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Sample records for insertions define distinct

  1. KRAS insertion mutations are oncogenic and exhibit distinct functional properties

    PubMed Central

    White, Yasmine; Bagchi, Aditi; Van Ziffle, Jessica; Inguva, Anagha; Bollag, Gideon; Zhang, Chao; Carias, Heidi; Dickens, David; Loh, Mignon; Shannon, Kevin; Firestone, Ari J.

    2016-01-01

    Oncogenic KRAS mutations introduce discrete amino acid substitutions that reduce intrinsic Ras GTPase activity and confer resistance to GTPase-activating proteins (GAPs). Here we discover a partial duplication of the switch 2 domain of K-Ras encoding a tandem repeat of amino acids G60_A66dup in a child with an atypical myeloproliferative neoplasm. K-Ras proteins containing this tandem duplication or a similar five amino acid E62_A66dup mutation identified in lung and colon cancers transform the growth of primary myeloid progenitors and of Ba/F3 cells. Recombinant K-RasG60_A66dup and K-RasE62_A66dup proteins display reduced intrinsic GTP hydrolysis rates, accumulate in the GTP-bound conformation and are resistant to GAP-mediated GTP hydrolysis. Remarkably, K-Ras proteins with switch 2 insertions are impaired for PI3 kinase binding and Akt activation, and are hypersensitive to MEK inhibition. These studies illuminate a new class of oncogenic KRAS mutations and reveal unexpected plasticity in oncogenic Ras proteins that has diagnostic and therapeutic implications. PMID:26854029

  2. Acute myeloid leukemia ontogeny is defined by distinct somatic mutations

    PubMed Central

    Lindsley, R. Coleman; Mar, Brenton G.; Mazzola, Emanuele; Grauman, Peter V.; Shareef, Sarah; Allen, Steven L.; Pigneux, Arnaud; Wetzler, Meir; Stuart, Robert K.; Erba, Harry P.; Damon, Lloyd E.; Powell, Bayard L.; Lindeman, Neal; Steensma, David P.; Wadleigh, Martha; DeAngelo, Daniel J.; Neuberg, Donna

    2015-01-01

    Acute myeloid leukemia (AML) can develop after an antecedent myeloid malignancy (secondary AML [s-AML]), after leukemogenic therapy (therapy-related AML [t-AML]), or without an identifiable prodrome or known exposure (de novo AML). The genetic basis of these distinct pathways of AML development has not been determined. We performed targeted mutational analysis of 194 patients with rigorously defined s-AML or t-AML and 105 unselected AML patients. The presence of a mutation in SRSF2, SF3B1, U2AF1, ZRSR2, ASXL1, EZH2, BCOR, or STAG2 was >95% specific for the diagnosis of s-AML. Analysis of serial samples from individual patients revealed that these mutations occur early in leukemogenesis and often persist in clonal remissions. In t-AML and elderly de novo AML populations, these alterations define a distinct genetic subtype that shares clinicopathologic properties with clinically confirmed s-AML and highlights a subset of patients with worse clinical outcomes, including a lower complete remission rate, more frequent reinduction, and decreased event-free survival. This trial was registered at www.clinicaltrials.gov as #NCT00715637. PMID:25550361

  3. Local interneurons define functionally distinct regions within lobster olfactory glomeruli

    PubMed

    Wachowiak; Diebel; Ache

    1997-01-01

    Whole-cell recording coupled with biocytin injection revealed four types of interneurons intrinsic to the olfactory lobe (OL) of the spiny lobster Panulirus argus. Each type of neuron had a distinct pattern of arborization within the three anatomically defined regions of OL glomeruli (cap, subcap and base). Type I interneurons innervated all three regions, while types II, III and IV branched only in the cap, subcap and base, respectively. Type I interneurons responded to electrical stimulation of the antennular (olfactory) nerve with a burst of 1­20 action potentials and a 1­10 s depolarization. Type II (cap) interneurons responded to the same input with a burst of 1­3 action potentials followed by a shorter hyperpolarization. Type III (subcap) interneurons responded with a burst of 1­6 action potentials followed by a delayed, 0.5­4 s depolarization. Type IV (base) interneurons responded with a brief depolarization or a burst of 1­3 action potentials followed by a 1 s hyperpolarization. The regionalized arborization and the different response properties of the type II, III and IV interneurons strongly imply that lobster olfactory glomeruli contain functionally distinct regions, a feature that should be useful in understanding the multiple synaptic pathways involved in processing olfactory input.

  4. Insertion and deletion events that define the pathogen Mycobacterium avium subsp. paratuberculosis.

    PubMed

    Alexander, David C; Turenne, Christine Y; Behr, Marcel A

    2009-02-01

    Mycobacterium avium comprises genetically related yet phenotypically distinct subspecies. Consistent with their common origin, whole-genome sequence comparisons have revealed extensive synteny among M. avium organisms. However, the sequenced strains also display numerous regions of heterogeneity that likely contribute to the diversity of the individual subspecies. Starting from a phylogenetic framework derived by multilocus sequence analysis, we examined the distribution of 25 large sequence polymorphisms across a panel of genetically defined M. avium strains. This distribution was most variable among M. avium subsp. hominissuis isolates. In contrast, M. avium subsp. paratuberculosis strains exhibited a characteristic profile, with all isolates containing a set of genomic insertions absent from other M. avium strains. The emergence of the pathogen from its putative M. avium subsp. hominissuis ancestor entailed the acquisition of approximately 125 kb of novel genetic material, followed by a second phase, characterized by reductive genomics. One genomic deletion is common to all isolates while additional deletions distinguish two major lineages of M. avium subsp. paratuberculosis. For the average strain, these losses total at least 38 kb (sheep lineage) to 90 kb (cattle lineage). This biphasic pattern of evolution, characterized by chromosomal gene acquisition with subsequent gene loss, describes the emergence of M. avium subsp. paratuberculosis and may serve as a general model for the origin of pathogenic mycobacteria.

  5. Distinct Oral Neutrophil Subsets Define Health and Periodontal Disease States.

    PubMed

    Fine, N; Hassanpour, S; Borenstein, A; Sima, C; Oveisi, M; Scholey, J; Cherney, D; Glogauer, M

    2016-07-01

    Neutrophils exit the vasculature and swarm to sites of inflammation and infection. However, these cells are abundant in the healthy, inflammation-free human oral environment, suggesting a unique immune surveillance role within the periodontium. We hypothesize that neutrophils in the healthy oral cavity occur in an intermediary parainflammatory state that allows them to interact with and contain the oral microflora without eliciting a marked inflammatory response. Based on a high-throughput screen of neutrophil CD (cluster of differentiation) marker expression and a thorough literature review, we developed multicolor flow cytometry panels to determine the surface marker signatures of oral neutrophil subsets in periodontal health and disease. We define here 3 distinct neutrophil subsets: resting/naive circulatory neutrophils, parainflammatory neutrophils found in the healthy oral cavity, and proinflammatory neutrophils found in the oral cavity during chronic periodontal disease. Furthermore, parainflammatory neutrophils manifest as 2 distinct subpopulations-based on size, granularity, and expression of specific CD markers-and exhibit intermediate levels of activation as compared with the proinflammatory oral neutrophils. These intermediately activated parainflammatory populations occur in equal proportions in the healthy oral cavity, with a shift to one highly activated proinflammatory neutrophil population in chronic periodontal disease. This work is the first to identify and characterize oral parainflammatory neutrophils that interact with commensal biofilms without inducing an inflammatory response, thereby demonstrating that not all neutrophils trafficking through periodontal tissues are fully activated. In addition to establishing possible diagnostic and treatment monitoring biomarkers, this oral neutrophil phenotype model builds on existing literature suggesting that the healthy periodontium may be in a parainflammatory state. © International & American

  6. Subaxial cervical pedicle screw insertion with newly defined entry point and trajectory: accuracy evaluation in cadavers.

    PubMed

    Zheng, Xiujun; Chaudhari, Rahul; Wu, Chunhui; Mehbod, Amir A; Transfeldt, Ensor E

    2010-01-01

    Successful placement of cervical pedicle screws requires accurate identification of both entry point and trajectory. However, literature has not provided consistent recommendations regarding the direction of pedicle screw insertion and entry point location. The objective of this study was to define a guideline regarding the optimal entry point and trajectory in placing subaxial cervical pedicle screws and to evaluate the screw accuracy in cadaver cervical spines. The guideline for entry point and trajectory for each vertebra was established based on the recently published morphometric data. Six fresh frozen cervical spines (C3-C7) were used. There were two men and four women. After posterior exposure, the entry point was determined and the cortical bone of the entry point was removed using a 2-mm burr. Pilot holes were created with a cervical probe based on the guideline using fluoroscopy. After tapping, 3.5-mm screws with appropriate length were inserted. After screw insertion, every vertebra was dissected and inspected for pedicle breach. The pedicle width, height, pedicle transverse angulation and actual screw insertion angle were measured. A total of 60 pedicle screws were inserted. No statistical difference in pedicle width and height was found between the left and right sides for each level. The overall accuracy of pedicle screws was 83.3%. The remaining 13.3% screws had noncritical breach, and 3.3% had critical breach. The critical breach was not caused by the guideline. There was no statistical difference between the pedicle transverse angulation and the actual screw trajectory created using the guideline. There was statistical difference in pedicle width between the breach and non-breach screws. In conclusion, high success rate of subaxial cervical pedicle screw placement can be achieved using the recently proposed operative guideline and oblique views of fluoroscopy. However, careful preoperative planning and good surgical skills are still required to

  7. Distinct clinical phenotypes of airways disease defined by cluster analysis.

    PubMed

    Weatherall, M; Travers, J; Shirtcliffe, P M; Marsh, S E; Williams, M V; Nowitz, M R; Aldington, S; Beasley, R

    2009-10-01

    Airways disease is currently classified using diagnostic labels such as asthma, chronic bronchitis and emphysema. The current definitions of these classifications may not reflect the phenotypes of airways disease in the community, which may have differing disease processes, clinical features or responses to treatment. The aim of the present study was to use cluster analysis to explore clinical phenotypes in a community population with airways disease. A random population sample of 25-75-yr-old adults underwent detailed investigation, including a clinical questionnaire, pulmonary function tests, nitric oxide measurements, blood tests and chest computed tomography. Cluster analysis was performed on the subgroup with current respiratory symptoms or obstructive spirometric results. Subjects with a complete dataset (n = 175) were included in the cluster analysis. Five clusters were identified with the following characteristics: cluster 1: severe and markedly variable airflow obstruction with features of atopic asthma, chronic bronchitis and emphysema; cluster 2: features of emphysema alone; cluster 3: atopic asthma with eosinophilic airways inflammation; cluster 4: mild airflow obstruction without other dominant phenotypic features; and cluster 5: chronic bronchitis in nonsmokers. Five distinct clinical phenotypes of airflow obstruction were identified. If confirmed in other populations, these findings may form the basis of a modified taxonomy for the disorders of airways obstruction.

  8. Distinct transcriptomes define rostral and caudal serotonin neurons

    PubMed Central

    Wylie, Christi J.; Hendricks, Timothy J.; Zhang, Bing; Wang, Lily; Lu, Pengcheng; Leahy, Patrick; Fox, Stephanie; Maeno, Hiroshi; Deneris, Evan S.

    2012-01-01

    The molecular architecture of developing serotonin (5HT) neurons is poorly understood yet its determination is likely to be essential for elucidating functional heterogeneity of these cells and the contribution of serotonergic dysfunction to disease pathogenesis. Here, we describe the purification of postmitotic embryonic 5HT neurons by flow cytometry for whole genome microarray expression profiling of this unitary monoaminergic neuron type. Our studies identified significantly enriched expression of hundreds of unique genes in 5HT neurons thus providing an abundance of new serotonergic markers. Furthermore, we identified several hundred transcripts encoding homeodomain, axon guidance, cell adhesion, intracellular signaling, ion transport, and imprinted genes associated with various neurodevelopmental disorders that were differentially enriched in developing rostral and caudal 5HT neurons. These findings suggested a homeodomain code that distinguishes rostral and caudal 5HT neurons. Indeed, verification studies demonstrated that Hmx homeodomain and Hox gene expression defined an Hmx+ rostral subtype and Hox+ caudal subtype. Expression of engrailed genes in a subset of 5HT neurons in the rostral domain further distinguished two subtypes defined as Hmx+En+ and Hmx+En-. The differential enrichment of gene sets for different canonical pathways and gene ontology categories provided additional evidence for heterogeneity between rostral and caudal 5HT neurons. These findings demonstrate a deep transcriptome and biological pathway duality for neurons that give rise to the ascending and descending serotonergic subsystems. Our databases provide a rich, clinically relevant, resource for definition of 5HT neuron subtypes and elucidation of the genetic networks required for serotonergic function. PMID:20071532

  9. Modified Direct Insertion/Cancellation Method Based Sample Rate Conversion for Software Defined Radio

    NASA Astrophysics Data System (ADS)

    Bostamam, Anas Muhamad; Sanada, Yukitoshi; Minami, Hideki

    In this paper, a new fractional sample rate conversion (SRC) scheme based on a direct insertion/cancellation scheme is proposed. This scheme is suitable for signals that are sampled at a high sample rate and converted to a lower sample rate. The direct insertion/cancellation scheme may achieve low-complexity and lower power consumption as compared to the other SRC techniques. However, the direct insertion/cancellation technique suffers from large aliasing and distortion. The aliasing from an adjacent channel interferes the desired signal and degrades the performance. Therefore, a modified direct insertion/cancellation scheme is proposed in order to realize high performance resampling.

  10. Biologically distinct subtypes of Mycobacterium avium differ in possession of insertion sequence IS901.

    PubMed

    Kunze, Z M; Portaels, F; McFadden, J J

    1992-09-01

    Mycobacterium avium causes disease, principally tuberculosis in immunocompromised individuals. It is the most frequent cause of disseminated infections in AIDS patients in the West. The pathogen is also associated with disease in animals, chiefly birds and livestock, and may be isolated from environmental samples such as soil and water. Analysis of strains of M. avium isolated from clinical, veterinary, and environmental sources for the presence of the mycobacterial insertion sequences IS900 and IS901 demonstrates the specific association of IS901 to animal pathogenic M. avium strains. In contrast, most clinical M. avium strains and all AIDS-derived strains examined so far lacked IS901. Significant differences in the plasmid contents and serotypes of strains with and without IS901 were also found. We therefore suggest that the presence of IS901 divides M. avium into two clearly distinct subtypes with differing host range, virulence, plasmid possession, and serotyping antigens. By using DNA sequence data from IS901 and M. avium DNA, a set of polymerase chain reactions were developed for the specific detection and differentiation of these subtypes.

  11. Distinct germline progenitor subsets defined through Tsc2–mTORC1 signaling

    PubMed Central

    Hobbs, Robin M; La, Hue M; Mäkelä, Juho-Antti; Kobayashi, Toshiyuki; Noda, Tetsuo; Pandolfi, Pier Paolo

    2015-01-01

    Adult tissue maintenance is often dependent on resident stem cells; however, the phenotypic and functional heterogeneity existing within this self-renewing population is poorly understood. Here, we define distinct subsets of undifferentiated spermatogonia (spermatogonial progenitor cells; SPCs) by differential response to hyperactivation of mTORC1, a key growth-promoting pathway. We find that conditional deletion of the mTORC1 inhibitor Tsc2 throughout the SPC pool using Vasa-Cre promotes differentiation at the expense of self-renewal and leads to germline degeneration. Surprisingly, Tsc2 ablation within a subset of SPCs using Stra8-Cre did not compromise SPC function. SPC activity also appeared unaffected by Amh-Cre-mediated Tsc2 deletion within somatic cells of the niche. Importantly, we find that differentiation-prone SPCs have elevated mTORC1 activity when compared to SPCs with high self-renewal potential. Moreover, SPCs insensitive to Tsc2 deletion are preferentially associated with mTORC1-active committed progenitor fractions. We therefore delineate SPC subsets based on differential mTORC1 activity and correlated sensitivity to Tsc2 deletion. We propose that mTORC1 is a key regulator of SPC fate and defines phenotypically distinct SPC subpopulations with varying propensities for self-renewal and differentiation. PMID:25700280

  12. Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires

    PubMed Central

    Yang, Yang; Wang, Chunlin; Yang, Qunying; Kantor, Aaron B; Chu, Hiutung; Ghosn, Eliver EB; Qin, Guang; Mazmanian, Sarkis K; Han, Jian; Herzenberg, Leonore A

    2015-01-01

    Processes that define immunoglobulin repertoires are commonly presumed to be the same for all murine B cells. However, studies here that couple high-dimensional FACS sorting with large-scale quantitative IgH deep-sequencing demonstrate that B-1a IgH repertoire differs dramatically from the follicular and marginal zone B cells repertoires and is defined by distinct mechanisms. We track B-1a cells from their early appearance in neonatal spleen to their long-term residence in adult peritoneum and spleen. We show that de novo B-1a IgH rearrangement mainly occurs during the first few weeks of life, after which their repertoire continues to evolve profoundly, including convergent selection of certain V(D)J rearrangements encoding specific CDR3 peptides in all adults and progressive introduction of hypermutation and class-switching as animals age. This V(D)J selection and AID-mediated diversification operate comparably in germ-free and conventional mice, indicating these unique B-1a repertoire-defining mechanisms are driven by antigens that are not derived from microbiota. DOI: http://dx.doi.org/10.7554/eLife.09083.001 PMID:26422511

  13. Distinct mechanisms define murine B cell lineage immunoglobulin heavy chain (IgH) repertoires.

    PubMed

    Yang, Yang; Wang, Chunlin; Yang, Qunying; Kantor, Aaron B; Chu, Hiutung; Ghosn, Eliver Eb; Qin, Guang; Mazmanian, Sarkis K; Han, Jian; Herzenberg, Leonore A

    2015-09-30

    Processes that define immunoglobulin repertoires are commonly presumed to be the same for all murine B cells. However, studies here that couple high-dimensional FACS sorting with large-scale quantitative IgH deep-sequencing demonstrate that B-1a IgH repertoire differs dramatically from the follicular and marginal zone B cells repertoires and is defined by distinct mechanisms. We track B-1a cells from their early appearance in neonatal spleen to their long-term residence in adult peritoneum and spleen. We show that de novo B-1a IgH rearrangement mainly occurs during the first few weeks of life, after which their repertoire continues to evolve profoundly, including convergent selection of certain V(D)J rearrangements encoding specific CDR3 peptides in all adults and progressive introduction of hypermutation and class-switching as animals age. This V(D)J selection and AID-mediated diversification operate comparably in germ-free and conventional mice, indicating these unique B-1a repertoire-defining mechanisms are driven by antigens that are not derived from microbiota.

  14. Genes expressed in the brain define three distinct neuronal nicotinic acetylcholine receptors.

    PubMed Central

    Nef, P; Oneyser, C; Alliod, C; Couturier, S; Ballivet, M

    1988-01-01

    Four genes encode the related protein subunits that assemble to form the nicotinic acetylcholine receptor (nAChR) at the motor endplate of vertebrates. We have isolated from the chicken genome four additional members of the same gene family whose protein products, termed alpha 2, alpha 3, alpha 4 and n alpha (non-alpha) probably define three distinct neuronal nAChR subtypes. The neuronal nAChR genes have identical structures consisting of six protein-coding exons and specify proteins that are best aligned with the chicken endplate alpha subunit, whose gene we have also characterized. mRNA transcripts encoding alpha 4 and n alpha are abundant in embryonic and in adult avian brain, whereas alpha 2 and alpha 3 transcripts are much scarcer. The same set of neuronal genes probably exists in all vertebrates since their counterparts have also been identified in the rat genome. Images PMID:3267226

  15. The C-terminal Domains of Apoptotic BH3-only Proteins Mediate Their Insertion into Distinct Biological Membranes.

    PubMed

    Andreu-Fernández, Vicente; García-Murria, María J; Bañó-Polo, Manuel; Martin, Juliette; Monticelli, Luca; Orzáez, Mar; Mingarro, Ismael

    2016-11-25

    Changes in the equilibrium of pro- and anti-apoptotic members of the B-cell lymphoma-2 (Bcl-2) protein family in the mitochondrial outer membrane (MOM) induce structural changes that commit cells to apoptosis. Bcl-2 homology-3 (BH3)-only proteins participate in this process by either activating pro-apoptotic effectors or inhibiting anti-apoptotic components and by promoting MOM permeabilization. The association of BH3-only proteins with MOMs is necessary for the activation and amplification of death signals; however, the nature of this association remains controversial, as these proteins lack a canonical transmembrane sequence. Here we used an in vitro expression system to study the insertion capacity of hydrophobic C-terminal regions of the BH3-only proteins Bik, Bim, Noxa, Bmf, and Puma into microsomal membranes. An Escherichia coli complementation assay was used to validate the results in a cellular context, and peptide insertions were modeled using molecular dynamics simulations. We also found that some of the C-terminal domains were sufficient to direct green fluorescent protein fusion proteins to specific membranes in human cells, but the domains did not activate apoptosis. Thus, the hydrophobic regions in the C termini of BH3-only members associated in distinct ways with various biological membranes, suggesting that a detailed investigation of the entire process of apoptosis should include studying the membranes as a setting for protein-protein and protein-membrane interactions. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. VgrG and PAAR Proteins Define Distinct Versions of a Functional Type VI Secretion System

    PubMed Central

    Cianfanelli, Francesca R.; Alcoforado Diniz, Juliana; Guo, Manman; De Cesare, Virginia; Trost, Matthias; Coulthurst, Sarah J.

    2016-01-01

    The Type VI secretion system (T6SS) is widespread among bacterial pathogens and acts as an effective weapon against competitor bacteria and eukaryotic hosts by delivering toxic effector proteins directly into target cells. The T6SS utilises a bacteriophage-like contractile machinery to expel a puncturing device based on a tube of Hcp topped with a VgrG spike, which can be extended by a final tip from a PAAR domain-containing protein. Effector proteins are believed to be delivered by specifically associating with particular Hcp, VgrG or PAAR proteins, either covalently (‘specialised’) or non-covalently (‘cargo’ effectors). Here we used the T6SS of the opportunistic pathogen Serratia marcescens, together with integratecd genetic, proteomic and biochemical approaches, to elucidate the role of specific VgrG and PAAR homologues in T6SS function and effector specificity, revealing new aspects and unexpected subtleties in effector delivery by the T6SS. We identified effectors, both cargo and specialised, absolutely dependent on a particular VgrG for delivery to target cells, and discovered that other cargo effectors can show a preference for a particular VgrG. The presence of at least one PAAR protein was found to be essential for T6SS function, consistent with designation as a ‘core’ T6SS component. We showed that specific VgrG-PAAR combinations are required to assemble a functional T6SS and that the three distinct VgrG-PAAR assemblies in S. marcescens exhibit distinct effector specificity and efficiency. Unexpectedly, we discovered that two different PAAR-containing Rhs proteins can functionally pair with the same VgrG protein. Showing that accessory EagR proteins are involved in these interactions, native VgrG-Rhs-EagR complexes were isolated and specific interactions between EagR and cognate Rhs proteins identified. This study defines an essential yet flexible role for PAAR proteins in the T6SS and highlights the existence of distinct versions of the

  17. Molecular classification defines 4 prognostically distinct glioma groups irrespective of diagnosis and grade.

    PubMed

    Mur, Pilar; Mollejo, Manuela; Hernández-Iglesias, Teresa; de Lope, Ángel Rodríguez; Castresana, Javier S; García, Juan F; Fiaño, Concepción; Ribalta, Teresa; Rey, Juan A; Meléndez, Barbara

    2015-03-01

    According to World Health Organization criteria, diffuse gliomas are divided into several histological subtypes, including astrocytomas, oligodendrogliomas, and oligoastrocytomas, and 4 malignancy grades (I-IV). Molecular alterations, such as the isocitrate dehydrogenase gene (IDH) mutation or 1p/19q loss, are found in these tumors but are not included in the current classification system. Recently, mutation of α thalassemia/mental retardation syndrome X-linked (ATRX) gene and its loss of expression have been reported in infiltrating gliomas. We evaluated ATRX protein expression in 272 gliomas and its association with molecular and clinical features. Loss of ATRX expression was more common in tumors with an astrocytic component (astrocytomas II/III, 46.4%; oligoastrocytomas, 47.5%) but was uncommon in oligodendrogliomas (7.3%) and glioblastomas (0.9%). In astrocytic tumors, loss of ATRX expression was significantly associated with longer overall survival. Remarkably, on the basis of IDH mutation, 1p/19q codeletion, and ATRX expression, our study defined 4 molecularly and prognostically different groups of gliomas, showing the relevance of ATRX expression as a new marker for refining the molecular classification of gliomas and for distinguishing clinically distinct prognostic subgroups of patients.

  18. Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas.

    PubMed

    Clark, Victoria E; Harmancı, Akdes Serin; Bai, Hanwen; Youngblood, Mark W; Lee, Tong Ihn; Baranoski, Jacob F; Ercan-Sencicek, A Gulhan; Abraham, Brian J; Weintraub, Abraham S; Hnisz, Denes; Simon, Matthias; Krischek, Boris; Erson-Omay, E Zeynep; Henegariu, Octavian; Carrión-Grant, Geneive; Mishra-Gorur, Ketu; Durán, Daniel; Goldmann, Johanna E; Schramm, Johannes; Goldbrunner, Roland; Piepmeier, Joseph M; Vortmeyer, Alexander O; Günel, Jennifer Moliterno; Bilgüvar, Kaya; Yasuno, Katsuhito; Young, Richard A; Günel, Murat

    2016-10-01

    RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes, including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO, we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features.

  19. Recurrent somatic mutations in POLR2A define a distinct subset of meningiomas

    PubMed Central

    Clark, Victoria E; Harmancı, Akdes Serin; Bai, Hanwen; Youngblood, Mark W; Lee, Tong Ihn; Baranoski, Jacob F; Ercan-Sencicek, A Gulhan; Abraham, Brian J; Weintraub, Abraham S; Hnisz, Denes; Simon, Matthias; Krischek, Boris; Erson-Omay, E Zeynep; Henegariu, Octavian; Carrión-Grant, Geneive; Mishra-Gorur, Ketu; Durán, Daniel; Goldmann, Johanna E; Schramm, Johannes; Goldbrunner, Roland; Piepmeier, Joseph M; Vortmeyer, Alexander O; Günel, Jennifer Moliterno; Bilgüvar, Kaya; Yasuno, Katsuhito; Young, Richard A; Günel, Murat

    2016-01-01

    RNA polymerase II mediates the transcription of all protein-coding genes in eukaryotic cells, a process that is fundamental to life. Genomic mutations altering this enzyme have not previously been linked to any pathology in humans, which is a testament to its indispensable role in cell biology. On the basis of a combination of next-generation genomic analyses of 775 meningiomas, we report that recurrent somatic p.Gln403Lys or p.Leu438_His439del mutations in POLR2A, which encodes the catalytic subunit of RNA polymerase II (ref. 1), hijack this essential enzyme and drive neoplasia. POLR2A mutant tumors show dysregulation of key meningeal identity genes2, 3, including WNT6 and ZIC1/ZIC4. In addition to mutations in POLR2A, NF2, SMARCB1, TRAF7, KLF4, AKT1, PIK3CA, and SMO4, 5, 6, 7, 8, we also report somatic mutations in AKT3, PIK3R1, PRKAR1A, and SUFU in meningiomas. Our results identify a role for essential transcriptional machinery in driving tumorigenesis and define mutually exclusive meningioma subgroups with distinct clinical and pathological features. PMID:27548314

  20. MicroRNAs define distinct human neuroblastoma cell phenotypes and regulate their differentiation and tumorigenicity

    PubMed Central

    2014-01-01

    Background Neuroblastoma (NB) is the most common extracranial solid tumor in children. NB tumors and derived cell lines are phenotypically heterogeneous. Cell lines are classified by phenotype, each having distinct differentiation and tumorigenic properties. The neuroblastic phenotype is tumorigenic, has neuronal features and includes stem cells (I-cells) and neuronal cells (N-cells). The non-neuronal phenotype (S-cell) comprises cells that are non-tumorigenic with features of glial/smooth muscle precursor cells. This study identified miRNAs associated with each distinct cell phenotypes and investigated their role in regulating associated differentiation and tumorigenic properties. Methods A miRNA microarray was performed on the three cell phenotypes and expression verified by qRT-PCR. miRNAs specific for certain cell phenotypes were modulated using miRNA inhibitors or stable transfection. Neuronal differentiation was induced by RA; non-neuronal differentiation by BrdU. Changes in tumorigenicity were assayed by soft agar colony forming ability. N-myc binding to miR-375 promoter was assayed by chromatin-immunoprecipitation. Results Unsupervised hierarchical clustering of miRNA microarray data segregated neuroblastic and non-neuronal cell lines and showed that specific miRNAs define each phenotype. qRT-PCR validation confirmed that increased levels of miR-21, miR-221 and miR-335 are associated with the non-neuronal phenotype, whereas increased levels of miR-124 and miR-375 are exclusive to neuroblastic cells. Downregulation of miR-335 in non-neuronal cells modulates expression levels of HAND1 and JAG1, known modulators of neuronal differentiation. Overexpression of miR-124 in stem cells induces terminal neuronal differentiation with reduced malignancy. Expression of miR-375 is exclusive for N-myc-expressing neuroblastic cells and is regulated by N-myc. Moreover, miR-375 downregulates expression of the neuronal-specific RNA binding protein HuD. Conclusions Thus, mi

  1. Identification of myosin XI receptors in Arabidopsis defines a distinct class of transport vesicles.

    PubMed

    Peremyslov, Valera V; Morgun, Eva A; Kurth, Elizabeth G; Makarova, Kira S; Koonin, Eugene V; Dolja, Valerian V

    2013-08-01

    To characterize the mechanism through which myosin XI-K attaches to its principal endomembrane cargo, a yeast two-hybrid library of Arabidopsis thaliana cDNAs was screened using the myosin cargo binding domain as bait. This screen identified two previously uncharacterized transmembrane proteins (hereinafter myosin binding proteins or MyoB1/2) that share a myosin binding, conserved domain of unknown function 593 (DUF593). Additional screens revealed that MyoB1/2 also bind myosin XI-1, whereas myosin XI-I interacts with the distantly related MyoB7. The in vivo interactions of MyoB1/2 with myosin XI-K were confirmed by immunoprecipitation and colocalization analyses. In epidermal cells, the yellow fluorescent protein-tagged MyoB1/2 localize to vesicles that traffic in a myosin XI-dependent manner. Similar to myosin XI-K, MyoB1/2 accumulate in the tip-growing domain of elongating root hairs. Gene knockout analysis demonstrated that functional cooperation between myosin XI-K and MyoB proteins is required for proper plant development. Unexpectedly, the MyoB1-containing vesicles did not correspond to brefeldin A-sensitive Golgi and post-Golgi or prevacuolar compartments and did not colocalize with known exocytic or endosomal compartments. Phylogenomic analysis suggests that DUF593 emerged in primitive land plants and founded a multigene family that is conserved in all flowering plants. Collectively, these findings indicate that MyoB are membrane-anchored myosin receptors that define a distinct, plant-specific transport vesicle compartment.

  2. (Non-V600) BRAF Mutations Define a Clinically Distinct Molecular Subtype of Metastatic Colorectal Cancer.

    PubMed

    Jones, Jeremy C; Renfro, Lindsay A; Al-Shamsi, Humaid O; Schrock, Alexa B; Rankin, Andrew; Zhang, Ben Y; Kasi, Pashtoon M; Voss, Jesse S; Leal, Alexis D; Sun, James; Ross, Jeffrey; Ali, Siraj M; Hubbard, Joleen M; Kipp, Benjamin R; McWilliams, Robert R; Kopetz, Scott; Wolff, Robert A; Grothey, Axel

    2017-08-10

    Purpose Molecular diagnostic testing has become an integral part of the evaluation of patients with metastatic colorectal cancer (CRC). Expanded mutational testing, such as next-generation sequencing (NGS), often identifies mutations with unclear clinical or prognostic implications. One such example is BRAF mutations that occur outside of codon 600 ((non-V600) BRAF mutations). Methods We conducted this multicenter, retrospective cohort study to characterize the clinical, pathologic, and survival implications of (non-V600) BRAF mutations in metastatic CRC. We pooled patients in whom (non-V600) BRAF mutations were identified from NGS databases at three large molecular genetics reference laboratories. Results A total of 9,643 patients with metastatic CRC underwent NGS testing. We identified 208 patients with (non-V600) BRAF mutations, which occurred in 2.2% of all patients tested and accounted for 22% of all BRAF mutations identified. Cancers with (non-V600) BRAF mutations, compared with cancers with V600E BRAF ((V600E) BRAF) mutations, were found in patients who were significantly younger (58 v 68 years, respectively), fewer female patients (46% v 65%, respectively), and patients who had fewer high-grade tumors (13% v 64%, respectively) or right-sided primary tumors (36% v 81%, respectively). Median overall survival was significantly longer in patients with (non-V600) BRAF-mutant metastatic CRC compared with those with both (V600E) BRAF-mutant and wild-type BRAF metastatic CRC (60.7 v 11.4 v 43.0 months, respectively; P < .001). In multivariable analysis, (non-V600) BRAF mutation was independently associated with improved overall survival (hazard ratio, 0.18; P < .001). Conclusion (Non-V600) BRAF mutations occur in approximately 2.2% of patients with metastatic CRC and define a clinically distinct subtype of CRC with an excellent prognosis.

  3. Distinct prion strains are defined by amyloid core structure and chaperone binding site dynamics.

    PubMed

    Frederick, Kendra K; Debelouchina, Galia T; Kayatekin, Can; Dorminy, Tea; Jacavone, Angela C; Griffin, Robert G; Lindquist, Susan

    2014-02-20

    Yeast prions are self-templating protein-based mechanisms of inheritance whose conformational changes lead to the acquisition of diverse new phenotypes. The best studied of these is the prion domain (NM) of Sup35, which forms an amyloid that can adopt several distinct conformations (strains) that produce distinct phenotypes. Using magic-angle spinning nuclear magnetic resonance spectroscopy, we provide a detailed look at the dynamic properties of these forms over a broad range of timescales. We establish that different prion strains have distinct amyloid structures, with many side chains in different chemical environments. Surprisingly, the prion strain with a larger fraction of rigid residues also has a larger fraction of highly mobile residues. Differences in mobility correlate with differences in interaction with the prion-partitioning factor Hsp104 in vivo, perhaps explaining strain-specific differences in inheritance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. Reliability, Dimensionality, and Internal Consistency as Defined by Cronbach: Distinct Albeit Related Concepts

    ERIC Educational Resources Information Center

    Davenport, Ernest C.; Davison, Mark L.; Liou, Pey-Yan; Love, Quintin U.

    2015-01-01

    This article uses definitions provided by Cronbach in his seminal paper for coefficient a to show the concepts of reliability, dimensionality, and internal consistency are distinct but interrelated. The article begins with a critique of the definition of reliability and then explores mathematical properties of Cronbach's a. Internal consistency…

  5. Distinct T cell signatures define subsets of patients with multiple sclerosis

    PubMed Central

    Johnson, Mark C.; Pierson, Emily R.; Spieker, Andrew J.; Nielsen, A. Scott; Posso, Sylvia; Kita, Mariko; Buckner, Jane H.

    2016-01-01

    Objective: We investigated T cell responses to myelin proteins in the blood of healthy controls and 2 groups of patients with relapsing-remitting multiple sclerosis (RRMS) who exhibited lesions either predominantly in the brain or predominantly in the spinal cord in order to assess whether distinct neuroinflammatory patterns were associated with different myelin protein–specific T cell effector function profiles and whether these profiles differed from healthy controls. Methods: Peripheral blood mononuclear cells were obtained from patients with brain-predominant RRMS, patients with spinal cord–predominant RRMS, and age-matched healthy controls and analyzed by enzyme-linked immunosorbent spot assays to quantify interferon gamma–secreting (Th1) and interleukin 17–secreting (Th17) cells responding directly ex vivo to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG). Results: Although MBP and MOG elicited different responses, patients with multiple sclerosis (MS) who had spinal cord–predominant lesions exhibited significantly higher Th17:Th1 ratios in response to both MBP and MOG compared to patients with brain-predominant MS. Incorporating the cytokine responses to both antigens into logistic regression models showed that these cytokine responses were able to provide good discrimination between patients with distinct neuroinflammatory patterns. Conclusions: Our findings suggest that the localization of lesions within the brain vs the spinal cord in patients with MS is associated with different effector T cell responses to myelin proteins. Further investigation of the relationship between T cell effector function, antigen specificities, and lesion sites may reveal features of pathogenic pathways that are distinct to patients with different neuroinflammatory patterns. PMID:27606354

  6. Expression of Piwi protein MIWI2 defines a distinct population of multiciliated cells.

    PubMed

    Wasserman, Gregory A; Szymaniak, Aleksander D; Hinds, Anne C; Yamamoto, Kazuko; Kamata, Hirofumi; Smith, Nicole Ms; Hilliard, Kristie L; Carrieri, Claudia; Labadorf, Adam T; Quinton, Lee J; Ai, Xingbin; Varelas, Xaralabos; Chen, Felicia; Mizgerd, Joseph P; Fine, Alan; O'Carroll, Dónal; Jones, Matthew R

    2017-10-02

    P-element-induced wimpy testes (Piwi) proteins are known for suppressing retrotransposon activation in the mammalian germline. However, whether Piwi protein or Piwi-dependent functions occur in the mammalian soma is unclear. Contrary to germline-restricted expression, we observed that Piwi-like Miwi2 mRNA is indeed expressed in epithelial cells of the lung in adult mice and that it is induced during pneumonia. Further investigation revealed that MIWI2 protein localized to the cytoplasm of a discrete population of multiciliated airway epithelial cells. Isolation and next-generation sequencing of MIWI2-positive multiciliated cells revealed that they are phenotypically distinct from neighboring MIWI2-negative multiciliated cells. Mice lacking MIWI2 exhibited an altered balance of airway epithelial cells, demonstrating fewer multiciliated cells and an increase in club cells. During pneumococcal pneumonia, Miwi2-deficient mice exhibited increased expression of inflammatory mediators and increased immune cell recruitment, leading to enhanced bacterial clearance. Taken together, our data delineate MIWI2-dependent functions outside of the germline and demonstrate the presence of distinct subsets of airway multiciliated cells that can be discriminated by MIWI2 expression. By demonstrating roles for MIWI2 in airway cell identity and pulmonary innate immunity, these studies elucidate unanticipated physiological functions for Piwi proteins in somatic tissues.

  7. Defining the boundaries of atypical depression: evidence from the HPA axis supports course of illness distinctions.

    PubMed

    Stewart, Jonathan W; Quitkin, Frederic M; McGrath, Patrick J; Klein, Donald F

    2005-06-01

    Treatment outcome and brain laterality differ between early onset (<20 years) chronically (no well-being >2 months) depressed patients with atypical features (early/chronic atypical) and those with either later onset or less chronic illness (late/nonchronic atypical). Because hypothalamic-pituitary-adrenal (HPA) axis abnormalities have been hypothesized to distinguish atypical depression from melancholia, we examined whether HPA measures would also differentiate these two groups of depressed patients with atypical features. Three-hour afternoon cortisol levels, stimulation of cortisol by afternoon dextroamphetamine, and suppression of cortisol by dexamethasone were investigated in 85 depressed patients with atypical features. The latter group was divided into early/chronic atypical and late/nonchronic atypical based on chart review of course of illness. Patients with early/chronic atypical had significantly lower mean 3 h afternoon cortisol levels (N=21) and 4:00 p.m. post-dexamethasone cortisol levels (N=20) than did those with late/nonchronic atypical (N=43 with afternoon cortisol; N=26 with post-dexamethasone cortisol). Post-dextroamphetamine cortisol levels were numerically higher in the early/chronic atypical group (N=15 vs. 19), but this failed to reach conventional significance (0.05distinctions of normal and abnormal did not separate these groups on any of the tests. Lack of demonstrated reliability of the chart review and retrospective determination of atypical features and course of illness limit the generalizability of these findings. These HPA data are consistent with earlier treatment and brain laterality findings that course of illness distinguishes biologically distinct groups within depressed patients with atypical features. The DSM should consider adding course of illness requirements to its criteria for atypical features.

  8. Lrig1 expression defines a distinct multipotent stem cell population in mammalian epidermis.

    PubMed

    Jensen, Kim B; Collins, Charlotte A; Nascimento, Elisabete; Tan, David W; Frye, Michaela; Itami, Satoshi; Watt, Fiona M

    2009-05-08

    Lrig1 is a marker of human interfollicular epidermal stem cells and helps maintain stem cell quiescence. We show that, in mouse epidermis, Lrig1 defines the hair follicle junctional zone adjacent to the sebaceous glands and infundibulum. Lrig1 is a Myc target gene; loss of Lrig1 increases the proliferative capacity of stem cells in culture and results in epidermal hyperproliferation in vivo. Lrig1-expressing cells can give rise to all of the adult epidermal lineages in skin reconstitution assays. However, during homeostasis and on retinoic acid stimulation, they are bipotent, contributing to the sebaceous gland and interfollicular epidermis. beta-catenin activation increases the size of the junctional zone compartment, and loss of Lrig1 causes a selective increase in beta-catenin-induced ectopic hair follicle formation in the interfollicular epidermis. Our results suggest that Lrig1-positive cells constitute a previously unidentified reservoir of adult mouse interfollicular epidermal stem cells.

  9. Lrig1 Expression Defines a Distinct Multipotent Stem Cell Population in Mammalian Epidermis

    PubMed Central

    Jensen, Kim B.; Collins, Charlotte A.; Nascimento, Elisabete; Tan, David W.; Frye, Michaela; Itami, Satoshi; Watt, Fiona M.

    2009-01-01

    Summary Lrig1 is a marker of human interfollicular epidermal stem cells and helps maintain stem cell quiescence. We show that, in mouse epidermis, Lrig1 defines the hair follicle junctional zone adjacent to the sebaceous glands and infundibulum. Lrig1 is a Myc target gene; loss of Lrig1 increases the proliferative capacity of stem cells in culture and results in epidermal hyperproliferation in vivo. Lrig1-expressing cells can give rise to all of the adult epidermal lineages in skin reconstitution assays. However, during homeostasis and on retinoic acid stimulation, they are bipotent, contributing to the sebaceous gland and interfollicular epidermis. β-catenin activation increases the size of the junctional zone compartment, and loss of Lrig1 causes a selective increase in β-catenin-induced ectopic hair follicle formation in the interfollicular epidermis. Our results suggest that Lrig1-positive cells constitute a previously unidentified reservoir of adult mouse interfollicular epidermal stem cells. PMID:19427292

  10. Hox genes define distinct progenitor sub-domains within the second heart field.

    PubMed

    Bertrand, Nicolas; Roux, Marine; Ryckebüsch, Lucile; Niederreither, Karen; Dollé, Pascal; Moon, Anne; Capecchi, Mario; Zaffran, Stéphane

    2011-05-15

    Much of the heart, including the atria, right ventricle and outflow tract (OFT) is derived from a progenitor cell population termed the second heart field (SHF) that contributes progressively to the embryonic heart during cardiac looping. Several studies have revealed anterior-posterior patterning of the SHF, since the anterior region (anterior heart field) contributes to right ventricular and OFT myocardium whereas the posterior region gives rise to the atria. We have previously shown that Retinoic Acid (RA) signal participates to this patterning. We now show that Hoxb1, Hoxa1, and Hoxa3, as downstream RA targets, are expressed in distinct sub-domains within the SHF. Our genetic lineage tracing analysis revealed that Hoxb1, Hoxa1 and Hoxa3-expressing cardiac progenitor cells contribute to both atria and the inferior wall of the OFT, which subsequently gives rise to myocardium at the base of pulmonary trunk. By contrast to Hoxb1(Cre), the contribution of Hoxa1-enhIII-Cre and Hoxa3(Cre)-labeled cells is restricted to the distal regions of the OFT suggesting that proximo-distal patterning of the OFT is related to SHF sub-domains characterized by combinatorial Hox genes expression. Manipulation of RA signaling pathways showed that RA is required for the correct deployment of Hox-expressing SHF cells. This report provides new insights into the regulatory gene network in SHF cells contributing to the atria and sub-pulmonary myocardium.

  11. Brief reports: A distinct DNA methylation signature defines breast cancer stem cells and predicts cancer outcome.

    PubMed

    El Helou, Rita; Wicinski, Julien; Guille, Arnaud; Adélaïde, Jose; Finetti, Pascal; Bertucci, François; Chaffanet, Max; Birnbaum, Daniel; Charafe-Jauffret, Emmanuelle; Ginestier, Christophe

    2014-11-01

    Self-renewal and differentiation are two epigenetic programs that regulate stem cells fate. Dysregulation of these two programs leads to the development of cancer stem cells (CSCs). Recent evidence suggests that CSCs are relatively resistant to conventional therapies and responsible for metastasis formation. Deciphering these processes will help understand oncogenesis and allow the development of new targeted therapies. Here, we have used a whole genome promoter microarray to establish the DNA methylation portraits of breast cancer stem cells (bCSCs) and non-bCSCs. A total of 68 differentially methylated regions (DMRs) were more hypomethylated in bCSCs than in non-bCSCs. Using a differentiation assay we demonstrated that DMRs are rapidly hypermethylated within the first 6 hours following induction of CSC differentiation whereas the cells reached the steady-state within 6 days, suggesting that these DMRs are linked to early CSC epigenetic regulation. These DMRs were significantly enriched in genes coding for TGF-β signaling-related proteins. Interestingly, DMRs hypomethylation was correlated to an overexpression of TGF-β signaling genes in a series of 109 breast tumors. Moreover, patients with tumors harboring the bCSC DMRs signature had a worse prognosis than those with non-bCSC DMRs signature. Our results show that bCSCs have a distinct DNA methylation landscape with TGF-β signaling as a key epigenetic regulator of bCSCs differentiation.

  12. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders

    PubMed Central

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary “myopathic” changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions. PMID:26999347

  13. Mutational signatures in esophageal adenocarcinoma define etiologically distinct subgroups with therapeutic relevance.

    PubMed

    Secrier, Maria; Li, Xiaodun; de Silva, Nadeera; Eldridge, Matthew D; Contino, Gianmarco; Bornschein, Jan; MacRae, Shona; Grehan, Nicola; O'Donovan, Maria; Miremadi, Ahmad; Yang, Tsun-Po; Bower, Lawrence; Chettouh, Hamza; Crawte, Jason; Galeano-Dalmau, Núria; Grabowska, Anna; Saunders, John; Underwood, Tim; Waddell, Nicola; Barbour, Andrew P; Nutzinger, Barbara; Achilleos, Achilleas; Edwards, Paul A W; Lynch, Andy G; Tavaré, Simon; Fitzgerald, Rebecca C

    2016-10-01

    Esophageal adenocarcinoma (EAC) has a poor outcome, and targeted therapy trials have thus far been disappointing owing to a lack of robust stratification methods. Whole-genome sequencing (WGS) analysis of 129 cases demonstrated that this is a heterogeneous cancer dominated by copy number alterations with frequent large-scale rearrangements. Co-amplification of receptor tyrosine kinases (RTKs) and/or downstream mitogenic activation is almost ubiquitous; thus tailored combination RTK inhibitor (RTKi) therapy might be required, as we demonstrate in vitro. However, mutational signatures showed three distinct molecular subtypes with potential therapeutic relevance, which we verified in an independent cohort (n = 87): (i) enrichment for BRCA signature with prevalent defects in the homologous recombination pathway; (ii) dominant T>G mutational pattern associated with a high mutational load and neoantigen burden; and (iii) C>A/T mutational pattern with evidence of an aging imprint. These subtypes could be ascertained using a clinically applicable sequencing strategy (low coverage) as a basis for therapy selection.

  14. Distinct forms of mitochondrial TOM-TIM supercomplexes define signal-dependent states of preprotein sorting.

    PubMed

    Chacinska, Agnieszka; van der Laan, Martin; Mehnert, Carola S; Guiard, Bernard; Mick, David U; Hutu, Dana P; Truscott, Kaye N; Wiedemann, Nils; Meisinger, Chris; Pfanner, Nikolaus; Rehling, Peter

    2010-01-01

    Mitochondrial import of cleavable preproteins occurs at translocation contact sites, where the translocase of the outer membrane (TOM) associates with the presequence translocase of the inner membrane (TIM23) in a supercomplex. Different views exist on the mechanism of how TIM23 mediates preprotein sorting to either the matrix or inner membrane. On the one hand, two TIM23 forms were proposed, a matrix transport form containing the presequence translocase-associated motor (PAM; TIM23-PAM) and a sorting form containing Tim21 (TIM23(SORT)). On the other hand, it was reported that TIM23 and PAM are permanently associated in a single-entity translocase. We have accumulated distinct transport intermediates of preproteins to analyze the translocases in their active, preprotein-carrying state. We identified two different forms of active TOM-TIM23 supercomplexes, TOM-TIM23(SORT) and TOM-TIM23-PAM. These two supercomplexes do not represent separate pathways but are in dynamic exchange during preprotein translocation and sorting. Depending on the signals of the preproteins, switches between the different forms of supercomplex and TIM23 are required for the completion of preprotein import.

  15. Distinct Muscle Biopsy Findings in Genetically Defined Adult-Onset Motor Neuron Disorders.

    PubMed

    Jokela, Manu; Huovinen, Sanna; Raheem, Olayinka; Lindfors, Mikaela; Palmio, Johanna; Penttilä, Sini; Udd, Bjarne

    2016-01-01

    The objective of this study was to characterize and compare muscle histopathological findings in 3 different genetic motor neuron disorders. We retrospectively re-assessed muscle biopsy findings in 23 patients with autosomal dominant lower motor neuron disease caused by p.G66V mutation in CHCHD10 (SMAJ), 10 X-linked spinal and bulbar muscular atrophy (SBMA) and 11 autosomal dominant c9orf72-mutated amyotrophic lateral sclerosis (c9ALS) patients. Distinct large fiber type grouping consisting of non-atrophic type IIA muscle fibers were 100% specific for the late-onset spinal muscular atrophies (SMAJ and SBMA) and were never observed in c9ALS. Common, but less specific findings included small groups of highly atrophic rounded type IIA fibers in SMAJ/SBMA, whereas in c9ALS, small group atrophies consisting of small-caliber angular fibers involving both fiber types were more characteristic. We also show that in the 2 slowly progressive motor neuron disorders (SMAJ and SBMA) the initial neurogenic features are often confused with considerable secondary "myopathic" changes at later disease stages, such as rimmed vacuoles, myofibrillar aggregates and numerous fibers reactive for fetal myosin heavy chain (dMyHC) antibodies. Based on our findings, muscle biopsy may be valuable in the diagnostic work-up of suspected motor neuron disorders in order to avoid a false ALS diagnosis in patients without clear findings of upper motor neuron lesions.

  16. The distinct metabolic phenotype of lung squamous cell carcinoma defines selective vulnerability to glycolytic inhibition.

    PubMed

    Goodwin, Justin; Neugent, Michael L; Lee, Shin Yup; Choe, Joshua H; Choi, Hyunsung; Jenkins, Dana M R; Ruthenborg, Robin J; Robinson, Maddox W; Jeong, Ji Yun; Wake, Masaki; Abe, Hajime; Takeda, Norihiko; Endo, Hiroko; Inoue, Masahiro; Xuan, Zhenyu; Yoo, Hyuntae; Chen, Min; Ahn, Jung-Mo; Minna, John D; Helke, Kristi L; Singh, Pankaj K; Shackelford, David B; Kim, Jung-Whan

    2017-05-26

    Adenocarcinoma (ADC) and squamous cell carcinoma (SqCC) are the two predominant subtypes of non-small cell lung cancer (NSCLC) and are distinct in their histological, molecular and clinical presentation. However, metabolic signatures specific to individual NSCLC subtypes remain unknown. Here, we perform an integrative analysis of human NSCLC tumour samples, patient-derived xenografts, murine model of NSCLC, NSCLC cell lines and The Cancer Genome Atlas (TCGA) and reveal a markedly elevated expression of the GLUT1 glucose transporter in lung SqCC, which augments glucose uptake and glycolytic flux. We show that a critical reliance on glycolysis renders lung SqCC vulnerable to glycolytic inhibition, while lung ADC exhibits significant glucose independence. Clinically, elevated GLUT1-mediated glycolysis in lung SqCC strongly correlates with high (18)F-FDG uptake and poor prognosis. This previously undescribed metabolic heterogeneity of NSCLC subtypes implicates significant potential for the development of diagnostic, prognostic and targeted therapeutic strategies for lung SqCC, a cancer for which existing therapeutic options are clinically insufficient.

  17. Hox genes define distinct progenitor sub-domains within the second heart field

    PubMed Central

    Bertrand, Nicolas; Roux, Marine; Ryckebüsch, Lucile; Niederreither, Karen; Dollé, Pascal; Moon, Anne; Capecchi, Mario; Zaffran, Stéphane

    2011-01-01

    Much of the heart, including the atria, right ventricle and outflow tract (OFT) is derived from a progenitor cell population termed the second heart field (SHF) that contributes progressively to the embryonic heart during cardiac looping. Several studies have revealed anterior-posterior patterning of the SHF, since the anterior region (anterior heart field) contributes to right ventricular and OFT myocardium whereas the posterior region gives rise to the atria. We have previously shown that Retinoic Acid (RA) signal participates to this patterning. We now show that Hoxb1, Hoxa1, and Hoxa3, as downstream RA targets, are expressed in distinct sub-domains within the SHF. Our genetic lineage tracing analysis revealed that Hoxb1, Hoxa1 and Hoxa3-expressing cardiac progenitor cells contribute to both atria and the inferior wall of the OFT, which subsequently gives rise to myocardium at the base of pulmonary trunk. By contrast to Hoxb1Cre, the contribution of Hoxa1-enhIII-Cre and Hoxa3Cre-labeled cells is restricted to the distal regions of the OFT suggesting that proximo-distal patterning of the OFT is related to SHF sub-domains characterized by combinatorial Hox genes expression. Manipulation of RA signaling pathways showed that RA is required for the correct deployment of Hox-expressing SHF cells. This report provides new insights into the regulatory gene network in SHF cells contributing to the atria and sub-pulmonary myocardium. PMID:21385575

  18. Multi-gene phylogenies define Ceratocystiopsis and Grosmannia distinct from Ophiostoma

    PubMed Central

    Zipfel, Renate D.; de Beer, Z. Wilhelm; Jacobs, Karin; Wingfield, Brenda D.; Wingfield, Michael J.

    2006-01-01

    Ophiostoma species have diverse morphological features and are found in a large variety of ecological niches. Many different classification schemes have been applied to these fungi in the past based on teleomorph and anamorph features. More recently, studies based on DNA sequence comparisions have shown that Ophiostoma consists of different phylogenetic groups, but the data have not been sufficient to define clear monophyletic lineages represented by practical taxonomic units. We used DNA sequence data from combined partial nuclear LSU and β-tubulin genes to consider the phylogenetic relationships of 50 Ophiostoma species, representing all the major morphological groups in the genus. Our data showed three well-supported, monophyletic lineages in Ophiostoma. Species with Leptographium anamorphs grouped together and to accommodate these species the teleomorph-genus Grosmannia (type species G. penicillata), including 27 species and 24 new combinations, is re-instated. Another well-defined lineage includes species that are cycloheximide-sensitive with short perithecial necks, falcate ascospores and Hyalorhinocladiella anamorphs. For these species, the teleomorph-genus Ceratocystiopsis (type species O. minuta), including 11 species and three new combinations, is re-instated. A third group of species with either Sporothrix or Pesotum anamorphs includes species from various ecological niches such as Protea infructescences in South Africa. This group also includes O. piliferum, the type species of Ophiostoma, and these species are retained in that genus. Ophiostoma is redefined to reflect the changes resulting from new combinations in Grosmannia and Ceratocystiopsis. Our data have revealed additional lineages in Ophiostoma linked to morphological characters. However, these species are retained in Ophiostoma until further data for a larger number of species can be obtained to confirm monophyly of the apparent lineages. PMID:18490973

  19. DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes.

    PubMed

    Dougherty, Gerard W; Loges, Niki T; Klinkenbusch, Judith A; Olbrich, Heike; Pennekamp, Petra; Menchen, Tabea; Raidt, Johanna; Wallmeier, Julia; Werner, Claudius; Westermann, Cordula; Ruckert, Christian; Mirra, Virginia; Hjeij, Rim; Memari, Yasin; Durbin, Richard; Kolb-Kokocinski, Anja; Praveen, Kavita; Kashef, Mohammad A; Kashef, Sara; Eghtedari, Fardin; Häffner, Karsten; Valmari, Pekka; Baktai, György; Aviram, Micha; Bentur, Lea; Amirav, Israel; Davis, Erica E; Katsanis, Nicholas; Brueckner, Martina; Shaposhnykov, Artem; Pigino, Gaia; Dworniczak, Bernd; Omran, Heymut

    2016-08-01

    Primary ciliary dyskinesia (PCD) is a recessively inherited disease that leads to chronic respiratory disorders owing to impaired mucociliary clearance. Conventional transmission electron microscopy (TEM) is a diagnostic standard to identify ultrastructural defects in respiratory cilia but is not useful in approximately 30% of PCD cases, which have normal ciliary ultrastructure. DNAH11 mutations are a common cause of PCD with normal ciliary ultrastructure and hyperkinetic ciliary beating, but its pathophysiology remains poorly understood. We therefore characterized DNAH11 in human respiratory cilia by immunofluorescence microscopy (IFM) in the context of PCD. We used whole-exome and targeted next-generation sequence analysis as well as Sanger sequencing to identify and confirm eight novel loss-of-function DNAH11 mutations. We designed and validated a monoclonal antibody specific to DNAH11 and performed high-resolution IFM of both control and PCD-affected human respiratory cells, as well as samples from green fluorescent protein (GFP)-left-right dynein mice, to determine the ciliary localization of DNAH11. IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia and loss of DNAH11 in individuals with PCD with certain loss-of-function DNAH11 mutations. GFP-left-right dynein mice confirmed proximal DNAH11 localization in tracheal cilia. DNAH11 retained proximal localization in respiratory cilia of individuals with PCD with distinct ultrastructural defects, such as the absence of outer dynein arms (ODAs). TEM tomography detected a partial reduction of ODAs in DNAH11-deficient cilia. DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography.

  20. DNAH11 Localization in the Proximal Region of Respiratory Cilia Defines Distinct Outer Dynein Arm Complexes

    PubMed Central

    Dougherty, Gerard W.; Loges, Niki T.; Klinkenbusch, Judith A.; Olbrich, Heike; Pennekamp, Petra; Menchen, Tabea; Raidt, Johanna; Wallmeier, Julia; Werner, Claudius; Westermann, Cordula; Ruckert, Christian; Mirra, Virginia; Hjeij, Rim; Memari, Yasin; Durbin, Richard; Kolb-Kokocinski, Anja; Praveen, Kavita; Kashef, Mohammad A.; Kashef, Sara; Eghtedari, Fardin; Häffner, Karsten; Valmari, Pekka; Baktai, György; Aviram, Micha; Bentur, Lea; Amirav, Israel; Davis, Erica E.; Katsanis, Nicholas; Brueckner, Martina; Shaposhnykov, Artem; Pigino, Gaia; Dworniczak, Bernd

    2016-01-01

    Primary ciliary dyskinesia (PCD) is a recessively inherited disease that leads to chronic respiratory disorders owing to impaired mucociliary clearance. Conventional transmission electron microscopy (TEM) is a diagnostic standard to identify ultrastructural defects in respiratory cilia but is not useful in approximately 30% of PCD cases, which have normal ciliary ultrastructure. DNAH11 mutations are a common cause of PCD with normal ciliary ultrastructure and hyperkinetic ciliary beating, but its pathophysiology remains poorly understood. We therefore characterized DNAH11 in human respiratory cilia by immunofluorescence microscopy (IFM) in the context of PCD. We used whole-exome and targeted next-generation sequence analysis as well as Sanger sequencing to identify and confirm eight novel loss-of-function DNAH11 mutations. We designed and validated a monoclonal antibody specific to DNAH11 and performed high-resolution IFM of both control and PCD-affected human respiratory cells, as well as samples from green fluorescent protein (GFP)–left–right dynein mice, to determine the ciliary localization of DNAH11. IFM analysis demonstrated native DNAH11 localization in only the proximal region of wild-type human respiratory cilia and loss of DNAH11 in individuals with PCD with certain loss-of-function DNAH11 mutations. GFP–left–right dynein mice confirmed proximal DNAH11 localization in tracheal cilia. DNAH11 retained proximal localization in respiratory cilia of individuals with PCD with distinct ultrastructural defects, such as the absence of outer dynein arms (ODAs). TEM tomography detected a partial reduction of ODAs in DNAH11-deficient cilia. DNAH11 mutations result in a subtle ODA defect in only the proximal region of respiratory cilia, which is detectable by IFM and TEM tomography. PMID:26909801

  1. Using Polymorphisms in FKBP5 to Define Biologically Distinct Subtypes of Posttraumatic Stress Disorder

    PubMed Central

    Mehta, Divya; Gonik, Mariya; Klengel, Torsten; Rex-Haffner, Monika; Menke, Andreas; Rubel, Jennifer; Mercer, Kristina B.; Pütz, Benno; Bradley, Bekh; Holsboer, Florian; Ressler, Kerry J.; Müller-Myhsok, Bertram; Binder, Elisabeth B.

    2013-01-01

    that the inheritance of GR sensitivity–moderating FKBP5 polymorphisms can determine specific types of hypothalamic-pituitary-adrenal axis dysfunction within PTSD, which are also reflected in gene-expression changes of a subset of GR-responsive genes. Thus, these findings indicate that functional variants in FKBP5 are associated with biologically distinct subtypes of PTSD. PMID:21536970

  2. Comparison of Diagnostic Tests in Distinct Well-Defined Conditions Related to Dry Eye Disease

    PubMed Central

    Alves, Monica; Reinach, Peter Sol; Paula, Jayter Silva; Vellasco e Cruz, Antonio Augusto; Bachette, Leticia; Faustino, Jacqueline; Aranha, Francisco Penteado; Vigorito, Afonso; de Souza, Carmino Antonio; Rocha, Eduardo Melani

    2014-01-01

    Purpose This study compares signs, symptoms and predictive tools used to diagnose dry eye disease (DED) and ocular surface disorders in six systemic well-defined and non-overlapping diseases. It is well known that these tests are problematic because of a lack of agreement between them in identifying these conditions. Accordingly, we provide here a comparative clinical profile analysis of these different diseases. Methods A spontaneous and continuous sample of patients with Sjögren's syndrome (SS) (n = 27), graft-versus-host-disease (GVHD) (n = 28), Graves orbitopathy (n = 28), facial palsy (n = 8), diabetes mellitus without proliferative retinopathy (n = 14) and glaucoma who chronically received topical drugs preserved with benzalkonium chloride (n = 20) were enrolled. Evaluation consisted of a comprehensive protocol encompassing: (1) structured questionnaire - Ocular Surface Disease Index (OSDI); (2) tear osmolarity (TearLab Osmolarity System - Ocusense); (3) tear film break-up time (TBUT); (4) fluorescein and lissamine green staining; (5) Schirmer test and (6) severity grading. Results One hundred and twenty five patients (aged 48.8 years-old±14.1, male:female ratio = 0.4) were enrolled in the study, along with 24 age and gender matched controls. Higher scores on DED tests were obtained in Sjögren Syndrome (P<0.05), except for tear film osmolarity that was higher in diabetics (P<0.001) and fluorescein staining, that was higher in facial palsy (P<0.001). TFBUT and OSDI correlated better with other tests. The best combination of diagnostic tests for DED was OSDI, TBUT and Schirmer test (sensitivity 100%, specificity 95% and accuracy 99.3%). Conclusions DED diagnostic test results present a broad range of variability among different conditions. Vital stainings and TBUT correlated best with one another whereas the best test combination to detect DED was: OSDI/TBUT/Schirmer. PMID:24848115

  3. Distinct retroelement classes define evolutionary breakpoints demarcating sites of evolutionary novelty

    PubMed Central

    Longo, Mark S; Carone, Dawn M; Green, Eric D; O'Neill, Michael J; O'Neill, Rachel J

    2009-01-01

    Background Large-scale genome rearrangements brought about by chromosome breaks underlie numerous inherited diseases, initiate or promote many cancers and are also associated with karyotype diversification during species evolution. Recent research has shown that these breakpoints are nonrandomly distributed throughout the mammalian genome and many, termed "evolutionary breakpoints" (EB), are specific genomic locations that are "reused" during karyotypic evolution. When the phylogenetic trajectory of orthologous chromosome segments is considered, many of these EB are coincident with ancient centromere activity as well as new centromere formation. While EB have been characterized as repeat-rich regions, it has not been determined whether specific sequences have been retained during evolution that would indicate previous centromere activity or a propensity for new centromere formation. Likewise, the conservation of specific sequence motifs or classes at EBs among divergent mammalian taxa has not been determined. Results To define conserved sequence features of EBs associated with centromere evolution, we performed comparative sequence analysis of more than 4.8 Mb within the tammar wallaby, Macropus eugenii, derived from centromeric regions (CEN), euchromatic regions (EU), and an evolutionary breakpoint (EB) that has undergone convergent breakpoint reuse and past centromere activity in marsupials. We found a dramatic enrichment for long interspersed nucleotide elements (LINE1s) and endogenous retroviruses (ERVs) and a depletion of short interspersed nucleotide elements (SINEs) shared between CEN and EBs. We analyzed the orthologous human EB (14q32.33), known to be associated with translocations in many cancers including multiple myelomas and plasma cell leukemias, and found a conserved distribution of similar repetitive elements. Conclusion Our data indicate that EBs tracked within the class Mammalia harbor sequence features retained since the divergence of marsupials

  4. Distinct cyclosporin a doses are required to enhance bone formation induced by cyclic and rest-inserted loading in the senescent skeleton.

    PubMed

    Srinivasan, Sundar; Threet, Dewayne; Worton, Leah E; Ausk, Brandon J; Bain, Steven D; Gardiner, Edith M; Kwon, Ronald Y; Gross, Ted S

    2014-01-01

    Age-related decline in periosteal adaptation negatively impacts the ability to utilize exercise to enhance bone mass and strength in the elderly. We recently observed that in senescent animals subject to cyclically applied loading, supplementation with Cyclosporin A (CsA) substantially enhanced the periosteal bone formation rates to levels observed in young animals. We therefore speculated that if the CsA supplement could enhance bone response to a variety of types of mechanical stimuli, this approach could readily provide the means to expand the range of mild stimuli that are robustly osteogenic at senescence. Here, we specifically hypothesized that a given CsA supplement would enhance bone formation induced in the senescent skeleton by both cyclic (1-Hz) and rest-inserted loading (wherein a 10-s unloaded rest interval is inserted between each load cycle). To examine this hypothesis, the right tibiae of senescent female C57BL/6 mice (22 Mo) were subjected to cyclic or rest-inserted loading supplemented with CsA at 3.0 mg/kg. As previously, we initially found that while the periosteal bone formation rate (p.BFR) induced by cyclic loading was enhanced when supplemented with 3.0 mg/kg CsA (by 140%), the response to rest-inserted loading was not augmented at this CsA dosage. In follow-up experiments, we observed that while a 30-fold lower CsA dosage (0.1 mg/kg) significantly enhanced p.BFR induced by rest-inserted loading (by 102%), it was ineffective as a supplement with cyclic loading. Additional experiments and statistical analysis confirmed that the dose-response relations were significantly different for cyclic versus rest-inserted loading, only because the two stimuli required distinct CsA dosages for efficacy. While not anticipated a priori, clarifying the complexity underlying the observed interaction between CsA dosage and loading type holds potential for insight into how bone response to a broad range of mechanical stimuli may be substantially enhanced in

  5. New Mecyclothorax spp. (Coleoptera, Carabidae, Moriomorphini) define Mont Mauru, eastern Tahiti Nui, as a distinct area of endemism.

    PubMed

    Liebherr, James K

    2012-01-01

    Seven species of Mecyclothorax Sharp precinctive to Mont Mauru, Tahiti, Society Islands are newly described: Mecyclothorax tuteisp. n., Mecyclothorax tihotiisp. n., Mecyclothorax putaputasp. n., Mecyclothorax toretoresp. n., Mecyclothorax anaanasp. n., Mecyclothorax pirihaosp. n., and Mecyclothorax porosp. n. These seven constitute the first representative Mecyclothorax species recorded from Mauru, and their geographic restriction to this isolated massif defines it as a distinct area of endemism along the highly dissected eastern versant of the Tahiti Nui volcano. Each of the new species has a closest relative on another massif of Tahiti Nui, supporting speciation associated with vicariance caused by extensive erosional valley formation, especially the development of Papenoo Valley. Comparison of the known elevational distributions of the new discoveries on Mont Mauru to the elevational diversity profile of the comparatively well-sampled Mont Marau, northwest Tahiti Nui, suggests that numerous Mecyclothorax species remain to be discovered in higher-elevation habitats of Mont Mauru.

  6. New Mecyclothorax spp. (Coleoptera, Carabidae, Moriomorphini) define Mont Mauru, eastern Tahiti Nui, as a distinct area of endemism

    PubMed Central

    Liebherr, James K.

    2012-01-01

    Abstract Seven species of Mecyclothorax Sharp precinctive to Mont Mauru, Tahiti, Society Islands are newly described: Mecyclothorax tutei sp. n., Mecyclothorax tihotii sp. n., Mecyclothorax putaputa sp. n., Mecyclothorax toretore sp. n., Mecyclothorax anaana sp. n., Mecyclothorax pirihao sp. n., and Mecyclothorax poro sp. n. These seven constitute the first representative Mecyclothorax species recorded from Mauru, and their geographic restriction to this isolated massif defines it as a distinct area of endemism along the highly dissected eastern versant of the Tahiti Nui volcano. Each of the new species has a closest relative on another massif of Tahiti Nui, supporting speciation associated with vicariance caused by extensive erosional valley formation, especially the development of Papenoo Valley. Comparison of the known elevational distributions of the new discoveries on Mont Mauru to the elevational diversity profile of the comparatively well-sampled Mont Marau, northwest Tahiti Nui, suggests that numerous Mecyclothorax species remain to be discovered in higher-elevation habitats of Mont Mauru. PMID:23166465

  7. Distinct projection targets define subpopulations of mouse brainstem vagal neurons that express the autism-associated MET receptor tyrosine kinase.

    PubMed

    Kamitakahara, Anna; Wu, Hsiao-Huei; Levitt, Pat

    2017-07-31

    Detailed anatomical tracing and mapping of the viscerotopic organization of the vagal motor nuclei has provided insight into autonomic function in health and disease. To further define specific cellular identities, we paired information based on visceral connectivity with a cell-type specific marker of a subpopulation of neurons in the dorsal motor nucleus of the vagus (DMV) and nucleus ambiguus (nAmb) that express the autism-associated MET receptor tyrosine kinase. As gastrointestinal disturbances are common in children with autism spectrum disorder (ASD), we sought to define the relationship between MET-expressing (MET+) neurons in the DMV and nAmb, and the gastrointestinal tract. Using wholemount tissue staining and clearing, or retrograde tracing in a MET(EGFP) transgenic mouse, we identify three novel subpopulations of EGFP+ vagal brainstem neurons: (a) EGFP+ neurons in the nAmb projecting to the esophagus or laryngeal muscles, (b) EGFP+ neurons in the medial DMV projecting to the stomach, and (b) EGFP+ neurons in the lateral DMV projecting to the cecum and/or proximal colon. Expression of the MET ligand, hepatocyte growth factor (HGF), by tissues innervated by vagal motor neurons during fetal development reveal potential sites of HGF-MET interaction. Furthermore, similar cellular expression patterns of MET in the brainstem of both the mouse and nonhuman primate suggests that MET expression at these sites is evolutionarily conserved. Together, the data suggest that MET+ neurons in the brainstem vagal motor nuclei are anatomically positioned to regulate distinct portions of the gastrointestinal tract, with implications for the pathophysiology of gastrointestinal comorbidities of ASD. © 2017 Wiley Periodicals, Inc.

  8. CRAF gene fusions in pediatric low-grade gliomas define a distinct drug response based on dimerization profiles.

    PubMed

    Jain, P; Fierst, T M; Han, H J; Smith, T E; Vakil, A; Storm, P J; Resnick, A C; Waanders, A J

    2017-08-14

    Pediatric low-grade gliomas (PLGGs) are commonly associated with BRAF gene fusions that aberrantly activate the mitogen-activated protein kinase (MAPK) signaling pathway. This has led to PLGG clinical trials utilizing RAF- and MAPK pathway-targeted therapeutics. Whole-genome profiling of PLGGs has also identified rare gene fusions involving another RAF isoform, CRAF/RAF1, in PLGGs and cancers occuring in adults. Whereas BRAF fusions primarily dysregulate MAPK signaling, the CRAF fusions QKI-RAF1 and SRGAP3-RAF1 aberrantly activate both the MAPK and phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) signaling pathways. Although ATP-competitive, first-generation RAF inhibitors (vemurafenib/PLX4720, RAFi) cause paradoxical activation of the MAPK pathway in BRAF-fusion tumors, inhibition can be achieved with 'paradox breaker' RAFi, such as PLX8394. Here we report that, unlike BRAF fusions, CRAF fusions are unresponsive to both generations of RAFi, vemurafenib and PLX8394, highlighting a distinct responsiveness of CRAF fusions to clinically relevant RAFi. Whereas PLX8394 decreased BRAF-fusion dimerization, CRAF-fusion dimerization is unaffected primarily because of robust protein-protein interactions mediated by the N-terminal non-kinase fusion partner, such as QKI. The pan-RAF dimer inhibitor, LY3009120, could suppress CRAF-fusion oncogenicity by inhibiting dimer-mediated signaling. In addition, as CRAF fusions activate both the MAPK and PI3K/mTOR signaling pathways, we identify combinatorial inhibition of the MAPK/mTOR pathway as a potential therapeutic strategy for CRAF-fusion-driven tumors. Overall, we define a mechanistic distinction between PLGG-associated BRAF- and CRAF/RAF1 fusions in response to RAFi, highlighting the importance of molecularly classifying PLGG patients for targeted therapy. Furthermore, our study uncovers an important contribution of the non-kinase fusion partner to oncogenesis and potential therapeutic strategies against PLGG

  9. Identification of Myosin XI Receptors in Arabidopsis Defines a Distinct Class of Transport Vesicles[W][OPEN

    PubMed Central

    Peremyslov, Valera V.; Morgun, Eva A.; Kurth, Elizabeth G.; Makarova, Kira S.; Koonin, Eugene V.; Dolja, Valerian V.

    2013-01-01

    To characterize the mechanism through which myosin XI-K attaches to its principal endomembrane cargo, a yeast two-hybrid library of Arabidopsis thaliana cDNAs was screened using the myosin cargo binding domain as bait. This screen identified two previously uncharacterized transmembrane proteins (hereinafter myosin binding proteins or MyoB1/2) that share a myosin binding, conserved domain of unknown function 593 (DUF593). Additional screens revealed that MyoB1/2 also bind myosin XI-1, whereas myosin XI-I interacts with the distantly related MyoB7. The in vivo interactions of MyoB1/2 with myosin XI-K were confirmed by immunoprecipitation and colocalization analyses. In epidermal cells, the yellow fluorescent protein–tagged MyoB1/2 localize to vesicles that traffic in a myosin XI–dependent manner. Similar to myosin XI-K, MyoB1/2 accumulate in the tip-growing domain of elongating root hairs. Gene knockout analysis demonstrated that functional cooperation between myosin XI-K and MyoB proteins is required for proper plant development. Unexpectedly, the MyoB1-containing vesicles did not correspond to brefeldin A–sensitive Golgi and post-Golgi or prevacuolar compartments and did not colocalize with known exocytic or endosomal compartments. Phylogenomic analysis suggests that DUF593 emerged in primitive land plants and founded a multigene family that is conserved in all flowering plants. Collectively, these findings indicate that MyoB are membrane-anchored myosin receptors that define a distinct, plant-specific transport vesicle compartment. PMID:23995081

  10. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2

    PubMed Central

    Poirier, John T.; Gardner, Eric E.; Connis, Nick; Moreira, Andre L.; de Stanchina, Elisa; Hann, Christine L.; Rudin, Charles M.

    2015-01-01

    Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy, and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDXs) and cell lines at single nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, while PDXs maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth. PMID:25746006

  11. DNA methylation in small cell lung cancer defines distinct disease subtypes and correlates with high expression of EZH2.

    PubMed

    Poirier, J T; Gardner, E E; Connis, N; Moreira, A L; de Stanchina, E; Hann, C L; Rudin, C M

    2015-11-26

    Small cell lung cancer (SCLC) is an aggressive malignancy characterized by early metastasis, rapid development of resistance to chemotherapy and genetic instability. This study profiles DNA methylation in SCLC, patient-derived xenografts (PDX) and cell lines at single-nucleotide resolution. DNA methylation patterns of primary samples are distinct from those of cell lines, whereas PDX maintain a pattern closely consistent with primary samples. Clustering of DNA methylation and gene expression of primary SCLC revealed distinct disease subtypes among histologically indistinguishable primary patient samples with similar genetic alterations. SCLC is notable for dense clustering of high-level methylation in discrete promoter CpG islands, in a pattern clearly distinct from other lung cancers and strongly correlated with high expression of the E2F target and histone methyltransferase gene EZH2. Pharmacologic inhibition of EZH2 in a SCLC PDX markedly inhibited tumor growth.

  12. IDH1/2 mutation status combined with Ki-67 labeling index defines distinct prognostic groups in glioma.

    PubMed

    Zeng, Ailiang; Hu, Qi; Liu, Yanwei; Wang, Zheng; Cui, Xiaoming; Li, Rui; Yan, Wei; You, Yongping

    2015-10-06

    The current World Health Organization (WHO) classification of human gliomas is mainly based on morphology. However, it has limitations in prognostic prediction. We examined whether combining isocitrate dehydrogenase (IDH) 1/2 mutation status with the Ki-67 labeling index would improve the definition of prognostically distinct entities. We investigated the correlation of Ki-67 expression with IDH1/2 mutation status and their impact on clinical outcome in 703 gliomas. Low Ki-67 expression closely overlapped with IDH1/2 mutation in our cohort (P < 0.0001). Patients with IDH1/2 mutation survived significantly longer than patients with wild-type IDH1/2 did (P < 0.0001); higher Ki-67 expression was associated with shorter progression-free survival and overall survival (OS) (P < 0.0001). IDH1/2 combined with Ki-67 was used to re-classify glioma patients into five groups. IDH1/2 mutant patients with low and moderate Ki-67 expression (Group1) had the best prognosis, whereas patients with wild-type IDH1/2 and high Ki-67 expression (Group5) had the worst prognosis (Median OS = 1527 vs. 355 days, P < 0.0001). To summarize, our new classification model distinguishes biologically distinct subgroups and provides prognostic information regardless of the conventional WHO grade. Classification based on IDH1/2 mutation status and Ki-67 expression level could be more convenient for clinical application and guide personalized treatment in malignant gliomas.

  13. Distinct α-intercalated cell morphology and its modification by acidosis define regions of the collecting duct

    PubMed Central

    Purkerson, Jeffrey M.; Schwaderer, Andrew L.; Nakamori, Aya

    2015-01-01

    During metabolic acidosis, the cortical collecting duct (CCD) of the rabbit reverses the polarity of bicarbonate flux from net secretion to net absorption, and this is accomplished by increasing the proton secretory rate by α-intercalated cells (ICs) and decreasing bicarbonate secretion by β-ICs. To better characterize dynamic changes in H+-secreting α-ICs, we examined their morphology in collecting ducts microdissected from kidneys of normal, acidotic, and recovering rabbits. α-ICs in defined axial regions varied in number and basolateral anion exchanger (AE)1 morphology, which likely reflects their relative activity and function along the collecting duct. Upon transition from CCD to outer medullary collecting duct from the outer stripe to the inner stripe, the number of α-ICs increases from 11.0 ± 1.2 to 15.4 ± 1.11 and to 32.0 ± 1.3 cells/200 μm, respectively. In the CCD, the basolateral structure defined by AE1 typically exhibited a pyramidal or conical shape, whereas in the medulla the morphology was elongated and shallow, resulting in a more rectangular shape. Furthermore, acidosis reversibly induced α-ICs in the CCD to acquire a more rectangular morphology concomitant with a transition from diffusely cytoplasmic to increased basolateral surface distribution of AE1 and apical polarization of B1-V-ATPase. The latter results are consistent with the supposition that morphological adaptation from the pyramidal to rectangular shape reflects a transition toward a more “active” configuration. In addition, α-ICs in the outer medullary collecting duct from the outer stripe exhibited cellular morphology strikingly similar to dendritic cells that may reflect a newly defined ancillary function in immune defense of the kidney. PMID:26084929

  14. Distinct integrin-dependent signals define requirements for lytic granule convergence and polarization in natural killer cells.

    PubMed

    Hsu, Hsiang-Ting; Orange, Jordan S

    2014-10-07

    Lytic granules in natural killer (NK) cells represent a dangerous cargo that is targeted for secretion to destroy diseased cells. The appropriate management of these organelles enables the mounting of a precise and valuable host defense. The process of NK cell adhesion to a target cell through engagement of the integrin LFA-1 (lymphocyte function-associated antigen 1) promotes lytic granule organization through complex cellular mechanics and a signaling pathway characterized by Zhang et al. in this issue of Science Signaling. A set of signaling molecules was defined for their ability to promote the polarization of NK cell lytic granules and the microtubule organizing center (MTOC) toward the interface with a target cell. A subset of these signaling molecules was also required for the convergence of lytic granules on the MTOC. Copyright © 2014, American Association for the Advancement of Science.

  15. Structural and haemostatic features of pharmaceutical heparins from different animal sources: challenges to define thresholds separating distinct drugs

    PubMed Central

    Tovar, Ana M. F.; Santos, Gustavo R. C.; Capillé, Nina V.; Piquet, Adriana A.; Glauser, Bianca F.; Pereira, Mariana S.; Vilanova, Eduardo; Mourão, Paulo A. S.

    2016-01-01

    Heparins extracted from different animal sources have been conventionally considered effective anticoagulant and antithrombotic agents despite of their pharmacological dissimilarities. We performed herein a systematic analysis on the physicochemical properties, disaccharide composition, in vitro anticoagulant potency and in vivo antithrombotic and bleeding effects of several batches of pharmaceutical grade heparins obtained from porcine intestine, bovine intestine and bovine lung. Each of these three heparin types unambiguously presented differences in their chemical structures, physicochemical properties and/or haemostatic effects. We also prepared derivatives of these heparins with similar molecular weight differing exclusively in their disaccharide composition. The derivatives from porcine intestinal and bovine lung heparins were structurally more similar with each other and hence presented close anticoagulant activities whereas the derivative from bovine intestinal heparin had a higher proportion of 6-desulfated α-glucosamine units and about half anticoagulant activity. Our findings reasonably indicate that pharmaceutical preparations of heparin from different animal sources constitute distinct drugs, thus requiring specific regulatory rules and therapeutic evaluations. PMID:27752111

  16. Structural and haemostatic features of pharmaceutical heparins from different animal sources: challenges to define thresholds separating distinct drugs.

    PubMed

    Tovar, Ana M F; Santos, Gustavo R C; Capillé, Nina V; Piquet, Adriana A; Glauser, Bianca F; Pereira, Mariana S; Vilanova, Eduardo; Mourão, Paulo A S

    2016-10-18

    Heparins extracted from different animal sources have been conventionally considered effective anticoagulant and antithrombotic agents despite of their pharmacological dissimilarities. We performed herein a systematic analysis on the physicochemical properties, disaccharide composition, in vitro anticoagulant potency and in vivo antithrombotic and bleeding effects of several batches of pharmaceutical grade heparins obtained from porcine intestine, bovine intestine and bovine lung. Each of these three heparin types unambiguously presented differences in their chemical structures, physicochemical properties and/or haemostatic effects. We also prepared derivatives of these heparins with similar molecular weight differing exclusively in their disaccharide composition. The derivatives from porcine intestinal and bovine lung heparins were structurally more similar with each other and hence presented close anticoagulant activities whereas the derivative from bovine intestinal heparin had a higher proportion of 6-desulfated α-glucosamine units and about half anticoagulant activity. Our findings reasonably indicate that pharmaceutical preparations of heparin from different animal sources constitute distinct drugs, thus requiring specific regulatory rules and therapeutic evaluations.

  17. Mutations in a tRNA import signal define distinct receptors at the two membranes of Leishmania mitochondria.

    PubMed

    Bhattacharyya, S N; Mukherjee, S; Adhya, S

    2000-10-01

    Nucleus-encoded tRNAs are selectively imported into the mitochondrion of Leishmania, a kinetoplastid protozoan. An oligoribonucleotide constituting the D stem-loop import signal of tRNA(Tyr)(GUA) was efficiently transported into the mitochondrial matrix in organello as well as in vivo. Transfer through the inner membrane could be uncoupled from that through the outer membrane and was resistant to antibody against the outer membrane receptor TAB. A number of mutations in the import signal had differential effects on outer and inner membrane transfer. Some mutants which efficiently traversed the outer membrane were unable to enter the matrix. Conversely, restoration of the loop-closing GC pair in reverse resulted in reversion of transfer through the inner, but not the outer, membrane, and binding of the RNA to the inner membrane was restored. These experiments indicate the presence at the two membranes of receptors with distinct specificities which mediate stepwise transfer into the mitochondrial matrix. The combination of oligonucleotide mutagenesis and biochemical fractionation may provide a general tool for the identification of tRNA transport factors.

  18. fMRI resting state networks define distinct modes of long-distance interactions in the human brain.

    PubMed

    De Luca, M; Beckmann, C F; De Stefano, N; Matthews, P M; Smith, S M

    2006-02-15

    Functional magnetic resonance imaging (fMRI) studies of the human brain have suggested that low-frequency fluctuations in resting fMRI data collected using blood oxygen level dependent (BOLD) contrast correspond to functionally relevant resting state networks (RSNs). Whether the fluctuations of resting fMRI signal in RSNs are a direct consequence of neocortical neuronal activity or are low-frequency artifacts due to other physiological processes (e.g., autonomically driven fluctuations in cerebral blood flow) is uncertain. In order to investigate further these fluctuations, we have characterized their spatial and temporal properties using probabilistic independent component analysis (PICA), a robust approach to RSN identification. Here, we provide evidence that: i. RSNs are not caused by signal artifacts due to low sampling rate (aliasing); ii. they are localized primarily to the cerebral cortex; iii. similar RSNs also can be identified in perfusion fMRI data; and iv. at least 5 distinct RSN patterns are reproducible across different subjects. The RSNs appear to reflect "default" interactions related to functional networks related to those recruited by specific types of cognitive processes. RSNs are a major source of non-modeled signal in BOLD fMRI data, so a full understanding of their dynamics will improve the interpretation of functional brain imaging studies more generally. Because RSNs reflect interactions in cognitively relevant functional networks, they offer a new approach to the characterization of state changes with pathology and the effects of drugs.

  19. Genetic profiling by single-nucleotide polymorphism-based array analysis defines three distinct subtypes of orbital meningioma.

    PubMed

    Ho, Cheng-Ying; Mosier, Stacy; Safneck, Janice; Salomao, Diva R; Miller, Neil R; Eberhart, Charles G; Gocke, Christopher D; Batista, Denise A S; Rodriguez, Fausto J

    2015-03-01

    Orbital meningiomas can be classified as primary optic nerve sheath (ON) meningiomas, primary intraorbital ectopic (Ob) meningiomas and spheno-orbital (Sph-Ob) meningiomas based on anatomic site. Single-nucleotide polymorphism (SNP)-based array analysis with the Illumina 300K platform was performed on formalin-fixed, paraffin-embedded tissue from 19 orbital meningiomas (5 ON, 4 Ob and 10 Sph-Ob meningiomas). Tumors were World Health Organization (WHO) grade I except for two grade II meningiomas, and one was NF2-associated. We found genomic alterations in 68% (13 of 19) of orbital meningiomas. Sph-Ob tumors frequently exhibited monosomy 22/22q loss (70%; 7/10) and deletion of chromosome 1p, 6q and 19p (50% each; 5/10). Among genetic alterations, loss of chromosome 1p and 6q were more frequent in clinically progressive tumors. Chromosome 22q loss also was detected in the majority of Ob meningiomas (75%; 3/4) but was infrequent in ON meningiomas (20%; 1/5). In general, Ob tumors had fewer chromosome alterations than Sph-Ob and ON tumors. Unlike Sph-Ob meningiomas, most of the Ob and ON meningiomas did not progress even after incomplete excision, although follow-up was limited in some cases. Our study suggests that ON, Ob and Sph-Ob meningiomas are three molecularly distinct entities. Our results also suggest that molecular subclassification may have prognostic implications.

  20. Mutations in IDH1, IDH2, and in the TERT promoter define clinically distinct subgroups of adult malignant gliomas

    PubMed Central

    Healy, Patrick; Reitman, Zachary J.; Lipp, Eric; Rasheed, B. Ahmed; Yang, Rui; Diplas, Bill H.; Wang, Zhaohui; Greer, Paula K.; Zhu, Huishan; Wang, Catherine Y.; Carpenter, Austin B.; Friedman, Henry; Friedman, Allan H.; Keir, Stephen T.; He, Jie; He, Yiping; McLendon, Roger E.; Herndon II, James E.; Yan, Hai; Bigner, Darell D.

    2014-01-01

    Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or occur exclusively of one another in glioma subtypes presents a unique opportunity to guide glioma classification and prognosis. We analyzed the relationship between overall survival (OS) and the presence of IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We hypothesized and show that genetic signatures capable of distinguishing among several types of gliomas could be established providing clinically relevant information that can serve as an adjunct to histopathological diagnosis. We found that mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. In oligodendrogliomas, TERT promoter and IDH1/2 mutations co-occurred in 79% of cases. Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months. Analyzing gliomas based on their genetic signatures allows for the stratification of these patients into distinct cohorts, with unique prognosis and survival. PMID:24722048

  1. Characterization of two distinct antigens expressed on either resting or activated human B cells as defined by monoclonal antibodies.

    PubMed Central

    Kokai, Y; Ishii, Y; Kikuchi, K

    1986-01-01

    Two antigen systems (L29 & L30) expressed on two distinct human B cell subpopulations were identified by using BL1-4D6 and TB3-7D5 monoclonal antibodies, respectively. L29 was expressed on approximately one-third of B cells in human lymphoid tissues. These B cells associated with L29 were large activated B cells located in the germinal centres of lymphoid follicles. L30, on the other hand, existed on approximately two-thirds of B cells mainly located in the mantle zone of lymphoid follicles, most of which also expressed IgM and IgD on their cell membrane. In addition, L30 was shared on mature granulocytes. With the use of polyclonal activators such as pokeweek mitogen (PWM) and protein A-bearing staphylococci (SAC), L29 antigen was inducible on PWM- or SAC-stimulated B cells in correspondence with the emergence of Tac and T10 antigens of these B cells. In contrast, L30 antigen on the B cells stimulated by the polyclonal activators was decreased in its expression and was finally lost from these B cells. Although none of L29 and L30 was expressed on normal, non-activated human thymus and peripheral T cells, L29 but not L30 was expressed on concanavalin A-activated T cells. Immunochemical studies showed that L30 consist of a single polypeptide with mol. wt of 40,000. L29 antigen is presently under study. Images Fig. 2 Fig. 4 PMID:3527505

  2. Yeast heat shock mRNAs are exported through a distinct pathway defined by Rip1p

    PubMed Central

    Saavedra, Claudio A.; Hammell, Christopher M.; Heath, Catherine V.; Cole, Charles N.

    1997-01-01

    We reported previously that heat or ethanol shock in Saccharomyces cerevisiae leads to nuclear retention of most poly(A)+ RNA but heat shock mRNAs (encoding Hsp70 proteins Ssa1p and Ssa4p) are efficiently exported in a process that is independent of the small GTPase Ran/Gsp1p, which is essential for most nucleocytoplasmic transport. To gain further insights into proteins essential or nonessential for export of heat shock mRNAs, in situ hybridization analyses to detect mRNA and pulse-labeling of proteins were used to examine several yeast mutant strains for their ability to export heat shock mRNAs following stress. Rip1p is a 42-kD protein associated with nuclear pore complexes and contains nucleoporin-like repeat sequences. It is dispensable for growth of yeast cells under normal conditions, but we report that it is essential for the export of heat shock mRNAs following stress. When SSA4 mRNA was induced from a GAL promoter in the absence of stress, it was efficiently exported in a strain lacking RIP1, indicating that Rip1p is required for export of heat shock mRNAs only following stress. Npl3p, a key mediator of export of poly(A)+ RNA, was not required for heat shock mRNA export, whereas Rss1p/Gle1p, a NES-containing factor essential for poly(A)+ RNA export, was also required for export of heat shock mRNAs after stress. High-level expression of the HIV-1 Rev protein, but not of Rev mutants, led to a partial block in export of heat shock mRNAs following stress. The data suggest a model wherein the requirement for Npl3p defines the mRNA export pathway, the requirement for Rip1p defines a pathway used for export of heat shock mRNAs after stress, and additional factors, including Rss1p/Gle1p and several nucleoporins (Rat7p/Nup159p, Rat2p/Nup120p, and Nup145p/Rat10p), are required in both pathways. PMID:9353254

  3. Use of HCA in Subproteome-immunization and Screening of Hybridoma Supernatants to Define Distinct Antibody Binding Patterns

    PubMed Central

    Szafran, Adam T.; Mancini, Maureen G.; Nickerson, Jeffrey A.; Edwards, Dean P.; Mancini, Michael A.

    2016-01-01

    Understanding the properties and functions of complex biological systems depends upon knowing the proteins present and the interactions between them. Recent advances in mass spectrometry have given us greater insights into the participating proteomes, however, monoclonal antibodies remain key to understanding the structures, functions, locations and macromolecular interactions of the involved proteins. The traditional single immunogen method to produce monoclonal antibodies using hybridoma technology are time, resource and cost intensive, limiting the number of reagents that are available. Using a high content analysis screening approach, we have developed a method in which a complex mixture of proteins (e.g., subproteome) is used to generate a panel of monoclonal antibodies specific to a subproteome located in a defined subcellular compartment such as the nucleus. The immunofluorescent images in the primary hybridoma screen are analyzed using an automated processing approach and classified using a recursive partitioning forest classification model derived from images obtained from the Human Protein Atlas. Using an ammonium sulfate purified nuclear matrix fraction as an example of reverse proteomics, we identified 866 hybridoma supernatants with a positive immunofluorescent signal. Of those, 402 produced a nuclear signal from which patterns similar to known nuclear matrix associated proteins were identified. Detailed here is our method, the analysis techniques, and a discussion of the application to further in vivo antibody production. PMID:26521976

  4. BRAF-V600E expression in precursor versus differentiated dendritic cells defines clinically distinct LCH risk groups

    PubMed Central

    Berres, Marie-Luise; Lim, Karen Phaik Har; Peters, Tricia; Price, Jeremy; Takizawa, Hitoshi; Salmon, Hélène; Idoyaga, Juliana; Ruzo, Albert; Lupo, Philip J.; Hicks, M. John; Shih, Albert; Simko, Stephen J.; Abhyankar, Harshal; Chakraborty, Rikhia; Leboeuf, Marylene; Beltrão, Monique; Lira, Sérgio A.; Heym, Kenneth M.; Clausen, Björn E.; Bigley, Venetia; Collin, Matthew; Manz, Markus G.; McClain, Kenneth

    2014-01-01

    Langerhans cell histiocytosis (LCH) is a clonal disorder with elusive etiology, characterized by the accumulation of CD207+ dendritic cells (DCs) in inflammatory lesions. Recurrent BRAF-V600E mutations have been reported in LCH. In this study, lesions from 100 patients were genotyped, and 64% carried the BRAF-V600E mutation within infiltrating CD207+ DCs. BRAF-V600E expression in tissue DCs did not define specific clinical risk groups but was associated with increased risk of recurrence. Strikingly, we found that patients with active, high-risk LCH also carried BRAF-V600E in circulating CD11c+ and CD14+ fractions and in bone marrow (BM) CD34+ hematopoietic cell progenitors, whereas the mutation was restricted to lesional CD207+ DC in low-risk LCH patients. Importantly, BRAF-V600E expression in DCs was sufficient to drive LCH-like disease in mice. Consistent with our findings in humans, expression of BRAF-V600E in BM DC progenitors recapitulated many features of the human high-risk LCH, whereas BRAF-V600E expression in differentiated DCs more closely resembled low-risk LCH. We therefore propose classification of LCH as a myeloid neoplasia and hypothesize that high-risk LCH arises from somatic mutation of a hematopoietic progenitor, whereas low-risk disease arises from somatic mutation of tissue-restricted precursor DCs. PMID:24638167

  5. Targeting of distinct signaling cascades and cancer-associated fibroblasts define the efficacy of Sorafenib against prostate cancer cells

    PubMed Central

    Kharaziha, P; Rodriguez, P; Li, Q; Rundqvist, H; Björklund, A-C; Augsten, M; Ullén, A; Egevad, L; Wiklund, P; Nilsson, S; Kroemer, G; Grander, D; Panaretakis, T

    2012-01-01

    Sorafenib, a multi-tyrosine kinase inhibitor, kills more effectively the non-metastatic prostate cancer cell line 22Rv1 than the highly metastatic prostate cancer cell line PC3. In 22Rv1 cells, constitutively active STAT3 and ERK are targeted by sorafenib, contrasting with PC3 cells, in which these kinases are not active. Notably, overexpression of a constitutively active MEK construct in 22Rv1 cells stimulates the sustained phosphorylation of Bad and protects from sorafenib-induced cell death. In PC3 cells, Src and AKT are constitutively activated and targeted by sorafenib, leading to an increase in Bim protein levels. Overexpression of constitutively active AKT or knockdown of Bim protects PC3 cells from sorafenib-induced killing. In both PC3 and 22Rv1 cells, Mcl-1 depletion is required for the induction of cell death by sorafenib as transient overexpression of Mcl-1 is protective. Interestingly, co-culturing of primary cancer-associated fibroblasts (CAFs) with 22Rv1 or PC3 cells protected the cancer cells from sorafenib-induced cell death, and this protection was largely overcome by co-administration of the Bcl-2 antagonist, ABT737. In summary, the differential tyrosine kinase profile of prostate cancer cells defines the cytotoxic efficacy of sorafenib and this profile is modulated by CAFs to promote resistance. The combination of sorafenib with Bcl-2 antagonists, such as ABT737, may constitute a promising therapeutic strategy against prostate cancer. PMID:22278289

  6. Distinct developmental profile of lower-body adipose tissue defines resistance against obesity-associated metabolic complications.

    PubMed

    Pinnick, Katherine E; Nicholson, George; Manolopoulos, Konstantinos N; McQuaid, Siobhán E; Valet, Philippe; Frayn, Keith N; Denton, Nathan; Min, Josine L; Zondervan, Krina T; Fleckner, Jan; McCarthy, Mark I; Holmes, Chris C; Karpe, Fredrik

    2014-11-01

    Upper- and lower-body fat depots exhibit opposing associations with obesity-related metabolic disease. We defined the relationship between DEXA-quantified fat depots and diabetes/cardiovascular risk factors in a healthy population-based cohort (n = 3,399). Gynoid fat mass correlated negatively with insulin resistance after total fat mass adjustment, whereas the opposite was seen for abdominal fat. Paired transcriptomic analysis of gluteal subcutaneous adipose tissue (GSAT) and abdominal subcutaneous adipose tissue (ASAT) was performed across the BMI spectrum (n = 49; 21.4-45.5 kg/m(2)). In both depots, energy-generating metabolic genes were negatively associated and inflammatory genes were positively associated with obesity. However, associations were significantly weaker in GSAT. At the systemic level, arteriovenous release of the proinflammatory cytokine interleukin-6 (n = 34) was lower from GSAT than ASAT. Isolated preadipocytes retained a depot-specific transcriptional "memory" of embryonic developmental genes and exhibited differential promoter DNA methylation of selected genes (HOTAIR, TBX5) between GSAT and ASAT. Short hairpin RNA-mediated silencing identified TBX5 as a regulator of preadipocyte proliferation and adipogenic differentiation in ASAT. In conclusion, intrinsic differences in the expression of developmental genes in regional adipocytes provide a mechanistic basis for diversity in adipose tissue (AT) function. The less inflammatory nature of lower-body AT offers insight into the opposing metabolic disease risk associations between upper- and lower-body obesity. © 2014 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  7. Two distinct mechanisms of alkyne insertion into the metal-sulfur bond: combined experimental and theoretical study and application in catalysis.

    PubMed

    Ananikov, Valentine P; Gayduk, Konstantin A; Orlov, Nikolay V; Beletskaya, Irina P; Khrustalev, Victor N; Antipin, Mikhail Yu

    2010-02-15

    The present study reports the evidence for the multiple carbon-carbon bond insertion into the metal-heteroatom bond via a five-coordinate metal complex. Detailed analysis of the model catalytic reaction of the carbon-sulfur (C-S) bond formation unveiled the mechanism of metal-mediated alkyne insertion: a new pathway of C-S bond formation without preliminary ligand dissociation was revealed based on experimental and theoretical investigations. According to this pathway alkyne insertion into the metal-sulfur bond led to the formation of intermediate metal complex capable of direct C-S reductive elimination. In contrast, an intermediate metal complex formed through alkyne insertion through the traditional pathway involving preliminary ligand dissociation suffered from "improper" geometry configuration, which may block the whole catalytic cycle. A new catalytic system was developed to solve the problem of stereoselective S-S bond addition to internal alkynes and a cost-efficient Ni-catalyzed synthetic procedure is reported to furnish formation of target vinyl sulfides with high yields (up to 99%) and excellent Z/E selectivity (>99:1).

  8. Human pluripotent stem cells differentiated in fully defined medium generate hematopoietic CD34- and CD34+ progenitors with distinct characteristics.

    PubMed

    Chicha, Laurie; Feki, Anis; Boni, Alessandro; Irion, Olivier; Hovatta, Outi; Jaconi, Marisa

    2011-02-25

    Differentiation of pluripotent stem cells in vitro provides a powerful means to investigate early developmental fates, including hematopoiesis. In particular, the use of a fully defined medium (FDM) would avoid biases induced by unidentified factors contained in serum, and would also allow key molecular mediators involved in such a process to be identified. Our goal was to induce in vitro, the differentiation of human embryonic stem cells (ESC) and induced pluripotent stem cells (iPSC) into morphologically and phenotypically mature leukocytes and erythrocytes, in the complete absence of serum and feeder cells. ESC and iPSC were sequentially induced in liquid cultures for 4 days with bone morphogenic protein-4, and for 4 days with FLT3-ligand, stem cell factor, thrombopoietin and vascular endothelium growth factor. Cell differentiation status was investigated by both mRNA expression and FACS expression profiles. Cells were further sorted and assayed for their hematopoietic properties in colony-forming unit (CFU) assays. In liquid cultures, cells progressively down-modulated Oct-4 expression while a sizeable cell fraction expressed CD34 de novo. SCL/Tal1 and Runx1 transcripts were exclusively detected in CD34(+) cells. In clonal assays, both ESC and iPSC-derived cells generated CFU, albeit with a 150-fold lower efficacy than cord blood (CB) CD34(+) cells. ESC-derived CD34(+) cells generated myeloid and fully hemoglobinized erythroid cells whereas CD34(-) cells almost exclusively generated small erythroid colonies. Both ESC and iPSC-derived erythroid cells expressed embryonic and fetal globins but were unable to synthesize adult β-globin in contrast with CB cells, suggesting that they had differentiated from primitive rather than from definitive hematopoietic progenitors. Short-term, animal protein-free culture conditions are sufficient to sustain the differentiation of human ESC and iPSC into primitive hematopoietic progenitors, which, in turn, produce more mature

  9. white+ transgene insertions presenting a dorsal/ventral pattern define a single cluster of homeobox genes that is silenced by the polycomb-group proteins in Drosophila melanogaster.

    PubMed Central

    Netter, S; Fauvarque, M O; Diez del Corral, R; Dura, J M; Coen, D

    1998-01-01

    We used the white gene as an enhancer trap and reporter of chromatin structure. We collected white+ transgene insertions presenting a peculiar pigmentation pattern in the eye: white expression is restricted to the dorsal half of the eye, with a clear-cut dorsal/ventral (D/V) border. This D/V pattern is stable and heritable, indicating that phenotypic expression of the white reporter reflects positional information in the developing eye. Localization of these transgenes led us to identify a unique genomic region encompassing 140 kb in 69D1-3 subject to this D/V effect. This region contains at least three closely related homeobox-containing genes that are constituents of the iroquois complex (IRO-C). IRO-C genes are coordinately regulated and implicated in similar developmental processes. Expression of these genes in the eye is regulated by the products of the Polycomb-group (Pc-G) and trithorax-group (trx-G) genes but is not modified by classical modifiers of position-effect variegation. Our results, together with the report of a Pc-G binding site in 69D, suggest that we have identified a novel cluster of target genes for the Pc-G and trx-G products. We thus propose that ventral silencing of the whole IRO-C in the eye occurs at the level of chromatin structure in a manner similar to that of the homeotic gene complexes, perhaps by local compaction of the region into a heterochromatin-like structure involving the Pc-G products. PMID:9584101

  10. The Arf6 GTPase-activating Proteins ARAP2 and ACAP1 Define Distinct Endosomal Compartments That Regulate Integrin α5β1 Traffic*

    PubMed Central

    Chen, Pei-Wen; Luo, Ruibai; Jian, Xiaoying; Randazzo, Paul A.

    2014-01-01

    Arf6 and the Arf6 GTPase-activating protein (GAP) ACAP1 are established regulators of integrin traffic important to cell adhesion and migration. However, the function of Arf6 with ACAP1 cannot explain the range of Arf6 effects on integrin-based structures. We propose that Arf6 has different functions determined, in part, by the associated Arf GAP. We tested this idea by comparing the Arf6 GAPs ARAP2 and ACAP1. We found that ARAP2 and ACAP1 had opposing effects on apparent integrin β1 internalization. ARAP2 knockdown slowed, whereas ACAP1 knockdown accelerated, integrin β1 internalization. Integrin β1 association with adaptor protein containing a pleckstrin homology (PH) domain, phosphotyrosine-binding (PTB) domain, and leucine zipper motif (APPL)-positive endosomes and EEA1-positive endosomes was affected by ARAP2 knockdown and depended on ARAP2 GAP activity. ARAP2 formed a complex with APPL1 and colocalized with Arf6 and APPL in a compartment distinct from the Arf6/ACAP1 tubular recycling endosome. In addition, although ACAP1 and ARAP2 each colocalized with Arf6, they did not colocalize with each other and had opposing effects on focal adhesions (FAs). ARAP2 overexpression promoted large FAs, but ACAP1 overexpression reduced FAs. Taken together, the data support a model in which Arf6 has at least two sites of opposing action defined by distinct Arf6 GAPs. PMID:25225293

  11. Rab11-family interacting proteins define spatially and temporally distinct regions within the dynamic Rab11a-dependent recycling system.

    PubMed

    Baetz, Nicholas W; Goldenring, James R

    2013-03-01

    The Rab11-family interacting proteins (Rab11-FIPs) facilitate Rab11-dependent vesicle recycling. We hypothesized that Rab11-FIPs define discrete subdomains and carry out temporally distinct roles within the recycling system. We used live-cell deconvolution microscopy of HeLa cells expressing chimeric fluorescent Rab11-FIPs to examine Rab11-FIP localization, transferrin passage through Rab11-FIP-containing compartments, and overlap among Rab11-FIPs within the recycling system. FIP1A, FIP2, and FIP5 occupy widely distributed mobile tubules and vesicles, whereas FIP1B, FIP1C, and FIP3 localize to perinuclear tubules. Internalized transferrin entered Rab11-FIP-containing compartments within 5 min, reaching maximum colocalization with FIP1B and FIP2 early in the time course, whereas localization with FIP1A, FIP1C, FIP3, and FIP5 was delayed until 10 min or later. Whereas direct interactions with FIP1A were only observed for FIP1B and FIP1C, FIP1A also associated with membranes containing FIP3. Live-cell dual-expression studies of Rab11-FIPs revealed the tubular dynamics of Rab11-FIP-containing compartments and demonstrated a series of selective associations among Rab11-FIPs in real time. These findings suggest that Rab11-FIP1 proteins participate in spatially and temporally distinct steps of the recycling process along a complex and dynamic tubular network in which Rab11-FIPs occupy discrete domains.

  12. Rab11-family interacting proteins define spatially and temporally distinct regions within the dynamic Rab11a-dependent recycling system

    PubMed Central

    Baetz, Nicholas W.; Goldenring, James R.

    2013-01-01

    The Rab11-family interacting proteins (Rab11-FIPs) facilitate Rab11-dependent vesicle recycling. We hypothesized that Rab11-FIPs define discrete subdomains and carry out temporally distinct roles within the recycling system. We used live-cell deconvolution microscopy of HeLa cells expressing chimeric fluorescent Rab11-FIPs to examine Rab11-FIP localization, transferrin passage through Rab11-FIP–containing compartments, and overlap among Rab11-FIPs within the recycling system. FIP1A, FIP2, and FIP5 occupy widely distributed mobile tubules and vesicles, whereas FIP1B, FIP1C, and FIP3 localize to perinuclear tubules. Internalized transferrin entered Rab11-FIP–containing compartments within 5 min, reaching maximum colocalization with FIP1B and FIP2 early in the time course, whereas localization with FIP1A, FIP1C, FIP3, and FIP5 was delayed until 10 min or later. Whereas direct interactions with FIP1A were only observed for FIP1B and FIP1C, FIP1A also associated with membranes containing FIP3. Live-cell dual-expression studies of Rab11-FIPs revealed the tubular dynamics of Rab11-FIP–containing compartments and demonstrated a series of selective associations among Rab11-FIPs in real time. These findings suggest that Rab11-FIP1 proteins participate in spatially and temporally distinct steps of the recycling process along a complex and dynamic tubular network in which Rab11-FIPs occupy discrete domains. PMID:23283983

  13. Co-occurring genomic alterations define major subsets of KRAS-mutant lung adenocarcinoma with distinct biology, immune profiles, and therapeutic vulnerabilities.

    PubMed

    Skoulidis, Ferdinandos; Byers, Lauren A; Diao, Lixia; Papadimitrakopoulou, Vassiliki A; Tong, Pan; Izzo, Julie; Behrens, Carmen; Kadara, Humam; Parra, Edwin R; Canales, Jaime Rodriguez; Zhang, Jianjun; Giri, Uma; Gudikote, Jayanthi; Cortez, Maria A; Yang, Chao; Fan, Youhong; Peyton, Michael; Girard, Luc; Coombes, Kevin R; Toniatti, Carlo; Heffernan, Timothy P; Choi, Murim; Frampton, Garrett M; Miller, Vincent; Weinstein, John N; Herbst, Roy S; Wong, Kwok-Kin; Zhang, Jianhua; Sharma, Padmanee; Mills, Gordon B; Hong, Waun K; Minna, John D; Allison, James P; Futreal, Andrew; Wang, Jing; Wistuba, Ignacio I; Heymach, John V

    2015-08-01

    The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma are poorly characterized. We performed an integrative analysis of genomic, transcriptomic, and proteomic data from early-stage and chemorefractory lung adenocarcinoma and identified three robust subsets of KRAS-mutant lung adenocarcinoma dominated, respectively, by co-occurring genetic events in STK11/LKB1 (the KL subgroup), TP53 (KP), and CDKN2A/B inactivation coupled with low expression of the NKX2-1 (TTF1) transcription factor (KC). We further revealed biologically and therapeutically relevant differences between the subgroups. KC tumors frequently exhibited mucinous histology and suppressed mTORC1 signaling. KL tumors had high rates of KEAP1 mutational inactivation and expressed lower levels of immune markers, including PD-L1. KP tumors demonstrated higher levels of somatic mutations, inflammatory markers, immune checkpoint effector molecules, and improved relapse-free survival. Differences in drug sensitivity patterns were also observed; notably, KL cells showed increased vulnerability to HSP90-inhibitor therapy. This work provides evidence that co-occurring genomic alterations identify subgroups of KRAS-mutant lung adenocarcinoma with distinct biology and therapeutic vulnerabilities. Co-occurring genetic alterations in STK11/LKB1, TP53, and CDKN2A/B-the latter coupled with low TTF1 expression-define three major subgroups of KRAS-mutant lung adenocarcinoma with distinct biology, patterns of immune-system engagement, and therapeutic vulnerabilities. ©2015 American Association for Cancer Research.

  14. Single amino acid charge switch defines clinically distinct proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1)-associated inflammatory diseases.

    PubMed

    Holzinger, Dirk; Fassl, Selina Kathleen; de Jager, Wilco; Lohse, Peter; Röhrig, Ute F; Gattorno, Marco; Omenetti, Alessia; Chiesa, Sabrina; Schena, Francesca; Austermann, Judith; Vogl, Thomas; Kuhns, Douglas B; Holland, Steven M; Rodríguez-Gallego, Carlos; López-Almaraz, Ricardo; Arostegui, Juan I; Colino, Elena; Roldan, Rosa; Fessatou, Smaragdi; Isidor, Bertrand; Poignant, Sylvaine; Ito, Koichi; Epple, Hans-Joerg; Bernstein, Jonathan A; Jeng, Michael; Frankovich, Jennifer; Lionetti, Geraldina; Church, Joseph A; Ong, Peck Y; LaPlant, Mona; Abinun, Mario; Skinner, Rod; Bigley, Venetia; Sachs, Ulrich J; Hinze, Claas; Hoppenreijs, Esther; Ehrchen, Jan; Foell, Dirk; Chae, Jae Jin; Ombrello, Amanda; Aksentijevich, Ivona; Sunderkoetter, Cord; Roth, Johannes

    2015-11-01

    Hyperzincemia and hypercalprotectinemia (Hz/Hc) is a distinct autoinflammatory entity involving extremely high serum concentrations of the proinflammatory alarmin myeloid-related protein (MRP) 8/14 (S100A8/S100A9 and calprotectin). We sought to characterize the genetic cause and clinical spectrum of Hz/Hc. Proline-serine-threonine phosphatase-interacting protein 1 (PSTPIP1) gene sequencing was performed in 14 patients with Hz/Hc, and their clinical phenotype was compared with that of 11 patients with pyogenic arthritis, pyoderma gangrenosum, and acne (PAPA) syndrome. PSTPIP1-pyrin interactions were analyzed by means of immunoprecipitation and Western blotting. A structural model of the PSTPIP1 dimer was generated. Cytokine profiles were analyzed by using the multiplex immunoassay, and MRP8/14 serum concentrations were analyzed by using an ELISA. Thirteen patients were heterozygous for a missense mutation in the PSTPIP1 gene, resulting in a p.E250K mutation, and 1 carried a mutation resulting in p.E257K. Both mutations substantially alter the electrostatic potential of the PSTPIP1 dimer model in a region critical for protein-protein interaction. Patients with Hz/Hc have extremely high MRP8/14 concentrations (2045 ± 1300 μg/mL) compared with those with PAPA syndrome (116 ± 74 μg/mL) and have a distinct clinical phenotype. A specific cytokine profile is associated with Hz/Hc. Hz/Hc mutations altered protein binding of PSTPIP1, increasing interaction with pyrin through phosphorylation of PSTPIP1. Mutations resulting in charge reversal in the y-domain of PSTPIP1 (E→K) and increased interaction with pyrin cause a distinct autoinflammatory disorder defined by clinical and biochemical features not found in patients with PAPA syndrome, indicating a unique genotype-phenotype correlation for mutations in the PSTPIP1 gene. This is the first inborn autoinflammatory syndrome in which inflammation is driven by uncontrolled release of members of the alarmin family. Copyright

  15. Local Circuits of V1 Layer 4B Neurons Projecting to V2 Thick Stripes Define Distinct Cell Classes and Avoid Cytochrome Oxidase Blobs

    PubMed Central

    Yarch, Jeff; Federer, Frederick

    2017-01-01

    Decades of anatomical studies on the primate primary visual cortex (V1) have led to a detailed diagram of V1 intrinsic circuitry, but this diagram lacks information about the output targets of V1 cells. Understanding how V1 local processing relates to downstream processing requires identification of neuronal populations defined by their output targets. In primates, V1 layers (L)2/3 and 4B send segregated projections to distinct cytochrome oxidase (CO) stripes in area V2: neurons in CO blob columns project to thin stripes while neurons outside blob columns project to thick and pale stripes, suggesting functional specialization of V1-to-V2 CO streams. However, the conventional diagram of V1 shows all L4B neurons, regardless of their soma location in blob or interblob columns, as projecting selectively to CO blobs in L2/3, suggesting convergence of blob/interblob information in L2/3 blobs and, possibly, some V2 stripes. However, it is unclear whether all L4B projection neurons show similar local circuitries. Using viral-mediated circuit tracing, we have identified the local circuits of L4B neurons projecting to V2 thick stripes in macaque. Consistent with previous studies, we found the somata of this L4B subpopulation to reside predominantly outside blob columns; however, unlike previous descriptions of local L4B circuits, these cells consistently projected outside CO blob columns in all layers. Thus, the local circuits of these L4B output neurons, just like their extrinsic projections to V2, preserve CO streams. Moreover, the intra-V1 laminar patterns of axonal projections identify two distinct neuron classes within this L4B subpopulation, including a rare novel neuron type, suggestive of two functionally specialized output channels. SIGNIFICANCE STATEMENT Conventional diagrams of primate primary visual cortex (V1) depict neuronal connections within and between different V1 layers, but lack information about the cells' downstream targets. This information is critical

  16. Feeding tube insertion - gastrostomy

    MedlinePlus

    ... tube insertion; G-tube insertion; PEG tube insertion; Stomach tube insertion; Percutaneous endoscopic gastrostomy tube insertion ... and down the esophagus, which leads to the stomach. After the endoscopy tube is inserted, the skin ...

  17. Local Circuits of V1 Layer 4B Neurons Projecting to V2 Thick Stripes Define Distinct Cell Classes and Avoid Cytochrome Oxidase Blobs.

    PubMed

    Yarch, Jeff; Federer, Frederick; Angelucci, Alessandra

    2017-01-11

    Decades of anatomical studies on the primate primary visual cortex (V1) have led to a detailed diagram of V1 intrinsic circuitry, but this diagram lacks information about the output targets of V1 cells. Understanding how V1 local processing relates to downstream processing requires identification of neuronal populations defined by their output targets. In primates, V1 layers (L)2/3 and 4B send segregated projections to distinct cytochrome oxidase (CO) stripes in area V2: neurons in CO blob columns project to thin stripes while neurons outside blob columns project to thick and pale stripes, suggesting functional specialization of V1-to-V2 CO streams. However, the conventional diagram of V1 shows all L4B neurons, regardless of their soma location in blob or interblob columns, as projecting selectively to CO blobs in L2/3, suggesting convergence of blob/interblob information in L2/3 blobs and, possibly, some V2 stripes. However, it is unclear whether all L4B projection neurons show similar local circuitries. Using viral-mediated circuit tracing, we have identified the local circuits of L4B neurons projecting to V2 thick stripes in macaque. Consistent with previous studies, we found the somata of this L4B subpopulation to reside predominantly outside blob columns; however, unlike previous descriptions of local L4B circuits, these cells consistently projected outside CO blob columns in all layers. Thus, the local circuits of these L4B output neurons, just like their extrinsic projections to V2, preserve CO streams. Moreover, the intra-V1 laminar patterns of axonal projections identify two distinct neuron classes within this L4B subpopulation, including a rare novel neuron type, suggestive of two functionally specialized output channels. Conventional diagrams of primate primary visual cortex (V1) depict neuronal connections within and between different V1 layers, but lack information about the cells' downstream targets. This information is critical to understanding how

  18. Tricho- and atrichoblast cell files show distinct PIN2 auxin efflux carrier exploitations and are jointly required for defined auxin-dependent root organ growth.

    PubMed

    Löfke, Christian; Scheuring, David; Dünser, Kai; Schöller, Maria; Luschnig, Christian; Kleine-Vehn, Jürgen

    2015-08-01

    The phytohormone auxin is a vital growth regulator in plants. In the root epidermis auxin steers root organ growth. However, the mechanisms that allow adjacent tissues to integrate growth are largely unknown. Here, the focus is on neighbouring epidermal root tissues to assess the integration of auxin-related growth responses. The pharmacologic, genetic, and live-cell imaging approaches reveal that PIN2 auxin efflux carriers are differentially controlled in tricho- and atrichoblast cells. PIN2 proteins show lower abundance at the plasma membrane of trichoblast cells, despite showing higher rates of intracellular trafficking in these cells. The data suggest that PIN2 proteins display distinct cell-type-dependent trafficking rates to the lytic vacuole for degradation. Based on this insight, it is hypothesized that auxin-dependent processes are distinct in tricho- and atrichoblast cells. Moreover, genetic interference with epidermal patterning supports this assumption and suggests that tricho- and atrichoblasts have distinct importance for auxin-sensitive root growth and gravitropic responses.

  19. Insertion Sequences

    PubMed Central

    Mahillon, Jacques; Chandler, Michael

    1998-01-01

    Insertion sequences (ISs) constitute an important component of most bacterial genomes. Over 500 individual ISs have been described in the literature to date, and many more are being discovered in the ongoing prokaryotic and eukaryotic genome-sequencing projects. The last 10 years have also seen some striking advances in our understanding of the transposition process itself. Not least of these has been the development of various in vitro transposition systems for both prokaryotic and eukaryotic elements and, for several of these, a detailed understanding of the transposition process at the chemical level. This review presents a general overview of the organization and function of insertion sequences of eubacterial, archaebacterial, and eukaryotic origins with particular emphasis on bacterial elements and on different aspects of the transposition mechanism. It also attempts to provide a framework for classification of these elements by assigning them to various families or groups. A total of 443 members of the collection have been grouped in 17 families based on combinations of the following criteria: (i) similarities in genetic organization (arrangement of open reading frames); (ii) marked identities or similarities in the enzymes which mediate the transposition reactions, the recombinases/transposases (Tpases); (iii) similar features of their ends (terminal IRs); and (iv) fate of the nucleotide sequence of their target sites (generation of a direct target duplication of determined length). A brief description of the mechanism(s) involved in the mobility of individual ISs in each family and of the structure-function relationships of the individual Tpases is included where available. PMID:9729608

  20. Turbine vane segment and impingement insert configuration for fail-safe impingement insert retention

    DOEpatents

    Burdgick, Steven Sebastian; Kellock, Iain Robertson

    2003-05-13

    An impingement insert sleeve is provided that is adapted to be disposed in a coolant cavity defined through a stator vane. The insert has a generally open inlet end and first and second pairs of diametrically opposed side walls, and at least one fail-safe tab defined at a longitudinal end of the insert for limiting radial displacement of the insert with respect to the stator vane.

  1. Alternatively spliced type II procollagen mRNAs define distinct populations of cells during vertebral development: differential expression of the amino-propeptide

    PubMed Central

    1991-01-01

    Type II collagen is a major component of cartilage providing structural integrity to the tissue. Type II procollagen can be expressed in two forms by differential splicing of the primary gene transcript. The two mRNAs either include (type IIA) or exclude (type IIB) an exon (exon 2) encoding the major portion of the amino (NH2)-propeptide (Ryan, M. C., and L. J. Sandell. 1990. J. Biol. Chem. 265:10334-10339). The expression of the two procollagens was examined in order to establish a potential functional significance for the two type II procollagen mRNAs. First, to establish whether the two mRNAs are functional, we showed that both mRNAs can be translated and the proteins secreted into the extracellular environment. Both proteins were identified as type II procollagens. Secondly, to test the hypothesis that differential expression of type II procollagens may be a marker for a distinct population of cells, specific procollagen mRNAs were localized in tissue by in situ hybridization to oligonucleotides spanning the exon junctions. Embryonic vertebral column was chosen as a source of tissue undergoing rapid chondrogenesis, allowing the examination of a variety of cell types related to cartilage. In this issue, each procollagen mRNA had a distinct tissue distribution during chondrogenesis with type IIB expressed in chondrocytes and type IIA expressed in cells surrounding cartilage in prechondrocytes. The morphology of the cells expressing the two collagen types was distinct: the cells expressing type IIA are narrow, elongated, and "fibroblastic" in appearance while the cells expressing type IIB are large and round. The expression of type IIB appears to be correlated with abundant synthesis and accumulation of cartilagenous extracellular matrix. The expression of type IIB is spatially correlated with the high level expression of the cartilage proteoglycan, aggrecan, establishing type IIB procollagen and aggrecan as markers for the chondrocyte phenotype. Transcripts of

  2. Genome-Wide Identification of Binding Sites Defines Distinct Functions for Caenorhabditis elegans PHA-4/FOXA in Development and Environmental Response

    PubMed Central

    Zhong, Mei; Niu, Wei; Lu, Zhi John; Sarov, Mihail; Murray, John I.; Janette, Judith; Raha, Debasish; Sheaffer, Karyn L.; Lam, Hugo Y. K.; Preston, Elicia; Slightham, Cindie; Hillier, LaDeana W.; Brock, Trisha; Agarwal, Ashish; Auerbach, Raymond; Hyman, Anthony A.; Gerstein, Mark; Mango, Susan E.; Kim, Stuart K.; Waterston, Robert H.; Reinke, Valerie; Snyder, Michael

    2010-01-01

    Transcription factors are key components of regulatory networks that control development, as well as the response to environmental stimuli. We have established an experimental pipeline in Caenorhabditis elegans that permits global identification of the binding sites for transcription factors using chromatin immunoprecipitation and deep sequencing. We describe and validate this strategy, and apply it to the transcription factor PHA-4, which plays critical roles in organ development and other cellular processes. We identified thousands of binding sites for PHA-4 during formation of the embryonic pharynx, and also found a role for this factor during the starvation response. Many binding sites were found to shift dramatically between embryos and starved larvae, from developmentally regulated genes to genes involved in metabolism. These results indicate distinct roles for this regulator in two different biological processes and demonstrate the versatility of transcription factors in mediating diverse biological roles. PMID:20174564

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

    SciTech Connect

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

    1990-01-15

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

  4. Thought Insertion Clarified

    PubMed Central

    Ratcliffe, Matthew; Wilkinson, Sam

    2016-01-01

    ‘Thought insertion’ in schizophrenia involves somehow experiencing one’s own thoughts as someone else’s. Some philosophers try to make sense of this by distinguishing between ownership and agency: one still experiences oneself as the owner of an inserted thought but attributes it to another agency. In this paper, we propose that thought insertion involves experiencing thought contents as alien, rather than episodes of thinking. To make our case, we compare thought insertion to certain experiences of ‘verbal hallucination’ and show that they amount to different descriptions of the same phenomenon: a quasi-perceptual experience of thought content. We add that the agency/ownership distinction is unhelpful here. What requires explanation is not why a person experiences a type of intentional state without the usual sense of agency, but why she experiences herself as the agent of one type of intentional state rather than another. We conclude by sketching an account of how this might happen. PMID:28123340

  5. Two Distinct Binding Modes Define the Interaction of Brox with the C-Terminal Tails of CHMP5 and CHMP4B

    SciTech Connect

    Mu, Ruiling; Dussupt, Vincent; Jiang, Jiansheng; Sette, Paola; Rudd, Victoria; Chuenchor, Watchalee; Bello, Nana F.; Bouamr, Fadila; Xiao, Tsan Sam

    2012-05-21

    Interactions of the CHMP protein carboxyl terminal tails with effector proteins play important roles in retroviral budding, cytokinesis, and multivesicular body biogenesis. Here we demonstrate that hydrophobic residues at the CHMP4B C-terminal amphipathic {alpha} helix bind a concave surface of Brox, a mammalian paralog of Alix. Unexpectedly, CHMP5 was also found to bind Brox and specifically recruit endogenous Brox to detergent-resistant membrane fractions through its C-terminal 20 residues. Instead of an {alpha} helix, the CHMP5 C-terminal tail adopts a tandem {beta}-hairpin structure that binds Brox at the same site as CHMP4B. Additional Brox:CHMP5 interface is furnished by a unique CHMP5 hydrophobic pocket engaging the Brox residue Y348 that is not conserved among the Bro1 domains. Our studies thus unveil a {beta}-hairpin conformation of the CHMP5 protein C-terminal tail, and provide insights into the overlapping but distinct binding profiles of ESCRT-III and the Bro1 domain proteins.

  6. The A- and B-type cyclins of Drosophila are accumulated and destroyed in temporally distinct events that define separable phases of the G2-M transition.

    PubMed Central

    Whitfield, W G; Gonzalez, C; Maldonado-Codina, G; Glover, D M

    1990-01-01

    We show that the sequence of Drosophila cyclin B has greater identity with B-type cyclins from other animal phyla than with Drosophila cyclin A, suggesting that the two cyclins have distinct roles that have been maintained in evolution. Cyclin A is not detectable in unfertilized eggs and is present at low levels prior to cellularization of the syncytial embryo. In contrast, the levels of cyclin B remain uniformly high throughout these developmental stages. In cells within cellularized embryos and the larval brain, cyclin A accumulates to peak levels in prophase and is degraded throughout the period in which chromosomes are becoming aligned on the metaphase plate. The degradation of cyclin B, on the other hand, does not occur until the metaphase-anaphase transition. In cells arrested at c-metaphase by treating with microtubule destabilizing drugs to prevent spindle formation, cyclin A has been degraded in the arrested cells, whereas cyclin B is maintained at high levels. These observations suggest that cyclin A has a role in the G2-M transition that is independent of spindle formation, and that entry into anaphase is a key requirement for the degradation of cyclin B. Images Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. PMID:2142452

  7. Pseudomonas aeruginosa Cif defines a distinct class of α/β epoxide hydrolases utilizing a His/Tyr ring-opening pair

    PubMed Central

    Bahl, Christopher D.; Madden, Dean R.

    2012-01-01

    The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that secretes a multitude of virulence factors during the course of infection. Among these is Cif, an epoxide hydrolase (EH) that reduces the functional localization of the cystic fibrosis transmembrane conductance regulator in epithelial cells. In addition to being the first reported EH virulence factor, Cif possesses unique sequence deviations from canonical EH motifs. Foremost among these is the substitution of a histidine for the second epoxide ring-opening tyrosine in the active site. To test the functional equivalence of the Tyr and His side chains at this position, we have generated the mutant Cif-H177Y. Structural analysis confirms that both the WT His and mutant Tyr side chains can be accommodated without large-scale conformational changes. However, the Tyr mutation is functionally inactive. Based on a detailed analysis of the structure of the Tyr mutant, it appears that Cif's main-chain conformation imposes a functional requirement for a His at this position. Comparison with canonical EH structures reveals additional conformational differences, which are coupled to divergent sequence characteristics. When used to probe the genomes of other opportunistic pathogens, these sequence-structure criteria uncover candidate sequences that appear to form a distinct subfamily of Cif-like epoxide hydrolases characterized by a conserved His/Tyr ring-opening pair. PMID:21933119

  8. Pseudomonas aeruginosa Cif defines a distinct class of α/β epoxide hydrolases utilizing a His/Tyr ring-opening pair.

    PubMed

    Bahl, Christopher D; Madden, Dean R

    2012-02-01

    The Gram-negative bacterium Pseudomonas aeruginosa is an opportunistic pathogen that secretes a multitude of virulence factors during the course of infection. Among these is Cif, an epoxide hydrolase (EH) that reduces the functional localization of the cystic fibrosis transmembrane conductance regulator in epithelial cells. In addition to being the first reported EH virulence factor, Cif possesses unique sequence deviations from canonical EH motifs. Foremost among these is the substitution of a histidine for the first epoxide ring-opening tyrosine in the active site. To test the functional equivalence of Tyr and His side chains at this position, we have generated the mutant Cif-H177Y. Structural analysis confirms that both the WT His and mutant Tyr side chains can be accommodated without large-scale conformational changes. However, the Tyr mutant is functionally inactive. Based on a detailed analysis of the structure of the Tyr mutant, it appears that Cif's main-chain conformation imposes a functional requirement for a His at this position. Comparison with canonical EH structures reveals additional conformational differences, which are coupled to divergent sequence characteristics. When used to probe the genomes of other opportunistic pathogens, these sequence-structure criteria uncover candidate sequences that appear to form a distinct subfamily of Cif-like epoxide hydrolases characterized by a conserved His/Tyr ring-opening pair.

  9. Distinct H3F3A and H3F3B driver variants define chondroblastoma and giant cell tumour of bone

    PubMed Central

    Presneau, Nadège; Scheipl, Susanne; Pillay, Nischalan; Van Loo, Peter; Wedge, David C; Cooke, Susanna L; Gundem, Gunes; Davies, Helen; Nik-Zainal, Serena; Martin, Sancha; McLaren, Stuart; Goodie, Victoria; Robinson, Ben; Butler, Adam; Teague, Jon W; Halai, Dina; Khatri, Bhavisha; Myklebost, Ola; Baumhoer, Daniel; Jundt, Gernot; Hamoudi, Rifat; Tirabosco, Roberto; Amary, M Fernanda; Futreal, P Andrew; Stratton, Michael R; Campbell, Peter J; Flanagan, Adrienne M

    2013-01-01

    It is recognised that some mutated cancer genes contribute to the development of many cancer types whilst others are cancer-type specific. Amongst genes that affect multiple cancer classes, mutations are usually similar in the different cancer types. Here, however, we observed exquisite tumour-type specificity of different histone 3.3 driver mutations. In 73/77 (95%) cases of chondroblastoma we found K36M mutations predominantly in H3F3B, which is one of two genes encoding histone 3.3. By contrast, 92% (49/53) of giant cell tumours of bone harboured histone 3.3 variants exclusively in H3F3A, which were G34W or, in one case, G34L. The mutations were restricted to the stromal cell population and not detected in osteoclasts or their precursors. In the context of previously reported H3F3A K27M and G34R/V mutations of childhood brain tumours, a remarkable picture of tumour-type specificity of histone 3.3 mutations emerges, indicating distinct functions of histone 3.3 residues, mutations and genes. PMID:24162739

  10. Kelp Fly Virus: a Novel Group of Insect Picorna-Like Viruses as Defined by Genome Sequence Analysis and a Distinctive Virion Structure

    PubMed Central

    Hartley, C. J.; Greenwood, D. R.; Gilbert, R. J. C.; Masoumi, A.; Gordon, K. H. J.; Hanzlik, T. N.; Fry, E. E.; Stuart, D. I.; Scotti, P. D.

    2005-01-01

    The complete genomic sequence of kelp fly virus (KFV), originally isolated from the kelp fly, Chaetocoelopa sydneyensis, has been determined. Analyses of its genomic and structural organization and phylogeny show that it belongs to a hitherto undescribed group within the picorna-like virus superfamily. The single-stranded genomic RNA of KFV is 11,035 nucleotides in length and contains a single large open reading frame encoding a polypeptide of 3,436 amino acids with 5′ and 3′ untranslated regions of 384 and 343 nucleotides, respectively. The predicted amino acid sequence of the polypeptide shows that it has three regions. The N-terminal region contains sequences homologous to the baculoviral inhibitor of apoptosis repeat domain, an inhibitor of apoptosis commonly found in animals and in viruses with double-stranded DNA genomes. The second region contains at least two capsid proteins. The third region has three sequence motifs characteristic of replicase proteins of many plant and animal viruses, including a helicase, a 3C chymotrypsin-like protease, and an RNA-dependent RNA polymerase. Phylogenetic analysis of the replicase motifs shows that KFV forms a distinct and distant taxon within the picorna-like virus superfamily. Cryoelectron microscopy and image reconstruction of KFV to a resolution of 15 Å reveals an icosahedral structure, with each of its 12 fivefold vertices forming a turret from the otherwise smooth surface of the 20-Å-thick capsid. The architecture of the KFV capsid is unique among the members of the picornavirus superfamily for which structures have previously been determined. PMID:16227260

  11. Comprehensive assessment of the expression of the SWI/SNF complex defines two distinct prognostic subtypes of ovarian clear cell carcinoma.

    PubMed

    Abou-Taleb, Hisham; Yamaguchi, Ken; Matsumura, Noriomi; Murakami, Ryusuke; Nakai, Hidekatsu; Higasa, Koichiro; Amano, Yasuaki; Abiko, Kaoru; Yoshioka, Yumiko; Hamanishi, Junzo; Koshiyama, Masafumi; Baba, Tsukasa; Yamada, Ryo; Matsuda, Fumihiko; Konishi, Ikuo; Mandai, Masaki

    2016-08-23

    Somatic mutations in the ARID1A tumor-suppressor gene have been frequently identified in ovarian clear cell carcinoma (CCC) cases. BAF250a encoded by ARID1A is a member of the SWI/SNF complex, but the expression and mutation status of other SWI/SNF subunits have not been explored. The current study aimed to elucidate the biological and clinical significance of the SWI/SNF complex subunits, by assessing the expression and mutation status of SWI/SNF subunits, and distinct genomic aberrations associated with their expression. Of 82 CCC specimens, 38 samples presented no BAF250a expression, and 50 samples exhibited the loss of at least one subunit of the SWI/SNF complex. Cases which lack at least one SWI/SNF complex component exhibited significantly more advanced stages, faster growth and stronger nuclear atypia compared with SWI/SNF-positive samples (p<0.05). Although BAF250a expression is not related to poor prognosis, the group presenting the loss of at least one SWI/SNF complex subunit exhibited significantly shorter overall and progression-free survivals (p<0.05). A multivariate analysis suggested that the expression status of the SWI/SNF complex serves as an independent prognostic factor (p<0.005). The cases positive for all SWI/SNF subunits demonstrated significantly greater DNA copy number alterations, such as amplification at chromosomes 8q.24.3 and 20q.13.2-20q.13.33 (including ZNF217) and deletion at chromosomes 13q12.11-13q14.3 (including RB1), 17p13.2-17p13.1 (including TP53) and 19p13.2-19p13.12. In conclusion, the CCCs exhibiting the loss of one or multiple SWI/SNF complex subunits demonstrated aggressive behaviors and poor prognosis, whereas the CCCs with positive expression for all SWI/SNF components presented more copy number alterations and a favorable prognosis.

  12. Comprehensive assessment of the expression of the SWI/SNF complex defines two distinct prognostic subtypes of ovarian clear cell carcinoma

    PubMed Central

    Abou-Taleb, Hisham; Yamaguchi, Ken; Matsumura, Noriomi; Murakami, Ryusuke; Nakai, Hidekatsu; Higasa, Koichiro; Amano, Yasuaki; Abiko, Kaoru; Yoshioka, Yumiko; Hamanishi, Junzo; Koshiyama, Masafumi; Baba, Tsukasa; Yamada, Ryo; Matsuda, Fumihiko; Konishi, Ikuo; Mandai, Masaki

    2016-01-01

    Somatic mutations in the ARID1A tumor-suppressor gene have been frequently identified in ovarian clear cell carcinoma (CCC) cases. BAF250a encoded by ARID1A is a member of the SWI/SNF complex, but the expression and mutation status of other SWI/SNF subunits have not been explored. The current study aimed to elucidate the biological and clinical significance of the SWI/SNF complex subunits, by assessing the expression and mutation status of SWI/SNF subunits, and distinct genomic aberrations associated with their expression. Of 82 CCC specimens, 38 samples presented no BAF250a expression, and 50 samples exhibited the loss of at least one subunit of the SWI/SNF complex. Cases which lack at least one SWI/SNF complex component exhibited significantly more advanced stages, faster growth and stronger nuclear atypia compared with SWI/SNF-positive samples (p<0.05). Although BAF250a expression is not related to poor prognosis, the group presenting the loss of at least one SWI/SNF complex subunit exhibited significantly shorter overall and progression-free survivals (p<0.05). A multivariate analysis suggested that the expression status of the SWI/SNF complex serves as an independent prognostic factor (p<0.005). The cases positive for all SWI/SNF subunits demonstrated significantly greater DNA copy number alterations, such as amplification at chromosomes 8q.24.3 and 20q.13.2-20q.13.33 (including ZNF217) and deletion at chromosomes 13q12.11-13q14.3 (including RB1), 17p13.2-17p13.1 (including TP53) and 19p13.2-19p13.12. In conclusion, the CCCs exhibiting the loss of one or multiple SWI/SNF complex subunits demonstrated aggressive behaviors and poor prognosis, whereas the CCCs with positive expression for all SWI/SNF components presented more copy number alterations and a favorable prognosis. PMID:27340867

  13. Plant and Bacterial Symbiotic Mutants Define Three Transcriptionally Distinct Stages in the Development of the Medicago truncatula/Sinorhizobium meliloti Symbiosis1

    PubMed Central

    Mitra, Raka Mustaphi; Long, Sharon Rugel

    2004-01-01

    In the Medicago truncatula/Sinorhizobium meliloti symbiosis, the plant undergoes a series of developmental changes simultaneously, creating a root nodule and allowing bacterial entry and differentiation. Our studies of plant genes reveal novel transcriptional regulation during the establishment of the symbiosis and identify molecular markers that distinguish classes of plant and bacterial symbiotic mutants. We have identified three symbiotically regulated plant genes encoding a β,1–3 endoglucanase (MtBGLU1), a lectin (MtLEC4), and a cysteine-containing protein (MtN31). MtBGLU1 is down-regulated in the plant 24 h after exposure to the bacterial signal, Nod factor. The non-nodulating plant mutant dmi1 is defective in the ability to down-regulate MtBGLU1. MtLEC4 and MtN31 are induced 1 and 2 weeks after bacterial inoculation, respectively. We examined the regulation of these two genes and three previously identified genes (MtCAM1, ENOD2, and MtLB1) in plant symbiotic mutants and wild-type plants inoculated with bacterial symbiotic mutants. Plant (bit1, rit1, and Mtsym1) and bacterial (exoA and exoH) mutants with defects in the initial stages of invasion are unable to induce MtLEC4, MtN31, MtCAM1, ENOD2, and MtLB1. Bacterial mutants (fixJ and nifD) and a subset of plant mutants (dnf2, dnf3, dnf4, dnf6, and dnf7) defective for nitrogen fixation induce the above genes. The bacA bacterial mutant, which senesces upon deposition into plant cells, and two plant mutants with defects in nitrogen fixation (dnf1 and dnf5) induce MtLEC4 and ENOD2 but not MtN31, MtCAM1, or MtLB1. These data suggest the presence of at least three transcriptionally distinct developmental stages during invasion of M. truncatula by S. meliloti. PMID:14739349

  14. Chest tube insertion

    MedlinePlus

    Chest drainage tube insertion; Insertion of tube into chest; Tube thoracostomy; Pericardial drain ... When your chest tube is inserted, you will lie on your side or sit partly upright, with one arm over your head. Sometimes, ...

  15. Dihalocarbene Insertion Experiment

    ERIC Educational Resources Information Center

    Goh, S. H.

    1975-01-01

    Describes the insertion reaction using the insertion of carbenes into carbon-hydrogen bonds as an example. Outlines an experiment that will illustrate dihalocarbene insertions into diisopropyl ether. (GS)

  16. Nozzle insert for mixed mode fuel injector

    DOEpatents

    Lawrence, Keith E.

    2006-11-21

    A fuel injector includes a homogenous charge nozzle outlet set and a conventional nozzle outlet set controlled respectively, by first and second needle valve members. The homogeneous charged nozzle outlet set is defined by a nozzle insert that is attached to an injector body, which defines the conventional nozzle outlet set. The nozzle insert is a one piece metallic component with a large diameter segment separated from a small diameter segment by an annular engagement surface. One of the needle valve members is guided on an outer surface of the nozzle insert, and the nozzle insert has an interference fit attachment to the injector body.

  17. Activating NOTCH1 Mutations Define a Distinct Subgroup of Patients With Adenoid Cystic Carcinoma Who Have Poor Prognosis, Propensity to Bone and Liver Metastasis, and Potential Responsiveness to Notch1 Inhibitors.

    PubMed

    Ferrarotto, Renata; Mitani, Yoshitsugu; Diao, Lixia; Guijarro, Irene; Wang, Jing; Zweidler-McKay, Patrick; Bell, Diana; William, William N; Glisson, Bonnie S; Wick, Michael J; Kapoun, Ann M; Patnaik, Amita; Eckhardt, Gail; Munster, Pamela; Faoro, Leonardo; Dupont, Jakob; Lee, J Jack; Futreal, Andrew; El-Naggar, Adel K; Heymach, John V

    2017-01-20

    Purpose Adenoid cystic carcinomas (ACCs) represent a heterogeneous group of chemotherapy refractory tumors, with a subset demonstrating an aggressive phenotype. We investigated the molecular underpinnings of this phenotype and assessed the Notch1 pathway as a potential therapeutic target. Methods We genotyped 102 ACCs that had available pathologic and clinical data. Notch1 activation was assessed by immunohistochemistry for Notch1 intracellular domain. Luciferase reporter assays were used to confirm Notch1 target gene expression in vitro. The Notch1 inhibitor brontictuzumab was tested in patient-derived xenografts from patients with ACC and in a patient with ACC who was enrolled in a phase I study. Results NOTCH1 mutations occurred predominantly (14 of 15 patients) in the negative regulatory region and Pro-Glu-Ser-Thr-rich domains, the same two hotspots seen in T-cell acute lymphoblastic leukemias, and led to pathway activation in vitro. NOTCH1-mutant tumors demonstrated significantly higher levels of Notch1 pathway activation than wild-type tumors on the basis of Notch1 intracellular domain staining ( P = .004). NOTCH1 mutations define a distinct aggressive ACC subgroup with a significantly higher likelihood of solid subtype ( P < .001), advanced-stage disease at diagnosis ( P = .02), higher rate of liver and bone metastasis ( P ≤ .02), shorter relapse-free survival (median, 13 v 34 months; P = .01), and shorter overall survival (median 30 v 122 months; P = .001) when compared with NOTCH1 wild-type tumors. Significant tumor growth inhibition with brontictuzumab was observed exclusively in the ACC patient-derived xenograft model that harbored a NOTCH1 activating mutation. Furthermore, an index patient with NOTCH1-mutant ACC had a partial response to brontictuzumab. Conclusion NOTCH1 mutations define a distinct disease phenotype characterized by solid histology, liver and bone metastasis, poor prognosis, and potential responsiveness to Notch1 inhibitors. Clinical

  18. Activating NOTCH1 Mutations Define a Distinct Subgroup of Patients With Adenoid Cystic Carcinoma Who Have Poor Prognosis, Propensity to Bone and Liver Metastasis, and Potential Responsiveness to Notch1 Inhibitors

    PubMed Central

    Mitani, Yoshitsugu; Diao, Lixia; Guijarro, Irene; Wang, Jing; Zweidler-McKay, Patrick; Bell, Diana; William, William N.; Glisson, Bonnie S.; Wick, Michael J.; Kapoun, Ann M.; Patnaik, Amita; Eckhardt, Gail; Munster, Pamela; Faoro, Leonardo; Dupont, Jakob; Lee, J. Jack; Futreal, Andrew; El-Naggar, Adel K.; Heymach, John V.

    2017-01-01

    Purpose Adenoid cystic carcinomas (ACCs) represent a heterogeneous group of chemotherapy refractory tumors, with a subset demonstrating an aggressive phenotype. We investigated the molecular underpinnings of this phenotype and assessed the Notch1 pathway as a potential therapeutic target. Methods We genotyped 102 ACCs that had available pathologic and clinical data. Notch1 activation was assessed by immunohistochemistry for Notch1 intracellular domain. Luciferase reporter assays were used to confirm Notch1 target gene expression in vitro. The Notch1 inhibitor brontictuzumab was tested in patient-derived xenografts from patients with ACC and in a patient with ACC who was enrolled in a phase I study. Results NOTCH1 mutations occurred predominantly (14 of 15 patients) in the negative regulatory region and Pro-Glu-Ser-Thr–rich domains, the same two hotspots seen in T-cell acute lymphoblastic leukemias, and led to pathway activation in vitro. NOTCH1-mutant tumors demonstrated significantly higher levels of Notch1 pathway activation than wild-type tumors on the basis of Notch1 intracellular domain staining (P = .004). NOTCH1 mutations define a distinct aggressive ACC subgroup with a significantly higher likelihood of solid subtype (P < .001), advanced-stage disease at diagnosis (P = .02), higher rate of liver and bone metastasis (P ≤ .02), shorter relapse-free survival (median, 13 v 34 months; P = .01), and shorter overall survival (median 30 v 122 months; P = .001) when compared with NOTCH1 wild-type tumors. Significant tumor growth inhibition with brontictuzumab was observed exclusively in the ACC patient-derived xenograft model that harbored a NOTCH1 activating mutation. Furthermore, an index patient with NOTCH1-mutant ACC had a partial response to brontictuzumab. Conclusion NOTCH1 mutations define a distinct disease phenotype characterized by solid histology, liver and bone metastasis, poor prognosis, and potential responsiveness to Notch1 inhibitors. Clinical

  19. Chair Inserts for Preschoolers.

    ERIC Educational Resources Information Center

    Horn, Eva; And Others

    1987-01-01

    The article provides detailed procedures (with diagrams) for constructing cardboard chair inserts to meet the needs of preschool children with minimal to severe physical limitations. The inserts offer reduced expense and increased flexibility allowing a customized fit. (DB)

  20. Most cases of cryptococcal meningitis in HIV-uninfected patients in Vietnam are due to a distinct amplified fragment length polymorphism-defined cluster of Cryptococcus neoformans var. grubii VN1.

    PubMed

    Day, Jeremy N; Hoang, Thu N; Duong, Anh V; Hong, Chau T T; Diep, Pham T; Campbell, James I; Sieu, Tran P M; Hien, Tran T; Bui, Tien; Boni, Maciej F; Lalloo, David G; Carter, Dee; Baker, Stephen; Farrar, Jeremy J

    2011-02-01

    Cryptococcal disease most commonly occurs in patients with an underlying immune deficit, most commonly HIV infection, and is due to Cryptococcus neoformans var. grubii. Occasionally disease due to this variety occurs in apparently immunocompetent patients. The relationship between strains infecting immunosuppressed and immunocompetent patients is not clear. Amplified fragment length polymorphism (AFLP) analysis was used to characterize the relationship between strains infecting HIV-infected and uninfected patients. Isolates from 51 HIV-uninfected patients and 100 HIV-infected patients with cryptococcal meningitis were compared. C. neoformans var. grubii VNI was responsible for infections in 73% of HIV-uninfected and 100% of HIV-infected patients. AFLP analysis defined two distinct clusters, VNIγ and VNIδ. The majority (84%) of isolates from HIV-uninfected patients were VNIγ, compared with only 38% of isolates from HIV-infected patients (odds ratio, 8.30; 95% confidence interval [CI], 3.04 to 26.6; P < 0.0001). In HIV-uninfected patients, underlying disease was less frequent in those with VNIγ infections. Two clusters of C. neoformans var. grubii VN1 are responsible for the majority of cases of cryptococcal meningitis in Vietnam. The distribution of these clusters differs according to the immune status of the host.

  1. Clinical use of an insert earphone.

    PubMed

    Clemis, J D; Ballad, W J; Killion, M C

    1986-01-01

    There are several applications of and advantages to using an insert earphone. An insert earphone has three parts: a transducer to convert electrical energy to sound, a conduit to deliver the sound into the ear canal, and a coupler connecting the device to the canal. The data from this study indicate that there is a distinct advantage in using insert earphones over TDH-49 phones (standard headphones) in the attenuation of low frequency ambient noise. The use of insert earphones will permit one to test hearing in areas of higher ambient noise than was previously possible. Insert earphones are used to shorten the hearing aid selection process. A technique is described in which only one real ear measurement is required for an accurate hearing aid fitting. Most, but not all, of the masking dilemmas that are encountered with standard headphones are circumvented or eliminated by using insert earphones. In brain stem auditory evoked response testing, the insert earphone reduces the stimulus artifact without influencing the acoustic signal. Finally, the insert earphone solves the collapsing ear canal problem.

  2. Recessed impingement insert metering plate for gas turbine nozzles

    DOEpatents

    Itzel, Gary Michael; Burdgick, Steven Sebastian

    2002-01-01

    An impingement insert sleeve is provided that is adapted to be disposed in a coolant cavity defined through a stator vane. The insert has a generally open inlet end and first and second diametrically opposed, perforated side walls. A metering plate having at least one opening defined therethrough for coolant flow is mounted to the side walls to generally transverse a longitudinal axis of the insert, and is disposed downstream from said inlet end. The metering plate improves flow distribution while reducing ballooning stresses within the insert and allowing for a more flexible insert attachment.

  3. Bulkhead insert for an internal combustion engine

    DOEpatents

    Maki, Clifford E.; Chottiner, Jeffrey Eliot; Williams, Rick L.; Thibault, Mark W.; Ervin, James Douglas; Boileau, James Maurice; McKeough, Bryan

    2017-08-01

    An engine includes a cylinder block defining at least one main bearing bulkhead adjacent to a cylinder, and a crankshaft rotatably housed within the block by a main bearing. A bulkhead insert has a cap portion, and an insert portion provided within the bulkhead. The insert portion has having first and second end regions connected by first and second straps. Each strap having a flanged beam cross section. The first and second ends of the insert portion are configured to connect a main bearing cap column to a cylinder head column. Each of the first and second end regions define at least one protrusion having a surface substantially normal to engine combustion and reactive loads. The cap portion is configured to mate with the first end region at the main bearing cap column and support the main bearing.

  4. Efficient instruction sequencing with Inline Target Insertion

    NASA Technical Reports Server (NTRS)

    Hwu, Wen-Mei W.; Chang, Pohua P.

    1992-01-01

    Inline target insertion, a specific compiler and pipeline implementation method for delayed branches with squashing, is defined. The method is shown to offer two important features not discovered in previous studies. First, branches inserted into branch slots are correctly executed. Second, the execution returns correctly from interrupts or exceptions with only one program counter. These two features result in better performance and less software/hardware complexity than conventional delayed branching mechanisms.

  5. Insertion sequence elements in Lactococcus garvieae.

    PubMed

    Eraclio, Giovanni; Ricci, Giovanni; Fortina, Maria Grazia

    2015-01-25

    Insertion sequences are the simplest intracellular Mobile Genetic Elements which can occur in very high numbers in prokaryotic genomes, where they play an important evolutionary role by promoting genome plasticity. As such, the studies on the diversity and distribution of insertion sequences in genomes not yet investigated can contribute to improve the knowledge on a bacterial species and to identify new transposable elements. The present work describes the occurrence of insertion sequences in Lactococcus garvieae, an opportunistic emerging zoonotic and human pathogen, also associated with different food matrices. To date, no insertion elements have been described for L. garvieae in the IS element database. The analysis of the twelve published L. garvieae genomes identified 15 distinct insertion sequences that are members of the IS3, IS982, IS6, IS21 and IS256 families, including five new elements. Most of the insertion sequences in L. garvieae show substantial homology to the Lactococcus lactis elements, suggesting the movement of IS between these two species phylogenetically closely related. ISLL6 elements belonging to IS3 family were most abundant, with several copies distributed in 9 of the 12 genomes analyzed. An alignment analysis of two complete genomes carrying multi-copies of this insertion sequence indicates a possible involvement of ISLL6 in chromosomal rearrangement.

  6. Grommet Having Metal Insert

    DTIC Science & Technology

    1998-09-28

    axially with respect to the body. The 1 means for releasably securing a tool to the insert comprises 2 female threads formed on an inner surface of the...below 10 the flange 32. These surfaces 34, 36 are threaded ( female 11 threads) so that the end of a tool 38 having male threads can 12 engage the...further includes a rigid insert secured to the body in the 12 centrally located aperture. The insert has female threads formed 13 therein for releasably

  7. Method Of Wire Insertion For Electric Machine Stators

    DOEpatents

    Brown, David L; Stabel, Gerald R; Lawrence, Robert Anthony

    2005-02-08

    A method of inserting coils in slots of a stator is provided. The method includes interleaving a first set of first phase windings and a first set of second phase windings on an insertion tool. The method also includes activating the insertion tool to radially insert the first set of first phase windings and the first set of second phase windings in the slots of the stator. In one embodiment, interleaving the first set of first phase windings and the first set of second phase windings on the insertion tool includes forming the first set of first phase windings in first phase openings defined in the insertion tool, and forming the first set of second phase windings in second phase openings defined in the insertion tool.

  8. Plastic pipe insertion

    SciTech Connect

    Diskin, J.

    1987-05-01

    In March 1987 KPL changed all that when the utility inserted 1,000 ft of 16-in. SDR 15.5 Phillips Driscopipe 8000 pipe with a wall thickness of 1.032-in., into an abandoned 24-in. cast-iron line in downtown Kansas City. This is believed to be the largest diameter insert removal job ever done for gas distribution in the U.S. For KPL it was a natural progression from the smaller sizes used earlier. The procedure is the same, and the operation was quick and comparatively simple. Lower construction costs were the bottom line because with insert renewal there is no need to cut up the streets, a major expense in any urban pipeline work. There are other significant costs savings as well because the insert renewal construction process is faster than other techniques.

  9. Ear tube insertion - slideshow

    MedlinePlus

    ... this page: //medlineplus.gov/ency/presentations/100045.htm Ear tube insertion - series—Normal anatomy To use the ... 4 Overview The eardrum (tympanic membrane) separates the ear canal from the middle ear. Review Date 8/ ...

  10. Hydrocephalus Defined

    MedlinePlus

    ... narrow pathways. CSF is in constant production and absorption; it has a defined pathway from the lateral ... there is an imbalance of production and/or absorption. With most types of hydrocephalus, the fluid gets ...

  11. ALS insertion devices

    NASA Astrophysics Data System (ADS)

    Hoyer, E.; Chin, J.; Halbach, K.; Hassenzahl, W. V.; Humphries, D.; Kincaid, B.; Lancaster, H.; Plate, D.

    1991-08-01

    The Advanced Light Source (ALS), the first US third generation synchrotron radiation source, is currently under construction at the Lawrence Berkeley Laboratory. The low-emittance, 1.5 GeV electron storage ring and the insertion devices are specifically designed to produce high brightness beams in the UV to soft X-Ray range. The planned initial complement of insertion devices includes four 4.6 m long undulators, with period lengths of 3.9 cm, 5.0 cm (2) and 8.0 cm, and a 2.9 m long wiggler of 16 cm period length. Undulator design is well advanced and fabrication has begun on the 5.0 cm and 8.0 cm period length undulators. This paper discusses ALS insertion device requirements; general design philosophy; and design of the magnetic structure, support structure/drive systems, control system and vacuum system.

  12. Nozzle cavity impingement/area reduction insert

    DOEpatents

    Yu, Yufeng Phillip; Itzel, Gary Michael; Osgood, Sarah Jane

    2002-01-01

    A turbine vane segment is provided that has inner and outer walls spaced from one another, a vane extending between the inner and outer walls and having leading and trailing edges and pressure and suction sides, the vane including discrete leading edge, intermediate, aft and trailing edge cavities between the leading and trailing edges and extending lengthwise of the vane for flowing a cooling medium; and an insert sleeve within at least one of the cavities and spaced from interior wall surfaces thereof. The insert sleeve has an inlet for flowing the cooling medium into the insert sleeve and has impingement holes defined in first and second walls thereof that respectively face the pressure and suction sides of the vane. The impingement holes of at least one of those first and second walls are defined along substantially only a first, upstream portion thereof, whereby the cooling flow is predominantly impingement cooling along a first region of the insert wall corresponding to the first, upstream portion and the cooling flow is predominantly convective cooling along a second region corresponding to a second, downstream portion of the at least one wall of the insert sleeve.

  13. Insertion in Persian

    ERIC Educational Resources Information Center

    Kambuziya, Aliyeh Kord-e Zafaranlu; Dehghan, Masoud

    2011-01-01

    This paper investigates epenthesis process in Persian to catch some results in relating to vowel and consonant insertion in Persian lexicon. This survey has a close relationship to the description of epenthetic consonants and the conditions in which these consonants are used. Since no word in Persian may begin with a vowel, so that hiatus can't be…

  14. MELFI Sample Insertion

    NASA Image and Video Library

    2010-06-28

    ISS024-E-006699 (28 June 2010) --- NASA astronaut Doug Wheelock, Expedition 24 flight engineer, prepares to insert biological samples into trays in the Minus Eighty Laboratory Freezer for ISS-2 (MELFI-2) in the Destiny laboratory of the International Space Station.

  15. MELFI Sample Insertion

    NASA Image and Video Library

    2010-07-02

    ISS024-E-007346 (2 July 2010) --- NASA astronauts Tracy Caldwell Dyson (background) and Shannon Walker, both Expedition 24 flight engineers, prepare to insert biological samples in a dewar tray in the Minus Eighty Laboratory Freezer for ISS (MELFI-1) in the Kibo laboratory of the International Space Station.

  16. MELFI Sample Insertion

    NASA Image and Video Library

    2010-06-28

    ISS024-E-006697 (28 June 2010) --- NASA astronaut Doug Wheelock, Expedition 24 flight engineer, prepares to insert biological samples into trays in the Minus Eighty Laboratory Freezer for ISS-2 (MELFI-2) in the Destiny laboratory of the International Space Station.

  17. High Speed Video Insertion

    NASA Astrophysics Data System (ADS)

    Janess, Don C.

    1984-11-01

    This paper describes a means of inserting alphanumeric characters and graphics into a high speed video signal and locking that signal to an IRIG B time code. A model V-91 IRIG processor, developed by Instrumentation Technology Systems under contract to Instrumentation Marketing Corporation has been designed to operate in conjunction with the NAC model FHS-200 High Speed Video Camera which operates at 200 fields per second. The system provides for synchronizing the vertical and horizontal drive signals such that the vertical sync precisely coincides with five millisecond transitions in the IRIG time code. Additionally, the unit allows for the insertion of an IRIG time message as well as other data and symbols.

  18. CD30 expression defines a novel subgroup of diffuse large B-cell lymphoma with favorable prognosis and distinct gene expression signature: a report from the International DLBCL Rituximab-CHOP Consortium Program Study

    PubMed Central

    Hu, Shimin; Xu-Monette, Zijun Y.; Balasubramanyam, Aarthi; Manyam, Ganiraju C.; Visco, Carlo; Tzankov, Alexander; Liu, Wei-min; Miranda, Roberto N.; Zhang, Li; Montes-Moreno, Santiago; Dybkær, Karen; Chiu, April; Orazi, Attilio; Zu, Youli; Bhagat, Govind; Richards, Kristy L.; Hsi, Eric D.; Choi, William W. L.; Han van Krieken, J.; Huang, Qin; Huh, Jooryung; Ai, Weiyun; Ponzoni, Maurilio; Ferreri, Andrés J. M.; Zhao, Xiaoying; Winter, Jane N.; Zhang, Mingzhi; Li, Ling; Møller, Michael B.; Piris, Miguel A.; Li, Yong; Go, Ronald S.; Wu, Lin; Medeiros, L. Jeffrey; Young, Ken H.

    2013-01-01

    CD30, originally identified as a cell-surface marker of Reed-Sternberg and Hodgkin cells of classical Hodgkin lymphoma, is also expressed by several types of non-Hodgkin lymphoma, including a subset of diffuse large B-cell lymphoma (DLBCL). However, the prognostic and biological importance of CD30 expression in DLBCL is unknown. Here we report that CD30 expression is a favorable prognostic factor in a cohort of 903 de novo DLBCL patients. CD30 was expressed in ∼14% of DLBCL patients. Patients with CD30+ DLBCL had superior 5-year overall survival (CD30+, 79% vs CD30–, 59%; P = .001) and progression-free survival (P = .003). The favorable outcome of CD30 expression was maintained in both the germinal center B-cell and activated B-cell subtypes. Gene expression profiling revealed the upregulation of genes encoding negative regulators of nuclear factor κB activation and lymphocyte survival, and downregulation of genes encoding B-cell receptor signaling and proliferation, as well as prominent cytokine and stromal signatures in CD30+ DLBCL patients, suggesting a distinct molecular basis for its favorable outcome. Given the superior prognostic value, unique gene expression signature, and significant value of CD30 as a therapeutic target for brentuximab vedotin in ongoing successful clinical trials, it seems appropriate to consider CD30+ DLBCL as a distinct subgroup of DLBCL. PMID:23343832

  19. Defining chaos

    SciTech Connect

    Hunt, Brian R.; Ott, Edward

    2015-09-15

    In this paper, we propose, discuss, and illustrate a computationally feasible definition of chaos which can be applied very generally to situations that are commonly encountered, including attractors, repellers, and non-periodically forced systems. This definition is based on an entropy-like quantity, which we call “expansion entropy,” and we define chaos as occurring when this quantity is positive. We relate and compare expansion entropy to the well-known concept of topological entropy to which it is equivalent under appropriate conditions. We also present example illustrations, discuss computational implementations, and point out issues arising from attempts at giving definitions of chaos that are not entropy-based.

  20. The carpal insertions of the transverse carpal ligament.

    PubMed

    Manley, Mollie; Boardman, Matthew; Goitz, Robert J

    2013-04-01

    To quantitatively define the anatomic insertions of the transverse carpal ligament (TCL) to the carpals. We dissected 5 fresh-frozen cadaver limbs, isolating the TCL. The ligament insertion sites into bone were clearly marked and photographed. We then used computer software to measure the area of insertion into the individual carpals. The TCL had consistent insertion sites into the scaphoid, trapezium, pisiform, and hamate. The average insertion of the TCL on the scaphoid was 6 × 6 mm (proximal to distal × radial to ulnar maximum distance), trapezium 13 × 6 mm, pisiform 9 × 6 mm, and hamate 11 × 5 mm. The area of ligament insertion on the scaphoid was 29 mm(2), trapezium was 42 mm(2), pisiform was 38 mm(2), and hamate was 40 mm(2). The perimeter of the ligament insertion on the scaphoid was 21 mm, trapezium was 28 mm, pisiform was 25 mm, and hamate was 29 mm. The TCL has a broad but definable footprint on the trapezium and scaphoid on the radial side and the hamate and the pisiform on the ulnar side of the carpal tunnel. The distal carpal insertion sites are longer and oblong, whereas the proximal insertion sites are more circular. Precise knowledge of TCL attachment sites may allow the surgeon greater confidence and safety during procedures that involve its release, such as carpal tunnel release, trapeziectomy, hook of hamate excision, or Guyon canal release. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  1. Defining excellence.

    PubMed

    Mehl, B

    1993-05-01

    Excellence in the pharmacy profession, particularly pharmacy management, is defined. Several factors have a significant effect on the ability to reach a given level of excellence. The first is the economic and political climate in which pharmacists practice. Stricter controls, reduced resources, and the velocity of change all necessitate nurturing of values and a work ethic to maintain excellence. Excellence must be measured by the services provided with regard to the resources available; thus, the ability to achieve excellence is a true test of leadership and innovation. Excellence is also time dependent, and today's innovation becomes tomorrow's standard. Programs that raise the level of patient care, not those that aggrandize the profession, are the most important. In addition, basic services must be practiced at a level of excellence. Quality assessment is a way to improve care and bring medical treatment to a higher plane of excellence. For such assessment to be effective and not punitive, the philosophy of the program must be known, and the goal must be clear. Excellence in practice is dependent on factors such as political and social norms, standards of practice, available resources; perceptions, time, the motivation to progress to a higher level, and the continuous innovation required to reshape the profession to meet the needs of society.

  2. Ocular inserts — Advancement in therapy of eye diseases

    PubMed Central

    Kumari, Anita; Sharma, Pramod K.; Garg, Vipin K.; Garg, Garima

    2010-01-01

    The ocular insert represents a significant advancement in the therapy of eye disease. Ocular inserts are defined as sterile, thin, multilayered, drug-impregnated, solid or semisolid consistency devices placed into the cul-de-sac or conjuctival sac, whose size and shape are especially designed for ophthalmic application. They are composed of a polymeric support that may or may not contain a drug. The drug can later be incorporated as dispersion or a solution in the polymeric support. They offer several advantages as increased ocular residence and sustained release of medication into the eye. The insert includes a body portion sized to position within a lachrymal canaliculus of the eyelid. The inserts are classified according to their solubility as insoluble, soluble, or bioerodible inserts. The release of drug from the insert depends upon the diffusion, osmosis, and bioerosion of the drug, and this article is an attempt to present a brief about this newer drug delivery system. PMID:22247860

  3. Defining GERD.

    PubMed

    Sontag, S J

    1999-01-01

    "It is not the death of GERD that I seek, but that it turns from its evil ways and follows the path of righteousness." The reflux world is fully aware of what GERD is and what GERD does. What the world does not know, however, is the answer to the most important yet least asked question surrounding GERD's raison-d'etre: Why is GERD here and why do we have it? What GERD is: abnormal gastric reflux into the esophagus that causes any type of mischief. What GERD does: causes discomfort and/or pain with or without destroying the mucosa; causes stricture or stenosis, preventing food from being swallowed; sets the stage for the development of esophageal adenocarcinoma; invades the surrounding lands to harass the peaceful oropharyngeal, laryngeal and broncho-pulmonary territories; reminds us that we are not only human, but that we are dust and ashes. Why GERD is here: We propose three separate and distinct etiologies of GERD, and we offer the following three hypotheses to explain why, after 1.5 million years of standing erect, we have evolved into a species (specifically Homosapiens sapiens) that is destined to live with the scourge of GERD. Hypothesis 1: congenital. The antireflux barrier, comprising the smooth-muscled lower esophageal sphincter, the skeletal-muscled right crural diaphragm and the phreno-esophageal ligament does not completely develop due to a developmental anomaly or incomplete gestation. Hypothesis 2: acute trauma: The antireflux barrier in adults suffering acute traumatic injury to the abdomen or chest is permanently disrupted by unexpected forces, such as motor vehicle accidents (with steering wheel crush impact), blows to the abdomen (from activities such as boxing, etc.), heavy lifting or moving (e.g., pianos, refrigerators) or stress positions (e.g., hand stands on parallel gym bars). The trauma creates a hiatal hernia that renders the antireflux mechanism useless and incapable of preventing GERD. Hypothesis 3: chronic trauma: The antireflux barrier

  4. Timing of the IUD insertion.

    PubMed

    Edelman, D A; Zipper, J; Rivera, M; Medel, M

    1979-05-01

    The relationship between the time in the menstrual cycle when a TCu-200 or Cu-7-200 is inserted and subsequent IUD-related events was evaluated. For women who had either TCus or Cu-7s inserted, the pregnancy, expulsion and medical removal rates were similar for insertions performed at any time of the menstrual cycle.

  5. Metal and cofactor insertion.

    PubMed

    Mendel, Ralf R; Smith, Alison G; Marquet, Andree; Warren, Martin J

    2007-10-01

    Cells require metal ions as cofactors for the assembly of metalloproteins. Principally one has to distinguish between metal ions that are directly incorporated into their cognate sites on proteins and those metal ions that have to become part of prosthetic groups, cofactors or complexes prior to insertion of theses moieties into target proteins. Molybdenum is only active as part of the molybdenum cofactor, iron can be part of diverse Fe-S clusters or of the heme group, while copper ions are directly delivered to their targets. We will focus in greater detail on molybdenum metabolism because molybdenum metabolism is a good example for demonstrating the role and the network of metals in metabolism: each of the three steps in the pathway of molybdenum cofactor formation depends on a different metal (iron, copper, molybdenum) and also the enzymes finally harbouring the molybdenum cofactor need additional metal-containing groups to function (iron sulfur-clusters, heme-iron).

  6. Ty1-copia elements reveal diverse insertion sites linked to polymorphisms among flax (Linum usitatissimum L.) accessions.

    PubMed

    Galindo-González, Leonardo; Mhiri, Corinne; Grandbastien, Marie-Angèle; Deyholos, Michael K

    2016-12-07

    Initial characterization of the flax genome showed that Ty1-copia retrotransposons are abundant, with several members being recently inserted, and in close association with genes. Recent insertions indicate a potential for ongoing transpositional activity that can create genomic diversity among accessions, cultivars or varieties. The polymorphisms generated constitute a good source of molecular markers that may be associated with phenotype if the insertions alter gene activity. Flax, where accessions are bred mainly for seed nutritional properties or for fibers, constitutes a good model for studying the relationship of transpositional activity with diversification and breeding. In this study, we estimated copy number and used a type of transposon display known as Sequence-Specific Amplification Polymorphisms (SSAPs), to characterize six families of Ty1-copia elements across 14 flax accessions. Polymorphic insertion sites were sequenced to find insertions that could potentially alter gene expression, and a preliminary test was performed with selected genes bearing transposable element (TE) insertions. Quantification of six families of Ty1-copia elements indicated different abundances among TE families and between flax accessions, which suggested diverse transpositional histories. SSAPs showed a high level of polymorphism in most of the evaluated retrotransposon families, with a trend towards higher levels of polymorphism in low-copy number families. Ty1-copia insertion polymorphisms among cultivars allowed a general distinction between oil and fiber types, and between spring and winter types, demonstrating their utility in diversity studies. Characterization of polymorphic insertions revealed an overwhelming association with genes, with insertions disrupting exons, introns or within 1 kb of coding regions. A preliminary test on the potential transcriptional disruption by TEs of four selected genes evaluated in three different tissues, showed one case of significant

  7. Function search in a large transcription factor gene family in Arabidopsis: assessing the potential of reverse genetics to identify insertional mutations in R2R3 MYB genes.

    PubMed Central

    Meissner, R C; Jin, H; Cominelli, E; Denekamp, M; Fuertes, A; Greco, R; Kranz, H D; Penfield, S; Petroni, K; Urzainqui, A; Martin, C; Paz-Ares, J; Smeekens, S; Tonelli, C; Weisshaar, B; Baumann, E; Klimyuk, V; Marillonnet, S; Patel, K; Speulman, E; Tissier, A F; Bouchez, D; Jones, J J; Pereira, A; Wisman, E

    1999-01-01

    More than 92 genes encoding MYB transcription factors of the R2R3 class have been described in Arabidopsis. The functions of a few members of this large gene family have been described, indicating important roles for R2R3 MYB transcription factors in the regulation of secondary metabolism, cell shape, and disease resistance, and in responses to growth regulators and stresses. For the majority of the genes in this family, however, little functional information is available. As the first step to characterizing these genes functionally, the sequences of >90 family members, and the map positions and expression profiles of >60 members, have been determined previously. An important second step in the functional analysis of the MYB family, through a process of reverse genetics that entails the isolation of insertion mutants, is described here. For this purpose, a variety of gene disruption resources has been used, including T-DNA-insertion populations and three distinct populations that harbor transposon insertions. We report the isolation of 47 insertions into 36 distinct MYB genes by screening a total of 73 genes. These defined insertion lines will provide the foundation for subsequent detailed functional analyses for the assignment of specific functions to individual members of the R2R3 MYB gene family. PMID:10521515

  8. Defining the fascial system.

    PubMed

    Adstrum, Sue; Hedley, Gil; Schleip, Robert; Stecco, Carla; Yucesoy, Can A

    2017-01-01

    Fascia is a widely used yet indistinctly defined anatomical term that is concurrently applied to the description of soft collagenous connective tissue, distinct sections of membranous tissue, and a body pervading soft connective tissue system. Inconsistent use of this term is causing concern due to its potential to confuse technical communication about fascia in global, multiple discipline- and multiple profession-spanning discourse environments. The Fascia Research Society acted to address this issue by establishing a Fascia Nomenclature Committee (FNC) whose purpose was to clarify the terminology relating to fascia. This committee has since developed and defined the terms a fascia, and, more recently, the fascial system. This article reports on the FNC's proposed definition of the fascial system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Facility target insert shielding assessment

    SciTech Connect

    Mocko, Michal

    2015-10-06

    Main objective of this report is to assess the basic shielding requirements for the vertical target insert and retrieval port. We used the baseline design for the vertical target insert in our calculations. The insert sits in the 12”-diameter cylindrical shaft extending from the service alley in the top floor of the facility all the way down to the target location. The target retrieval mechanism is a long rod with the target assembly attached and running the entire length of the vertical shaft. The insert also houses the helium cooling supply and return lines each with 2” diameter. In the present study we focused on calculating the neutron and photon dose rate fields on top of the target insert/retrieval mechanism in the service alley. Additionally, we studied a few prototypical configurations of the shielding layers in the vertical insert as well as on the top.

  10. Impedance calculation for ferrite inserts

    SciTech Connect

    Breitzmann, S.C.; Lee, S.Y.; Ng, K.Y.; /Fermilab

    2005-01-01

    Passive ferrite inserts were used to compensate the space charge impedance in high intensity space charge dominated accelerators. They study the narrowband longitudinal impedance of these ferrite inserts. they find that the shunt impedance and the quality factor for ferrite inserts are inversely proportional to the imaginary part of the permeability of ferrite materials. They also provide a recipe for attaining a truly passive space charge impedance compensation and avoiding narrowband microwave instabilities.

  11. Mechanisms for Complex Chromosomal Insertions

    PubMed Central

    Szafranski, Przemyslaw; Akdemir, Zeynep Coban; Yuan, Bo; Cooper, Mitchell L.; Magriñá, Maria A.; Bacino, Carlos A.; Lalani, Seema R.; Patel, Ankita; Song, Rodger H.; Bi, Weimin; Cheung, Sau Wai; Carvalho, Claudia M. B.; Lupski, James R.

    2016-01-01

    Chromosomal insertions are genomic rearrangements with a chromosome segment inserted into a non-homologous chromosome or a non-adjacent locus on the same chromosome or the other homologue, constituting ~2% of nonrecurrent copy-number gains. Little is known about the molecular mechanisms of their formation. We identified 16 individuals with complex insertions among 56,000 individuals tested at Baylor Genetics using clinical array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH). Custom high-density aCGH was performed on 10 individuals with available DNA, and breakpoint junctions were fine-mapped at nucleotide resolution by long-range PCR and DNA sequencing in 6 individuals to glean insights into potential mechanisms of formation. We observed microhomologies and templated insertions at the breakpoint junctions, resembling the breakpoint junction signatures found in complex genomic rearrangements generated by replication-based mechanism(s) with iterative template switches. In addition, we analyzed 5 families with apparently balanced insertion in one parent detected by FISH analysis and found that 3 parents had additional small copy-number variants (CNVs) at one or both sides of the inserting fragments as well as at the inserted sites. We propose that replicative repair can result in interchromosomal complex insertions generated through chromothripsis-like chromoanasynthesis involving two or three chromosomes, and cause a significant fraction of apparently balanced insertions harboring small flanking CNVs. PMID:27880765

  12. Mechanisms for Complex Chromosomal Insertions.

    PubMed

    Gu, Shen; Szafranski, Przemyslaw; Akdemir, Zeynep Coban; Yuan, Bo; Cooper, Mitchell L; Magriñá, Maria A; Bacino, Carlos A; Lalani, Seema R; Breman, Amy M; Smith, Janice L; Patel, Ankita; Song, Rodger H; Bi, Weimin; Cheung, Sau Wai; Carvalho, Claudia M B; Stankiewicz, Paweł; Lupski, James R

    2016-11-01

    Chromosomal insertions are genomic rearrangements with a chromosome segment inserted into a non-homologous chromosome or a non-adjacent locus on the same chromosome or the other homologue, constituting ~2% of nonrecurrent copy-number gains. Little is known about the molecular mechanisms of their formation. We identified 16 individuals with complex insertions among 56,000 individuals tested at Baylor Genetics using clinical array comparative genomic hybridization (aCGH) and fluorescence in situ hybridization (FISH). Custom high-density aCGH was performed on 10 individuals with available DNA, and breakpoint junctions were fine-mapped at nucleotide resolution by long-range PCR and DNA sequencing in 6 individuals to glean insights into potential mechanisms of formation. We observed microhomologies and templated insertions at the breakpoint junctions, resembling the breakpoint junction signatures found in complex genomic rearrangements generated by replication-based mechanism(s) with iterative template switches. In addition, we analyzed 5 families with apparently balanced insertion in one parent detected by FISH analysis and found that 3 parents had additional small copy-number variants (CNVs) at one or both sides of the inserting fragments as well as at the inserted sites. We propose that replicative repair can result in interchromosomal complex insertions generated through chromothripsis-like chromoanasynthesis involving two or three chromosomes, and cause a significant fraction of apparently balanced insertions harboring small flanking CNVs.

  13. Insertion device and method for accurate and repeatable target insertion

    DOEpatents

    Gubeli, III, Joseph F.; Shinn, Michelle D.; Bevins, Michael E.; Dillon-Townes, Lawrence; Neil, George R.

    2017-07-04

    The present invention discloses a device and a method for inserting and positioning a target within a free electron laser, particle accelerator, or other such device that generates or utilizes a beam of energy or particles. The system includes a three-point registration mechanism that insures angular and translational accuracy and repeatability of positioning upon multiple insertions within the same structure.

  14. Small genomic insertions form enhancers that misregulate oncogenes

    PubMed Central

    Abraham, Brian J.; Hnisz, Denes; Weintraub, Abraham S.; Kwiatkowski, Nicholas; Li, Charles H.; Li, Zhaodong; Weichert-Leahey, Nina; Rahman, Sunniyat; Liu, Yu; Etchin, Julia; Li, Benshang; Shen, Shuhong; Lee, Tong Ihn; Zhang, Jinghui; Look, A. Thomas; Mansour, Marc R.; Young, Richard A.

    2017-01-01

    The non-coding regions of tumour cell genomes harbour a considerable fraction of total DNA sequence variation, but the functional contribution of these variants to tumorigenesis is ill-defined. Among these non-coding variants, somatic insertions are among the least well characterized due to challenges with interpreting short-read DNA sequences. Here, using a combination of Chip-seq to enrich enhancer DNA and a computational approach with multiple DNA alignment procedures, we identify enhancer-associated small insertion variants. Among the 102 tumour cell genomes we analyse, small insertions are frequently observed in enhancer DNA sequences near known oncogenes. Further study of one insertion, somatically acquired in primary leukaemia tumour genomes, reveals that it nucleates formation of an active enhancer that drives expression of the LMO2 oncogene. The approach described here to identify enhancer-associated small insertion variants provides a foundation for further study of these abnormalities across human cancers. PMID:28181482

  15. Comparison of intramenstrual IUD insertion with insertion following menstrual regulation.

    PubMed

    Otolorin, E O; Ladipo, O A

    1985-03-01

    To evaluate the use-effectiveness and safety of IUD insertion immediately after menstrual regulation (MR) for delayed menses, a Lippes Loop D (LLD) intrauterine device was inserted in each of 100 consecutive clients at the University College Hospital, Ibadan, immediately after menstrual regulation. Pertinent event rates after 12 months of use were compared with those of 100 consecutive women who had the LLD inserted during menstruation. The cumulative net expulsion rate after 12 months of use was 8% for the study group and 4% for the controls. The overall rate of removals was 15% for the study group and 16% for the control group. None of the observed differences was statistically significant. The continuation rates at 12 months were comparable for both groups (78% and 80%, respectively). There were no accidental pregnancies during the study period. The authors suggest that IUD insertion immediately after menstrual regulation is as effective and safe as intramenstrual insertion, provided prophylactic antibiotics are given.

  16. Sink Inserts for Flood Prevention

    NASA Astrophysics Data System (ADS)

    Fleming, Fraser F.; Bodnar, Daniel J.; Hardesty, David L.

    2004-09-01

    A simple, inexpensive insert is described for preventing flooding in lab sinks. The insert is essentially a tube with slots cut into the side that fits snugly into the drain outlet, preventing water buildup and providing additional drainage sites to avoid constriction by small lab items and paper towels.

  17. Multiple Distinct Targeting Signals in Integral Peroxisomal Membrane Proteins

    PubMed Central

    Jones, Jacob M.; Morrell, James C.; Gould, Stephen J.

    2001-01-01

    Peroxisomal proteins are synthesized on free polysomes and then transported from the cytoplasm to peroxisomes. This process is mediated by two short well-defined targeting signals in peroxisomal matrix proteins, but a well-defined targeting signal has not yet been described for peroxisomal membrane proteins (PMPs). One assumption in virtually all prior studies of PMP targeting is that a given protein contains one, and only one, distinct targeting signal. Here, we show that the metabolite transporter PMP34, an integral PMP, contains at least two nonoverlapping sets of targeting information, either of which is sufficient for insertion into the peroxisome membrane. We also show that another integral PMP, the peroxin PEX13, also contains two independent sets of peroxisomal targeting information. These results challenge a major assumption of most PMP targeting studies. In addition, we demonstrate that PEX19, a factor required for peroxisomal membrane biogenesis, interacts with the two minimal targeting regions of PMP34. Together, these results raise the interesting possibility that PMP import may require novel mechanisms to ensure the solubility of integral PMPs before their insertion in the peroxisome membrane, and that PEX19 may play a central role in this process. PMID:11402059

  18. Urinary proteomics can define distinct diagnostic inflammatory arthritis subgroups

    PubMed Central

    Siebert, Stefan; Porter, Duncan; Paterson, Caron; Hampson, Rosie; Gaya, Daniel; Latosinska, Agnieszka; Mischak, Harald; Schanstra, Joost; Mullen, William; McInnes, Iain

    2017-01-01

    Current diagnostic tests applied to inflammatory arthritis lack the necessary specificity to appropriately categorise patients. There is a need for novel approaches to classify patients with these conditions. Herein we explored whether urinary proteomic biomarkers specific for different forms of arthritis (rheumatoid arthritis (RA), psoriatic arthritis (PsA), osteoarthritis (OA)) or chronic inflammatory conditions (inflammatory bowel disease (IBD)) can be identified. Fifty subjects per group with RA, PsA, OA or IBD and 50 healthy controls were included in the study. Two-thirds of these populations were randomly selected to serve as a training set, while the remaining one-third was reserved for validation. Sequential comparison of one group to the other four enabled identification of multiple urinary peptides significantly associated with discrete pathological conditions. Classifiers for the five groups were developed and subsequently tested blind in the validation test set. Upon unblinding, the classifiers demonstrated excellent performance, with an area under the curve between 0.90 and 0.97 per group. Identification of the peptide markers pointed to dysregulation of collagen synthesis and inflammation, but also novel inflammatory markers. We conclude that urinary peptide signatures can reliably differentiate between chronic arthropathies and inflammatory conditions with discrete pathogenesis. PMID:28091549

  19. Optimal Distinctiveness Signals Membership Trust.

    PubMed

    Leonardelli, Geoffrey J; Loyd, Denise Lewin

    2016-07-01

    According to optimal distinctiveness theory, sufficiently small minority groups are associated with greater membership trust, even among members otherwise unknown, because the groups are seen as optimally distinctive. This article elaborates on the prediction's motivational and cognitive processes and tests whether sufficiently small minorities (defined by relative size; for example, 20%) are associated with greater membership trust relative to mere minorities (45%), and whether such trust is a function of optimal distinctiveness. Two experiments, examining observers' perceptions of minority and majority groups and using minimal groups and (in Experiment 2) a trust game, revealed greater membership trust in minorities than majorities. In Experiment 2, participants also preferred joining minorities over more powerful majorities. Both effects occurred only when minorities were 20% rather than 45%. In both studies, perceptions of optimal distinctiveness mediated effects. Discussion focuses on the value of relative size and optimal distinctiveness, and when membership trust manifests.

  20. Tool Removes Coil-Spring Thread Inserts

    NASA Technical Reports Server (NTRS)

    Collins, Gerald J., Jr.; Swenson, Gary J.; Mcclellan, J. Scott

    1991-01-01

    Tool removes coil-spring thread inserts from threaded holes. Threads into hole, pries insert loose, grips insert, then pulls insert to thread it out of hole. Effects essentially reverse of insertion process to ease removal and avoid further damage to threaded inner surface of hole.

  1. Non-insertional Achilles tendinopathy

    PubMed Central

    Pearce, Christopher J.; Tan, Audrey

    2016-01-01

    Non-insertional Achilles tendinopathy is a degenerative condition characterised by pain on activity. Eccentric stretching is the most effective treatment. Surgical treatment is reserved for recalcitrant cases. Minimally-invasive and tendinoscopic treatments are showing promising results. Cite this article: Pearce CJ, Tan A. Non-insertional Achilles tendinopathy. EFORT Open Rev 2016;1:383-390. DOI: 10.1302/2058-5241.1.160024. PMID:28461917

  2. The genomic landscape of polymorphic human nuclear mitochondrial insertions

    PubMed Central

    Dayama, Gargi; Emery, Sarah B.; Kidd, Jeffrey M.; Mills, Ryan E.

    2014-01-01

    The transfer of mitochondrial genetic material into the nuclear genomes of eukaryotes is a well-established phenomenon that has been previously limited to the study of static reference genomes. The recent advancement of high throughput sequencing has enabled an expanded exploration into the diversity of polymorphic nuclear mitochondrial insertions (NumtS) within human populations. We have developed an approach to discover and genotype novel Numt insertions using whole genome, paired-end sequencing data. We have applied this method to a thousand individuals in 20 populations from the 1000 Genomes Project and other datasets and identified 141 new sites of Numt insertions, extending our current knowledge of existing NumtS by almost 20%. We find that recent Numt insertions are derived from throughout the mitochondrial genome, including the D-loop, and have integration biases that differ in some respects from previous studies on older, fixed NumtS in the reference genome. We determined the complete inserted sequence for a subset of these events and have identified a number of nearly full-length mitochondrial genome insertions into nuclear chromosomes. We further define their age and origin of insertion and present an analysis of their potential impact to ongoing studies of mitochondrial heteroplasmy and disease. PMID:25348406

  3. Wireless cardiac action potential transmission with ultrasonically inserted silicon microprobes

    NASA Astrophysics Data System (ADS)

    Shen, C. J.; Ramkumar, A.; Lal, A.; Gilmour, R. F., Jr.

    2011-05-01

    This paper reports on the integration of ultrasonically inserted horn-shaped cardiac probes with wireless transmission of 3D cardiac action potential measurement for applications in ex vivo preparations such as monitoring the onset of ventricular fibrillation. Ultrasonically inserted silicon horn probes permit reduced penetration force during insertion, allowing silicon, a brittle material, to penetrate cardiac tissue. The probes also allow recording from multiple sites that are lithographically defined. An application-specific integrated circuit has been designed with a 40 dB amplifying stage and a frequency modulating oscillator at 95 MHz to wirelessly transmit the recorded action potentials. This ultrasonically inserted microprobe wireless system demonstrates the initial results in wireless monitoring of 3D action potential propagation, and the extraction of parameters of interest including the action potential duration and diastolic interval.

  4. Mammalian NUMT insertion is non-random

    PubMed Central

    Tsuji, Junko; Frith, Martin C.; Tomii, Kentaro; Horton, Paul

    2012-01-01

    It is well known that remnants of partial or whole copies of mitochondrial DNA, known as Nuclear MiTochondrial sequences (NUMTs), are found in nuclear genomes. Since whole genome sequences have become available, many bioinformatics studies have identified putative NUMTs and from those attempted to infer the factors involved in NUMT creation. These studies conclude that NUMTs represent randomly chosen regions of the mitochondrial genome. There is less consensus regarding the nuclear insertion sites of NUMTs — previous studies have discussed the possible role of retrotransposons, but some recent ones have reported no correlation or even anti-correlation between NUMT sites and retrotransposons. These studies have generally defined NUMT sites using BLAST with default parameters. We analyze a redefined set of human NUMTs, computed with a carefully considered protocol. We discover that the inferred insertion points of NUMTs have a strong tendency to have high-predicted DNA curvature, occur in experimentally defined open chromatin regions and often occur immediately adjacent to A + T oligomers. We also show clear evidence that their flanking regions are indeed rich in retrotransposons. Finally we show that parts of the mitochondrial genome D-loop are under-represented as a source of NUMTs in primate evolution. PMID:22761406

  5. Gene Insertion Patterns and Sites

    NASA Astrophysics Data System (ADS)

    Vain, Philippe; Thole, Vera

    During the past 25 years, the molecular analysis of transgene insertion patterns and sites in plants has greatly contributed to our understanding of the mechanisms underlying transgene integration, expression, and stability in the nuclear genome. Molecular characterization is also an essential step in the safety assessment of genetically modified crops. This chapter describes the standard experimental procedures used to analyze transgene insertion patterns and loci in cereals and grasses transformed using Agrobacterium tumefaciens or direct transfer of DNA. Methods and protocols enabling the determination of the number and configuration of transgenic loci via a combination of inheritance studies, polymerase chain reaction, and Southern analyses are presented. The complete characterization of transgenic inserts in plants is, however, a holistic process relying on a wide variety of experimental approaches. In this chapter, these additional approaches are not detailed but references to relevant bibliographic records are provided.

  6. MELFI Urine Sample First Insertion

    NASA Image and Video Library

    2009-04-11

    ISS019-E-005715 (11 April 2009) --- Astronaut Michael Barratt, Expedition 19/20 flight engineer, performs an insertion of urine samples into the Minus Eighty Degree Laboratory Freezer for ISS (MELFI) as part of the Nutritional Status Assessment (NUTRITION) study in the Japanese Kibo laboratory of the International Space Station.

  7. Inter-aural attenuation with insert earphones.

    PubMed

    Munro, Kevin J; Contractor, Alia

    2010-10-01

    The aim of the present study was to determine inter-aural attenuation (IA) values for pure tones and a broadband click obtained using an ER-3A insert earphone with a foam plug and with a customized hard acrylic earmould. Participants were 15 adults with a longstanding unilateral dead ear. IA was operationally defined as the difference between the good-ear and poorer-ear not-masked air conduction threshold. Minimum IA values for the foam earplug were 50 dB and 55 dB for pure tones and broadband click, respectively. Minimum IA values for the hard acrylic earmould were 45 dB and 50 dB for pure tones and broadband click, respectively.

  8. Population polymorphism of nuclear mitochondrial DNA insertions reveals widespread diploidy associated with loss of heterozygosity in Debaryomyces hansenii.

    PubMed

    Jacques, Noémie; Sacerdot, Christine; Derkaoui, Meriem; Dujon, Bernard; Ozier-Kalogeropoulos, Odile; Casaregola, Serge

    2010-03-01

    Debaryomyces hansenii, a yeast that participates in the elaboration of foodstuff, displays important genetic diversity. Our recent phylogenetic classification of this species led to the subdivision of the species into three distinct clades. D. hansenii harbors the highest number of nuclear mitochondrial DNA (NUMT) insertions known so far for hemiascomycetous yeasts. Here we assessed the intraspecific variability of the NUMTs in this species by testing their presence/absence first in 28 strains, with 21 loci previously detected in the completely sequenced strain CBS 767(T), and second in a larger panel of 77 strains, with 8 most informative loci. We were able for the first time to structure populations in D. hansenii, although we observed little NUMT insertion variability within the clades. We determined the chronology of the NUMT insertions, which turned out to correlate with the previously defined taxonomy and provided additional evidence that colonization of nuclear genomes by mitochondrial DNA is a dynamic process in yeast. In combination with flow cytometry experiments, the NUMT analysis revealed the existence of both haploid and diploid strains, the latter being heterozygous and resulting from at least four crosses among strains from the various clades. As in the diploid pathogen Candida albicans, to which D. hansenii is phylogenetically related, we observed a differential loss of heterozygosity in the diploid strains, which can explain some of the large genetic diversity found in D. hansenii over the years.

  9. Population Polymorphism of Nuclear Mitochondrial DNA Insertions Reveals Widespread Diploidy Associated with Loss of Heterozygosity in Debaryomyces hansenii ▿ †

    PubMed Central

    Jacques, Noémie; Sacerdot, Christine; Derkaoui, Meriem; Dujon, Bernard; Ozier-Kalogeropoulos, Odile; Casaregola, Serge

    2010-01-01

    Debaryomyces hansenii, a yeast that participates in the elaboration of foodstuff, displays important genetic diversity. Our recent phylogenetic classification of this species led to the subdivision of the species into three distinct clades. D. hansenii harbors the highest number of nuclear mitochondrial DNA (NUMT) insertions known so far for hemiascomycetous yeasts. Here we assessed the intraspecific variability of the NUMTs in this species by testing their presence/absence first in 28 strains, with 21 loci previously detected in the completely sequenced strain CBS 767T, and second in a larger panel of 77 strains, with 8 most informative loci. We were able for the first time to structure populations in D. hansenii, although we observed little NUMT insertion variability within the clades. We determined the chronology of the NUMT insertions, which turned out to correlate with the previously defined taxonomy and provided additional evidence that colonization of nuclear genomes by mitochondrial DNA is a dynamic process in yeast. In combination with flow cytometry experiments, the NUMT analysis revealed the existence of both haploid and diploid strains, the latter being heterozygous and resulting from at least four crosses among strains from the various clades. As in the diploid pathogen Candida albicans, to which D. hansenii is phylogenetically related, we observed a differential loss of heterozygosity in the diploid strains, which can explain some of the large genetic diversity found in D. hansenii over the years. PMID:20048048

  10. Insertion device calculations with mathematica

    SciTech Connect

    Carr, R.; Lidia, S.

    1995-02-01

    The design of accelerator insertion devices such as wigglers and undulators has usually been aided by numerical modeling on digital computers, using code in high level languages like Fortran. In the present era, there are higher level programming environments like IDL{reg_sign}, MatLab{reg_sign}, and Mathematica{reg_sign} in which these calculations may be performed by writing much less code, and in which standard mathematical techniques are very easily used. The authors present a suite of standard insertion device modeling routines in Mathematica to illustrate the new techniques. These routines include a simple way to generate magnetic fields using blocks of CSEM materials, trajectory solutions from the Lorentz force equations for given magnetic fields, Bessel function calculations of radiation for wigglers and undulators and general radiation calculations for undulators.

  11. Ultrasound guided spine needle insertion

    NASA Astrophysics Data System (ADS)

    Chen, Elvis C. S.; Mousavi, Parvin; Gill, Sean; Fichtinger, Gabor; Abolmaesumi, Purang

    2010-02-01

    An ultrasound (US) guided, CT augmented, spine needle insertion navigational system is introduced. The system consists of an electromagnetic (EM) sensor, an US machine, and a preoperative CT volume of the patient anatomy. Three-dimensional (3D) US volume is reconstructed intraoperatively from a set of two-dimensional (2D) freehand US slices, and is coregistered with the preoperative CT. This allows the preoperative CT volume to be used in the intraoperative clinical coordinate. The spatial relationship between the patient anatomy, surgical tools, and the US transducer are tracked using the EM sensor, and are displayed with respect to the CT volume. The pose of the US transducer is used to interpolate the CT volume, providing the physician with a 2D "x-ray vision" to guide the needle insertion. Many of the system software components are GPU-accelerated, allowing real-time performance of the guidance system in a clinical setting.

  12. Simulation of the optimal femoral insertion site in medial patellofemoral ligament reconstruction.

    PubMed

    Oka, Shinya; Matsushita, Takehiko; Kubo, Seiji; Matsumoto, Tomoyuki; Tajimi, Hiroyuki; Kurosaka, Masahiro; Kuroda, Ryosuke

    2014-10-01

    To develop and validate a new simulation system to predict the optimal femoral insertion site of the medial patellofemoral ligament (MPFL) using preprogrammed conditions of graft length change. A computed tomography scan was performed for constructing bone surface models of the patella and the femur. Lateral radiographs of the knee and axial radiographs of the patellofemoral joint at knee flexion were used for constructing a three-dimensional patellofemoral joint model by 3D-2D image matching at each knee flexion angle. To determine the optimal femoral insertion site, the following three conditions were devised: (1) MPFL behaves isometric from 0° to 60°, (2) MPFL is most taut at full extension, and (3) MPFL is slack at more than 60° of knee flexion. Every condition was applied to the femoral bone surface model, and the area that fulfilled all three conditions was defined as the optimal femoral insertion site of MPFL. Twenty knees of ten healthy volunteers were assessed to verify the simulation. Comparison between simulated optimal femoral insertion and anatomical insertion was done. The mean simulated optimal femoral insertion was close to the anatomical insertion site. There were no significant differences in the proximal-distal position and anterior-posterior position between the simulated insertion and the anatomical insertion sites. The system can be useful for predicting the optimal femoral insertion site as a part of a preoperative plan for MPFL reconstruction, and it may help surgeons to determine the optimal femoral insertion site during MPFL reconstruction.

  13. Inserting Agility in System Development

    DTIC Science & Technology

    2012-07-01

    Agile IT Acquisition, IT Box, Scrum Inserting Agility in System Development Matthew R. Kennedy and Lt Col Dan Ward, USAF With the fast-paced nature...1,700 individuals and 71 countries, found Scrum and eXtreme Programming to be the most widely followed method- ologies (VersionOne, 2007). Other...University http://www.dau.mil 259 Defense ARJ, July 2012, Vol. 19 No. 3 : 249–264 Scrum Scrum is a framework used for project management, which is

  14. Diversity of Shiga Toxin-Producing Escherichia coli (STEC) O26:H11 Strains Examined via stx Subtypes and Insertion Sites of Stx and EspK Bacteriophages

    PubMed Central

    Bonanno, Ludivine; Loukiadis, Estelle; Mariani-Kurkdjian, Patricia; Oswald, Eric; Garnier, Lucille; Michel, Valérie

    2015-01-01

    Shiga toxin-producing Escherichia coli (STEC) is a food-borne pathogen that may be responsible for severe human infections. Only a limited number of serotypes, including O26:H11, are involved in the majority of serious cases and outbreaks. The main virulence factors, Shiga toxins (Stx), are encoded by bacteriophages. Seventy-four STEC O26:H11 strains of various origins (including human, dairy, and cattle) were characterized for their stx subtypes and Stx phage chromosomal insertion sites. The majority of food and cattle strains possessed the stx1a subtype, while human strains carried mainly stx1a or stx2a. The wrbA and yehV genes were the main Stx phage insertion sites in STEC O26:H11, followed distantly by yecE and sbcB. Interestingly, the occurrence of Stx phages inserted in the yecE gene was low in dairy strains. In most of the 29 stx-negative E. coli O26:H11 strains also studied here, these bacterial insertion sites were vacant. Multilocus sequence typing of 20 stx-positive or stx-negative E. coli O26:H11 strains showed that they were distributed into two phylogenetic groups defined by sequence type 21 (ST21) and ST29. Finally, an EspK-carrying phage was found inserted in the ssrA gene in the majority of the STEC O26:H11 strains but in only a minority of the stx-negative E. coli O26:H11 strains. The differences in the stx subtypes and Stx phage insertion sites observed in STEC O26:H11 according to their origin might reflect that strains circulating in cattle and foods are clonally distinct from those isolated from human patients. PMID:25819955

  15. Field errors in hybrid insertion devices

    SciTech Connect

    Schlueter, R.D.

    1995-02-01

    Hybrid magnet theory as applied to the error analyses used in the design of Advanced Light Source (ALS) insertion devices is reviewed. Sources of field errors in hybrid insertion devices are discussed.

  16. Insert metering plates for gas turbine nozzles

    DOEpatents

    Burdgick, Steven S.; Itzel, Gary; Chopra, Sanjay; Abuaf, Nesim; Correia, Victor H.

    2004-05-11

    The invention comprises a metering plate which is assembled to an impingement insert for use in the nozzle of a gas turbine. The metering plate can have one or more metering holes and is used to balance the cooling flow within the nozzle. A metering plate with multiple holes reduces static pressure variations which result from the cooling airflow through the metering plate. The metering plate can be assembled to the insert before or after the insert is inserted into the nozzle.

  17. Ketamine improves nasogastric tube insertion.

    PubMed

    Nejati, Amir; Golshani, Keihan; Moradi Lakeh, Maziar; Khashayar, Patricia; Moharari, Reza Shariat

    2010-08-01

    Nasogastric (NG) intubation is one of the most common procedures performed in the emergency department (ED) and other hospital settings. The aim of this study was to compare the level of pain during NG tube insertion in groups receiving local ketamine plus water-soluble lubricating gel and water-soluble lubricating gel alone (the latter is the common practice in our hospital). It was hypothesised that ketamine has local anaesthetic effects in reducing the pain of NG tube insertion in the ED. This prospective double-blind randomised clinical trial was performed on alert haemodynamically stable subjects aged >18 years who required NG tube placement for diagnostic or therapeutic purposes in the ED of a teaching hospital during January and June 2008. The subjects were divided into two groups using randomised allocation software. The ketamine group received intranasal ketamine, while an equivalent volume of sterile water was instilled into the nasal cavity in the control group. The same amount of lubricating gel was used in both groups. The pain of NG tube placement was measured using a standard 100 mm visual analogue scale (VAS). The physician was asked to evaluate the difficulty of the procedure using a 5-point Likert scale. Seventy-two subjects were enrolled in the study (36 subjects in each group). There was a significant difference between the pain score of the ketamine and control groups (19.03+/-3.56 vs 33.33+/-5.31), while the difficulty score was not statistically different between the two groups (2.39+/-1.25 vs 2.78+/-1.56). Intranasal ketamine is an effective agent in reducing pain during NG tube insertion among patients without serious underlying illness.

  18. JT/LJT connector insert material evaluation

    SciTech Connect

    Baca, J.R.F.

    1991-10-01

    Different insert (insulator) materials are undergoing evaluation to replace the Fiberite E-3938 BE96 material currently used. Also being evaluated is the reconfiguration of the insert and metal shell-edge geometries for the purpose of reducing the alleged interference principally responsible for insert damage.

  19. Insert earphone depth and the occlusion effect.

    PubMed

    Dean, M S; Martin, F N

    2000-12-01

    Twenty individuals were tested to determine the occlusion effect caused by supraaural earphones and by insert earphones with shallow and deep insertion of its foam eartip. The bone-conduction oscillator was placed both on the forehead and the mastoid. It was concluded that using deeply inserted earphones is the most practical way in which to carry out clinical bone-conduction measurements.

  20. A robust protocol for efficient generation, and genomic characterization of insertional mutants of Chlamydomonas reinhardtii.

    PubMed

    Pollock, Steve V; Mukherjee, Bratati; Bajsa-Hirschel, Joanna; Machingura, Marylou C; Mukherjee, Ananya; Grossman, Arthur R; Moroney, James V

    2017-01-01

    Random insertional mutagenesis of Chlamydomonas reinhardtii using drug resistance cassettes has contributed to the generation of tens of thousands of transformants in dozens of labs around the world. In many instances these insertional mutants have helped elucidate the genetic basis of various physiological processes in this model organism. Unfortunately, the insertion sites of many interesting mutants are never defined due to experimental difficulties in establishing the location of the inserted cassette in the Chlamydomonas genome. It is fairly common that several months, or even years of work are conducted with no result. Here we describe a robust method to identify the location of the inserted DNA cassette in the Chlamydomonas genome. Insertional mutants were generated using a DNA cassette that confers paromomycin resistance. This protocol identified the cassette insertion site for greater than 80% of the transformants. In the majority of cases the insertion event was found to be simple, without large deletions of flanking genomic DNA. Multiple insertions were observed in less than 10% of recovered transformants. The method is quick, relatively inexpensive and does not require any special equipment beyond an electroporator. The protocol was tailored to ensure that the sequence of the Chlamydomonas genomic DNA flanking the random insertion is consistently obtained in a high proportion of transformants. A detailed protocol is presented to aid in the experimental design and implementation of mutant screens in Chlamydomonas.

  1. Analysis of inserts in prokaryote genomes

    NASA Astrophysics Data System (ADS)

    Cristea, Paul Dan; Tuduce, Rodica Aurora

    2008-02-01

    Nucleotide genomic signals satisfy regularities that reveal restrictions in the distribution of nucleotides and pairs of nucleotides along DNA sequences. Structurally, a chromosome appears to be more than a plain text, by satisfying symmetry constrains that evoke the rhythm and rhyme in poems. These regularities make it easy to identify exogenous inserts in the genomes of prokaryotes, because such inserts obey different regularities than the background sequence. The paper presents instances of inserts found in the genomes of Bacillus subtilis, Mycobacterium tuberculosis and other prokaryotes. Inserts of exogenous material are frequently accompanied by complementary inserts tending to restore the original constrains.

  2. Large scale screen for transposon insertions into cloned genes.

    PubMed Central

    Hamilton, B A; Palazzolo, M J; Chang, J H; VijayRaghavan, K; Mayeda, C A; Whitney, M A; Meyerowitz, E M

    1991-01-01

    We describe a method of screening for transposon insertions in or near Drosophila loci that correspond to cloned DNA sequences. We mobilize a modified P element transposon that carries a bacterial plasmid origin of replication and a drug-resistance marker. The genomic sequences flanking each transposon insertion site can then be rescued as a plasmid in Escherichia coli. Libraries of such plasmids, representing pools of transposon-mutagenized individuals, are used as hybridization probes against cloned sequences to determine whether a transposon has inserted next to a particular site in the genome. The number of loci that can be screened simultaneously by this procedure is quite large. We have screened an array of cDNA clones representing almost 700 distinct loci against libraries representing 760 mutagenized flies, and we obtained hybridization signals to 7 different cDNAs. Three of these events have been analyzed in detail and represent genuine insertions near genomic sequences that correspond to the cDNAs. Images PMID:1849274

  3. Defining needs, defining systems: a critical analysis.

    PubMed

    Dill, A

    1993-08-01

    This article examines the model of need assessment commonly used in social service programs for older adults. Whereas this model defines need as an individual attribute, remediable through programmatic intervention, an alternative formulation suggests that organizational imperatives shape the definition of client need while obscuring their own role in the production of this information. A case study and historical analysis assess the roots of this process and its consequences for clients, staff, and aging programs.

  4. Quench Module Insert (QMI) and the Diffusion Module Insert (DMI) Furnace Development

    NASA Technical Reports Server (NTRS)

    Crouch, Myscha; Carswell, William; Farmer, Jeff; Rose, Fred; Tidwell, Paul

    2000-01-01

    This paper presents, in viewgraph form, QMI (Quench Module Insert) and DMI (Diffusion Module Insert) furnace development. The topics include: 1) Furnace Module in Rack; 2) Quench Module Insert; 3) QMI in MSL Core; 4) Diffusion Module Insert; 5) QMI; and 6) QMI Development and Testing.

  5. Insertional Polymorphisms of Endogenous Feline Leukemia Viruses

    PubMed Central

    Roca, Alfred L.; Nash, William G.; Menninger, Joan C.; Murphy, William J.; O'Brien, Stephen J.

    2005-01-01

    The number, chromosomal distribution, and insertional polymorphisms of endogenous feline leukemia viruses (enFeLVs) were determined in four domestic cats (Burmese, Egyptian Mau, Persian, and nonbreed) using fluorescent in situ hybridization and radiation hybrid mapping. Twenty-nine distinct enFeLV loci were detected across 12 of the 18 autosomes. Each cat carried enFeLV at only 9 to 16 of the loci, and many loci were heterozygous for presence of the provirus. Thus, an average of 19 autosomal copies of enFeLV were present per cat diploid genome. Only five of the autosomal enFeLV sites were present in all four cats, and at only one autosomal locus, B4q15, was enFeLV present in both homologues of all four cats. A single enFeLV occurred in the X chromosome of the Burmese cat, while three to five enFeLV proviruses occurred in each Y chromosome. The X chromosome and nine autosomal enFeLV loci were telomeric, suggesting that ectopic recombination between nonhomologous subtelomeres may contribute to enFeLV distribution. Since endogenous FeLVs may affect the infectiousness or pathogenicity of exogenous FeLVs, genomic variation in enFeLVs represents a candidate for genetic influences on FeLV leukemogenesis in cats. PMID:15767400

  6. Mars Observer Orbit Insertion Briefing

    NASA Technical Reports Server (NTRS)

    1993-01-01

    Steve Wall is the host of this video entitled, "Return to the Red Planet". Live animation of the Mars Observer orbiting Mars is presented. Steve Wall explains the spacecraft insertion maneuver and also explains the purpose for the Mars Observer launch. Live coverage of the Cape Canaveral launch of the Mars Observer is also presented. Suzanne Dodd, Chief of the Mission Planning team describes the burn start and how the spacecraft will be captured by Mars' gravity. Glenn Cunningham, Mars Observer Project Manager, gives background information on the Mars Observer and describes the organizations behind the Mars Observer Spacecraft, such as the Deep Space Network, the Mission Operation Support Office, Science Investigators, the Flight Engineering Office, Operations Office, and the Ground Data System Office. Dr. William Piotrowski, Acting Director, Solar System Exploration Division, NASA, talks about the purpose of the Mars Pathfinder which is to develop the technology and systems for landing small science packages on Mars. Mr. Roger Gibbs, Former Mars Observer Spacecraft Systems Engineer, tells us how the Mars Observer was built and describes the structural elements on the Mars Observer. The 11-month cruise period for the spacecraft is given by Joseph Beerer, Manager of the Engineering office. The thrust for the Mars Orbit Insertion is described by Ronald Klemetson, Technical Manager, Propulsion Subsystem Jet Propulsion Laboratory (JPL). George Chen, Lead Engineer Attitude and Articulation Subsystem Spacecraft Team, explains the importance of the attitude control engines on the Spacecraft. Marvin Traxler, Manager of Tracking and Data Acquisition, describes how searching for a signal from the Mars Observer works. See NONP-NASA-VT-2000081555 for a continuation of this discussion with Marvin Traxler.

  7. Flexibility in targeting and insertion during bacterial membrane protein biogenesis

    SciTech Connect

    Bloois, Edwin van; Hagen-Jongman, Corinne M. ten; Luirink, Joen

    2007-10-26

    The biogenesis of Escherichia coli inner membrane proteins (IMPs) is assisted by targeting and insertion factors such as the signal recognition particle (SRP), the Sec-translocon and YidC with translocation of (large) periplasmic domains energized by SecA and the proton motive force (pmf). The use of these factors and forces is probably primarily determined by specific structural features of an IMP. To analyze these features we have engineered a set of model IMPs based on endogenous E. coli IMPs known to follow distinct targeting and insertion pathways. The modified model IMPs were analyzed for altered routing using an in vivo protease mapping approach. The data suggest a facultative use of different combinations of factors.

  8. Parametrically defined differential equations

    NASA Astrophysics Data System (ADS)

    Polyanin, A. D.; Zhurov, A. I.

    2017-01-01

    The paper deals with nonlinear ordinary differential equations defined parametrically by two relations. It proposes techniques to reduce such equations, of the first or second order, to standard systems of ordinary differential equations. It obtains the general solution to some classes of nonlinear parametrically defined ODEs dependent on arbitrary functions. It outlines procedures for the numerical solution of the Cauchy problem for parametrically defined differential equations.

  9. Peripherally Inserted Central Catheters and Hemodialysis Outcomes.

    PubMed

    McGill, Rita L; Ruthazer, Robin; Meyer, Klemens B; Miskulin, Dana C; Weiner, Daniel E

    2016-08-08

    Use of peripherally inserted central catheters has expanded rapidly, but the consequences for patients who eventually require hemodialysis are undefined. Our national, population-based analysis included 33,918 adult Medicare beneficiaries from the US Renal Data System who initiated hemodialysis with central venous catheters as their sole vascular access in 2010 and 2011. We used linked Medicare claims to identify peripherally inserted central catheter exposures and evaluate the associations of peripherally inserted central catheter placement with transition to working arteriovenous fistulas or grafts and patient survival using a Cox model with time-dependent variables. Among 33,918 individuals initiating hemodialysis with a catheter as sole access, 12.6% had received at least one peripherally inserted central catheter. Median follow-up was 404 days (interquartile range, 103-680 days). Among 6487 peripherally inserted central catheters placed, 3435 (53%) were placed within the 2 years before hemodialysis initiation, and 3052 (47%) were placed afterward. Multiple peripherally inserted central catheters were placed in 30% of patients exposed to peripherally inserted central catheters. Recipients of peripherally inserted central catheters were more likely to be women and have comorbid diagnoses and less likely to have received predialysis nephrology care. After adjustment for clinical and demographic factors, peripherally inserted central catheters placed before or after hemodialysis initiation were independently associated with lower likelihoods of transition to any working fistula or graft (hazard ratio for prehemodialysis peripherally inserted central catheter, 0.85; 95% confidence interval, 0.79 to 0.91; hazard ratio for posthemodialysis peripherally inserted central catheter, 0.81; 95% confidence interval, 0.73 to 0.89). Peripherally inserted central catheter placement was common and associated with adverse vascular access outcomes. Recognition of potential long

  10. Local palmitoylation cycles define activity-regulated postsynaptic subdomains

    PubMed Central

    Fukata, Yuko; Dimitrov, Ariane; Boncompain, Gaelle; Vielemeyer, Ole

    2013-01-01

    Distinct PSD-95 clusters are primary landmarks of postsynaptic densities (PSDs), which are specialized membrane regions for synapses. However, the mechanism that defines the locations of PSD-95 clusters and whether or how they are reorganized inside individual dendritic spines remains controversial. Because palmitoylation regulates PSD-95 membrane targeting, we combined a conformation-specific recombinant antibody against palmitoylated PSD-95 with live-cell super-resolution imaging and discovered subsynaptic nanodomains composed of palmitoylated PSD-95 that serve as elementary units of the PSD. PSD-95 in nanodomains underwent continuous de/repalmitoylation cycles driven by local palmitoylating activity, ensuring the maintenance of compartmentalized PSD-95 clusters within individual spines. Plasma membrane targeting of DHHC2 palmitoyltransferase rapidly recruited PSD-95 to the plasma membrane and proved essential for postsynaptic nanodomain formation. Furthermore, changes in synaptic activity rapidly reorganized PSD-95 nano-architecture through plasma membrane–inserted DHHC2. Thus, the first genetically encoded antibody sensitive to palmitoylation reveals an instructive role of local palmitoylation machinery in creating activity-responsive PSD-95 nanodomains, contributing to the PSD (re)organization. PMID:23836932

  11. Analysis of HIV-2 Vpx by modeling and insertional mutagenesis

    SciTech Connect

    Mahnke, Lisa A. . E-mail: lmahnke@im.wustl.edu; Belshan, Michael; Ratner, Lee . E-mail: lratner@im.wustl.edu

    2006-04-25

    Vpx facilitates HIV-2 nuclear localization by a poorly understood mechanism. We have compared Vpx to an NMR structure HIV-1 Vpr in a central helical domain and probed regions of Vpx by insertional mutagenesis. A predicted loop between helices two and three appears to be unique, overlapping with a known novel nuclear localization signal. Overall, Vpx was found to be surprisingly flexible, tolerating a series of large insertions. We found that insertion within the polyproline-containing C-terminus destabilizes nuclear localization, whereas mutating a second helix in the central domain disrupts viral packaging. Other insertional mutants in the predicted loop and in a linker region between the central domain and the C-terminus may be useful as sites of intramolecular tags as they could be packaged adequately and retained preintegration complex associated integration activity in a serum starvation assay. An unexpected result was found within a previously defined nuclear localization motif near aa 71. This mutant retained robust nuclear localization in a GFP fusion assay and was competent for preintegration complex associated nuclear import. In summary, we have modeled helical content in Vpx and assessed potential sites of intramolecular tags which may prove useful for protein-protein interactions studies.

  12. Sequential cooling insert for turbine stator vane

    DOEpatents

    Jones, Russel B

    2017-04-04

    A sequential flow cooling insert for a turbine stator vane of a small gas turbine engine, where the impingement cooling insert is formed as a single piece from a metal additive manufacturing process such as 3D metal printing, and where the insert includes a plurality of rows of radial extending impingement cooling air holes alternating with rows of radial extending return air holes on a pressure side wall, and where the insert includes a plurality of rows of chordwise extending second impingement cooling air holes on a suction side wall. The insert includes alternating rows of radial extending cooling air supply channels and return air channels that form a series of impingement cooling on the pressure side followed by the suction side of the insert.

  13. Insertion devices at the advanced photon source

    SciTech Connect

    Moog, E.R.

    1996-07-01

    The insertion devices being installed at the Advanced Photon Source cause the stored particle beam to wiggle, emitting x-rays with each wiggle. These x-rays combine to make an intense beam of radiation. Both wiggler and undulator types of insertion devices are being installed; the characteristics of the radiation produced by these two types of insertion devices are discussed, along with the reasons for those characteristics.

  14. Properties of a symmetric RHIC insertion

    SciTech Connect

    Lee, S.Y.

    1991-07-01

    This report evaluates the lattice functions of the symmetric insertion proposed by A.G. Ruggiero for the RHIC insertion. The crossing geometry, Inner and Outer matching sections, and chromatic properties are studied in detail. Some properties of the missing dipole dispersion correction scheme are also discussed. We found that the chromatic properties of the symmetric insertion is not better than the antisymmetric insertion. The problem is that the four family sextupole correction scheme seems not able to improve the chromatic distortion. Analytic understanding of the failure of the four family sextupole correction scheme will be very useful. 9 figs., 1 tab.

  15. Automatic Steering of Manually Inserted Needles

    PubMed Central

    Wu, Guofan; Li, Xiao; Lehocky, Craig A.; Riviere, Cameron N.

    2014-01-01

    Bevel-tipped flexible needles can be robotically steered to reach clinical targets along curvilinear paths in 3D. Manual needle insertion allows the clinician to control the insertion speed, ensuring patient safety. This paper presents a control law for automatic 3D steering of manually inserted flexible needles, enabling path-following control. A look-ahead proportional controller for position and orientation is presented. The look-ahead distance is a linear function of insertion speed. Simulations in a 3D brain-like environment demonstrate the performance of the proposed controller. Experimental results also show the feasibility of this technique in 2D and 3D environments. PMID:24752485

  16. Pericarditis following permanent pacemaker insertion.

    PubMed

    Levy, Yair; Shovman, Ora; Granit, Chava; Luria, David; Gurevitz, Osnat; Bar-Lev, David; Eldar, Michael; Shoenfeld, Yehuda; Glikson, Michael

    2004-10-01

    The appearance of pericarditis following insertion of a permanent pacemaker is not widely acknowledged in the literature. To describe our experience with pericarditis following 395 permanent pacemaker implantations over 2 years. We retrospectively reviewed the medical records of 395 consecutive patients in whom new pacing systems or pacemaker leads had been implanted over a 2 year period. We searched the records for pericarditis that developed within 1 month after pacemaker implantation according to the ICD-9 code. The incidence, clinical picture, response to treatment, and relationship to lead design and location were studied. Eight cases (2%) of pericarditis following implantation were detected. Clinical manifestations in all patients were similar to those of post-pericardiotomy syndrome and included chest pain (n = 7), friction rub (n = 1), fever (n = 2), fatigue (n = 2), pleural effusion (n = 2), new atrial fibrillation (n = 2), elevated erythrocyte sedimentation rate (n = 4), and echcardiographic evidence of pericardial effusion (n = 8). All affected patients had undergone active fixation (screw-in) lead implantation in the atrial position. The incidence of pericarditis with screw-in atrial leads was 3% compared to 0% in other cases (P < 0.05). Pericarditis is not uncommon following pacemaker implantation with active fixation atrial leads. Special attention should be paid to identifying pericardial complications following pacemaker implantation, especially when anticoagulant therapy is resumed or initiated. The use of passive fixation leads is likely to reduce the incidence of pericarditis but this issue should be further investigated.

  17. Defining Overweight and Obesity

    MedlinePlus

    ... this? Submit Button Our Division About Us Nutrition Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Defining Adult Overweight and Obesity Recommend on Facebook ...

  18. Multipurpose Transposon-Insertion Libraries in Yeast.

    PubMed

    Kumar, Anuj

    2016-06-01

    Libraries of transposon-insertion alleles constitute powerful and versatile tools for large-scale analysis of yeast gene function. Transposon-insertion libraries are constructed most simply through mutagenesis of a plasmid-based genomic DNA library; modification of the mutagenizing transposon by incorporation of yeast selectable markers, recombination sites, and an epitope tag enables the application of insertion alleles for phenotypic screening and protein localization. In particular, yeast genomic DNA libraries have been mutagenized with modified bacterial transposons carrying the URA3 marker, lox recombination sites, and sequence encoding multiple copies of the hemagglutinin (HA) epitope. Mutagenesis with these transposons has yielded a large resource of insertion alleles affecting nearly 4000 yeast genes in total. Through well-established protocols, these insertion libraries can be introduced into the desired strain backgrounds and the resulting insertional mutants can be screened or systematically analyzed. Relative to alternative methods of UV irradiation or chemical mutagenesis, transposon-insertion alleles can be easily identified by PCR-based approaches or high-throughput sequencing. Transposon-insertion libraries also provide a cost-effective alternative to targeted deletion approaches, although, in contrast to start-codon to stop-codon deletions, insertion alleles might not represent true null-mutants. For protein-localization studies, transposon-insertion alleles can provide encoded epitope tags in-frame with internal codons; in many cases, these transposon-encoded epitope tags can provide a more accurate localization for proteins in which terminal sequences are crucial for intracellular targeting. Thus, overall, transposon-insertion libraries can be used quickly and economically and have a particular utility in screening for desired phenotypes and localization patterns in nonstandard genetic backgrounds. © 2016 Cold Spring Harbor Laboratory Press.

  19. Anaerobically Grown Escherichia coli Has an Enhanced Mutation Rate and Distinct Mutational Spectra

    PubMed Central

    Shewaramani, Sonal; Finn, Thomas J.; Kassen, Rees; Rainey, Paul B.

    2017-01-01

    Oxidative stress is a major cause of mutation but little is known about how growth in the absence of oxygen impacts the rate and spectrum of mutations. We employed long-term mutation accumulation experiments to directly measure the rates and spectra of spontaneous mutation events in Escherichia coli populations propagated under aerobic and anaerobic conditions. To detect mutations, whole genome sequencing was coupled with methods of analysis sufficient to identify a broad range of mutational classes, including structural variants (SVs) generated by movement of repetitive elements. The anaerobically grown populations displayed a mutation rate nearly twice that of the aerobic populations, showed distinct asymmetric mutational strand biases, and greater insertion element activity. Consistent with mutation rate and spectra observations, genes for transposition and recombination repair associated with SVs were up-regulated during anaerobic growth. Together, these results define differences in mutational spectra affecting the evolution of facultative anaerobes. PMID:28103245

  20. [Cloning and insertion mutagenesis of DNA fragment coding for the luminescent system of Photobacterium leiognathi].

    PubMed

    Ptitsyn, L R; Gurevich, V B; Barsanova, T G; Shenderov, A N; Khaĭkinson, M Ia

    1988-10-01

    Fragments of DNA, obtained from the luminescent bacterium Photobacterium leiognathi and inserted into the plasmid pBR322, were found to code for the luminescence expressed in E. coli cells. The genetic functions necessary for light production in E. coli are localized on a DNA fragment of about 7 kbp. The insertion mutagenesis was used to define the luminescence functions encoded by the hybrid plasmid.

  1. Structure-Function Studies of Escherichia coli RpoH (σ32) by In Vitro Linker Insertion Mutagenesis

    PubMed Central

    Narberhaus, Franz; Balsiger, Sylvia

    2003-01-01

    The sigma factor RpoH (σ32) is the key regulator of the heat shock response in Escherichia coli. Many structural and functional properties of the sigma factor are poorly understood. To gain further insight into RpoH regions that are either important or dispensable for its cellular activity, we generated a collection of tetrapeptide insertion variants by a recently established in vitro linker insertion mutagenesis technique. Thirty-one distinct insertions were obtained, and their sigma factor activity was analyzed by using a groE-lacZ reporter fusion in an rpoH-negative background. Our study provides a map of permissive sites which tolerate linker insertions and of functionally important regions at which a linker insertion impairs sigma factor activity. Selected linker insertion mutants will be discussed in the light of known sigma factor properties and in relation to a modeled structure of an RpoH fragment containing region 2. PMID:12700252

  2. Structure-function studies of Escherichia coli RpoH (sigma32) by in vitro linker insertion mutagenesis.

    PubMed

    Narberhaus, Franz; Balsiger, Sylvia

    2003-05-01

    The sigma factor RpoH (sigma(32)) is the key regulator of the heat shock response in Escherichia coli. Many structural and functional properties of the sigma factor are poorly understood. To gain further insight into RpoH regions that are either important or dispensable for its cellular activity, we generated a collection of tetrapeptide insertion variants by a recently established in vitro linker insertion mutagenesis technique. Thirty-one distinct insertions were obtained, and their sigma factor activity was analyzed by using a groE-lacZ reporter fusion in an rpoH-negative background. Our study provides a map of permissive sites which tolerate linker insertions and of functionally important regions at which a linker insertion impairs sigma factor activity. Selected linker insertion mutants will be discussed in the light of known sigma factor properties and in relation to a modeled structure of an RpoH fragment containing region 2.

  3. Intradermal normal saline solution, self-selected music, and insertion difficulty effects on intravenous insertion pain.

    PubMed

    Jacobson, A F

    1999-01-01

    To examine the effect of listening to self-selected music versus an intradermal injection of normal saline solution on the intensity and distress of intravenous (IV) catheter insertion pain. Prospective, randomized, controlled study. Inpatient and outpatient units in 2 university-affiliated southwestern medical centers. One hundred ten adult inpatients and outpatients undergoing IV therapy. Pain intensity, pain distress, and IV insertion difficulty visual analog scales. Patients were randomly assigned to receive an intradermal injection of normal saline solution, listen with headphones to self-selected music, or be in a control group for IV insertion. A MANOVA revealed no statistically significant multivariate or univariate differences in pain by treatment group, but significantly higher pain distress scores with failed IV insertions. The pain intensity and distress scores were significantly higher in the saline solution group when compared with the music and control groups combined. Insertion difficulty was significantly positively correlated with pain intensity and distress for the entire sample, with weak, nonsignificant correlations in the music group. Intradermal unpreserved saline solution contributes to greater pain intensity and distress, greater insertion difficulty, and a higher failure rate than the use of music or routine IV insertion. Listening to preferred music attenuates the effect of insertion difficulty on IV insertion pain. Intravenous insertion attempts were unsuccessful in more than one third of the subjects, resulting in higher pain distress scores. Further research is needed on interventions to reduce IV insertion pain and on factors contributing to IV insertion failure.

  4. Defining Risk Drinking

    PubMed Central

    Dawson, Deborah A.

    2011-01-01

    Many efforts to prevent alcohol-related harm are aimed at reducing risk drinking. This article outlines the many conceptual and methodological challenges to defining risk drinking. It summarizes recent evidence regarding associations of various aspects of alcohol consumption with chronic and acute alcohol-related harms, including mortality, morbidity, injury, and alcohol use disorders, and summarizes the study designs most appropriate to defining risk thresholds for these types of harm. In addition, it presents an international overview of low-risk drinking guidelines from more than 20 countries, illustrating the wide range of interpretations of the scientific evidence related to risk drinking. This article also explores the impact of drink size on defining risk drinking and describes variation in what is considered to be a standard drink across populations. Actual and standard drink sizes differ in the United States, and this discrepancy affects definitions of risk drinking and prevention efforts. PMID:22330212

  5. Central Solenoid Insert Technical Specification

    SciTech Connect

    Martovetsky, Nicolai N; Smirnov, Alexandre

    2011-09-01

    The US ITER Project Office (USIPO) is responsible for the ITER central solenoid (CS) contribution to the ITER project. The Central Solenoid Insert (CSI) project will allow ITER validation the appropriate lengths of the conductors to be used in the full-scale CS coils under relevant conditions. The ITER Program plans to build and test a CSI to verify the performance of the CS conductor. The CSI is a one-layer solenoid with an inner diameter of 1.48 m and a height of 4.45 m between electric terminal ends. The coil weight with the terminals is approximately 820 kg without insulation. The major goal of the CSI is to measure the temperature margin of the CS under the ITER direct current (DC) operating conditions, including determining sensitivity to load cycles. Performance of the joints, ramp rate sensitivity, and stability against thermal or electromagnetic disturbances, electrical insulation, losses, and instrumentation are addressed separately and therefore are not major goals in this project. However, losses and joint performance will be tested during the CSI testing campaign. The USIPO will build the CSI that will be tested at the Central Solenoid Model Coil (CSMC) Test Facility at the Japan Atomic Energy Agency (JAEA), Naka, Japan. The industrial vendors (the Suppliers) will report to the USIPO (the Company). All approvals to proceed will be issued by the Company, which in some cases, as specified in this document, will also require the approval of the ITER Organization. Responsibilities and obligations will be covered by respective contracts between the USIPO, called Company interchangeably, and the industrial Prime Contractors, called Suppliers. Different stages of work may be performed by more than one Prime Contractor, as described in this specification. Technical requirements of the contract between the Company and the Prime Contractor will be covered by the Fabrication Specifications developed by the Prime Contractor based on this document and approved by

  6. Defining the Human Microbiome

    PubMed Central

    Ursell, Luke K; Metcalf, Jessica L; Parfrey, Laura Wegener; Knight, Rob

    2012-01-01

    Rapidly developing sequencing methods and analytical techniques are enhancing our ability to understand the human microbiome, and, indeed, how we define the microbiome and its constituents. In this review we highlight recent research that expands our ability to understand the human microbiome on different spatial and temporal scales, including daily timeseries datasets spanning months. Furthermore, we discuss emerging concepts related to defining operational taxonomic units, diversity indices, core versus transient microbiomes and the possibility of enterotypes. Additional advances in sequencing technology and in our understanding of the microbiome will provide exciting prospects for exploiting the microbiota for personalized medicine. PMID:22861806

  7. Transition Coordinators: Define Yourselves.

    ERIC Educational Resources Information Center

    Asselin, Susan B.; Todd-Allen, Mary; deFur, Sharon

    1998-01-01

    Describes a technique that was used successfully to identify the changing roles and responsibilities of special educators as transition coordinators. The Developing a Curriculum (DACUM) model uses people who are currently working in the occupation to define job responsibilities. The duties of a transition coordinator are identified. (CR)

  8. Defining Effective Teaching

    ERIC Educational Resources Information Center

    Layne, L.

    2012-01-01

    The author looks at the meaning of specific terminology commonly used in student surveys: "effective teaching." The research seeks to determine if there is a difference in how "effective teaching" is defined by those taking student surveys and those interpreting the results. To investigate this difference, a sample group of professors and students…

  9. Defining Mathematical Giftedness

    ERIC Educational Resources Information Center

    Parish, Linda

    2014-01-01

    This theoretical paper outlines the process of defining "mathematical giftedness" for a present study on how primary school teaching shapes the mindsets of children who are mathematically gifted. Mathematical giftedness is not a badge of honour or some special value attributed to a child who has achieved something exceptional.…

  10. On Defining Mass

    ERIC Educational Resources Information Center

    Hecht, Eugene

    2011-01-01

    Though central to any pedagogical development of physics, the concept of mass is still not well understood. Properly defining mass has proven to be far more daunting than contemporary textbooks would have us believe. And yet today the origin of mass is one of the most aggressively pursued areas of research in all of physics. Much of the excitement…

  11. Defining Supports Geometry

    ERIC Educational Resources Information Center

    Stephan, Michelle L.; McManus, George E.; Dickey, Ashley L.; Arb, Maxwell S.

    2012-01-01

    The process of developing definitions is underemphasized in most mathematics instruction. Investing time in constructing meaning is well worth the return in terms of the knowledge it imparts. In this article, the authors present a third approach to "defining," called "constructive." It involves modifying students' previous understanding of a term…

  12. On Defining Mass

    ERIC Educational Resources Information Center

    Hecht, Eugene

    2011-01-01

    Though central to any pedagogical development of physics, the concept of mass is still not well understood. Properly defining mass has proven to be far more daunting than contemporary textbooks would have us believe. And yet today the origin of mass is one of the most aggressively pursued areas of research in all of physics. Much of the excitement…

  13. Defining the Language Arts.

    ERIC Educational Resources Information Center

    Barth, Patte, Ed.

    1994-01-01

    This issue of "Basic Education" presents articles that discuss, respectively, defining the language arts, an agenda for English, the benefits of two languages, a new teacher (presently teaching English in a foreign country) looking ahead, and the Shaker Fellowships awarded by the school district in Shaker Heights, Ohio. Articles in the…

  14. Defined by Limitations

    ERIC Educational Resources Information Center

    Arriola, Sonya; Murphy, Katy

    2010-01-01

    Undocumented students are a population defined by limitations. Their lack of legal residency and any supporting paperwork (e.g., Social Security number, government issued identification) renders them essentially invisible to the American and state governments. They cannot legally work. In many states, they cannot legally drive. After the age of…

  15. Defining in Classroom Activities.

    ERIC Educational Resources Information Center

    Mariotti, Maria Alessandra; Fischbein, Efraim

    1997-01-01

    Discusses some aspects of the defining process in geometrical context in the reference frame of the theory of "figural concepts." Presents analysis of some examples taken from a teaching experiment at the sixth-grade level. Contains 30 references. (Author/ASK)

  16. IUD insertion immediately after incomplete abortion.

    PubMed

    Goldsmith, A; Goldberg, R; Eyzaguirre, H; Lizana, L

    1972-04-01

    All women who were admitted to the Felix Bulnes Hospital, Santiaog, Chile, for incomplete abortion between July 1968 and June 1969 were given instruction in family planning and contraceptive services. A total of 584 women chose to have an IUD insertion. Although all the women thought they had received an IUD, 1 group had a Lippes loop D inserted immediately after curettage and the other group had no insertion. The attending doctor had no prior knowledge as to which women were to receive the device nor did the doctor at the follow-up know until after the physical exam had taken place. 30 days after discharge from the hospital, the women returned from check-up and follow-up. At this time the women who had not received an IUD were given an insertion. Differences between the group with insertion and the one without were significant only for the interval between curettage and first menses and for the quantity of flow in relation to previous menstruation. The difference between the 2 groups for duration of menstrual flow was of borderline significance at the .05 significance level. It is concluded from the study that in the absence of psychologi cal bias of the patient to the IUD insertion, and possibly bias in its use by the doctor, there are no serious complications in the first month following immediate postabortal IUD insertion even where the abortion was a septic incomplete one.

  17. Reversible Alkene Insertion into the Pd–N Bond of Pd(II)-Sulfonamidates and Implications for Catalytic Amidation Reactions

    PubMed Central

    White, Paul B.; Stahl, Shannon S.

    2011-01-01

    Alkene insertion into Pd–N bonds is a key step in Pd-catalyzed oxidative amidation of alkenes. A series of well-defined Pd(II)-sulfonamidate complexes have been prepared and shown to react via insertion of a tethered alkene. The Pd–amidate and resulting Pd–alkyl species have been crystallographically characterized. The alkene insertion reaction is found to be reversible, but complete conversion to oxidative amination products is observed in the presence of O2. Electronic-effect studies reveal that alkene insertion into the Pd–N bond is favored kinetically and thermodynamically with electron-rich amidates. PMID:22007610

  18. Reversible alkene insertion into the Pd-N bond of Pd(II)-sulfonamidates and implications for catalytic amidation reactions.

    PubMed

    White, Paul B; Stahl, Shannon S

    2011-11-23

    Alkene insertion into Pd-N bonds is a key step in Pd-catalyzed oxidative amidation of alkenes. A series of well-defined Pd(II)-sulfonamidate complexes have been prepared and shown to react via insertion of a tethered alkene. The Pd-amidate and resulting Pd-alkyl species have been crystallographically characterized. The alkene insertion reaction is found to be reversible, but complete conversion to oxidative amination products is observed in the presence of O(2). Electronic-effect studies reveal that alkene insertion into the Pd-N bond is favored kinetically and thermodynamically with electron-rich amidates.

  19. Assessment of heat generation during implant insertion.

    PubMed

    Sumer, Mahmut; Keskiner, Ilker; Mercan, Ugur; Misir, Ferhat; Cankaya, Soner

    2014-09-01

    Many studies have investigated the heat generated during implant preparation, but data are needed to better predict heat generation during implant insertion. The purpose of this study was to measure the heat generated during insertion of an implant at speeds of 30, 50, and 100 rpm, and with manual insertion. Sixty-four uniform fresh bovine femoral cortical bone specimens were used. After the cortical bone was drilled, 3 different implant insertion speeds and the manual insertion of the implant were evaluated for 2 different implant diameters. The temperature was measured with 2 Teflon-insulated, type K thermocouples. Data were analyzed by 2-way ANOVA, and the Tukey honestly significant difference test (α=.05). The highest thermal change for 4.1-mm-diameter implants was found at a speed of 100 rpm (9.81°C ±2.29°C), and the lowest thermal change was 3.69°C ±0.85°C at a speed of 30 rpm. A statistically significant difference was found between 100 rpm and the other 3 insertion procedures. The highest thermal change for a 4.8-mm-diameter implant was found at a speed of 100 rpm (8.79°C ±1.53°C), and the lowest thermal change was 4.48°C ±0.85°C at a speed of 30 rpm. No statistical difference was observed with manual, 30 rpm, and 50 rpm; however, a statistically significant difference was found between 100 rpm and the other 3 insertion procedures. Manual implant insertion and at speeds of 30 rpm and 50 rpm generated lower heat compared with insertion at 100 rpm. Copyright © 2014 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

  20. Sequential cooling insert for turbine stator vane

    SciTech Connect

    Jones, Russell B; Krueger, Judson J; Plank, William L

    2014-04-01

    A sequential impingement cooling insert for a turbine stator vane that forms a double impingement for the pressure and suction sides of the vane or a triple impingement. The insert is formed from a sheet metal formed in a zigzag shape that forms a series of alternating impingement cooling channels with return air channels, where pressure side and suction side impingement cooling plates are secured over the zigzag shaped main piece. Another embodiment includes the insert formed from one or two blocks of material in which the impingement channels and return air channels are machined into each block.

  1. Sequential cooling insert for turbine stator vane

    SciTech Connect

    Jones, Russel B; Krueger, Judson J; Plank, William L

    2014-11-04

    A sequential impingement cooling insert for a turbine stator vane that forms a double impingement for the pressure and suction sides of the vane or a triple impingement. The insert is formed from a sheet metal formed in a zigzag shape that forms a series of alternating impingement cooling channels with return air channels, where pressure side and suction side impingement cooling plates are secured over the zigzag shaped main piece. Another embodiment includes the insert formed from one or two blocks of material in which the impingement channels and return air channels are machined into each block.

  2. Elliptically polarizing adjustable phase insertion device

    DOEpatents

    Carr, Roger

    1995-01-01

    An insertion device for extracting polarized electromagnetic energy from a beam of particles is disclosed. The insertion device includes four linear arrays of magnets which are aligned with the particle beam. The magnetic field strength to which the particles are subjected is adjusted by altering the relative alignment of the arrays in a direction parallel to that of the particle beam. Both the energy and polarization of the extracted energy may be varied by moving the relevant arrays parallel to the beam direction. The present invention requires a substantially simpler and more economical superstructure than insertion devices in which the magnetic field strength is altered by changing the gap between arrays of magnets.

  3. Arthroscopic classification of posterior labrum glenoid insertion.

    PubMed

    Nourissat, G; Radier, C; Aim, F; Lacoste, S

    2014-04-01

    We performed a prospective arthroscopic study to explore the variability of the posterior labrum glenoid insertion. We aimed to classify the insertions and to explore whether these insertions can be identified by pre-operative arthro-CT scan. From January to December 2011, 86 patients were prospectively included in the current study. During arthroscopy, anterior labrum was evaluated and posterior labrum was assessed in 3 different locations: superior, medial, and inferior. For each segment, the labrum was considered normally inserted (directly to the glenoid cartilage), medialized (inserted at the posterior part of the glenoid bone, without direct contact with the cartilage), torn (macroscopic degenerative changes, tears, fragments) or absent (agenesis). Imaging was analyzed segment by segment by an experienced osteoarticular radiologist, using the same classification. Four types of posterior labrum insertions were identified. Type 1, 60% of the cases, corresponded to a posterior labrum totally inserted in the glenoid, with direct contact with the cartilage. Type 2, 20% of the cases, represented medialized insertion of the superior segment. Type 3, 15% of the cases, represented an associated medialization of the superior and medial segment of the posterior labrum. Type 4 is a medialized insertion of the all-posterior labrum. Fifty-six shoulders were used for arthro-CT and arthroscopy correlation: for the superior segment (n=22/56), the sensitivity of arthro-CT to identify an abnormal insertion when the labrum is medialized was 68.18%, specificity 70.59%, positive predictive value (PPV) 60%, and negative predictive value (NPV) 77.42%. For the medial segment (n=16/56), the sensitivity of arthro-CT to identify an abnormal insertion when the labrum is medialized was 81.25%, specificity 57.50%, PPV 43.33% and NPV 88.46%. For the inferior segment (n=5/56), the sensitivity was 100%, specificity 47.60%, PPV 15.63% and NPV 100%. The current study points out the high

  4. Insertion Profiles of 4 Headless Compression Screws

    PubMed Central

    Hart, Adam; Harvey, Edward J.; Lefebvre, Louis-Philippe; Barthelat, Francois; Rabiei, Reza; Martineau, Paul A.

    2013-01-01

    Purpose In practice, the surgeon must rely on screw position (insertion depth) and tactile feedback from the screwdriver (insertion torque) to gauge compression. In this study, we identified the relationship between interfragmentary compression and these 2 factors. Methods The Acutrak Standard, Acutrak Mini, Synthes 3.0, and Herbert-Whipple implants were tested using a polyurethane foam scaphoid model. A specialized testing jig simultaneously measured compression force, insertion torque, and insertion depth at half-screw-turn intervals until failure occurred. Results The peak compression occurs at an insertion depth of −3.1 mm, −2.8 mm, 0.9 mm, and 1.5 mm for the Acutrak Mini, Acutrak Standard, Herbert-Whipple, and Synthes screws respectively (insertion depth is positive when the screw is proud above the bone and negative when buried). The compression and insertion torque at a depth of −2 mm were found to be 113 ± 18 N and 0.348 ± 0.052 Nm for the Acutrak Standard, 104 ± 15 N and 0.175 ± 0.008 Nm for the Acutrak Mini, 78 ± 9 N and 0.245 ± 0.006 Nm for the Herbert-Whipple, and 67 ± 2N, 0.233 ± 0.010 Nm for the Synthes headless compression screws. Conclusions All 4 screws generated a sizable amount of compression (> 60 N) over a wide range of insertion depths. The compression at the commonly recommended insertion depth of −2 mm was not significantly different between screws; thus, implant selection should not be based on compression profile alone. Conically shaped screws (Acutrak) generated their peak compression when they were fully buried in the foam whereas the shanked screws (Synthes and Herbert-Whipple) reached peak compression before they were fully inserted. Because insertion torque correlated poorly with compression, surgeons should avoid using tactile judgment of torque as a proxy for compression. Clinical relevance Knowledge of the insertion profile may improve our understanding of the implants, provide a better basis for comparing screws

  5. Distinct functions for ERKs?

    PubMed Central

    Lloyd, Alison C

    2006-01-01

    The Ras/Raf/MEK/ERK signaling pathway is one of the best understood signal routes in cells. Recent studies add complexity to this cascade by indicating that the two ERK kinases, ERK1 (p44ERK1) and ERK2 (p42ERK2), may have distinct functions. PMID:16879721

  6. [Comparison of three different insertion techniques with LMA-Unique™ in adults: results of a randomized trial].

    PubMed

    Eglen, Merih; Kuvaki, Bahar; Günenç, Ferim; Ozbilgin, Sule; Küçükgüçlü, Semih; Polat, Ebru; Pekel, Emel

    The triple airway maneuver insertion technique allowed faster insertion of the LMA. This study compared three different insertion techniques of the laryngeal mask airway-Unique™. One hundred and eighty ASA I-II patients aged 18-65 years were included into the study. Patients were randomly allocated to the standard, rotational and triple airway maneuver (triple) group. In the standard group (n=60), the LMA (Laryngeal Mask Airway) was inserted with digital intraoral manipulation. In the triple group (n=60), the LMA was inserted with triple airway maneuver (mouth opening, head extension and jaw thrust). In the rotational group (n=60), LMA was inserted back-to-front, like a Guedel airway. Successful insertion at first attempt, time for successful insertion, fiber optic assessment, airway morbidity and hemodynamic responses were assessed. Successful insertion at the first attempt was 88.3% for the standard, 78.3% for the rotational and 88.3% for the triple group. Overall success rate (defined as successful insertion at first and second attempt) was 93% for the standard, 90% for the rotational and 95% for the triple group. Time for successful insertion was significantly shorter in the triple group (mean [range] 8.63 [5-19]s) compared with the standard (11.78 [6-24]s) and rotational group (11.57 [5-31]s). Fiber optic assessment, airway morbidity and hemodynamic responses were similar in all groups. Rotational and triple airway maneuver insertion techniques are acceptable alternatives. Triple airway maneuver technique shows higher overall success rates and allows shorter insertion time for LMA insertion and should therefore be kept in mind for emergent situations. Copyright © 2016 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

  7. Defining Dynamic Route Structure

    NASA Technical Reports Server (NTRS)

    Zelinski, Shannon; Jastrzebski, Michael

    2011-01-01

    This poster describes a method for defining route structure from flight tracks. Dynamically generated route structures could be useful in guiding dynamic airspace configuration and helping controllers retain situational awareness under dynamically changing traffic conditions. Individual merge and diverge intersections between pairs of flights are identified, clustered, and grouped into nodes of a route structure network. Links are placed between nodes to represent major traffic flows. A parametric analysis determined the algorithm input parameters producing route structures of current day flight plans that are closest to todays airway structure. These parameters are then used to define and analyze the dynamic route structure over the course of a day for current day flight paths. Route structures are also compared between current day flight paths and more user preferred paths such as great circle and weather avoidance routing.

  8. [To define internet addiction].

    PubMed

    Tonioni, Federico

    2013-01-01

    Internet addiction is a new behavioral disorder difficult to define, especially when referring to young teenagers who make great use of web-mediated relationships. It's necessary to separate the cases of overt dependency on those in which the abuse of internet seems to have a different value, offering the only way to achieve the possible relationship. Internet is mediating a new way of communicating and thinking, this may favor the onset of clinical phenomena intended to surprise.

  9. Defining and Diagnosing Sepsis.

    PubMed

    Scott, Michael C

    2017-02-01

    Sepsis is a heterogeneous clinical syndrome that encompasses infections of many different types and severity. Not surprisingly, it has confounded most attempts to apply a single definition, which has also limited the ability to develop a set of reliable diagnostic criteria. It is perhaps best defined as the different clinical syndromes produced by an immune response to infection that causes harm to the body beyond that of the local effects of the infection.

  10. Insertable fluid flow passage bridgepiece and method

    DOEpatents

    Jones, Daniel O.

    2000-01-01

    A fluid flow passage bridgepiece for insertion into an open-face fluid flow channel of a fluid flow plate is provided. The bridgepiece provides a sealed passage from a columnar fluid flow manifold to the flow channel, thereby preventing undesirable leakage into and out of the columnar fluid flow manifold. When deployed in the various fluid flow plates that are used in a Proton Exchange Membrane (PEM) fuel cell, bridgepieces of this invention prevent mixing of reactant gases, leakage of coolant or humidification water, and occlusion of the fluid flow channel by gasket material. The invention also provides a fluid flow plate assembly including an insertable bridgepiece, a fluid flow plate adapted for use with an insertable bridgepiece, and a method of manufacturing a fluid flow plate with an insertable fluid flow passage bridgepiece.

  11. Utility Bill Insert for Wastewater Services

    EPA Pesticide Factsheets

    Intended for use by wastewater and water supply utilities, one side of the utility bill insert has information for customers that discharge to sanitary sewer systems; the other side is for customers with septic systems.

  12. Clinical applicability of insert earphones for audiometry.

    PubMed

    Borton, T E; Nolen, B L; Luks, S B; Meline, N C

    1989-01-01

    Insert transducers for audiometry are available which may offer significant advantages over older 'standard' headphones. Clinicians have remained cautious in using such devices due to the paucity of experimental data demonstrating their comparability with more widely used devices. The purpose of this investigation was to compare and contrast pure-tone audiometric thresholds obtained using insert earphones with those measured utilizing conventional supra-aural transducers in normal and hearing-impaired subjects. A second purpose was to examine the differential effects on the hearing threshold level of two coupling systems for the insert device. There were no clinically significant differences among pure-tone thresholds measured with the three earphone/coupler arrangements for subjects with normal and impaired hearing. Advantages and limitations of insert earphones are discussed.

  13. The effects of insertion method and force on hand clearance envelopes for rubber hose insertion tasks.

    PubMed

    Grieshaber, D Christian; Armstrong, Thomas J; Chaffin, Don B; Keyserling, W Monroe; Ashton-Miller, James

    2009-04-01

    The aim of this study was to determine how hand space for manual insertion of flexible hoses is affected by insertion method and force. Adequate space is needed during assembly tasks in which workers join parts together with their hands. Hose installations are an example of such a task. Hand clearance envelopes for insertion tasks that involve cylindrical objects, such as a hose, are currently unavailable in the literature. Participants inserted a flexible 25-mm rubber hose onto a stationary flange using simulated methods similar to those observed in field studies of automotive assembly tasks. Markers placed on the back of the hand and wrists were used to measure postures during the insertion task. Hand clearance envelopes for high-force insertions were significantly larger across methods by an average of 15% for both male (p < .05) and female (p < .01) participants. Rocking insertions resulted in the largest hand clearance envelopes compared with other insertion methods. Rocking and twisting the hose resulted in mean increases in the cross-sectional area of the hand clearance envelopes of 35% and 24%, respectively, compared with the straight push. Differences were significant (p < .05) for male and female participants for both bead height conditions. Both required insertion force and method affect hand clearance envelopes during simulated insertions. These methods can be used by engineers to determine if there is adequate clearance for the hand to grip selected objects.

  14. Shrink-Fit Solderable Inserts Seal Hermetically

    NASA Technical Reports Server (NTRS)

    Croucher, William C.

    1992-01-01

    Shrink-fit stainless-steel insert in aluminum equipment housing allows electrical connectors to be replaced by soldering, without degrading hermeticity of housing or connector. Welding could destroy electrostatic-sensitive components and harm housing and internal cables. Steel insert avoids problems because connector soldered directly to it rather than welded to housing. Seals between flange and housing, and between connector and flange resistant to leaks, even after mechanical overloading and thermal shocking.

  15. Small Unit Space Transport and Insertion (SUSTAIN)

    DTIC Science & Technology

    2009-01-01

    Small Unit Space Transport and Insertion ( SUSTAIN ) Study prepared for: LTC Paul E. Damphousse, USMC National Security Space Office Chief of...failing to comply with a collection of information if it does not display a currently valid OMB control number. 1. REPORT DATE 2009 2. REPORT TYPE N/A...3. DATES COVERED - 4. TITLE AND SUBTITLE Small Unit Space Transport and Insertion ( SUSTAIN ) 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM

  16. Insert earphones for speech recognition testing.

    PubMed

    Martin, F N; Severance, G K; Thibodeau, L

    1991-01-01

    Performance-intensity functions for PB word lists were run on 19 normal-hearing subjects and 15 subjects with sensorineural hearing losses. Comparisons were made between standard supra-aural earphones (TDH-49P) and insert phones (ER-3A). Results showed that, at least for the higher sensation levels where word recognition tests are usually performed, the phones may be used interchangeably. Using insert earphones for word recognition tests can have several beneficial effects with respect to cross hearing and masking.

  17. Shrink-Fit Solderable Inserts Seal Hermetically

    NASA Technical Reports Server (NTRS)

    Croucher, William C.

    1992-01-01

    Shrink-fit stainless-steel insert in aluminum equipment housing allows electrical connectors to be replaced by soldering, without degrading hermeticity of housing or connector. Welding could destroy electrostatic-sensitive components and harm housing and internal cables. Steel insert avoids problems because connector soldered directly to it rather than welded to housing. Seals between flange and housing, and between connector and flange resistant to leaks, even after mechanical overloading and thermal shocking.

  18. Strength of inserts in titanium alloy machining

    NASA Astrophysics Data System (ADS)

    Kozlov, V.; Huang, Z.; Zhang, J.

    2016-04-01

    In this paper, a stressed state of a non-worn cutting wedge in a machined titanium alloy (Ti6Al2Mo2Cr) is analyzed. The distribution of contact loads on the face of a cutting tool was obtained experimentally with the use of a ‘split cutting tool’. Calculation of internal stresses in the indexable insert made from cemented carbide (WC8Co) was carried out with the help of ANSYS 14.0 software. Investigations showed that a small thickness of the cutting insert leads to extremely high compressive stresses near the cutting edge, stresses that exceed the ultimate compressive strength of cemented carbide. The face and the base of the insert experience high tensile stresses, which approach the ultimate tensile strength of cemented carbide and increase a probability of cutting insert destruction. If the thickness of the cutting insert is bigger than 5 mm, compressive stresses near the cutting edge decrease, and tensile stresses on the face and base decrease to zero. The dependences of the greatest normal and tangential stresses on thickness of the cutting insert were found. Abbreviation and symbols: m/s - meter per second (cutting speed v); mm/r - millimeter per revolution (feed rate f); MPa - mega Pascal (dimension of specific contact loads and stresses); γ - rake angle of the cutting tool [°] α - clearance angle of the sharp cutting tool [°].

  19. Z-2 Threaded Insert Design and Testing

    NASA Technical Reports Server (NTRS)

    Ross, Amy; Rhodes, Richard; Jones, Robert J.; Graziosi, David; Ferl, Jinny; Sweeny, Mitch; Scarborough, Stephen

    2016-01-01

    NASA's Z-2 prototype space suit contains several components fabricated from an advanced hybrid composite laminate consisting of IM10 carbon fiber and fiber glass. One requirement was to have removable, replaceable helicoil inserts to which other suit components would be fastened. An approach utilizing bonded in inserts with helicoils inside of them was implemented. During initial assembly, cracking sounds were heard followed by the lifting of one of the blind inserts out of its hole when the screws were torqued. A failure investigation was initiated to understand the mechanism of the failure. Ultimately, it was determined that the pre-tension caused by torqueing the fasteners is a much larger force than induced from the pressure loads of the suit which was not considered in the insert design. Bolt tension is determined by dividing the torque on the screw by a k value multiplied by the thread diameter of the bolt. The k value is a factor that accounts for friction in the system. A common value used for k for a non-lubricated screw is 0.2. The k value can go down by as much as 0.1 if the screw is lubricated which means for the same torque, a much larger tension could be placed on the bolt and insert. This paper summarizes the failure investigation that was performed to identify the root cause of the suit failure and details how the insert design was modified to resist a higher pull out tension.

  20. High-Pressure Trocar Insertion Technique

    PubMed Central

    Reich, Harry; Conti Ribeiro, Sergio; Rasmussen, Carsten; Rosenberg, Jay

    1999-01-01

    Background: The majority of laparoscopic complications occur at the time of Veress needle and trocar insertion. Although not very frequent, they increase the morbidity and mortality of both diagnostic and operative laparoscopic procedures. Alternative techniques of trocar insertion have been described but have not completely eliminated the risk of injury. Technique: After Veress needle insertion and establishment of pneumoperitoneum to 25 to 30 mm Hg, insertion of a short trocar is performed in the deepest part of the umbilicus without elevation of the anterior abdominal wall. The result is a parietal peritoneal puncture directly beneath the umbilicus. The high-pressure setting used during initial insertion of the trocar is lowered as soon as safe abdominal entry is documented. Experience: The trocar insertion technique described above was performed in 3041 procedures. No vascular injury occurred. There were two bowel perforations. No complications related to the increased intra-abdominal pressure were observed. Conclusion: The high-pressure abdominal entry technique has the advantage of reducing intra-abdominal trocar-related injuries without requiring additional instrumentation or additional training. PMID:10323169

  1. Rectal suppository: commonsense and mode of insertion.

    PubMed

    Abd-el-Maeboud, K H; el-Naggar, T; el-Hawi, E M; Mahmoud, S A; Abd-el-Hay, S

    1991-09-28

    Rectal suppository is a well-known form of medication and its use is increasing. The commonest shape is one with an apex (pointed end) tapering to a base (blunt end). Because of a general lack of information about mode of insertion, we asked 360 lay subjects (Egyptians and non-Egyptians) and 260 medical personnel (physicians, pharmacists, and nurses) by questionnaire which end they inserted foremost. Apart from 2 individuals, all subjects suggested insertion with the apex foremost. Commonsense was the most frequent basis for this practice (86.9% of lay subjects and 84.6% of medical personnel) followed by information from a relative, a friend, or medical personnel, or from study at medical school. Suppository insertion with the base or apex foremost was compared in 100 subjects (60 adults, 40 infants and children). Retention with the former method was more easily achieved in 98% of the cases, with no need to introduce a finger in the anal canal (1% vs 83%), and lower expulsion rate (0% vs 3%). The designer of the "torpedo-shaped" suppository suggested its insertion with apex foremost. Our data suggest that a suppository is better inserted with the base foremost. Reversed vermicular contractions or pressure gradient of the anal canal might press it inwards.

  2. afa-8 Gene cluster is carried by a pathogenicity island inserted into the tRNA(Phe) of human and bovine pathogenic Escherichia coli isolates.

    PubMed

    Lalioui, L; Le Bouguénec, C

    2001-02-01

    We recently described a new afimbrial adhesin, AfaE-VIII, produced by animal strains associated with diarrhea and septicemia and by human isolates associated with extraintestinal infections. Here, we report that the afa-8 operon, encoding AfaE-VIII adhesin, from the human blood isolate Escherichia coli AL862 is carried by a 61-kb genomic region with characteristics typical of a pathogenicity island (PAI), including a size larger than 10 kb, the presence of an integrase-encoding gene, the insertion into a tRNA locus (pheR), and the presence of a small direct repeat at each extremity. Moreover, the G+C content of the afa-8 operon (46.4%) is lower than that of the E. coli K-12/MG1655 chromosome (50.8%). Within this PAI, designated PAI I(AL862), we identified open reading frames able to code for products similar to proteins involved in sugar utilization. Four probes spanning these sequences hybridized with 74.3% of pathogenic afa-8-positive E. coli strains isolated from humans and animals, 25% of human pathogenic afa-8-negative E. coli strains, and only 8% of fecal strains (P = 0.05), indicating that these sequences are strongly associated with the afa-8 operon and that this genetic association may define a PAI widely distributed among human and animal afa-8-positive strains. One of the distinctive features of this study is that E. coli AL862 also carries another afa-8-containing PAI (PAI II(AL862)), which appeared to be similar in size and genetic organization to PAI I(AL862) and was inserted into the pheV gene. We investigated the insertion sites of afa-8-containing PAI in human and bovine pathogenic E. coli strains and found that this PAI preferentially inserted into the pheV gene.

  3. Defining functional dyspepsia.

    PubMed

    Mearin, Fermín; Calleja, José Luis

    2011-12-01

    Dyspepsia and functional dyspepsia represent a highly significant public health issue. A good definition of dyspepsia is key for helping us to better approach symptoms, decision making, and therapy indications.During the last few years many attempts were made at establishing a definition of dyspepsia. Results were little successful on most occasions, and clear discrepancies arose on whether symptoms should be associated with digestion, which types of symptoms were to be included, which anatomic location should symptoms have, etc.The Rome III Committee defined dyspepsia as "a symptom or set of symptoms that most physicians consider to originate from the gastroduodenal area", including the following: postprandial heaviness, early satiety, and epigastric pain or burning. Two new entities were defined: a) food-induced dyspeptic symptoms (postprandial distress syndrome); and b) epigastric pain (epigastric pain syndrome). These and other definitions have shown both strengths and weaknesses. At times they have been much too complex, at times much too simple; furthermore, they have commonly erred on the side of being inaccurate and impractical. On the other hand, some (the most recent ones) are difficult to translate into the Spanish language. In a meeting of gastroenterologists with a special interest in digestive functional disorders, the various aspects of dyspepsia definition were discussed and put to the vote, and the following conclusions were arrived at: dyspepsia is defined as a set of symptoms, either related or unrelated to food ingestion, localized on the upper half of the abdomen. They include: a) epigastric discomfort (as a category of severity) or pain; b) postprandial heaviness; and c) early satiety. Associated complaints include: nausea, belching, bloating, and epigastric burn (heartburn). All these must be scored according to severity and frequency. Furthermore, psychological factors may be involved in the origin of functional dyspepsia. On the other hand

  4. A stochastic evolution model for residue Insertion-Deletion Independent from Substitution.

    PubMed

    Lèbre, Sophie; Michel, Christian J

    2010-12-01

    We develop here a new class of stochastic models of gene evolution based on residue Insertion-Deletion Independent from Substitution (IDIS). Indeed, in contrast to all existing evolution models, insertions and deletions are modeled here by a concept in population dynamics. Therefore, they are not only independent from each other, but also independent from the substitution process. After a separate stochastic analysis of the substitution and the insertion-deletion processes, we obtain a matrix differential equation combining these two processes defining the IDIS model. By deriving a general solution, we give an analytical expression of the residue occurrence probability at evolution time t as a function of a substitution rate matrix, an insertion rate vector, a deletion rate and an initial residue probability vector. Various mathematical properties of the IDIS model in relation with time t are derived: time scale, time step, time inversion and sequence length. Particular expressions of the nucleotide occurrence probability at time t are given for classical substitution rate matrices in various biological contexts: equal insertion rate, insertion-deletion only and substitution only. All these expressions can be directly used for biological evolutionary applications. The IDIS model shows a strongly different stochastic behavior from the classical substitution only model when compared on a gene dataset. Indeed, by considering three processes of residue insertion, deletion and substitution independently from each other, it allows a more realistic representation of gene evolution and opens new directions and applications in this research field. Copyright © 2010 Elsevier Ltd. All rights reserved.

  5. High throughput fingerprint analysis of large-insert clones.

    PubMed

    Marra, M A; Kucaba, T A; Dietrich, N L; Green, E D; Brownstein, B; Wilson, R K; McDonald, K M; Hillier, L W; McPherson, J D; Waterston, R H

    1997-11-01

    As part of the Human Genome Project, the Washington University Genome Sequencing Center has commenced systematic sequencing of human chromsome 7. To organize and supply the effort, we have undertaken the construction of sequence-ready physical maps for defined chromosomal intervals. Map construction is a serial process composed of three main activities. First, candidate STS-positive large-insert PAC and BAC clones are identified. Next, these candidate clones are subjected to fingerprint analysis. Finally, the fingerprint data are used to assemble sequence-ready maps. The fingerprinting method we have devised is key to the success of the overall approach. We present here the details of the method and show that the fingerprints are of sufficient quality to permit the construction of megabase-size contigs in defined regions of the human genome. We anticipate that the high throughput and precision characteristic of our fingerprinting method will make it of general utility.

  6. Defining periodontal health

    PubMed Central

    2015-01-01

    Assessment of the periodontium has relied exclusively on a variety of physical measurements (e.g., attachment level, probing depth, bone loss, mobility, recession, degree of inflammation, etc.) in relation to various case definitions of periodontal disease. Periodontal health was often an afterthought and was simply defined as the absence of the signs and symptoms of a periodontal disease. Accordingly, these strict and sometimes disparate definitions of periodontal disease have resulted in an idealistic requirement of a pristine periodontium for periodontal health, which makes us all diseased in one way or another. Furthermore, the consequence of not having a realistic definition of health has resulted in potentially questionable recommendations. The aim of this manuscript was to assess the biological, environmental, sociological, economic, educational and psychological relationships that are germane to constructing a paradigm that defines periodontal health using a modified wellness model. The paradigm includes four cardinal characteristics, i.e., 1) a functional dentition, 2) the painless function of a dentition, 3) the stability of the periodontal attachment apparatus, and 4) the psychological and social well-being of the individual. Finally, strategies and policies that advocate periodontal health were appraised. I'm not sick but I'm not well, and it's a sin to live so well. Flagpole Sitta, Harvey Danger PMID:26390888

  7. Defined contribution health benefits.

    PubMed

    Fronstin, P

    2001-03-01

    This Issue Brief discusses the emerging issue of "defined contribution" (DC) health benefits. The term "defined contribution" is used to describe a wide variety of approaches to the provision of health benefits, all of which have in common a shift in the responsibility for payment and selection of health care services from employers to employees. DC health benefits often are mentioned in the context of enabling employers to control their outlay for health benefits by avoiding increases in health care costs. DC health benefits may also shift responsibility for choosing a health plan and the associated risks of choosing a plan from employers to employees. There are three primary reasons why some employers currently are considering some sort of DC approach. First, they are once again looking for ways to keep their health care cost increases in line with overall inflation. Second, some employers are concerned that the public "backlash" against managed care will result in new legislation, regulations, and litigation that will further increase their health care costs if they do not distance themselves from health care decisions. Third, employers have modified not only most employee benefit plans, but labor market practices in general, by giving workers more choice, control, and flexibility. DC-type health benefits have existed as cafeteria plans since the 1980s. A cafeteria plan gives each employee the opportunity to determine the allocation of his or her total compensation (within employer-defined limits) among various employee benefits (primarily retirement or health). Most types of DC health benefits currently being discussed could be provided within the existing employment-based health insurance system, with or without the use of cafeteria plans. They could also allow employees to purchase health insurance directly from insurers, or they could drive new technologies and new forms of risk pooling through which health care services are provided and financed. DC health

  8. Intrauterine device insertion during the postpartum period: a systematic review.

    PubMed

    Kapp, Nathalie; Curtis, Kathryn M

    2009-10-01

    Insertion of an intrauterine device (IUD) at different times or by different routes during the postpartum period may increase the risk of complications. We searched Medline, Lilacs and Cochrane Collaboration databases for articles in any language, between database inception until December 2008, which compared outcomes of postpartum IUD insertion time intervals. Search terms included postpartum, puerperium, postcesarean delivery, cesarean section, IUD(s), IUCD(s), intrauterine device(s) and insertion. From 297 articles, we identified 15 for inclusion in this review: all studies examined the outcomes from copper IUD insertions within the postpartum time period compared to other time intervals or compared routes (vaginal or via hysterotomy) of postpartum insertion. No studies of levonorgestrel IUDs were identified. Immediate IUD insertion (within 10 min of placental delivery) was safe when compared with later postpartum time periods and interval insertion. Immediate postpartum IUD insertion demonstrated lower expulsion rates when compared with delayed postpartum insertion but with higher rates than interval insertion. Immediate insertion following cesarean delivery demonstrated lower expulsion rates than immediate insertion following vaginal delivery. Poor to fair quality evidence from 15 articles demonstrated no increase in risk of complications among women who had an IUD inserted during the postpartum period; however, some increase in expulsion rates occurred with delayed postpartum insertion when compared to immediate insertion and with immediate insertion when compared to interval insertion. Postplacental placements during cesarean delivery are associated with lower expulsion rates than postplacental vaginal insertions, without increasing rates of postoperative complications.

  9. euL1db: the European database of L1HS retrotransposon insertions in humans

    PubMed Central

    Mir, Ashfaq A.; Philippe, Claude; Cristofari, Gaël

    2015-01-01

    Retrotransposons account for almost half of our genome. They are mobile genetics elements—also known as jumping genes—but only the L1HS subfamily of Long Interspersed Nuclear Elements (LINEs) has retained the ability to jump autonomously in modern humans. Their mobilization in germline—but also some somatic tissues—contributes to human genetic diversity and to diseases, such as cancer. Here, we present euL1db, the European database of L1HS retrotransposon insertions in humans (available at http://euL1db.unice.fr). euL1db provides a curated and comprehensive summary of L1HS insertion polymorphisms identified in healthy or pathological human samples and published in peer-reviewed journals. A key feature of euL1db is its sample-wise organization. Hence L1HS insertion polymorphisms are connected to samples, individuals, families and clinical conditions. The current version of euL1db centralizes results obtained in 32 studies. It contains >900 samples, >140 000 sample-wise insertions and almost 9000 distinct merged insertions. euL1db will help understanding the link between L1 retrotransposon insertion polymorphisms and phenotype or disease. PMID:25352549

  10. Surface Damage on Dental Implants with Release of Loose Particles after Insertion into Bone.

    PubMed

    Senna, Plinio; Antoninha Del Bel Cury, Altair; Kates, Stephen; Meirelles, Luiz

    2015-08-01

    Modern dental implants present surface features of distinct dimensions that can be damaged during the insertion procedure into bone. The aims of this study were (1) to quantify by means of roughness parameters the surface damage caused by the insertion procedure of dental implants and (2) to investigate the presence of loose particles at the interface. Three groups of dental implants representing different surface topographies were inserted in fresh cow rib bone blocks. The surface roughness was characterized by interferometry on the same area before and after the insertion. Scanning electron microscopy (SEM)-back-scattered electron detector (BSD) analysis was used to identify loose particles at the interface. The amplitude and hybrid roughness parameters of all three groups were lower after insertion. The surface presenting predominance of peaks (Ssk [skewness] > 0) associated to higher structures (height parameters) presented higher damage associated to more pronounced reduction of material volume. SEM-BSD images revealed loose titanium and aluminum particles at the interface mainly at the crestal cortical bone level. Shearing forces during the insertion procedure alters the surface of dental implants. Loose metal particles can be generated at bone-implant interface especially around surfaces composed mainly by peaks and with increased height parameters. © 2013 Wiley Periodicals, Inc.

  11. TAPERED DEFINING SLOT

    DOEpatents

    Pressey, F.W.

    1959-09-01

    An improvement is reported in the shape and formation of the slot or opening in the collimating slot member which forms part of an ion source of the type wherein a vapor of the material to be ionized is bombarded by electrons in a magnetic field to strike an arc-producing ionization. The defining slot is formed so as to have a substantial taper away from the cathode, causing the electron bombardment from the cathode to be dispersed over a greater area reducing its temperature and at the same time bringing the principal concentration of heat from the electron bombardment nearer the anode side of the slot, thus reducing deterioration and prolonging the life of the slot member during operation.

  12. Reactivity of methacrylates in insertion polymerization.

    PubMed

    Rünzi, Thomas; Guironnet, Damien; Göttker-Schnetmann, Inigo; Mecking, Stefan

    2010-11-24

    Polymerization of ethylene by complexes [{(P^O)PdMe(L)}] (P^O = κ(2)-(P,O)-2-(2-MeOC(6)H(4))(2)PC(6)H(4)SO(3))) affords homopolyethylene free of any methyl methacrylate (MMA)-derived units, even in the presence of substantial concentrations of MMA. In stoichiometric studies, reactive {(P^O)Pd(Me)L} fragments generated by halide abstraction from [({(P^O)Pd(Me)Cl}μ-Na)(2)] insert MMA in a 1,2- as well as 2,1-mode. The 1,2-insertion product forms a stable five-membered chelate by coordination of the carbonyl group. Thermodynamic parameters for MMA insertion are ΔH(++) = 69.0(3.1) kJ mol(-1) and ΔS(++) = -103(10) J mol(-1) K(-1) (total average for 1,2- and 2,1-insertion), in comparison to ΔH(++) = 48.5(3.0) kJ mol(-1) and ΔS(++) = -138(7) J mol(-1) K(-1) for methyl acrylate (MA) insertion. These data agree with an observed at least 10(2)-fold preference for MA incorporation vs MMA incorporation (not detected) under polymerization conditions. Copolymerization of ethylene with a bifunctional acrylate-methacrylate monomer yields linear polyethylenes with intact methacrylate substituents. Post-polymerization modification of the latter was exemplified by free-radical thiol addition and by cross-metathesis.

  13. The LORE1 insertion mutant resource.

    PubMed

    Małolepszy, Anna; Mun, Terry; Sandal, Niels; Gupta, Vikas; Dubin, Manu; Urbański, Dorian; Shah, Niraj; Bachmann, Asger; Fukai, Eigo; Hirakawa, Hideki; Tabata, Satoshi; Nadzieja, Marcin; Markmann, Katharina; Su, Junyi; Umehara, Yosuke; Soyano, Takashi; Miyahara, Akira; Sato, Shusei; Hayashi, Makoto; Stougaard, Jens; Andersen, Stig U

    2016-10-01

    Long terminal repeat (LTR) retrotransposons are closely related to retroviruses, and their activities shape eukaryotic genomes. Here, we present a complete Lotus japonicus insertion mutant collection generated by identification of 640 653 new insertion events following de novo activation of the LTR element Lotus retrotransposon 1 (LORE1) (http://lotus.au.dk). Insertion preferences are critical for effective gene targeting, and we exploit our large dataset to analyse LTR element characteristics in this context. We infer the mechanism that generates the consensus palindromes typical of retroviral and LTR retrotransposon insertion sites, identify a short relaxed insertion site motif, and demonstrate selective integration into CHG-hypomethylated genes. These characteristics result in a steep increase in deleterious mutation rate following activation, and allow LORE1 active gene targeting to approach saturation within a population of 134 682 L. japonicus lines. We suggest that saturation mutagenesis using endogenous LTR retrotransposons with germinal activity can be used as a general and cost-efficient strategy for generation of non-transgenic mutant collections for unrestricted use in plant research.

  14. Peptide partitioning properties from direct insertion studies

    SciTech Connect

    Ulmschneider, Martin; Smith, Jeremy C; Ulmschneider, Jakob

    2010-06-01

    Partitioning properties of polypeptides are at the heart of biological membrane phenomena and their precise quantification is vital for ab-initio structure prediction and the accurate simulation of membrane protein folding and function. Recently the cellular translocon machinery has been employed to determine membrane insertion propensities and transfer energetics for a series of polyleucine segments embedded in a carrier sequence. We show here that the insertion propensity, pathway, and transfer energetics into synthetic POPC bilayers can be fully described by direct atomistic peptide partitioning simulations. The insertion probability as a function of peptide length follows two-state Boltzmann statistics, in agreement with the experiments. The simulations expose a systematic offset between translocon-mediated and direct insertion free energies. Compared to the experiment the insertion threshold is shifted toward shorter peptides by 2 leucine residues. The simulations reveal many hitherto unknown atomic-resolution details about the partitioning process and promise to provide a powerful tool for urgently needed calibration of lipid parameters to match experimentally observed peptide transfer energies.

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

    ERIC Educational Resources Information Center

    Hager, Paul; Laurent, John

    1990-01-01

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

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

    ERIC Educational Resources Information Center

    Hager, Paul; Laurent, John

    1990-01-01

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

  17. Establishing learning curve for Tenckhoff catheter insertion by interventional nephrologist using CUSUM analysis: how many procedures and in which situation?

    PubMed

    Goh, Bak Leong; Ganeshadeva Yudisthra, M; Lim, Teck Onn

    2009-01-01

    Peritoneal dialysis (PD) catheter insertion success rate is known to vary among different operators, and peritoneoscope PD catheter insertion demands mastery of a steep learning curve. Defining a learning curve using a continuous monitoring tool such as a Cumulative Summation (CUSUM) chart is useful for planning training programs. We aimed to analyze the learning curve of a trainee nephrologist in performing peritoneoscope PD catheter implantation with CUSUM chart. This was a descriptive single-center study using collected data from all PD patients who underwent peritoneoscope PD catheter insertion in our hospital. CUSUM model was used to evaluate the learning curve for peritoneoscope PD catheter insertion. Unacceptable primary failure rate (i.e., catheter malfunction within 1 month of insertion) was defined at >40% and acceptable performance was defined at <25%. CUSUM chart showed the learning curve of a trainee in acquiring new skill. As the trainee became more skillful with training, the CUSUM curve flattened. Technical proficiency of the trainee nephrologist in performing peritoneoscope Tenckhoff catheter insertion (<25% primary catheter malfunction) was attained after 23 procedures. We also noted earlier in our program that Tenckhoff catheters directed to the right iliac fossae had poorer survival as compared to catheters directed to the left iliac fossae. Survival of catheters directed to the left iliac fossae was 94.6% while the survival for catheters directed to the right iliac fossae was 48.6% (p < 0.01). We advocate that quality control of Tenckhoff catheter insertion is performed using CUSUM charting as described to monitor primary catheter dysfunction (i.e., failure of catheter function within 1 month of insertion), primary leak (i.e., within 1 month of catheter insertion), and primary peritonitis (i.e., within 2 weeks of catheter insertion).

  18. Paleontological evidence for defining the Anthropocene

    NASA Astrophysics Data System (ADS)

    Barnosky, A. D.

    2012-12-01

    Paleontological criteria formed the basis for defining most of the geological eras, periods, epochs, and ages that are commonly recognized. By the same token, the Anthropocene can be defined by paleontological distinctiveness in accordance with commonly accepted biostratigraphic and biochronologic practice. Here I focus on the utility of defining the Anthropocene by the distinctive fossils (or potential fossils of the future) that have accumulated and are accumulating in the sedimentary record. I discuss what kinds of biostratrigraphic criteria would be of most use in recognizing the Anthropocene's base and temporal extent, including pros and cons of definitions based on range zones, interval zones, lineage zones, assemblage zones, and abundance zones, as well as implications for potential reference sections. Key paleontological criteria useful in formally defining the Anthropocene as a geological epoch include (1) anthropogenic trace fossils such as buildings, roads, plastics, etc; (2) abundance zones based on remains of domesticated species and humans; and (3) assemblage zones based on species transported around the globe by people. The magnitude of paleontologically-recognizable changes that have occurred since humans became the dominant species on Earth is at least as great as the paleontological differences that distinguish other Cenozoic epochs, and supports recognition of the Anthropocene as a formal stratigraphic unit.

  19. Elliptically polarizing adjustable phase insertion device

    DOEpatents

    Carr, R.

    1995-01-17

    An insertion device for extracting polarized electromagnetic energy from a beam of particles is disclosed. The insertion device includes four linear arrays of magnets which are aligned with the particle beam. The magnetic field strength to which the particles are subjected is adjusted by altering the relative alignment of the arrays in a direction parallel to that of the particle beam. Both the energy and polarization of the extracted energy may be varied by moving the relevant arrays parallel to the beam direction. The present invention requires a substantially simpler and more economical superstructure than insertion devices in which the magnetic field strength is altered by changing the gap between arrays of magnets. 3 figures.

  20. Interactive simulation of needle insertion models.

    PubMed

    DiMaio, Simon P; Salcudean, Septimiu E

    2005-07-01

    A novel interactive virtual needle insertion simulation is presented. The simulation models are based on measured planar tissue deformations and needle insertion forces. Since the force-displacement relationship is only of interest along the needle shaft, a condensation technique is shown to reduce the computational complexity of linear simulation models significantly. As the needle penetrates or is withdrawn from the tissue model, the boundary conditions that determine the tissue and needle motion change. Boundary condition and local material coordinate changes are facilitated by fast low-rank matrix updates. A large-strain elastic needle model is coupled to the tissue models to account for needle deflection and bending during simulated insertion. A haptic environment, based on these novel interactive simulation techniques, allows users to manipulate a three-degree-of-freedom virtual needle as it penetrates virtual tissue models, while experiencing steering torques and lateral needle forces through a planar haptic interface.

  1. Rack Insertion End Effector (RIEE) automation

    NASA Technical Reports Server (NTRS)

    Malladi, Narasimha

    1993-01-01

    NASA is developing a mechanism to manipulate and insert Racks into the Space Station Logistic modules. The mechanism consists of the following: a base with three motorized degrees of freedom, a 3 section motorized boom that goes from 15 to 44 feet in length, and a Rack Insertion End Effector (RIEE) with 5 hand wheels for precise alignment. The robotics section was tasked with the automation of the RIEE unit. In this report, for the automation of the RIEE unit, application of the Perceptics Vision System was conceptually developed to determine the position and orientation of the RIEE relative to the logistic module, and a MathCad program is written to display the needed displacements for precise alignment and final insertion of the Rack. The uniqueness of this report is that the whole report is in fact a MathCad program including text, derivations, and executable equations with example inputs and outputs.

  2. The microstructure and micromechanics of the tendon-bone insertion

    NASA Astrophysics Data System (ADS)

    Rossetti, L.; Kuntz, L. A.; Kunold, E.; Schock, J.; Müller, K. W.; Grabmayr, H.; Stolberg-Stolberg, J.; Pfeiffer, F.; Sieber, S. A.; Burgkart, R.; Bausch, A. R.

    2017-06-01

    The exceptional mechanical properties of the load-bearing connection of tendon to bone rely on an intricate interplay of its biomolecular composition, microstructure and micromechanics. Here we identify that the Achilles tendon-bone insertion is characterized by an interface region of ~500 μm with a distinct fibre organization and biomolecular composition. Within this region, we identify a heterogeneous mechanical response by micromechanical testing coupled with multiscale confocal microscopy. This leads to localized strains that can be larger than the remotely applied strain. The subset of fibres that sustain the majority of loading in the interface area changes with the angle of force application. Proteomic analysis detects enrichment of 22 proteins in the interfacial region that are predominantly involved in cartilage and skeletal development as well as proteoglycan metabolism. The presented mechanisms mark a guideline for further biomimetic strategies to rationally design hard-soft interfaces.

  3. Defining the Anthropocene

    NASA Astrophysics Data System (ADS)

    Lewis, Simon; Maslin, Mark

    2016-04-01

    Time is divided by geologists according to marked shifts in Earth's state. Recent global environmental changes suggest that Earth may have entered a new human-dominated geological epoch, the Anthropocene. Should the Anthropocene - the idea that human activity is a force acting upon the Earth system in ways that mean that Earth will be altered for millions of years - be defined as a geological time-unit at the level of an Epoch? Here we appraise the data to assess such claims, first in terms of changes to the Earth system, with particular focus on very long-lived impacts, as Epochs typically last millions of years. Can Earth really be said to be in transition from one state to another? Secondly, we then consider the formal criteria used to define geological time-units and move forward through time examining whether currently available evidence passes typical geological time-unit evidence thresholds. We suggest two time periods likely fit the criteria (1) the aftermath of the interlinking of the Old and New Worlds, which moved species across continents and ocean basins worldwide, a geologically unprecedented and permanent change, which is also the globally synchronous coolest part of the Little Ice Age (in Earth system terms), and the beginning of global trade and a new socio-economic "world system" (in historical terms), marked as a golden spike by a temporary drop in atmospheric CO2, centred on 1610 CE; and (2) the aftermath of the Second World War, when many global environmental changes accelerated and novel long-lived materials were increasingly manufactured, known as the Great Acceleration (in Earth system terms) and the beginning of the Cold War (in historical terms), marked as a golden spike by the peak in radionuclide fallout in 1964. We finish by noting that the Anthropocene debate is politically loaded, thus transparency in the presentation of evidence is essential if a formal definition of the Anthropocene is to avoid becoming a debate about bias. The

  4. Mosaic retroposon insertion patterns in placental mammals

    PubMed Central

    Churakov, Gennady; Kriegs, Jan Ole; Baertsch, Robert; Zemann, Anja; Brosius, Jürgen; Schmitz, Jürgen

    2009-01-01

    One and a half centuries after Charles Darwin and Alfred Russel Wallace outlined our current understanding of evolution, a new scientific era is dawning that enables direct observations of genetic variation. However, pure sequence-based molecular attempts to resolve the basal origin of placental mammals have so far resulted only in apparently conflicting hypotheses. By contrast, in the mammalian genomes where they were highly active, the insertion of retroelements and their comparative insertion patterns constitute a neutral, virtually homoplasy-free archive of evolutionary histories. The “presence” of a retroelement at an orthologous genomic position in two species indicates their common ancestry in contrast to its “absence” in more distant species. To resolve the placental origin controversy we extracted ∼2 million potentially phylogenetically informative, retroposon-containing loci from representatives of the major placental mammalian lineages and found highly significant evidence challenging all current single hypotheses of their basal origin. The Exafroplacentalia hypothesis (Afrotheria as the sister group to all remaining placentals) is significantly supported by five retroposon insertions, the Epitheria hypothesis (Xenarthra as the sister group to all remaining placentals) by nine insertion patterns, and the Atlantogenata hypothesis (a monophyletic clade comprising Xenarthra and Afrotheria as the sister group to Boreotheria comprising all remaining placentals) by eight insertion patterns. These findings provide significant support for a “soft” polytomy of the major mammalian clades. Ancestral successive hybridization events and/or incomplete lineage sorting associated with short speciation intervals are viable explanations for the mosaic retroposon insertion patterns of recent placental mammals and for the futile search for a clear root dichotomy. PMID:19261842

  5. True anteroposterior view pedicle screw insertion technique

    PubMed Central

    Bai, Jia-yue; Zhang, Wei; An, Ji-long; Sun, Ya-peng; Ding, Wen-yuan; Shen, Yong

    2016-01-01

    Background The wide use of minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) surgery in the treatment of degenerative disc disease of lumbar spine in spinal surgery highlights the gradual decrease in the use of traditional pedicle screw insertion technology. This study aims to analyze the accuracy of the true anteroposterior view pedicle screw insertion technique in MIS-TLIF surgery, compare it with conventional pedicle screw insertion technology, and discuss its clinical application value. Methods Fifty-two patients undergoing true anteroposterior view (group A) and 87 patients undergoing conventional pedicle screw insertion (group B) were diagnosed with lumbar disc herniation or lumbar spinal stenosis. Time for screw placement, intraoperative irradiation exposure, accuracy rate of pedicle screw insertion, and incidence of neurovascular injury were compared between the two groups. Results The time for screw placement and intraoperative irradiation exposure was significantly less in group A. Penetration rates of the paries lateralis of vertebral pedicle, medial wall of vertebral pedicle, and anterior vertebral wall were 1.44%, 0%, and 2.40%, respectively, all of which were significantly lower than that in group B. No additional serious complications caused by the placement of screw were observed during the follow-up period in patients in group A, but two patients with medial penetration underwent revision for unbearable radicular pain. Conclusion The application of true anteroposterior view pedicle screw insertion technique in MIS-TLIF surgery shortens time for screw placement and reduces the intraoperative irradiation exposure along with a higher accuracy rate of screw placement, which makes it a safe, accurate, and efficient technique. PMID:27418828

  6. Mosaic retroposon insertion patterns in placental mammals.

    PubMed

    Churakov, Gennady; Kriegs, Jan Ole; Baertsch, Robert; Zemann, Anja; Brosius, Jürgen; Schmitz, Jürgen

    2009-05-01

    One and a half centuries after Charles Darwin and Alfred Russel Wallace outlined our current understanding of evolution, a new scientific era is dawning that enables direct observations of genetic variation. However, pure sequence-based molecular attempts to resolve the basal origin of placental mammals have so far resulted only in apparently conflicting hypotheses. By contrast, in the mammalian genomes where they were highly active, the insertion of retroelements and their comparative insertion patterns constitute a neutral, virtually homoplasy-free archive of evolutionary histories. The "presence" of a retroelement at an orthologous genomic position in two species indicates their common ancestry in contrast to its "absence" in more distant species. To resolve the placental origin controversy we extracted approximately 2 million potentially phylogenetically informative, retroposon-containing loci from representatives of the major placental mammalian lineages and found highly significant evidence challenging all current single hypotheses of their basal origin. The Exafroplacentalia hypothesis (Afrotheria as the sister group to all remaining placentals) is significantly supported by five retroposon insertions, the Epitheria hypothesis (Xenarthra as the sister group to all remaining placentals) by nine insertion patterns, and the Atlantogenata hypothesis (a monophyletic clade comprising Xenarthra and Afrotheria as the sister group to Boreotheria comprising all remaining placentals) by eight insertion patterns. These findings provide significant support for a "soft" polytomy of the major mammalian clades. Ancestral successive hybridization events and/or incomplete lineage sorting associated with short speciation intervals are viable explanations for the mosaic retroposon insertion patterns of recent placental mammals and for the futile search for a clear root dichotomy.

  7. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics.

    PubMed

    Arcila, Maria E; Nafa, Khedoudja; Chaft, Jamie E; Rekhtman, Natasha; Lau, Christopher; Reva, Boris A; Zakowski, Maureen F; Kris, Mark G; Ladanyi, Marc

    2013-02-01

    In contrast to other primary epidermal growth factor receptor (EGFR) mutations in lung adenocarcinomas, insertions in exon 20 of EGFR have been generally associated with resistance to EGFR-tyrosine kinase inhibitors. Their molecular spectrum, clinicopathologic characteristics, and prevalence are not well established. Tumors harboring EGFR exon 20 insertions were identified through an algorithmic screen of 1,500 lung adenocarcinomas. Cases were first tested for common mutations in EGFR (exons 19 and 21) and KRAS (exon 2) and, if negative, further analyzed for EGFR exon 20 insertions. All samples underwent extended genotyping for other driver mutations in EGFR, KRAS, BRAF, ERBB2/HER2, NRAS, PIK3CA, MEK1, and AKT by mass spectrometry; a subset was evaluated for ALK rearrangements. We identified 33 EGFR exon 20 insertion cases [2.2%, 95% confidence interval (CI), 1.6-3.1], all mutually exclusive with mutations in the other genes tested (except PIK3CA). They were more common among never-smokers (P < 0.0001). There was no association with age, sex, race, or stage. Morphologically, tumors were similar to those with common EGFR mutations but with frequent solid histology. Insertions were highly variable in position and size, ranging from 3 to 12 bp, resulting in 13 different insertions, which, by molecular modeling, are predicted to have potentially different effects on erlotinib binding. EGFR exon 20 insertion testing identifies a distinct subset of lung adenocarcinomas, accounting for at least 9% of all EGFR-mutated cases, representing the third most common type of EGFR mutation after exon 19 deletions and L858R. Insertions are structurally heterogeneous with potential implications for response to EGFR inhibitors.

  8. Insertion sequence-caused large-scale rearrangements in the genome of Escherichia coli.

    PubMed

    Lee, Heewook; Doak, Thomas G; Popodi, Ellen; Foster, Patricia L; Tang, Haixu

    2016-09-06

    A majority of large-scale bacterial genome rearrangements involve mobile genetic elements such as insertion sequence (IS) elements. Here we report novel insertions and excisions of IS elements and recombination between homologous IS elements identified in a large collection of Escherichia coli mutation accumulation lines by analysis of whole genome shotgun sequencing data. Based on 857 identified events (758 IS insertions, 98 recombinations and 1 excision), we estimate that the rate of IS insertion is 3.5 × 10(-4) insertions per genome per generation and the rate of IS homologous recombination is 4.5 × 10(-5) recombinations per genome per generation. These events are mostly contributed by the IS elements IS1, IS2, IS5 and IS186 Spatial analysis of new insertions suggest that transposition is biased to proximal insertions, and the length spectrum of IS-caused deletions is largely explained by local hopping. For any of the ISs studied there is no region of the circular genome that is favored or disfavored for new insertions but there are notable hotspots for deletions. Some elements have preferences for non-coding sequence or for the beginning and end of coding regions, largely explained by target site motifs. Interestingly, transposition and deletion rates remain constant across the wild-type and 12 mutant E. coli lines, each deficient in a distinct DNA repair pathway. Finally, we characterized the target sites of four IS families, confirming previous results and characterizing a highly specific pattern at IS186 target-sites, 5'-GGGG(N6/N7)CCCC-3'. We also detected 48 long deletions not involving IS elements. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Insertion sequence-caused large-scale rearrangements in the genome of Escherichia coli

    PubMed Central

    Lee, Heewook; Doak, Thomas G.; Popodi, Ellen; Foster, Patricia L.; Tang, Haixu

    2016-01-01

    A majority of large-scale bacterial genome rearrangements involve mobile genetic elements such as insertion sequence (IS) elements. Here we report novel insertions and excisions of IS elements and recombination between homologous IS elements identified in a large collection of Escherichia coli mutation accumulation lines by analysis of whole genome shotgun sequencing data. Based on 857 identified events (758 IS insertions, 98 recombinations and 1 excision), we estimate that the rate of IS insertion is 3.5 × 10−4 insertions per genome per generation and the rate of IS homologous recombination is 4.5 × 10−5 recombinations per genome per generation. These events are mostly contributed by the IS elements IS1, IS2, IS5 and IS186. Spatial analysis of new insertions suggest that transposition is biased to proximal insertions, and the length spectrum of IS-caused deletions is largely explained by local hopping. For any of the ISs studied there is no region of the circular genome that is favored or disfavored for new insertions but there are notable hotspots for deletions. Some elements have preferences for non-coding sequence or for the beginning and end of coding regions, largely explained by target site motifs. Interestingly, transposition and deletion rates remain constant across the wild-type and 12 mutant E. coli lines, each deficient in a distinct DNA repair pathway. Finally, we characterized the target sites of four IS families, confirming previous results and characterizing a highly specific pattern at IS186 target-sites, 5′-GGGG(N6/N7)CCCC-3′. We also detected 48 long deletions not involving IS elements. PMID:27431326

  10. Neurobehavioral Perspectives on the Distinction between Fear and Anxiety

    ERIC Educational Resources Information Center

    Perusini, Jennifer N.; Fanselow, Michael S.

    2015-01-01

    In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the…

  11. Neurobehavioral Perspectives on the Distinction between Fear and Anxiety

    ERIC Educational Resources Information Center

    Perusini, Jennifer N.; Fanselow, Michael S.

    2015-01-01

    In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the…

  12. Defining hypercalciuria in nephrolithiasis

    PubMed Central

    Pak, Charles Y.C.; Sakhaee, Khashayar; Moe, Orson W.; Poindexter, John; Adams-Huet, Beverley

    2014-01-01

    The classic definition of hypercalciuria, an upper normal limit of 200 mg/day, is based on a constant diet restricted in calcium, sodium, and animal protein; however, random diet data challenge this. Here our retrospective study determined the validity of the classic definition of hypercalciuria by comparing data from 39 publications analyzing urinary calcium excretion on a constant restricted diet and testing whether hypercalciuria could be defined when extraneous dietary influences were controlled. These papers encompassed 300 non-stone-forming patients, 208 patients with absorptive hypercalciuria type I (presumed due to high intestinal calcium absorption), and 234 stone formers without absorptive hypercalciuria; all evaluated on a constant restricted diet. In non-stone formers, the mean urinary calcium was well below 200 mg/day, and the mean for all patients was 127±46 mg/day with an upper limit of 219 mg/day. In absorptive hypercalciuria type I, the mean urinary calcium significantly exceeded 200 mg/day in all studies with a combined mean of 259±55 mg/day. Receiver operating characteristic curve analysis showed the optimal cutoff point for urinary calcium excretion was 172 mg/day on a restricted diet, a value that approximates the traditional limit of 200 mg/day. Thus, on a restricted diet, a clear demarcation was seen between urinary calcium excretion of kidney stone formers with absorptive hypercalciuria type I and normal individuals. When dietary variables are controlled, the classic definition of hypercalciuria of nephrolithiasis appears valid. PMID:21775970

  13. Defining equity in health

    PubMed Central

    Braveman, P; Gruskin, S

    2003-01-01

    Study objective: To propose a definition of health equity to guide operationalisation and measurement, and to discuss the practical importance of clarity in defining this concept. Design: Conceptual discussion. Setting, Patients/Participants, and Main results: not applicable. Conclusions: For the purposes of measurement and operationalisation, equity in health is the absence of systematic disparities in health (or in the major social determinants of health) between groups with different levels of underlying social advantage/disadvantage—that is, wealth, power, or prestige. Inequities in health systematically put groups of people who are already socially disadvantaged (for example, by virtue of being poor, female, and/or members of a disenfranchised racial, ethnic, or religious group) at further disadvantage with respect to their health; health is essential to wellbeing and to overcoming other effects of social disadvantage. Equity is an ethical principle; it also is consonant with and closely related to human rights principles. The proposed definition of equity supports operationalisation of the right to the highest attainable standard of health as indicated by the health status of the most socially advantaged group. Assessing health equity requires comparing health and its social determinants between more and less advantaged social groups. These comparisons are essential to assess whether national and international policies are leading toward or away from greater social justice in health. PMID:12646539

  14. Defining Neonatal Sepsis

    PubMed Central

    Wynn, James L.

    2016-01-01

    Purpose of the review Although infection rates have modestly decreased in the neonatal intensive care unit (NICU) as a result of ongoing quality improvement measures, neonatal sepsis remains a frequent and devastating problem among hospitalized preterm neonates. Despite multiple attempts to address this unmet need, there have been minimal advances in clinical management, outcomes, and accuracy of diagnostic testing options over the last three decades. One strong contributor to a lack of medical progress is a variable case definition of disease. The inability to agree on a precise definition greatly reduces the likelihood of aligning findings from epidemiologists, clinicians, and researchers, which, in turn, severely hinders progress towards improving outcomes. Recent findings Pediatric consensus definitions for sepsis are not accurate in term infants and are not appropriate for preterm infants. In contrast to the defined multi-stage criteria for other devastating diseases encountered in the NICU (e.g., bronchopulmonary dysplasia), there is significant variability in the criteria used by investigators to substantiate the diagnosis of neonatal sepsis. Summary The lack of an accepted consensus definition for neonatal sepsis impedes our efforts towards improved diagnostic and prognostic options as well as accurate outcomes information for this vulnerable population. PMID:26766602

  15. Compact insert design for cryogenic pressure vessels

    DOEpatents

    Aceves, Salvador M.; Ledesma-Orozco, Elias Rigoberto; Espinosa-Loza, Francisco; Petitpas, Guillaume; Switzer, Vernon A.

    2017-06-14

    A pressure vessel apparatus for cryogenic capable storage of hydrogen or other cryogenic gases at high pressure includes an insert with a parallel inlet duct, a perpendicular inlet duct connected to the parallel inlet. The perpendicular inlet duct and the parallel inlet duct connect the interior cavity with the external components. The insert also includes a parallel outlet duct and a perpendicular outlet duct connected to the parallel outlet duct. The perpendicular outlet duct and the parallel outlet duct connect the interior cavity with the external components.

  16. RERTR-12 Insertion 2 Irradiation Summary Report

    SciTech Connect

    D. M. Perez; G. S. Chang; D. M. Wachs; G. A. Roth; N. E. Woolstenhulme

    2012-09-01

    The Reduced Enrichment for Research and Test Reactor (RERTR) experiment RERTR-12 was designed to provide comprehensive information on the performance of uranium-molybdenum (U-Mo) based monolithic fuels for research reactor applications.1 RERTR-12 insertion 2 includes the capsules irradiated during the last three irradiation cycles. These capsules include Z, Y1, Y2 and Y3 type capsules. The following report summarizes the life of the RERTR-12 insertion 2 experiment through end of irradiation, including as-run neutronic analysis results, thermal analysis results and hydraulic testing results.

  17. Interaural attenuation using insert earphones: electrocochleographic approach.

    PubMed

    Sobhy, O A; Gould, H J

    1993-03-01

    We measured the interaural attenuation for click stimuli using insert earphones. Electrocochleographic thresholds were determined when clicks were presented both ipsilaterally and contralaterally to the recording ear. The interaural attenuation was calculated as the difference between ipsilateral and contralateral thresholds. Results from normal listeners showed that crossover occurred. Results agree with previous investigators who used a different approach. Results confirm that one may need to mask the nontest ear in clinical evoked potential testing even though insert earphones are used. Several approaches to the question of when to mask are proposed.

  18. Circular permutant GFP insertion folding reporters

    SciTech Connect

    Waldo, Geoffrey S.; Cabantous, Stephanie

    2013-04-16

    Provided are methods of assaying and improving protein folding using circular permutants of fluorescent proteins, including circular permutants of GFP variants and combinations thereof. The invention further provides various nucleic acid molecules and vectors incorporating such nucleic acid molecules, comprising polynucleotides encoding fluorescent protein circular permutants derived from superfolder GFP, which polynucleotides include an internal cloning site into which a heterologous polynucleotide may be inserted in-frame with the circular permutant coding sequence, and which when expressed are capable of reporting on the degree to which a polypeptide encoded by such an inserted heterologous polynucleotide is correctly folded by correlation with the degree of fluorescence exhibited.

  19. Circular permutant GFP insertion folding reporters

    DOEpatents

    Waldo, Geoffrey S.; Cabantous, Stephanie

    2008-06-24

    Provided are methods of assaying and improving protein folding using circular permutants of fluorescent proteins, including circular permutants of GFP variants and combinations thereof. The invention further provides various nucleic acid molecules and vectors incorporating such nucleic acid molecules, comprising polynucleotides encoding fluorescent protein circular permutants derived from superfolder GFP, which polynucleotides include an internal cloning site into which a heterologous polynucleotide may be inserted in-frame with the circular permutant coding sequence, and which when expressed are capable of reporting on the degree to which a polypeptide encoded by such an inserted heterologous polynucleotide is correctly folded by correlation with the degree of fluorescence exhibited.

  20. Circular permutant GFP insertion folding reporters

    DOEpatents

    Waldo, Geoffrey S; Cabantous, Stephanie

    2013-02-12

    Provided are methods of assaying and improving protein folding using circular permutants of fluorescent proteins, including circular permutants of GFP variants and combinations thereof. The invention further provides various nucleic acid molecules and vectors incorporating such nucleic acid molecules, comprising polynucleotides encoding fluorescent protein circular permutants derived from superfolder GFP, which polynucleotides include an internal cloning site into which a heterologous polynucleotide may be inserted in-frame with the circular permutant coding sequence, and which when expressed are capable of reporting on the degree to which a polypeptide encoded by such an inserted heterologous polynucleotide is correctly folded by correlation with the degree of fluorescence exhibited.

  1. Circular permutant GFP insertion folding reporters

    DOEpatents

    Waldo, Geoffrey S.; Cabantous, Stephanie

    2011-06-14

    Provided are methods of assaying and improving protein folding using circular permutants of fluorescent proteins, including circular permutants of GFP variants and combinations thereof. The invention further provides various nucleic acid molecules and vectors incorporating such nucleic acid molecules, comprising polynucleotides encoding fluorescent protein circular permutants derived from superfolder GFP, which polynucleotides include an internal cloning site into which a heterologous polynucleotide may be inserted in-frame with the circular permutant coding sequence, and which when expressed are capable of reporting on the degree to which a polypeptide encoded by such an inserted heterologous polynucleotide is correctly folded by correlation with the degree of fluorescence exhibited.

  2. Traumatic insertion of eyelashes into corneal stroma.

    PubMed

    Casswell, Edward J; Anikina, Evgenia V; Mearza, Ali A

    2014-10-01

    An unusual case of eyelashes being traumatically inserted into the corneal stroma is presented. A 75-year-old hit her right eye with her own fist, presenting with intra-corneal eyelashes. All remained entirely within the cornea, with no breach of the endothelium. They seemed to have tracked there first through the superior conjunctiva and then the superior limbus. The lashes were surgically removed, with good visual recovery. The authors present a short review of intra-ocular eyelash insertion. Copyright © 2014 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.

  3. Friction force measurement during cochlear implant insertion: application to a force-controlled insertion tool design.

    PubMed

    Miroir, Mathieu; Nguyen, Yann; Kazmitcheff, Guillaume; Ferrary, Evelyne; Sterkers, Olivier; Grayeli, Alexis Bozorg

    2012-08-01

    The aim of the study was to evaluate force profiles during array insertion in human cochlea specimens and to evaluate a mechatronic inserter using a 1-axis force sensor. Today, the surgical challenge in cochlear implantation is the preservation of the anatomic structures and the residual hearing. In routine practice, the electrode array is inserted manually with a limited sensitive feedback. Hifocus 1J electrode arrays were studied. The bench test comprised a mechatronic inserter combined to a 1-axis force sensor between the inserter and the base of the array and a 6-axis force sensor beneath the cochlea model. Influence of insertion tube material, speed (0.15, 0.5, and 1.5 mm/s) and lubricant on frictions forces were studied (no-load). Different models were subsequently evaluated: epoxy scala tympani model and temporal bones. Frictions forces were lower in the plastic tube compared with those in the metal tube (0.09 ± 0.028 versus 0.14 ± 0.034 at 0.5 mm/s, p < 0.001) and with the use of hyaluronic acid gel. Speed did not influence frictions forces in our study. Insertion force profiles provided by the 1- and 6-axis force sensors were similar when friction forces inside the insertion tool (no-load measurements) were subtracted from the 1-axis sensor data in the epoxy and temporal bone models (mean error, 0.01 ± 0.001 N). Using a sensor included in the inserter, we were able to measure array insertion forces. This tool can be potentially used to provide real-time information to the surgeon during the procedure.

  4. Insertional Achilles tendinitis and Haglund's deformity.

    PubMed

    Kang, Steve; Thordarson, David B; Charlton, Timothy P

    2012-06-01

    Haglund's deformity is an enlargement of the posterosuperior prominence of the calcaneus, which is frequently associated with insertional Achilles tendinitis. To our knowledge, no study has been done successfully correlating the characteristics of a Haglund's deformity with insertional Achilles tendinitis. The purpose of our study was to analyze the characteristics of a Haglund's deformity in patients with and without insertional Achilles tendinitis to see if there was a correlation. The study was a retrospective radiographic review of a single surgeon's patients with insertional Achilles tendinitis from 2005 to 2008. Our study population consisted of 44 patients, 48 heels (22 male, 22 female) with insertional Achilles tendinitis, with a mean age of 52 (range, 23 to 79) years. Our control population consisted of 50 patients (25 males, 25 females) and 50 heels without insertional Achilles tendinitis with a mean age of 55.6 (range, 18 to 89) years. We introduced two new measurements of the Haglund's deformity in this study: the Haglund's deformity height and peak angle. A standing lateral foot or ankle radiograph was analyzed for each patient and the following measurements were made: Haglund deformity height and peak angle; Bohler's angle; Fowler-Philip angle; and parallel pitch sign. We also looked for the presence of calcification in the study group and the length and width of the calcification. Unpaired t-test was used to analyze the measurements between the groups. Ten patients' radiographs were re-measured and correlation coefficients were obtained to assess the reliability of the measuring techniques. For the insertional Achilles tendinitis group, the mean Haglund's deformity height was 9.6 (range, 5.3 to 15.3) mm and the mean Haglund's deformity peak angle was 105 (range, 87 to 123) degrees. Calcification was present in 35 of 48 or (73%) of patients with a mean length of 13.3 (range, 3.2 to 41.9) mm and mean width of 4.5 (range, 1.0 to 10.4) mm. In the control

  5. Touch communicates distinct emotions.

    PubMed

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

    2006-08-01

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

  6. Multiple Independent Retroelement Insertions in the Promoter of a Stress Response Gene Have Variable Molecular and Functional Effects in Drosophila

    PubMed Central

    Merenciano, Miriam; Ullastres, Anna; González, Josefa

    2016-01-01

    Promoters are structurally and functionally diverse gene regulatory regions. The presence or absence of sequence motifs and the spacing between the motifs defines the properties of promoters. Recent alternative promoter usage analyses in Drosophila melanogaster revealed that transposable elements significantly contribute to promote diversity. In this work, we analyzed in detail one of the transposable element insertions, named FBti0019985, that has been co-opted to drive expression of CG18446, a candidate stress response gene. We analyzed strains from different natural populations and we found that besides FBti0019985, there are another eight independent transposable elements inserted in the proximal promoter region of CG18446. All nine insertions are solo-LTRs that belong to the roo family. We analyzed the sequence of the nine roo insertions and we investigated whether the different insertions were functionally equivalent by performing 5’-RACE, gene expression, and cold-stress survival experiments. We found that different insertions have different molecular and functional consequences. The exact position where the transposable elements are inserted matters, as they all showed highly conserved sequences but only two of the analyzed insertions provided alternative transcription start sites, and only the FBti0019985 insertion consistently affects CG18446 expression. The phenotypic consequences of the different insertions also vary: only FBti0019985 was associated with cold-stress tolerance. Interestingly, the only previous report of transposable elements inserting repeatedly and independently in a promoter region in D. melanogaster, were also located upstream of a stress response gene. Our results suggest that functional validation of individual structural variants is needed to resolve the complexity of insertion clusters. PMID:27517860

  7. 21 CFR 886.5420 - Contact lens inserter/remover.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Contact lens inserter/remover. 886.5420 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5420 Contact lens inserter/remover. (a) Identification. A contact lens inserter/remover is a handheld device intended to insert or...

  8. 21 CFR 886.5420 - Contact lens inserter/remover.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Contact lens inserter/remover. 886.5420 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5420 Contact lens inserter/remover. (a) Identification. A contact lens inserter/remover is a handheld device intended to insert or...

  9. 21 CFR 886.5420 - Contact lens inserter/remover.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Contact lens inserter/remover. 886.5420 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5420 Contact lens inserter/remover. (a) Identification. A contact lens inserter/remover is a handheld device intended to insert or...

  10. 21 CFR 886.5420 - Contact lens inserter/remover.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Contact lens inserter/remover. 886.5420 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5420 Contact lens inserter/remover. (a) Identification. A contact lens inserter/remover is a handheld device intended to insert or...

  11. 21 CFR 886.5420 - Contact lens inserter/remover.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Contact lens inserter/remover. 886.5420 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Therapeutic Devices § 886.5420 Contact lens inserter/remover. (a) Identification. A contact lens inserter/remover is a handheld device intended to insert or...

  12. Mass-flow-rate-controlled fluid flow in nanochannels by particle insertion and deletion

    NASA Astrophysics Data System (ADS)

    Barclay, Paul L.; Lukes, Jennifer R.

    2016-12-01

    A nonequilibrium molecular dynamics method to induce fluid flow in nanochannels, the insertion-deletion method (IDM), is introduced. IDM inserts and deletes particles within distinct regions in the domain, creating locally high and low pressures. The benefits of IDM are that it directly controls a physically meaningful quantity, the mass flow rate, allows for pressure and density gradients to develop in the direction of flow, and permits treatment of complex aperiodic geometries. Validation of IDM is performed, yielding good agreement with the analytical solution of Poiseuille flow in a planar channel. Comparison of IDM to existing methods indicates that it is best suited for gases, both because it intrinsically accounts for compressibility effects on the flow and because the computational cost of particle insertion is lowest for low-density fluids.

  13. Mass-flow-rate-controlled fluid flow in nanochannels by particle insertion and deletion.

    PubMed

    Barclay, Paul L; Lukes, Jennifer R

    2016-12-01

    A nonequilibrium molecular dynamics method to induce fluid flow in nanochannels, the insertion-deletion method (IDM), is introduced. IDM inserts and deletes particles within distinct regions in the domain, creating locally high and low pressures. The benefits of IDM are that it directly controls a physically meaningful quantity, the mass flow rate, allows for pressure and density gradients to develop in the direction of flow, and permits treatment of complex aperiodic geometries. Validation of IDM is performed, yielding good agreement with the analytical solution of Poiseuille flow in a planar channel. Comparison of IDM to existing methods indicates that it is best suited for gases, both because it intrinsically accounts for compressibility effects on the flow and because the computational cost of particle insertion is lowest for low-density fluids.

  14. Embedded Multiprocessor Technology for VHSIC Insertion

    NASA Technical Reports Server (NTRS)

    Hayes, Paul J.

    1990-01-01

    Viewgraphs on embedded multiprocessor technology for VHSIC insertion are presented. The objective was to develop multiprocessor system technology providing user-selectable fault tolerance, increased throughput, and ease of application representation for concurrent operation. The approach was to develop graph management mapping theory for proper performance, model multiprocessor performance, and demonstrate performance in selected hardware systems.

  15. Lymphatic Leak Complicating Central Venous Catheter Insertion

    SciTech Connect

    Barnacle, Alex M. Kleidon, Tricia M.

    2005-12-15

    Many of the risks associated with central venous access are well recognized. We report a case of inadvertent lymphatic disruption during the insertion of a tunneled central venous catheter in a patient with raised left and right atrial pressures and severe pulmonary hypertension, which led to significant hemodynamic instability. To our knowledge, this rare complication is previously unreported.

  16. Thermal Performance of the XRS Helium Insert

    NASA Technical Reports Server (NTRS)

    Breon, Susan R.; DiPirro, Michael J.; Tuttle, James G.; Shirron, Peter J.; Warner, Brent A.; Boyle, Robert F.; Canavan, Edgar R.

    1999-01-01

    The X-Ray Spectrometer (XRS) is an instrument on the Japanese Astro-E satellite, scheduled for launch early in the year 2000. The XRS Helium Insert comprises a superfluid helium cryostat, an Adiabatic Demagnetization Refrigerator (ADR), and the XRS calorimeters with their cold electronics. The calorimeters are capable of detecting X-rays over the energy range 0.1 to 10 keV with a resolution of 12 eV. The Helium Insert completed its performance and verification testing at Goddard in January 1999. It was shipped to Japan, where it has been integrated with the neon dewar built by Sumitomo Heavy Industries. The Helium Insert was given a challenging lifetime requirement of 2.0 years with a goal of 2.5 years. Based on the results of the thermal performance tests, the predicted on-orbit lifetime is 2.6 years with a margin of 30%. This is the result of both higher efficiency in the ADR cycle and the low temperature top-off, more than compensating for an increase in the parasitic heat load. This paper presents a summary of the key design features and the results of the thermal testing of the XRS Helium Insert.

  17. Peripherally inserted central catheters. Intravenous Nurses Society.

    PubMed

    1997-01-01

    The Intravenous Nurses Society (INS) recognizes the need for uniform terminology for peripherally inserted central catheters (PICCs) to encourage standardization for indications, care, and maintenance strategies for these devices. It also recognizes the need for recommendations regarding the choice, use, management, and discontinuation of PICCs to promote positive patient outcomes and enhance patient comfort, safety, and satisfaction.

  18. Patients' experiences of the PICC insertion procedure.

    PubMed

    Nicholson, Jackie; Davies, Louise

    Peripherally inserted central catheters (PICCs) are a type of central venous access device used to deliver a variety of intravenous therapies, including chemotherapy. PICCs may be placed by interventional radiologists, anaesthetists or, as is increasingly common, by specialist nurses in the hospital setting. However, little is known about how patients feel regarding the PICC insertion procedure. The aim of this study was to interview patients who had undergone a recent PICC insertion in the chemotherapy day unit to identify their experiences. On analysis of the qualitative data obtained from the semi-structured interview, five themes emerged: the context of cancer; expectations; levels of pain and anxiety; coping strategies; and explanation. The findings of this study support some previously described elements of procedural experiences; however, new understanding has provided implications for practice in the areas of expectations, allaying anxiety levels, supporting individual coping strategies and providing explanation. The major limitation of the study was the homogenous sample of oncology patients with a clear link between the patient experience of the PICC insertion and the context of cancer. The main recommendation for further research would be to repeat this study with a broader patient population.

  19. Insertion Loss of Personal Protective Clothing

    SciTech Connect

    Shull D.J.; Biesel, V.B.; Cunefare, K.A.

    1999-05-13

    'The use of personal protective clothing that covers the head is a common practice in many industries. Such personal protective clothing will impact the sound pressure level and the frequency content of sounds to which the wearer will be exposed. The use of such clothing, then, may impact speech and alarm audibility. A measure of the impact of such clothing is its insertion loss. Insertion loss measurements were performed on four types of personal protective clothing in use by Westinghouse Savannah River Company personnel which utilize cloth and plastic hood configurations to protect the head. All clothing configurations tested at least partially cover the ears. The measurements revealed that insertion loss of the items tested was notable at frequencies above 1000 Hz only and was a function of material stiffness and acoustic flanking paths to the ear. Further, an estimate of the clothing''s noise reduction rating reveals poor performance in that regard, even though the insertion loss of the test articles was significant at frequencies at and above 1000 Hz.'

  20. Immediate postabortal insertion of intrauterine devices.

    PubMed

    Okusanya, Babasola O; Oduwole, Olabisi; Effa, Emmanuel E

    2014-07-28

    Background The use of an effective contraceptive may be necessary after an abortion. Insertion of an intrauterine device (IUD) may be done the same day or later. Immediate IUD insertion is an option since the woman is not pregnant, pain of insertion is less because the cervical os is open, and her motivation to use contraception may be high. However, insertion of an IUD immediately after a pregnancy ends carries risks, such as spontaneous expulsion.Objectives To assess the safety and efficacy of IUD insertion immediately after spontaneous or induced abortion.Search methods We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, POPLINE, ClinicalTrials.gov,and ICTRP in January 27, 2014. We also contacted investigators to identify other trials.Selection criteria We sought all randomised controlled trials (RCTs) with at least one treatment arm that involved IUD insertion immediately after an induced abortion or after curettage for spontaneous abortion.Data collection and analysis We evaluated the methodological quality of each report and abstracted the data. We focused on discontinuation rates for accidental pregnancy, perforation, expulsion, and pelvic inflammatory disease.We computed the weighted average of the rate ratios.We compute drisk ratios (RRs) with 95% Confidence Intervals (CIs).We performed an intention-to-treat (ITT) analysis by including all randomised participants in the analysis according to the Cochrane Handbook for Systematic Reviews of Interventions.Main results We identified 12 trials most of which are of moderate risk of bias involving 7,119 participants which described random assignment.Five trials randomised to either immediate or delayed insertion of IUD. One of them randomised to immediate versus delayed insertion of Copper 7 showed immediate insertion of the Copper 7 was associated with a higher risk of expulsion than was delayed insertion(RR 11.98, 95% CI 1.61 to 89.35,1 study, 259 participants); the

  1. Frequency, Gradience, and Variation in Consonant Insertion

    ERIC Educational Resources Information Center

    An, Young-ran

    2010-01-01

    This dissertation addresses the extent to which linguistic behavior can be described in terms of the projection of patterns from existing lexical items, through an investigation of Korean reduplication. Korean has a productive pattern of reduplication in which a consonant is inserted in a vowel-initial base, illustrated by forms such as "alok"--"t…

  2. Mars Observer Lecture: Mars Orbit Insertion

    NASA Technical Reports Server (NTRS)

    Dodd, Suzanne R. (Personal Name)

    1993-01-01

    The Mars Observer mission spacecraft was primarily designed for exploring Mars and the Martian environment. The Mars Observer was launched on September 25, 1992. The spacecraft was lost in the vicinity of Mars on August 21, 1993 when the spacecraft began its maneuvering sequence for Martian orbital insertion. This videotape shows a lecture by Suzanne R. Dodd, the Mission Planning Team Chief for the Mars Observer Project. Ms Dodd begins with a brief overview of the mission and the timeline from the launch to orbital insertion. Ms Dodd then reviews slides showing the trajectory of the spacecraft on its trip to Mars. Slides of the spacecraft being constructed are also shown. She then discusses the Mars orbit insertion and the events that will occur to move the spacecraft from the capture orbit into a mapping orbit. During the trip to Mars, scientists at JPL had devised a new strategy, called Power In that would allow for an earlier insertion into the mapping orbit. The talk summarizes this strategy, showing on a slide the planned transition orbits. There are shots of the Martian moon, Phobos, taken from the Viking spacecraft, as Ms Dodd explains that the trajectory will allow the orbiter to make new observations of that moon. She also explains the required steps to prepare for mapping after the spacecraft has achieved the mapping orbit around Mars. The lecture ends with a picture of Mars from the Observer on its approach to the planet.

  3. Inserting new technology into small missions

    NASA Technical Reports Server (NTRS)

    Deutsch, L. J.

    2001-01-01

    Part of what makes small missions small is that they have less money. Executing missions at low cost implies extensive use of cost sharing with other missions or use of existing solutions. Luckily, there are methods for creating new technology and inserting it into faster-better-cheaper missions.

  4. A design for vertical crossing insertions

    SciTech Connect

    Garren, A.

    1985-10-01

    A crossing insertion designed for an SSC with vertically separated 1-in-1 beam lines is presented in this note. The author supposes that the beam lines consist of separate magnets in separate cryostats separated by about 70 cm. He then describes the design, where vertical separation is done with four vertical dipoles producing a steplike beam line.

  5. Insertion loads and forearm muscle activity during flexible hose insertion tasks.

    PubMed

    Grieshaber, D Christian; Armstrong, Thomas J

    2007-10-01

    To quantify the physical demands of hose insertion tasks in automotive assembly operations and how they are affected by method and the mechanical interference between the hose and the flange. Insertion tasks were identified by workers as physically demanding and can often lead to fatigue or losses in production attributable to pain or injury. Six male and 6 female participants pushed a 25.4-mm flexible rubber hose onto a stationary flange during simulated insertions. Three insertion methods -- rock, straight, and twist -- were examined in the study. Muscle activity of the finger flexors was recorded to estimate grip effort during the simulated insertions. The twist method (114.8 N) resulted in a 26% reduction in axial force compared with the straight method (155.7 N). Average muscle activity ranged from a low of 14% maximum voluntary contraction (MVC; men, straight method) to a high of 67% MVC (women, twist method). Hose resultant forces ranged from a low of 52.2 N to a high of 461.1 N for all participants. Men exerted 6% higher resultant forces with 37% less muscle activity than women. There are situations when the 26% reduction in the axial force attributable to twisting may be helpful during an insertion, despite the fact that forearm muscle activity was highest for both male and female participants during twisting insertions. The results of this study can be applied to the future design of tasks that involve the joining of two parts such as a hose and flange.

  6. Prenatal diagnosis of abnormal umbilical cord insertion: a rare case of furcate insertion.

    PubMed

    Fujita, Yasuyuki; Yumoto, Yasuo; Kato, Kiyoko

    2017-04-01

    Furcate insertion (FI) is an extremely rare abnormality of umbilical cord insertion. One of the complications associated with FI is hemorrhage from the umbilical vein at the site of FI of the umbilical cord, which can cause sudden intrauterine fetal death. Because of its rarity, no prenatal diagnosis of FI has been reported. A 31-year-old woman at 34 weeks' gestation was referred to us for suspected abnormal cord insertion. Ultrasonography showed normal fetal growth and amniotic fluid volume, with no fetal anomalies. Although the umbilical cord contained three vessels inserted at the center of the placenta, the umbilical vessels separated from the cord substance before their insertion to the placenta. Based on these findings, the patient was diagnosed with FI. During labor at 37 weeks' gestation, fetal heart rate was normal and a healthy neonate was delivered. At macroscopic examination, the umbilical cord was inserted in the middle of the placenta, and the placental parenchymal tissue just under the cord insertion was deficient and had been changed to white, elastic hard tissue. Pathological examination of the white tissue revealed fibrin deposition and focal infarction. Although FI is a very rare condition, prenatal diagnosis can be achieved through detailed color Doppler ultrasound studies. Therefore, taking precautions and keeping in mind the poor fetal outcome associated with FI are preferred.

  7. Penoscrotal porokeratosis: A distinct entity

    PubMed Central

    Joshi, Rajiv; Jadhav, Yatin

    2015-01-01

    A 26-year-old man presented with five months history of redness associated with itching and burning over the scrotum and shaft of the penis with a persistent rash on those sites. There had been no response to topical steroid and antifungal creams. Clinical examination revealed a large well-circumscribed erythematous plaque with a thready raised border with a tiny groove at its summit that involved almost two-thirds of the ventral part of the shaft of the penis. Ill-defined erythema with a granular surface was seen over the anterior scrotal skin. A 4 mm punch biopsy of the plaque on the penile shaft revealed multiple cornoid lamellae located adjacent to one another. The patient was treated with topical emollients. Follow up after four months revealed almost complete resolution of the plaque on the penile shaft. Penoscrotal porokeratosis appears to be a distinct entity in the family of porokeratotic diseases, described only in young males in their twenties with involvement of the penile shaft and anterior scrotum with severe burning and itching and histologically associated with multiple cornoid lamellae. It may represent an unusual epidermal porokeratotic reaction pattern and may be a self-resolving condition. PMID:26500866

  8. Consolidation and disposal of PWR fuel inserts

    SciTech Connect

    Wakeman, B.H. )

    1992-08-01

    Design and licensing of the Surry Power Station Independent Spent Fuel Storage Installation was initiated in 1982 by Virginia Power as part of a comprehensive strategy to increase spent fuel storage capacity at the Station. Designed to use large, metal dry storage casks, the Surry Installation will accommodate 84 such casks with a total storage capacity of 811 MTU of spent pressurized water reactor fuel assemblies. Virginia Power provided three storage casks for testing at the Idaho National Engineerinq Laboratory's Test Area North and the testing results have been published by the Electric Power Research Institute. Sixty-nine spent fuel assemblies were transported in truck casks from the Surry Power Station to Test Area North for testing in the three casks. Because of restrictions imposed by the cask testing equipment at Test Area North, the irradiated insert components stored in these fuel assemblies at Surry were removed prior to transport of the fuel assemblies. Retaining these insert components proved to be a problem because of a shortage of spent fuel assemblies in the spent fuel storage pool that did not already contain insert components. In 1987 Virginia Power contracted with Chem-Nuclear Systems, Inc. to process and dispose of 136 irradiated insert components consisting of 125 burnable poison rod assemblies, 10 thimble plugging devices and 1 part-length rod cluster control assembly. This work was completed in August and September 1987, culminating in the disposal at the Barnwell, SC low-level radioactive waste facility of two CNS 3-55 liners containing the consolidated insert components.

  9. Distal Insertions of the Biceps Femoris

    PubMed Central

    Branch, Eric A.; Anz, Adam W.

    2015-01-01

    Background: Avulsion of the biceps femoris from the fibula and proximal tibia is encountered in clinical practice. While the anatomy of the primary posterolateral corner structures has been qualitatively and quantitatively described, a quantitative analysis regarding the insertions of the biceps femoris on the fibula and proximal tibia is lacking. Purpose: To quantitatively assess the insertions of the biceps femoris, fibular collateral ligament (FCL), and anterolateral ligament (ALL) on the fibula and proximal tibia as well as establish relationships among these structures and to pertinent surgical anatomy. Study Design: Descriptive laboratory study. Methods: Dissections were performed on 12 nonpaired, fresh-frozen cadaveric specimens identifying the biceps femoris, FCL, and ALL, and their insertions on the proximal tibia and fibula. The footprint areas, orientations, and distances from relevant osseous landmarks were measured using a 3-dimensional coordinate measurement device. Results: Dissection produced 6 easily identifiable and reproducible anatomic footprints. Tibial footprints included the insertion of the ALL and an insertion of the biceps femoris (TBF). Fibular footprints included the insertion of the FCL, a distal insertion of the biceps femoris (DBF), a medial footprint of the biceps femoris (MBF), and a proximal footprint of the biceps femoris (PBF). The mean area of these footprints (95% CI) was as follows: ALL, 53.0 mm2 (38.4-67.6); TBF, 93.9 mm2 (72.0-115.8); FCL, 86.8 mm2 (72.3-101.2); DBF, 119 mm2 (91.1-146.9); MBF, 46.8 mm2 (29.0-64.5); and PBF, 215 mm2 (192.4-237.5). The mean distance (95% CI) from the Gerdy tubercle to the center of the ALL footprint was 24.3 mm (21.6-27.0) and to the center of the TBF was 22.5 mm (21.0-24.0). The center of the DBF was 8.68 mm (7.0-10.3) from the anterior border of the fibula, the center of the FCL was 14.6 mm (12.5-16.7) from the anterior border of the fibula and 20.7 mm (19.0-22.4) from the tip of the fibular

  10. Foundations of Distinctive Feature Theory.

    ERIC Educational Resources Information Center

    Baltaxe, Christiane A. M.

    This treatise on the theoretical and historical foundations of distinctive feature theory traces the evolution of the distinctive features concept in the context of related notions current in linguistic theory, discusses the evolution of individual distinctive features, and criticizes certain acoustic and perceptual correlates attributed to these…

  11. Foundations of Distinctive Feature Theory.

    ERIC Educational Resources Information Center

    Baltaxe, Christiane A. M.

    This treatise on the theoretical and historical foundations of distinctive feature theory traces the evolution of the distinctive features concept in the context of related notions current in linguistic theory, discusses the evolution of individual distinctive features, and criticizes certain acoustic and perceptual correlates attributed to these…

  12. Mechanistic insights on acrylate insertion polymerization.

    PubMed

    Guironnet, Damien; Caporaso, Lucia; Neuwald, Boris; Göttker-Schnetmann, Inigo; Cavallo, Luigi; Mecking, Stefan

    2010-03-31

    Complexes [{(PwedgeO)PdMe}(n)] (1(n); PwedgeO = kappa(2)-P,O-Ar(2)PC(6)H(4)SO(2)O with Ar = 2-MeOC(6)H(4)) are a single-component precursor of the (PwedgeO)PdMe fragment devoid of additional coordinating ligands, which also promotes the catalytic oligomerization of acrylates. Exposure of 1(n) to methyl acrylate afforded the two diastereomeric chelate complexes [(PwedgeO)Pd{kappa(2)-C,O-CH(C(O)OMe)CH(2)CH(C(O)OMe)CH(2)CH(3)}] (3-meso and 3-rac) resulting from two consecutive 2,1-insertions of methyl acrylate into the Pd-Me bond with the same or opposite stereochemistry, respectively, in a 3:2 ratio as demonstrated by comprehensive NMR spectroscopic studies and single crystal X-ray diffraction. These six-membered chelate complexes are direct key models for intermediates of acrylate insertion polymerization, and also ethylene-acrylate copolymerization to high acrylate content copolymers. Studies of the binding of various substrates (pyridine, dmso, ethylene and methyl acrylate) to 3-meso and 3-rac show that hindered displacement of the chelating carbonyl moiety by pi-coordination of incoming monomer significantly retards, but does not prohibit, polymerization. For 3-meso,3-rac + C(2)H(4) right arrow over left arrow 3-meso-C(2)H(4,) 3-rac-C(2)H(4) an equilibrium constant K(353 K) approximately 2 x 10(-3) L mol(-1) was estimated. Reaction of 3-meso, 3-rac with methyl acrylate afforded higher insertion products [(PwedgeO)Pd(C(4)H(6)O(2))(n)Me] (n = 3, 4) as observed by electrospray ionization mass spectrometry (ESI-MS). Theoretical studies by DFT methods of consecutive acrylate insertion provide relative energies of intermediates and transition states, which are consistent with the aforementioned experimental observations, and give detailed insights to the pathways of multiple consecutive acrylate insertions. Acrylate insertion into 3-meso,3-rac is associated with an overall energy barrier of ca. 100 kJ mol(-1).

  13. Insertional mutagenesis by a hybrid piggyBac and sleeping beauty transposon in the rat.

    PubMed

    Furushima, Kenryo; Jang, Chuan-Wei; Chen, Diane W; Xiao, Ningna; Overbeek, Paul A; Behringer, Richard R

    2012-12-01

    A hybrid piggyBac/Sleeping Beauty transposon-based insertional mutagenesis system that can be mobilized by simple breeding was established in the rat. These transposons were engineered to include gene trap sequences and a tyrosinase (Tyr) pigmentation reporter to rescue the albinism of the genetic background used in the mutagenesis strategy. Single-copy transposon insertions were transposed into the rat genome by co-injection of plasmids carrying the transposon and RNA encoding piggyBac transposase into zygotes. The levels of transgenic Tyr expression were influenced by chromosomal context, leading to transgenic rats with different pigmentation that enabled visual genotyping. Transgenic rats designed to ubiquitously express either piggyBac or Sleeping Beauty transposase were generated by standard zygote injection also on an albino background. Bigenic rats carrying single-copy transposons at known loci and transposase transgenes exhibited coat color mosaicism, indicating somatic transposition. PiggyBac or Sleeping Beauty transposase bigenic rats bred with wild-type albino rats yielded offspring with pigmentation distinct from the initial transposon insertions as a consequence of germline transposition to new loci. The germline transposition frequency for Sleeping Beauty and piggyBac was ∼10% or about one new insertion per litter. Approximately 50% of the insertions occurred in introns. Chimeric transcripts containing endogenous and gene trap sequences were identified in Gabrb1 mutant rats. This mutagenesis system based on simple crosses and visual genotyping can be used to generate a collection of single-gene mutations in the rat.

  14. Insertional Mutagenesis by a Hybrid PiggyBac and Sleeping Beauty Transposon in the Rat

    PubMed Central

    Furushima, Kenryo; Jang, Chuan-Wei; Chen, Diane W.; Xiao, Ningna; Overbeek, Paul A.; Behringer, Richard R.

    2012-01-01

    A hybrid piggyBac/Sleeping Beauty transposon-based insertional mutagenesis system that can be mobilized by simple breeding was established in the rat. These transposons were engineered to include gene trap sequences and a tyrosinase (Tyr) pigmentation reporter to rescue the albinism of the genetic background used in the mutagenesis strategy. Single-copy transposon insertions were transposed into the rat genome by co-injection of plasmids carrying the transposon and RNA encoding piggyBac transposase into zygotes. The levels of transgenic Tyr expression were influenced by chromosomal context, leading to transgenic rats with different pigmentation that enabled visual genotyping. Transgenic rats designed to ubiquitously express either piggyBac or Sleeping Beauty transposase were generated by standard zygote injection also on an albino background. Bigenic rats carrying single-copy transposons at known loci and transposase transgenes exhibited coat color mosaicism, indicating somatic transposition. PiggyBac or Sleeping Beauty transposase bigenic rats bred with wild-type albino rats yielded offspring with pigmentation distinct from the initial transposon insertions as a consequence of germline transposition to new loci. The germline transposition frequency for Sleeping Beauty and piggyBac was ∼10% or about one new insertion per litter. Approximately 50% of the insertions occurred in introns. Chimeric transcripts containing endogenous and gene trap sequences were identified in Gabrb1 mutant rats. This mutagenesis system based on simple crosses and visual genotyping can be used to generate a collection of single-gene mutations in the rat. PMID:23023007

  15. Insertional Mutation on Mouse Chromosome 18 with Vestibular and Craniofacial Abnormalities

    PubMed Central

    Ting, C. N.; Kohrman, D.; Burgess, D. L.; Boyle, A.; Altschuler, R. A.; Gholizadeh, G.; Samuelson, L. C.; Jang, W.; Meisler, M. H.

    1994-01-01

    A dominant mutation was generated in transgenic mice as a consequence of insertional mutation. Heterozygous mice from transgenic line 9257 (Tg(9257)) are hyperactive with bidirectional circling behavior and have a distinctive facial appearance due to hypoplasia of the nasal bone. Morphological analysis of the inner ear revealed asymmetric abnormalities of the horizontal canal and flattening or invagination of the crista ampullaris, which can account for the circling behavior. The sensory epithelium appeared to be normal. The transgene insertion site was localized by in situ hybridization to the B1 band of mouse chromosome 18. Genetic mapping in an interspecific backcross demonstrated the gene order centromere--Tg(9257)--8.8 +/- 3.4--Grl-1, Egr-1, Fgf-1, Apc--14.7 +/- 4.3--Pdgfr. The phenotype and the mapping data suggest that the transgene may be inserted at the Twirler locus. Homozygosity for the transgene results in prenatal lethality, but compound heterozygotes carrying the Tw allele and the transgene are viable. The function of the closely linked ataxia locus is not disrupted by the transgene insertion. This insertional mutant will provide molecular access to genes located in the Twirler region of mouse chromosome 18. PMID:7511123

  16. A Macaque's-Eye View of Human Insertions and Deletions: Differences in Mechanisms

    PubMed Central

    Kvikstad, Erika M; Tyekucheva, Svitlana; Chiaromonte, Francesca; Makova, Kateryna D

    2007-01-01

    Insertions and deletions (indels) cause numerous genetic diseases and lead to pronounced evolutionary differences among genomes. The macaque sequences provide an opportunity to gain insights into the mechanisms generating these mutations on a genome-wide scale by establishing the polarity of indels occurring in the human lineage since its divergence from the chimpanzee. Here we apply novel regression techniques and multiscale analyses to demonstrate an extensive regional indel rate variation stemming from local fluctuations in divergence, GC content, male and female recombination rates, proximity to telomeres, and other genomic factors. We find that both replication and, surprisingly, recombination are significantly associated with the occurrence of small indels. Intriguingly, the relative inputs of replication versus recombination differ between insertions and deletions, thus the two types of mutations are likely guided in part by distinct mechanisms. Namely, insertions are more strongly associated with factors linked to recombination, while deletions are mostly associated with replication-related features. Indel as a term misleadingly groups the two types of mutations together by their effect on a sequence alignment. However, here we establish that the correct identification of a small gap as an insertion or a deletion (by use of an outgroup) is crucial to determining its mechanism of origin. In addition to providing novel insights into insertion and deletion mutagenesis, these results will assist in gap penalty modeling and eventually lead to more reliable genomic alignments. PMID:17941704

  17. A distinctly disorganised dwarf

    NASA Image and Video Library

    2016-03-28

    Despite being less famous than their elliptical and spiral galactic cousins, irregular dwarf galaxies, such as the one captured in this NASA/ESA Hubble Space Telescope image, are actually one of the most common types of galaxy in the Universe. Known as UGC 4459, this dwarf galaxy is located approximately 11 million light-years away in the constellation of Ursa Major (The Great Bear), a constellation that is also home to the Pinwheel Galaxy (M101), the Owl Nebula (M97), Messier 81, Messier 82 and several other galaxies all part of the M81 group. UGC 4459’s diffused and disorganised appearance is characteristic of an irregular dwarf galaxy. Lacking a distinctive structure or shape, irregular dwarf galaxies are often chaotic in appearance, with neither a nuclear bulge — a huge, tightly packed central group of stars — nor any trace of spiral arms — regions of stars extending from the centre of the galaxy. Astronomers suspect that some irregular dwarf galaxies were once spiral or elliptical galaxies, but were later deformed by the gravitational pull of nearby objects. Rich with young blue stars and older red stars, UGC 4459 has a stellar population of several billion. Though seemingly impressive, this is small when compared to the 200 to 400 billion stars in the Milky Way! Observations with Hubble have shown that because of their low masses, star formation is very low compared to larger galaxies. Only very little of their original gas has been turned into stars. Thus, these small galaxies are interesting to study to better understand primordial environments and the star formation process.

  18. The interaction of alphavirus E1 protein with exogenous domain III defines stages in virus-membrane fusion.

    PubMed

    Roman-Sosa, Gleyder; Kielian, Margaret

    2011-12-01

    Alphaviruses such as Semliki Forest virus (SFV) are enveloped viruses that infect cells through a low-pH-triggered membrane fusion reaction mediated by the transmembrane fusion protein E1. E1 drives fusion by insertion of its hydrophobic fusion loop into the cell membrane and refolding to a stable trimeric hairpin. In this postfusion conformation, the immunoglobulin-like domain III (DIII) and the stem region pack against the central core of the trimer. Membrane fusion and infection can be specifically inhibited by exogenous DIII, which binds to an intermediate in the E1 refolding pathway. Here we characterized the properties of the E1 target for interaction with exogenous DIII. The earliest target for DIII binding was an extended membrane-inserted E1 trimer, which was not detectable by assays for the stable postfusion hairpin. DIII binding provided a tool to detect this extended trimer and to define a series of SFV fusion-block mutants. DIII binding studies showed that the mutants were blocked in distinct steps in fusion protein refolding. Our results suggested that formation of the initial extended trimer was reversible and that it was stabilized by the progressive fold-back of the DIII and stem regions.

  19. Effect of Off-Axis Screw Insertion, Insertion Torque, and Plate Contouring on Locked Screw Strength

    PubMed Central

    Gallagher, Bethany; Silva, Matthew J.; Ricci, William M.

    2015-01-01

    Objectives This study quantifies the effects of insertion torque, off-axis screw angulation, and plate contouring on the strength of locking plate constructs. Methods Groups of locking screws (n = 6–11 screws) were inserted at 50%, 100%, 150%, and 200% of the manufacturer-recommended torque (3.2 Nm) into locking compression plates at various angles: orthogonal (control), 5-degree angle off-axis, and 10-degree angle off-axis. Screws were loaded to failure by a transverse force (parallel to the plate) either in the same (“+”) or opposite direction (“−”) of the initial screw angulation. Separately, locking plates were bent to 5 and 10-degree angles, with the bend apex at a screw hole. Locking screws inserted orthogonally into the apex hole at 100% torque were loaded to failure. Results Orthogonal insertion resulted in the highest average load to failure, 2577 ± 141 N (range, 2413–2778 N), whereas any off-axis insertion significantly weakened constructs (165–1285 N, at 100% torque) (P < 0.05). For “+” loading, torque beyond 100% did not increase strength, but 50% torque reduced screw strength (P < 0.05). Loading in the “−” direction consistently resulted in higher strengths than “+” loading (P < 0.05). Plate contouring of 5-degree angle did not significantly change screw strength compared with straight plates but contouring of 10-degree angle significantly reduced load to failure (P < 0.05). Conclusions To maximize the screw plate interface strength, locking screws should be inserted without cross-threading. The mechanical stability of locked screws is significantly compromised by loose insertion, off-axis insertion, or severe distortion of the locking mechanism. PMID:24343255

  20. Descemet's Stripping Automated Endothelial Keratoplasty Tissue Insertion Devices

    PubMed Central

    Khan, Salman Nasir; Shiakolas, Panos S.; Mootha, Venkateswara Vinod

    2015-01-01

    This review study provides information regarding the construction, design, and use of six commercially available endothelial allograft insertion devices applied for Descemet's stripping automated endothelial keratoplasty (DSAEK). We also highlight issues being faced in DSAEK and discuss the methods through which medical devices such as corneal inserters may alleviate these issues. Inserter selection is of high importance in the DSAEK procedure since overcoming the learning curve associated with the use of an insertion device is a time and energy consuming process. In the present review, allograft insertion devices were compared in terms of design, construction material, insertion technique, dimensions, incision requirements and endothelial cell loss to show their relative merits and capabilities based on available data in the literature. Moreover, the advantages/disadvantages of various insertion devices used for allograft insertion in DSAEK are reviewed and compared. The information presented in this review can be utilized for better selection of an insertion device for DSAEK. PMID:27051492

  1. A Monte Carlo study of peptide insertion into lipid bilayers: equilibrium conformations and insertion mechanisms.

    PubMed Central

    Maddox, Michael W; Longo, Marjorie L

    2002-01-01

    The membrane insertion behavior of two peptides, Magainin2 and M2 delta, was investigated by applying the Monte Carlo simulation technique to a theoretical model. The model included many novel aspects, such as a new semi-empirical lipid bilayer model and a new set of semi-empirical transfer energies, which reproduced the experimental insertion behavior of Magainin2 and M2 delta without parameter fitting. Additionally, we have taken into account diminished internal (intramolecular) hydrogen bonding at the N- and C-termini of helical peptides. All simulations were carried out at 305 K, above the membrane thermal phase transition temperature, and at pH 7.0. The peptide equilibrium conformations are discussed for a range of bilayers with tail polarities varying from octanol-like to alkane-like. Probability distributions of the individual amino-acid-residue positions show the dynamic nature of these equilibrium conformations. Two different insertion mechanisms for M2 delta, and a translocation mechanism for Magainin2, are described. A study of the effect of bilayer thickness on M2 delta insertion suggests a critical thickness above which insertion is unfavorable. Additionally, we did not need to use an orientational potential or array of hard cylinders to persuade M2 delta to insert perpendicular to the membrane surface. Instead, we found that diminished internal hydrogen bonding in the helical conformation anchored the termini in the headgroups and resulted in a nearly perpendicular orientation. PMID:11751313

  2. Two cases of anaphylaxis after laminaria insertion.

    PubMed Central

    Kim, Sang-Hoon; Chang, Yun-Hae; Kim, Woo-Kyoung; Kim, Yoon-Keun; Cho, Sang-Heon; Kim, You-Young; Min, Kyung-Up

    2003-01-01

    Anaphylaxis following laminaria insertion rarely occurs but may be a life-threatening condition. Laminaria tents, prepared from natural sea kelp, are commonly used prior to elective termination of pregnancy to achieve cervical dilatation. We report herein two cases of anaphylaxis caused by IgE-mediated hypersensitivity to laminaria. Two women, each of whom had undergone at least one previous abortion where a laminaria had been utilized, developed anaphylactic reaction following laminaria insertion. The reaction included urticaria, nausea, breathing difficulty, and hypotension. The patients subsequently underwent skin testing and measurement of serum specific IgE level to laminaria extract, and were shown to elicit positive responses to laminaria. The implication and impact of laminaria allergy on gynecologic procedures are significant and this allergy should be included in the list of differential diagnoses for hypersensitive reaction in gynecologic procedures. PMID:14676449

  3. INSERTION DEVICE ACTIVITIES FOR NSLS-II.

    SciTech Connect

    TANABE,T.; HARDER, D.A.; HULBERT, S.; RAKOWSKI, G.; SKARITKA, J.

    2007-06-25

    National Synchrotron Light Source-II (NSLS-II) will be a medium energy storage ring of 3GeV electron beam energy with sub-nm.rad horizontal emittance and top-off capability at 500mA. Damping wigglers will be used not only to reduce the beam emittance but also used as broadband sources for users. Cryo-Permanent Magnet Undulators (CPMUs) are considered for hard X-ray linear device, and permanent magnet based elliptically polarized undulators (EPUs) for variable polarization devices for soft X-ray. 6T superconducting wiggler with minimal fan angle will be installed in the second phase as well as quasi-periodic EPU for VUV and possibly high-temperature superconducting undulator. R&D plans have been established to pursue the performance enhancement of the baseline devices and to design new types of insertion devices. A new insertion device development laboratory will also be established.

  4. A small, insertable oven for boronization

    SciTech Connect

    Brouchous, D.A.; Diebold, D.A.; Doczy, M.L.

    1996-04-01

    A small insertable oven for benchmarking the boronizing characteristics of solid compounds, such as decaborane and carborane, has been developed for the Phaedrus-T tokamak. Assembly and installation of the oven are relatively easy as the oven design utilizes a Langmuir probe drive assembly, which is standard equipment on most tokamaks and allows the oven to be inserted into the tokamak without requiring a vent. Films deposited by heating carborane into the vapor state with the oven are found to be spatially nonuniform in both thickness and in the ratio of boron to carbon as compared to films deposited with trimethylboron, a gaseous compound. Overall plasma performance is not found to be greatly affected by whether decaborane, carborane or trimethylboron is used for boronization in Phaedrus-T. {copyright} {ital 1996 American Institute of Physics.} {lt}ii;010512{gt}

  5. The Evaluation of Some Threaded Inserts

    DTIC Science & Technology

    1979-10-01

    29 600 AVE z 30,400 44 AFML- TR- 78-10/ TABLE 26 RESULTS OF FATIGUE TESTS OF 7078 -T73 ALUMINUM ALLOY WITH 1/4-28 THREADED INSERTS ONLY SPEC. .. NSRT_...PAT INHAT MAX. CYCLES TO C0WMENTS NO. O-BOLT MANUFACTURNA PART NR , INSTALLED STRESS PAILURE INSERT BY AILURE ONLY LOCATION 2-4 -- KAYNAR X8000-4 AFMK...Q r-4C’.1t-- N b C-4 t-4 #-4- w 4) 4J (N(’ IN Nrr N N 04 NINe. N NN Nr -(-N mI I iI IImI -- A",ý ý- . 1.ý ýý ý6%ý - I 79 AFML-TR-78-1 07 I I! I 4. zzI

  6. Perception and Action in Teleoperated Needle Insertion

    PubMed Central

    Nisky, Ilana; Pressman, Assaf; Pugh, Carla M.; Mussa-Ivaldi, Ferdinando A.; Karniel, Amir

    2015-01-01

    We studied the effect of delay on perception and action in contact with a force field that emulates elastic soft tissue with a rigid nonlinear boundary. Such field is similar to forces exerted on a needle during teleoperated needle insertion. We found that delay causes motor underestimation of the stiffness of this nonlinear soft tissue, without perceptual change. These experimental results are supported by simulation of a simplified mechanical model of the arm and neural controller, and a model for perception of stiffness, which is based on regression in the force-position space. In addition, we show that changing the gain of the teleoperation channel cancels the motor effect of delay without adding perceptual distortion. We conclude that it is possible to achieve perceptual and motor transparency in virtual one-dimensional remote needle insertion task. PMID:26379813

  7. Probe Insertion Apparatus with Inflatable Seal

    NASA Technical Reports Server (NTRS)

    Trimarchi, Paul A.

    1991-01-01

    A sealing apparatus for inserting a probe into a pressure vessel having an elongated opening includes Ii pair of resiliently defQrmable seals opposingly disposed in sealing engagement with each other. A retainer is connected to the pressure vessel around the elongated opening and holds the pair of seals rigidly to the pressure vessel. A wedge is engageable with the pair of seals and carries the probe, for longitudinally translating the probe in the pressure vessel.

  8. Comparison of Insertional RNA Editing in Myxomycetes

    PubMed Central

    Chen, Cai; Frankhouser, David; Bundschuh, Ralf

    2012-01-01

    RNA editing describes the process in which individual or short stretches of nucleotides in a messenger or structural RNA are inserted, deleted, or substituted. A high level of RNA editing has been observed in the mitochondrial genome of Physarum polycephalum. The most frequent editing type in Physarum is the insertion of individual Cs. RNA editing is extremely accurate in Physarum; however, little is known about its mechanism. Here, we demonstrate how analyzing two organisms from the Myxomycetes, namely Physarum polycephalum and Didymium iridis, allows us to test hypotheses about the editing mechanism that can not be tested from a single organism alone. First, we show that using the recently determined full transcriptome information of Physarum dramatically improves the accuracy of computational editing site prediction in Didymium. We use this approach to predict genes in the mitochondrial genome of Didymium and identify six new edited genes as well as one new gene that appears unedited. Next we investigate sequence conservation in the vicinity of editing sites between the two organisms in order to identify sites that harbor the information for the location of editing sites based on increased conservation. Our results imply that the information contained within only nine or ten nucleotides on either side of the editing site (a distance previously suggested through experiments) is not enough to locate the editing sites. Finally, we show that the codon position bias in C insertional RNA editing of these two organisms is correlated with the selection pressure on the respective genes thereby directly testing an evolutionary theory on the origin of this codon bias. Beyond revealing interesting properties of insertional RNA editing in Myxomycetes, our work suggests possible approaches to be used when finding sequence motifs for any biological process fails. PMID:22383871

  9. J85 Rejuvenation Through Technology Insertion

    DTIC Science & Technology

    2000-10-01

    and Sabre 75 business addition to military production, the J85 was jets . Number Model Produced Aircraft Type(s) Engine Type Thrust (lbs) J85-GE-4 740...REJUVENATION THROUGH TECHNOLOGY INSERTION T.A. Brisken, P.N. Howell, A.C. Ewing Military Engines Operation GE Aircraft Engines 1 Neumann Way Cincinnati...OH 45215, USA Summary thrust to weight ratio turbojet engines with potential application to early cruise missiles and drones. The history of the

  10. Anionic phospholipids modulate peptide insertion into membranes.

    PubMed

    Liu, L P; Deber, C M

    1997-05-06

    While the insertion of a hydrophobic peptide or membrane protein segment into the bilayer can be spontaneous and driven mainly by the hydrophobic effect, anionic lipids, which comprise ca. 20% of biological membranes, provide a source of electrostatic attractions for binding of proteins/peptides into membranes. To unravel the interplay of hydrophobicity and electrostatics in the binding of peptides into membranes, we designed peptides de novo which possess the typical sequence Lys-Lys-Ala-Ala-Ala-X-Ala-Ala-Ala-Ala-Ala-X-Ala-Ala-Trp-Ala-Ala-X-Ala-Al a-Ala-Lys-Lys-Lys-Lys-amide, where X residues correspond to "guest" residues which encompass a range of hydrophobicity (Leu, Ile, Gly, and Ser). Circular dichroism spectra demonstrated that peptides were partially (40-90%) random in aqueous buffer but were promoted to form 100% alpha-helical structures by anionic lipid micelles. In neutral lipid micelles, only the relatively hydrophobic peptides (X = L and I) spontaneously adopted the alpha-helical conformation, but when 25% of negatively charged lipids were mixed in to mimic the content of anionic lipids in biomembranes, the less hydrophobic (X = S and G) peptides then formed alpha-helical conformations. Consistent with these findings, fluorescence quenching by the aqueous-phase quencher iodide indicated that in anionic (dimyristoylphosphatidylglycerol) vesicles, the peptide Trp residue was buried in the lipid vesicle hydrophobic core, while in neutral (dimyristoylphosphatidylcholine) vesicles, only hydrophobic (X = L and I) peptides were shielded from the aqueous solution. Trp emission spectra of peptides in the presence of phospholipids doxyl-labeled at the 5-, 7-, 10-, 12-, and 16-fatty acid positions implied not only a transbilayer orientation for inserted peptides but also that mixed peptide populations (transbilayer + surface-associated) may arise. Overall results suggest that for hydrophobic peptides with segmental threshold hydrophobicity below that which

  11. Thermally Activated Retainers For Insertion In Gaps

    NASA Technical Reports Server (NTRS)

    Grimaldi, Margaret E.; Hartz, Leslie S.

    1992-01-01

    Mechanical retainers of new type for use with gap filler easy to install and to attach themselves securely. Concept based on shape-memory properties of metal alloy Nitinol, alloy of nickel and titanium. Retainers conceived for use with Space Shuttle insulating tiles but used on other assemblies of blocks or tiles configured similarly. Tabs bent outward made flush by cooling below memory transition temperature. After insertion in gap and reheating, tabs spring outward.

  12. Umbilical cord insertion: normal location in neonates.

    PubMed

    Salgado, L; Paz, J E

    1992-12-01

    The distances between the xyphoid appendix and the insertion point of the umbilical cord (XU) and between the xyphoid appendix and upper edge of the pubic symphysis (XP) were measured in 201 newborn infants. The mean ratio XU/XP was 0.62 (S.D. 0.044) with no differences between sexes nor correlations with weight or length. Ratios lying between 0.53 and 0.71 can be considered as within the normal range.

  13. Comparison of insertional RNA editing in Myxomycetes.

    PubMed

    Chen, Cai; Frankhouser, David; Bundschuh, Ralf

    2012-01-01

    RNA editing describes the process in which individual or short stretches of nucleotides in a messenger or structural RNA are inserted, deleted, or substituted. A high level of RNA editing has been observed in the mitochondrial genome of Physarum polycephalum. The most frequent editing type in Physarum is the insertion of individual Cs. RNA editing is extremely accurate in Physarum; however, little is known about its mechanism. Here, we demonstrate how analyzing two organisms from the Myxomycetes, namely Physarum polycephalum and Didymium iridis, allows us to test hypotheses about the editing mechanism that can not be tested from a single organism alone. First, we show that using the recently determined full transcriptome information of Physarum dramatically improves the accuracy of computational editing site prediction in Didymium. We use this approach to predict genes in the mitochondrial genome of Didymium and identify six new edited genes as well as one new gene that appears unedited. Next we investigate sequence conservation in the vicinity of editing sites between the two organisms in order to identify sites that harbor the information for the location of editing sites based on increased conservation. Our results imply that the information contained within only nine or ten nucleotides on either side of the editing site (a distance previously suggested through experiments) is not enough to locate the editing sites. Finally, we show that the codon position bias in C insertional RNA editing of these two organisms is correlated with the selection pressure on the respective genes thereby directly testing an evolutionary theory on the origin of this codon bias. Beyond revealing interesting properties of insertional RNA editing in Myxomycetes, our work suggests possible approaches to be used when finding sequence motifs for any biological process fails.

  14. STS-115 Preflight Documentation - Post Insertion Training

    NASA Image and Video Library

    2005-12-12

    JSC2005-E-47411 (12 Dec. 2005) --- Astronauts Heidemarie M. Stefanyshyn-Piper (foreground) and Joseph R. (Joe) Tanner, both STS-115 mission specialists, give a thumbs-up signal to indicate preparedness for a training session in one of the full-scale trainers in the Space Vehicle Mockup Facility at Johnson Space Center. Attired in training versions of the shuttle launch and entry suit, the two are seated on the middeck for a post insertion training session.

  15. Probe insertion apparatus with inflatable seal

    NASA Technical Reports Server (NTRS)

    Trimarchi, Paul A. (Inventor)

    1990-01-01

    A sealing apparatus is disclosed for inserting a probe into a pressure vessel having an elongated opening includes a pair of resiliently deformable seals opposingly disposed in sealing engagement with each other. A retainer is connected to the pressure vessel around the elongated opening and holds the pair of seals rigidly to the pressure vessel. A wedge is engageable with the pair of seals and carries the probe, for longitudinally translating the probe in pressure vessel.

  16. Thermally Activated Retainers For Insertion In Gaps

    NASA Technical Reports Server (NTRS)

    Grimaldi, Margaret E.; Hartz, Leslie S.

    1992-01-01

    Mechanical retainers of new type for use with gap filler easy to install and to attach themselves securely. Concept based on shape-memory properties of metal alloy Nitinol, alloy of nickel and titanium. Retainers conceived for use with Space Shuttle insulating tiles but used on other assemblies of blocks or tiles configured similarly. Tabs bent outward made flush by cooling below memory transition temperature. After insertion in gap and reheating, tabs spring outward.

  17. Inserting new technology into small missions

    NASA Technical Reports Server (NTRS)

    Deutsch, L. J.

    2001-01-01

    Part of what makes small missions small is that they have less money. Executing missions at low cost implies extensive use of cost sharing with other missions or use of existing solutions. However, in order to create many small missions, new technology must be developed, applied, and assimilated. Luckily, there are methods for creating new technology and inserting it into faster-better-cheaper (FBC) missions.

  18. DEVICE FOR CONTROLLING INSERTION OF ROD

    DOEpatents

    Beaty, B.J.

    1958-10-14

    A device for rapidly inserting a safety rod into a nuclear reactor upon a given signal or in the event of a power failure in order to prevent the possibility of extensive damage caused by a power excursion is described. A piston is slidably mounted within a vertical cylinder with provision for an electromagnetic latch at the top of the cylinder. This assembly, with a safety rod attached to the piston, is mounted over an access port to the core region of the reactor. The piston is normally latched at the top of the cylinder with the safety rod clear of the core area, however, when the latch is released, the piston and rod drop by their own weight to insert the rod. Vents along the side of the cylinder permit the escape of the air entrapped under the piston over the greater part of the distance, however, at the end of the fall the entrapped air is compressed thereby bringing the safety rod gently to rest, thus providing for a rapid automatic insertion of the rod with a minimum of structural shock.

  19. Beamline Insertions Manager at Jefferson Lab

    SciTech Connect

    Johnson, Michael C.

    2015-09-01

    The beam viewer system at Jefferson Lab provides operators and beam physicists with qualitative and quantitative information on the transverse electron beam properties. There are over 140 beam viewers installed on the 12 GeV CEBAF accelerator. This paper describes an upgrade consisting of replacing the EPICS-based system tasked with managing all viewers with a mixed system utilizing EPICS and high-level software. Most devices, particularly the beam viewers, cannot be safely inserted into the beam line during high-current beam operations. Software is partly responsible for protecting the machine from untimely insertions. The multiplicity of beam-blocking and beam-vulnerable devices motivates us to try a data-driven approach. The beamline insertions application components are centrally managed and configured through an object-oriented software framework created for this purpose. A rules-based engine tracks the configuration and status of every device, along with the beam status of the machine segment containing the device. The application uses this information to decide on which device actions are allowed at any given time.

  20. App-assisted external ventricular drain insertion.

    PubMed

    Eftekhar, Behzad

    2016-09-01

    The freehand technique for insertion of an external ventricular drain (EVD) is based on fixed anatomical landmarks and does not take individual variations into consideration. A patient-tailored approach based on augmented-reality techniques using devices such as smartphones can address this shortcoming. The Sina neurosurgical assist (Sina) is an Android mobile device application (app) that was designed and developed to be used as a simple intraoperative neurosurgical planning aid. It overlaps the patient's images from previously performed CT or MRI studies on the image seen through the device camera. The device is held by an assistant who aligns the images and provides information about the relative position of the target and EVD to the surgeon who is performing EVD insertion. This app can be used to provide guidance and continuous monitoring during EVD placement. The author describes the technique of Sina-assisted EVD insertion into the frontal horn of the lateral ventricle and reports on its clinical application in 5 cases as well as the results of ex vivo studies of ease of use and precision. The technique has potential for further development and use with other augmented-reality devices.

  1. U-insertion/deletion Edited Sequence Database.

    PubMed

    Simpson, L; Wang, S H; Thiemann, O H; Alfonzo, J D; Maslov, D A; Avila, H A

    1998-01-01

    Uridine insertion/deletion RNA editing is a post-transcriptional RNA modification occurring in the mitochondria of kinetoplastid protozoa. The U-insertion/deletion Edited Sequence Database is a compilation of mitochondrial genes and edited mRNAs from five kinetoplastid species. It contains separate files with the DNA, mRNA (both unedited and edited) and predicted protein sequences, as well as alignments of the Leishmania tarentolae and Trypanosoma brucei protein sequences from edited and unedited genes. The sequence files are in GCG format. A 'map' sequence file showing the location of U-deletions, U-insertions and the translated amino acid sequences is also provided for each gene. Genomic maps for each species are also provided with clickable genes, including maxicircle-encoded gRNAs. Sets of aligned nuclear rRNA sequences from kinetoplastid protozoa are also provided, which were used for phylogenetic reconstructions in an analysis of the origin of RNA editing. The database is available through the World Wide Web as an HTML document at the URLhttp://www.lifesci.ucla.edu/RNA/trypanosome/ database.html

  2. Rack Insertion End Effector (RIEE) guidance

    NASA Technical Reports Server (NTRS)

    Malladi, Narasimha S.

    1994-01-01

    NASA-KSC has developed a mechanism to handle and insert Racks into the Space Station Logistic Modules. This mechanism consists of a Base with 3 motorized degrees of freedom, a 3 section motorized Boom that goes from 15 to 44 feet in length, and a Rack Insertion End Effector (RIEE) with 5 hand wheels for precise alignment. During the 1993 NASA-ASEE Summer Faculty Fellowship Program at KSC, I designed an Active Vision (Camera) Arrangement and developed an algorithm to determine (1) the displacements required by the Room for its initial positioning and (2) the rotations required at the five hand-wheels of the RIEE, for the insertion of the Rack, using the centroids fo the Camera Images of the Location Targets in the Logistic Module. Presently, during the summer of '94, I completed the preliminary design of an easily portable measuring instrument using encoders to obtain the 3-Dimensional Coordinates of Location Targets in the Logistics Module relative to the RIEE mechanism frame. The algorithm developed in '93 can use the output of this instrument also. Simplification of the '93 work and suggestions for the future work are discussed.

  3. Insights into the buffer effect observed in blended lithium insertion electrodes

    NASA Astrophysics Data System (ADS)

    Heubner, C.; Liebmann, T.; Lämmel, C.; Schneider, M.; Michaelis, A.

    2017-09-01

    Blending of lithium insertion compounds is a promising approach to design advanced electrodes for lithium-ion batteries. In spite of considerable improvements regarding the power density, some basic interactions between the constituents of the blend are still under discussion. Herein we quantify the so-called buffer effect observed in blended insertion electrodes for the first time by using a special experimental setup and a model-like blended insertion electrode. Internal dynamics of the blend are investigated during defined pulse loads and subsequent relaxation. The results reveal significant electrochemical interactions between the constituents, depending on the applied current and the overpotential, respectively. These interactions are attributed to thermodynamic factors of emerging and converging equilibrium potentials of the constituents during charging-discharging and subsequent relaxation. This buffer effect enables the preparation of electrodes with high energy density and very good rate capability by combining active materials with high specific capacity and fast kinetics.

  4. Force measurement of insertion of cochlear implant electrode arrays in-vitro: Comparison of surgeon to automated insertion tool

    PubMed Central

    Majdani, O; Hussong, A; Rau, TS; Wittkopf, J; Lenarz, T; Labadie, RF

    2016-01-01

    Conclusions We have demonstrated that an automated insertion tool (a.k.a. robot) can be used to duplicate a complex surgical motion in inserting cochlear implant electrode arrays via the “advance-off-stylet” technique (AOS). As compared to human operators, the forces generated by the robot were slightly larger but the robot was more reliable (i.e. less force maxima). Objectives We present force data collected during cochlear implant electrode insertion by human operators and by an automated insertion tool (a.k.a. robot). Methods Using a three-dimensional, anatomically-correct, translucent model of the scala tympani chamber of the cochlea, cochlear implant electrodes were inserted either by one of three surgeons (26 insertions) or by the robotic insertion tool (8 insertions). Force was recorded using a load beam cell calibrated for expected forces of less than 0.1 Newtons. The insertions were also videotaped to allow correlation of force with depth of penetration into the cochlea and speed of insertion. Results Average insertion force by the surgeons was 0.004±0.001N and for the insertion tool 0.005±0.014N (p < 0.00001, Student’s t-test). While the average insertion force of the automated tool was larger than that of the surgeons, the surgeons did have intermittent peaks during the AOS component of the insertion (between 120° and 200°). PMID:19484593

  5. Epidural insertion simulator of higher insertion resistance & drop rate after puncture.

    PubMed

    Naemura, K; Sakai, A; Hayashi, T; Saito, H

    2008-01-01

    Accidents such as dural puncture remain one of the problems of epidural anesthesia, and unskilled doctors can repeat such accidents. The purpose of the current research was to provide a new simulator for epidural insertion training. No reference data regarding the resistance force used when inserting a needle into patients have been reported. A comparative study was conducted to aid in the development of a new simulator. Pork loin (n=5) were employed as a substitute for patients. Thickness was set at 2 cm so as to improve the reproducibility. The authors took the conventional simulator apart, and picked a block as an analogue of muscle and ligamentum flavum. A new simulator was made of a melamine foam resin block and a latex rubber sheet. An epidural needle fixed on a motorized stage was inserted at the speed of 2 mm per second. The reaction force was measured while the needle was inserted into each specimen. Waveform of the pork loin exhibited two slopes of different inclines up to peaks and then falls after puncture. The conventional simulator showed a simple increase up to peak and a slow fall after puncture. In contrast, the new simulator showed two slopes up to peak and then a sudden fall after puncture. The insertion resistances were 2.5 N/s for the porcine, 0.8 N/s for the conventional and 2.1 N/s for the new simulator. The drop rates were 5 N/s for the porcine, 0.6 N/s for the conventional and 24 N/s for the new simulator. The higher insertion resistance and drop rate for the new simulator than the conventional simulator will be suitable for epidural insertion training.

  6. Can a virtual reality assessment of fine motor skill predict successful central line insertion?

    PubMed

    Mohamadipanah, Hossein; Parthiban, Chembian; Nathwani, Jay; Rutherford, Drew; DiMarco, Shannon; Pugh, Carla

    2016-10-01

    Due to the increased use of peripherally inserted central catheter lines, central lines are not performed as frequently. The aim of this study is to evaluate whether a virtual reality (VR)-based assessment of fine motor skills can be used as a valid and objective assessment of central line skills. Surgical residents (N = 43) from 7 general surgery programs performed a subclavian central line in a simulated setting. Then, they participated in a force discrimination task in a VR environment. Hand movements from the subclavian central line simulation were tracked by electromagnetic sensors. Gross movements as monitored by the electromagnetic sensors were compared with the fine motor metrics calculated from the force discrimination tasks in the VR environment. Long periods of inactivity (idle time) during needle insertion and lack of smooth movements, as detected by the electromagnetic sensors, showed a significant correlation with poor force discrimination in the VR environment. Also, long periods of needle insertion time correlated to the poor performance in force discrimination in the VR environment. This study shows that force discrimination in a defined VR environment correlates to needle insertion time, idle time, and hand smoothness when performing subclavian central line placement. Fine motor force discrimination may serve as a valid and objective assessment of the skills required for successful needle insertion when placing central lines. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Needle steering for robot-assisted insertion into soft tissue: A survey

    NASA Astrophysics Data System (ADS)

    Gao, Dedong; Lei, Yong; Zheng, Haojun

    2012-07-01

    Needle insertion is a common surgical procedure used in diagnosis and treatment. The needle steering technologies make continuous developments in theoretical and practical aspects along with the in-depth research on needle insertion. It is necessary to summarize and analyze the existing results to promote the future development of theories and applications of needle insertion. Thus, a survey of the state of the art of research is presented on algorithms of needle steering techniques, the surgical robots and devices. Based on the analysis of the needle insertion procedure, the concept of needle steering is defined as a kinematics problem, which is to place the needle at the target and avoid the obstacles. The needle steering techniques, including the artificial potential field method and the nonholonomic model, are introduced to control the needles for improving the accuracy. Based on the quasi-static thinking, the virtual spring model and the cantilever-beam model are developed to calculate the amount of needle deflection and generate the needle path. The phantoms instead of the real tissue are used to verify the models mentioned in most of the experimentations. For the desired needle trajectories, the image-guided robotic devices and some novel needles are presented to achieve the needle steering. Finally, the challenges are provided involving the controllability of the long flexible needle and the properties of soft tissue. The results and investigations can be used for further study on the precision and accuracy of needle insertion.

  8. Nano-composite insert in 1D waveguides for control of elastic power flow.

    PubMed

    Vignesh, P S; Mitra, Mira; Gopalakrishnan, S

    2007-01-24

    In this paper, carbon nanotube embedded polymer composite/nano-composites are used to regulate power flow from its source to other parts of the structure. This is done by inserting nano-composite strips in the waveguides which are modelled here as isotropic Euler-Bernoulli beams with axial, transverse and rotational degrees of freedom. The power flow is due to wave propagation resulting from a high frequency broadband impulse load. The underlying concept is that the high stiffness of the insert reduces the wave transmission between different parts of the structures. The simulations are done using a wavelet based spectral finite element (WSFE) technique which is specially tailored for such high frequency wave propagation analysis. Numerical experiments are performed to illustrate the use of inserts in maintaining the power flow in a certain region of the structure below a given threshold value which may be specified depending on various applications. The effects of parameters such as the volume fraction of carbon nanotube (CNT) in the polymer, and the length and position of the inserts are also studied. These studies help in defining the optimal volume fraction of CNT and length of the insert for a specified structural configuration.

  9. An Algorithm for Defining Somatization in Children

    PubMed Central

    Postilnik, Inna; Eisman, Howard D.; Price, Rebecca; Fogel, Joshua

    2006-01-01

    Introduction Defining somatization in pediatric populations presents a unique challenge, because DSM-IV somatization criteria may be inadequate for identifying a child with somatization. Two approaches exist. Child somatization has frequently been rooted in a questionnaire model, focusing on child or parent responses to assess how well a child conforms to a specific mental health profile. Others use a medical diagnosis model, designating a child with somatization as those for whom a limited number of medical measures have failed to reveal a pathological source of symptoms. Method We incorporate concepts based upon a literature review from January 1994 to June 2005 of PubMed, PsycINFO, and CINAHL on classification and diagnosis of somatization in children ages 6 to 12. Our goal is to understand in depth the topic and suggest a way to better understand and classify somatization in children. Results We incorporate an integrative approach toward defining child somatization and propose an algorithm to step-by-step classify children with somatic symptoms into three distinct groups: sick, somatizers, and well. This approach includes information from self-report questionnaire, physician questionnaire, and the child’s medical chart. Conclusion This new algorithm suggests an approach for differentiating primary care pediatric clinic visitors into three distinct groups. Although used in clinical practice, empirical validation is necessary to further validate this algorithm. PMID:18392196

  10. 38. INTERIOR VIEW, DENISON MULTIPRESS FOR INSERTION OF WEDGES ONTO ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    38. INTERIOR VIEW, DENISON MULTI-PRESS FOR INSERTION OF WEDGES ONTO HANDLES AND CUTTING OFF SCRAP END OF HANDLE FOLLOWING WEDGE INSERTION, BRIAN KIMBLE, OPERATOR - Warwood Tool Company, Foot of Nineteenth Street, Wheeling, Ohio County, WV

  11. Estimation of insertion depth angle based on cochlea diameter and linear insertion depth: a prediction tool for the CI422.

    PubMed

    Franke-Trieger, Annett; Mürbe, Dirk

    2015-11-01

    Beside the cochlear size, the linear insertion depth (LID) influences the insertion depth angle of cochlear implant electrode arrays. For the specific implant CI422 the recommended LID is not fixed but can vary continuously between 20 and 25 mm. In the current study, the influence of cochlea size and LID on the final insertion depth angle was investigated to develop a prediction tool for the insertion depth angle by means of cochlea diameter and LID. Preoperative estimation of insertion depth angles might help surgeons avoid exceeding an intended insertion depth, especially with respect to low-frequency residual hearing preservation. Postoperative, high-resolution 3D-radiographs provided by Flat Panel Computed Volume Tomography (FPCT) were used to investigate the insertion depth angle in 37 CI422 recipients. Furthermore, the FPCT images were used to measure linear insertion depth and diameter of the basal turn of the cochlea. A considerable variation of measured insertion depth angles ranging from 306° to 579° was identified. The measured linear insertion depth ranged from -18.6 to 26.2 mm and correlated positively with the insertion depth angle. The cochlea diameter ranged from 8.11 to 10.42 mm and correlated negatively with the insertion depth angle. The results suggest that preoperatively measured cochlea diameter combined with the option of different array positions by means of LID may act as predictors for the final insertion depth angle.

  12. Tail-anchored Protein Insertion in Mammals

    PubMed Central

    Cardani, Silvia; Maroli, Annalisa; Vitiello, Adriana; Soffientini, Paolo; Crespi, Arianna; Bram, Richard F.

    2016-01-01

    The GET (guided entry of tail-anchored proteins)/TRC (transmembrane recognition complex) pathway for tail-anchored protein targeting to the endoplasmic reticulum (ER) has been characterized in detail in yeast and is thought to function similarly in mammals, where the orthologue of the central ATPase, Get3, is known as TRC40 or Asna1. Get3/TRC40 function requires an ER receptor, which in yeast consists of the Get1/Get2 heterotetramer and in mammals of the WRB protein (tryptophan-rich basic protein), homologous to yeast Get1, in combination with CAML (calcium-modulating cyclophilin ligand), which is not homologous to Get2. To better characterize the mammalian receptor, we investigated the role of endogenous WRB and CAML in tail-anchored protein insertion as well as their association, concentration, and stoichiometry in rat liver microsomes and cultured cells. Functional proteoliposomes, reconstituted from a microsomal detergent extract, lost their activity when made with an extract depleted of TRC40-associated proteins or of CAML itself, whereas in vitro synthesized CAML and WRB together were sufficient to confer insertion competence to liposomes. CAML was found to be in ∼5-fold excess over WRB, and alteration of this ratio did not inhibit insertion. Depletion of each subunit affected the levels of the other one; in the case of CAML silencing, this effect was attributable to destabilization of the WRB transcript and not of WRB protein itself. These results reveal unanticipated complexity in the mutual regulation of the TRC40 receptor subunits and raise the question as to the role of the excess CAML in the mammalian ER. PMID:27226539

  13. Analytic closed orbit analysis for RHIC insertion

    SciTech Connect

    Lee, S.Y. . Dept. of Physics); Tepikian, S. )

    1991-01-01

    Analytic closed orbit analysis is performed to evaluate the tolerance of quadrupole misalignment and dipole errors (b{sub 0},a{sub 0}) in the RHIC insertion. Sensitivity coefficients of these errors are tabulated for different {beta}{sup 0} values. Using these sensitivity tables, we found that the power supplies ripple of 10{sup {minus}4} can cause closed orbit motion of 0.05 mm at the IP in comparison with the rms beam size of 0.3 mm. It is desirable to have the power supply ripple less than 10{sup {minus}5}. 2 refs., 1 fig., 2 tabs.

  14. Phoenix's Probe Inserted in Martian Soil

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Phoenix Mars lander's robotic-arm camera took this image of the spacecraft's thermal and electrical-conductivity probe (TECP) inserted into Martian soil on day 149 of the mission. Phoenix landed on Mars' northern plains on May 25, 2008, landing.

    The robotic-arm camera acquired this image at 16:02:41 local solar time. The camera pointing was elevation -72.6986 degrees and azimuth 2.1093 degrees.

    The Phoenix mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  15. Compiler-assisted static checkpoint insertion

    NASA Technical Reports Server (NTRS)

    Long, Junsheng; Fuchs, W. K.; Abraham, Jacob A.

    1992-01-01

    This paper describes a compiler-assisted approach for static checkpoint insertion. Instead of fixing the checkpoint location before program execution, a compiler enhanced polling mechanism is utilized to maintain both the desired checkpoint intervals and reproducible checkpoint 1ocations. The technique has been implemented in a GNU CC compiler for Sun 3 and Sun 4 (Sparc) processors. Experiments demonstrate that the approach provides for stable checkpoint intervals and reproducible checkpoint placements with performance overhead comparable to a previously presented compiler assisted dynamic scheme (CATCH) utilizing the system clock.

  16. Photograph of moon after transearth insertion

    NASA Image and Video Library

    1969-05-24

    AS10-27-3956 (24 May 1969) --- This photograph of the moon was taken after trans-Earth insertion when the Apollo 10 spacecraft was high above the lunar equator near 27 degrees east longitude. North is about 20 degrees left of the top of the photograph. Apollo Landing Site 3 is on the lighted side of the terminator in a dark area just north of the equator. Apollo Landing Site 2 is near the lower left margin of the Sea of Tranquility (Mare Tranquillitatis), which is the large, dark area near the center of the photograph.

  17. New percutaneously inserted spinal fixation system.

    PubMed

    Teitelbaum, George P; Shaolian, Samuel; McDougall, Cameron G; Preul, Mark C; Crawford, Neil R; Sonntag, Volker K H

    2004-03-15

    We describe a new percutaneous minimally invasive spinal fixation system based on pedicle screws and inflatable rods. The rods are inserted in a flexible state and harden following deployment. We test this system in terms of biocompatibility, ferromagnetism, magnetic resonance artifact production, bench top mechanical testing, ease of insertion within cadavers, potential thermal damage to paraspinous muscles in pigs, and long-term device tolerability in sheep. To determine the safety and utility of this system before its use in human subjects. Composite materials and epoxy compounds have been used safely in a variety of implanted medical devices for years with no signs of systemic toxicity or significant device failures. Long-term biocompatibility test of system components was conducted according to International Standards Organization 10993 and Food and Drug Administration Blue Book Memorandum #G95-1 standards. Device components were assessed for magnetic deflection and torque and imaged in a 1.5 Tesla magnetic resonance unit. Full constructs of the system were tested for compression strength, torque, and fatigue per American Society for Testing and Materials F1717 standards. The system was deployed using C-arm fluoroscopic guidance in 11 cadavers and 2 live sheep. Further, the inflatable rods were tested for exothermic damage to paraspinous musculature in 2 pigs. All system components were found to be biocompatible, nonferromagnetic, and produce little magnetic resonance artifact. Compression and torque results for the new system were found to be comparable to standard metallic pedicle screw and rod fixation systems. However, the new system displayed a superior modulus of elasticity relative to standard surgical systems. The new system endured 5 million cycles of repetitive compressions without breakage or significant wear. All cadaver and sheep insertions were performed successfully. Sheep suffered no complications, and minimal blood loss occurred during device

  18. Artists's Conception of Cassini Saturn Orbit Insertion

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This is an artists concept of Cassini during the Saturn Orbit Insertion (SOI) maneuver, just after the main engine has begun firing. The spacecraft is moving out of the plane of the page and to the right (firing to reduce its spacecraft velocity with respect to Saturn) and has just crossed the ring plane.

    The SOI maneuver, which is approximately 90 minutes long, will allow Cassini to be captured by Saturn's gravity into a five-month orbit.Cassini's close proximity to the planet after the maneuver offers a unique opportunity to observe Saturn and its rings at extremely high resolution.

  19. Phoenix's Probe Inserted in Martian Soil

    NASA Technical Reports Server (NTRS)

    2008-01-01

    The Phoenix Mars lander's robotic-arm camera took this image of the spacecraft's thermal and electrical-conductivity probe (TECP) inserted into Martian soil on day 149 of the mission. Phoenix landed on Mars' northern plains on May 25, 2008, landing.

    The robotic-arm camera acquired this image at 16:02:41 local solar time. The camera pointing was elevation -72.6986 degrees and azimuth 2.1093 degrees.

    The Phoenix mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  20. Cassini magnetometer observations during Saturn orbit insertion.

    PubMed

    Dougherty, M K; Achilleos, N; Andre, N; Arridge, C S; Balogh, A; Bertucci, C; Burton, M E; Cowley, S W H; Erdos, G; Giampieri, G; Glassmeier, K-H; Khurana, K K; Leisner, J; Neubauer, F M; Russell, C T; Smith, E J; Southwood, D J; Tsurutani, B T

    2005-02-25

    Cassini's successful orbit insertion has provided the first examination of Saturn's magnetosphere in 23 years, revealing a dynamic plasma and magnetic environment on short and long time scales. There has been no noticeable change in the internal magnetic field, either in its strength or its near-alignment with the rotation axis. However, the external magnetic field is different compared with past spacecraft observations. The current sheet within the magnetosphere is thinner and more extended, and we observed small diamagnetic cavities and ion cyclotron waves of types that were not reported before.

  1. Commercial Generic Bioprocessing Apparatus Science Insert - 03

    NASA Technical Reports Server (NTRS)

    Moreno, Nancy; Stodieck, Louis; Cushing, Paula; Stowe, Mark; Hamilton, Mary Ann; Werner, Ken

    2008-01-01

    Commercial Generic Bioprocessing Apparatus Science Insert - 03 (CSI-03) is the third set of investigations in the CSI program series. The CSI program provides the K-12 community opportunities to utilize the unique microgravity environment of the International Space Station as part of the regular classroom to encourage learning and interest in science, technology, engineering and math. CSI-03 will examine the complete life cycle of the painted lady butterfly and the ability of an orb weaving spider to spin a web, eat and remain healthy in space.

  2. 21 CFR 529.1940 - Progesterone intravaginal inserts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 6 2010-04-01 2010-04-01 false Progesterone intravaginal inserts. 529.1940... Progesterone intravaginal inserts. (a) Specifications. Each insert contains: (1) 1.38 grams (g) progesterone in molded silicone over a nylon spine. (2) 0.3 g progesterone in molded silicone over a flexible nylon spine...

  3. 21 CFR 529.1940 - Progesterone intravaginal inserts.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 6 2011-04-01 2011-04-01 false Progesterone intravaginal inserts. 529.1940... Progesterone intravaginal inserts. (a) Specifications. Each insert contains: (1) 1.38 grams (g) progesterone in molded silicone over a nylon spine. (2) 0.3 g progesterone in molded silicone over a flexible nylon spine...

  4. 21 CFR 529.1940 - Progesterone intravaginal inserts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 6 2013-04-01 2013-04-01 false Progesterone intravaginal inserts. 529.1940... Progesterone intravaginal inserts. (a) Specifications. Each insert contains: (1) 1.38 grams (g) progesterone in molded silicone over a nylon spine. (2) 0.3 g progesterone in molded silicone over a flexible nylon spine...

  5. 21 CFR 529.1940 - Progesterone intravaginal inserts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 6 2014-04-01 2014-04-01 false Progesterone intravaginal inserts. 529.1940... Progesterone intravaginal inserts. (a) Specifications. Each insert contains: (1) 1.38 grams (g) progesterone in molded silicone over a nylon spine. (2) 0.3 g progesterone in molded silicone over a flexible nylon spine...

  6. 21 CFR 529.1940 - Progesterone intravaginal inserts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 6 2012-04-01 2012-04-01 false Progesterone intravaginal inserts. 529.1940... Progesterone intravaginal inserts. (a) Specifications. Each insert contains: (1) 1.38 grams (g) progesterone in molded silicone over a nylon spine. (2) 0.3 g progesterone in molded silicone over a flexible nylon spine...

  7. T-tube insertion for sclerotic subglottic stenosis.

    PubMed

    Goto, Taichiro; Kato, Ryoichi

    2014-02-01

    T-tube insertion is effective treatment for subglottic stenosis, but it is generally difficult due to bending of the T-tube. In a 52-year-old woman with relapsing polychondritis, a T-tube was inserted after predilatation using Hegar dilators. We describe the details of our T-tube insertion methods for sclerotic subglottic stenosis.

  8. 21 CFR 310.515 - Patient package inserts for estrogens.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Patient package inserts for estrogens. 310.515... package inserts for estrogens. (a) Requirement for a patient package insert. FDA concludes that the safe and effective use of drug products containing estrogens requires that patients be fully informed of...

  9. Quench Module Insert (QMI) and the Diffusion Module Insert (DMI) Furnace Development

    NASA Technical Reports Server (NTRS)

    Crouch, Myscha R.; Carswell, William E.; Farmer, Jeff; Rose, Fred; Tidwell, Paul H., II

    2000-01-01

    The Quench Module Insert (QMI) and the Diffusion Module Insert (DMI) are microgravity furnaces under development at Marshall Space Flight Center. The furnaces are being developed for the first Materials Science Research Rack (MSRR-1) of the Materials Science Research Facility (MSRF), one of the first International Space Station (ISS) scientific payloads. QMI is a Bridgman furnace with quench capability for studying interface behavior during directional solidification of metallic and alloy materials. DMI will be a Bridgman-Stockbarger furnace to study diffusion processes in semiconductors. The design for each insert, both QMI and DMI, is driven by specific science, operations and safety requirements, as well as by constraints arising from resource limitations, such as volume, mass and power. Preliminary QMI analysis and testing indicates that the design meets these requirements.

  10. The internal dimensions of the cochlear scalae with special reference to cochlear electrode insertion trauma.

    PubMed

    Biedron, Slavomir; Prescher, Andreas; Ilgner, Justus; Westhofen, Martin

    2010-07-01

    To investigate the intracochlear micromorphology with regard to frequent patterns of cochlear electrode insertion trauma. Cochlear implantation is a widely accepted treatment for deafness and high-grade sensorineural hearing loss. Although the device and the implantation methods are continuously optimized, damage of intracochlear structures due to electrode insertion is a frequent finding in temporal bone studies. Reduction of insertional trauma is important for the preservation of residual hearing and on the background of increasing numbers of cochlear implant recipients. This study was performed with histologic specimens from the "Wittmaack temporal bone collection" (Hamburg, Germany) to examine the diameters of intracochlear spaces and to correlate the micromorphology of cochlear ducts to frequent patterns of intracochlear insertion trauma. The diameter of the scala tympani decreases by approximately 300 microm during the ascending part of the basal turn. In this region, the intersegmental decrease exceeds the assumed linear diameter decrease significantly (p < or = 0.001). The regression of the cross-sectional diameter is accompanied by a shift of the spiral osseous lamina toward the scala tympani and by narrowing of the bony capsule of the cochlea. Various attempts have been made to evaluate the dimensions of the cochlea related to cochlear implantation. Little attention was paid to the distinct narrowing of the scala tympani in the region of the ascending part of the cochlear duct, although from the literature, it is known that electrode insertion trauma frequently occurs here. Individual variations of the cochlear micromorphology may additionally contribute to the failure of preformed electrode arrays, but the challenge of guiding the electrode array around the first bend of the cochlear turn, that is, the pars ascendens, is obviously impaired by the interindividually constant narrowing in this area. Therefore, this finding may have implications on the

  11. Insertion torque versus mechanical resistance of mini-implants inserted in different cortical thickness

    PubMed Central

    Santos, Renata de Faria; Ruellas, Antonio Carlos de Oliveira; Fernandes, Daniel Jogaib; Elias, Carlos Nelson

    2014-01-01

    Objective This study aimed to measure insertion torque, tip mechanical resistance to fracture and transmucosal neck of mini-implants (MI) (Conexão Sistemas de PróteseT), as well as to analyze surface morphology. Methods Mechanical tests were carried out to measure the insertion torque of MIs in different cortical thicknesses, and tip mechanical resistance to fracture as well as transmucosal neck of MIs. Surface morphology was assessed by scanning electron microscopy (SEM) before and after the mechanical tests. Results Values of mechanical resistance to fracture (22.14 N.cm and 54.95 N.cm) were higher and statistically different (P < 0.05) from values of insertion torque for 1-mm (7.60 N.cm) and 2-mm (13.27 N.cm) cortical thicknesses. Insertion torque was statistically similar (P > 0.05) to torsional fracture in the tip of MI (22.14 N.cm) when 3 mm cortical thickness (16.11 N.cm) and dense bone (23.95 N.cm) were used. Torsional fracture of the transmucosal neck (54.95 N.cm) was higher and statistically different (P < 0.05) from insertion torsional strength in all tested situations. SEM analysis showed that the MIs had the same smooth surface when received from the manufacturer and after the mechanical tests were performed. Additionally, no significant marks resulting from the manufacturing process were observed. Conclusion All mini-implants tested presented adequate surface morphology. The resistance of mini-implants to fracture safely allows placement in 1 and 2-mm cortical thickness. However, in 3-mm cortical thickness and dense bones, pre-drilling with a bur is recommended before insertion. PMID:25162571

  12. Development of Distinctive Feature Theory.

    ERIC Educational Resources Information Center

    Meyer, Peggy L.

    Since the beginning of man's awareness of his language capabilities and language structure, he has assumed that speech is composed of discrete entities. The linguist attempts to establish a model of the workings of these distinctive sounds in a language. Utilizing an historical basis for discussion, this general survey of the distinctive feature…

  13. Counselor Identity: Conformity or Distinction?

    ERIC Educational Resources Information Center

    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.

  14. Is Face Distinctiveness Gender Based?

    ERIC Educational Resources Information Center

    Baudouin, Jean-Yves; Gallay, Mathieu

    2006-01-01

    Two experiments were carried out to study the role of gender category in evaluations of face distinctiveness. In Experiment 1, participants had to evaluate the distinctiveness and the femininity-masculinity of real or artificial composite faces. The composite faces were created by blending either faces of the same gender (sexed composite faces,…

  15. Is Face Distinctiveness Gender Based?

    ERIC Educational Resources Information Center

    Baudouin, Jean-Yves; Gallay, Mathieu

    2006-01-01

    Two experiments were carried out to study the role of gender category in evaluations of face distinctiveness. In Experiment 1, participants had to evaluate the distinctiveness and the femininity-masculinity of real or artificial composite faces. The composite faces were created by blending either faces of the same gender (sexed composite faces,…

  16. CD161 defines a transcriptional and functional phenotype across distinct human T cell lineages.

    PubMed

    Fergusson, Joannah R; Smith, Kira E; Fleming, Vicki M; Rajoriya, Neil; Newell, Evan W; Simmons, Ruth; Marchi, Emanuele; Björkander, Sophia; Kang, Yu-Hoi; Swadling, Leo; Kurioka, Ayako; Sahgal, Natasha; Lockstone, Helen; Baban, Dilair; Freeman, Gordon J; Sverremark-Ekström, Eva; Davis, Mark M; Davenport, Miles P; Venturi, Vanessa; Ussher, James E; Willberg, Christian B; Klenerman, Paul

    2014-11-06

    The C-type lectin CD161 is expressed by a large proportion of human T lymphocytes of all lineages, including a population known as mucosal-associated invariant T (MAIT) cells. To understand whether different T cell subsets expressing CD161 have similar properties, we examined these populations in parallel using mass cytometry and mRNA microarray approaches. The analysis identified a conserved CD161++/MAIT cell transcriptional signature enriched in CD161+CD8+ T cells, which can be extended to CD161+ CD4+ and CD161+TCRγδ+ T cells. Furthermore, this led to the identification of a shared innate-like, TCR-independent response to interleukin (IL)-12 plus IL-18 by different CD161-expressing T cell populations. This response was independent of regulation by CD161, which acted as a costimulatory molecule in the context of T cell receptor stimulation. Expression of CD161 hence identifies a transcriptional and functional phenotype, shared across human T lymphocytes and independent of both T cell receptor (TCR) expression and cell lineage. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

  17. deep-orange and carnation define distinct stages in late endosomal biogenesis in Drosophila melanogaster.

    PubMed

    Sriram, V; Krishnan, K S; Mayor, Satyajit

    2003-05-12

    Endosomal degradation is severely impaired in primary hemocytes from larvae of eye color mutants of Drosophila. Using high resolution imaging and immunofluorescence microscopy in these cells, products of eye color genes, deep-orange (dor) and carnation (car), are localized to large multivesicular Rab7-positive late endosomes containing Golgi-derived enzymes. These structures mature into small sized Dor-negative, Car-positive structures, which subsequently fuse to form tubular lysosomes. Defective endosomal degradation in mutant alleles of dor results from a failure of Golgi-derived vesicles to fuse with morphologically arrested Rab7-positive large sized endosomes, which are, however, normally acidified and mature with wild-type kinetics. This locates the site of Dor function to fusion of Golgi-derived vesicles with the large Rab7-positive endocytic compartments. In contrast, endosomal degradation is not considerably affected in car1 mutant; fusion of Golgi-derived vesicles and maturation of large sized endosomes is normal. However, removal of Dor from small sized Car-positive endosomes is slowed, and subsequent fusion with tubular lysosomes is abolished. Overexpression of Dor in car1 mutant aggravates this defect, implicating Car in the removal of Dor from endosomes. This suggests that, in addition to an independent role in fusion with tubular lysosomes, the Sec1p homologue, Car, regulates Dor function.

  18. Distinct histone modifications define initiation and repair of meiotic recombination in the mouse.

    PubMed

    Buard, Jérôme; Barthès, Pauline; Grey, Corinne; de Massy, Bernard

    2009-09-02

    Little is known about the factors determining the location and activity of the rapidly evolving meiotic crossover hotspots that shape genome diversity. Here, we show that several histone modifications are enriched at the active mouse Psmb9 hotspot, and we distinguish those marks that precede from those that follow hotspot recombinational activity. H3K4Me3, H3K4Me2 and H3K9Ac are specifically enriched in the chromatids that carry an active initiation site, and in the absence of DNA double-strand breaks (DSBs) in Spo11(-/-) mice. We thus propose that these marks are part of the substrate for recombination initiation at the Psmb9 hotspot. In contrast, hyperacetylation of H4 is increased as a consequence of DSB formation, as shown by its dependency on Spo11 and by the enrichment detected on both recombining chromatids. In addition, the comparison with another hotspot, Hlx1, strongly suggests that H3K4Me3 and H4 hyperacetylation are common features of DSB formation and repair, respectively. Altogether, the chromatin signatures of the Psmb9 and Hlx1 hotspots provide a basis for understanding the distribution of meiotic recombination.

  19. Distinct histone modifications define initiation and repair of meiotic recombination in the mouse

    PubMed Central

    Buard, Jérôme; Barthès, Pauline; Grey, Corinne; de Massy, Bernard

    2009-01-01

    Little is known about the factors determining the location and activity of the rapidly evolving meiotic crossover hotspots that shape genome diversity. Here, we show that several histone modifications are enriched at the active mouse Psmb9 hotspot, and we distinguish those marks that precede from those that follow hotspot recombinational activity. H3K4Me3, H3K4Me2 and H3K9Ac are specifically enriched in the chromatids that carry an active initiation site, and in the absence of DNA double-strand breaks (DSBs) in Spo11−/− mice. We thus propose that these marks are part of the substrate for recombination initiation at the Psmb9 hotspot. In contrast, hyperacetylation of H4 is increased as a consequence of DSB formation, as shown by its dependency on Spo11 and by the enrichment detected on both recombining chromatids. In addition, the comparison with another hotspot, Hlx1, strongly suggests that H3K4Me3 and H4 hyperacetylation are common features of DSB formation and repair, respectively. Altogether, the chromatin signatures of the Psmb9 and Hlx1 hotspots provide a basis for understanding the distribution of meiotic recombination. PMID:19644444

  20. Differential Thy-1 expression by splenic fibroblasts defines functionally distinct subsets.

    PubMed

    Borrello, M A; Phipps, R P

    1996-11-01

    Fibroblasts have an important structural role in the spleen, as they provide a scaffold of extracellular matrix in which cells of the immune system reside. Aside from their vague recognition as "stromal" or "reticular" components of the spleen, these cells have not been characterized. In this study, normal fibroblast lines from mouse [B6D2(F1)] spleen were established. The fibroblast phenotype of these lines was confirmed by their morphology, expression of vimentin, as well as their lack of epithelial and endothelial cell markers, their failure to display the hematopoietic marker CD45, and their inability to phagocytize. Interestingly, 50-65% of the splenic fibroblasts expressed the Thy-1 antigen, while a subpopulation of Thy-1-negative fibroblasts existed. FACS on the basis of Thy-1, as well as limiting dilution cloning, yielded stable lines and clones of Thy-1+ and Thy-1- splenic fibroblasts. Phenotypic characterization revealed that both subsets synthesized collagen and expressed class I MHC, ICAM-1, VCAM-1, and CD44 constitutively. However, intriguing differences existed between the fibroblast subpopulations. Thy-1+ splenic fibroblasts produced significantly greater levels of IL-6 than did their Thy-1- counterparts. After treatment with IFN-gamma (150 U/ml, 72 hr), Thy-1-, but not Thy-1+, splenic fibroblasts expressed class II MHC and presented antigen to an I-A(b)-restricted T cell line. This suggests that the Thy-1- fibroblasts may present antigen to T lymphocytes in vivo under inflammatory conditions. Thus, splenic fibroblasts are a heterogeneous and dynamic cell type poised in an immunologically relevant location to interact with bone marrow-derived cells under normal and fibrotic conditions.

  1. Defining Distinct Negative Beliefs about Uncertainty: Validating the Factor Structure of the Intolerance of Uncertainty Scale

    ERIC Educational Resources Information Center

    Sexton, Kathryn A.; Dugas, Michel J.

    2009-01-01

    This study examined the factor structure of the English version of the Intolerance of Uncertainty Scale (IUS; French version: M. H. Freeston, J. Rheaume, H. Letarte, M. J. Dugas, & R. Ladouceur, 1994; English version: K. Buhr & M. J. Dugas, 2002) using a substantially larger sample than has been used in previous studies. Nonclinical…

  2. Lithium Insertion Chemistry of Some Iron Vanadates

    SciTech Connect

    Patoux, Sebastien; Richardson, Thomas J.

    2007-02-02

    Lithium insertion into various iron vanadates has been investigated. Fe{sub 2}V{sub 4}O{sub 13} and Fe{sub 4}(V{sub 2}O{sub 7}){sub 3} {center_dot} 3H{sub 2}O have discharge capacities approaching 200 mAh/g above 2.0 V vs. Li{sup +}/Li. Although the potential profiles change significantly between the first and subsequent discharges, capacity retention is unexpectedly good. Other phases, structurally related to FeVO{sub 4}, containing copper and/or sodium ions were also studied. One of these, {beta}-Cu{sub 3}Fe{sub 4}(VO{sub 4}){sub 6}, reversibly consumes almost 10 moles of electrons per formula unit (ca. 240 mAh g{sup -1}) between 3.6 and 2.0 V vs. Li{sup +}/Li, in a non-classical insertion process. It is proposed that both copper and vanadium are electrochemically active, whereas iron(III) reacts to form LiFe{sup III}O{sub 2}. The capacity of the Cu{sub 3}Fe{sub 4}(VO{sub 4}){sub 6}/Li system is nearly independent of cycling rate, stabilizing after a few cycles at 120-140 mAh g{sup -1}. Iron vanadates exhibit better capacities than their phosphate analogues, whereas the latter display more constant discharge potentials.

  3. Model of a Hollow Cathode Insert Plasma

    NASA Technical Reports Server (NTRS)

    Mikellides, Ioannis G.; Katz, Ira; Goebel, Dan M.; Polk, James E.

    2004-01-01

    A 2-D axisymmetric fluid model of the plasma in the insert region of a hollow cathode is presented. The level of sophistication included in the model is motivated in part by the need to determine quantitatively plasma fluxes to the emitter surface. The ultimate goal is to assess whether plasma effects can degrade the life of impregnated inserts beyond those documented throughout the 30-50 year history of vacuum cathode technologies. Results from simulations of a 1.2-cm diameter cathode operating at a discharge current of 25 A, and a gas flow rate of 5 sccm, suggest that approximately 10 A of electron current, and 3.5 A of ion current return to the emitter surface. The total emitted electron current computed by the model is about 35 A. Comparisons with plasma measurements suggest that anomalous heating of the plasma due to two-stream instabilities is possible near the orifice region. Solution to the heavy species energy equation, with classical transport and no viscous effects, predicts heavy species temperatures as high as 2640 K.

  4. Phoenix Conductivity Probe Inserted in Martian Soil

    NASA Technical Reports Server (NTRS)

    2008-01-01

    This series of six images from the Robotic Arm Camera on NASA's Phoenix Mars Lander records the first time that the four spikes of the lander's thermal and electrical conductivity probe were inserted into Martian soil.

    The images were taken on July 8, 2008, during the Phoenix mission's 43rd Martian day, or sol, since landing. The insertion visible from the shadows cast on the ground on that sol was a validation test of the procedure. The spikes on the probe are about 1.5 centimeters or half an inch long.

    The science team will use the probe tool to assess how easily heat and electricity move through the soil from one spike to another. Such measurements can provide information about frozen or unfrozen water in the soil. The probe is mounted on the 'knuckle' of Phoenix's Robotic Arm. It has already been used for assessing water vapor in the atmosphere when it is held above the ground.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is led by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  5. Cell line fingerprinting using retroelement insertion polymorphism.

    PubMed

    Ustyugova, Svetlana V; Amosova, Anna L; Lebedev, Yuri B; Sverdlov, Eugene D

    2005-04-01

    Human cell lines are an indispensable tool for functional studies of living entities in their numerous manifestations starting with integral complex systems such as signal pathways and networks, regulation of gene ensembles, epigenetic factors, and finishing with pathological changes and impact of artificially introduced elements, such as various transgenes, on the behavior of the cell. Therefore, it is highly desirable to have reliable cell line identification techniques to make sure that the cell lines to be used in experiments are exactly what is expected. To this end, we developed a set of informative markers based on insertion polymorphism of human retroelements (REs). The set includes 47 pairs of PCR primers corresponding to introns of the human genes with dimorphic LINE1 (L1) and Alu insertions. Using locus-specific PCR assays, we have genotyped 10 human cell lines of various origins. For each of these cell lines, characteristic fingerprints were obtained. An estimated probability that two different cell lines possess the same marker genotype is about 10-18. Therefore, the proposed set of markers provides a reliable tool for cell line identification.

  6. Radiological Insertion and Management of Peritoneovenous Shunt

    SciTech Connect

    Bratby, M. J.; Hussain, F. F. Lopez, A. J.

    2007-06-15

    The purpose of the study was to report our experience of the management of complications following the insertion of a peritoneovenous shunt for intractable malignant ascites. From June 1999 to January 2006, 26 patients underwent insertion of a peritoneovenous shunt for ascites by interventional radiologists. We have used ultrasound and shuntography to assist in the diagnosis of the cause of shunt blockage. Successful techniques for the restoration of the shunt function include port- pumping, stripping of any fibrin sheath, and revision of either the venous or peritoneal catheter. The procedure was initially successful in all patients with continued patency until death in 17. A further four patients are still alive with a functioning shunt. There was one rapid postprocedure death resulting from pulmonary edema. Two patients developed pneumothorax, managed successfully with either a chest drain or aspiration. Shunt dysfunction occurred eight times in seven patients. There were five successful revisions in four patients. Overall, shunt patency has been maintained in 80.1% of patients. Shunt dysfunction is seen in a significant number of patients, but successful revision of the shunt can be achieved in the majority.

  7. Model of a Hollow Cathode Insert Plasma

    NASA Technical Reports Server (NTRS)

    Mikellides, Ioannis G.; Katz, Ira; Goebel, Dan M.; Polk, James E.

    2004-01-01

    A 2-D axisymmetric fluid model of the plasma in the insert region of a hollow cathode is presented. The level of sophistication included in the model is motivated in part by the need to determine quantitatively plasma fluxes to the emitter surface. The ultimate goal is to assess whether plasma effects can degrade the life of impregnated inserts beyond those documented throughout the 30-50 year history of vacuum cathode technologies. Results from simulations of a 1.2-cm diameter cathode operating at a discharge current of 25 A, and a gas flow rate of 5 sccm, suggest that approximately 10 A of electron current, and 3.5 A of ion current return to the emitter surface. The total emitted electron current computed by the model is about 35 A. Comparisons with plasma measurements suggest that anomalous heating of the plasma due to two-stream instabilities is possible near the orifice region. Solution to the heavy species energy equation, with classical transport and no viscous effects, predicts heavy species temperatures as high as 2640 K.

  8. Insertional mutagenesis and illegitimate recombination in mycobacteria.

    PubMed Central

    Kalpana, G V; Bloom, B R; Jacobs, W R

    1991-01-01

    Mycobacteria, particularly Mycobacterium tuberculosis, Mycobacterium leprae, and Mycobacterium avium, are major pathogens of man. Although insertional mutagenesis has been an invaluable genetic tool for analyzing the mechanisms of microbial pathogenesis, it has not yet been possible to apply it to the mycobacteria. To overcome intrinsic difficulties in directly manipulating the genetics of slow-growing mycobacteria, including M. tuberculosis and bacille Calmette-Guérin (BCG) vaccine strains, we developed a system for random shuttle mutagenesis. A genomic library of Mycobacterium smegmatis was subjected to transposon mutagenesis with Tn5 seq1, a derivative of Tn5, in Escherichia coli and these transposon-containing recombinant plasmids were reintroduced into mycobacterial chromosomes by homologous recombination. This system has allowed us to isolate several random auxotrophic mutants of M. smegmatis. To extend this strategy to M. tuberculosis and BCG, targeted mutagenesis was performed using a cloned BCG methionine gene that was subjected to Tn5 seq1 mutagenesis in E. coli and reintroduced into the mycobacteria. Surprisingly for prokaryotes, both BCG and M. tuberculosis were found to incorporate linear DNA fragments into illegitimate sites throughout the mycobacterial genomes at a frequency of 10(-5) to 10(-4) relative to the number of transformants obtained with autonomously replicating vectors. Thus the efficient illegitimate recombination of linear DNA fragments provides the basis for an insertional mutagenesis system for M. tuberculosis and BCG. Images PMID:2052623

  9. Horizontally separated 1-in-1 crossing insertions

    SciTech Connect

    Syphers, M.J.

    1985-10-01

    Previous to this workshop, realistic lattices have been developed for vertically separated l-in-l (e.g., D.E. Johnson, A.A. Garren) and 2-in-1 (e.g., S. Heifets) magnets as well as for horizontally separated 2-in-l magnets (e.g., SSC RDS). Bringing together the widely separated ({approximately}60-70 cm) beams in a reasonable length of tunnel and keeping the dispersion zero at the interaction point has been difficult in the vertical l-in-l case. Most designs have required spacial 2-in-1 quadrupoles near the interaction point where the beams are separated by 15 cm or less. It is not clear that such magnets, as dictated by some of these lattice designs, can easily be built. The purpose of this exercise is to provide a crossing insertion for a realistic lattice which involves horizontally separated l-in-l magnets. The following horizontal crossing insertions, which incorporate the dispersion suppressors and phase trombones into the major arcs, need no special 2-in-1 magnets near the interaction point. The dispersion at the IP created by the horizontal crossing can be cancelled by the dispersion suppressor and one set of triplets.

  10. Clarifying and Defining Library Services.

    ERIC Educational Resources Information Center

    Shubert, Joseph F., Ed.; Josey, E. J., Ed.

    1991-01-01

    This issue presents articles which, in some way, help to clarify and define library services. It is hoped that this clarification in library service will serve to secure the resources libraries need to serve the people of New York. The following articles are presented: (1) Introduction: "Clarifying and Defining Library Services" (Joseph…

  11. Heat transfer by laminar flow in a vertical pipe with twisted-tape inserts

    NASA Astrophysics Data System (ADS)

    Klaczak, A.

    Heat transfer for laminar flow of water in an air-cooled vertical copper pipe with four twisted-tape inserts was determined experimentally. The tests were executed for laminar flow within 110<=Re<=1500, 8.1<=Gz <= 82.0 and 1.62<=y<=5.29. The correlation equation for heat transfer was defined for the tested range. The obtained results were compared to the results of other authors.

  12. Insertion of coherence requests for debugging a multiprocessor

    DOEpatents

    Blumrich, Matthias A.; Salapura, Valentina

    2010-02-23

    A method and system are disclosed to insert coherence events in a multiprocessor computer system, and to present those coherence events to the processors of the multiprocessor computer system for analysis and debugging purposes. The coherence events are inserted in the computer system by adding one or more special insert registers. By writing into the insert registers, coherence events are inserted in the multiprocessor system as if they were generated by the normal coherence protocol. Once these coherence events are processed, the processing of coherence events can continue in the normal operation mode.

  13. Speciation without Pre-Defined Fitness Functions.

    PubMed

    Gras, Robin; Golestani, Abbas; Hendry, Andrew P; Cristescu, Melania E

    2015-01-01

    The forces promoting and constraining speciation are often studied in theoretical models because the process is hard to observe, replicate, and manipulate in real organisms. Most models analyzed to date include pre-defined functions influencing fitness, leaving open the question of how speciation might proceed without these built-in determinants. To consider the process of speciation without pre-defined functions, we employ the individual-based ecosystem simulation platform EcoSim. The environment is initially uniform across space, and an evolving behavioural model then determines how prey consume resources and how predators consume prey. Simulations including natural selection (i.e., an evolving behavioural model that influences survival and reproduction) frequently led to strong and distinct phenotypic/genotypic clusters between which hybridization was low. This speciation was the result of divergence between spatially-localized clusters in the behavioural model, an emergent property of evolving ecological interactions. By contrast, simulations without natural selection (i.e., behavioural model turned off) but with spatial isolation (i.e., limited dispersal) produced weaker and overlapping clusters. Simulations without natural selection or spatial isolation (i.e., behaviour model turned off and high dispersal) did not generate clusters. These results confirm the role of natural selection in speciation by showing its importance even in the absence of pre-defined fitness functions.

  14. Assessment of infants with peripherally inserted central catheters: Part 1. Detecting the most frequently occurring complications.

    PubMed

    Pettit, Janet

    2002-12-01

    Inserting, maintaining, and monitoring vascular access are integral components of neonatal care. Advances in vascular access technology have led to the insertion of peripherally inserted central catheters (PICC) to provide stable venous access for early and aggressive parenteral nutrition. Medications that are irritating or damaging, or those with a high osmolality or a nonphysiologic pH, can also be safely administered into the central venous system. The need for repeated peripheral intravenous attempts, as well as the associated pain and physiologic instability, are virtually eliminated once a PICC line is placed. Complications related to PICCs may occur at any phase of therapy: during insertion, while indwelling, or after discontinuing the line. The risk factors associated with PICCs are distinctly different from peripheral intravenous lines because of their long dwell time, central placement, and potential to migrate. Part 1 of Focus on the Physical offers a review of the relevant anatomy of the vascular system and a discussion of the appropriate sites for catheter tip placement. Guidelines for a systematic physical assessment, along with recommendations for standardized PICC documentation, are provided. A review of the signs and symptoms of more frequently occurring complications, such as catheter occlusion and bloodstream infections, is presented to enhance awareness of PICC-specific complications in the neonate and to expedite early detection and treatment. Part 2 of this series will focus on systematic assessment for less common complications such as catheter migration, dislodgement, breakage, and thrombosis, as well as the life-threatening complications of pleural and pericardial effusion.

  15. Quantitative Mapping of Matrix Content and Distribution across the Ligament-to-Bone Insertion

    PubMed Central

    Spalazzi, Jeffrey P.; Boskey, Adele L.; Pleshko, Nancy; Lu, Helen H.

    2013-01-01

    The interface between bone and connective tissues such as the Anterior Cruciate Ligament (ACL) constitutes a complex transition traversing multiple tissue regions, including non-calcified and calcified fibrocartilage, which integrates and enables load transfer between otherwise structurally and functionally distinct tissue types. The objective of this study was to investigate region-dependent changes in collagen, proteoglycan and mineral distribution, as well as collagen orientation, across the ligament-to-bone insertion site using Fourier transform infrared spectroscopic imaging (FTIR-I). Insertion site-related differences in matrix content were also evaluated by comparing tibial and femoral entheses. Both region- and site-related changes were observed. Collagen content was higher in the ligament and bone regions, while decreasing across the fibrocartilage interface. Moreover, interfacial collagen fibrils were aligned parallel to the ligament-bone interface near the ligament region, assuming a more random orientation through the bulk of the interface. Proteoglycan content was uniform on average across the insertion, while its distribution was relatively less variable at the tibial compared to the femoral insertion. Mineral was only detected in the calcified interface region, and its content increased exponentially across the mineralized fibrocartilage region toward bone. In addition to new insights into matrix composition and organization across the complex multi-tissue junction, findings from this study provide critical benchmarks for the regeneration of soft tissue-to-bone interfaces and integrative soft tissue repair. PMID:24019964

  16. Assessment of a simplified insertion technique for intrauterine devices.

    PubMed

    Christenson, Kamilee; Lerma, Klaira; Shaw, Kate A; Blumenthal, Paul D

    2016-07-01

    To explore a simplified technique for intrauterine device (IUD) insertion. The present prospective longitudinal study enrolled patients aged at least 18years presenting at the gynecology clinic of Stanford University for IUD insertion between June 1, 2013 and June 30, 2014. No pelvic examination or uterine sounding was performed prior to IUD insertion. Transvaginal ultrasonography was performed immediately after insertion and at 4-6weeks to confirm device placement. The primary outcome was successful IUD placement. The study enrolled 50 patients. IUD insertion was completed successfully without any cervical manipulation in 40 (80%) participants. Sounding was not needed for any procedures. A cervical dilator was required to locate the internal os for 10 (20%) patients. The mean distance between IUDs and the endometrial verge immediately following insertion was 2.9mm. IUD insertion was rated "difficult" by the physician performing the procedure in 3 (6%) patients. No perforations were recorded. IUD expulsion occurred in 3 (6%) patients; menorrhagia was the indication for IUD insertion in two of these patients. IUD insertion without prior pelvic examination and sounding was feasible; this technique could reduce the need for instrument use during insertion and, consequently, the pain associated with insertion. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  17. Hawkins and Stevens revisited with insert earphones (L)

    NASA Astrophysics Data System (ADS)

    Houtsma, Adrianus J. M.

    2004-03-01

    The classical experiment on masking of pure tones by white noise by Hawkins and Stevens [J. Acoust. Soc. Am. 22, 6-13 (1950)] has left two general notions about broadband masking that are still being echoed in present-day textbooks on hearing. One is that broadband masking is linear (i.e., if the noise power level increases, the signal threshold level increases by exactly the same amount). The other is the existence of a nonmonotonic function of frequency, the critical ratio (CR) which, unlike the critical band (CB) or equivalent rectangular bandwidth (ERB) functions, shows a distinct upturn below 300 Hz. Exploring the possibility that Hawkins and Stevens' measurements may have been adversely affected by acoustic leakage at the headphones at low frequencies, the experiment was repeated with insert earphones. The resulting critical ratio function shows a monotonic dependence on frequency down to 90 Hz, similar to CB and ERB functions. Moreover, the CR function appears to closely approximate the ERB function when the dependence of each filter's detection efficiency on masker energy uncertainty is incorporated. Masking appears to be linear below 1000 Hz, but thresholds, expressed as S/N0 ratios, were found to increase systematically with increasing masker intensity at higher frequencies.

  18. Insertions/Deletions-Associated Nucleotide Polymorphism in Arabidopsis thaliana

    PubMed Central

    Guo, Changjiang; Du, Jianchang; Wang, Long; Yang, Sihai; Mauricio, Rodney; Tian, Dacheng; Gu, Tingting

    2016-01-01

    Although high levels of within-species variation are commonly observed, a general mechanism for the origin of such variation is still lacking. Insertions and deletions (indels) are a widespread feature of genomes and we hypothesize that there might be an association between indels and patterns of nucleotide polymorphism. Here, we investigate flanking sequences around 18 indels (>100 bp) among a large number of accessions of the plant, Arabidopsis thaliana. We found two distinct haplotypes, i.e., a nucleotide dimorphism, present around each of these indels and dimorphic haplotypes always corresponded to the indel-present/-absent patterns. In addition, the peaks of nucleotide diversity between the two divergent alleles were closely associated with these indels. Thus, there exists a close association between indels and dimorphisms. Further analysis suggests that indel-associated substitutions could be an important component of genetic variation shaping nucleotide polymorphism in Arabidopsis. Finally, we suggest a mechanism by which indels might generate these highly divergent haplotypes. This study provides evidence that nucleotide dimorphisms, which are frequently regarded as evidence of frequency-dependent selection, could be explained simply by structural variation in the genome. PMID:27965694

  19. [Drug package inserts and the adequacy of patient's drug information].

    PubMed

    da Silva, T; Dal-Pizzol, F; Bello, C M; Mengue, S S; Schenkel, E P

    2000-04-01

    To investigate the adequacy of the content and format of the patient information section in package inserts of commonly prescribed drugs at the internal medicine service of a school hospital. Forty eight package inserts were collected from six pharmacies of the city of Porto Alegre in June 1998. The presence of mandatory notification and other information required by Brazilian laws that regulate inserts content was examined. No one package inserts contained all the notification required by law. Warnings about medication storage and expiration date were the most frequently information found in package inserts analyzed. Important information for the drug user was not presented in package inserts analyzed, limiting the purpose of inserts as an instrument for patient education.

  20. Recurrent bacteraemia by 2 different Bacillus cereus strains related to 2 distinct central venous catheters.

    PubMed

    Koch, Andrea; Arvand, Mardjan

    2005-01-01

    A 14-y-old girl with osteosarcoma developed 3 episodes of catheter-related bacteraemia by Bacillus cereus. After removal of the first and insertion of a second Hickman catheter, further episodes of B. cereus bacteraemia occurred. PFGE analysis revealed that bacteraemic episodes related to each catheter were caused by a distinct B. cereus strain.

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

    NASA Astrophysics Data System (ADS)

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

    2016-07-01

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

  2. Non-insertional tendinopathy of the subscapularis.

    PubMed

    Dierckman, Brian D; Shah, Nirav R; Larose, Connor R; Gerbrandt, Stacey; Getelman, Mark H

    2013-07-01

    (1) Describe a previously unreported finding involving the intra-articular portion of the subscapularis, the Conrad lesion. (2) Describe a novel classification system for the spectrum of non-insertional tendinopathy of the subscapularis. (3) Report the outcomes of surgical treatment of this spectrum of pathology. Outcomes of 34 patients (23 males and 11 females, mean age 60.5 ± 7.5) with non-insertional tendinopathy of the subscapularis treated arthroscopically were retrospectively reviewed. All patients had anterior shoulder pain with no weakness during belly-press testing and no subscapularis footprint involvement on magnetic resonance imaging. All patients were managed with subscapularis tendon debridement and side-to-side repair along with treatment of concomitant pathology. Seven patients had a Type I lesion (so-called Conrad lesion) - a nodule on the leading edge of the subscapularis. Eighteen patients had a Type II lesion - a visible split tear with degeneration in the upper ½ of the intra-articular tendon. Nine patients had a Type III lesion - more extensive splitting in the tendon with advanced tendon degeneration. At a mean follow-up of 24 months, 97% of patients were completely satisfied. Significant improvements were seen in forward elevation (152 ± 12° to 172 ± 5°, P < 0.001) and visual analog scale pain scores (5.9 ± 1.7-0.6 ± 1.0, P < 0.001). Internal rotation strength and external rotation motion at the side were maintained. ASES scores averaged 95.4 ± 7.4, disabilities of arm, shoulder and hand scores averaged 6.19 ± 9.8, Western Ontario Rotator Cuff scores averaged 91.7 ± 9.3 and the average University of California at Los Angeles score was 33.1 ± 2.4. We present a previously unreported finding of the subscapularis, the Conrad lesion, along with a novel classification system for non-insertional tendinopathy of the subscapularis. Arthroscopic treatment of this spectrum of tendinopathy along with concomitant shoulder pathology eliminated

  3. Intermetallic insertion anodes for lithium batteries.

    SciTech Connect

    Thackeray, M. M.; Vaughey, J.; Johnson, C. S.; Kepler, K. D.

    1999-11-12

    Binary intermetallic compounds containing lithium, or lithium alloys, such as Li{sub x}Al, Li{sub x}Si and Li{sub x}Sn have been investigated in detail in the past as negative electrode materials for rechargeable lithium batteries. It is generally acknowledged that the major limitation of these systems is the large volumetric expansion that occurs when lithium reacts with the host metal. Such large increases in volume limit the practical use of lithium-tin electrodes in electrochemical cells. It is generally recognized that metal oxide electrodes, MO{sub y}, in lithium-ion cells operate during charge and discharge by means of a reversible lithium insertion/extraction process, and that the cells offer excellent cycling behavior when the crystallographic changes to the unit cell parameters and unit cell volume of the Li{sub x}MO{sub y} electrode are kept to a minimum. An excellent example of such an electrode is the spinel Li{sub 4}Ti{sub 5}O{sub 12}, which maintains its cubic symmetry without any significant change to the lattice parameter (and hence unit cell volume) during lithium insertion to the rock-salt composition Li{sub 7}Ti{sub 5}O{sub 12}. This spinel electrode is an example of a ternary Li{sub x}MO{sub y} system in which a binary MO{sub y} framework provides a stable host structure for lithium. With this approach, the authors have turned their attention to exploring ternary intermetallic systems Li{sub x}MM{prime} in the hope of finding a system that is not subject to the high volumetric expansion that typifies many binary systems. In this paper, the authors present recent data of their investigations of lithium-copper-tin and lithium-indium-antimonide electrodes in lithium cells. The data show that lithium can be inserted reversibly into selected intermetallic compounds with relatively small expansion of the lithiated intermetallic structures.

  4. UDEC - A Generalised Distinct Element Program for Modelling Jointed Rock.

    DTIC Science & Technology

    1980-03-01

    7 AD-AO87 610 CUNDALL (PETER ) ASSOCIATES VIRGINIA WATER (ENGLAND FIG 8/7 MA0 C UNALDJ39C04C ENERALISED DISTINCT ELEMENT PROGR AM FOR MODELLING SOl I...circular linked-list that corresponds to its boundary. Each corner on the boundary is represented by an array of words that stores the coordinates of...come into contact their corner lists are broken at the points of contact and an array of words (corresponding to a contact) is inserted into the break

  5. A Behavioral Approach in Defining and Teaching Educational Psychology.

    ERIC Educational Resources Information Center

    Dolly, John P.

    Behaviorists define the purpose of educational psychology as that of teaching teachers to predict, control, and modify classroom behavior. This conceptualization is contrasted with the approach which views educational psychology as a comprehensive content area emphasizing information rather than skills. A basic distinction between behaviorists and…

  6. Depth of electrode insertion and postoperative performance in humans with cochlear implants: a histopathologic study.

    PubMed

    Lee, Joonhan; Nadol, Joseph B; Eddington, Donald K

    2010-01-01

    The depth of electrode insertion of a multichannel cochlear implant has been suggested as a clinical variable that may correlate with word recognition using the implant. The current study evaluates this relationship using the human temporal bone collection at the Massachusetts Eye and Ear Infirmary. Twenty-seven temporal bones of subjects with cochlear implants were studied. Temporal bones were removed at autopsy, fixed and prepared for histological study by standard techniques. Specimens were then serially sectioned, and reconstructed by two-dimensional methods. Three measures of length were made from each subject's reconstruction: (1) depth of insertion (DI) of the cochlear implant electrode array, from the round window to the array's apical tip; (2) inserted length (IL) from the cochleostomy to the apical tip of the array, and (3) cochlear duct length (CDL) from the round window to the helicotrema. The active electrode length (AEL) was defined as the distance between the most apical and most basal electrodes of the array. Stepwise regression was used to identify whether subsets of six metrics associated with insertion depth (DI, DI/AEL, DI/CDL, IL, IL/AEL and IL/CDL), duration of deafness, sound-processing strategy, potential for central impairment and age at implantation accounted for significant across-subject variance in the last recorded NU-6 word score measured during each subject's life. Age at implantation and potential for central impairment account for significant percentages of the across-subject variance in NU-6 word scores for the 27 subjects studied. None of the insertion metrics accounted for significant performance variance, even when the variance associated with the other variables was controlled. These results, together with those of previous studies, are consistent with a relatively weak association between electrode insertion depth and speech reception.

  7. Polymorphic Alu insertions among Mayan populations.

    PubMed

    Herrera, R J; Rojas, D P; Terreros, M C

    2007-01-01

    The Mayan homeland within Mesoamerica spans five countries: Belize, El Salvador, Guatemala, Honduras and Mexico. There are indications that the people we call the Maya migrated from the north to the highlands of Guatemala as early as 4000 B.C. Their existence was village-based and agricultural. The culture of these Preclassic Mayans owes much to the earlier Olmec civilization, which flourished in the southern portion of North America. In this study, four different Mayan groups were examined to assess their genetic variability. Ten polymorphic Alu insertion (PAI) loci were employed to ascertain the genetic affinities among these Mayan groups. North American, African, European and Asian populations were also examined as reference populations. Our results suggest that the Mayan groups examined in this study are not genetically homogeneous.

  8. INSERTION DEVICE UPGRADE PLANS AT THE NSLS.

    SciTech Connect

    TANABE, T.; BLEDNYKH, A.; HARDER, D.; LEHECKA, M.; RAKOWSKY, G.; SKARITKA, J.

    2005-05-16

    This paper describes plans to upgrade insertion devices (IDs) at the National Synchrotron Light Source (NSLS), Brookhaven National Laboratory, U.S.A. The aging wiggler (W120) at X25 is being replaced by a 1 m long in-vacuum mini-gap undulator (MGU-X25) optimized for a dedicated macromolecular crystallography program. A new, 1/3 m long, undulator (MGU or SCU-X9), will be installed between a pair of RF cavities at X9, and will serve a new beamline dedicated for small angle x-ray scattering (SAXS). Both IDs will have provision for cryocooling the NdFeB hybrid arrays to 150K to raise the field and K-value and to obtain better spectral coverage. Design issues of the devices and other considerations, especially magnetic measurement at low temperature, will be discussed.

  9. [Inserts and shoes for foot deformities].

    PubMed

    Hien, N M

    2003-02-01

    Prevention of habitual or shoe-induced foot and toe deformities in children and treatment of congenital or developing malformations require a change of view towards functional aspects and the use of modern technical possibilities based on our traditional knowledge.Statics, functional anatomy, biomechanics, neuromotor and psychomotor activity, and developmental physiology have to be considered as well as the broad variety of physiological interindividual differences. Modern materials and fabrication techniques make it easier to produce anatomically and functionally correct and appealing shoes, inserts, and orthoses. New means of invasive treatment improve the preconditions for orthotic management. Cultural and cosmetic expectations and the real extent of disability, impairment, and handicap have to be carefully differentiated for the sake of every single child.

  10. How to insert a peripheral cannula.

    PubMed

    Shaw, Sally Jane

    2016-11-16

    Rationale and key points This article aims to assist practitioners to undertake the safe and effective insertion of a peripheral cannula. It provides information on best practice related to peripheral cannulation with an open-ported safety cannula. The same principles for practice apply to non-ported open safety cannulae. » Peripheral cannulation enables venous access, the administration of intravenous medication, infusion therapy and total parenteral nutrition. It also enables blood samples to be obtained. » Peripheral cannulation is a common procedure that requires high standards of care and management to optimise patient outcomes. Reflective activity 'How to' articles can help update your practice and ensure it remains evidence-based. Apply this article to your practice. Reflect on and write a short account of: » How you think this article has changed your practice when performing peripheral cannulation. » How you could use this resource to assist with supporting colleagues.

  11. Impact of Orthodontic Decompensation on Bone Insertion

    PubMed Central

    Guedes, Fabio Pinto; Capelozza Filho, Leopoldino; Garib, Daniela Gamba; Nary Filho, Hugo; Borgo, Evandro José; Cardoso, Mauricio de Almeida

    2014-01-01

    There has always been concern in determining the relationship between orthodontic tooth movement and the consequent biological costs to the periodontium and tooth root. The possibility of evaluating the tooth and bone morphology by CBCT allows more accurate analysis of qualitative and quantitative aspects of these processes. This paper presents a case report of a 20-year-old male patient with Class III malocclusion and hyperdivergent facial pattern, who was surgically treated. A significant amount of labial movement of mandibular incisors was performed during orthodontic treatment before surgery. CBCT was used for evaluation of buccal and lingual bone plates before and after tooth decompensation. The changes in the bone insertion level of maxillary and mandibular incisors in the present case encourage a reflection on the treatment protocol in individuals with dentoskeletal discrepancies. PMID:25436157

  12. Effect of the Starting Point of Half-Pin Insertion on the Insertional Torque of the Pin at the Tibia

    PubMed Central

    Kim, Sung-Jae; Kim, Sung-Hwan; Kim, Young-Hwan

    2015-01-01

    Purpose The authors have observed a failure to achieve secure fixation in elderly patients when inserting a half-pin at the anteromedial surface of the tibia. The purpose of this study was to compare two methods for inserting a half-pin at tibia diaphysis in elderly patients. Materials and Methods Twenty cadaveric tibias were divided into Group C or V. A half-pin was inserted into the tibias of Group C via the conventional method, from the anteromedial surface to the interosseous border of the tibia diaphysis, and into the tibias of Group V via the vertical method, from the anterior border to the posterior surface at the same level. The maximum insertion torque was measured during the bicortical insertion with a torque driver. The thickness of the cortex was measured by micro-computed tomography. The relationship between the thickness of the cortex engaged and the insertion torque was investigated. Results The maximum insertion torque and the thickness of the cortex were significantly higher in Group V than Group C. Both groups exhibited a statistically significant linear correlation between torque and thickness by Spearman's rank correlation analysis. Conclusion Half-pins inserted by the vertical method achieved purchase of more cortex than those inserted by the conventional method. Considering that cortical thickness and insertion torque in Group V were significantly greater than those in Group C, we suggest that the vertical method of half-pin insertion may be an alternative to the conventional method in elderly patients. PMID:25510759

  13. Regulatory perspective on incomplete control rod insertions

    SciTech Connect

    Chatterton, M.

    1997-01-01

    The incomplete control rod insertions experienced at South Texas Unit 1 and Wolf Creek are of safety concern to the NRC staff because they represent potential precursors to loss of shutdown margin. Even before it was determined if these events were caused by the control rods or by the fuel there was an apparent correlation of the problem with high burnup fuel. It was determined that there was also a correlation between high burnup and high drag forces as well as with rod drop time histories and lack of rod recoil. The NRC staff initial actions were aimed at getting a perspective on the magnitude of the problem as far as the number of plants and the amount of fuel that could be involved, as well as the safety significance in terms of shutdown margin. As tests have been performed and data has been analyzed the focus has shifted more toward understanding the problem and the ways to eliminate it. At this time the staff`s understanding of the phenomena is that it was a combination of factors including burnup, power history and temperature. The problem appears to be very sensitive to these factors, the interaction of which is not clearly understood. The model developed by Westinghouse provides a possible explanation but there is not sufficient data to establish confidence levels and sensitivity studies involving the key parameters have not been done. While several fixes to the problem have been discussed, no definitive fixes have been proposed. Without complete understanding of the phenomena, or fixes that clearly eliminate the problem the safety concern remains. The safety significance depends on the amount of shutdown margin lost due to incomplete insertion of the control rods. Were the control rods to stick high in the core, the reactor could not be shutdown by the control rods and other means such as emergency boration would be required.

  14. The Problem of Defining Intelligence.

    ERIC Educational Resources Information Center

    Lubar, David

    1981-01-01

    The major philosophical issues surrounding the concept of intelligence are reviewed with respect to the problems surrounding the process of defining and developing artificial intelligence (AI) in computers. Various current definitions and problems with these definitions are presented. (MP)

  15. Crack-Defined Electronic Nanogaps.

    PubMed

    Dubois, Valentin; Niklaus, Frank; Stemme, Göran

    2016-03-16

    Achieving near-atomic-scale electronic nanogaps in a reliable and scalable manner will facilitate fundamental advances in molecular detection, plasmonics, and nanoelectronics. Here, a method is shown for realizing crack-defined nanogaps separating TiN electrodes, allowing parallel and scalable fabrication of arrays of sub-10 nm electronic nanogaps featuring individually defined gap widths. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  16. Insertion of intrauterine contraceptive devices by registered nurses in Australia.

    PubMed

    Kemeny, Fiona; Digiusto, Erol; Bateson, Deborah

    2016-02-01

    In spite of many advantages, intrauterine contraception (IUC) is underutilised in Australia: only 5% of Australian women using contraceptive methods in 2011 were using IUC. In 2012, Family Planning New South Wales (FPNSW) commenced training registered nurses (RNs) to insert IUC. This article reports outcomes of insertion attempts by the first four trained RNs and suggests strategies for increasing IUC utilisation in Australia. Data regarding client characteristics and outcomes of insertion attempts, including relevant adverse events that occurred during a 6-month follow-up period after the IUC insertions, were retrospectively extracted from the FPNSW clinical record system and analysed in SPSS. Of 207 insertion attempts by RNs, 91% were successful without Medical Officer (MO) assistance. The likelihood of insertion attempts being successful did not differ significantly between nulliparous and parous clients. Incidence of a postinsertion adverse event was equal to or less than rates in previous studies. All adverse events involved parous clients. We have shown that RNs who undertook competency-based IUC insertion training had a high rate of successful insertions and a low rate of adverse outcomes. Utilisation of IUC in Australia could be increased by engaging RNs as inserters, and it is timely to review the barriers that make it difficult for private medical services to employ RNs to insert IUC. © 2015 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

  17. Bruxism defined and graded: an international consensus.

    PubMed

    Lobbezoo, F; Ahlberg, J; Glaros, A G; Kato, T; Koyano, K; Lavigne, G J; de Leeuw, R; Manfredini, D; Svensson, P; Winocur, E

    2013-01-01

    To date, there is no consensus about the definition and diagnostic grading of bruxism. A written consensus discussion was held among an international group of bruxism experts as to formulate a definition of bruxism and to suggest a grading system for its operationalisation. The expert group defined bruxism as a repetitive jaw-muscle activity characterised by clenching or grinding of the teeth and/or by bracing or thrusting of the mandible. Bruxism has two distinct circadian manifestations: it can occur during sleep (indicated as sleep bruxism) or during wakefulness (indicated as awake bruxism). For the operationalisation of this definition, the expert group proposes a diagnostic grading system of 'possible', 'probable' and 'definite' sleep or awake bruxism. The proposed definition and grading system are suggested for clinical and research purposes in all relevant dental and medical domains.

  18. Detecting Statistically Significant Common Insertion Sites in Retroviral Insertional Mutagenesis Screens

    PubMed Central

    de Ridder, Jeroen; Uren, Anthony; Kool, Jaap; Reinders, Marcel; Wessels, Lodewyk

    2006-01-01

    Retroviral insertional mutagenesis screens, which identify genes involved in tumor development in mice, have yielded a substantial number of retroviral integration sites, and this number is expected to grow substantially due to the introduction of high-throughput screening techniques. The data of various retroviral insertional mutagenesis screens are compiled in the publicly available Retroviral Tagged Cancer Gene Database (RTCGD). Integrally analyzing these screens for the presence of common insertion sites (CISs, i.e., regions in the genome that have been hit by viral insertions in multiple independent tumors significantly more than expected by chance) requires an approach that corrects for the increased probability of finding false CISs as the amount of available data increases. Moreover, significance estimates of CISs should be established taking into account both the noise, arising from the random nature of the insertion process, as well as the bias, stemming from preferential insertion sites present in the genome and the data retrieval methodology. We introduce a framework, the kernel convolution (KC) framework, to find CISs in a noisy and biased environment using a predefined significance level while controlling the family-wise error (FWE) (the probability of detecting false CISs). Where previous methods use one, two, or three predetermined fixed scales, our method is capable of operating at any biologically relevant scale. This creates the possibility to analyze the CISs in a scale space by varying the width of the CISs, providing new insights in the behavior of CISs across multiple scales. Our method also features the possibility of including models for background bias. Using simulated data, we evaluate the KC framework using three kernel functions, the Gaussian, triangular, and rectangular kernel function. We applied the Gaussian KC to the data from the combined set of screens in the RTCGD and found that 53% of the CISs do not reach the significance

  19. Correlation between Extension-Block K-wire Insertion Angle and Postoperative Extension Loss in Mallet Finger Fracture.

    PubMed

    Lee, S K; Kim, Y H; Moon, K H; Choy, W S

    2017-10-09

    Extension-block pinning represents a simple and reliable surgical technique. Although this procedure is commonly performed successfully, some patients develop postoperative extension loss. To date, the relationship between extension-block Kirschner wire (K-wire) insertion angle and postoperative extension loss in mallet finger fracture remains unclear. We aimed to clarify this relationship and further evaluate how various operative and non-operative factors affect postoperative extension loss after extension-block pinning for mallet finger fracture. A retrospective study was conducted to investigate a relationship between extension block K-wire insertion angle and postoperative extension loss. The inclusion criteria were: 1) a dorsal intra-articular fracture fragment involving 30% of the base of the distal phalanx with or without volar subluxation of the distal phalanx; and (2)<3 weeks delay from the injury without treatment. Extension-block K-wire insertion angle and fixation angle of the distal interphalangeal (DIP) joint were assessed using lateral radiograph at immediate postoperative time. Postoperative extension loss was assessed by using lateral radiograph at latest follow-up. Extension-block K-wire insertion angle was defined as the acute angle between extension block K-wire and longitudinal axis of middle phalangeal head. DIP joint fixation angle was defined as the acute angle between the distal phalanx and middle phalanx longitudinal axes. Seventy five patients were included. The correlation analysis revealed that extension-block K-wire insertion angle had a negative correlation with postoperative extension loss, whereas fracture size and time to operation had a positive correlation. (correlation coefficient for extension block K-wire angle: -0.66, facture size:+0.67, time to operation:+0.60) When stratifying patients in terms of negative and positive fixation angle of the DIP joint,the independent t-test showed that mean postoperative extension loss is

  20. Improvement of the insertion axis for cochlear implantation with a robot-based system.

    PubMed

    Torres, Renato; Kazmitcheff, Guillaume; De Seta, Daniele; Ferrary, Evelyne; Sterkers, Olivier; Nguyen, Yann

    2017-02-01

    It has previously reported that alignment of the insertion axis along the basal turn of the cochlea was depending on surgeon' experience. In this experimental study, we assessed technological assistances, such as navigation or a robot-based system, to improve the insertion axis during cochlear implantation. A preoperative cone beam CT and a mastoidectomy with a posterior tympanotomy were performed on four temporal bones. The optimal insertion axis was defined as the closest axis to the scala tympani centerline avoiding the facial nerve. A neuronavigation system, a robot assistance prototype, and software allowing a semi-automated alignment of the robot were used to align an insertion tool with an optimal insertion axis. Four procedures were performed and repeated three times in each temporal bone: manual, manual navigation-assisted, robot-based navigation-assisted, and robot-based semi-automated. The angle between the optimal and the insertion tool axis was measured in the four procedures. The error was 8.3° ± 2.82° for the manual procedure (n = 24), 8.6° ± 2.83° for the manual navigation-assisted procedure (n = 24), 5.4° ± 3.91° for the robot-based navigation-assisted procedure (n = 24), and 3.4° ± 1.56° for the robot-based semi-automated procedure (n = 12). A higher accuracy was observed with the semi-automated robot-based technique than manual and manual navigation-assisted (p < 0.01). Combination of a navigation system and a manual insertion does not improve the alignment accuracy due to the lack of friendly user interface. On the contrary, a semi-automated robot-based system reduces both the error and the variability of the alignment with a defined optimal axis.

  1. Immediate post-partum insertion of intrauterine devices.

    PubMed

    Grimes, David A; Lopez, Laureen M; Schulz, Kenneth F; Van Vliet, Huib Aam; Stanwood, Nancy L

    2010-05-12

    Insertion of an intrauterine device (IUD) immediately after delivery is appealing for several reasons. The woman is known not to be pregnant, her motivation for contraception may be high, and the setting may be convenient for both the woman and her provider. However, the risk of spontaneous expulsion may be unacceptably high. To assess the efficacy and feasibility of IUD insertion immediately after expulsion of the placenta. Our a priori hypothesis was that this practice is safe but associated with higher expulsion rates than interval IUD insertion. We searched MEDLINE, CENTRAL, POPLINE, EMBASE, ClinicalTrials.gov, and ICTRP. We also contacted investigators to identify other trials. We sought all randomized controlled trials (RCTs) with at least one treatment arm that involved immediate post-partum (within 10 minutes of placental expulsion) insertion of an IUD. Comparisons could include different IUDs, different insertion techniques, immediate versus delayed post-partum insertion, or immediate versus interval insertion (unrelated to pregnancy). Studies could include either vaginal or cesarean deliveries. We evaluated the methodological quality of each report and sought to identify duplicate reporting of data from multicenter trials. Two authors abstracted the data. Principal outcome measures were pregnancy, expulsion, and continuation rates. Because the trials did not have uniform interventions, we were unable to aggregate them in a meta-analysis. We found nine RCTs; one directly compared immediate post-partum insertion with delayed insertion. Expulsion by six months was more likely for the immediate group than the delayed insertion group (OR 6.77; 95% CI 1.43 to 32.14). In trials of immediate insertion alone, modifications of existing devices, such as adding absorbable sutures or additional appendages, did not appear beneficial. Most studies showed no important differences between insertions done by hand or by instruments. Lippes Loop and Progestasert devices did

  2. The BDGP gene disruption project: Single transposon insertions associated with 40 percent of Drosophila genes

    SciTech Connect

    Bellen, Hugo J.; Levis, Robert W.; Liao, Guochun; He, Yuchun; Carlson, Joseph W.; Tsang, Garson; Evans-Holm, Martha; Hiesinger, P. Robin; Schulze, Karen L.; Rubin, Gerald M.; Hoskins, Roger A.; Spradling, Allan C.

    2004-01-13

    The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila gene by the insertion of a single transposable element. As part of this effort, transposons in more than 30,000 fly strains were localized and analyzed relative to predicted Drosophila gene structures. Approximately 6,300 lines that maximize genomic coverage were selected to be sent to the Bloomington Stock Center for public distribution, bringing the size of the BDGP gene disruption collection to 7,140 lines. It now includes individual lines predicted to disrupt 5,362 of the 13,666 currently annotated Drosophila genes (39 percent). Other lines contain an insertion at least 2 kb from others in the collection and likely mutate additional incompletely annotated or uncharacterized genes and chromosomal regulatory elements. The remaining strains contain insertions likely to disrupt alternative gene promoters or to allow gene mis-expression. The expanded BDGP gene disruption collection provides a public resource that will facilitate the application of Drosophila genetics to diverse biological problems. Finally, the project reveals new insight into how transposons interact with a eukaryotic genome and helps define optimal strategies for using insertional mutagenesis as a genomic tool.

  3. The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes.

    PubMed Central

    Bellen, Hugo J; Levis, Robert W; Liao, Guochun; He, Yuchun; Carlson, Joseph W; Tsang, Garson; Evans-Holm, Martha; Hiesinger, P Robin; Schulze, Karen L; Rubin, Gerald M; Hoskins, Roger A; Spradling, Allan C

    2004-01-01

    The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila gene by the insertion of a single transposable element. As part of this effort, transposons in >30,000 fly strains were localized and analyzed relative to predicted Drosophila gene structures. Approximately 6300 lines that maximize genomic coverage were selected to be sent to the Bloomington Stock Center for public distribution, bringing the size of the BDGP gene disruption collection to 7140 lines. It now includes individual lines predicted to disrupt 5362 of the 13,666 currently annotated Drosophila genes (39%). Other lines contain an insertion at least 2 kb from others in the collection and likely mutate additional incompletely annotated or uncharacterized genes and chromosomal regulatory elements. The remaining strains contain insertions likely to disrupt alternative gene promoters or to allow gene misexpression. The expanded BDGP gene disruption collection provides a public resource that will facilitate the application of Drosophila genetics to diverse biological problems. Finally, the project reveals new insight into how transposons interact with a eukaryotic genome and helps define optimal strategies for using insertional mutagenesis as a genomic tool. PMID:15238527

  4. Automated fit quantification of tibial nail designs during the insertion using computer three-dimensional modelling.

    PubMed

    Amarathunga, Jayani P; Schuetz, Michael A; Yarlagadda, Prasad Kvd; Schmutz, Beat

    2014-12-01

    Intramedullary nailing is the standard fixation method for displaced diaphyseal fractures of the tibia. An optimal nail design should both facilitate insertion and anatomically fit the bone geometry at its final position in order to reduce the risk of stress fractures and malalignments. Due to the nonexistence of suitable commercial software, we developed a software tool for the automated fit assessment of nail designs. Furthermore, we demonstrated that an optimised nail, which fits better at the final position, is also easier to insert. Three-dimensional models of two nail designs and 20 tibiae were used. The fitting was quantified in terms of surface area, maximum distance, sum of surface areas and sum of maximum distances by which the nail was protruding into the cortex. The software was programmed to insert the nail into the bone model and to quantify the fit at defined increment levels. On average, the misfit during the insertion in terms of the four fitting parameters was smaller for the Expert Tibial Nail Proximal bend (476.3 mm(2), 1.5 mm, 2029.8 mm(2), 6.5 mm) than the Expert Tibial Nail (736.7 mm(2), 2.2 mm, 2491.4 mm(2), 8.0 mm). The differences were statistically significant (p ≤ 0.05). The software could be used by nail implant manufacturers for the purpose of implant design validation.

  5. Neonatal peripherally inserted central catheters: recommendations for prevention of insertion and postinsertion complications.

    PubMed

    Paulson, Pamela R; Miller, Kellee M

    2008-01-01

    Peripherally inserted central catheters (PICCs) continue to be necessary in neonatal care. They benefit many premature infants and those needing long-term intravenous access. An experienced inserter, early recognition of PICC candidates, early PICC placement, knowledge of anatomy, and correct choice of vein all increase placement success. As with any invasive procedure, there are risks. These include pain, difficulty advancing the catheter, damage to vessels, catheter malposition, and bleeding. Utilizing assessment skills, following the product manufacturer's instructions, and carefully placing the catheter should minimize most of these risks. Additional risks include postinsertion complications such as occlusions, thrombosis, catheter failure, infection, and catheter malposition. Proper nursing care--which includes controlling infection, properly securing the catheter, and changing the dressing as needed--is key to preventing complications and maintaining the PICC until treatment has been completed.

  6. Core Vessel Insert Handling Robot for the Spallation Neutron Source

    SciTech Connect

    Graves, Van B; Dayton, Michael J

    2011-01-01

    The Spallation Neutron Source provides the world's most intense pulsed neutron beams for scientific research and industrial development. Its eighteen neutron beam lines will eventually support up to twenty-four simultaneous experiments. Each beam line consists of various optical components which guide the neutrons to a particular instrument. The optical components nearest the neutron moderators are the core vessel inserts. Located approximately 9 m below the high bay floor, these inserts are bolted to the core vessel chamber and are part of the vacuum boundary. They are in a highly radioactive environment and must periodically be replaced. During initial SNS construction, four of the beam lines received Core Vessel Insert plugs rather than functional inserts. Remote replacement of the first Core Vessel Insert plug was recently completed using several pieces of custom-designed tooling, including a highly complicated Core Vessel Insert Robot. The design of this tool are discussed.

  7. Neurobehavioral perspectives on the distinction between fear and anxiety

    PubMed Central

    Perusini, Jennifer N.

    2015-01-01

    In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the neurobiological literature. A strong distinction should specify the difference in conditions that lead to fear versus anxiety. Additionally, fear and anxiety should generate distinct sets of behaviors. Ideally, the two states should be supported by distinguishable neuroanatomical circuits. Such a conceptualization would be consistent with the National Institute of Mental Health's Research Domain Criteria (RDoc). The majority of neurobiological approaches to the fear versus anxiety distinction fail to differentiate the two states in terms of behavior, often using the exact same behavioral measures as indicators. Of the two that do, only Predatory Imminence Theory provides a distinction both in terms of cause and effect. Indeed, that approach provides a ready distinction of anxiety, fear, and panic in terms of both antecedent conditions and response selection rules. Additionally, it appeals to distinct neural circuits to generate these modes of action. PMID:26286652

  8. Fluoroscopic determination of the tibial insertion of the posterior cruciate ligament in the sagittal plane.

    PubMed

    Salim, Rodrigo; Salzler, Matthew J; Bergin, Mark A; Zheng, Liying; Carey, Robert E; Kfuri, Mauricio; Zhang, Xudong; Harner, Christopher D

    2015-05-01

    Currently, placement of the tibial tunnel for arthroscopic transtibial posterior cruciate ligament (PCL) reconstruction relies on a limited arthroscopic view of the native insertion or the use of intraoperative imaging. No widely accepted method exists for intraoperative determination of PCL tibial tunnel placement, and current descriptions are cumbersome. To identify the center of the PCL's anatomic tibial insertion site as a percentage of the PCL facet length on a lateral radiograph of the knee so that it may be reliably located in the sagittal plane during surgical reconstruction. Descriptive laboratory study. Twenty fresh-frozen cadaveric knees were dissected and the tibial insertions of the PCL were digitized with an optical tracing system. The digitized PCL footprints were mapped onto 3-dimensional computed tomography-acquired tibial models, and their center points were determined. A K-wire was then inserted into the center of the PCL's tibial insertion under direct visualization, a direct lateral radiograph was obtained, and the center point was measured. The center locations for both methods were defined as a percentage of PCL facet length from anterior and proximal to posterior and distal, and intraobserver and interobserver reliability was tested with 4 different observers. The average location of the PCL center on the 3-dimensional bone model method was 71.7%±5.6% along the PCL facet from anterior/proximal to posterior/distal. In the lateral radiographic method, the center of the PCL was at an average of 69.7%±4.9% of the facet length. There was no significant difference between the percentage measurements of the 2 methods (P=.13). Interobserver reliability (κ=0.57) and intraobserver reliability (κ=0.71) were moderate to strong. Locating the center of the tibial PCL insertion with fluoroscopy at a point that is 70% of the PCL tibial facet length on a true lateral radiograph is a reliable method for locating the PCL tibial insertion. The method

  9. Hanatoxin inserts into phospholipid membranes without pore formation.

    PubMed

    Lou, Kuo-Long; Hsieh, Meng-Hsuan; Chen, Wei-Jung; Cheng, Yu-Che; Jian, Jia-Nan; Lee, Ming-Tao; Lin, Tsang-Lang; Shiau, Yu-Shuan; Liou, Horng-Huei

    2017-05-01

    Hanatoxin (HaTx), a 35-residue polypeptide from spider venom, functions as an inhibitor of Kv2.1 channels by interacting with phospholipids prior to affecting the voltage-sensor. However, how this water-soluble peptide modifies the gating remains poorly understood, as the voltage-sensor is deeply embedded within the bilayer. To determine how HaTx interacts with phospholipid bilayers, in this study, we examined the toxin-induced partitioning of liposomal membranes. HPLC-results from high-speed spin-down vesicles with HaTx demonstrated direct binding. Dynamic light scattering (DLS) and leakage assay results further indicated that neither membrane pores nor membrane fragmentations were observed in the presence of HaTx. To clarify the binding details, Langmuir trough experiments were performed with phospholipid monolayers by mimicking the external leaflet of membrane bilayers, indicating the involvement of acyl chains in such interactions between HaTx and phospholipids. Our current study thus describes the interaction pattern of HaTx with vesicle membranes, defining a membrane-partitioning mechanism for peptide insertion involving the membrane hydrocarbon core without pore formation. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Comparison of Postoperative Drain Insertion versus No Drain Insertion in Thyroidectomies

    PubMed Central

    Al-Habsi, Asma S.; Al-Sulaimani, Al-Anood K.; Taqi, Kadhim M.; Al-Qadhi, Hani A.

    2016-01-01

    Objectives A thyroidectomy is a frequently performed surgical procedure which can result in life-threatening complications. The insertion of a drain after a thyroidectomy has been suggested to prevent such complications. This study aimed to evaluate the use of surgical drains following thyroidectomies in relation to postoperative complications and mass sizes. Methods This retrospective case-control study included all thyroidectomies conducted at the Sultan Qaboos University Hospital, Muscat, Oman, from January 2011 to December 2013. Length of hospital stay, readmission, postoperative complications and mass size were evaluated. Results During the study period, 250 surgeries were carried out on 241 patients. The majority of patients were female (87.2%). Drains were inserted postoperatively after 202 surgeries (80.8%) compared to 48 surgeries (19.2%) without drains. A total of 32 surgeries (12.8%) were conducted on patients with thyroid masses <1 cm, 138 (55.2%) on those with masses between 1–4 cm and 80 (32.0%) on those with masses >4 cm. The association between drain use and mass size was not significant (P = 0.439). Although postoperative complications were more prevalent in patients with drains, the relationship between these factors was not significant (P >0.050). Length of hospital stay was significantly longer among patients with postoperative drains (P <0.010). Conclusion The routine insertion of drains after thyroid surgeries was found to result in longer hospital stays and did not reduce rates of post-thyroidectomy complications. Thyroid mass size should not be used as an indicator for the insertion of a drain after thyroidectomy. PMID:28003893

  11. Large insert environmental genomic library production.

    PubMed

    Taupp, Marcus; Lee, Sangwon; Hawley, Alyse; Yang, Jinshu; Hallam, Steven J

    2009-09-23

    The vast majority of microbes in nature currently remain inaccessible to traditional cultivation methods. Over the past decade, culture-independent environmental genomic (i.e. metagenomic) approaches have emerged, enabling researchers to bridge this cultivation gap by capturing the genetic content of indigenous microbial communities directly from the environment. To this end, genomic DNA libraries are constructed using standard albeit artful laboratory cloning techniques. Here we describe the construction of a large insert environmental genomic fosmid library with DNA derived from the vertical depth continuum of a seasonally hypoxic fjord. This protocol is directly linked to a series of connected protocols including coastal marine water sampling [1], large volume filtration of microbial biomass [2] and a DNA extraction and purification protocol [3]. At the outset, high quality genomic DNA is end-repaired with the creation of 5 -phosphorylated blunt ends. End-repaired DNA is subjected to pulsed-field gel electrophoresis (PFGE) for size selection and gel extraction is performed to recover DNA fragments between 30 and 60 thousand base pairs (Kb) in length. Size selected DNA is purified away from the PFGE gel matrix and ligated to the phosphatase-treated blunt-end fosmid CopyControl vector pCC1 (EPICENTRE http://www.epibio.com/item.asp?ID=385). Linear concatemers of pCC1 and insert DNA are subsequently headfull packaged into phage particles by lambda terminase, with subsequent infection of phage-resistant E. coli cells. Successfully transduced clones are recovered on LB agar plates under antibiotic selection and archived in 384-well plate format using an automated colony picking robot (Qpix2, GENETIX). The current protocol draws from various sources including the CopyControl Fosmid Library Production Kit from EPICENTRE and the published works of multiple research groups [4-7]. Each step is presented with best practice in mind. Whenever possible we highlight subtleties

  12. Defining the states of consciousness.

    PubMed

    Tassi, P; Muzet, A

    2001-03-01

    Consciousness remains an elusive concept due to the difficulty to define what has been regarded for many years as a subjective experience, therefore irrelevant for scientific study. Recent development in this field of research has allowed to provide some new insight to a possible way to define consciousness. Going through the extensive literature in this domain, several perspectives are proposed to define this concept. (1) Consciousness and Attention may not reflect the same process. (2) Consciousness during wake and sleep may not involve the same mechanisms. (3) Besides physiological states of consciousness, human beings can experience modified states of consciousness either by self-training (transcendental meditation, hypnosis, etc.) or by drug intake (hallucinogens, anaesthetics, etc.). Altogether, we address the question of a more precise terminology, given the theoretical weight words can convey. To this respect, we propose different definitions for concepts like consciousness, vigilance, arousal and alertness as candidates to separate functional entities.

  13. Technical Note: Computer-Manufactured Inserts for Prosthetic Sockets

    PubMed Central

    Sanders, Joan E.; McLean, Jake B.; Cagle, John C.; Gardner, David W.; Allyn, Katheryn J.

    2016-01-01

    The objective of this research was to use computer-aided design software and a tabletop 3-D additive manufacturing system to design and fabricate custom plastic inserts for trans-tibial prosthesis users. Shape quality of inserts was tested right after they were inserted into participant’s test sockets and again after four weeks of wear. Inserts remained properly positioned and intact throughout testing. Right after insertion the inserts caused the socket to be slightly under-sized, by a mean of 0.11 mm, approximately 55% of the thickness of a nylon sheath. After four weeks of wear the under-sizing was less, averaging 0.03 mm, approximately 15% of the thickness of a nylon sheath. Thus the inserts settled into the sockets over time. If existing prosthetic design software packages were enhanced to conduct insert design and to automatically generate fabrication files for manufacturing, then computer manufactured inserts may offer advantages over traditional methods in terms of speed of fabrication, ease of design, modification, and record keeping. PMID:27212209

  14. Development of collimator insert for linac based stereotactic irradiation.

    PubMed

    Singh, I R; Brindha, S; Ravindran, B P; John, S; Rajshekhar, V; Rangad, F V; Roul, R K

    1999-10-01

    The aim of this study is to develop collimator inserts of various sizes which are either not commercially available or are expensive to import. The dosimetry parameters such as tissue maximum ratio (TMR), off-axis ratio (OAR) and output factor of the developed collimator insert are compared with that of the commercial collimator insert (Radionics). In order to check the suitability of the collimator insert developed locally for clinical use and to standardize the method of development, a collimator insert of 15 mm identical to the one supplied by Radionics is developed with low-melting alloy (Cerrobend). Moreover for the clinical use of the developed collimator insert, certain acceptance tests are performed which include a collimator concentricity test, beam size check and radiation leakage test. The dose verification is carried out with a thermoluminescent dosimeter (7LiF rods) and an FBX chemical dosimeter in a human-head-shaped Perspex phantom filled with water. The variation between the calculated and measured dose is found to be within +2.4% for 7LiF rods and -2.0% for the FBX chemical dosimeter thus ensuring the suitability of the developed collimator insert for clinical use. This has encouraged us to standardize the method adapted to develop the collimator insert and to develop collimator inserts of different field sizes.

  15. Threaded insert for compact cryogenic-capable pressure vessels

    DOEpatents

    Espinosa-Loza, Francisco; Ross, Timothy O.; Switzer, Vernon A.; Aceves, Salvador M.; Killingsworth, Nicholas J.; Ledesma-Orozco, Elias

    2015-06-16

    An insert for a cryogenic capable pressure vessel for storage of hydrogen or other cryogenic gases at high pressure. The insert provides the interface between a tank and internal and external components of the tank system. The insert can be used with tanks with any or all combinations of cryogenic, high pressure, and highly diffusive fluids. The insert can be threaded into the neck of a tank with an inner liner. The threads withstand the majority of the stress when the fluid inside the tank that is under pressure.

  16. Effect of vibration frequency on biopsy needle insertion force.

    PubMed

    Tan, Lei; Qin, Xuemei; Zhang, Qinhe; Zhang, Hongcai; Dong, Hongjian; Guo, Tuodang; Liu, Guowei

    2017-05-01

    Needle insertion is critical in many clinical medicine procedures, such as biopsy, brachytherapy, and injection therapy. A platform with two degrees of freedom was set up to study the effect of vibration frequency on needle insertion force. The gel phantom deformation at the needle cutting edge and the Voigt model are utilized to develop a dynamic model to explain the relationship between the insertion force and needle-tip velocity. The accuracy of this model was verified by performing needle insertions into phantom gel. The effect of vibration on insertion force can be explained as the vibration increasing the needle-tip velocity and subsequently increasing the insertion force. In a series of needle insertion experiments with different vibration frequencies, the peak forces were selected for comparison to explore the effect of vibration frequency on needle insertion force. The experimental results indicate that the insertion force at 500Hz increases up to 17.9% compared with the force at 50Hz. Copyright © 2017 IPEM. Published by Elsevier Ltd. All rights reserved.

  17. Insertion kinetics of small nucleotides through single walled carbon nanotube.

    PubMed

    Clavier, A; Kraszewski, S; Ramseyer, C; Picaud, F

    2013-03-10

    We report molecular dynamic simulations showing that a DNA molecule constituted by five unique bases can be spontaneously inserted into single walled carbon nanotube (SWCNT) in normal conditions (P, T and water environment) depending on the tube radius value. The van der Waals and electrostatic interactions play a central role for the rapid insertion process. Our study shows also that the Guanine molecule inserts the fastest compared to thymine, adenine and cytosine bases, respectively. The differences of insertion time could be exploited for applications concerning for example DNA sequencing. Copyright © 2012 Elsevier B.V. All rights reserved.

  18. Optimal point of insertion of the needle in neuraxial blockade using a midline approach: study in a geometrical model

    PubMed Central

    Vogt, Mark; van Gerwen, Dennis J; van den Dobbelsteen, John J; Hagenaars, Martin

    2016-01-01

    Performance of neuraxial blockade using a midline approach can be technically difficult. It is therefore important to optimize factors that are under the influence of the clinician performing the procedure. One of these factors might be the chosen point of insertion of the needle. Surprisingly few data exist on where between the tips of two adjacent spinous processes the needle should be introduced. A geometrical model was adopted to gain more insight into this issue. Spinous processes were represented by parallelograms. The length, the steepness relative to the skin, and the distance between the parallelograms were varied. The influence of the chosen point of insertion of the needle on the range of angles at which the epidural and subarachnoid space could be reached was studied. The optimal point of insertion was defined as the point where this range is the widest. The geometrical model clearly demonstrated, that the range of angles at which the epidural or subarachnoid space can be reached, is dependent on the point of insertion between the tips of the adjacent spinous processes. The steeper the spinous processes run, the more cranial the point of insertion should be. Assuming that the model is representative for patients, the performance of neuraxial blockade using a midline approach might be improved by choosing the optimal point of insertion. PMID:27570462

  19. Feedback-reactivity time-dependencies for a negative reactivity insertion in EBR-II

    SciTech Connect

    Grimm, K.N.; Meneghetti, D.

    1987-01-01

    Knowledge of time-dependencies (and magnitudes) of feedback components is necessary for interpretation and understanding of transient behaviors. Described herein is one analysis of negative insertion (approx. 36 cents) of a control rod from full power during Experimental Breeder Reactor-II (EBR-II) run 93a. The time-dependencies of the component feedbacks have been analyzed using 24 channels in the EROS computer code. Seventy distinct temperature coefficients of reactivity were used in conjunction with this 24-channel EBR-II model. These temperature coefficients of reactivity were obtained using an addition (TEMCO) to the EBRPOCO code.

  20. [Insertion of biliary endoprosthesis as ambulatory procedure].

    PubMed

    Güitrón, A; Adalid, R; Barinagarrementería, R; Gutiérrez-Bermúdez, J A

    2001-01-01

    Because of possible complications, it has been common practice to admit to the hospital most if not all patients undergoing therapeutic ERCP. Therefore, little descriptive data exist on the safety of out-patient therapeutic ERCP for endobiliary stent placement. To assure quality patient care and patient safety, we reviewed our experience with out-patient therapeutic ERCP for palliation of benign and malignant common bile duct obstruction by means of endobiliary stent insertion. PATIENTS-METHODS AND RESULTS: A retrospective review of all therapeutic ERCPs for palliation of benign and malignant common bile duct obstruction with endobiliary stents was performed from January 1, 1998, through December 31, 1999. One hundred forty therapeutic ERCPs were performed to place an endobiliary stent for benign and malignant common bile duct obstruction. Seventy-two procedures were performed on out-patients, sixty-eight on in-patients. There was no significant difference between out-patient and in-patient groups with regard to age, gender, need for endoscopic sphincterotomy, and complication rate. In patients had one procedure-related complication; out patients had four. There was no procedure-related mortality in either group. Therapeutic ERCP for palliation of benign and malignant common bile duct obstruction with endobiliary stents can be safely and successfully performed on an out-patient basis for selected patients. This should result in substantial cost savings.

  1. Biosynthesis and Insertion of the Molybdenum Cofactor.

    PubMed

    Magalon, Axel; Mendel, Ralf R

    2015-01-01

    The transition element molybdenum (Mo) is of primordial importance for biological systems, because it is required by enzymes catalyzing key reactions in the global carbon, sulfur, and nitrogen metabolism. To gain biological activity, Mo has to be complexed by a special cofactor. With the exception of bacterial nitrogenase, all Mo-dependent enzymes contain a unique pyranopterin-based cofactor coordinating a Mo atom at their catalytic site. Various types of reactions are catalyzed by Mo-enzymes in prokaryotes including oxygen atom transfer, sulfur or proton transfer, hydroxylation, or even nonredox reactions. Mo-enzymes are widespread in prokaryotes and many of them were likely present in the Last Universal Common Ancestor. To date, more than 50--mostly bacterial--Mo-enzymes are described in nature. In a few eubacteria and in many archaea, Mo is replaced by tungsten bound to the same unique pyranopterin. How Mo-cofactor is synthesized in bacteria is reviewed as well as the way until its insertion into apo-Mo-enzymes.

  2. Insertion devices for DORIS III (invited)

    NASA Astrophysics Data System (ADS)

    Pflüger, J.

    1992-01-01

    Recently, a major reconstruction of the electron storage ring DORIS II, the DORIS III project, has been completed [W. Brefeld, H. Nesemann, and J. Rossbach, Proceedings of the European Particle Accelerator Conference, Rome (World Scientific, Singapore, 1988), p. 2389]. Figure 1 shows an overview of the new ring. Originally DORIS II had a twofold symmetry. In part C each of the two dipole magnets adjacing to the 65-m-long straight section was replaced by three corresponding weaker ones. In this way a total of seven straight sections for insertion devices are provided. Six of them are 4-m long and the one in the center is only 2.7-m long. After extensive discussions with the user groups involved, four x-ray wigglers, one asymmetric hybrid structure, one x-ray undulator, and one XUV multiple undulator of the revolver type have been proposed for six of the sections [J. Pflüger and P. Gurtler, Nucl. Instrum. Methods A 287, 628 (1990)]. One section is presently still free. All devices are either in construction or have already been completed and installed. In this contribution the mechanical and magnetic design of these devices will be described. Results of magnetic measurements of those devices which are already completed will be given in more detail.

  3. Phoenix Conductivity Probe Inserted into Martian Soil

    NASA Technical Reports Server (NTRS)

    2008-01-01

    NASA's Phoenix Mars Lander inserted the four needles of its thermal and conductivity probe into Martian soil during the 98th Martian day, or sol, of the mission and left it in place until Sol 99 (Sept. 4, 2008).

    The Robotic Arm Camera on Phoenix took this image on the morning of Sol 99 while the probe's needles were in the ground. The science team informally named this soil target 'Gandalf.'

    The thermal and conductivity probe measures how fast heat and electricity move from one needle to an adjacent one through the soil or air between the needles. Conductivity readings can be indicators about water vapor, water ice and liquid water.

    The probe is part of Phoenix's Microscopy, Electrochemistry and Conductivity suite of instruments.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  4. Replicative resolution of integron cassette insertion

    PubMed Central

    Loot, Céline; Ducos-Galand, Magaly; Escudero, José Antonio; Bouvier, Marie; Mazel, Didier

    2012-01-01

    Site-specific recombination catalyzed by tyrosine recombinases follows a common pathway consisting of two consecutive strand exchanges. The first strand exchange generates a Holliday junction (HJ), which is resolved by a second strand exchange. In integrons, attC sites recombine as folded single-stranded substrates. Only one of the two attC site strands, the bottom one, is efficiently bound and cleaved by the integrase during the insertion of gene cassettes at the double-stranded attI site. Due to the asymmetry of this complex, a second strand exchange on the attC bottom strand (bs) would form linearized abortive recombination products. We had proposed that HJ resolution would rely on an uncharacterized mechanism, probably replication. Using an attC site carried on a plasmid with each strand specifically tagged, we followed the destiny of each strand after recombination. We demonstrated that only one strand, the one carrying the attC bs, is exchanged. Furthermore, we show that the recombination products contain the attC site bs and its entire de novo synthesized complementary strand. Therefore, we demonstrate the replicative resolution of single-strand recombination in integrons and rule out the involvement of a second strand exchange of any kind in the attC × attI reaction. PMID:22740653

  5. ACE insert/delete polymorphism and atherosclerosis.

    PubMed

    Scheer, W Douglas; Boudreau, Donald A; Hixson, James E; McGill, Henry C; Newman, William P; Tracy, Richard E; Zieske, Arthur W; Strong, Jack P

    2005-02-01

    We report on the results of a large autopsy study focusing upon the hypothesis that deletion of the Alu insert in the angiotensin converting enzyme (ACE) gene is associated with: (a) greater prevalence or extent of atherosclerosis in the aorta and coronary arteries; and (b) microscopic qualities of established atherosclerotic plaques in the coronary arteries. This study was conducted in young US black (n=290) and white (n=379) males using available materials and data from the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study, a multi-center cooperative autopsy study organized in 1985 to explore the relationships of known cardiovascular risk factors to atherosclerosis in victims of accidents, homicides, or suicides in the age range of 15-34 years. The results provide strong evidence that ACE genotype may not be a predictor of either the prevalence or the extent of the lesions of atherosclerosis in the right coronary artery or the aorta of young adults, an observation that confirms previous studies that estimated the prevalence and extent of atherosclerosis using coronary angiography. In addition, the results suggest that ACE genotype does not contribute to the formation of atherosclerotic lesions that have the characteristics of vulnerable plaques in the left anterior descending coronary artery of young adults.

  6. Antibody binding loop insertions as diversity elements

    PubMed Central

    Kiss, Csaba; Fisher, Hugh; Pesavento, Emanuele; Dai, Minghua; Valero, Rosa; Ovecka, Milan; Nolan, Rhiannon; Phipps, M. Lisa; Velappan, Nileena; Chasteen, Leslie; Martinez, Jennifer S.; Waldo, Geoffrey S.; Pavlik, Peter; Bradbury, Andrew R.M.

    2006-01-01

    In the use of non-antibody proteins as affinity reagents, diversity has generally been derived from oligonucleotide-encoded random amino acids. Although specific binders of high-affinity have been selected from such libraries, random oligonucleotides often encode stop codons and amino acid combinations that affect protein folding. Recently it has been shown that specific antibody binding loops grafted into heterologous proteins can confer the specific antibody binding activity to the created chimeric protein. In this paper, we examine the use of such antibody binding loops as diversity elements. We first show that we are able to graft a lysozyme-binding antibody loop into green fluorescent protein (GFP), creating a fluorescent protein with lysozyme-binding activity. Subsequently we have developed a PCR method to harvest random binding loops from antibodies and insert them at predefined sites in any protein, using GFP as an example. The majority of such GFP chimeras remain fluorescent, indicating that binding loops do not disrupt folding. This method can be adapted to the creation of other nucleic acid libraries where diversity is flanked by regions of relative sequence conservation, and its availability sets the stage for the use of antibody loop libraries as diversity elements for selection experiments. PMID:17023486

  7. IYA2009 newspaper insert in your community

    NASA Astrophysics Data System (ADS)

    Harvey, J.

    2008-06-01

    The Gemini PIO (Public Information Officer) offers suggestions on how to approach your local newspaper about a newspaper insert for your community being published during IYA2009. Local government support, articles by astronomers, advertisers, and appointing someone within your organisation to manage the content will be discussed. We will explain the timeline required, the number of personnel hours required, developmental stages and income a local newspaper would have to generate to produce a quality, table-top supplement. In 2003, over 30,000 copies of Stars over Mauna Kea, a special supplement in tabloid format were produced and distributed in the local newspapers in Hilo, Hawaii. The publication, 48 pages in total, featured profiles of the observatories on Mauna Kea, stories about the geology and legends of Mauna Kea, and historical information about the evolution of astronomy in Hawaii. In additionthe publication included a series of essays titled In their own words. These articles were written by key members of the astronomy community. Sixty thousand copies of Stars over Mauna Kea II were printed as a follow-up to the first edition in 2005. This second edition included an article on the `Imiloa Astronomy Education Center, explanations about the types of telescopes on Mauna Kea and columns written by scientists about the fascinating and significant discoveries made on Hawaii. Personal stories about careers in astronomy were also highlighted. In Chile, a similar eight-page supplement, featuring Gemini, CTIO and SOAR telescopes, was published in 2005 and 5000 copies were distributed throughout the country.

  8. Phoenix Conductivity Probe Inserted into Martian Soil

    NASA Technical Reports Server (NTRS)

    2008-01-01

    NASA's Phoenix Mars Lander inserted the four needles of its thermal and conductivity probe into Martian soil during the 98th Martian day, or sol, of the mission and left it in place until Sol 99 (Sept. 4, 2008).

    The Robotic Arm Camera on Phoenix took this image on the morning of Sol 99 while the probe's needles were in the ground. The science team informally named this soil target 'Gandalf.'

    The thermal and conductivity probe measures how fast heat and electricity move from one needle to an adjacent one through the soil or air between the needles. Conductivity readings can be indicators about water vapor, water ice and liquid water.

    The probe is part of Phoenix's Microscopy, Electrochemistry and Conductivity suite of instruments.

    The Phoenix Mission is led by the University of Arizona, Tucson, on behalf of NASA. Project management of the mission is by NASA's Jet Propulsion Laboratory, Pasadena, Calif. Spacecraft development is by Lockheed Martin Space Systems, Denver.

  9. Study of Uranium Oxide Insertion Compounds

    DTIC Science & Technology

    1993-01-01

    the strong uranyl group, UO2 2 ", present in all but one of the U0 3 allotropes as a distinctive 0 linear [O=U=O] 2 ÷ moiety. The electronic structure...electrolyte@ based on sulfur wait looked at next. The first, sulfolane, looked very attractive as can be seen from its physical properties at 30"C (11): O0FY...while bubbling N2 through the mixture. Flowing nitrogen is essential in removing sulfur dioxide and butadiene, the decomposition products of 3-sulfolene

  10. Defining "Folklore" in the Classroom.

    ERIC Educational Resources Information Center

    Falke, Anne

    Folklore, a body of traditional beliefs of a people conveyed orally or by means of custom, is very much alive, involves all people, and is not the study of popular culture. In studying folklore, the principal tasks of the folklorist have been defined as determining definition, classification, source (the folk), origin (who composed folklore),…

  11. Defining and Measuring Psychomotor Performance

    ERIC Educational Resources Information Center

    Autio, Ossi

    2007-01-01

    Psychomotor performance is fundamental to human existence. It is important in many real world activities and nowadays psychomotor tests are used in several fields of industry, army, and medical sciences in employee selection. This article tries to define psychomotor activity by introducing some psychomotor theories. Furthermore the…

  12. Defined by Word and Space

    ERIC Educational Resources Information Center

    Brisco, Nicole D.

    2010-01-01

    In the author's art class, she found that many of her students in an intro art class have some technical skill, but lack the ability to think conceptually. Her goal was to create an innovative project that combined design, painting, and sculpture into a compact unit that asked students how they define themselves. In the process of answering this…

  13. Defined by Word and Space

    ERIC Educational Resources Information Center

    Brisco, Nicole D.

    2010-01-01

    In the author's art class, she found that many of her students in an intro art class have some technical skill, but lack the ability to think conceptually. Her goal was to create an innovative project that combined design, painting, and sculpture into a compact unit that asked students how they define themselves. In the process of answering this…

  14. Defining and Differentiating the Makerspace

    ERIC Educational Resources Information Center

    Dousay, Tonia A.

    2017-01-01

    Many resources now punctuate the maker movement landscape. However, some schools and communities still struggle to understand this burgeoning movement. How do we define these spaces and differentiate them from previous labs and shops? Through a multidimensional framework, stakeholders should consider how the structure, access, staffing, and tools…

  15. In vivo evaluation of needle force and friction stress during insertion at varying insertion speed into the brain.

    PubMed

    Casanova, Fernando; Carney, Paul R; Sarntinoranont, Malisa

    2014-11-30

    Convection enhanced delivery (CED) infuses drugs directly into brain tissue. Needle insertion is required and results in tissue damage which can promote flowback along the needle track and improper targeting. The goal of this study was to evaluate friction stress (calculated from needle insertion force) as a measure of tissue contact and damage during needle insertion for varying insertion speeds. Forces and surface dimpling during needle insertion were measured in rat brain in vivo. Needle retraction forces were used to calculate friction stresses. These measures were compared to track damage from a previous study. Differences between brain tissues and soft hydrogels were evaluated for varying insertion speeds: 0.2, 2, and 10mm/s. In brain tissue, average insertion force and surface dimpling increased with increasing insertion speed. Average friction stress along the needle-tissue interface decreased with insertion speed (from 0.58 ± 0.27 to 0.16 ± 0.08 kPa). Friction stress varied between brain regions: cortex (0.227 ± 0.27 kPa), external capsule (0.222 ± 0.19 kPa), and CPu (0.383 ± 0.30 kPa). Hydrogels exhibited opposite trends for dimpling and friction stress with insertion speed. Previously, increasing needle damage with insertion speed has been measured with histological methods. Friction stress appears to decrease with increasing tissue damage and decreasing tissue contact, providing the potential for in vivo and real time evaluation along the needle track. Force derived friction stress decreased with increasing insertion speed and was smaller within white matter regions. Hydrogels exhibited opposite trends to brain tissue. Copyright © 2014 Elsevier B.V. All rights reserved.

  16. Tandem insertion sequence-like elements define the expression site for variable antigen genes of Borrelia hermsii.

    PubMed Central

    Barbour, A G; Carter, C J; Burman, N; Freitag, C S; Garon, C F; Bergström, S

    1991-01-01

    The spirochete Borrelia hermsii avoids the immune response of its mammalian host through multiphasic antigenic variation. Serotype specificity is determined by variable antigens, Vmp proteins, in the outer membrane. Through nonreciprocal recombination between linear plasmids, a formerly silent vmp gene replaces another vmp gene downstream from a common expression site. To further characterize this activating site, we determined the nucleotide sequence of 6.9 kb of the common upstream expression region of strain HS1 of B. hermsii. Preceding the vmp gene promoter and a poly(dT.dA) run were three imperfectly repeated segments of 2 kb. Each of the 2-kb segments contained 1-kb elements with inverted repeats of approximately 0.2 kb each at their termini. The potential of the 1-kb elements to form stem-and-loop structures was demonstrated by heteroduplex analysis. There was no evidence of the presence of the elements elsewhere in the genome of B. hermsii. One or more of these elements may confer the unidirectionality that characterizes vmp gene switches. Images PMID:1987053

  17. Identifying pitfalls in chest tube insertion: improving teaching and performance.

    PubMed

    Davis, James S; Garcia, George D; Jouria, Jassin M; Wyckoff, Mary M; Alsafran, Salman; Graygo, Jill M; Withum, Kelly F; Schulman, Carl I

    2013-01-01

    Chest tube thoracostomies are common surgical procedures, but little is known about how practitioners learn the skill. This study evaluates the frequency with which correctly performed tasks are executed by subjects during chest tube thoracostomies. In this prospective study, we developed a mobile-learning module, containing stepwise multimedia guidance on chest tube insertion. Next, we developed and tested a 14-item checklist, modeled after key skills in the module. Participants, defined as "novice" (fewer than 10 chest tubes placed) or "expert" (10 or more placed), were assigned to either the video or control group. A trained clinician used the checklist to rate participants while they inserted a chest tube on a TraumaMan simulator. University of Miami, Miller School of Medicine, a tertiary care academic institution. Current medical students, residents, and the United States Army Forward Surgical Team members rotating through the institution. One hundred twenty-eight subjects entered and finished the study. One hundred twenty-eight subjects enrolled in the study; 86 (67%) were residents or US Army Forward Surgical Team members, 66 (77%) were novices, and 20 (23%) were experts. Novices most frequently connected the tube to suction (91%), adequately dissected the soft tissue (82%), and scrubbed or anesthetized appropriately (80%). They least frequently completed full finger sweeps (33%), avoided the neurovascular bundle (35%), and performed a controlled pleural puncture (39%). Comparing the novice video group with the novice control group, the video group was more likely to correctly perform a finger sweep (42%, p<0.001) and clamp the distal end of the chest tube (42%, p<0.001). Of all the steps, experts least frequently completed full finger sweeps (70%) and avoided the neurovascular bundle (75%). Comparing the expert video group with the expert control group, the video group was more likely to correctly perform finger sweeps, the incision, and clamping the distal

  18. Roles of carboxyl groups in the transmembrane insertion of peptides

    PubMed Central

    Barrera, Francisco N.; Weerakkody, Dhammika; Anderson, Michael; Andreev, Oleg A.; Reshetnyak, Yana K.; Engelman, Donald M.

    2011-01-01

    We have used the pHLIP® peptide to study the roles of carboxyl groups in transmembrane peptide insertion. The pH (low) insertion peptide (pHLIP) binds to the surface of a lipid bilayer as a disordered peptide at neutral pH, and when the pH is lowered it inserts across the membrane to form a transmembrane helix. Peptide insertion is reversed when the pH is raised above the characteristic pKa (6.0). A key event facilitating the membrane insertion is the protonation of aspartic (Asp) and/or glutamic (Glu) acid residues, since at neutral pH their negatively charged side chains hinder membrane insertion. In order to gain mechanistic understanding, we studied the membrane insertion and exit of a series of pHLIP variants where the four Asp residues were sequentially mutated to nonacidic residues, including histidine (His). Our results show that the presence of His residues does not prevent the pH-dependent peptide membrane insertion at ~pH 4 driven by the protonation of carboxyl groups at the inserting end of the peptide. A further pH drop leads to the protonation of His residues in the TM part of peptide, which induces peptide exit from the bilayer. We also find that the number of ionizable residues that undergo a change in protonation during membrane insertion correlates with the pH-dependent insertion into and exit from the lipid bilayer, and that cooperativity increases with their number. We expect that our understanding will be used to improve the targeting of acidic diseased tissue by pHLIP peptides. PMID:21888917

  19. Wetlands Restoration Definitions and Distinctions

    EPA Pesticide Factsheets

    Ecological restoration is a valuable endeavor that has proven very difficult to define. The term indicates that degraded and destroyed natural wetland systems will be reestablished to sites where they once existed. But, what wetland ecosystems are we talki

  20. Qualitative and Quantitative Distinctions in Personality Disorder

    PubMed Central

    Wright, Aidan G. C.

    2011-01-01

    The “categorical-dimensional debate” has catalyzed a wealth of empirical advances in the study of personality pathology. However, this debate is merely one articulation of a broader conceptual question regarding whether to define and describe psychopathology as a quantitatively extreme expression of normal functioning or as qualitatively distinct in its process. In this paper I argue that dynamic models of personality (e.g., object-relations, cognitive-affective processing system) offer the conceptual scaffolding to reconcile these seemingly incompatible approaches to characterizing the relationship between normal and pathological personality. I propose that advances in personality assessment that sample behavior and experiences intensively provide the empirical techniques, whereas interpersonal theory offers an integrative theoretical framework, for accomplishing this goal. PMID:22804676

  1. Acute jejunoileitis. A distinct entity?

    PubMed

    Levine, J; Schmidt, M H; Burrell, M I; Hopkins, M S

    1992-01-01

    A 44-year-old man with acute jejunoileitis of unknown etiology developed small bowel obstruction. Intermittent abdominal pain, bloody diarrhea, ascites, and leukocytosis were prominent features. All stool cultures were negative. On steroid treatment, symptoms and radiographic features completely resolved. We suggest, in agreement with an earlier report, that acute jejunoileitis may be regarded as a distinct clinical entity.

  2. China English: Its Distinctive Features

    ERIC Educational Resources Information Center

    Yang, Wei-dong; Dai, Wei-ping

    2011-01-01

    This paper attempts to expound that China English boasting its own distinctive features on the levels of phonology, words, sentences and discourse has been playing an irreplaceable role in intercultural activities, though still in its infancy and in the process of developing and perfecting itself, and it now makes every effort to move towards…

  3. Distinctiveness Maps for Image Matching

    NASA Technical Reports Server (NTRS)

    Manduchi, Roberto; Tomasi, Carlo

    2000-01-01

    Stereo correspondence is hard because different image features can look alike. We propose a measure for the ambiguity of image points that allows matching distinctive points first and breaks down the matching task into smaller and separate subproblems. Experiments with an algorithm based on this measure demonstrate the ensuing efficiency and low likelihood of incorrect matches.

  4. Educational Psychology: The Distinctive Contribution

    ERIC Educational Resources Information Center

    Cameron, R. J.

    2006-01-01

    This paper, written in the twenty-first anniversary year of the journal "Educational Psychology in Practice", attempts to uncover those distinctive aspects of the discipline and the practice of applied psychology in general and educational psychology in particular. After considering some of the reasons for attempting this task at this point in…

  5. Educational Psychology: The Distinctive Contribution

    ERIC Educational Resources Information Center

    Cameron, R. J.

    2006-01-01

    This paper, written in the twenty-first anniversary year of the journal "Educational Psychology in Practice", attempts to uncover those distinctive aspects of the discipline and the practice of applied psychology in general and educational psychology in particular. After considering some of the reasons for attempting this task at this point in…

  6. Evaluating Risks of Insertional Mutagenesis by DNA Transposons in Gene Therapy

    PubMed Central

    Hackett, Perry B.; Largaespada, David A.; Switzer, Kirsten C.; Cooper, Laurence J.N.

    2013-01-01

    Investigational therapy can be successfully undertaken using viral- and non-viral-mediated ex vivo gene transfer. Indeed, recent clinical trials have established the potential for genetically modified T cells to improve and restore health. Recently the Sleeping Beauty (SB) transposon/transposase system has been applied in clinical trials to stably insert a chimeric antigen receptor (CAR) to redirect T-cell specificity. We discuss the context in which the SB system can be harnessed for gene therapy and describe the human application of SB-modified CAR+ T cells. We have focused on theoretical issues relating to insertional mutagenesis in the context of human genomes that are naturally subjected to remobilization of transposons and the experimental evidence over the last decade of employing SB transposons for defining genes that induce cancer. These findings are put into the context of the use of SB transposons in the treatment of human disease. PMID:23313630

  7. Evaluating risks of insertional mutagenesis by DNA transposons in gene therapy.

    PubMed

    Hackett, Perry B; Largaespada, David A; Switzer, Kirsten C; Cooper, Laurence J N

    2013-04-01

    Investigational therapy can be successfully undertaken using viral- and nonviral-mediated ex vivo gene transfer. Indeed, recent clinical trials have established the potential for genetically modified T cells to improve and restore health. Recently, the Sleeping Beauty (SB) transposon/transposase system has been applied in clinical trials to stably insert a chimeric antigen receptor (CAR) to redirect T-cell specificity. We discuss the context in which the SB system can be harnessed for gene therapy and describe the human application of SB-modified CAR(+) T cells. We have focused on theoretical issues relating to insertional mutagenesis in the context of human genomes that are naturally subjected to remobilization of transposons and the experimental evidence over the last decade of employing SB transposons for defining genes that induce cancer. These findings are put into the context of the use of SB transposons in the treatment of human disease.

  8. Hydrophobic Clusters Raise the Threshold Hydrophilicity for Insertion of Transmembrane Sequences in Vivo.

    PubMed

    Stone, Tracy A; Schiller, Nina; Workewych, Natalie; von Heijne, Gunnar; Deber, Charles M

    2016-10-11

    Insertion of a nascent membrane protein segment by the translocon channel into the bilayer is naturally promoted by high segmental hydrophobicity, but its selection as a transmembrane (TM) segment is complicated by the diverse environments (aqueous vs lipidic) the protein encounters and by the fact that most TM segments contain a substantial amount (∼30%) of polar residues, as required for protein structural stabilization and/or function. To examine the contributions of these factors systematically, we designed and synthesized a peptide library consisting of pairs of compositionally identical, but sequentially different, peptides with 19-residue core sequences varying (i) in Leu positioning (with five or seven Leu residues clustered into a contiguous "block" in the middle of the segment or "scrambled" throughout the sequence) and (ii) in Ser content (0-6 residues). The library was analyzed by a combination of biophysical and biological techniques, including HPLC retention times, circular dichroism measurements of helicity in micelle and phospholipid bilayer media, and relative blue shifts in Trp fluorescence maxima, as well as by the extent of membrane insertion in a translocon-mediated assay using microsomal membranes from dog pancreas endoplasmic reticulum. We found that local blocks of high hydrophobicity heighten the translocon's propensity to insert moderately hydrophilic sequences, until a "threshold hydrophilicity" is surpassed whereby segments no longer insert even in the presence of Leu blocks. This study codifies the prerequisites of apolar/polar content and residue positioning that define nascent TM segments, illustrates the accuracy in their prediction, and highlights how a single disease-causing mutation can tip the balance toward anomalous translocation/insertion.

  9. Bacterial repetitive extragenic palindromic sequences are DNA targets for Insertion Sequence elements

    PubMed Central

    Tobes, Raquel; Pareja, Eduardo

    2006-01-01

    Background Mobile elements are involved in genomic rearrangements and virulence acquisition, and hence, are important elements in bacterial genome evolution. The insertion of some specific Insertion Sequences had been associated with repetitive extragenic palindromic (REP) elements. Considering that there are a sufficient number of available genomes with described REPs, and exploiting the advantage of the traceability of transposition events in genomes, we decided to exhaustively analyze the relationship between REP sequences and mobile elements. Results This global multigenome study highlights the importance of repetitive extragenic palindromic elements as target sequences for transposases. The study is based on the analysis of the DNA regions surrounding the 981 instances of Insertion Sequence elements with respect to the positioning of REP sequences in the 19 available annotated microbial genomes corresponding to species of bacteria with reported REP sequences. This analysis has allowed the detection of the specific insertion into REP sequences for ISPsy8 in Pseudomonas syringae DC3000, ISPa11 in P. aeruginosa PA01, ISPpu9 and ISPpu10 in P. putida KT2440, and ISRm22 and ISRm19 in Sinorhizobium meliloti 1021 genome. Preference for insertion in extragenic spaces with REP sequences has also been detected for ISPsy7 in P. syringae DC3000, ISRm5 in S. meliloti and ISNm1106 in Neisseria meningitidis MC58 and Z2491 genomes. Probably, the association with REP elements that we have detected analyzing genomes is only the tip of the iceberg, and this association could be even more frequent in natural isolates. Conclusion Our findings characterize REP elements as hot spots for transposition and reinforce the relationship between REP sequences and genomic plasticity mediated by mobile elements. In addition, this study defines a subset of REP-recognizer transposases with high target selectivity that can be useful in the development of new tools for genome manipulation. PMID

  10. Modular Evolution of TnGBSs, a New Family of Integrative and Conjugative Elements Associating Insertion Sequence Transposition, Plasmid Replication, and Conjugation for Their Spreading

    PubMed Central

    Guérillot, Romain; Da Cunha, Violette; Sauvage, Elisabeth; Bouchier, Christiane

    2013-01-01

    Integrative and conjugative elements (ICEs) have a major impact on gene flow and genome dynamics in bacteria. The ICEs TnGBS1 and TnGBS2, first identified in Streptococcus agalactiae, use a DDE transposase, unlike most characterized ICEs, which depend on a phage-like integrase for their mobility. Here we identified 56 additional TnGBS-related ICEs by systematic genome analysis. Interestingly, all except one are inserted in streptococcal genomes. Sequence comparison of the proteins conserved among these ICEs defined two subtypes related to TnGBS1 or TnGBS2. We showed that both types encode different conjugation modules: a type IV secretion system, a VirD4 coupling protein, and a relaxase and its cognate oriT site, shared with distinct lineages of conjugative elements of Firmicutes. Phylogenetic analysis suggested that TnGBSs evolved from two conjugative elements of different origins by the successive recruitment of a transposition module derived from insertion sequences (ISs). Furthermore, TnGBSs share replication modules with different plasmids. Mutational analyses and conjugation experiments showed that TnGBS1 and TnGBS2 combine replication and transposition upstream promoters for their transfer and stabilization. Despite an evolutionarily successful horizontal dissemination within the genus Streptococcus, these ICEs have a restricted host range. However, we reveal that for TnGBS1 and TnGBS2, this host restriction is not due to a transfer incompatibility linked to the conjugation machineries but most likely to their ability for transient maintenance through replication after their transfer. PMID:23435978

  11. Modular evolution of TnGBSs, a new family of integrative and conjugative elements associating insertion sequence transposition, plasmid replication, and conjugation for their spreading.

    PubMed

    Guérillot, Romain; Da Cunha, Violette; Sauvage, Elisabeth; Bouchier, Christiane; Glaser, Philippe

    2013-05-01

    Integrative and conjugative elements (ICEs) have a major impact on gene flow and genome dynamics in bacteria. The ICEs TnGBS1 and TnGBS2, first identified in Streptococcus agalactiae, use a DDE transposase, unlike most characterized ICEs, which depend on a phage-like integrase for their mobility. Here we identified 56 additional TnGBS-related ICEs by systematic genome analysis. Interestingly, all except one are inserted in streptococcal genomes. Sequence comparison of the proteins conserved among these ICEs defined two subtypes related to TnGBS1 or TnGBS2. We showed that both types encode different conjugation modules: a type IV secretion system, a VirD4 coupling protein, and a relaxase and its cognate oriT site, shared with distinct lineages of conjugative elements of Firmicutes. Phylogenetic analysis suggested that TnGBSs evolved from two conjugative elements of different origins by the successive recruitment of a transposition module derived from insertion sequences (ISs). Furthermore, TnGBSs share replication modules with different plasmids. Mutational analyses and conjugation experiments showed that TnGBS1 and TnGBS2 combine replication and transposition upstream promoters for their transfer and stabilization. Despite an evolutionarily successful horizontal dissemination within the genus Streptococcus, these ICEs have a restricted host range. However, we reveal that for TnGBS1 and TnGBS2, this host restriction is not due to a transfer incompatibility linked to the conjugation machineries but most likely to their ability for transient maintenance through replication after their transfer.

  12. Nora's lesion, a distinct radiological entity?

    PubMed

    Dhondt, E; Oudenhoven, L; Khan, S; Kroon, H M; Hogendoorn, P C; Nieborg, A; Bloem, J L; De Schepper, A

    2006-07-01

    To describe the radiological findings of "Bizarre parosteal osteochondromatous proliferation"(BPOP)-otherwise known as Nora's lesion, to describe the natural evolution of BPOP and to assess radiologically if BPOP is indeed part of a spectrum of reactive lesions including florid reactive periostitis and turret exostosis. Four experienced musculoskeletal radiologists studied plain radiographs and other imaging documents of histologically-proven Nora's lesions, looking for soft-tissue changes, periosteal reaction/calcification and calcified/ossified pseudotumours, and compared those findings with findings on pathology reviewed by a peer group of pathologists. Twenty-four Nora's lesions originating from a series of 200 consecutive, histologically-verified bone (pseudo)tumours of the hand, seen by the "Netherlands Committee on Bone Tumours" for review and second opinion. Nora's lesions have a recognised presentation on radiographs without specific MR characteristics. Natural evolution could be assessed retrospectively in four cases. Recurrent lesions were seen in seven cases and are difficult to differentiate from primary lesions. Nora's lesion, defined as a "well-marginated mass of heterotopic mineralization arising from the periosteal aspect of an intact cortex, without medullary changes" has a distinct radiological presentation and is part of a spectrum of reactive lesions which includes florid reactive periostitis and turret exostosis. As it has a distinct radiological appearance, differential diagnosis of malignant lesions such as osteosarcoma and chondrosarcoma should be clear. It does not require immediate biopsy unless the natural evolution is unspecific.

  13. Cruciate retaining and cruciate substituting ultra-congruent insert

    PubMed Central

    Deledda, Davide; Rosso, Federica; Ratto, Nicola; Bruzzone, Matteo; Bonasia, Davide Edoardo; Rossi, Roberto

    2016-01-01

    The posterior cruciate ligament (PCL) conservation and the polyethylene insert constraint in total knee arthroplasty (TKA) are still debated. The PCL is one of the primary stabilizers of the joint, but cruciate retaining (CR) implants have the disadvantage of a difficult balancing of the PCL. Postero-stabilized (PS) implants were introduced to reduce this problem. However, also the PS implants have some disadvantages, due to the cam-mechanism, such as high risk of cam-mechanism polyethylene wear. To minimize the polyethylene wear of the cam-mechanism and the bone sacrifice due to the intercondylar box, different types of inserts were developed, trying to increase the implant conformity and to reduce stresses on the bone-implant interface. In this scenario ultra-congruent (UC) inserts were developed. Those inserts are characterized by a high anterior wall and a deep-dished plate. This conformation should guarantee a good stability without the posterior cam. Few studies on both kinematic and clinical outcomes of UC inserts are available. Clinical and radiological outcomes, as well as kinematic data are similar between UC mobile bearing (MB) and standard PS MB inserts at short to mid-term follow-up. In this manuscript biomechanics and clinical outcomes of UC inserts will be described, and they will be compared to standard PS or CR inserts. PMID:26855938

  14. Rhinosinusitis; A Potential Hazard of Nasogastric Tube Insertion

    PubMed Central

    Adeyemo, Adebolajo A.; Fasunla, Ayotunde J.; Adeosun, Aderemi A.; Abdullahi, Hamisu

    2007-01-01

    The nasogastric tube has been used frequently for enteral feeding and as an intranasal oxygen catheter. This practice is however associated with complications. We present a case of rhinosinusitis and sepsis in a diabetic patient following the insertion of a nasogastric tube. Physicians should be aware of sinusitis as a possible cause of sepsis in patients with nasogastric tube insertion. PMID:25161433

  15. Astronaut John Glenn practices insertion into Mercury spacecraft

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Astronaut John H. Glenn Jr., pilot of the Mercury-Atlas 6 mission, practices insertion into the Mercury 'Friendship 7' spacecraft during MA-6 preflight training activity at Cape Canveral, Florida. He is wearing the full pressure suit and helmet (00993); Glenn practices insertion into Mercury capsule with help of a McDonnell Aircraft Corporation technician (00994).

  16. Load beam unit replaceable inserts for dry coal extrusion pumps

    DOEpatents

    Saunders, Timothy; Brady, John D.

    2012-11-13

    A track assembly for a particulate material extrusion pump according to an exemplary aspect of the present disclosure includes a link assembly with a roller bearing. An insert mounted to a load beam located such that the roller bearing contacts the insert.

  17. Combined plasma and thermal hollow cathode insert model

    NASA Technical Reports Server (NTRS)

    Katz, Ira; Polk, James E.; Mikellides, Ionnis G.; Goebel, Dan m.; Hornbeck, Sarah E.

    2005-01-01

    In this paper, we present the first results from a Hollow Cathode Thermal (HCThermal) model that uses the spatially distributed plasma fluxes calculated by the InsertRegion of an Orificed Cathode (IROrCa2D) code as the heat source to predict the hollow cathode and insert temperatures.

  18. A Microscopic View of Phospholipid Insertion into Biological Membranes

    PubMed Central

    Vermaas, Josh V.; Tajkhorshid, Emad

    2014-01-01

    Understanding the process of membrane insertion is an essential step in developing a detailed mechanism, e.g., for peripheral membrane protein association and membrane fusion. The Highly Mobile Membrane Mimetic (HMMM) has been used to accelerate the membrane association and binding of peripheral membrane proteins in simulations by increasing the lateral diffusion of phospholipid headgroups while retaining an atomistic description of the interface. Through a comparative study, we assess the difference in insertion rate of a free phospholipid into an HMMM as well as into a conventional phospholipid bilayer, and develop a detailed mechanistic model of free phospholipid insertion into biological membranes. The mechanistic insertion model shows that successful, irreversible association of the free phospholipid to the membrane interface, which results in its insertion, is the rate limiting step. Association is followed by independent, sequential insertion of the acyl tails of the free phospholipid into the membrane, with splayed acyl tail intermediates. Use of the HMMM is found to replicate the same intermediate insertion states as in the full phospholipid bilayer, however it accelerates overall insertion by approximately a factor of three, with the probability of successful association of phospholipid to the membrane being significantly enhanced. PMID:24313792

  19. Orbit Insertion by Mars Reconnaissance Orbiter (Artist's Concept)

    NASA Technical Reports Server (NTRS)

    2005-01-01

    This is an artist's concept of NASA's Mars Reconnaissance Orbiter during the critical process of Mars orbit insertion. In order to be captured into orbit around Mars, the spacecraft must conduct a 25-minute rocket burn when it is just shy of reaching the planet. As pictured, it will pass under the red planet's southern hemisphere as it begins the insertion burn.

  20. Tube thoracostomy: Increased angle of insertion is associated with complications.

    PubMed

    Hernandez, Matthew C; Laan, Danuel V; Zimmerman, Stacey L; Naik, Nimesh D; Schiller, Henry J; Aho, Johnathon M

    2016-08-01

    Tube thoracostomy (TT), considered a routine procedure, has significant complications. Current recommendations for placement rely on surface anatomy. There is no information to guide operators regarding angle of insertion relative to chest wall. We aim to determine if angle of insertion is associated with complications of TT. We performed a retrospective review of adult trauma patients who necessitated TT at a Level I trauma center over a 2-year period (January 2012 to December 2013). Tube thoracostomies performed intraoperatively or using radiological guidance were excluded. Thoracic anteroposterior or posteroanterior radiographs were reviewed to determine the angle of insertion of TT relative to the thoracic wall. A previously validated classification method was used to categorize complications. Descriptive and univariate statistics were used to compare angle of insertion and complicated versus uncomplicated TT. Review identified 154 patients who underwent a total of 246 TT placed for emergent trauma. All patients had a postprocedural chest x-ray. We identified 90 complications (37%) over the study period. One hundred forty-four of the TTs reviewed had an angle of insertion less than 45 degrees of which there were 27 complications (19%). One hundred two of the TTs had an angle greater than 45 degrees and 63 complications (62%); p < 0.0001. Tube thoracostomy insertion is inherently dangerous. Placement of TT using a higher angle of insertion greater than 45 degrees is associated with increased complications. Further prospective studies quantifying TT angle of insertion on outcomes are needed. Therapeutic study, level IV.

  1. [Umbilical and peripherally inserted venous central catheterization of the newborn].

    PubMed

    Bouissou, A; Rakza, T; Storme, L; Lafarghe, A; Fily, A; Diependaele, J-F; Dalmas, S

    2008-09-01

    Umbilical venous and peripherally inserted venous central catheters are widely used to perfuse low-weight preterm and term newborns in intensive care units. This catheter must be inserted carefully and monitored rigorously to prevent complications. This paper develops today's knowledge on the use and complications in the newborn population.

  2. Gastrostomy tube insertion in children: the Edmonton experience.

    PubMed

    Ackroyd, Ryan; Saincher, Meghana; Cheng, Simon; El-Matary, Wael

    2011-05-01

    Although gastrostomy tube insertion - whether endoscopic or open - is generally safe, procedure-related complications have been reported. To compare gastrostomy tube insertion-related complications between percutaneous endoscopic gastrostomy and open gastrostomy at a single pediatric centre. The charts of children (younger than 17 years of age at the time of tube insertion) who underwent endoscopic or open gastrostomy tube insertion from January 2005 to December 2007 at the Stollery Children's Hospital (Edmonton, Alberta) were examined. A total of 298 children underwent gastrostomy tube insertion over a period of three years. After excluding patients with incomplete charts, 160 children (91 boys, mean [± SD] age 3.18 ± 4.73 years) were included. Eighty-five children (mean age 4.50 ± 5.40 years) had their gastrostomy tube inserted endoscopically, while the remaining 75 (mean age 1.68 ± 3.27 years; P<0.001) underwent an open procedure. The overall rate of major complications was 10.2% for the endoscopic technique and 8.6% for the open technique (P=0.1). Major infections were higher in the endoscopic technique group, while persistent gastrocutaneous fistulas after tube removal were more common in the open technique group. Although the rate of major complications was similar between the endoscopic and open tube insertion groups, major infections were more common among children who underwent endoscopic gastrostomy. The decision for gastrostomy tube insertion was primarily based on clinical background.

  3. Piezo-Driven Vibrating Insertion Device for Microelectrode Array

    NASA Astrophysics Data System (ADS)

    Noda, Takahiro; Kanzaki, Ryohei; Takahashi, Hirokazu

    Microelectrode arrays are commonly used to measure neural activities in the brain, and arrays with some 100 electrodes are commercially available to date. However, insertion of a dense grid array deforms the brain, resulting in deterioration of the measurements. In order to overcome this problem, we propose a piezo-driven vibrating insertion device to reduce the insertion-induced deformation of the brain. We attempted under various conditions to insert the array into an agarose substrate, whose hardness was adjusted to that of the cerebral cortex of rats. Our experiments demonstrated that inverse-sawtooth vibration reduced the insertion-induced deformation of the substrate in proportion to the logarithm of an upstroke velocity when the velocity was higher than 10 mm/s, and vibrating insertion of the maximum velocity at 36.7 mm/s reduced the deformation by up to 40% as compared to insertion without vibration. In addition, we tested the vibrating insertion device in an electrophysiological experiment in the rat auditory cortex in vivo, and successfully measured tone-evoked neuronal activities.

  4. Combined plasma and thermal hollow cathode insert model

    NASA Technical Reports Server (NTRS)

    Katz, Ira; Polk, James E.; Mikellides, Ionnis G.; Goebel, Dan m.; Hornbeck, Sarah E.

    2005-01-01

    In this paper, we present the first results from a Hollow Cathode Thermal (HCThermal) model that uses the spatially distributed plasma fluxes calculated by the InsertRegion of an Orificed Cathode (IROrCa2D) code as the heat source to predict the hollow cathode and insert temperatures.

  5. Interface study of insertion layers in organic semiconductor devices

    NASA Astrophysics Data System (ADS)

    Ding, Huanjun; Irfan, "; So, Franky; Gao, Yongli

    2009-08-01

    Inserting an ultra-thin interlayer has been an important means in modifying the performance of organic semiconductor devices. Using photoemission and inverse photoemission spectroscopy (UPS, XPS and IPES), we have investigated the electronic structure of a number of insertion layers widely used in organic semiconductor devices. We found that inserting alkali metal compound thin layers such as LiF between the electron transport layer (ETL) and the cathode can induce energy level shift in the ETL that reduces the electron injection barrier. The reduction is attributed to the release of the alkali metal that n-doped the ETL, and as such it depends on the cathode material deposited on top of the insertion layer. For thin metal oxide insertion layers, such as MoO3, between the anode and the hole transport layer (HTL), reduction of the hole injection barrier is also observed. This reduction, however, is due to the large workfunction of the oxide that subsequently moves the highest occupied molecular orbital (HOMO) toward the anode Fermi level. Effects of other insertion layers, such as metal insertion layer in organic bistable device (OBD) and organic insertion layer in bipolar organic thin film transistors (OTFT) will also be discussed.

  6. Tuning the Insertion Properties of pHLIP

    PubMed Central

    Musial-Siwek, Monika; Karabadzhak, Alexander; Andreev, Oleg A.; Reshetnyak, Yana K.; Engelman, Donald M.

    2009-01-01

    The pH (low) insertion peptide (pHLIP) has exceptional characteristics: at neutral pH it is an unstructured monomer in solution or when bound to lipid bilayer surfaces, and it inserts across a lipid bilayer as a monomeric alpha-helix at acidic pH. The peptide targets acidic tissues in vivo, and may be useful in cancer biology for delivery of imaging or therapeutic molecules to acidic tumors. To find ways to vary its useful properties, we have designed and analyzed pHLIP sequence variants. We find that each of the Asp residues in the transmembrane segment is critical for solubility and pH-dependent membrane insertion of the peptide. Changing both of the Asp residues in the transmembrane segment to Glu, inserting an additional Asp into the transmembrane segment, or replacing either of the Asp residues with Ala leads to aggregation and/or loss of pH-dependent membrane insertion of the peptide. However, variants with either of the Asp residues changed to Glu remained soluble in an aqueous environment and inserted into the membrane at acidic pH with a higher pKapp of membrane insertion. Variation of the pH at which insertion occurs may broaden the potential uses of the pHLIP technology by allowing targeting of tissues with different acidity levels. PMID:19766589

  7. RAG1/2 induces genomic insertions by mobilizing DNA into RAG1/2-independent breaks

    PubMed Central

    2017-01-01

    The RAG recombinase (RAG1/2) plays an essential role in adaptive immunity by mediating V(D)J recombination in developing lymphocytes. In contrast, aberrant RAG1/2 activity promotes lymphocyte malignancies by causing chromosomal translocations and DNA deletions at cancer genes. RAG1/2 can also induce genomic DNA insertions by transposition and trans-V(D)J recombination, but only few such putative events have been documented in vivo. We used next-generation sequencing techniques to examine chromosomal rearrangements in primary murine B cells and discovered that RAG1/2 causes aberrant insertions by releasing cleaved antibody gene fragments that subsequently reintegrate into DNA breaks induced on a heterologous chromosome. We confirmed that RAG1/2 also mobilizes genomic DNA into independent physiological breaks by identifying similar insertions in human lymphoma and leukemia. Our findings reveal a novel RAG1/2-mediated insertion pathway distinct from DNA transposition and trans-V(D)J recombination that destabilizes the genome and shares features with reported oncogenic DNA insertions. PMID:28179379

  8. In vivo dynamics of equine infectious anemia viruses emerging during febrile episodes: insertions/duplications at the principal neutralizing domain.

    PubMed Central

    Zheng, Y H; Sentsui, H; Nakaya, T; Kono, Y; Ikuta, K

    1997-01-01

    Equine infectious anemia virus (EIAV) is a good model for studying mechanisms generating escaped retrovirus variants. We previously sequenced the entire gp90-encoding region of 22 cDNA clones obtained from five antigenically distinct isolates (F1V to F5V) recovered during febrile episodes in horse 493 experimentally infected with the Japanese virulent EIAV strain V70. The results showed that the mutations occurred in the principal neutralizing domain (PND) by insertions/duplications. In this study, we further characterized the PND of virus isolates sequentially recovered during 22 febrile episodes in seven horses newly infected with V70 or one of the V70-derived variants. Sequencing of 70 cDNA clones derived from the 22 episodes confirmed the generation of various new viral quasispecies with insertions/duplications in the PND. Although the insertion/duplication sequences in a total of 92 cDNA clones were extensively heterogeneous, we hypothesized that all the insertions/duplications occurred during reverse transcription from viral genomic RNA to minus strand DNA. The insertion/duplication regions were derived from a part of the PND sequence, which consisted of five small units. These small units, some with various substitutions and/or deletions, were also generated, especially in regions with insertions/duplications. Of particular note was that all these virus variants, except for two cDNA variants, were generated by essentially four different duplication pathways. Thus, these results extend the significance of insertions/duplications in the PND to the novel generation of EIAV in vivo during febrile episodes. PMID:9188568

  9. Defining Our National Cyberspace Boundaries

    DTIC Science & Technology

    2010-02-17

    invention of the World Wide Web in 19 1989, the Internet Corporation for Assigned Names and Numbers ( ICANN ) (the international organization that...anonymity in cyberspace could be accomplished through the issuing of IP addresses as the Internet transitions from IPv4 to IPv6. ICANN should issue...agreement (MOA) between the U.S. Department of Commerce and ICANN . This new MOA should define which blocks of IP addresses will be used for entities

  10. Z-2 Threaded Insert Design and Testing Abstract

    NASA Technical Reports Server (NTRS)

    Rhodes, RIchard; Graziosi, Dave; Jones, Bobby; Ferl, Jinny; Scarborough, Steve; Sweeney, Mitch

    2016-01-01

    The Z-2 Prototype Planetary Extravehicular Space Suit Assembly is a continuation of NASA's Z series of spacesuits. The Z-2 is another step in the NASA's technology development roadmap leading to human exploration of the Martian surface. To meet a more challenging set of requirements than previous suit systems standard design features, such as threaded inserts, have been re-analyzed and improved. NASA's Z-2 prototype space suit contains several components fabricated from an advanced hybrid composite laminate consisting of IM10 carbon fiber and fiber glass. One requirement NASA levied on the suit composites was the ability to have removable, replaceable helicoil inserts to which other suit components would be fastened. An approach utilizing bonded in inserts with helicoils inside of them was implemented. The design of the interface flanges of the composites allowed some of the inserts to be a "T" style insert that was installed through the entire thickness of the laminate. The flange portion of the insert provides a mechanical lock as a redundancy to the adhesive aiding in the pullout load that the insert can withstand. In some locations it was not possible to utilize at "T" style insert and a blind insert was used instead. These inserts rely completely on the bond strength of the adhesive to resist pullout. It was determined during the design of the suit that the inserts did not need to withstand loads induced from pressure cycling but instead tension induced from torqueing the screws to bolt on hardware which creates a much higher stress on them. Bolt tension is determined by dividing the torque on the screw by a k value multiplied by the thread diameter of the bolt. The k value is a factor that accounts for friction in the system. A common value used for k for a non-lubricated screw is 0.2. The k value can go down by as much as 0.1 if the screw is lubricated which means for the same torque, a much larger tension could be placed on the bolt and insert. This paper

  11. How to define green adjuvants.

    PubMed

    Beck, Bert; Steurbaut, Walter; Spanoghe, Pieter

    2012-08-01

    The concept 'green adjuvants' is difficult to define. This paper formulates an answer based on two approaches. Starting from the Organisation for Economic Cooperation and Development (OECD) definition for green chemistry, production-based and environmental-impact-based definitions for green adjuvants are proposed. According to the production-based approach, adjuvants are defined as green if they are manufactured using renewable raw materials as much as possible while making efficient use of energy, preferably renewable energy. According to the environmental impact approach, adjuvants are defined as green (1) if they have a low human and environmental impact, (2) if they do not increase active ingredient environmental mobility and/or toxicity to humans and non-target organisms, (3) if they do not increase the exposure to these active substances and (4) if they lower the impact of formulated pesticides by enhancing the performance of active ingredients, thus potentially lowering the required dosage of active ingredients. Based on both approaches, a tentative definition for 'green adjuvants' is given, and future research and legislation directions are set out.

  12. How do people define moderation?

    PubMed

    vanDellen, Michelle R; Isherwood, Jennifer C; Delose, Julie E

    2016-06-01

    Eating in moderation is considered to be sound and practical advice for weight maintenance or prevention of weight gain. However, the concept of moderation is ambiguous, and the effect of moderation messages on consumption has yet to be empirically examined. The present manuscript examines how people define moderate consumption. We expected that people would define moderate consumption in ways that justified their current or desired consumption rather than view moderation as an objective standard. In Studies 1 and 2, moderate consumption was perceived to involve greater quantities of an unhealthy food (chocolate chip cookies, gummy candies) than perceptions of how much one should consume. In Study 3, participants generally perceived themselves to eat in moderation and defined moderate consumption as greater than their personal consumption. Furthermore, definitions of moderate consumption were related to personal consumption behaviors. Results suggest that the endorsement of moderation messages allows for a wide range of interpretations of moderate consumption. Thus, we conclude that moderation messages are unlikely to be effective messages for helping people maintain or lose weight. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. What Defines the "Kingdom" Fungi?

    PubMed

    Richards, Thomas A; Leonard, Guy; Wideman, Jeremy G

    2017-06-01

    The application of environmental DNA techniques and increased genome sequencing of microbial diversity, combined with detailed study of cellular characters, has consistently led to the reexamination of our understanding of the tree of life. This has challenged many of the definitions of taxonomic groups, especially higher taxonomic ranks such as eukaryotic kingdoms. The Fungi is an example of a kingdom which, together with the features that define it and the taxa that are grouped within it, has been in a continual state of flux. In this article we aim to summarize multiple lines of data pertinent to understanding the early evolution and definition of the Fungi. These include ongoing cellular and genomic comparisons that, we will argue, have generally undermined all attempts to identify a synapomorphic trait that defines the Fungi. This article will also summarize ongoing work focusing on taxon discovery, combined with phylogenomic analysis, which has identified novel groups that lie proximate/adjacent to the fungal clade-wherever the boundary that defines the Fungi may be. Our hope is that, by summarizing these data in the form of a discussion, we can illustrate the ongoing efforts to understand what drove the evolutionary diversification of fungi.

  14. Intraaortic balloon pump insertion through the subclavian artery. Subclavian artery insertion of IABP.

    PubMed

    Marcu, Constantin B; Donohue, Thomas J; Ferneini, Antoine; Ghantous, Andre E

    2006-04-01

    The intraaortic balloon pump (IABP) is frequently used in the management of cardiac failure in the setting of myocardial infarction or as a bridge for coronary revascularisation surgery. The IABP is usually inserted through the femoral artery. Occasionally severe aorto-iliac occlusive disease prevents the retrograde passage of the balloon, in which case an anterograde route, usually through the ascending aorta is used. We describe four patients in whom an IABP was placed through the subclavian artery by the joint efforts of cardiologists and vascular surgeons.

  15. Measurement of Vein Diameter for Peripherally Inserted Central Catheter (PICC) Insertion: An Observational Study.

    PubMed

    Sharp, Rebecca; Cummings, Melita; Childs, Jessie; Fielder, Andrea; Mikocka-Walus, Antonina; Grech, Carol; Esterman, Adrian

    2015-01-01

    Choosing an appropriately sized vein reduces the risk of venous thromboembolism associated with peripherally inserted central catheters. This observational study described the diameters of the brachial, basilic, and cephalic veins and determined the effect of patient factors on vein size. Ultrasound was used to measure the veins of 176 participants. Vein diameter was similar in both arms regardless of hand dominance and side. Patient factors-including greater age, height, and weight, as well as male gender-were associated with increased vein diameter. The basilic vein tended to have the largest diameter statistically. However, this was the case in only 55% of patients.

  16. Hybrid polymer-lipid films as platforms for directed membrane protein insertion.

    PubMed

    Kowal, Justyna; Wu, Dalin; Mikhalevich, Viktoria; Palivan, Cornelia G; Meier, Wolfgang

    2015-05-05

    Hybrids composed of amphiphilic block copolymers and lipids constitute a new generation of biological membrane-inspired materials. Hybrid membranes resulting from self-assembly of lipids and polymers represent adjustable models for interactions between artificial and natural membranes, which are of key importance, e.g., when developing systems for drug delivery. By combining poly(dimethylsiloxane)-block-poly(2-methyl-2-oxazoline) amphiphilic copolymers (PDMS-b-PMOXA) with various phospholipids, we obtained hybrid films with modulated properties and topology, based on phase separation, and the formation of distinct domains. By understanding the factors driving the phase separation in these hybrid lipid-polymer films, we were able to use them as platforms for directed insertion of membrane proteins. Tuning the composition of the polymer-lipids mixtures favored successful insertion of membrane proteins with desired topological distributions (in polymer or/and lipid regions). Controlled insertion and location of membrane proteins in hybrid films make these hybrids ideal candidates for numerous applications where specific spatial functionality is required.

  17. Eph and Ephrin function in dispersal and epithelial insertion of pigmented immunocytes in sea urchin embryos

    PubMed Central

    Krupke, Oliver A; Zysk, Ivona; Mellott, Dan O; Burke, Robert D

    2016-01-01

    The mechanisms that underlie directional cell migration are incompletely understood. Eph receptors usually guide migrations of cells by exclusion from regions expressing Ephrin. In sea urchin embryos, pigmented immunocytes are specified in vegetal epithelium, transition to mesenchyme, migrate, and re-enter ectoderm, distributing in dorsal ectoderm and ciliary band, but not ventral ectoderm. Immunocytes express Sp-Eph and Sp-Efn is expressed throughout dorsal and ciliary band ectoderm. Interfering with expression or function of Sp-Eph results in rounded immunocytes entering ectoderm but not adopting a dendritic form. Expressing Sp-Efn throughout embryos permits immunocyte insertion in ventral ectoderm. In mosaic embryos, immunocytes insert preferentially in ectoderm expressing Sp-Efn. We conclude that Sp-Eph signaling is necessary and sufficient for epithelial insertion. As well, we propose that immunocytes disperse when Sp-Eph enhances adhesion, causing haptotactic movement to regions of higher ligand abundance. This is a distinctive example of Eph/Ephrin signaling acting positively to pattern migrating cells. DOI: http://dx.doi.org/10.7554/eLife.16000.001 PMID:27474796

  18. Detection for processing history of seam insertion and contrast enhancement

    NASA Astrophysics Data System (ADS)

    Li, Jianwei; Zhao, Yao; Ni, Rongrong

    2014-11-01

    With the development of manipulations techniques of digital images, digital image forensic technology is becoming more and more necessary. However, the determination of processing history of multi-operation is still a challenge problem. In this paper, we improve the traditional seam insertion algorithm, and propose corresponding detection method. Then an algorithm that focuses on detecting the processing history of seam insertion and contrast enhancement is proposed, which can be widely used in practical image forgery. Based on comprehensive analysis, we have discovered the inherent relationship between seam insertion and contrast enhancement. Different orders of processing make different impacts on images. By using the newly proposed algorithm, both contrast enhancement followed by seam insertion and seam insertion followed by contrast enhancement can be detected correctly. Plenty of experiments have been implemented to prove the accuracy.

  19. Gas turbine nozzle vane insert and methods of installation

    DOEpatents

    Miller, William John; Predmore, Daniel Ross; Placko, James Michael

    2002-01-01

    A pair of hollow elongated insert bodies are disposed in one or more of the nozzle vane cavities of a nozzle stage of a gas turbine. Each insert body has an outer wall portion with apertures for impingement-cooling of nozzle wall portions in registration with the outer wall portion. The insert bodies are installed into the cavity separately and spreaders flex the bodies toward and to engage standoffs against wall portions of the nozzle whereby the designed impingement gap between the outer wall portions of the insert bodies and the nozzle wall portions is achieved. The spreaders are secured to the inner wall portions of the insert bodies and the bodies are secured to one another and to the nozzle vane by welding or brazing.

  20. Smart structures for shock wave attenuation using ER inserts

    NASA Astrophysics Data System (ADS)

    Kim, Jaehwan; Kim, Jung-Yup; Choi, Seung-Bok; Kim, Kyung-Su

    2001-08-01

    This Paper demonstrates the possibility of shock wave attenuation propagating through a smart structure that incorporates ER insert. The wave transmission of ER inserted beam is theoretically derived using Mead & Markus model and the theoretical results are compared with the finite element analysis results. To experimentally verify the shock wave attenuation, ER insert in an aluminum plate is made and two piezoceramic disks are used as transmitter and receiver of the wave. The transmitter sends a sine pulse signal such that a component of shock wave travels through the plate structure and the receiver gets the transmitted wave signal. Wave propagation of the ER insert can be adjusted by changing the applied electric field on the ER insert. Details of the experiment are addressed and the possibility of shock wave attenuation is experimentally verified. This kind of smart structure can be used for warship and submarine hull structures to protect fragile and important equipment.

  1. Method for improving the durability of ion insertion materials

    DOEpatents

    Lee, Se-Hee; Tracy, C. Edwin; Cheong, Hyeonsik M.

    2002-01-01

    The invention provides a method of protecting an ion insertion material from the degradative effects of a liquid or gel-type electrolyte material by disposing a protective, solid ion conducting, electrically insulating, layer between the ion insertion layer and the liquid or gel-type electrolyte material. The invention further provides liquid or gel-type electrochemical cells having improved durability having a pair of electrodes, a pair of ion insertion layers sandwiched between the pair of electrodes, a pair of solid ion conducting layers sandwiched between the ion insertion layers, and a liquid or gel-type electrolyte material disposed between the solid ion conducting layers, where the solid ion conducting layer minimizes or prevents degradation of the faces of the ion insertion materials facing the liquid or gel-type electrolyte material. Electrochemical cells of this invention having increased durability include secondary lithium batteries and electrochromic devices.

  2. Thought Insertion as a Self-Disturbance: An Integration of Predictive Coding and Phenomenological Approaches

    PubMed Central

    Sterzer, Philipp; Mishara, Aaron L.; Voss, Martin; Heinz, Andreas

    2016-01-01

    Current theories in the framework of hierarchical predictive coding propose that positive symptoms of schizophrenia, such as delusions and hallucinations, arise from an alteration in Bayesian inference, the term inference referring to a process by which learned predictions are used to infer probable causes of sensory data. However, for one particularly striking and frequent symptom of schizophrenia, thought insertion, no plausible account has been proposed in terms of the predictive-coding framework. Here we propose that thought insertion is due to an altered experience of thoughts as coming from “nowhere”, as is already indicated by the early 20th century phenomenological accounts by the early Heidelberg School of psychiatry. These accounts identified thought insertion as one of the self-disturbances (from German: “Ichstörungen”) of schizophrenia and used mescaline as a model-psychosis in healthy individuals to explore the possible mechanisms. The early Heidelberg School (Gruhle, Mayer-Gross, Beringer) first named and defined the self-disturbances, and proposed that thought insertion involves a disruption of the inner connectedness of thoughts and experiences, and a “becoming sensory” of those thoughts experienced as inserted. This account offers a novel way to integrate the phenomenology of thought insertion with the predictive coding framework. We argue that the altered experience of thoughts may be caused by a reduced precision of context-dependent predictions, relative to sensory precision. According to the principles of Bayesian inference, this reduced precision leads to increased prediction-error signals evoked by the neural activity that encodes thoughts. Thus, in analogy with the prediction-error related aberrant salience of external events that has been proposed previously, “internal” events such as thoughts (including volitions, emotions and memories) can also be associated with increased prediction-error signaling and are thus imbued

  3. Histological analysis of the tibial anterior cruciate ligament insertion.

    PubMed

    Oka, Shinya; Schuhmacher, Peter; Brehmer, Axel; Traut, Ulrike; Kirsch, Joachim; Siebold, Rainer

    2016-03-01

    This study was performed to investigate the morphology of the tibial anterior cruciate ligament (ACL) by histological assessment. The native (undissected) tibial ACL insertion of six fresh-frozen cadaveric knees was cut into four sagittal sections parallel to the long axis of the medial tibial spine. For histological evaluation, the slices were stained with haematoxylin and eosin, Safranin O and Russell-Movat pentachrome. All slices were digitalized and analysed at a magnification of 20×. The anterior tibial ACL insertion was bordered by a bony anterior ridge. The most medial ACL fibres inserted from the medial tibial spine and were adjacent to the articular cartilage of the medial tibial plateau. Parts of the bony insertions of the anterior and posterior horns of the lateral meniscus were in close contact with the lateral part of the tibial ACL insertion. A small fat pad was located just posterior to the functional ACL fibres. The anterior-posterior length of the medial ACL insertion was an average of 10.8 ± 1.1 mm compared with the lateral, which was only 6.2 ± 1.1 mm (p < 0.001). There were no central or posterolateral inserting ACL fibres. The shape of the bony tibial ACL insertion was 'duck-foot-like'. In contrast to previous findings, the functional mid-substance fibres arose from the most posterior part of the 'duck-foot' in a flat and 'c-shaped' way. The most anterior part of the tibial ACL insertion was bordered by a bony anterior ridge and the most medial by the medial tibial spine. No posterolateral fibres nor ACL bundles have been found histologically. This histological investigation may improve our understanding of the tibial ACL insertion and may provide important information for anatomical ACL reconstruction.

  4. [Advantages and disadvantages of IUD insertion immediately after abortion].

    PubMed

    Matrljan, I; Randić, L

    1982-01-01

    In 672 women the interval insertion of intrauterine contraception devices (IUD) was applied: Lippes loop D in 138 women. In 530 women the insertion was applied immediately after artificial abortion: Lippes loop C in 390 and Lippes loop D in 140 cases. Data on the effectiveness of intrauterine contraception were biostatistically treated. One- and two-year gross cumulative rates of pregnancy were 4.4 and 6.4, respectively 3.7 and 6.3 for the interval insertion of Lippes loop C and D, and 2.1 and 4.5, respectively 4.2 and 11.2 for the postabortion insertion of the same devices. Two-year cumulative rates of spontaneous expulsions of 18.5 and 8.1 for interval insertions were significantly higher than in the group of women in whom the insertion of the same devices was performed immediately after abortion and in whom these rates were 11.1 and 5.9. The removal of intrauterine contraception devices because of bleeding and pain, or because of both, with the rates of 6.4 and 3.2 in 100 women after a two-year use, was less frequent in the group of women in whom interval insertion was performed than in the group of postabortion insertions with the corresponding rates of 7.3 and 9.9, respectively. To prevent repeated abortions, a frequent use of postabortion IUD insertion is recommended. Only when an intensified bleeding is expected, it is advisable to postpone insertion at least until the first menstruation.

  5. Modulation of the pHLIP Transmembrane Helix Insertion Pathway

    PubMed Central

    Karabadzhak, Alexander G.; Weerakkody, Dhammika; Wijesinghe, Dayanjali; Thakur, Mak S.; Engelman, Donald M.; Andreev, Oleg A.; Markin, Vladislav S.; Reshetnyak, Yana K.

    2012-01-01

    The membrane-associated folding/unfolding of pH (low) insertion peptide (pHLIP) provides an opportunity to study how sequence variations influence the kinetics and pathway of peptide insertion into bilayers. Here, we present the results of steady-state and kinetics investigations of several pHLIP variants with different numbers of charged residues, with attached polar cargoes at the peptide's membrane-inserting end, and with three single-Trp variants placed at the beginning, middle, and end of the transmembrane helix. Each pHLIP variant exhibits a pH-dependent interaction with a lipid bilayer. Although the number of protonatable residues at the inserting end does not affect the ultimate formation of helical structure across a membrane, it correlates with the time for peptide insertion, the number of intermediate states on the folding pathway, and the rates of unfolding and exit. The presence of polar cargoes at the peptide's inserting end leads to the appearance of intermediate states on the insertion pathway. Cargo polarity correlates with a decrease of the insertion rate. We conclude that the existence of intermediate states on the folding and unfolding pathways is not mandatory and, in the simple case of a polypeptide with a noncharged and nonpolar inserting end, the folding and unfolding appears as an all-or-none transition. We propose a model for membrane-associated insertion/folding and exit/unfolding and discuss the importance of these observations for the design of new delivery agents for direct translocation of polar therapeutic and diagnostic cargo molecules across cellular membranes. PMID:22768940

  6. Identifying gene expression modules that define human cell fates.

    PubMed

    Germanguz, I; Listgarten, J; Cinkornpumin, J; Solomon, A; Gaeta, X; Lowry, W E

    2016-05-01

    Using a compendium of cell-state-specific gene expression data, we identified genes that uniquely define cell states, including those thought to represent various developmental stages. Our analysis sheds light on human cell fate through the identification of core genes that are altered over several developmental milestones, and across regional specification. Here we present cell-type specific gene expression data for 17 distinct cell states and demonstrate that these modules of genes can in fact define cell fate. Lastly, we introduce a web-based database to disseminate the results. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  7. Grima: A Distinct Emotion Concept?

    PubMed Central

    Schweiger Gallo, Inge; Fernández-Dols, José-Miguel; Gollwitzer, Peter M.; Keil, Andreas

    2017-01-01

    People experience an unpleasant sensation when hearing a scratch on a board or plate. The present research focuses on this aversive experience known in Spanish as ‘grima’ with no equivalent term in English and German. We hypothesized that this aversive experience constitutes a distinctive, separate emotional concept. In Study 1, we found that the affective meaning of ‘grima’ was closer to disgust than to other emotion concepts. Thus, in Study 2 we explored the features of grima and compared them with disgust. As grima was reported to be predominantly elicited by certain auditory stimuli and associated with a distinctive physiological pattern, Study 3 used direct measures of physiological arousal to test the assumption of a distinctive pattern of physiological responses elicited by auditory stimuli of grima and disgust, and found different effects on heart rate but not on skin conductance. In Study 4, we hypothesized that only participants with an implementation intention geared toward down-regulating grima would be able to successfully weaken the grima- but not disgust- experience. Importantly, this effect was specific as it held true for the grima-eliciting sounds only, but did not affect disgust-related sounds. Finally, Study 5 found that English and German speakers lack a single accessible linguistic label for the pattern of aversive reactions termed by Spanish speaking individuals as ‘grima’, whereas the elicitors of other emotions were accessible and accurately identified by German, English, as well as Spanish speakers. PMID:28217102

  8. Grima: A Distinct Emotion Concept?

    PubMed

    Schweiger Gallo, Inge; Fernández-Dols, José-Miguel; Gollwitzer, Peter M; Keil, Andreas

    2017-01-01

    People experience an unpleasant sensation when hearing a scratch on a board or plate. The present research focuses on this aversive experience known in Spanish as 'grima' with no equivalent term in English and German. We hypothesized that this aversive experience constitutes a distinctive, separate emotional concept. In Study 1, we found that the affective meaning of 'grima' was closer to disgust than to other emotion concepts. Thus, in Study 2 we explored the features of grima and compared them with disgust. As grima was reported to be predominantly elicited by certain auditory stimuli and associated with a distinctive physiological pattern, Study 3 used direct measures of physiological arousal to test the assumption of a distinctive pattern of physiological responses elicited by auditory stimuli of grima and disgust, and found different effects on heart rate but not on skin conductance. In Study 4, we hypothesized that only participants with an implementation intention geared toward down-regulating grima would be able to successfully weaken the grima- but not disgust- experience. Importantly, this effect was specific as it held true for the grima-eliciting sounds only, but did not affect disgust-related sounds. Finally, Study 5 found that English and German speakers lack a single accessible linguistic label for the pattern of aversive reactions termed by Spanish speaking individuals as 'grima', whereas the elicitors of other emotions were accessible and accurately identified by German, English, as well as Spanish speakers.

  9. Cyberbullying: the challenge to define.

    PubMed

    Langos, Colette

    2012-06-01

    Cyberbullying is a reality of the digital age. To address this phenomenon, it becomes imperative to understand exactly what cyberbullying is. Thus, establishing a workable and theoretically sound definition is essential. This article contributes to the existing literature in relation to the definition of cyberbullying. The specific elements of repetition, power imbalance, intention, and aggression, regarded as essential criteria of traditional face-to-face bullying, are considered in the cyber context. It is posited that the core bullying elements retain their importance and applicability in relation to cyberbullying. The element of repetition is in need of redefining, given the public nature of material in the online environment. In this article, a clear distinction between direct and indirect cyberbullying is made and a model definition of cyberbullying is offered. Overall, the analysis provided lends insight into how the essential bullying elements have evolved and should apply in our parallel cyber universe.

  10. Genomic structure and insertion sites of Helicobacter pylori prophages from various geographical origins

    PubMed Central

    Vale, Filipa F.; Nunes, Alexandra; Oleastro, Mónica; Gomes, João P.; Sampaio, Daniel A.; Rocha, Raquel; Vítor, Jorge M. B.; Engstrand, Lars; Pascoe, Ben; Berthenet, Elvire; Sheppard, Samuel K.; Hitchings, Matthew D.; Mégraud, Francis; Vadivelu, Jamuna; Lehours, Philippe

    2017-01-01

    Helicobacter pylori genetic diversity is known to be influenced by mobile genomic elements. Here we focused on prophages, the least characterized mobile elements of H. pylori. We present the full genomic sequences, insertion sites and phylogenetic analysis of 28 prophages found in H. pylori isolates from patients of distinct disease types, ranging from gastritis to gastric cancer, and geographic origins, covering most continents. The genome sizes of these prophages range from 22.6–33.0 Kbp, consisting of 27–39 open reading frames. A 36.6% GC was found in prophages in contrast to 39% in H. pylori genome. Remarkably a conserved integration site was found in over 50% of the cases. Nearly 40% of the prophages harbored insertion sequences (IS) previously described in H. pylori. Tandem repeats were frequently found in the intergenic region between the prophage at the 3′ end and the bacterial gene. Furthermore, prophage genomes present a robust phylogeographic pattern, revealing four distinct clusters: one African, one Asian and two European prophage populations. Evidence of recombination was detected within the genome of some prophages, resulting in genome mosaics composed by different populations, which may yield additional H. pylori phenotypes. PMID:28205536

  11. Inherited Creutzfeldt-Jakob disease in a British family associated with a novel 144 base pair insertion of the prion protein gene.

    PubMed Central

    Nicholl, D; Windl, O; de Silva, R; Sawcer, S; Dempster, M; Ironside, J W; Estibeiro, J P; Yuill, G M; Lathe, R; Will, R G

    1995-01-01

    A case of familial Creutzfeldt-Jakob disease associated with a 144 base pair insertion in the open reading frame of the prion protein gene is described. Sequencing of the mutated allele showed an arrangement of six octapeptide repeats, distinct from that of a recently described British family with an insertion of similar size. Thirteen years previously the brother of the proband had died from "Huntington's disease", but re-examination of his neuropathology revealed spongiform encephalopathy and anti-prion protein immunocytochemistry gave a positive result. The independent evolution of at least two distinct pathological 144 base pair insertions in Britain is proposed. The importance of maintaining a high index of suspicion of inherited Creutzfeldt-Jakob disease in cases of familial neurodegenerative disease is stressed. Images PMID:7823070

  12. BK Polyomavirus Genotypes Represent Distinct Serotypes with Distinct Entry Tropism

    PubMed Central

    Pastrana, Diana V.; Ray, Upasana; Magaldi, Thomas G.; Schowalter, Rachel M.; Çuburu, Nicolas

    2013-01-01

    BK polyomavirus (BKV) causes significant urinary tract pathogenesis in immunosuppressed individuals, including kidney and bone marrow transplant recipients. It is currently unclear whether BKV-neutralizing antibodies can moderate or prevent BKV disease. We developed reporter pseudoviruses based on seven divergent BKV isolates and performed neutralization assays on sera from healthy human subjects. The results demonstrate that BKV genotypes I, II, III, and IV are fully distinct serotypes. While nearly all healthy subjects had BKV genotype I-neutralizing antibodies, a majority of subjects did not detectably neutralize genotype III or IV. Surprisingly, BKV subgenotypes Ib1 and Ib2 can behave as fully distinct serotypes. This difference is governed by as few as two residues adjacent to the cellular glycan receptor-binding site on the virion surface. Serological analysis of mice given virus-like particle (VLP)-based BKV vaccines confirmed these findings. Mice administered a multivalent VLP vaccine showed high-titer serum antibody responses that potently cross-neutralized all tested BKV genotypes. Interestingly, each of the neutralization serotypes bound a distinct spectrum of cell surface receptors, suggesting a possible connection between escape from recognition by neutralizing antibodies and cellular attachment mechanisms. The finding implies that different BKV genotypes have different cellular tropisms and pathogenic potentials in vivo. Individuals who are infected with one BKV serotype may remain humorally vulnerable to other BKV serotypes after implementation of T cell immunosuppression. Thus, prevaccinating organ transplant recipients with a multivalent BKV VLP vaccine might reduce the risk of developing posttransplant BKV disease. PMID:23843634

  13. Patient Self-Defined Goals.

    PubMed

    Schellinger, Sandra Ellen; Anderson, Eric Worden; Frazer, Monica Schmitz; Cain, Cindy Lynn

    2017-01-01

    This research, a descriptive qualitative analysis of self-defined serious illness goals, expands the knowledge of what goals are important beyond the physical-making existing disease-specific guidelines more holistic. Integration of goals of care discussions and documentation is standard for quality palliative care but not consistently executed into general and specialty practice. Over 14 months, lay health-care workers (care guides) provided monthly supportive visits for 160 patients with advanced heart failure, cancer, and dementia expected to die in 2 to 3 years. Care guides explored what was most important to patients and documented their self-defined goals on a medical record flow sheet. Using definitions of an expanded set of whole-person domains adapted from the National Consensus Project (NCP) Clinical Practice Guidelines for Quality Palliative Care, 999 goals and their associated plans were deductively coded and examined. Four themes were identified-medical, nonmedical, multiple, and global. Forty percent of goals were coded into the medical domain; 40% were coded to nonmedical domains-social (9%), ethical (7%), family (6%), financial/legal (5%), psychological (5%), housing (3%), legacy/bereavement (3%), spiritual (1%), and end-of-life care (1%). Sixteen percent of the goals were complex and reflected a mix of medical and nonmedical domains, "multiple" goals. The remaining goals (4%) were too global to attribute to an NCP domain. Self-defined serious illness goals express experiences beyond physical health and extend into all aspects of whole person. It is feasible to elicit and record serious illness goals. This approach to goals can support meaningful person-centered care, decision-making, and planning that accords with individual preferences of late life.

  14. Effect of Mg-Al insertion on magnetotransport properties in epitaxial Fe/sputter-deposited MgAl2O4/Fe(001) magnetic tunnel junctions

    NASA Astrophysics Data System (ADS)

    Belmoubarik, Mohamed; Sukegawa, Hiroaki; Ohkubo, Tadakatsu; Mitani, Seiji; Hono, Kazuhiro

    2017-05-01

    We investigated the effect of an Mg-Al layer insertion at the bottom interface of epitaxial Fe/MgAl2O4/Fe(001) magnetic tunnel junctions (MTJs) on their spin-dependent transport properties. The tunnel magnetoresistance (TMR) ratio and differential conductance spectra for the parallel magnetic configuration exhibited clear dependence on the inserted Mg-Al thickness. A slight Mg-Al insertion (thickness < 0.1 nm) was effective for obtaining a large TMR ratio above 200% at room temperature and observing a distinct local minimum structure in conductance spectra. In contrast, thicker Mg-Al (> 0.2 nm) induced a reduction of TMR ratios and featureless conductance spectra, indicating a degradation of the bottom-Fe/MgAl2O4 interface. Therefore, a minimal Mg-Al insertion was found to be effective to maximize the TMR ratio for a sputtered MgAl2O4-based MTJ.

  15. Substitution of Feline Leukemia Virus Long Terminal Repeat Sequences into Murine Leukemia Virus Alters the Pattern of Insertional Activation and Identifies New Common Insertion Sites

    PubMed Central

    Johnson, Chassidy; Lobelle-Rich, Patricia A.; Puetter, Adriane; Levy, Laura S.

    2005-01-01

    The recombinant retrovirus, MoFe2-MuLV (MoFe2), was constructed by replacing the U3 region of Moloney murine leukemia virus (M-MuLV) with homologous sequences from the FeLV-945 LTR. NIH/Swiss mice neonatally inoculated with MoFe2 developed T-cell lymphomas of immature thymocyte surface phenotype. MoFe2 integrated infrequently (0 to 9%) near common insertion sites (CISs) previously identified for either parent virus. Using three different strategies, CISs in MoFe2-induced tumors were identified at six loci, none of which had been previously reported as CISs in tumors induced by either parent virus in wild-type animals. Two of the newly identified CISs had not previously been implicated in lymphoma in any retrovirus model. One of these, designated 3-19, encodes the p101 regulatory subunit of phosphoinositide-3-kinase-gamma. The other, designated Rw1, is predicted to encode a protein that functions in the immune response to virus infection. Thus, substitution of FeLV-945 U3 sequences into the M-MuLV long terminal repeat (LTR) did not alter the target tissue for M-MuLV transformation but significantly altered the pattern of CIS utilization in the induction of T-cell lymphoma. These observations support a growing body of evidence that the distinctive sequence and/or structure of the retroviral LTR determines its pattern of insertional activation. The findings also demonstrate the oligoclonal nature of retrovirus-induced lymphomas by demonstrating proviral insertions at CISs in subdominant populations in the tumor mass. Finally, the findings demonstrate the utility of novel recombinant retroviruses such as MoFe2 to contribute new genes potentially relevant to the induction of lymphoid malignancy. PMID:15596801

  16. Defining and Achieving Decisive Victory

    DTIC Science & Technology

    2002-04-01

    developing a long-term strategy. In this process, nothing is more important than defining victory. In this monograph, Dr. Colin Gray, one of the world’s...Dr. Gray has written 17 books , most recently Modern Strategy (1999). In 2002 he will publish Strategy for Chaos: RMA Theory and the Evidence of...aims.4 But on the first page of Book One, Chapter 1, Clausewitz insists that “War is thus an act of force to compel our enemy to do our will.”5 He rams

  17. Diagnostic errors with inserted tubes, lines and catheters in children.

    PubMed

    Fuentealba, Isabel; Taylor, George A

    2012-11-01

    Tubes and catheters are frequently used in the care of hospitalized children. Yet little is known about errors in diagnosis in commonly implanted devices in a pediatric population. The purpose of this study was to determine the frequency and range of diagnostic errors with inserted devices in a pediatric population. During a 9-year period 142,041 cases were reviewed as part of our ongoing quality-assurance process. Of 4,084 disagreements in diagnosis encountered, 50 cases with diagnostic errors related to endovascular catheters, gastrointestinal, genitourinary and neurosurgical tubes, and pacemaker wires were identified and retrospectively reviewed. Diagnostic error was defined as a diagnosis that was unintentionally delayed, wrong or missed. These errors were classified as perceptual, cognitive, system-related or unavoidable and were graded according to potential clinical impact using a scale from 1 to 4, with 4 being the most serious. Device-related diagnostic errors accounted for 1.2% of all discrepancies identified and 10% of errors potentially leading to a change in therapy. Seventeen of the 50 diagnostic errors were related to vascular catheters (34%), including wrong anatomical location of catheter tip (12) and missed catheter fracture or migration (5). Twenty-seven errors (54%) were related to non-vascular catheters and involved enteric tube location (15), ventricular drainage catheters (7), endotracheal tubes (3) and genitourinary catheters (2). Six additional errors involved a vascular stent, endovascular cuff, needle, chest tube and epicardial wire placement (2). Device-related diagnostic errors are not frequent in complex pediatric patients. However, they can have a clinically significant impact on patient outcomes and management. High-risk situations include altered patient anatomy, poor or limited image quality, inconspicuous lines and incomplete review of prior studies.

  18. Insertion of sequential glaucoma drainage implant in a piggyback manner.

    PubMed

    Välimäki, J

    2015-10-01

    This pilot study, the first of its type, was conducted to determine the clinical outcome of a sequential glaucoma drainage implant (GDI) inserted in piggyback manner, that is into the bleb of a primary GDI. This was a retrospective chart study with a minimum 1-year follow-up involving 16 eyes of 14 uncontrolled glaucoma patients who had previously undergone sequential GDI performed using a technique to convert a one-plate into a two-plate implant system. Surgical success was defined as intraocular pressure (IOP) <21 mm Hg with at least a 30% reduction in IOP from baseline on two consecutive follow-up visits, IOP >5 mm Hg on two consecutive follow-up visits, and neither reoperation of glaucoma nor loss of light perception vision. The mean ±SD baseline IOP was 29.2±5.2 mm Hg, and the mean postoperative IOP was 17.3±3.4 mm Hg, with a mean pressure drop of 39.4±10.4% (P<0.001). Life-table analysis showed an 88% success rate after 12 months of follow-up. The mean preoperative best corrected visual acuity (BCVA) was 0.2±0.2 logMAR (Snellen equivalent 6/9.5), compared with 0.3±0.3 logMAR postoperatively (Snellen equivalent 6/12; P=0.497). Postoperative complications included a flat anterior chamber and choroidal detachment (one eye), uveitis and cataract (one eye), diplopia (one eye), and worsening of pre-existing pseudophakic bullous keratopathy (one eye). In glaucoma eyes with useful vision the piggyback GDI seems to provide a significant IOP lowering with minimal complications in patients in whom an initial GDI had failed to control the IOP.

  19. Insertion of sequential glaucoma drainage implant in a piggyback manner

    PubMed Central

    Välimäki, J

    2015-01-01

    Purpose This pilot study, the first of its type, was conducted to determine the clinical outcome of a sequential glaucoma drainage implant (GDI) inserted in piggyback manner, that is into the bleb of a primary GDI. Methods This was a retrospective chart study with a minimum 1-year follow-up involving 16 eyes of 14 uncontrolled glaucoma patients who had previously undergone sequential GDI performed using a technique to convert a one-plate into a two-plate implant system. Surgical success was defined as intraocular pressure (IOP) <21 mm Hg with at least a 30% reduction in IOP from baseline on two consecutive follow-up visits, IOP >5 mm Hg on two consecutive follow-up visits, and neither reoperation of glaucoma nor loss of light perception vision. Results The mean ±SD baseline IOP was 29.2±5.2 mm Hg, and the mean postoperative IOP was 17.3±3.4 mm Hg, with a mean pressure drop of 39.4±10.4% (P<0.001). Life-table analysis showed an 88% success rate after 12 months of follow-up. The mean preoperative best corrected visual acuity (BCVA) was 0.2±0.2 logMAR (Snellen equivalent 6/9.5), compared with 0.3±0.3 logMAR postoperatively (Snellen equivalent 6/12; P=0.497). Postoperative complications included a flat anterior chamber and choroidal detachment (one eye), uveitis and cataract (one eye), diplopia (one eye), and worsening of pre-existing pseudophakic bullous keratopathy (one eye). Conclusions In glaucoma eyes with useful vision the piggyback GDI seems to provide a significant IOP lowering with minimal complications in patients in whom an initial GDI had failed to control the IOP. PMID:26113501

  20. Mydriatic insert and intracameral injections compared with mydriatic eyedrops in cataract surgery: controlled studies.

    PubMed

    Behndig, Anders; Korobelnik, Jean-François

    2015-07-01

    Mydriatic eyedrops are the standard method for pupil dilation in cataract surgery, but their limitations have prompted a search for alternative techniques. Two alternatives-an ophthalmic insert containing phenylephrine and tropicamide and intracameral injections of various combinations of lidocaine, cyclopentolate, and phenylephrine, with or without epinephrine in the irrigating solution-have been assessed in prospective controlled studies, including randomized controlled trials (RCTs). We reviewed the safety and efficacy of mydriatic ophthalmic inserts and intracameral mydriatic injections compared with the safety and efficacy of mydriatic eyedrops using a systematic PubMed search (1963 to 2014). We identified 9 prospective studies (7 RCTs, 637 patients) of the mydriatic ophthalmic insert and 15 prospective studies (14 RCTs, 1020 patients) of intracameral mydriatic injections; 7 of the RCTs compared intracameral mydriatic injections and mydriatic eyedrops and 7 RCTs studied the optimum intracameral mydriatic injection protocol. The latter showed that a lidocaine and phenylephrine-based solution, without irrigating epinephrine, was optimum for intracameral mydriatic injections. The mydriatic ophthalmic insert and intracameral mydriatic injections were consistently shown to be safe and as effective as mydriatic eyedrops. Each method has distinct advantages and limitations. Dr. Behndig has received fees from Théa Pharma GmbH as a member of the European Team for the Prophylaxis of Infection in Cataract Surgery group. Dr. Korobelnik has received consultancy fees from Alcon Surgical, Inc.; Allergan, Inc.; Alimera, Inc.; Bayer HealthCare AG; Carl Zeiss Meditec AG; Novartis Corp.; Roche Innovatis AG; and Théa Pharma GmbH. Copyright © 2015 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.