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Sample records for insertions define distinct

  1. Axon degeneration: context defines distinct pathways.

    PubMed

    Geden, Matthew J; Deshmukh, Mohanish

    2016-08-01

    Axon degeneration is an essential part of development, plasticity, and injury response and has been primarily studied in mammalian models in three contexts: 1) Axotomy-induced Wallerian degeneration, 2) Apoptosis-induced axon degeneration (axon apoptosis), and 3) Axon pruning. These three contexts dictate engagement of distinct pathways for axon degeneration. Recent advances have identified the importance of SARM1, NMNATs, NAD+ depletion, and MAPK signaling in axotomy-induced Wallerian degeneration. Interestingly, apoptosis-induced axon degeneration and axon pruning have many shared mechanisms both in signaling (e.g. DLK, JNKs, GSK3α/β) and execution (e.g. Puma, Bax, caspase-9, caspase-3). However, the specific mechanisms by which caspases are activated during apoptosis versus pruning appear distinct, with apoptosis requiring Apaf-1 but not caspase-6 while pruning requires caspase-6 but not Apaf-1. PMID:27197022

  2. 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

  3. 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. PMID:27270666

  4. Well-defined binuclear chiral spiro copper catalysts for enantioselective N-H insertion.

    PubMed

    Zhu, Shou-Fei; Xu, Bin; Wang, Guo-Peng; Zhou, Qi-Lin

    2012-01-11

    An asymmetric N-H insertion of α-diazoesters with anilines catalyzed by well-defined copper complexes of chiral spiro bisoxazoline ligands was studied in detail. The copper-catalyzed asymmetric N-H insertion of a wide range of α-alkyl-α-diazoacetates with anilines was accomplished with excellent enantioselectivity (up to 98% ee) and provided an efficient method for the preparation of optically active α-amino acid derivatives. A correlation study of the electronic properties of the substrates with the enantioselectivity of the N-H insertion reaction supports a stepwise insertion mechanism, and the significant first-order kinetic isotope effect proves that the proton transfer is most likely the rate-limiting step. A binuclear chiral spiro copper catalyst having 14-electron copper centers, a trans coordination model, a perfect C(2)-symmetric chiral pocket, and significant Cu-Cu interaction was isolated and extensively studied. The novel structure of the binuclear chiral spiro copper catalyst leads to unique reactivity as well as enantioselectivity in the N-H insertion reaction. PMID:22066865

  5. Proteolytic activation defines distinct lymphangiogenic mechanisms for VEGFC and VEGFD

    PubMed Central

    Bui, Hung M.; Enis, David; Robciuc, Marius R.; Nurmi, Harri J.; Cohen, Jennifer; Chen, Mei; Yang, Yiqing; Dhillon, Veerpal; Johnson, Kathy; Zhang, Hong; Kirkpatrick, Robert; Traxler, Elizabeth; Alitalo, Kari

    2016-01-01

    Lymphangiogenesis is supported by 2 homologous VEGFR3 ligands, VEGFC and VEGFD. VEGFC is required for lymphatic development, while VEGFD is not. VEGFC and VEGFD are proteolytically cleaved after cell secretion in vitro, and recent studies have implicated the protease a disintegrin and metalloproteinase with thrombospondin motifs 3 (ADAMTS3) and the secreted factor collagen and calcium binding EGF domains 1 (CCBE1) in this process. It is not well understood how ligand proteolysis is controlled at the molecular level or how this process regulates lymphangiogenesis, because these complex molecular interactions have been difficult to follow ex vivo and test in vivo. Here, we have developed and used biochemical and cellular tools to demonstrate that an ADAMTS3-CCBE1 complex can form independently of VEGFR3 and is required to convert VEGFC, but not VEGFD, into an active ligand. Consistent with these ex vivo findings, mouse genetic studies revealed that ADAMTS3 is required for lymphatic development in a manner that is identical to the requirement of VEGFC and CCBE1 for lymphatic development. Moreover, CCBE1 was required for in vivo lymphangiogenesis stimulated by VEGFC but not VEGFD. Together, these studies reveal that lymphangiogenesis is regulated by two distinct proteolytic mechanisms of ligand activation: one in which VEGFC activation by ADAMTS3 and CCBE1 spatially and temporally patterns developing lymphatics, and one in which VEGFD activation by a distinct proteolytic mechanism may be stimulated during inflammatory lymphatic growth. PMID:27159393

  6. Ionic currents of morphologically distinct peptidergic neurons in defined culture.

    PubMed

    Meyers, D E; Graf, R A; Cooke, I M

    1992-05-01

    1. The X-organ sinus gland is a major peptidergic neurosecretory system in Crustacea, analogous to the vertebrate hypothalamoneurohypophyseal system. Neuronal somata isolated from the crab (Cardisoma carnifex) X-organ and maintained in primary culture in unconditioned, fully defined medium show immediate regenerative outgrowth. Outgrowth occurring as broad lamellipodia ("veiled") distinguishes neurons consistently showing crustacean hyperglycemic hormone immunoreactivity. Neurons that are immunoreactive against molt-inhibiting hormone and red pigment concentrating hormone antisera give rise to branched neurites ("branched"). 2. The whole-cell variation of the patch-clamp technique was used to study the electrophysiology of these two cell types 24-48 h after plating. Under current clamp, only veiled neurons fired overshooting action potentials either spontaneously or in response to depolarization. 3. Under voltage clamp, net current was predominantly outward. When solutions that suppressed outward current were used, only veiled neurons showed significant inward current. These included a tetrodotoxin (TTX)-sensitive Na current and a slow (time to peak 6-10 ms at 0 mV) Cd-sensitive Ca current (ICa) that was activated at potentials less than -30 mV, was maximal at 0 to +20 mV, and did not reverse at potentials up to +60 mV. 4. In TTX, the form of the Ca current I(V) curve was unchanged by changes of holding potential between -40 and -80 mV, and 75-100% of ICa was available from -40 mV. 5. ICa inactivated slowly and incompletely. Analysis with two-pulse regimes suggested that both inactivation and facilitation mechanisms were present. 6. Outward current was examined in the presence and absence of 0.5 mM Cd2+ (1 microM TTX was always present in the external medium). Cd2+ ions slightly reduced the peak outward current, usually by less than 10% (Vc = -10 to +20 mV; Vh = -80 mV). All additional observations were in the presence of TTX and Cd2+. 7. Both cell types expressed

  7. 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.

  8. DNA Methylome of Familial Breast Cancer Identifies Distinct Profiles Defined by Mutation Status

    PubMed Central

    Flanagan, James M.; Cocciardi, Sibylle; Waddell, Nic; Johnstone, Cameron N.; Marsh, Anna; Henderson, Stephen; Simpson, Peter; da Silva, Leonard; Khanna, Kumkum; Lakhani, Sunil; Boshoff, Chris; Chenevix-Trench, Georgia

    2010-01-01

    It is now understood that epigenetic alterations occur frequently in sporadic breast carcinogenesis, but little is known about the epigenetic alterations associated with familial breast tumors. We performed genome-wide DNA-methylation profiling on familial breast cancers (n = 33) to identify patterns of methylation specific to the different mutation groups (BRCA1, BRCA2, and BRCAx) or intrinsic subtypes of breast cancer (basal, luminal A, luminal B, HER2-amplified, and normal-like). We used methylated DNA immunoprecipitation (MeDIP) on Affymetrix promoter chips to interrogate methylation profiles across 25,500 distinct transcripts. Using a support vector machine classification algorithm, we demonstrated that genome-wide methylation profiles predicted tumor mutation status with estimated error rates of 19% (BRCA1), 31% (BRCA2), and 36% (BRCAx) but did not accurately predict the intrinsic subtypes defined by gene expression. Furthermore, using unsupervised hierarchical clustering, we identified a distinct subgroup of BRCAx tumors defined by methylation profiles. We validated these findings in the 33 tumors in the test set, as well as in an independent validation set of 47 formalin-fixed, paraffin-embedded familial breast tumors, by pyrosequencing and Epityper. Finally, gene-expression profiling and SNP CGH array previously performed on the same samples allowed full integration of methylation, gene-expression, and copy-number data sets, revealing frequent hypermethylation of genes that also displayed loss of heterozygosity, as well as of genes that show copy-number gains, providing a potential mechanism for expression dosage compensation. Together, these data show that methylation profiles for familial breast cancers are defined by the mutation status and are distinct from the intrinsic subtypes. PMID:20206335

  9. 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

  10. 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

  11. 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

  12. Distinct neurohumoral biomarker profiles in children with hemodynamically defined orthostatic intolerance may predict treatment options.

    PubMed

    Wagoner, Ashley L; Shaltout, Hossam A; Fortunato, John E; Diz, Debra I

    2016-02-01

    Studies of adults with orthostatic intolerance (OI) have revealed altered neurohumoral responses to orthostasis, which provide mechanistic insights into the dysregulation of blood pressure control. Similar studies in children with OI providing a thorough neurohumoral profile are lacking. The objective of the present study was to determine the cardiovascular and neurohumoral profile in adolescent subjects presenting with OI. Subjects at 10-18 yr of age were prospectively recruited if they exhibited two or more traditional OI symptoms and were referred for head-up tilt (HUT) testing. Circulating catecholamines, vasopressin, aldosterone, renin, and angiotensins were measured in the supine position and after 15 min of 70° tilt. Heart rate and blood pressure were continuously measured. Of the 48 patients, 30 patients had an abnormal tilt. Subjects with an abnormal tilt had lower systolic, diastolic, and mean arterial blood pressures during tilt, significantly higher levels of vasopressin during HUT, and relatively higher catecholamines and ANG II during HUT than subjects with a normal tilt. Distinct neurohumoral profiles were observed when OI subjects were placed into the following groups defined by the hemodynamic response: postural orthostatic tachycardia syndrome (POTS), orthostatic hypotension (OH), syncope, and POTS/syncope. Key characteristics included higher HUT-induced norepinephrine in POTS subjects, higher vasopressin in OH and syncope subjects, and higher supine and HUT aldosterone in OH subjects. In conclusion, children with OI and an abnormal response to tilt exhibit distinct neurohumoral profiles associated with the type of the hemodynamic response during orthostatic challenge. Elevated arginine vasopressin levels in syncope and OH groups are likely an exaggerated response to decreased blood flow not compensated by higher norepinephrine levels, as observed in POTS subjects. These different compensatory mechanisms support the role of measuring neurohumoral

  13. Analysis of Gpr126 function defines distinct mechanisms controlling the initiation and maturation of myelin

    PubMed Central

    Glenn, Thomas D.; Talbot, William S.

    2013-01-01

    In peripheral nerves, Schwann cells form the myelin sheath, which allows the efficient propagation of action potentials along axons. The transcription factor Krox20 regulates the initiation of myelination in Schwann cells and is also required to maintain mature myelin. The adhesion G protein-coupled receptor (GPCR) Gpr126 is essential for Schwann cells to initiate myelination, but previous studies have not addressed the role of Gpr126 signaling in myelin maturation and maintenance. Through analysis of Gpr126 in zebrafish, we define two distinct mechanisms controlling the initiation and maturation of myelin. We show that gpr126 mutant Schwann cells elaborate mature myelin sheaths and maintain krox20 expression for months, provided that the early signaling defect is bypassed by transient elevation of cAMP. At the onset of myelination, Gpr126 and protein kinase A (PKA) function as a switch that allows Schwann cells to initiate krox20 expression and myelination. After myelination is initiated, krox20 expression is maintained and myelin maturation proceeds independently of Gpr126 signaling. Transgenic analysis indicates that the Krox20 cis-regulatory myelinating Schwann cell element (MSE) becomes active at the onset of myelination and that this activity is dependent on Gpr126 signaling. Activity of the MSE declines after initiation, suggesting that other elements are responsible for maintaining krox20 expression in mature nerves. We also show that elevated cAMP does not initiate myelination in the absence of functional Neuregulin 1 (Nrg1) signaling. These results indicate that the mechanisms regulating the initiation of myelination are distinct from those mediating the maturation and maintenance of myelin. PMID:23804499

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

    PubMed

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

    2016-06-01

    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 machinery with

  15. 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

  16. Distinct Mammalian Precursors Are Committed to Generate Neurons with Defined Dendritic Projection Patterns

    PubMed Central

    Kelsch, Wolfgang; Mosley, Colleen P; Lin, Chia-Wei; Lois, Carlos

    2007-01-01

    The mechanisms that regulate how dendrites target different neurons to establish connections with specific cell types remain largely unknown. In particular, the formation of cell-type–specific connectivity during postnatal neurogenesis could be either determined by the local environment of the mature neuronal circuit or by cell-autonomous properties of the immature neurons, already determined by their precursors. Using retroviral fate mapping, we studied the lamina-specific dendritic targeting of one neuronal type as defined by its morphology and intrinsic somatic electrical properties in neonatal and adult neurogenesis. Fate mapping revealed the existence of two separate populations of neuronal precursors that gave rise to the same neuronal type with two distinct patterns of dendritic targeting—innervating either a deep or superficial lamina, where they connect to different types of principal neurons. Furthermore, heterochronic and heterotopic transplantation demonstrated that these precursors were largely restricted to generate neurons with a predetermined pattern of dendritic targeting that was independent of the host environment. Our results demonstrate that, at least in the neonatal and adult mammalian brain, the pattern of dendritic targeting of a given neuron is a cell-autonomous property of their precursors. PMID:18001150

  17. Human colonic goblet cells. Demonstration of distinct subpopulations defined by mucin-specific monoclonal antibodies.

    PubMed Central

    Podolsky, D K; Fournier, D A; Lynch, K E

    1986-01-01

    We studied glycoprotein content of human colonic goblet cells, using a library of monoclonal antibodies (MAbs) directed against purified human colonic mucin (HCM). Using indirect immunofluorescence (IIF), we found that 17 of 23 anti-HCM MAbs stained some or all goblet cells of normal human colonic mucosa. We observed a variety of cellular staining patterns, including (a) diffuse (homogeneous) staining of intracellular mucin, (b) speckled (inhomogeneous) staining of mucin droplets, (c) peripheral staining of intracellular droplets, (d) cytoplasmic staining of goblet cells, and (e) apical (luminal) surface staining. Staining patterns were not associated with particular HCM species. In addition to variable patterns of IIF within individual cells, anti-HCM MAbs varied in the proportion of goblet cells stained. Some MAbs stained all goblet cells, while others stained a limited number of goblet cells. Although each goblet cell contained more than one type mucin, HCM species III, and IV and V appeared to exist in mutually exclusive goblet cell populations and it was possible to define at least seven subpopulations of goblet cells in colonic mucosa by their content of various combinations of HCM species. Anti-HCM MAbs stained goblet cells from other sites within the gastrointestinal tract to a varying extent. Anti-HCM MAbs also showed extensive cross-reactivity with rodent, rabbit, and monkey colonic mucosa. However, several anti-HCM MAbs stained only human colonic mucosa. These data show that human colonic mucosa contains discrete subpopulations of goblet cells that produce distinctive combinations of specific mucin glycoprotein species. Images PMID:2420829

  18. 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. PMID:24485763

  19. 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…

  20. 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

  1. Adult mouse basal forebrain harbors two distinct cholinergic populations defined by their electrophysiology

    PubMed Central

    Unal, Cagri T.; Golowasch, Jorge P.; Zaborszky, Laszlo

    2012-01-01

    We performed whole-cell recordings from basal forebrain (BF) cholinergic neurons in transgenic mice expressing enhanced green fluorescent protein (eGFP) under the control of the choline acetyltransferase promoter. BF cholinergic neurons can be differentiated into two electrophysiologically identifiable subtypes: early and late firing neurons. Early firing neurons (∼70%) are more excitable, show prominent spike frequency adaptation and are more susceptible to depolarization blockade, a phenomenon characterized by complete silencing of the neuron following initial action potentials. Late firing neurons (∼30%), albeit being less excitable, could maintain a tonic discharge at low frequencies. In voltage clamp analysis, we have shown that early firing neurons have a higher density of low voltage activated (LVA) calcium currents. These two cholinergic cell populations might be involved in distinct functions: the early firing group being more suitable for phasic changes in cortical acetylcholine release associated with attention while the late firing neurons could support general arousal by maintaining tonic acetylcholine levels. PMID:22586380

  2. New DNA polymorphisms define ethnically distinct haplotypes in the human transferrin receptor gene.

    PubMed

    Van Landeghem, G F; Beckman, L E; Sikström, C; Saha, N; Kucinskas, V; Beckman, L

    1998-01-01

    In a study of transferrin receptor (TFR) polymorphism in different ethnic groups using PCR and restriction cleavage we found a new Hin6I polymorphism in intron 7 and confirmed a tentative BanI polymorphism in exon 4 reported by Evans and Kemp [Gene 1997;199:123-131]. In all ethnic groups there was a complete and highly significant (p < 10(-10)) linkage disequilibrium where all BanI 1 alleles were linked to Hin6I 1 alleles. Furthermore in the European populations, but not in the Chinese, there was a close correlation between the three BanI-Hin6I haplotypes and the alleles of a previously described three-allelic RsaI polymorphism in the TFR gene studied by Southern blotting. There were distinct ethnic differences in TFR allele and haplotype frequencies. Thus the Saamis were significantly different from the other European ethnic groups, and the Lithuanians had a significantly increased frequency of the BanI 2-Hin6I 1 haplotype, suggesting that this marker may be informative in tracing prehistoric migrations and admixture by Baltic peoples. The new TFR polymorphisms and haplotypes may also be useful markers in studies of interactions with the transferrin and hemochromatosis genes, the genetic influence on body iron stores and disease associations. PMID:9748693

  3. GC skew defines distinct RNA polymerase pause sites in CpG island promoters.

    PubMed

    Kellner, Wendy A; Bell, Joshua S K; Vertino, Paula M

    2015-11-01

    CpG islands (CGIs) are associated with over half of human gene promoters and are characterized by a unique chromatin environment and high levels of bidirectional transcriptional activity relative to surrounding genomic regions, suggesting that RNA polymerase (Pol II) progression past the CGI boundaries is restricted. Here we describe a novel transcriptional regulatory step wherein Pol II encounters an additional barrier to elongation distinct from the promoter-proximal pause and occurring at the downstream boundary of the CGI domain. For most CGI-associated promoters, Pol II exhibits a dominant pause at either the promoter-proximal or this distal site that correlates, both in position and in intensity, with local regions of high GC skew, a sequence feature known to form unique secondary structures. Upon signal-induced gene activation, long-range enhancer contacts at the dominant pause site are selectively enhanced, suggesting a new role for enhancers at the downstream pause. These data point to an additional level of control over transcriptional output at a subset of CGI-associated genes that is linked to DNA sequence and the integrity of the CGI domain. PMID:26275623

  4. 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

  5. GC skew defines distinct RNA polymerase pause sites in CpG island promoters

    PubMed Central

    Kellner, Wendy A.; Bell, Joshua S.K.; Vertino, Paula M.

    2015-01-01

    CpG islands (CGIs) are associated with over half of human gene promoters and are characterized by a unique chromatin environment and high levels of bidirectional transcriptional activity relative to surrounding genomic regions, suggesting that RNA polymerase (Pol II) progression past the CGI boundaries is restricted. Here we describe a novel transcriptional regulatory step wherein Pol II encounters an additional barrier to elongation distinct from the promoter-proximal pause and occurring at the downstream boundary of the CGI domain. For most CGI-associated promoters, Pol II exhibits a dominant pause at either the promoter-proximal or this distal site that correlates, both in position and in intensity, with local regions of high GC skew, a sequence feature known to form unique secondary structures. Upon signal-induced gene activation, long-range enhancer contacts at the dominant pause site are selectively enhanced, suggesting a new role for enhancers at the downstream pause. These data point to an additional level of control over transcriptional output at a subset of CGI-associated genes that is linked to DNA sequence and the integrity of the CGI domain. PMID:26275623

  6. 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. PMID:26909801

  7. Defining Essential Stem Cell Characteristics in Adipose-Derived Stromal Cells Extracted from Distinct Anatomical Sites

    PubMed Central

    Sachs, Patrick C.; Francis, Michael P.; Zhao, Min; Brumelle, Jenni; Rao, Raj R.; Elmore, Lynne W.; Holt, Shawn E.

    2013-01-01

    The discovery of adipose-derived stromal cells (ASCs) has created many opportunities for the development of patient-specific cell-based replacement therapies. We have isolated multiple cell strains of ASCs from various anatomical sites (abdomen, arms/legs, breast, buttocks), indicating wide-spread distribution of ASCs throughout the body. Unfortunately, there exists a general lack of agreement in the literature as to their “stem cell” characteristics. We find that telomerase activity and expression of its catalytic subunit in ASCs are both below the levels of detection, independent of age and culturing conditions. ASCs also undergo telomere attrition and eventually senesce, while maintaining a stable karyotype without the development of spontaneous tumor-associated abnormalities. Using a set of cell surface markers that have been promoted to identify ASCs, we find that they failed to distinguish ASCs from normal fibroblasts, as both are positive for CD29, CD73, and CD105 and negative for CD14, CD31, and CD45. All of the ASC isolates are multipotent, capable of differentiating into osteocytes, chondrocytes, and adipocytes, while fibroblasts show no differentiation potential. Our ASC strains also show elevated expression of genes associated with pluripotent cells, Oct-4, SOX2, and NANOG when compared to fibroblasts and bone marrow-derived mesenchymal stem cells (BM-MSCs), although the levels were lower than induced pluripotent stem cells (iPS). Together, our data suggest that while the cell surface profile of ASCs does not distinguish them from normal fibroblasts, their differentiation capacity and the expression of genes closely linked to pluripotency clearly define ASCs as multipotent stem cells, regardless of tissue isolation location. PMID:22628159

  8. 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

  9. Histone H3 Acetylation and H3 K4 Methylation Define Distinct Chromatin Regions Permissive for Transgene Expression

    PubMed Central

    Yan, Chunhong; Boyd, Douglas D.

    2006-01-01

    Histone modifications are associated with distinct transcription states and serve as heritable epigenetic markers for chromatin structure and function. While H3 K9 methylation defines condensed heterochromatin that is able to silence a nearby gene, how gene silencing within euchromatin regions is achieved remains elusive. We report here that histone H3 K4 methylation or K9/K14 acetylation defines distinct chromatin regions permissive or nonpermissive for transgene expression. A permissive chromatin region is enriched in H3 K4 methylation and H3 acetylation, while a nonpermissive region is poor in or depleted of these two histone modifications. The histone modification states of the permissive chromatin can spread to transgenic promoters. However, de novo histone H3 acetylation and H3 K4 methylation at a transgenic promoter in a nonpermissive chromatin region are stochastic, leading to variegated transgene expression. Moreover, nonpermissive chromatin progressively silences a transgene, an event that is accompanied by the reduction of H3 K4 methylation and H3 acetylation levels at the transgenic promoter. These repressive effects of nonpermissive chromatin cannot be completely countered by strong transcription activators, indicating the dominance of the chromatin effects. We therefore propose a model in which histone H3 acetylation and H3 K4 methylation localized to discrete sites in the mammalian genome mark distinct chromatin functions that dictate transgene expression or silencing. PMID:16914722

  10. 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

  11. Co-Activation of Epidermal Growth Factor Receptor and c-MET Defines a Distinct Subset of Lung Adenocarcinomas

    PubMed Central

    Matsubara, Daisuke; Ishikawa, Shumpei; Sachiko, Oguni; Aburatani, Hiroyuki; Fukayama, Masashi; Niki, Toshiro

    2010-01-01

    Epidermal growth factor receptor (EGFR) and MET are molecular targets for lung cancer treatment. The relationships between expression, activation, and gene abnormalities of these two targets are currently unclear. Here, we demonstrate that a panel of 40 lung cancer cell lines could be classified into two groups. Group I was characterized by (1) high phosphorylations of MET and EGFR, (2) frequent mutation or amplification of EGFR, MET, and human epidermal growth factor receptor-2 (HER2), (3) high expressions of bronchial epithelial markers (thyroid transcription factor-1 (TTF-1), MUC1, and Cytokeratin 7 (CK7)); and (4) high expressions of MET, human epidermal growth factor receptor-3, E-cadherin, cyclooxygenase-2, and laminin gamma2. In contrast, Group II exhibited little or no phosphorylation of MET and EGFR; no mutation or amplification of EGFR, MET, and HER2; were triple-negative for TTF-1, MUC1, and CK7; and showed high expressions of vimentin, fibroblast growth factor receptor-1, and transcription factor 8. Importantly, Group I was more sensitive to gefitinib and more resistant to cisplatin and paclitaxel than Group II. The clinical relevance was confirmed in publicly available data on 442 primary lung adenocarcinoma patients; survival benefits by postoperative chemotherapy were seen in only patients with tumors corresponding to Group II. Overall, co-activation of EGFR and MET defines a distinct subgroup of lung carcinoma with characteristic genetic abnormalities, gene expression pattern, and response to chemotherapeutic reagents. PMID:20934974

  12. BRAF Mutation and CDKN2A Deletion Define a Clinically Distinct Subgroup of Childhood Secondary High-Grade Glioma

    PubMed Central

    Mistry, Matthew; Zhukova, Nataliya; Merico, Daniele; Rakopoulos, Patricia; Krishnatry, Rahul; Shago, Mary; Stavropoulos, James; Alon, Noa; Pole, Jason D.; Ray, Peter N.; Navickiene, Vilma; Mangerel, Joshua; Remke, Marc; Buczkowicz, Pawel; Ramaswamy, Vijay; Guerreiro Stucklin, Ana; Li, Martin; Young, Edwin J.; Zhang, Cindy; Castelo-Branco, Pedro; Bakry, Doua; Laughlin, Suzanne; Shlien, Adam; Chan, Jennifer; Ligon, Keith L.; Rutka, James T.; Dirks, Peter B.; Taylor, Michael D.; Greenberg, Mark; Malkin, David; Huang, Annie; Bouffet, Eric; Hawkins, Cynthia E.; Tabori, Uri

    2015-01-01

    Purpose To uncover the genetic events leading to transformation of pediatric low-grade glioma (PLGG) to secondary high-grade glioma (sHGG). Patients and Methods We retrospectively identified patients with sHGG from a population-based cohort of 886 patients with PLGG with long clinical follow-up. Exome sequencing and array CGH were performed on available samples followed by detailed genetic analysis of the entire sHGG cohort. Clinical and outcome data of genetically distinct subgroups were obtained. Results sHGG was observed in 2.9% of PLGGs (26 of 886 patients). Patients with sHGG had a high frequency of nonsilent somatic mutations compared with patients with primary pediatric high-grade glioma (HGG; median, 25 mutations per exome; P = .0042). Alterations in chromatin-modifying genes and telomere-maintenance pathways were commonly observed, whereas no sHGG harbored the BRAF-KIAA1549 fusion. The most recurrent alterations were BRAF V600E and CDKN2A deletion in 39% and 57% of sHGGs, respectively. Importantly, all BRAF V600E and 80% of CDKN2A alterations could be traced back to their PLGG counterparts. BRAF V600E distinguished sHGG from primary HGG (P = .0023), whereas BRAF and CDKN2A alterations were less commonly observed in PLGG that did not transform (P < .001 and P < .001 respectively). PLGGs with BRAF mutations had longer latency to transformation than wild-type PLGG (median, 6.65 years [range, 3.5 to 20.3 years] v 1.59 years [range, 0.32 to 15.9 years], respectively; P = .0389). Furthermore, 5-year overall survival was 75% ± 15% and 29% ± 12% for children with BRAF mutant and wild-type tumors, respectively (P = .024). Conclusion BRAF V600E mutations and CDKN2A deletions constitute a clinically distinct subtype of sHGG. The prolonged course to transformation for BRAF V600E PLGGs provides an opportunity for surgical interventions, surveillance, and targeted therapies to mitigate the outcome of sHGG. PMID:25667294

  13. Genetic Profiling by Single-Nucleotide Polymorphism-Based Array Analysis Defines Three Distinct Subtypes of Orbital Meningioma

    PubMed Central

    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.

    2015-01-01

    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. PMID:24773246

  14. 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. PMID:16260155

  15. 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

  16. 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

  17. B lymphocyte reconstitution after human bone marrow transplantation. Leu-1 antigen defines a distinct population of B lymphocytes.

    PubMed Central

    Antin, J H; Ault, K A; Rappeport, J M; Smith, B R

    1987-01-01

    Differences in the expression of Leu-1 (CD5) define two populations of recovering B cells after human marrow transplantation, Leu-1+ and Leu-1- B cells. The Leu-1+ B cells were polyclonal, of donor origin, and did not express detectable interleukin 2 receptor. Leu-1+ B cells generally appeared 2-4 wk after marrow grafting and often preceded the recovery of Leu-1- B cells. Acute and chronic graft vs. host disease (GvHD) resulted in the recovery of significantly fewer Leu-1+ B cells, whereas Leu-1- B cells were only decreased in acute GvHD. Multivariate analysis showed no significant effect of age, disease, prednisone or azathioprine, or ex vivo treatment of the marrow with anti-Leu-1 and complement on recovery of Leu-1+ and Leu-1- B cells, independent of the effects of GvHD. Leu-1+ B cells are a major lymphocyte population posttransplant. They may reflect a stage of differentiation of normal B cells or a separate B cell lineage. PMID:3112184

  18. 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

  19. HER2, MET and FGFR2 oncogenic driver alterations define distinct molecular segments for targeted therapies in gastric carcinoma

    PubMed Central

    Liu, Y J; Shen, D; Yin, X; Gavine, P; Zhang, T; Su, X; Zhan, P; Xu, Y; Lv, J; Qian, J; Liu, C; Sun, Y; Qian, Z; Zhang, J; Gu, Y; Ni, X

    2014-01-01

    Background: Gastric cancer (GC) is a leading cause of cancer deaths worldwide. Since the approval of trastuzumab, targeted therapies are emerging as promising treatment options for the disease. This study aimed to explore the molecular segmentation of several known therapeutics targets, human epidermal growth factor receptor 2 (HER2), MET and fibroblast growth factor receptor 2 (FGFR2), within GC using clinically approved or investigational kits and scoring criteria. Knowledge of how these markers are segmented in the same cohort of GC patients could improve future clinical trial designs. Methods: Using immunohistochemistry (IHC) and FISH methods, overexpression and amplification of HER2, FGFR2 and MET were profiled in a cohort of Chinese GC samples. The correlations between anti-tumour sensitivity and the molecular segments of HER2, MET and FGFR2 alterations were further tested in a panel of GC cell lines and the patient-derived GC xenograft (PDGCX) model using the targeted inhibitors. Results: Of 172 GC patients, positivity for HER2, MET and FGFR2 alternations was found in 23 (13.4%), 21 (12.2%) and 9 (5.2%) patients, respectively. Positivity for MET was found in 3 of 23 HER2-positive GC patients. Co-positivity for FGFR2 and MET was found in 1 GC patient, and amplification of the two genes was found in different tumour cells. Our study in a panel of GC cell lines showed that in most cell lines, amplification or high expression of a particular molecular marker was mutually exclusive and in vitro sensitivity to the targeted agents lapatinib, PD173074 and crizotinib was only observed in cell lines with the corresponding high expression of the drugs' target protein. SGC031, an MET-positive PDGCX mouse model, responded to crizotinib but not to lapatinib or PD173074. Conclusions: Human epidermal growth factor receptor 2, MET and FGFR2 oncogenic driver alterations (gene amplification and overexpression) occur in three largely distinct molecular segments in GC. A

  20. When pain is not only pain: inserting needles into the body evokes distinct reward-related brain responses in the context of a treatment.

    PubMed

    Lee, In-Seon; Wallraven, Christian; Kong, Jian; Chang, Dong-Seon; Lee, Hyejung; Park, Hi-Joon; Chae, Younbyoung

    2015-03-01

    The aim of this study was to compare behavioral and functional brain responses to the act of inserting needles into the body in two different contexts, treatment and stimulation, and to determine whether the behavioral and functional brain responses to a subsequent pain stimulus were also context dependent. Twenty-four participants were randomly divided into two groups: an acupuncture treatment (AT) group and an acupuncture stimulation (AS) group. Each participant received three different types of stimuli, consisting of tactile, acupuncture, and pain stimuli, and was given behavioral assessments during fMRI scanning. Although the applied stimuli were physically identical in both groups, the verbal instructions differed: participants in the AS group were primed to consider the acupuncture as a painful stimulus, whereas the participants in the AT group were told that the acupuncture was part of therapeutic treatment. Acupuncture yielded greater brain activation in reward-related brain areas (ventral striatum) of the brain in the AT group when compared to the AS group. Brain activation in response to pain stimuli was significantly attenuated in the bilateral secondary somatosensory cortex and the right dorsolateral prefrontal cortex after prior acupuncture needle stimulation in the AT group but not in the AS group. Inserting needles into the body in the context of treatment activated reward circuitries in the brain and modulated pain responses in the pain matrix. Our findings suggest that pain induced by therapeutic tools in the context of a treatment is modulated differently in the brain, demonstrating the power of context in medical practice. PMID:25528104

  1. 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

  2. Efficient Hydrogenation of Ketones and Aldehydes Catalyzed by Well-Defined Iron(II) PNP Pincer Complexes: Evidence for an Insertion Mechanism

    PubMed Central

    2014-01-01

    We have prepared and structurally characterized a new class of Fe(II) PNP pincer hydride complexes [Fe(PNP-iPr)(H)(CO)(L)]n (L = Br–, CH3CN, pyridine, PMe3, SCN–, CO, BH4–; n = 0, +1) based on the 2,6-diaminopyridine scaffold where the PiPr2 moieties of the PNP ligand are connected to the pyridine ring via NH and/or NMe spacers. Complexes [Fe(PNP-iPr)(H)(CO)(L)]n with labile ligands (L = Br–, CH3CN, BH4–) and NH spacers are efficient catalysts for the hydrogenation of both ketones and aldehydes to alcohols under mild conditions, while those containing inert ligands (L = pyridine, PMe3, SCN–, CO) are catalytically inactive. Interestingly, complex [Fe(PNPMe-iPr)(H)(CO)(Br)], featuring NMe spacers, is an efficient catalyst for the chemoselective hydrogenation of aldehydes. The first type of complexes involves deprotonation of the PNP ligand as well as heterolytic dihydrogen cleavage via metal-alkoxide cooperation, but no reversible aromatization/deprotonation of the PNP ligand. In the case of the N-methylated complex the mechanism remains unclear, but obviously does not allow bifunctional activation of dihydrogen. The experimental results complemented by DFT calculations strongly support an insertion of the C=O bond of the carbonyl compound into the Fe–H bond.

  3. K27M mutation in histone H3.3 defines clinically and biologically distinct subgroups of pediatric diffuse intrinsic pontine gliomas.

    PubMed

    Khuong-Quang, Dong-Anh; Buczkowicz, Pawel; Rakopoulos, Patricia; Liu, Xiao-Yang; Fontebasso, Adam M; Bouffet, Eric; Bartels, Ute; Albrecht, Steffen; Schwartzentruber, Jeremy; Letourneau, Louis; Bourgey, Mathieu; Bourque, Guillaume; Montpetit, Alexandre; Bourret, Genevieve; Lepage, Pierre; Fleming, Adam; Lichter, Peter; Kool, Marcel; von Deimling, Andreas; Sturm, Dominik; Korshunov, Andrey; Faury, Damien; Jones, David T; Majewski, Jacek; Pfister, Stefan M; Jabado, Nada; Hawkins, Cynthia

    2012-09-01

    Pediatric glioblastomas (GBM) including diffuse intrinsic pontine gliomas (DIPG) are devastating brain tumors with no effective therapy. Here, we investigated clinical and biological impacts of histone H3.3 mutations. Forty-two DIPGs were tested for H3.3 mutations. Wild-type versus mutated (K27M-H3.3) subgroups were compared for HIST1H3B, IDH, ATRX and TP53 mutations, copy number alterations and clinical outcome. K27M-H3.3 occurred in 71 %, TP53 mutations in 77 % and ATRX mutations in 9 % of DIPGs. ATRX mutations were more frequent in older children (p < 0.0001). No G34V/R-H3.3, IDH1/2 or H3.1 mutations were identified. K27M-H3.3 DIPGs showed specific copy number changes, including all gains/amplifications of PDGFRA and MYC/PVT1 loci. Notably, all long-term survivors were H3.3 wild type and this group of patients had better overall survival. K27M-H3.3 mutation defines clinically and biologically distinct subgroups and is prevalent in DIPG, which will impact future therapeutic trial design. K27M- and G34V-H3.3 have location-based incidence (brainstem/cortex) and potentially play distinct roles in pediatric GBM pathogenesis. K27M-H3.3 is universally associated with short survival in DIPG, while patients wild-type for H3.3 show improved survival. Based on prognostic and therapeutic implications, our findings argue for H3.3-mutation testing at diagnosis, which should be rapidly integrated into the clinical decision-making algorithm, particularly in atypical DIPG. PMID:22661320

  4. 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 ...

  5. 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. PMID:26041320

  6. 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

  7. 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

  8. Genome-wide identification of binding sites defines distinct functions for Caenorhabditis elegans PHA-4/FOXA in development and environmental response.

    PubMed

    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

    2010-02-01

    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

  9. 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.

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

    PubMed Central

    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, You Hong; 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.

    2015-01-01

    The molecular underpinnings that drive the heterogeneity of KRAS-mutant lung adenocarcinoma (LUAC) are poorly characterized. We performed an integrative analysis of genomic, transcriptomic and proteomic data from early-stage and chemo-refractory LUAC and identified three robust subsets of KRAS-mutant LUAC 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 reveal 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 LUAC with distinct biology and therapeutic vulnerabilities. PMID:26069186

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

    SciTech Connect

    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.

  12. Novel homodimeric and heterodimeric rat gamma-hydroxybutyrate synthases that associate with the Golgi apparatus define a distinct subclass of aldo-keto reductase 7 family proteins.

    PubMed Central

    Kelly, Vincent P; Sherratt, Philip J; Crouch, Dorothy H; Hayes, John D

    2002-01-01

    The aldo-keto reductase (AKR) 7 family is composed of the dimeric aflatoxin B(1) aldehyde reductase (AFAR) isoenzymes. In the rat, two AFAR subunits exist, designated rAFAR1 and rAFAR2. Herein, we report the molecular cloning of rAFAR2, showing that it shares 76% sequence identity with rAFAR1. By contrast with rAFAR1, which comprises 327 amino acids, rAFAR2 contains 367 amino acids. The 40 extra residues in rAFAR2 are located at the N-terminus of the polypeptide as an Arg-rich domain that may form an amphipathic alpha-helical structure. Protein purification and Western blotting have shown that the two AFAR subunits are found in rat liver extracts as both homodimers and as a heterodimer. Reductase activity in rat liver towards 2-carboxybenzaldehyde (CBA) was resolved by anion-exchange chromatography into three peaks containing rAFAR1-1, rAFAR1-2 and rAFAR2-2 dimers. These isoenzymes are functionally distinct; with NADPH as cofactor, rAFAR1-1 has a low K(m) and high activity with CBA, whereas rAFAR2-2 exhibits a low K(m) and high activity towards succinic semialdehyde. These data suggest that rAFAR1-1 is a detoxication enzyme, while rAFAR2-2 serves to synthesize the endogenous neuromodulator gamma-hydroxybutyrate (GHB). Subcellular fractionation of liver extracts showed that rAFAR1-1 was recovered in the cytosol whereas rAFAR2-2 was associated with the Golgi apparatus. The distinct subcellular localization of the rAFAR1 and rAFAR2 subunits was confirmed by immunocytochemistry in H4IIE cells. Association of rAFAR2-2 with the Golgi apparatus presumably facilitates secretion of GHB, and the novel N-terminal domain may either determine the targeting of the enzyme to the Golgi or regulate the secretory process. A murine AKR protein of 367 residues has been identified in expressed sequence tag databases that shares 91% sequence identity with rAFAR2 and contains the Arg-rich extended N-terminus of 40 amino acids. Further bioinformatic evidence is presented that full

  13. 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

  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 ...

  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. 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.

  18. [Suprapubic catheter insertion].

    PubMed

    Neumann, Eva; Schwentner, Christian

    2016-01-01

    The suprapubic catheter enables a percutaneous drainage of urine. The insertion is made superior of the pubic bone through the abdominal wall into the bladder. It allows a permanent drainage of urine bypassing the urethra. The insertion of a suprapubic catheter requires knowledge and expertise. This paper summarizes the basic background and allows to follow the practical application step by step. PMID:26800072

  19. 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.

  20. 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. Update Date 8/ ...

  1. PEG tube insertion -- discharge

    MedlinePlus

    ... Search Search MedlinePlus GO GO About MedlinePlus Site ... To use the sharing features on this page, please enable JavaScript. A PEG (percutaneous endoscopic gastrostomy) feeding tube insertion is the placement of ...

  2. Chest tube insertion

    MedlinePlus

    ... leaks from inside the lung into the chest ( pneumothorax ) Fluid buildup in the chest (called a pleural ... on the reason a chest tube is inserted. Pneumothorax usually improves, but sometimes needs minimally invasive surgery. ...

  3. 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.

  4. Mechanism of alamethicin insertion into lipid bilayers.

    PubMed Central

    He, K; Ludtke, S J; Heller, W T; Huang, H W

    1996-01-01

    Alamethicin adsorbs on the membrane surface at low peptide concentrations. However, above a critical peptide-to-lipid ratio (P/L), a fraction of the peptide molecules insert in the membrane. This critical ratio is lipid dependent. For diphytanoyl phosphatidylcholine it is about 1/40. At even higher concentrations P/L > or = 1/15, all of the alamethicin inserts into the membrane and forms well-defined pores as detected by neutron in-plane scattering. A previous x-ray diffraction measurement showed that alamethicin adsorbed on the surface has the effect of thinning the bilayer in proportion to the peptide concentration. A theoretical study showed that the energy cost of membrane thinning can indeed lead to peptide insertion. This paper extends the previous studies to the high-concentration region P/L > 1/40. X-ray diffraction shows that the bilayer thickness increases with the peptide concentration for P/L > 1/23 as the insertion approaches 100%. The thickness change with the percentage of insertion is consistent with the assumption that the hydrocarbon region of the bilayer matches the hydrophobic region of the inserted peptide. The elastic energy of a lipid bilayer including both adsorption and insertion of peptide is discussed. The Gibbs free energy is calculated as a function of P/L and the percentage of insertion phi in a simplified one-dimensional model. The model exhibits an insertion phase transition in qualitative agreement with the data. We conclude that the membrane deformation energy is the major driving force for the alamethicin insertion transition. Images FIGURE 1 PMID:8913604

  5. Inserting IUDs safely.

    PubMed

    Burnhill, M S

    1989-01-01

    A comprehensive discussion of safe insertion of IUDs in the contemporary U.S. setting, when any IUD complication may provoke litigation, includes explanations of complications listed on package inserts, what to look for in the pelvic exam, now to handle the inserter, whether to give prophylactic antibiotics or a cervical block, follow-up management, and advice on safe sex and hygiene. The similarities and differences in listed contraindications for the ParaGard and Progestasert IUDs are analyzed. It is important to know these listed contraindications to avoid being the sole defendant in a court case. Neither explicitly rules out nulliparas, and some women who have completed childbearing may be willing to risk ectopic pregnancy. The physician must be sure to avoid any possible risks of pelvic infection, however. It is important to postpone IUD insertion if there is any suggestion of lower genital tract infection. Similarly, IUD insertion is intended to last for years, so a paracervical block is recommended if access is difficult. Tips for ensuring scrupulous asepsis are suggested. Women for whom prophylactic antibiotics are advised include diabetics, those with heart valve disease or transplants. IUD patients should be clearly identified when they call in with complaints, and seen urgently. Finally, a sexual history should be taken to avoid candidates who engage in anal sex practices. PMID:12284992

  6. ALS insertion devices

    SciTech Connect

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

    1990-11-01

    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. 18 refs., 9 figs., 5 tabs.

  7. Defining "Development".

    PubMed

    Pradeu, Thomas; Laplane, Lucie; Prévot, Karine; Hoquet, Thierry; Reynaud, Valentine; Fusco, Giuseppe; Minelli, Alessandro; Orgogozo, Virginie; Vervoort, Michel

    2016-01-01

    Is it possible, and in the first place is it even desirable, to define what "development" means and to determine the scope of the field called "developmental biology"? Though these questions appeared crucial for the founders of "developmental biology" in the 1950s, there seems to be no consensus today about the need to address them. Here, in a combined biological, philosophical, and historical approach, we ask whether it is possible and useful to define biological development, and, if such a definition is indeed possible and useful, which definition(s) can be considered as the most satisfactory. PMID:26969977

  8. Defining Infertility

    MedlinePlus

    ... of the American Society for Reproductive Medicine Defining infertility What is infertility? Infertility is “the inability to conceive after 12 months ... to conceive after 6 months is generally considered infertility. How common is it? Infertility affects 10%-15% ...

  9. Defining Risk.

    ERIC Educational Resources Information Center

    Tholkes, Ben F.

    1998-01-01

    Defines camping risks and lists types and examples: (1) objective risk beyond control; (2) calculated risk based on personal choice; (3) perceived risk; and (4) reckless risk. Describes campers to watch ("immortals" and abdicators), and several "treatments" of risk: avoidance, safety procedures and well-trained staff, adequate insurance, and a…

  10. Interfacial insert for electrical connectors

    NASA Technical Reports Server (NTRS)

    Macavay, D.

    1975-01-01

    The development of interfacial inserts for improved electric connectors is discussed. The inserts were manufactured from epoxy resins. The design features of the inserts and the manufacturing equipment are described. The reliability test program is reported. Drawings of the interfacial inserts are provided.

  11. 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…

  12. Defining cure.

    PubMed

    Hilton, Paul; Robinson, Dudley

    2011-06-01

    This paper is a summary of the presentations made as Proposal 2-"Defining cure" to the 2nd Annual meeting of the ICI-Research Society, in Bristol, 16th June 2010. It reviews definitions of 'cure' and 'outcome', and considers the impact that varying definition may have on prevalence studies and cure rates. The difference between subjective and objective outcomes is considered, and the significance that these different outcomes may have for different stakeholders (e.g. clinicians, patients, carers, industry etc.) is discussed. The development of patient reported outcome measures and patient defined goals is reviewed, and consideration given to the use of composite end-points. A series of proposals are made by authors and discussants as to how currently validated outcomes should be applied, and where our future research activity in this area might be directed. PMID:21661023

  13. [Orthopedic shoe treatment : Inserts].

    PubMed

    Schuh, R; Windhager, R

    2016-03-01

    The use of inserts and orthopedic shoe adjustment represents an essential component of the conservative therapy of degenerative diseases and deformities of the musculoskeletal system. Inserts can have supportive, bedding and corrective effects and are used in particular for complaints of the feet and ankles. The combination of diverse materials allows a high level of cushioning and supporting features and corresponding longevity to be accomplished. The production is carried out on an individual basis and if necessary computer-assisted in order to achieve an optimal fit. For severe and rigid deformities the formation of pressure ulcers can be prevented by orthopedic shoe adjustment and by the use of orthopedic tailor-made shoes. PMID:26861757

  14. The spatiotemporal segregation of GAD forms defines distinct GABA signaling functions in the developing mouse olfactory system and provides novel insights into the origin and migration of GnRH neurons.

    PubMed

    Vastagh, Csaba; Schwirtlich, Marija; Kwakowsky, Andrea; Erdélyi, Ferenc; Margolis, Frank L; Yanagawa, Yuchio; Katarova, Zoya; Szabó, Gábor

    2015-03-01

    Gamma-aminobutyric acid (GABA) has a dual role as an inhibitory neurotransmitter in the adult central nervous system (CNS) and as a signaling molecule exerting largely excitatory actions during development. The rate-limiting step of GABA synthesis is catalyzed by two glutamic acid decarboxylase isoforms GAD65 and GAD67 coexpressed in the GABAergic neurons of the CNS. Here we report that the two GADs show virtually nonoverlapping expression patterns consistent with distinct roles in the developing peripheral olfactory system. GAD65 is expressed exclusively in undifferentiated neuronal progenitors confined to the proliferative zones of the sensory vomeronasal and olfactory epithelia In contrast GAD67 is expressed in a subregion of the nonsensory epithelium/vomeronasal organ epithelium containing the putative Gonadotropin-releasing hormone (GnRH) progenitors and GnRH neurons migrating from this region through the frontonasal mesenchyme into the basal forebrain. Only GAD67+, but not GAD65+ cells accumulate detectable GABA. We further demonstrate that GAD67 and its embryonic splice variant embryonic GAD (EGAD) concomitant with GnRH are dynamically regulated during GnRH neuronal migration in vivo and in two immortalized cell lines representing migratory (GN11) and postmigratory (GT1-7) stage GnRH neurons, respectively. Analysis of GAD65/67 single and double knock-out embryos revealed that the two GADs play complementary (inhibitory) roles in GnRH migration ultimately modulating the speed and/or direction of GnRH migration. Our results also suggest that GAD65 and GAD67/EGAD characterized by distinct subcellular localization and kinetics have disparate functions during olfactory system development mediating proliferative and migratory responses putatively through specific subcellular GABA pools. PMID:25125027

  15. Chest tube insertion - slideshow

    MedlinePlus

    ... Go to slide 4 out of 4 Normal anatomy Overview The pleural space is the space between ... M. is among the first to achieve this important distinction for online health information and services. Learn ...

  16. 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.

  17. Presence or absence of a known DKA precipitant defines distinct syndromes of “A-β+” Ketosis-Prone Diabetes (KPD) based on long-term beta cell function, HLA class II alleles, and gender predilection

    PubMed Central

    Nalini, Ramaswami; Ozer, Kerem; Maldonado, Mario; Patel, Sanjeet G.; Hampe, Christiane S.; Guthikonda, Anu; Villanueva, Jesus; Smith, E. O'Brian; Gaur, Lakshmi K.; Balasubramanyam, Ashok

    2010-01-01

    Objective Ketosis prone diabetes (KPD) is heterogeneous. Longitudinal follow-up revealed that patients with “A-β+” KPD (absent autoantibodies and preserved beta cell function) segregated into two subgroups with distinct evolution of beta cell function and glycemic control. Generalized linear analysis demonstrated that the variable that most significantly differentiated them was presence of a clinically evident precipitating event for the index DKA. Hence we performed a comprehensive analysis of A-β+ KPD patients presenting with “provoked” compared to “unprovoked” DKA. Methods Clinical, biochemical and beta cell functional characteristics were compared between provoked and unprovoked A-β+ KPD patients followed prospectively for 1-8 years. HLA class II allele frequencies were compared between these two groups and population controls. Results Unprovoked A-β+ KPD patients (n=83) had greater BMI, male preponderance, higher frequency of women with oligo/anovulation, more frequent African-American ethnicity and less frequent family history of diabetes than provoked A-β+ KPD patients (n=64). The provoked group had higher frequencies of the HLA class II type 1 diabetes susceptibility alleles DQB1*0302 (than the unprovoked group or population controls), and DRB1*04 (than the unprovoked group), while the unprovoked group had a higher frequency of the protective allele DQB1*0602. Beta cell secretory reserve and glycemic control improved progressively in the unprovoked group, but declined in the provoked group. The differences persisted in comparisons restricted to patients with new-onset diabetes. Conclusions “Unprovoked” A-β+ KPD is a distinct syndrome characterized by reversible beta cell dysfunction with male predominance and increased frequency of DQB1*0602, while “provoked” A-β+ KPD is characterized by progressive loss of beta cell reserve and increased frequency of DQB1*0302 and DRB1*04. Unprovoked DKA predicts long-term beta cell functional

  18. Defining GERD.

    PubMed Central

    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

  19. Inserts Automatically Lubricate Ball Bearings

    NASA Technical Reports Server (NTRS)

    Hager, J. A.

    1983-01-01

    Inserts on ball-separator ring of ball bearings provide continuous film of lubricant on ball surfaces. Inserts are machined or molded. Small inserts in ball pockets provide steady supply of lubricant. Technique is utilized on equipment for which maintenance is often poor and lubrication interval is uncertain, such as household appliances, automobiles, and marine engines.

  20. 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

  1. 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.

  2. 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.

  3. Single copy insertion of transgenes in C. elegans

    PubMed Central

    Frøkjær-Jensen, Christian; Davis, M. Wayne; Hopkins, Christopher E.; Newman, Blake; Thummel, Jason M.; Olesen, Søren-Peter; Grunnet, Morten; Jorgensen, Erik M.

    2009-01-01

    Currently transgenes in C. elegans are generated by injecting DNA into the germline. The DNA assembles into a semi-stable extrachromosomal array composed of many copies of injected DNA. These transgenes are typically overexpressed in somatic cells and silenced in the germline. We have developed a method called MosSCI (Mos1-mediated Single Copy Insertion) that inserts a single copy of a transgene into a defined site. Mobilization of a Mos1 transposon generates a double strand break in non-coding DNA. The break is repaired by copying DNA from an extrachromosomal template into the chromosomal site. Homozygous single copy insertions can be obtained in less than two weeks by injecting approximately twenty animals. We have successfully inserted transgenes as long as 9 kb and verified that single copies are inserted at the targeted site. Single copy transgenes are expressed at endogenous levels and can be expressed in the female and male germlines. PMID:18953339

  4. 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. PMID:27140657

  5. Insertion device vacuum system designs

    SciTech Connect

    Hoyer, E.

    1988-05-01

    Synchrotron light source insertion device vacuum systems now in operation and systems proposed for the future are reviewed. An overview of insertion devices is given and four generic vacuum chamber designs, transition section design and pumping considerations are discussed. Examples of vacuum chamber systems are presented.

  6. Percutaneously inserted central catheter - infants

    MedlinePlus

    PICC - infants; PQC - infants; Pic line - infants; Per-Q cath - infants ... A percutaneously inserted central catheter (PICC) is a long, very thin, soft plastic tube that is put into a small blood vessel. This article addresses PICCs in ...

  7. 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.

  8. 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

  9. 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.

  10. Reactions of a cerium(iii) amide with heteroallenes: insertion, silyl-migration and de-insertion.

    PubMed

    Yin, Haolin; Carroll, Patrick J; Schelter, Eric J

    2016-07-28

    Reactions of Ce[N(SiMe3)Ph(F)]3 (-Ph(F) = pentafluorophenyl) toward small molecules of the type E1[double bond, length as m-dash]C[double bond, length as m-dash]E2 (E1, E2 = O, S, NR), including carbon disulfide, carbodiimide, carbon dioxide, isocyanate and isothiocyanate are reported, resulting in distinct products, including cerium(iii) dithiocarbamate, cerium(iii) guanidinate, isocyanates and unsymmetric carbodiimides. These reactions were rationalized as three consecutive stages of the same reaction pathway: insertion, silyl-migration and de-insertion. PMID:27416923

  11. Precise-Conductance Valve Insert

    NASA Technical Reports Server (NTRS)

    Outlaw, R. A.; Hoyt, R. F.

    1986-01-01

    Valve modification provides two operating modes fully open and small, precise leak. Copper insert with radially oriented holes allows small, controllable, precise effusion rate when valve closed or nearly unobstructed flow when valve open. Numerous applications in surface physics, vacuum physics, materials science, gas kinetics, thin films, and other areas of research requiring measured flows of gas into or out of system.

  12. Insertion device for pressure testing

    NASA Technical Reports Server (NTRS)

    Howland, B. T.; Maurin, A. L.

    1969-01-01

    Test device which introduces either pressure or vacuum into a test pipe or tube, is insertable into the tested item where it secures itself into position and requires no external support. The unit has an operating range from zero to 25,000 psig and to any vacuum level that available equipment can reach.

  13. 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.

  14. 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.

  15. MECHANISM AND HYDROPHOBIC FORCES DRIVING MEMBRANE PROTEIN INSERTION OF SUBUNIT II OF CYTOCHROME BO OXIDASE

    PubMed Central

    Celebi, Nil; Dalbey, Ross E.; Yuan, Jijun

    2009-01-01

    Subunit II (CyoA) of cytochrome bo oxidase, which spans the inner membrane twice in bacteria, has several unusual features in membrane biogenesis. It is synthesized with an amino-terminal signal peptide. In addition, distinct pathways are used to insert the two ends of the protein. The amino-terminal domain is inserted by the YidC pathway whereas the large carboxyl-terminal domain is translocated by the SecYEG pathway. Insertion of the protein is also pmf-independent. In this study we examined the topogenic requirements and mechanism of insertion of CyoA in bacteria. We find that both the signal peptide and the first membrane spanning region are required for insertion of the amino-terminal periplasmic loop. The pmf-independence of insertion of the first periplasmic loop is due to the loop’s neutral net charge. We observe also that the introduction of negatively charged residues into the periplasmic loop makes insertion pmf dependent, whereas the addition of positively charged residues prevents insertion unless the pmf is abolished. Insertion of the carboxyl-terminal domain in the full-length CyoA occurs by a sequential mechanism even when the CyoA amino and carboxyl-terminal domains are swapped with other domains. However, when a long spacer peptide is added to increase the distance between the amino-terminal and carboxyl-terminal domains, insertion no longer occurs by a sequential mechanism. PMID:18155041

  16. Disease of distinction.

    PubMed

    Schwartz, Stephan A

    2006-01-01

    Gout is one of the rare diseases that defines its sufferers by class and culture. It is also one of the first chronic diseases to be clinically described. The Egyptians had identified gout as a distinct disorder by 2640 bce. This paper traces the history of gout from its earliest recorded period down to modern times, with a particular emphasis on the cultural, political, geopolitical, and social aspects. Included is a discussion of its role in the American Revolution. Today, gout is a well-understood clinically managed arthritic disease that excites little comment. This is an entirely modern perspective. For most of human history, gout was a disease of distinction that dominated much of medicine, playing the same role in Rome's third century bce aristocracy it would later play in the aristocracies of 17th and 18th century France and England, when each of these countries dominated the world. Because it was considered a disease of lifestyle until modern times, when genetics began to be understood, gout was associated with rich, high status Caucasian men and their excessive consumption of drink and rich foods. It was virtually unknown in Asia, until Western dietary practices became widespread there. From earliest history, gout has been linked with high IQ and sexual promiscuity, which made it grist for artists and writers, and their social commentary up to the time of Dickens; this is discussed, with examples. Because of its association with the rich, gout also developed a powerful moralistic aspect, particularly during the Christian era when the concept of sin was a cultural fundamental. The loose living and indulgence of the rich and the gout it produced made the disease a parable of Christian ethics. The Italian poet Francesco Petrarch (1304-1374) was one of the first to establish this nuance, and it influenced how gout was seen for centuries. Part of what gave gout its special character was that while it tortured, it rarely killed. Indeed, when death was a

  17. Shoe Inserts and Prescription Custom Orthotics

    MedlinePlus

    ... Feet » Foot Health Information Shoe Inserts and Prescription Custom Orthotics What are Shoe Inserts? You've seen ... hold on to your receipt.) What are Prescription Custom Orthotics? Custom orthotics are specially-made devices designed ...

  18. 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.

  19. 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.

  20. Porous pseudoalloy electrode gap inserts

    SciTech Connect

    Pustogarov, A.V.; Chernyshev, L.I.; Kostornov, A.G.; Mel'nikov, G.N.

    1985-06-01

    The authors make a comparative assessment of the service characteristics of porous electrode gap inserts (EGI) made of tungsten, molybdenum, and W-Cu and Mo-Cu pseudoalloys, tested using a high pressure apparatus. Charts present the data gathered on maximum thermal flux entering the EGI wall with specific nitrogen flow rates; variation of temperature of the inner surface of the EGI wall with thermal conductivity of the material; and variation of viscous and inertia coefficients of hydraulic resistance of pseudoalloys with duration of EGI operation. The authors conclude that porous EGIs made of W-Cu and Mo-Cu pseudoalloys are characterized by the same operating performance.

  1. Using ΦC31 integrase to mediate insertion of DNA in Xenopus embryos.

    PubMed

    Li, You E; Allen, Bryan G; Weeks, Daniel L

    2012-01-01

    The two most common methods used to generate transgenic Xenopus embryos, restriction enzyme-mediated insertion, and I-SceI meganuclease take advantage of relatively common but spatially unpredictable double-stranded breaks in sperm, egg, or early embryo genomes. These methods also tend to insert multimeric copies of the transgene. An alternative is to use bacteriophage- or transposon-derived integrase or recombinase to mediate more site-specific insertion of the transgene. The use of phiC31 integrase requires a defined sequence for insertion and is compatible with insertion of a single copy of the transgene. We describe the protocol we use to facilitate phiC31 integrase transgene insertion including the use of insulator sequences to reduce position effect disruption of transgene activity. PMID:22956091

  2. Phenotypes Associated with Second Chromosome P Element Insertions in Drosophila melanogaster.

    PubMed

    Kahsai, Lily; Millburn, Gillian H; Cook, Kevin R

    2016-01-01

    In Drosophila melanogaster, P element transposition has been a productive means of insertional mutagenesis. Thousands of genes have been tagged with natural and engineered P element constructs. Nevertheless, chromosomes carrying P element insertions tend to have high levels of background mutations from P elements inserting and excising during transposition. Consequently, the phenotypes seen when P element-bearing chromosomes are homozygous are often not attributable to the P insertions themselves. In this study, 178 strains in the Bloomington Drosophila Stock Center collection with P insertions on the second chromosome were complementation tested against molecularly defined chromosomal deletions and previously characterized single-gene mutations to determine if recessive lethality or sterility is associated with the P insertions rather than background mutations. This information should prove valuable to geneticists using these strains for experimental studies of gene function. PMID:27317776

  3. Phenotypes Associated with Second Chromosome P Element Insertions in Drosophila melanogaster

    PubMed Central

    Kahsai, Lily; Millburn, Gillian H.; Cook, Kevin R.

    2016-01-01

    In Drosophila melanogaster, P element transposition has been a productive means of insertional mutagenesis. Thousands of genes have been tagged with natural and engineered P element constructs. Nevertheless, chromosomes carrying P element insertions tend to have high levels of background mutations from P elements inserting and excising during transposition. Consequently, the phenotypes seen when P element-bearing chromosomes are homozygous are often not attributable to the P insertions themselves. In this study, 178 strains in the Bloomington Drosophila Stock Center collection with P insertions on the second chromosome were complementation tested against molecularly defined chromosomal deletions and previously characterized single-gene mutations to determine if recessive lethality or sterility is associated with the P insertions rather than background mutations. This information should prove valuable to geneticists using these strains for experimental studies of gene function. PMID:27317776

  4. 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

  5. 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.

  6. 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.

  7. 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.

  8. Mars Observer Orbit Insertion Briefing

    NASA Technical Reports Server (NTRS)

    1993-01-01

    For the first part of this briefing, see NONP-NASA-VT-2000081556. Marvin Traxler continues his discussion on signal tracking from the Mars Observer. Julie Webster, Lead Engineer, Telecommunications Subsystem, is introduced. She explains how signals coming back from Mars are detected. Dr. Pasquale Esposito talks about flyby orbits and capture orbits. He says that frequencies coming from the spacecraft can determine if the spacecraft has flown by Mars, or if a capture orbit has occurred. Charles Whetsel, System Engineer Spacecraft Team, presents a computer program. He shows where the signal will appear on the computer from the Spacecraft. Suzanne Dodd presents orbit insertion geometry. Dr. Arden Albee, Project Scientist Mars Observer Project, Cal Tech tech, says that Mars is studied to get more data to confirm their hypotheses derived from previous Mars Missions such as the Viking Mars Program and the Mariner Program. Dr. Albee also describes instrumentation on the Mars Observer such as the Ultra Stable Oscillator, Mars Orbiter Laser Altimeter, and Magnetometer. The camera on the spacecraft is similar to a fax machine because it scans one line at a time as the spacecraft orbits Mars. Dr. Michael Malin, Principle Investigator Mars Observer Camera, Malin Space Science Systems, Inc., describe this process.

  9. Multipurpose Transposon-Insertion Libraries in Yeast.

    PubMed

    Kumar, Anuj

    2016-01-01

    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. PMID:27250950

  10. Defining Overweight and Obesity

    MedlinePlus

    ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs Defining Adult Overweight and ... Physical Activity Overweight & Obesity Healthy Weight Breastfeeding Micronutrient Malnutrition State and Local Programs File Formats Help: How ...

  11. Interpolation and Definability

    NASA Astrophysics Data System (ADS)

    Gabbay, Dov M.; Maksimova, Larisa L.

    This chapter is on interpolation and definability. This notion is not only central in pure logic, but has significant meaning and applicability in all areas where logic itself is applied, especially in computer science, artificial intelligence, logic programming, philosophy of science and natural language. The notion may sometimes appear to the reader as too technical/mathematical but it does also have a general meaning in terms of expressibility and definability.

  12. Insertion Sequence Diversity in Archaea

    PubMed Central

    Filée, J.; Siguier, P.; Chandler, M.

    2007-01-01

    Insertion sequences (ISs) can constitute an important component of prokaryotic (bacterial and archaeal) genomes. Over 1,500 individual ISs are included at present in the ISfinder database (www-is.biotoul.fr), and these represent only a small portion of those in the available prokaryotic genome sequences and those that are being discovered in ongoing sequencing projects. In spite of this diversity, the transposition mechanisms of only a few of these ubiquitous mobile genetic elements are known, and these are all restricted to those present in bacteria. This review presents an overview of ISs within the archaeal kingdom. We first provide a general historical summary of the known properties and behaviors of archaeal ISs. We then consider how transposition might be regulated in some cases by small antisense RNAs and by termination codon readthrough. This is followed by an extensive analysis of the IS content in the sequenced archaeal genomes present in the public databases as of June 2006, which provides an overview of their distribution among the major archaeal classes and species. We show that the diversity of archaeal ISs is very great and comparable to that of bacteria. We compare archaeal ISs to known bacterial ISs and find that most are clearly members of families first described for bacteria. Several cases of lateral gene transfer between bacteria and archaea are clearly documented, notably for methanogenic archaea. However, several archaeal ISs do not have bacterial equivalents but can be grouped into Archaea-specific groups or families. In addition to ISs, we identify and list nonautonomous IS-derived elements, such as miniature inverted-repeat transposable elements. Finally, we present a possible scenario for the evolutionary history of ISs in the Archaea. PMID:17347521

  13. Amyloid protein unfolding and insertion kinetics on neuronal membrane mimics

    NASA Astrophysics Data System (ADS)

    Qiu, Liming; Buie, Creighton; Vaughn, Mark; Cheng, Kwan

    2010-03-01

    Atomistic details of beta-amyloid (Aβ ) protein unfolding and lipid interaction kinetics mediated by the neuronal membrane surface are important for developing new therapeutic strategies to prevent and cure Alzheimer's disease. Using all-atom MD simulations, we explored the early unfolding and insertion kinetics of 40 and 42 residue long Aβ in binary lipid mixtures with and without cholesterol that mimic the cholesterol-depleted and cholesterol-enriched lipid nanodomains of neurons. The protein conformational transition kinetics was evaluated from the secondary structure profile versus simulation time plot. The extent of membrane disruption was examined by the calculated order parameters of lipid acyl chains and cholesterol fused rings as well as the density profiles of water and lipid headgroups at defined regions across the lipid bilayer from our simulations. Our results revealed that both the cholesterol content and the length of the protein affect the protein-insertion and membrane stability in our model lipid bilayer systems.

  14. Insertion-Duplication Mutagenesis in Streptococcus pneumoniae: Targeting Fragment Length Is a Critical Parameter in Use as a Random Insertion Tool

    PubMed Central

    Lee, Myeong S.; Seok, Chaok; Morrison, Donald A.

    1998-01-01

    To examine whether insertion-duplication mutagenesis with chimeric DNA as a transformation donor could be valuable as a gene knockout tool for genomic analysis in Streptococcus pneumoniae, we studied the transformation efficiency and targeting specificity of the process by using a nonreplicative vector with homologous targeting inserts of various sizes. Insertional recombination was very specific in targeting homologous sites. While the recombination rate did not depend on which site or region was targeted, it did depend strongly on the size of the targeting insert in the donor plasmid, in proportion to the fifth power of its length for inserts of 100 to 500 bp. The dependence of insertion-duplication events on the length of the targeting homology was quite different from that for linear allele replacement and places certain limits on the design of mutagenesis experiments. The number of independent pneumococcal targeting fragments of uniform size required to knock out any desired fraction of the genes in a model genome with a defined probability was calculated from these data by using a combinatorial theory with simplifying assumptions. The results show that efficient and thorough mutagenesis of a large part of the pneumococcal genome should be practical when using insertion-duplication mutagenesis. PMID:9835564

  15. Recognition of DNA insertion/deletion mismatches by an activity in Saccharomyces cerevisiae.

    PubMed

    Miret, J J; Parker, B O; Lahua, R S

    1996-02-15

    An activity in nuclear extracts of S.cerevisiae binds specifically to heteroduplexes containing four to nine extra bases in one strand. The specificity of this activity (IMR, for insertion mismatch recognition) in band shift assays was confirmed by competition experiments. IMR is biochemically and genetically distinct from the MSH2 dependent, single base mismatch binding activity. The two activities migrate differently during electrophoresis, they are differentially competable and their spectra of mispair binding are distinct. Furthermore, IMR activity is observed in extracts from an msh2- msh3- msh4- strain. IMR exhibits specificity for insertion mispairs in two different sequence contexts. Binding is influenced by the structure of the mismatch since an insertion with a hairpin configuration is not recognized by this activity. IMR does not result from single-strand binding because single-stranded probes to not yield IMR complex and single-stranded competitors are unable to displace insertion heteroduplexes from the complex. Similar results with intrinsically bent duplexes make it unlikely that recognition is conferred by a bend alone. Heteroduplexes bound by IMR do not contain any obvious damage. These findings are consistent with the idea that yeast contains a distinct recognition factor, IMR that is specific for insertion/deletion mismatches. PMID:8604316

  16. 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

  17. Vector insert-targeted integrative antisense expression system for plasmid stabilization.

    PubMed

    Luke, Jeremy M; Carnes, Aaron E; Hodgson, Clague P; Williams, James A

    2011-01-01

    Some DNA vaccine and gene therapy vector-encoded transgenes are toxic to the E. coli plasmid production host resulting in poor production yields. For plasmid products undergoing clinical evaluation, sequence modification to eliminate toxicity is undesirable because an altered vector is a new chemical entity. We hypothesized that: (1) insert-encoded toxicity is mediated by unintended expression of a toxic insert-encoded protein from spurious bacterial promoters; and (2) that toxicity could be eliminated with antisense RNA-mediated translation inhibition. We developed the pINT PR PL vector, a chromosomally integrable RNA expression vector, and utilized it to express insert-complementary (anti-insert) RNA from a single defined site in the bacterial chromosome. Anti-insert RNA eliminated leaky fluorescent protein expression from a target plasmid. A toxic retroviral gag pol helper plasmid produced in a gag pol anti-insert strain had fourfold improved plasmid fermentation yields. Plasmid fermentation yields were also fourfold improved when a DNA vaccine plasmid containing a toxic Influenza serotype H1 hemagglutinin transgene was grown in an H1 sense strand anti-insert production strain, suggesting that in this case toxicity was mediated by an antisense alternative reading frame-encoded peptide. This anti-insert chromosomal RNA expression technology is a general approach to improve production yields with plasmid-based vectors that encode toxic transgenes, or toxic alternative frame peptides. PMID:20607625

  18. The enthesis: a review of the tendon-to-bone insertion

    PubMed Central

    Apostolakos, John; Durant, Thomas JS; Dwyer, Corey R.; Russell, Ryan P.; Weinreb, Jeffrey H.; Alaee, Farhang; Beitzel, Knut; McCarthy, Mary Beth; Cote, Mark P.; Mazzocca, Augustus D.

    2014-01-01

    Summary The integration of tendon into bone occurs at a specialized interface known as the enthesis. The fibrous tendon to bone enthesis is established through a structurally continuous gradient from uncalcified tendon to calcified bone. The enthesis exhibits gradients in tissue organization classified into four distinct zones with varying cellular compositions, mechanical properties, and functions in order to facilitate joint movement. Damage to tendinous insertions is common in the field of orthopaedic medicine and often involves surgical intervention that requires the attempted recreation of the natural organization of tendon into bone. The difficulty associated with recreating the distinct organization may account for the surgical challenges associated with reconstruction of damaged insertion sites. These procedures are often associated with high failure rates and consequently require revision procedures. Management of tendinous injuries and reconstruction of the insertion site is becoming a popular topic in the field of orthopaedic medicine. PMID:25489552

  19. Insertion of N-Tosylacetimidates/Acetimidamides onto Arynes via [2 + 2] Cycloaddition.

    PubMed

    Kranthikumar, Ramagonolla; Chegondi, Rambabu; Chandrasekhar, Srivari

    2016-03-18

    A novel insertion reaction of N-tosylacetimidates and N-tosylacetimidamides onto arynes via a benzocyclobutene intermediate followed by ring cleavage is developed to afford o-benzylbenzoic acid derivatives in good yields. Interestingly, the use of cyclic 2-sulfonyliminoindolines provided two distinct products such as azepanimines via [2 + 2] cycloaddition and indolamines via protonation based on solvent medium. PMID:26930224

  20. The interface between bone and tendon at an insertion site: a study of the quadriceps tendon insertion

    PubMed Central

    CLARK, JOHN; STECHSCHULTE, DANIEL J.

    1998-01-01

    Traumatic avulsions of ligament or tendon insertions rarely occur at the actual interface with bone, which suggests that this attachment is strong or otherwise protected from injury by the structure of the insertion complex. In this study we describe the terminal extent of quadriceps tendon fibres where they insert into the patellae of adult rabbits, humans, dogs and sheep. Specimens were examined by scanning electron microscopy (SEM) and light microscopy (LM). To facilitate tracing of tendon fibres the specimens were decalcified for SEM, and polarised light microscopy (PLM) was used in the LM segment of the study. By SEM it was possible to identify mature bone by the presence of osteocytes and a lamellar organisation. PLM and SEM showed that, unlike tendon fibres elsewhere, those in the calcified fibrocartilage were not crimped. No specific cement line was identified by SEM. Tendon fibres interdigitated among separate bone lamellar systems, (osteons or marrow spaces), but did not merge with the collagen systems of individual lamellae. The interdigitation was more extensive and the margin between tendon and bone was less distinct in the anterior third of the insertion. The segment of calcified tendon which interdigitated with bone stained less intensely blue and was less cellular than the more proximal calcified fibrocartilage zone adjacent to the tidemark. Lamellar collagen fibres of the bony trabeculae in the anterior patella were unusually parallel and longitudinal in orientation, making distinction of interposed tendon fibres difficult on LM and PLM sections. LM, SEM and transmission electron microscopy of rabbit patellae at birth revealed that anterior quadriceps tendon fibres extended over the patella in a fibrous cellular layer. By 2 wk of age, this layer had acquired chondroid features (i.e. cell lacunae and metachromasia) and contained vessels extending from patellar marrow. At 6 wk of age, part of this fibrocartilaginous layer was replaced by mature bone

  1. Device for inserting tubular members together

    SciTech Connect

    Milberger, L.J.

    1992-03-17

    This patent describes a well, a lower tubular member with a sealing surface located in the well, an upper tubular member which inserts into engagement with the lower tubular member during running in, the upper and lower tubular members being exposed to well fluid pressure, an improved means for sliding the upper tubular member into engagement with the lower tubular member. It comprises the upper tubular member having a first side and a second side, the second side having a sealing section which mates with the sealing surface of the lower tubular sidewall; axially spaced apart seal means located on the running tool sidewall for sealingly engaging the first side of the upper tubular member above and below the sealing section during running in, for defining a low pressure area between the running tool and the first side which is isolated from the well fluid pressure; the sealing section of the upper tubular member being exposed to well fluid pressure during running in, resulting in a pressure difference across the upper tubular member between the first side of the tubular member and the sealing section, means for eliminating the pressure difference across the upper tubular member between the first side and the sealing section after the upper tubular member has reached its engaged position with the lower tubular member, allowing the sealing section to move radially into engagement with the sealing surface. This patent also describes a method for sliding an upper tubular member into engagement with a sealing surface of a lower tubular member in a well having well fluid pressure, comprising in combination: providing the upper tubular member with a first side and a second side and providing the second side with a sealing section for mating with the sealing surface of the lower tubular member.

  2. Defining Airflow Obstruction

    PubMed Central

    Eschenbacher, William L.

    2016-01-01

    Airflow obstruction has been defined using spirometric test results when the forced expiratory volume in 1 second (FEV1) to forced vital capacity (FVC) ratio is below a fixed cutoff (<70%) or lower limits of normal (LLN) from reference equations that are based on values from a normal population. However, similar to other positive or abnormal diagnostic test results that are used to identify the presence of disease, perhaps airflow obstruction should be defined based on the values of FEV1/FVC for a population of individuals with known disease such as chronic obstructive pulmonary disease (COPD). Unfortunately, we do not know such a distribution of values of FEV1/FVC for patients with COPD since there is no gold standard for this syndrome or condition. Yet, we have used this physiologic definition of airflow obstruction based on a normal population to identify patients with COPD. In addition, we have defined airflow obstruction as either being present or absent. Instead, we should use a different approach to define airflow obstruction based on the probability or likelihood that the airflow obstruction is present which in turn would give us the probability or likelihood of a disease state such as COPD. PMID:27239557

  3. Defining Equality in Education

    ERIC Educational Resources Information Center

    Benson, Ronald E.

    1977-01-01

    Defines equality of education in three areas: 1) by the degree of integration of school systems; 2) by a comparison of material resources and assets in education; and 3) by the effects of schooling as measured by the mean scores of groups on standardized tests. Available from: College of Education, 107 Quadrangle, Iowa State University, Ames, Iowa…

  4. 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…

  5. 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…

  6. 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…

  7. Defining structural limit zones

    NASA Technical Reports Server (NTRS)

    Merchant, D. H.

    1978-01-01

    Method for defining limit loads uses probability distribution of largest load occurring during given time intervals. Method is compatible with both deterministic and probabilistic structural design criteria. It also rationally accounts for fact that longer structure is exposed to random loading environment, greater is possibility that it will experience extreme load.

  8. Defining Faculty Work.

    ERIC Educational Resources Information Center

    Gray, Peter J.; Diamond, Robert M.

    1994-01-01

    A process of planned change is proposed for redefining college faculty work. Legitimate faculty work is defined in broad terms, and information sources and methods for collecting information to support redefinition are identified. The final step in the redefinition process is the development of new mission statements for the institution and its…

  9. 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…

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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.

  16. 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.

  17. Defining the paramedic process.

    PubMed

    Carter, Holly; Thompson, James

    2015-01-01

    The use of a 'process of care' is well established in several health professions, most evidently within the field of nursing. Now ingrained within methods of care delivery, it offers a logical approach to problem solving and ensures an appropriate delivery of interventions that are specifically suited to the individual patient. Paramedicine is a rapidly advancing profession despite a wide acknowledgement of limited research provisions. This frequently results in the borrowing of evidence from other disciplines. While this has often been useful, there are many concerns relating to the acceptable limit of evidence transcription between professions. To date, there is no formally recognised 'process of care'-defining activity within the pre-hospital arena. With much current focus on the professional classification of paramedic work, it is considered timely to formally define a formula that underpins other professional roles such as nursing. It is hypothesised that defined processes of care, particularly the nursing process, may have features that would readily translate to pre-hospital practice. The literature analysed was obtained through systematic searches of a range of databases, including Ovid MEDLINE, Cumulative Index to Nursing and Allied Health. The results demonstrated that the defined process of care provides nursing with more than just a structure for practice, but also has implications for education, clinical governance and professional standing. The current nursing process does not directly articulate to the complex and often unstructured role of the paramedic; however, it has many principles that offer value to the paramedic in their practice. Expanding the nursing process model to include the stages of Dispatch Considerations, Scene Assessment, First Impressions, Patient History, Physical Examination, Clinical Decision-Making, Interventions, Re-evaluation, Transport Decisions, Handover and Reflection would provide an appropriate model for pre

  18. Earth boring tool with improved inserts

    SciTech Connect

    Dill, H.; Scales, S.

    1980-07-08

    A description is given of an improved earth boring tool of the type having at least one sintered tungsten carbide insert with a substantially cylindrical retaining surface interferringly secured to the wall of a retaining hole, the improvement comprising said retaining surface roughened such that in any lineal increment of at least 010 inch, there are at least three asperities at least 0.001 in ch long and at least 0.00005 inch deep when measured with a stylus point with a 0.00005 inch radius. An improved method of retaining tungsten carbide inserts in an earth boring tool, said method comprising the steps of: drilling and reaming a plurality of holes in selected locations on the earth boring tool; sintering a plurality of tungsten carbide inserts with a binder selected from the group consisting of cobalt, nickel or iron; grinding a substantially cylindrical wall surface on the inserts that are nominally larger in diameter than the drilled and reamed holes; roughening the wall surface of the inserts such that any lineal increment of at least 0.010 inch has at least three asperities which are at least 0.001 inch long and at least 00005 inch deep when measured with a stylus point with a 0.00005 inch radius; and forcing the inserts interferringly into the mating drilled and reamed holes.

  19. The Basques according to polymorphic Alu insertions.

    PubMed

    de Pancorbo, M M; López-Martínez, M; Martínez-Bouzas, C; Castro, A; Fernández-Fernández, I; de Mayolo, G A; de Mayolo, A A; de Mayolo, P A; Rowold, D J; Herrera, R J

    2001-08-01

    Polymorphic Alu insertions provide a set of DNA markers of interest in human population genetics. Approximately 1000-2000 of these insertions have not reached fixation within the human genome. Each one of these polymorphic loci most probably resulted from a unique insertional event, and therefore all individuals possessing the insertion are related by descent not just state. In addition, the direction of mutational change is toward the gain of the Alu element at a particular locus. Therefore, the improved knowledge of both the ancestral state and the direction of mutational change greatly facilitates the analysis of population relationships. As a result, Alu insertion polymorphisms represent a significant tool for population genetic studies. In this study, polymorphic Alu insertions have been employed to ascertain phylogenetic relationships among Basque groups and worldwide populations. The Basques are considered to be a geographic isolate with a unique language and customs. They may be direct descendants of Cro-Magnon enclaves from the upper Paleolithic (38,000 to 10,000 years). The Basques are distributed among narrow valleys in northeastern Spain with little migration between them until recently. This characteristic may have had an effect on allelic frequency distributions. With the aim of studying this possible effect, we have analyzed six autosomal polymorphic Alu loci from four different sites within the Spanish Basque region in order to ascertain any genetic heterogeneity among the Basques. The results are consistent with a lack of homogeneity among these four autochthonous Basque groups. PMID:11511929

  20. 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. PMID:1681170

  1. 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.

  2. 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 [°].

  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. 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

  5. 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…

  6. 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. PMID:16938094

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

    PubMed Central

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

    2015-01-01

    Background Modern dental implants present surface features of distinct dimensions that can be damaged during the insertion procedure into bone. Purpose 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. Materials and Methods 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. SEM-BSD analysis was used to identify loose particles at the interface. Results The amplitude and hybrid roughness parameters of all three groups were lower after insertion. The surface presenting predominance of peaks (Ssk>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. Conclusions 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. PMID:24283455

  8. Characterization of broadly pleiotropic phenotypes caused by an hfq insertion mutation in Escherichia coli K-12.

    PubMed

    Tsui, H C; Leung, H C; Winkler, M E

    1994-07-01

    The region immediately downstream from the miaA tRNA modification gene at 94.8 min contains the hfq gene and the hflA region, which are important in the bacteriophage Q beta and lambda life cycles. The roles of these genes in bacteria remain largely unknown. We report here the characterization of two chromosomal hfq insertion mutations. An omega (omega) cassette insertion near the end of hfq resulted in phenotypes only slightly different from the parent, although transcript mapping demonstrated that the insertion was completely polar on hflX expression. In contrast, an equally polar omega cassette insertion near the beginning of hfq caused pronounced pleiotropic phenotypes, including decreased growth rates and yields, decreased negative supercoiling of plasmids in stationary phase, increased cell size, osmosensitivity, increased oxidation of carbon sources, increased sensitivity to ultraviolet light, and suppression of bgl activation by hns mutations. hfq::omega mutant phenotypes were distinct from those caused by omega insertions early in the miaA tRNA modification gene. On the other hand, both hfq insertions interfered with lambda phage plaque formation, probably by means of polarity at the hflA region. Together, these results show that hfq function plays a fundamental role in Escherichia coli physiology and that hfq and the hflA-region are in the amiB-mutL-miaA-hfq-hflX superoperon. PMID:7984093

  9. 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.

  10. 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.

  11. The Nucleoid Binding Protein H-NS Biases Genome-Wide Transposon Insertion Landscapes

    PubMed Central

    Kimura, Satoshi; Hubbard, Troy P.; Davis, Brigid M.

    2016-01-01

    ABSTRACT Transposon insertion sequencing (TIS; also known as TnSeq) is a potent approach commonly used to comprehensively define the genetic loci that contribute to bacterial fitness in diverse environments. A key presumption underlying analyses of TIS datasets is that loci with a low frequency of transposon insertions contribute to fitness. However, it is not known whether factors such as nucleoid binding proteins can alter the frequency of transposon insertion and thus whether TIS output may systematically reflect factors that are independent of the role of the loci in fitness. Here, we investigated whether the histone-like nucleoid structuring (H-NS) protein, which preferentially associates with AT-rich sequences, modulates the frequency of Mariner transposon insertion in the Vibrio cholerae genome, using comparative analysis of TIS results from wild-type (wt) and Δhns V. cholerae strains. These analyses were overlaid on gene classification based on GC content as well as on extant genome-wide identification of H-NS binding loci. Our analyses revealed a significant dearth of insertions within AT-rich loci in wt V. cholerae that was not apparent in the Δhns insertion library. Additionally, we observed a striking correlation between genetic loci that are overrepresented in the Δhns insertion library relative to their insertion frequency in wt V. cholerae and loci previously found to physically interact with H-NS. Collectively, our findings reveal that factors other than genetic fitness can systematically modulate the frequency of transposon insertions in TIS studies and add a cautionary note to interpretation of TIS data, particularly for AT-rich sequences. PMID:27578758

  12. 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.

  13. 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.

  14. Membrane Protein Insertion at the Endoplasmic Reticulum

    PubMed Central

    Shao, Sichen; Hegde, Ramanujan S.

    2014-01-01

    Integral membrane proteins of the cell surface and most intracellular compartments of eukaryotic cells are assembled at the endoplasmic reticulum. Two highly conserved and parallel pathways mediate membrane protein targeting to and insertion into this organelle. The classical cotranslational pathway, utilized by most membrane proteins, involves targeting by the signal recognition particle followed by insertion via the Sec61 translocon. A more specialized posttranslational pathway, employed by many tail-anchored membrane proteins, is composed of entirely different factors centered around a cytosolic ATPase termed TRC40 or Get3. Both of these pathways overcome the same biophysical challenges of ferrying hydrophobic cargo through an aqueous milieu, selectively delivering it to one among several intracellular membranes and asymmetrically integrating its transmembrane domain(s) into the lipid bilayer. Here, we review the conceptual and mechanistic themes underlying these core membrane protein insertion pathways, the complexities that challenge our understanding, and future directions to over-come these obstacles. PMID:21801011

  15. 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

  16. Penoscrotal porokeratosis: A distinct entity.

    PubMed

    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

  17. 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

  18. 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

  19. 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. PMID:19261842

  20. 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

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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…

  8. Neutron absorber inserts for 55-gal drums

    SciTech Connect

    Wilson, R.E.; Kim, Y.S.; Toffer, H.

    2000-07-01

    Transport and temporary storage of more than 200 g of fissile material in 55-gal drums at the Rocky Flats Environmental Technology Site (RFETS) have received significant attention during the cleanup mission. This paper discusses successful applications and results of extensive computer studies. Interim storage and movement of fissile material in excess of standard drum limits (200 g) in a safe configuration have been accomplished using special drum inserts. Such inserts have constrained the contents of a drum to two 4-{ell} bottles. The content of the bottles was limited to 600 g Pu or U in solution or a total of 1200 g for the entire drum. The inserts were a simple design constructed of stainless steel, forming a vertical cylindrical pipe into which two bottles, one on top of the other, could be centered in the drum. The remaining drum volume was configured to preclude any additional bottle placement external to the vertical cylinder. Such inserts in drums were successfully used in moving high-concentration solution from one building to another for chemical processing. Concern about the knowledge of fissile material concentration in bottles prompted another study for drum inserts. The past practice had been to load up to fourteen 4-{ell} bottles into 55-gal drums, provided the fissile material concentration was <6 g fissile/{ell}, and the total drum contents of 200 g fissile was not exceeded. Only one determination of the solution concentration was needed. An extensive safety analysis concluded that a single measurement of bottle content could not ensure compliance with double-contingency-criterion requirements. A second determination of the bottle contents was required before bottles could be placed in a 55-gal drum. Al alternative to a dual-measurement protocol, which is for bolstering administrative control, was to develop an engineered safety feature that would eliminate expensive tests and administrative decisions. A drum insert design was evaluated that

  9. Defining an emerging disease.

    PubMed

    Moutou, F; Pastoret, P-P

    2015-04-01

    Defining an emerging disease is not straightforward, as there are several different types of disease emergence. For example, there can be a 'real' emergence of a brand new disease, such as the emergence of bovine spongiform encephalopathy in the 1980s, or a geographic emergence in an area not previously affected, such as the emergence of bluetongue in northern Europe in 2006. In addition, disease can emerge in species formerly not considered affected, e.g. the emergence of bovine tuberculosis in wildlife species since 2000 in France. There can also be an unexpected increase of disease incidence in a known area and a known species, or there may simply be an increase in our knowledge or awareness of a particular disease. What all these emerging diseases have in common is that human activity frequently has a role to play in their emergence. For example, bovine spongiform encephalopathy very probably emerged as a result of changes in the manufacturing of meat-and-bone meal, bluetongue was able to spread to cooler climes as a result of uncontrolled trade in animals, and a relaxation of screening and surveillance for bovine tuberculosis enabled the disease to re-emerge in areas that had been able to drastically reduce the number of cases. Globalisation and population growth will continue to affect the epidemiology of diseases in years to come and ecosystems will continue to evolve. Furthermore, new technologies such as metagenomics and high-throughput sequencing are identifying new microorganisms all the time. Change is the one constant, and diseases will continue to emerge, and we must consider the causes and different types of emergence as we deal with these diseases in the future. PMID:26470448

  10. 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...

  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. 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...

  13. 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...

  14. 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...

  15. 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.

  16. Immediate postabortal insertion of intrauterine devices.

    PubMed

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

    2014-01-01

    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

  17. 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.

  18. 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.

  19. 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.

  20. 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.'

  1. 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.

  2. Magnetic measurements on insertion devices at NSLS

    SciTech Connect

    Decker, G.; Galayda, J.; Solomon, L.; Kitamura, M.

    1989-07-01

    Magnetic measurements on three insertion devices for use in the National Synchrotron Light Source (NSLS) x-ray ring are described. Hall probes were used for field mapping, and rotating long coils were used to determine integrated multipole coefficients. Results are presented for an iron pole-REC hybrid indulator, a vanadium permendur pole-REC hybrid wiggler, and a 5 T superconducting wiggler.

  3. 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…

  4. 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.

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

    PubMed

    Merenciano, Miriam; Ullastres, Anna; de Cara, M A R; Barrón, Maite G; González, Josefa

    2016-08-01

    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

  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. Association between Peripherally Inserted Central Venous Catheter Insertion Site and Complication Rates in Preterm Infants.

    PubMed

    Bashir, Rani A; Swarnam, Kamala; Vayalthrikkovil, Sakeer; Yee, Wendy; Soraisham, Amuchou S

    2016-08-01

    Objective To examine whether there is an association between peripherally inserted central venous catheter (PICC) insertion site and complication rates among preterm infants. Design We performed a retrospective analysis of the first PICCs placed in preterm infants in a tertiary neonatal intensive care unit between January 2006 and December 2010. The PICC-related complications resulting in catheter removal were compared based on site of insertion. Results Of the 827 PICCs, 593 (72%) were inserted in upper extremity. Lower extremity PICC group infants had higher illness severity (SNAP-II) score and more likely to be inserted later as compared with the upper extremity group. There was no significant difference in the total PICC-related complications between upper and lower extremity PICCs (31.3 vs. 26%; p > 0.05). Logistic regression analysis after adjusting for gestational age, day of line insertion, and SNAP-II score revealed that upper extremity PICCs were associated with increased risk of line infiltration (adjusted odds ratio [aOR], 2.41; 95% confidence interval [CI], 1.36-4.29) but not the total PICC complication (aOR, 1.29; 95% CI, 0.91-1.83). Conclusion There is no difference in total PICC-related complication between upper and lower extremity PICCs; however, the PICC-related mechanical complications vary depending on the site of insertion in preterm infants. PMID:27057766

  8. THE EFFECT OF ANTERIOR CRUCIATE HEALING ON THE UNINJURED LIGAMENT INSERTION SITE

    PubMed Central

    Haus, BM; Mastrangelo, AN; Murray, MM

    2011-01-01

    PURPOSE Changes in the insertion site of the ACL after enhanced suture repair with collagen-platelet-composites (CPC) have not yet been defined. In this study, we hypothesized that fibroblasts and osteoclasts would participate in generating histologic changes in insertion site morphology after transection and bioenhanced repair of the ACL, and that these changes would be age-dependent. METHODS Skeletally immature, adolescent, and adult Yucatan mini-pigs underwent ACL transection and bioenhanced suture repair. The histologic response to repair of the insertion site was evaluated at 1, 2, 4 and 15 weeks. RESULTS In young and adolescent animals treated with bioenhanced suture repair with CPC, changes in the insertion site included: (1) fibroblastic proliferation with loss and return of collagen alignment in the fibrous zone; (2) osteoclastic resorption within fibrocartilage zones at 2–4 weeks; and (3) partial reappearance of fibrocartilage zones at 15 weeks. In adult animals; however, degenerative changes were noted by 15 weeks: (1) loss of parallel arrangement of collagen fibers in the fibrous zone; and (2) increasing disorganization and loss of columnation of chondrocytes in the fibrocartilage zone. CONCLUSIONS These results suggest that fibroblasts and osteoclasts mediate histologic changes at the insertion site during bioenhanced suture repair of the ACL which may prevent insertion site degeneration, and that the magnitude of these changes may be a function of skeletal maturity. PMID:21748793

  9. 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.

  10. Distinct Pathways Mediate the Sorting of Tail-Anchored Proteins to the Plastid Outer Envelope

    PubMed Central

    Dhanoa, Preetinder K.; Richardson, Lynn G. L.; Smith, Matthew D.; Gidda, Satinder K.; Henderson, Matthew P. A.; Andrews, David W.; Mullen, Robert T.

    2010-01-01

    Background Tail-anchored (TA) proteins are a distinct class of membrane proteins that are sorted post-translationally to various organelles and function in a number of important cellular processes, including redox reactions, vesicular trafficking and protein translocation. While the molecular targeting signals and pathways responsible for sorting TA proteins to their correct intracellular destinations in yeasts and mammals have begun to be characterized, relatively little is known about TA protein biogenesis in plant cells, especially for those sorted to the plastid outer envelope. Methodology/Principal Findings Here we investigated the biogenesis of three plastid TA proteins, including the 33-kDa and 34-kDa GTPases of the translocon at the outer envelope of chloroplasts (Toc33 and Toc34) and a novel 9-kDa protein of unknown function that we define here as an outer envelope TA protein (OEP9). Using a combination of in vivo and in vitro assays we show that OEP9 utilizes a different sorting pathway than that used by Toc33 and Toc34. For instance, while all three TA proteins interact with the cytosolic OEP chaperone/receptor, AKR2A, the plastid targeting information within OEP9 is distinct from that within Toc33 and Toc34. Toc33 and Toc34 also appear to differ from OEP9 in that their insertion is dependent on themselves and the unique lipid composition of the plastid outer envelope. By contrast, the insertion of OEP9 into the plastid outer envelope occurs in a proteinaceous-dependent, but Toc33/34-independent manner and membrane lipids appear to serve primarily to facilitate normal thermodynamic integration of this TA protein. Conclusions/Significance Collectively, the results provide evidence in support of at least two sorting pathways for plastid TA outer envelope proteins and shed light on not only the complex diversity of pathways involved in the targeting and insertion of proteins into plastids, but also the molecular mechanisms that underlie the delivery of TA

  11. Screw-Thread Inserts As Temporary Flow Restrictors

    NASA Technical Reports Server (NTRS)

    Trimarchi, Paul

    1992-01-01

    Coil-spring screw-thread inserts found useful as temporary flow restrictors. Inserts placed in holes through which flow restricted, effectively reducing cross sections available for flow. Friction alone holds inserts against moderate upstream pressures. Use of coil-spring thread inserts as flow restrictors conceived as inexpensive solution to problem of adjusting flow of oxygen through orifices in faceplate into hydrogen/oxygen combustion chamber. Installation and removal of threaded inserts gentle enough not to deform orifice tubes.

  12. 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

  13. 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

  14. Recent stable insertion of mitochondrial DNA into an Arabidopsis polyubiquitin gene by nonhomologous recombination.

    PubMed

    Sun, C W; Callis, J

    1993-01-01

    Sequence analysis of a newly identified polyubiquitin gene (UBQ13) from the Columbia ecotype of Arabidopsis thaliana revealed that the gene contained a 3.9-kb insertion in the coding region. All subclones of the 3.9-kb insert hybridized to isolated mitochondrial DNA. The insert was found to consist of at least two, possibly three, distinct DNA segments from the mitochondrial genome. A 590-bp region of the insert is nearly identical to the Arabidopsis mitochondrial nad1 gene. UBQ13 restriction fragments in total cellular DNA from ecotypes Ler, No-0, Be-0, WS, and RLD were identified and, with the exception of Be-0, their sizes were equivalent to that predicted from the corresponding ecotype Columbia UBQ13 restriction fragment without the mitochondrial insert. Isolation by polymerase chain reaction and sequence determination of UBQ13 sequences from the other ecotypes showed that all lacked the mitochondrial insert. All ecotypes examined, except Columbia, contain intact open reading frames in the region of the insert, including four ubiquitin codons which Columbia lacks. This indicates that the mitochondrial DNA in UBQ13 in ecotype Columbia is the result of an integration event that occurred after speciation of Arabidopsis rather than a deletion event that occurred in all ecotypes except Columbia. This stable movement of mitochondrial DNA to the nucleus is so recent that there are few nucleotide changes subsequent to the transfer event. This allows for precise analysis of the sequences involved and elucidation of the possible mechanism. The presence of intron sequences in the transferred nucleic acid indicates that DNA was the transfer intermediate. The lack of sequence identity between the integrating sequence and the target site, represented by the other Arabidopsis ecotypes, suggests that integration occurred via nonhomologus recombination. This nuclear/organellar gene transfer event is strikingly similar to the experimentally accessible process of nuclear

  15. Plasmids captured in C. metallidurans CH34: defining the PromA family of broad-host-range plasmids.

    PubMed

    Van der Auwera, Géraldine A; Król, Jaroslaw E; Suzuki, Haruo; Foster, Brian; Van Houdt, Rob; Brown, Celeste J; Mergeay, Max; Top, Eva M

    2009-08-01

    The self-transmissible, broad-host-range (BHR) plasmid pMOL98 was previously isolated from polluted soil using a triparental plasmid capture approach and shown to possess a replicon similar to that of the BHR plasmids pSB102 and pIPO2. Here, complete sequence analysis and comparative genomics reveal that the 55.5 kb nucleotide sequence of pMOL98 shows extensive sequence similarity and synteny with the BHR plasmid family that now includes pIPO2, pSB102, pTER331, and pMRAD02. They share a plasmid backbone comprising replication, partitioning and conjugative transfer functions. Comparison of the variable accessory regions of these plasmids shows that the majority of natural transposons, as well as the mini-transposon used to mark the plasmids, are inserted in the parA locus. The transposon unique to pMOL98 appears to have inserted from the chromosome of the recipient strain used in the plasmid capture procedure. This demonstrates the necessity for careful screening of plasmids and host chromosomes to avoid mis-interpretation of plasmid genome content. The presence of very similar BHR plasmids with different accessory genes in geographically distinct locations suggests an important role in horizontal gene exchange and bacterial adaptation for this recently defined plasmid group, which we propose to name "PromA". PMID:19259779

  16. Human Diallelic Insertion/Deletion Polymorphisms

    PubMed Central

    Weber, James L.; David, Donna; Heil, Jeremy; Fan, Ying; Zhao, Chengfeng; Marth, Gabor

    2002-01-01

    We report the identification and characterization of 2,000 human diallelic insertion/deletion polymorphisms (indels) distributed throughout the human genome. Candidate indels were identified by comparison of overlapping genomic or cDNA sequences. Average confirmation rate for indels with a ⩾2-nt allele-length difference was 58%, but the confirmation rate for indels with a 1-nt length difference was only 14%. The vast majority of the human diallelic indels were monomorphic in chimpanzees and gorillas. The ratio of deletion:insertion mutations was 4.1. Allele frequencies for the indels were measured in Europeans, Africans, Japanese, and Native Americans. New alleles were generally lower in frequency than old alleles. This tendency was most pronounced for the Africans, who are likely to be closest among the four groups to the original modern human population. Diallelic indels comprise ∼8% of all human polymorphisms. Their abundance and ease of analysis make them useful for many applications. PMID:12205564

  17. 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.

  18. 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}

  19. 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

  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. 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.

  2. Magnetic measurements on insertion devices at NSLS

    SciTech Connect

    Decker, G.; Galayda, J.; Kitamura, M.; Solomon, L.

    1988-01-01

    Magnetic measurements on three insertion devices for use in the NSLS x-ray ring are described. Hall probes were used for field mapping, and rotating long coils were used to determine integrated multipole coefficients. Results are presented for an iron pole-REC hybrid undulator, a vanadium permendur pole-REC wiggler and a 5 Tesla superconducting wiggler. 6 refs., 8 figs., 2 tabs.

  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. 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.

  4. Anomalous insertion of the medial menisci.

    PubMed

    Jung, Y B; Yum, J K; Bae, Y J; Song, K S

    1998-01-01

    Many types of meniscal anomalies have been reported. The authors encountered two cases of anomalous insertion of the anterior horn of the medial menisci to the lateral femoral condyle, which ran up along the course of the anterior cruciate ligament (ACL), but was independent of the ACL. These anomalies were noted during arthroscopic examination and surgery of the ipsilateral knee for a torn discoid meniscus and a patellar fracture. A 34-year-old woman had a horizontal tear of the lateral discoid meniscus. We performed arthroscopic partial meniscectomy of the inner torn portion of the lateral discoid meniscus and contoured it to resemble a normal meniscus. An anomalous insertion of the medial meniscus was found on examination of the joint during surgery. A 32-year-old man had a patellar fracture and we performed reduction under arthroscopy and internal fixation with cannulated screws. The same anomalous insertion of the medial meniscus was also found on examination of the joint during surgery. We report the cases with a review of the literature. PMID:9681544

  5. 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.

  6. 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.

  7. Mesh insertion as an aid for pleurodesis.

    PubMed

    Sugarmann, W M; Widmann, W D; Mysh, D; Sattari, R

    1996-12-01

    With the application of video-assisted thoracic surgery (VATS) for the treatment of pneumothorax, there has been an increase in the failure rate of treatment because of inadequate pleurodesis. We sought to determine whether mesh insertion into the pleural cavity with or without pleural abrasion results in predictable pleurodesis appropriate for clinical trial as an adjunct to VATS treatment of pneumothorax. There have been no prior studies on the use of absorbable or nonabsorbable mesh in the thoracic cavity. The effects of intra-thoracic absorbable polyglactin (Vicryl) and non-absorbable polypropylene (Marlex) mesh were studied in rats. Polyglactin without abrasion caused filmy adhesions in 5/5, 1/7, and 0/5 rats studied at 1, 2, and 3 months. Polypropylene incites an extensive and dense pleural reaction not suitable for clinical use becaues it induces a fibrothorax. Pleural abrasion alone caused variable adhesions studied at 3-4 months (4/6 none, 1/6 filmy, 1/6 firm). Polyglactin plus pleural abrasion resulted in appropriate firm adhesions in 7/8 rats studied at 3-4 months with 1/8 showing filmy adhesions. Polyglactin alone results in transient filmy adhesions. Pleural abrasion alone results in inadequate pleural symphysis. However, when absorbable mesh insertion is coupled with pleural abrasion, appropriate pleurodesis is predictably achieved. Clinical application of polyglactin mesh insertion with pleural abrasion as an adjunct in the VATS treatment of pneumothorax has begun and has been successful. PMID:10064371

  8. 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.

  9. Roles for retrotransposon insertions in human disease.

    PubMed

    Hancks, Dustin C; Kazazian, Haig H

    2016-01-01

    Over evolutionary time, the dynamic nature of a genome is driven, in part, by the activity of transposable elements (TE) such as retrotransposons. On a shorter time scale it has been established that new TE insertions can result in single-gene disease in an individual. In humans, the non-LTR retrotransposon Long INterspersed Element-1 (LINE-1 or L1) is the only active autonomous TE. In addition to mobilizing its own RNA to new genomic locations via a "copy-and-paste" mechanism, LINE-1 is able to retrotranspose other RNAs including Alu, SVA, and occasionally cellular RNAs. To date in humans, 124 LINE-1-mediated insertions which result in genetic diseases have been reported. Disease causing LINE-1 insertions have provided a wealth of insight and the foundation for valuable tools to study these genomic parasites. In this review, we provide an overview of LINE-1 biology followed by highlights from new reports of LINE-1-mediated genetic disease in humans. PMID:27158268

  10. Probabilistic phylogenetic inference with insertions and deletions.

    PubMed

    Rivas, Elena; Eddy, Sean R

    2008-01-01

    A fundamental task in sequence analysis is to calculate the probability of a multiple alignment given a phylogenetic tree relating the sequences and an evolutionary model describing how sequences change over time. However, the most widely used phylogenetic models only account for residue substitution events. We describe a probabilistic model of a multiple sequence alignment that accounts for insertion and deletion events in addition to substitutions, given a phylogenetic tree, using a rate matrix augmented by the gap character. Starting from a continuous Markov process, we construct a non-reversible generative (birth-death) evolutionary model for insertions and deletions. The model assumes that insertion and deletion events occur one residue at a time. We apply this model to phylogenetic tree inference by extending the program dnaml in phylip. Using standard benchmarking methods on simulated data and a new "concordance test" benchmark on real ribosomal RNA alignments, we show that the extended program dnamlepsilon improves accuracy relative to the usual approach of ignoring gaps, while retaining the computational efficiency of the Felsenstein peeling algorithm. PMID:18787703

  11. Sleep Related Scratching: A Distinct Parasomnia?

    PubMed Central

    Nigam, Gaurav; Riaz, Muhammad; Hershner, Shelley D.; Goldstein, Cathy A.; Chervin, Ronald D.

    2016-01-01

    Pruritus (itching) during the sleep period can present as a symptom of dermatological or systemic disease, or as a parasomnia. Sleep related scratching as a primary parasomnia, exclusively confined to sleep in the absence of coexisting dermatological disorders, has not been well described. This case series describes three such patients, and discusses potentially relevant pathophysiology that can underlie itching or pain. Such cases of sleep related scratching may merit nosologic classification apart from previously defined parasomnias. Citation: Nigam G, Riaz M, Hershner SD, Goldstein CA, Chervin RD. Sleep related scratching: a distinct parasomnia? J Clin Sleep Med 2016;12(1):139–142. PMID:26285112

  12. 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,…

  13. Master device for teleoperated needle insertion-type interventional robotic system.

    PubMed

    Woo, Hyun Soo; Cho, Jang Ho; Kim, Chul Seung; Lee, Hyuk Jin

    2015-08-01

    This paper proposes a new master device for teleoperated needle insertion-type interventional robotic system. The 5-DOF master device is optimally designed based on the newly defined interventional procedures and the physicians' requirements. It comprises a 2-DOF rotational mechanism for adjustment of needle orientation, a 2-DOF translational mechanism for fine-tuning of needle entry point, and a handle assembly. The handle assembly includes a 1-DOF translational mechanism for needle insertion and buttons for operation mode selection. The passive actuation modules of the rotational mechanism and the active actuation modules of the translational mechanism are controlled appropriately for the selected mode according to the procedure phase. The needle insertion mechanism also warns the user by vibrating the shaft when the needle reaches the dangerous region. PMID:26737379

  14. Transposition of a plasmid deoxyribonucleic acid sequence that mediates ampicillin resistance: independence from host rec functions and orientation of insertion.

    PubMed Central

    Rubens, C; Heffron, F; Falkow, S

    1976-01-01

    Insertion of the transposable deoxyribonucleic acid sequence that specifies the TEM beta-lactamase (TnA) occurred in at least 19 sites on the 5.5 x 10(6)-dalton plasmid RSF1010. There was no significant difference in the frequency of transposition or in the distribution of TnA insertion sites for recombinant plasmids isolated from recombination-proficient (rec+) or recombination-deficient (rec-) bacterial host cells. The site and orientation of TnA insertions were determined by both heteroduplex analysis and enzymatic digestion with restriction endonucleases. Insertion in the gene encoding for sulfonamide resistance occurred without circular permutation in one or the other of two distinct orientations. Insertions in orientation P were strongly polar on distal gene expression, whereas insertions in orientation M were mutagenic but not polar. In addition, we have observed that TnA elements from different R plasmids show fine structural heterogeneity, and that TnA insertion at a site adjacent to the origin of replication causes an increase in plasmid copy number. Images PMID:789346

  15. 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. PMID:19163400

  16. Software-implemented fault insertion: An FTMP example

    NASA Technical Reports Server (NTRS)

    Czeck, Edward W.; Siewiorek, Daniel P.; Segall, Zary Z.

    1987-01-01

    This report presents a model for fault insertion through software; describes its implementation on a fault-tolerant computer, FTMP; presents a summary of fault detection, identification, and reconfiguration data collected with software-implemented fault insertion; and compares the results to hardware fault insertion data. Experimental results show detection time to be a function of time of insertion and system workload. For the fault detection time, there is no correlation between software-inserted faults and hardware-inserted faults; this is because hardware-inserted faults must manifest as errors before detection, whereas software-inserted faults immediately exercise the error detection mechanisms. In summary, the software-implemented fault insertion is able to be used as an evaluation technique for the fault-handling capabilities of a system in fault detection, identification and recovery. Although the software-inserted faults do not map directly to hardware-inserted faults, experiments show software-implemented fault insertion is capable of emulating hardware fault insertion, with greater ease and automation.

  17. Autodirected insertion: preinserted VDAC channels greatly shorten the delay to the insertion of new channels.

    PubMed Central

    Xu, X; Colombini, M

    1997-01-01

    VDAC, a mitochondrial outer membrane channel, has the ability to catalyze and direct the insertion of other VDAC channels into planar phospholipid membranes. The spontaneous rate of insertion of detergent-solubilized VDAC channels into phospholipid membranes is estimated to be 1.5 x 10(-5) channels min-1 micron-2. VDAC channels already in the membrane can increase this rate by a factor of 10(9). The presence of 5 M urea on the opposite side of the membrane increases this 10-fold to 4.5 x 10(5) channels min-1 microns-2. Similar but weaker effects are observed with Triton X100 addition (10(-3)% (v/v)). These agents are not acting on uninserted channels because they do not affect the delay from sample addition to first insertion. Under the chosen conditions, this delay is long (240 s) without preinserted channels. However, the presence of a few VDAC channels in the membrane reduces this delay to 14 s, close to the diffusion limit. Therefore, urea and Triton, added to the side of the membrane opposite that to which the VDAC sample was added, likely increase the flexibility of the VDAC channels in the membrane, allowing them to be more efficient catalysts for VDAC insertion. There are obvious implications for membrane protein insertion and targeting. PMID:9129814

  18. 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

  19. Chronic insertional Achilles tendinopathy: surgical outcomes

    PubMed Central

    Oshri, Yael; Palmanovich, Ezequiel; Brin, Yaron Shagra; Karpf, Ronen; Massarwe, Sabri; Kish, Benny; Nyska, Meir

    2012-01-01

    Summary Background and objective: insertional Achilles tendinopathy is a common condition among athletes and joggers. One fifth of the injuries involves the insertion of the tendon. The etiology is either due to mechanical overuse related to sports activity, or a systemic inflammatory disease. The clinical appearance includes pain and movement restriction. The primary treatment is conservative. The surgery referred to in this study (Calcaneal Osteotomy) is performed by decompression of the posterior margin of the calcaneus. If the tendon is degenerative, debridement is needed. There is controversy on the surgical outcome and the surgical approach. A retrospective analytic observational study. Methods: 20 patients who were diagnosed with IAT (21 feet) and were operated on between the years 2000–2007 by calcaneal osteotomy. Main outcome measures: the primary measure of success was diminished pain. It was demonstrated in the AOFAS score and in the VAS scale of pain. Results: the average grade in the AOFAS questionnaire improved by 20 points, and the average grading of pain in the VAS scale was decreased by 4.21. The median satisfaction rate was 8, the average was 5.81. 62% of the patients would repeat the surgery/recommend it. We found a significant relationship (p=0.022) between patients who avoided sports activity while suffering from insertional Achilles tendinopathy and the satisfaction rate from the surgery. Conclusions: using the calcaneal osteotomy technique as a surgical treatment for IAT is successful, and improves measures of pain and function. Low compliance with avoiding sports activity while suffering from an IAT might lead to a need for surgery. PMID:23738280

  20. 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. PMID:12743107

  1. Cladribine and Fludarabine Nucleotides Induce Distinct Hexamers Defining a Common Mode of Reversible RNR Inhibition.

    PubMed

    Wisitpitthaya, Somsinee; Zhao, Yi; Long, Marcus J C; Li, Minxing; Fletcher, Elaine A; Blessing, William A; Weiss, Robert S; Aye, Yimon

    2016-07-15

    The enzyme ribonucleotide reductase (RNR) is a major target of anticancer drugs. Until recently, suicide inactivation in which synthetic substrate analogs (nucleoside diphosphates) irreversibly inactivate the RNR-α2β2 heterodimeric complex was the only clinically proven inhibition pathway. For instance, this mechanism is deployed by the multifactorial anticancer agent gemcitabine diphosphate. Recently reversible targeting of RNR-α-alone coupled with ligand-induced RNR-α-persistent hexamerization has emerged to be of clinical significance. To date, clofarabine nucleotides are the only known example of this mechanism. Herein, chemoenzymatic syntheses of the active forms of two other drugs, phosphorylated cladribine (ClA) and fludarabine (FlU), allow us to establish that reversible inhibition is common to numerous drugs in clinical use. Enzyme inhibition and fluorescence anisotropy assays show that the di- and triphosphates of the two nucleosides function as reversible (i.e., nonmechanism-based) inhibitors of RNR and interact with the catalytic (C site) and the allosteric activity (A site) sites of RNR-α, respectively. Gel filtration, protease digestion, and FRET assays demonstrate that inhibition is coupled with formation of conformationally diverse hexamers. Studies in 293T cells capable of selectively inducing either wild-type or oligomerization-defective mutant RNR-α overexpression delineate the central role of RNR-α oligomerization in drug activity, and highlight a potential resistance mechanism to these drugs. These data set the stage for new interventions targeting RNR oligomeric regulation. PMID:27159113

  2. Defined DNA sequences promote the assembly of a bacterial protein into distinct amyloid nanostructures

    PubMed Central

    Giraldo, Rafael

    2007-01-01

    RepA, the replication initiator protein of Pseudomonas pPS10 plasmid, is made of two winged-helix (WH) domains. RepA dimers undergo a structural transformation upon binding to origin DNA sequences (iterons), resulting in monomerization and α-helix into β-strand conversion. This affects the N-terminal domain (WH1) and generates a metastable intermediate. Here it is shown that the interaction of short dsDNA oligonucleotides, including iteron or operator RepA targets, with the isolated WH1 domain promotes the assembly of different nanostructures. These range from irregular aggregates to amyloid spheroids and fibers. Their intrinsic order inversely correlates with the extent of the transformation induced by each DNA sequence on RepA. However, DNA is not a constituent of the assembled fibers, in agreement with the protein-only principle for amyloid structure. Thus, the RepA-WH1 domain on DNA binding mimics the behavior of the mammalian prion protein. The stretch of amino acids responsible for WH1 aggregation has been identified, leading to the design of mutants with enhanced or reduced amyloidogenicity and the synthesis of a peptide that assembles into a cross-β structure. RepA amyloid assemblies could have a role in the negative regulation of plasmid replication. This article underlines the potential of specific nucleic acid sequences in promoting protein amyloidogenesis at nearly physiological conditions. PMID:17959784

  3. 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 undergraduate…

  4. Competition of two distinct actin networks for actin defines a bistable switch for cell polarization

    PubMed Central

    Lomakin, Alexis J.; Lee, Kun-Chun; Han, Sangyoon J.; Bui, D A.; Davidson, Michael; Mogilner, Alex; Danuser, Gaudenz

    2015-01-01

    Symmetry-breaking polarization enables functional plasticity of cells and tissues and is yet not well understood. Here we show that epithelial cells, hard-wired to maintain a static morphology and to preserve tissue organization, can spontaneously switch to a migratory polarized phenotype upon relaxation of the actomyosin cytoskeleton. We find that myosin-II engages actin in the formation of cortical actomyosin bundles and thus makes it unavailable for deployment in the process of dendritic growth normally driving cell motility. At low contractility regimes epithelial cells polarize in a front-back manner due to emergence of actin retrograde flows powered by dendritic polymerization of actin. Coupled to cell movement, the flows transport myosin-II from the front to the back of the cell, where the motor locally “locks” actin in contractile bundles. This polarization mechanism could be employed by embryonic and cancer epithelial cells in microenvironments where high contractility-driven cell motion is inefficient. PMID:26414403

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

    PubMed Central

    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

    2014-01-01

    The C-type lectin CD161 is expressed by a large proportion of human T lymphocytes of all lineages, including a novel 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, that can be extended to CD161+ CD4+ and CD161+TCRγδ+ T cells. Further, 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 TCR expression and cell lineage. PMID:25437561

  6. Microsatellite instability and ploidy status define three categories with distinctive prognostic impact in endometrioid endometrial cancer

    PubMed Central

    Bilbao-Sieyro, Cristina; Ramírez-Moreno, Raquel; Rodríguez-González, Germán; Falcón, Orlando; León, Laureano; Torres, Santiago; Fernández, Leandro; Alonso, Sergio; Díaz-Chico, Nicolás; Perucho, Manuel; Díaz-Chico, Juan Carlos

    2014-01-01

    Microsatellite instability (MSI) and aneuploidy are inversely related phenomena. We tested whether ploidy status influences the clinical impact of MSI in endometrioid endometrial cancer (EEC). We analyzed 167 EECs for MSI and ploidy. Tumors were classified in three categories according to MSI and ploidy status. Associations with clinicopathological and molecular variables, survival, and treatment response were assessed. All MSI tumors (23%) were scored as diploid, and 14% of microsatellite stable (MSS) tumors presented aneuploidy. MSI tumors associated with older age at diagnosis, non-obesity, high histological grade, and advanced surgical stage. MSS-aneuploid tumors also associated with higher grade and advanced stage. In multivariate survival analysis MSI did not influence disease-free survival (DFS) or cancer-specific survival (CSS). However, when just diploid tumors were considered for the analysis, MSI significantly contributed to worse DFS and CSS, and the same was observed for aneuploidy when MSS tumors were analyzed alone. In diploid tumors, a differential response to postoperative radiotherapy (RT) was observed according to MSI, since it predicted poor DFS and CSS in the multivariate analysis. We conclude that ploidy status influences the clinical impact of MSI in EEC. Among diploid tumors those with MSI have poor clinical outcome and respond worse to RT. PMID:25026289

  7. Assessment with Distinctly Defined Criteria: A Research Study of a National Project

    ERIC Educational Resources Information Center

    Hopfenbeck, Therese N.; Throndsen, Inger; Lie, Svein; Dale, Erling Lars

    2012-01-01

    This article explores changes in teachers' beliefs and practice concerning assessment after participating in a project for improving assessment practices in Norwegian schools. The project was initiated by the Norwegian Directorate for Education and Training in 2008, and included a total of 77 schools, more than 600 teachers and a sample of their…

  8. 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. PMID:15731444

  9. 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.

  10. 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.

  11. 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.

  12. Transcatheter aortic valve insertion (TAVI): a review

    PubMed Central

    Morgan-Hughes, G; Roobottom, C

    2014-01-01

    The introduction of transcatheter aortic valve insertion (TAVI) has transformed the care provided for patients with severe aortic stenosis. The uptake of this procedure is increasing rapidly, and clinicians from all disciplines are likely to increasingly encounter patients being assessed for or having undergone this intervention. Successful TAVI heavily relies on careful and comprehensive imaging assessment, before, during and after the procedure, using a range of modalities. This review outlines the background and development of TAVI, describes the nature of the procedure and considers the contribution of imaging techniques, both to successful intervention and to potential complications. PMID:24258463

  13. 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.

  14. 21 CFR 310.515 - Patient package inserts for estrogens.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 5 2010-04-01 2010-04-01 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...

  15. 21 CFR 310.515 - Patient package inserts for estrogens.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 5 2013-04-01 2013-04-01 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...

  16. 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...

  17. 21 CFR 310.515 - Patient package inserts for estrogens.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 5 2012-04-01 2012-04-01 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...

  18. 21 CFR 310.515 - Patient package inserts for estrogens.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 5 2014-04-01 2014-04-01 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...

  19. 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.

  20. 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

  1. Construction of small-insert and large-insert metagenomic libraries.

    PubMed

    Simon, Carola; Daniel, Rolf

    2010-01-01

    The vast majority of the Earth's biological diversity is hidden in uncultured and yet uncharacterized microbial genomes. The construction of metagenomic libraries is a cultivation-independent molecular approach to assess this unexplored genetic reservoir. In the last few years, a high number of novel biocatalysts have been identified by function-based or sequence-based screening of metagenomic libraries. Here, we describe detailed protocols for the construction of metagenomic small-insert and large-insert libraries in plasmids and fosmids, respectively, from environmental DNA. PMID:20830554

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Two new insertion devices for Aladdin

    NASA Astrophysics Data System (ADS)

    Younger, F. C.; Pearce, W. Jorge; Ng, B.

    1994-08-01

    The Brobeck Division of Maxwell Laboratories, Inc., is designing and building two new insertion devices to be installed in the Aladdin ring at the Synchrotron Radiation Center (SRC), University of Wisconsin-Madison. One insertion device is an electromagnetic undulator being built for Iowa State University. It will have a peak magnetic field of 0.12 T and produce photons in the energy range from 15 to 30 eV. The tuning range is provided by varying the field excitation current. This device has a fixed gap and 14 periods. Magnetic field mapping shows that high field quality is being achieved. The second device for SRC is a pure current-sheet-equivalent material (CSEM) undulator designed to provide intense photons in the energy range from 7.5 to 230 eV. This undulator, which uses NdBFe magnets, will be installed in a 4-m straight section of the Aladdin ring, and will have 48 full periods with a peak magnetic field of 0.7 T. It will become the source for an intense, high resolution, and variable polarization beamline project. Stringent requirements on field quality have been established to achieve the desired radiation performance and to minimize the disturbance to the storage ring.

  8. Ceramic inserts do not generally improve resin composite margins.

    PubMed

    Strobel, W O; Petschelt, A; Kemmoona, M; Frankenberger, R

    2005-08-01

    summary Ceramic inserts are reported to possibly reduce polymerization shrinkage for posterior resin composite fillings. The aim of the present investigation was to evaluate the effect of different insert systems before and after thermomechanical loading. Sixty sound human third molars received occlusomesial Class II cavities, 40 with proximal margins 2 mm above and 20 with proximal margins 1 mm below the cementum-enamel junction. The specimens were randomly assigned to one of the six experimental groups (n = 10). The enamel-bordered cavities were restored with Syntac classic and Tetric Ceram (ST), Syntac classic, Tetric Ceram and beta-quartz inserts (TB), Syntac classic, Tetric Ceram and Cerana inserts (TC), Syntac classic, Tetric flow and SonicSys approx inserts (TS). The dentin-limited cavities were filled with Syntac classic and Tetic Ceram (DT), Syntac classic, Tetric flow and SonicSys approx inserts (DS). Before and after thermomechanical loading (100 000 x 50 N, 2500 x 5 degrees C/55 degrees C), replicas were made and both interfaces tooth/composite and insert/composite were examined under a scanning electron microscope at 200x. The Cerana and SonicSys insert groups showed significantly less gaps in enamel (P < 0.05). With beta-quartz inserts, no reduction of gaps was found (P > 0.05). Marginal integrity in dentine-bordered specimens could not be improved with SonicSys inserts (P > 0.05). The bonding performance insert/composite was promising for all IPS Empress inserts (Cerana, SonicSys enamel) but worse for beta-quartz inserts. Regarding gap formation between resin composite and tooth, Cerana and SonicSys inserts significantly reduced gaps. The use of SonicSys inserts in deep proximal cavities cannot be recommended. PMID:16011640

  9. 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 F.…

  10. Crack-Defined Electronic Nanogaps.

    PubMed

    Dubois, Valentin; Niklaus, Frank; Stemme, Göran

    2016-03-01

    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. PMID:26784270