of dog-owner relationships. Copyright © 2014 Elsevier B.V. All rights reserved.
MHF1-2/CENP-S-X performs distinct roles in centromere metabolism and genetic recombination.

Science.gov (United States)

Bhattacharjee, Sonali; Osman, Fekret; Feeney, Laura; Lorenz, Alexander; Bryer, Claire; Whitby, Matthew C

2013-09-11

The histone-fold proteins Mhf1/CENP-S and Mhf2/CENP-X perform two important functions in vertebrate cells. First, they are components of the constitutive centromere-associated network, aiding kinetochore assembly and function. Second, they work with the FANCM DNA translocase to promote DNA repair. However, it has been unclear whether there is crosstalk between these roles. We show that Mhf1 and Mhf2 in fission yeast, as in vertebrates, serve a dual function, aiding DNA repair/recombination and localizing to centromeres to promote chromosome segregation. Importantly, these functions are distinct, with the former being dependent on their interaction with the FANCM orthologue Fml1 and the latter not. Together with Fml1, they play a second role in aiding chromosome segregation by processing sister chromatid junctions. However, a failure of this activity does not manifest dramatically increased levels of chromosome missegregation due to the Mus81-Eme1 endonuclease, which acts as a failsafe to resolve DNA junctions before the end of mitosis.
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.
Data management plan for the Oak Ridge Environmental Information System, Version 1.1. Enviornmental Restoration Program

Energy Technology Data Exchange (ETDEWEB)

1992-08-04

The Data Management Plan (DMP) describes the data management objectives, system components, data base structure and contents, system maintenance, data processing, and user interface for the prototype phase of the Oak Ridge Environmental Information System (OREIS). The major goals of OREIS data management are to compile data of known quality, to maintain the integrity of the data base, and to provide data to users. The DMP defines the requirements, describes the responsibilities, and references the procedures for meeting the data management objectives. Emphasis is on management of measurement data and the associated metadata used to support its proper interpretation and legal defensibility. The DMP covers transmittal, processing, storage, and data access activities associated with OREIS. The OREIS data dictionary is provided as an appendix.
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
Are medical treatments for individuals and groups like single-play and multiple-play gambles?

Directory of Open Access Journals (Sweden)

Michael L. DeKay

2006-11-01

Full Text Available People are often more likely to accept risky monetary gambles with positive expected values when the gambles will be played more than once. We investigated whether this distinction between single-play and multiple-play gambles extends to medical treatments for individual patients and groups of patients. Resident physicians and medical students (extit{n} = 69 and undergraduates (extit{n} = 99 ranked 9 different flu shots and a no-flu-shot option in 1 of 4 combinations of perspective (individual patient vs. group of 1000 patients and uncertainty frame (probability vs. frequency. The rank of the no-flu-shot option (a measure of preference for treatment vs. no treatment was not significantly related to perspective or participant population. The main effect of uncertainty frame and the interaction between perspective and uncertainty frame approached significance (0.1 {extgreater} extit{p} {extgreater} 0.05, with the no-flu-shot option faring particularly poorly (treatment faring particularly well when decisions about many patients were based on frequency information. Undergraduate participants believed that the no-flu-shot option would be less attractive (treatment would be more attractive in decisions about many patients, but these intuitions were inconsistent with the actual ranks. These results and those of other studies suggest that medical treatments for individuals and groups are not analogous to single-play and multiple-play monetary gambles, perhaps because many people are unwilling to aggregate treatment outcomes over patients in the same way that they would compute net gains or losses over monetary gambles.
Curing behaviors and properties of an extrinsic toughened epoxy/anhydride system and an intrinsic toughened epoxy/anhydride system

International Nuclear Information System (INIS)

Fan, Mengjin; Liu, Jialin; Li, Xiangyuan; Cheng, Jue; Zhang, Junying

2013-01-01

Highlights: ► Two curing systems (ETRS and ITRS) with similar chemical composite were prepared. ► The curing kinetics of the ETRS and the novel ITRS were comparatively studied. ► Crosslinking density can affect the kinetic schemes of the two curing systems. ► Their mechanical properties and thermal stabilities were also comparatively studied. ► Crosslinking density may play an influential role in mechanical properties. - Abstract: The curing kinetics of an extrinsic toughened epoxy (mixture of diglycidyl ether of bisphenol-A and 1,4-butanediol epoxy resin, DGEBA/DGEBD) and an intrinsic toughened epoxy (ethoxylated bisphenol-A epoxy resin with two oxyethylene units, DGEBAEO-2) using hexahydrophthalic anhydride (HHPA) as curing agent and tris-(dimethylaminomethyl) phenol (DMP-30) as accelerator were comparatively studied by non-isothermal DSC with a model-fitting Málek approach and a model-free advanced isoconversional method of Vyazovkin. The dynamic mechanical properties and thermal stabilities of the cured materials were investigated by DMTA and TGA, respectively. The results showed that Šesták–Berggren model can generally simulate well the reaction rates of these two systems. The activation energy of DGEBA/DGEBD/HHPA/DMP-30 at high fractional conversion changed much higher than that of DGEBAEO-2/HHPA/DMP-30, indicating the increased steric hindrance mainly affected the reaction kinetic scheme of DGEBA/DGEBD/HHPA/DMP-30. The T g and storage moduli of cured DGEBAEO-2/HHPA/DMP-30 were lower than those of cured DGEBA/DGEBD/HHPA/DMP-30 according to DMTA while TGA showed that the thermal stabilities of these two cured systems were similar
Curing behaviors and properties of an extrinsic toughened epoxy/anhydride system and an intrinsic toughened epoxy/anhydride system

Energy Technology Data Exchange (ETDEWEB)

Fan, Mengjin; Liu, Jialin; Li, Xiangyuan [Key Laboratory of Carbon Fiber and Functional Polymers, Ministry of Education, Beijing University of Chemical Technology, Beijing 100029 (China); Cheng, Jue, E-mail: chengjue@mail.buct.edu.cn [Key Laboratory of Carbon Fiber and Functional Polymers, Ministry of Education, Beijing University of Chemical Technology, Beijing 100029 (China); Zhang, Junying, E-mail: zjybuct@gmail.com [Key Laboratory of Carbon Fiber and Functional Polymers, Ministry of Education, Beijing University of Chemical Technology, Beijing 100029 (China)

2013-02-20

Highlights: ► Two curing systems (ETRS and ITRS) with similar chemical composite were prepared. ► The curing kinetics of the ETRS and the novel ITRS were comparatively studied. ► Crosslinking density can affect the kinetic schemes of the two curing systems. ► Their mechanical properties and thermal stabilities were also comparatively studied. ► Crosslinking density may play an influential role in mechanical properties. - Abstract: The curing kinetics of an extrinsic toughened epoxy (mixture of diglycidyl ether of bisphenol-A and 1,4-butanediol epoxy resin, DGEBA/DGEBD) and an intrinsic toughened epoxy (ethoxylated bisphenol-A epoxy resin with two oxyethylene units, DGEBAEO-2) using hexahydrophthalic anhydride (HHPA) as curing agent and tris-(dimethylaminomethyl) phenol (DMP-30) as accelerator were comparatively studied by non-isothermal DSC with a model-fitting Málek approach and a model-free advanced isoconversional method of Vyazovkin. The dynamic mechanical properties and thermal stabilities of the cured materials were investigated by DMTA and TGA, respectively. The results showed that Šesták–Berggren model can generally simulate well the reaction rates of these two systems. The activation energy of DGEBA/DGEBD/HHPA/DMP-30 at high fractional conversion changed much higher than that of DGEBAEO-2/HHPA/DMP-30, indicating the increased steric hindrance mainly affected the reaction kinetic scheme of DGEBA/DGEBD/HHPA/DMP-30. The T{sub g} and storage moduli of cured DGEBAEO-2/HHPA/DMP-30 were lower than those of cured DGEBA/DGEBD/HHPA/DMP-30 according to DMTA while TGA showed that the thermal stabilities of these two cured systems were similar.

The two Na+ sites in the human serotonin transporter play distinct roles in the ion coupling and electrogenicity of transport.

Science.gov (United States)

Felts, Bruce; Pramod, Akula Bala; Sandtner, Walter; Burbach, Nathan; Bulling, Simon; Sitte, Harald H; Henry, L Keith

2014-01-17

Neurotransmitter transporters of the SLC6 family of proteins, including the human serotonin transporter (hSERT), utilize Na(+), Cl(-), and K(+) gradients to induce conformational changes necessary for substrate translocation. Dysregulation of ion movement through monoamine transporters has been shown to impact neuronal firing potentials and could play a role in pathophysiologies, such as depression and anxiety. Despite multiple crystal structures of prokaryotic and eukaryotic SLC transporters indicating the location of both (or one) conserved Na(+)-binding sites (termed Na1 and Na2), much remains uncertain in regard to the movements and contributions of these cation-binding sites in the transport process. In this study, we utilize the unique properties of a mutation of hSERT at a single, highly conserved asparagine on TM1 (Asn-101) to provide several lines of evidence demonstrating mechanistically distinct roles for Na1 and Na2. Mutations at Asn-101 alter the cation dependence of the transporter, allowing Ca(2+) (but not other cations) to functionally replace Na(+) for driving transport and promoting 5-hydroxytryptamine (5-HT)-dependent conformational changes. Furthermore, in two-electrode voltage clamp studies in Xenopus oocytes, both Ca(2+) and Na(+) illicit 5-HT-induced currents in the Asn-101 mutants and reveal that, although Ca(2+) promotes substrate-induced current, it does not appear to be the charge carrier during 5-HT transport. These findings, in addition to functional evaluation of Na1 and Na2 site mutants, reveal separate roles for Na1 and Na2 and provide insight into initiation of the translocation process as well as a mechanism whereby the reported SERT stoichiometry can be obtained despite the presence of two putative Na(+)-binding sites.
The Two Na+ Sites in the Human Serotonin Transporter Play Distinct Roles in the Ion Coupling and Electrogenicity of Transport*

Science.gov (United States)

Felts, Bruce; Pramod, Akula Bala; Sandtner, Walter; Burbach, Nathan; Bulling, Simon; Sitte, Harald H.; Henry, L. Keith

2014-01-01

Neurotransmitter transporters of the SLC6 family of proteins, including the human serotonin transporter (hSERT), utilize Na+, Cl−, and K+ gradients to induce conformational changes necessary for substrate translocation. Dysregulation of ion movement through monoamine transporters has been shown to impact neuronal firing potentials and could play a role in pathophysiologies, such as depression and anxiety. Despite multiple crystal structures of prokaryotic and eukaryotic SLC transporters indicating the location of both (or one) conserved Na+-binding sites (termed Na1 and Na2), much remains uncertain in regard to the movements and contributions of these cation-binding sites in the transport process. In this study, we utilize the unique properties of a mutation of hSERT at a single, highly conserved asparagine on TM1 (Asn-101) to provide several lines of evidence demonstrating mechanistically distinct roles for Na1 and Na2. Mutations at Asn-101 alter the cation dependence of the transporter, allowing Ca2+ (but not other cations) to functionally replace Na+ for driving transport and promoting 5-hydroxytryptamine (5-HT)-dependent conformational changes. Furthermore, in two-electrode voltage clamp studies in Xenopus oocytes, both Ca2+ and Na+ illicit 5-HT-induced currents in the Asn-101 mutants and reveal that, although Ca2+ promotes substrate-induced current, it does not appear to be the charge carrier during 5-HT transport. These findings, in addition to functional evaluation of Na1 and Na2 site mutants, reveal separate roles for Na1 and Na2 and provide insight into initiation of the translocation process as well as a mechanism whereby the reported SERT stoichiometry can be obtained despite the presence of two putative Na+-binding sites. PMID:24293367
The Aurora Kinase in Trypanosoma brucei plays distinctive roles in metaphase-anaphase transition and cytokinetic initiation.

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Ziyin Li

2009-09-01

Full Text Available Aurora B kinase is an essential regulator of chromosome segregation with the action well characterized in eukaryotes. It is also implicated in cytokinesis, but the detailed mechanism remains less clear, partly due to the difficulty in separating the latter from the former function in a growing cell. A chemical genetic approach with an inhibitor of the enzyme added to a synchronized cell population at different stages of the cell cycle would probably solve this problem. In the deeply branched parasitic protozoan Trypanosoma brucei, an Aurora B homolog, TbAUK1, was found to control both chromosome segregation and cytokinetic initiation by evidence from RNAi and dominant negative mutation. To clearly separate these two functions, VX-680, an inhibitor of TbAUK1, was added to a synchronized T. brucei procyclic cell population at different cell cycle stages. The unique trans-localization pattern of the chromosomal passenger complex (CPC, consisting of TbAUK1 and two novel proteins TbCPC1 and TbCPC2, was monitored during mitosis and cytokinesis by following the migration of the proteins tagged with enhanced yellow fluorescence protein in live cells with time-lapse video microscopy. Inhibition of TbAUK1 function in S-phase, prophase or metaphase invariably arrests the cells in the metaphase, suggesting an action of TbAUK1 in promoting metaphase-anaphase transition. TbAUK1 inhibition in anaphase does not affect mitotic exit, but prevents trans-localization of the CPC from the spindle midzone to the anterior tip of the new flagellum attachment zone for cytokinetic initiation. The CPC in the midzone is dispersed back to the two segregated nuclei, while cytokinesis is inhibited. In and beyond telophase, TbAUK1 inhibition has no effect on the progression of cytokinesis or the subsequent G1, S and G2 phases until a new metaphase is attained. There are thus two clearly distinct points of TbAUK1 action in T. brucei: the metaphase-anaphase transition and
β1-adrenergic receptors activate two distinct signaling pathways in striatal neurons

Science.gov (United States)

Meitzen, John; Luoma, Jessie I.; Stern, Christopher M.; Mermelstein, Paul G.

2010-01-01

Monoamine action in the dorsal striatum and nucleus accumbens plays essential roles in striatal physiology. Although research often focuses on dopamine and its receptors, norepinephrine and adrenergic receptors are also crucial in regulating striatal function. While noradrenergic neurotransmission has been identified in the striatum, little is known regarding the signaling pathways activated by β-adrenergic receptors in this brain region. Using cultured striatal neurons, we characterized a novel signaling pathway by which activation of β1-adrenergic receptors leads to the rapid phosphorylation of cAMP Response Element Binding Protein (CREB), a transcription-factor implicated as a molecular switch underlying long-term changes in brain function. Norepinephrine-mediated CREB phosphorylation requires β1-adrenergic receptor stimulation of a receptor tyrosine kinase, ultimately leading to the activation of a Ras/Raf/MEK/MAPK/MSK signaling pathway. Activation of β1-adrenergic receptors also induces CRE-dependent transcription and increased c-fos expression. In addition, stimulation of β1-adrenergic receptors produces cAMP production, but surprisingly, β1-adrenergic receptor activation of adenylyl cyclase was not functionally linked to rapid CREB phosphorylation. These findings demonstrate that activation of β1-adrenergic receptors on striatal neurons can stimulate two distinct signaling pathways. These adrenergic actions can produce long-term changes in gene expression, as well as rapidly modulate cellular physiology. By elucidating the mechanisms by which norepinephrine and β1-adrenergic receptor activation affects striatal physiology, we provide the means to more fully understand the role of monoamines in modulating striatal function, specifically how norepinephrine and β1-adrenergic receptors may affect striatal physiology. PMID:21143600
Isl1 expression at the venous pole identifies a novel role for the second heart field in cardiac development.

Science.gov (United States)

Snarr, Brian S; O'Neal, Jessica L; Chintalapudi, Mastan R; Wirrig, Elaine E; Phelps, Aimee L; Kubalak, Steven W; Wessels, Andy

2007-11-09

The right ventricle and outflow tract of the developing heart are derived from mesodermal progenitor cells from the second heart field (SHF). SHF cells have been characterized by expression of the transcription factor Islet-1 (Isl1). Although Isl1 expression has also been reported in the venous pole, the specific contribution of the SHF to this part of the heart is unknown. Here we show that Isl1 is strongly expressed in the dorsal mesenchymal protrusion (DMP), a non-endocardially-derived mesenchymal structure involved in atrioventricular septation. We further demonstrate that abnormal development of the SHF-derived DMP is associated with the pathogenesis of atrioventricular septal defects. These results identify a novel role for the SHF.
Better lipid target achievement for secondary prevention through disease management programs for diabetes mellitus and coronary heart disease in clinical practice in Germany.

Science.gov (United States)

Gitt, Anselm K; Sonntag, Frank; Jannowitz, Christina; Weizel, Achim; Karmann, Barbara; Schaefer, Juergen R; Pittrow, David; Hildemann, Steven K

2016-01-01

Disease management programs (DMP) for diabetes mellitus (DM) or coronary heart disease (CHD) address the treatment of lipid disorders. The current registry aimed to compare drug utilization, lipid lowering effects and further outcomes of outpatients at high cardiovascular risk in DMP for DM or CHD compared to patients in routine care (no-DMP). This was a prospective non-interventional registry with a 1 year follow-up which enrolled consecutive patients with known DM and/or any vascular disease on simvastatin 40 mg monotherapy, to document lipid target achievement in clinical practice in Germany according to existing guidelines. Drug use (maintenance, add-on, switch, discontinuation) and other components of care were upon the discretion of the treating physician. Of a total of 12,154 patients (mean age 65.8 years, 61.2% males), 3273 were in DMP CHD, 3265 in DMP DM and 1760 in DMP CHD + DM. In DMP patients compared to no-DMP patients, comorbidities/risk factors were more frequent. More patients in the DMP groups attained the target level of low density lipoprotein (LDL-C) <70 mg/dl (1.8 mmol/l) at baseline (8.5% DMP vs. 5.7% no-DMP), at 6 month (10.3% vs. 7.4%) and 12 month follow-up (10.1% vs. 7.1%). Cholesterol absorption inhibitors were added in 16% of the patients at the end of the baseline or at the follow-up visits, while statin treatment (including mean dose) remained largely unchanged. Target achievement rates were highest for all time points in the DMP CHD + DM group. With respect to limitations, this study was restricted to lipid disorders as qualifying diagnosis and simvastatin as qualifying treatment, which is a potential cause of selection bias. Information on non-pharmacological measures was not collected, and the 12-month follow-up period was relatively short. Patients in DMP compared to those not in DMP achieved better LDL-C lowering and higher control rates, but overall lipid target achievement rates need to be improved. Longer
Data Management Plan

DEFF Research Database (Denmark)

Hansen, Ernst Jan de Place; Vogelsang, Stefan; Freudenberg, Peggy

2015-01-01

This document describes the Data Management Plan (DMP) (first version), relating to RIBuild WP8, deliverable D8.1. The DMP include description of data sets, standards and metadata, data sharing and archiving and preservation of data.......This document describes the Data Management Plan (DMP) (first version), relating to RIBuild WP8, deliverable D8.1. The DMP include description of data sets, standards and metadata, data sharing and archiving and preservation of data....
Is there a survival benefit within a German primary care-based disease management program?

Science.gov (United States)

Miksch, Antje; Laux, Gunter; Ose, Dominik; Joos, Stefanie; Campbell, Stephen; Riens, Burgi; Szecsenyi, Joachim

2010-01-01

To compare the mortality rate of patients with type 2 diabetes who were enrolled in the German diabetes disease management program (DMP) with the mortality rate of those who were not enrolled. This observational study was part of the ELSID study (Evaluation of a Large Scale Implementation of disease management programs) in Germany. Participants had type 2 diabetes and were either enrolled or not enrolled in the DMP. The DMP provides systems-based, multifaceted, and patient-centered interventions. To reduce imbalances between the groups, a matched sample was created using sex, age, retirement status, federal state, pharmacy-based cost groups, and diagnostic-cost groups as matching criteria. Cox proportional hazards regression model and the Kaplan-Meier method were used to assess overall mortality. The observation period was 3 years beginning on January 1, 2006. A total of 11,079 patients were included in the analysis. As of January 1, 2006, 2300 patients were enrolled in the DMP and 8779 were receiving routine care. There were 1927 matched pairs of patients in the DMP group and the non-DMP group. The overall mortality rate was 11.3% in the DMP and 14.4% in the non-DMP group (log-rank test P German diabetes DMP and reduced mortality. This reduced mortality cannot be attributed directly to the DMP. However, further research should evaluate whether a primary care-based DMP contributes to increased life expectancy in patients with diabetes.
TET1 knockdown inhibits the odontogenic differentiation potential of human dental pulp cells.

Science.gov (United States)

Rao, Li-Jia; Yi, Bai-Cheng; Li, Qi-Meng; Xu, Qiong

2016-06-30

Human dental pulp cells (hDPCs) possess the capacity to differentiate into odontoblast-like cells and generate reparative dentin in response to exogenous stimuli or injury. Ten-eleven translocation 1 (TET1) is a novel DNA methyldioxygenase that plays an important role in the promotion of DNA demethylation and transcriptional regulation in several cell lines. However, the role of TET1 in the biological functions of hDPCs is unknown. To investigate the effect of TET1 on the proliferation and odontogenic differentiation potential of hDPCs, a recombinant shRNA lentiviral vector was used to knock down TET1 expression in hDPCs. Following TET1 knockdown, TET1 was significantly downregulated at both the mRNA and protein levels. Proliferation of the hDPCs was suppressed in the TET1 knockdown groups. Alkaline phosphatase activity, the formation of mineralized nodules, and the expression levels of DSPP and DMP1 were all reduced in the TET1-knockdown hDPCs undergoing odontogenic differentiation. Based on these results, we concluded that TET1 knockdown can prevent the proliferation and odontogenic differentiation of hDPCs, which suggests that TET1 may play an important role in dental pulp repair and regeneration.
The two different isoforms of the RSC chromatin remodeling complex play distinct roles in DNA damage responses.

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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.
Distinct regulatory functions of calpain 1 and 2 during neural stem cell self-renewal and differentiation.

Directory of Open Access Journals (Sweden)

Daniela M Santos

Full Text Available Calpains are calcium regulated cysteine proteases that have been described in a wide range of cellular processes, including apoptosis, migration and cell cycle regulation. In addition, calpains have been implicated in differentiation, but their impact on neural differentiation requires further investigation. Here, we addressed the role of calpain 1 and calpain 2 in neural stem cell (NSC self-renewal and differentiation. We found that calpain inhibition using either the chemical inhibitor calpeptin or the endogenous calpain inhibitor calpastatin favored differentiation of NSCs. This effect was associated with significant changes in cell cycle-related proteins and may be regulated by calcium. Interestingly, calpain 1 and calpain 2 were found to play distinct roles in NSC fate decision. Calpain 1 expression levels were higher in self-renewing NSC and decreased with differentiation, while calpain 2 increased throughout differentiation. In addition, calpain 1 silencing resulted in increased levels of both neuronal and glial markers, β-III Tubulin and glial fibrillary acidic protein (GFAP. Calpain 2 silencing elicited decreased levels of GFAP. These results support a role for calpain 1 in repressing differentiation, thus maintaining a proliferative NSC pool, and suggest that calpain 2 is involved in glial differentiation.
Where do the children play? The influence of playground equipment on physical activity of children in free play.

Science.gov (United States)

Farley, Thomas A; Meriwether, Rebecca A; Baker, Erin T; Rice, Janet C; Webber, Larry S

2008-03-01

Promotion of physical activity in children depends on an understanding of how children use play equipment. We conducted observations over 2 years of children in 2nd through 8th grades in a schoolyard with 5 distinct play areas with different amounts of play equipment. Children were more likely to play in areas with more installed play equipment, with densities of children in equipped areas 3.3 to 12.6 times higher than in an open grassy field. There were no significant differences by play area in the percent of children who were physically active at all, but children were more likely to be very active in areas with basketball goals and an installed play structure than in an open field. Playground equipment appeared to have a strong influence on where children played and a moderate influence on levels of activity. To maximize physical activity in children, playgrounds should be designed with ample and diverse play equipment.
Dmp53, basket and drICE gene knockdown and polyphenol gallic acid increase life span and locomotor activity in a Drosophila Parkinson's disease model

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Hector Flavio Ortega-Arellano

2013-01-01

Full Text Available Understanding the mechanism(s by which dopaminergic (DAergic neurons are eroded in Parkinson's disease (PD is critical for effective therapeutic strategies. By using the binary tyrosine hydroxylase (TH-Gal4/UAS-X RNAi Drosophila melanogaster system, we report that Dmp53, basket and drICE gene knockdown in dopaminergic neurons prolong life span (p < 0.05; log-rank test and locomotor activity (p < 0.05; χ² test in D. melanogaster lines chronically exposed to (1 mM paraquat (PQ, oxidative stress (OS generator compared to untreated transgenic fly lines. Likewise, knockdown flies displayed higher climbing performance than control flies. Amazingly, gallic acid (GA significantly protected DAergic neurons, ameliorated life span, and climbing abilities in knockdown fly lines treated with PQ compared to flies treated with PQ only. Therefore, silencing specific gene(s involved in neuronal death might constitute an excellent tool to study the response of DAergic neurons to OS stimuli. We propose that a therapy with antioxidants and selectively "switching off" death genes in DAergic neurons could provide a means for pre-clinical PD individuals to significantly ameliorate their disease condition.
Rumen-protected lysine, methionine, and histidine increase milk protein yield in dairy cows fed a metabolizable protein-deficient diet.

Science.gov (United States)

Lee, C; Hristov, A N; Cassidy, T W; Heyler, K S; Lapierre, H; Varga, G A; de Veth, M J; Patton, R A; Parys, C

2012-10-01

The objective of this experiment was to evaluate the effect of supplementing a metabolizable protein (MP)-deficient diet with rumen-protected (RP) Lys, Met, and specifically His on dairy cow performance. The experiment was conducted for 12 wk with 48 Holstein cows. Following a 2-wk covariate period, cows were blocked by DIM and milk yield and randomly assigned to 1 of 4 diets, based on corn silage and alfalfa haylage: control, MP-adequate diet (ADMP; MP balance: +9 g/d); MP-deficient diet (DMP; MP balance: -317 g/d); DMP supplemented with RPLys (AminoShure-L, Balchem Corp., New Hampton, NY) and RPMet (Mepron; Evonik Industries AG, Hanau, Germany; DMPLM); and DMPLM supplemented with an experimental RPHis preparation (DMPLMH). The analyzed crude protein content of the ADMP and DMP diets was 15.7 and 13.5 to 13.6%, respectively. The apparent total-tract digestibility of all measured nutrients, plasma urea-N, and urinary N excretion were decreased by the DMP diets compared with ADMP. Milk N secretion as a proportion of N intake was greater for the DMP diets compared with ADMP. Compared with ADMP, dry matter intake (DMI) tended to be lower for DMP, but was similar for DMPLM and DMPLMH (24.5, 23.0, 23.7, and 24.3 kg/d, respectively). Milk yield was decreased by DMP (35.2 kg/d), but was similar to ADMP (38.8 kg/d) for DMPLM and DMPLMH (36.9 and 38.5kg/d, respectively), paralleling the trend in DMI. The National Research Council 2001model underpredicted milk yield of the DMP cows by an average (±SE) of 10.3 ± 0.75 kg/d. Milk fat and true protein content did not differ among treatments, but milk protein yield was increased by DMPLM and DMPLMH compared with DMP and was not different from ADMP. Plasma essential amino acids (AA), Lys, and His were lower for DMP compared with ADMP. Supplementation of the DMP diets with RP AA increased plasma Lys, Met, and His. In conclusion, MP deficiency, approximately 15% below the National Research Council requirements from 2001, decreased
Exome sequencing identifies mutations in ABCD1 and DACH2 in two brothers with a distinct phenotype.

Science.gov (United States)

Zhang, Yanliang; Liu, Yanhui; Li, Ya; Duan, Yong; Zhang, Keyun; Wang, Junwang; Dai, Yong

2014-09-19

We report on two brothers with a distinct syndromic phenotype and explore the potential pathogenic cause. Cytogenetic tests and exome sequencing were performed on the two brothers and their parents. Variants detected by exome sequencing were validated by Sanger sequencing. The main phenotype of the two brothers included congenital language disorder, growth retardation, intellectual disability, difficulty in standing and walking, and urinary and fecal incontinence. To the best of our knowledge, no similar phenotype has been reported previously. No abnormalities were detected by G-banding chromosome analysis or array comparative genomic hybridization. However, exome sequencing revealed novel mutations in the ATP-binding cassette, sub-family D member 1 (ABCD1) and Dachshund homolog 2 (DACH2) genes in both brothers. The ABCD1 mutation was a missense mutation c.1126G > C in exon 3 leading to a p.E376Q substitution. The DACH2 mutation was also a missense mutation c.1069A > T in exon 6, leading to a p.S357C substitution. The mother was an asymptomatic heterozygous carrier. Plasma levels of very-long-chain fatty acids were increased in both brothers, suggesting a diagnosis of adrenoleukodystrophy (ALD); however, their phenotype was not compatible with any reported forms of ALD. DACH2 plays an important role in the regulation of brain and limb development, suggesting that this mutation may be involved in the phenotype of the two brothers. The distinct phenotype demonstrated by these two brothers might represent a new form of ALD or a new syndrome. The combination of mutations in ABCD1 and DACH2 provides a plausible mechanism for this phenotype.
30 CFR 75.1720-1 - Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced...

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Distinctively colored hard hats, or hard caps... STANDARDS-UNDERGROUND COAL MINES Miscellaneous § 75.1720-1 Distinctively colored hard hats, or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color...
Ire1 Has Distinct Catalytic Mechanisms for XBP1/HAC1 Splicing and RIDD

Directory of Open Access Journals (Sweden)

Arvin B. Tam

2014-11-01

Full Text Available An evolutionarily conserved unfolded protein response (UPR component, IRE1, cleaves XBP1/HAC1 introns in order to generate spliced mRNAs that are translated into potent transcription factors. IRE1 also cleaves endoplasmic-reticulum-associated RNAs leading to their decay, an activity termed regulated IRE1-dependent decay (RIDD; however, the mechanism by which IRE1 differentiates intron cleavage from RIDD is not well understood. Using in vitro experiments, we found that IRE1 has two different modes of action: XBP1/HAC1 is cleaved by IRE1 subunits acting cooperatively within IRE1 oligomers, whereas a single subunit of IRE1 performs RIDD without cooperativity. Furthermore, these distinct activities can be separated by complementation of catalytically inactive IRE1 RNase and mutations at oligomerization interfaces. Using an IRE1 RNase inhibitor, STF-083010, selective inhibition of XBP1 splicing indicates that XBP1 promotes cell survival, whereas RIDD leads to cell death, revealing modulation of IRE1 activities as a drug-development strategy.
Motivations to play specifically predict excessive involvement in massively multiplayer online role-playing games: evidence from an online survey.

Science.gov (United States)

Zanetta Dauriat, Francesca; Zermatten, Ariane; Billieux, Joël; Thorens, Gabriel; Bondolfi, Guido; Zullino, Daniele; Khazaal, Yasser

2011-01-01

Several studies have linked massively multiplayer online role-playing games (MMORPGs) with possible problematic usage or internet addiction. The main goal of the present study was to assess links between motivations to play in MMORPGs and addictive involvement in such types of games. A total of 696 gamers responded to an online survey. Five distinct motivations to play were identified in gamers: achievement, socializing, immersion, relaxing and escaping. Multiple regression analysis revealed that addictive MMORPG use patterns are predicted by achievement, escapism and socializing motives. Gender was also a significant predictor of problematic involvement in MMORPGs. Moreover, addictive MMORPG use positively correlated with the weekly time devoted to playing MMORPGs. Copyright © 2011 S. Karger AG, Basel.
Multiple Hfq-Crc target sites are required to impose catabolite repression on (methyl)phenol metabolism in Pseudomonas putida CF600.

Science.gov (United States)

Wirebrand, Lisa; Madhushani, Anjana W K; Irie, Yasuhiko; Shingler, Victoria

2018-01-01

The dmp-system encoded on the IncP-2 pVI150 plasmid of Pseudomonas putida CF600 confers the ability to assimilate (methyl)phenols. Regulation of the dmp-genes is subject to sophisticated control, which includes global regulatory input to subvert expression of the pathway in the presence of preferred carbon sources. Previously we have shown that in P. putida, translational inhibition exerted by the carbon repression control protein Crc operates hand-in-hand with the RNA chaperon protein Hfq to reduce translation of the DmpR regulator of the Dmp-pathway. Here, we show that Crc and Hfq co-target four additional sites to form riboprotein complexes within the proximity of the translational initiation sites of genes encoding the first two steps of the Dmp-pathway to mediate two-layered control in the face of selection of preferred substrates. Furthermore, we present evidence that Crc plays a hitherto unsuspected role in maintaining the pVI150 plasmid within a bacterial population, which has implications for (methyl)phenol degradation and a wide variety of other physiological processes encoded by the IncP-2 group of Pseudomonas-specific mega-plasmids. © 2017 Society for Applied Microbiology and John Wiley & Sons Ltd.
Embriões liofilizados e flocos de Artemia no cultivo pós-larval de Litopenaeus vannamei (Boone, 1931 = Use of freeze-dried embryos and Artemia flakes in the post-larval culture of Litopenaeus vannamei (Boone, 1931

Directory of Open Access Journals (Sweden)

Pedro Hercílio de Oliveira Cavalcante

2008-01-01

Full Text Available O objetivo do estudo foi avaliar o crescimento e sobrevivência de 1pós-larvas de Litopenaeus vannamei que receberam embriões liofilizados (EMB e flocos (FLO de Artemia como suplementos alimentares a uma dieta microparticulada (DMP. Nos tratamentos T1,T2 e T3, os camarões receberam DMP e após 2h, acréscimos de FLO (T1; de EMB (T2; e da mesma DMP, anteriormente, ofertada (T3. No T4, as pós-larvas foram alimentadas com DMP, mas sem suplementações posteriores. Não houve diferença significativa (p > 0,05 na sobrevivência dos camarões após o período experimental de 21 dias. Por outro lado, o ganho de peso absoluto (mg peso seco das pós-larvas, cuja dieta foi suplementada com BEM, foi significativamente superior (p The objective of the study was to evaluate the growth and survival of Litopenaeus vannamei post-larvae fed with freeze-driedembryos and Artemia flakes as feeding supplements to a microparticulate diet (DMP. In treatments T1, T2 and T3, the shrimp were fed with DMP and after 2 hours, received supplements of FLO (T1; EMB (T2; and the same DMP previously offered (T3. In T4,post-larvae were fed with DMP but without additional supplementation. There was no significant difference (p > 0.05 in shrimp survival after the experimental period of 21 days. On the other hand, the absolute weight gain (mg of dry weight of post-larvae whose dietwas supplemented with EMB (T2 was significantly higher (p < 0.05 than growth found in the other experimental groups (T1, T3 and T4. Shrimp fed with DMP and EMB obtained a significantly higher absolute weight gain (6.7 mg than those found in treatments that used DMP and FLO (5.4 mg or DMP alone (5.8 mg in T3 and 5.7 mg in T4. Theseresults underline the nutritional value of freeze-dried Artemia embryos and recommend their inclusion in the post-larval diet of Litopenaeus vannamei.

Data Management and Preservation Planning for Big Science

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Juan Bicarregui

2013-06-01

Full Text Available ‘Big Science’ - that is, science which involves large collaborations with dedicated facilities, and involving large data volumes and multinational investments – is often seen as different when it comes to data management and preservation planning. Big Science handles its data differently from other disciplines and has data management problems that are qualitatively different from other disciplines. In part, these differences arise from the quantities of data involved, but possibly more importantly from the cultural, organisational and technical distinctiveness of these academic cultures. Consequently, the data management systems are typically and rationally bespoke, but this means that the planning for data management and preservation (DMP must also be bespoke.These differences are such that ‘just read and implement the OAIS specification’ is reasonable Data Management and Preservation (DMP advice, but this bald prescription can and should be usefully supported by a methodological ‘toolkit’, including overviews, case-studies and costing models to provide guidance on developing best practice in DMP policy and infrastructure for these projects, as well as considering OAIS validation, audit and cost modelling.In this paper, we build on previous work with the LIGO collaboration to consider the role of DMP planning within these big science scenarios, and discuss how to apply current best practice. We discuss the result of the MaRDI-Gross project (Managing Research Data Infrastructures – Big Science, which has been developing a toolkit to provide guidelines on the application of best practice in DMP planning within big science projects. This is targeted primarily at projects’ engineering managers, but intending also to help funders collaborate on DMP plans which satisfy the requirements imposed on them.
Essential and distinct roles of the F-box and helicase domains of Fbh1 in DNA damage repair

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Shinagawa Hideo

2008-03-01

Full Text Available Abstract Background DNA double-strand breaks (DSBs are induced by exogenous insults such as ionizing radiation and chemical exposure, and they can also arise as a consequence of stalled or collapsed DNA replication forks. Failure to repair DSBs can lead to genomic instability or cell death and cancer in higher eukaryotes. The Schizosaccharomyces pombe fbh1 gene encodes an F-box DNA helicase previously described to play a role in the Rhp51 (an orthologue of S. cerevisiae RAD51-dependent recombinational repair of DSBs. Fbh1 fused to GFP localizes to discrete nuclear foci following DNA damage. Results To determine the functional roles of the highly conserved F-box and helicase domains, we have characterized fbh1 mutants carrying specific mutations in these domains. We show that the F-box mutation fbh1-fb disturbs the nuclear localization of Fbh1, conferring an fbh1 null-like phenotype. Moreover, nuclear foci do not form in fbh1-fb cells with DNA damage even if Fbh1-fb is targeted to the nucleus by fusion to a nuclear localization signal sequence. In contrast, the helicase mutation fbh1-hl causes the accumulation of Fbh1 foci irrespective of the presence of DNA damage and confers damage sensitivity greater than that conferred by the null allele. Additional mutation of the F-box alleviates the hypermorphic phenotype of the fbh1-hl mutant. Conclusion These results suggest that the F-box and DNA helicase domains play indispensable but distinct roles in Fbh1 function. Assembly of the SCFFbh1 complex is required for both the nuclear localization and DNA damage-induced focus formation of Fbh1 and is therefore prerequisite for the Fbh1 recombination function.
Play as the main event in international and UK culture.

OpenAIRE

Woudhuysen, James

2003-01-01

Since Johan Huizinga’s Homo Ludens, 1938, few books have treated adult play at an abstract level using psychology. These works lack empirical statistics. On the other hand, most market research into consumer leisure lacks clear theoretical frameworks. ‘Play as the Main Event’ overcomes these twin deficiencies. It develops Huizinga and the major international theorists of play to define five distinctive features of contemporary play, applying this framework to five sub-sectors of consumer leis...
Understanding Positive Play: An Exploration of Playing Experiences and Responsible Gambling Practices.

Science.gov (United States)

Wood, Richard T A; Griffiths, Mark D

2015-12-01

This study is one of the first to explore in detail the behaviors, attitudes and motivations of players that show no signs of at-risk or problem gambling behavior (so-called 'positive players'). Via an online survey, 1484 positive players were compared with 209 problem players identified using the Lie/Bet screen. The study identified two distinct groups of positive players defined according to their motivations to play and their engagement with responsible gambling (RG) practices. Those positive players that played most frequently employed the most personal RG strategies. Reasons that positive players gave for gambling were focused on leisure (e.g., playing for fun, being entertained, and/or winning a prize). By contrast, problem gamblers were much more focused upon modifying mood states (e.g., excitement, relaxation, depression and playing when bored or upset). The present study also suggests that online gambling is not, by default, inherently riskier than gambling in more traditional ways, as online gambling was the most popular media by which positive players gambled. Furthermore, most positive players reported that it was easier to stick to their limits when playing the National Lottery online compared to traditional retail purchasing of tickets. Problem players were significantly more likely than positive players to gamble with family and friends, suggesting that, contrary to a popular RG message, social play may not be inherently safer than gambling alone. It is proposed that players (generally) may identify more with the term 'positive play' than the term 'RG' which is frequently interpreted as being aimed at people with gambling problems, rather than all players.
No selection, but higher satisfaction of people participating in the disease management programme diabetes type 2 in Germany.

Science.gov (United States)

Kellner, Christiane; Kuniss, Nadine; Kloos, Christof; Müller, Ulrich Alfons; Müller, Nicolle

2018-04-01

We analysed metabolic control, complications and satisfaction in people with and without DMP participation. We retrospectively analysed the German data of the GUIDANCE study. The general practices included (n = 38) were selected from the physicians' register of the Thuringian Association of Statutory Health Insurance Physicians. Half of the practices (n = 19) participated in the DMP "Diabetes mellitus type 2". Nine hundred and fifty-nine people were included in the analysis. Of these, 541 (56.4%) were enrolled in the DMP and 418 (43.6%) not. There was no difference between the two groups (DMP vs. no DMP) regarding age (67.8 vs. 67.6y), gender (female 50.6 vs. 52.2%), diabetes duration (9.8 vs. 9.5y), BMI (31.3 vs. 30.7 kg/m 2 ), HbA1c (7.2 vs. 7.2%), systolic blood pressure (139 vs. 140 mm Hg) or antihypertensive drug (89.5 vs. 88.8%). More DMP participants had regular screening of diabetic late complications: retinopathy 84.7 versus 69.9% (p < 0.001); polyneuropathy 93.0 versus 52.6% (p < 0.001). Chronic kidney disease was more frequent in DMP participants (15.0 vs. 9.3%, p = 0.005). Treatment satisfaction was higher in participants enrolled in the DMP (31.1 vs. 30.0; p = 0.002). DMP participants do not exhibit positive selection. Process quality and treatment satisfaction are higher in DMP participants.
Distinct HbA1c trajectories in a type 2 diabetes cohort

NARCIS (Netherlands)

Walraven, I.; Mast, M.R.; Hoekstra, T.; Jansen, A.P.D.; van der Heijden, A.A.W.A.; Rauh, S.P.; Rutters, F.; van 't Riet, E.; Elders, P.J.M.; Moll, A.C.; Polak, B.C.P.; Dekker, J.M.; Nijpels, G.

2015-01-01

Aims: The aim of this study was to identify subgroups of type 2 diabetes mellitus patients with distinct hemoglobin A1c (HbA1c) trajectories. Subgroup characteristics were determined and the prevalence of microvascular complications over time was investigated. Study design and setting: Data from a
Learning, Play, and Your 1- to 3-Month-Old

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... Staying Safe Videos for Educators Search English Español Learning, Play, and Your 1- to 3-Month-Old ... Baby to Learn Print What Your Baby Is Learning After learning to recognize your voice, your face, ...
Biodegradation of dimethyl phthalate by Sphingomonas sp. isolated from phthalic-acid-degrading aerobic granules.

Science.gov (United States)

Zeng, Ping; Moy, Benjamin Yan-Pui; Song, Yong-Hui; Tay, Joo-Hwa

2008-10-01

Phthalic acid esters (PAEs) contamination in water, air, and soil is one of the major environmental concerns in many countries. Besides the PAE biodegradation process, the PAE degrading bacteria have become one of the focuses of study. This study reports the successful isolation of one kind of indigenous bacterium PA-02 from phthalic acid (PA)-degrading aerobic granules. Based on its 16S ribosomal DNA sequence, isolate PA-02 was identified as Sphingomonas genus with 100% similarity to Sphingomonas sp. strain D84532. Strain PA-02 was a Gram-negative, rod-shaped bacterium with strong auto-aggregation ability. In particular, the strain PA-02 possessed PAE-degrading ability without acclimation. Results of growth tests showed that strain PA-02 could degrade dimethyl phthalate (DMP), dibutyl phthalate, and diethylhexyl phthalate. The specific degradation rates of DMP and PA were concentration-dependent with maximum values of 0.4 g-DMP g(-1) biomass h(-1) and 1.3 g-PA g(-1) biomass h(-1), respectively. Kinetic studies also revealed that PA-02 was robust under high concentrations of DMP and PA. Even when the PA concentration was increased to 1,000.0 mg l(-1), the specific PA degradation rate was about 0.25 g-PA g(-1) biomass h(-1). The corresponding value for DMP was 0.067 g-DMP g(-1) biomass h(-1) at 1,000 mg l(-1).
HIF-1alpha and HIF-2alpha are differentially activated in distinct cell populations in retinal ischaemia.

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Freya M Mowat

2010-06-01

Full Text Available Hypoxia plays a key role in ischaemic and neovascular disorders of the retina. Cellular responses to oxygen are mediated by hypoxia-inducible transcription factors (HIFs that are stabilised in hypoxia and induce the expression of a diverse range of genes. The purpose of this study was to define the cellular specificities of HIF-1alpha and HIF-2alpha in retinal ischaemia, and to determine their correlation with the pattern of retinal hypoxia and the expression profiles of induced molecular mediators.We investigated the tissue distribution of retinal hypoxia during oxygen-induced retinopathy (OIR in mice using the bio-reductive drug pimonidazole. We measured the levels of HIF-1alpha and HIF-2alpha proteins by Western blotting and determined their cellular distribution by immunohistochemistry during the development of OIR. We measured the temporal expression profiles of two downstream mediators, vascular endothelial growth factor (VEGF and erythropoietin (Epo by ELISA. Pimonidazole labelling was evident specifically in the inner retina. Labelling peaked at 2 hours after the onset of hypoxia and gradually declined thereafter. Marked binding to Müller glia was evident during the early hypoxic stages of OIR. Both HIF-1alpha and HIF-2alpha protein levels were significantly increased during retinal hypoxia but were evident in distinct cellular distributions; HIF-1alpha stabilisation was evident in neuronal cells throughout the inner retinal layers whereas HIF-2alpha was restricted to Müller glia and astrocytes. Hypoxia and HIF-alpha stabilisation in the retina were closely followed by upregulated expression of the downstream mediators VEGF and EPO.Both HIF-1alpha and HIF-2alpha are activated in close correlation with retinal hypoxia but have contrasting cell specificities, consistent with differential roles in retinal ischaemia. Our findings suggest that HIF-2alpha activation plays a key role in regulating the response of Müller glia to hypoxia.
Distinct and conserved prominin-1/CD133-positive retinal cell populations identified across species.

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József Jászai

2011-03-01

Full Text Available Besides being a marker of various somatic stem cells in mammals, prominin-1 (CD133 plays a role in maintaining the photoreceptor integrity since mutations in the PROM1 gene are linked with retinal degeneration. In spite of that, little information is available regarding its distribution in eyes of non-mammalian vertebrates endowed with high regenerative abilities. To address this subject, prominin-1 cognates were isolated from axolotl, zebrafish and chicken, and their retinal compartmentalization was investigated and compared to that of their mammalian orthologue. Interestingly, prominin-1 transcripts--except for the axolotl--were not strictly restricted to the outer nuclear layer (i.e., photoreceptor cells, but they also marked distinct subdivisions of the inner nuclear layer (INL. In zebrafish, where the prominin-1 gene is duplicated (i.e., prominin-1a and prominin-1b, a differential expression was noted for both paralogues within the INL being localized either to its vitreal or scleral subdivision, respectively. Interestingly, expression of prominin-1a within the former domain coincided with Pax-6-positive cells that are known to act as progenitors upon injury-induced retino-neurogenesis. A similar, but minute population of prominin-1-positive cells located at the vitreal side of the INL was also detected in developing and adult mice. In chicken, however, prominin-1-positive cells appeared to be aligned along the scleral side of the INL reminiscent of zebrafish prominin-1b. Taken together our data indicate that in addition to conserved expression of prominin-1 in photoreceptors, significant prominin-1-expressing non-photoreceptor retinal cell populations are present in the vertebrate eye that might represent potential sources of stem/progenitor cells for regenerative therapies.
Molecular energy dissipation in nanoscale networks of Dentin Matrix Protein 1 is strongly dependent on ion valence

Science.gov (United States)

Adams, J; Fantner, G E; Fisher, L W; Hansma, P K

2008-01-01

The fracture resistance of biomineralized tissues such as bone, dentin, and abalone is greatly enhanced through the nanoscale interactions of stiff inorganic mineral components with soft organic adhesive components. A proper understanding of the interactions that occur within the organic component, and between the organic and inorganic components, is therefore critical for a complete understanding of the mechanics of these tissues. In this paper, we use Atomic Force Microscope (AFM) force spectroscopy and dynamic force spectroscopy to explore the effect of ionic interactions within a nanoscale system consisting of networks of Dentin Matrix Protein 1 (DMP1) (a component of both bone and dentin organic matrix), a mica surface, and an AFM tip. We find that DMP1 is capable of dissipating large amounts of energy through an ion-mediated mechanism, and that the effectiveness increases with increasing ion valence. PMID:18843380
Molecular energy dissipation in nanoscale networks of dentin matrix protein 1 is strongly dependent on ion valence

International Nuclear Information System (INIS)

Adams, J; Fantner, G E; Hansma, P K; Fisher, L W

2008-01-01

The fracture resistance of biomineralized tissues such as bone, dentin, and abalone is greatly enhanced through the nanoscale interactions of stiff inorganic mineral components with soft organic adhesive components. A proper understanding of the interactions that occur within the organic component, and between the organic and inorganic components, is therefore critical for a complete understanding of the mechanics of these tissues. In this paper, we use atomic force microscope (AFM) force spectroscopy and dynamic force spectroscopy to explore the effect of ionic interactions within a nanoscale system consisting of networks of dentin matrix protein 1 (DMP1) (a component of both bone and dentin organic matrix), a mica surface and an AFM tip. We find that DMP1 is capable of dissipating large amounts of energy through an ion-mediated mechanism, and that the effectiveness increases with increasing ion valence
Molecular energy dissipation in nanoscale networks of dentin matrix protein 1 is strongly dependent on ion valence

Energy Technology Data Exchange (ETDEWEB)

Adams, J; Fantner, G E; Hansma, P K [Department of Physics, Broida Hall, University of California, Santa Barbara, CA 93106 (United States); Fisher, L W [Craniofacial and Skeletal Diseases Branch, NIDCR, NIH, DHHS, Bethesda, MD 20892 (United States)], E-mail: adams@physics.ucsb.edu, E-mail: fantner@physics.ucsb.edu, E-mail: lfisher@dir.nidcr.nih.gov, E-mail: prasant@physics.ucsb.edu

2008-09-24

The fracture resistance of biomineralized tissues such as bone, dentin, and abalone is greatly enhanced through the nanoscale interactions of stiff inorganic mineral components with soft organic adhesive components. A proper understanding of the interactions that occur within the organic component, and between the organic and inorganic components, is therefore critical for a complete understanding of the mechanics of these tissues. In this paper, we use atomic force microscope (AFM) force spectroscopy and dynamic force spectroscopy to explore the effect of ionic interactions within a nanoscale system consisting of networks of dentin matrix protein 1 (DMP1) (a component of both bone and dentin organic matrix), a mica surface and an AFM tip. We find that DMP1 is capable of dissipating large amounts of energy through an ion-mediated mechanism, and that the effectiveness increases with increasing ion valence.
Bingo! Holy play in experience-oriented society

NARCIS (Netherlands)

de Groot, Kees

2017-01-01

What place is there for holy play in experience-oriented society? Is it possible and useful to make analytic distinctions between the liturgical quality of events? I explored these questions by doing research on the boundaries between the religious field and the field of leisure. Fifty site visits
Physiological and morphological characterization of organotypic cocultures of the chick forebrain area MNH and its main input area DMA/DMP.

Science.gov (United States)

Endepols, H; Jungnickel, J; Braun, K

2001-01-01

Cocultures of the learning-relevant forebrain region mediorostral neostriatum and hyperstriatum ventrale (MNH) and its main glutamatergic input area nucleus dorsomedialis anterior thalami/posterior thalami were morphologically and physiologically characterized. Synaptic contacts of thalamic fibers were light- and electron-microscopically detected on MNH neurons by applying the fluorescence tracer DiI-C18(3) into the thalamus part of the coculture. Most thalamic synapses on MNH neurons were symmetric and located on dendritic shafts, but no correlation between Gray-type ultrastructure and dendritic localization was found. Using intracellular current clamp recordings, we found that the electrophysiological properties, such as input resistance, time constant, action potential threshold, amplitude, and duration of MNH neurons, remain stable for over 30 days in vitro. Pharmacological blockade experiments revealed glutamate as the main neurotransmitter of thalamic synapses on MNH neurons, which were also found on inhibitory neurons. High frequency stimulation of thalamic inputs evoked synaptic potentiation in 22% of MNH neurons. The results indicate that DMA/DMP-MNH cocultures, which can be maintained under stable conditions for at least 4 weeks, provide an attractive in vitro model for investigating synaptic plasticity in the avian brain.
Equilibrium and ab initio computational studies on the adduct formation of 1,3-diketonato-lithium(I), -sodium(I) and -potassium(I) with 1,10-phenanthroline and its 2,9-dimethyl derivatives.

Science.gov (United States)

Ishimori, Ken-ichiro; Mori, Seiji; Ito, Yuji; Ohashi, Kousaburo; Imura, Hisanori

2009-06-15

Highly effective and selective synergistic extraction of Li+ has been found using 2-naphthoyltrifluoroacetone (Hnta) as an acidic chelating agent and 2,9-dimethyl-1,10-phenanthroline (dmp) or 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (dmdpp) as a neutral ligand (denoted as L) in toluene. The synergism was ascribed to the adduct formation in the organic phase, and the composition and the formation constants of the adducts for alkali metal ions (M+) were determined by the extraction equilibrium analysis. The adducts found were M(nta)L for Li+ and Na+, while M(nta)L and M(nta)L2 for K+. To understand thermodynamics of the adduct formation with the bidentate amines, quantum chemical calculations of the 1:1 and 1:2 adduct formations with dmp and 1,10-phenanthroline (phen) were performed. The electronic and steric effects of the methyl groups at 2,9-positions of phen on the thermodynamic functions of adduct formation as well as the high lithium selectivity were quantitatively elucidated.
Distinct Calcium Signaling Pathways Regulate Calmodulin Gene Expression in Tobacco1

Science.gov (United States)

van der Luit, Arnold H.; Olivari, Claudio; Haley, Ann; Knight, Marc R.; Trewavas, Anthony J.

1999-01-01

Cold shock and wind stimuli initiate Ca2+ transients in transgenic tobacco (Nicotiana plumbaginifolia) seedlings (named MAQ 2.4) containing cytoplasmic aequorin. To investigate whether these stimuli initiate Ca2+ pathways that are spatially distinct, stress-induced nuclear and cytoplasmic Ca2+ transients and the expression of a stress-induced calmodulin gene were compared. Tobacco seedlings were transformed with a construct that encodes a fusion protein between nucleoplasmin (a major oocyte nuclear protein) and aequorin. Immunocytochemical evidence indicated targeting of the fusion protein to the nucleus in these plants, which were named MAQ 7.11. Comparison between MAQ 7.11 and MAQ 2.4 seedlings confirmed that wind stimuli and cold shock invoke separate Ca2+ signaling pathways. Partial cDNAs encoding two tobacco calmodulin genes, NpCaM-1 and NpCaM-2, were identified and shown to have distinct nucleotide sequences that encode identical polypeptides. Expression of NpCaM-1, but not NpCaM-2, responded to wind and cold shock stimulation. Comparison of the Ca2+ dynamics with NpCaM-1 expression after stimulation suggested that wind-induced NpCaM-1 expression is regulated by a Ca2+ signaling pathway operational predominantly in the nucleus. In contrast, expression of NpCaM-1 in response to cold shock is regulated by a pathway operational predominantly in the cytoplasm. PMID:10557218
30 CFR 77.1710-1 - Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced...

Science.gov (United States)

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Distinctively colored hard hats or hard caps... Distinctively colored hard hats or hard caps; identification for newly employed, inexperienced miners. Hard hats or hard caps distinctively different in color from those worn by experienced miners shall be worn at...
XRCC1 and PCNA are loading platforms with distinct kinetic properties and different capacities to respond to multiple DNA lesions

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Leonhardt Heinrich

2007-09-01

Full Text Available Abstract Background Genome integrity is constantly challenged and requires the coordinated recruitment of multiple enzyme activities to ensure efficient repair of DNA lesions. We investigated the dynamics of XRCC1 and PCNA that act as molecular loading platforms and play a central role in this coordination. Results Local DNA damage was introduced by laser microirradation and the recruitment of fluorescent XRCC1 and PCNA fusion proteins was monitored by live cell microscopy. We found an immediate and fast recruitment of XRCC1 preceding the slow and continuous recruitment of PCNA. Fluorescence bleaching experiments (FRAP and FLIP revealed a stable association of PCNA with DNA repair sites, contrasting the high turnover of XRCC1. When cells were repeatedly challenged with multiple DNA lesions we observed a gradual depletion of the nuclear pool of PCNA, while XRCC1 dynamically redistributed even to lesions inflicted last. Conclusion These results show that PCNA and XRCC1 have distinct kinetic properties with functional consequences for their capacity to respond to successive DNA damage events.
XRCC1 and PCNA are loading platforms with distinct kinetic properties and different capacities to respond to multiple DNA lesions

Science.gov (United States)

Mortusewicz, Oliver; Leonhardt, Heinrich

2007-01-01

Background Genome integrity is constantly challenged and requires the coordinated recruitment of multiple enzyme activities to ensure efficient repair of DNA lesions. We investigated the dynamics of XRCC1 and PCNA that act as molecular loading platforms and play a central role in this coordination. Results Local DNA damage was introduced by laser microirradation and the recruitment of fluorescent XRCC1 and PCNA fusion proteins was monitored by live cell microscopy. We found an immediate and fast recruitment of XRCC1 preceding the slow and continuous recruitment of PCNA. Fluorescence bleaching experiments (FRAP and FLIP) revealed a stable association of PCNA with DNA repair sites, contrasting the high turnover of XRCC1. When cells were repeatedly challenged with multiple DNA lesions we observed a gradual depletion of the nuclear pool of PCNA, while XRCC1 dynamically redistributed even to lesions inflicted last. Conclusion These results show that PCNA and XRCC1 have distinct kinetic properties with functional consequences for their capacity to respond to successive DNA damage events. PMID:17880707

Discrete maximum principle for the P1 - P0 weak Galerkin finite element approximations

Science.gov (United States)

Wang, Junping; Ye, Xiu; Zhai, Qilong; Zhang, Ran

2018-06-01

This paper presents two discrete maximum principles (DMP) for the numerical solution of second order elliptic equations arising from the weak Galerkin finite element method. The results are established by assuming an h-acute angle condition for the underlying finite element triangulations. The mathematical theory is based on the well-known De Giorgi technique adapted in the finite element context. Some numerical results are reported to validate the theory of DMP.
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
Preliminary site survey report for the Uniroyal Chemical Company, formerly the Diamond Magnesium Company, 720 Fairport-Nursery Road, Painesville, Ohio (DMP001)

International Nuclear Information System (INIS)

Foley, R.D.; Floyd, L.M.

1990-03-01

At the request of the US Department of Energy (DOE), a group from Oak Ridge National Laboratory conducted a preliminary radiological survey at the Uniroyal Chemical Company, formerly the Diamond Magnesium Company, 720 Fairport-Nursery Road, Painesville, Ohio (DMP001), in 1988. The purpose of the survey was to determine whether the property was contaminated with radioactive residues from the former Manhattan Engineer District (MED) project. The scope of this preliminary survey primarily covered the area west of the buildings around the railroad car spill containment basin. The survey included direct measurement of gamma radiation levels at the surface and soil sampling for radionuclide analyses. Results of the survey demonstrated radionuclide concentrations in excess of the DOE Formerly Utilized Sites Remedial Action Program criteria for both 238 U and 226 Ra in soil. Based on the results of this radiological assessment, it is recommended that a follow-up, detailed radiological survey of both surface and subsurface environs be performed to more precisely define the extent of the contamination. 5 refs., 10 figs., 3 tabs
TOPOISOMERASE1α Acts through Two Distinct Mechanisms to Regulate Stele and Columella Stem Cell Maintenance.

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Zhang, Yonghong; Zheng, Lanlan; Hong, Jing Han; Gong, Ximing; Zhou, Chun; Pérez-Pérez, José Manuel; Xu, Jian

2016-05-01

TOPOISOMERASE1 (TOP1), which releases DNA torsional stress generated during replication through its DNA relaxation activity, plays vital roles in animal and plant development. In Arabidopsis (Arabidopsis thaliana), TOP1 is encoded by two paralogous genes (TOP1α and TOP1β), of which TOP1α displays specific developmental functions that are critical for the maintenance of shoot and floral stem cells. Here, we show that maintenance of two different populations of root stem cells is also dependent on TOP1α-specific developmental functions, which are exerted through two distinct novel mechanisms. In the proximal root meristem, the DNA relaxation activity of TOP1α is critical to ensure genome integrity and survival of stele stem cells (SSCs). Loss of TOP1α function triggers DNA double-strand breaks in S-phase SSCs and results in their death, which can be partially reversed by the replenishment of SSCs mediated by ETHYLENE RESPONSE FACTOR115 In the quiescent center and root cap meristem, TOP1α is epistatic to RETINOBLASTOMA-RELATED (RBR) in the maintenance of undifferentiated state and the number of columella stem cells (CSCs). Loss of TOP1α function in either wild-type or RBR RNAi plants leads to differentiation of CSCs, whereas overexpression of TOP1α mimics and further enhances the effect of RBR reduction that increases the number of CSCs Taken together, these findings provide important mechanistic insights into understanding stem cell maintenance in plants. © 2016 American Society of Plant Biologists. All Rights Reserved.
Schizophrenia-like symptoms in narcolepsy type 1: shared and distinctive clinical characteristics.

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Plazzi, Giuseppe; Fabbri, Chiara; Pizza, Fabio; Serretti, Alessandro

2015-01-01

The occurrence of psychotic symptoms in narcolepsy type 1 (NT1) has been reported as responsible for delayed diagnosis due to the misdiagnosis of schizophrenia. This study aimed to identify shared and distinctive clinical characteristics between NT1 and schizophrenia, with the focus on psychotic symptoms. A total of 28 NT1 and 21 schizophrenia patients were included. Hallucination characteristics and PANSS (Positive and Negative Syndrome Scale), HRSD (Hamilton Rating Scale for Depression), DES (Dissociative Experiences Scale), and STAI (State-Trait Anxiety Inventory) scores were collected. Symptom overlap was investigated by χ(2), Fisher's or t tests and multiple logistic regression models. Hallucinations and illusions frequently occurred in both diseases. Unimodal hallucinations were more common in schizophrenia (p = 6.30e-07) and multimodal hallucinations in NT1, but no clear difference was identified in their sensory modality. Hypnagogic/hypnopompic hallucinations were typical of NT1 (p = 5.22e-07), and 25% of NT1 patients exhibited some degree of insight deficit. Hypnagogic/hypnopompic hallucinations, unimodal hallucinations and PANSS score were the most distinctive clinical characteristics. Clinical overlap was found in the dissociative and anxiety domains, while higher depressive scores were observed in schizophrenia. The overlap between NT1 and schizophrenia should be further investigated under a clinical and pathogenetic point of view to improve diagnostic and therapeutic approaches. © 2015 S. Karger AG, Basel.
The power of possibility: causal learning, counterfactual reasoning, and pretend play.

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Buchsbaum, Daphna; Bridgers, Sophie; Skolnick Weisberg, Deena; Gopnik, Alison

2012-08-05

We argue for a theoretical link between the development of an extended period of immaturity in human evolution and the emergence of powerful and wide-ranging causal learning mechanisms, specifically the use of causal models and Bayesian learning. We suggest that exploratory childhood learning, childhood play in particular, and causal cognition are closely connected. We report an empirical study demonstrating one such connection--a link between pretend play and counterfactual causal reasoning. Preschool children given new information about a causal system made very similar inferences both when they considered counterfactuals about the system and when they engaged in pretend play about it. Counterfactual cognition and causally coherent pretence were also significantly correlated even when age, general cognitive development and executive function were controlled for. These findings link a distinctive human form of childhood play and an equally distinctive human form of causal inference. We speculate that, during human evolution, computations that were initially reserved for solving particularly important ecological problems came to be used much more widely and extensively during the long period of protected immaturity.
Rhinovirus infection induces distinct transcriptome profiles in polarized human macrophages.

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Rajput, Charu; Walsh, Megan P; Eder, Breanna N; Metitiri, Ediri E; Popova, Antonia P; Hershenson, Marc B

2018-05-01

Infections with rhinovirus (RV) cause asthma exacerbations. Recent studies suggest that macrophages play a role in asthmatic airway inflammation and the innate immune response to RV infection. Macrophages exhibit phenotypes based on surface markers and gene expression. We hypothesized that macrophage polarization state alters gene expression in response to RV infection. Cells were derived from human peripheral blood derived monocytes. M1 and M2 polarization was carried out by using IFN-γ and IL-4, respectively, and RNA was extracted for Affymetrix Human Gene ST2.1 exon arrays. Selected genes were validated by quantitative (q)PCR. Treatment of nonactivated (M0) macrophages with IFN-γ and IL-4 induced the expression of 252 and 153 distinct genes, respectively, including previously-identified M1 and M2 markers. RV infection of M0 macrophages induced upregulation of 232 genes; pathway analysis showed significant overrepresentation of genes involved in IFN-α/β signaling and cytokine signaling in the immune system. RV infection induced differential expression of 195 distinct genes in M1-like macrophages but only seven distinct genes in M2-like-polarized cells. In a secondary analysis, comparison between M0-, RV-infected, and M1-like-polarized, RV-infected macrophages revealed differential expression of 227 genes including those associated with asthma and its exacerbation. qPCR demonstrated increased expression of CCL8, CXCL10, TNFSF10, TNFSF18, IL6, NOD2, and GSDMD and reduced expression of VNN1, AGO1, and AGO2. Together, these data show that, in contrast to M2-like-polarized macrophages, gene expression of M1-like macrophages is highly regulated by RV.
Synergistic extraction of manganese(II) with thenoyltrifluoroacetone and neutral unidentate and bidentate ligands

International Nuclear Information System (INIS)

Nakamura, S.; Imura, H.; Suzuki, N.

1984-01-01

Synergistic effect of neutral bidentate ligands, L, such as 1,10-phenanthroline(phen), 2,9-dimethyl-1,10-phenanthroline(dmp) and 2,2'-bipyridine(bpy) and of neutral unidentate ligands TBP and TOPO have been studied in the extraction of Mn(II) labelled with 54 Mn using 2-thenoyl-trifluoroacetone(HTTA) in various organic solvents. The following factors play important role in the synergistic extraction involving bidentate ligands: a two-phase partition of bidentate ligands, and their protonation and complex formation with Mn(II) in the aqueous phase. The mixed ligand complex, Mn(TTA) 2 L is formed in all bidentate ligand systems. The adduct formation constant (βsub(s,1)) decreases in the following order: phen (lg βsub(s,1)=12.64)>dmp(11.32)>.bpy(8.54) in the cyclohexane system. This order is ascribed to the bacisity and the steric effect of the bidentate ligands. Organic solvents influence both the adduct formation and the partition of the ligands, and βsub(s,1) decreases in the order cyclohexane > carbon tetrachloride > cholrobenzene approx.= benzene > chloroform. (author)
Incidence of retinal complications in a cohort of newly diagnosed diabetic patients.

Directory of Open Access Journals (Sweden)

Elisa Martín-Merino

Full Text Available PURPOSE: We aimed at estimating the incidence of diabetic retinopathy (DR and maculopathy (DMP among newly diagnosed type 1 (t1DM and type 2 diabetic patients (t2DM in the United Kingdom primary care system. The incidence of DMP among patients with DR was also estimated. METHOD: We conducted a cohort study using The Health Improvement Network database. The cohort included 64,983 incident diabetic patients (97.3% were t2DM aged 1-84 years diagnosed between 2000 and 2007. This cohort was followed from the date of diabetes diagnosis until recording of DR or DMP in two separate follow-ups. Follow-up was censored at 85 years of age, death, or end of 2008. An additional follow-up was conducted from DR to DMP diagnosis using similar censoring reasons. DR and DMP cumulative incidences were calculated as well as incidence rates (IR; cases per 1,000 person-years per calendar period (2000-2001 and 2006-2007. RESULTS: Follow-up for DR: 9 years after diabetes diagnosis, 28% of t2DM and 24% of t1DM patients had developed DR (7,899 incident DR cases. During the first 2 years with diabetes, the IR was almost 2 times higher in patients diagnosed with diabetes in 2006-2007 (47.7 than among those diagnosed in 2000-2001 (24.5. Follow-up for DMP: 9 years after diabetes diagnosis, 3.6% of t2DM and 4.4% of t2DM patients had developed DMP (912 incident DMP cases. During the first 2 years with diabetes, the IR was three times higher in patients diagnosed with diabetes in 2006-2007 (5.8 than among those diagnosed in 2000-2001 (1.8. Macular oedema occurred in 0.8% of patients. CONCLUSIONS: In a cohort of incident diabetes, 28% of patients developed retinopathy and 4% maculopathy within the first 9 years. The 2-year IRs of DR and DMP were higher in patients diagnosed with diabetes during the period 2006-2007 than in those diagnosed during the 2000-2001 period.
Collaborative enhancement of antibody binding to distinct PECAM-1 epitopes modulates endothelial targeting.

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Ann-Marie Chacko

Full Text Available Antibodies to platelet endothelial cell adhesion molecule-1 (PECAM-1 facilitate targeted drug delivery to endothelial cells by "vascular immunotargeting." To define the targeting quantitatively, we investigated the endothelial binding of monoclonal antibodies (mAbs to extracellular epitopes of PECAM-1. Surprisingly, we have found in human and mouse cell culture models that the endothelial binding of PECAM-directed mAbs and scFv therapeutic fusion protein is increased by co-administration of a paired mAb directed to an adjacent, yet distinct PECAM-1 epitope. This results in significant enhancement of functional activity of a PECAM-1-targeted scFv-thrombomodulin fusion protein generating therapeutic activated Protein C. The "collaborative enhancement" of mAb binding is affirmed in vivo, as manifested by enhanced pulmonary accumulation of intravenously administered radiolabeled PECAM-1 mAb when co-injected with an unlabeled paired mAb in mice. This is the first demonstration of a positive modulatory effect of endothelial binding and vascular immunotargeting provided by the simultaneous binding a paired mAb to adjacent distinct epitopes. The "collaborative enhancement" phenomenon provides a novel paradigm for optimizing the endothelial-targeted delivery of therapeutic agents.
Bingo! Holy play in experience-oriented society.

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De Groot, Kees

2017-06-01

What place is there for holy play in experience-oriented society? Is it possible and useful to make analytic distinctions between the liturgical quality of events? I explored these questions by doing research on the boundaries between the religious field and the field of leisure. Fifty site visits to public events in the Netherlands (2006-2014) resulted in a collection of ethnographic data. I used the concept of play as introduced by the Dutch historian Johan Huizinga and the tools of ritual studies to explore whether these could help to produce an account of the liturgical quality of ritualized meetings. Holy play might be found in unexpected places, such as in a bingo hall. Huizinga's broad diagnosis of modernity may be outdated, but the tools he introduced remain useful to distinguish the elements that constitute late-modern meetings as more or less playful - even when this involves combinations that seem contradictory from Huizinga's own point of view.
Case Study 1: Playful Team Reflection Using LEGO® Serious Play®

Science.gov (United States)

Seidl, Tobias

2017-01-01

Teamwork and cooperation are important 21st century skills and therefore important parts of the higher education curriculum. Following Kolb's "experiential learning cycle" model a combination of project work and moderated reflection can help students to acquire these skills. This article elaborates how LEGO® Serious Play® (LSP) can be…
Absurdity:Analysis of Features of the Style of Harold Pinter's Plays

Institute of Scientific and Technical Information of China (English)

南华; 王佳佳

2016-01-01

Absurdity is the most distinctive feature of the early works of Harold Pinter. The nature of absurdity is the purposeless-ness of life without the balance and harmony between men and environment. This paper analyzes the distinctive style of Pinter to mainly analyze the application and reflection of the absurd style of Pinter in his plays, and highlight its expressing forms through the analysis on the plot, characters and languages.
SiglecF+Gr1hi eosinophils are a distinct subpopulation within the lungs of allergen-challenged mice.

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Percopo, Caroline M; Brenner, Todd A; Ma, Michelle; Kraemer, Laura S; Hakeem, Reem M A; Lee, James J; Rosenberg, Helene F

2017-01-01

Although eosinophils as a group are readily identified by their unique morphology and staining properties, flow cytometry provides an important means for identification of subgroups based on differential expression of distinct surface Ags. Here, we characterize an eosinophil subpopulation defined by high levels of expression of the neutrophil Ag Gr1 (CD45 + CD11c - SiglecF + Gr1 hi ). SiglecF + Gr1 hi eosinophils, distinct from the canonical SiglecF + Gr1 - eosinophil population, were detected in allergen-challenged wild-type and granule protein-deficient (EPX -/- and MBP-1 -/- ) mice, but not in the eosinophil-deficient ΔdblGATA strain. In contrast to Gr1 + neutrophils, which express both cross-reacting Ags Ly6C and Ly6G, SiglecF + Gr1 hi eosinophils from allergen-challenged lung tissue are uniquely Ly6G + Although indistinguishable from the more-numerous SiglecF + Gr1 - eosinophils under light microscopy, FACS-isolated populations revealed prominent differences in cytokine contents. The lymphocyte-targeting cytokines CXCL13 and IL-27 were identified only in the SiglecF + Gr1 hi eosinophil population (at 3.9 and 4.8 pg/10 6 cells, respectively), as was the prominent proinflammatory mediator IL-13 (72 pg/10 6 cells). Interestingly, bone marrow-derived (SiglecF + ), cultured eosinophils include a more substantial Gr1 + subpopulation (∼50%); Gr1 + bmEos includes primarily a single Ly6C + and a smaller, double-positive (Ly6C + Ly6G + ) population. Taken together, our findings characterize a distinct SiglecF + Gr1 hi eosinophil subset in lungs of allergen-challenged, wild-type and granule protein-deficient mice. SiglecF + Gr1 hi eosinophils from wild-type mice maintain a distinct subset of cytokines, including those active on B and T lymphocytes. These cytokines may facilitate eosinophil-mediated immunomodulatory responses in the allergen-challenged lung as well as in other distinct microenvironments. © Society for Leukocyte Biology.
Engineering Klebsiella sp. 601 multicopper oxidase enhances the catalytic efficiency towards phenolic substrates.

Science.gov (United States)

Li, Yadong; Gong, Zijun; Li, Xin; Li, Yang; Wang, Xing-Guo

2011-05-31

Structural comparison between bacterial CueO and fungal laccases has suggested that a charged residue Glu (E106) in CueO replaces the corresponding residue Phe in fungal laccases at the gate of the tunnel connecting type II copper to the protein surface and an extra α-helix (L351-G378) near the type I copper site covers the substrate binding pocket and might compromise the electron transfer from substrate to type I copper. To test this hypothesis, several mutants were made in Klebsiella sp. 601 multicopper oxidase, which is highly homologous to E. coli CueO with a similarity of 90% and an identity of 78%. The E106F mutant gave smaller K(m) (2.4-7 fold) and k(cat) (1-4.4 fold) values for all three substrates DMP, ABTS and SGZ as compared with those for the wild-type enzyme. Its slightly larger k(cat)/K(m) values for three substrates mainly come from the decreased K(m). Deleting α-helix (L351-G378) resulted in the formation of inactive inclusion body when the mutant (Δ)α351-378 was expressed in E. coli. Another mutant α351-380M was then made via substitution of seven amino acid residues in the α-helix (L351-G378) region. The α351-380M mutant was active, and displayed a far-UV CD spectrum markedly different from that for wild-type enzyme. Kinetic studies showed the α351-380M mutant gave very low K(m) values for DMP, ABTS and SGZ, 4.5-, 1.9- and 7-fold less than those for the wild type. In addition, k(cat)/K(m) values were increased, 9.4-fold for DMP, similar for ABTS and 3-fold for SGZ. The Glu residue at position 106 appears not to be the only factor affecting the copper binding, and it may also play a role in maintaining enzyme conformation. The α-helix (L351-G378) may not only block access to the type I copper site but also play a role in substrate specificities of bacterial MCOs. The α351-380M mutant catalyzing oxidation of the phenolic substrate DMP effectively would be very useful in green chemistry.
Problematic Game Play: The Diagnostic Value of Playing Motives, Passion, and Playing Time in Men

Directory of Open Access Journals (Sweden)

Julia Kneer

2015-04-01

Full Text Available Internet gaming disorder is currently listed in the DSM—not in order to diagnose such a disorder but to encourage research to investigate this phenomenon. Even whether it is still questionable if Internet Gaming Disorder exists and can be judged as a form of addiction, problematic game play is already very well researched to cause problems in daily life. Approaches trying to predict problematic tendencies in digital game play have mainly focused on playing time as a diagnostic criterion. However, motives to engage in digital game play and obsessive passion for game play have also been found to predict problematic game play but have not yet been investigated together. The present study aims at (1 analyzing if obsessive passion can be distinguished from problematic game play as separate concepts, and (2 testing motives of game play, passion, and playing time for their predictive values for problematic tendencies. We found (N = 99 males, Age: M = 22.80, SD = 3.81 that obsessive passion can be conceptually separated from problematic game play. In addition, the results suggest that compared to solely playing time immersion as playing motive and obsessive passion have added predictive value for problematic game play. The implications focus on broadening the criteria in order to diagnose problematic playing.
Problematic game play: the diagnostic value of playing motives, passion, and playing time in men.

Science.gov (United States)

Kneer, Julia; Rieger, Diana

2015-04-30

Internet gaming disorder is currently listed in the DSM-not in order to diagnose such a disorder but to encourage research to investigate this phenomenon. Even whether it is still questionable if Internet Gaming Disorder exists and can be judged as a form of addiction, problematic game play is already very well researched to cause problems in daily life. Approaches trying to predict problematic tendencies in digital game play have mainly focused on playing time as a diagnostic criterion. However, motives to engage in digital game play and obsessive passion for game play have also been found to predict problematic game play but have not yet been investigated together. The present study aims at (1) analyzing if obsessive passion can be distinguished from problematic game play as separate concepts, and (2) testing motives of game play, passion, and playing time for their predictive values for problematic tendencies. We found (N = 99 males, Age: M = 22.80, SD = 3.81) that obsessive passion can be conceptually separated from problematic game play. In addition, the results suggest that compared to solely playing time immersion as playing motive and obsessive passion have added predictive value for problematic game play. The implications focus on broadening the criteria in order to diagnose problematic playing.
(Liquid + liquid) equilibria of {benzene + cyclohexane + two ionic liquids} at different temperature and atmospheric pressure

International Nuclear Information System (INIS)

Sakal, Salem A.; Shen, Chong; Li, Chun-xi

2012-01-01

Highlights: ► (Liquid + liquid) equilibrium for two quaternary and two ternary systems were measured. ► The components include cyclohexane, benzene, [MIM][BF4], [MIM][ClO4] and [MMIM][DMP]. ► The (liquid + liquid) equilibrium data can be well correlated by the NRTL model. ► Separation of benzene and cyclohexane by pure ILs and their mixtures were discussed. - Abstract: (Liquid + liquid) equilibrium data of the following ternary and quaternary systems at different temperatures and mass fractions of ionic liquids (ILs) were measured at atmospheric pressure, i.e., {cyclohexane + benzene + 1,3-dimethylimidazolium dimethylphosphate ([MMIM][DMP])} at 298.2 K, {cyclohexane + benzene + 1-methylimidazolium tetrafluoroborate ([MIM][BF 4 ])} at 338.2 K, {cyclohexane + benzene + [MIM][BF 4 ] + [MMIM][DMP]} at (298.2 and 313.2) K, and {cyclohexane + benzene + 1-methylimidazolium perchlorate [MIM][ClO 4 ] + [MMIM][DMP]} at 298.2 K. The results indicate that both selectivity and distribution factor of the IL mixture for benzene are lower than that of pure IL [MMIM][DMP] at a specified condition, and decrease with the increase of the mass fraction of [MIM][BF 4 ] or [MIM][ClO 4 ] in its mixture of [MMIM][DMP] and the mole fraction of benzene. The extremely high selectivity of [MIM][BF 4 ] and [MIM][ClO 4 ] for aromatic compounds as predicted by the COSMOS-RS model is not justified by the present experimental results, and on the contrary, they show a relatively lower selectivity and extraction capacity for benzene than [MMIM][DMP].
Brain evolution relating to family, play, and the separation call.

Science.gov (United States)

MacLean, P D

1985-04-01

Mammals stem from the mammal-like reptiles (therapsids) that were widely prevalent in Pangaea 250 million years ago. In the evolutionary transition from reptiles to mammals, three key developments were (1) nursing, in conjunction with maternal care; (2) audiovocal communication for maintaining maternal-offspring contact; and (3) play. The separation call perhaps ranks as the earliest and most basic mammalian vocalization, while play may have functioned originally to promote harmony in the nest. How did such family related behavior develop? In its evolution, the forebrain of advanced mammals has expanded as a triune structure that anatomically and chemically reflects ancestral commonalities with reptiles, early mammals, and late mammals. Recent findings suggest that the development of the behavioral triad in question may have depended on the evolution of the thalamocingulate division of the limbic system, a derivative from early mammals. The thalamocingulate division (which has no distinctive counterpart in the reptilian brain) is, in turn, geared in with the prefrontal neocortex that, in human beings, may be inferred to play a key role in familial acculturation.
Snake River Plain Play Fairway Analysis – Phase 1 Report

Energy Technology Data Exchange (ETDEWEB)

Shervais, John W. [Utah State Univ., Logan, UT (United States). Dept. of Geology; Glen, Jonathan M. [US Geological Survey, Menlo Park, CA (United States); Liberty, Lee M. [Boise State Univ., ID (United States). Center for Geophysical Investigation of the Shallow Subsurface; Dobson, Patrick [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Gasperikova, Erika [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2015-09-01

The Snake River volcanic province (SRP) overlies a thermal anomaly that extends deep into the mantle; it represents one of the highest heat flow provinces in North America. Our goals for this Phase 1 study are to: (1) adapt the methodology of Play Fairway Analysis for geothermal exploration to create a formal basis for its application to geothermal systems, (2) assemble relevant data for the SRP from publicly available and private sources, and (3) build a geothermal play fairway model for the SRP and identify the most promising plays, using software tools that are standard in the petroleum industry. The success of play fairway analysis in geothermal exploration depends critically on defining a systematic methodology that is grounded in theory (as developed within the petroleum industry over the last two decades) and within the geologic and hydrologic framework of real geothermal systems. Our preliminary assessment of the data suggests that important undiscovered geothermal resources may be located in several areas of the SRP, including the western SRP (associated with buried lineaments defined by gravity or magnetic anomalies, and capped by extensive deposits of lacustrine sediment), at lineament intersections in the central SRP (along the Banbury-Hagerman trend NW of Twin Falls, and along the northern margin of the Mt Bennett Hills-Camas Prairie area), and along the margins of the eastern SRP. Additional high temperature resources are likely associated with rhyolite domes and crypto-domes in the eastern SRP, but are masked by shallow groundwater flow leading to low upper crustal heat flow values. These blind resources may be exploitable with existing deep drilling technology. Groundwater modeling planned for later phases of the PFA project will address whether temperatures at viable producing depths are sufficient to support electricity production.

Do PhD supervisors play a role in bridging academic cultures?

DEFF Research Database (Denmark)

Elliot, Dely; Kobayashi, Sofie

Our study reports a phenomenological investigation of ten international PhD students’ and nine supervisors’ first-hand experience of being in doctoral supervisory relationships in a Danish setting. In-depth qualitative data were gathered through face-to-face individual interviews, which explored...... differences and challenges experienced as a result of diversity with respect to their educational background and practices, particularly the pedagogic variation. In the same way that the literature suggests that educators play a crucial role in mediating such diversity in the teaching and learning contexts...... relationship (that crosses over academic and non-academic concerns) and the distinct role it plays deserves further attention. Cotterall, S. (2013). More than just a brain: emotions and the doctoral experience. Higher Education Research & Development, 1-14. Wright, T. (2003). Postgraduate research students...
Selection effects may account for better outcomes of the German Disease Management Program for type 2 diabetes.

Science.gov (United States)

Schäfer, Ingmar; Küver, Claudia; Gedrose, Benjamin; von Leitner, Eike-Christin; Treszl, András; Wegscheider, Karl; van den Bussche, Hendrik; Kaduszkiewicz, Hanna

2010-12-31

The nationwide German disease management program (DMP) for type 2 diabetes was introduced in 2003. Meanwhile, results from evaluation studies were published, but possible baseline differences between DMP and usual-care patients have not been examined. The objective of our study was therefore to find out if patient characteristics as socio-demographic variables, cardiovascular risk profile or motivation for life style changes influence the chance of being enrolled in the German DMP for type 2 diabetes and may therefore account for outcome differences between DMP and usual-care patients. Case control study comparing DMP patients with usual-care patients at baseline and follow up; mean follow-up period of 36 ± 14 months. We used chart review data from 51 GP surgeries. Participants were 586 DMP and 250 usual-care patients with type 2 diabetes randomly selected by chart registry. Data were analysed by multivariate logistic and linear regression analyses. Significance levels were p ≤ 0.05. There was a better chance for enrolment if patients a) had a lower risk status for diabetes complications, i.e. non-smoking (odds ratio of 1.97, 95% confidence interval of 1.11 to 3.48) and lower systolic blood pressure (1.79 for 120 mmHg vs. 160 mmHg, 1.15 to 2.81); b) had higher activity rates, i.e. were practicing blood glucose self-monitoring (1.67, 1.03 to 2.76) and had been prescribed a diabetes patient education before enrolment (2.32, 1.29 to 4.19) c) were treated with oral medication (2.17, 1.35 to 3.49) and d) had a higher GP-rated motivation for diabetes education (4.55 for high motivation vs. low motivation, 2.21 to 9.36). At baseline, future DMP patients had a lower risk for diabetes complications, were treated more intensively and were more active and motivated in managing their disease than usual-care patients. This finding a) points to the problem that the German DMP may not reach the higher risk patients and b) selection bias may impair the assessment of differences
Distinctive phenotype in 9 patients with deletion of chromosome 1q24-q25.

Science.gov (United States)

Burkardt, Deepika D'Cunha; Rosenfeld, Jill A; Helgeson, Maria L; Angle, Brad; Banks, Valerie; Smith, Wendy E; Gripp, Karen W; Moline, Jessica; Moran, Rocio T; Niyazov, Dmitriy M; Stevens, Cathy A; Zackai, Elaine; Lebel, Robert Roger; Ashley, Douglas G; Kramer, Nancy; Lachman, Ralph S; Graham, John M

2011-06-01

Reports of individuals with deletions of 1q24→q25 share common features of prenatal onset growth deficiency, microcephaly, small hands and feet, dysmorphic face and severe cognitive deficits. We report nine individuals with 1q24q25 deletions, who show distinctive features of a clinically recognizable 1q24q25 microdeletion syndrome: prenatal-onset microcephaly and proportionate growth deficiency, severe cognitive disability, small hands and feet with distinctive brachydactyly, single transverse palmar flexion creases, fifth finger clinodactyly and distinctive facial features: upper eyelid fullness, small ears, short nose with bulbous nasal tip, tented upper lip, and micrognathia. Radiographs demonstrate disharmonic osseous maturation with markedly delayed bone age. Occasional features include cleft lip and/or palate, cryptorchidism, brain and spinal cord defects, and seizures. Using oligonucleotide-based array comparative genomic hybridization, we defined the critical deletion region as 1.9 Mb at 1q24.3q25.1 (chr1: 170,135,865-172,099,327, hg18 coordinates), containing 13 genes and including CENPL, which encodes centromeric protein L, a protein essential for proper kinetochore function and mitotic progression. The growth deficiency in this syndrome is similar to what is seen in other types of primordial short stature with microcephaly, such as Majewski osteodysplastic primordial dwarfism, type II (MOPD2) and Seckel syndrome, which result from loss-of-function mutations in genes coding for centrosomal proteins. DNM3 is also in the deleted region and expressed in the brain, where it participates in the Shank-Homer complex and increases synaptic strength. Therefore, DNM3 is a candidate for the cognitive disability, and CENPL is a candidate for growth deficiency in this 1q24q25 microdeletion syndrome. Copyright © 2011 Wiley-Liss, Inc.
Deep Play. Rationality in the Life World with Special Reference to Sailing

Science.gov (United States)

Goold, Patrick

2014-01-01

In an essay on the rationality of play, the author characterizes rationality by the three distinct demands it makes on the individual--demands for autonomy, solidarity, and integrity. He develops each of these as they apply to the sport of sailing, using the example of two deep-ocean expeditions to arrive at a concept of deep play he sees as one…
Diabetic mastopathy: Imaging features and the role of image-guided biopsy in its diagnosis

Energy Technology Data Exchange (ETDEWEB)

Kim, Jong Hyeon; Kim, Eun Kyung; Kim, Min Jung; Moon, Hee Jung; Yoon, Jung Hyun [Dept. of Radiology, Research Institute of Radiological Science, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2016-03-15

The goal of this study was to evaluate the imaging features of diabetic mastopathy (DMP) and the role of image-guided biopsy in its diagnosis. Two experienced radiologists retrospectively reviewed the mammographic and sonographic images of 19 pathologically confirmed DMP patients. The techniques and results of the biopsies performed in each patient were also reviewed. Mammograms showed negative findings in 78% of the patients. On ultrasonography (US), 13 lesions were seen as masses and six as non-mass lesions. The US features of the mass lesions were as follows: irregular shape (69%), oval shape (31%), indistinct margin (69%), angular margin (15%), microlobulated margin (8%), well-defined margin (8%), heterogeneous echogenicity (62%), hypoechoic echogenicity (38%), posterior shadowing (92%), parallel orientation (100%), the absence of calcifications (100%), and the absence of vascularity (100%). Based on the US findings, 17 lesions (89%) were classified as Breast Imaging Reporting and Data System category 4 and two (11%) as category 3. US-guided core biopsy was performed in 18 patients, and 10 (56%) were diagnosed with DMP on that basis. An additional vacuum-assisted biopsy was performed in seven patients and all were diagnosed with DMP. The US features of DMP were generally suspicious for malignancy, whereas the mammographic findings were often negative or showed only focal asymmetry. Core biopsy is an adequate method for initial pathological diagnosis. However, since it yields non-diagnostic results in a considerable number of cases, the evaluation of correlations between imaging and pathology plays an important role in the diagnostic process.
Diabetic mastopathy: Imaging features and the role of image-guided biopsy in its diagnosis

International Nuclear Information System (INIS)

Kim, Jong Hyeon; Kim, Eun Kyung; Kim, Min Jung; Moon, Hee Jung; Yoon, Jung Hyun

2016-01-01

The goal of this study was to evaluate the imaging features of diabetic mastopathy (DMP) and the role of image-guided biopsy in its diagnosis. Two experienced radiologists retrospectively reviewed the mammographic and sonographic images of 19 pathologically confirmed DMP patients. The techniques and results of the biopsies performed in each patient were also reviewed. Mammograms showed negative findings in 78% of the patients. On ultrasonography (US), 13 lesions were seen as masses and six as non-mass lesions. The US features of the mass lesions were as follows: irregular shape (69%), oval shape (31%), indistinct margin (69%), angular margin (15%), microlobulated margin (8%), well-defined margin (8%), heterogeneous echogenicity (62%), hypoechoic echogenicity (38%), posterior shadowing (92%), parallel orientation (100%), the absence of calcifications (100%), and the absence of vascularity (100%). Based on the US findings, 17 lesions (89%) were classified as Breast Imaging Reporting and Data System category 4 and two (11%) as category 3. US-guided core biopsy was performed in 18 patients, and 10 (56%) were diagnosed with DMP on that basis. An additional vacuum-assisted biopsy was performed in seven patients and all were diagnosed with DMP. The US features of DMP were generally suspicious for malignancy, whereas the mammographic findings were often negative or showed only focal asymmetry. Core biopsy is an adequate method for initial pathological diagnosis. However, since it yields non-diagnostic results in a considerable number of cases, the evaluation of correlations between imaging and pathology plays an important role in the diagnostic process
On play and playing.

Science.gov (United States)

Rudan, Dusko

2013-12-01

The paper offers a review of the development of the concept of play and playing. The true beginnings of the development of the theories of play are set as late as in the 19th century. It is difficult to define play as such; it may much more easily be defined through its antipode--work. In the beginning, play used to be connected with education; it was not before Freud's theory of psychoanalysis and Piaget's developmental psychology that the importance of play in a child's development began to be explained in more detail. The paper further tackles the role of play in the adult age. Detailed attention is paid to psychodynamic and psychoanalytic authors, in particular D. W. Winnicott and his understanding of playing in the intermediary (transitional) empirical or experiential space. In other words, playing occupies a space and time of its own. The neuroscientific concept of playing is also tackled, in the connection with development as well.
Butyrate and deoxycholic acid play common and distinct roles in HCT116 human colon cell proliferation.

Science.gov (United States)

Zeng, Huawei; Claycombe, Kate J; Reindl, Katie M

2015-10-01

Consumption of a high-fat diet causes an increase in bile acid deoxycholic acid (DCA) in colon lumen and colon cancer risk, while butyrate, an intestinal microbiota metabolite of dietary fiber, has been shown to exhibit colon cancer-preventive effects. To distinguish these opposing effects of DCA and butyrate (two major metabolites in colon lumen), we examined the effects of physiologically relevant doses of butyrate (0.5-2 mmol/l) and DCA (0.05-0.3 mmol/l) on colon cell proliferation. We hypothesize that butyrate and DCA each modulates the cell cycle and apoptosis via common and distinct cellular signaling targets. In this study, we demonstrated that both butyrate and DCA inhibited cell proliferation by up to 89% and 92% and increased cell apoptosis rate by up to 3.1- and 4.5-fold, respectively. Cell cycle analyses revealed that butyrate led to an increase in G1 and G2 fractions with a concomitant drop in the S-phase fraction, but DCA induced an increase in only G1 fraction with a concomitant drop in the S-phase fraction when compared with the untreated cells. The examination of early cellular signaling revealed that DCA but not butyrate increased intracellular reactive oxygen species, genomic DNA breakage, the activation of ERK1/2, caspase-3 and PARP. In contrast, DCA decreased activated Rb protein level, and butyrate but not DCA increased p21 expression. Collectively, although both butyrate and DCA inhibit colonic cell proliferation, butyrate increases tumor suppressor gene expression, whereas DCA decreases tumor suppressor activation in cell cycle and apoptosis pathways. Published by Elsevier Inc.
Playful Interaction

DEFF Research Database (Denmark)

2003-01-01

The video Playful Interaction describes a future architectural office, and envisions ideas and concepts for playful interactions between people, materials and appliances in a pervasive and augmented working environment. The video both describes existing developments, technologies and designs...... as well as ideas not yet implemented such as playful modes of interaction with an augmented ball. Playful Interaction has been used as a hybrid of a vision video and a video prototype (1). Externally the video has been used to visualising our new ideas, and internally the video has also worked to inspire...
Effects of dietary protein concentration and coconut oil supplementation on nitrogen utilization and production in dairy cows.

Science.gov (United States)

Lee, C; Hristov, A N; Heyler, K S; Cassidy, T W; Long, M; Corl, B A; Karnati, S K R

2011-11-01

The objective of this study was to investigate the effect of metabolizable protein (MP) deficiency and coconut oil supplementation on N utilization and production in lactating dairy cows. The hypothesis of the study was that a decrease in ruminal protozoal counts with coconut oil would increase microbial protein synthesis in the rumen, thus compensating for potential MP deficiency. The experiment was conducted for 10 wk with 36 cows (13 primiparous and 23 multiparous), including 6 ruminally cannulated cows. The experimental period, 6 wk, was preceded by 2-wk adaptation and 2-wk covariate periods. Cows were blocked by parity, days in milk, milk yield, and rumen cannulation and randomly assigned to one of the following diets: a diet with a positive MP balance (+44 g/d) and 16.7% dietary crude protein (CP) concentration (AMP); a diet deficient in MP (-156 g/d) and 14.8% CP concentration (DMP); or DMP supplemented with approximately 500 g of coconut oil/head per day (DMPCO). Ruminal ammonia tended to be greater and plasma urea N (20.1, 12.8, and 13.1 mg/dL, for AMP, DMP, and DMPCO diets, respectively) and milk urea N (12.5, 8.3, and 9.5mg/dL, respectively) were greater for AMP compared with DMP and DMPCO. The DMPCO diet decreased total protozoa counts (by 60%) compared with DMP, but had no effect on the methanogens profile in the rumen. Total tract apparent digestibility of dry matter and CP was decreased by DMP compared with AMP. Fiber digestibility was lower for both DMP and DMPCO compared with AMP. Urinary N excretion was decreased (by 37%) by both DMP and DMPCO compared with AMP. The DMP and DMPCO diets resulted in greater milk N efficiency compared with AMP (32.0 and 35.1 vs. 27.6%, respectively). Milk yield was decreased by both DMP and DMPCO compared with AMP (36.2, 34.4, and 39.3 kg/d, respectively) and coconut oil supplementation suppressed feed intake and caused milk fat depression. Coconut oil supplementation decreased short-chain fatty acid (C4:0, C6:0, and
Structure property relationship of a new nonlinear optical organic crystal: 1-(3,4-Dimethoxyphenyl-3-(3-fluorophenylprop-2-en-1-one for optical power limiting applications

Directory of Open Access Journals (Sweden)

S. Raghavendra

Full Text Available A new organic potential nonlinear optical (NLO material 1-(3,4-dimethoxyphenyl-3-(3-fluorophenylprop-2-en-1-one (DMP3FP is crystallized in acetone. The single crystal X-ray diffraction data shows that material crystallizes into centro-symmetric orthorhombic space group Pbca with a = 15.6552(6 Å, b = 8.5571(3 Å, c = 20.7697(7 Å. The functional groups in DMP3FP molecule are identified by Fourier Transfer Infrared (FTIR spectra. The thermal stability and melting point are determined using thermo gravimetric analysis/differential thermal analysis (TGA/DTA. Using UV Visible spectral studies direct band gap energy of the crystal is determined to be 3.19 eV. The nonlinear absorption coefficient and optical power limiting of the crystal was studied using Z-scan technique. The crystal exhibits a self-focusing effect at a wavelength of 532 nm showing optical limiting and reverse saturable absorption by having excited state absorption coefficient greater than ground state absorption coefficient. Keywords: Nonlinear, Optical power limiting, Z-scan, Self-focusing
Flow shear stress differentially regulates endothelial uptake of nanocarriers targeted to distinct epitopes of PECAM-1.

Science.gov (United States)

Han, Jingyan; Shuvaev, Vladimir V; Davies, Peter F; Eckmann, David M; Muro, Silvia; Muzykantov, Vladimir R

2015-07-28

Targeting nanocarriers (NC) to endothelial cell adhesion molecules including Platelet-Endothelial Cell Adhesion Molecule-1 (PECAM-1 or CD31) improves drug delivery and pharmacotherapy of inflammation, oxidative stress, thrombosis and ischemia in animal models. Recent studies unveiled that hydrodynamic conditions modulate endothelial endocytosis of NC targeted to PECAM-1, but the specificity and mechanism of effects of flow remain unknown. Here we studied the effect of flow on endocytosis by human endothelial cells of NC targeted by monoclonal antibodies Ab62 and Ab37 to distinct epitopes on the distal extracellular domain of PECAM. Flow in the range of 1-8dyn/cm(2), typical for venous vasculature, stimulated the uptake of spherical Ab/NC (~180nm diameter) carrying ~50 vs 200 Ab62 and Ab37 per NC, respectively. Effect of flow was inhibited by disruption of cholesterol-rich plasmalemma domains and deletion of PECAM-1 cytosolic tail. Flow stimulated endocytosis of Ab62/NC and Ab37/NC via eliciting distinct signaling pathways mediated by RhoA/ROCK and Src Family Kinases, respectively. Therefore, flow stimulates endothelial endocytosis of Ab/NC in a PECAM-1 epitope specific manner. Using ligands of binding to distinct epitopes on the same target molecule may enable fine-tuning of intracellular delivery based on the hemodynamic conditions in the vascular area of interest. Copyright © 2015 Elsevier B.V. All rights reserved.
Suppressor of Cytokine Signaling (SOCS 5 utilises distinct domains for regulation of JAK1 and interaction with the adaptor protein Shc-1.

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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.
Mammalian play: training for the unexpected.

Science.gov (United States)

Spinka, M; Newberry, R C; Bekoff, M

2001-06-01

In this review, we present a new conceptual framework for the study of play behavior, a hitherto puzzling array of seemingly purposeless and unrelated behavioral elements that are recognizable as play throughout the mammalian lineage. Our major new functional hypothesis is that play enables animals to develop flexible kinematic and emotional responses to unexpected events in which they experience a sudden loss of control. Specifically, we propose that play functions to increase the versatility of movements used to recover from sudden shocks such as loss of balance and falling over, and to enhance the ability of animals to cope emotionally with unexpected stressful situations. To obtain this "training for the unexpected," we suggest that animals actively seek and create unexpected situations in play through self-handicapping; that is, deliberately relaxing control over their movements or actively putting themselves into disadvantageous positions and situations. Thus, play is comprised of sequences in which the players switch rapidly between well-controlled movements similar to those used in "serious" behavior and self-handicapping movements that result in temporary loss of control. We propose that this playful switching between in-control and out-of-control elements is cognitively demanding, setting phylogenetic and ontogenetic constraints on play, and is underlain by neuroendocrinological responses that produce a complex emotional state known as "having fun." Furthermore, we propose that play is often prompted by relatively novel or unpredictable stimuli, and is thus related to, although distinct from, exploration. We present 24 predictions that arise from our new theoretical framework, examining the extent to which they are supported by the existing empirical evidence and contrasting them with the predictions of four major alternative hypotheses about play. We argue that our "training for the unexpected" hypothesis can account for some previously puzzling
Direction of technical and tactical skill in athletes playing team sports, playing with light position

Directory of Open Access Journals (Sweden)

Doroshenko Eduard Iur'evich

2011-10-01

Full Text Available A new method for evaluating the effectiveness of technical and tactical activities in basketball. A distinctive feature of the technique is presented key components of the accounting games, length of stay in the athletes play and the specific features of the game line. Established the specific means of correction of the training process taking into account the magnitude and direction of the load. Identified ways of solving the problem of optimal evaluation of gaming activities, taking into account the length of stay player on the court and its role. Refine management training process in team sports.
Biodegradation of Dimethyl Phthalate by Freshwater Unicellular Cyanobacteria

Science.gov (United States)

Zhang, Xiaohui; Liu, Lincong; Zhang, Siping; Pan, Yan; Li, Jing; Pan, Hongwei

2016-01-01

The biodegradation characteristics of dimethyl phthalate (DMP) by three freshwater unicellular organisms were investigated in this study. The findings revealed that all the organisms were capable of metabolizing DMP; among them, Cyanothece sp. PCC7822 achieved the highest degradation efficiency. Lower concentration of DMP supported the growth of the Cyanobacteria; however, with the increase of DMP concentration growth of Cyanobacteria was inhibited remarkably. Phthalic acid (PA) was detected to be an intermediate degradation product of DMP and accumulated in the culture solution. The optimal initial pH value for the degradation was detected to be 9.0, which mitigated the decrease of pH resulting from the production of PA. The optimum temperature for DMP degradation of the three species of organisms is 30°C. After 72 hours' incubation, no more than 11.8% of the residual of DMP aggregated in Cyanobacteria cells while majority of DMP remained in the medium. Moreover, esterase was induced by DMP and the activity kept increasing during the degradation process. This suggested that esterase could assist in the degradation of DMP. PMID:28078293
Biodegradation of Dimethyl Phthalate by Freshwater Unicellular Cyanobacteria.

Science.gov (United States)

Zhang, Xiaohui; Liu, Lincong; Zhang, Siping; Pan, Yan; Li, Jing; Pan, Hongwei; Xu, Shiguo; Luo, Feng

2016-01-01

The biodegradation characteristics of dimethyl phthalate (DMP) by three freshwater unicellular organisms were investigated in this study. The findings revealed that all the organisms were capable of metabolizing DMP; among them, Cyanothece sp. PCC7822 achieved the highest degradation efficiency. Lower concentration of DMP supported the growth of the Cyanobacteria; however, with the increase of DMP concentration growth of Cyanobacteria was inhibited remarkably. Phthalic acid (PA) was detected to be an intermediate degradation product of DMP and accumulated in the culture solution. The optimal initial pH value for the degradation was detected to be 9.0, which mitigated the decrease of pH resulting from the production of PA. The optimum temperature for DMP degradation of the three species of organisms is 30°C. After 72 hours' incubation, no more than 11.8% of the residual of DMP aggregated in Cyanobacteria cells while majority of DMP remained in the medium. Moreover, esterase was induced by DMP and the activity kept increasing during the degradation process. This suggested that esterase could assist in the degradation of DMP.
Branchial Cilia and Sperm Flagella Recruit Distinct Axonemal Components

Science.gov (United States)

Konno, Alu; Shiba, Kogiku; Cai, Chunhua; Inaba, Kazuo

2015-01-01

Eukaryotic cilia and flagella have highly conserved 9 + 2 structures. They are functionally diverged to play cell-type-specific roles even in a multicellular organism. Although their structural components are therefore believed to be common, few studies have investigated the molecular diversity of the protein components of the cilia and flagella in a single organism. Here we carried out a proteomic analysis and compared protein components between branchial cilia and sperm flagella in a marine invertebrate chordate, Ciona intestinalis. Distinct feature of protein recruitment in branchial cilia and sperm flagella has been clarified; (1) Isoforms of α- and β-tubulins as well as those of actins are distinctly used in branchial cilia or sperm flagella. (2) Structural components, such as dynein docking complex, tektins and an outer dense fiber protein, are used differently by the cilia and flagella. (3) Sperm flagella are specialized for the cAMP- and Ca2+-dependent regulation of outer arm dynein and for energy metabolism by glycolytic enzymes. Our present study clearly demonstrates that flagellar or ciliary proteins are properly recruited according to their function and stability, despite their apparent structural resemblance and conservation. PMID:25962172
What Play Means to Us: Exploring Children's Perspectives on Play in an English Year 1 Classroom

Science.gov (United States)

Howe, Sally

2016-01-01

Opportunities for play and self-initiated activity, considered to be an important part of children's learning in early childhood settings, diminish as children progress into school. Previous studies suggest that losing time for play/self-initiated activity can impact negatively on children's attitudes to school learning. This article discusses the…
Play, Playfulness, Creativity and Innovation

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Patrick Bateson

2014-05-01

Full Text Available Play, as defined by biologists and psychologists, is probably heterogeneous. On the other hand, playfulness may be a unitary motivational state. Playful play as opposed to activities that merge into aggression is characterized by positive mood, intrinsic motivation, occurring in a protected context and easily disrupted by stress. Playful play is a good measure of positive welfare. It can occupy a substantial part of the waking-life of a young mammal or bird. Numerous functions for play have been proposed and they are by no means mutually exclusive, but some evidence indicates that those individual animals that play most are most likely to survive and reproduce. The link of playful play to creativity and hence to innovation in humans is strong. Considerable evidence suggests that coming up with new ideas requires a different mindset from usefully implementing a new idea.

Electrochemical incineration of dimethyl phthalate by anodic oxidation with boron-doped diamond electrode

Institute of Scientific and Technical Information of China (English)

HOU Yining; QU Jiuhui; ZHAO Xu; LIU Huijuan

2009-01-01

The anodic oxidation of aqueous solutions containing dimethyl phthalate (DMP) up to 125 mg/L with sodium sulfate (Na2SO4) as supporting electrolyte within the pH range 2.0-10.0 was studied using a one-compartment batch reactor employing a boron-doped diamond (BDD) as anode. Electrolyses were carried out at constant current density (1.5-4.5 mA/cm2). Complete mineralization was always achieved owing to the great concentration of hydroxyl radical (·OH) generated at the BDD surface. The effect of pH, apparent current density and initial DMP concentration on the degradation rate of DMP, the specific charge required for its total mineralization and mineralization current efficiency was investigated systematically. The mineralization rate of DMP was found to be pH-independent and to increase with increasing applied current density. Results indicated that this electrochemical process was subjected, at least partially, to the mass transfer of organics onto the BDD surface. Kinetic analysis of the temporal change of DMP concentration during electrolysis determined by High Performance Liquid Chromatography (HPLC) revealed that DMP decay under all tested conditions followed a pseudo first-order reaction. Aromatic intermediates and generated carboxylic acids were identified by Gas Chromatography-Mass Spectrometry (GC-MS) and a general pathway for the electrochemical incineration of DMP on BDD was proposed.
Play as mediator for knowledge-creation in Problem Based Learning

DEFF Research Database (Denmark)

Thorsted, Ann Charlotte; Bing, Rie Grønbeck; Kristensen, Michael

2015-01-01

the students find that this experience enhanced a different learning form, from the one they knew from their earlier PBL processes? What was it the playful approach to PBL as a learning method had mediated? The article leads on to a distinction and a model encircling three different knowledge forms based...
Inhibitory Neural Regulation of the Ca2+ Transients in Intramuscular Interstitial Cells of Cajal in the Small Intestine

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Salah A. Baker

2018-04-01

Full Text Available Gastrointestinal motility is coordinated by enteric neurons. Both inhibitory and excitatory motor neurons innervate the syncytium consisting of smooth muscle cells (SMCs interstitial cells of Cajal (ICC and PDGFRα+ cells (SIP syncytium. Confocal imaging of mouse small intestines from animals expressing GCaMP3 in ICC were used to investigate inhibitory neural regulation of ICC in the deep muscular plexus (ICC-DMP. We hypothesized that Ca2+ signaling in ICC-DMP can be modulated by inhibitory enteric neural input. ICC-DMP lie in close proximity to the varicosities of motor neurons and generate ongoing Ca2+ transients that underlie activation of Ca2+-dependent Cl− channels and regulate the excitability of SMCs in the SIP syncytium. Electrical field stimulation (EFS caused inhibition of Ca2+ for the first 2–3 s of stimulation, and then Ca2+ transients escaped from inhibition. The NO donor (DEA-NONOate inhibited Ca2+ transients and Nω-Nitro-L-arginine (L-NNA or a guanylate cyclase inhibitor (ODQ blocked inhibition induced by EFS. Purinergic neurotransmission did not affect Ca2+ transients in ICC-DMP. Purinergic neurotransmission elicits hyperpolarization of the SIP syncytium by activation of K+ channels in PDGFRα+ cells. Generalized hyperpolarization of SIP cells by pinacidil (KATP agonist or MRS2365 (P2Y1 agonist also had no effect on Ca2+ transients in ICC-DMP. Peptidergic transmitter receptors (VIP and PACAP are expressed in ICC and can modulate ICC-DMP Ca2+ transients. In summary Ca2+ transients in ICC-DMP are blocked by enteric inhibitory neurotransmission. ICC-DMP lack a voltage-dependent mechanism for regulating Ca2+ release, and this protects Ca2+ handling in ICC-DMP from membrane potential changes in other SIP cells.
Two distinct affinity binding sites for IL-1 on human cell lines

International Nuclear Information System (INIS)

Bensimon, C.; Wakasugi, N.; Tagaya, Y.; Takakura, K.; Yodoi, J.; Tursz, T.; Wakasugi, H.

1989-01-01

We used two human cell lines, NK-like YT-C3 and an EBV-containing B cell line, 3B6, as models to study the receptor(s) for IL-1. Two distinct types of saturable binding sites were found on both cell lines at 37 degrees C. Between 1 pM and 100 pM of 125I-IL-1-alpha concentration, saturable binding sites were detected on the YT-C3 cells with a K of 4 x 10(-11) M. The K found for the IL-1-alpha binding sites on 3B6 cells was 7.5 x 10(-11) M. An additional binding curve was detected above 100 pM on YT-C3 cells with a K of 7 x 10(-9) M and on 3B6 cells with a K of 5 x 10(-9) M. Scatchard plot analysis revealed 600 sites/cell with high affinity binding and 7000 sites/cell with low affinity for YT-C3 cells and 300 sites/cell with high affinity binding and 6000 sites/cell with low affinity for 3B6 cells. At 37 degrees C, the internalization of 125I-labeled IL-1 occurred via both high and low affinity IL-1R on both YT-C3 and 3B6 cells, whereas the rates of internalization for high affinity binding sites on YT-C3 cells were predominant in comparison to that of low affinity binding sites. In chemical cross-linking studies of 125 I-IL-1-alpha to 3B6 and YT-C3 cells, two protein bands were immunoprecipitated with Mr around 85 to 90 kDa leading to an estimation of the Mr of the IL-1R around 68 to 72 kDa. In similar experiments, the Mr found for the IL-1R expressed on the murine T cell line EL4 was slightly higher (around 80 kDa). Whether these distinct affinity binding sites are shared by a single molecule or by various chains remains to be elucidated
Sketch for a model of four epistemological positions toward computer game play

DEFF Research Database (Denmark)

Leino, Olli

2008-01-01

The paper attempts to sketch out four distinct epistemological positions toward the player, who is understood as derived from play and game. To map out the problem field, two equally challenged positions toward computer game play are observed, emerging from inadequate treatment of the differences...... of playing a game is seen as independent of what goes on in the player’s mind (actually, the player might not even be the true subject of the game). Similar polarities are postulated regarding a game; from an exclusive viewpoint .game. is a signifying shorthand for objects, which, when observed from...
Molecular Tracers of Saturated and Polycyclic Aromatic Hydrocarbon Inputs into Central Park Lake, New York City

Science.gov (United States)

YAN, BEIZHAN; ABRAJANO, TEOFILO A.; BOPP, RICHARD F.; CHAKY, DAMON A.; BENEDICT, LUCILLE A.; CHILLRUD, STEVEN N.

2011-01-01

Saturated hydrocarbons (SH) and polycyclic aromatic hydrocarbons (PAHs) have been quantified in a sediment core obtained from Central Park Lake, New York City. Radionuclides 210Pb and 137Cs were used to assign approximate dates to each individual section in the core. The dating profile based on 210Pb matches very well with the time constraints provided by 137Cs. Radionuclide-derived depositional dates are consistent with temporal information from the petroleum-indicator ratio U/R [the ratio of unresolved complex mixture (UCM) to saturated hydrocarbons in the aliphatic fraction] and the history of fuel use in the NYC area. Ratios of 1,7-dimethylphenanthrane (DMP) to 1,7-DMP plus 2,6-DMP [1,7/(1,7 + 2,6)-DMP], retene to retene plus chrysene [Ret/(Ret + Chy)], and fluoranthene to fluoranthene plus pyrene [Fl/(Fl + Py)] provide additional source discrimination throughout the core. Results show that the ratio U/R is sensitive to petroleum inputs and Ret/(Ret + Chy) is responsive to contributions from softwood combustion, whereas both Fl/(Fl + Py) and 1,7/(1,7 + 2,6)-DMP can be used to discriminate among wood, coal, and petroleum combustion sources. Combined use of these ratios suggests that in New York City, wood combustion dominated 100 years ago, with a shift to coal combustion occurring from the 1900s to the 1950s. Petroleum use began around the 1920s and has dominated since the 1940s. PMID:16201624
L1 Korean and L1 Mandarin L2 English Learners' Acquisition of the Count/Mass Distinction in English

Science.gov (United States)

Choi, Sea Hee; Ionin, Tania; Zhu, Yeqiu

2018-01-01

This study investigates the second language (L2) acquisition of the English count/mass distinction by speakers of Korean and Mandarin Chinese, with a focus on the semantics of atomicity. It is hypothesized that L1-Korean and L1-Mandarin L2-English learners are influenced by atomicity in the use of the count/mass morphosyntax in English. This…
Plasma Cell Alloantigen 1 and IL-10 Secretion Define Two Distinct Peritoneal B1a B Cell Subsets With Opposite Functions, PC1high Cells Being Protective and PC1low Cells Harmful for the Growing Fetus

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Anne Schumacher

2018-05-01

Full Text Available B cells possess various immuno regulatory functions. However, research about their participation in tolerance induction toward the fetus is just emerging. Accumulating evidence supports the idea that B cells can play seemingly conflicting roles during pregnancy, either protecting or harming the fetus. Previous findings indicated the presence of two different peritoneal B cell subsets, defined by the expression of the plasma cell alloantigen 1 (PC1 and with distinct immune modulatory functions. Here, we aimed to study the participation of these two B cell subsets, on pregnancy outcome in a murine model of disturbed fetal tolerance. The frequencies and cell numbers of peritoneal and splenic CD19+IL-10+ and CD19+CD5+IL-10+PC1+ cells were assessed in virgin as well as normal pregnant (NP and abortion-prone (AP females during the course of gestation. Peritoneal PC1low or PC1high B1a B cells were sorted, analyzed for their ability to secrete IL-10 and adoptively transferred into NP or AP females. On gestation day (gd 12, the abortion rate as well as the frequencies and cell numbers of regulatory T cells, TH1 and TH17 cells were determined in spleens and decidua. In addition, mRNA expression of IL-10, TGF-β, IFN-γ, and TNF-α was analyzed in decidual tissue. Peritoneal CD19+IL-10+ and CD19+CD5+IL-10+PC1+ frequencies fluctuated during the progression of normal pregnancies while no significant changes were observed in spleen. AP females showed significantly reduced frequencies of both B cell populations and exhibited an altered peritoneal PC1high/PC1low ratio at gd10. Adoptive transfers of PC1low B1a B cells into NP females increased the abortion rate in association with a reduced splenic regulatory T/TH17 ratio. By contrast, the transfer of PC1high B1a B cells into AP females significantly diminished the fetal rejection rate and significantly reduced the numbers of splenic TH17 cells. Our results suggest that the peritoneum harbors two distinct B1a B
Osteocytes, not Osteoblasts or Lining Cells, are the Main Source of the RANKL Required for Osteoclast Formation in Remodeling Bone.

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Jinhu Xiong

Full Text Available The cytokine receptor activator of nuclear factor kappa B ligand (RANKL, encoded by the Tnfsf11 gene, is essential for osteoclastogenesis and previous studies have shown that deletion of the Tnfsf11 gene using a Dmp1-Cre transgene reduces osteoclast formation in cancellous bone by more than 70%. However, the Dmp1-Cre transgene used in those studies leads to recombination in osteocytes, osteoblasts, and lining cells making it unclear whether one or more of these cell types produce the RANKL required for osteoclast formation in cancellous bone. Because osteoblasts, osteocytes, and lining cells have distinct locations and functions, distinguishing which of these cell types are sources of RANKL is essential for understanding the orchestration of bone remodeling. To distinguish between these possibilities, we have now created transgenic mice expressing the Cre recombinase under the control of regulatory elements of the Sost gene, which is expressed in osteocytes but not osteoblasts or lining cells in murine bone. Activity of the Sost-Cre transgene in osteocytes, but not osteoblast or lining cells, was confirmed by crossing Sost-Cre transgenic mice with tdTomato and R26R Cre-reporter mice, which express tdTomato fluorescent protein or LacZ, respectively, only in cells expressing the Cre recombinase or their descendants. Deletion of the Tnfsf11 gene in Sost-Cre mice led to a threefold decrease in osteoclast number in cancellous bone and increased cancellous bone mass, mimicking the skeletal phenotype of mice in which the Tnfsf11 gene was deleted using the Dmp1-Cre transgene. These results demonstrate that osteocytes, not osteoblasts or lining cells, are the main source of the RANKL required for osteoclast formation in remodeling cancellous bone.
Skeletal muscle, but not cardiovascular function, is altered in a mouse model of autosomal recessive hypophosphatemic rickets

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Michael J. Wacker

2016-05-01

Full Text Available Autosomal recessive hypophosphatemic rickets (ARHR is a heritable disorder characterized by hypophosphatemia, osteomalacia, and poor bone development. ARHR results from inactivating mutations in the DMP1 gene with the human phenotype being recapitulated in the Dmp1 null mouse model which displays elevated plasma fibroblast growth factor 23. While the bone phenotype has been well characterized, it is not known what effects ARHR may also have on skeletal, cardiac, or vascular smooth muscle function, which is critical to understand to treat patients suffering from this condition. In this study, the extensor digitorum longus (EDL- fast-twitch muscle, soleus (SOL- slow-twitch muscle, heart, and aorta were removed from Dmp1 null mice and ex-vivo functional tests were simultaneously performed in collaboration by three different laboratories. Dmp1 null EDL and SOL muscles produced less force than wildtype muscles after normalization for physiological cross sectional area of the muscles. Both EDL and SOL muscles from Dmp1 null mice also produced less force after the addition of caffeine (which releases calcium from the sarcoplasmic reticulum which may indicate problems in excitation contraction coupling in these mice. While the body weights of the Dmp1 null were smaller than wildtype, the heart weight to body weight ratio was higher. However, there were no differences in pathological hypertrophic gene expression compared to wildtype and maximal force of contraction was not different indicating that there may not be cardiac pathology under the tested conditions. We did observe a decrease in the rate of force development generated by cardiac muscle in the Dmp1 null which may be related to some of the deficits observed in skeletal muscle. There were no differences observed in aortic contractions induced by PGF2a or 5-HT or in endothelium-mediated acetylcholine-induced relaxations or endothelium-independent sodium nitroprusside-induced relaxations. In
Interaction between EphrinB1 and CNK1 Found to Play Role in Tumor Progression | Poster

Science.gov (United States)

By Nancy Parrish, Staff Writer The family of proteins known as ephrins plays a critical role in a variety of biological processes. In a recent article in the Journal of Biological Chemistry, Hee Jun Cho, Ph.D., and colleagues report on the interaction between proteins CNK1 and ephrinB1 that promotes cell movement. Their findings may have an important implication in developing
The effectiveness of German disease management programs (DMPs) in patients with type 2 diabetes mellitus and coronary heart disease: results from an observational longitudinal study.

Science.gov (United States)

Laxy, Michael; Stark, Renée; Meisinger, Christa; Kirchberger, Inge; Heier, Margit; von Scheidt, Wolfgang; Holle, Rolf

2015-01-01

Although the population-based German disease management programs (DMPs) for diabetes mellitus (DM) and coronary heart disease (CHD) are among the biggest worldwide, evidence on the effectiveness of these programs is still inconclusive or missing, particularly for high risk patients with comorbidities. The objective of this study was therefore to analyze the impact of DMPs on process and outcome parameters in patients with both, type 2 DM and CHD. Analyses are based on two postal surveys of patients from the KORA myocardial infarction registry (southern Germany) with type 2 DM and on two postal validation studies with patients' general physicians (2006, n = 312 and 2011, n = 212). The association between DMP enrollment (being enrolled in either DMP-DM or DMP-CHD) and guideline care (defined by several process indicators) at baseline (2006) and its development until follow-up (2011) was analyzed using logistic regression models accounting for the repeated measurements structure. The impact of DMP enrollment/guideline care on cumulated (quality-adjusted) life years ((QA)LYs) over a 4-year time horizon (2006-2010) was assessed using multiple linear regression methods. Logistic regression models were applied to analyze the association between DMP status and patient self-management at follow-up. Being enrolled in a DMP was associated with better guideline care at baseline [OR = 2.3 (95 % CI 1.27-4.03)], but not at follow-up [OR = 0.80 (95 % CI 0.40-1.58); p value for time-interaction management than patients not being enrolled into a DMP. The results of this study concerning the effectiveness of DMPs in patients with DM and CHD are mixed, but are weakly in favor of DMPs. However, we found a clear positive impact of guideline care on quality adjusted survival in this patient group. The development of the association between DMP enrollment and guideline care over the follow-up time indicates some external effects, which should be the subject of further
Risk of Nonfatal Stroke in Type 2 Diabetes Mellitus Patients: A Retrospective Comparison Between Disease Management Programs and Standard Care.

Science.gov (United States)

Wiefarn, Stefan; Heumann, Christian; Rettelbach, Anja; Kostev, Karel

2017-07-01

The present retrospective study examines the influence of disease management programs on nonfatal stroke in type 2 diabetes mellitus (T2DM) patients in Germany. The evaluation is based on retrospective patient data from the Disease Analyzer (IMS Health). The analysis included 169 414 T2DM patients aged 40 years and older with an initial prescription of antihyperglycemic therapy between January 2004 and December 2014. A total of 86 713 patients participated in a disease management program (DMP) for T2DM and 82 701 patients received standard care. The main outcome measure of this study was nonfatal stroke. Kaplan-Meier curves of DMP and SC patients were compared using log rank test. The Cox proportional hazards model was used to provide an adjusted estimate of the DMP effect. It is apparent from the baseline characteristics that the general health of patients receiving standard care was poorer than that of patients participating in a DMP. The baseline HbA1c value was 7.6% in the DMP group and 7.8% in the SC group. Furthermore, the SC group had a higher proportion of preexisting conditions, such as coronary heart disease (CHD), peripheral arterial occlusive disease (pAOD), and renal insufficiency. The proportion of patients who received insulin in first year therapy was higher in the SC group. Time to event analysis showed that DMP was associated with a delayed occurrence of stroke, because stroke occurred an average of 350 days later in DMP patients than in patients receiving SC (DMP: 1.216 days, RV: 866 days). The Cox model with covariable adjustment confirmed the significant association of DMPs with nonfatal stroke in patients with type 2 diabetes mellitus (HR 0.71; 95% CI: 0.69-0.74). The present study indicates that DMPs are positively associated with stroke. The possible reasons for this must be verified in further studies.
Internal Transcribed Spacer 1 (ITS1 based sequence typing reveals phylogenetically distinct Ascaris population

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Koushik Das

2015-01-01

Full Text Available Taxonomic differentiation among morphologically identical Ascaris species is a debatable scientific issue in the context of Ascariasis epidemiology. To explain the disease epidemiology and also the taxonomic position of different Ascaris species, genome information of infecting strains from endemic areas throughout the world is certainly crucial. Ascaris population from human has been genetically characterized based on the widely used genetic marker, internal transcribed spacer1 (ITS1. Along with previously reported and prevalent genotype G1, 8 new sequence variants of ITS1 have been identified. Genotype G1 was significantly present among female patients aged between 10 to 15 years. Intragenic linkage disequilibrium (LD analysis at target locus within our study population has identified an incomplete LD value with potential recombination events. A separate cluster of Indian isolates with high bootstrap value indicate their distinct phylogenetic position in comparison to the global Ascaris population. Genetic shuffling through recombination could be a possible reason for high population diversity and frequent emergence of new sequence variants, identified in present and other previous studies. This study explores the genetic organization of Indian Ascaris population for the first time which certainly includes some fundamental information on the molecular epidemiology of Ascariasis.
Timing the Generation of Distinct Retinal Cells by Homeobox Proteins

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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
Timing the generation of distinct retinal cells by homeobox proteins.

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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.
Disease management programmes for patients with coronary heart disease--an empirical study of German programmes.

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Gapp, Oliver; Schweikert, Bernd; Meisinger, Christa; Holle, Rolf

2008-12-01

To evaluate healthcare and outcomes of disease management programmes (DMPs) for patients with coronary heart disease (CHD) in primary care, and to assess selection of enrollment for these programmes. A cross-sectional survey of 2330 statutorily insured patients with a history of acute myocardial infarction (AMI) was performed in 2006 by the population-based KORA Myocardial Infarction Register from the region of Augsburg, Germany. Patients enrolled in DMP-CHDs receive evidence-based care, with patients not enrolled receiving standard care. To control for selection bias, a propensity score approach was used. Main factors influencing DMP participation were age (OR 0.98, 95% CI 0.96-0.99), diabetes (OR 1.56, CI 1.25-1.95) and time since last heart attack (OR 0.98, CI 0.95-0.99). Significantly more patients enrolled in DMP-CHDs stated that they received medical counselling for smoking (OR 3.77, CI 1.07-13.34), nutrition (OR 2.15, 1.69-2.74) and for physical activity (OR 2.58, 1.99-3.35). Furthermore, prescription of statins (OR 1.58, CI 1.24-2.00), antiplatelets (OR 1.96, CI 1.43-2.69) and beta-blockers (not significant) were higher in the DMP group. With respect to outcomes, we did not see relevant differences in quality of life and body mass index, and only a minor reduction in smoking. Enrollment into DMPs for CHD exhibits systematic selection effects. Participants tend to experience--at least on a short to medium term and for AMI patients--better quality of healthcare services. However, since DMP-CHDs were initiated only 2 years ago, we were unable to identify significant improvements in health outcomes. Only the reduction in smoking provides a first indication of better quality outcomes following DMP-CHD. Thus, policy-makers must provide appropriate incentives to sickness funds and physicians in order to ensure initiation and continuation of high quality DMPs.
Analysing playing using the note-time playing path.

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de Graaff, Deborah L E; Schubert, Emery

2011-03-01

This article introduces a new method of data analysis that represents the playing of written music as a graph. The method, inspired by Miklaszewski, charts low-level note timings from a sound recording of a single-line instrument using high-precision audio-to-MIDI conversion software. Note onset times of pitch sequences are then plotted against the score-predicted timings to produce a Note-Time Playing Path (NTPP). The score-predicted onset time of each sequentially performed note (horizontal axis) unfolds in performed time down the page (vertical axis). NTPPs provide a visualisation that shows (1) tempo variations, (2) repetitive practice behaviours, (3) segmenting of material, (4) precise note time positions, and (5) time spent on playing or not playing. The NTPP can provide significant new insights into behaviour and cognition of music performance and may also be used to complement established traditional approaches such as think-alouds, interviews, and video coding.
AMADEUS Project Deliverable 1.2: Data Management Plan

OpenAIRE

Ana Belén Cristobal

2018-01-01

This document describes the initial Data Management Plan (DMP) for AMADEUS project. It addresses Project administration data collected as part of the execution and management of a disruptive research that could be in the market in the incoming years.
Ionic Liquids as a New Platform for Fiber Brittleness Removal

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Zhili Zhang

2015-08-01

Full Text Available In the present study, three ionic liquids, 1-butyl-3-methylimidazolium chloride ([BMIM]Cl, 1-allyl-3-methylimidazolium ([AMIM]Cl, and 1-ethyl-3-methylimidazolium chloride dimethyphosphate ([EMIM]DMP, were used to eliminate the brittleness of recycled fibers. The results showed that the pretreatments with ionic liquids were able to modify and improve the properties of recycled fibers even at high moisture contents. [EMIM]DMP gave better performance compared to [BMIM]Cl and [AMIM]Cl, which can tolerate higher moisture contents. The optimal conditions of EMIM]DMP pretreatment were moisture content of 65%, [EMIM]DMP dosage of 20 wt-%, 80 °C, and 60 min, for which a higher brittleness removal was obtained. The tensile index, bursting index, and tearing index of handsheets were increased by 32.4%, 57.0%, and 46.5%, respectively. Fiber quality was improved as demonstrated by fiber length, lowered fines content, and increased swellability. Such results imply that ionic liquids pretreatment can promote the swelling of recycled fibers and remove their brittleness.

The mitochondrial elongation factors MIEF1 and MIEF2 exert partially distinct functions in mitochondrial dynamics

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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
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
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.
Living with a crucial decision: a qualitative study of parental narratives three years after the loss of their newborn in the NICU.

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Laurence Caeymaex

Full Text Available BACKGROUND: The importance of involving parents in the end-of-life decision-making-process (EOL DMP for their child in the neonatal intensive care unit (NICU is recognised by ethical guidelines in numerous countries. However, studies exploring parents' opinions on the type of involvement report conflicting results. This study sought to explore parents' experience of the EOL DMP for their child in the NICU. METHODS: The study used a retrospective longitudinal design with a qualitative analysis of parental experience 3 years after the death of their child in four NICUs in France. 53 face-to-face interviews and 80 telephone interviews were conducted with 164 individuals. Semi-structured interviews were conducted to explore how parents perceived their role in the decision process, what they valued about physicians' attitudes in this situation and whether their long-term emotional well being varied according to their perceived role in the EOL DMP. FINDINGS: Qualitative analysis identified four types of perceived role in the DMP: shared, medical, informed parental decision, and no decision. Shared DM was the most appreciated by parents. Medical DM was experienced as positive only when it was associated with communication. Informed parental DM was associated with feelings of anxiousness and abandonment. The physicians' attitudes that were perceived as helpful in the long term were explicit sharing of responsibility, clear expression of staff preferences, and respectful care and language toward the child. INTERPRETATION: Parents find it valuable to express their opinion in the EOL DMP of their child. Nonetheless, they do need continuous emotional support and an explicit share of the responsibility for the decision. As involvement preferences and associated feelings can vary, parents should be able to decide what role they want to play. However, our study suggests that fully autonomous decisions should be misadvised in these types of tragic choices.
Aping expressions? Chimpanzees produce distinct laugh types when responding to laughter of others.

Science.gov (United States)

Davila-Ross, Marina; Allcock, Bethan; Thomas, Chris; Bard, Kim A

2011-10-01

Humans have the ability to replicate the emotional expressions of others even when they undergo different emotions. Such distinct responses of expressions, especially positive expressions, play a central role in everyday social communication of humans and may give the responding individuals important advantages in cooperation and communication. The present work examined laughter in chimpanzees to test whether nonhuman primates also use their expressions in such distinct ways. The approach was first to examine the form and occurrence of laugh replications (laughter after the laughter of others) and spontaneous laughter of chimpanzees during social play and then to test whether their laugh replications represented laugh-elicited laugh responses (laughter triggered by the laughter of others) by using a quantitative method designed to measure responses in natural social settings. The results of this study indicated that chimpanzees produce laugh-elicited laughter that is distinct in form and occurrence from their spontaneous laughter. These findings provide the first empirical evidence that nonhuman primates have the ability to replicate the expressions of others by producing expressions that differ in their underlying emotions and social implications. The data further showed that the laugh-elicited laugh responses of the subjects were closely linked to play maintenance, suggesting that chimpanzees might gain important cooperative and communicative advantages by responding with laughter to the laughter of their social partners. Notably, some chimpanzee groups of this study responded more with laughter than others, an outcome that provides empirical support of a socialization of expressions in great apes similar to that of humans.
Play Practices and Play Moods

DEFF Research Database (Denmark)

Karoff, Helle Skovbjerg

2013-01-01

The aim of this article is to develop a view of play as a relation between play practices and play moods based on an empirical study of children's everyday life and by using Bateson's term of ‘framing’ [(1955/2001). In Steps to an ecology of mind (pp. 75–80). Chicago: University of Chicago Press......], Schmidt's notion of ‘commonness’ [(2005). Om respekten. København: Danmarks Pædagogiske Universitets Forlag; (2011). On respect. Copenhagen: Danish School of Education University Press] and Heidegger's term ‘mood’ [(1938/1996). Time and being. Cornwall: Wiley-Blackwell.]. Play mood is a state of being...... in which we are open and ready, both to others and their production of meaning and to new opportunities for producing meaning. This play mood is created when we engage with the world during play practices. The article points out four types of play moods – devotion, intensity, tension and euphorica – which...
A prospective examination of disease management program use by complex cardiac outpatients.

Science.gov (United States)

Gravely, Shannon; Reid, Robert D; Oh, Paul; Ross, Heather; Stewart, Donna E; Grace, Sherry L

2012-01-01

The use of disease management programs (DMPs) by patients with cardiovascular disease (CVD) is associated with improved outcomes. Although rates of cardiac rehabilitation (CR) use are well established, less is known about other DMPs. The objectives of this study were to describe the degree of DMP utilization by CVD outpatients, and examine factors related to use. This study represents a secondary analysis of a larger prospective cohort study. In hospital, 2635 CVD inpatients from 11 hospitals in Ontario Canada completed a survey that assessed factors affecting DMP utilization. One year later, 1803 participants completed a mailed survey that assessed DMP utilization. One thousand seventy-three (59.5%) participants reported using at least 1 DMP. Overall, 951 (52.7%) reported participating in cardiac rehabilitation, and among participants with a comorbid indication, 212 (41.2%) reported attending a diabetes education centre, 28 (25.9%) attended stroke rehabilitation, 35 (12.9%) used a heart failure clinic, and 13 (11.7%) attended a smoking cessation program. A multinomial logistic regression analysis showed that compared with no DMP use, participants that attended 1 or multiple programs were younger, married, diagnosed with a myocardial infarction, less likely to have had a percutaneous coronary intervention and had higher perceptions of personal control over their heart condition. There were few differences between participants that used 1 vs multiple DMPs, however, having diabetes or comorbid stroke significantly increased the likelihood of multiple DMP use. Approximately 40% of CVD outpatients do not access DMPs. An integrated approach to vascular disease management appears warranted. Copyright © 2012 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
Designing Out the Play: Accessibility and Playfulness in Inclusive Play.

Science.gov (United States)

Holt, Raymond; Beckett, Angharad

2017-01-01

Play is an important part of child development, yet disabled children are often excluded from the opportunity to play, either due to lack of accessible toys and games, or social pressures. This paper presents a case study reflecting on the development of Button Bash: a switch accessible game intended to encourage inclusive play between disabled and non-disabled children. In particular, the paper focuses on how changes intended to make the game more accessible tended to make it less playful, and reflects on the relationship between playfulness and accessibility.
Health promoting schools and children's oral health related quality of life.

Science.gov (United States)

Yusof, Zamros Y M; Jaafar, Nasruddin

2013-12-10

The study objective was to compare children's oral health related quality of life (OHRQoL) in schools with 6 years of implementation of a health promoting school model in Malaysia, i.e. the Doktor Muda Programme (DMP) and in schools without the DMP. This report was part of a larger study to evaluate the DMP impact on schoolchildren's oral health knowledge, attitudes, behaviour, caries progression and OHRQoL. It was conducted in Negri Sembilan state. The sample comprised 3455, Year 6 (11-12 year old) children; 1282 from DMP (intervention) and 2173 from non-DMP (control) schools. The Malay Child-OIDP index was used to evaluate children's levels of oral impacts on 8 daily performances after 6 years of DMP implementation (2006-2011). Prevalence, score, impact intensity, causes and extent of impacts were compared. Chi-square and Mann-Whitney tests were used in the data analysis. Overall response rate was 95.1%. Prevalence of overall impacts was 57.8% and 60.8% (mean total impact score was 7.10 and 7.77) in the intervention and control group, respectively. The three most frequently affected performances in both groups were eating, cleaning teeth and emotional stability. Significantly less DMP children had oral impact on cleaning teeth (p = 0.034). The majority of children with impacts in both groups reported 'very little' to 'moderate' levels of impact intensity. Significantly more DMP children reported having 'very little' and 'little' levels of impact intensity on cleaning teeth (p = 0.037) and emotional stability (p = 0.020), respectively. Significantly less DMP children reported having 'very severe' level of impact intensity on speaking (p = 0.038). The most prevalent cause of impacts in both groups was toothache. Significantly less DMP children reported bleeding gums (p = 0.016) and presence of plaque/calculus as causes of impacts (p = 0.032). About 75% of children with impacts in both groups reported having up to four daily performances affected. This study showed
Gain-of-function SOS1 mutations cause a distinctive form of noonansyndrome

Energy Technology Data Exchange (ETDEWEB)

Tartaglia, Marco; Pennacchio, Len A.; Zhao, Chen; Yadav, KamleshK.; Fodale, Valentina; Sarkozy, Anna; Pandit, Bhaswati; Oishi, Kimihiko; Martinelli, Simone; Schackwitz, Wendy; Ustaszewska, Anna; Martin, Joes; Bristow, James; Carta, Claudio; Lepri, Francesca; Neri, Cinzia; Vasta,Isabella; Gibson, Kate; Curry, Cynthia J.; Lopez Siguero, Juan Pedro; Digilio, Maria Cristina; Zampino, Giuseppe; Dallapiccola, Bruno; Bar-Sagi, Dafna; Gelb, Brude D.

2006-09-01

Noonan syndrome (NS) is a developmental disordercharacterized by short stature, facial dysmorphia, congenital heartdefects and skeletal anomalies1. Increased RAS-mitogenactivated proteinkinase (MAPK) signaling due to PTPN11 and KRAS mutations cause 50 percentof NS2-6. Here, we report that 22 of 129 NS patients without PTPN11 orKRAS mutation (17 percent) have missense mutations in SOS1, which encodesa RAS-specific guanine nucleotide exchange factor (GEF). SOS1 mutationscluster at residues implicated in the maintenance of SOS1 in itsautoinhibited form and ectopic expression of two NS-associated mutantsinduced enhanced RAS activation. The phenotype associated with SOS1defects is distinctive, although within NS spectrum, with a highprevalence of ectodermal abnormalities but generally normal developmentand linear growth. Our findings implicate for the first timegain-of-function mutations in a RAS GEF in inherited disease and define anew mechanism by which upregulation of the RAS pathway can profoundlychange human development.
The impact of a disease management programme for type 2 diabetes on health-related quality of life: multilevel analysis of a cluster-randomised controlled trial.

Science.gov (United States)

Panisch, Sigrid; Johansson, Tim; Flamm, Maria; Winkler, Henrike; Weitgasser, Raimund; Sönnichsen, Andreas C

2018-01-01

Type 2 diabetes is a chronic disease associated with poorer health outcomes and decreased health related quality of life (HRQoL). The aim of this analysis was to explore the impact of a disease management programme (DMP) in type 2 diabetes on HRQoL. A multilevel model was used to explain the variation in EQ-VAS. A cluster-randomized controlled trial-analysis of the secondary endpoint HRQoL. Our study population were general practitioners and patients in the province of Salzburg. The DMP "Therapie-Aktiv" was implemented in the intervention group, and controls received usual care. Outcome measure was a change in EQ-VAS after 12 months. For comparison of rates, we used Fisher's Exact test; for continuous variables the independent T test or Welch test were used. In the multilevel modeling, we examined various models, continuously adding variables to explain the variation in the dependent variable, starting with an empty model, including only the random intercept. We analysed random effects parameters in order to disentangle variation of the final EQ-VAS. The EQ-VAS significantly increased within the intervention group (mean difference 2.19, p = 0.005). There was no significant difference in EQ-VAS between groups (mean difference 1.00, p = 0.339). In the intervention group the improvement was more distinct in women (2.46, p = 0.036) compared to men (1.92, p = 0.063). In multilevel modeling, sex, age, family and work circumstances, any macrovascular diabetic complication, duration of diabetes, baseline body mass index and baseline EQ-VAS significantly influence final EQ-VAS, while DMP does not. The final model explains 28.9% (EQ-VAS) of the total variance. Most of the unexplained variance was found on patient-level (95%) and less on GP-level (5%). DMP "Therapie-Aktiv" has no significant impact on final EQ-VAS. The impact of DMPs in type 2 diabetes on HRQoL is still unclear and future programmes should focus on patient specific needs and predictors in
Erotic Language as Dramatic Action in Plays by Lyly and Shakespeare

Science.gov (United States)

Knoll, Gillian

2012-01-01

This study closely examines the language of desire in the dramatic works of John Lyly and William Shakespeare, and argues that contemplative and analytical speeches about desire function as modes of action in their plays. Erotic speeches do more than express desire in a purely descriptive or perlocutionary capacity distinct from the action of the…
HJV and HFE Play Distinct Roles in Regulating Hepcidin.

Science.gov (United States)

Wu, Qian; Wang, Hao; An, Peng; Tao, Yunlong; Deng, Jiali; Zhang, Zhuzhen; Shen, Yuanyuan; Chen, Caiyong; Min, Junxia; Wang, Fudi

2015-05-20

Hereditary hemochromatosis (HH) is an iron overload disease that is caused by mutations in HFE, HJV, and several other genes. However, whether HFE-HH and HJV-HH share a common pathway via hepcidin regulation is currently unclear. Recently, some HH patients have been reported to carry concurrent mutations in both the HFE and HJV genes. To dissect the roles and molecular mechanisms of HFE and/or HJV in the pathogenesis of HH, we studied Hfe(-/-), Hjv(-/-), and Hfe(-/-)Hjv(-/-) double-knockout mouse models. Hfe(-/-)Hjv(-/-) mice developed iron overload in multiple organs at levels comparable to Hjv(-/-) mice. After an acute delivery of iron, the expression of hepcidin (i.e., Hamp1 mRNA) was increased in the livers of wild-type and Hfe(-/-) mice, but not in either Hjv(-/-) or Hfe(-/-)Hjv(-/-) mice. Furthermore, iron-induced phosphorylation of Smad1/5/8 was not detected in the livers of Hjv(-/-) or Hfe(-/-)Hjv(-/-) mice. We generated and phenotypically characterized Hfe(-/-)Hjv(-/-) double-knockout mice. In addition, because they faithfully phenocopy clinical HH patients, these mouse models are an invaluable tool for mechanistically dissecting how HFE and HJV regulate hepcidin expression. Based on our results, we conclude that HFE may depend on HJV for transferrin-dependent hepcidin regulation. The presence of residual hepcidin in the absence of HFE suggests either the presence of an unknown regulator (e.g., TFR2) that is synergistic with HJV or that HJV is sufficient to maintain basal levels of hepcidin.
BAP1 PLAYS A SURVIVAL ROLE IN CUTANEOUS MELANOMA

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Kumar, Raj; Taylor, Michael; Miao, Benchun; Ji, Zhenyu; Njauw, Jenny Ching-Ni; Jönsson, Göran; Frederick, Dennie Tompers; Tsao, Hensin

2014-01-01

Although the pattern of BAP1 inactivation in ocular melanoma specimens and in the BAP1 cutaneous/ocular melanoma (CM/OM) predisposition syndrome suggests a tumor suppressor function, the specific role of this gene in the pathogenesis of cutaneous melanoma is not fully understood. We thus set out to characterize BAP1 in cutaneous melanoma and discovered an unexpected pro-survival effect of this protein. Tissue and cell lines analysis showed that BAP1 expression was maintained, rather than lost, in primary melanomas compared to nevi and normal skin. Genetic depletion of BAP1 in melanoma cells reduced proliferation and colony forming capability, induced apoptosis and inhibited melanoma tumor growth in vivo. On the molecular level, suppression of BAP1 led to a concomitant drop in the protein levels of survivin a member of anti-apoptotic proteins and a known mediator of melanoma survival. Restoration of survivin in melanoma cells partially rescued the growth-retarding effects of BAP1 loss. In contrast to melanoma cells, stable overexpression of BAP1 into immortalized but non-transformed melanocytes did suppress proliferation and reduce survivin. Taken together, these studies demonstrate that BAP1 may play a growth-sustaining role in melanoma cells, but that its impact on ubiquitination underpins a complex physiology which is context and cell dependent. PMID:25521456
Tp53 gene mediates distinct dopaminergic neuronal damage in different dopaminergic neurotoxicant models

Directory of Open Access Journals (Sweden)

Tao Lu

2017-01-01

Full Text Available Tp53, a stress response gene, is involved in diverse cell death pathways and its activation is implicated in the pathogenesis of Parkinson's disease. However, whether the neuronal Tp53 protein plays a direct role in regulating dopaminergic (DA neuronal cell death or neuronal terminal damage in different neurotoxicant models is unknown. In our recent studies, in contrast to the global inhibition of Tp53 function by pharmacological inhibitors and in traditional Tp53 knock-out mice, we examined the effects of DA-specific Tp53 gene deletion after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and methamphetamine exposure. Our data suggests that the Tp53 gene might be involved in both neuronal apoptosis and neuronal terminal damage caused by different neurotoxicants. Additional results from other studies also suggest that as a master regulator of many pathways that regulate apoptosis and synaptic terminal damage, it is possible that Tp53 may function as a signaling hub to integrate different signaling pathways to mediate distinctive target pathways. Tp53 protein as a signaling hub might be able to evaluate the microenvironment of neurons, assess the forms and severities of injury incurred, and determine whether apoptotic cell death or neuronal terminal degeneration occurs. Identification of the precise mechanisms activated in distinct neuronal damage caused by different forms and severities of injuries might allow for development of specific Tp53 inhibitors or ways to modulate distinct downstream target pathways involved.
Rac1 GTPase activates the WAVE regulatory complex through two distinct binding sites

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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
Biorhythms in the activity of children during free play1

Science.gov (United States)

Wade, M. G.; Ellis, M. J.; Bohrer, R. E.

1973-01-01

The interaction between the arousal to action of environmental stimuli and recovery from that activity was presumed to generate biorhythms in the activity level of children. The level of environmental stimuli was manipulated by varying the play-group size and the apparatus, and higher environmental complexity was expected to produce more pronounced rhythms. The heart rates of 16 subjects playing in monad, dyad, and tetrad group sizes, in two playroom configurations, were monitored and spectral analysis used to locate significant biorhythms. There was a tendency toward 40-min (slow frequency) and 15-min (fast frequency) biorhythms. The group size manipulation produced the strongest biorhythmic behavior in the dyadic groups. Apparatus differences were not significant but the configuration containing a minimum quantity of play apparatus produced more variable activity than the configuration containing a large amount of play apparatus. PMID:4714575
Effects of Metabolic Programming on Juvenile Play Behavior and Gene Expression in the Prefrontal Cortex of Rats.

Science.gov (United States)

Hehar, Harleen; Ma, Irene; Mychasiuk, Richelle

2016-01-01

Early developmental processes, such as metabolic programming, can provide cues to an organism, which allow it to make modifications that are predicted to be beneficial for survival. Similarly, social play has a multifaceted role in promoting survival and fitness of animals. Play is a complex behavior that is greatly influenced by motivational and reward circuits, as well as the energy reserves and metabolism of an organism. This study examined the association between metabolic programming and juvenile play behavior in an effort to further elucidate insight into the consequences that early adaptions have on developmental trajectories. The study also examined changes in expression of four genes (Drd2, IGF1, Opa1, and OxyR) in the prefrontal cortex known to play significant roles in reward, bioenergetics, and social-emotional functioning. Using four distinct variations in developmental programming (high-fat diet, caloric restriction, exercise, or high-fat diet combined with exercise), we found that dietary programming (high-fat diet vs. caloric restriction) had the greatest impact on play behavior and gene expression. However, exercise also induced changes in both measures. This study demonstrates that metabolic programming can alter neural circuits and bioenergetics involved in play behavior, thus providing new insights into mechanisms that allow programming to influence the evolutionary success of an organism. © 2016 S. Karger AG, Basel.
Unusual Synthetic Pathway for an {Fe(NO)₂}⁹ Dinitrosyl Iron Complex (DNIC) and Insight into DNIC Electronic Structure via Nuclear Resonance Vibrational Spectroscopy

Energy Technology Data Exchange (ETDEWEB)

Speelman, Amy L.; Zhang, Bo; Silakov, Alexey; Skodje, Kelsey M.; Alp, E. Ercan; Zhao, Jiyong; Hu, Michael Y.; Kim, Eunsuk; Krebs, Karsten; Lehnert, Nicolai

2016-06-06

Dinitrosyl iron complexes (DNICs) are among the most abundant NO-derived cellular species. Monomeric DNICs can exist in the {Fe(NO)₂}⁹ or {Fe(NO)₂}¹⁰ oxidation state (in the Enemark -Feltham notation). However, experimental studies of analogous DNICs in both oxidation states are rare, which prevents a thorough understanding of the di ff erences in the electronic structures of these species. Here, the {Fe(NO)₂}⁹ DNIC [Fe(dmp)(NO)₂](OTf) ( 1 ; dmp = 2,9-dimethyl-1,10- phenanthroline) is synthesized from a ferrous precursor via an unusual pathway, involving disproportionation of an {FeNO}⁷ complex to yield the {Fe(NO)₂}⁹ DNIC and a ferric species, which is subsequently reduced by NO gas to generate a ferrous complex that re-enters the reaction cycle. In contrast to most {Fe(NO)₂}⁹ DNICs with neutral N-donor ligands, 1 exhibits high solution stability and can be characterized structurally and spectroscopically. Reduction of 1 yields the corresponding {Fe(NO)₂}¹⁰ DNIC [Fe(dmp)(NO)₂](2). The Mo ssbauer isomer shift of 2 is 0.08 mm/s smaller than that of 1 , which indicates that the iron center is slightly more oxidized in the reduced complex. The nuclear resonance vibrational spectra (NRVS) of 1 and 2 are distinct and provide direct experimental insight into di ff erences in bonding in these complexes. In particular, the symmetric out-of-plane Fe -N - O bending mode is shifted to higher energy by 188 cm^-1 in 2 in comparison to 1 . Using quantum chemistry centered normal coordinate analysis (QCC-NCA), this is shown to arise from an increase in Fe - NO bond order and a sti ff ening of the Fe(NO)₂ unit upon reduction of 1 to 2 . DFT calculations demonstrate that the changes in bonding arise from an iron- centered reduction which leads to a distinct increase in Fe - NO π -back-bonding in
Effects of canonical NF-κB signaling pathway on the proliferation and odonto/osteogenic differentiation of human stem cells from apical papilla.

Science.gov (United States)

Li, Junjun; Yan, Ming; Wang, Zilu; Jing, Shuanglin; Li, Yao; Liu, Genxia; Yu, Jinhua; Fan, Zhipeng

2014-01-01

NF-κB signaling pathway plays a complicated role in the biological functions of mesenchymal stem cells. However, the effects of NF-κB pathway on the odonto/osteogenic differentiation of stem cells from apical papilla (SCAPs) remain unclear. The present study was designed to evaluate the effects of canonical NF-κB pathway on the osteo/odontogenic capacity of SCAPs in vitro. Western blot results demonstrated that NF-κB pathway in SCAPs was successfully activated by TNF-α or blocked by BMS-345541. NF-κB pathway-activated SCAPs presented a higher proliferation activity compared with control groups, as indicated by dimethyl-thiazol-diphenyl tetrazolium bromide assay (MTT) and flow cytometry assay (FCM). Wound scratch assay revealed that NF-κB pathway-activated SCAPs presented an improved migration capacity, enhanced alkaline phosphatase (ALP) activity, and upregulated mineralization capacity of SCAPs, as compared with control groups. Meanwhile, the odonto/osteogenic markers (ALP/ALP, RUNX2/RUNX2, OSX/OSX, OCN/OCN, OPN/OPN, BSP/BSP, DSPP/DSP, and DMP-1/DMP-1) in NF-κB pathway-activated SCAPs were also significantly upregulated as compared with control groups at both protein and mRNA levels. However, NF-κB pathway-inhibited SCAPs exhibited a lower proliferation/migration capacity, and decreased odonto/osteogenic ability in comparison with control groups. Our findings suggest that classical NF-κB pathway plays a paramount role in the proliferation and committed differentiation of SCAPs.

Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context

Science.gov (United States)

Bredewold, Remco; Smith, Caroline J. W.; Dumais, Kelly M.; Veenema, Alexa H.

2014-01-01

We recently demonstrated that vasopressin (AVP) in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments) affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT) modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage) as opposed to familiar (home cage) social environments. Administration of the specific AVP V1a receptor (V1aR) antagonist (CH2)5Tyr(Me2)AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH2)5−[Tyr(Me)2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze), but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior. PMID:24982623
Sex-specific modulation of juvenile social play behavior by vasopressin and oxytocin depends on social context

Directory of Open Access Journals (Sweden)

Remco eBredewold

2014-06-01

Full Text Available We recently demonstrated that vasopressin (AVP in the lateral septum modulates social play behavior differently in male and female juvenile rats. However, the extent to which different social contexts (i.e., exposure to an unfamiliar play partner in different environments affect the regulation of social play remains largely unknown. Given that AVP and the closely related neuropeptide oxytocin (OXT modulate social behavior as well as anxiety-like behavior, we hypothesized that these neuropeptides may regulate social play behavior differently in novel (novel cage as opposed to familiar (home cage social environments. Administration of the specific AVP V1a receptor (V1aR antagonist (CH25Tyr(Me2AVP into the lateral septum enhanced home cage social play behavior in males but reduced it in females, confirming our previous findings. These effects were context-specific because V1aR blockade did not alter novel cage social play behavior in either sex. Furthermore, social play in females was reduced by AVP in the novel cage and by OXT in the home cage. Additionally, females administered the specific OXT receptor antagonist desGly-NH2,d(CH25-[Tyr(Me2,Thr4]OVT showed less social play in the novel as compared to the home cage. AVP enhanced anxiety-related behavior in males (tested on the elevated plus-maze, but failed to do so in females, suggesting that exogenous AVP alters social play and anxiety-related behavior via distinct and sex-specific mechanisms. Moreover, none of the other drug treatments that altered social play had an effect on anxiety, suggesting that these drug-induced behavioral alterations are relatively specific to social behavior. Overall, we showed that AVP and OXT systems in the lateral septum modulate social play in juvenile rats in neuropeptide-, sex- and social context-specific ways. These findings underscore the importance of considering not only sex, but also social context, in how AVP and OXT modulate social behavior.
Beyond self-selection in video game play: an experimental examination of the consequences of massively multiplayer online role-playing game play.

Science.gov (United States)

Smyth, Joshua M

2007-10-01

There is burgeoning interest in the study of video games. Existing work is limited by the use of correlational designs and is thus unable to make causal inferences or remove self-selection biases from observed results. The recent development of online, socially integrated video games (massively multiplayer online role-playing games [MMORPGs]) has created a new experience for gamers. This randomized, longitudinal study examined the effects of being assigned to play different video game types on game usage, health, well-being, sleep, socializing, and academics. One hundred 18- to 20-year-old participants (73% male; 68% Caucasian) were randomly assigned to play arcade, console, solo computer, or MMORPG games for 1 month. The MMORPG group differed significantly from other groups after 1 month, reporting more hours spent playing, worse health, worse sleep quality, and greater interference in "real-life" socializing and academic work. In contrast, this group also reported greater enjoyment in playing, greater interest in continuing to play, and greater acquisition of new friendships. MMORPGs represent a different gaming experience with different consequences than other types of video games and appear to pose both unique risks and benefits from their use.
Gene regulatory and signaling networks exhibit distinct topological distributions of motifs

Science.gov (United States)

Ferreira, Gustavo Rodrigues; Nakaya, Helder Imoto; Costa, Luciano da Fontoura

2018-04-01

The biological processes of cellular decision making and differentiation involve a plethora of signaling pathways and gene regulatory circuits. These networks in turn exhibit a multitude of motifs playing crucial parts in regulating network activity. Here we compare the topological placement of motifs in gene regulatory and signaling networks and observe that it suggests different evolutionary strategies in motif distribution for distinct cellular subnetworks.
The differences in physical activity levels in preschool children during free play recess and structured play recess

Directory of Open Access Journals (Sweden)

Megan L. Frank

2018-04-01

Full Text Available Background/Objective: Physical activity (PA is important in reducing childhood obesity, yet a majority of children are not meeting PA guidelines. Schools have been identified as a place to promote childhood PA. The purpose of this study was to determine the best type of physically active recess period to increase preschool-aged children's PA. Methods: PA was measured via accelerometers in preschool-aged children (n = 29 during three, 30-min recess conditions (control; structured play; free play on separate school days. Tertile splits were performed based on PA during the free play condition and children were divided into three groups: highly, moderately and least active. Results: For the aggregated sample, children were more (p ≤ 0.001 active during the free play (1282 ± 662 counts. min−1 and structured play (1416 ± 448 counts. min−1 recess versus the control condition (570 ± 460 counts. min−1 and activity was not different between the free play and structured conditions. However, children who were the most active during free play (1970 ± 647 counts·min−1 decreased (p ≤ 0.05 activity during structured play (1462 ± 535 counts·min−1, whereas children who were moderately active (1031 ± 112 counts·min−1 or the least (530 ± 239 counts·min−1 active during free play increased activity during structured play (1383 ± 345 counts·min−1 moderately active, 1313 ± 413 counts·min−1 least active. Conclusion: Providing a physically-active recess period will contribute to preschool-aged children meeting the recommended PA guidelines; however, different children may respond in a different way based upon the structure of the recess period.
Research on the degradation mechanism of dimethyl phthalate in drinking water by strong ionization discharge

Science.gov (United States)

Hong, ZHAO; Chengwu, YI; Rongjie, YI; Huijuan, WANG; Lanlan, YIN; I, N. MUHAMMAD; Zhongfei, MA

2018-03-01

The degradation mechanism of dimethyl phthalate (DMP) in the drinking water was investigated using strong ionization discharge technology in this study. Under the optimized condition, the degradation efficiency of DMP in drinking water was up to 93% in 60 min. A series of analytical techniques including high-performance liquid chromatography, liquid chromatography mass spectrometry, total organic carbon analyzer and ultraviolet-visible spectroscopy were used in the study. It was found that a high concentration of ozone (O3) produced by dielectric barrier discharge reactor was up to 74.4 mg l-1 within 60 min. Tert-butanol, isopropyl alcohol, carbonate ions ({{{{CO}}}3}2-) and bicarbonate ions ({{{{HCO}}}3}-) was added to the sample solution to indirectly prove the presence and effect of hydroxyl radicals (·OH). These analytical findings indicate that mono-methyl phthalate, phthalic acid (PA) and methyl ester PA were detected as the major intermediates in the process of DMP degradation. Finally, DMP and all products were mineralized into carbon dioxide (CO2) and water (H2O) ultimately. Based on these analysis results, the degradation pathway of DMP by strong ionization discharge technology were proposed.
Can we reduce preventable heart failure readmissions in patients enrolled in a Disease Management Programme?

LENUS (Irish Health Repository)

Phelan, D

2012-02-01

BACKGROUND: Disease Management Programmes (DMPs) are successful in reducing hospital readmissions in heart failure (HF). However, there remain a number of patients enrolled in a DMP who are readmitted with HF. The primary aim of the study was to determine the proportion of preventable readmissions (PR). The secondary aim was to recognise patient characteristics which would identify certain patients at risk of having a PR. METHODS: A retrospective chart search was performed on patients readmitted over a 1-year period. RESULTS: 38.5% of readmissions were classified as PR. None of these patients made prior contact with the DMP. Admission levels of BNP, potassium, urea and creatinine were significantly lower in the PR group. CONCLUSION: DMP have proven benefits in reducing hospital readmission nonetheless a significant proportion of these readmissions are preventable. Further work is required to prospectively analyse why these patients fail to contact the DMP.
Efficiency of the Austrian disease management program for diabetes mellitus type 2: a historic cohort study based on health insurance provider’s routine data

Science.gov (United States)

2012-01-01

Background The Austrian diabetes disease management program (DMP) was introduced in 2007 in order to improve health care delivery for diabetics via the promotion of treatment according to guidelines. Considering the current low participation rates in the DMP and the question of further promotion of the program, it is of particular interest for health insurance providers in Austria to assess whether enrollment in the DMP leads to differences in the pattern of the provision of in- and outpatient services, as well as to the subsequent costs in order to determine overall program efficiency. Methods Historic cohort study comparing average annual levels of in- and outpatient health services utilization and its associated costs for patients enrolled and not enrolled in the DMP before (2006) and 2 years after (2009) the implementation of the program in Austria. Data on the use of services and data on costs were extracted from the records of the Austrian Social Insurance Institution for Business. 12,199 persons were identified as diabetes patients treated with anti-diabetic medication or anti-diabetics with insulin throughout the study period. 314 diabetics were enrolled in the DMP. Results Patients enrolled in the diabetes DMP received a more evolved pattern of outpatient care, featuring higher numbers of services provided by general practitioners and specialists (79 vs. 62), more diagnostic services (22 vs. 15) as well as more services provided by outpatient care centers (9 vs. 6) in line with increased levels of participation in medical assessments as recommended by the treatment guideline in 2009. Hospitalization was lower for DMP patients spending 3.75 days in hospital, as compared to 6.03 days for diabetes patients in regular treatment. Overall, increases in costs of care and medication throughout the study period were lower for enrolled patients (€ 718 vs. € 1.684), resulting in overall costs of € 5,393 p.c. for DMP patients and € 6,416 p.c. for the
Efficiency of the Austrian disease management program for diabetes mellitus type 2: a historic cohort study based on health insurance provider’s routine data

Directory of Open Access Journals (Sweden)

Ostermann Herwig

2012-06-01

Full Text Available Abstract Background The Austrian diabetes disease management program (DMP was introduced in 2007 in order to improve health care delivery for diabetics via the promotion of treatment according to guidelines. Considering the current low participation rates in the DMP and the question of further promotion of the program, it is of particular interest for health insurance providers in Austria to assess whether enrollment in the DMP leads to differences in the pattern of the provision of in- and outpatient services, as well as to the subsequent costs in order to determine overall program efficiency. Methods Historic cohort study comparing average annual levels of in- and outpatient health services utilization and its associated costs for patients enrolled and not enrolled in the DMP before (2006 and 2 years after (2009 the implementation of the program in Austria. Data on the use of services and data on costs were extracted from the records of the Austrian Social Insurance Institution for Business. 12,199 persons were identified as diabetes patients treated with anti-diabetic medication or anti-diabetics with insulin throughout the study period. 314 diabetics were enrolled in the DMP. Results Patients enrolled in the diabetes DMP received a more evolved pattern of outpatient care, featuring higher numbers of services provided by general practitioners and specialists (79 vs. 62, more diagnostic services (22 vs. 15 as well as more services provided by outpatient care centers (9 vs. 6 in line with increased levels of participation in medical assessments as recommended by the treatment guideline in 2009. Hospitalization was lower for DMP patients spending 3.75 days in hospital, as compared to 6.03 days for diabetes patients in regular treatment. Overall, increases in costs of care and medication throughout the study period were lower for enrolled patients (€ 718 vs. € 1.684, resulting in overall costs of € 5,393 p.c. for DMP patients and �
Playing with social identities

DEFF Research Database (Denmark)

Winther-Lindqvist, Ditte Alexandra

2013-01-01

as pretence, children’s play is understood as an activity involving rules of the social order (roles and positions) as well as identification processes (imagined situations). The theoretical argumentation builds on empirical examples obtained in two different Danish day-care centres. The chapter is informed...... by ethnographic observations and draws on illustrative examples with symbolic group play as well as game-play with rules (soccer) among 5 year old boys. Findings suggest that day-care children’s play, involves negotiation of roles, positioning and identification, and rules – and that these negotiations......This chapter offers support for Vygotsky’s claim that all play involves both an imagined situation as well as rules. Synthesising Schousboe’s comprehensive model of spheres of realities in playing (see Chapter 1, this volume) with Lev Vygotskys insight that all playing involve rules as well...
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.
Distinct domains within the NITROGEN LIMITATION ADAPTATION protein mediate its subcellular localization and function in the nitrate-dependent phosphate homeostasis pathway

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The NITROGEN LIMITATION ADAPTATION (NLA) protein is a RING-type E3 ubiquitin ligase that plays an essential role in the regulation of nitrogen and phosphate homeostasis. NLA is localized to two distinct subcellular sites, the plasma membrane and nucleus, and contains four distinct domains: i) a RING...
Quantifying genre: an operational definition of tragedy and comedy based on Shakespeare's plays.

Science.gov (United States)

Whissell, Cynthia

2007-08-01

Emotion and imagery in the words of Shakespeare's plays, as measured by the Dictionary of Affect in Language, were used to predict genre (tragedy or comedy). Genre distinctions, which were associated with small effect sizes, were established on the basis of 23 plays and then applied to other plays. A discriminant function which combined lower emotional Pleasantness with higher emotional Activation or arousal and more pictorial Imagery successfully (91% of the time) predicted whether a play was a tragedy or a comedy. The genre-discriminating formula provided meaningful categorizations of 23 additional plays. As hypothesized, comedies employed more Pleasant words than tragedies. Tragedies employed more Active words (p comedies rather than tragedies employed words with lower Imagery (greater Abstraction). The predicted elevation of language in tragedy was noted instead in the use of more verse, fewer common words, and fewer personal pronouns (less subjectivity).
The disease management program for type 2 diabetes in Germany enhances process quality of diabetes care - a follow-up survey of patient's experiences.

Science.gov (United States)

Schäfer, Ingmar; Küver, Claudia; Gedrose, Benjamin; Hoffmann, Falk; Russ-Thiel, Barbara; Brose, Hans-Peter; van den Bussche, Hendrik; Kaduszkiewicz, Hanna

2010-03-03

In summer 2003 a disease management program (DMP) for type 2 diabetes was introduced on a nationwide basis in Germany. Patient participation and continuity of care within the DMP are important factors to achieve long-term improvements in clinical endpoints. Therefore it is of interest, if patients experience any positive or negative effects of the DMP on their treatment that would support or hamper further participation. The main objective of the study was to find out if the German Disease Management Program (DMP) for type 2 diabetes improves process and outcome quality of medical care for patients in the light of their subjective experiences over a period of one year. Cohort study with a baseline interview and a follow-up after 10.4 +/- 0.64 months. Data on process and outcome measures were collected by telephone interviews with 444 patients enrolled and 494 patients not enrolled in the German DMP for type 2 diabetes. Data were analyzed by multivariate logistic regression analyses. DMP enrolment was significantly associated with a higher process quality of care. At baseline enrolled patients more often reported that they had attended a diabetes education course (OR = 3.4), have > or = 4 contacts/year with the attending physician (OR = 3.3), have at least one annual foot examination (OR = 3.1) and one referral to an ophthalmologist (OR = 3.4) and possess a diabetes passport (OR = 2.4). Except for the annual referral to an ophthalmologist these parameters were also statistically significant at follow-up. In contrast, no differences between enrolled and not enrolled patients were found concerning outcome quality indicators, e.g. self-rated health, Glycated hemoglobin (GHb) and blood pressure. However, 16-36% of the DMP participants reported improvements of body weight and/or GHb and/or blood pressure values due to enrolment - unchanged within one year of follow-up. In the light of patient's experiences the DMP enhances the process quality of medical care for type 2
Solid state luminescence of CuI and CuNCS complexes with phenanthrolines and a new tris (aminomethyl) phosphine derived from N-methyl-2-phenylethanamine

International Nuclear Information System (INIS)

Starosta, Radosław; Komarnicka, Urszula K.; Puchalska, Małgorzata

2014-01-01

A new tris (aminomethyl) phosphine derived from N-methyl-2-phenylethanamine P(CH 2 N(CH 3 )CH 2 CH 2 Ph) 3 (1) has been synthesized and characterized by the NMR spectra. Also, three new copper(I) iodide or isothiocyanate complexes with 1 1,10-phenanthroline (phen) and 2,9-dimethyl-1,10-phenanthroline (dmp) [CuI(phen)P(CH 2 N(CH 3 )CH 2 CH 2 Ph) 3 ] (1P) CuI(dmp)P(CH 2 N(CH 3 )CH 2 CH 2 Ph) 3 ] (1I) and [CuNCS(dmp)P(CH 2 N(CH 3 )CH 2 CH 2 Ph) 3 ] (1T), have been synthesized and characterized by elemental analysis as well as studied by NMR, UV–vis, IR and luminescence spectroscopies. An X-ray structure of 1P complex revealed that the geometry around Cu(I) center in this complex is distorted pseudo-tetrahedral. Investigated complexes exhibit orange, rather weak photoluminescence in the solid state. This relatively low intensity may be related to the high flattening deformations of the molecular geometries in the excited triplet states On the basis of TDDFT calculations we confirmed that the absorbance and luminescence bands of (MX,MPR 3 )LCT as well as of (MX)LCT types result mainly from the transitions from the copper–iodine (or isothiocyanate) bonds and a small admixture of copper–phosphine bonds to antibonding orbitals of phen or dmp diimines. -- Highlights: • A novel tris(aminomethyl)phosphine is obtained from N-methyl-2-phenylethanamine. • Three new CuI and CuNCS complexes with phen or dmp and a novel phosphine are presented. • The obtained complexes are luminescent in the solid state. • Main absorbance and luminescence bands are of (MX,MPR 3 )LCT as well as (MX)LCT types
A Distinct Population of Microglia Supports Adult Neurogenesis in the Subventricular Zone

DEFF Research Database (Denmark)

Ribeiro Xavier, Anna L.; Kress, Benjamin T.; Goldman, Steven A.

2015-01-01

found that microglia residing in the SVZ and adjacent rostral migratory stream (RMS) comprise a morphologically and antigenically distinct phenotype of immune effectors. Whereas exhibiting characteristics of alternatively activated microglia, the SVZ/RMS microglia were clearly distinguished by their low...... STATEMENT: Microglial cells are a specialized population of macrophages in the CNS, playing key roles as immune mediators. As integral components in the CNS, the microglia stand out for using the same mechanisms, phagocytosis and cytochemokine release, to promote homeostasis, synaptic pruning, and neural...... toward olfactory bulb layers. In addition to other unique populations residing in the SVZ niche, microglia display distinct morphofunctional properties that boost neuronal progenitor survival and migration in the mammalian brain....
Play Matters

DEFF Research Database (Denmark)

Sicart (Vila), Miguel Angel

? In Play Matters, Miguel Sicart argues that to play is to be in the world; playing is a form of understanding what surrounds us and a way of engaging with others. Play goes beyond games; it is a mode of being human. We play games, but we also play with toys, on playgrounds, with technologies and design......, but not necessarily fun. Play can be dangerous, addictive, and destructive. Along the way, Sicart considers playfulness, the capacity to use play outside the context of play; toys, the materialization of play--instruments but also play pals; playgrounds, play spaces that enable all kinds of play; beauty...
Selective enrollment in Disease Management Programs for coronary heart disease in Germany - An analysis based on cross-sectional survey and administrative claims data.

Science.gov (United States)

Röttger, Julia; Blümel, Miriam; Busse, Reinhard

2017-04-04

In 2002, Disease Management Programs (DMPs) were introduced within the German healthcare system with the aim to increase the quality of chronic disease care. Due to the enrollment procedures, it can be assumed a) that only certain patients actively decide to enroll in a DMP and/or b) that only certain patients get the recommendation for DMP enrollment from their physician. How strong this assumed effect of self- and/or professional selection is, is still unclear. We used data from a cross-sectional postal-survey linked on individual level with administrative claims data from a German sickness fund. The sample consisted of individuals suffering from coronary heart disease (CHD) who i) were either enrolled in the respective DMP or ii) fulfilled the disease related criteria for enrollment but were not enrolled. We applied multivariate logistic regression analyses to assess factors on patient level associated with DMP enrollment. We included 7070 individuals in our analyses. Male sex, higher age and receiving old age pension, a higher Charlson Score and a diagnosis of type 2 diabetes increased the odds for DMP-CHD enrollment significantly. Individuals with a diagnosed myocardial infarction (MI) were also more likely to be enrolled in the DMP-CHD. We found a significant interaction effect for MI and sex, indicating that the association between MI and DMP enrollment is stronger for women than for men. DMP-enrollees and non-enrollees differ in various factors. Studies analyzing the effectiveness of DMP-CHD should carefully take into account these group differences. Furthermore, the results suggest that the DMP-CHD assessed reaches men better than women.
Selective phenol methylation to 2,6-dimethylphenol in a fluidized bed of iron-chromium mixed oxide catalyst with o-cresol circulation.

Science.gov (United States)

Zukowski, Witold; Berkowicz, Gabriela; Baron, Jerzy; Kandefer, Stanisław; Jamanek, Dariusz; Szarlik, Stefan; Wielgosz, Zbigniew; Zielecka, Maria

2014-01-01

2,6-dimethylphenol (2,6-DMP) is a product of phenol methylation, especially important for the plastics industry. The process of phenol methylation in the gas phase is strongly exothermic. In order to ensure good temperature equalization in the catalyst bed, the process was carried out using a catalyst in the form of a fluidized bed - in particular, the commercial iron-chromium catalyst TZC-3/1. Synthesis of 2,6-dimethylphenol from phenol and methanol in fluidized bed of iron-chromium catalyst was carried out and the fluidization of the catalyst was examined. Stable state of fluidized bed of iron-chromium catalyst was achieved. The measured velocities allowed to determine the minimum flow of reactants, ensuring introduction of the catalyst bed in the reactor into the state of fluidization. Due to a high content of o-cresol in products of 2,6-dimethylphenol synthesis, circulation in the technological node was proposed. A series of syntheses with variable amount of o-cresol in the feedstock allowed to determine the parameters of stationary states. A stable work of technological node with o-cresol circulation is possible in the temperature range of350-380°C, and o-cresolin/phenolin molar ratio of more than 0.48. Synthesis of 2,6-DMP over the iron-chromium catalyst is characterized by more than 90% degree of phenol conversion. Moreover, the O-alkylation did not occur (which was confirmed by GC-MS analysis). By applying o-cresol circulation in the 2,6-DMP process, selectivity of more than 85% degree of 2,6-DMP was achieved. The participation levels of by-products: 2,4-DMP and 2,4,6-TMP were low. In the optimal conditions based on the highest yield of 2,6-DMP achieved in the technological node applying o-cresol circulation, there are 2%mol. of 2,4-DMP and 6%mol. of 2,4,6-TMP in the final mixture, whereas 2,4,6-TMP can be useful as a chain stopper and polymer's molar mass regulator during the polymerization of 2,6-DMP.
Health related quality of life and comorbidity. A descriptive analysis comparing EQ-5D dimensions of patients in the German disease management program for type 2 diabetes and patients in routine care.

Science.gov (United States)

Ose, Dominik; Miksch, Antje; Urban, Elisabeth; Natanzon, Iris; Szecsenyi, Joachim; Kunz, Cornelia Ursula; Freund, Tobias

2011-08-02

The co-occurance of multiple medical conditions has a negative impact on health related quality of life (HRQoL) for patients with type 2 diabetes. These patients demand for intensified care programs. Participation in a disease management program (DMP) for type 2 diabetes has shown to counterbalance this effect. However, it remains unclear which dimensions of HRQoL are influenced by the DMP. The aim of this study was to explore the HRQoL dimensions of patients with type 2 diabetes in the German DMP and patients in routine care (RC). This analysis is part of a comparative evaluation of the German DMP for patients with type 2 diabetes. A questionnaire, including the HRQoL measure EQ-5D, was mailed to a random sample of 3,546 patients with type 2 diabetes (59.3% female). The EQ-5D dimensions were analyzed by grouping patients according to their participation in the German DMP for diabetes into DMP and RC. Compared to patients in DMP, patients in RC reported more problems for the dimensions mobility (P German DMP for type 2 diabetes mellitus show significantly higher ratings of their HRQoL in the dimensions mobility, self care and performing usual activities compared to patients in RC. This difference can also be observed in patients with significant comorbidities. As these dimensions are known to be essential for diabetes care, the German DMP may contribute to improved care even for comorbid diabetes patients.

Distinct roles of two ceramide synthases, CaLag1p and CaLac1p, in the morphogenesis of Candida albicans

DEFF Research Database (Denmark)

Cheon, Seon Ah; Bal, Jyotiranjan; Song, Yunkyoung

2012-01-01

p) and Lac1p (CaLac1p) are functionally distinct. Lack of CaLag1p, but not CaLac1p, caused severe defects in the growth and hyphal morphogenesis of C. albicans. Deletion of CaLAG1 decreased expression of the hypha-specific HWP1 and ECE1 genes. Moreover, overexpression of CaLAG1 induced pseudohyphal...... growth in this organism under non-hypha-inducing conditions, suggesting that CaLag1p is necessary for relaying signals to induce hypha-specific gene expression. Analysis of ceramide and sphingolipid composition revealed that CaLag1p predominantly synthesizes ceramides with C24:0/C26:0 fatty acid moieties...
Distinct HIC1-SIRT1-p53 Loop Deregulation in Lung Squamous Carcinoma and Adenocarcinoma Patients

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Ruo-Chia Tseng

2009-08-01

Full Text Available A HIC1-SIRT1-p53 circular loop in which hypermethylation in cancer 1 (HIC1 represses the transcription of SIRT1 that deacetylates and inactivates p53 thus leading to HIC1 inactivation has been identified in cell and animal models. However, the alteration and prognostic effects of HIC1-SIRT1-p53 circular loop have never been demonstrated in human cancer patients. We examine the HIC1-SIRT1-p53 alterations in 118 lung cancer patients to define their etiological roles in tumorigenesis. We found that patients with lung squamous cell carcinoma with low p53 acetylation and SIRT1 expression mostly showed low HIC1 expression, confirming deregulation of HIC1-SIRT1-p53 circular loop in the clinical model. Interestingly, the expression of deleted in breast cancer 1 (DBC1, which blocks the interaction between SIRT1 deacetylase and p53, led to acetylated p53 in patients with lung adenocarcinoma. However, epigenetic alteration of HIC1 promoter by posttranslational modifications of histones and promoter hypermethylation favoring the compacted chromatin production attenuated the transcriptional induction by acetylated p53. Importantly, lung cancer patients with altered HIC1-SIRT1-p53 circular regulation showed poor prognosis. Our data show the first valid clinical evidence of the deregulation of HIC1-SIRT1-p53 loop in lung tumorigenesis and prognosis. Distinct status of p53 acetylation/deacetylation and HIC1 alteration mechanism result from different SIRT1-DBC1 control and epigenetic alteration in lung squamous cell carcinoma and lung adenocarcinoma.
Differential autoshaping to common and distinctive elements of positive and negative discriminative stimuli1

Science.gov (United States)

Wasserman, Edward A.; Anderson, Patricia A.

1974-01-01

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. PMID:16811812
Mycobacterial secretion systems ESX-1 and ESX-5 play distinct roles in host cell death and inflammasome activation

KAUST Repository

Abdallah, Abdallah; Bestebroer, Jovanka; Savage, Nigel D L; De Punder, Karin; Van Zon, Maaike; Wilson, Louis D.; Korbee, Cees J.; Van Der Sar, Astrid M.; Ottenhoff, Tom Hm M; Van Der Wel, Nicole N.; Bitter, Wilbert M.; Peters, Peter J.

2011-01-01

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
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.
Electrochemical degradation of dimethyl phthalate ester on a DSA® electrode

Energy Technology Data Exchange (ETDEWEB)

Souza, Fernanda L.; Aquino, Jose M.; Miwa, Douglas W.; Motheo, Artur J. [Universidade de Sao Paulo (USP), Sao Carlos, SP (Brazil). Instituto de Quimica; Rodrigo, Manuel A., E-mail: artur@iqsc.usp.br [Department of Chemical Engineering, Faculty of Chemical Sciences and Technologies, Universidad de Castilla - La Mancha, Ciudad Real (Spain)

2014-03-15

The electrochemical degradation of dimethyl phthalate (DMP) using a one-compartment filter press flow cell and a commercial dimensionally stable anode (DSA®) is presented. The best electrolysis conditions were determined by the analysis of the influence of the nature and concentration of the support electrolyte, pH, current density and temperature. The abatement of DMP concentration and total organic carbon (TOC) removal were superior in the presence of NaCl, as well as the apparent first order kinetic constants. Using constant ionic strength at 0.15 mol dm{sup -3} by adding Na{sub 2}SO{sub 4}, DMP concentration decreases faster at relative low NaCl concentrations while the TOC removal after 1 h of electrolysis increases with NaCl concentration. The DMP removal was very similar for all the current densities investigated at acidic solutions. When electric energy saving is considered, since the electrochemical system was under mass transport conditions, the best operational option is to use low current density values. (author)
Impact of Changes in Playing Time on Playing-Related Musculoskeletal Pain in String Music Students.

Science.gov (United States)

Robitaille, Judith; Tousignant-Laflamme, Yannick; Guay, Manon

2018-03-01

During their training, musicians must develop good work habits that they will carry on throughout their professional career in order to avoid potential chronic health problems, such as musculoskeletal pain. The effect of sudden changes in instrument playing-time on the development of playing-related musculoskeletal pain (PRMP) has not been thoroughly investigated in music students playing bowed string instruments (BSI), even though they are regularly exposed to such changes to perfect their playing skills. To explore the association between sudden changes in instrument playing-time and changes in PRMP in BSI players. A prospective cohort study was completed with BSI students attending a summer music camp offering high-level training. Participants completed a self-administered 23-item questionnaire designed for the study upon arrival at camp (T1) and then 7 days later (T2). Ninety-three BSI students (16±4 yrs old) completed the questionnaires, for a 23% response rate. Their playing-time increased by 23±14 hrs between T1 and T2. Complaints in pain frequency (e.g., from never to most of the time) and intensity (19±24 mm on VAS) significantly increased between T1 and T2 and were correlated with an increase in playing-time. A sudden increase in playing-time, such as that experienced by elite BSI students attending an intensive music camp, was related to an increase in PRMP. However, in this study, changes in pain characteristics were only partly explained by the change in playing-time.
Approaching the Distinction between Intuition and Insight.

Science.gov (United States)

Zhang, Zhonglu; Lei, Yi; Li, Hong

2016-01-01

Intuition and insight share similar cognitive and neural basis. Though, there are still some essential differences between the two. Here in this short review, we discriminated between intuition, and insight in two aspects. First, intuition, and insight are toward different aspects of information processing. Whereas intuition involves judgment about "yes or no," insight is related to "what" is the solution. Second, tacit knowledge play different roles in between intuition and insight. On the one hand, tacit knowledge is conducive to intuitive judgment. On the other hand, tacit knowledge may first impede but later facilitate insight occurrence. Furthermore, we share theoretical, and methodological views on how to access the distinction between intuition and insight.
Ex-Th17 (Nonclassical Th1) Cells Are Functionally Distinct from Classical Th1 and Th17 Cells and Are Not Constrained by Regulatory T Cells.

Science.gov (United States)

Basdeo, Sharee A; Cluxton, Deborah; Sulaimani, Jamal; Moran, Barry; Canavan, Mary; Orr, Carl; Veale, Douglas J; Fearon, Ursula; Fletcher, Jean M

2017-03-15

Th17 cells are an important therapeutic target in autoimmunity. However, it is known that Th17 cells exhibit considerable plasticity, particularly at sites of autoimmune inflammation. Th17 cells can switch to become ex-Th17 cells that no longer produce IL-17 but produce IFN-γ. These ex-Th17 cells are also called nonclassical Th1 cells because of their ability to produce IFN-γ, similar to Th1 cells; however, it is unclear whether they resemble Th1 or Th17 cells in terms of their function and regulation, and whether they have a pathogenic role in autoimmunity. We compared the phenotypic and functional features of human Th17, Th1, and ex-Th17 cell populations. Our data showed that despite their loss of IL-17 expression, ex-Th17 cells were more polyfunctional in terms of cytokine production than either Th1 or bona fide Th17 cells, and produced increased amounts of proinflammatory cytokines. The proliferative brake on Th17 cells appeared to be lifted because ex-Th17 cells proliferated more than Th17 cells after stimulation. In contrast with Th1 and Th17 cells, ex-Th17 cells were highly resistant to suppression of proliferation and cytokines by regulatory T cells. Finally, we showed that ex-Th17 cells accumulated in the joints of rheumatoid arthritis patients. Taken together, these data indicate that human ex-Th17 cells are functionally distinct from Th1 and Th17 cells, and suggest that they may play a pathogenic role at sites of autoimmunity, such as the rheumatoid arthritis joint where they accumulate. These findings have implications for therapeutic strategies that target IL-17, because these may not inhibit pathogenic ex-Th17 cells. Copyright © 2017 by The American Association of Immunologists, Inc.
Water Play

Science.gov (United States)

Cline, Jane E.; Smith, Brandy A.

2016-01-01

The inclusion of activities to develop sensory awareness, spatial thinking, and physical dexterity, operationalized through hands-on science lessons such as water play, have long been part of early childhood education. This practical article addresses Next Generation Science Standards K-2 ETS1-3 and K-2 ETS1-2 by having four-year-old…
Distinct HLA associations of LGI1 and CASPR2-antibody diseases.

Science.gov (United States)

Binks, Sophie; Varley, James; Lee, Wanseon; Makuch, Mateusz; Elliott, Katherine; Gelfand, Jeffrey M; Jacob, Saiju; Leite, M Isabel; Maddison, Paul; Chen, Mian; Geschwind, Michael D; Grant, Eleanor; Sen, Arjune; Waters, Patrick; McCormack, Mark; Cavalleri, Gianpiero L; Barnardo, Martin; Knight, Julian C; Irani, Sarosh R

2018-05-18

The recent biochemical distinction between antibodies against leucine-rich, glioma-inactivated-1 (LGI1), contactin-associated protein-2 (CASPR2) and intracellular epitopes of voltage-gated potassium-channels (VGKCs) demands aetiological explanations. Given established associations between human leucocyte antigen (HLA) alleles and adverse drug reactions, and our clinical observation of frequent adverse drugs reactions in patients with LGI1 antibodies, we compared HLA alleles between healthy controls (n = 5553) and 111 Caucasian patients with VGKC-complex autoantibodies. In patients with LGI1 antibodies (n = 68), HLA-DRB1*07:01 was strongly represented [odds ratio = 27.6 (95% confidence interval 12.9-72.2), P = 4.1 × 10-26]. In contrast, patients with CASPR2 antibodies (n = 31) showed over-representation of HLA-DRB1*11:01 [odds ratio = 9.4 (95% confidence interval 4.6-19.3), P = 5.7 × 10-6]. Other allelic associations for patients with LGI1 antibodies reflected linkage, and significant haplotypic associations included HLA-DRB1*07:01-DQA1*02:01-DQB1*02:02, by comparison to DRB1*11:01-DQA1*05:01-DQB1*03:01 in CASPR2-antibody patients. Conditional analysis in LGI1-antibody patients resolved further independent class I and II associations. By comparison, patients with both LGI1 and CASPR2 antibodies (n = 3) carried yet another complement of HLA variants, and patients with intracellular VGKC antibodies (n = 9) lacked significant HLA associations. Within LGI1- or CASPR2-antibody patients, HLA associations did not correlate with clinical features. In silico predictions identified unique CASPR2- and LGI1-derived peptides potentially presented by the respective over-represented HLA molecules. These highly significant HLA associations dichotomize the underlying immunology in patients with LGI1 or CASPR2 antibodies, and inform T cell specificities and cellular interactions at disease initiation.
Cloning of human basic A1, a distinct 59-kDa dystrophin-associated protein encoded on chromosome 8q23-24

Energy Technology Data Exchange (ETDEWEB)

Ahn, A.H. [Harvard Medical School, Boston, MA (United States); Yoshida, Mikiharu; Hagiwara, Yasuko; Ozawa, Eijiro [National Institute of Neuroscience, Ogawa Higashi, Kodaira (Japan); Anderson, M.S.; Feener, C.A.; Selig, S. [Howard Hughes Medical Institute at Children`s Hospital, Boston, MA (United States); Kunkel, L.M. [Harvard Medical School, Boston, MA (United States)]|[Howard Hughes Medical Institute at Children`s Hosptial, Boston, MA (United States)

1994-05-10

Duchenne and Becker muscular dystrophies are caused by defects of dystrophin, which forms a part of the membrane cytoskeleton of specialized cells such as muscle. It has been previously shown that the dystrophin-associated protein A1 (59-kDa DAP) is actually a heterogeneous group of phosphorylated proteins consisting of an acidic ({alpha}-A1) and a distinct basic ({beta}-A1) component. Partial peptide sequence of the A1 complex purified from rabbit muscle permitted the design of oligonucleotide probes that were used to isolate a cDNA for one human isoform of A1. This cDNA encodes a basic A1 isoform that is distinct from the recently described syntrophins in Torpedo and mouse and is expressed in many tissues with at least five distinct mRNA species of 5.9, 4.8, 4.3, 3.1, and 1.5 kb. A comparison of the human cDNA sequence with the GenBank expressed sequence tag (EST) data base has identified a relative from human skeletal muscle, EST25263, which is probably a human homologue of the published mouse syntrophin 2. The authors have mapped the human basic component of A1 and EST25263 genes to chromosomes 8q23-24 and 16, respectively.
Self-Play and Using an Expert to Learn to Play Backgammon with Temporal Difference Learning

NARCIS (Netherlands)

Wiering, Marco A.

2010-01-01

A promising approach to learn to play board games is to use reinforcement learning algorithms that can learn a game position evaluation function. In this paper we examine and compare three different methods for generating training games: 1) Learning by self-play, 2) Learning by playing against an
Dual roles of hydroxyl radicals and effects of competition on ozonation kinetics of two phenazone-type pollutants

Directory of Open Access Journals (Sweden)

Siyu Zhang

2015-11-01

Full Text Available Ozonation has been proved to be a promising approach for eliminating emerging pollutants in wastewater. In previous studies, emerging pollutants including diverse pharmaceuticals were found to exhibit significantly different ozonation reactivity. However, how the structural differences of emerging pollutants determine ozonation reactivity and mechanisms are still ambiguous. In this work, ozonation of dimethylaminophenazone (DMP and acetylaminophenazone (AAA with the same parent structure of phenazone but different substitution groups was investigated, in order to probe influencing mechanisms of structural differences on ozonation reactivity. Results show that DMP reacts with ozone and HO·≡ almost 2 and 1 order of magnitude faster than AAA, respectively. At pH 8, HO·≡ accelerates ozonation of DMP, but decreases ozonation of AAA. Competition simultaneously decreases degradation rate of the two phenazones, but effects on AAA are more significant than that on DMP. According to theoretical calculation results, differences in ozonation reactivity and mechanisms of the two phenazones can be mainly attributed to different substitution groups. The dimethylamino group in the structure of DMP increases the ozonation reactivity of phenazone by increasing reaction orbital energies and altering reaction sites, while the acetylamino group in the structure of AAA decreases the reaction orbital energy and therefore lowers the reactivity.
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.
The influence of context on distinct facial expressions of disgust.

Science.gov (United States)

Reschke, Peter J; Walle, Eric A; Knothe, Jennifer M; Lopez, Lukas D

2018-06-11

Face perception is susceptible to contextual influence and perceived physical similarities between emotion cues. However, studies often use structurally homogeneous facial expressions, making it difficult to explore how within-emotion variability in facial configuration affects emotion perception. This study examined the influence of context on the emotional perception of categorically identical, yet physically distinct, facial expressions of disgust. Participants categorized two perceptually distinct disgust facial expressions, "closed" (i.e., scrunched nose, closed mouth) and "open" (i.e., scrunched nose, open mouth, protruding tongue), that were embedded in contexts comprising emotion postures and scenes. Results demonstrated that the effect of nonfacial elements was significantly stronger for "open" disgust facial expressions than "closed" disgust facial expressions. These findings provide support that physical similarity within discrete categories of facial expressions is mutable and plays an important role in affective face perception. (PsycINFO Database Record (c) 2018 APA, all rights reserved).
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...
Two Distinct Myeloid Subsets at the Term Human Fetal–Maternal Interface

Directory of Open Access Journals (Sweden)

Maria Laura Costa

2017-10-01

Full Text Available During pregnancy, immune cells infiltrate the placenta at different stages of fetal development. NK cells and macrophages are the most predominant cell types. These immune cells play pleiotropic roles, as they control spiral artery remodeling to ensure appropriate blood supply and maintain long-term tolerance to a true allograft; yet, they must be able to mount appropriate immune defenses to pathogens that may threaten the fetus. Whether the same cell type accomplishes all these tasks or if there are dedicated subsets remains controversial. Here, we identify and characterize two distinct subsets of myeloid cells that differ in their pro-inflammatory/regulatory capacity. While one subset predominantly produces the immune-modulating cytokine IL-10, the second subset has superior capacity to secrete pro-inflammatory mediators, such as IL-1β and IL-6. The putative regulatory myeloid cells also express high levels of inhibitory receptors and their ligands, including programmed cell death 1 (PD1 ligands. Importantly, a large fraction of CD8 and CD4 cells in normal term human placenta are PD1 positive, suggesting that the PD1/PD1 ligands axis might be critical to maintain tolerance during pregnancy.
The corrosion mechanism of the sintered (Ce, Nd)-Fe-B magnets prepared by double main phase and single main phase approaches

Science.gov (United States)

Shi, Xiaoning; Zhu, Minggang; Zhou, Dong; Song, Liwei; Guo, Zhaohui; Li, Jia; Li, Wei

2018-05-01

The sintered (Ce, Nd)-Fe-B magnets were produced widely by Double Main Phase (DMP) method in China as the magnetic properties of the DMP magnets are superior to those of single main phase (SMP) magnets with the same nominal composition. In this work, the microstructure and corrosion mechanism of the sintered (Ce0.2Nd0.8)30FebalB (wt.%) magnets prepared by DMP and SMP method were studied in detail. Compared to SMP magnets, the DMP magnets have more positive corrosion potential, lower corrosion current density, larger electron transfer resistance, and lower mass loss of the free corrosion experiment in 0.5mol/l Na2SO4 aqueous solution. All of the results show that the DMP magnets have better corrosion resistance than SMP magnets. The back scattered electron images show that the crystalline grains of the DMP magnets are sphericity with a smooth surface while the SMP ones have plenty of edges and corners. Besides, the distribution of Ce/Nd is much more uneven in both magnetic phase and rare earth (Re)-rich phase of the DMP magnets than those of SMP magnets. After corrosion, DMP magnets show eroded magnetic phase and intact Re-rich phase, which indicate that galvanic corrosion of the Re-rich phase acting as the cathode appears.
Excessive computer game playing among Norwegian adults: self-reported consequences of playing and association with mental health problems.

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Wenzel, H G; Bakken, I J; Johansson, A; Götestam, K G; Øren, Anita

2009-12-01

Computer games are the most advanced form of gaming. For most people, the playing is an uncomplicated leisure activity; however, for a minority the gaming becomes excessive and is associated with negative consequences. The aim of the present study was to investigate computer game-playing behaviour in the general adult Norwegian population, and to explore mental health problems and self-reported consequences of playing. The survey includes 3,405 adults 16 to 74 years old (Norway 2007, response rate 35.3%). Overall, 65.5% of the respondents reported having ever played computer games (16-29 years, 93.9%; 30-39 years, 85.0%; 40-59 years, 56.2%; 60-74 years, 25.7%). Among 2,170 players, 89.8% reported playing less than 1 hr. as a daily average over the last month, 5.0% played 1-2 hr. daily, 3.1% played 2-4 hr. daily, and 2.2% reported playing > 4 hr. daily. The strongest risk factor for playing > 4 hr. daily was being an online player, followed by male gender, and single marital status. Reported negative consequences of computer game playing increased strongly with average daily playing time. Furthermore, prevalence of self-reported sleeping problems, depression, suicide ideations, anxiety, obsessions/ compulsions, and alcohol/substance abuse increased with increasing playing time. This study showed that adult populations should also be included in research on computer game-playing behaviour and its consequences.

Distinct patterns of ALDH1A1 expression predict metastasis and poor outcome of colorectal carcinoma

Science.gov (United States)

Xu, Sen-Lin; Zeng, Dong-Zu; Dong, Wei-Guo; Ding, Yan-Qing; Rao, Jun; Duan, Jiang-Jie; Liu, Qing; Yang, Jing; Zhan, Na; Liu, Ying; Hu, Qi-Ping; Zhang, Xia; Cui, You-Hong; Kung, Hsiang-Fu; Yu, Shi-Cang; Bian, Xiu-Wu

2014-01-01

Purpose: Aldehyde dehydrogenase 1A1 (ALDH1A1) has been proposed as a candidate biomarker for colorectal carcinoma (CRC). However, the heterogeneity of its expression makes it difficult to predict the outcome of CRC. The aim of this study was to evaluate the diagnostic and prognostic value of this molecule in CRC. Methods and Results: In this study, we examined ALDH1A1 expression by immunohistochemistry including 406 cases of primary CRC with corresponding adjacent mucosa, with confirmation of real-time PCR and Western blotting. We found that the expression patterns of ALDH1A1 were heterogeneous in the CRC and corresponding adjacent tissues. We defined the ratio of ALDH1A1 level in adjacent mucosa to that in tumor tissues as RA/C and found that the capabilities of tumor invasion and metastasis in the tumors with RA/C < 1 were significantly higher than those with RA/C ≥ 1. Follow-up data showed the worse prognoses in the CRC patients with RA/C < 1. For understanding the underlying mechanism, the localization of β-catenin was detected in the CRC tissues with different patterns of ALDH1A1 expression from 221 patients and β-catenin was found preferentially expressed in cell nuclei of the tumors with RA/C < 1 and ALDH1A1high expression of HT29 cell line, indicating that nuclear translocation of β-catenin might contribute to the increased potentials of invasion and metastasis. Conclusion: Our results indicate that RA/C is a novel biomarker to reflect the distinct expression patterns of ALDH1A1 for predicting metastasis and prognosis of CRC. PMID:25031716
Role of codeposited impurities during growth. I. Explaining distinctive experimental morphology on Cu(0 0 1)

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Hamouda, Ajmi Bh.; Sathiyanarayanan, Rajesh; Pimpinelli, Alberto; Einstein, T. L.

2011-01-01

A unified explanation of the physics underlying all the distinctive features of the growth instabilities observed on Cu vicinals has long eluded theorists. Recently, kinetic Monte Carlo studies showed that codeposition of impurities during growth could account for the key distinctive experimental observations [Hamouda , Phys. Rev. BPLRBAQ0556-280510.1103/PhysRevB.77.245430 77, 245430 (2008)]. To identify the responsible impurity atom, we compute the nearest-neighbor binding energies (ENN) and terrace diffusion barriers (Ed) for several candidate impurity atoms on Cu(0 0 1) using DFT-based VASP. Our calculations show that codeposition (with Cu) of midtransition elements, such as Fe, Mn, and W, could—in conjunction with substantial Ehrlich-Schwoebel barriers—cause the observed instabilities; when the experimental setup is considered, W emerges to be the most likely candidate. We discuss the role of impurities in nanostructuring of surfaces.
Proportional relationship between intercepted solar radiation and dry matter production in a mulberry [Morus] field

International Nuclear Information System (INIS)

Aqueel, S.A.; Ito, D.; Naoi, T.

1999-01-01

In order to investigate the relationship between dry matter production (DMP) and the amount of intercepted solar radiation (S), and to analyze the fluctuations in the radiation conversion efficiency (DMP/S), summer-pruned mulberry (Morus alba L.) trees under a standard planting density were subjected to a shading treatment using a cheesecloth. Then, using a non-destructive method, DMP was examined for 5 plants from each plot every 15 days from July to September. DMP was also examined for mulberry trees under a high planting density. Rates of radiation that penetrated onto the ground and beneath the cheesecloth were measured to calculate S from the incoming solar radiation. In the shading plots, DMP decreased depending on the degree of shading throughout the experimental period. Compared with the control plot, 70 and 60 % DMP were produced finally under 71 and 53 % S. Therefore, DMP was considered to be almost proportional to S even in a broad-leaf population like mulberry. Radiation conversion efficiency gradually decreased with growth regardless of the planting density. At the late growth stage, radiation conversion efficiency was lower in the densely planted field than in the standard density field
Molecular Evolution of Two Distinct dmrt1 Promoters for Germ and Somatic Cells in Vertebrate Gonads.

Science.gov (United States)

Mawaribuchi, Shuuji; Musashijima, Masato; Wada, Mikako; Izutsu, Yumi; Kurakata, Erina; Park, Min Kyun; Takamatsu, Nobuhiko; Ito, Michihiko

2017-03-01

The transcription factor DMRT1 has important functions in two distinct processes, somatic-cell masculinization and germ-cell development in mammals. However, it is unknown whether the functions are conserved during evolution, and what mechanism underlies its expression in the two cell lineages. Our analysis of the Xenopus laevis and Silurana tropicalis dmrt1 genes indicated the presence of two distinct promoters: one upstream of the noncoding first exon (ncEx1), and one within the first intron. In contrast, only the ncEx1-upstream promoter was detected in the dmrt1 gene of the agnathan sand lamprey, which expressed dmrt1 exclusively in the germ cells. In X. laevis, the ncEx1- and exon 2-upstream promoters were predominantly used for germ-cell and somatic-cell transcription, respectively. Importantly, knockdown of the ncEx1-containing transcript led to reduced germ-cell numbers in X. laevis gonads. Intriguingly, two genetically female individuals carrying the knockdown construct developed testicles. Analysis of the reptilian leopard gecko dmrt1 revealed the absence of ncEx1. We propose that dmrt1 regulated germ-cell development in the vertebrate ancestor, then acquired another promoter in its first intron to regulate somatic-cell masculinization during gnathostome evolution. In the common ancestor of reptiles and mammals, only one promoter got function for both the two cell lineages, accompanied with the loss of ncEx1. In addition, we found a conserved noncoding sequence (CNS) in the dmrt1 5'-flanking regions only among amniote species, and two CNSs in the introns among most vertebrates except for agnathans. Finally, we discuss relationships between these CNSs and the promoters of dmrt1 during vertebrate evolution. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
The Distinction Between Curative and Assistive Technology.

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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.
Synergistic mosquito-repellent activity of Curcuma longa, Pogostemon heyneanus and Zanthoxylum limonella essential oils.

Science.gov (United States)

Das, N G; Dhiman, Sunil; Talukdar, P K; Rabha, Bipul; Goswami, Diganta; Veer, Vijay

2015-01-01

Mosquito repellents play an important role in preventing man-mosquito contact. In the present study, we evaluated the synergistic mosquito-repellent activity of Curcuma longa, Pogostemon heyneanus and Zanthoxylum limonella essential oils. The mosquito repellent efficacies of three essential oils were evaluated separately and in combination under laboratory and field conditions. N,N-Diethylphenylacetamide (DEPA) and dimethylphthalate (DMP) were used for comparison of the protection time of the mixture of essential oils. At an optimum concentration of 20%, the essential oils of C. longa, Z. limonella and P. heyneanus provided complete protection times (CPTs) of 96.2, 91.4 and 123.4 min, respectively, against Aedes albopictus mosquitoes in the laboratory. The 1:1:2 mixture of the essential oils provided 329.4 and 391.0 min of CPT in the laboratory and field trials, respectively. The percent increases in CPTs for the essential oil mixture were 30 for DMP and 55 for N,N-diethylphenylacetamide (DEPA). The synergistic repellent activity of the essential oils used in the present study might be useful for developing safer alternatives to synthetic repellents for personal protection against mosquitoes. Copyright © 2015 King Saud Bin Abdulaziz University for Health Sciences. Published by Elsevier Ltd. All rights reserved.
Enhanced dimethyl phthalate biodegradation by accelerating phthalic acid di-oxygenation.

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Tang, Yingxia; Zhang, Yongming; Jiang, Ling; Yang, Chao; Rittmann, Bruce E

2017-12-01

The aerobic biodegradation of dimethyl phthalate (DMP) is initiated with two hydrolysis reactions that generate an intermediate, phthalic acid (PA), that is further biodegraded through a two-step di-oxygenation reaction. DMP biodegradation is inhibited when PA accumulates, but DMP's biodegradation can be enhanced by adding an exogenous electron donor. We evaluated the effect of adding succinate, acetate, or formate as an exogenous electron donor. PA removal rates were increased by 15 and 30% for initial PA concentrations of 0.3 and 0.6 mM when 0.15 and 0.30 mM succinate, respectively, were added as exogenous electron donor. The same electron-equivalent additions of acetate and formate had the same acceleration impacts on PA removal. Consequently, the DMP-removal rate, even PA coexisting with DMP simultaneously, was accelerated by 37% by simultaneous addition of 0.3 mM succinate. Thus, lowering the accumulation of PA by addition of an electron increased the rate of DMP biodegradation.
Role of distinct CD4(+) T helper subset in pathogenesis of oral lichen planus.

Science.gov (United States)

Wang, Hui; Zhang, Dunfang; Han, Qi; Zhao, Xin; Zeng, Xin; Xu, Yi; Sun, Zheng; Chen, Qianming

2016-07-01

Oral lichen planus (OLP) is one of the most common chronic inflammatory oral mucosal diseases with T-cell-mediated immune pathogenesis. In subepithelial and lamina propria of OLP local lesions, the presence of CD4(+) T helper (CD4(+) Th) cells appeared as the major lymphocytes. These CD4(+) T lymphocytes can differentiate into distinct Th cell types such as Th1, Th2, Treg, Th17, Th22, Th9, and Tfh within the context of certain cytokines environment. Growing evidence indicated that Th1/Th2 imbalance may greatly participate into the cytokine network of OLP immunopathology. In addition, Th1/Th2 imbalance can be regulated by the Treg subset and also greatly influenced by the emerging novel CD4(+) Th subset Th17. Furthermore, the presence of novel subsets Th22, Th9 and Tfh in OLP patients is yet to be clarified. All these Th subsets and their specific cytokines may play a critical role in determining the character, extent and duration of immune responses in OLP pathogenesis. Therefore, we review the roles of distinct CD4(+) Th subsets and their signature cytokines in determining disease severity and susceptibility of OLP and also reveal the novel therapeutic strategies based on T lymphocytes subsets in OLP treatment. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
SIRT1 may play a crucial role in overload-induced hypertrophy of skeletal muscle.

Science.gov (United States)

Koltai, Erika; Bori, Zoltán; Chabert, Clovis; Dubouchaud, Hervé; Naito, Hisashi; Machida, Shuichi; Davies, Kelvin Ja; Murlasits, Zsolt; Fry, Andrew C; Boldogh, Istvan; Radak, Zsolt

2017-06-01

Silent mating type information regulation 2 homologue 1 (SIRT1) activity and content increased significantly in overload-induced hypertrophy. SIRT1-mediated signalling through Akt, the endothelial nitric oxide synthase mediated pathway, regulates anabolic process in the hypertrophy of skeletal muscle. The regulation of catabolic signalling via forkhead box O 1 and protein ubiquitination is SIRT1 dependent. Overload-induced changes in microRNA levels regulate SIRT1 and insulin-like growth factor 1 signalling. Significant skeletal muscle mass guarantees functional wellbeing and is important for high level performance in many sports. Although the molecular mechanism for skeletal muscle hypertrophy has been well studied, it still is not completely understood. In the present study, we used a functional overload model to induce plantaris muscle hypertrophy by surgically removing the soleus and gastrocnemius muscles in rats. Two weeks of muscle ablation resulted in a 40% increase in muscle mass, which was associated with a significant increase in silent mating type information regulation 2 homologue 1 (SIRT1) content and activity (P overload-induced hypertrophy. These findings, along with the well-known regulatory roles that SIRT1 plays in modulating both anabolic and catabolic pathways, allow us to propose the hypothesis that SIRT1 may actually play a crucial causal role in overload-induced hypertrophy of skeletal muscle. This hypothesis will now require rigorous direct and functional testing. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.
Two distinct calmodulin binding sites in the third intracellular loop and carboxyl tail of angiotensin II (AT(1A receptor.

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Renwen Zhang

Full Text Available In this study, we present data that support the presence of two distinct calmodulin binding sites within the angiotensin II receptor (AT(1A, at juxtamembrane regions of the N-terminus of the third intracellular loop (i3, amino acids 214-231 and carboxyl tail of the receptor (ct, 302-317. We used bioluminescence resonance energy transfer assays to document interactions of calmodulin with the AT(1A holo-receptor and GST-fusion protein pull-downs to demonstrate that i3 and ct interact with calmodulin in a Ca²⁺-dependent fashion. The former is a 1-12 motif and the latter belongs to 1-5-10 calmodulin binding motif. The apparent Kd of calmodulin for i3 is 177.0±9.1 nM, and for ct is 79.4±7.9 nM as assessed by dansyl-calmodulin fluorescence. Replacement of the tryptophan (W219 for alanine in i3, and phenylalanine (F309 or F313 for alanine in ct reduced their binding affinities for calmodulin, as predicted by computer docking simulations. Exogenously applied calmodulin attenuated interactions between G protein βγ subunits and i3 and ct, somewhat more so for ct than i3. Mutations W219A, F309A, and F313A did not alter Gβγ binding, but reduced the ability of calmodulin to compete with Gβγ, suggesting that calmodulin and Gβγ have overlapping, but not identical, binding requirements for i3 and ct. Calmodulin interference with the Gβγ binding to i3 and ct regions of the AT(1A receptor strongly suggests that calmodulin plays critical roles in regulating Gβγ-dependent signaling of the receptor.
Two Distinct Calmodulin Binding Sites in the Third Intracellular Loop and Carboxyl Tail of Angiotensin II (AT1A) Receptor

Science.gov (United States)

Zhang, Renwen; Liu, Zhijie; Qu, Youxing; Xu, Ying; Yang, Qing

2013-01-01

In this study, we present data that support the presence of two distinct calmodulin binding sites within the angiotensin II receptor (AT1A), at juxtamembrane regions of the N-terminus of the third intracellular loop (i3, amino acids 214–231) and carboxyl tail of the receptor (ct, 302–317). We used bioluminescence resonance energy transfer assays to document interactions of calmodulin with the AT1A holo-receptor and GST-fusion protein pull-downs to demonstrate that i3 and ct interact with calmodulin in a Ca2+-dependent fashion. The former is a 1–12 motif and the latter belongs to 1-5-10 calmodulin binding motif. The apparent Kd of calmodulin for i3 is 177.0±9.1 nM, and for ct is 79.4±7.9 nM as assessed by dansyl-calmodulin fluorescence. Replacement of the tryptophan (W219) for alanine in i3, and phenylalanine (F309 or F313) for alanine in ct reduced their binding affinities for calmodulin, as predicted by computer docking simulations. Exogenously applied calmodulin attenuated interactions between G protein βγ subunits and i3 and ct, somewhat more so for ct than i3. Mutations W219A, F309A, and F313A did not alter Gβγ binding, but reduced the ability of calmodulin to compete with Gβγ, suggesting that calmodulin and Gβγ have overlapping, but not identical, binding requirements for i3 and ct. Calmodulin interference with the Gβγ binding to i3 and ct regions of the AT1A receptor strongly suggests that calmodulin plays critical roles in regulating Gβγ-dependent signaling of the receptor. PMID:23755207
Photochemical Degradation of Dimethyl Phthalate by Fe(III)/tartrate/H{sub 2}O{sub 2} System

Energy Technology Data Exchange (ETDEWEB)

Feng, Xianghua; Ding, Shimin; Xie, Faping [Yangtze Normal Univ., Fuling (China)

2012-11-15

Photochemical degradation of dimethyl phthalate (DMP) in Fe(III)/tartrate/H{sub 2}O{sub 2} system was investigated utilizing fluorescent lamps as the primary light source. Effects of initial pH, light source, and initial concentration of each reactant on DMP photodegradation was examined. The results show that the system was able to effectively photodegrade DMP utilizing visible light. Fluorescent lamp, halide lamp, UV lamp and sunlight could all be used as the light sources. The optimal pH ranged among 3.0-4.0 for the system. Increases of the initial concentrations of Fe(III) and H{sub 2}O{sub 2} accelerated the photodegradation of DMP, whereas excessively high initial tartrate concentration resulted in the decrease of photodegradation efficiency and rate of DMP.
N,N-diethyl phenylacetamide (DEPA): A safe and effective repellent for personal protection against hematophagous arthropods.

Science.gov (United States)

Kalyanasundaram, Muthuswami; Mathew, Nisha

2006-05-01

Repellents play an important role in protecting humans from the bites of insect pests. An effective and safe repellent will be useful in reducing human-vector contact and thereby help in the interruption of vector borne disease transmission. Because of the unavailability of m-toluic acid in India for the manufacture of N,N-diethyl m-toluamide (DEET), there is a need to develop an alternate effective and safe insect repellent. In total, 120 substituted amides were synthesized and tested for repellency at 1.0 mg/cm2 under laboratory conditions. Among these amides, N,N-diethyl phenylacetamide (DEPA), applied at 1.0 mg/cm2 in different oil bases, was found to exhibit promising repellency (6-8 h) in the laboratory when tested against Aedes aegypti (L.) The repellent DEPA was evaluated on army personnel in comparison with dimethylphthalate (DMP) and DEET against mosquitoes, black flies, and land leeches under field condition in the North-East Frontier area of India. Both DEPA and DEET displayed broad-spectrum repellency. DEPA was more effective than DMP against all test organisms. However, no significant difference was noticed between DEPA and DEET for repellency at 0.25 and 0.5 mg/cm2 against black flies and mosquitoes. DMP was the least effective among the three compounds in the field studies. The relative potency of DEPA in comparison with DEET and DMP for repellency against Phlebotomine sand flies also was determined. At 0.1 mg/cm2, both DEPA and DEET were found to be equally effective with a protection time from 4.37 +/- 0.08 to 4.45 +/- 0.15 h. Both compounds were significantly more effective than DMP. At 0.2 mg/cm2, DEPA and DEET provided protection times of 6.52 +/- 0.08 and 7.15 +/- 0.15 h, respectively. DEPA was formulated into a vanishing cream, a pharmacologically safe polymer-based liquid, and a liposphere lotion. The vanishing cream and the two-polymer liquid formulations enhanced protection times from 4.4 to 6.5 and 7.13 h, respectively, compared with an
Spontaneous Ca2+ transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine

Science.gov (United States)

Baker, Salah A.; Drumm, Bernard T.; Saur, Dieter; Hennig, Grant W.; Ward, Sean M.

2016-01-01

Key points Interstitial cells of Cajal at the level of the deep muscular plexus (ICC‐DMP) in the small intestine generate spontaneous Ca2+ transients that consist of localized Ca2+ events and limited propagating Ca2+ waves.Ca2+ transients in ICC‐DMP display variable characteristics: from discrete, highly localized Ca2+ transients to regionalized Ca2+ waves with variable rates of occurrence, amplitude, duration and spatial spread.Ca2+ transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells.Ca2+ transients in ICC‐DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s).Functional intracellular Ca2+ stores are essential for spontaneous Ca2+ transients, and the sarco/endoplasmic reticulum Ca2+‐ATPase (SERCA) pump is necessary for maintenance of spontaneity.Ca2+ release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3Rs). Release from these channels is interdependent.ICC express transcripts of multiple RyRs and InsP3Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Abstract Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC‐DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC‐DMP are mediated by activation of Ca2+‐activated Cl− channels; thus, Ca2+ signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca2+ transients in ICC‐DMP within intact jejunal muscles expressing a genetically encoded Ca2+ indicator (GCaMP3) selectively in ICC. ICC‐DMP displayed spontaneous Ca2+ transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca2+ transients was highly variable, and it was
Spontaneous Ca(2+) transients in interstitial cells of Cajal located within the deep muscular plexus of the murine small intestine.

Science.gov (United States)

Baker, Salah A; Drumm, Bernard T; Saur, Dieter; Hennig, Grant W; Ward, Sean M; Sanders, Kenton M

2016-06-15

Interstitial cells of Cajal at the level of the deep muscular plexus (ICC-DMP) in the small intestine generate spontaneous Ca(2+) transients that consist of localized Ca(2+) events and limited propagating Ca(2+) waves. Ca(2+) transients in ICC-DMP display variable characteristics: from discrete, highly localized Ca(2+) transients to regionalized Ca(2+) waves with variable rates of occurrence, amplitude, duration and spatial spread. Ca(2+) transients fired stochastically, with no cellular or multicellular rhythmic activity being observed. No correlation was found between the firing sites in adjacent cells. Ca(2+) transients in ICC-DMP are suppressed by the ongoing release of inhibitory neurotransmitter(s). Functional intracellular Ca(2+) stores are essential for spontaneous Ca(2+) transients, and the sarco/endoplasmic reticulum Ca(2+) -ATPase (SERCA) pump is necessary for maintenance of spontaneity. Ca(2+) release mechanisms involve both ryanodine receptors (RyRs) and inositol triphosphate receptors (InsP3 Rs). Release from these channels is interdependent. ICC express transcripts of multiple RyRs and InsP3 Rs, with Itpr1 and Ryr2 subtypes displaying the highest expression. Interstitial cells of Cajal in the deep muscular plexus of the small intestine (ICC-DMP) are closely associated with varicosities of enteric motor neurons and generate responses contributing to neural regulation of intestinal motility. Responses of ICC-DMP are mediated by activation of Ca(2+) -activated Cl(-) channels; thus, Ca(2+) signalling is central to the behaviours of these cells. Confocal imaging was used to characterize the nature and mechanisms of Ca(2+) transients in ICC-DMP within intact jejunal muscles expressing a genetically encoded Ca(2+) indicator (GCaMP3) selectively in ICC. ICC-DMP displayed spontaneous Ca(2+) transients that ranged from discrete, localized events to waves that propagated over variable distances. The occurrence of Ca(2+) transients was highly variable, and it
Data Management Plan

DEFF Research Database (Denmark)

Hansen, Ernst Jan de Place; Sørensen, Nils Lykke

2016-01-01

This document describes the Data Management Plan (DMP) (second version), relating to RIBuild WP8, deliverable D8.1. It draws the first lines for how data can be made findable, accessible, interoperable and re-usable after the project period.......This document describes the Data Management Plan (DMP) (second version), relating to RIBuild WP8, deliverable D8.1. It draws the first lines for how data can be made findable, accessible, interoperable and re-usable after the project period....
Asthma management practices in adults--findings from the German Health Update (GEDA) 2010 and the German National Health Interview and Examination Survey (DEGS1) 2008-2011.

Science.gov (United States)

Steppuhn, Henriette; Langen, Ute; Mueters, Stephan; Dahm, Stefan; Knopf, Hildtraud; Keil, Thomas; Scheidt-Nave, Christa

2016-01-01

In Germany, population-wide data on adherence to national asthma management guidelines are lacking, and performance measures (PM) for quality assurance in asthma care are systematically monitored for patients with German national asthma disease management program (DMP) enrollment only. We used national health survey data to assess variation in asthma care PM with respect to patient characteristics and care context, including DMP enrollment. Among adults 18-79 years with self-reported physician-diagnosed asthma in the past 12 months identified from a recent German National Health Interview Survey (GEDA 2010: N = 1096) and the German National Health interview and Examination Survey 2008-2011 (DEGS1: N = 333), variation in asthma care PM was analyzed using logistic regression analysis. Overall, 38.4% (95% confidence interval: 32.5-44.6%) of adults with asthma were on current inhaled corticosteroid therapy. Regarding non-drug asthma management, low coverage was observed for inhaler technique monitoring (35.2%; 31.2-39.3%) and for provision of an asthma management plan (27.3%; 24.2-30.7%), particularly among those with low education. Specific PM were more complete among persons with than without asthma DMP enrollment (adjusted odds ratios ranging up to 10.19; 5.23-19.86), even if asthma patients were regularly followed in a different care context. Guideline adherence appears to be suboptimal, particularly with respect to PM related to patient counseling. Barriers to the translation of recommendations into practice need to be identified and continuous monitoring of asthma care PM at the population level needs to be established.
[Ambulatory care of patients with asthma in Germany and disease management program for asthma from the view of statutory health insured patients. A postal survey of statutory health insured patients].

Science.gov (United States)

Bücker, B; Löscher, S; Schürer, C; Schaper, K; Abholz, H-H; Wilm, S

2015-03-01

In spite of a decline in mortality due to asthma in Germany various studies point towards deficits in asthma care. Our investigation should collect data about ambulatory care from the view of statutory health insured patients (SHI), who participate in the disease management program asthma (DMP-P) or do not (NP). Primary question was, if there is a difference between asthma control. Secondary questions referred to process parameters. The postal inquiry was conducted in 2010 with 8000 randomly selected members of a SHI company with asthma (4000 DMP-P and 4000 NP). The descriptive evaluation of categorical items was performed with cross-tables. The absolute risk reduction (ARR) and 97.5 %-confidence interval (CI; multiple level 5 %) was used to evaluate the primary question. Secondary questions were analysed by ARR and 95 %-CI. The response rate of the questionnaire accounted for 31.1 % (2565). 49.2 % of all respondents lived with an uncontrolled asthma with no differences between DMP-P and NP (ARR -2.7 %, 97.5 %-CI -7.9 -2.4 %). Results did not alter after adjustment for sex and age. The secondary questions revealed significant differences (DMP-P vs. NP) in participation in asthma trainings 50.6 vs. 32.3 %, use of a peak-flow-meter 49.3 vs. 25.3 % and asthma action plan within reach 21.7 vs. 11.0 %. Half of all respondents lives selfreported - even in the DMP-group - with an uncontrolled asthma. Process parameters showed better results in the DMP-group. It can be considered, that the DMP has its desired effect on patient-centered care, but does not lead to a better therapeutic outcome. Explanations can only be assumed: insufficient impact of the process parameters on the outcome, patient behavior, that minimizes a possible effect, or selection effects, if patients, who were more sick and at the same time more motivated, were mainly included in the DMP. These aspects should be addressed in studies with a prospective design. © Georg Thieme
The neural cell adhesion molecule L1 is distinct from the N-CAM related group of surface antigens BSP-2 and D2

DEFF Research Database (Denmark)

Faissner, A; Kruse, J; Goridis, C

1984-01-01

The neural cell adhesion molecule L1 and the group of N-CAM related molecules, BSP-2 and D2 antigen, are immunochemically distinct molecular species. The two groups of surface molecules are also functionally distinct entities, since inhibition of Ca2+-independent adhesion among early post-natal m...
Unhappy families: using tabletop games as a technology to understand play in education

Directory of Open Access Journals (Sweden)

John Lean

2018-05-01

Full Text Available In this article, we argue that tabletop games provide a helpful means of rethinking the affordances of digital games in pedagogy. We argue that tabletop games offer a distinctive technology from digital games in exploring the idea of play as experience, providing a sociable, accessible and tactile platform that can easily be adapted by players to suit their needs. At a workshop session at an international conference on play in education, we used tabletop games to enable discussion and observation of play. This workshop suggested that, rather than a singular definition, tabletop play means different things to different people, and what is ‘counted as’ play depends upon both individual and group interactions. Building upon this discussion, in this article, we return to both tabletop and digital games to discuss the idea of play as experience, especially with regard to the use of technology in educational settings, and how games might be seen as less ‘predictable’ than other technologies. We hope that this discussion provides future inspiration to other scholars who are considering the use of tabletop games in both pedagogical and technological research.

Decomposition and Mineralization of Dimethyl Phthalate in an Aqueous Solution by Wet Oxidation

Directory of Open Access Journals (Sweden)

Dar-Ren Ji

2015-01-01

Full Text Available Dimethyl phthalate (DMP was treated via wet oxygen oxidation process (WOP. The decomposition efficiency ηDMP of DMP and mineralization efficiency ηTOC of total organic carbons were measured to evaluate the effects of operation parameters on the performance of WOP. The results revealed that reaction temperature T is the most affecting factor, with a higher T offering higher ηDMP and ηTOC as expected. The ηDMP increases as rotating speed increases from 300 to 500 rpm with stirring enhancement of gas liquid mass transfer. However, it exhibits reduction effect at 700 rpm due to purging of dissolved oxygen by overstirring. Regarding the effects of pressure PT, a higher PT provides more oxygen for the forward reaction with DMP, while overhigh PT increases the absorption of gaseous products such as CO2 and decomposes short-chain hydrocarbon fragments back into the solution thus hindering the forward reaction. For the tested PT of 2.41 to 3.45 MPa, the results indicated that 2.41 MPa is appropriate. A longer reaction time of course gives better performance. At 500 rpm, 483 K, 2.41 MPa, and 180 min, the ηDMP and ηTOC are 93 and 36%, respectively.
Play and playfulness, basic features of early childhood education

NARCIS (Netherlands)

Singer, E.

2013-01-01

This article argues that play and playfulness are basic features in early childhood education, but that play curricula can have serious drawbacks. The starting point is the play theory of the Dutch historian Johan Huizinga, a radical critic of the focus on the educational benefits of play. According
Play and playfulness in early childhood education and care.

Directory of Open Access Journals (Sweden)

Singer E.

2015-06-01

Full Text Available Play and playfulness are basic features in early childhood education. The elements of play are pleasure, a sense of freedom, and the co-construction of shared meaning through the use of rules or rhythms. Play and learning are closely related in early childhood. But when the focus on the educational benefits of play becomes too strong, the most essential feature of play is lost: children’s pleasure. Young children in group settings often have to adapt to the teachers’ demands related to security, hygiene, and social norms and values. But the playfulness of the teachers helps to overcome differences in power in the caregiver-child relationship and prevents young children from becoming overburdened with strict rules and group discipline. Play and playfulness are a resource of shared pleasure and creativity in learning processes.
Universal, developmental, and variable aspects of young children's play: a cross-cultural comparison of pretending at home.

Science.gov (United States)

Haight, W L; Wang, X L; Fung, H H; Williams, K; Mintz, J

1999-01-01

Using longitudinal data from five Irish American families in the United States and nine Chinese families in Taiwan, in conjunction with an emerging body of evidence in the cultural psychology literature, we propose universal, culturally variable, and developmental dimensions of young children's pretend play. Possible universal dimensions include the use of objects, and the predominantly social nature of pretend play. Developmental dimensions include increases in the proportion of social pretend play initiated by the child, the proportion of partner initiations elaborated upon by the child, and caregivers' use of pretend play initiations to serve other, nonplay social functions. Culturally variable dimensions include the centrality of objects, the participation of specific play partners, the extent of child initiations of social pretend play with caregivers, the various functions of social pretend play in interaction, and specific themes. These findings raise the theoretical issue of how universal and variable dimensions of pretend play interact in specific communities to create distinctive development pathways.
Toward a Neuroscientific Understanding of Play: A Dimensional Coding Framework for Analyzing Infant–Adult Play Patterns

Directory of Open Access Journals (Sweden)

Dave Neale

2018-03-01

Full Text Available Play during early life is a ubiquitous activity, and an individual’s propensity for play is positively related to cognitive development and emotional well-being. Play behavior (which may be solitary or shared with a social partner is diverse and multi-faceted. A challenge for current research is to converge on a common definition and measurement system for play – whether examined at a behavioral, cognitive or neurological level. Combining these different approaches in a multimodal analysis could yield significant advances in understanding the neurocognitive mechanisms of play, and provide the basis for developing biologically grounded play models. However, there is currently no integrated framework for conducting a multimodal analysis of play that spans brain, cognition and behavior. The proposed coding framework uses grounded and observable behaviors along three dimensions (sensorimotor, cognitive and socio-emotional, to compute inferences about playful behavior in a social context, and related social interactional states. Here, we illustrate the sensitivity and utility of the proposed coding framework using two contrasting dyadic corpora (N = 5 of mother-infant object-oriented interactions during experimental conditions that were either non-conducive (Condition 1 or conducive (Condition 2 to the emergence of playful behavior. We find that the framework accurately identifies the modal form of social interaction as being either non-playful (Condition 1 or playful (Condition 2, and further provides useful insights about differences in the quality of social interaction and temporal synchronicity within the dyad. It is intended that this fine-grained coding of play behavior will be easily assimilated with, and inform, future analysis of neural data that is also collected during adult–infant play. In conclusion, here, we present a novel framework for analyzing the continuous time-evolution of adult–infant play patterns, underpinned by
Toward a Neuroscientific Understanding of Play: A Dimensional Coding Framework for Analyzing Infant-Adult Play Patterns.

Science.gov (United States)

Neale, Dave; Clackson, Kaili; Georgieva, Stanimira; Dedetas, Hatice; Scarpate, Melissa; Wass, Sam; Leong, Victoria

2018-01-01

Play during early life is a ubiquitous activity, and an individual's propensity for play is positively related to cognitive development and emotional well-being. Play behavior (which may be solitary or shared with a social partner) is diverse and multi-faceted. A challenge for current research is to converge on a common definition and measurement system for play - whether examined at a behavioral, cognitive or neurological level. Combining these different approaches in a multimodal analysis could yield significant advances in understanding the neurocognitive mechanisms of play, and provide the basis for developing biologically grounded play models. However, there is currently no integrated framework for conducting a multimodal analysis of play that spans brain, cognition and behavior. The proposed coding framework uses grounded and observable behaviors along three dimensions (sensorimotor, cognitive and socio-emotional), to compute inferences about playful behavior in a social context, and related social interactional states. Here, we illustrate the sensitivity and utility of the proposed coding framework using two contrasting dyadic corpora ( N = 5) of mother-infant object-oriented interactions during experimental conditions that were either non-conducive (Condition 1) or conducive (Condition 2) to the emergence of playful behavior. We find that the framework accurately identifies the modal form of social interaction as being either non-playful (Condition 1) or playful (Condition 2), and further provides useful insights about differences in the quality of social interaction and temporal synchronicity within the dyad. It is intended that this fine-grained coding of play behavior will be easily assimilated with, and inform, future analysis of neural data that is also collected during adult-infant play. In conclusion, here, we present a novel framework for analyzing the continuous time-evolution of adult-infant play patterns, underpinned by biologically informed
Playful Membership

DEFF Research Database (Denmark)

Åkerstrøm Andersen, Niels; Pors, Justine Grønbæk

2014-01-01

This article studies the implications of current attempts by organizations to adapt to a world of constant change by introducing the notion of playful organizational membership. To this end we conduct a brief semantic history of organizational play and argue that when organizations play, employees...... are expected to engage in playful exploration of alternative selves. Drawing on Niklas Luhmann's theory of time and decision-making and Gregory Bateson's theory of play, the article analyses three empirical examples of how games play with conceptions of time. We explore how games represent an organizational...
Concepts and Theories, Methods and Reasons: Why Do the Children (Pretend) Play? Reply to Weisberg, Hirsh-Pasek, and Golinkoff (2013); Bergen (2013); and Walker and Gopnik (2013)

Science.gov (United States)

Lillard, Angeline S.; Hopkins, Emily J.; Dore, Rebecca A.; Palmquist, Carolyn M.; Lerner, Matthew D.; Smith, Eric D.

2013-01-01

We greatly appreciate the astute comments on Lillard et al. (2013) and the opportunity to reply. Here we point out the importance of keeping conceptual distinctions clear regarding play, pretend play, and exploration. We also discuss methodological issues with play research. We end with speculation that if pretend play did not emerge because it…
Seductive play in digital games

DEFF Research Database (Denmark)

Jørgensen, Ida Kathrine Hammeleff

2015-01-01

play. It is important here to point towards Baudrillard’s distinction between rules and the law. Rules are upheld by a pact between seducer and seduced or between player and game whereas the law relies on an idea of an end that can be transgressed. Rules on the other hand cannot be transgressed...... they can only be observed. If a player fails to observe the rules the pact between the player and the game is void and no game takes place (Baudrillard, 1990 [1979], p 140). This is in stark contrast to Sicart’s description of the rules of digital games as non-negotiable and ultimately upheld...... by the computer (Sicart, 2009, p. 27). This paper argues that this is exactly what distinguishes a game like I don't even game from more conventional digital games. I don't even game is completely empty of significance, and there are no non-negotiable rules governed by the system. As such the game only exists...
Rolie-Poly fluid flowing through constrictions: Two distinct instabilities

KAUST Repository

Reis, T.; Wilson, H.J.

2013-01-01

Elastic instabilities of entangled polymer melts are common in industrial processes but the physics responsible is not well understood. We present a numerical linear stability study of a molecular based constitutive model which grants us physical insight into the underlying mechanics involved. Two constriction flows are considered - one shear dominated, the other extension dominated - and two distinct instabilities are found. The influence of the molecular structure and the behaviour of the polymer dynamics are investigated and in both cases chain relaxation and orientation play a crucial role. This suggests a molecular-based physical interpretation of the underlying mechanisms responsible for flow instabilities. © 2013 Elsevier B.V.
Rolie-Poly fluid flowing through constrictions: Two distinct instabilities

KAUST Repository

Reis, T.

2013-05-01

Elastic instabilities of entangled polymer melts are common in industrial processes but the physics responsible is not well understood. We present a numerical linear stability study of a molecular based constitutive model which grants us physical insight into the underlying mechanics involved. Two constriction flows are considered - one shear dominated, the other extension dominated - and two distinct instabilities are found. The influence of the molecular structure and the behaviour of the polymer dynamics are investigated and in both cases chain relaxation and orientation play a crucial role. This suggests a molecular-based physical interpretation of the underlying mechanisms responsible for flow instabilities. © 2013 Elsevier B.V.
Rice cytochrome P450 MAX1 homologs catalyze distinct steps in strigolactone biosynthesis

KAUST Repository

Zhang, Yanxia; van Dijk, Aalt D J; Scaffidi, Adrian; Flematti, Gavin R.; Hofmann, Manuel; Charnikhova, Tatsiana; Verstappen, Francel; Hepworth, Jo; van der Krol, Sander; Leyser, Ottoline; Smith, Steven M.; Zwanenburg, Binne; Al-Babili, Salim; Ruyter-Spira, Carolien; Bouwmeester, Harro J.

2014-01-01

Strigolactones (SLs) are a class of phytohormones and rhizosphere signaling compounds with high structural diversity. Three enzymes, carotenoid isomerase DWARF27 and carotenoid cleavage dioxygenases CCD7 and CCD8, were previously shown to convert all-trans-β-carotene to carlactone (CL), the SL precursor. However, how CL is metabolized to SLs has remained elusive. Here, by reconstituting the SL biosynthetic pathway in Nicotiana benthamiana, we show that a rice homolog of Arabidopsis More Axillary Growth 1 (MAX1), encodes a cytochrome P450 CYP711 subfamily member that acts as a CL oxidase to stereoselectively convert CL into ent-2'-epi-5-deoxystrigol (B-C lactone ring formation), the presumed precursor of rice SLs. A protein encoded by a second rice MAX1 homolog then catalyzes the conversion of ent-2'-epi-5-deoxystrigol to orobanchol. We therefore report that two members of CYP711 enzymes can catalyze two distinct steps in SL biosynthesis, identifying the first enzymes involved in B-C ring closure and a subsequent structural diversification step of SLs.
Rice cytochrome P450 MAX1 homologs catalyze distinct steps in strigolactone biosynthesis

KAUST Repository

Zhang, Yanxia

2014-10-26

Strigolactones (SLs) are a class of phytohormones and rhizosphere signaling compounds with high structural diversity. Three enzymes, carotenoid isomerase DWARF27 and carotenoid cleavage dioxygenases CCD7 and CCD8, were previously shown to convert all-trans-β-carotene to carlactone (CL), the SL precursor. However, how CL is metabolized to SLs has remained elusive. Here, by reconstituting the SL biosynthetic pathway in Nicotiana benthamiana, we show that a rice homolog of Arabidopsis More Axillary Growth 1 (MAX1), encodes a cytochrome P450 CYP711 subfamily member that acts as a CL oxidase to stereoselectively convert CL into ent-2\\'-epi-5-deoxystrigol (B-C lactone ring formation), the presumed precursor of rice SLs. A protein encoded by a second rice MAX1 homolog then catalyzes the conversion of ent-2\\'-epi-5-deoxystrigol to orobanchol. We therefore report that two members of CYP711 enzymes can catalyze two distinct steps in SL biosynthesis, identifying the first enzymes involved in B-C ring closure and a subsequent structural diversification step of SLs.
Media and human capital development: Can video game playing make you smarter?1

Science.gov (United States)

Suziedelyte, Agne

2015-01-01

According to the literature, video game playing can improve such cognitive skills as problem solving, abstract reasoning, and spatial logic. I test this hypothesis using The Child Development Supplement to the Panel Study of Income Dynamics. The endogeneity of video game playing is addressed by using panel data methods and controlling for an extensive list of child and family characteristics. To address the measurement error in video game playing, I instrument children's weekday time use with their weekend time use. After taking into account the endogeneity and measurement error, video game playing is found to positively affect children's problem solving ability. The effect of video game playing on problem solving ability is comparable to the effect of educational activities. PMID:25705064
PDGFRα plays a crucial role in connective tissue remodeling.

Science.gov (United States)

Horikawa, Shinjiro; Ishii, Yoko; Hamashima, Takeru; Yamamoto, Seiji; Mori, Hisashi; Fujimori, Toshihiko; Shen, Jie; Inoue, Ran; Nishizono, Hirofumi; Itoh, Hiroshi; Majima, Masataka; Abraham, David; Miyawaki, Toshio; Sasahara, Masakiyo

2015-12-07

Platelet derived growth factor (PDGF) plays a pivotal role in the remodeling of connective tissues. Emerging data indicate the distinctive role of PDGF receptor-α (PDGFRα) in this process. In the present study, the Pdgfra gene was systemically inactivated in adult mouse (α-KO mouse), and the role of PDGFRα was examined in the subcutaneously implanted sponge matrices. PDGFRα expressed in the fibroblasts of Pdgfra-preserving control mice (Flox mice), was significantly reduced in the sponges in α-KO mice. Neovascularized areas were largely suppressed in the α-KO mice than in the Flox mice, whereas the other parameters related to the blood vessels and endothelial cells were similar. The deposition of collagen and fibronectin and the expression of collagen 1a1 and 3a1 genes were significantly reduced in α-KO mice. There was a significantly decrease in the number and dividing fibroblasts in the α-KO mice, and those of macrophages were similar between the two genotypes. Hepatocyte growth factor (Hgf) gene expression was suppressed in Pdgfra-inactivated fibroblasts and connective tissue. The findings implicate the role of PDGFRα-dependent ECM and HGF production in fibroblasts that promotes the remodeling of connective tissue and suggest that PDGFRα may be a relevant target to regulate connective tissue remodeling.
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...
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.
Clay Play

Science.gov (United States)

Rogers, Liz; Steffan, Dana

2009-01-01

This article describes how to use clay as a potential material for young children to explore. As teachers, the authors find that their dialogue about the potential of clay as a learning medium raises many questions: (1) What makes clay so enticing? (2) Why are teachers noticing different play and conversation around the clay table as compared to…
Development and validation of the attitudes toward outdoor play scales for children.

Science.gov (United States)

Beyer, Kirsten; Bizub, Jessica; Szabo, Aniko; Heller, Beth; Kistner, Amy; Shawgo, Erin; Zetts, Corey

2015-05-01

The natural world has long been associated with health and described as a therapeutic landscape, and a growing body of research demonstrates the benefits of interacting with nature for mental and physical health. However, concern is growing that children have lost connection to the natural world and spend less time outdoors, despite the known health benefits of doing so. It is likely that healthy behaviors related to engagement with nature are mediated by beliefs about the value and safety of play in nature. While the literature abounds with qualitative examinations of children's attitudes toward outdoor play, there exist few instruments to quantitatively measure these attitudes. Informed by health behavior change theories, we describe the development and validation of the Attitudes toward Outdoor Play (ATOP) scales. As part of a community-academic partnership project called More Than a Pretty Place, the development of the ATOP scales unfolded in stages: (1) item generation based on a comprehensive literature review and consensus among the project team, (2) interviews with environmental educators, (3) initial pilot testing, (4) scale refinement, (5) administration during 2012 and 2013 to a sample of school children ages 9-13 (n = 362) in Milwaukee, WI, USA, and (6) quantitative psychometric evaluation. Two distinct scales emerged: ATOP-benefits (alpha = 0.79) and ATOP-fears (alpha = 0.79). Validity analyses found that both scales correlated as expected with measures of engagement in outdoor play, parental support for outdoor play, and sedentary behaviors. The ATOP scales are reliable and valid instruments for measuring attitudes toward outdoor play that may mediate children's outdoor activity in natural settings. The ATOP scales could be useful for evaluating the effects of programming, such as environmental education programming, on improving children's attitudes toward the benefits of nature and reducing their fears, and may predict more distal outcomes
IR-induced autophagy plays a role in survival of HeLa cells

International Nuclear Information System (INIS)

Kang, Mi Young; Jang, Eun Yeong; Ryu, Tae Ho; Chung, Dong Min; Kim, Jin Hong; Kim, Jin Kyu

2014-01-01

Cells respond to stress with repair, or are diverted into irreversible cell cycle exit (senescence) or are eliminated through programmed cell death. There are two major morphologically distinctive forms of programmed cell death, apoptosis and autophagic cell death. Apoptosis contribute to cell death, whereas autophagy can play a dual role in mediating either cell survival or death in response to various stress stimuli. Here we analysed cellular responses induced by IR. The understanding of an appropriate cellular stress response is of crucial importance in foreseeing the cell fate. Apoptotic feagures were not detected in HeLa under our experimental irradiation condition. Autophagic cell death in HeLa may play an important role in cell protection and can result in cell survival

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.
Word Play: Scaffolding Language Development through Child-Directed Play

Science.gov (United States)

Wasik, Barbara A.; Jacobi-Vessels, Jill L.

2017-01-01

Play is an important activity in young children's lives. It is how children explore their world and build knowledge. Although free play, which is play that is totally child directed, contributes to children's learning, self-regulation and motivation, adults' participation in children's play is critical in their development, especially their…
Physiological characteristics of badminton match play.

Science.gov (United States)

Faude, Oliver; Meyer, Tim; Rosenberger, Friederike; Fries, Markus; Huber, Günther; Kindermann, Wilfried

2007-07-01

The present study aimed at examining the physiological characteristics and metabolic demands of badminton single match play. Twelve internationally ranked badminton players (eight women and four men) performed an incremental treadmill test [VO(2peak = )50.3 +/- 4.1 ml min(-1) kg(-1) (women) and 61.8 +/- 5.9 ml min(-1) kg(-1) (men), respectively]. On a separate day, they played a simulated badminton match of two 15 min with simultaneous gas exchange (breath-by-breath) and heart rate measurements. Additionally, blood lactate concentrations were determined before, after 15 min and at the end of the match. Furthermore, the duration of rallies and rests in between, the score as well as the number of shots per rally were recorded. A total of 630 rallies was analysed. Mean rally and rest duration were 5.5 +/- 4.4 s and 11.4 +/- 6.0 s, respectively, with an average 5.1 +/- 3.9 shots played per rally. Mean oxygen uptake (VO(2)), heart rate (HR), and blood lactate concentrations during badminton matches were 39.6 +/- 5.7 ml min(-1) kg(-1) (73.3% VO(2peak)), 169 +/- 9 min(-1) (89.0% HR(peak)) and 1.9 +/- 0.7 mmol l(-1), respectively. For a single subject 95% confidence intervals for VO(2) and HR during match play were on average 45.7-100.9% VO(2peak) and 78.3-99.8% HR(peak). High average intensity of badminton match play and considerable variability of several physiological variables demonstrate the importance of anaerobic alactacid and aerobic energy production in competitive badminton. A well-developed aerobic endurance capacity seems necessary for fast recovery between rallies or intensive training workouts.
Playful Literacy

DEFF Research Database (Denmark)

Froes, Isabel

these practices, which compose the taxonomy of tablet play. My contribution lies in identifying and proposing a series of theoretical concepts that complement recent theories related to play and digital literacy studies. The data collected through observations informed some noteworthy aspects, including how...... with tablets’ physical and digital affordances shape children’s digital play. This thesis presents how young children’s current practices when playing with tablets inform digital experiences in Denmark and Japan. Through an interdisciplinary lens and a grounded theory approach, I have identified and mapped...... vocabulary in children’s digital play experiences. These early digital experiences set the rules for the playgrounds and assert digital tablets as twenty-first-century toys, shaping young children’s playful literacy....
Temporal dynamics of distinct CA1 cell populations during unconscious state induced by ketamine.

Directory of Open Access Journals (Sweden)

Hui Kuang

2010-12-01

Full Text Available Ketamine is a widely used dissociative anesthetic which can induce some psychotic-like symptoms and memory deficits in some patients during the post-operative period. To understand its effects on neural population dynamics in the brain, we employed large-scale in vivo ensemble recording techniques to monitor the activity patterns of simultaneously recorded hippocampal CA1 pyramidal cells and various interneurons during several conscious and unconscious states such as awake rest, running, slow wave sleep, and ketamine-induced anesthesia. Our analyses reveal that ketamine induces distinct oscillatory dynamics not only in pyramidal cells but also in at least seven different types of CA1 interneurons including putative basket cells, chandelier cells, bistratified cells, and O-LM cells. These emergent unique oscillatory dynamics may very well reflect the intrinsic temporal relationships within the CA1 circuit. It is conceivable that systematic characterization of network dynamics may eventually lead to better understanding of how ketamine induces unconsciousness and consequently alters the conscious mind.
Vegetation Evaluation and Recommendations: Dredge Material Placement Areas and Adjacent Lands, Kaskaskia River Navigation Project, New Athens to Fayetteville.

Science.gov (United States)

1981-06-03

cottonwood), Salix interior (sandbar willow), Salix nigra (black willow), and Ulmus rubra * ( slippery elm ) . Somewhat drier sites with a predominance of fine...Dutch Elm Disease. *Ulmus rubra Muhl. SLIPPERY ELM . Common tree in floodplain woods; also occasional in DMP. *Valerianella radiata (L.) Dufr. CORN... elm ), Carya tomentosa (mocker- nut hickory), and Quercus bicolor (swamp white oak). Shrubs and woody vines play a major role in the ecology of these
Play Therapy

Science.gov (United States)

Lawver, Timothy; Blankenship, Kelly

2008-01-01

Play therapy is a treatment modality in which the therapist engages in play with the child. Its use has been documented in a variety of settings and with a variety of diagnoses. Treating within the context of play brings the therapist and the therapy to the level of the child. By way of an introduction to this approach, a case is presented of a six-year-old boy with oppositional defiant disorder. The presentation focuses on the events and interactions of a typical session with an established patient. The primary issues of the session are aggression, self worth, and self efficacy. These themes manifest themselves through the content of the child’s play and narration of his actions. The therapist then reflects these back to the child while gently encouraging the child toward more positive play. Though the example is one of nondirective play therapy, a wide range of variation exists under the heading of play therapy. PMID:19724720
Interleukin-1β modulates smooth muscle cell phenotype to a distinct inflammatory state relative to PDGF-DD via NF-κB-dependent mechanisms.

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Alexander, Matthew R; Murgai, Meera; Moehle, Christopher W; Owens, Gary K

2012-04-02

Smooth muscle cell (SMC) phenotypic modulation in atherosclerosis and in response to PDGF in vitro involves repression of differentiation marker genes and increases in SMC proliferation, migration, and matrix synthesis. However, SMCs within atherosclerotic plaques can also express a number of proinflammatory genes, and in cultured SMCs the inflammatory cytokine IL-1β represses SMC marker gene expression and induces inflammatory gene expression. Studies herein tested the hypothesis that IL-1β modulates SMC phenotype to a distinct inflammatory state relative to PDGF-DD. Genome-wide gene expression analysis of IL-1β- or PDGF-DD-treated SMCs revealed that although both stimuli repressed SMC differentiation marker gene expression, IL-1β distinctly induced expression of proinflammatory genes, while PDGF-DD primarily induced genes involved in cell proliferation. Promoters of inflammatory genes distinctly induced by IL-1β exhibited over-representation of NF-κB binding sites, and NF-κB inhibition in SMCs reduced IL-1β-induced upregulation of proinflammatory genes as well as repression of SMC differentiation marker genes. Interestingly, PDGF-DD-induced SMC marker gene repression was not NF-κB dependent. Finally, immunofluorescent staining of mouse atherosclerotic lesions revealed the presence of cells positive for the marker of an IL-1β-stimulated inflammatory SMC, chemokine (C-C motif) ligand 20 (CCL20), but not the PDGF-DD-induced gene, regulator of G protein signaling 17 (RGS17). Results demonstrate that IL-1β- but not PDGF-DD-induced phenotypic modulation of SMC is characterized by NF-κB-dependent activation of proinflammatory genes, suggesting the existence of a distinct inflammatory SMC phenotype. In addition, studies provide evidence for the possible utility of CCL20 and RGS17 as markers of inflammatory and proliferative state SMCs within atherosclerotic plaques in vivo.
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.
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.
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...
[11C]d-threo-methylphenidate PET in patients with Parkinson's disease and essential tremor

International Nuclear Information System (INIS)

Breit, S.; Reimold, M.; Reischl, G.; Klockgether, T.; Wuellner, U.

2006-01-01

Twenty Parkinson's disease (PD) patients, 6 patients with essential tremor and 10 healthy controls were studied with the dopamine transporter ligand [ 11 C]d-threo-methylphenidate ([ 11 C]dMP) and positron emission tomography (PET) to assess dopamine terminal loss in relation to disease duration and motor disability. Dopamine transporter availability was expressed as [11C]dMP binding potential (BP dMP ) in percentage of the mean of healthy controls. In PD patients (age at onset 57.7 ± 8.9 ys; disease duration 5.2 ± 3.3 ys; UPDRS motor score 24.2 ± 9.8; Hoehn and Yahr 2.1 ± 0.8; mean ± SD) BP dMP was reduced to 30 % (range: 11 - 55 %) in the putamen and 52 % (range: 14 - 96 %) in the caudate nucleus. BPdMP in the putamen closely correlated with the UPDRS motor score (r = -0.79, p dMP . Interestingly, when plotted over disease duration, PD patients with severe asymmetry of symptoms showed significantly lower BP dMP in the contralateral putamen (exponential fit: 34 % at onset) than the other PD patients (41 % at onset), indicating a different symptomatic threshold of these subgroups and an even closer correlation with the hypothetical 'true' disease duration. The exponential fit across all patients indicated a mean symptomatic threshold of 37 % contra- and 62 % ipsilateral, corresponding with an observed mean BP dMP of 51 % (average contra- and ipsilateral) in those patients with disease duration less than one year. No differences in BP dMP were observed between patients with essential tremor and healthy controls. [ 11 C]dMP appears to be a useful and sensitive marker of dopaminergic dysfunction in PD and can be used to assess and monitor disease severity. (author)
Disease management programs for patients with COPD in Germany: a longitudinal evaluation of routinely collected patient records.

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Mehring, Michael; Donnachie, Ewan; Fexer, Johannes; Hofmann, Frank; Schneider, Antonius

2014-07-01

The primary aim of the disease management program (DMP) for patients with COPD is to improve health outcomes and thereby to reduce overall costs. Six years after its introduction in Germany, no consensus has yet been reached as to whether the DMP has been effective in reaching these goals. The objective of the study was an evaluation of the DMP for COPD in Bavaria using routinely collected subject medical records. A longitudinal population-based study, comparing the total DMP population of up to 86,560 patients with a stable cohort of 17,549 subjects over a period of 5 years. The effect of subject dropout in the cohort is further estimated by means of inverse probability weighting. The proportion of subjects in the total population who were prescribed and received treatment with oral corticosteroids declined at a constant rate of 1.0% per year (P management education. While the proportion of smokers in the total population remained constant because of the effect of newly enrolled subjects, the proportion of smokers decreased significantly even after dropout adjustment, from 29% to 21%. The occurrence of exacerbations decreased steadily at a rate of 0.9% (total population) or 0.7% (cohort) per year. While the occurrence of emergency hospital admissions decreased in the total population, an increase was observed within the cohort. Summarizing all results leads to the suggestion that the German DMP for COPD has been effective in enhancing the quality of care in regard to an improved adherence to guidelines, pharmacotherapy, exacerbations, and self-management education. However, the DMP was not able to prevent an increase in emergency hospital admissions for the stable population in the cohort. Copyright © 2014 by Daedalus Enterprises.
Potential toxicity of phthalic acid esters plasticizer: interaction of dimethyl phthalate with trypsin in vitro.

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Wang, Yaping; Zhang, Guowen; Wang, Langhong

2015-01-14

Dimethyl phthalate (DMP) is widely used as a plasticizer in industrial processes and has been reported to possess potential toxicity to the human body. In this study, the interaction between DMP and trypsin in vitro was investigated. The results of fluorescence, UV–vis, circular dichroism, and Fourier transform infrared spectra along with cyclic voltammetric measurements indicated that the remarkable fluorescence quenching and conformational changes of trypsin resulted from the formation of a DMP–trypsin complex, which was driven mainly by hydrophobic interactions. The molecular docking and trypsin activity assay showed that DMP primarily interacted with the catalytic triad of trypsin and led to the inhibition of trypsin activity. The dimensions of the individual trypsin molecules were found to become larger after binding with DMP by atomic force microscopy imaging. This study offers a comprehensive picture of DMP–trypsin interaction, which is expected to provide insights into the toxicological effect of DMP.
Design for Play

DEFF Research Database (Denmark)

Feder, Karen

2017-01-01

Abstract The purpose of the new Design for Play initiative is to inspire and educate designers to design for the future of play. To create “play ambassadors” equipped with excellent tools, methods, approaches and mind-sets to design for the playful human being in an ever-changing world. To teach...... and inspire children to grow up to be creative designers of their own life and the world around them. The Design for Play research team will study the interplay between people, processes and products in design for play and support the development of playful designers, playful solutions and playful experiences...
Single-molecule spectroscopy of LHCSR1 protein dynamics identifies two distinct states responsible for multi-timescale photosynthetic photoprotection

Science.gov (United States)

Kondo, Toru; Pinnola, Alberta; Chen, Wei Jia; Dall'Osto, Luca; Bassi, Roberto; Schlau-Cohen, Gabriela S.

2017-08-01

In oxygenic photosynthesis, light harvesting is regulated to safely dissipate excess energy and prevent the formation of harmful photoproducts. Regulation is known to be necessary for fitness, but the molecular mechanisms are not understood. One challenge has been that ensemble experiments average over active and dissipative behaviours, preventing identification of distinct states. Here, we use single-molecule spectroscopy to uncover the photoprotective states and dynamics of the light-harvesting complex stress-related 1 (LHCSR1) protein, which is responsible for dissipation in green algae and moss. We discover the existence of two dissipative states. We find that one of these states is activated by pH and the other by carotenoid composition, and that distinct protein dynamics regulate these states. Together, these two states enable the organism to respond to two types of intermittency in solar intensity—step changes (clouds and shadows) and ramp changes (sunrise), respectively. Our findings reveal key control mechanisms underlying photoprotective dissipation, with implications for increasing biomass yields and developing robust solar energy devices.
Concurrent topological design of composite structures and materials containing multiple phases of distinct Poisson's ratios

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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.
Cannabinoid CB1 receptors in distinct circuits of the extended amygdala determine fear responsiveness to unpredictable threat.

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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.
Synthesis and characterization of a family of structurally characterized dysprosium alkoxides for improved fatigue-resistance characteristics of PDyZT thin films.

Science.gov (United States)

Boyle, Timothy J; Bunge, Scott D; Clem, Paul G; Richardson, Jacob; Dawley, Jeffrey T; Ottley, Leigh Anna M; Rodriguez, Mark A; Tuttle, Bruce A; Avilucea, Gabriel R; Tissot, Ralph G

2005-03-07

Using either an ammoniacal route, the reaction between DyCl3, Na0, and HOR in liquid ammonia, or preferentially reacting Dy(N(SiMe3)2)3 with HOR in a solvent, we isolated a family of dysprosium alkoxides as [Dy(mu-ONep)2(ONep)]4 (1), (ONep)2Dy[(mu3-ONep)(mu-ONep)Dy(ONep)(THF)]2(mu-ONep) (2), (ONep)2Dy[(mu3-ONep)(mu-ONep)Dy(ONep)(py)]2(mu-ONep) (3), [Dy3(mu3-OBut)2(mu-OBut3(OBut)4(HOBut)2] (4), [Dy3(mu3-OBut)2(mu-OBut)3(OBut)4(THF)2] (5), [Dy3(mu3-OBut)2(mu-OBut)3(OBut)4(py)2] (6), (DMP)Dy(mu-DMP)4[Dy(DMP)2(NH3)]2 (7), [Dy(eta6-DMP)(DMP)2]2 (8), Dy(DMP)3(THF)3 (9), Dy(DMP)3(py)3 (10), Dy(DIP)3(NH3)2 (11), [Dy(eta6-DIP)(DIP)2]2 (12), Dy(DIP)3(THF)2 (13), Dy(DIP)3(py)3 (14), Dy(DBP)3(NH3) (15), Dy(DBP)3 (16), Dy(DBP)3(THF) (17), Dy(DBP)3(py)2 (18), [Dy(mu-TPS)(TPS2]2 (19), Dy(TPS)3(THF)3 (20), and Dy(TPS)3(py)3 (21), where ONep = OCH2CMe3, OBut) = OCMe3, DMP = OC6H3(Me)(2)-2,6, DIP = OC6H3(CHMe2)(2)-2,6, DBP = OC6H3(CMe3)(2)-2,6, TPS = OSi(C6H5)3, tol = toluene, THF = tetrahydrofuran, and py = pyridine. We were not able to obtain X-ray quality crystals of compounds 2, 8, and 9. The structures observed and data collected for the Dy compounds are consistent with those reported for its other congeners. A number of these precursors were used as Dy dopants in Pb(Zr0.3Ti0.7)O3 (PZT 30/70) thin films, with compound 12 yielding the highest-quality films. The resulting Pb0.94Dy0.04(Zr0.3Ti0.7)O3 [PDyZT (4/30/70)] had similar properties to PZT (30/70), but showed substantial resistance to polarization reversal fatigue.
FairyPlay

DEFF Research Database (Denmark)

Toft, Herdis

2018-01-01

in a play culture where children recycle them in transmitted, transformed and transgressive modes. His fairy tales function as raw materials – trash – for play-production, and these contemporary children muddle, mingle, remix their formulas and elements with other materials and adjust them to a play context......Hans Christian Andersen is a cultural icon in the Danish community, and his fairy tales are canonized as treasured Danish cultural heritage. However, situated as they are today in a crosscultural mix between folklore, booklore and medialore, they also may be analysed as useful, treasured trash...... through improvisations. So they perform what we shall name FairyPlay - just like Hans Christian Andersen himself did. We show Hans Christian Andersen as an intimate connoisseur of play culture, a homo ludens, a trash-sculptor and a thing-finder, like Pippi Longstocking and like children in play. Examples...

Using the Ubiquitin-modified Proteome to Monitor Distinct and Spatially Restricted Protein Homeostasis Dysfunction.

Science.gov (United States)

Gendron, Joshua M; Webb, Kristofor; Yang, Bing; Rising, Lisa; Zuzow, Nathan; Bennett, Eric J

2016-08-01

Protein homeostasis dysfunction has been implicated in the development and progression of aging related human pathologies. There is a need for the establishment of quantitative methods to evaluate global protein homoeostasis function. As the ubiquitin (ub) proteasome system plays a key role in regulating protein homeostasis, we applied quantitative proteomic methods to evaluate the sensitivity of site-specific ubiquitylation events as markers for protein homeostasis dysfunction. Here, we demonstrate that the ub-modified proteome can exceed the sensitivity of engineered fluorescent reporters as a marker for proteasome dysfunction and can provide unique signatures for distinct proteome challenges which is not possible with engineered reporters. We demonstrate that combining ub-proteomics with subcellular fractionation can effectively separate degradative and regulatory ubiquitylation events on distinct protein populations. Using a recently developed potent inhibitor of the critical protein homeostasis factor p97/VCP, we demonstrate that distinct insults to protein homeostasis function can elicit robust and largely unique alterations to the ub-modified proteome. Taken together, we demonstrate that proteomic approaches to monitor the ub-modified proteome can be used to evaluate global protein homeostasis and can be used to monitor distinct functional outcomes for spatially separated protein populations. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
Play Therapy: Facilitative Use of Child's Play in Elementary School Counseling.

Science.gov (United States)

Landreth, Garry L.

1987-01-01

Reviews five major developments in play therapy: psychoanalysis, release therapy, relationship therapy, nondirective therapy, and play therapy in school settings. Suggests ways school counselors can use play therapy. Describes play therapy facilities, location selection, and play materials. Lists objectives of play therapy and how teachers can aid…
Autophagy plays an important role in protecting Pacific oysters from OsHV-1 and Vibrio aestuarianus infections.

Science.gov (United States)

Moreau, Pierrick; Moreau, Kevin; Segarra, Amélie; Tourbiez, Delphine; Travers, Marie-Agnès; Rubinsztein, David C; Renault, Tristan

2015-01-01

Recent mass mortality outbreaks around the world in Pacific oysters, Crassostrea gigas, have seriously affected the aquaculture economy. Although the causes for these mortality outbreaks appear complex, infectious agents are involved. Two pathogens are associated with mass mortality outbreaks, the virus ostreid herpesvirus 1 (OsHV-1) and the bacterium Vibrio aestuarianus. Here we describe the interactions between these 2 pathogens and autophagy, a conserved intracellular pathway playing a key role in innate immunity. We show for the first time that autophagy pathway is present and functional in Pacific oysters and plays an important role to protect animals from infections. This study contributes to better understand the innate immune system of Pacific oysters.
Mediatized play

DEFF Research Database (Denmark)

Johansen, Stine Liv

Children’s play must nowadays be understood as a mediatized field in society and culture. Media – understood in a very broad sense - holds severe explanatory power in describing and understanding the practice of play, since play happens both with, through and inspired by media of different sorts........ In this presentation the case of ‘playing soccer’ will be outlined through its different mediated manifestations, including soccer games and programs on TV, computer games, magazines, books, YouTube videos and soccer trading cards....
Interleukin-1 exerts distinct actions on different cell types of the brain in vitro

Directory of Open Access Journals (Sweden)

Ying An

2011-01-01

Full Text Available Ying An, Qun Chen, Ning QuanDepartment of Oral Biology, Ohio State University, Columbus, OH, USAAbstract: Interleukin-1 (IL-1 is a critical neuroinflammatory mediator in the central nervous system (CNS. In this study, we investigated the effect of IL-1 on inducing inflammation-related gene expression in three astrocyte, two microglial, and one brain endothelial cell line. Interleukin-1 beta (IL-1β is found to be produced by the two microglial cell lines constitutively, but these cells do not respond to IL-1β stimulation. The three astrocyte cell lines responded to IL-1ß stimulation by expressing MCP-1, CXCL-1, and VCAM-1, but different subtypes of astrocytes exhibited different expression profiles after IL-1β stimulation. The brain endothelial cells showed strongest response to IL-1β by producing MCP-1, CXCL-1, VCAM-1, ICAM-1, IL-6, and COX-2 mRNA. The induction of endothelial COX-2 mRNA is shown to be mediated by p38 MAPK pathway, whereas the induction of other genes is mediated by the NF-κB pathway. These results demonstrate that IL-1 exerts distinct cell type-specific action in CNS cells and suggest that IL-1-mediated neuroinflammation is the result of the summation of multiple responses from different cell types in the CNS to IL-1.Keywords: astrocyte, microglia, endothelial cells, signal transduction pathways, gene expression
Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

International Nuclear Information System (INIS)

Press, Joshua Z; Smith, Margaret; Spellman, Paul T; Wang, Yuker; Miller, Dianne M; Horsman, Doug; Faham, Malek; Gilks, C Blake; Gray, Joe; Huntsman, David G; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E; Blood, Katherine A

2008-01-01

Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumours were high-grade serous or undifferentiated type. None of the endometrioid (n = 5), clear cell (n = 4), or low grade serous (n = 2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumours with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways
Ovarian carcinomas with genetic and epigenetic BRCA1 loss have distinct molecular abnormalities

Energy Technology Data Exchange (ETDEWEB)

Gilks, C. Blake; Press, Joshua Z.; De Luca, Alessandro; Boyd, Niki; Young, Sean; Troussard, Armelle; Ridge, Yolanda; Kaurah, Pardeep; Kalloger, Steve E.; Blood, Katherine A.; Smith, Margaret; Spellman, Paul T.; Wang, Yuker; Miller, Dianne M.; Horsman, Doug; Faham, Malek; Gilks, C. Blake; Gray, Joe; Huntsman, David G.

2008-05-02

Subclassification of ovarian carcinomas can be used to guide treatment and determine prognosis. Germline and somatic mutations, loss of heterozygosity (LOH), and epigenetic events such as promoter hypermethylation can lead to decreased expression of BRCA1/2 in ovarian cancers. The mechanism of BRCA1/2 loss is a potential method of subclassifying high grade serous carcinomas. A consecutive series of 49 ovarian cancers was assessed for mutations status of BRCA1 and BRCA2, LOH at the BRCA1 and BRCA2 loci, methylation of the BRCA1 promoter, BRCA1, BRCA2, PTEN, and PIK3CA transcript levels, PIK3CA gene copy number, and BRCA1, p21, p53, and WT-1 immunohistochemistry. Eighteen (37%) of the ovarian carcinomas had germline or somatic BRCA1 mutations, or epigenetic loss of BRCA1. All of these tumors were high-grade serous or undifferentiated type. None of the endometrioid (n=5), clear cell (n=4), or low grade serous (n=2) carcinomas showed loss of BRCA1, whereas 47% of the 38 high-grade serous or undifferentiated carcinomas had loss of BRCA1. It was possible to distinguish high grade serous carcinomas with BRCA1 mutations from those with epigenetic BRCA1 loss: tumors with BRCA1 mutations typically had decreased PTEN mRNA levels while those with epigenetic loss of BRCA1 had copy number gain of PIK3CA. Overexpression of p53 with loss of p21 expression occurred significantly more frequently in high grade serous carcinomas with epigenetic loss of BRCA1, compared to high grade serous tumors without loss of BRCA1. High grade serous carcinomas can be subclassified into three groups: BRCA1 loss (genetic), BRCA1 loss (epigenetic), and no BRCA1 loss. Tumors in these groups show distinct molecular alterations involving the PI3K/AKT and p53 pathways.
Distinct Signaling Pathways After Higher or Lower Doses of Radiation in Three Closely Related Human Lymphoblast Cell Lines

International Nuclear Information System (INIS)

Lu, T.-P.; Lai, L.-C.; Lin, B.-I.; Chen, L.-H.; Hsiao, T.-H.; Liber, Howard L.; Cook, John A.; Mitchell, James B.; Tsai, M.-H.; Chuang, Eric Y.

2010-01-01

Purpose: The tumor suppressor p53 plays an essential role in cellular responses to DNA damage caused by ionizing radiation; therefore, this study aims to further explore the role that p53 plays at different doses of radiation. Materials and Methods: The global cellular responses to higher-dose (10 Gy) and lower dose (iso-survival dose, i.e., the respective D0 levels) radiation were analyzed using microarrays in three human lymphoblast cell lines with different p53 status: TK6 (wild-type p53), NH32 (p53-null), and WTK1 (mutant p53). Total RNAs were extracted from cells harvested at 0, 1, 3, 6, 9, and 24 h after higher and lower dose radiation exposures. Template-based clustering, hierarchical clustering, and principle component analysis were applied to examine the transcriptional profiles. Results: Differential expression profiles between 10 Gy and iso-survival radiation in cells with different p53 status were observed. Moreover, distinct gene expression patterns were exhibited among these three cells after 10 Gy radiation treatment, but similar transcriptional responses were observed in TK6 and NH32 cells treated with iso-survival radiation. Conclusions: After 10 Gy radiation exposure, the p53 signaling pathway played an important role in TK6, whereas the NFkB signaling pathway appeared to replace the role of p53 in WTK1. In contrast, after iso-survival radiation treatment, E2F4 seemed to play a dominant role independent of p53 status. This study dissected the impacts of p53, NFkB and E2F4 in response to higher or lower doses of γ-irradiation.
The level of detail required in a deformable phantom to accurately perform quality assurance of deformable image registration

Science.gov (United States)

Saenz, Daniel L.; Kim, Hojin; Chen, Josephine; Stathakis, Sotirios; Kirby, Neil

2016-09-01

The primary purpose of the study was to determine how detailed deformable image registration (DIR) phantoms need to adequately simulate human anatomy and accurately assess the quality of DIR algorithms. In particular, how many distinct tissues are required in a phantom to simulate complex human anatomy? Pelvis and head-and-neck patient CT images were used for this study as virtual phantoms. Two data sets from each site were analyzed. The virtual phantoms were warped to create two pairs consisting of undeformed and deformed images. Otsu’s method was employed to create additional segmented image pairs of n distinct soft tissue CT number ranges (fat, muscle, etc). A realistic noise image was added to each image. Deformations were applied in MIM Software (MIM) and Velocity deformable multi-pass (DMP) and compared with the known warping. Images with more simulated tissue levels exhibit more contrast, enabling more accurate results. Deformation error (magnitude of the vector difference between known and predicted deformation) was used as a metric to evaluate how many CT number gray levels are needed for a phantom to serve as a realistic patient proxy. Stabilization of the mean deformation error was reached by three soft tissue levels for Velocity DMP and MIM, though MIM exhibited a persisting difference in accuracy between the discrete images and the unprocessed image pair. A minimum detail of three levels allows a realistic patient proxy for use with Velocity and MIM deformation algorithms.
Disease management programs for patients with type 2 diabetes mellitus in Germany: a longitudinal population-based descriptive study.

Science.gov (United States)

Mehring, Michael; Donnachie, Ewan; Bonke, Florian Cornelius; Werner, Christoph; Schneider, Antonius

2017-01-01

The primary aim of the disease management program (DMP) for patients with diabetes mellitus type 2 is to improve the quality of health care and the treatment process. 12 years after its introduction in Germany, there is still no consensus as to whether DMP has been effective in reaching these goals. A retrospective longitudinal population-based study between 2004 and 2015 were conducted to evaluate the DMP for type 2 diabetes in Bavaria using routinely collected patient medical records hold from the National Association of Statutory Health Insurance Physicians of Bavaria. During the first 12 years of DMP, the number of participants increased continually to reach 580,222 in 2015. The proportion of participants older than 70 years increased during the observation from 41.6 to 51.1%. The percentage of smokers increased slightly from 9 to 11%. Similarly, the distribution of body mass index remained constant with approximately 50% of patients having a body mass index >30 kg/m 2 . Control of HbA1c was without an appreciable change over the course, with between 8.3 and 9.4% of all patients with uncontrolled values higher than 8.5%. Prescription of metformin increased from 40.5% in 2004 to 54.1% in 2015. Among patients receiving insulin, the proportion receiving a combined therapy with metformin increased from 28.4% in 2004 to 50.8% in 2015. In contrast, the percentage with insulin monotherapy decreased from 55.4 to 33.7%. The proportion of patients with a diabetic education increased within the course from 12.8 to 29.3%. Data from the German DMP for type 2 diabetes demonstrates an improvement in the quality of care with respect to pharmacotherapy and patient education and therefore to an improved adherence to guidelines. However, no appreciable improvement was observed with regard to smoking status, obesity or HbA1c control.
Disease management programs for patients with asthma in Germany: a longitudinal population-based study.

Science.gov (United States)

Mehring, Michael; Donnachie, Ewan; Mutschler, Robert; Hofmann, Frank; Keller, Manfred; Schneider, Antonius

2013-07-01

The primary aim of the disease management program (DMP) for patients with asthma is to improve health outcomes and to reduce costs. Five years after its introduction in Germany, no consensus has yet been reached as to whether DMP has been effective in reaching these goals. To evaluate the DMP for asthma in Bavaria using routinely collected subject medical records. A longitudinal population-based study encompassing over 100,000 DMP participants between 2006 (when the program began) and 2010. The prescription rate of oral corticosteroids dropped from 15.7% in 2006 to 13.6% in 2007, and again from 7.5% in 2008 to 5.9% in 2010 (P management education increased from 4.4% to 23.4% (P management. The proportion of subjects requiring hospitalization decreased. Our results suggest that the German DMP for asthma has been effective in enhancing the quality of care in regard to an improved symptom frequency, adherence to guidelines, pharmacotherapy, and hospitalization.
Treatment of phthalic acid esters by electrocoagulation with stainless steel electrodes using dimethyl phthalate as a model compound.

Science.gov (United States)

Kabdaşli, Işik; Keleş, Asuman; Olmez-Hanci, Tuğba; Tünay, Olcay; Arslan-Alaton, Idil

2009-11-15

In this study, treatment of phthalates by electrocoagulation employing stainless steel electrodes was investigated using dimethyl phthalate (DMP) as a model compound. DMP was completely destructed within 30 min up to the high initial concentration of 100mg/L while total mineralization was also obtained within a couple of hours. The applied current density of 22.5 mA/cm(2) and electrolyte (NaCl) concentrations varying between 1000 and 1500 mg/L as chloride resulted in the highest treatment performance. The initial solution pH (2-6) had practically no effect on the process efficiency. Desorption experiments and the reaction rates obtained for DMP, COD and TOC abatements appeared to be a strong evidence of an oxidative removal mechanism. DMP removal fitted first order kinetics. COD and TOC removals began after the total DMP removal and also fitted first order kinetics. Activated sludge inhibition experiments revealed that toxicity could be significantly reduced by electrocoagulation application.
The RabGAP TBC1D1 plays a central role in exercise-regulated glucose metabolism in skeletal muscle

DEFF Research Database (Denmark)

Stöckli, Jacqueline; Meoli, Christopher C; Hoffman, Nolan J

2015-01-01

Insulin and exercise stimulate glucose uptake into skeletal muscle via different pathways. Both stimuli converge on the translocation of the glucose transporter GLUT4 from intracellular vesicles to the cell surface. Two Rab guanosine triphosphatases-activating proteins (GAPs) have been implicated...... weight, insulin action, and exercise. TBC1D1(-/-) mice showed normal glucose and insulin tolerance, with no difference in body weight compared with wild-type littermates. GLUT4 protein levels were reduced by ∼40% in white TBC1D1(-/-) muscle, and TBC1D1(-/-) mice showed impaired exercise endurance...... together with impaired exercise-mediated 2-deoxyglucose uptake into white but not red muscles. These findings indicate that the RabGAP TBC1D1 plays a key role in regulating GLUT4 protein levels and in exercise-mediated glucose uptake in nonoxidative muscle fibers....
Play at Work

DEFF Research Database (Denmark)

Meier Sørensen, Bent; Spoelstra, Sverre

2012-01-01

The interest in organizational play is growing, both in popular business discourse and organization studies. As the presumption that play is dysfunctional for organizations is increasingly discarded, the existing positions may be divided into two camps; one proposes ‘serious play’ as an engine fo...... workplaces engage in play: play as a (serious) continuation of work, play as a (critical) intervention into work and play as an (uninvited) usurpation of work....
The role of play themes in non-directive play therapy.

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Ryan, Virginia; Edge, Andrew

2012-07-01

Describing the processes underlying play therapy is important for evidence based practice in child therapy. Employing play themes to describe children's play session contents is in widespread use by practitioners, but an adequate classification of these themes for non-directive play therapy practice has not yet been established. This article sets out to fill this gap by first describing how themes can be distinguished and distilled from the contents of play therapy contents. Second, a classification of main themes and sub-themes with exemplars to illustrate these concepts which is compatible with non-directive play therapy practice is set out. Finally a pilot project with experienced play therapists to test this classification in practice is suggested, along with the research questions that will need to be investigated in the shorter and longer terms.
Surface modification of nanoparticles enables selective evasion of phagocytic clearance by distinct macrophage phenotypes

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Qie, Yaqing; Yuan, Hengfeng; von Roemeling, Christina A.; Chen, Yuanxin; Liu, Xiujie; Shih, Kevin D.; Knight, Joshua A.; Tun, Han W.; Wharen, Robert E.; Jiang, Wen; Kim, Betty Y. S.

2016-05-01

Nanomedicine is a burgeoning industry but an understanding of the interaction of nanomaterials with the immune system is critical for clinical translation. Macrophages play a fundamental role in the immune system by engulfing foreign particulates such as nanoparticles. When activated, macrophages form distinct phenotypic populations with unique immune functions, however the mechanism by which these polarized macrophages react to nanoparticles is unclear. Furthermore, strategies to selectively evade activated macrophage subpopulations are lacking. Here we demonstrate that stimulated macrophages possess higher phagocytic activities and that classically activated (M1) macrophages exhibit greater phagocytic capacity than alternatively activated (M2) macrophages. We show that modification of nanoparticles with polyethylene-glycol results in decreased clearance by all macrophage phenotypes, but importantly, coating nanoparticles with CD47 preferentially lowers phagocytic activity by the M1 phenotype. These results suggest that bio-inspired nanoparticle surface design may enable evasion of specific components of the immune system and provide a rational approach for developing immune tolerant nanomedicines.
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

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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
Activity-based anorexia activates nesfatin-1 immunoreactive neurons in distinct brain nuclei of female rats.

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Scharner, Sophie; Prinz, Philip; Goebel-Stengel, Miriam; Lommel, Reinhard; Kobelt, Peter; Hofmann, Tobias; Rose, Matthias; Stengel, Andreas

2017-12-15

Activity-based anorexia (ABA) is an established animal model for the eating disorder anorexia nervosa (AN). The pathophysiology of AN and the involvement of food intake-regulatory peptides is still poorly understood. Nesfatin-1, an anorexigenic peptide also involved in the mediation of stress, anxiety and depression might be a likely candidate involved in the pathogenesis of AN. Therefore, activation of nesfatin-1 immunoreactive (ir) brain nuclei was investigated under conditions of ABA. Female Sprague-Dawley rats were used and divided into four groups (n=6/group): activity-based anorexia (ABA), restricted feeding (RF), activity (AC) and ad libitum fed (AL). After the 21-day experimental period and development of ABA, brains were processed for c-Fos/nesfatin-1 double labeling immunohistochemistry. ABA increased the number of nesfatin-1 immunopositive neurons in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, locus coeruleus and in the rostral part of the nucleus of the solitary tract compared to AL and AC groups (p0.05). Moreover, we observed significantly more c-Fos and nesfatin-1 ir double-labeled cells in ABA rats compared to RF, AL and AC in the supraoptic nucleus (p<0.05) and compared to AL and AC in the paraventricular nucleus, arcuate nucleus, dorsomedial hypothalamic nucleus, dorsal raphe nucleus and the rostral raphe pallidus (p<0.05). Since nesfatin-1 plays a role in the inhibition of food intake and the response to stress, we hypothesize that the observed changes of brain nesfatin-1 might play a role in the pathophysiology and symptomatology under conditions of ABA and potentially also in patients with AN. Copyright © 2017 Elsevier B.V. All rights reserved.
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.
"I'm Just Playing iPad": Comparing Prekindergarteners' and Preservice Teachers' Social Interactions While Using Tablets for Learning

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Moore, Holly Carrell; Adair, Jennifer Keys

2015-01-01

In this article we share descriptive findings from two qualitative, grounded theory (Glaser, 1978, 1992, 1998) studies on how two distinct groups of learners--prekindergarteners and preservice teachers in early childhood education coursework--used touch-screen tablets in their playful, discovery-based learning processes. We found similarities…

Imagination, Playfulness, and Creativity in Children's Play with Different Toys

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Mo????ller, Signe?? Juhl?

2015-01-01

Based on a four-month experimental study of preschool children's play with creative-construction and social-fantasy toys, the author examines the in?uence of both types of toys on the play of preschool children. Her comparative analysis considers the impact of transformative play on the development of imagination during play activities and…
German diabetes disease management programs are appropriate for restructuring care according to the chronic care model: an evaluation with the patient assessment of chronic illness care instrument.

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Szecsenyi, Joachim; Rosemann, Thomas; Joos, Stefanie; Peters-Klimm, Frank; Miksch, Antje

2008-06-01

With the introduction of diabetes disease management programs (DMPs) in Germany, there is a necessity to evaluate whether patients receive care that is congruent to the Chronic Care Model (CCM) and evidence-based behavioral counseling. We examined differences as perceived and experienced by patients with type 2 diabetes between those enrolled in a DMP compared with patients receiving usual care in two federal states of Germany. A random, heterogeneous sample of 3,546 patients (59.3% female) received a mailed questionnaire from their regional health fund, including the German version of the Patient Assessment of Chonic Illness Care (PACIC) instrument, which had additional items for behavioral advice (5A). Two weeks later, a general reminder was sent out. A total of 1,532 questionnaires were returned (response rate 42.2%), and valid data could be obtained for 1,399 patients. Mean age of responders was 70.3 years, of which 53.6% were female. Overall, patients enrolled in a DMP scored significantly higher (3.21 of a possible 5) than patients not enrolled in a DMP (2.86) (P < 0.001). Significant differences in the same direction were found on all five subscales of the PACIC. For the 5A scales, similar differences were found for all five subscales plus the sum score (P < 0.001; mean for DMP = 3.08, mean for non-DMP = 2.78). DMPs, as currently established in primary care in Germany, may impact provided care significantly. The changes in daily practice that have been induced by the DMPs are recognized by patients as care that is more structured and that to a larger extent reflects the core elements of the CCM and evidence-based counseling compared with usual care.
Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus.

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Hernández, Vivian M; Hegeman, Daniel J; Cui, Qiaoling; Kelver, Daniel A; Fiske, Michael P; Glajch, Kelly E; Pitt, Jason E; Huang, Tina Y; Justice, Nicholas J; Chan, C Savio

2015-08-26

Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping expression of the
Parvalbumin+ Neurons and Npas1+ Neurons Are Distinct Neuron Classes in the Mouse External Globus Pallidus

Science.gov (United States)

Hernández, Vivian M.; Hegeman, Daniel J.; Cui, Qiaoling; Kelver, Daniel A.; Fiske, Michael P.; Glajch, Kelly E.; Pitt, Jason E.; Huang, Tina Y.; Justice, Nicholas J.

2015-01-01

Compelling evidence suggests that pathological activity of the external globus pallidus (GPe), a nucleus in the basal ganglia, contributes to the motor symptoms of a variety of movement disorders such as Parkinson's disease. Recent studies have challenged the idea that the GPe comprises a single, homogenous population of neurons that serves as a simple relay in the indirect pathway. However, we still lack a full understanding of the diversity of the neurons that make up the GPe. Specifically, a more precise classification scheme is needed to better describe the fundamental biology and function of different GPe neuron classes. To this end, we generated a novel multicistronic BAC (bacterial artificial chromosome) transgenic mouse line under the regulatory elements of the Npas1 gene. Using a combinatorial transgenic and immunohistochemical approach, we discovered that parvalbumin-expressing neurons and Npas1-expressing neurons in the GPe represent two nonoverlapping cell classes, amounting to 55% and 27% of the total GPe neuron population, respectively. These two genetically identified cell classes projected primarily to the subthalamic nucleus and to the striatum, respectively. Additionally, parvalbumin-expressing neurons and Npas1-expressing neurons were distinct in their autonomous and driven firing characteristics, their expression of intrinsic ion conductances, and their responsiveness to chronic 6-hydroxydopamine lesion. In summary, our data argue that parvalbumin-expressing neurons and Npas1-expressing neurons are two distinct functional classes of GPe neurons. This work revises our understanding of the GPe, and provides the foundation for future studies of its function and dysfunction. SIGNIFICANCE STATEMENT Until recently, the heterogeneity of the constituent neurons within the external globus pallidus (GPe) was not fully appreciated. We addressed this knowledge gap by discovering two principal GPe neuron classes, which were identified by their nonoverlapping
Ultrafast dynamics of two copper bis-phenanthroline complexes measured by x-ray transient absorption spectroscopy

DEFF Research Database (Denmark)

Kelley, Matthew S.; Shelby, Megan L.; Mara, Michael W.

2017-01-01

have the general formula [Cu(I)(R)2]+, where R = 2,9-dimethyl-1,10-phenanthroline (dmp) and 2,9-diphenyl-1,10-phenanthroline disulfonic acid disodium salt (dpps). [Cu(I)(dmp)2]+ has methyl groups at the 2,9 positions of phenanthroline (phen) and adopts a pseudo-tetrahedral geometry. In contrast, [Cu......(I)(dpps)2]+ possesses two bulky phenyl-sulfonate groups attached to each phen ligand that force the molecule to adopt a flattened tetrahedral geometry in the ground state. Previously, optical transient absorption (OTA) and synchrotron based XTA experiments with 100 ps time resolution have been employed...
Highly Active and Isospecific Styrene Polymerization Catalyzed by Zirconium Complexes Bearing Aryl-substituted [OSSO]-Type Bis(phenolate Ligands

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Norio Nakata

2016-01-01

Full Text Available [OSSO]-type dibenzyl zirconium(IV complexes 9 and 10 possessing aryl substituents ortho to the phenoxide moieties (ortho substituents, phenyl and 2,6-dimethylphenyl (Dmp were synthesized and characterized. Upon activation with dMAO (dried methylaluminoxane, complex 9 was found to promote highly isospecific styrene polymerizations ([mm] = 97.5%–99% with high molecular weights Mw up to 181,000 g·mmol−1. When the Dmp-substituted pre-catalyst 10/dMAO system was used, the highest activity, over 7700 g·mmol(10−1·h−1, was recorded involving the formation of precisely isospecific polystyrenes of [mm] more than 99%.
Supported Nanosized α-FeOOH Improves Efficiency of Photoelectro-Fenton Process with Reaction-Controlled pH Adjustment for Sustainable Water Treatment

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Chuan Wang

2012-01-01

Full Text Available The overall photoelectro-Fenton (PE-Fenton process for water treatment with neutral initial pH includes three steps of pH reduction, PE-Fenton reaction, and pH elevation. Reaction-controlled pH adjustment (RCpA, which utilizes the intrinsic electrochemical reactions instead of chemical addition, has been employed to lower the pH, maintain the lowered pH for the Fenton reaction, and recover the pH for final effluent discharge. This study demonstrated that the overall efficiency of this sustainable PE-Fenton process was improved by rapidly recycling the iron substance. Nanosized iron oxide was prepared and employed to ensure such rapid recycling. SEM and XRD results showed that the as-prepared iron oxide was α-FeOOH with 20 nm in size. The experimental results of dimethyl phthalate (DMP degradation showed that diatomite-supported α-FeOOH (N-α-FeOOH/diatomite could efficiently reduce the DMP concentration and total organic carbon. Furthermore, compared with Fe3+, the N-α-FeOOH/diatomite saved 160 min for iron settlement at 20 mg L−1 DMP concentration. Also, with the increment in the initial DMP concentration, extra energy consumed by the individual step of PE-Fenton reaction using the N-α-FeOOH/diatomite became negligible compared with that using free iron ions with the increment in the initial DMP concentration. This development is expected to be a major step of the PE-Fenton process with RCpA towards actual water treatment.
Playful biometrics: controversial technology through the lens of play.

Science.gov (United States)

Ellerbrok, Ariane

2011-01-01

This article considers the role of play in the context of technological emergence and expansion, particularly as it relates to recently emerging surveillance technologies. As a case study, I consider the trajectory of automated face recognition—a biometric technology of numerous applications, from its more controversial manifestations under the rubric of national security to a clearly emerging orientation toward play. This shift toward “playful” biometrics—or from a technology traditionally coded as “hard” to one now increasingly coded as “soft”—is critical insofar as it renders problematic the traditional modes of critique that have, up until this point, challenged the expansion of biometric systems into increasingly ubiquitous realms of everyday life. In response to this dynamic, I propose theorizing the expansion of face recognition specifically in relation to “play,” a step that allows us to broaden the critical space around newly emerging playful biometrics, as well as playful surveillance more generally. In addition, play may also have relevance for theorizing other forms of controversial technology, particularly given its potential role in processes of obfuscation, normalization, and marginalization.
Distinct signalling properties of insulin receptor substrate (IRS)-1 and IRS-2 in mediating insulin/IGF-1 action.

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Rabiee, Atefeh; Krüger, Marcus; Ardenkjær-Larsen, Jacob; Kahn, C Ronald; Emanuelli, Brice

2018-07-01

Insulin/IGF-1 action is driven by a complex and highly integrated signalling network. Loss-of-function studies indicate that the major insulin/IGF-1 receptor substrate (IRS) proteins, IRS-1 and IRS-2, mediate different biological functions in vitro and in vivo, suggesting specific signalling properties despite their high degree of homology. To identify mechanisms contributing to the differential signalling properties of IRS-1 and IRS-2 in the mediation of insulin/IGF-1 action, we performed comprehensive mass spectrometry (MS)-based phosphoproteomic profiling of brown preadipocytes from wild type, IRS-1 -/- and IRS-2 -/- mice in the basal and IGF-1-stimulated states. We applied stable isotope labeling by amino acids in cell culture (SILAC) for the accurate quantitation of changes in protein phosphorylation. We found ~10% of the 6262 unique phosphorylation sites detected to be regulated by IGF-1. These regulated sites included previously reported substrates of the insulin/IGF-1 signalling pathway, as well as novel substrates including Nuclear Factor I X and Semaphorin-4B. In silico prediction suggests the protein kinase B (PKB), protein kinase C (PKC), and cyclin-dependent kinase (CDK) as the main mediators of these phosphorylation events. Importantly, we found preferential phosphorylation patterns depending on the presence of either IRS-1 or IRS-2, which was associated with specific sets of kinases involved in signal transduction downstream of these substrates such as PDHK1, MAPK3, and PKD1 for IRS-1, and PIN1 and PKC beta for IRS-2. Overall, by generating a comprehensive phosphoproteomic profile from brown preadipocyte cells in response to IGF-1 stimulation, we reveal both common and distinct insulin/IGF-1 signalling events mediated by specific IRS proteins. Copyright © 2018 Elsevier Inc. All rights reserved.
Are empathy and concern psychologically distinct?

Science.gov (United States)

Jordan, Matthew R; Amir, Dorsa; Bloom, Paul

2016-12-01

Researchers have long been interested in the relationship between feeling what you believe others feel-often described as empathy-and caring about the welfare of others-often described as compassion or concern. Many propose that empathy is a prerequisite for concern and is therefore the ultimate motivator of prosocial actions. To assess this hypothesis, the authors developed the Empathy Index, which consists of 2 novel scales, and explored their relationship to a measure of concern as well as to measures of cooperative and altruistic behavior. A series of factor analyses reveal that empathy and concern consistently load on different factors. Furthermore, they show that empathy and concern motivate different behaviors: concern for others is a uniquely positive predictor of prosocial action whereas empathy is either not predictive or negatively predictive of prosocial actions. Together these studies suggest that empathy and concern are psychologically distinct and empathy plays a more limited role in our moral lives than many believe. (PsycINFO Database Record (c) 2016 APA, all rights reserved).
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.
Distinct distribution of specific members of protein 4.1 genefamily in the mouse nephron

Energy Technology Data Exchange (ETDEWEB)

Ramez, Mohamed; Blot-Chabaud, Marcel; Cluzeaud, Francoise; Chanan, Sumita; Patterson, Michael; Walensky, Loren D.; Marfatia, Shirin; Baines, Anthony J.; Chasis, Joel A.; Conboy, John G.; Mohandas, Narla; Gascard, Philippe

2002-12-11

Background: Protein 4.1 is an adapter protein which linksthe actin cytoskeleton to various transmembrane proteins. 4.1 proteinsare encoded by four homologous genes, 4.1R, 4.1G, 4.1N, and 4.1B, whichundergo complex alternative splicing. Here we performed a detailedcharacterization of the expression of specific 4.1 proteins in the mousenephron. Methods: Distribution of renal 4.1 proteins was investigated bystaining of paraformaldehyde fixed mouse kidney sections with antibodieshighly specific for each 4.1 protein. Major 4.1 splice forms, amplifiedfrom mouse kidney marathon cDNA, were expressed in transfected COS-7cells in order to assign species of known exon composition to proteinsdetected in kidney. Results: A 105kDa4.1R splice form, initiating atATG-2 translation initiation site and lacking exon 16, but including exon17B, was restricted to thick ascending limb of Henle's loop. A 95kDa 4.1Nspliceform,lacking exons 15 and 17D, was expressed in either descendingor ascending thin limb of Henle'sloop, distal convoluted tubule and allregions of the collecting duct system. A major 108kDa 4.1B spliceform,initiating at a newly characterized ATG translation initiation site, andlacking exons 15, 17B, and 21, was present only in Bowman's capsule andproximal convoluted tubule (PCT). There was no expression of 4.1G inkidney. Conclusion: Distinct distribution of 4.1 proteins along thenephron suggests their involvement in targeting of selected transmembraneproteins in kidney epithelium andtherefore in regulation of specifickidney functions.
Lipoxin A4 stable analogs reduce allergic airway responses via mechanisms distinct from CysLT1 receptor antagonism.

Science.gov (United States)

Levy, Bruce D; Lukacs, Nicholas W; Berlin, Aaron A; Schmidt, Birgitta; Guilford, William J; Serhan, Charles N; Parkinson, John F

2007-12-01

Cellular recruitment during inflammatory/immune responses is tightly regulated. The ability to dampen inflammation is imperative for prevention of chronic immune responses, as in asthma. Here we investigated the ability of lipoxin A4 (LXA4) stable analogs to regulate airway responses in two allergen-driven models of inflammation. A 15-epi-LXA4 analog (ATLa) and a 3-oxa-15-epi-LXA4 analog (ZK-994) prevented excessive eosinophil and T lymphocyte accumulation and activation after mice were sensitized and aerosol-challenged with ovalbumin. At 50% and to a greater extent than equivalent doses of the CysLT1 receptor antagonist montelukast. Distinct from montelukast, ATLa treatment led to marked reductions in cysteinyl leukotrienes, interleukin-4 (IL-4), and IL-10, and both ATLa and ZK-994 inhibited levels of IL-13. In cockroach allergen-induced airway responses, both intraperitoneal and oral administration of ZK-994 significantly reduced parameters of airway inflammation and hyper-responsiveness in a dose-dependent manner. ZK-994 also significantly changed the balance of Th1/Th2-specific cytokine levels. Thus, the ATLa/LXA4 analog actions are distinct from CysLT1 antagonism and potently block both allergic airway inflammation and hyper-reactivity. Moreover, these results demonstrate these analogs' therapeutic potential as new agonists for the resolution of inflammation.
Different HLA-DRB1 allele distributions in distinct clinical subgroups of sarcoidosis patients

Directory of Open Access Journals (Sweden)

Nisell Magnus

2010-02-01

Full Text Available Abstract Background A strong genetic influence by the MHC class II region has been reported in sarcoidosis, however in many studies with different results. This may possibly be caused by actual differences between distinct ethnic groups, too small sample sizes, or because of lack of accurate clinical subgrouping. Subjects and methods In this study we HLA typed a large patient population (n = 754 recruited from one single centre. Patients were sub-grouped into those with Löfgren's syndrome (LS (n = 302 and those without (non-Löfgren's (n = 452, and the majority of them were clinically classified into those with recovery within two years (resolving and those with signs of disease for more than two years (non-resolving. PCR was used for determination of HLA-DRB1 alleles. Swedish healthy blood donors (n = 1366 served as controls. Results There was a dramatic difference in the distribution of HLA alleles in LS compared to non-LS patients (p = 4 × 10-36. Most notably, DRB1*01, DRB1*03 and DRB1*14, clearly differed in LS and non-LS patients. In relation to disease course, DRB1*07, DRB1*14 and DRB1*15 generally associated with, while DRB1*01 and DRB1*03 protected against, a non-resolving disease. Interestingly, the clinical influence of DRB1*03 (good prognosis dominated over that of DRB1*15 (bad prognosis. Conclusions We found several significant differences between LS and non-LS patients and we therefore suggest that genetic association studies in sarcoidosis should include a careful clinical characterisation and sub-grouping of patients, in order to reveal true genetic associations. This may be particularly accurate to do in the heterogeneous non-LS group of patients.
Autoshaping with common and distinctive stimulus elements, compact and dispersed arrays1

Science.gov (United States)

Sperling, Sally E.; Perkins, Mark E.

1979-01-01

Four groups of pigeons were trained with a standard autoshaping procedure in which a brief fixed-duration interval always followed by a grain delivery alternated with a longer variable-duration interval never associated with grain delivery. One of two stimuli was always presented during each interval. One of them contained three black dots and a black star on a green background; the other contained four black dots on a green background. The four elements of each stimulus were arranged in a more compact array for two groups and in a more dispersed array for the other two groups. Which of the two stimuli preceded grain delivery was counterbalanced within each pair of groups. The speed of occurrence of the first autoshaped peck was not affected by whether the stimulus containing the distinctive star element preceded grain delivery, but autoshaping was faster when the stimulus arrays were compact than when they were dispersed. During 560 response-independent training trials that followed the first autoshaped peck, this pattern reversed; both discriminative control over responding and the relative frequency of pecking the stimulus that preceded grain delivery were greater for the two groups where this stimulus contained the discriminative element than for the two groups where it contained only common elements. During subsequent testing with stimuli containing only a single element each, the distinctive feature was responded to proportionately more often by the two groups for which it had been an element of the stimulus preceding grain delivery than by the two groups for which it had been an element of the stimulus complex that never was associated with grain delivery. These data add further support to the hypothesis that the initial occurrence of autoshaped responding and its subsequent maintenance are not affected by the same variables. They also suggest that automaintenance is as sensitive as response-dependent training to the presence or absence of a distinctive
Internalization of interleukin 1 (IL 1) correlates with IL 1-induced IL 2 receptor expression and IL 2 secretion of EL4 thymoma cells

OpenAIRE

Von Hoegen, I.; Falk, Werner; Kojouharoff, G.; Krammer, P. H.

1989-01-01

The cytokine interleukin 1 (IL 1) plays an important role in the induction of IL 2 secretion and high-affinity IL 2 receptor (IL 2R) expression by T cells. The events that follow binding of IL 1 to IL 1R, however, are still unknown. In this study we describe two variants of the murine thymoma EL4 (5D3 and D6/76) that express comparable numbers of cell surface IL 1 receptors and bind IL 1 with the same affinity, but show distinct IL 1-dependent IL 2 secretion and IL 2R expression. In the prese...
Distinct genetic alterations in colorectal cancer.

Directory of Open Access Journals (Sweden)

Hassan Ashktorab

Full Text Available BACKGROUND: Colon cancer (CRC development often includes chromosomal instability (CIN leading to amplifications and deletions of large DNA segments. Epidemiological, clinical, and cytogenetic studies showed that there are considerable differences between CRC tumors from African Americans (AAs and Caucasian patients. In this study, we determined genomic copy number aberrations in sporadic CRC tumors from AAs, in order to investigate possible explanations for the observed disparities. METHODOLOGY/PRINCIPAL FINDINGS: We applied genome-wide array comparative genome hybridization (aCGH using a 105k chip to identify copy number aberrations in samples from 15 AAs. In addition, we did a population comparative analysis with aCGH data in Caucasians as well as with a widely publicized list of colon cancer genes (CAN genes. There was an average of 20 aberrations per patient with more amplifications than deletions. Analysis of DNA copy number of frequently altered chromosomes revealed that deletions occurred primarily in chromosomes 4, 8 and 18. Chromosomal duplications occurred in more than 50% of cases on chromosomes 7, 8, 13, 20 and X. The CIN profile showed some differences when compared to Caucasian alterations. CONCLUSIONS/SIGNIFICANCE: Chromosome X amplification in male patients and chromosomes 4, 8 and 18 deletions were prominent aberrations in AAs. Some CAN genes were altered at high frequencies in AAs with EXOC4, EPHB6, GNAS, MLL3 and TBX22 as the most frequently deleted genes and HAPLN1, ADAM29, SMAD2 and SMAD4 as the most frequently amplified genes. The observed CIN may play a distinctive role in CRC in AAs.
Teachers and Children Playing with Factorization

DEFF Research Database (Denmark)

Valente, Andrea; Marchetti, Emanuela

2013-01-01

adventure game and a logic puzzle game. The game design was informed by the results obtained in a 1 year field study exploring and assessing techniques for transposing dynamic and complex domain-specific knowledge into games. Empirical results suggest that children may prefer different forms of play, mainly...... two were individuated: a competitive form of play, which was mapped into the 2D adventure game, and a designerly-creative play, which was mapped into a puzzle game (Valente and Marchetti 2011). This paper presents empirical results of a qualitative test, conducted with Danish primary school students......Teachers and children playing with factorization: putting Prime Slaughter to the test. Last year the prime slaughter game was designed and implemented, to enable primary and early secondary school students to play with prime numbers and factorization, within two different game contexts: a 2D...
The human LIS1 is downregulated in hepatocellular carcinoma and plays a tumor suppressor function

International Nuclear Information System (INIS)

Xing, Zhen; Tang, Xin; Gao, Yuan; Da, Liang; Song, Hai; Wang, Suiquan; Tiollais, Pierre; Li, Tsaiping; Zhao, Mujun

2011-01-01

Highlights: → LIS1 mRNA and protein levels are decreased in 70% HCC tissues. → Downregulation of LIS1 expression induces oncogenic transformation of QSG7701 and NIH3T3 cells in vitro and in vivo. → LIS1 downregulation leads to mitotic errors including spindle and chromosome defects. → Ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. → Our results suggest that LIS1 plays a potential tumor suppressor role in the development and progression of HCC. -- Abstract: The human lissencephaly-1 gene (LIS1) is a disease gene responsible for Miller-Dieker lissencephaly syndrome (MDL). LIS1 gene is located in the region of chromosome 17p13.3 that is frequency deleted in MDL patients and in human liver cancer cells. However, the expression and significance of LIS1 in liver cancer remain unknown. Here, we investigated the expression of LIS1 in hepatocellular carcinoma (HCC) tissues by real-time PCR, Western blot, and immunohistochemistry. The results indicated that the mRNA and protein levels of LIS1 were downregulated in about 70% of HCC tissues, and this downregulation was significantly associated with tumor progression. Functional studies showed that the reduction of LIS1 expression in the normal human liver cell line QSG7701 or the mouse fibroblast cell line NIH3T3 by shRNA resulted in colony formation in soft agar and xenograft tumor formation in nude mice, demonstrating that a decrease in the LIS1 level can promote the oncogenic transformation of cells. We also observed that the phenotypes of LIS1-knockdown cells displayed various defective mitotic structures, suggesting that the mechanism by which reduced LIS1 levels results in tumorigenesis is associated with its role in mitosis. Furthermore, we demonstrated that ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. Our results suggest that LIS1 plays a potential tumor suppressor role in the development and
The human LIS1 is downregulated in hepatocellular carcinoma and plays a tumor suppressor function

Energy Technology Data Exchange (ETDEWEB)

Xing, Zhen; Tang, Xin; Gao, Yuan; Da, Liang; Song, Hai; Wang, Suiquan [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Tiollais, Pierre [Unite' d' Organisation Nucleaire et Oncogenese, INSERM U.579, Institut Pasteur, Paris (France); Li, Tsaiping [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China); Zhao, Mujun, E-mail: mjzhao@sibs.ac.cn [State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai (China)

2011-06-03

Highlights: {yields} LIS1 mRNA and protein levels are decreased in 70% HCC tissues. {yields} Downregulation of LIS1 expression induces oncogenic transformation of QSG7701 and NIH3T3 cells in vitro and in vivo. {yields} LIS1 downregulation leads to mitotic errors including spindle and chromosome defects. {yields} Ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. {yields} Our results suggest that LIS1 plays a potential tumor suppressor role in the development and progression of HCC. -- Abstract: The human lissencephaly-1 gene (LIS1) is a disease gene responsible for Miller-Dieker lissencephaly syndrome (MDL). LIS1 gene is located in the region of chromosome 17p13.3 that is frequency deleted in MDL patients and in human liver cancer cells. However, the expression and significance of LIS1 in liver cancer remain unknown. Here, we investigated the expression of LIS1 in hepatocellular carcinoma (HCC) tissues by real-time PCR, Western blot, and immunohistochemistry. The results indicated that the mRNA and protein levels of LIS1 were downregulated in about 70% of HCC tissues, and this downregulation was significantly associated with tumor progression. Functional studies showed that the reduction of LIS1 expression in the normal human liver cell line QSG7701 or the mouse fibroblast cell line NIH3T3 by shRNA resulted in colony formation in soft agar and xenograft tumor formation in nude mice, demonstrating that a decrease in the LIS1 level can promote the oncogenic transformation of cells. We also observed that the phenotypes of LIS1-knockdown cells displayed various defective mitotic structures, suggesting that the mechanism by which reduced LIS1 levels results in tumorigenesis is associated with its role in mitosis. Furthermore, we demonstrated that ectopic expression of LIS1 could significantly inhibit HCC cell proliferation and colony formation. Our results suggest that LIS1 plays a potential tumor suppressor role in the

The solvent effects on dimethyl phthalate investigated by FTIR characterization, solvent parameter correlation and DFT computation

Science.gov (United States)

Chen, Yi; Zhang, Hui; Zhou, Wenzhao; Deng, Chao; Liao, Jian

2018-06-01

This study set out with the aim of investigating the solvent effects on dimethyl phthalate (DMP) using FTIR characterization, solvent parameter correlation and DFT calculation. DMP exposed to 17 organic solvents manifested varying shift in the carbonyl stretching vibration frequency (νCdbnd O). Non-alkanols induced Band I and alkanols produced Band I and Band II. Through correlating the νCdbnd O with the empirical solvent scales including acceptor parameter (AN), Schleyer's linear free energy parameter (G), and linear free salvation energy relationships (LSER), Band I was mainly ascribed to non-specific effects from either non-alkanols or alkanol polymers ((alkanol)n). νCdbnd O of the latter indicated minor red shift and less variability compared to the former. An assumption was made and validated about the sequestering of hydroxyl group by the bulky hydrophobic chain in (alkanol)n, creating what we refer to as "screening effects". Ab initio calculation, on the other hand, provided insights for possible hydrogen binding between DMP and (ethanol)n or between ethanol monomers. The two components of Band I observed in inert solvents were assigned to the two Cdbnd O groups adopting differentiated conformations. This in turn prompted our consideration that hydrogen binding was highly selective in favor of lowly associated (alkanol)n and the particular Cdbnd O group having relatively less steric hindrance and stronger electron-donating capacity. Band II was therefore believed to derive from hydrogen-bond interactions mainly in manner of 1:1 and 1:2 DMP-(alkanol)n complexes.
Experimental Crossing of Two Distinct Species of Leopard Geckos, Eublepharis angramainyu and E. macularius: Viability, Fertility and Phenotypic Variation of the Hybrids.

Directory of Open Access Journals (Sweden)

Jitka Jančúchová-Lásková

Full Text Available Hybridization between distinct species of animals and subsequent genetic introgression plays a considerable role in the speciation process and the emergence of adaptive characters. Fitness of between-species hybrids usually sharply decreases with the divergence time of the concerned species and the divergence depth, which still allows for a successful crossing differs among principal clades of vertebrates. Recently, a review of hybridization events among distinct lizard species revealed that lizards belong to vertebrates with a highly developed ability to hybridize. In spite of this, reliable reports of experimental hybridizations between genetically fairly divergent species are only exceptional. Here, we show the results of the crossing of two distinct allopatric species of eyelid geckos possessing temperature sex determination and lacking sex chromosomes: Eublepharis macularius distributed in Pakistan/Afghanistan area and E. angramainyu, which inhabits Mesopotamia and adjacent areas. We demonstrated that F1 hybrids were viable and fertile, and the introgression of E. angramainyu genes into the E. macularius genome can be enabled via a backcrossing. The examined hybrids (except those of the F2 generation displayed neither malformations nor a reduced survival. Analyses of morphometric and coloration traits confirmed phenotypic distinctness of both parental species and their F1 hybrids. These findings contrast with long-term geographic and an evolutionary separation of the studied species. Thus, the occurrence of fertile hybrids of comparably divergent species, such as E. angramainyu and E. macularius, may also be expected in other taxa of squamates. This would violate the current estimates of species diversity in lizards.
Experimental Crossing of Two Distinct Species of Leopard Geckos, Eublepharis angramainyu and E. macularius: Viability, Fertility and Phenotypic Variation of the Hybrids.

Science.gov (United States)

Jančúchová-Lásková, Jitka; Landová, Eva; Frynta, Daniel

2015-01-01

Hybridization between distinct species of animals and subsequent genetic introgression plays a considerable role in the speciation process and the emergence of adaptive characters. Fitness of between-species hybrids usually sharply decreases with the divergence time of the concerned species and the divergence depth, which still allows for a successful crossing differs among principal clades of vertebrates. Recently, a review of hybridization events among distinct lizard species revealed that lizards belong to vertebrates with a highly developed ability to hybridize. In spite of this, reliable reports of experimental hybridizations between genetically fairly divergent species are only exceptional. Here, we show the results of the crossing of two distinct allopatric species of eyelid geckos possessing temperature sex determination and lacking sex chromosomes: Eublepharis macularius distributed in Pakistan/Afghanistan area and E. angramainyu, which inhabits Mesopotamia and adjacent areas. We demonstrated that F1 hybrids were viable and fertile, and the introgression of E. angramainyu genes into the E. macularius genome can be enabled via a backcrossing. The examined hybrids (except those of the F2 generation) displayed neither malformations nor a reduced survival. Analyses of morphometric and coloration traits confirmed phenotypic distinctness of both parental species and their F1 hybrids. These findings contrast with long-term geographic and an evolutionary separation of the studied species. Thus, the occurrence of fertile hybrids of comparably divergent species, such as E. angramainyu and E. macularius, may also be expected in other taxa of squamates. This would violate the current estimates of species diversity in lizards.
Enhancement of photocatalytic degradation of dimethyl phthalate with nano-TiO2 immobilized onto hydrophobic layered double hydroxides: a mechanism study.

Science.gov (United States)

Huang, Zhujian; Wu, Pingxiao; Lu, Yonghong; Wang, Xiaorong; Zhu, Nengwu; Dang, Zhi

2013-02-15

The organic layered double hydroxides (LHDs)/TiO(2) composites with various mass ratios were prepared by the reconstruction of mixed metal oxides to photodegrade dimethyl phthalate (DMP). The physicochemical properties of the obtained products were analyzed by X-ray diffraction (XRD) spectra, X-ray photoelectron spectra (XPS), UV-vis diffuse reflectance spectroscope and scanning electron microscope (SEM). The results showed that the TiO(2) particles and the organic LDHs were combined together through chemical bonds, and TiO(2) particles were well distributed on the surface of the interconnecting organic LDHs nano-flakes. According to the experimental results of adsorptive and photodegradation of DMP, the organic LDHs with flaky structure could effectively adsorb the DMP molecules and the adsorption isotherm by the composites modeled well with the Langmuir equation. The enrichment of DMP onto the composites and the external hydroxyl groups of the composites produce a synergistic effect leading to greatly enhance the rate of DMP photocatalytic degradation by the obtained composites. Copyright © 2012 Elsevier B.V. All rights reserved.
An example of genetically distinct HIV type 1 variants in cerebrospinal fluid and plasma during suppressive therapy.

Science.gov (United States)

Dahl, Viktor; Gisslen, Magnus; Hagberg, Lars; Peterson, Julia; Shao, Wei; Spudich, Serena; Price, Richard W; Palmer, Sarah

2014-05-15

We sequenced the genome of human immunodeficiency virus type 1 (HIV-1) recovered from 70 cerebrospinal fluid (CSF) specimens and 29 plasma samples and corresponding samples obtained before treatment initiation from 17 subjects receiving suppressive therapy. More CSF sequences than plasma sequences were hypermutants. We determined CSF sequences and plasma sequences in specimens obtained from 2 subjects after treatment initiation. In one subject, we found genetically distinct CSF and plasma sequences, indicating that they came from HIV-1 from 2 different compartments, one potentially the central nervous system, during suppressive therapy. In addition, there was little evidence of viral evolution in the CSF during therapy, suggesting that continuous virus replication is not the major cause of viral persistence in the central nervous system.
A DISTINCTIVE DISK-JET COUPLING IN THE SEYFERT-1 ACTIVE GALACTIC NUCLEUS NGC 4051

International Nuclear Information System (INIS)

King, A. L.; Miller, J. M.; Gueltekin, K.; Reynolds, M. T.; Cackett, E. M.; Fabian, A. C.; Markoff, S.; Nowak, M. A.; Rupen, M.

2011-01-01

We report on the results of a simultaneous monitoring campaign employing eight Chandra X-ray (0.5-10 keV) and six Very Large Array/Extended Very Large Array (8.4 GHz) radio observations of NGC 4051 over seven months. Evidence for compact jets is observed in the 8.4 GHz radio band; this builds on mounting evidence that jet production may be prevalent even in radio-quiet Seyferts. Assuming comparatively negligible local diffuse emission in the nucleus, the results also demonstrate an inverse correlation of L radio ∝ L -0.72±0.04 X-ray . If the A configuration is excluded in the case where diffuse emission plays a significant role, the relation is still L radio ∝ L X-ray -0.12±0.05 . Current research linking the mass of supermassive black holes and stellar-mass black holes in the 'low/hard' state to X-ray luminosities and radio luminosities suggests a 'fundamental plane of accretion onto black holes' that has a positive correlation of L radio ∝ L 0.67±0.12 X-ray . Our simultaneous results differ from this relation by more than 11σ (6σ excluding the A configuration), indicating that a separate mode of accretion and ejection may operate in this system. A review of the literature shows that the inverse correlation seen in NGC 4051 is seen in three other black hole systems, all of which accrete at near 10% of their Eddington luminosity, perhaps suggesting a distinct mode of disk-jet coupling at high Eddington fractions. We discuss our results in the context of disks and jets in black holes and accretion across the black hole mass scale.
Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function

Science.gov (United States)

Kara, Firas M.; Chitu, Violeta; Sloane, Jennifer; Axelrod, Matthew; Fredholm, Bertil B.; Stanley, E. Richard; Cronstein, Bruce N.

2010-01-01

Adenosine regulates a wide variety of physiological processes via interaction with one or more G-protein-coupled receptors (A1R, A2AR, A2BR, and A3R). Because A1R occupancy promotes fusion of human monocytes to form giant cells in vitro, we determined whether A1R occupancy similarly promotes osteoclast function and formation. Bone marrow cells (BMCs) were harvested from C57Bl/6 female mice or A1R-knockout mice and their wild-type (WT) littermates and differentiated into osteoclasts in the presence of colony stimulating factor-1 and receptor activator of NF-κB ligand in the presence or absence of the A1R antagonist 1,3-dipropyl-8-cyclopentyl xanthine (DPCPX). Osteoclast morphology was analyzed in tartrate-resistant acid phosphatase or F-actin-stained samples, and bone resorption was evaluated by toluidine blue staining of dentin. BMCs from A1R-knockout mice form fewer osteoclasts than BMCs from WT mice, and the A1R antagonist DPCPX inhibits osteoclast formation (IC50=1 nM), with altered morphology and reduced ability to resorb bone. A1R blockade increased ubiquitination and degradation of TRAF6 in RAW264.7 cells induced to differentiate into osteoclasts. These studies suggest a critical role for adenosine in bone homeostasis via interaction with adenosine A1R and further suggest that A1R may be a novel pharmacologic target to prevent the bone loss associated with inflammatory diseases and menopause.—Kara, F. M., Chitu, V., Sloane, J., Axelrod, M., Fredholm, B. B., Stanley, R., Cronstein, B. N. Adenosine A1 receptors (A1Rs) play a critical role in osteoclast formation and function. PMID:20181934
[Play therapy--psychotherapy with play as the medium: II. New developments].

Science.gov (United States)

von Gontard, Alexander; Lehmkuhl, Gerd

2003-02-01

A wide array of new forms and combinations of play therapy have been developed. The aim of the second part of this paper is to present an overview of these newer approaches, including: focussed therapies for specific disorders; behavioural approaches like the Cognitive-Behavioral Play Therapy and the Parent-Child Interaction Therapy; various combinations with family therapy; and therapies especially for preschool children like Filial Therapy, Developmental Play Therapy and Thera-play. Following a phase of experiments and combinations, the empirical evaluation of many play-therapy forms is needed. Especially questions of the differential indication of specific play-therapies and their effectiveness in the therapeutical practice need to be studied.
A comparison of HFrEF vs HFpEF's clinical workload and cost in the first year following hospitalization and enrollment in a disease management program.

Science.gov (United States)

Murphy, T M; Waterhouse, D F; James, S; Casey, C; Fitzgerald, E; O'Connell, E; Watson, C; Gallagher, J; Ledwidge, M; McDonald, K

2017-04-01

Admission with heart failure (HF) is a milestone in the progression of the disease, often resulting in higher intensity medical care and ensuing readmissions. Whilst there is evidence supporting enrolling patients in a heart failure disease management program (HF-DMP), not all reported HF-DMPs have systematically enrolled patients with HF with preserved ejection fraction (HFpEF) and there is a scarcity of literature differentiating costs based on HF-phenotype. 1292 consenting, consecutive patients admitted with a primary diagnosis of HF were enrolled in a hospital based HF-DMP and categorized as HFpEF (EF≥45%) or HFrEF (EFHospitalizations, primary care, medications, and DMP workload with associated costs were evaluated assessing DMP clinic-visits, telephonic contact, medication changes over 1year using a mixture of casemix and micro-costing techniques. The total average annual cost per patient was marginally higher in patients with HFrEF €13,011 (12,011, 14,078) than HFpEF, €12,206 (11,009, 13,518). However, emergency non-cardiovascular admission rates and average cost per patient were higher in the HFpEF vs HFrEF group (0.46 vs 0.31 per patient/12months) & €655 (318, 1073) vs €584 (396, 812). In the first 3months of the outpatient HF-DMP the HFrEF population cost more on average €791 (764, 819) vs €693 (660, 728). There are greater short-term (3-month) costs of HFrEF versus HFpEF as part of a HF-DMP following an admission. However, long-term (3-12month) costs of HFpEF are greater because of higher non-cardiovascular rehospitalisations. As HFpEF becomes the dominant form of HF, more work is required in HF-DMPs to address prevention of non-cardiovascular rehospitalisations and to integrate hospital based HF-DMPs into primary healthcare structures. Copyright Â© 2017 Elsevier Ireland Ltd. All rights reserved.
Health system responsiveness and chronic disease care - What is the role of disease management programs? An analysis based on cross-sectional survey and administrative claims data.

Science.gov (United States)

Röttger, Julia; Blümel, Miriam; Linder, Roland; Busse, Reinhard

2017-07-01

Health system responsiveness is an important aspect of health systems performance. The concept of responsiveness relates to the interpersonal and contextual aspects of health care. While disease management programs (DMPs) aim to improve the quality of health care (e.g. by improving the coordination of care), it has not been analyzed yet whether these programs improve the perceived health system responsiveness. Our study aims to close this gap by analyzing the differences in the perceived health system responsiveness between DMP-participants and non-participants. We used linked survey- and administrative claims data from 7037 patients with coronary heart disease in Germany. Of those, 5082 were enrolled and 1955 were not enrolled in the DMP. Responsiveness was assessed with an adapted version of the WHO responsiveness questionnaire in a postal survey in 2013. The survey covered 9 dimensions of responsiveness and included 17 items for each, GP and specialist care. Each item had five answer categories (very good - very bad). We handled missing values in the covariates by multiple imputation and applied propensity score matching (PSM) to control for differences between the two groups (DMP/non-DMP). We used Wilcoxon-signed-rank and McNemar test to analyze differences regarding the reported responsiveness. The PSM led to a matched and well balanced sample of 1921 pairs. Overall, DMP-participants rated the responsiveness of care more positive. The main difference was found for the coordination of care at the GP, with 62.0% of 1703 non-participants reporting a "good" or "very good" experience, compared to 69.1% of 1703 participants (p < 0.001). The results of our study indicate an overall high responsiveness for CHD-care, as well for DMP-participants as for non-participants. Yet, the results also clearly indicate that there is still a need to improve the coordination of care. Copyright © 2017 Elsevier Ltd. All rights reserved.
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...
Maternal attitude and child interest in various play activities before and after mother-child play sessions

Directory of Open Access Journals (Sweden)

Soedjatmiko Soedjatmiko

2018-01-01

Full Text Available Background Play stimulates children’s growth and development. When mothers and their children play, a positive attitude from the mother and adequate interest from the child is required. Little is known about the play activities that effectively stimulate such positive maternal attitude and child interest. Objective To assess for associations between various play activities with maternal attitude and child interest before and after mother-child play sessions. Methods Pre-post intervention questionnaires were distributed to mothers before and after playing with their children. Children were aged 1-5 years, from two play sites (in Surabaya and Makassar, and included using purposive sampling. Eight types of toys/play activities were provided. The allocated time for answering the 17-question survey was 15 minutes. Average scores before and after the mother-child play sessions were analyzed using paired T-test. Results We collected 264 valid questionnaires, 235 in Surabaya and 29 in Makassar. Improvement of maternal attitude after the mother-child play session was found in 132 mothers [mean diff. 0.07 (SD 0.42; 95%CI -0.117 to -0.015; P=0.011]. Play activities with significant improvements in maternal attitude were jigsaw puzzle [mean diff. 0.09 (SD 0.66; 95% CI 0.007 to 0.167;P= 0.033, Lego blocks (mean diff.-0.10 (SD 0.69; 95%CI -0.186 to -0.018; P=0.017, mini-gardening (mean diff. -0.15 (SD 0.75; 95%CI -0.238 to -0.057; P=0.002, sandbox [mean diff.-0.24 (SD 0.83; 95%CI -0.339 to – 0.138; P < 0.001], fishing [mean diff. -0.17 (SD 0.68; 95%CI -0.253 to -0.088; P < 0.001], and animal figurines [mean diff. -0.21 (SD 0.75; 95%CI -0.3 to -0.117;P <0.001]. Improvement of child interest was found in 161 children [mean diff. 0.20 (SD 0.52; 95%CI -0.264 to -0.116; P<0.001]. Play activities with significant improvements in child interest were jigsaw puzzle, Lego blocks, origami, mini-gardening, fishing, and animal figurines. Conclusion Some mother
Play. Learn. Innovate

DEFF Research Database (Denmark)

Sproedt, Henrik

study were to better understand the theoretical foundations and practical implications of complex social interaction in organizational innovation settings. As I did not find any existing models or hypotheses that I was interested in testing I set out to discover how I could grasp complex social...... evidence that play and games could be interesting perspectives to take in order to understand complex social interaction. I come to the conclusion that – in innovation settings – the social dynamics that affect the process are essentially about transformation of knowledge across boundaries. I propose......„Play. Learn. Innovate. – Grasping the Social Dynamics of Participatory Innovation“ the title of this thesis describes how the complex interplay of unexpected events led to some burning questions and eventually to this thesis, which one could call an innovation*1*. During several years...
Concepts of Play and Play Culture for the 21st Century

DEFF Research Database (Denmark)

Nørgård, Rikke Toft; Toft, Herdis; Karoff, Helle Skovbjerg

2014-01-01

, Associate professor Carsten Jessen, Aarhus University, Assistant professor Helle Skovbjerg Karoff, University of Aalborg and Assistant professor Rikke Toft Nørgård, Aarhus University. This panel represents and discusses different concepts of play and play culture in both diachronic and synchronic dimensions......BIN Norden conference 2014 Accepted panel ________________________________________ Concepts of Play and Play Culture for the 21st Century Participants in the panel are: Associate professor Herdis Toft, University of Southern Denmark (organizer), Professor Beth Juncker, University of Copenhagen....... For several centuries western theorists, for instance Baumgarten, Schiller, Huizinga, Caillois, Sutton Smith, Vygotsky, Bateson, Salen & Zimmerman, Flemming Mouritsen and later on the panel participants, have discussed the concept of play and play culture. They have presented their own theoretical...
Love Games that Insects Play

Indian Academy of Sciences (India)

Home; Journals; Resonance – Journal of Science Education; Volume 3; Issue 1. Love Games that Insects Play - The Evolution of Sexual Behaviours in Insects ... Author Affiliations. K N Ganeshaiah1. Department of Genetics & Plant Breeding University of Agricultural Sciences, GKVK Bangalore 560 065, India ...
Playing on the edge

DEFF Research Database (Denmark)

Cermak-Sassenrath, Daniel

2018-01-01

and specific ways. For instance, gambling for money, party and drinking games, professional play and show sports, art installations, violent and military propaganda computer games, pervasive/mobile gaming, live-action role playing, festivals, performances, and games such as Ghosting and Planking. It is argued......Everything gets more interesting, challenging, or intense the closer it gets to the edge, and so does play. How edgy can play become and still be play? Based on Huizinga’s notion of play, this chapter discusses how a wide range of playful activities pushes the boundaries of play in different...... that in concert with a number of characteristics that mark an activity as play, play is essentially a subjective perspective and individual decision of the player. Huizinga calls this attitude the play spirit, which informs a player’s actions and is in turn sustained by them. Edgy digital or mobile games do...
Play Therapy: A Review

Science.gov (United States)

Porter, Maggie L.; Hernandez-Reif, Maria; Jessee, Peggy

2009-01-01

This article discusses the current issues in play therapy and its implications for play therapists. A brief history of play therapy is provided along with the current play therapy approaches and techniques. This article also touches on current issues or problems that play therapists may face, such as interpreting children's play, implementing…
Well Played: The Origins and Future of Playfulness

Science.gov (United States)

Gordon, Gwen

2014-01-01

In this article, the author synthesizes research from several disciplines to shed light on play's central role in healthy development. Gordon builds on research in attachment theory that correlates secure attachment in infancy with adult well-being to demonstrate how playfulness might be a lifelong outcome of secure attachment and a primary…
Depression and play in early childhood. Play behavior of depressed and nondepressed 3- to 6-year olds in various play situations

NARCIS (Netherlands)

Mol Lous, A.; Wit, C.A.M. de; Bruyn, E.E.J. De; Riksen-Walraven, J.M.A.; Rost, H.

2000-01-01

The behavior of seven depressed and seven nondepressed 3- to 6-year-olds was compared in three play situations: solitary free play, interactive free play, and play narratives. Depressed children played significantly less than their nondepressed controls. This was mainly due to differences in
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.

Deep-water northern Gulf of Mexico hydrocarbon plays

International Nuclear Information System (INIS)

Peterson, R.H.; Cooke, D.W.

1995-01-01

The geologic setting in the deep-water (depths greater than 1,500 feet) Gulf of Mexico is very favorable for the existence of large, commercial hydrocarbon accumulations. These areas have active salt tectonics that create abundant traps, underlying mature Mesozoic source rocks that can be observed expelling oil and gas to the ocean surface, and good quality reservoirs provided by turbidite sand deposits. Despite the limited amount of drilling in the deep-water Gulf of Mexico, 11 deep-water accumulations have been discovered which, when developed, will rank in the top 100 largest fields in the Gulf of Mexico. Proved field discoveries (those with announced development plans) have added over 1 billion barrels of oil equivalent to Gulf of Mexico reserves, and unproved field discoveries may add to additional billion barrels of oil equivalent. The Minerals Management Service, United States Department of the Interior, has completed a gulf-wide review of over 1,086 oil and gas fields and placed every pay sand in each field into a hydrocarbon play (plays are defined by chronostratigraphy, lithostratigraph, structure, and production). Seven productive hydrocarbon plays were identified in the deep-water northern Gulf of Mexico. Regional maps illustrate the productive limits of each play. In addition, field data, dry holes, and wells with sub-economic pay were added to define the facies and structural limits for each play. Areas for exploration potential are identified for each hydrocarbon play. A type field for each play is chosen to demonstrate the play's characteristics
Play as Self-Realization: Toward a General Theory of Play

Science.gov (United States)

Henricks, Thomas S.

2014-01-01

In a wide-ranging essay that reviews the major theories of plays and relates them to significant notions of the self, the author addresses the question of why we play. He does so to argue that play is a biologically driven project of self-understanding and self-realization, one that humans--although they also share the experience with other…
Patients with type 2 diabetes benefit from primary care-based disease management: a propensity score matched survival time analysis.

Science.gov (United States)

Drabik, Anna; Büscher, Guido; Thomas, Karsten; Graf, Christian; Müller, Dirk; Stock, Stephanie

2012-08-01

This study aimed to assess the impact of a nationwide German diabetes mellitus disease management program (DMP) on survival time and costs in comparison to routine care. The authors conducted a retrospective observational cohort study using routine administration data from Germany's largest sickness fund to identify insured suffering from diabetes in 2002. A total of 95,443 insured with type 2 diabetes mellitus who were born before January 1, 1962 met the defined inclusion criteria, resulting in 19,888 pairs of DMP participants and nonparticipants matched for socioeconomic and health status using propensity score matching methods. This is the first time propensity score matching has been used to evaluate a survival benefit of DMPs. In the time frame analyzed (3 years), mean survival time for the DMP group was 1045 days vs. 985 days for the routine care group (Ptime. They also incurred lower costs compared to propensity score matched insured in routine care.
Polyphosphate induces matrix metalloproteinase-3-mediated proliferation of odontoblast-like cells derived from induced pluripotent stem cells

Energy Technology Data Exchange (ETDEWEB)

Ozeki, Nobuaki; Hase, Naoko; Yamaguchi, Hideyuki; Hiyama, Taiki; Kawai, Rie [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651 (Japan); Kondo, Ayami [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan); Nakata, Kazuhiko [Department of Endodontics, School of Dentistry, Aichi Gakuin University, 2-11 Suemori-dori, Chikusa-ku, Nagoya, Aichi 464-8651 (Japan); Mogi, Makio, E-mail: makio@dpc.agu.ac.jp [Department of Medicinal Biochemistry, School of Pharmacy, Aichi Gakuin University, 1-100 Kusumoto, Chikusa-ku, Nagoya 464-8650 (Japan)

2015-05-01

Inorganic polyphosphate [Poly(P)] may represent a physiological source of phosphate and has the ability to induce bone differentiation in osteoblasts. We previously reported that cytokine-induced matrix metalloproteinase (MMP)-3 accelerates the proliferation of purified odontoblast-like cells. In this study, MMP-3 small interfering RNA (siRNA) was transfected into odontoblast-like cells derived from induced pluripotent stem cells to investigate whether MMP-3 activity is induced by Poly(P) and/or is associated with cell proliferation and differentiation into odontoblast-like cells. Treatment with Poly(P) led to an increase in both cell proliferation and additional odontoblastic differentiation. Poly(P)-treated cells showed a small but significant increase in dentin sialophosphoprotein (DSPP) and dentin matrix protein-1 (DMP-1) mRNA expression, which are markers of mature odontoblasts. The cells also acquired additional odontoblast-specific properties including adoption of an odontoblastic phenotype typified by high alkaline phosphatase (ALP) activity and a calcification capacity. In addition, Poly(P) induced expression of MMP-3 mRNA and protein, and increased MMP-3 activity. MMP-3 siRNA-mediated disruption of the expression of these effectors potently suppressed the expression of odontoblastic biomarkers ALP, DSPP, and DMP-1, and blocked calcification. Interestingly, upon siRNA-mediated silencing of MMP-3, we noted a potent and significant decrease in cell proliferation. Using specific siRNAs, we revealed that a unique signaling cascade, Poly(P)→MMP-3→DSPP and/or DMP-1, was intimately involved in the proliferation of odontoblast-like cells. - Highlights: • Polyphosphate increases proliferation of iPS cell-derived odontoblast-like cells. • Polyphosphate-induced MMP-3 results in an increase of cell proliferation. • Induced cell proliferation involves MMP-3, DSPP, and/or DMP-1 sequentially. • Induced MMP-3 also results in an increase of odontoblastic
Conditional TNF-α Overexpression in the Tooth and Alveolar Bone Results in Painful Pulpitis and Osteitis.

Science.gov (United States)

Hall, B E; Zhang, L; Sun, Z J; Utreras, E; Prochazkova, M; Cho, A; Terse, A; Arany, P; Dolan, J C; Schmidt, B L; Kulkarni, A B

2016-02-01

Tumor necrosis factor-α (TNF-α) is a proalgesic cytokine that is commonly expressed following tissue injury. TNF-α expression not only promotes inflammation but can also lead to pain hypersensitivity in nociceptors. With the established link between TNF-α and inflammatory pain, we identified its increased expression in the teeth of patients affected with caries and pulpitis. We generated a transgenic mouse model (TNF-α(glo)) that could be used to conditionally overexpress TNF-α. These mice were bred with a dentin matrix protein 1 (DMP1)-Cre line for overexpression of TNF-α in both the tooth pulp and bone to study oral pain that would result from subsequent development of pulpitis and bone loss. The resulting DMP1/TNF-α(glo) mice show inflammation in the tooth pulp that resembles pulpitis while also displaying periodontal bone loss. Inflammatory infiltrates and enlarged blood vessels were observed in the tooth pulp. Pulpitis and osteitis affected the nociceptive neurons innervating the orofacial region by causing increased expression of inflammatory cytokines within the trigeminal ganglia. With this new mouse model morphologically mimicking pulpitis and osteitis, we tested it for signs of oral pain with an oral function assay (dolognawmeter). This assay/device records the time required by a mouse to complete a discrete gnawing task. The duration of gnawing required by the DMP1/TNF-α(glo) mice to complete the task was greater than that for the controls; extended gnaw time in a dolognawmeter indicates reduced orofacial function. With the DMP1/TNF-α(glo) mice, we have shown that TNF-α expression alone can produce inflammation similar to pulpitis and osteitis and that this mouse model can be used to study dental inflammatory pain. © International & American Associations for Dental Research 2015.
Play and play occupation: a survey of paediatric occupational therapy practice in Ireland

Directory of Open Access Journals (Sweden)

Alice Moore

2017-04-01

Full Text Available Purpose - Play occupation has been identified as an essential part of children’s lives, and it subsequently features in paediatric occupational therapy. However, few studies address the current place of play and play occupation in occupational therapy practice. This study aims to address this gap in knowledge by exploring paediatric occupational therapists’ perspectives on the place of play and play occupation in occupational therapy practice in Ireland. Design/methodology/approach - A cross-sectional online survey was conducted to gather data about the current use of play in the occupational therapy for children under 12 years. Convenience sampling and snowball recruitment techniques were used to recruit paediatric occupational therapists. Data were analysed using descriptive statistics and qualitative content analysis. Findings - In total, 65 therapists responded to the survey (estimated response rate, 32%. Results are organised into four sections: demographics and practice context, play assessment practices, use of play in practice and perceived barriers to play-centred practice. Respondents reported that they valued play as a childhood occupation. However, the survey findings identified that the primary focus was on play as a means to an end. Lack of education on play (research, theory and interventions and pressures in the workplace have been identified as barriers to play-centred practice. Research limitations/implications - Findings indicate that there is a mismatch between therapists valuing play as an occupation and how play is used in occupational therapy practice. Unless clarifications are made about play occupation as being different to skills acquisition in childhood, play occupation will continue to get overlooked as an authentic concern of occupation-centred practice. Thus, play as occupation deserves further attention from educators, researchers and practitioners as a means of strengthening occupation-centred practice, in
76 FR 58167 - Safety Standard for Play Yards

Science.gov (United States)

2011-09-20

... subject matter expert. Thus, EWS contains the best data to support the play yard regulatory work. 1... compressed the airway. One toddler was killed when the play yard collapsed unexpectedly. The child was... hospitalization was caused by the presence of soft bedding in the play yard. This was a severe injury to a 7-week...
An exploratory study of the association between online gaming addiction and enjoyment motivations for playing massively multiplayer online role-playing games

OpenAIRE

Hussain, Z; Williams, GA; Griffiths, MD

2015-01-01

Massively multiplayer online role-playing games (MMORPGs) are a popular form of entertainment used by millions of gamers worldwide. Potential problems relating to MMORPG play have emerged, particularly in relation to being addicted to playing in such virtual environments. In the present study, factors relating to online gaming addiction and motivations for playing in MMORPGs were examined to establish whether they were associated with addiction. A sample comprised 1,167 gamers who were survey...
Mother-Infant and Extra-Dyadic Interactions with a New Social Partner: Developmental Trajectories of Early Social Abilities during Play.

Science.gov (United States)

Fadda, Roberta; Lucarelli, Loredana

2017-01-01

Mother-infant interactions during feeding and play are pivotal experiences in the development of infants' early social abilities (Stern, 1985, 1995; Biringen, 2000). Stern indicated distinctive characteristics of mother-infant interactions, respectively, during feeding and play, suggesting to evaluate both to better describe the complexity of such early affective and social experiences (Stern, 1996). Moreover, during the first years of life, infants acquire cognitive and social skills that allow them to interact with new social partners in extra-dyadic interactions. However, the relations between mother-child interactions and infants' social skills in extra-dyadic interactions are still unknown. We investigated longitudinally the relations between mother-child interactions during feeding and play and child's pre-verbal communicative abilities in extra-dyadic interactions during play. 20 dyads were evaluated at T 1 (infants aged between 9-22 months) and 6 months later, at T 2 . The interdyadic differences in mother-infant interactions during feeding and play were evaluated, respectively, with the "Feeding Scale" (Chatoor et al., 1997) and with the "Play Scale" (Chatoor, 2006) and the socio-communicative abilities of children with a new social partner during play were evaluated with the "Early Social Communication Scales" (Mundy et al., 2003). We distinguished the dyads into two categories: dyads with functional interactions (high dyadic reciprocity, low dyadic conflict) and dyads with dysfunctional interactions (lower dyadic reciprocity, higher dyadic conflict). At T 1 , infants belonging to dyads with dysfunctional interactions were significantly lower in "Initiating Joint Attention" and in "Responding to Joint Attention" in interaction with a new social partner compared to the infants belonging to dyads with functional interactions. At T 2 , infants belonging to dyads with dysfunctional interactions were significantly lower in "Initiating Social Interactions" with
The play grid

DEFF Research Database (Denmark)

Fogh, Rune; Johansen, Asger

2013-01-01

In this paper we propose The Play Grid, a model for systemizing different play types. The approach is psychological by nature and the actual Play Grid is based, therefore, on two pairs of fundamental and widely acknowledged distinguishing characteristics of the ego, namely: extraversion vs. intro...
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.
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.
Decision Gate Process for Assessment of a Technology Development Portfolio

Science.gov (United States)

Kohli, Rajiv; Fishman, Julianna; Hyatt, Mark

2012-01-01

The NASA Dust Management Project (DMP) was established to provide technologies (to TRL 6 development level) required to address adverse effects of lunar dust to humans and to exploration systems and equipment, which will reduce life cycle cost and risk, and will increase the probability of sustainable and successful lunar missions. The technology portfolio of DMP consisted of different categories of technologies whose final product is either a technology solution in itself, or one that contributes toward a dust mitigation strategy for a particular application. A Decision Gate Process (DGP) was developed to assess and validate the achievement and priority of the dust mitigation technologies as the technologies progress through the development cycle. The DGP was part of continuous technology assessment and was a critical element of DMP risk management. At the core of the process were technology-specific criteria developed to measure the success of each DMP technology in attaining the technology readiness levels assigned to each decision gate. The DGP accounts for both categories of technologies and qualifies the technology progression from technology development tasks to application areas. The process provided opportunities to validate performance, as well as to identify non-performance in time to adjust resources and direction. This paper describes the overall philosophy of the DGP and the methodology for implementation for DMP, and describes the method for defining the technology evaluation criteria. The process is illustrated by example of an application to a specific DMP technology.
Decision Gate Process for Assessment of a NASA Technology Development Portfolio

Science.gov (United States)

Kohli, Rajiv; Fishman, Julianna L.; Hyatt, Mark J.

2012-01-01

The NASA Dust Management Project (DMP) was established to provide technologies (to Technology Readiness Level (TRL) 6) required to address adverse effects of lunar dust to humans and to exploration systems and equipment, to reduce life cycle cost and risk, and to increase the probability of sustainable and successful lunar missions. The technology portfolio of DMP consisted of different categories of technologies whose final product was either a technology solution in itself, or one that contributes toward a dust mitigation strategy for a particular application. A Decision Gate Process (DGP) was developed to assess and validate the achievement and priority of the dust mitigation technologies as the technologies progress through the development cycle. The DGP was part of continuous technology assessment and was a critical element of DMP risk management. At the core of the process were technology-specific criteria developed to measure the success of each DMP technology in attaining the technology readiness levels assigned to each decision gate. The DGP accounts for both categories of technologies and qualifies the technology progression from technology development tasks to application areas. The process provided opportunities to validate performance, as well as to identify non-performance in time to adjust resources and direction. This paper describes the overall philosophy of the DGP and the methodology for implementation for DMP, and describes the method for defining the technology evaluation criteria. The process is illustrated by example of an application to a specific DMP technology.
Enhancement of photocatalytic degradation of dimethyl phthalate with nano-TiO{sub 2} immobilized onto hydrophobic layered double hydroxides: A mechanism study

Energy Technology Data Exchange (ETDEWEB)

Huang, Zhujian [College of Environmental Science and Engineering, South China University of Technology, Guangzhou 510006 (China); The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, Guangzhou 510006 (China); Wu, Pingxiao, E-mail: pppxwu@scut.edu.cn [College of Environmental Science and Engineering, South China University of Technology, Guangzhou 510006 (China); The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, Guangzhou 510006 (China); The Key Laboratory of Environmental Protection and Eco-Remediation of Guangdong Regular Higher Education Institutions (China); Lu, Yonghong; Wang, Xiaorong; Zhu, Nengwu [College of Environmental Science and Engineering, South China University of Technology, Guangzhou 510006 (China); The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, Guangzhou 510006 (China); Dang, Zhi [College of Environmental Science and Engineering, South China University of Technology, Guangzhou 510006 (China); The Key Lab of Pollution Control and Ecosystem Restoration in Industry Clusters, Ministry of Education, Guangzhou 510006 (China); The Key Laboratory of Environmental Protection and Eco-Remediation of Guangdong Regular Higher Education Institutions (China)

2013-02-15

Highlights: ► The reconstructed organic LDHs are consisted of the interconnecting nano-flakes. ► It is confirmed that organic LDHs/TiO{sub 2} composites are combined together by chemical bonds. ► The organic LDHs with flaky structure effectively enrich DPM onto the composite. ► The abundant external hydroxyl groups of organic LDHs promote the production of ·OH. ► TiO{sub 2} immobilized onto organic LDHs greatly enhances the photodegradation of DMP. -- Abstract: The organic layered double hydroxides (LHDs)/TiO{sub 2} composites with various mass ratios were prepared by the reconstruction of mixed metal oxides to photodegrade dimethyl phthalate (DMP). The physicochemical properties of the obtained products were analyzed by X-ray diffraction (XRD) spectra, X-ray photoelectron spectra (XPS), UV–vis diffuse reflectance spectroscope and scanning electron microscope (SEM). The results showed that the TiO{sub 2} particles and the organic LDHs were combined together through chemical bonds, and TiO{sub 2} particles were well distributed on the surface of the interconnecting organic LDHs nano-flakes. According to the experimental results of adsorptive and photodegradation of DMP, the organic LDHs with flaky structure could effectively adsorb the DMP molecules and the adsorption isotherm by the composites modeled well with the Langmuir equation. The enrichment of DMP onto the composites and the external hydroxyl groups of the composites produce a synergistic effect leading to greatly enhance the rate of DMP photocatalytic degradation by the obtained composites.
Alibis for Adult Play

Science.gov (United States)

2017-01-01

The social meanings of play sit at odds with norms of responsible and productive adult conduct. To be “caught” playing as an adult therefore risks embarrassment. Still, many designers want to create enjoyable, nonembarrassing play experiences for adults. To address this need, this article reads instances of spontaneous adult play through the lens of Erving Goffman’s theory of the interaction order to unpack conditions and strategies for nonembarrassing adult play. It identifies established frames, segregated audiences, scripts supporting smooth performance, managing audience awareness, role distancing, and, particularly, alibis for play: Adults routinely provide alternative, adult-appropriate motives to account for their play, such as child care, professional duties, creative expression, or health. Once legitimized, the norms and rules of play themselves then provide an alibi for behavior that would risk being embarrassing outside play.
Playing Muller Games in a Hurry

Directory of Open Access Journals (Sweden)

John Fearnley

2010-06-01

Full Text Available This work studies the following question: can plays in a Muller game be stopped after a finite number of moves and a winner be declared. A criterion to do this is sound if Player 0 wins an infinite-duration Muller game if and only if she wins the finite-duration version. A sound criterion is presented that stops a play after at most 3^n moves, where n is the size of the arena. This improves the bound (n!+1^n obtained by McNaughton and the bound n!+1 derived from a reduction to parity games.
Playing Muller Games in a Hurry

OpenAIRE

Fearnley, John; Zimmermann, Martin

2010-01-01

This work studies the following question: can plays in a Muller game be stopped after a finite number of moves and a winner be declared. A criterion to do this is sound if Player 0 wins an infinite-duration Muller game if and only if she wins the finite-duration version. A sound criterion is presented that stops a play after at most 3^n moves, where n is the size of the arena. This improves the bound (n!+1)^n obtained by McNaughton and the bound n!+1 derived from a reduction to parity games.
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.
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.

Alibis for Adult Play: A Goffmanian Account of Escaping Embarrassment in Adult Play.

Science.gov (United States)

Deterding, Sebastian

2018-05-01

The social meanings of play sit at odds with norms of responsible and productive adult conduct. To be "caught" playing as an adult therefore risks embarrassment. Still, many designers want to create enjoyable, nonembarrassing play experiences for adults. To address this need, this article reads instances of spontaneous adult play through the lens of Erving Goffman's theory of the interaction order to unpack conditions and strategies for nonembarrassing adult play. It identifies established frames, segregated audiences, scripts supporting smooth performance, managing audience awareness, role distancing, and, particularly, alibis for play: Adults routinely provide alternative, adult-appropriate motives to account for their play, such as child care, professional duties, creative expression, or health. Once legitimized, the norms and rules of play themselves then provide an alibi for behavior that would risk being embarrassing outside play.
Playing Shakespeare.

Science.gov (United States)

Bashian, Kathleen Ryniker

1993-01-01

Describes a yearlong project at 12 Catholic middle schools in the Diocese of Arlington, Virginia, to incorporate the plays of William Shakespeare into the curriculum. Teachers attended university lectures and directed students in performances of the plays. Concludes that Shakespeare can be understood and enjoyed by middle school students. (BCY)
Virtual Playgrounds? Assessing the Playfulness of Massively Multiplayer Online Role-Playing Games

Science.gov (United States)

Graham, Kerrie Lewis

2010-01-01

Millions of children and adults devote much of their leisure time to playing massively multiplayer online role-playing games (MMORPGs). Most observers commonly categorize computer games as a play activity, but this article asks whether MMORPGs contain activities that might not be play. The author examines the phenomenon of online gaming and…
Contribuição para o diagóstico diferencial da distrofia muscular progressiva

Directory of Open Access Journals (Sweden)

José Antonio Levy

1964-06-01

Full Text Available Os dados fornecidos pela anamnese assim como a sintomatologia nem sempre permitem estabelecer, com segurança, o diagnóstico de distrofia muscular progressiva (DMP; o diagnótico é facilitado quando são obtidos dados heredológicos depondo por afecção de caráter familiar ou quando se trate de casos de longa evolução, mostrando a característica fundamental da irreversibilidade. As provas laboratoriais propostas até agora, embora úteis para a avaliação do estado da consunção do tecido muscular, não fornecem elementos seguros para o diagnóstico diferencial, pois os resultados podem ser idênticos tanto na DMP (especialmente nas fases, iniciais ou de evolução subaguda como nas polimiosites e nas neuromiosites. De grande importância para o diagnóstico diferencial são a eletromio-grafia e a biopsia muscular: a eletromiografia mostra, na DMP, diminuição da voltagem e redução da duração média dos potenciais de ação, com elevada incidência de potenciais polifásicos; o exame histológico mostra grande variação no calibre e degeneração das fibras musculares com proliferação de tecido conjuntivo, sem infiltrações de caráter inflamatório e sem atividade regenerativa útil. Entretanto, êstes exames complementares não bastam, por si sós, para o diagnóstico diferencial de todos os casos e seus resultados devem ser interpretados cuidadosamente. Neste trabalho são referidos 21 casos que exigiram cuidadoso diagnóstico diferencial. Em 17 (casos 1 a 17, com base na anamnese e na sintomatologia, fôra feito o diagnóstico de DMP; entretanto em todos êles o exame mais minucioso, acrescido de dados fornecidos pela eletromiografia e especialmente pela biopsia, conduziu à formulação de outro diagnóstico. Em dois casos (18 e 19, ambos de moléstia de Charcot-Marie-Tooth, o exame histo-patológico sugeria o diagnóstico de DMP. Em um caso (20 o quadro clínico sugeria DMP e o exame eletromiográfico indicava haver les
Distinct licensing of IL-18 and IL-1β secretion in response to NLRP3 inflammasome activation.

Directory of Open Access Journals (Sweden)

Rebecca L Schmidt

Full Text Available Inflammasome activation permits processing of interleukins (IL-1β and 18 and elicits cell death (pyroptosis. Whether these responses are independently licensed or are "hard-wired" consequences of caspase-1 (casp1 activity has not been clear. Here, we show that that each of these responses is independently regulated following activation of NLRP3 inflammasomes by a "non-canonical" stimulus, the secreted Listeria monocytogenes (Lm p60 protein. Primed murine dendritic cells (DCs responded to p60 stimulation with reactive oxygen species (ROS production and secretion of IL-1β and IL-18 but not pyroptosis. Inhibitors of ROS production inhibited secretion of IL-1β, but did not impair IL-18 secretion. Furthermore, DCs from caspase-11 (casp11-deficient 129S6 mice failed to secrete IL-1β in response to p60 but were fully responsive for IL-18 secretion. These findings reveal that there are distinct licensing requirements for processing of IL-18 versus IL-1β by NLRP3 inflammasomes.
POLG1 mutations and stroke like episodes: a distinct clinical entity rather than an atypical MELAS syndrome.

Science.gov (United States)

Cheldi, Antonella; Ronchi, Dario; Bordoni, Andreina; Bordo, Bianca; Lanfranconi, Silvia; Bellotti, Maria Grazia; Corti, Stefania; Lucchini, Valeria; Sciacco, Monica; Moggio, Maurizio; Baron, Pierluigi; Comi, Giacomo Pietro; Colombo, Antonio; Bersano, Anna

2013-01-15

POLG1 mutations have been associated with MELAS-like phenotypes. However given several clinical differences it is unknown whether POLG1 mutations are possible causes of MELAS or give raise to a distinct clinical and genetic entity, named POLG1-associated encephalopathy. We describe a 74 years old man carrying POLG1 mutations presenting with strokes, myopathy and ragged red fibers with some atypical aspects for MELAS such as late onset, lack of cerebral calcification and presence of frontal and occipital MRI lesions better consistent with the POLG associated-encephalopathy spectrum. The lack of available data hampers a definite diagnosis in our patient as well as makes it difficult to compare MELAS, which is a clearly defined clinical syndrome, with POLG1-associated encephalopathy, which is so far a purely molecularly defined syndrome with a quite heterogeneous clinical picture. However, the present report contributes to expand the phenotypic spectrum of POLG1 mutations underlining the importance of searching POLG1 mutations in patients with mitochondrial signs and MELAS like phenotypes but negative for common mtDNA mutations.
Playing to (self-)rehabilitate

DEFF Research Database (Denmark)

Knoche, Hendrik; Hald, Kasper; Richter, Dorte

2016-01-01

We designed and evaluated a whack-a-mole (WAM) style game (see Figure 1) in a clinical randomized controlled trial (RCT) with reminder-assisted but self-initiated use over the period of a month with 43 participants from a post-lesion pool. While game play did not moderate rehabilitative progress...
Distinct roles of jasmonates and aldehydes in plant-defense responses.

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E Wassim Chehab

Full Text Available BACKGROUND: Many inducible plant-defense responses are activated by jasmonates (JAs, C(6-aldehydes, and their corresponding derivatives, produced by the two main competing branches of the oxylipin pathway, the allene oxide synthase (AOS and hydroperoxide lyase (HPL branches, respectively. In addition to competition for substrates, these branch-pathway-derived metabolites have substantial overlap in regulation of gene expression. Past experiments to define the role of C(6-aldehydes in plant defense responses were biased towards the exogenous application of the synthetic metabolites or the use of genetic manipulation of HPL expression levels in plant genotypes with intact ability to produce the competing AOS-derived metabolites. To uncouple the roles of the C(6-aldehydes and jasmonates in mediating direct and indirect plant-defense responses, we generated Arabidopsis genotypes lacking either one or both of these metabolites. These genotypes were subsequently challenged with a phloem-feeding insect (aphids: Myzus persicae, an insect herbivore (leafminers: Liriomyza trifolii, and two different necrotrophic fungal pathogens (Botrytis cinerea and Alternaria brassicicola. We also characterized the volatiles emitted by these plants upon aphid infestation or mechanical wounding and identified hexenyl acetate as the predominant compound in these volatile blends. Subsequently, we examined the signaling role of this compound in attracting the parasitoid wasp (Aphidius colemani, a natural enemy of aphids. PRINCIPAL FINDINGS: This study conclusively establishes that jasmonates and C(6-aldehydes play distinct roles in plant defense responses. The jasmonates are indispensable metabolites in mediating the activation of direct plant-defense responses, whereas the C(6-aldehyes are not. On the other hand, hexenyl acetate, an acetylated C(6-aldehyde, is the predominant wound-inducible volatile signal that mediates indirect defense responses by directing tritrophic
CHILDREN'S MOVEMENT SKILLS WHEN PLAYING ACTIVE VIDEO GAMES.

Science.gov (United States)

Hulteen, Ryan M; Johnson, Tara M; Ridgers, Nicola D; Mellecker, Robin R; Barnett, Lisa M

2015-12-01

Active video games (AVGs) may be useful for movement skill practice. This study examined children's skill execution while playing Xbox Kinect™ and during movement skill assessment. Nineteen children (10 boys, 9 girls; M age=7.9 yr., SD=1.4) had their skills assessed before AVG play and then were observed once a week for 6 wk. while playing AVGs for 50 min. While AVG play showed evidence of correct skill performance (at least 30-50% of the time when playing table tennis, tennis, and baseball), nearly all skills were more correctly performed during skill assessment (generally more than 50% of the time). This study may help researchers to better understand the role AVGs could play in enhancing real life movement skills.
Play and Adversity: How the Playful Mammalian Brain Withstands Threats and Anxieties

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Siviy, Stephen M.

2010-01-01

Most mammals play, but they do so in a dangerous world. The dynamic relationship between the stresses created by their world and the activity of play helps to explain the evolution of play in mammals, as the author demonstrates in evidence garnered from experiments that introduce elements of fear to rats at play. The author describes the resulting…
Cultural influence on aims of inclusion of mothers in pre-school children's play

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Mihić-Lisul Ivana

2002-01-01

Full Text Available Child is introduced with the contents of culture at first through numerous influences culture has on family life, especially on defining parenting roles. Patriarchal culture, still strong in Yugoslavia, is full of norms that clearly define roles of elders and men, and excellently demarcates differences between father's and mother's role in bringing up their children, defined by the level of responsibility attached to parents in upbringing and educating a child. Research conducted in Novi Sad, Yugoslavia in January 2002, with the primary aim of diagnosing differences in frequency and quality of parent-pre-school children play concerning many relevant correlates, most important of which is the sex of the parent. Data show high distinctive quality difference in types and approaches to play in regard of the parent in question. Differences show that patriarchal culture's influence is still very strong. The results show that mothers are burdened with the higher level of responsibility, inevitably leading to higher parenting stress. The level of parenting stress can then influence the quality of meeting the requests put to parents, as well as raising level of general anxiety in all the activities concerning the child, therefore the play itself as well.
Time perspective as a predictor of massive multiplayer online role-playing game playing.

Science.gov (United States)

Lukavska, Katerina

2012-01-01

This article focuses on the relationship between the time perspective (TP) personality trait and massive multiplayer online role-playing game (MMORPG) playing. We investigate the question of frequency of playing. The TP was measured with Zimbardo's TP Inventory (ZTPI), which includes five factors-past negative, past positive, present hedonistic, present fatalistic, and future. The study used data from 154 MMORPG players. We demonstrated that TP partially explained differences within a group of players with respect to the frequency of playing. Significant positive correlations were found between present factors and the amount of time spent playing MMORPGs, and significant negative correlation was found between the future factor and the time spent playing MMORPGs. Our study also revealed the influence of future-present balance on playing time. Players who scored lower in future-present balance variables (their present score was relatively high compared with their future score) reported higher values in playing time. In contrast to referential studies on TP and drug abuse and gambling, present fatalistic TP was demonstrated to be a stronger predictor of extensive playing than present hedonistic TP, which opened the question of motivation for playing. The advantage of our study compared with other personality-based studies lies in the fact that TP is a stable but malleable personality trait with a direct link to playing behavior. Therefore, TP is a promising conceptual resource for excessive playing therapy.
The contribution of distinct subregions of the ventromedial frontal cortex to emotion, social behavior, and decision making.

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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.
Distinct transcriptomic changes in E14.5 mouse skeletal muscle lacking RYR1 or Cav1.1 converge at E18.5

Science.gov (United States)

Henry, Margit; Rotshteyn, Tamara; Brunn, Anna; Carstov, Mariana; Deckert, Martina; Hescheler, Jürgen; Sachinidis, Agapios; Pfitzer, Gabriele

2018-01-01

In skeletal muscle the coordinated actions of two mechanically coupled Ca2+ channels—the 1,4-dihydropyridine receptor (Cav1.1) and the type 1 ryanodine receptor (RYR1)–underlie the molecular mechanism of rapid cytosolic [Ca2+] increase leading to contraction. While both [Ca2+]i and contractile activity have been implicated in the regulation of myogenesis, less is known about potential specific roles of Cav1.1 and RYR1 in skeletal muscle development. In this study, we analyzed the histology and the transcriptomic changes occurring at E14.5 –the end of primary myogenesis and around the onset of intrauterine limb movement, and at E18.5 –the end of secondary myogenesis, in WT, RYR1-/-, and Cav1.1-/- murine limb skeletal muscle. At E14.5 the muscle histology of both mutants exhibited initial alterations, which became much more severe at E18.5. Immunohistological analysis also revealed higher levels of activated caspase-3 in the Cav1.1-/- muscles at E14.5, indicating an increase in apoptosis. With WT littermates as controls, microarray analyses identified 61 and 97 differentially regulated genes (DEGs) at E14.5, and 493 and 1047 DEGs at E18.5, in RYR1-/- and Cav1.1-/- samples, respectively. Gene enrichment analysis detected no overlap in the affected biological processes and pathways in the two mutants at E14.5, whereas at E18.5 there was a significant overlap of DEGs in both mutants, affecting predominantly processes linked to muscle contraction. Moreover, the E18.5 vs. E14.5 comparison revealed multiple genotype-specific DEGs involved in contraction, cell cycle and miRNA-mediated signaling in WT, neuronal and bone development in RYR1-/-, and lipid metabolism in Cav1.1-/- samples. Taken together, our study reveals discrete changes in the global transcriptome occurring in limb skeletal muscle from E14.5 to E18.5 in WT, RYR1-/- and Cav1.1-/- mice. Our results suggest distinct functional roles for RYR1 and Cav1.1 in skeletal primary and secondary myogenesis. PMID
Play and optimal welfare: Does play indicate the presence of positive affective states?

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Ahloy-Dallaire, Jamie; Espinosa, Julia; Mason, Georgia

2017-11-16

Play is commonly used to assess affective states in both humans and non-human animals. Play appears to be most common when animals are well-fed and not under any direct threats to fitness. Could play and playfulness therefore indicate pre-existing positive emotions, and thence optimal animal welfare? We examine this question by surveying the internal and external conditions that promote or suppress play in a variety of species, starting with humans. We find that negative affective states and poor welfare usually do suppress play (although there are notable exceptions where the opposite occurs). Furthermore, research in children suggests that beyond the frequency or total duration of play, poor welfare may additionally be reflected in qualitative aspects of this heterogeneous behaviour (e.g. display of solitary over social play; and the 'fragmentation' of play bouts) that are often overlooked in animals. There are surprisingly few studies of play in subjects with pre-existing optimal welfare or in unambiguously highly positive affective states, making it currently impossible to determine whether play can distinguish optimal or good welfare from merely neutral welfare. This therefore represents an important and exciting area for future research. Copyright © 2017 Elsevier B.V. All rights reserved.
Does Playing Pay? The Fitness-Effect of Free Play during Childhood

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Werner Greve

2014-04-01

Full Text Available Evolutionary developmental psychology claims that the sequences and processes of human development, in fact the mere fact of ontogeny itself, have to be viewed as evolutionary products. However, although the functional benefits of childish behavior (child playing for cognitive and emotional development have been shown repeatedly, claiming evolutionary adaptiveness of playing in childhood suggests that childish play supports evolutionary success in mature stages of development. This hypothesis is tested in a study with N = 134 adults (93 females; age range 20–66 years. Participants were asked to recollect their play experiences during childhood in detail, and to report their current developmental status with respect to several aspects of social success. Results show that the opportunity for and the promotion of free play in childhood significantly predict some indicators of social success. Additional analyses strive to explore mediating processes for this relationship. In particular, the mediating role of individual adaptivity (flexibility of goal adjustment is investigated. Results suggest that freely playing in childhood promotes developmental resources, in particular individual adaptivity in adulthood, which, in turn, promote developmental success.
Does playing pay? The fitness-effect of free play during childhood.

Science.gov (United States)

Greve, Werner; Thomsen, Tamara; Dehio, Cornelia

2014-04-29

Evolutionary developmental psychology claims that the sequences and processes of human development, in fact the mere fact of ontogeny itself, have to be viewed as evolutionary products. However, although the functional benefits of childish behavior (child playing) for cognitive and emotional development have been shown repeatedly, claiming evolutionary adaptiveness of playing in childhood suggests that childish play supports evolutionary success in mature stages of development. This hypothesis is tested in a study with N=134 adults (93 females; age range 20-66 years). Participants were asked to recollect their play experiences during childhood in detail, and to report their current developmental status with respect to several aspects of social success. Results show that the opportunity for and the promotion of free play in childhood significantly predict some indicators of social success. Additional analyses strive to explore mediating processes for this relationship. In particular, the mediating role of individual adaptivity (flexibility of goal adjustment) is investigated. Results suggest that freely playing in childhood promotes developmental resources, in particular individual adaptivity in adulthood, which, in turn, promote developmental success.
Efficient and Stable Carbon-coated Nickel Foam Cathodes for the Electro-Fenton Process

International Nuclear Information System (INIS)

Song, Shuqin; Wu, Mingmei; Liu, Yuhui; Zhu, Qiping; Tsiakaras, Panagiotis; Wang, Yi

2015-01-01

Highlights: • Carbon-coated nickel foam (C@NF) was prepared by cycle coating carbon process. • Ni leaching can be effectively controlled at C@NF4 (4 cycle coating times) cathode. • C@NF4 exhibits excellent electro-Fenton performance with desirable stability. • C@NF4 exhibits low energy consumption for DMP degradation. - Abstract: Carbon-coated nickel foam (C@NF) electrodes are prepared via a simple and effective method, hydrothermal-carbonization cycle coating process, characterized by scanning electron microscopy (SEM) with energy dispersive spectrometer (EDS) and employed as the electro-Fenton (E-Fenton) cathode for degrading dimethyl phthalate (DMP) in aqueous solution. For the sake of comparison, nickel foam (NF) electrode and the conventional E-Fenton cathode (graphite gas diffusion electrode (GDE)) are also tested and compared. Experimental results indicate that nickel leaching can be effectively controlled at C@NF4 cathode (4 times cycle coating process), having great significance for promoting the application of NF in E-Fenton system. Moreover, C@NF4 cathode still presents excellent and effective performance on DMP degradation. DMP can be completely degraded within 2 h at −0.5 V and the total organic carbon (TOC) removal reaches as high as 82.1 %, which is almost 3 times as high as that at graphite GDE. Futhermore, the current efficiency for H 2 O 2 generation at C@NF4 is enhanced by 12 times compared to that at NF, and consequently the energy consumption during DMP degradation at C@NF4 is obvious lower than that at both NF cathode and graphite GDE. From the obtained results it can be deduced that C@NF4 is promising to be an attractive alternative E-Fenton cathode for removing organic pollutants in wastewater
Endogenous ovarian hormones affect mitochondrial efficiency in cerebral endothelium via distinct regulation of PGC-1 isoforms.

Science.gov (United States)

Kemper, Martin F; Zhao, Yuanzi; Duckles, Sue P; Krause, Diana N

2013-01-01

Mitochondria support the energy-intensive functions of brain endothelium but also produce damaging-free radicals that lead to disease. Previously, we found that estrogen treatment protects cerebrovascular mitochondria, increasing capacity for ATP production while decreasing reactive oxygen species (ROS). To determine whether these effects occur specifically in endothelium in vivo and also explore underlying transcriptional mechanisms, we studied freshly isolated brain endothelial preparations from intact and ovariectomized female mice. This preparation reflects physiologic influences of circulating hormones, hemodynamic forces, and cell-cell interactions of the neurovascular unit. Loss of ovarian hormones affected endothelial expression of the key mitochondrial regulator family, peroxisome proliferator-activated receptor γ coactivator 1 (PGC-1), but in a unique way. Ovariectomy increased endothelial PGC-1α mRNA but decreased PGC-1β mRNA. The change in PGC-1β correlated with decreased mRNA for crucial downstream mitochondrial regulators, nuclear respiratory factor 1 and mitochondrial transcription factor A, as well as for ATP synthase and ROS protection enzymes, glutamate-cysteine ligase and manganese superoxide dismutase. Ovariectomy also decreased mitochondrial biogenesis (mitochondrial/nuclear DNA ratio). These results indicate ovarian hormones normally act through a distinctive regulatory pathway involving PGC-1β to support cerebral endothelial mitochondrial content and guide mitochondrial function to favor ATP coupling and ROS protection.
Child's Play: Therapist's Narrative

Science.gov (United States)

Reddy, Rajakumari P.; Hirisave, Uma

2014-01-01

Play has been recognized as an essential component to children's healthy development. Schools of play therapy differ philosophically and technically, but they all embrace the therapeutic and developmental properties of play. This case report is an illustration of how a 6-year-old child with emotional disorder was facilitated to express concerns in child-centered play therapy. The paper discusses the therapist's narration of the child's play. PMID:24860228

Short-term effects of playing computer games on attention.

Science.gov (United States)

Tahiroglu, Aysegul Yolga; Celik, Gonca Gul; Avci, Ayse; Seydaoglu, Gulsah; Uzel, Mehtap; Altunbas, Handan

2010-05-01

The main aim of the present study is to investigate the short-term cognitive effects of computer games in children with different psychiatric disorders and normal controls. One hundred one children are recruited for the study (aged between 9 and 12 years). All participants played a motor-racing game on the computer for 1 hour. The TBAG form of the Stroop task was administered to all participants twice, before playing and immediately after playing the game. Participants with improved posttest scores, compared to their pretest scores, used the computer on average 0.67 +/- 1.1 hr/day, while the average administered was measured at 1.6 +/- 1.4 hr/day and 1.3 +/- 0.9 hr/day computer use for participants with worse or unaltered scores, respectively. According to the regression model, male gender, younger ages, duration of daily computer use, and ADHD inattention type were found to be independent risk factors for worsened posttest scores. Time spent playing computer games can exert a short-term effect on attention as measured by the Stroop test.
MMTV-Wnt1 and -DeltaN89beta-catenin induce canonical signaling in distinct progenitors and differentially activate Hedgehog signaling within mammary tumors.

Directory of Open Access Journals (Sweden)

Brigitte Teissedre

Full Text Available Canonical Wnt/beta-catenin signaling regulates stem/progenitor cells and, when perturbed, induces many human cancers. A significant proportion of human breast cancer is associated with loss of secreted Wnt antagonists and mice expressing MMTV-Wnt1 and MMTV-DeltaN89beta-catenin develop mammary adenocarcinomas. Many studies have assumed these mouse models of breast cancer to be equivalent. Here we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin transgenes induce tumors with different phenotypes. Using axin2/conductin reporter genes we show that MMTV-Wnt1 and MMTV-DeltaN89beta-catenin activate canonical Wnt signaling within distinct cell-types. DeltaN89beta-catenin activated signaling within a luminal subpopulation scattered along ducts that exhibited a K18(+ER(-PR(-CD24(highCD49f(low profile and progenitor properties. In contrast, MMTV-Wnt1 induced canonical signaling in K14(+ basal cells with CD24/CD49f profiles characteristic of two distinct stem/progenitor cell-types. MMTV-Wnt1 produced additional profound effects on multiple cell-types that correlated with focal activation of the Hedgehog pathway. We document that large melanocytic nevi are a hitherto unreported hallmark of early hyperplastic Wnt1 glands. These nevi formed along the primary mammary ducts and were associated with Hedgehog pathway activity within a subset of melanocytes and surrounding stroma. Hh pathway activity also occurred within tumor-associated stromal and K14(+/p63(+ subpopulations in a manner correlated with Wnt1 tumor onset. These data show MMTV-Wnt1 and MMTV-DeltaN89beta-catenin induce canonical signaling in distinct progenitors and that Hedgehog pathway activation is linked to melanocytic nevi and mammary tumor onset arising from excess Wnt1 ligand. They further suggest that Hedgehog pathway activation maybe a critical component and useful indicator of breast tumors arising from unopposed Wnt1 ligand.
Distinct roles for RDE-1 and RDE-4 during RNA interference in Caenorhabditis elegans.

Science.gov (United States)

Parrish, S; Fire, A

2001-10-01

RNA interference (RNAi) is a cellular defense mechanism that uses double-stranded RNA (dsRNA) as a sequence-specific trigger to guide the degradation of homologous single-stranded RNAs. RNAi is a multistep process involving several proteins and at least one type of RNA intermediate, a population of small 21-25 nt RNAs (called siRNAs) that are initially derived from cleavage of the dsRNA trigger. Genetic screens in Caenorhabditis elegans have identified numerous mutations that cause partial or complete loss of RNAi. In this work, we analyzed cleavage of injected dsRNA to produce the initial siRNA population in animals mutant for rde-1 and rde-4, two genes that are essential for RNAi but that are not required for organismal viability or fertility. Our results suggest distinct roles for RDE-1 and RDE-4 in the interference process. Although null mutants lacking rde-1 show no phenotypic response to dsRNA, the amount of siRNAs generated from an injected dsRNA trigger was comparable to that of wild-type. By contrast, mutations in rde-4 substantially reduced the population of siRNAs derived from an injected dsRNA trigger. Injection of chemically synthesized 24- or 25-nt siRNAs could circumvent RNAi resistance in rde-4 mutants, whereas no bypass was observed in rde-1 mutants. These results support a model in which RDE-4 is involved before or during production of siRNAs, whereas RDE-1 acts after the siRNAs have been formed.
Structure of N-Terminal Domain of NPC1 Reveals Distinct Subdomains for Binding and Transfer of Cholesterol

Energy Technology Data Exchange (ETDEWEB)

Kwon, Hyock Joo; Abi-Mosleh, Lina; Wang, Michael L.; Deisenhofer, Johann; Goldstein, Joseph L.; Brown, Michael S.; Infante, Rodney E.; (UTSMC)

2010-09-21

LDL delivers cholesterol to lysosomes by receptor-mediated endocytosis. Exit of cholesterol from lysosomes requires two proteins, membrane-bound Niemann-Pick C1 (NPC1) and soluble NPC2. NPC2 binds cholesterol with its isooctyl side chain buried and its 3{beta}-hydroxyl exposed. Here, we describe high-resolution structures of the N-terminal domain (NTD) of NPC1 and complexes with cholesterol and 25-hydroxycholesterol. NPC1(NTD) binds cholesterol in an orientation opposite to NPC2: 3{beta}-hydroxyl buried and isooctyl side chain exposed. Cholesterol transfer from NPC2 to NPC1(NTD) requires reorientation of a helical subdomain in NPC1(NTD), enlarging the opening for cholesterol entry. NPC1 with point mutations in this subdomain (distinct from the binding subdomain) cannot accept cholesterol from NPC2 and cannot restore cholesterol exit from lysosomes in NPC1-deficient cells. We propose a working model wherein after lysosomal hydrolysis of LDL-cholesteryl esters, cholesterol binds NPC2, which transfers it to NPC1(NTD), reversing its orientation and allowing insertion of its isooctyl side chain into the outer lysosomal membranes.
Play Therapy. ERIC Digest.

Science.gov (United States)

Landreth, Garry; Bratton, Sue

Play therapy is based on developmental principles and, thus, provides, through play, developmentally appropriate means of expression and communication for children. Therefore, skill in using play therapy is an essential tool for mental health professionals who work with children. Therapeutic play allows children the opportunity to express…
The role of play

NARCIS (Netherlands)

Schouten, B.A.M.

2011-01-01

Play is seen as an activity that is fun, voluntary, offers escape, and is fundamentally exciting. Play is however, more than that; it is a working model of flexibility! There is a vital link between play, psychological development and learning. Moreover, the importance of play has gained importance
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
Blue copper model complexes with distorted tetragonal geometry acting as effective electron-transfer mediators in dye-sensitized solar cells.

Science.gov (United States)

Hattori, Shigeki; Wada, Yuji; Yanagida, Shozo; Fukuzumi, Shunichi

2005-07-06

The electron self-exchange rate constants of blue copper model complexes, [(-)-sparteine-N,N'](maleonitriledithiolato-S,S')copper ([Cu(SP)(mmt)])(0/)(-), bis(2,9-dimethy-1,10-phenanthroline)copper ([Cu(dmp)(2)](2+/+)), and bis(1,10-phenanthroline)copper ([Cu(phen)(2)](2+/+)) have been determined from the rate constants of electron transfer from a homologous series of ferrocene derivatives to the copper(II) complexes in light of the Marcus theory of electron transfer. The resulting electron self-exchange rate constant increases in the order: [Cu(phen)(2)](2+/+) geometry. The dye-sensitized solar cells (DSSC) were constructed using the copper complexes as redox couples to compare the photoelectrochemical responses with those using the conventional I(3)(-)/I(-) couple. The light energy conversion efficiency (eta) values under illumination of simulated solar light irradiation (100 mW/cm(2)) of DSSCs using [Cu(phen)(2)](2+/+), [Cu(dmp)(2)](2+/+), and [Cu(SP)(mmt)](0/)(-) were recorded as 0.1%, 1.4%, and 1.3%, respectively. The maximum eta value (2.2%) was obtained for a DSSC using the [Cu(dmp)(2)](2+/+) redox couple under the light irradiation of 20 mW/cm(2) intensity, where a higher open-circuit voltage of the cell was attained as compared to that of the conventional I(3)(-)/I(-) couple.
Design and evaluation of a personal robot playing a self-management education game with children with diabetes type 1

NARCIS (Netherlands)

Blanson Henkemans, O.A.; Bierman, B.P.B.; Janssen, J.; Looije, R.; Neerincx, M.A.; Dooren, M.M.M. van; Vries, J.L.E. de; Burg, G.J. van der; Huisman, S.D.

2017-01-01

Objective To assess the effects of a personal robot, providing diabetes self-management education in a clinical setting on the pleasure, engagement and motivation to play a diabetes quiz of children (7–12) with type 1 diabetes mellitus (T1DM), and on their acquisition of knowledge about their
Plectin regulates the signaling and trafficking of the HIV-1 co-receptor CXCR4 and plays a role in HIV-1 infection

International Nuclear Information System (INIS)

Ding Yun; Zhang Li; Goodwin, J. Shawn; Wang Ziqing; Liu Bingdong; Zhang Jingwu; Fan Guohuang

2008-01-01

The CXC chemokine CXCL12 and its cognate receptor CXCR4 play an important role in inflammation, human immunodeficiency virus (HIV) infection and cancer metastasis. The signal transduction and intracellular trafficking of CXCR4 are involved in these functions, but the underlying mechanisms remain incompletely understood. In the present study, we demonstrated that the CXCR4 formed a complex with the cytolinker protein plectin in a ligand-dependent manner in HEK293 cells stably expressing CXCR4. The glutathione-S-transferase (GST)-CXCR4 C-terminal fusion proteins co-precipitated with the full-length and the N-terminal fragments of plectin isoform 1 but not with the N-terminal deletion mutants of plectin isoform 1, thereby suggesting an interaction between the N-terminus of plectin and the C-terminus of CXCR4. This interaction was confirmed by confocal microscopic reconstructions showing co-distribution of these two proteins in the internal vesicles after ligand-induced internalization of CXCR4 in HEK293 cells stably expressing CXCR4. Knockdown of plectin with RNA interference (RNAi) significantly inhibited ligand-dependent CXCR4 internalization and attenuated CXCR4-mediated intracellular calcium mobilization and activation of extracellular signal regulated kinase 1/2 (ERK1/2). CXCL12-induced chemotaxis of HEK293 cells stably expressing CXCR4 and of Jurkat T cells was inhibited by the plectin RNAi. Moreover, CXCR4 tropic HIV-1 infection in MAGI (HeLa-CD4-LTR-Gal) cells was inhibited by the RNAi of plectin. Thus, plectin appears to interact with CXCR4 and plays an important role in CXCR4 signaling and trafficking and HIV-1 infection
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.
Group play

DEFF Research Database (Denmark)

Tychsen, Anders; Hitchens, Michael; Brolund, Thea

2008-01-01

Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects of the v......Role-playing games (RPGs) are a well-known game form, existing in a number of formats, including tabletop, live action, and various digital forms. Despite their popularity, empirical studies of these games are relatively rare. In particular there have been few examinations of the effects...... of the various formats used by RPGs on the gaming experience. This article presents the results of an empirical study, examining how multi-player tabletop RPGs are affected as they are ported to the digital medium. Issues examined include the use of disposition assessments to predict play experience, the effect...... of group dynamics, the influence of the fictional game characters and the comparative play experience between the two formats. The results indicate that group dynamics and the relationship between the players and their digital characters, are integral to the quality of the gaming experience in multiplayer...
Potentialities of a Membrane Reactor with Laccase Grafted Membranes for the Enzymatic Degradation of Phenolic Compounds in Water

Directory of Open Access Journals (Sweden)

Vorleak Chea

2014-10-01

Full Text Available This paper describes the degradation of phenolic compounds by laccases from Trametes versicolor in an enzymatic membrane reactor (EMR. The enzymatic membranes were prepared by grafting laccase on a gelatine layer previously deposited onto α-alumina tubular membranes. The 2,6-dimethoxyphenol (DMP was selected from among the three different phenolic compounds tested (guaiacol, 4-chlorophenol and DMP to study the performance of the EMR in dead end configuration. At the lowest feed substrate concentration tested (100 mg·L−1, consumption increased with flux (up to 7.9 × 103 mg·h−1·m−2 at 128 L·h−1·m−2, whereas at the highest substrate concentration (500 mg·L−1, it was shown that the reaction was limited by the oxygen content.
Examining Motivations to Play Pokémon GO and Their Influence on Perceived Outcomes and Physical Activity.

Science.gov (United States)

Marquet, Oriol; Alberico, Claudia; Adlakha, Deepti; Hipp, J Aaron

2017-10-24

Pokémon GO is the most played augmented reality game in history. With more than 44 million players at the peak of its popularity, the game has sparked interest on its effects on the young population's health. This pilot study examined motivations to start playing Pokémon GO among a sample of US college students, and how motivations were associated with perceived outcomes of the playing experience and physical activity derived while playing. In November 2016, we asked a sample of 47 US college students (all Pokémon GO players) to complete online surveys and install an ecological momentary assessment (EMA) tool and step counter on their smartphones. The EMA tool prompted a set of questions on playing behavior and physical activity, 3 times per day (12:00 PM, 7:00 PM, and 10:00 PM), for 7 days. We used a factorial analysis to identify 3 distinctive groups of players based on their motivations to start playing Pokémon GO. We tested differences across motivation groups related to 5 unique outcomes using 1-way analysis of variance. We extracted 3 interpretable factors from the clustering of motivations to start playing Pokémon GO: Pokémon and video game fans (n=26, 55% of the sample), physical activity seekers (n=8, 17%), and curious & social (n=13, 28%). The clusters differed significantly on the enjoyment of different aspects of the game, particularly battling, discovering new places, and meeting new people, as well as differences in agreement that playing improved mood and made them more social. Days when playing Pokémon GO were associated with higher number of steps reported at the end of the day, especially among physical activity seekers, but also for Pokémon and video game fans. All groups perceived traffic as a major threat to playing. Days during which Pokémon GO was played were positively associated with a set of beneficial health behaviors, including higher physical activity levels, more socialization, and better mood. Results, however, depended on
Eat lunch first or play first? Inconsistent associations with fruit and vegetable consumption in elementary school.

Science.gov (United States)

Fenton, Keenan; Rosen, Nila J; Wakimoto, Patricia; Patterson, Tracey; Goldstein, Lauren H; Ritchie, Lorrene D

2015-04-01

Scheduling play before eating lunch has been suggested as a relatively simple environmental strategy to increase fruit and vegetable (FV) intake among elementary school students. However, the few small studies to date have had mixed findings. The primary aim of this observational study was to evaluate the possible relationship between the relative order of play and eating and students' lunch intake of FV. A secondary aim was to examine whether any differences existed in this relationship by student sex, ethnicity, language spoken at home, and school lunch source. A diary-assisted 24-hour recall was collected during the 2011-2012 school year from 2,167 fourth- and fifth-graders attending 31 elementary schools in California. The association of play before eating with FV intake was estimated using Generalized Estimation Equations. Overall, lunch FV intake was not significantly higher for students who had a play-before-eating vs a play-after-eating lunch schedule at school. However, variables included in the model showed significant interaction with play before eating, resulting in the need for separate effect estimates for distinct strata based on sex, ethnicity, language spoken at home, and school lunch source. For 10 of the 16 strata, no significant effect of play before eating was observed on lunch FV intake, while increases in intake were observed in four strata and decreases in two strata. Before rescheduling play before eating for the purpose of improving student FV intake, additional research is recommended. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.
Why do Dolphins Play?

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Stan A. Kuczaj

2014-05-01

Full Text Available Play is an important aspect of dolphin life, perhaps even an essential one. Play provides opportunities for dolphin calves to practice and perfect locomotor skills, including those involved in foraging and mating strategies and behaviors. Play also allows dolphin calves to learn important social skills and acquire information about the characteristics and predispositions of members of their social group, particularly their peers. In addition to helping dolphin calves learn how to behave, play also provides valuable opportunities for them to learn how to think. The ability to create and control play contexts enables dolphins to create novel experiences for themselves and their playmates under relatively safe conditions. The behavioral variability and individual creativity that characterize dolphin play yield ample opportunities for individual cognitive development as well as social learning, and sometimes result in innovations that are reproduced by other members of the group. Although adults sometimes produce innovative play, calves are the primary source of such innovations. Calves are also more likely to imitate novel play behaviors than are adults, and so calves contribute significantly to both the creation and transmission of novel play behaviors within a group. Not unexpectedly, then, the complexity of dolphin play increases with the involvement of peers. As a result, the opportunity to observe and/or interact with other dolphin calves enhances the effects of play on the acquisition and maintenance of flexible problem solving skills, the emergence and strengthening of social and communicative competencies, and the establishment of social relationships. It seems that play may have evolved to help young dolphins learn to adapt to novel situations in both their physical and social worlds, the beneficial result being a set of abilities that increases the likelihood that an individual survives and reproduces.
The Play of Psychotherapy

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Marks-Tarlow, Terry

2012-01-01

The author reviews the role of play within psychotherapy. She does not discuss the formal play therapy especially popular for young children, nor play from the Jungian perspective that encourages the use of the sand tray with adults. Instead, she focuses on the informal use of play during psychotherapy as it is orchestrated intuitively. Because…
Towards a playful organization ideal-type : Values of a playful organizational culture

NARCIS (Netherlands)

Warmelink, H.J.G.

2011-01-01

Numerous organizations have embarked on playful endeavors such as serious gaming (playing games with a learning/training purpose) and ‘gamification’ (applying game technology and principles to make existing practices more game-like). One could consequently theorize about the dawn of playful or
Playing with Mathematics: Play in Early Childhood as a Context for Mathematical Learning

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Mathematics Education Research Group of Australasia, 2010

2010-01-01

Play is an essential part of young children's lives. This symposium highlights the integral role of play in young children's mathematics learning and examines the teacher's role in facilitating and extending this. Papers examine key tenets of play, contributing to theoretical understandings and presenting data on teacher's perceptions of play and…
Figure-ground segregation requires two distinct periods of activity in V1: a transcranial magnetic stimulation study.

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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.

17beta-estradiol promotes the odonto/osteogenic differentiation of stem cells from apical papilla via mitogen-activated protein kinase pathway.

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Li, Yao; Yan, Ming; Wang, Zilu; Zheng, Yangyu; Li, Junjun; Ma, Shu; Liu, Genxia; Yu, Jinhua

2014-11-17

Estrogen plays an important role in the osteogenic differentiation of mesenchymal stem cells, while stem cells from apical papilla (SCAP) can contribute to the formation of dentin/bone-like tissues. To date, the effects of estrogen on the differentiation of SCAP remain unclear. SCAP was isolated and treated with 10⁻⁷ M 17beta-estradiol (E2). The odonto/osteogenic potency and the involvement of mitogen-activated protein kinase (MAPK) signaling pathway were subsequently investigated by using methyl-thiazolyl-tetrazolium (MTT) assay, and other methods. MTT and flow cytometry results demonstrated that E2 treatment had no effect on the proliferation of SCAP in vitro, while alkaline phosphatase (ALP) assay and alizarin red staining showed that E2 can significantly promote ALP activity and mineralization ability in SCAP. Real-time reverse transcription polymerase chain reaction (RT-PCR) and western blot assay revealed that the odonto/osteogenic markers (ALP, DMP1/DMP1, DSPP/DSP, RUNX2/RUNX2, OSX/OSX and OCN/OCN) were significantly upregulated in E2-treated SCAP. In addition, the expression of phosphor-p38 and phosphor-JNK in these stem cells was enhanced by E2 treatment, as was the expression of the nuclear downstream transcription factors including phosphor-Sp1, phosphor-Elk-1, phosphor-c-Jun and phosphor-c-Fos, indicating the activation of MAPK signaling pathway during the odonto/osteogenic differentiation of E2-treated SCAP. Conversely, the differentiation of E2-treated SCAP was inhibited in the presence of MAPK specific inhibitors. The ondonto/osteogenic differentiation of SCAP is enhanced by 10⁻⁷ M 17beta-estradiol via the activation of MAPK signaling pathway.
Bmi-1 plays a critical role in the protection from acute tubular necrosis by mobilizing renal stem/progenitor cells

International Nuclear Information System (INIS)

Lv, Xianhui; Yu, Zhenzhen; Xie, Chunfeng; Dai, Xiuliang; Li, Qing; Miao, Dengshun; Jin, Jianliang

2017-01-01

The regeneration of injured tubular cell occurs primarily from intrinsic renal stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal, differentiation and aging of multiple adult stem cells and progenitor cells. Bmi-1 was rapidly elevated in the induction of adult kidney regeneration by renal injury. To determine whether Bmi-1 maintained mobilization of RSCs in the protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild type (WT) and Bmi-1-deficient (Bmi-1 −/− ) mice. Their ATN phenotypes were analyzed; CD24 and CD133 double positive (CD24 + CD133 + ) cells were measured; and the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected. We found that CD24 + CD133 + RSCs were mobilized in WT ATN mice with the increased expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN.
The Correlation of Playing Role-playing Games and Students' Reading Comprehension of Narrative Text

OpenAIRE

Putra, Praditya

2014-01-01

This research investigates the correlation of playing Role-Playing Games and students' reading comprehension of narrative text. Thirty (30) ninth grade students who play Role-Playing Games participated in this study. Their frequency in playing Role-Playing Games and their ability in reading comprehension of narrative text are analyzed by using correlation research design. Correlation research design was used in this study in order to find out the tendency of relation between students' frequen...
Distinct pigmentary and melanocortin 1 receptor-dependent components of cutaneous defense against ultraviolet radiation.

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Craig S April

2007-01-01

Full Text Available Genetic variation at the melanocortin 1 receptor (MC1R is an important risk factor for developing ultraviolet (UV radiation-induced skin cancer, the most common form of cancer in humans. The underlying mechanisms by which the MC1R defends against UV-induced skin cancer are not known. We used neonatal mouse skin (which, like human skin, contains a mixture of melanocytes and keratinocytes to study how pigment cells and Mc1r genotype affect the genome-level response to UV radiation. Animals without viable melanocytes (Kit(W-v/Kit(W-v or animals lacking a functional Mc1r (Mc1r(e/Mc1r(e were exposed to sunburn-level doses of UVB radiation, and the patterns of large-scale gene expression in the basal epidermis were compared to each other and to nonmutant animals. Our analysis revealed discrete Kit- and Mc1r-dependent UVB transcriptional responses in the basal epidermis. The Kit-dependent UVB response was characterized largely by an enrichment of oxidative and endoplasmic reticulum stress genes, highlighting a distinctive role for pigmented melanocytes in mediating antioxidant defenses against genotoxic stresses within the basal epidermal environment. By contrast, the Mc1r-dependent UVB response contained an abundance of genes associated with regulating the cell cycle and oncogenesis. To test the clinical relevance of these observations, we analyzed publicly available data sets for primary melanoma and melanoma metastases and found that the set of genes specific for the Mc1r-dependent UVB response was able to differentiate between different clinical subtypes. Our analysis also revealed that the classes of genes induced by UVB differ from those repressed by UVB with regard to their biological functions, their overall number, and their size. The findings described here offer new insights into the transcriptional nature of the UV response in the skin and provide a molecular framework for the underlying mechanisms by which melanocytes and the Mc1r
A chemical-genetic strategy reveals distinct temporal requirements for SAD-1 kinase in neuronal polarization and synapse formation

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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.
Role-Playing Mitosis.

Science.gov (United States)

Wyn, Mark A.; Stegink, Steven J.

2000-01-01

Introduces a role playing activity that actively engages students in the learning process of mitosis. Students play either chromosomes carrying information, or cells in the cell membrane. (Contains 11 references.) (Author/YDS)
Corticosteroid receptors adopt distinct cyclical transcriptional signatures.

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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.
Distinct mechanisms underlying tolerance to intermittent and constant hypoxia in Drosophila melanogaster.

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Priti Azad

Full Text Available BACKGROUND: Constant hypoxia (CH and intermittent hypoxia (IH occur during several pathological conditions such as asthma and obstructive sleep apnea. Our research is focused on understanding the molecular mechanisms that lead to injury or adaptation to hypoxic stress using Drosophila as a model system. Our current genome-wide study is designed to investigate gene expression changes and identify protective mechanism(s in D. melanogaster after exposure to severe (1% O(2 intermittent or constant hypoxia. METHODOLOGY/PRINCIPAL FINDINGS: Our microarray analysis has identified multiple gene families that are up- or down-regulated in response to acute CH or IH. We observed distinct responses to IH and CH in gene expression that varied in the number of genes and type of gene families. We then studied the role of candidate genes (up-or down-regulated in hypoxia tolerance (adult survival for longer periods (CH-7 days, IH-10 days under severe CH or IH. Heat shock proteins up-regulation (specifically Hsp23 and Hsp70 led to a significant increase in adult survival (as compared to controls of P-element lines during CH. In contrast, during IH treatment the up-regulation of Mdr49 and l(208717 genes (P-element lines provided survival advantage over controls. This suggests that the increased transcript levels following treatment with either paradigm play an important role in tolerance to severe hypoxia. Furthermore, by over-expressing Hsp70 in specific tissues, we found that up-regulation of Hsp70 in heart and brain play critical role in tolerance to CH in flies. CONCLUSIONS/SIGNIFICANCE: We observed that the gene expression response to IH or CH is specific and paradigm-dependent. We have identified several genes Hsp23, Hsp70, CG1600, l(208717 and Mdr49 that play an important role in hypoxia tolerance whether it is in CH or IH. These data provide further clues about the mechanisms by which IH or CH lead to cell injury and morbidity or adaptation and survival.
The Power of Outdoor Play and Play in Natural Environments

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Kemple, Kristen M.; Oh, JiHyun; Kenney, Elizabeth; Smith-Bonahue, Tina

2016-01-01

Young children's outdoor play serves important and diverse purposes, including physical exercise and opportunities for growth in all developmental areas. Unfortunately, the amount of time that children spend engaged in unstructured, child-directed outdoor play has diminished significantly in the past generation. In this article, the authors…
Identification of chemicals emitted by calling males of the Sapote fruit fly, Anastrepha serpentina.

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Robacker, David C; Aluja, Martin; Bartelt, Robert J; Patt, Joseph

2009-05-01

Emissions from sexually active Anastrepha serpentina males were collected by solid-phase microextraction. Calling behavior of wild-type males showed no clear peak during the day, except that it was evident less frequently immediately after daybreak and just before dark. Calling by laboratory males was highest between 8 and 11 h after onset of the photophase, and mating by wild flies occurred mostly between 6 and 10 h after onset of the photophase. Two major components of male emissions were identified as 2,5-dimethylpyrazine (DMP) and 3,6-dihydro-2,5-dimethylpyrazine (DHDMP). DHDMP was synthesized, and the identity of the natural product confirmed by comparison of gas chromatographic retention times and mass spectrum. Emissions of DMP and DHMP were greatest during peak calling behavior, with males emitting up to 1.8 and 3.3 microg/h of DMP and DHDMP, respectively. A minor component, which did not vary with time of day, was identified as 2,3,5-trimethylpyrazine. To our knowledge, this is the first report of 3,6-dihydro-2,5-dimethylpyrazine in nature.
[Play therapy in hospital].

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Gold, Katharina; Grothues, Dirk; Leitzmann, Michael; Gruber, Hans; Melter, Michael

2012-01-01

The following article presents an overview of current research studies on play therapy in the hospital. It highlights individual diagnoses for which play therapy has shown reasonable success. The aim of this review is to describe the current status of the scientific debate on play therapy for sick children in order to allow conclusions regarding the indications for which play therapy is or might be useful.
The Striatal Balancing Act in Drug Addiction: Distinct Roles of Direct and Indirect Pathway Medium Spiny Neurons

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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.
Evidence for distinct roles of the SEPALLATA gene LEAFY HULL STERILE1 in Eleusine indica and Megathyrsus maximus (Poaceae).

Science.gov (United States)

Reinheimer, Renata; Malcomber, Simon T; Kellogg, Elizabeth A

2006-01-01

LEAFY HULL STERILE1 (LHS1) is an MIKC-type MADS-box gene in the SEPALLATA class. Expression patterns of LHS1 homologs vary among species of grasses, and may be involved in determining palea and lemma morphology, specifying the terminal floret of the spikelet, and sex determination. Here we present LHS1 expression data from Eleusine indica (subfamily Chloridoideae) and Megathyrsus maximus (subfamily Panicoideae) to provide further insights into the hypothesized roles of the gene. E. indica has spikelets with three to eight florets that mature acropetally; E. indica LHS1 (EiLHS1) is expressed in the palea and lemma of all florets. In contrast, M. maximus has spikelets with two florets that mature basipetally; M. maximus LHS1 (MmLHS1) is expressed in the palea and lemma of the distal floret only. These data are consistent with the hypothesis that LHS1 plays a role in determining palea and lemma morphology and specifies the terminal floret of basipetally maturing grass spikelets. However, LHS1 expression does not correlate with floret sex expression; MmLHS1 is restricted to the bisexual distal floret, whereas EiLHS1 is expressed in both sterile and bisexual floret meristems. Phylogenetic analyses reconstruct a complex pattern of LHS1 expression evolution in grasses. LHS1 expression within the gynoecium has apparently been lost twice, once before diversification of a major clade within tribe Paniceae, and once in subfamily Chloridoideae. These data suggest that LHS1 has multiple roles during spikelet development and may have played a role in the diversification of spikelet morphology.
Playing God in Frankenstein's Footsteps: Synthetic Biology and the Meaning of Life.

Science.gov (United States)

van den Belt, Henk

2009-12-01

The emergent new science of synthetic biology is challenging entrenched distinctions between, amongst others, life and non-life, the natural and the artificial, the evolved and the designed, and even the material and the informational. Whenever such culturally sanctioned boundaries are breached, researchers are inevitably accused of playing God or treading in Frankenstein's footsteps. Bioethicists, theologians and editors of scientific journals feel obliged to provide an authoritative answer to the ambiguous question of the 'meaning' of life, both as a scientific definition and as an explication with wider existential connotations. This article analyses the arguments mooted in the emerging societal debates on synthetic biology and the way its practitioners respond to criticism, mostly by assuming a defiant posture or professing humility. It explores the relationship between the 'playing God' theme and the Frankenstein motif and examines the doctrinal status of the 'playing God' argument. One particularly interesting finding is that liberal theologians generally deny the religious character of the 'playing God' argument-a response which fits in with the curious fact that this argument is used mainly by secular organizations. Synthetic biology, it is therefore maintained, does not offend so much the God of the Bible as a deified Nature. While syntheses of artificial life forms cause some vague uneasiness that life may lose its special meaning, most concerns turn out to be narrowly anthropocentric. As long as synthetic biology creates only new microbial life and does not directly affect human life, it will in all likelihood be considered acceptable.
Playing with the city

DEFF Research Database (Denmark)

Tosca, Susana; Marquez, Israel

2017-01-01

In this paper we introduce and describe the phenomenon of videogame street art as a specific kind of street art. We consider its materiality and significance, and conceptualize it in the light of a double manifestation of play: the playful appropriation of the city by the artist and the fact...... that street art encapsulates the act of playing videogames in a visual form. Digital play spills out of our computer screens and occupies the urban space with the explicit intention of involving spectators, who are invited to play in symbolic ways that actualize nostalgic memories of gaming and can be related...
Expressivity in Open-ended Constructive Play: Building and Playing Musical Lego Instruments

DEFF Research Database (Denmark)

Jakobsen, Kasper; Stougaard, Jeppe; Petersen, Marianne Graves

2016-01-01

This paper presents the findings from a case study in designing for open-ended constructive play for children. The study is based on a workshop where more that 150 children in ages 3-13 built and played their own musical instruments from Lego. The children used different sensors for playing...
To Play or Not to Play: Diverse Motives for Latino and Euro-American Parent-Child Play in a Children's Museum

Science.gov (United States)

DiBianca Fasoli, Allison

2014-01-01

A popular social discourse in the United States is that play is important for children's learning and that parental involvement maximizes play's learning potential. Past research has concluded that parents who hold this view of play are more likely to play with their children than those who do not. This study investigated the prevalence…
Pentacene on Au(1 1 1), Ag(1 1 1) and Cu(1 1 1): From physisorption to chemisorption.

Science.gov (United States)

Lu, Meng-Chao; Wang, Rong-Bin; Yang, Ao; Duhm, Steffen

2016-03-09

We measured the electronic and the molecular surface structure of pentacene deposited on the (1 1 1)-surfaces of coinage metals by means of ultraviolet photoelectron spectroscopy (UPS) and low-energy electron diffraction (LEED). Pentacene is almost flat-lying in monolayers on all three substrates and highly ordered on Au(1 1 1) and on Cu(1 1 1). On Ag(1 1 1), however, weak chemisorption leads to almost disordered monolayers, both, at room temperature and at 78 K. On Cu(1 1 1) pentacene is strongly chemisorbed and the lowest unoccupied molecular orbital becomes observable in UPS by a charge transfer from the substrate. On Ag(1 1 1) and Cu(1 1 1) multilayers adopt a tilted orientation and a high degree of crystallinity. On Au(1 1 1), most likely, also in multilayers the molecular short and long axes are parallel to the substrate, leading to a distinctively different electronic structure than on Ag(1 1 1) and Cu(1 1 1). Overall, it could be demonstrated that the substrate not only determines the geometric and electronic characteristics of molecular monolayer films but also plays a crucial role for multilayer film growth.
Playing Videogames: The Electronic Friend.

Science.gov (United States)

Selnow, Gary W.

1984-01-01

Concluded that the children in this study (ages 10-14) played video games in arcades for some of the same reasons they watched television: (1) escape; (2) a sense of personal involvement in the action; and (3) a source of or substitute for companionship. (PD)
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

Disneyization: A framework for understanding illicit drug use in bounded play spaces.

Science.gov (United States)

Turner, Tim

2018-05-17

This paper combines evidence from an ethnographic study of illicit drug use amongst tourists in Ibiza with Bryman's (2004) theoretical model of Disneyization. The principal aim was to construct a new conceptual framework that may help scholars, practitioners and policy makers make sense of dynamic patterns of illegal drug use across bounded play spaces such as tourist resorts, music festivals and nightclubs. Ethnographic fieldwork employing a grounded theory design was undertaken over three summers in tourist locations on the Balearic island of Ibiza, including nightclubs, bars, cafes, beaches, airports and hotels. Field notes from participant observation were supplemented with data from semi-structured interviews (n = 56) and secondary sources gathered from tourist marketing. The framework of Disneyization has been discussed in terms of 5 constructs: theming, hybrid consumption, branding, performative labour and atmospheres; each having a specific role in relation to understanding illicit drug use in bounded play spaces. Thus: Theming sets the stage, by physically and symbolically demarcating space with indelible themes of hedonism that open up the possibility of illicit drug use. Hybrid-consumption blurs the distinction between legal and illegal forms of intoxication, making the trading and consumption of illegal drugs appear like a natural feature of the consumer space. Branding demonstrates how participants construct intricate hierarchies of taste and credibility related to drug of choice. Performative labour re-enforces hybrid consumption, with participants working in the bounded play spaces of Ibiza immersed within the illicit drug market. Atmospheres represents the alchemic synergy of bounded play space and is important to understanding illicit drug use as a sensorial, deeply immersive but transitory experience. This research offers Disneyization as a new conceptual framework for making sense of deeply complex spatial, socio-cultural, psychological and
Social conformity despite individual preferences for distinctiveness.

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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.
Systematic observation of play behavior in autistic children.

Science.gov (United States)

Black, M; Freeman, B J; Montgomery, J

1975-12-01

The play behavior, defined as interaction with peers and objects, of five autistic children was systematically observed in four environments, i.e., a stark environment, a theraplay unit, a playroom, and an outside play deck. The preliminary results suggested that (1) with some children environment has little or no effect on their play behavior; (2) with multiple objects, autistic children frequently related to the objects rather than to their peers; (3) object play was most frequently at the manipulative stage and often included repetitive and negative behavior; (4) within a confined space with no objects present, autistic children frequently engaged in solitary repetitive behavior; and (5) within a confined space designed to facilitate a movement flow (theraplay), autistic children modeled and imitated and were involved in gross motor play together.
Facilitating play through communication: significance of teeth exposure in the gorilla play face.

Science.gov (United States)

Waller, Bridget M; Cherry, Lyndsay

2012-02-01

Primate facial expressions (FEs) likely play an important role in primate society: through facial signals, individuals can potentially send and receive information and may benefit from coordinating their behavior accordingly. Many primates use a relaxed open mouth (ROM) facial display or “play face” (PF) during play behavior, where the mouth is open but teeth are covered. In addition to this conventional PF, however, Western Lowland gorillas (Gorilla gorilla gorilla) also use a full PF where the upper teeth are exposed. As the teeth are similarly exposed in the bared-teeth expression (which is a signal of appeasement, submission and/or affiliation), the full PF may be a blend of the PF and bared-teeth face, and have a different signal function to the PF alone. Focal animal sampling of captive Western Lowland gorillas (N=10) showed that the full PF was more often observed in intense rather than gentle play, and intense play bouts that featured the full PF were longer than those that featured only the PF. Both expressions were associated with an increase in affinitive behavior between sender and receiver postplay, but only the full PF was associated with an increase higher than that of play alone. Overall, the findings suggest that the full PF has an additional role in coordinating and maintaining play, possibly though reducing uncertainty in the receiver and confirming that play is only play.
Playfulness, Imagination, and Creativity in Play with Toys: A Cultural-Historical Approach

Science.gov (United States)

Møller, Signe Juhl

2016-01-01

The aim of this article is to present a wholeness perspective on the relation between creative imagination and children's activity when playing with toys. This is explored through a case retrieved from a 4-month experimental research project, specifically from a social fantasy play session. In order to analyse and examine children's play, the…
Playing with the Multiple Intelligences: How Play Helps Them Grow

Science.gov (United States)

Eberle, Scott G.

2011-01-01

Howard Gardner first posited a list of "multiple intelligences" as a liberating alternative to the assumptions underlying traditional IQ testing in his widely read study "Frames of Mind" (1983). Play has appeared only in passing in Gardner's thinking about intelligence, however, even though play instructs and trains the verbal, interpersonal,…
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.
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.
Play the Mosquito Game

Science.gov (United States)

... and Work Teachers' Questionnaire Malaria Play the Mosquito Game Play the Parasite Game About the games Malaria is one of the world's most common ... last will in Paris. Play the Blood Typing Game Try to save some patients and learn about ...
Sigma-1 Receptor Plays a Negative Modulation on N-type Calcium Channel

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Kang Zhang

2017-05-01

Full Text Available The sigma-1 receptor is a 223 amino acids molecular chaperone with a single transmembrane domain. It is resident to eukaryotic mitochondrial-associated endoplasmic reticulum and plasma membranes. By chaperone-mediated interactions with ion channels, G-protein coupled receptors and cell-signaling molecules, the sigma-1 receptor performs broad physiological and pharmacological functions. Despite sigma-1 receptors have been confirmed to regulate various types of ion channels, the relationship between the sigma-1 receptor and N-type Ca2+ channel is still unclear. Considering both sigma-1 receptors and N-type Ca2+ channels are involved in intracellular calcium homeostasis and neurotransmission, we undertake studies to explore the possible interaction between these two proteins. In the experiment, we confirmed the expression of the sigma-1 receptors and the N-type calcium channels in the cholinergic interneurons (ChIs in rat striatum by using single-cell reverse transcription-polymerase chain reaction (scRT-PCR and immunofluorescence staining. N-type Ca2+ currents recorded from ChIs in the brain slice of rat striatum was depressed when sigma-1 receptor agonists (SKF-10047 and Pre-084 were administrated. The inhibition was completely abolished by sigma-1 receptor antagonist (BD-1063. Co-expression of the sigma-1 receptors and the N-type calcium channels in Xenopus oocytes presented a decrease of N-type Ca2+ current amplitude with an increase of sigma-1 receptor expression. SKF-10047 could further depress N-type Ca2+ currents recorded from oocytes. The fluorescence resonance energy transfer (FRET assays and co-immunoprecipitation (Co-IP demonstrated that sigma-1 receptors and N-type Ca2+ channels formed a protein complex when they were co-expressed in HEK-293T (Human Embryonic Kidney -293T cells. Our results revealed that the sigma-1 receptors played a negative modulation on N-type Ca2+ channels. The mechanism for the inhibition of sigma-1 receptors on
Play vs. Procedures

DEFF Research Database (Denmark)

Hammar, Emil

Through the theories of play by Gadamer (2004) and Henricks (2006), I will show how the relationship between play and game can be understood as dialectic and disruptive, thus challenging understandings of how the procedures of games determine player activity and vice versa. As such, I posit some...... analytical consequences for understandings of digital games as procedurally fixed (Boghost, 2006; Flannagan, 2009; Bathwaite & Sharp, 2010). That is, if digital games are argued to be procedurally fixed and if play is an appropriative and dialectic activity, then it could be argued that the latter affects...... and alters the former, and vice versa. Consequently, if the appointed procedures of a game are no longer fixed and rigid in their conveyance of meaning, qua the appropriative and dissolving nature of play, then understandings of games as conveying a fixed meaning through their procedures are inadequate...
OCT2, SSX and SAGE1 reveal the phenotypic heterogeneity of spermatocytic seminoma reflecting distinct subpopulations of spermatogonia

DEFF Research Database (Denmark)

Lim, Jasmine; Goriely, Anne; Turner, Gareth Dh

2011-01-01

in the normal adult testis. We analysed the expression pattern of OCT2, SSX2-4, and SAGE1 in 36 SS cases and four intratubular SS (ISS) as well as a series of normal testis samples throughout development. We describe for the first time two different types of SS characterized by OCT2 or SSX2-4 immunoexpression......, whilst SAGE1 was exclusively present in a subset of post-pubertal germ cells, most likely B spermatogonia. The presence of OCT2 and SSX2-4 in distinct subsets of germ cells implies that these markers represent germ cells at different maturation stages. Analysis of SAGE1 and SSX2-4 in ISS showed spatial...... differences suggesting ongoing maturation of germ cells during progression of SS tumourigenesis. We conclude that the expression pattern of OCT2, SSX2-4, and SAGE1 supports the origin of SS from spermatogonia and provides new evidence for heterogeneity of this tumour, potentially linked either to the cellular...
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

Electrophysiological research has isolated neural signatures of decision formation in a variety of brain regions. Studies in rodents and monkeys have focused primarily on effector-selective signals that translate the emerging decision into a specific motor plan, but, more recently, research on the human brain has identified an abstract signature of evidence accumulation that does not appear to play any direct role in action preparation. The functional dissociations between these distinct signal types have only begun to be characterized, and their dynamics during decisions with deferred actions with or without foreknowledge of stimulus-effector mapping, a commonly studied task scenario in single-unit and functional imaging investigations, have not been established. Here we traced the dynamics of distinct abstract and effector-selective decision signals in the form of the broad-band centro-parietal positivity (CPP) and limb-selective β-band (8-16 and 18-30 Hz) EEG activity, respectively, during delayed-reported motion direction decisions with and without foreknowledge of direction-response mapping. With foreknowledge, the CPP and β-band signals exhibited a similar gradual build-up following evidence onset, but whereas choice-predictive β-band activity persisted up until the delayed response, the CPP dropped toward baseline after peaking. Without foreknowledge, the CPP exhibited identical dynamics, whereas choice-selective β-band activity was eliminated. These findings highlight qualitative functional distinctions between effector-selective and abstract decision signals and are of relevance to the assumptions founding functional neuroimaging investigations of decision-making. Neural signatures of evidence accumulation have been isolated in numerous brain regions. Although animal neurophysiology has largely concentrated on effector-selective decision signals that translate the emerging decision into a specific motor plan, recent research on the human brain has
Playing and understanding chemistry: Reinterpreting a traditional game for educational use

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Ana Carolina Rosa da Silva

2017-12-01

Full Text Available The importance of using educational games in the school context cannot be denied. Therefore, this article describes a study about the contributions of a game for teaching colligative properties. The game was used with a second-year class in a high school located in southeast Piauí, Brazil. It is a qualitative study; it used questionnaires for data collection and direct observation about phenomenological aspects that emerged during the application of the game. The results showed that the use of educational games is not common for the subjects observed. Their views on that use lead us to infer that the proposed playful activity has contributed to strengthen distinct aspects needed to improve the teaching and learning process in Chemistry
Evaluation of method for phthalate extraction from milk related to milk dilution ratio

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Milojković Danica S.

2015-01-01

Full Text Available Liquid-liquid extraction techniques were compared coupled with gas chromatography-mass spectrometry (GC-MS, for the extraction and the determination of four phthalates: dimethyl phthalate (DMP, di-n-butyl phthalate (DBP, benzyl butyl phthalate (BBP and di-(2-ethylhexyl phthalate (DEHP in six different kinds of milk-based samples. Extraction factors: sample preparation, organic solvent type and volume, salt effect, agitation and the extraction time were optimized. The ion of base peaks (m/z 149 for DBP, BBP and DEHP and m/z 163 for DMP for investigated phthalates were selected for the screening studies. The acquisition was performed at the selected ion monitoring mode. The MSD response for GC-MS phthalate calibration standards was linear between 0.25 and 2.50 μg mL-1 with calculated LODs between 0.01 μg mL-1 to 0.04 μg mL-1 and LOQs of 0.05 μg mL-1 to 0.12 μg mL-1, while repeatability was between 1.7 % to 4.9 % RSD. The study demonstrated an increase of the recovery of less polar phthalates in matrix milk standards by matrix dilution. Recovery for hydrophilic phthalates, like DMP, was not changed by matrix dilution and it was continuously low for the investigated method. Two spiking levels were tested for influence of matrix dilution on phthalate recovery, showed the same trend. [Projekat Ministarstva nauke Republike Srbije, br. 31060
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
Dynamic Recruitment of Functionally Distinct Swi/Snf Chromatin Remodeling Complexes Modulates Pdx1 Activity in Islet β Cells

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Brian McKenna

2015-03-01

Full Text Available Pdx1 is a transcription factor of fundamental importance to pancreas formation and adult islet β cell function. However, little is known about the positive- and negative-acting coregulators recruited to mediate transcriptional control. Here, we isolated numerous Pdx1-interacting factors possessing a wide range of cellular functions linked with this protein, including, but not limited to, coregulators associated with transcriptional activation and repression, DNA damage response, and DNA replication. Because chromatin remodeling activities are essential to developmental lineage decisions and adult cell function, our analysis focused on investigating the influence of the Swi/Snf chromatin remodeler on Pdx1 action. The two mutually exclusive and indispensable Swi/Snf core ATPase subunits, Brg1 and Brm, distinctly affected target gene expression in β cells. Furthermore, physiological and pathophysiological conditions dynamically regulated Pdx1 binding to these Swi/Snf complexes in vivo. We discuss how context-dependent recruitment of coregulatory complexes by Pdx1 could impact pancreas cell development and adult islet β cell activity.
Postphenomenological Play

DEFF Research Database (Denmark)

Hammar, Emil

This paper aims to identify an understanding of digital games in virtual environments by using Don Ihde’s (1990) postphenomenological approach to how technology mediates the world to human beings in conjunction with Hans-Georg Gadamer’s (1993) notion of play . Through this tentatively proposed am...... amalgamation of theories I point towards an alternative understanding of the relationship between play and game as not only dialectic, but also as socially and ethically relevant qua the design and implementation of the game as technology....
Playing Against the Modern World? : Role-Playing Games in Late Modernity

OpenAIRE

Harding, Tobias

2010-01-01

Playing Reality is an anthology of articles on live role-playing, a new art from where the Nordic countries are at the front edge. This book covers a wide range of topics and genres, from practical advice, historical reviews and visions of possible futures to semiotic and philosophical analysis. They Show some of the diversity of participatory arts, and will thus be of interest for anyone in the fields of art, education or performance. It wouldn't be misleading to claim that live role-playing...
Distinctive changes in plasma membrane phosphoinositides underlie differential regulation of TRPV1 in nociceptive neurons.

Science.gov (United States)

Lukacs, Viktor; Yudin, Yevgen; Hammond, Gerald R; Sharma, Esseim; Fukami, Kiyoko; Rohacs, Tibor

2013-07-10

Transient Receptor Potential Vanilloid 1 (TRPV1) is a polymodal, Ca(2+)-permeable cation channel crucial to regulation of nociceptor responsiveness. Sensitization of TRPV1 by G-protein coupled receptor (GPCR) agonists to its endogenous activators, such as low pH and noxious heat, is a key factor in hyperalgesia during tissue injury as well as pathological pain syndromes. Conversely, chronic pharmacological activation of TRPV1 by capsaicin leads to calcium influx-induced adaptation of the channel. Paradoxically, both conditions entail activation of phospholipase C (PLC) enzymes, which hydrolyze phosphoinositides. We found that in sensory neurons PLCβ activation by bradykinin led to a moderate decrease in phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2), but no sustained change in the levels of its precursor PI(4)P. Preventing this selective decrease in PI(4,5)P2 inhibited TRPV1 sensitization, while selectively decreasing PI(4,5)P2 independently of PLC potentiated the sensitizing effect of protein kinase C (PKC) on the channel, thereby inducing increased TRPV1 responsiveness. Maximal pharmacological TRPV1 stimulation led to a robust decrease of both PI(4,5)P2 and its precursor PI(4)P in sensory neurons. Attenuating the decrease of either lipid significantly reduced desensitization, and simultaneous reduction of PI(4,5)P2 and PI(4)P independently of PLC inhibited TRPV1. We found that, on the mRNA level, the dominant highly Ca(2+)-sensitive PLC isoform in dorsal root ganglia is PLCδ4. Capsaicin-induced desensitization of TRPV1 currents was significantly reduced, whereas capsaicin-induced nerve impulses in the skin-nerve preparation increased in mice lacking this isoform. We propose a comprehensive model in which differential changes in phosphoinositide levels mediated by distinct PLC isoforms result in opposing changes in TRPV1 activity.

On Hobbes’s distinction of accidents

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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.
MEPE, a new gene expressed in bone marrow and tumors causing osteomalacia.

Science.gov (United States)

Rowe, P S; de Zoysa, P A; Dong, R; Wang, H R; White, K E; Econs, M J; Oudet, C L

2000-07-01

Oncogenic hypophosphatemic osteomalacia (OHO) is characterized by a renal phosphate leak, hypophosphatemia, low-serum calcitriol (1,25-vitamin-D3), and abnormalities in skeletal mineralization. Resection of OHO tumors results in remission of the symptoms, and there is evidence that a circulating phosphaturic factor plays a role in the bone disease. This paper describes the characterization and cloning of a gene that is a candidate for the tumor-secreted phosphaturic factor. This new gene has been named MEPE (matrix extracellular phosphoglycoprotein) and has major similarities to a group of bone-tooth mineral matrix phospho-glycoproteins (osteopontin (OPN; HGMW-approved symbol SPP1), dentin sialo phosphoprotein (DSPP), dentin matrix protein 1 (DMP1), bone sialoprotein II (IBSP), and bone morphogenetic proteins (BMP). All the proteins including MEPE contain RGD sequence motifs that are proposed to be essential for integrin-receptor interactions. Of further interest is the finding that MEPE, OPN, DSPP, DMP1, IBSP, and BMP3 all map to a defined region in chromosome 4q. Refined mapping localizes MEPE to 4q21.1 between ESTs D4S2785 (WI-6336) and D4S2844 (WI-3770). MEPE is 525 residues in length with a short N-terminal signal peptide. High-level expression of MEPE mRNA occurred in all four OHO tumors screened. Three of 11 non-OHO tumors screened contained trace levels of MEPE expression (detected only after RT-PCR and Southern 32P analysis). Normal tissue expression was found in bone marrow and brain with very-low-level expression found in lung, kidney, and human placenta. Evidence is also presented for the tumor secretion of clusterin (HGMW-approved symbol CLU) and its possible role as a cytotoxic factor in one of the OHO patients described.
Bmi-1 plays a critical role in the protection from acute tubular necrosis by mobilizing renal stem/progenitor cells.

Science.gov (United States)

Lv, Xianhui; Yu, Zhenzhen; Xie, Chunfeng; Dai, Xiuliang; Li, Qing; Miao, Dengshun; Jin, Jianliang

2017-01-22

The regeneration of injured tubular cell occurs primarily from intrinsic renal stem/progenitor cells (RSCs) labeled with CD24 and CD133 after acute tubular necrosis (ATN). Bmi-1 plays a crucial role in regulating self-renewal, differentiation and aging of multiple adult stem cells and progenitor cells. Bmi-1 was rapidly elevated in the induction of adult kidney regeneration by renal injury. To determine whether Bmi-1 maintained mobilization of RSCs in the protection from ATN, glycerol-rhabdomyolysis-induced ATN were performed in wild type (WT) and Bmi-1-deficient (Bmi-1 -/- ) mice. Their ATN phenotypes were analyzed; CD24 and CD133 double positive (CD24 + CD133 + ) cells were measured; and the levels of serum urea nitrogen (SUN) and serum creatinine (SCr) were detected. We found that CD24 + CD133 + RSCs were mobilized in WT ATN mice with the increased expression of Bmi-1; Bmi-1 deficiency led to increased tubular cast formation and necrosis, elevated levels of SUN and SCr, decreased tubular proliferation, and immobilized ratio of RSCs in ATN. These findings indicated that Bmi-1 played a critical role in the protection from ATN by maintaining mobilization of RSCs and would be a novel therapeutic target for preventing the progression of ATN. Copyright © 2016 Elsevier Inc. All rights reserved.
Play your part

CERN Document Server

Ramsey, Gaynor

1978-01-01

Play your part is a collection of then situations in which students have to take on the roles of particular people and express their opinions, feelings or arguments about the situation. Play your part is intended for use with advanced students of English.
Penerapan Metode Role Playing Dalam Meningkatkan Motivasi Belajar Anak Usia Play Group

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Dwi Anita Alfiani

2015-06-01

Full Text Available AbstrakSalah satu faktor penting dalam kegiatan belajar (KBM untuk anak usia play group adalah guru yang memahami berbagai macam karakterisik peserta didik dan peduli terhadap kebutuhan anak didiknya.Namun Dari hasil penelitian dan kenyataan di lapangan, menunjukkan bahwa pelaksanaan kegiatan belajar mengajar (KBM untuk anak-anak usia play group masih banyak kelemahan dan kekurangannya karenanya guru juga harus mampu menguasai teknik dan metode dalam mengajar B untuk anak.Anak didik pada usia play group.Dengan demikian, metode pembelajaran merupakan alat untuk menciptakan proses belajar mengajar.Subana dan Sunarti (2000 : 20 Berpendapat metode adalah rencana penyajian bahan yang menyeluruh dengan urutan yang sistematis berdasarkan approach tertentu. Jadi metode merupakan cara melaksanakan pekerjaan, sedangkan approach, dapat tumbuh beberapan metode. Role Playing adalah suatu cara penguasaan bahan-bahan pelajaran melalui pengembangan imajinasi dan penghayatan siswa. Pengembangan imajinasi dan penghayatan dilakukan siswa dengan memerankannya sebagai tokoh hidup atau benda mati. Permainan ini pada umumnya dilakukan lebih dari satu orang, hal itu bergantung kepada apa yang diperankan.Role Playing yakni memainkan peranan dari peran-peran yang sudah pasti berdasarkan kejadian terdahulu, yang dimaksudkan untuk menciptakan kembali situasi sejarah/peristiwa masa lalu, menciptakan kemungkinan-kemungkinan kejadian masa yang akan datang, menciptakan peristiwa mutakhir yang dapat diperkaya atau mengkhayal situasi pada suatu tempat dan atau waktu tertentu. berarti metode (Role Playing adalah metode pembelajaran yang di dalamnya menampakkan adanya perilaku pura-pura dari siswa yang terlihat dan atau peniruan situasi dari tokoh-tokoh sejarah sedemikian rupa. Dengan demikian metode Bermain Peran (RolePlayingadalah metode yang melibatkan siswa untuk pura-pura memainkan peran/ tokoh yang terlibat dalam proses sejarah. Teknik ini juga digunakan untuk dapat
Distinct kinetics of serine and threonine dephosphorylation are essential for mitosis

DEFF Research Database (Denmark)

Hein, Jamin B; Hertz, Emil P T; Garvanska, Dimitriya H

2017-01-01

Protein phosphatase 2A (PP2A) in complex with B55 regulatory subunits reverses cyclin-dependent kinase 1 (Cdk1) phosphorylations at mitotic exit. Interestingly, threonine and serine residues phosphorylated by Cdk1 display distinct phosphorylation dynamics, but the biological significance remains ...
Art of Play

DEFF Research Database (Denmark)

Froes, Isabel Cristina G.; Walker, Kevin

2011-01-01

Play is a key element in cultural development, according to the Dutch historian Johan Huizinga. Nowadays many of us interact with other people in online games and social networks, through multiple digital devices. But harnessing playful activities for museum learning is mostly undeveloped. In thi...
The Pedagogy of Play

Science.gov (United States)

Giesbrecht, Sheila

2012-01-01

Play is important. Environmental educators Sobel and Louv write about the relationship between children and outside play and suggest that early transcendental experiences within nature allow children to develop empathetic orientations towards the natural world. Children who play out-of-doors develop an appreciation for the environment and…
THE NONLINEAR TRAJECTORY OF CHANGE IN PLAY PROFILES OF THREE CHILDREN IN PSYCHODYNAMIC PLAY THERAPY

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Sibel Halfon

2016-10-01

Full Text Available Aim: Even though there is substantial evidence that play based therapies produce significant change, the specific play processes in treatment remain unexamined. For that purpose, processes of change in long-term psychodynamic play therapy are assessed through a repeated systematic assessment of three children’s Play Profiles, which reflect patterns of organization among play variables that contribute to play activity in therapy, indicative of the children’s coping strategies, and an expression of their internal world. The main aims of the study are to investigate the kinds of Play Profiles expressed in treatment, and to test whether there is emergence of new and more adaptive Play Profiles using dynamic systems theory as a methodological framework.Methods and Procedures: Each session from the long-term psychodynamic treatment (mean number of sessions = 55 of three 6 year old good outcome cases presenting with Separation Anxiety were recorded, transcribed and coded using items from the Children's Play Therapy Instrument, created to assess the play activity of children in psychotherapy, generating discrete and measurable units of play activity arranged along a continuum of four play profiles: Adaptive, Inhibited, Impulsive, and Disorganized. The play profiles were clustered through K-means Algorithm, generating 7 discrete states characterizing the course of treatment and the transitions between these states were analyzed by Markov Transition Matrix, Recurrence Quantification Analysis (RQA and odds ratios comparing the first and second halves of psychotherapy.Results: The Markov Transitions between the states scaled almost perfectly and also showed the ergodicity of the system meaning that the child can reach any state or shift to another one in play. The RQA and odds ratios showed two trends of change, first concerning the decrease in the use of less adaptive strategies, second regarding the reduction of play interruptions.Conclusions: The
[Discussion on developing a data management plan and its key factors in clinical study based on electronic data capture system].

Science.gov (United States)

Li, Qing-na; Huang, Xiu-ling; Gao, Rui; Lu, Fang

2012-08-01

Data management has significant impact on the quality control of clinical studies. Every clinical study should have a data management plan to provide overall work instructions and ensure that all of these tasks are completed according to the Good Clinical Data Management Practice (GCDMP). Meanwhile, the data management plan (DMP) is an auditable document requested by regulatory inspectors and must be written in a manner that is realistic and of high quality. The significance of DMP, the minimum standards and the best practices provided by GCDMP, the main contents of DMP based on electronic data capture (EDC) and some key factors of DMP influencing the quality of clinical study were elaborated in this paper. Specifically, DMP generally consists of 15 parts, namely, the approval page, the protocol summary, role and training, timelines, database design, creation, maintenance and security, data entry, data validation, quality control and quality assurance, the management of external data, serious adverse event data reconciliation, coding, database lock, data management reports, the communication plan and the abbreviated terms. Among them, the following three parts are regarded as the key factors: designing a standardized database of the clinical study, entering data in time and cleansing data efficiently. In the last part of this article, the authors also analyzed the problems in clinical research of traditional Chinese medicine using the EDC system and put forward some suggestions for improvement.
Disease Management Project Breast Cancer in Hesse - 5-Year Survival Data: Successful Model of Intersectoral Communication for Quality Assurance.

Science.gov (United States)

Jackisch, C; Funk, A; König, K; Lubbe, D; Misselwitz, B; Wagner, U

2014-03-01

Introduction: The Disease Management Project Breast Cancer (DMP Breast Cancer) was first launched in Hesse in 2004. The project is supported by the health insurance companies in Hesse and the Professional Association of Gynaecologists in Hesse. The aim is to offer structured treatment programmes to all women diagnosed with breast cancer in Hesse by creating intersectoral cooperations between coordinating clinics, associated hospitals and gynaecologists in private practice who registered in the DMP programme. Method: Between 1 January 2005 and 30 June 2011, 13 973 women were enrolled in the DMP programme. Results: After data cleansing, survival rates were calculated for a total of 11 214 women. The 5-year overall survival (OS) rate was 86.3 %; survival rates according to tumour stage on presentation were 92.2 % (pT1) and 82.3 % (pT2), respectively. The impact of steroid hormone receptor status on survival (87.8 % for receptor-positive cancers vs. 78.9 % for receptor-negative cancers) and of age at first diagnosis on survival (≤ 35 years = 91 %) were calculated. Conclusion: The project showed that intersectoral cooperation led to significant improvements in the quality of treatment over time, as measured by quality indicators and outcomes after treatment.
Organophosphate Exposure: A Preliminary Assessment on the use of Pesticide Intensity Score to Evaluate Exposure among Fruit Growers

Directory of Open Access Journals (Sweden)

Tengku Hanidza T.I.

2010-01-01

Full Text Available This study examines the influence of work hours, personal protective equipment use, and pesticide ingestion on the amount of urinary metabolites among fruit growers applying organophosphate pesticide. Thirty nine urine samples were collected from seven applicators before and after organophosphate applications. All dimethyl metabolites were present in day 1 morning urine samples for all workers. The arithmetic means for day 1 ranged from 21.5-94.17 μg/L DMP, 6.25-81.25 μg/L DMTP, and < LOQ-153.17 μg/L DMDTP. Day 2 urine samples had the highest amount of metabolites. The arithmetic means ranged from 25.8-558 μg/L DMP, 15.75-398 μg/L DMTP, 21.5-568.57 μg/L DMDTP, and < LOQ-17.67 μg/L DEP. The arithmetic means for day 4 ranges from 19.2-182 μg/L DMP, 13.33-138 μg/L DMTP, 22.75-157.83 μg/L DMDTP, and < LOQ-26 μg/L DEP. From the questionnaire, the exposure algorithm based on duration of hours worked, PPE use and pesticide ingestion showed poor relationship with urine concentration (r=0.1847. The linear relationship is not established due to variability within and between applicators.
Play and Productivity: Enhancing the Creative Climate at Workplace Meetings with Play Cues

Science.gov (United States)

West, Samuel E.; Hoff, Eva; Carlsson, Ingegerd

2016-01-01

The authors investigate the links between playfulness and creative organizational climates established by other research, using play cues--objects and sweets--they provide participants halfway through workplace meetings. Their findings suggest such cues significantly enhance the creative climate and playfulness in workplace meetings without…
Free time, play and game

OpenAIRE

Božović Ratko R.

2008-01-01

Free time and play are mutually dependent categories that are always realized together. We either play because we have free time or we have free time because we play (E. Fink). Play, no matter whether it is children's or artistic play or a spontaneous sports game (excluding professional sports) most fully complements human existence and thereby realizes free time as a time in freedom and freedom of time. Therefore, free time exists and is most prominent in play. Moreover, one game releases it...
Playfulness and Openness

DEFF Research Database (Denmark)

Marchetti, Emanuela; Petersson, Eva

2011-01-01

What does it mean to design a playful learning tool? What is needed for a learning tool to be perceived by potential users as playful? These questions emerged reflecting on a Participatory Design process aimed at enhancing museum-learning practice from the perspective of primary school children...
Play framework cookbook

CERN Document Server

Reelsen, Alexander

2015-01-01

This book is aimed at advanced developers who are looking to harness the power of Play 2.x. This book will also be useful for professionals looking to dive deeper into web development. Play 2 .x is an excellent framework to accelerate your learning of advanced topics.
A Meta-Analysis of Circulating Microvesicles in Patients with Myocardial Infarction.

Science.gov (United States)

Wang, Zhida; Cai, Wang; Hu, Shaolan; Xia, Yufei; Wang, Yao; Zhang, Qi; Chen, Liming

2017-07-10

Cell-derived microvesicles (MVs) are vesicles released from activated or apoptotic cells. However, the levels of MVs in myocardial infarction have been found inconsistent in researches. To assess the association between MVs and myocardial infarction by conducting a meta-analysis. A systematic literature search on PubMed, Embase, Cochran, Google Scholar electronic database was conducted. Comparison of the MVs levels between myocardial infarction patients and healthy persons were included in our study. Standard Mean Difference (SMD) and 95% confidence interval (CI) in groups were calculated and meta-analyzed. 11 studies with a total of 436 participants were included. Compared with the health persons, AMVs [SMD = 3.65, 95% CI (1.03, 6.27)], PMVs [SMD = 2.88, 95% CI (1.82, 3.93),] and EMVs [SMD = 2.73, 95% CI (1.13, 4.34)], levels were higher in patients with myocardial infarction. However, LMVs levels [SMD = 0.73, 95% CI (-0.57, 2.03)] were not changed significantly in patients with myocardial infarction. AMVs, PMVs and EMVs might be potential biomarkers for myocardial infarction. As microvesículas derivadas de células (MVs) são vesículas liberadas de células ativadas ou apoptóticas. No entanto, os níveis de MVs no infarto do miocárdio foram encontrados inconsistentes nas pesquisas. Avaliar a associação entre MV e infarto do miocárdio por meio de uma meta-análise. Foi realizada uma pesquisa sistemática na literatura em PubMed, Embase, Cochran e no banco de dados eletrônico do Google Scholar. Uma comparação dos níveis de MV entre pacientes com infarto do miocárdio e pessoas saudáveis foi incluída no nosso estudo. A Diferença Média Padrão (DMP) e o intervalo de confiança (IC) de 95% nos grupos foram calculadas e meta-analisadas. Foram incluídos 11 estudos com um total de 436 participantes. Em comparação com as pessoas saudáveis, as MVA [DMP = 3,65, IC 95% (1,03, 6,27)], MVPs [DMP = 2,88, IC 95% (1,82, 3,93)] e MVEs [DMP = 2,73, IC 95% (1
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).
Free riders play fair

OpenAIRE

Takikawa, Hirohide

2012-01-01

After the demise of the social contract theory, the argument from fair play, which employs the principle of fair play, has been widely acknowledged as one of the most promising ways of justifying political obligation. First, I articulate the most promising version of the principle of fair play. Then, I show that free riders play fair, that is, that their moral fault lies not in unfairness but in the violation of a rule by appealing to the example of three-in-a-boat. Finally, I conclude that e...
Hippocampus duality: Memory and novelty detection are subserved by distinct mechanisms.

Science.gov (United States)

Barbeau, Emmanuel J; Chauvel, Patrick; Moulin, Christopher J A; Regis, Jean; Liégeois-Chauvel, Catherine

2017-04-01

The hippocampus plays a pivotal role both in novelty detection and in long-term memory. The physiological mechanisms underlying these behaviors have yet to be understood in humans. We recorded intracerebral evoked potentials within the hippocampus of epileptic patients (n = 10) during both memory and novelty detection tasks (targets in oddball tasks). We found that memory and detection tasks elicited late local field potentials in the hippocampus during the same period, but of opposite polarity (negative during novelty detection tasks, positive during memory tasks, ∼260-600 ms poststimulus onset, P < 0.05). Critically, these potentials had maximal amplitude on the same contact in the hippocampus for each patient. This pattern did not depend on the task as different types of memory and novelty detection tasks were used. It did not depend on the novelty of the stimulus or the difficulty of the task either. Two different hypotheses are discussed to account for this result: it is either due to the activation of CA1 pyramidal neurons by two different pathways such as the monosynaptic and trisynaptic entorhinal-hippocampus pathways, or to the activation of different neuronal populations, that is, differing either functionally (e.g., novelty/familiarity neurons) or located in different regions of the hippocampus (e.g., CA1/subiculum). In either case, these activities may integrate the activity of two distinct large-scale networks implementing externally or internally oriented, mutually exclusive, brain states. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

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.
Oxygen cost and physiological responses of recreational badminton match play.

Science.gov (United States)

Deka, Pallav; Berg, Kris; Harder, Jeanette; Batelaan, Herman; McGRATH, Melanie

2017-06-01

Badminton, as an Olympic sport, is popular worldwide. However, the benefits of recreational badminton match play are not well known. The purpose of the study was to determine the oxygen cost of recreational badminton match play. Heart rate (HR), blood lactate (BL), rating of perceived exertion (RPE), step count and energy expenditure were also assessed. Fourteen male recreational badminton players aged 35.9±6.62 years participated in test sessions to assess oxygen uptake (VO2) and the related physiological responses of match play. During the match play sessions, participants played singles badminton matches for 30 min while wearing a portable metabolic system. VO2 and HR were continuously recorded while blood lactate and RPE were determined following warm-up, at 15 minutes and 30 minutes of match play. Step count was recorded at 15 minutes and 30 minutes of play. VO2 over 30 minutes was 34.4±5.8 mL/kg/min which was 76.1% of maximal oxygen uptake. Across three 10-minute periods of play, VO2 was not significantly different while HR was higher in the third 10-minute period than the first and second 10-minute periods (P=0.001). Mean HR over 30 minutes was 167.9±9.4 bpm. BL was significantly higher at 15 and 30 minutes than following warm-up while RPE of 17.57±1.91 after 30 minutes was significantly higher (P=0.009) than RPE of 15.79±1.63 at 15 minutes. Step count did not vary between the two 15-minute periods of play with a total of 2404±360 steps while energy expenditure over 30 minutes of play was 391.7±66 kcal. Recreational badminton match play can be categorized as vigorous intensity suggesting that it can be a viable means of achieving recommended physical activity and improving aerobic fitness.
Targeting of Mesenchymal Stromal Cells by Cre-Recombinase Transgenes Commonly Used to Target Osteoblast Lineage Cells.

Science.gov (United States)

Zhang, Jingzhu; Link, Daniel C

2016-11-01

The targeting specificity of tissue-specific Cre-recombinase transgenes is a key to interpreting phenotypes associated with their use. The Ocn-Cre and Dmp1-Cre transgenes are widely used to target osteoblasts and osteocytes, respectively. Here, we used high-resolution microscopy of bone sections and flow cytometry to carefully define the targeting specificity of these transgenes. These transgenes were crossed with Cxcl12 gfp mice to identify Cxcl12-abundant reticular (CAR) cells, which are a perivascular mesenchymal stromal population implicated in hematopoietic stem/progenitor cell maintenance. We show that in addition to osteoblasts, Ocn-Cre targets a majority of CAR cells and arteriolar pericytes. Surprisingly, Dmp1-Cre also targets a subset of CAR cells, in which expression of osteoblast-lineage genes is enriched. Finally, we introduce a new tissue-specific Cre-recombinase, Tagln-Cre, which efficiently targets osteoblasts, a majority of CAR cells, and both venous sinusoidal and arteriolar pericytes. These data show that Ocn-Cre and Dmp1-Cre target broader stromal cell populations than previously appreciated and may aid in the design of future studies. Moreover, these data highlight the heterogeneity of mesenchymal stromal cells in the bone marrow and provide tools to interrogate this heterogeneity. © 2016 American Society for Bone and Mineral Research. © 2016 American Society for Bone and Mineral Research.
Experimental mesenteric ischemia. Radioisotopic diagnosis

International Nuclear Information System (INIS)

Alberti, Carlos; Dallaglio, Juan; Sarra, Luis; Obiols, Eugenio; Rodriguez Santos, Emilio; Delgado, Eduardo; Castelleti, Luis

1995-01-01

A non-invasive radionuclide technique with 99-Tc-DMP for the early diagnosis of small bowel infarction due to mesenteric artery compression, was evaluated. The usefulness of 99-Tc-DMP and critical pressure of mesenteric artery were demonstrated. The diagnosis was performed before one hour had passed from the beginning of the ischemia
Distinct Laterality in Forelimb-Movement Representations of Rat Primary and Secondary Motor Cortical Neurons with Intratelencephalic and Pyramidal Tract Projections.

Science.gov (United States)

Soma, Shogo; Saiki, Akiko; Yoshida, Junichi; Ríos, Alain; Kawabata, Masanori; Sakai, Yutaka; Isomura, Yoshikazu

2017-11-08

Two distinct motor areas, the primary and secondary motor cortices (M1 and M2), play crucial roles in voluntary movement in rodents. The aim of this study was to characterize the laterality in motor cortical representations of right and left forelimb movements. To achieve this goal, we developed a novel behavioral task, the Right-Left Pedal task, in which a head-restrained male rat manipulates a right or left pedal with the corresponding forelimb. This task enabled us to monitor independent movements of both forelimbs with high spatiotemporal resolution. We observed phasic movement-related neuronal activity (Go-type) and tonic hold-related activity (Hold-type) in isolated unilateral movements. In both M1 and M2, Go-type neurons exhibited bias toward contralateral preference, whereas Hold-type neurons exhibited no bias. The contralateral bias was weaker in M2 than M1. Moreover, we differentiated between intratelencephalic (IT) and pyramidal tract (PT) neurons using optogenetically evoked spike collision in rats expressing channelrhodopsin-2. Even in identified PT and IT neurons, Hold-type neurons exhibited no lateral bias. Go-type PT neurons exhibited bias toward contralateral preference, whereas IT neurons exhibited no bias. Our findings suggest a different laterality of movement representations of M1 and M2, in each of which IT neurons are involved in cooperation of bilateral movements, whereas PT neurons control contralateral movements. SIGNIFICANCE STATEMENT In rodents, the primary and secondary motor cortices (M1 and M2) are involved in voluntary movements via distinct projection neurons: intratelencephalic (IT) neurons and pyramidal tract (PT) neurons. However, it remains unclear whether the two motor cortices (M1 vs M2) and the two classes of projection neurons (IT vs PT) have different laterality of movement representations. We optogenetically identified these neurons and analyzed their functional activity using a novel behavioral task to monitor movements
Parents' Play Beliefs and Engagement in Young Children's Play at Home

Science.gov (United States)

Lin, Xunyi; Li, Hui

2018-01-01

Play is a fundamental concept in early childhood development and education. As partners in the child's learning, parents play a crucial role in how play is defined, valued, and practised. The present study explores the constructs of parents' beliefs about and engagement in young children's play in two coastal cities in China. A sample of 483…
Greek Myths: 8 Short Plays for the Classroom.

Science.gov (United States)

Rearick, John

Noting that myths are a powerful classroom tool, this book presents 8 short plays (in a readers' theater format) for grades 4-8. After an introduction that discusses getting started and using the book, plays in the book are: (1) "The Gods Must Be Crazy: The Story of Cupid and Psyche"; (2) "The Sound of Music Goes Underground: The…
Puppet Visual Adaptation on Playing Cards as Educational Media

Directory of Open Access Journals (Sweden)

Joko Wiyoso

2017-02-01

Full Text Available This study aims at presenting an effective media in a form of puppet picture playing cards as a means to introduce traditional puppet to the society. Research and Development (R&D was chosen as the method to develop the playing cards. Results were presented in a form of the design of puppet picture playing cards as many as 54 cards as well as 54 puppet characters as the background pictures. The design of the playing cards is adjusted to the common playing cards which are distributed widely in the society, including both the sizes and symbols, like the pictures of spade, heart, diamond, and club. In detail, the design comprises: (1 the size of playing cards which is 6 cm width of the upper and lower sides and 9 cm length for the left and right sides. (2 The playing cards’ background is in a bright color so does the puppet picture on the card can be seen clearly.
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.
The "State of Play" in Australia: Early Childhood Educators and Play-Based Learning

Science.gov (United States)

Sumsion, Jennifer; Grieshaber, Sue; McArdle, Felicity; Shield, Paul

2014-01-01

This article provides an overview of the Education Meets Play study that will investigate early childhood educators' use of play-based learning, now mandatory under the "National Quality Standard". By building on what can be gleaned about educators' approaches to play-based learning prior to the implementation of the "Early Years…
Nosing Around: Play in Pigs

Directory of Open Access Journals (Sweden)

Kristina Horback

2014-05-01

Full Text Available The predominant method of measuring welfare in swine focuses on overt physical ailments, such as skin lesions, lameness, and body condition. An alternative metric for assessing welfare in swine can be to measure the frequency and duration of positive behavioral states, such as play. Given that play occurs only when an animal's primary needs (food, comfort, safety, etc. have been satisfied, it has been suggested that play may be a sensitive indicator for assessing the welfare of non-human animals. Play has primarily been described in young piglets and is assessed via the occurrence of specific play markers. These play markers include overt bursts of energy like scamper, or more subtle social behaviors like nose-to-body contact. This review describes four areas of play for swine: locomotor, object, sow-piglet, and, peer play. From sporadic leaping to combative wrestling, play behavior allows for the fine-tuning of reflexive behavior which can enhance physical development, enrich cognitive abilities, and facilitate the maintenance of social bonds.
Late Modern Play Culture

DEFF Research Database (Denmark)

Karoff, Helle Skovbjerg

2008-01-01

and the Danish University of Education (among others) have been working with different kind of products, all referred to as PlAYWARE. Playware combines modern technology and knowledge about play culture in order to produce playful experiences for its players. This paper will exemplify how the concept of play can...... from one generation to the next. Because older children are no longer present as younger children grow up, the traditional "cultural leaders" are gone. They have taken with them much of the inspiration for play as well as important knowledge about how to organise a game. In that sense we can say...
Human phenotypically distinct TGFBI corneal dystrophies are linked to the stability of the fourth FAS1 domain of TGFBIp

DEFF Research Database (Denmark)

Runager, Kasper; Basaiawmoit, Rajiv Vaid; Deva, Taru

2011-01-01

Mutations in the human TGFBI gene encoding TGFBIp have been linked to protein deposits in the cornea leading to visual impairment. The protein consists of an N-terminal Cys-rich EMI domain and four consecutive fasciclin 1 (FAS1) domains. We have compared the stabilities of wild-type (WT) human...... TGFBIp and six mutants known to produce phenotypically distinct deposits in the cornea. Amino acid substitutions in the first FAS1 (FAS1-1) domain (R124H, R124L, and R124C) did not alter the stability. However, substitutions within the fourth FAS1 (FAS1-4) domain (A546T, R555Q, and R555W) affected...... the overall stability of intact TGFBIp revealing the following stability ranking R555W>WT>R555Q>A546T. Significantly, the stability ranking of the isolated FAS1-4 domains mirrored the behavior of the intact protein. In addition, it was linked to the aggregation propensity as the least stable mutant (A546T...
The therapeutic power of play: examining the play of young children with leukaemia.

Science.gov (United States)

Gariépy, N; Howe, N

2003-11-01

The therapeutic function of play has been investigated in relation to recognized stressors such as hospitalization, illness and medical treatments for ill children. While medical treatments in the past 30 years have improved survival rates, children's psychological experiences and quality of life during and after their illness have received limited attention. The present study investigated the therapeutic effects of play on 3- to 5-year-old children with leukaemia compared with a control group of healthy children. The participants with leukaemia (n = 11) were from the external oncology clinic of an urban children's hospital; control children (n = 11) attended a day care centre. Measures included children's experience of stress, social and cognitive play behaviours, and daily mood. A series of manova revealed that the children with leukaemia, compared with the control children, engaged in (a) significantly fewer total play behaviours, and in particular less (b) parallel, (c) group and (d) dramatic play. Pearson correlations revealed significant relationships between reports of 'being happy' and play only for children with leukaemia. Quantitative and qualitative analyses revealed a pattern of repetitive play activities week after week for children with leukaemia, but not controls. Findings are discussed in light of the theoretical and practical implications for children undergoing treatment for leukaemia.
Gender differences in game responses during badminton match play.

Science.gov (United States)

Fernandez-Fernandez, Jaime; de la Aleja Tellez, Jose G; Moya-Ramon, Manuel; Cabello-Manrique, David; Mendez-Villanueva, Alberto

2013-09-01

The aim of this study was to evaluate possible gender differences in match play activity pattern [rally duration, rest time between rallies, effective playing time, and strokes performed during a rally] and exercise intensity (heart rate [HR], blood lactate [La], and subjective ratings of perceived exertion [RPE]) during 9 simulated badminton matches in male (n = 8) and female (n = 8) elite junior (16.0 ± 1.4 years) players. Results showed significant differences (all p 0.05; ES = -0.33 to 0.08) were observed between female or male players in average HR (174 ± 7 vs. 170 ± 9 b·min(-1)), %HRmax (89.2 ± 4.0% vs. 85.9 ± 4.3%), La (2.5 ± 1.3 vs. 3.2 ± 1.8 mmol·L(-1)), and RPE values (14.2 ± 1.9 vs. 14.6 ± 1.8) during match play, although male players spent more time (moderate effect sizes) at intensities between 81 and 90% HRmax (35.3 ± 17.9 vs. 25.3 ± 13.6; p < 0.05; ES = 0.64) in the second game. There seemed to be a trend toward an increased playing intensity (i.e., higher HR, La, and RPE) from the first to the second game, highlighting the higher exercise intensity experienced during the last part of the match. The clear between-gender differences in activity patterns induced only slightly different physiological responses.
Guided play and free play in an enriched environment: Impact on motor development

Directory of Open Access Journals (Sweden)

Míriam Stock Palma

2014-06-01

Full Text Available The purpose of this study was to investigate the effects of guided play and free play in an enriched environmentintervention programs using motor skill development in kindergarten children. Seventy-one children attending kindergarten classes were assigned to two experimental groups and one control group. Participants performed the Test of Gross Motor Development-2 before and after the intervention period. Results revealed that both boys and girls in the guided play group showed motor skill improvement, whereas no changes were observed in motor development in the boys and girls assigned to the free play in enriched environment group, nor in those in the control group. These findings indicate that the teacher's role in the guided play intervention was crucial to help preschool children to improve their performance.
Play to Learn, Learn to Play: Language Learning through Gaming Culture

Science.gov (United States)

Ryu, Dongwan

2013-01-01

Many researchers have investigated learning through playing games. However, after playing games, players often go online to establish and participate in the online community where they enrich their game experiences, discuss game-related issues, and create fan-fictions, screenshots, or scenarios. Although these emerging activities are an essential…
Nanosatellite and Plug-and-Play Architecture 2 (NAPA 2)

Science.gov (United States)

2017-02-28

development of a 6U- format Space Plug-and-play Architecture (SPA) Research Cubesat (SPARC). SPARC-1 (first and only pursued under this PA) demonstrates...development of a six unit (6U)- format Space Plug-and-play Architecture (SPA) Research Cubesat (SPARC). SPARC-1 (first and only pursued under this PA...computers – More capable, more centralized, bigger wiring bundle Elimination of central computers, distribution of intelligence in systems Rad- hard
15 years of monitoring occupational exposure to respirable dust and quartz within the European industrial minerals sector.

Science.gov (United States)

Zilaout, Hicham; Vlaanderen, Jelle; Houba, Remko; Kromhout, Hans

2017-07-01

In 2000, a prospective Dust Monitoring Program (DMP) was started in which measurements of worker's exposure to respirable dust and quartz are collected in member companies from the European Industrial Minerals Association (IMA-Europe). After 15 years, the resulting IMA-DMP database allows a detailed overview of exposure levels of respirable dust and quartz over time within this industrial sector. Our aim is to describe the IMA-DMP and the current state of the corresponding database which due to continuation of the IMA-DMP is still growing. The future use of the database will also be highlighted including its utility for the industrial minerals producing sector. Exposure data are being obtained following a common protocol including a standardized sampling strategy, standardized sampling and analytical methods and a data management system. Following strict quality control procedures, exposure data are consequently added to a central database. The data comprises personal exposure measurements including auxiliary information on work and other conditions during sampling. Currently, the IMA-DMP database consists of almost 28,000 personal measurements which have been performed from 2000 until 2015 representing 29 half-yearly sampling campaigns. The exposure data have been collected from 160 different worksites owned by 35 industrial mineral companies and comes from 23 European countries and approximately 5000 workers. The IMA-DMP database provides the European minerals sector with reliable data regarding worker personal exposures to respirable dust and quartz. The database can be used as a powerful tool to address outstanding scientific issues on long-term exposure trends and exposure variability, and importantly, as a surveillance tool to evaluate exposure control measures. The database will be valuable for future epidemiological studies on respiratory health effects and will allow for estimation of quantitative exposure response relationships. Copyright © 2017 The
A scalable variational inequality approach for flow through porous media models with pressure-dependent viscosity

Science.gov (United States)

Mapakshi, N. K.; Chang, J.; Nakshatrala, K. B.

2018-04-01

Mathematical models for flow through porous media typically enjoy the so-called maximum principles, which place bounds on the pressure field. It is highly desirable to preserve these bounds on the pressure field in predictive numerical simulations, that is, one needs to satisfy discrete maximum principles (DMP). Unfortunately, many of the existing formulations for flow through porous media models do not satisfy DMP. This paper presents a robust, scalable numerical formulation based on variational inequalities (VI), to model non-linear flows through heterogeneous, anisotropic porous media without violating DMP. VI is an optimization technique that places bounds on the numerical solutions of partial differential equations. To crystallize the ideas, a modification to Darcy equations by taking into account pressure-dependent viscosity will be discretized using the lowest-order Raviart-Thomas (RT0) and Variational Multi-scale (VMS) finite element formulations. It will be shown that these formulations violate DMP, and, in fact, these violations increase with an increase in anisotropy. It will be shown that the proposed VI-based formulation provides a viable route to enforce DMP. Moreover, it will be shown that the proposed formulation is scalable, and can work with any numerical discretization and weak form. A series of numerical benchmark problems are solved to demonstrate the effects of heterogeneity, anisotropy and non-linearity on DMP violations under the two chosen formulations (RT0 and VMS), and that of non-linearity on solver convergence for the proposed VI-based formulation. Parallel scalability on modern computational platforms will be illustrated through strong-scaling studies, which will prove the efficiency of the proposed formulation in a parallel setting. Algorithmic scalability as the problem size is scaled up will be demonstrated through novel static-scaling studies. The performed static-scaling studies can serve as a guide for users to be able to select

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