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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. 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

  3. 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

  4. 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

  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. 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

  17. 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

  18. 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

  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. 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.

  5. 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

  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. 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.

  12. 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.

  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 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

  3. 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

  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 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…

  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 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…

  7. 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…

  8. 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.

  9. 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

  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. 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

  11. 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.

  12. 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.

  13. 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

  14. 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.

  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. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  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. 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.

  16. 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.'

  17. 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.

  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. 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…

  20. 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.

  1. 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.

  2. Mars Observer Lecture: Mars Orbit Insertion

    NASA Technical Reports Server (NTRS)

    Dodd, Suzanne R. (Personal Name)

    1993-01-01

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

  3. 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

  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. Consolidation and disposal of PWR fuel inserts

    SciTech Connect

    Wakeman, B.H. )

    1992-08-01

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

  9. 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

  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. 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

  10. 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

  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. 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

  1. 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

  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. 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

  6. 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

  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. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  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, 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...

  15. 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...

  16. 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...

  17. 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...

  18. 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...

  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

  11. Insertion of coherence requests for debugging a multiprocessor

    DOEpatents

    Blumrich, Matthias A.; Salapura, Valentina

    2010-02-23

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

  12. A strategy for developing a launch vehicle system for orbit insertion: Methodological aspects

    NASA Astrophysics Data System (ADS)

    Klyushnikov, V. Yu.; Kuznetsov, I. I.; Osadchenko, A. S.

    2014-12-01

    The article addresses methodological aspects of a development strategy to design a launch vehicle system for orbit insertion. The development and implementation of the strategy are broadly outlined. An analysis is provided of the criterial base and input data needed to define the main requirements for the launch vehicle system. Approaches are suggested for solving individual problems in working out the launch vehicle system development strategy.

  13. Speciation without Pre-Defined Fitness Functions

    PubMed Central

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

    2015-01-01

    The forces promoting and constraining speciation are often studied in theoretical models because the process is hard to observe, replicate, and manipulate in real organisms. Most models analyzed to date include pre-defined functions influencing fitness, leaving open the question of how speciation might proceed without these built-in determinants. To consider the process of speciation without pre-defined functions, we employ the individual-based ecosystem simulation platform EcoSim. The environment is initially uniform across space, and an evolving behavioural model then determines how prey consume resources and how predators consume prey. Simulations including natural selection (i.e., an evolving behavioural model that influences survival and reproduction) frequently led to strong and distinct phenotypic/genotypic clusters between which hybridization was low. This speciation was the result of divergence between spatially-localized clusters in the behavioural model, an emergent property of evolving ecological interactions. By contrast, simulations without natural selection (i.e., behavioural model turned off) but with spatial isolation (i.e., limited dispersal) produced weaker and overlapping clusters. Simulations without natural selection or spatial isolation (i.e., behaviour model turned off and high dispersal) did not generate clusters. These results confirm the role of natural selection in speciation by showing its importance even in the absence of pre-defined fitness functions. PMID:26372462

  14. Helix insertion into bilayers and the evolution of membrane proteins

    PubMed Central

    2010-01-01

    Polytopic α-helical membrane proteins cannot spontaneously insert into lipid bilayers without assistance from polytopic α-helical membrane proteins that already reside in the membrane. This raises the question of how these proteins evolved. Our current knowledge of the insertion of α-helices into natural and model membranes is reviewed with the goal of gaining insight into the evolution of membrane proteins. Topics include: translocon-dependent membrane protein insertion, antibiotic peptides and proteins, in vitro insertion of membrane proteins, chaperone-mediated insertion of transmembrane helices, and C-terminal tail-anchored (TA) proteins. Analysis of the E. coli genome reveals several predicted C-terminal TA proteins that may be descendents of proteins involved in pre-cellular membrane protein insertion. Mechanisms of pre-translocon polytopic α-helical membrane protein insertion are discussed. PMID:20039094

  15. A piezoelectric vibration-based syringe for reducing insertion force

    NASA Astrophysics Data System (ADS)

    Huang, Y. C.; Tsai, M. C.; Lin, C. H.

    2012-12-01

    Puncturing of the human skin with a needle is perhaps the most common invasive medical procedure. Clinical studies have revealed that tissue deformation and needle deflection are the primary problem for needle misplacement in percutaneous procedures. To avoid this, various techniques for reducing insertion forces during needle insertion have been considered. This paper presents a piezoelectric vibration-based syringe to reduce insertion force. AC power was applied to the piezoelectric elements to vibrate the needle with high frequency and thereby reduce the friction and cutting forces between the needle and tissue. Vibration mode shapes of the needle were observed by finite element analysis and verified by experimental results. Effects of reducing insertion force via the vibrating needle were also confirmed by inserting the needle into the porcine tissues. The proposed syringe, which minimizes the insertion force and overcomes limitations of needle materials, can be widely utilized in robot-assisted needle insertion systems.

  16. Macroscopic and microscopic observations of needle insertion into gels.

    PubMed

    van Veen, Youri R J; Jahya, Alex; Misra, Sarthak

    2012-06-01

    Needle insertion into soft tissue is one of the most common medical interventions. This study provides macroscopic and microscopic observations of needle-gel interactions. A gelatin mixture is used as a soft-tissue simulant. For the macroscopic studies, system parameters, such as insertion velocity, needle diameter, gel elasticity, needle tip shape (including bevel angle) and insertion motion profile, are varied, while the maximum insertion force and maximum needle deflection are recorded. The needle tip and gel interactions are observed using confocal microscopic images. Observations indicate that increasing the insertion velocity and needle diameter results in larger insertion forces and smaller needle deflections. Varying the needle bevel angle from 8 degrees to 82 degrees results in the insertion force increasing monotonically, while the needle deflection does not. These variations are due to the coupling between gel rupture and tip compression interactions, which are observed during microscopic studies. Increasing the gel elasticity results in larger insertion forces and needle deflections. Varying the tip shapes demonstrates that bevel-tipped needles produce the largest deflection, but insertion force does not vary among the tested tip shapes. Insertion with different motion profiles are performed. Results show that adding I Hz rotational motion during linear insertion decreases the needle deflection. Increasing the rotational motion from I Hz to 5 Hz decreases the insertion force, while the needle deflection remains the same. A high-velocity (250 mm/s and 300 mm/s) tapping during insertion yields no significant decrease in needle deflection and a slight increase in insertion force. PMID:22783760

  17. A Vocabulary of Motives: Understanding How Parents Define Quality Time

    ERIC Educational Resources Information Center

    Snyder, Karrie Ann

    2007-01-01

    Although discussions of parenting refer to quality time, parents' views of quality time have not been explored. Using the Sloan 500 Family Study, this article examines how 220 parents from 110 dual-parent families define the spending quality time with their families and finds 3 distinct views: Structured-planning parents saw it as planned family…

  18. Spectral characteristics and power distribution from insertion devices on a 6 to 7 GeV storage ring

    SciTech Connect

    Shenoy, G.K.; Viccaro, P.J.

    1986-06-01

    Two different types of insertion devices - undulators and wigglers - are described and compared. Each provides a periodic magnetic field that alters polarity, but whereas the spectral distribution from a wiggler is continuous and wide, the radiation of an undulator has spectrally narrow and discrete peaks. The distinction is determined by the deflection parameter. The energy spread in undulator peaks is calculated. Insertion device magnets and gap are discussed. Undulator tunability from gap variation is considered on a 6-GeV lattice and on a 7-GeV lattice. Also discussed is the angular distribution of power and the polarization from various sources. (LEW)

  19. INSERTION DEVICE UPGRADE PLANS AT THE NSLS.

    SciTech Connect

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

    2005-05-16

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

  20. Impact of Orthodontic Decompensation on Bone Insertion

    PubMed Central

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

    2014-01-01

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

  1. Stabilization of insertion electrodes for lithium batteries.

    SciTech Connect

    Thackeray, M. M.

    1998-09-03

    This paper discusses the techniques that are being employed to stabilize LiMn{sub 2}O{sub 4} spinel and composite Li{sub x}MnO{sub 2} positive electrodes. The critical role that spinel domains play in stabilizing these electrodes for operation at both 4 V and 3 V is highlighted. The concept of using an intermetallic electrode MM{prime} where M is an active alloying element and M{prime} is an inactive element (or elements) is proposed as an alternative negative electrode (to carbon) for lithium-ion cells. An analogy to metal oxide insertion electrodes, such as MnO{sub 2}, in which Mn is the electrochemically active ion and O is the inactive ion, is made. Performance data are given for the copper-tin electrode system, which includes the intermetallic phases eta-Cu{sub 6}Sn{sub 5} and Li{sub 2}CuSn.

  2. Sodium insertion/extraction from single-walled and multi-walled carbon nanotubes: The differences and similarities

    NASA Astrophysics Data System (ADS)

    Goonetilleke, Damian; Pramudita, James C.; Choucair, Mohammad; Rawal, Aditya; Sharma, Neeraj

    2016-05-01

    A comparative study on the sodium-ion insertion and extraction of commercially-available multi-wall and single-wall carbon nanotubes is reported. Single-wall carbon nanotubes exhibit charge/discharge capacities of 126 mA h g-1 and multi-wall carbon nanotubes produce a lower capacity of 28 mA h g-1 after 50 cycles at 25 mA g-1. To understand these differences, a combination of X-ray diffraction and solid state nuclear magnetic resonance measurements were performed at various states of sodium insertion and extraction.23Na nuclear magnetic resonance studies, a technique previously rarely used for characterising electrodes from sodium-ion batteries, shows differences in the sodium chemical environment near multi-wall compared to single-wall carbon nanotubes with distinct sodium sites found to be active during sodium insertion and extraction for the carbon nanotubes. Both types of carbon nanotubes show a similar amount of reversible sodium available for insertion/extraction reactions, but multi-wall carbon nanotubes feature half the initial insertion capacity relative to single-wall carbon nanotubes. The electrochemical performance of the carbon nanotube electrodes are discussed in relation to the observed mechanism of sodium insertion.

  3. Neurobehavioral perspectives on the distinction between fear and anxiety.

    PubMed

    Perusini, Jennifer N; Fanselow, Michael S

    2015-09-01

    In this review, we discuss the usefulness of the distinction between fear and anxiety. The clinical use of the labels is ambiguous, often defining one in terms of the other. We first consider what a useful, objective, and scientifically valid definition would entail and then evaluate several fear/anxiety distinctions that have been made in the neurobiological literature. A strong distinction should specify the difference in conditions that lead to fear versus anxiety. Additionally, fear and anxiety should generate distinct sets of behaviors. Ideally, the two states should be supported by distinguishable neuroanatomical circuits. Such a conceptualization would be consistent with the National Institute of Mental Health's Research Domain Criteria (RDoc). The majority of neurobiological approaches to the fear versus anxiety distinction fail to differentiate the two states in terms of behavior, often using the exact same behavioral measures as indicators. Of the two that do, only Predatory Imminence Theory provides a distinction both in terms of cause and effect. Indeed, that approach provides a ready distinction of anxiety, fear, and panic in terms of both antecedent conditions and response selection rules. Additionally, it appeals to distinct neural circuits to generate these modes of action. PMID:26286652

  4. Nramp defines a family of membrane proteins.

    PubMed Central

    Cellier, M; Privé, G; Belouchi, A; Kwan, T; Rodrigues, V; Chia, W; Gros, P

    1995-01-01

    Nramp (natural resistance-associated macrophage protein) is a newly identified family of integral membrane proteins whose biochemical function is unknown. We report on the identification of Nramp homologs from the fly Drosophila melanogaster, the plant Oryza sativa, and the yeast Saccharomyces cerevisiae. Optimal alignment of protein sequences required insertion of very few gaps and revealed remarkable sequence identity of 28% (yeast), 40% (plant), and 55% (fly) with the mammalian proteins (46%, 58%, and 73% similarity), as well as a common predicted transmembrane topology. This family is defined by a highly conserved hydrophobic core encoding 10 transmembrane segments. Other features of this hydrophobic core include several invariant charged residues, helical periodicity of sequence conservation suggesting conserved and nonconserved faces for several transmembrane helices, a consensus transport signature on the intracytoplasmic face of the membrane, and structural determinants previously described in ion channels. These characteristics suggest that the Nramp polypeptides form part of a group of transporters or channels that act on as yet unidentified substrates. Images Fig. 1 PMID:7479731

  5. Regulatory perspective on incomplete control rod insertions

    SciTech Connect

    Chatterton, M.

    1997-01-01

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

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

    PubMed Central

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

    2015-01-01

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

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

    PubMed

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

    2010-01-01

    The depth of electrode insertion of a multichannel cochlear implant has been suggested as a clinical variable that may correlate with word recognition using the implant. The current study evaluates this relationship using the human temporal bone collection at the Massachusetts Eye and Ear Infirmary. Twenty-seven temporal bones of subjects with cochlear implants were studied. Temporal bones were removed at autopsy, fixed and prepared for histological study by standard techniques. Specimens were then serially sectioned, and reconstructed by two-dimensional methods. Three measures of length were made from each subject's reconstruction: (1) depth of insertion (DI) of the cochlear implant electrode array, from the round window to the array's apical tip; (2) inserted length (IL) from the cochleostomy to the apical tip of the array, and (3) cochlear duct length (CDL) from the round window to the helicotrema. The active electrode length (AEL) was defined as the distance between the most apical and most basal electrodes of the array. Stepwise regression was used to identify whether subsets of six metrics associated with insertion depth (DI, DI/AEL, DI/CDL, IL, IL/AEL and IL/CDL), duration of deafness, sound-processing strategy, potential for central impairment and age at implantation accounted for significant across-subject variance in the last recorded NU-6 word score measured during each subject's life. Age at implantation and potential for central impairment account for significant percentages of the across-subject variance in NU-6 word scores for the 27 subjects studied. None of the insertion metrics accounted for significant performance variance, even when the variance associated with the other variables was controlled. These results, together with those of previous studies, are consistent with a relatively weak association between electrode insertion depth and speech reception. PMID:20203481

  8. Prediction of heating patterns of a microwave interstitial antenna array at various insertion depths.

    PubMed

    Zhang, Y; Joines, W T; Oleson, J R

    1991-01-01

    Measurements made on the interstitial microwave antennas used for hyperthermia cancer therapy indicate that the heating patterns vary with the insertion depths (defined as the distance from the antenna tip to air-tissue interface). The antennas are made of thin coaxial cables with a radiation gap or gaps on the outer conductor. The antennas are inserted into small polypropylene catheters implanted in the tumour volume. This type of antenna may be simulated as an asymmetric dipole with one arm being the tip section consisting of the expanded extension of the inner conductor, and the other arm being the section of the outer conductor from the gap to the insertion point (air-tissue interface). We use four of the antennas to form a 2 cm x 2 cm array. The antennas are positioned on the corners of a 2 cm square. Measurements on both single antennas and multi-antenna arrays show that the maximum heating is not stationary with position along the antenna when the depth of insertion is changed. This paper investigates the theoretical prediction of the changes in heating patterns of interstitial microwave antennas at different insertion depths. Each of the antennas in the array is simulated as an asymmetric dipole. The SAR (specific absorption rate) is computed by using the insulated dipole theory. The temperature distribution in absence of perfusion is obtained through a thermal simulation routine to convert the SAR pattern into the temperature pattern. Excellent qualitative agreement is found between the theoretical heating pattern and the measured pattern in a non-perfused phantom on a 2 cm x 2 antenna array. Since the insertion depths of the interstitial antennas are different from patient to patient, it is recommended that simulation of the heating be done before treatments, to confirm the delivery of power to the target region. PMID:2051073

  9. The Problem of Defining Intelligence.

    ERIC Educational Resources Information Center

    Lubar, David

    1981-01-01

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

  10. Unsupervised Definition of Chemically Distinct Provinces at Mars

    NASA Astrophysics Data System (ADS)

    Gasnault, O.

    2006-03-01

    A multivariate analysis of the Martian maps of H, Si, Fe, Cl, Th, and K shows that seven large provinces chemically distinct can be defined. The dimensionality of the problem can be reduced to 5, or even to 3, through a principal component analysis.

  11. Distinctive Characteristics of Educational Donors

    ERIC Educational Resources Information Center

    James, Russell N., III.

    2008-01-01

    Examining the charitable behavior of 56,663 US households, this paper evaluates the distinctive characteristics of educational donors as compared with donors to noneducational charitable organizations and with nondonors. In general, educational donors had significantly greater income, wealth, and education than other donors. Educational donors…

  12. China English: Its Distinctive Features

    ERIC Educational Resources Information Center

    Yang, Wei-dong; Dai, Wei-ping

    2011-01-01

    This paper attempts to expound that China English boasting its own distinctive features on the levels of phonology, words, sentences and discourse has been playing an irreplaceable role in intercultural activities, though still in its infancy and in the process of developing and perfecting itself, and it now makes every effort to move towards…

  13. Distinctiveness Maps for Image Matching

    NASA Technical Reports Server (NTRS)

    Manduchi, Roberto; Tomasi, Carlo

    2000-01-01

    Stereo correspondence is hard because different image features can look alike. We propose a measure for the ambiguity of image points that allows matching distinctive points first and breaks down the matching task into smaller and separate subproblems. Experiments with an algorithm based on this measure demonstrate the ensuing efficiency and low likelihood of incorrect matches.

  14. Educational Psychology: The Distinctive Contribution

    ERIC Educational Resources Information Center

    Cameron, R. J.

    2006-01-01

    This paper, written in the twenty-first anniversary year of the journal "Educational Psychology in Practice", attempts to uncover those distinctive aspects of the discipline and the practice of applied psychology in general and educational psychology in particular. After considering some of the reasons for attempting this task at this point in…

  15. Integrated transducer for color distinction

    NASA Astrophysics Data System (ADS)

    Kato, Hisao; Kojima, Masahiko; Yoshida, Akira

    1983-06-01

    A method for fabricating the improved version of an integrated transducer for color distinction is proposed. It consists of three SnO2(n)-Si(n) photodiodes on a Si wafer and a trichromatic filter prepared by arranging filters of the three primary colors (Eastman Kodak gelatin filters; Nos. 47B, 58, and 25) on an infrared glass filter (Hoya Glass; B-460). Its photoelectric characteristics and dependence of error of color distinction on the dimension of the transducer are reported. The photodiodes employed in this conversion assembly are produced by the simple spray method and are most suitable for detecting the low illumination. Since this transducer adapts the trichromatic color resolution method, highly accurate color distinction is possible. With this type of transducer, three photodiodes sensitive to the primary colors, red, green, and blue, respectively, are arranged on a plane. An error in color distinction can occur due to the differences in the strength of the light incident upon the respective photodiodes. This problem is reduced by making the transducer more compact. Finally, 11 kinds of colors are discerned in this experiment as an application of the transducer.

  16. Distinctive Qualities of Expert Teachers

    ERIC Educational Resources Information Center

    Tsui, Amy B. M.

    2009-01-01

    This paper attempts to identify the distinctive qualities of successful veteran teachers, referred to as "expert teachers", which separates them not only from novice teachers but more importantly from experienced non-expert teachers. Based on earlier case studies, this paper maintains that the critical differences between expert and non-expert…

  17. Peripherally inserted central catheter: compliance with evidence-based indications for insertion in an inpatient setting.

    PubMed

    Wojnar, Danuta G; Beaman, Margaret L

    2013-01-01

    A randomized, retrospective chart review was conducted at a medium-sized community hospital to verify appropriateness of peripherally inserted central catheter (PICC) use in 49 inpatient patients. Study results support the Infusion Nurses Society recommendation to use PICCs to facilitate either short- or long-term intravenous therapy of vesicants, irritants, and any medications with a pH less than 5 or greater than 9 and osmolarity greater than 600 mOsm/L. All PICC insertion criteria recommended by the Centers for Disease Control and Prevention were met except one--the intended duration of intravenous therapy of more than 6 days. Identical PICC selection criteria are needed to standardize clinical practice. PMID:23823005

  18. Neonatal peripherally inserted central catheters: recommendations for prevention of insertion and postinsertion complications.

    PubMed

    Paulson, Pamela R; Miller, Kellee M

    2008-01-01

    Peripherally inserted central catheters (PICCs) continue to be necessary in neonatal care. They benefit many premature infants and those needing long-term intravenous access. An experienced inserter, early recognition of PICC candidates, early PICC placement, knowledge of anatomy, and correct choice of vein all increase placement success. As with any invasive procedure, there are risks. These include pain, difficulty advancing the catheter, damage to vessels, catheter malposition, and bleeding. Utilizing assessment skills, following the product manufacturer's instructions, and carefully placing the catheter should minimize most of these risks. Additional risks include postinsertion complications such as occlusions, thrombosis, catheter failure, infection, and catheter malposition. Proper nursing care--which includes controlling infection, properly securing the catheter, and changing the dressing as needed--is key to preventing complications and maintaining the PICC until treatment has been completed. PMID:18697655

  19. A Distinct Structure inside the Galactic Bar

    NASA Astrophysics Data System (ADS)

    Nishiyama, Shogo; Nagata, Tetsuya; Baba, Daisuke; Haba, Yasuaki; Kadowaki, Ryota; Kato, Daisuke; Kurita, Mikio; Nagashima, Chie; Nagayama, Takahiro; Murai, Yuka; Nakajima, Yasushi; Tamura, Motohide; Nakaya, Hidehiko; Sugitani, Koji; Naoi, Takahiro; Matsunaga, Noriyuki; Tanabé, Toshihiko; Kusakabe, Nobuhiko; Sato, Shuji

    2005-03-01

    We present the result of a near-infrared (JHKs) survey along the Galactic plane, -10.5d<=l<=10.5d and b=+1deg, with the IRSF 1.4 m telescope and the SIRIUS camera. Ks versus H-Ks color-magnitude diagrams reveal a well-defined population of red clump stars whose apparent magnitude peak changes continuously along the Galactic plane, from Ks=13.4 at l=-10deg to Ks=12.2 at l=10deg after dereddening. This variation can be explained by the barlike structure found in previous studies, but we find an additional inner structure at |l|<~4deg, where the longitude-apparent magnitude relation is distinct from the outer bar and where the apparent magnitude peak changes by only ~0.1 mag over the central 8°. The exact nature of this inner structure is as yet uncertain.

  20. Mapping Between Distinct Reed-Solomon Codes

    NASA Technical Reports Server (NTRS)

    Perlman, Marvin

    1994-01-01

    One-to-one mapping between two Reed-Solomon (RS) codes devised to enable decoder designed for one of codes to operate on other one also. Codes in question must have same N and K parameters (defined below) but otherwise be two distinct RS codes. Mapping intended to enable same ground-based decoder to decode telemetry signals from two spacecraft in two different RS codes of (N,K) = (255,223). Also useful in purely terrestrial data communications and in optical and magnetic recording and playback of digitized audio and video signals. Implemented in interface circuitry and/or software to enable communication between coding systems of different manufacturers using different RS codes within same (N,K) family.

  1. Core Vessel Insert Handling Robot for the Spallation Neutron Source

    SciTech Connect

    Graves, Van B; Dayton, Michael J

    2011-01-01

    The Spallation Neutron Source provides the world's most intense pulsed neutron beams for scientific research and industrial development. Its eighteen neutron beam lines will eventually support up to twenty-four simultaneous experiments. Each beam line consists of various optical components which guide the neutrons to a particular instrument. The optical components nearest the neutron moderators are the core vessel inserts. Located approximately 9 m below the high bay floor, these inserts are bolted to the core vessel chamber and are part of the vacuum boundary. They are in a highly radioactive environment and must periodically be replaced. During initial SNS construction, four of the beam lines received Core Vessel Insert plugs rather than functional inserts. Remote replacement of the first Core Vessel Insert plug was recently completed using several pieces of custom-designed tooling, including a highly complicated Core Vessel Insert Robot. The design of this tool are discussed.

  2. The BDGP gene disruption project: Single transposon insertions associated with 40 percent of Drosophila genes

    SciTech Connect

    Bellen, Hugo J.; Levis, Robert W.; Liao, Guochun; He, Yuchun; Carlson, Joseph W.; Tsang, Garson; Evans-Holm, Martha; Hiesinger, P. Robin; Schulze, Karen L.; Rubin, Gerald M.; Hoskins, Roger A.; Spradling, Allan C.

    2004-01-13

    The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila gene by the insertion of a single transposable element. As part of this effort, transposons in more than 30,000 fly strains were localized and analyzed relative to predicted Drosophila gene structures. Approximately 6,300 lines that maximize genomic coverage were selected to be sent to the Bloomington Stock Center for public distribution, bringing the size of the BDGP gene disruption collection to 7,140 lines. It now includes individual lines predicted to disrupt 5,362 of the 13,666 currently annotated Drosophila genes (39 percent). Other lines contain an insertion at least 2 kb from others in the collection and likely mutate additional incompletely annotated or uncharacterized genes and chromosomal regulatory elements. The remaining strains contain insertions likely to disrupt alternative gene promoters or to allow gene mis-expression. The expanded BDGP gene disruption collection provides a public resource that will facilitate the application of Drosophila genetics to diverse biological problems. Finally, the project reveals new insight into how transposons interact with a eukaryotic genome and helps define optimal strategies for using insertional mutagenesis as a genomic tool.

  3. The BDGP gene disruption project: single transposon insertions associated with 40% of Drosophila genes.

    PubMed Central

    Bellen, Hugo J; Levis, Robert W; Liao, Guochun; He, Yuchun; Carlson, Joseph W; Tsang, Garson; Evans-Holm, Martha; Hiesinger, P Robin; Schulze, Karen L; Rubin, Gerald M; Hoskins, Roger A; Spradling, Allan C

    2004-01-01

    The Berkeley Drosophila Genome Project (BDGP) strives to disrupt each Drosophila gene by the insertion of a single transposable element. As part of this effort, transposons in >30,000 fly strains were localized and analyzed relative to predicted Drosophila gene structures. Approximately 6300 lines that maximize genomic coverage were selected to be sent to the Bloomington Stock Center for public distribution, bringing the size of the BDGP gene disruption collection to 7140 lines. It now includes individual lines predicted to disrupt 5362 of the 13,666 currently annotated Drosophila genes (39%). Other lines contain an insertion at least 2 kb from others in the collection and likely mutate additional incompletely annotated or uncharacterized genes and chromosomal regulatory elements. The remaining strains contain insertions likely to disrupt alternative gene promoters or to allow gene misexpression. The expanded BDGP gene disruption collection provides a public resource that will facilitate the application of Drosophila genetics to diverse biological problems. Finally, the project reveals new insight into how transposons interact with a eukaryotic genome and helps define optimal strategies for using insertional mutagenesis as a genomic tool. PMID:15238527

  4. Defining attitude for science educators

    NASA Astrophysics Data System (ADS)

    Shrigley, Robert L.; Koballa, Thomas R., Jr.; Simpson, Ronald D.

    A distinct and complex definition of attitude is evolving within the literature. A mental readiness to respond and a correlational consistency between attitude and behavior - although controversial and in need of further study and analysis - remain viable subcomponents within the definition. Most agree that evaluation is the heartbeat of attitude. The impact of social influence on attitudes is becoming increasingly important. Attitudes are learned and not inherited.

  5. Stereoselective 1,3-Insertions of Rhodium(II) Azavinyl Carbenes

    PubMed Central

    Chuprakov, Stepan; Worrell, Brady T.; Selander, Nicklas; Sit, Rakesh K.; Fokin, Valery V.

    2014-01-01

    Rhodium(II) azavinyl carbenes, conveniently generated from 1-sulfonyl-1,2,3-triazoles, undergo a facile, mild and convergent formal 1,3-insertion into N–H and O–H bonds of primary and secondary amides, various alcohols, and carboxylic acids to afford a wide range of vicinally bis-functionalized Z-olefins with perfect regio- and stereoselectively. Utilizing the distinctive functionality installed through these reactions, a number of subsequent rearrangements and cyclizations expand the repertoire of valuable organic building blocks constructed by reactions of transition metal carbene complexes, including α-allenyl ketones and amino-substituted heterocycles. PMID:24295389

  6. Membership of Defined Responses in Stimulus Classes

    PubMed Central

    Lionello-DeNolf, Karen M.; Braga-Kenyon, Paula

    2012-01-01

    Sidman (2000) has suggested that in addition to conditional and discriminative stimuli, class-consistent defined responses can also become part of an equivalence class. In the current study, this assertion was tested using a mixed-schedule procedure that allowed defined response patterns to be “presented” as samples in the absence of different occasioning stimuli. Four typically developing adults were first trained to make distinct response topographies to two visual color stimuli, and then were taught to match those color stimuli to two different form-sample stimuli in a matching task. Three separate tests were given in order to determine whether training had established two classes each comprised of a response, a color, and a form: a form-response test in which the forms were presented to test if the participants would make differential responses to them; and two response-matching tests to test if the participants would match visual stimulus comparisons to response-pattern samples. Three of the four participants showed class-consistent responding in the tests, although some participants needed additional training prior to passing the tests. In general, the data indicated that the different response patterns had entered into a class with the visual stimuli. These results add to a growing literature on the role of class-consistent responding in stimulus class formation, and provide support for the notion that differential responses themselves can become a part of an equivalence class. PMID:24778458

  7. Defining the genetic blueprint of kidney development.

    PubMed

    Potter, S Steven; Brunskill, Eric W; Patterson, Larry T

    2011-09-01

    Thousands of genes show differential expression patterns during kidney development, suggesting that the genetic program driving this process is complex. While great progress has been made in defining the outline of the genetic basis of nephrogenesis, it is clear that much remains to be learned. A global atlas of the gene expression profiles of the multiple elements of the developing kidney would allow the identification of novel growth factor-receptor interactions, identify additional molecular markers of distinct components, facilitate the generation of compartment specific GFP-CRE transgenic mouse tools, lend insights into the genetic regulatory circuits governing nephron formation, and fully characterize the waves of gene expression that impel nephrogenesis. Both microarrays and next generation deep sequencing of cDNA libraries can be used to define comprehensive, sensitive, and quantitative gene expression profiles. In addition, laser capture microdissection and transgenic GFP mice can be used to isolate specific compartments and pure cell types from the developing kidney. Advancing technologies are even allowing robust gene expression profiling of single cells. The final goal is the production of an exquisitely detailed atlas of the gene expression program that drives kidney development. PMID:21336810

  8. Threaded insert for compact cryogenic-capable pressure vessels

    SciTech Connect

    Espinosa-Loza, Francisco; Ross, Timothy O.; Switzer, Vernon A.; Aceves, Salvador M.; Killingsworth, Nicholas J.; Ledesma-Orozco, Elias

    2015-06-16

    An insert for a cryogenic capable pressure vessel for storage of hydrogen or other cryogenic gases at high pressure. The insert provides the interface between a tank and internal and external components of the tank system. The insert can be used with tanks with any or all combinations of cryogenic, high pressure, and highly diffusive fluids. The insert can be threaded into the neck of a tank with an inner liner. The threads withstand the majority of the stress when the fluid inside the tank that is under pressure.

  9. Insertion Structures for Transparent Metal Electrodes Prepared by Nanoimprint Lithography

    NASA Astrophysics Data System (ADS)

    Chen, Chia-Meng; Hsieh, Chih-Wei; Ho, Cheng-Fang; Sung, Cheng-Kuo

    2012-04-01

    This paper proposed an efficient process for manufacturing stable insertion structures inside poly(methyl methacrylate) (PMMA) substrates through only three steps, i.e., nanoimprint, metal deposition, and burnishing. The insertion structures with potential applications in transparent metal electrodes possess the advantages of being able to avoid the embedded nanostructure from damage due to contamination or stresses during packaging or transportation. In this paper, the Cu mesh of the insertion structure was successfully replicated into the PMMA substrate. The inserted Cu mesh electrode acquires an average optical transmittance of 84.6% in the visible regime and sheet resistance of 26.78 Ω/square.

  10. Optimal needle design for minimal insertion force and bevel length.

    PubMed

    Wang, Yancheng; Chen, Roland K; Tai, Bruce L; McLaughlin, Patrick W; Shih, Albert J

    2014-09-01

    This research presents a methodology for optimal design of the needle geometry to minimize the insertion force and bevel length based on mathematical models of cutting edge inclination and rake angles and the insertion force. In brachytherapy, the needle with lower insertion force typically is easier for guidance and has less deflection. In this study, the needle with lancet point (denoted as lancet needle) is applied to demonstrate the model-based optimization for needle design. Mathematical models to calculate the bevel length and inclination and rake angles for lancet needle are presented. A needle insertion force model is developed to predict the insertion force for lancet needle. The genetic algorithm is utilized to optimize the needle geometry for two cases. One is to minimize the needle insertion force. Using the geometry of a commercial lancet needle as the baseline, the optimized needle has 11% lower insertion force with the same bevel length. The other case is to minimize the bevel length under the same needle insertion force. The optimized design can reduce the bevel length by 46%. Both optimized needle designs were validated experimentally in ex vivo porcine liver needle insertion tests and demonstrated the methodology of the model-based optimal needle design. PMID:24957487

  11. Technical note: Computer-manufactured inserts for prosthetic sockets.

    PubMed

    Sanders, Joan E; McLean, Jake B; Cagle, John C; Gardner, David W; Allyn, Katheryn J

    2016-08-01

    The objective of this research was to use computer-aided design software and a tabletop 3-D additive manufacturing system to design and fabricate custom plastic inserts for trans-tibial prosthesis users. Shape quality of inserts was tested right after they were inserted into participant's test sockets and again after four weeks of wear. Inserts remained properly positioned and intact throughout testing. Right after insertion the inserts caused the socket to be slightly under-sized, by a mean of 0.11mm, approximately 55% of the thickness of a nylon sheath. After four weeks of wear the under-sizing was less, averaging 0.03mm, approximately 15% of the thickness of a nylon sheath. Thus the inserts settled into the sockets over time. If existing prosthetic design software packages were enhanced to conduct insert design and to automatically generate fabrication files for manufacturing, then computer manufactured inserts may offer advantages over traditional methods in terms of speed of fabrication, ease of design, modification, and record keeping. PMID:27212209

  12. Functional mapping of Cre recombinase by pentapeptide insertional mutagenesis.

    PubMed

    Petyuk, Vladislav; McDermott, Jeffrey; Cook, Malcolm; Sauer, Brian

    2004-08-27

    Cre is a site-specific recombinase from bacteriophage P1. It is a member of the tyrosine integrase family and catalyzes reciprocal recombination between specific 34-bp sites called loxP. To analyze the structure-function relationships of this enzyme, we performed large scale pentapeptide insertional mutagenesis to generate insertions of five amino acids at random positions in the protein. The high density of insertion mutations into Cre allowed us to identify an unexpected degree of functional tolerance to insertions into the 4-5 beta-hairpin and into the loop between helices J and K (both of which contact the DNA in the minor groove) and also into helix A. The phenotypes of the majority of inserts allowed us to confirm a variety of predictions made on the basis of sequence conservation, known three-dimensional structure, and proposed catalytic mechanism. In particular, most insertions into conserved regions or secondary structure elements inactivated Cre, and most insertions located in nonconserved, unstructured regions preserved Cre activity. Less expectedly, the non-conserved and poorly structured loops and linkers between helices A-B, E-F, and M-N did not tolerate insertions, thus identifying these as critical regions for recombinase activity. We purified and characterized in vitro several representatives of these "unexpected" Cre insertion mutants. The role of those regions in the recombination process is discussed. PMID:15218019

  13. Alu insertion loci and platyrrhine primate phylogeny.

    PubMed

    Ray, David A; Xing, Jinchuan; Hedges, Dale J; Hall, Michael A; Laborde, Meredith E; Anders, Bridget A; White, Brittany R; Stoilova, Nadica; Fowlkes, Justin D; Landry, Kate E; Chemnick, Leona G; Ryder, Oliver A; Batzer, Mark A

    2005-04-01

    Short INterspersed Elements (SINEs) make very useful phylogenetic markers because the integration of a particular element at a location in the genome is irreversible and of known polarity. These attributes make analysis of SINEs as phylogenetic characters an essentially homoplasy-free affair. Alu elements are primate-specific SINEs that make up a large portion of the human genome and are also widespread in other primates. Using a combination wet-bench and computational approach we recovered 190 Alu insertions, 183 of which are specific to the genomes of nine New World primates. We used these loci to investigate branching order and have produced a cladogram that supports a sister relationship between Atelidae (spider, woolly, and howler monkeys) and Cebidae (marmosets, tamarins, and owl monkeys) and then the joining of this two family clade to Pitheciidae (titi and saki monkeys). The data support these relationships with a homoplasy index of 0.00. In this study, we report one of the largest applications of SINE elements to phylogenetic analysis to date, and the results provide a robust molecular phylogeny for platyrrhine primates. PMID:15737586

  14. Phoenix Conductivity Probe Inserted into Martian Soil

    NASA Technical Reports Server (NTRS)

    2008-01-01

    NASA's Phoenix Mars Lander inserted the four needles of its thermal and conductivity probe into Martian soil during the 98th Martian day, or sol, of the mission and left it in place until Sol 99 (Sept. 4, 2008).

    The Robotic Arm Camera on Phoenix took this image on the morning of Sol 99 while the probe's needles were in the ground. The science team informally named this soil target 'Gandalf.'

    The thermal and conductivity probe measures how fast heat and electricity move from one needle to an adjacent one through the soil or air between the needles. Conductivity readings can be indicators about water vapor, water ice and liquid water.

    The probe is part of Phoenix's Microscopy, Electrochemistry and Conductivity suite of instruments.

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

  15. Insertion assembly for a pipe completion plug

    SciTech Connect

    Jiles, S.L.

    1991-08-13

    This patent describes an insertion assembly for installing a completion plug in a branching saddle having an internally-threaded pipe stub and a peripheral beveled seating surface in the pipe stub. It comprises a tube; a shaft extending through the tube; a spring-loaded socket extending partially into one end of the tube, resiliently biased against further movement into the tube and mounted on one end of the shaft so as to turn with it; a completion plug having an elastomeric disk with a beveled peripheral edge and a circular metal plate attached to the disk; a camming groove at the end of the tube and a camming pin extending from the hub to releasably retain the plate at the end of the tube, the groove having a radially-extending portion terminating in a pair of axially-extending recesses for receiving the pin and an axially-extending inlet slot between the recesses, whereby the completion plug may be lowered into place in the branching saddle by means of the tube and engaged so that its beveled edge seats against the beveled seating surface of the pipe stub by screwing the plate into the threaded pipe stub as the shaft is turned within the tube while the pin is seated in one of the recesses and may be left in place in the pipe stub by releasing the camming pin from the camming groove through the inlet slot.

  16. IYA2009 newspaper insert in your community

    NASA Astrophysics Data System (ADS)

    Harvey, J.

    2008-06-01

    The Gemini PIO (Public Information Officer) offers suggestions on how to approach your local newspaper about a newspaper insert for your community being published during IYA2009. Local government support, articles by astronomers, advertisers, and appointing someone within your organisation to manage the content will be discussed. We will explain the timeline required, the number of personnel hours required, developmental stages and income a local newspaper would have to generate to produce a quality, table-top supplement. In 2003, over 30,000 copies of Stars over Mauna Kea, a special supplement in tabloid format were produced and distributed in the local newspapers in Hilo, Hawaii. The publication, 48 pages in total, featured profiles of the observatories on Mauna Kea, stories about the geology and legends of Mauna Kea, and historical information about the evolution of astronomy in Hawaii. In additionthe publication included a series of essays titled In their own words. These articles were written by key members of the astronomy community. Sixty thousand copies of Stars over Mauna Kea II were printed as a follow-up to the first edition in 2005. This second edition included an article on the `Imiloa Astronomy Education Center, explanations about the types of telescopes on Mauna Kea and columns written by scientists about the fascinating and significant discoveries made on Hawaii. Personal stories about careers in astronomy were also highlighted. In Chile, a similar eight-page supplement, featuring Gemini, CTIO and SOAR telescopes, was published in 2005 and 5000 copies were distributed throughout the country.

  17. Optimal point of insertion of the needle in neuraxial blockade using a midline approach: study in a geometrical model

    PubMed Central

    Vogt, Mark; van Gerwen, Dennis J; van den Dobbelsteen, John J; Hagenaars, Martin

    2016-01-01

    Performance of neuraxial blockade using a midline approach can be technically difficult. It is therefore important to optimize factors that are under the influence of the clinician performing the procedure. One of these factors might be the chosen point of insertion of the needle. Surprisingly few data exist on where between the tips of two adjacent spinous processes the needle should be introduced. A geometrical model was adopted to gain more insight into this issue. Spinous processes were represented by parallelograms. The length, the steepness relative to the skin, and the distance between the parallelograms were varied. The influence of the chosen point of insertion of the needle on the range of angles at which the epidural and subarachnoid space could be reached was studied. The optimal point of insertion was defined as the point where this range is the widest. The geometrical model clearly demonstrated, that the range of angles at which the epidural or subarachnoid space can be reached, is dependent on the point of insertion between the tips of the adjacent spinous processes. The steeper the spinous processes run, the more cranial the point of insertion should be. Assuming that the model is representative for patients, the performance of neuraxial blockade using a midline approach might be improved by choosing the optimal point of insertion. PMID:27570462

  18. Modeling of friction force based on relative velocity between liver tissue and needle for needle insertion simulation.

    PubMed

    Kobayashi, Yo; Sato, Takahiro; Fujie, Masakatsu G

    2009-01-01

    Needle insertion treatments require accurate placement of the needle tip into the target cancer. However, it is difficult to insert the needle into the cancer because of cancer displacement due to the organ deformation. Then, a path planning using needle insertion simulation to analyze the deformation of the organ is important for the accurate needle insertion. A frictional model for needle insertion simulation is presented in this report. In particular, we focus on a model of frictional force based on the relative velocity between the needle and liver tissue ranging from hyper slow velocity. First, in vitro experiments using hog liver were performed at several relative velocities in order to measure the velocity dependence of the frictional force. Several needle insertion experiments were performed under identical conditions in order to deal with the variance of experimental data. The 60 frictional force data were used to obtain average data at each relative velocity. Second, the model of frictional force was developed using the averages of the experimental results. This model is defined according to the relative velocity ranging from hyper slow velocity. Finally, an evaluation experiment was carried out. The data obtained by the evaluation experiment reveals that the frictional force changes according to the relative velocity between the needle and liver tissue. The experimental results support the validity of proposed model of frictional force. PMID:19964671

  19. Defining "Folklore" in the Classroom.

    ERIC Educational Resources Information Center

    Falke, Anne

    Folklore, a body of traditional beliefs of a people conveyed orally or by means of custom, is very much alive, involves all people, and is not the study of popular culture. In studying folklore, the principal tasks of the folklorist have been defined as determining definition, classification, source (the folk), origin (who composed folklore),…

  20. Defined by Word and Space

    ERIC Educational Resources Information Center

    Brisco, Nicole D.

    2010-01-01

    In the author's art class, she found that many of her students in an intro art class have some technical skill, but lack the ability to think conceptually. Her goal was to create an innovative project that combined design, painting, and sculpture into a compact unit that asked students how they define themselves. In the process of answering this…

  1. Evaluating Risks of Insertional Mutagenesis by DNA Transposons in Gene Therapy

    PubMed Central

    Hackett, Perry B.; Largaespada, David A.; Switzer, Kirsten C.; Cooper, Laurence J.N.

    2013-01-01

    Investigational therapy can be successfully undertaken using viral- and non-viral-mediated ex vivo gene transfer. Indeed, recent clinical trials have established the potential for genetically modified T cells to improve and restore health. Recently the Sleeping Beauty (SB) transposon/transposase system has been applied in clinical trials to stably insert a chimeric antigen receptor (CAR) to redirect T-cell specificity. We discuss the context in which the SB system can be harnessed for gene therapy and describe the human application of SB-modified CAR+ T cells. We have focused on theoretical issues relating to insertional mutagenesis in the context of human genomes that are naturally subjected to remobilization of transposons and the experimental evidence over the last decade of employing SB transposons for defining genes that induce cancer. These findings are put into the context of the use of SB transposons in the treatment of human disease. PMID:23313630

  2. Astronaut John Glenn practices insertion into Mercury spacecraft

    NASA Technical Reports Server (NTRS)

    1962-01-01

    Astronaut John H. Glenn Jr., pilot of the Mercury-Atlas 6 mission, practices insertion into the Mercury 'Friendship 7' spacecraft during MA-6 preflight training activity at Cape Canveral, Florida. He is wearing the full pressure suit and helmet (00993); Glenn practices insertion into Mercury capsule with help of a McDonnell Aircraft Corporation technician (00994).

  3. Cruciate retaining and cruciate substituting ultra-congruent insert

    PubMed Central

    Deledda, Davide; Rosso, Federica; Ratto, Nicola; Bruzzone, Matteo; Bonasia, Davide Edoardo; Rossi, Roberto

    2016-01-01

    The posterior cruciate ligament (PCL) conservation and the polyethylene insert constraint in total knee arthroplasty (TKA) are still debated. The PCL is one of the primary stabilizers of the joint, but cruciate retaining (CR) implants have the disadvantage of a difficult balancing of the PCL. Postero-stabilized (PS) implants were introduced to reduce this problem. However, also the PS implants have some disadvantages, due to the cam-mechanism, such as high risk of cam-mechanism polyethylene wear. To minimize the polyethylene wear of the cam-mechanism and the bone sacrifice due to the intercondylar box, different types of inserts were developed, trying to increase the implant conformity and to reduce stresses on the bone-implant interface. In this scenario ultra-congruent (UC) inserts were developed. Those inserts are characterized by a high anterior wall and a deep-dished plate. This conformation should guarantee a good stability without the posterior cam. Few studies on both kinematic and clinical outcomes of UC inserts are available. Clinical and radiological outcomes, as well as kinematic data are similar between UC mobile bearing (MB) and standard PS MB inserts at short to mid-term follow-up. In this manuscript biomechanics and clinical outcomes of UC inserts will be described, and they will be compared to standard PS or CR inserts. PMID:26855938

  4. Load beam unit replaceable inserts for dry coal extrusion pumps

    DOEpatents

    Saunders, Timothy; Brady, John D.

    2012-11-13

    A track assembly for a particulate material extrusion pump according to an exemplary aspect of the present disclosure includes a link assembly with a roller bearing. An insert mounted to a load beam located such that the roller bearing contacts the insert.

  5. Rhinosinusitis; A Potential Hazard of Nasogastric Tube Insertion

    PubMed Central

    Adeyemo, Adebolajo A.; Fasunla, Ayotunde J.; Adeosun, Aderemi A.; Abdullahi, Hamisu

    2007-01-01

    The nasogastric tube has been used frequently for enteral feeding and as an intranasal oxygen catheter. This practice is however associated with complications. We present a case of rhinosinusitis and sepsis in a diabetic patient following the insertion of a nasogastric tube. Physicians should be aware of sinusitis as a possible cause of sepsis in patients with nasogastric tube insertion. PMID:25161433

  6. Integrated Process For Insertion And Beatup Of Fill Yarns

    NASA Technical Reports Server (NTRS)

    Farley, Gary L.

    1990-01-01

    Integrated apparatus and process devised for insertion and beatup of fill yarns during weaving of fabrics containing bias-oriented yarns. New technology supplants old shuttle method and modern water-jet method of insertion and conventional reed method of beatup. Intended for use in angle-ply or bias-direction weaving process.

  7. A semi-automated high-throughput approach to the generation of transposon insertion mutants in the nematode Caenorhabditis elegans.

    PubMed

    Duverger, Yohann; Belougne, Jérôme; Scaglione, Sarah; Brandli, Dominique; Beclin, Christophe; Ewbank, Jonathan J

    2007-01-01

    The generation of a large collection of defined transposon insertion mutants is of general interest to the Caenorhabditis elegans research community and has been supported by the European Union. We describe here a semi-automated high-throughput method for mutant production and screening, using the heterologous transposon Mos1. The procedure allows routine culture of several thousand independent nematode strains in parallel for multiple generations before stereotyped molecular analyses. Using this method, we have already generated >17 500 individual strains carrying Mos1 insertions. It could be easily adapted to forward and reverse genetic screens and may influence researchers faced with making a choice of model organism. PMID:17164286

  8. Measurement of Vein Diameter for Peripherally Inserted Central Catheter (PICC) Insertion: An Observational Study.

    PubMed

    Sharp, Rebecca; Cummings, Melita; Childs, Jessie; Fielder, Andrea; Mikocka-Walus, Antonina; Grech, Carol; Esterman, Adrian

    2015-01-01

    Choosing an appropriately sized vein reduces the risk of venous thromboembolism associated with peripherally inserted central catheters. This observational study described the diameters of the brachial, basilic, and cephalic veins and determined the effect of patient factors on vein size. Ultrasound was used to measure the veins of 176 participants. Vein diameter was similar in both arms regardless of hand dominance and side. Patient factors-including greater age, height, and weight, as well as male gender-were associated with increased vein diameter. The basilic vein tended to have the largest diameter statistically. However, this was the case in only 55% of patients. PMID:26339941

  9. Z-2 Threaded Insert Design and Testing Abstract

    NASA Technical Reports Server (NTRS)

    Rhodes, RIchard; Graziosi, Dave; Jones, Bobby; Ferl, Jinny; Scarborough, Steve; Sweeney, Mitch

    2016-01-01

    The Z-2 Prototype Planetary Extravehicular Space Suit Assembly is a continuation of NASA's Z series of spacesuits. The Z-2 is another step in the NASA's technology development roadmap leading to human exploration of the Martian surface. To meet a more challenging set of requirements than previous suit systems standard design features, such as threaded inserts, have been re-analyzed and improved. NASA's Z-2 prototype space suit contains several components fabricated from an advanced hybrid composite laminate consisting of IM10 carbon fiber and fiber glass. One requirement NASA levied on the suit composites was the ability to have removable, replaceable helicoil inserts to which other suit components would be fastened. An approach utilizing bonded in inserts with helicoils inside of them was implemented. The design of the interface flanges of the composites allowed some of the inserts to be a "T" style insert that was installed through the entire thickness of the laminate. The flange portion of the insert provides a mechanical lock as a redundancy to the adhesive aiding in the pullout load that the insert can withstand. In some locations it was not possible to utilize at "T" style insert and a blind insert was used instead. These inserts rely completely on the bond strength of the adhesive to resist pullout. It was determined during the design of the suit that the inserts did not need to withstand loads induced from pressure cycling but instead tension induced from torqueing the screws to bolt on hardware which creates a much higher stress on them. Bolt tension is determined by dividing the torque on the screw by a k value multiplied by the thread diameter of the bolt. The k value is a factor that accounts for friction in the system. A common value used for k for a non-lubricated screw is 0.2. The k value can go down by as much as 0.1 if the screw is lubricated which means for the same torque, a much larger tension could be placed on the bolt and insert. This paper

  10. Eph and Ephrin function in dispersal and epithelial insertion of pigmented immunocytes in sea urchin embryos

    PubMed Central

    Krupke, Oliver A; Zysk, Ivona; Mellott, Dan O; Burke, Robert D

    2016-01-01

    The mechanisms that underlie directional cell migration are incompletely understood. Eph receptors usually guide migrations of cells by exclusion from regions expressing Ephrin. In sea urchin embryos, pigmented immunocytes are specified in vegetal epithelium, transition to mesenchyme, migrate, and re-enter ectoderm, distributing in dorsal ectoderm and ciliary band, but not ventral ectoderm. Immunocytes express Sp-Eph and Sp-Efn is expressed throughout dorsal and ciliary band ectoderm. Interfering with expression or function of Sp-Eph results in rounded immunocytes entering ectoderm but not adopting a dendritic form. Expressing Sp-Efn throughout embryos permits immunocyte insertion in ventral ectoderm. In mosaic embryos, immunocytes insert preferentially in ectoderm expressing Sp-Efn. We conclude that Sp-Eph signaling is necessary and sufficient for epithelial insertion. As well, we propose that immunocytes disperse when Sp-Eph enhances adhesion, causing haptotactic movement to regions of higher ligand abundance. This is a distinctive example of Eph/Ephrin signaling acting positively to pattern migrating cells. DOI: http://dx.doi.org/10.7554/eLife.16000.001 PMID:27474796

  11. Eph and Ephrin function in dispersal and epithelial insertion of pigmented immunocytes in sea urchin embryos.

    PubMed

    Krupke, Oliver A; Zysk, Ivona; Mellott, Dan O; Burke, Robert D

    2016-01-01

    The mechanisms that underlie directional cell migration are incompletely understood. Eph receptors usually guide migrations of cells by exclusion from regions expressing Ephrin. In sea urchin embryos, pigmented immunocytes are specified in vegetal epithelium, transition to mesenchyme, migrate, and re-enter ectoderm, distributing in dorsal ectoderm and ciliary band, but not ventral ectoderm. Immunocytes express Sp-Eph and Sp-Efn is expressed throughout dorsal and ciliary band ectoderm. Interfering with expression or function of Sp-Eph results in rounded immunocytes entering ectoderm but not adopting a dendritic form. Expressing Sp-Efn throughout embryos permits immunocyte insertion in ventral ectoderm. In mosaic embryos, immunocytes insert preferentially in ectoderm expressing Sp-Efn. We conclude that Sp-Eph signaling is necessary and sufficient for epithelial insertion. As well, we propose that immunocytes disperse when Sp-Eph enhances adhesion, causing haptotactic movement to regions of higher ligand abundance. This is a distinctive example of Eph/Ephrin signaling acting positively to pattern migrating cells. PMID:27474796

  12. Young black women: defining health.

    PubMed

    Hargrove, H J; Keller, C

    1993-01-01

    The purpose of this study was to elicit a definition of health as described by young Black women and to characterize the factors related to their definitions of health. The research questions were: (a) How do young Black women define health and (b) what factors are related to their definition of health? Using interviews and open-ended questions, an exploratory descriptive design examined the factors which contribute to the definition of health. Twenty-two young Black women between the ages of 21 and 40 comprised the sample. A wide range of incomes, occupations, educational levels, marital status, and family sizes were represented. The informants defined health as comprising those characteristics, behaviors, and/or activities which include: (a) having or avoiding a disease, (b) the presence or absence of obesity, (c) experiencing and reducing stress, (d) good and bad health habits, (e) eating good and bad foods, and (f) engaging (or not) in exercise. PMID:8106873

  13. Defining and managing sustainable yield.

    PubMed

    Maimone, Mark

    2004-01-01

    Ground water resource management programs are paying increasing attention to the integration of ground water and surface water in the planning process. Many plans, however, show a sophistication in approach and presentation that masks a fundamental weakness in the overall analysis. The plans usually discuss issues of demand and yield, yet never directly address a fundamental issue behind the plan--how to define sustainable yield of an aquifer system. This paper points out a number of considerations that must be addressed in defining sustainable yield in order to make the definition more useful in practical water resource planning studies. These include consideration for the spatial and temporal aspects of the problem, the development of a conceptual water balance, the influence of boundaries and changes in technology on the definition, the need to examine water demand as well as available supply, the need for stakeholder involvement, and the issue of uncertainty in our understanding of the components of the hydrologic system. PMID:15584295

  14. Defined DNA/nanoparticle conjugates.

    PubMed

    Ackerson, Christopher J; Sykes, Michael T; Kornberg, Roger D

    2005-09-20

    Glutathione monolayer-protected gold clusters were reacted by place exchange with 19- or 20-residue thiolated oligonucleotides. The resulting DNA/nanoparticle conjugates could be separated on the basis of the number of bound oligonucleotides by gel electrophoresis and assembled with one another by DNA-DNA hybridization. This approach overcomes previous limitations of DNA/nanoparticle synthesis and yields conjugates that are precisely defined with respect to both gold and nucleic acid content. PMID:16155122

  15. Metallic glass mold insert for hot embossing of polymers

    NASA Astrophysics Data System (ADS)

    Ma, J.; Zhang, X.; Wang, W. H.

    2012-07-01

    Molding of micro components from thermoplastic polymers (TPs) has become a routinely used industrial production process. To find hard, ductile and durable material for mold insert and to fabricate the mold insert are two big challenges for the thermoplastic polymers fabrication techniques. We report that a Pd-based metallic glass (MG) mold insert was readily fabricated in its supercooled liquid region, and the atomic force microscope measurement and time-temperature-transformation analysis show that the metallic glass mold insert has very fine surface quality and long service life. We show that the metallic glasses, which have remarkable mechanical properties and excellent thermoplastic forming ability, are new ideal materials for hot embossing mold insert of thermoplastic polymers.

  16. Method for improving the durability of ion insertion materials

    DOEpatents

    Lee, Se-Hee; Tracy, C. Edwin; Cheong, Hyeonsik M.

    2002-01-01

    The invention provides a method of protecting an ion insertion material from the degradative effects of a liquid or gel-type electrolyte material by disposing a protective, solid ion conducting, electrically insulating, layer between the ion insertion layer and the liquid or gel-type electrolyte material. The invention further provides liquid or gel-type electrochemical cells having improved durability having a pair of electrodes, a pair of ion insertion layers sandwiched between the pair of electrodes, a pair of solid ion conducting layers sandwiched between the ion insertion layers, and a liquid or gel-type electrolyte material disposed between the solid ion conducting layers, where the solid ion conducting layer minimizes or prevents degradation of the faces of the ion insertion materials facing the liquid or gel-type electrolyte material. Electrochemical cells of this invention having increased durability include secondary lithium batteries and electrochromic devices.

  17. Gas turbine nozzle vane insert and methods of installation

    DOEpatents

    Miller, William John; Predmore, Daniel Ross; Placko, James Michael

    2002-01-01

    A pair of hollow elongated insert bodies are disposed in one or more of the nozzle vane cavities of a nozzle stage of a gas turbine. Each insert body has an outer wall portion with apertures for impingement-cooling of nozzle wall portions in registration with the outer wall portion. The insert bodies are installed into the cavity separately and spreaders flex the bodies toward and to engage standoffs against wall portions of the nozzle whereby the designed impingement gap between the outer wall portions of the insert bodies and the nozzle wall portions is achieved. The spreaders are secured to the inner wall portions of the insert bodies and the bodies are secured to one another and to the nozzle vane by welding or brazing.

  18. How do people define moderation?

    PubMed

    vanDellen, Michelle R; Isherwood, Jennifer C; Delose, Julie E

    2016-06-01

    Eating in moderation is considered to be sound and practical advice for weight maintenance or prevention of weight gain. However, the concept of moderation is ambiguous, and the effect of moderation messages on consumption has yet to be empirically examined. The present manuscript examines how people define moderate consumption. We expected that people would define moderate consumption in ways that justified their current or desired consumption rather than view moderation as an objective standard. In Studies 1 and 2, moderate consumption was perceived to involve greater quantities of an unhealthy food (chocolate chip cookies, gummy candies) than perceptions of how much one should consume. In Study 3, participants generally perceived themselves to eat in moderation and defined moderate consumption as greater than their personal consumption. Furthermore, definitions of moderate consumption were related to personal consumption behaviors. Results suggest that the endorsement of moderation messages allows for a wide range of interpretations of moderate consumption. Thus, we conclude that moderation messages are unlikely to be effective messages for helping people maintain or lose weight. PMID:26964691

  19. Cyberbullying: the challenge to define.

    PubMed

    Langos, Colette

    2012-06-01

    Cyberbullying is a reality of the digital age. To address this phenomenon, it becomes imperative to understand exactly what cyberbullying is. Thus, establishing a workable and theoretically sound definition is essential. This article contributes to the existing literature in relation to the definition of cyberbullying. The specific elements of repetition, power imbalance, intention, and aggression, regarded as essential criteria of traditional face-to-face bullying, are considered in the cyber context. It is posited that the core bullying elements retain their importance and applicability in relation to cyberbullying. The element of repetition is in need of redefining, given the public nature of material in the online environment. In this article, a clear distinction between direct and indirect cyberbullying is made and a model definition of cyberbullying is offered. Overall, the analysis provided lends insight into how the essential bullying elements have evolved and should apply in our parallel cyber universe. PMID:22703033

  20. Role of histone modifications in defining chromatin structure and function.

    PubMed

    Gelato, Kathy A; Fischle, Wolfgang

    2008-04-01

    Chromosomes in eukaryotic cell nuclei are not uniformly organized, but rather contain distinct chromatin elements, with each state having a defined biochemical structure and biological function. These are recognizable by their distinct architectures and molecular components, which can change in response to cellular stimuli or metabolic requirements. Chromatin elements are characterized by the fundamental histone and DNA components, as well as other associated non-histone proteins and factors. Post-translational modifications of histone proteins in particular often correlate with a specific chromatin structure and function. Patterns of histone modifications are implicated as having a role in directing the level of chromatin compaction, as well as playing roles in multiple functional pathways directing the readout of distinct regions of the genome. We review the properties of various chromatin elements and the apparent links of histone modifications with chromatin organization and functional output. PMID:18225984

  1. Defined DNA/nanoparticle conjugates

    NASA Astrophysics Data System (ADS)

    Ackerson, Christopher J.; Sykes, Michael T.; Kornberg, Roger D.

    2005-09-01

    Glutathione monolayer-protected gold clusters were reacted by place exchange with 19- or 20-residue thiolated oligonucleotides. The resulting DNA/nanoparticle conjugates could be separated on the basis of the number of bound oligonucleotides by gel electrophoresis and assembled with one another by DNA-DNA hybridization. This approach overcomes previous limitations of DNA/nanoparticle synthesis and yields conjugates that are precisely defined with respect to both gold and nucleic acid content. Freely available online through the PNAS open access option.

  2. Immediate post-placental IUD insertion: the expulsion problem.

    PubMed

    Thiery, M; Van Kets, H; Van der Pas, H

    1985-04-01

    This paper reports an evaluation of immediate post-placental insertion of a non-copper (Lippes Loop D) and several copper-bearing IUD models (TCu200, TCu220C, MLCu375, MLCu250, Nova T-PP, DimélysR). Based on the analysis of a total of 2,646 insertions and 55,794 woman-months of experience, we conclude that placement of an IUD within ten minutes of delivery of the placenta is a valuable alternative to interval insertion, because this method is safe and effective. Effectiveness was significantly lower for the Lippes Loop D than for the T- and ML-IUD models tested, the latter showing roughly comparable pertinent event rates. Pertinent event rates for copper IUDs were influenced by the skill of the operator; age of the recipient only had a significant effect on effectiveness, whereas parity had no significant effect on pertinent event rates. The single and still unsolved problem associated with immediate postpartum insertion is the greater likelihood of expulsion compared with interval insertion, and this hazard is significantly much greater for the Loop than for the copper-bearing devices assessed. The evolution of the expulsion rates shows a constant time-relationship. This pattern makes it obvious why follow-up of recipients, at least during the first trimester following insertion, is mandatory if immediate post-placental IUD insertion is to be optimally effective. PMID:4006467

  3. Toward automated cochlear implant insertion using tubular manipulators

    NASA Astrophysics Data System (ADS)

    Granna, Josephine; Rau, Thomas S.; Nguyen, Thien-Dang; Lenarz, Thomas; Majdani, Omid; Burgner-Kahrs, Jessica

    2016-03-01

    During manual cochlear implant electrode insertion the surgeon is at risk to damage the intracochlear fine-structure, as the electrode array is inserted through a small opening in the cochlea blindly with little force-feedback. This paper addresses a novel concept for cochlear electrode insertion using tubular manipulators to reduce risks of causing trauma during insertion and to automate the insertion process. We propose a tubular manipulator incorporated into the electrode array composed of an inner wire within a tube, both elastic and helically shaped. It is our vision to use this manipulator to actuate the initially straight electrode array during insertion into the cochlea by actuation of the wire and tube, i.e. translation and slight axial rotation. In this paper, we evaluate the geometry of the human cochlea in 22 patient datasets in order to derive design requirements for the manipulator. We propose an optimization algorithm to automatically determine the tube set parameters (curvature, torsion, diameter, length) for an ideal final position within the cochlea. To prove our concept, we demonstrate that insertion can be realized in a follow-the-leader fashion for 19 out of 22 cochleas. This is possible with only 4 different tube/wire sets.

  4. Insertion of isolated insulin receptors into placental membrane vesicles.

    PubMed Central

    Christiansen, K; Carlsen, J

    1992-01-01

    Purified human insulin receptors were inserted into placental plasma-membrane vesicles by fusion of membranes with receptor-lysophosphatidylcholine micelles. Scatchard analysis of insulin binding showed that about 10-15% of the added receptors became inserted into the membrane. The receptor number could be increased about 3-fold, corresponding to approx. 5 pmol of receptor/mg of membrane protein. The receptors became firmly bound to the membrane, as they could not be removed by extensive wash. The insertion of exogenous receptors could be demonstrated by immunoblotting. The inserted insulin receptor had the same insulin-binding affinity as the isolated receptor and the endogenous receptor of the membrane. Insulin binding in the presence or absence of Triton X-100 revealed that more than 80% of the exogenous receptors had a right-side-out orientation. Function of the inserted receptors, as observed by insulin-stimulated autophosphorylation, could be demonstrated. About 80% of the added lysophospholipid, corresponding to approx. 160 nmol of lysophospholipid/mg of membrane protein, became integrated into the membrane and was partly metabolized to phospholipid and to non-esterified fatty acid. The method of insertion of isolated insulin receptors using the natural detergent, lysophospholipid, may be a method for insertion of receptors into intact cells, where the lysophospholipid, as in the plasma-membrane vesicles, will be acylated to phospholipid. Images Fig. 3. Fig. 4. PMID:1736892

  5. Method of joining a vane cavity insert to a nozzle segment of a gas turbine

    DOEpatents

    Burdgick, Steven Sebastian

    2002-01-01

    An insert containing apertures for impingement cooling a nozzle vane of a nozzle segment in a gas turbine is inserted into one end of the vane. The leading end of the insert is positioned slightly past a rib adjacent the opposite end of the vane through which the insert is inserted. The end of the insert is formed or swaged into conformance with the inner margin of the rib. The insert is then brazed or welded to the rib.

  6. Landscape of insertion polymorphisms in the human genome.

    PubMed

    Onozawa, Masahiro; Goldberg, Liat; Aplan, Peter D

    2015-04-01

    Nucleotide substitutions, small (<50 bp) insertions or deletions (indels), and large (>50 bp) deletions are well-known causes of genetic variation within the human genome. We recently reported a previously unrecognized form of polymorphic insertions, termed templated sequence insertion polymorphism (TSIP), in which the inserted sequence was templated from a distant genomic region, and was inserted in the genome through reverse transcription of an RNA intermediate. TSIPs can be grouped into two classes based on nucleotide sequence features at the insertion junctions; class 1 TSIPs show target site duplication, polyadenylation, and preference for insertion at a 5'-TTTT/A-3' sequence, suggesting a LINE-1 based insertion mechanism, whereas class 2 TSIPs show features consistent with repair of a DNA double strand break by nonhomologous end joining. To gain a more complete picture of TSIPs throughout the human population, we evaluated whole-genome sequence from 52 individuals, and identified 171 TSIPs. Most individuals had 25-30 TSIPs, and common (present in >20% of individuals) TSIPs were found in individuals throughout the world, whereas rare TSIPs tended to cluster in specific geographic regions. The number of rare TSIPs was greater than the number of common TSIPs, suggesting that TSIP generation is an ongoing process. Intriguingly, mitochondrial sequences were a frequent template for class 2 insertions, used more commonly than any nuclear chromosome. Similar to single nucleotide polymorphisms and indels, we suspect that these TSIPs may be important for the generation of human diversity and genetic diseases, and can be useful in tracking historical migration of populations. PMID:25745018

  7. Islet amyloid polypeptide inserts into phospholipid monolayers as monomer.

    PubMed

    Engel, Maarten F M; Yigittop, HaciAli; Elgersma, Ronald C; Rijkers, Dirk T S; Liskamp, Rob M J; de Kruijff, Ben; Höppener, Jo W M; Antoinette Killian, J

    2006-02-24

    Amyloid deposits in the pancreatic islets of Langerhans are thought to be a main factor responsible for death of the insulin-producing islet beta-cells in type 2 diabetes. It is hypothesized that beta-cell death is related to interaction of the 37 amino acid residue human islet amyloid polypeptide (hIAPP), the major constituent of islet amyloid, with cellular membranes. However, the mechanism of hIAPP-membrane interactions is largely unknown. Here, we study the nature and the molecular details of the initial step of hIAPP-membrane interactions by using the monolayer technique. It is shown that both freshly dissolved hIAPP and the non-amyloidogenic mouse IAPP (mIAPP) have a pronounced ability to insert into phospholipid monolayers, even at lipid packing conditions that exceed the conditions that occur in biological membranes. In contrast, the fibrillar form of hIAPP has lost the ability to insert. These results, combined with the observations that both the insertion kinetics and the dependence of insertion on the initial surface pressure are similar for freshly dissolved hIAPP and mIAPP, indicate that hIAPP inserts into phospholipid monolayers most likely as a monomer. In addition, our results suggest that the N-terminal part of hIAPP, which is nearly identical with that of mIAPP, is largely responsible for insertion. This is supported by experiments with hIAPP fragments, which show that a peptide consisting of the 19 N-terminal residues of hIAPP efficiently inserts into phospholipid monolayers, whereas an amyloidogenic decapeptide, consisting of residues 20-29 of hIAPP, inserts much less efficiently. The results obtained here suggest that hIAPP monomers might insert with high efficiency in biological membranes in vivo. This process could play an important role as a first step in hIAPP-induced membrane damage in type 2 diabetes. PMID:16403520

  8. Genomic Loci of the Porphyromonas gingivalis Insertion Element IS1126

    PubMed Central

    Dong, Hong; Chen, Tsute; Dewhirst, Floyd E.; Fleischmann, Robert D.; Fraser, Claire M.; Duncan, Margaret J.

    1999-01-01

    The Porphyromonas gingivalis genome contains multiple copies of insertion element IS1126. When chromosomal DNA digests of different strains were probed with IS1126, between 25 and 35 hybridizing fragments per genome were detected, depending on the strain. Unrelated strains had very different restriction fragment length polymorphism (RFLP) patterns. When different laboratory copies of a specific strain were examined, the IS1126 RFLP patterns were very similar but small differences were observed, indicating that element-associated changes had occurred during laboratory passage. Within the next year, genome sequencing, assembly, and annotation for P. gingivalis W83 will be completed. Because repetitive elements complicate the assembly of randomly sequenced DNA fragments, we isolated and sequenced the flanking regions of IS1126 copies in strain W83. We also isolated and sequenced the flanking regions of IS1126 copies in strain ATCC 33277 in order to compare insertion sites in phylogenetically divergent strains. We identified 37 new sequences flanking IS1126 from strain ATCC 33277 and 30 from strain W83. The insertion element was found between genes except where it transposed into another insertion element. Examination of identifiable flanking genes or open reading frames indicated that the insertion sites were different in the two strains, except that both strains possess an insertion adjacent to the Lys-gingipain gene (J. P. Lewis and F. L. Macrina, Infect. Immun. 66:3035–3042, 1998). Most of the genes or sequences flanking IS1126 in ATCC 33277 were present in W83 but were contiguous and not insertion element associated. Thus, where genes were identified in both strains, their order was maintained, indicating that the two genomes are organized similarly, but the loci of IS1126 are different. In both strains, insertion element-associated duplicated target sites were lost from several copies of IS1126, providing evidence of homologous recombination between elements

  9. Defining Life: The Virus Viewpoint

    NASA Astrophysics Data System (ADS)

    Forterre, Patrick

    2010-04-01

    Are viruses alive? Until very recently, answering this question was often negative and viruses were not considered in discussions on the origin and definition of life. This situation is rapidly changing, following several discoveries that have modified our vision of viruses. It has been recognized that viruses have played (and still play) a major innovative role in the evolution of cellular organisms. New definitions of viruses have been proposed and their position in the universal tree of life is actively discussed. Viruses are no more confused with their virions, but can be viewed as complex living entities that transform the infected cell into a novel organism—the virus—producing virions. I suggest here to define life (an historical process) as the mode of existence of ribosome encoding organisms (cells) and capsid encoding organisms (viruses) and their ancestors. I propose to define an organism as an ensemble of integrated organs (molecular or cellular) producing individuals evolving through natural selection. The origin of life on our planet would correspond to the establishment of the first organism corresponding to this definition.

  10. Human islets contain four distinct subtypes of β cells.

    PubMed

    Dorrell, Craig; Schug, Jonathan; Canaday, Pamela S; Russ, Holger A; Tarlow, Branden D; Grompe, Maria T; Horton, Tamara; Hebrok, Matthias; Streeter, Philip R; Kaestner, Klaus H; Grompe, Markus

    2016-01-01

    Human pancreatic islets of Langerhans contain five distinct endocrine cell types, each producing a characteristic hormone. The dysfunction or loss of the insulin-producing β cells causes diabetes mellitus, a disease that harms millions. Until now, β cells were generally regarded as a single, homogenous cell population. Here we identify four antigenically distinct subtypes of human β cells, which we refer to as β1-4, and which are distinguished by differential expression of ST8SIA1 and CD9. These subpopulations are always present in normal adult islets and have diverse gene expression profiles and distinct basal and glucose-stimulated insulin secretion. Importantly, the β cell subtype distribution is profoundly altered in type 2 diabetes. These data suggest that this antigenically defined β cell heterogeneity is functionally and likely medically relevant. PMID:27399229

  11. Industrial stator vane with sequential impingement cooling inserts

    DOEpatents

    Jones, Russell B; Fedock, John A; Goebel, Gloria E; Krueger, Judson J; Rawlings, Christopher K; Memmen, Robert L

    2013-08-06

    A turbine stator vane for an industrial engine, the vane having two impingement cooling inserts that produce a series of impingement cooling from the pressure side to the suction side of the vane walls. Each insert includes a spar with a row of alternating impingement cooling channels and return air channels extending in a radial direction. Impingement cooling plates cover the two sides of the insert and having rows of impingement cooling holes aligned with the impingement cooling channels and return air openings aligned with the return air channel.

  12. International Workshop on Magnetic Measurements of Insertion Devices

    SciTech Connect

    Not Available

    1993-10-01

    The International Workshop on Magnetic Measurements of Insertion Devices was held at the Advanced Photon Source, Argonne National Laboratory, on September 28--29, 1993. The workshop brought together scientists and engineers from Europe, Japan, and the United States to discuss the following topics: Special techniques for magnetic measurements of insertion devices, magnetic tolerances of the insertion devices for third generation synchrotron radiation sources, methods for and accuracy of the multipole moments measurements, magnetic sensors, among other topics. The workshop included thirteen presentations that are collected in this volume.

  13. Kinematics Analysis of an Aided Robot for Needle Insertion

    NASA Astrophysics Data System (ADS)

    Li, Qiang; Gao, Dedong; Wang, Shan; Bai, Huiquan; Zheng, Haojun

    The kinematic relationship between the needle base and the robot's joints is analyzed. The analysis process is based on the aided needle-insertion robot built by our group. The thinking of needle-inserting procedure is confirming the needle base's posture before the needle inserted into tissue. The method of Denavit-Hartenberg (D-H) parameters is used to establish a link robot body-frames with the structural characteristics of the robot. After analysing kinematics, the kinematics equation is presented. The kinematics inverse solutions are obtained with the analytical method and geometry analysis method.

  14. Bax inserts into the mitochondrial outer membrane by different mechanisms.

    PubMed

    Cartron, Pierre-François; Bellot, Grégory; Oliver, Lisa; Grandier-Vazeille, Xavier; Manon, Stephen; Vallette, François M

    2008-09-01

    Bax insertion into the mitochondrial outer membrane is essential for the implementation of apoptosis. However, little is known about the first stage of Bax integration into the mitochondrial outer membrane. We have recently shown that TOM22, a mitochondrial outer membrane receptor, is important for insertion, although other reports have suggested that only mitochondrial lipids are involved in this process. Here, we show that monomers, but not dimers, of Bax require the presence of TOM22 and TOM40 to integrate into mitochondria. In addition we show that once inserted into the membrane, Bax can act as a receptor for cytosolic Bax. PMID:18687331

  15. Selection Of Cutting Inserts For Aluminum Alloys Machining By Using MCDM Method

    NASA Astrophysics Data System (ADS)

    Madić, Miloš; Radovanović, Miroslav; Petković, Dušan; Nedić, Bogdan

    2015-07-01

    Machining of aluminum and its alloys requires the use of cutting tools with special geometry and material. Since there exists a number of cutting tools for aluminum machining, each with unique characteristics, selection of the most appropriate cutting tool for a given application is very complex task which can be viewed as a multi-criteria decision making (MCDM) problem. This paper is focused on multi-criteria analysis of VCGT cutting inserts for aluminum alloys turning by applying recently developed MCDM method, i.e. weighted aggregated sum product assessment (WASPAS) method. The MCDM model was defined using the available catalogue data from cutting tool manufacturers.

  16. Small bowel injury after suprapubic catheter insertion presenting 3 years after initial insertion

    PubMed Central

    Gallagher, Kevin M; Good, Daniel W; Brush, John P; Al-hasso, Ammar; Stewart, Grant D

    2013-01-01

    A 77-year-old woman was referred to urology with blockages of her suprapubic catheter (SPC). The catheter was replaced easily in the emergency department, however, no urine was draining, only a cloudy green fluid was visible. On cystoscopy bilious material was identified in the bladder. There was no catheter visible. There seemed to be a fistulous tract entering the bladder at the left dome. The urethra was dilated, a urethral catheter was placed and the SPC was removed. A CT demonstrated that the SPC tract transfixed a loop of pelvic small bowel and entered the bladder with no intraperitoneal contrast leak. The patient recovered well and did not require laparotomy. This case emphasises that bowel perforation, although rare, must be considered as a complication of SPC placement even years after initial insertion when catheter problems arise. Unusually, we learn that this complication may not present with abdominal pain or peritonism. PMID:24326435

  17. Defining Life: Synthesis and Conclusions

    NASA Astrophysics Data System (ADS)

    Gayon, Jean

    2010-04-01

    The first part of the paper offers philosophical landmarks on the general issue of defining life. §1 defends that the recognition of “life” has always been and remains primarily an intuitive process, for the scientist as for the layperson. However we should not expect, then, to be able to draw a definition from this original experience, because our cognitive apparatus has not been primarily designed for this. §2 is about definitions in general. Two kinds of definition should be carefully distinguished: lexical definitions (based upon current uses of a word), and stipulative or legislative definitions, which deliberately assign a meaning to a word, for the purpose of clarifying scientific or philosophical arguments. The present volume provides examples of these two kinds of definitions. §3 examines three traditional philosophical definitions of life, all of which have been elaborated prior to the emergence of biology as a specific scientific discipline: life as animation (Aristotle), life as mechanism, and life as organization (Kant). All three concepts constitute a common heritage that structures in depth a good deal of our cultural intuitions and vocabulary any time we try to think about “life”. The present volume offers examples of these three concepts in contemporary scientific discourse. The second part of the paper proposes a synthesis of the major debates developed in this volume. Three major questions have been discussed. A first issue (§4) is whether we should define life or not, and why. Most authors are skeptical about the possibility of defining life in a strong way, although all admit that criteria are useful in contexts such as exobiology, artificial life and the origins of life. §5 examines the possible kinds of definitions of life presented in the volume. Those authors who have explicitly defended that a definition of life is needed, can be classified into two categories. The first category (or standard view) refers to two conditions

  18. Defining life: synthesis and conclusions.

    PubMed

    Gayon, Jean

    2010-04-01

    The first part of the paper offers philosophical landmarks on the general issue of defining life. Section 1 defends that the recognition of "life" has always been and remains primarily an intuitive process, for the scientist as for the layperson. However we should not expect, then, to be able to draw a definition from this original experience, because our cognitive apparatus has not been primarily designed for this. Section 2 is about definitions in general. Two kinds of definition should be carefully distinguished: lexical definitions (based upon current uses of a word), and stipulative or legislative definitions, which deliberately assign a meaning to a word, for the purpose of clarifying scientific or philosophical arguments. The present volume provides examples of these two kinds of definitions. Section 3 examines three traditional philosophical definitions of life, all of which have been elaborated prior to the emergence of biology as a specific scientific discipline: life as animation (Aristotle), life as mechanism, and life as organization (Kant). All three concepts constitute a common heritage that structures in depth a good deal of our cultural intuitions and vocabulary any time we try to think about "life". The present volume offers examples of these three concepts in contemporary scientific discourse. The second part of the paper proposes a synthesis of the major debates developed in this volume. Three major questions have been discussed. A first issue (Section 4) is whether we should define life or not, and why. Most authors are skeptical about the possibility of defining life in a strong way, although all admit that criteria are useful in contexts such as exobiology, artificial life and the origins of life. Section 5 examines the possible kinds of definitions of life presented in the volume. Those authors who have explicitly defended that a definition of life is needed, can be classified into two categories. The first category (or standard view) refers

  19. Three-dimensional theoretical temperature distributions produced by 915 MHz dipole antenna arrays with varying insertion depths in muscle tissue.

    PubMed

    Mechling, J A; Strohbehn, J W; Ryan, T P

    1992-01-01

    Interstitial microwave antenna array hyperthermia (IMAAH) systems are currently being used in the treatment of cancer. The insertion depth of an interstitial microwave antenna, defined as the length of the antenna from the tip to the point of insertion in tissue, affects its ability to produce uniform power deposition patterns in tumor volumes. The effect of varying insertion depths on the ability of an IMAAH system to heat two theoretical tumor models was examined. Four dipole microwave antennas were implanted in a 2 x 2 cm array and driven at 915 MHz in muscle tissue. The explicit power deposition patterns were calculated for each insertion depth using known theory. The bioheat transfer equation was solved for the 3-dimensional steady-state temperature distributions in cylindrical and ellipsoidal tumor models using a finite element method. Homogeneous and nonhomogeneous blood flow models were considered. As a basis of comparison of the various temperature distributions, the volume of tumor heated to greater than or equal to 43 degrees C was calculated. Under the conditions of this study, the insertion depth was shown to have a significant effect on the ability of an IMAAH system to heat the tumor volumes. A sharp decrease in the percentage of tumor volume heated to greater than or equal to 43 degrees C was seen for insertion depths between 7.8 and 14.6 cm. At an insertion depth of 11.7 cm (3/4 lambda) there was virtually no heating of the tumor. Regions of elevated power occurred outside of the desired treatment volume, stressing the importance of adequate thermometry techniques and demonstrating the need for hyperthermia treatment planning prior to implantation of an antenna array. Plots of the power deposition patterns and the corresponding temperatures produced in the diagonal plane of the antenna arrays are present. PMID:1727110

  20. Triple positive breast cancer: a distinct subtype?

    PubMed

    Vici, Patrizia; Pizzuti, Laura; Natoli, Clara; Gamucci, Teresa; Di Lauro, Luigi; Barba, Maddalena; Sergi, Domenico; Botti, Claudio; Michelotti, Andrea; Moscetti, Luca; Mariani, Luciano; Izzo, Fiorentino; D'Onofrio, Loretta; Sperduti, Isabella; Conti, Francesca; Rossi, Valentina; Cassano, Alessandra; Maugeri-Saccà, Marcello; Mottolese, Marcella; Marchetti, Paolo

    2015-02-01

    Breast cancer is a heterogeneous disease, and within the HER-2 positive subtype this is highly exemplified by the presence of substantial phenotypical and clinical heterogeneity, mostly related to hormonal receptor (HR) expression. It is well known how HER-2 positivity is commonly associated with a more aggressive tumor phenotype and decreased overall survival and, moreover, with a reduced benefit from endocrine treatment. Preclinical studies corroborate the role played by functional crosstalks between HER-2 and estrogen receptor (ER) signaling in endocrine resistance and, more recently, the activation of ER signaling is emerging as a possible mechanism of resistance to HER-2 blocking agents. Indeed, HER-2 positive breast cancer heterogeneity has been suggested to underlie the variability of response not only to endocrine treatments, but also to HER-2 blocking agents. Among HER-2 positive tumors, HR status probably defines two distinct subtypes, with dissimilar clinical behavior and different sensitivity to anticancer agents. The triple positive subtype, namely, ER/PgR/Her-2 positive tumors, could be considered the subset which most closely resembles the HER-2 negative/HR positive tumors, with substantial differences in biology and clinical outcome. We argue on whether in this subgroup the "standard" treatment may be considered, in selected cases, i.e., small tumors, low tumor burden, high expression of both hormonal receptors, an overtreatment. This article review the existing literature on biologic and clinical data concerning the HER-2/ER/PgR positive tumors, in an attempt to better define the HER-2 subtypes and to optimize the use of HER-2 targeted agents, chemotherapy and endocrine treatments in the various subsets. PMID:25554445

  1. Distinct responses to reduplicated chromosomes require distinct Mad2 responses

    PubMed Central

    Stormo, Benjamin M; Fox, Donald T

    2016-01-01

    Duplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromosome reduplication occurs in many contexts, including: polytene tissue development, polytene tumors, and following treatment with mitosis-blocking chemotherapeutics. However, mechanisms responding to or resolving polyteny during mitosis are poorly understood. Here, using Drosophila, we uncover two distinct reduplicated chromosome responses. First, when reduplicated polytene chromosomes persist into metaphase, an anaphase delay prevents tissue malformation and apoptosis. Second, reduplicated polytene chromosomes can also separate prior to metaphase through a spindle-independent mechanism termed Separation-Into-Recent-Sisters (SIRS). Both reduplication responses require the spindle assembly checkpoint protein Mad2. While Mad2 delays anaphase separation of metaphase polytene chromosomes, Mad2’s control of overall mitotic timing ensures efficient SIRS. Our results pinpoint mechanisms enabling continued proliferation after genome reduplication, a finding with implications for cancer progression and prevention. DOI: http://dx.doi.org/10.7554/eLife.15204.001 PMID:27159240

  2. Distinct responses to reduplicated chromosomes require distinct Mad2 responses.

    PubMed

    Stormo, Benjamin M; Fox, Donald T

    2016-01-01

    Duplicating chromosomes once each cell cycle produces sister chromatid pairs, which separate accurately at anaphase. In contrast, reduplicating chromosomes without separation frequently produces polytene chromosomes, a barrier to accurate mitosis. Chromosome reduplication occurs in many contexts, including: polytene tissue development, polytene tumors, and following treatment with mitosis-blocking chemotherapeutics. However, mechanisms responding to or resolving polyteny during mitosis are poorly understood. Here, using Drosophila, we uncover two distinct reduplicated chromosome responses. First, when reduplicated polytene chromosomes persist into metaphase, an anaphase delay prevents tissue malformation and apoptosis. Second, reduplicated polytene chromosomes can also separate prior to metaphase through a spindle-independent mechanism termed Separation-Into-Recent-Sisters (SIRS). Both reduplication responses require the spindle assembly checkpoint protein Mad2. While Mad2 delays anaphase separation of metaphase polytene chromosomes, Mad2's control of overall mitotic timing ensures efficient SIRS. Our results pinpoint mechanisms enabling continued proliferation after genome reduplication, a finding with implications for cancer progression and prevention. PMID:27159240

  3. The effect of ventilation tube insertion or trans-tympanic silicone plug insertion on a patulous Eustachian tube.

    PubMed

    Endo, Shiori; Mizuta, Kunihiro; Takahashi, Goro; Nakanishi, Hiroshi; Yamatodani, Takashi; Misawa, Kiyoshi; Hosokawa, Seiji; Mineta, Hiroyuki

    2016-06-01

    Conclusions This study suggests that long-term ventilation tube insertion is the first-choice surgical treatment for a 'sniff-type' patulous Eustachian tube (PET). When treating a refractory PET, it is important to determine whether the patient had a habitual sniff. Objectives PET patients were divided into two groups: patients with a habitual sniff (sniff-type PET) and those without a habitual sniff (non-sniff-type PET). This study examined the effects of ventilation tube insertion or silicone plug insertion in each group. Methods Surgical procedures such as ventilation tube insertion or trans-tympanic silicone plug insertion were performed for these patients. Tubotympanoaero-dynamic graphy (TTAG) was also performed to determine the mechanisms underlying these treatments. Results There were 11 cases (17 ears) of sniff-type PET and 20 cases (27 ears) of non-sniff-type PET. An improvement in symptoms was found in 72.7% of the patients who underwent silicone plug insertion (66.7% for sniff-type PET and 74.1% for non-sniff-type PET) and in 90.9% of the patients who underwent ventilation tube insertion for sniff-type PET. In TTAG assessments, many sniff-type PET patients showed significant synchronous changes at high levels of pressure (over 40 daPa) in the external auditory meatus and nasopharynx when performing a slight Valsalva manoeuvre (below 200 daPa). PMID:26903085

  4. Effect of insertion speed on tissue response and insertion mechanics of a chronically implanted silicon-based neural probe.

    PubMed

    Welkenhuysen, M; Andrei, A; Ameye, L; Eberle, W; Nuttin, B

    2011-11-01

    In this study, the effect of insertion speed on long-term tissue response and insertion mechanics was investigated. A dummy silicon parylene-coated probe was used in this context and implanted in the rat brain at 10 μm/s (n = 6) or 100 μm/s (n = 6) to a depth of 9 mm. The insertion mechanics were assessed by the dimpling distance, and the force at the point of penetration, at the end of the insertion phase, and after a 3-min rest period in the brain. After 6 weeks, the tissue response was evaluated by estimating the amount of gliosis, inflammation, and neuronal cell loss with immunohistochemistry. No difference in dimpling, penetration force, or the force after a 3-min rest period in the brain was observed. However, the force at the end of the insertion phase was significantly higher when inserting the probes at 100 μm/s compared to 10 μm/s. Furthermore, an expected tissue response was seen with an increase of glial and microglial reactivity around the probe. This reaction was similar along the entire length of the probe. However, evidence for a neuronal kill zone was observed only in the most superficial part of the implant. In this region, the lesion size was also greatest. Comparison of the tissue response between insertion speeds showed no differences. PMID:21896383

  5. Defining biocultural approaches to conservation.

    PubMed

    Gavin, Michael C; McCarter, Joe; Mead, Aroha; Berkes, Fikret; Stepp, John Richard; Peterson, Debora; Tang, Ruifei

    2015-03-01

    We contend that biocultural approaches to conservation can achieve effective and just conservation outcomes while addressing erosion of both cultural and biological diversity. Here, we propose a set of guidelines for the adoption of biocultural approaches to conservation. First, we draw lessons from work on biocultural diversity and heritage, social-ecological systems theory, integrated conservation and development, co-management, and community-based conservation to define biocultural approaches to conservation. Second, we describe eight principles that characterize such approaches. Third, we discuss reasons for adopting biocultural approaches and challenges. If used well, biocultural approaches to conservation can be a powerful tool for reducing the global loss of both biological and cultural diversity. PMID:25622889

  6. Three functional variants of IFN regulatory factor 5 (IRF5) define risk and protective haplotypes for human lupus

    PubMed Central

    Graham, Robert R.; Kyogoku, Chieko; Sigurdsson, Snaevar; Vlasova, Irina A.; Davies, Leela R. L.; Baechler, Emily C.; Plenge, Robert M.; Koeuth, Thearith; Ortmann, Ward A.; Hom, Geoffrey; Bauer, Jason W.; Gillett, Clarence; Burtt, Noel; Cunninghame Graham, Deborah S.; Onofrio, Robert; Petri, Michelle; Gunnarsson, Iva; Svenungsson, Elisabet; Rönnblom, Lars; Nordmark, Gunnel; Gregersen, Peter K.; Moser, Kathy; Gaffney, Patrick M.; Criswell, Lindsey A.; Vyse, Timothy J.; Syvänen, Ann-Christine; Bohjanen, Paul R.; Daly, Mark J.; Behrens, Timothy W.; Altshuler, David

    2007-01-01

    Systematic genome-wide studies to map genomic regions associated with human diseases are becoming more practical. Increasingly, efforts will be focused on the identification of the specific functional variants responsible for the disease. The challenges of identifying causal variants include the need for complete ascertainment of genetic variants and the need to consider the possibility of multiple causal alleles. We recently reported that risk of systemic lupus erythematosus (SLE) is strongly associated with a common SNP in IFN regulatory factor 5 (IRF5), and that this variant altered spicing in a way that might provide a functional explanation for the reproducible association to SLE risk. Here, by resequencing and genotyping in patients with SLE, we find evidence for three functional alleles of IRF5: the previously described exon 1B splice site variant, a 30-bp in-frame insertion/deletion variant of exon 6 that alters a proline-, glutamic acid-, serine- and threonine-rich domain region, and a variant in a conserved polyA+ signal sequence that alters the length of the 3′ UTR and stability of IRF5 mRNAs. Haplotypes of these three variants define at least three distinct levels of risk to SLE. Understanding how combinations of variants influence IRF5 function may offer etiological and therapeutic insights in SLE; more generally, IRF5 and SLE illustrates how multiple common variants of the same gene can together influence risk of common disease. PMID:17412832

  7. Miniature EVA Software Defined Radio

    NASA Technical Reports Server (NTRS)

    Pozhidaev, Aleksey

    2012-01-01

    As NASA embarks upon developing the Next-Generation Extra Vehicular Activity (EVA) Radio for deep space exploration, the demands on EVA battery life will substantially increase. The number of modes and frequency bands required will continue to grow in order to enable efficient and complex multi-mode operations including communications, navigation, and tracking applications. Whether conducting astronaut excursions, communicating to soldiers, or first responders responding to emergency hazards, NASA has developed an innovative, affordable, miniaturized, power-efficient software defined radio that offers unprecedented power-efficient flexibility. This lightweight, programmable, S-band, multi-service, frequency- agile EVA software defined radio (SDR) supports data, telemetry, voice, and both standard and high-definition video. Features include a modular design, an easily scalable architecture, and the EVA SDR allows for both stationary and mobile battery powered handheld operations. Currently, the radio is equipped with an S-band RF section. However, its scalable architecture can accommodate multiple RF sections simultaneously to cover multiple frequency bands. The EVA SDR also supports multiple network protocols. It currently implements a Hybrid Mesh Network based on the 802.11s open standard protocol. The radio targets RF channel data rates up to 20 Mbps and can be equipped with a real-time operating system (RTOS) that can be switched off for power-aware applications. The EVA SDR's modular design permits implementation of the same hardware at all Network Nodes concept. This approach assures the portability of the same software into any radio in the system. It also brings several benefits to the entire system including reducing system maintenance, system complexity, and development cost.

  8. Insertion Process of Ceramic Nanoporous Microneedles by Means of a Novel Mechanical Applicator Design

    PubMed Central

    Hartmann, Xavier H. M.; van der Linde, Peter; Homburg, Erik F. G. A.; van Breemen, Lambert C. A.; de Jong, Arthur M.; Luttge, Regina

    2015-01-01

    Arrays of microneedles (MNAs) are integrated in an out-of-plane fashion with a base plate and can serve as patches for the release of drugs and vaccines. We used soft-lithography and micromolding to manufacture ceramic nanoporous (np)MNAs. Failure modes of ceramic npMNAs are as yet poorly understood and the question remained: is our npMNA platform technology ready for microneedle (MN) assembly into patches? We investigated npMNAs by microindentation, yielding average crack fracture forces above the required insertion force for a single MN to penetrate human skin. We further developed a thumb pressure-actuated applicator-assisted npMNA insertion method, which enables anchoring of MNs in the skin by an adhesive in one handling step. Using a set of simple artificial skin models, we found a puncture efficiency of this insertion method a factor three times higher than by applying thumb pressure on the npMNA base plate directly. In addition, this new method facilitated zero MN-breakage due to a well-defined force distribution exerted onto the MNs and the closely surrounding area prior to bringing the adhesive into contact with the skin. Owing to the fact that such parameter space exists, we can conclude that npMNAs by soft lithography are a platform technology for MN assembly into a patch. PMID:26593939

  9. Insertion Process of Ceramic Nanoporous Microneedles by Means of a Novel Mechanical Applicator Design.

    PubMed

    Hartmann, Xavier H M; van der Linde, Peter; Homburg, Erik F G A; van Breemen, Lambert C A; de Jong, Arthur M; Luttge, Regina

    2015-01-01

    Arrays of microneedles (MNAs) are integrated in an out-of-plane fashion with a base plate and can serve as patches for the release of drugs and vaccines. We used soft-lithography and micromolding to manufacture ceramic nanoporous (np)MNAs. Failure modes of ceramic npMNAs are as yet poorly understood and the question remained: is our npMNA platform technology ready for microneedle (MN) assembly into patches? We investigated npMNAs by microindentation, yielding average crack fracture forces above the required insertion force for a single MN to penetrate human skin. We further developed a thumb pressure-actuated applicator-assisted npMNA insertion method, which enables anchoring of MNs in the skin by an adhesive in one handling step. Using a set of simple artificial skin models, we found a puncture efficiency of this insertion method a factor three times higher than by applying thumb pressure on the npMNA base plate directly. In addition, this new method facilitated zero MN-breakage due to a well-defined force distribution exerted onto the MNs and the closely surrounding area prior to bringing the adhesive into contact with the skin. Owing to the fact that such parameter space exists, we can conclude that npMNAs by soft lithography are a platform technology for MN assembly into a patch. PMID:26593939

  10. Pressure molding of powdered materials improved by rubber mold insert

    NASA Technical Reports Server (NTRS)

    1964-01-01

    Pressure molding tungsten microspheres is accomplished by applying hydraulic pressure to a silicone rubber mold insert with several barrel shaped chambers which is placed in a steel die cavity. This technique eliminates castings containing shear fractures.

  11. Management of insertional Achilles tendinopathy through a Cincinnati incision

    PubMed Central

    Carmont, Michael R; Maffulli, Nicola

    2007-01-01

    Background About 10% of patients not responding to 3–6 months of conservative management for insertional Achilles tendinopathy undergo surgery. Traditionally, surgery of the Achilles tendon is performed through longitudinal extensile incisions. Such surgery is prone to the complications of wound healing, wound breakdown and iatrogenic nerve injury. Methods We describe our current method of exposure of the Achilles tendon insertion and debridement of the peritendinous and tendon tissue with osteotomy of the calcaneum through a transverse skin incision at the level of the Achilles insertion. Results This method has been used since 2002 on over 40 patients for exposure of the Achilles tendon insertion and the distal Achilles tendon. Conclusion The Cincinnati incision allows adequate exposure, has minimal risk of symptomatic iatrogenic nerve injury, and has minimal problems related to the scar. PMID:17697370

  12. Ureteric access sheath aided insertion of resonance metal ureteric stent

    PubMed Central

    Winter, Matthew; Strahan, Stephen; Wines, Michael

    2014-01-01

    Ureteral obstruction caused by malignancy is a challenging and often complicated problem for urologists. We present a novel technique of ureteric access sheath aided insertion of a Resonance metal ureteric stent in the setting of a difficult obstruction. PMID:24879725

  13. The use of dimorphic Alu insertions in human DNA fingerprinting

    SciTech Connect

    Novick, G.E.; Gonzalez, T.; Garrison, J.; Novick, C.C.; Herrera, R.J.; Batzer, M.A.; Deininger, P.L.

    1992-12-04

    We have characterized certain Human Specific Alu Insertions as either dimorphic (TPA25, PV92, APO), sightly dimorphic (C2N4 and C4N4) or monomorphic (C3N1, C4N6, C4N2, C4N5, C4N8), based on studies of Caucasian, Asian, American Black and African Black populations. Our approach is based upon: (1) PCR amplification using primers directed to the sequences that flank the site of insertion of the different Alu elements studied; (2) gel electrophoresis and scoring according to the presence or absence of an Alu insertion in one or both homologous chromosomes; (3) allelic frequencies calculated and compared according to Hardy-Weinberg equilibrium. Our DNA fingerprinting procedure using PCR amplification of dimorphic Human Specific Alu insertions, is stable enough to be used not only as a tool for genetic mapping but also to characterize populations, study migrational patterns and track the inheritance of human genetic disorders.

  14. Interior, detail closeup shot of window with stained glass inserts ...

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

    Interior, detail closeup shot of window with stained glass inserts in top southeast room taken from ther west - J. Weingartner & Son Cigar Factory, 414 East Walnut Street, North Wales, Montgomery County, PA

  15. Fireplace insert and its parameters depend on the used glazing

    NASA Astrophysics Data System (ADS)

    Papučík, Štefan; Čaja, Alexander

    2016-06-01

    The contribution deals with the analysis of the impact of using double glass to change the performance and emission parameters of the fireplace insert. Conventional fireplace inserts are equipped with heat-resistant glass, which is resistant to high temperatures. For this type of inserts are required to be radiant constituent maximized. Prevailing part of heat is into the interior gets just by radiation through the glazed part. The hot water fireplace inserts is the requirement that the radiant constituent to the environment to a minimum. Therefore, instead of a single glass using double glazing which is intended to reduce this part of heat transfer. The temperature in the furnace is increased, and transmitted most of the heat into the water.

  16. Spontaneous Radiation Emission from Short, High Field Strength Insertion Devices

    SciTech Connect

    Geoffrey Krafft

    2005-09-15

    Since the earliest papers on undulaters were published, it has been known how to calculate the spontaneous emission spectrum from ''short'' undulaters when the magnetic field strength parameter is small compared to unity, or in ''single'' frequency sinusoidal undulaters where the magnetic field strength parameter is comparable to or larger than unity, but where the magnetic field amplitude is constant throughout the undulater. Fewer general results have been obtained in the case where the insertion device is both short, i.e., the magnetic field strength parameter changes appreciably throughout the insertion device, and the magnetic field strength is high enough that ponderomotive effects, radiation retardation, and harmonic generation are important physical phenomena. In this paper a general method is presented for calculating the radiation spectrum for short, high-field insertion devices. It is used to calculate the emission from some insertion device designs of recent interest.

  17. The release of insoluble antibiotics from collagen ocular inserts in vitro and their insertion into the conjunctival sac of cattle.

    PubMed

    Punch, P I; Costa, N D; Edwards, M E; Wilcox, G E

    1987-03-01

    The release rate of procaine penicillin, erythromycin and erythromycin estolate from soluble and insoluble collagen films was investigated in vitro to develop an ocular insert for the treatment of infectious bovine keratoconjunctivitis. The release rate and duration of release varied according to the selection of antibiotic and vehicle. The combination of erythromycin estolate and soluble collagen produced the most sustained drug-delivery system. However, due to the inappropriate physical properties of collagen and poor retention of ocular inserts, it was considered that the development of an antibiotic-impregnated collagen ocular insert requires further investigation. PMID:3586121

  18. Shoe inserts and orthotics for sport and physical activities.

    PubMed

    Nigg, B M; Nurse, M A; Stefanyshyn, D J

    1999-07-01

    The purposes of this paper were to discuss the perceived benefits of inserts and orthotics for sport activities and to propose a new concept for inserts and orthotics. There is evidence that inserts or orthotics reduce or prevent movement-related injuries. However, there is limited knowledge about the specific functioning an orthotic or insert provides. The same orthotic or insert is often proposed for different problems. Changes in skeletal movement due to inserts or orthotics seem to be small and not systematic. Based on the results of a study using bone pins, one may question the idea that a major function of orthotics or inserts consists in aligning the skeleton. Impact cushioning with shoe inserts or orthotics is typically below 10%. Such small reductions might not be important for injury reduction. It has been suggested that changes in material properties might produce adjustments in the muscular response of the locomotor system. The foot has various sensors to detect input signals with subject specific thresholds. Subjects with similar sensitivity threshold levels seem to respond in their movement pattern in a similar way. Comfort is an important variable. From a biomechanical point of view, comfort may be related to fit, additional stabilizing muscle work, fatigue, and damping of soft tissue vibrations. Based on the presented evidence, the concept of minimizing muscle work is proposed when using orthotics or inserts. A force signal acts as an input variable on the shoe. The shoe sole acts as a first filter, the insert or orthotic as a second filter, the plantar surface of the foot as a third filter for the force input signal. The filtered information is transferred to the central nervous system that provides a subject specific dynamic response. The subject performs the movement for the task at hand. For a given movement task, the skeleton has a preferred path. If an intervention supports/counteracts the preferred movement path, muscle activity can/must be

  19. Evolution of two distinct phylogenetic lineages of the emerging human pathogen Mycobacterium ulcerans

    PubMed Central

    Käser, Michael; Rondini, Simona; Naegeli, Martin; Stinear, Tim; Portaels, Francoise; Certa, Ulrich; Pluschke, Gerd

    2007-01-01

    Background Comparative genomics has greatly improved our understanding of the evolution of pathogenic mycobacteria such as Mycobacterium tuberculosis. Here we have used data from a genome microarray analysis to explore insertion-deletion (InDel) polymorphism among a diverse strain collection of Mycobacterium ulcerans, the causative agent of the devastating skin disease, Buruli ulcer. Detailed analysis of large sequence polymorphisms in twelve regions of difference (RDs), comprising irreversible genetic markers, enabled us to refine the phylogenetic succession within M. ulcerans, to define features of a hypothetical M. ulcerans most recent common ancestor and to confirm its origin from Mycobacterium marinum. Results M. ulcerans has evolved into five InDel haplotypes that separate into two distinct lineages: (i) the "classical" lineage including the most pathogenic genotypes – those that come from Africa, Australia and South East Asia; and (ii) an "ancestral" M. ulcerans lineage comprising strains from Asia (China/Japan), South America and Mexico. The ancestral lineage is genetically closer to the progenitor M. marinum in both RD composition and DNA sequence identity, whereas the classical lineage has undergone major genomic rearrangements. Conclusion Results of the InDel analysis are in complete accord with recent multi-locus sequence analysis and indicate that M. ulcerans has passed through at least two major evolutionary bottlenecks since divergence from M. marinum. The classical lineage shows more pronounced reductive evolution than the ancestral lineage, suggesting that there may be differences in the ecology between the two lineages. These findings improve the understanding of the adaptive evolution and virulence of M. ulcerans and pathogenic mycobacteria in general and will facilitate the development of new tools for improved diagnostics and molecular epidemiology. PMID:17900363

  20. DQw3 variants defined by cloned alloreactive T cells.

    PubMed

    Mickelson, E M; Nepom, G T; Nisperos, B; Hansen, J A

    1988-01-01

    The polymorphism of HLA class II molecules expressing the serologically defined alloantigen DQw3 was studied using cloned proliferative T lymphocytes. Two clones, IG9 and IC3, were selectively primed against DQw3-associated determinants and tested against a panel of 92 HLA-D homozygous cells. Both clones were specific for DQw3, but each showed a distinct response pattern. Clone IG9 recognized a DQw3-associated determinant expressed on a subset of DR4 and DR5 haplotypes and on all DRw6, 7, w8, and w9 haplotypes tested. In contrast, clone IC3 recognized a distinct DQw3-associated determinant expressed only on a subset of DR4 haplotypes. In monoclonal antibody inhibition experiments, anti-DQ, but not anti-DR or anti-DP antibodies, blocked reactivity of both clones IG9 and IC3, further demonstrating that the determinants defined by these clones are associated with DQ molecules. In DNA hybridization studies using a DQ beta probe, a correlation was observed between restriction site polymorphisms in the DQ beta gene, designated DQw"3.1" and "3.2," and the expression of the T-cell-defined IG9 and IC3 determinants. It is, thus, possible to demonstrate by cloned T-cell reactivity functionally relevant recognition sites on DQw3+ molecules that are associated with structural polymorphisms defined by molecular and genomic analysis. PMID:2452816

  1. Shared Decision Making and Office Insertion of Tympanostomy Tubes.

    PubMed

    Rosenfeld, Richard M

    2016-05-01

    Office insertion of tympanostomy tubes in young children without anesthesia is facilitated through shared decision making with families, including a candid discussion about anticipated pain (which is usually brief and transient) and how their child might react to being restrained. This commentary elaborates on the rationale for office tube insertion as an alternative to general anesthesia, including a clinical decision aid and suggestions for optimizing outcomes. PMID:27130946

  2. Metal-Matrix Composite Parts With Metal Inserts

    NASA Technical Reports Server (NTRS)

    Majkowski, T.; Kashalikar, U.

    1995-01-01

    Developmental fabrication process produces metal-matrix composite (MMC) parts with integral metal inserts. With inserts, MMC parts readily joined to similar parts by use of brazing, welding, or mechanical fasteners. Process conceived to make strong, lightweight components of structures erected in outer space. Also useful on Earth, in such automotive parts as rocker arms, cylinder liners, and pistons. Potential industrial applications include parts subjected to high stresses at high temperatures, as in power-generation, mining, and oil-drilling equipment.

  3. Production Recesses for Replaceable Cutting Inserts of Milling Tools

    NASA Astrophysics Data System (ADS)

    Kousal, Lukáš; Sadílek, Marek

    2014-12-01

    This article describes the production of recesses for replaceable cutting inserts of milling tools. The recess manufacture is exemplified on a D20 shanktype milling cutter with three replaceable cutting inserts. A new production technology and its operating cycle are demonstrated. A com-parison of the old and the new technologies shows the percentage saving of change cycles and used tools, including overall evaluation of the tech-nology.

  4. The ProDisc artificial disc: insertion technique.

    PubMed

    Aryan, Henry E; Acosta, Frank L; Ames, Christopher P

    2005-10-01

    The ProDisc artificial lumbar disc was designed for use in treatment of degenerative lumbar disease. The disc is implanted using an anterior approach to the lumbar spine with the assistance of intraoperative fluoroscopy. A variety of insertion instruments guide the surgeon through this process. The disc is implanted via an anterior approach, generally retroperitoneally but on occasion transperitoneally. The different approaches and insertion technique are described in this article. PMID:16326288

  5. Innovation in training for totally implanted port insertion.

    PubMed

    Kelly, Linda J; Moss, Jon

    2016-01-27

    This article discusses the use of fresh frozen cadavers as an innovative way to teach the procedure of totally implanted port insertion. In an attempt to increase the number of competent medical and nursing practitioners able to insert these devices, workshops have been devised and delivered at a university clinical anatomy skills centre. This method of teaching has had positive feedback from practitioners. PMID:27282699

  6. Evaluation of preferable insertion routes for esophagogastroduodenoscopy using ultrathin endoscopes

    PubMed Central

    Ono, Satoshi; Niimi, Keiko; Fujishiro, Mitsuhiro; Takahashi, Yu; Sakaguchi, Yoshiki; Nakayama, Chiemi; Minatsuki, Chihiro; Matsuda, Rie; Hirayama-Asada, Itsuko; Tsuji, Yosuke; Mochizuki, Satoshi; Kodashima, Shinya; Yamamichi, Nobutake; Ozeki, Atsuko; Matsumoto, Lumine; Ohike, Yumiko; Yamazaki, Tsutomu; Koike, Kazuhiko

    2014-01-01

    AIM: To evaluate the discomfort associated with esophagogastroduodenoscopy (EGD) using an ultrathin endoscope through different insertion routes. METHODS: This study (January 2012-March 2013) included 1971 consecutive patients [male/female (M/F), 1158/813, 57.5 ± 11.9 years] who visited a single institute for annual health checkups. Transnasal EGD was performed in 1394 patients and transoral EGD in 577. EGD-associated discomfort was assessed using a visual analog scale score (VAS score: 0-10). RESULTS: Multivariate analysis revealed gender (M vs F: 4.02 ± 2.15 vs 5.06 ± 2.43) as the only independent predictor of the VAS score in 180 patients who underwent EGD for the first time; whereas it revealed gender (M vs F 3.60 ± 2.20 vs 4.84 ± 2.37), operator, age group (A: < 39 years; B: 40-49 years; C: 50-59 years; D: 60-69 years; E: > 70 years; A/B/C/D/E: 4.99 ± 2.32/4.34 ± 2.49/4.19 ± 2.31/3.99 ± 2.27/3.63 ± 2.31), and type of insertion as independent predictors in the remaining patients. Subanalysis for gender, age group, and insertion route revealed that the VAS score decreased with age regardless of gender and insertion route, was high in female patients regardless of age and insertion route, and was low in males aged over 60 years who underwent transoral insertion. CONCLUSION: Although comprehensive analysis revealed that the insertion route may not be an independent predictor of the VAS score, transoral insertion may reduce EGD-associated discomfort in elderly patients. PMID:24803817

  7. Innovation in training for totally implanted port insertion.

    PubMed

    Kelly, Linda J; Moss, Jon

    This article discusses the use of fresh frozen cadavers as an innovative way to teach the procedure of totally implanted port insertion. In an attempt to increase the number of competent medical and nursing practitioners able to insert these devices, workshops have been devised and delivered at a university clinical anatomy skills centre. This method of teaching has had positive feedback from practitioners. PMID:27145548

  8. Impediments to rapid insertion of innovative displays and peripherals

    NASA Astrophysics Data System (ADS)

    Nicholson, Gail

    2012-06-01

    In order to optimize system performance and minimize cost for a system to fill capability gaps, an improvement to rapid insertion of innovative display and peripheral technology is required to take advantage of human-machine intersections. Current approaches to testing and integration impedes successful rapid insertion of innovative technology for new systems and incremental upgrades. Considerations to innovative displays and peripherals must occur further to the left of the lifecycle to be successful and key integration areas must be address for success.

  9. Deep electrode insertion and sound coding in cochlear implants.

    PubMed

    Hochmair, Ingeborg; Hochmair, Erwin; Nopp, Peter; Waller, Melissa; Jolly, Claude

    2015-04-01

    Present-day cochlear implants demonstrate remarkable speech understanding performance despite the use of non-optimized coding strategies concerning the transmission of tonal information. Most systems rely on place pitch information despite possibly large deviations from correct tonotopic placement of stimulation sites. Low frequency information is limited as well because of the constant pulse rate stimulation generally used and, being even more restrictive, of the limited insertion depth of the electrodes. This results in a compromised perception of music and tonal languages. Newly available flexible long straight electrodes permit deep insertion reaching the apical region with little or no insertion trauma. This article discusses the potential benefits of deep insertion which are obtained using pitch-locked temporal stimulation patterns. Besides the access to low frequency information, further advantages of deeply inserted long electrodes are the possibility to better approximate the correct tonotopic location of contacts, the coverage of a wider range of cochlear locations, and the somewhat reduced channel interaction due to the wider contact separation for a given number of channels. A newly developed set of strategies has been shown to improve speech understanding in noise and to enhance sound quality by providing a more "natural" impression, which especially becomes obvious when listening to music. The benefits of deep insertion should not, however, be compromised by structural damage during insertion. The small cross section and the high flexibility of the new electrodes can help to ensure less traumatic insertions as demonstrated by patients' hearing preservation rate. This article is part of a Special Issue entitled . PMID:25456089

  10. MTR MAIN FLOOR. MEN DEMONSTRATE INSERTION OF DUMMY PLUG INTO ...

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

    MTR MAIN FLOOR. MEN DEMONSTRATE INSERTION OF DUMMY PLUG INTO AN MTR BEAM HOLE. ONE MAN CHECKS RADIATION LEVEL AT THE END OF THE UNIVERSAL COFFIN, WHILE ANOTHER USES TOOL TO INSERT PLUG INTO HOLE THROUGH COFFIN. MEN WEAR "ANTI-C" (ANTI-CONTAMINATION) CLOTHING. INL NEGATIVE NO. 6198. R.G. Larsen, Photographer, 6/27/1952 - Idaho National Engineering Laboratory, Test Reactor Area, Materials & Engineering Test Reactors, Scoville, Butte County, ID

  11. Seamless Insertion of Pulmonary Nodules in Chest CT Images.

    PubMed

    Pezeshk, Aria; Sahiner, Berkman; Zeng, Rongping; Wunderlich, Adam; Chen, Weijie; Petrick, Nicholas

    2015-12-01

    The availability of large medical image datasets is critical in many applications, such as training and testing of computer-aided diagnosis systems, evaluation of segmentation algorithms, and conducting perceptual studies. However, collection of data and establishment of ground truth for medical images are both costly and difficult. To address this problem, we are developing an image blending tool that allows users to modify or supplement existing datasets by seamlessly inserting a lesion extracted from a source image into a target image. In this study, we focus on the application of this tool to pulmonary nodules in chest CT exams. We minimize the impact of user skill on the perceived quality of the composite image by limiting user involvement to two simple steps: the user first draws a casual boundary around a nodule in the source, and, then, selects the center of desired insertion area in the target. We demonstrate the performance of our system on clinical samples, and report the results of a reader study evaluating the realism of inserted nodules compared to clinical nodules. We further evaluate our image blending techniques using phantoms simulated under different noise levels and reconstruction filters. Specifically, we compute the area under the ROC curve of the Hotelling observer (HO) and noise power spectrum of regions of interest enclosing native and inserted nodules, and compare the detectability, noise texture, and noise magnitude of inserted and native nodules. Our results indicate the viability of our approach for insertion of pulmonary nodules in clinical CT images. PMID:26080378

  12. Evaluation of a high resolution silicon PET insert module

    NASA Astrophysics Data System (ADS)

    Grkovski, Milan; Brzezinski, Karol; Cindro, Vladimir; Clinthorne, Neal H.; Kagan, Harris; Lacasta, Carlos; Mikuž, Marko; Solaz, Carles; Studen, Andrej; Weilhammer, Peter; Žontar, Dejan

    2015-07-01

    Conventional PET systems can be augmented with additional detectors placed in close proximity of the region of interest. We developed a high resolution PET insert module to evaluate the added benefit of such a combination. The insert module consists of two back-to-back 1 mm thick silicon sensors, each segmented into 1040 1 mm2 pads arranged in a 40 by 26 array. A set of 16 VATAGP7.1 ASICs and a custom assembled data acquisition board were used to read out the signal from the insert module. Data were acquired in slice (2D) geometry with a Jaszczak phantom (rod diameters of 1.2-4.8 mm) filled with 18F-FDG and the images were reconstructed with ML-EM method. Both data with full and limited angular coverage from the insert module were considered and three types of coincidence events were combined. The ratio of high-resolution data that substantially improves quality of the reconstructed image for the region near the surface of the insert module was estimated to be about 4%. Results from our previous studies suggest that such ratio could be achieved at a moderate technological expense by using an equivalent of two insert modules (an effective sensor thickness of 4 mm).

  13. Cervical Lidocaine for IUD Insertional Pain: a Randomized Controlled Trial

    PubMed Central

    McNicholas, Colleen P.; Madden, Tessa; Zhao, Qiuhong; Secura, Gina; Allsworth, Jenifer E.; Peipert, Jeffrey F.

    2012-01-01

    Objective Anticipated pain with intrauterine device (IUD) insertion may be a barrier to widespread use. Our objective was to evaluate the efficacy of intracervical 2% lidocaine gel for pain relief with IUD insertion. Study Design We performed a double-blind, randomized controlled trial of women undergoing IUD insertion. Participants were randomly assigned to 2% lidocaine or placebo gel. Study gel (3ccs) wase placed 3 minutes prior to IUD insertion. Pain scores were measured at various time points using a 10-point visual analog scale. Results Of the 200 participants randomized, 199 completed the study. Pain scores among lidocaine and placebo arms were similar at tenaculum placement (lidocaine and placebo; median 4, range 0–10 p=0.15) as well as with insertion (lidocaine: median 5 range 1–10, placebo: median 6 range 0–10 p=0.16). These results did not differ by parity. Conclusions Topical or intracervical 2% lidocaine gel prior to IUD insertion does not decrease pain scores. PMID:23107081

  14. Retrotransposon insertions in the clonal evolution of pancreatic ductal adenocarcinoma.

    PubMed

    Rodić, Nemanja; Steranka, Jared P; Makohon-Moore, Alvin; Moyer, Allison; Shen, Peilin; Sharma, Reema; Kohutek, Zachary A; Huang, Cheng Ran; Ahn, Daniel; Mita, Paolo; Taylor, Martin S; Barker, Norman J; Hruban, Ralph H; Iacobuzio-Donahue, Christine A; Boeke, Jef D; Burns, Kathleen H

    2015-09-01

    Pancreatic ductal adenocarcinoma (PDAC) is typically diagnosed after the disease has metastasized; it is among the most lethal forms of cancer. We recently described aberrant expression of an open reading frame 1 protein, ORF1p, encoded by long interspersed element-1 (LINE-1; L1) retrotransposon, in PDAC. To test whether LINE-1 expression leads to somatic insertions of this mobile DNA, we used a targeted method to sequence LINE-1 insertion sites in matched PDAC and normal samples. We found evidence of 465 somatic LINE-1 insertions in 20 PDAC genomes, which were absent from corresponding normal samples. In cases in which matched normal tissue, primary PDAC and metastatic disease sites were available, insertions were found in primary and metastatic tissues in differing proportions. Two adenocarcinomas secondarily involving the pancreas, but originating in the stomach and duodenum, acquired insertions with a similar discordance between primary and metastatic sites. Together, our findings show that LINE-1 contributes to the genetic evolution of PDAC and suggest that somatic insertions are acquired discontinuously in gastrointestinal neoplasms. PMID:26259033

  15. Sensorless motion planning for medical needle insertion in deformable tissues.

    PubMed

    Alterovitz, Ron; Goldberg, Kenneth Y; Pouliot, Jean; Hsu, I-Chow Joe

    2009-03-01

    Minimally invasive medical procedures such as biopsies, anesthesia drug injections, and brachytherapy cancer treatments require inserting a needle to a specific target inside soft tissues. This is difficult because needle insertion displaces and deforms the surrounding soft tissues causing the target to move during the procedure. To facilitate physician training and preoperative planning for these procedures, we develop a needle insertion motion planning system based on an interactive simulation of needle insertion in deformable tissues and numerical optimization to reduce placement error. We describe a 2-D physically based, dynamic simulation of needle insertion that uses a finite-element model of deformable soft tissues and models needle cutting and frictional forces along the needle shaft. The simulation offers guarantees on simulation stability for mesh modifications and achieves interactive, real-time performance on a standard PC. Using texture mapping, the simulation provides visualization comparable to ultrasound images that the physician would see during the procedure. We use the simulation as a component of a sensorless planning algorithm that uses numerical optimization to compute needle insertion offsets that compensate for tissue deformations. We apply the method to radioactive seed implantation during permanent seed prostate brachytherapy to minimize seed placement error. PMID:19126473

  16. Defining Electron Backscatter Diffraction Resolution

    SciTech Connect

    El-Dasher, B S; Rollett, A D

    2005-02-07

    Automated electron backscatter diffraction (EBSD) mapping systems have existed for more than 10 years [1,2], and due to their versatility in characterizing multiple aspects of microstructure, they have become an important tool in microscale crystallographic studies. Their increasingly widespread use however raises questions about their accuracy in both determining crystallographic orientations, as well as ensuring that the orientation information is spatially correct. The issue of orientation accuracy (as defined by angular resolution) has been addressed previously [3-5]. While the resolution of EBSD systems is typically quoted to be on the order of 1{sup o}, it has been shown that by increasing the pattern quality via acquisition parameter adjustment, the angular resolution can be improved to sub-degree levels. Ultimately, the resolution is dependent on how it is identified. In some cases it can be identified as the orientation relative to a known absolute, in others as the misorientation between nearest neighbor points in a scan. Naturally, the resulting values can be significantly different. Therefore, a consistent and universal definition of resolution that can be applied to characterize any EBSD system is necessary, and is the focus of the current study. In this work, a Phillips (FEI) XL-40 FEGSEM coupled to a TexSEM Laboratories OIM system was used. The pattern capturing hardware consisted of both a 512 by 512 pixel SIT CCD camera and a 1300 by 1030 pixel Peltier cooled CCD camera. Automated scans of various sizes, each consisting of 2500 points, were performed on a commercial-grade single crystal silicon wafer used for angular resolution measurements. To adequately quantify angular resolution for all possible EBSD applications we define two angular values. The first is {omega}{sub center}, the mean of the misorientation angle distribution between all scan points and the scan point coincident to the calibration source (typically the scan center). The {omega

  17. Biologically distinct subsets of nevi.

    PubMed

    Rogers, Tova; Marino, Maria L; Raciti, Patricia; Jain, Manu; Busam, Klaus J; Marchetti, Michael A; Marghoob, Ashfaq A

    2016-08-01

    Melanocytic nevi (MN) encompass a range of benign tumors with varying microscopic and macroscopic features. Their development is a multifactorial process under genetic and environmental influences. The clinical importance of MN lies in distinguishing them from melanoma and in recognizing their associations with melanoma risk and cancer syndromes. Historically, the distinction between the different types of MN, as well as between MN and melanoma, was based on clinical history, gross morphology, and histopathological features. While histopathology with clinical correlation remains the gold standard for differentiating and diagnosing melanocytic lesions, in some cases, this may not be possible. The use of dermoscopy has allowed for the assessment of subsurface skin structures and has contributed to the clinical evaluation and classification of MN. Genetic profiling, while still in its early stages, has the greatest potential to refine the classification of MN by clarifying their developmental processes, biological behaviors, and relationships to melanoma. Here we review the most salient clinical, dermoscopic, histopathological, and genetic features of different MN subgroups. PMID:27119653

  18. Polar interactions trump hydrophobicity in stabilizing the self-inserting membrane protein Mistic.

    PubMed

    Broecker, Jana; Fiedler, Sebastian; Gimpl, Katharina; Keller, Sandro

    2014-10-01

    Canonical integral membrane proteins are attached to lipid bilayers through hydrophobic transmembrane helices, whose topogenesis requires sophisticated insertion machineries. By contrast, membrane proteins that, for evolutionary or functional reasons, cannot rely on these machineries need to resort to driving forces other than hydrophobicity. A striking example is the self-inserting Bacillus subtilis protein Mistic, which is involved in biofilm formation and has found application as a fusion tag supporting the recombinant production and bilayer insertion of other membrane proteins. Although this unusual protein contains numerous polar and charged residues and lacks characteristic membrane-interaction motifs, it is tightly bound to membranes in vivo and membrane-mimetic systems in vitro. Therefore, we set out to quantify the contributions from polar and nonpolar interactions to the coupled folding and insertion of Mistic. To this end, we defined conditions under which the protein can be unfolded completely and reversibly from various detergent micelles by urea in a two-state equilibrium and where the unfolded state is independent of the detergent used for solubilizing the folded state. This enabled equilibrium unfolding experiments previously used for soluble and β-barrel membrane proteins, revealing that polar interactions with ionic and zwitterionic headgroups and, presumably, the interfacial dipole potential stabilize the protein much more efficiently than nonpolar interactions with the micelle core. These findings unveil the forces that allow a protein to tightly interact with a membrane-mimetic environment without major hydrophobic contributions and rationalize the differential suitability of detergents for the extraction and solubilization of Mistic-tagged membrane proteins. PMID:25177765

  19. Defining the Stimulus - A Memoir

    PubMed Central

    Terrace, Herbert

    2010-01-01

    The eminent psychophysicist, S. S. Stevens, once remarked that, “the basic problem of psychology was the definition of the stimulus” (Stevens, 1951, p. 46). By expanding the traditional definition of the stimulus, the study of animal learning has metamorphosed into animal cognition. The main impetus for that change was the recognition that it is often necessary to postulate a representation between the traditional S and R of learning theory. Representations allow a subject to re-present a stimulus it learned previously that is currently absent. Thus, in delayed-matching-to-sample, one has to assume that a subject responds to a representation of the sample during test if it responds correctly. Other examples, to name but a few, include concept formation, spatial memory, serial memory, learning a numerical rule, imitation and metacognition. Whereas a representation used to be regarded as a mentalistic phenomenon that was unworthy of scientific inquiry, it can now be operationally defined. To accommodate representations, the traditional discriminative stimulus has to be expanded to allow for the role of representations. The resulting composite can account for a significantly larger portion of the variance of performance measures than the exteroceptive stimulus could by itself. PMID:19969047

  20. Endothelial progenitor cells: identity defined?

    PubMed Central

    Timmermans, Frank; Plum, Jean; Yöder, Mervin C; Ingram, David A; Vandekerckhove, Bart; Case, Jamie

    2009-01-01

    Abstract In the past decade, researchers have gained important insights on the role of bone marrow (BM)-derived cells in adult neovascularization. A subset of BM-derived cells, called endothelial progenitor cells (EPCs), has been of particular interest, as these cells were suggested to home to sites of neovascularization and neoendothelialization and differentiate into endothelial cells (ECs) in situ, a process referred to as postnatal vasculogenesis. Therefore, EPCs were proposed as a potential regenerative tool for treating human vascular disease and a possible target to restrict vessel growth in tumour pathology. However, conflicting results have been reported in the field, and the identification, characterization, and exact role of EPCs in vascular biology is still a subject of much discussion. The focus of this review is on the controversial issues in the field of EPCs which are related to the lack of a unique EPC marker, identification challenges related to the paucity of EPCs in the circulation, and the important phenotypical and functional overlap between EPCs, haematopoietic cells and mature ECs. We also discuss our recent findings on the origin of endothelial outgrowth cells (EOCs), showing that this in vitro defined EC population does not originate from circulating CD133+ cells or CD45+ haematopoietic cells. PMID:19067770

  1. DYRK1A haploinsufficiency causes a new recognizable syndrome with microcephaly, intellectual disability, speech impairment, and distinct facies.

    PubMed

    Ji, Jianling; Lee, Hane; Argiropoulos, Bob; Dorrani, Naghmeh; Mann, John; Martinez-Agosto, Julian A; Gomez-Ospina, Natalia; Gallant, Natalie; Bernstein, Jonathan A; Hudgins, Louanne; Slattery, Leah; Isidor, Bertrand; Le Caignec, Cédric; David, Albert; Obersztyn, Ewa; Wiśniowiecka-Kowalnik, Barbara; Fox, Michelle; Deignan, Joshua L; Vilain, Eric; Hendricks, Emily; Horton Harr, Margaret; Noon, Sarah E; Jackson, Jessi R; Wilkens, Alisha; Mirzaa, Ghayda; Salamon, Noriko; Abramson, Jeff; Zackai, Elaine H; Krantz, Ian; Innes, A Micheil; Nelson, Stanley F; Grody, Wayne W; Quintero-Rivera, Fabiola

    2015-11-01

    Dual-specificity tyrosine-(Y)-phosphorylation-regulated kinase 1 A (DYRK1A ) is a highly conserved gene located in the Down syndrome critical region. It has an important role in early development and regulation of neuronal proliferation. Microdeletions of chromosome 21q22.12q22.3 that include DYRK1A (21q22.13) are rare and only a few pathogenic single-nucleotide variants (SNVs) in the DYRK1A gene have been described, so as of yet, the landscape of DYRK1A disruptions and their associated phenotype has not been fully explored. We have identified 14 individuals with de novo heterozygous variants of DYRK1A; five with microdeletions, three with small insertions or deletions (INDELs) and six with deleterious SNVs. The analysis of our cohort and comparison with published cases reveals that phenotypes are consistent among individuals with the 21q22.12q22.3 microdeletion and those with translocation, SNVs, or INDELs within DYRK1A. All individuals shared congenital microcephaly at birth, intellectual disability, developmental delay, severe speech impairment, short stature, and distinct facial features. The severity of the microcephaly varied from -2 SD to -5 SD. Seizures, structural brain abnormalities, eye defects, ataxia/broad-based gait, intrauterine growth restriction, minor skeletal abnormalities, and feeding difficulties were present in two-thirds of all affected individuals. Our study demonstrates that haploinsufficiency of DYRK1A results in a new recognizable syndrome, which should be considered in individuals with Angelman syndrome-like features and distinct facial features. Our report represents the largest cohort of individuals with DYRK1A disruptions to date, and is the first attempt to define consistent genotype-phenotype correlations among subjects with 21q22.13 microdeletions and DYRK1A SNVs or small INDELs. PMID:25944381

  2. System design of the Pioneer Venus spacecraft. Volume 10: Propulsion/orbit insertion subsystem studies

    NASA Technical Reports Server (NTRS)

    Rosenstein, B. J.

    1973-01-01

    The Pioneer Venus orbiter and multiprobe missions require spacecraft maneuvers for successful accomplishment. This report presents the results of studies performed to define the propulsion subsystems required to perform those maneuvers. Primary goals were to define low mass subsystems capable of performing the required missions with a high degree of reliability for low cost. A review was performed of all applicable propellants and thruster types, as well as propellant management techniques. Based on this review, a liquid monopropellant hydrazine propulsion subsystem was selected for all multiprobe mission maneuvers, and for all orbiter mission maneuvers except orbit insertion. A pressure blowdown operating mode was selected using helium as the pressurizing gas. The forces associated with spacecraft rotations were used to control the liquid-gas interface and resulting propellant orientation within the tank.

  3. Focus on peripherally inserted central catheters in critically ill patients

    PubMed Central

    Cotogni, Paolo; Pittiruti, Mauro

    2014-01-01

    Venous access devices are of pivotal importance for an increasing number of critically ill patients in a variety of disease states and in a variety of clinical settings (emergency, intensive care, surgery) and for different purposes (fluids or drugs infusions, parenteral nutrition, antibiotic therapy, hemodynamic monitoring, procedures of dialysis/apheresis). However, healthcare professionals are commonly worried about the possible consequences that may result using a central venous access device (CVAD) (mainly, bloodstream infections and thrombosis), both peripherally inserted central catheters (PICCs) and centrally inserted central catheters (CICCs). This review aims to discuss indications, insertion techniques, and care of PICCs in critically ill patients. PICCs have many advantages over standard CICCs. First of all, their insertion is easy and safe -due to their placement into peripheral veins of the arm- and the advantage of a central location of catheter tip suitable for all osmolarity and pH solutions. Using the ultrasound-guidance for the PICC insertion, the risk of hemothorax and pneumothorax can be avoided, as well as the possibility of primary malposition is very low. PICC placement is also appropriate to avoid post-procedural hemorrhage in patients with an abnormal coagulative state who need a CVAD. Some limits previously ascribed to PICCs (i.e., low flow rates, difficult central venous pressure monitoring, lack of safety for radio-diagnostic procedures, single-lumen) have delayed their start up in the intensive care units as common practice. Though, the recent development of power-injectable PICCs overcomes these technical limitations and PICCs have started to spread in critical care settings. Two important take-home messages may be drawn from this review. First, the incidence of complications varies depending on venous accesses and healthcare professionals should be aware of the different clinical performance as well as of the different risks

  4. Minimally disruptive needle insertion: a biologically inspired solution.

    PubMed

    Leibinger, Alexander; Oldfield, Matthew J; Rodriguez Y Baena, Ferdinando

    2016-06-01

    The mobility of soft tissue can cause inaccurate needle insertions. Particularly in steering applications that employ thin and flexible needles, large deviations can occur between pre-operative images of the patient, from which a procedure is planned, and the intra-operative scene, where a procedure is executed. Although many approaches for reducing tissue motion focus on external constraining or manipulation, little attention has been paid to the way the needle is inserted and actuated within soft tissue. Using our biologically inspired steerable needle, we present a method of reducing the disruptiveness of insertions by mimicking the burrowing mechanism of ovipositing wasps. Internal displacements and strains in three dimensions within a soft tissue phantom are measured at the needle interface, using a scanning laser-based image correlation technique. Compared to a conventional insertion method with an equally sized needle, overall displacements and strains in the needle vicinity are reduced by 30% and 41%, respectively. The results show that, for a given net speed, needle insertion can be made significantly less disruptive with respect to its surroundings by employing our biologically inspired solution. This will have significant impact on both the safety and targeting accuracy of percutaneous interventions along both straight and curved trajectories. PMID:27274797

  5. Insertion of nanoparticles into polymer brush under variable solvent conditions.

    PubMed

    Egorov, S A

    2012-10-01

    In this work, two-dimensional lattice-based self-consistent field theory is used to study the free energy cost associated with the insertion of a nanoparticle into a polymer brush. The nanoparticle is modeled as a cylinder and the self-consistent field equations are formulated on a cylindrical lattice. The use of two-dimensional formalism makes it possible to take into account the distortion of the brush density profile due to the embedded nanoinclusion. The insertion free energy penalty is analyzed as a function of the particle size, the brush grafting density, and the solvent quality. In agreement with the earlier simulation work, we find that the insertion free energy cost increases both with the particle size and the brush grafting density and decreases with deteriorating solvent quality. For nanoparticles located deep inside the brush, the insertion free energy is shown to scale with either squared (good solvent) or cubed (poor solvent) monomer volume fraction profile, in agreement with the earlier theoretical results. For shallow nanoinclusions located close to the brush surface, the insertion free energy is shown to scale linearly with the monomer volume fraction profile under both good and theta solvent conditions, again in agreement with the earlier work. PMID:23039611

  6. Insertion of nanoparticles into polymer brush under variable solvent conditions

    NASA Astrophysics Data System (ADS)

    Egorov, S. A.

    2012-10-01

    In this work, two-dimensional lattice-based self-consistent field theory is used to study the free energy cost associated with the insertion of a nanoparticle into a polymer brush. The nanoparticle is modeled as a cylinder and the self-consistent field equations are formulated on a cylindrical lattice. The use of two-dimensional formalism makes it possible to take into account the distortion of the brush density profile due to the embedded nanoinclusion. The insertion free energy penalty is analyzed as a function of the particle size, the brush grafting density, and the solvent quality. In agreement with the earlier simulation work, we find that the insertion free energy cost increases both with the particle size and the brush grafting density and decreases with deteriorating solvent quality. For nanoparticles located deep inside the brush, the insertion free energy is shown to scale with either squared (good solvent) or cubed (poor solvent) monomer volume fraction profile, in agreement with the earlier theoretical results. For shallow nanoinclusions located close to the brush surface, the insertion free energy is shown to scale linearly with the monomer volume fraction profile under both good and theta solvent conditions, again in agreement with the earlier work.

  7. Mechanisms of integral membrane protein insertion and folding

    PubMed Central

    2014-01-01

    The biogenesis, folding, and structure of α-helical membrane proteins (MPs) are important to understand because they underlie virtually all physiological processes in cells including key metabolic pathways, such as the respiratory chain and the photosystems, and the transport of solutes and signals across membranes. Nearly all MPs require translocons—often referred to as protein-conducting channels—for proper insertion into their target membrane. Remarkable progress toward understanding the structure and functioning of translocons has been made during the past decade. Here we review and assess this progress critically. All available evidence indicates that MPs are equilibrium structures that achieve their final structural states by folding along thermodynamically controlled pathways. The main challenge for cells is the targeting and membrane insertion of highly hydrophobic amino acid sequences. Targeting and insertion are managed in cells principally by interactions between ribosomes and membrane-embedded translocons. Our review examines the biophysical and biological boundaries of membrane protein insertion and the folding of polytopic membrane proteins in vivo. A theme of the review is the under-appreciated role of basic thermodynamic principles in MP folding and assembly. Thermodynamics not only dictates the final folded structure, it is the driving force for the evolution of the ribosome-translocon system of assembly. We conclude the review with a perspective suggesting a new view of translocon-guided MP insertion. PMID:25277655

  8. Some physical and chemical indices of clique-inserted lattices

    NASA Astrophysics Data System (ADS)

    Zhang, Zuhe

    2013-10-01

    The operation of replacing every vertex of an r-regular lattice H by a complete graph of order r is called clique-insertion, and the resulting lattice is called the clique-inserted lattice of H. For any given r-regular lattice, applying this operation iteratively, an infinite family of r-regular lattices is generated. Some interesting lattices including the 3-12-12 lattice can be constructed this way. In this paper, we recall the relationship between the spectra of an r-regular lattice and that of its clique-inserted lattice, and investigate the graph energy and resistance distance statistics. As an application, the asymptotic energy per vertex and average resistance distance of the 3-12-12 and 3-6-24 lattices are computed. We also give formulae expressing the numbers of spanning trees and dimer coverings of the kth iterated clique-inserted lattices in terms of those of the original one. Moreover, we show that new families of expander graphs can be constructed from the known ones by clique-insertion.

  9. Direct insertion of metal ions into tetrasulfonated phthalocyanine

    SciTech Connect

    Linkous, C.A.; Shea, C.E.; Jaber, M.R.A. )

    1989-07-01

    A series of metal salts were reacted with aqueous solutions of the tetrasulfonated free base phthalocyanine (H{sub 2}TsPc) in an attempt to prepare the corresponding metal TsPc derivative by direct insertion instead of the usual template reaction in a urea melt. Spectrophotometric analysis showed that Ni{sup 2+}, Cu{sup 2+}, Zn{sup 2+}, Co{sup 2+}, Fe{sup 2+}, Mn{sup 2+}, Pd{sup 2+}, Cd{sup 2+}, and Sn{sup 2+} could be successfully inserted; higher oxidation states as well as Pb{sup 2+} caused precipitation. Reducing species such as Cr{sup 2+} and V{sup 2+} reduced H{sub 2}TsPc but did not insert; Sn{sup 2+} inserted with formation of an air-sensitive intermediate species. Mg{sup 2+}, VO{sup 2+}, Pt{sup 2+}, and Hg{sup 2+} were unreactive. It is recommended that insertion may be the preferable method for synthesis of the MTsPc's listed above when air sensitivity, reaction time, and microscale are important issues in an overall synthetic scheme. 24 refs., 4 figs.

  10. Transposable element insertions have strongly affected human evolution

    PubMed Central

    Britten, Roy J.

    2010-01-01

    Comparison of a full collection of the transposable element (TE) sequences of vertebrates with genome sequences shows that the human genome makes 655 perfect full-length matches. The cause is that the human genome contains many active TEs that have caused TE inserts in relatively recent times. These TE inserts in the human genome are several types of young Alus (AluYa5, AluYb8, AluYc1, etc.). Work in many laboratories has shown that such inserts have many effects including changes in gene expression, increases in recombination, and unequal crossover. The time of these very effective changes in the human lineage genome extends back about 4 million years according to these data and very likely much earlier. Rapid human lineage-specific evolution, including brain size is known to have also occurred in the last few million years. Alu insertions likely underlie rapid human lineage evolution. They are known to have many effects. Examples are listed in which TE sequences have influenced human-specific genes. The proposed model is that the many TE insertions created many potentially effective changes and those selected were responsible for a part of the striking human lineage evolution. The combination of the results of these events that were selected during human lineage evolution was apparently effective in producing a successful and rapidly evolving species. PMID:21041622

  11. Customizable engineered blood vessels using 3D printed inserts.

    PubMed

    Pinnock, Cameron B; Meier, Elizabeth M; Joshi, Neeraj N; Wu, Bin; Lam, Mai T

    2016-04-15

    Current techniques for tissue engineering blood vessels are not customizable for vascular size variation and vessel wall thickness. These critical parameters vary widely between the different arteries in the human body, and the ability to engineer vessels of varying sizes could increase capabilities for disease modeling and treatment options. We present an innovative method for producing customizable, tissue engineered, self-organizing vascular constructs by replicating a major structural component of blood vessels - the smooth muscle layer, or tunica media. We utilize a unique system combining 3D printed plate inserts to control construct size and shape, and cell sheets supported by a temporary fibrin hydrogel to encourage cellular self-organization into a tubular form resembling a natural artery. To form the vascular construct, 3D printed inserts are adhered to tissue culture plates, fibrin hydrogel is deposited around the inserts, and human aortic smooth muscle cells are then seeded atop the fibrin hydrogel. The gel, aided by the innate contractile properties of the smooth muscle cells, aggregates towards the center post insert, creating a tissue ring of smooth muscle cells. These rings are then stacked into the final tubular construct. Our methodology is robust, easily repeatable and allows for customization of cellular composition, vessel wall thickness, and length of the vessel construct merely by varying the size of the 3D printed inserts. This platform has potential for facilitating more accurate modeling of vascular pathology, serving as a drug discovery tool, or for vessel repair in disease treatment. PMID:26732049

  12. Recombination of an intrachromosomal paracentric insertion of chromosome 3

    SciTech Connect

    Best, R.G.; Burnett, W.J.; Brock, J.K.

    1994-09-01

    Cytogenetic studies were initiated on a newborn female due to multiple congenital anomalies including microcephaly, clinodactyly, abnormal positioning of hands, left facial palsy, heart defect, sacral dimple, and facial dysmorphic features. Facial features were described as low set rotated ears, nystagmus, and a small, flattened nose. A structural rearrangement of the long arm of chromosome 3 was observed with a complex banding pattern. Study of parental chromosomes revealed a normal male pattern for the father, and an intrachromosomal insertion on the long arm of chromosome 3 for the mother described as 46,XX,dir ins(3)(q21q23q26.2). Further characterization of the proband`s structurally abnormal chromosome 3 revealed a karyotype best described as: 46,XX,rec(3),dupq23{r_arrow}q26.2::q21{r_arrow}q23,dir ins(3)(q21q23q26.2), which is a partial duplication of both the inserted segment as well as the intervening segment between the inserted segment and the insertion site. This would appear to be the result of a three-strand double cross-over within the insertion loop. Molecular cytogenetic studies are presently underway to further elucidate chromosome structure of the proband and her mother.

  13. Insertion of Totally Implantable Central Venous Access Devices by Surgeons

    PubMed Central

    An, Hyeonjun; Ryu, Chun-Geun; Jung, Eun-Joo; Kang, Hyun Jong; Paik, Jin Hee; Yang, Jung-Hyun

    2015-01-01

    Purpose The aim of this study is to evaluate the results for the insertion of totally implantable central venous access devices (TICVADs) by surgeons. Methods Total 397 patients, in whom TICVADs had been inserted for intravenous chemotherapy between September 2008 and June 2014, were pooled. This procedure was performed under local anesthesia in an operation room. The insertion site for the TICVAD was mainly in the right-side subclavian vein. In the case of breast cancer patients, the subclavian vein opposite the surgical site was used for insertion. Results The 397 patients included 73 males and 324 females. Primary malignant tumors were mainly colorectal and breast cancer. The mean operation time was 54 minutes (18-276 minutes). Operation-related complications occurred in 33 cases (8.3%). Early complications developed in 15 cases with catheter malposition and puncture failure. Late complications, which developed after 24 hours, included inflammation in 6 cases, skin necrosis in 6 cases, hematoma in 3 cases, port malfunction in 1 case, port migration in 1 case, and intractable pain at the port site in 1 case. Conclusion Insertion of a TICVAD under local anesthesia by a surgeon is a relatively safe procedure. Meticulous undermining of the skin and carefully managing the TICVAD could minimize complications. PMID:25960974

  14. Insertion of Isocyanides into N-Si Bonds: Multicomponent Reactions with Azines Leading to Potent Antiparasitic Compounds.

    PubMed

    Kishore, Kranti G; Ghashghaei, Ouldouz; Estarellas, Carolina; Mestre, M Mar; Monturiol, Cristina; Kielland, Nicola; Kelly, John M; Francisco, Amanda Fortes; Jayawardhana, Shiromani; Muñoz-Torrero, Diego; Pérez, Belén; Luque, F Javier; Gámez-Montaño, Rocío; Lavilla, Rodolfo

    2016-07-25

    Trimethylsilyl chloride is an efficient activating agent for azines in isocyanide-based reactions, which then proceed through a key insertion of the isocyanide into a N-Si bond. The reaction is initiated by N activation of the azine, followed by nucleophilic attack of an isocyanide in a Reissert-type process. Finally, a second equivalent of the same or a different isocyanide inserts into the N-Si bond leading to the final adduct. The use of distinct nucleophiles leads to a variety of α-substituted dihydroazines after a selective cascade process. Based on computational studies, a mechanistic hypothesis for the course of these reactions was proposed. The resulting products exhibit significant activity against Trypanosoma brucei and T. cruzi, featuring favorable drug-like properties and safety profiles. PMID:27314630

  15. Comparison of large-insert, small-insert and pyrosequencing libraries for metagenomic analysis.

    PubMed

    Danhorn, Thomas; Young, Curtis R; DeLong, Edward F

    2012-11-01

    The development of DNA sequencing methods for characterizing microbial communities has evolved rapidly over the past decades. To evaluate more traditional, as well as newer methodologies for DNA library preparation and sequencing, we compared fosmid, short-insert shotgun and 454 pyrosequencing libraries prepared from the same metagenomic DNA samples. GC content was elevated in all fosmid libraries, compared with shotgun and 454 libraries. Taxonomic composition of the different libraries suggested that this was caused by a relative underrepresentation of dominant taxonomic groups with low GC content, notably Prochlorales and the SAR11 cluster, in fosmid libraries. While these abundant taxa had a large impact on library representation, we also observed a positive correlation between taxon GC content and fosmid library representation in other low-GC taxa, suggesting a general trend. Analysis of gene category representation in different libraries indicated that the functional composition of a library was largely a reflection of its taxonomic composition, and no additional systematic biases against particular functional categories were detected at the level of sequencing depth in our samples. Another important but less predictable factor influencing the apparent taxonomic and functional library composition was the read length afforded by the different sequencing technologies. Our comparisons and analyses provide a detailed perspective on the influence of library type on the recovery of microbial taxa in metagenomic libraries and underscore the different uses and utilities of more traditional, as well as contemporary 'next-generation' DNA library construction and sequencing technologies for exploring the genomics of the natural microbial world. PMID:22534608

  16. Comparison of large-insert, small-insert and pyrosequencing libraries for metagenomic analysis

    PubMed Central

    Danhorn, Thomas; Young, Curtis R; DeLong, Edward F

    2012-01-01

    The development of DNA sequencing methods for characterizing microbial communities has evolved rapidly over the past decades. To evaluate more traditional, as well as newer methodologies for DNA library preparation and sequencing, we compared fosmid, short-insert shotgun and 454 pyrosequencing libraries prepared from the same metagenomic DNA samples. GC content was elevated in all fosmid libraries, compared with shotgun and 454 libraries. Taxonomic composition of the different libraries suggested that this was caused by a relative underrepresentation of dominant taxonomic groups with low GC content, notably Prochlorales and the SAR11 cluster, in fosmid libraries. While these abundant taxa had a large impact on library representation, we also observed a positive correlation between taxon GC content and fosmid library representation in other low-GC taxa, suggesting a general trend. Analysis of gene category representation in different libraries indicated that the functional composition of a library was largely a reflection of its taxonomic composition, and no additional systematic biases against particular functional categories were detected at the level of sequencing depth in our samples. Another important but less predictable factor influencing the apparent taxonomic and functional library composition was the read length afforded by the different sequencing technologies. Our comparisons and analyses provide a detailed perspective on the influence of library type on the recovery of microbial taxa in metagenomic libraries and underscore the different uses and utilities of more traditional, as well as contemporary ‘next-generation' DNA library construction and sequencing technologies for exploring the genomics of the natural microbial world. PMID:22534608

  17. Studies with sample conductivity, insertion rates, and particle deflection in a continuous flow electrophoresis system

    NASA Technical Reports Server (NTRS)

    Williams, G., Jr.

    1982-01-01

    The continuous flow electrophoresis system makes electrophoresis possible in a free-flowing film of aqueous electrolyte medium. The sample continuously enters the electrolyte at the top of the chamber and is subjected to the action of a lateral dc field. This divides the sample into fractions since each component has a distinctive electrophoretic mobility. Tests were made using monodisperse polystyrene latex microspheres to determine optimum sample conductivity, insertion rates and optimum electric field applications as baseline data for future STS flight experiments. Optimum sample flow rates for the selected samples were determined to be approximately 26 micro-liters/min. Experiments with samples in deionized water yielded best results and voltages in the 20 V/cm to 30 V/cm range were optimum. Deflections of formaldehyde fixed turkey and bovine erythrocytes were determined using the continuous flow electrophoresis system. The effects of particle interactions on sample resolution and migration in the chamber was also evaluated.

  18. Nuclear-receptor-mediated telomere insertion leads to genome instability in ALT cancers.

    PubMed

    Marzec, Paulina; Armenise, Claudia; Pérot, Gaëlle; Roumelioti, Fani-Marlen; Basyuk, Eugenia; Gagos, Sarantis; Chibon, Frédéric; Déjardin, Jérôme

    2015-02-26

    The breakage-fusion-bridge cycle is a classical mechanism of telomere-driven genome instability in which dysfunctional telomeres are fused to other chromosomal extremities, creating dicentric chromosomes that eventually break at mitosis. Here, we uncover a distinct pathway of telomere-driven genome instability, specifically occurring in cells that maintain telomeres with the alternative lengthening of telomeres mechanism. We show that, in these cells, telomeric DNA is added to multiple discrete sites throughout the genome, corresponding to regions regulated by NR2C/F transcription factors. These proteins drive local telomere DNA addition by recruiting telomeric chromatin. This mechanism, which we name targeted telomere insertion (TTI), generates potential common fragile sites that destabilize the genome. We propose that TTI driven by NR2C/F proteins contributes to the formation of complex karyotypes in ALT tumors. PMID:25723166

  19. Distinct optical properties of relativistically degenerate matter

    NASA Astrophysics Data System (ADS)

    Akbari-Moghanjoughi, M.

    2014-06-01

    In this paper, we use the collisional quantum magnetohydrodynamic (CQMHD) model to derive the transverse dielectric function of a relativistically degenerate electron fluid and investigate various optical parameters, such as the complex refractive index, the reflection and absorption coefficients, the skin-depth and optical conductivity. In this model we take into accounts effects of many parameters such as the atomic-number of the constituent ions, the electron exchange, electron diffraction effect and the electron-ion collisions. Study of the optical parameters in the solid-density, the warm-dense-matter, the big-planetary core, and the compact star number-density regimes reveals that there are distinct differences between optical characteristics of the latter and the former cases due to the fundamental effects of the relativistic degeneracy and other quantum mechanisms. It is found that in the relativistic degeneracy plasma regime, such as found in white-dwarfs and neutron star crusts, matter possess a much sharper and well-defined step-like reflection edge beyond the x-ray electromagnetic spectrum, including some part of gamma-ray frequencies. It is also remarked that the magnetic field intensity only significantly affects the plasma reflectivity in the lower number-density regime, rather than the high density limit. Current investigation confirms the profound effect of relativistic degeneracy on optical characteristics of matter and can provide an important plasma diagnostic tool for studying the physical processes within the wide scope of quantum plasma regimes be it the solid-density, inertial-confined, or astrophysical compact stars.

  20. Distinct optical properties of relativistically degenerate matter

    SciTech Connect

    Akbari-Moghanjoughi, M.

    2014-06-15

    In this paper, we use the collisional quantum magnetohydrodynamic (CQMHD) model to derive the transverse dielectric function of a relativistically degenerate electron fluid and investigate various optical parameters, such as the complex refractive index, the reflection and absorption coefficients, the skin-depth and optical conductivity. In this model we take into accounts effects of many parameters such as the atomic-number of the constituent ions, the electron exchange, electron diffraction effect and the electron-ion collisions. Study of the optical parameters in the solid-density, the warm-dense-matter, the big-planetary core, and the compact star number-density regimes reveals that there are distinct differences between optical characteristics of the latter and the former cases due to the fundamental effects of the relativistic degeneracy and other quantum mechanisms. It is found that in the relativistic degeneracy plasma regime, such as found in white-dwarfs and neutron star crusts, matter possess a much sharper and well-defined step-like reflection edge beyond the x-ray electromagnetic spectrum, including some part of gamma-ray frequencies. It is also remarked that the magnetic field intensity only significantly affects the plasma reflectivity in the lower number-density regime, rather than the high density limit. Current investigation confirms the profound effect of relativistic degeneracy on optical characteristics of matter and can provide an important plasma diagnostic tool for studying the physical processes within the wide scope of quantum plasma regimes be it the solid-density, inertial-confined, or astrophysical compact stars.

  1. Structural basis of outer membrane protein insertion by the BAM complex.

    PubMed

    Gu, Yinghong; Li, Huanyu; Dong, Haohao; Zeng, Yi; Zhang, Zhengyu; Paterson, Neil G; Stansfeld, Phillip J; Wang, Zhongshan; Zhang, Yizheng; Wang, Wenjian; Dong, Changjiang

    2016-03-01

    All Gram-negative bacteria, mitochondria and chloroplasts have outer membrane proteins (OMPs) that perform many fundamental biological processes. The OMPs in Gram-negative bacteria are inserted and folded into the outer membrane by the β-barrel assembly machinery (BAM). The mechanism involved is poorly understood, owing to the absence of a structure of the entire BAM complex. Here we report two crystal structures of the Escherichia coli BAM complex in two distinct states: an inward-open state and a lateral-open state. Our structures reveal that the five polypeptide transport-associated domains of BamA form a ring architecture with four associated lipoproteins, BamB-BamE, in the periplasm. Our structural, functional studies and molecular dynamics simulations indicate that these subunits rotate with respect to the integral membrane β-barrel of BamA to induce movement of the β-strands of the barrel and promote insertion of the nascent OMP. PMID:26901871

  2. A LAIR-1 insertion generates broadly reactive antibodies against malaria variant antigens

    PubMed Central

    Abdi, Abdirahman; Perez, Mathilde Foglierini; Geiger, Roger; Tully, Claire Maria; Jarrossay, David; Maina Ndungu, Francis; Wambua, Juliana; Bejon, Philip; Fregni, Chiara Silacci; Fernandez-Rodriguez, Blanca; Barbieri, Sonia; Bianchi, Siro; Marsh, Kevin; Thathy, Vandana; Corti, Davide; Sallusto, Federica

    2016-01-01

    Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies1–4. Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here, we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 100 amino acid collagen-binding domain of LAIR-1, an Ig superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B cell clone and carry distinct somatic mutations in the LAIR-1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine. PMID:26700814

  3. A LAIR1 insertion generates broadly reactive antibodies against malaria variant antigens.

    PubMed

    Tan, Joshua; Pieper, Kathrin; Piccoli, Luca; Abdi, Abdirahman; Foglierini, Mathilde; Geiger, Roger; Tully, Claire Maria; Jarrossay, David; Ndungu, Francis Maina; Wambua, Juliana; Bejon, Philip; Fregni, Chiara Silacci; Fernandez-Rodriguez, Blanca; Barbieri, Sonia; Bianchi, Siro; Marsh, Kevin; Thathy, Vandana; Corti, Davide; Sallusto, Federica; Bull, Peter; Lanzavecchia, Antonio

    2016-01-01

    Plasmodium falciparum antigens expressed on the surface of infected erythrocytes are important targets of naturally acquired immunity against malaria, but their high number and variability provide the pathogen with a powerful means of escape from host antibodies. Although broadly reactive antibodies against these antigens could be useful as therapeutics and in vaccine design, their identification has proven elusive. Here we report the isolation of human monoclonal antibodies that recognize erythrocytes infected by different P. falciparum isolates and opsonize these cells by binding to members of the RIFIN family. These antibodies acquired broad reactivity through a novel mechanism of insertion of a large DNA fragment between the V and DJ segments. The insert, which is both necessary and sufficient for binding to RIFINs, encodes the entire 98 amino acid collagen-binding domain of LAIR1, an immunoglobulin superfamily inhibitory receptor encoded on chromosome 19. In each of the two donors studied, the antibodies are produced by a single expanded B-cell clone and carry distinct somatic mutations in the LAIR1 domain that abolish binding to collagen and increase binding to infected erythrocytes. These findings illustrate, with a biologically relevant example, a novel mechanism of antibody diversification by interchromosomal DNA transposition and demonstrate the existence of conserved epitopes that may be suitable candidates for the development of a malaria vaccine. PMID:26700814

  4. A comparison of dense transposon insertion libraries in the Salmonella serovars Typhi and Typhimurium

    PubMed Central

    Barquist, Lars; Langridge, Gemma C.; Turner, Daniel J.; Phan, Minh-Duy; Turner, A. Keith; Bateman, Alex; Parkhill, Julian; Wain, John; Gardner, Paul P.

    2013-01-01

    Salmonella Typhi and Typhimurium diverged only ∼50 000 years ago, yet have very different host ranges and pathogenicity. Despite the availability of multiple whole-genome sequences, the genetic differences that have driven these changes in phenotype are only beginning to be understood. In this study, we use transposon-directed insertion-site sequencing to probe differences in gene requirements for competitive growth in rich media between these two closely related serovars. We identify a conserved core of 281 genes that are required for growth in both serovars, 228 of which are essential in Escherichia coli. We are able to identify active prophage elements through the requirement for their repressors. We also find distinct differences in requirements for genes involved in cell surface structure biogenesis and iron utilization. Finally, we demonstrate that transposon-directed insertion-site sequencing is not only applicable to the protein-coding content of the cell but also has sufficient resolution to generate hypotheses regarding the functions of non-coding RNAs (ncRNAs) as well. We are able to assign probable functions to a number of cis-regulatory ncRNA elements, as well as to infer likely differences in trans-acting ncRNA regulatory networks. PMID:23470992

  5. The Competition Between Insertion and Surface Binding of Benzene to the Water Heptamer

    NASA Astrophysics Data System (ADS)

    Walsh, Patrick S.; Tabor, Daniel P.; Sibert, Edwin; Zwier, Timothy S.

    2015-06-01

    Previous work on the benzene-(water)n clusters with n=7 have focused attention on the main conformer, whose S0-S1 610 R2PI transition appears +138 wn above the benzene monomer. Using resonant ion-dip infrared spectroscopy with a higher resolution IR source, we have recently returned to this cluster to record improved OH stretch infrared spectra and more thoroughly consider the possible Bz-(H2O)7 structures that might give rise to it. Analysis of that spectrum led to its assignment as an inserted cube structure with pseudo-S4 symmetry. This talk will consider the spectrum and structure of a minor conformer of Bz-(H2O)7 with R2PI transition ~65 wn to the blue of the monomer. This spectrum, recorded for the first time, shows a distinctive OH stretch infrared spectrum that is best matched with an expanded prism structure in which the seventh water molecule inserts into one edge of the hexamer prism. In this case, benzene acts as acceptor for an OH...π H-bond, sitting on the surface of a preformed water heptamer structure. The infrared spectra of the two Bz-(H2O)7 structures are compared, and the results of a local mode Hamiltonian model are applied to make an assignment for the observed structure. The monomer Hamiltonians resulting from this model shed light on the unique two- and three-coordinate water molecules found in this structure.

  6. How ticks get under your skin: insertion mechanics of the feeding apparatus of Ixodes ricinus ticks.

    PubMed

    Richter, Dania; Matuschka, Franz-Rainer; Spielman, Andrew; Mahadevan, L

    2013-12-22

    The tick Ixodes ricinus uses its mouthparts to penetrate the skin of its host and to remain attached for about a week, during which time Lyme disease spirochaetes may pass from the tick to the host. To understand how the tick achieves both tasks, penetration and attachment, with the same set of implements, we recorded the insertion events by cinematography, interpreted the mouthparts' function by scanning electron microscopy and identified their points of articulation by confocal microscopy. Our structural dynamic observations suggest that the process of insertion and attachment occurs via a ratchet-like mechanism with two distinct stages. Initially, the two telescoping chelicerae pierce the skin and, by moving alternately, generate a toehold. Subsequently, a breaststroke-like motion, effected by simultaneous flexure and retraction of both chelicerae, pulls in the barbed hypostome. This combination of a flexible, dynamic mechanical ratchet and a static holdfast thus allows the tick to solve the problem of how to penetrate skin and also remain stuck for long periods of time. PMID:24174106

  7. How ticks get under your skin: insertion mechanics of the feeding apparatus of Ixodes ricinus ticks

    PubMed Central

    Richter, Dania; Matuschka, Franz-Rainer; Spielman, Andrew; Mahadevan, L.

    2013-01-01

    The tick Ixodes ricinus uses its mouthparts to penetrate the skin of its host and to remain attached for about a week, during which time Lyme disease spirochaetes may pass from the tick to the host. To understand how the tick achieves both tasks, penetration and attachment, with the same set of implements, we recorded the insertion events by cinematography, interpreted the mouthparts’ function by scanning electron microscopy and identified their points of articulation by confocal microscopy. Our structural dynamic observations suggest that the process of insertion and attachment occurs via a ratchet-like mechanism with two distinct stages. Initially, the two telescoping chelicerae pierce the skin and, by moving alternately, generate a toehold. Subsequently, a breaststroke-like motion, effected by simultaneous flexure and retraction of both chelicerae, pulls in the barbed hypostome. This combination of a flexible, dynamic mechanical ratchet and a static holdfast thus allows the tick to solve the problem of how to penetrate skin and also remain stuck for long periods of time. PMID:24174106

  8. Peroneus Brevis Tendon Variant Insertion on the Calcaneus

    PubMed Central

    Cecava, Nathan D.; Campbell, Scot E.

    2015-01-01

    Insertion of the peroneus brevis tendon normally occurs at the lateral aspect of the fifth metatarsal base. However, there is new evidence that congenital variant insertion of the tendon on the calcaneal peroneal tubercle occurs in a small segment of the population. We report a case of 24-year old male presenting with non-traumatic ankle pain who underwent ankle magnetic resonance imaging. Imaging demonstrated insertion of the peroneus brevis tendon on the calcaneal peroneal tubercle with absence of the tendon distal to the calcaneus. Furthermore, in reviewing 200 consecutive ankle magnetic resonance examinations, the authors discovered one additional case of this variant. We discuss the magnetic resonance imaging characteristics of this anatomic variant, the implications for clinical management, and review the literature on peroneal anatomic variations. PMID:26622930

  9. Insertion of liquid crystal molecules into hydrocarbon monolayers.

    PubMed

    Popov, Piotr; Lacks, Daniel J; Jákli, Antal; Mann, Elizabeth K

    2014-08-01

    Atomistic molecular dynamics simulations were carried out to investigate the molecular mechanisms of vertical surface alignment of liquid crystals. We study the insertion of nCB (4-Cyano-4'-n-biphenyl) molecules with n = 0,…,6 into a bent-core liquid crystal monolayer that was recently found to provide good vertical alignment for liquid crystals. The results suggest a complex-free energy landscape for the liquid crystal within the layer. The preferred insertion direction of the nCB molecules (core or tail first) varies with n, which can be explained by entropic considerations. The role of the dipole moments was found to be negligible. As vertical alignment is the leading form of present day liquid crystal displays (LCD), these results will help guide improvement of the LCD technology, as well as lend insight into the more general problem of insertion of biological and other molecules into lipid and surfactant layers. PMID:25106607

  10. Feasibility of a free-standing insertable heat source

    NASA Astrophysics Data System (ADS)

    Munger, A. C.; Mohler, J. H.; Kelly, M. D.

    The feasibility of a free-standing insertable heat source to replace an existing heat powder charge has been demonstrated. Successful development of this design eliminates the need for three laser weld joints, a high pressure interface and various manufacturing processes in the next assembly. Previous work yielded a component consisting of a stainless steel tube loaded with Fe/KC104 heat powder and a pyrotechnic ignitor. Although this design is adequate for the function, the advantages of an insertable heat source prompted the present development. The initial concept was to load a heat powder into a thin-walled container that could be inserted later. Varying air gaps prevented proper heat transmission. A freestanding thermite compact pressed to the inside contour of the stainless steel tube was then developed. This compact was attached to an ignitor which could then be threaded into the next assembly. Various thermite materials were evaluated.

  11. Gene Insertion Into Genomic Safe Harbors for Human Gene Therapy.

    PubMed

    Papapetrou, Eirini P; Schambach, Axel

    2016-04-01

    Genomic safe harbors (GSHs) are sites in the genome able to accommodate the integration of new genetic material in a manner that ensures that the newly inserted genetic elements: (i) function predictably and (ii) do not cause alterations of the host genome posing a risk to the host cell or organism. GSHs are thus ideal sites for transgene insertion whose use can empower functional genetics studies in basic research and therapeutic applications in human gene therapy. Currently, no fully validated GSHs exist in the human genome. Here, we review our formerly proposed GSH criteria and discuss additional considerations on extending these criteria, on strategies for the identification and validation of GSHs, as well as future prospects on GSH targeting for therapeutic applications. In view of recent advances in genome biology, gene targeting technologies, and regenerative medicine, gene insertion into GSHs can potentially catalyze nearly all applications in human gene therapy. PMID:26867951

  12. Improved technique for insertion of intra-aortic balloon pump.

    PubMed

    Cutler, B S; Vander Salm, T J

    1980-06-01

    Polytetrafluoroethylene (PTFE, Gortex) grafts have several advantages over woven Dacron grafts for the insertion of intra-aortic balloons (IABP). Because of the smooth inner surface of the PTFE graft, an 8-mm graft may be used instead of the 10-mm minimum size with Dacron. The pliability of the PTFE graft makes it easier to sew with fine suture material, and its comformability permits a "blood tight" seal to be obtained with a single Dacron umbilical tape tie. We have used PTFE grafts for IABP insertion in 24 patients, with no infectious or thrombotic complications. This graft material seems to offer substantial technical advantages over woven Dacron for the insertion of IABP and subsequent arterial repair. PMID:7387373

  13. Ear projection and the posterior auricular muscle insertion.

    PubMed

    Guyuron, B; DeLuca, L

    1997-08-01

    Prominent ears is a common congenital anomaly affecting approximately 5 percent of the general population. The etiology has been attributed to three basic deformities in the ear structure: valgus of the concha with a cranioauricular angle greater than 40 degrees, underfolding of the anthelix, and rarely, hypertrophy of the concha. It is believed that by virtue of its insertion onto the ponticulus, the cranial surface of the concha, the posterior auricular muscle may function to pull the auricle back toward the head. A proximally (anteromedially) displaced insertion site would decrease the length of the effective momentum of the muscle, leading to protrusion of the auricle. This study was conducted to determine if indeed a relationship between the posterior muscle insertion site and ear projection could be established clinically by measuring these parameters intraoperatively in patients presenting for otoplasty and in patients without prominent ears who required conchal cartilage grafts for other procedures. PMID:9252616

  14. Purification and characterization of YACs containing large inserts.

    PubMed

    Gemmill, R M; Bolin, R; Strauss, W M; Pavan, W

    2001-05-01

    This unit provides protocols for characterizing DNA segments cloned in YACs and for purifying YACs from yeast chromosomes. The first basic protocol describes Southern blotting and partial-digest restriction analysis of YACs. These methods are useful for determining the size and complexity of the cloned insert DNA, the presence and location of particular restriction sites or sequences, and even the species of origin of the insert DNA (indicated by hybridization to species-specific repetitive elements such as Alu repeats). The second basic protocol describes gel purification of YACs for use in procedures requiring pure YAC DNA, such as mammalian-cell transformation and subcloning into smaller insert vectors. The third basic protocol details characterizing and analyzing YACs: in vivo fragmentation via homologous recombination with specialized fragmentation vectors containing specific probe sequences or repetitive elements, followed by Southern blotting with YAC- and human-derived probes. PMID:18428294

  15. Insertion of liquid crystal molecules into hydrocarbon monolayers

    SciTech Connect

    Popov, Piotr Mann, Elizabeth K.; Lacks, Daniel J.; Jákli, Antal

    2014-08-07

    Atomistic molecular dynamics simulations were carried out to investigate the molecular mechanisms of vertical surface alignment of liquid crystals. We study the insertion of nCB (4-Cyano-4{sup ′}-n-biphenyl) molecules with n = 0,…,6 into a bent-core liquid crystal monolayer that was recently found to provide good vertical alignment for liquid crystals. The results suggest a complex-free energy landscape for the liquid crystal within the layer. The preferred insertion direction of the nCB molecules (core or tail first) varies with n, which can be explained by entropic considerations. The role of the dipole moments was found to be negligible. As vertical alignment is the leading form of present day liquid crystal displays (LCD), these results will help guide improvement of the LCD technology, as well as lend insight into the more general problem of insertion of biological and other molecules into lipid and surfactant layers.

  16. Synchronized monochromator and insertion device energy scans at SLS

    SciTech Connect

    Krempasky, J.; Flechsig, U.; Korhonen, T.; Zimoch, D.; Quitmann, Ch.; Nolting, F.

    2010-06-23

    Synchronous monochromator and insertion device energy scans were implemented at the Surfaces/Interfaces:Microscopy (SIM) beamline in order to provide the users fast X-ray magnetic dichroism studies (XMCD). A simple software control scheme is proposed based on a fast monochromator run-time energy readback which quickly updates the insertion device requested energy during an on-the-fly X-ray absorption scan (XAS). In this scheme the Plain Grating Monochromator (PGM) motion control, being much slower compared with the insertion device (APPLE-II type undulator), acts as a 'master' controlling the undulator 'slave' energy position. This master-slave software implementation exploits EPICS distributed device control over computer network and allows for a quasi-synchronous motion control combined with data acquisition needed for the XAS or XMCD experiment.

  17. Improving patient safety during insertion of peripheral venous catheters: an observational intervention study

    PubMed Central

    Kampf, Günter; Reise, Gesche; James, Claudia; Gittelbauer, Kirsten; Gosch, Jutta; Alpers, Birgit

    2013-01-01

    Background: Peripheral venous catheters are frequently used in hospitalized patients but increase the risk of nosocomial bloodstream infection. Evidence-based guidelines describe specific steps that are known to reduce infection risk. However, the degree of guideline implementation in clinical practice is not known. The aim of this study was to determine the use of specific steps for insertion of peripheral venous catheters in clinical practice and to implement a multimodal intervention aimed at improving both compliance and the optimum order of the steps. Methods: The study was conducted at University Hospital Hamburg. An optimum procedure for inserting a peripheral venous catheter was defined based on three evidence-based guidelines (WHO, CDC, RKI) including five steps with 1A or 1B level of evidence: hand disinfection before patient contact, skin antisepsis of the puncture site, no palpation of treated puncture site, hand disinfection before aseptic procedure, and sterile dressing on the puncture site. A research nurse observed and recorded procedures for peripheral venous catheter insertion for healthcare workers in four different departments (endoscopy, central emergency admissions, pediatrics, and dermatology). A multimodal intervention with 5 elements was established (teaching session, dummy training, e-learning tool, tablet and poster, and direct feedback), followed by a second observation period. During the last observation week, participants evaluated the intervention. Results: In the control period, 207 insertions were observed, and 202 in the intervention period. Compliance improved significantly for four of five steps (e.g., from 11.6% to 57.9% for hand disinfection before patient contact; p<0.001, chi-square test). Compliance with skin antisepsis of the puncture site was high before and after intervention (99.5% before and 99.0% after). Performance of specific steps in the correct order also improved (e.g., from 7.7% to 68.6% when three of five steps

  18. Mechanics of the mitral valve strut chordae insertion region.

    PubMed

    Padala, Muralidhar; Sacks, Michael S; Liou, Shasan W; Balachandran, Kartik; He, Zhaoming; Yoganathan, Ajit P

    2010-08-01

    Interest in developing durable mitral valve repair methods is growing, underscoring the need to better understand the native mitral valve mechanics. In this study, the authors investigate the dynamic deformation of the mitral valve strut chordae-to-anterior leaflet transition zone using a novel stretch mapping method and report the complex mechanics of this region for the first time. Eight structurally normal porcine mitral valves were studied in a pulsatile left heart simulator under physiological hemodynamic conditions -120 mm peak transvalvular pressure, 5 l/min cardiac output at 70 bpm. The chordal insertion region was marked with a structured array of 31 miniature markers, and their motions throughout the cardiac cycle were tracked using two high speed cameras. 3D marker coordinates were calculated using direct linear transformation, and a second order continuous surface was fit to the marker cloud at each time frame. Average areal stretch, principal stretch magnitudes and directions, and stretch rates were computed, and temporal changes in each parameter were mapped over the insertion region. Stretch distribution was heterogeneous over the entire strut chordae insertion region, with the highest magnitudes along the edges of the chordal insertion region and the least along the axis of the strut chordae. At early systole, radial stretch was predominant, but by mid systole, significant stretch was observed in both radial and circumferential directions. The compressive stretches measured during systole indicate a strong coupling between the two principal directions, explaining the small magnitude of the systolic areal stretch. This study for the first time provides the dynamic kinematics of the strut chordae insertion region in the functioning mitral valve. A heterogeneous stretch pattern was measured, with the mechanics of this region governed by the complex underlying collagen architecture. The insertion region seemed to be under stretch during both systole and

  19. Characterisation of protein stability in rod-insert vaginal rings.

    PubMed

    Pattani, Aditya; Lowry, Deborah; Curran, Rhonda M; McGrath, Stephanie; Kett, Vicky L; Andrews, Gavin P; Malcolm, R Karl

    2012-07-01

    A major goal in vaccine development is elimination of the 'cold chain', the transport and storage system for maintenance and distribution of the vaccine product. This is particularly pertinent to liquid formulation of vaccines. We have previously described the rod-insert vaginal ring (RiR) device, comprising an elastomeric body into which are inserted lyophilised, rod-shaped, solid drug dosage forms, and having potential for sustained mucosal delivery of biomacromolecules, such as HIV envelope protein-based vaccine candidates. Given the solid, lyophilised nature of these insert dosage forms, we hypothesised that antigen stability may be significantly increased compared with more conventional solubilised vaginal gel format. In this study, we prepared and tested vaginal ring devices fitted with lyophilised rod inserts containing the model antigen bovine serum albumin (BSA). Both the RiRs and the gels that were freeze-dried to prepare the inserts were evaluated for BSA stability using PAGE, turbidimetry, microbial load, MALDI-TOF and qualitative precipitate solubility measurements. When stored at 4 °C, but not when stored at 40 °C/75% RH, the RiR formulation offered protection against structural and conformational changes to BSA. The insert also retained matrix integrity and release characteristics. The results demonstrate that lypophilised gels can provide relative protection against degradation at lower temperatures compared to semi-solid gels. The major mechanism of degradation at 40 °C/75% RH was shown to be protein aggregation. Finally, in a preliminary study, we found that addition of trehalose to the formulation significantly reduces the rate of BSA degradation compared to the original formulation when stored at 40 °C/75% RH. Establishing the mechanism of degradation, and finding that degradation is decelerated in the presence of trehalose, will help inform further development of RiRs specifically and polymer based freeze-dried systems in general. PMID

  20. African origin of human-specific polymorphic Alu insertions

    SciTech Connect

    Batzer, M.A.; Alegria-Hartman, M. ); Stoneking, M. ); Bazan, H.; Kass, D.H.; Shaikh, T.H.; Scheer, W.D. ); Novick, G.E.; Herrera, R.J. ); Ioannou, P.A. )

    1994-12-06

    Alu elements are a family of interspersed repeats that have mobilized throughout primate genomes by retroposition from a few [open quotes]master[close quotes] genes. Among the 500,000 Alu elements in the human genome are members of the human-specific subfamily that are not fixed in the human species. Four such polymorphic human-specific Alu insertions were analyzed by a rapid, PCR-based assay. These four polymorphic Alu insertions were shown to be absent from the genomes of a number of nonhuman primates, consistent with their arising as human genetic polymorphisms sometime after the human/African ape divergence. Analysis of 664 unrelated individuals from 16 population groups from around the world revealed substantial levels of variation within population groups and significant genetic differentiation among groups. No significant associations were found among the four loci, consistent with their location on different chromosomes. A maximum-likelihood tree of population relationships showed four major groupings consisting of Africa, Europe, Asia/Americas, and Australia/New Guinea, which is concordant with similar trees based on other loci. A particularly useful feature of the polymorphic Alu insertions is that the ancestral state is known to be the absence of the Alu element, and the presence of the Alu element at a particular chromosomal site reflects a single, unique event in human evolution. A hypothetical ancestral group can then be included in the tree analysis, with the frequency of each insertion set to zero. The ancestral group connected to the maximum-likelihood tree within the African branch, which suggests an African origin of these polymorphic Alu insertions. These data are concordant with other diverse data sets, which lends further support to the recent African origin hypothesis for modern humans. Polymorphic Alu insertions represent a source of genetic variation for studying human population structure and evolution. 45 refs., 2 figs., 1 tab.

  1. Metallocene Catalytic Insertion Polymerization of 1-Silene to Polycarbosilanes

    NASA Astrophysics Data System (ADS)

    Tian, Yuelong; Ge, Min; Zhang, Weigang; Lv, Xiaoxu; Yu, Shouquan

    2015-11-01

    Metallocene of zirconium were used as a catalyst for an insertion polymerization of 1-methylsilene directly into pre-ceramic precursor polyzirconocenecarbosilane (PZCS) during dechlorination of dichlorodimethylesilane by sodium, which exhibits high catalytic effectiveness with the maximum conversion ratio of polycarbosilane up to 91%. The average molecular weights of polymers synthesized are less than 1400, all with very narrow polymolecularities. The mechanism of catalytic polymerization was assumed to be similar to a coordination insertion polymerization of 1-olefins by metallocenes. The obtained PZCS show high ceramic yields with formation of composite ceramics of ZrC-SiC, which are novel polymeric precursors of ultra-high temperature ceramic (UHTC) fiber and composite.

  2. Insertion of lithium into electrochromic devices after completion

    SciTech Connect

    Berland, Brian Spencer; Lanning, Bruce Roy; Frey, Jonathan Mack; Barrett, Kathryn Suzanne; DuPont, Paul Damon; Schaller, Ronald William

    2015-12-22

    The present disclosure describes methods of inserting lithium into an electrochromic device after completion. In the disclosed methods, an ideal amount of lithium can be added post-fabrication to maximize or tailor the free lithium ion density of a layer or the coloration range of a device. Embodiments are directed towards a method to insert lithium into the main device layers of an electrochromic device as a post-processing step after the device has been manufactured. In an embodiment, the methods described are designed to maximize the coloration range while compensating for blind charge loss.

  3. Advanced photon source experience with vacuum chambers for insertion devices

    SciTech Connect

    Hartog, P.D.; Grimmer, J.; Xu, S.; Trakhtenberg, E.; Wiemerslage, G.

    1997-08-01

    During the last five years, a new approach to the design and fabrication of extruded aluminum vacuum chambers for insertion devices was developed at the Advanced Photon Source (APS). With this approach, three different versions of the vacuum chamber, with vertical apertures of 12 mm, 8 mm, and 5 mm, were manufactured and tested. Twenty chambers were installed into the APS vacuum system. All have operated with beam, and 16 have been coupled with insertion devices. Two different vacuum chambers with vertical apertures of 16 mm and 11 mm were developed for the BESSY-II storage ring and 3 of 16 mm chambers were manufactured.

  4. Method of modifying a volume mesh using sheet insertion

    DOEpatents

    Borden, Michael J.; Shepherd, Jason F.

    2006-08-29

    A method and machine-readable medium provide a technique to modify a hexahedral finite element volume mesh using dual generation and sheet insertion. After generating a dual of a volume stack (mesh), a predetermined algorithm may be followed to modify (refine) the volume mesh of hexahedral elements. The predetermined algorithm may include the steps of locating a sheet of hexahedral mesh elements, determining a plurality of hexahedral elements within the sheet to refine, shrinking the plurality of elements, and inserting a new sheet of hexahedral elements adjacently to modify the volume mesh. Additionally, another predetermined algorithm using mesh cutting may be followed to modify a volume mesh.

  5. Ultrasonic airborne insertion loss measurements at normal incidence (L).

    PubMed

    Farley, Jayrin; Anderson, Brian E

    2010-12-01

    Transmission loss and insertion loss measurements of building materials at audible frequencies are commonly made using plane wave tubes or as a panel between reverberant rooms. These measurements provide information for noise isolation control in architectural acoustics and in product development. Airborne ultrasonic sound transmission through common building materials has not been fully explored. Technologies and products that utilize ultrasonic frequencies are becoming increasingly more common, hence the need to conduct such measurements. This letter presents preliminary measurements of the ultrasonic insertion loss levels for common building materials over a frequency range of 28-90 kHz using continuous-wave excitation. PMID:21218864

  6. Rectal fist insertion. An unusual form of sexual behavior.

    PubMed

    Shook, L L; Whittle, R; Rose, E F

    1985-12-01

    Rectal fist insertion (fist fucking) is an uncommon and potentially dangerous sexual practice. This is usually a homosexual activity, but can also be a heterosexual or an autoerotic practice. One known death has been reported associated with rectal fist insertion, in which the complications of anal and colonic tears and bleeding had occurred (see Editor's note). The possibility of drug overdose is also probable, as drugs and alcohol are commonly introduced into the rectum to promote sphincter relaxation and to ease the discomfort of anal dilatation. PMID:4072987

  7. Integral fill yarn insertion and beatup method using inflatable membrane

    NASA Technical Reports Server (NTRS)

    Farley, Gary L. (Inventor)

    1993-01-01

    An apparatus and method for integral fill yarn insertion and beatup are disclosed. A modified rapier contains a channel for holding fill yarn. The channel is covered with a flexible and inflatable boot, and an inflating apparatus for this boot is also attached. Fill yarn is inserted into the channel, and the rapier is extended into a shed formed by warp yarn. Next, the rapier is pushed into the fell of the fabric, and the flexible and inflatable cover inflated, which both pushes the yarn into the fell of the fabric and performs beatup. The rapier is withdrawn and the shed closed to complete one step of the weaving process.

  8. Transposon-free insertions for insect genetic engineering.

    PubMed

    Dafa'alla, Tarig H; Condon, George C; Condon, Kirsty C; Phillips, Caroline E; Morrison, Neil I; Jin, Li; Epton, Matthew J; Fu, Guoliang; Alphey, Luke

    2006-07-01

    Methods involving the release of transgenic insects in the field hold great promise for controlling vector-borne diseases and agricultural pests. Insect transformation depends on nonautonomous transposable elements as gene vectors. The resulting insertions are stable in the absence of suitable transposase, however, such absence cannot always be guaranteed. We describe a method for post-integration elimination of all transposon sequences in the pest insect Medfly, Ceratitis capitata. The resulting insertions lack transposon sequences and are therefore impervious to transposase activity. PMID:16823373

  9. Tension Pneumothorax and Subcutaneous Emphysema Complicating Insertion of Nasogastric Tube

    PubMed Central

    AL Saif, Narjis; Hammodi, Adel; Al-Azem, M. Ali; Al-Hubail, Rasheed

    2015-01-01

    Nasogastric tube has a key role in the management of substantial number of hospitalized patients particularly the critically ill. In spite of the apparent simple insertion technique, nasogastric tube placement has its serious perhaps fatal complications which need to be carefully assessed. Pulmonary misplacement and associated complications are commonplace during nasogastric tube procedure. We present a case of tension pneumothorax and massive surgical emphysema in critically ill ventilated patient due to inadvertent nasogastric tube insertion and also discussed the risk factors, complication list, and arrays of techniques for safer tube placement. PMID:26448883

  10. GREATER DIVERSITY OF SHIGA TOXIN-ENCODING BACTERIOPHAGE INSERTION SITES AMONG ESCHERICHA COLI O157:H7 ISOLATES FROM CATTLE THAN IN THOSE FROM HUMANS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Escherichia coli O157:H7, a zoonotic human pathogen with reservoir in domestic cattle, produces Shiga toxin(s) encoded by bacteriophages. Chromosomal insertion sites of these bacteriophages define three principal genotypes (Clusters 1 - 3 ) among clinical isolates of E. coli O157:H7. ...

  11. Distinct hippocampal functional networks revealed by tractography-based parcellation.

    PubMed

    Adnan, Areeba; Barnett, Alexander; Moayedi, Massieh; McCormick, Cornelia; Cohn, Melanie; McAndrews, Mary Pat

    2016-07-01

    Recent research suggests the anterior and posterior hippocampus form part of two distinct functional neural networks. Here we investigate the structural underpinnings of this functional connectivity difference using diffusion-weighted imaging-based parcellation. Using this technique, we substantiated that the hippocampus can be parcellated into distinct anterior and posterior segments. These structurally defined segments did indeed show different patterns of resting state functional connectivity, in that the anterior segment showed greater connectivity with temporal and orbitofrontal cortex, whereas the posterior segment was more highly connected to medial and lateral parietal cortex. Furthermore, we showed that the posterior hippocampal connectivity to memory processing regions, including the dorsolateral prefrontal cortex, parahippocampal, inferior temporal and fusiform gyri and the precuneus, predicted interindividual relational memory performance. These findings provide important support for the integration of structural and functional connectivity in understanding the brain networks underlying episodic memory. PMID:26206251

  12. Pigmentation-based insertional mutagenesis is a simple and potent screening approach for identifying neurocristopathy-associated genes in mice.

    PubMed

    Pilon, Nicolas

    2016-01-01

    Neurocristopathies form a specific group of rare genetic diseases in which a defect in neural crest cell development is causal. Because of the large number of neural crest cell derivatives, distinct structures/cell types (isolated or in combination) are affected in each neurocristopathy. The most important issues in this research field is that the underlying genetic cause and associated pathogenic mechanism of most cases of neurocristopathy are poorly understood. This article describes how a relatively simple insertional mutagenesis approach in the mouse has proved useful for identifying new candidate genes and pathogenic mechanisms for diverse neurocristopathies. PMID:27141416

  13. Pigmentation-based insertional mutagenesis is a simple and potent screening approach for identifying neurocristopathy-associated genes in mice

    PubMed Central

    Pilon, Nicolas

    2016-01-01

    ABSTRACT Neurocristopathies form a specific group of rare genetic diseases in which a defect in neural crest cell development is causal. Because of the large number of neural crest cell derivatives, distinct structures/cell types (isolated or in combination) are affected in each neurocristopathy. The most important issues in this research field is that the underlying genetic cause and associated pathogenic mechanism of most cases of neurocristopathy are poorly understood. This article describes how a relatively simple insertional mutagenesis approach in the mouse has proved useful for identifying new candidate genes and pathogenic mechanisms for diverse neurocristopathies. PMID:27141416

  14. Retrospective Review of Current Nasojejunal Tube Insertion Practice

    PubMed Central

    Sheikh, Natasha; Falkiner, Michelle

    2015-01-01

    Repeated fluoroscopically guided nasojejunal tube (NJT) insertions, particularly in children, can pose health risks through increased radiation exposure. We analyzed frequency of NJT reinsertions and associated radiation exposure through retrospective evaluation of children <18 years at our institution who underwent fluoroscopically guided NJT insertions from 2007 to 2012. Age and weight, reinsertion frequency per patient, radiation dose (dose actual percentage [DAP]), time interval between, and indication for reinsertion were recorded. A total of 252 children (3 days to17 years, 11 months) had 449 NJT insertions. Reinsertions occurred in 105 (41.7%) patients with 14 (5.6%) having ≥5 reinsertions, and 67.6% of reinsertions occurring in patients <1 year. Mean DAP increased with frequency of reinsertion, along with age and weight. Most common indication for reinsertion was a pulled NJT (34.0%). Fluoroscopic NJT reinsertion was most frequent in younger, smaller patients. Self-guided, bedside NJT insertion, and/or earlier instigation of definitive nutritional therapy delivery should be considered. PMID:27335939

  15. Insertional mutagenesis using Tnt1 retrotransposon in potato

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Potato is the third most important food crop in the world. However, genetics and genomics research of potato has lagged behind many major crop species due to its autotetraploidy and a highly heterogeneous genome. Insertional mutagenesis using T-DNA or transposable elements, which is available in sev...

  16. Force modeling for needle insertion into soft tissue.

    PubMed

    Okamura, Allison M; Simone, Christina; O'Leary, Mark D

    2004-10-01

    The modeling of forces during needle insertion into soft tissue is important for accurate surgical simulation, preoperative planning, and intelligent robotic assistance for percutaneous therapies. We present a force model for needle insertion and experimental procedures for acquiring data from ex vivo tissue to populate that model. Data were collected from bovine livers using a one-degree-of-freedom robot equipped with a load cell and needle attachment. computed tomography imaging was used to segment the needle insertion process into phases identifying different relative velocities between the needle and tissue. The data were measured and modeled in three parts: 1) capsule stiffness, a nonlinear spring model; 2) friction, a modified Karnopp model; and 3) cutting, a constant for a given tissue. In addition, we characterized the effects of needle diameter and tip type on insertion force using a silicone rubber phantom. In comparison to triangular and diamond tips, a bevel tip causes more needle bending and is more easily affected by tissue density variations. Forces for larger diameter needles are higher due to increased cutting and friction forces. PMID:15490818

  17. Contrast-free endoscopic stent insertion in malignant biliary obstruction

    PubMed Central

    De Palma, Giovanni D; Lombardi, Giovanni; Rega, Maria; Simeoli, Immacolata; Masone, Stefania; Siciliano, Saverio; Maione, Francesco; Salvatori, Francesca; Balzano, Antonio; Persico, Giovanni

    2007-01-01

    AIM: To present a case series of MRCP-guided endoscopic biliary stent placement, performed entirely without contrast injection. METHODS: Contrast-free endoscopic biliary drainage was attempted in 20 patients with malignant obstruction, unsuitable for resection on the basis of tumor extent or medical illness. MRCP images were used to confirm the diagnosis of tumor, to exclude other biliary diseases and to demonstrate the stenoses as well as dilation of proximal liver segments. The procedure was carried out under conscious sedation. Patients were placed in the left lateral decubitus position. The endoscope was inserted, the papilla identified and cannulated by a papillotome. A guide wire was inserted and guided deeply into the biliary tree, above the stenosis, by fluoroscopy. A papillotomy approximately 1 cm. long was performed and the papillotome was exchanged with a guiding-catheter. A 10 Fr, Amsterdam-type plastic stent, 7 to 15 cm long, was finally inserted over the guide wire/guiding catheter by a pusher tube system. RESULTS: Successful stent insertion was achieved in all patients. There were no major complications. Successful drainage, with substantial reduction in bilirubin levels, was achieved in all patients. CONCLUSION: This new method of contrast-free endoscopic stenting in malignant biliary obstruction is a safe and effective method of palliation. However, a larger, randomized study comparing this new approach with the standard procedure is needed to confirm the findings of the present study. PMID:17663512

  18. Discovery of unfixed endogenous retrovirus insertions in diverse human populations.

    PubMed

    Wildschutte, Julia Halo; Williams, Zachary H; Montesion, Meagan; Subramanian, Ravi P; Kidd, Jeffrey M; Coffin, John M

    2016-04-19

    Endogenous retroviruses (ERVs) have contributed to more than 8% of the human genome. The majority of these elements lack function due to accumulated mutations or internal recombination resulting in a solitary (solo) LTR, although members of one group of human ERVs (HERVs), HERV-K, were recently active with members that remain nearly intact, a subset of which is present as insertionally polymorphic loci that include approximately full-length (2-LTR) and solo-LTR alleles in addition to the unoccupied site. Several 2-LTR insertions have intact reading frames in some or all genes that are expressed as functional proteins. These properties reflect the activity of HERV-K and suggest the existence of additional unique loci within humans. We sought to determine the extent to which other polymorphic insertions are present in humans, using sequenced genomes from the 1000 Genomes Project and a subset of the Human Genome Diversity Project panel. We report analysis of a total of 36 nonreference polymorphic HERV-K proviruses, including 19 newly reported loci, with insertion frequencies ranging from <0.0005 to >0.75 that varied by population. Targeted screening of individual loci identified three new unfixed 2-LTR proviruses within our set, including an intact provirus present at Xq21.33 in some individuals, with the potential for retained infectivity. PMID:27001843

  19. Chemo-port insertion: A cause of vocal cord palsy.

    PubMed

    Alazzawi, Sarmad; Hindi, Khalid; Malik, Ausama; Wee, Chong Aun; Prepageran, Narayanan

    2015-11-01

    We describe extremely rare cases of vocal cord palsy following surgical insertion of a chemo port. Our cohort consisted of patients with cancer who developed hoarseness immediately after central venous line placement for the administration of chemotherapy, with vocal cord palsy confirmed with flexible laryngoscopy. Given the timing, central venous line placement appears to be the most likely cause. PMID:26108861

  20. Proper Angle of Sono-guided Central Venous Line Insertion

    PubMed Central

    Barzegari, Hassan; Forouzan, Arash; Fahimi, Mohammad Ali; Zohrevandi, Behzad; Ghanavati, Mandana

    2016-01-01

    Introduction: Determining the proper angle for inserting central venous catheter (CV line) is of great importance for decreasing the complications and increasing success rate. The present study was designed to determine the proper angle of needle insertion for internal jugular vein catheterization. Methods: In the present case series study, candidate patients for catheterization of the right internal jugular vein under guidance of ultrasonography were studied. At the time of proper placing of the catheter, photograph was taken and Auto Cad 2014 software was used to measure the angles of the needle in the sagittal and axial planes, as well as patient’s head rotation. Result: 114 patients with the mean age of 56.96 ± 14.71 years were evaluated (68.4% male). The most common indications of catheterization were hemodialysis (55.3%) and shock state (24.6%). The mean angles of needle insertion were 102.15 ± 6.80 for axial plane, 36.21 ± 3.12 for sagittal plane and the mean head rotation angle was 40.49 ± 5.09. Conclusion: Based on the results of the present study it seems that CV line insertion under the angles 102.15 ± 6.80 degrees in the axial plane, 36.21 ± 3.12 in the sagittal plane and 40.49 ± 5.09 head rotation yield satisfactory results. PMID:27299146

  1. Electromagnetically tracked placement of a peripherally inserted central catheter

    NASA Astrophysics Data System (ADS)

    Sacolick, Laura; Patel, Neilesh; Tang, Jonathan; Levy, Elliot; Cleary, Kevin R.

    2004-05-01

    This paper describes a computer program to utilize electromagnetic tracking guidance during insertion of peripherally inserted central catheters. Placement of a Peripherally Inserted Central Catheter (PICC) line is a relatively simple, routine procedure in which a catheter is inserted into the veins of the lower arm and threaded up the arm to the vena cava to sit just above the heart. However, the procedure requires x-ray verification of the catheter position and is usually done under continuous fluoroscopic guidance. The computer program is designed to replace fluoroscopic guidance in this procedure and make PICC line placement a bedside procedure. This would greatly reduce the time and resources dedicated to this procedure. The physician first goes through a quick registration procedure to register the patient space with the computer screen coordinates. Once registration is completed, the program provides a continuous, real-time display of the position of the catheter tip overlaid on an x-ray image of the patient on an adjacent computer screen. Both the position and orientation of the catheter tip is shown. The display is very similar to that shown when using fluoroscopy.

  2. Folding and insertion thermodynamics of the transmembrane WALP peptide.

    PubMed

    Bereau, Tristan; Bennett, W F Drew; Pfaendtner, Jim; Deserno, Markus; Karttunen, Mikko

    2015-12-28

    The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA)n (L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide's insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum-in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence. PMID:26723612

  3. Root cause of incomplete control rod insertions at Westinghouse reactors

    SciTech Connect

    Ray, S.

    1997-01-01

    Within the past year, incomplete RCCA insertions have been observed on high burnup fuel assemblies at two Westinghouse PWRs. Initial tests at the Wolf Creek site indicated that the direct cause of the incomplete insertions observed at Wolf Creek was excessive fuel assembly thimble tube distortion. Westinghouse committed to the NRC to perform a root cause analysis by the end of August, 1996. The root cause analysis process used by Westinghouse included testing at ten sites to obtain drag, growth and other characteristics of high burnup fuel assemblies. It also included testing at the Westinghouse hot cell of two of the Wolf Creek incomplete insertion assemblies. A mechanical model was developed to calculate the response of fuel assemblies when subjected to compressive loads. Detailed manufacturing reviews were conducted to determine if this was a manufacturing related issue. In addition, a review of available worldwide experience was performed. Based on the above, it was concluded that the thimble tube distortion observed on the Wolf Creek incomplete insertion assemblies was caused by unusual fuel assembly growth over and above what would typically be expected as a result of irradiation exposure. It was determined that the unusual growth component is a combination of growth due to oxide accumulation and accelerated growth, and would only be expected in high temperature plants on fuel assemblies that see long residence times and high power duties.

  4. 31. Photocopy of map. Insert from Master Plan Notes Prepared ...

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

    31. Photocopy of map. Insert from Master Plan Notes Prepared by Environmental Planning and Design, Pittsburgh, Pa. Original at Missouri Botanical Garden. 1972 MASTER PLAN 32. 'THE TREE,' SCULPTURE BY ALEXANDER CALDER, 1966 - Missouri Botanical Garden, 2345 Tower Grove Avenue, Saint Louis, Independent City, MO

  5. External Tank (ET) Bipod Fitting Bolted Attachment Locking Insert Performance

    NASA Technical Reports Server (NTRS)

    Larsen, Curtis E.; Wilson, Tim R.; Elliott, Kenny B.; Raju, Ivatury S.; McManamen, John

    2008-01-01

    Following STS-107, the External Tank (ET) Project implemented corrective actions and configuration changes at the ET bipod fitting. Among the corrective actions, the existing bolt lock wire which provided resistance to potential bolt rotation was removed. The lock wire removal was because of concerns with creating voids during foam application and potential for lock wire to become debris. The bolts had been previously lubricated to facilitate assembly but, because of elimination of the lock wire, the ET Project wanted to enable the locking feature of the insert. Thus, the lubrication was removed from bolt threads and instead applied to the washer under the bolt head. Lubrication is necessary to maximize joint pre-load while remaining within the bolt torque specification. The locking feature is implemented by thread crimping in at four places in the insert. As the bolt is torqued into the insert the bolt threads its way past the crimped parts of the insert. This provides the locking of the bolt, as torque is required to loosen the joint after clamping.

  6. Computerized planning of prostate cryosurgery using variable cryoprobe insertion depth.

    PubMed

    Rossi, Michael R; Tanaka, Daigo; Shimada, Kenji; Rabin, Yoed

    2010-02-01

    The current study presents a computerized planning scheme for prostate cryosurgery using a variable insertion depth strategy. This study is a part of an ongoing effort to develop computerized tools for cryosurgery. Based on typical clinical practices, previous automated planning schemes have required that all cryoprobes be aligned at a single insertion depth. The current study investigates the benefit of removing this constraint, in comparison with results based on uniform insertion depth planning as well as the so-called "pullback procedure". Planning is based on the so-called "bubble-packing method", and its quality is evaluated with bioheat transfer simulations. This study is based on five 3D prostate models, reconstructed from ultrasound imaging, and cryoprobe active length in the range of 15-35 mm. The variable insertion depth technique is found to consistently provide superior results when compared to the other placement methods. Furthermore, it is shown that both the optimal active length and the optimal number of cryoprobes vary among prostate models, based on the size and shape of the target region. Due to its low computational cost, the new scheme can be used to determine the optimal cryoprobe layout for a given prostate model in real time. PMID:19111714

  7. Folding and insertion thermodynamics of the transmembrane WALP peptide

    NASA Astrophysics Data System (ADS)

    Bereau, Tristan; Bennett, W. F. Drew; Pfaendtner, Jim; Deserno, Markus; Karttunen, Mikko

    2015-12-01

    The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA)n (L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide's insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum—in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence.

  8. Folding and insertion thermodynamics of the transmembrane WALP peptide

    SciTech Connect

    Bereau, Tristan; Bennett, W. F. Drew; Pfaendtner, Jim; Deserno, Markus; Karttunen, Mikko

    2015-12-28

    The anchor of most integral membrane proteins consists of one or several helices spanning the lipid bilayer. The WALP peptide, GWW(LA){sub n} (L)WWA, is a common model helix to study the fundamentals of protein insertion and folding, as well as helix-helix association in the membrane. Its structural properties have been illuminated in a large number of experimental and simulation studies. In this combined coarse-grained and atomistic simulation study, we probe the thermodynamics of a single WALP peptide, focusing on both the insertion across the water-membrane interface, as well as folding in both water and a membrane. The potential of mean force characterizing the peptide’s insertion into the membrane shows qualitatively similar behavior across peptides and three force fields. However, the Martini force field exhibits a pronounced secondary minimum for an adsorbed interfacial state, which may even become the global minimum—in contrast to both atomistic simulations and the alternative PLUM force field. Even though the two coarse-grained models reproduce the free energy of insertion of individual amino acids side chains, they both underestimate its corresponding value for the full peptide (as compared with atomistic simulations), hinting at cooperative physics beyond the residue level. Folding of WALP in the two environments indicates the helix as the most stable structure, though with different relative stabilities and chain-length dependence.

  9. Stability analysis of chickpea large genomic DNA inserts in Agrobacterium.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Agrobacterium tumefaciens-mediated transformation of large DNA inserts directly into plants facilitates the transfer of gene clusters and flanking regulatory elements. It is recommended that the integrity of large genomic fragments in Agrobacterium be verified prior to plant transformation. In this ...

  10. Quench Module Insert Capabilities and Development Test Results

    NASA Technical Reports Server (NTRS)

    Carswell, B.; Crouch, M.; Farmer, J.; Breeding, S.; Rose, F.; Whitaker, Ann F. (Technical Monitor)

    2001-01-01

    Quench Module Insert is a directional solidification furnace, which will fly in the Materials Science Research Facility. The QMI provides high thermal gradient and quench capabilities for processing metals and alloys in microgravity. This paper will describe the capabilities and present of on-going analysis and development testing.

  11. Synthesis of Aryl Ketoamides via Aryne Insertion into Imides.

    PubMed

    Wright, Austin C; Haley, Christopher K; Lapointe, Guillaume; Stoltz, Brian M

    2016-06-17

    An insertion of arenes into both imides and anhydrides via reactive aryne intermediates is presented. The reaction is performed under exceptionally mild conditions, and the corresponding ketoamide products are amenable to derivatization to deliver a variety of synthetically useful motifs such as quinolones, indoles, and ketoanilines. PMID:27266278

  12. Observations on rotating needle insertions using a brachytherapy robot

    NASA Astrophysics Data System (ADS)

    Meltsner, M. A.; Ferrier, N. J.; Thomadsen, B. R.

    2007-09-01

    A robot designed for prostate brachytherapy implantations has the potential to greatly improve treatment success. Much of the research in robotic surgery focuses on measuring accuracy. However, there exist many factors that must be optimized before an analysis of needle placement accuracy can be determined. Some of these parameters include choice of the needle type, insertion velocity, usefulness of the rotating needle and rotation speed. These parameters may affect the force at which the needle interacts with the tissue. A reduction in force has been shown to decrease the compression of the prostate and potentially increase the accuracy of seed position. Rotating the needle as it is inserted may reduce frictional forces while increasing accuracy. However, needle rotations are considered to increase tissue damage due to the drilling nature of the insertion. We explore many of the factors involved in optimizing a brachytherapy robot, and the potential effects each parameter may have on the procedure. We also investigate the interaction of rotating needles in gel and suggest the rotate-cannula-only method of conical needle insertion to minimize any tissue damage while still maintaining the benefits of reduced force and increased accuracy.

  13. 9. Detail of castiron insert E wall of Engine Room ...

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

    9. Detail of cast-iron insert E wall of Engine Room that supported main drive shaft to the shops - Central of Georgia Railway, Savannah Repair Shops & Terminal Facilities, Engine Boiler & Pattern Building, Bounded by West Broad, Jones, West Boundary & Hull Streets, Savannah, Chatham County, GA

  14. PiggyBac Transgene Insertion Site GIZA Strain

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetically modified New World screwworms were analyzed by inverse PCR and several sequences of genomic DNA flanking the transposon insertion sites were obtained. One transgenic strain, designated GIZA, exhibited the properties of a lethal genetic mutation. Classic genetic crosses of these insects r...

  15. Computer Modeling of Protocellular Functions: Peptide Insertion in Membranes

    NASA Technical Reports Server (NTRS)

    Rodriquez-Gomez, D.; Darve, E.; Pohorille, A.

    2006-01-01

    Lipid vesicles became the precursors to protocells by acquiring the capabilities needed to survive and reproduce. These include transport of ions, nutrients and waste products across cell walls and capture of energy and its conversion into a chemically usable form. In modem organisms these functions are carried out by membrane-bound proteins (about 30% of the genome codes for this kind of proteins). A number of properties of alpha-helical peptides suggest that their associations are excellent candidates for protobiological precursors of proteins. In particular, some simple a-helical peptides can aggregate spontaneously and form functional channels. This process can be described conceptually by a three-step thermodynamic cycle: 1 - folding of helices at the water-membrane interface, 2 - helix insertion into the lipid bilayer and 3 - specific interactions of these helices that result in functional tertiary structures. Although a crucial step, helix insertion has not been adequately studied because of the insolubility and aggregation of hydrophobic peptides. In this work, we use computer simulation methods (Molecular Dynamics) to characterize the energetics of helix insertion and we discuss its importance in an evolutionary context. Specifically, helices could self-assemble only if their interactions were sufficiently strong to compensate the unfavorable Free Energy of insertion of individual helices into membranes, providing a selection mechanism for protobiological evolution.

  16. Effects of Rotational Motion in Robotic Needle Insertion

    PubMed Central

    Ramezanpour, H.; Yousefi, H.; Rezaei, M.; Rostami, M.

    2015-01-01

    Background Robotic needle insertion in biological tissues has been known as one the most applicable procedures in sampling, robotic injection and different medical therapies and operations. Objective In this paper, we would like to investigate the effects of angular velocity in soft tissue insertion procedure by considering force-displacement diagram. Non-homogenous camel liver can be exploited as a tissue sample under standard compression test with Zwick/Roell device employing 1-D axial load-cell. Methods Effects of rotational motion were studied by running needle insertion experiments in 5, 50 and 200 mm/min in two types of with or without rotational velocity of 50, 150 and 300 rpm. On further steps with deeper penetrations, friction force of the insertion procedure in needle shaft was acquired by a definite thickness of the tissue. Results Designed mechanism of fixture for providing different frequencies of rotational motion is available in this work. Results for comparison of different force graphs were also provided. Conclusion Derived force-displacement graphs showed a significant difference between two procedures; however, tissue bleeding and disorganized micro-structure would be among unavoidable results. PMID:26688800

  17. Effects of lithium insertion on thermal conductivity of silicon nanowires

    SciTech Connect

    Xu, Wen; Zhang, Gang; Li, Baowen

    2015-04-27

    Recently, silicon nanowires (SiNWs) have been applied as high-performance Li battery anodes, since they can overcome the pulverization and mechanical fracture during lithiation. Although thermal stability is one of the most important parameters that determine safety of Li batteries, thermal conductivity of SiNWs with Li insertion remains unclear. In this letter, using molecular dynamics simulations, we study room temperature thermal conductivity of SiNWs with Li insertion. It is found that compared with the pristine SiNW, there is as much as 60% reduction in thermal conductivity with 10% concentration of inserted Li atoms, while under the same impurity concentration the reduction in thermal conductivity of the mass-disordered SiNW is only 30%. With lattice dynamics calculations and normal mode decomposition, it is revealed that the phonon lifetimes in SiNWs decrease greatly due to strong scattering of phonons by vibrational modes of Li atoms, especially for those high frequency phonons. The observed strong phonon scattering phenomenon in Li-inserted SiNWs is similar to the phonon rattling effect. Our study serves as an exploration of thermal properties of SiNWs as Li battery anodes or weakly coupled with impurity atoms.

  18. Defining moments in leadership character development.

    PubMed

    Bleich, Michael R

    2015-06-01

    Critical moments in life define one's character and clarify true values. Reflective leadership is espoused as an important practice for transformational leaders. Professional development educators can help surface and explore defining moments, strengthen leadership behavior with defining moments as a catalyst for change, and create safe spaces for leaders to expand their leadership capacity. PMID:26057159

  19. Defined contribution: a part of our future.

    PubMed Central

    Baugh, Reginald F.

    2003-01-01

    Rising employer health care costs and consumer backlash against managed care are trends fostering the development of defined contribution plans. Defined contribution plans limit employer responsibility to a fixed financial contribution rather than a benefit program and dramatically increase consumer responsibility for health care decision making. Possible outcomes of widespread adoption of defined contribution plans are presented. PMID:12934869

  20. 7 CFR 29.9201 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Terms defined. 29.9201 Section 29.9201 Agriculture... Tobacco Produced and Marketed in a Quota Area Definitions § 29.9201 Terms defined. As used in this subpart... hereinafter defined shall have the indicated meanings so assigned....

  1. 7 CFR 1206.200 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1206.200 Section 1206.200 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... INFORMATION Rules and Regulations § 1206.200 Terms defined. Unless otherwise defined in this subpart,...

  2. 7 CFR 1210.500 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Terms defined. 1210.500 Section 1210.500 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... PLAN Rules and Regulations Definitions § 1210.500 Terms defined. Unless otherwise defined in...

  3. 7 CFR 29.12 - Terms defined.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 2 2011-01-01 2011-01-01 false Terms defined. 29.12 Section 29.12 Agriculture... INSPECTION Regulations Definitions § 29.12 Terms defined. As used in this subpart and in all instructions, forms, and documents in connection therewith, the words and phrases hereinafter defined shall have...

  4. 16 CFR 502.2 - Terms defined.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 16 Commercial Practices 1 2010-01-01 2010-01-01 false Terms defined. 502.2 Section 502.2... FAIR PACKAGING AND LABELING ACT Definitions § 502.2 Terms defined. As used in this part, unless the... those terms are defined under part 500 of this chapter. (b) The term packager and labeler means...

  5. 20 CFR 725.703 - Physician defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 3 2011-04-01 2011-04-01 false Physician defined. 725.703 Section 725.703... defined. The term “physician” includes only doctors of medicine (MD) and osteopathic practitioners within the scope of their practices as defined by State law. No treatment or medical services performed...

  6. 29 CFR 779.107 - Goods defined.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 3 2010-07-01 2010-07-01 false Goods defined. 779.107 Section 779.107 Labor Regulations... Engaged in Commerce Or in the Production of Goods for Commerce § 779.107 Goods defined. The term goods is defined in section 3(i) of the Act and has a well established meaning under the Act since it has...

  7. 20 CFR 404.429 - Earnings; defined.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 20 Employees' Benefits 2 2011-04-01 2011-04-01 false Earnings; defined. 404.429 Section 404.429...- ) Deductions; Reductions; and Nonpayments of Benefits § 404.429 Earnings; defined. (a) General. The term... purpose of the earnings test under this subpart: (i) If you reach full retirement age, as defined in §...

  8. 29 CFR 779.107 - Goods defined.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 3 2011-07-01 2011-07-01 false Goods defined. 779.107 Section 779.107 Labor Regulations... Engaged in Commerce Or in the Production of Goods for Commerce § 779.107 Goods defined. The term goods is defined in section 3(i) of the Act and has a well established meaning under the Act since it has...

  9. 20 CFR 725.703 - Physician defined.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 20 Employees' Benefits 3 2010-04-01 2010-04-01 false Physician defined. 725.703 Section 725.703... AND HEALTH ACT, AS AMENDED Medical Benefits and Vocational Rehabilitation § 725.703 Physician defined... scope of their practices as defined by State law. No treatment or medical services performed by...

  10. Teenage Drinking, Symbolic Capital and Distinction

    ERIC Educational Resources Information Center

    Jarvinen, Margaretha; Gundelach, Peter

    2007-01-01

    This article analyses alcohol-related lifestyles among Danish teenagers. Building on Bourdieu's reasoning on symbolic capital and distinction, we analyse three interrelated themes. First, we show that alcohol-related variables (drinking patterns, drinking debut, experience of intoxication, etc.) can be used to identify some very distinctive life…

  11. Triton College: One Institution's Search for Distinctiveness.

    ERIC Educational Resources Information Center

    Townsend, Barbara K.; Catanzaro, James L.

    1989-01-01

    Recounts Triton College's efforts to identify its distinctive elements. Reviews empirical evidence showing that Triton's school schedule, curricular offerings, and continuing education and support services are distinctive among local colleges. Discusses students' and staff members' perceptions of Triton. Considers the value of the research to the…

  12. Evidence for a Distinct Kind of Noun.

    ERIC Educational Resources Information Center

    Soja, Nancy N.

    1994-01-01

    Examined the spontaneous speech of four children and their parents for use of determiners with NP-type nouns and count nouns. Found that the parents made a clear distinction between the two kinds of nouns, omitting determiners with the NP-type nouns but not with the count nouns. The children all made the same distinction by four years of age. (HTH)

  13. How to define valvular atrial fibrillation?

    PubMed

    Fauchier, Laurent; Philippart, Raphael; Clementy, Nicolas; Bourguignon, Thierry; Angoulvant, Denis; Ivanes, Fabrice; Babuty, Dominique; Bernard, Anne

    2015-10-01

    Atrial fibrillation (AF) confers a substantial risk of stroke. Recent trials comparing vitamin K antagonists (VKAs) with non-vitamin K antagonist oral anticoagulants (NOACs) in AF were performed among patients with so-called "non-valvular" AF. The distinction between "valvular" and "non-valvular" AF remains a matter of debate. Currently, "valvular AF" refers to patients with mitral stenosis or artificial heart valves (and valve repair in North American guidelines only), and should be treated with VKAs. Valvular heart diseases, such as mitral regurgitation, aortic stenosis (AS) and aortic insufficiency, do not result in conditions of low flow in the left atrium, and do not apparently increase the risk of thromboembolism brought by AF. Post-hoc analyses suggest that these conditions probably do not make the thromboembolic risk less responsive to NOACs compared with most forms of "non-valvular" AF. The pathogenesis of thrombosis is probably different for blood coming into contact with a mechanical prosthetic valve compared with what occurs in most other forms of AF. This may explain the results of the only trial performed with a NOAC in patients with a mechanical prosthetic valve (only a few of whom had AF), where warfarin was more effective and safer than dabigatran. By contrast, AF in the presence of a bioprosthetic heart valve or after valve repair appears to have a risk of thromboembolism that is not markedly different from other forms of "non-valvular" AF. Obviously, we should no longer consider the classification of AF as "valvular" (or not) for the purpose of defining the aetiology of the arrhythmia, but for the determination of a different risk of thromboembolic events and the need for a specific antithrombotic strategy. As long as there is no better new term or widely accepted definition, "valvular AF" refers to patients with mitral stenosis or artificial heart valves. Patients with "non-valvular AF" may have other types of valvular heart disease. One should

  14. [Discussion on different methods of painless needle insertion based on positions].

    PubMed

    Chen, Chao; Shi, Xuemin

    2016-03-01

    Based on multiple painless needle insertion skills in clinic combined with own experience, the authors propose the opinion that different painless needle insertion methods need to be used according to the positions where acupoints are. The appropriate needle insertion mean must be selected in accord with the anatomical characteristic of acupoint position, namely, tapping insertion is applied in scalp part, skin-pinching up needle insertion is used in forehead and superficial nerve trunk, fingernail-pressure needle insertion in ocular region and positions where large blood vessels distribute, flying acupuncture insertion in face and finger tip, vibrating needle in occipitonuchal region, quivering insertion in abdomen, quick pricking by single hand in the four limbs and back, and chop acupuncture in palm and pelma. The insertion methods are systematically discussed in terms of preparation, acupoint position, manipulation and attention, etc, so that to provide the reference for painless needle insertion. PMID:27344834

  15. Choice of Tevatron tune with matched low-. beta. insertions

    SciTech Connect

    Month, M.

    1984-06-20

    The Tevatron lattice, following closely the Main Ring lattice, is made up of approximately 90 FODO cells with six straight sections equally spaced. The straight sections are identical (neglecting the special high-..beta.. straight section used for resonant extraction) providing six-fold symmetry. Each straight section is comprised mainly of a pair of doublets, one at each end, in an antisymmetric configuration. The ..beta..-functions are matched to the building block cells but the dispersion function is not. The ..beta..-function matching implies that the structure is not sensitive to the tune of the sextant (i.e., structure resonances); however, the dispersion mismatch excites off-momentum dipole resonances and the dispersion structure of the ring is therefore sensitive to sextant tunes near an integer. The introduction of low-..beta.. insertions can be accomplished by replacing a standard insertion (expanded somewhat from the doublet pair straight section) with a low-..beta.. insertion. By matching the ends of the replacement units with respect to ..beta..-functions and dispersion function, the full lattice is made insensitive to linear structure resonances. Procedures are described here for introducing into the idealized Tevatron lattice considered here a single matched low-..beta.. insertion at BO, and two matched low-..beta.. insertions at BO and DO. The main consequence is the need for a significant number of independently powered quadrupoles. Another conclusion is related to the choice of tune, where it is found that the arbitrary rule of maintaining a fixed tune for all configurations should be modified.

  16. Lithium-inserted vanadium dioxide (LixVO2) thin films

    NASA Astrophysics Data System (ADS)

    Khan, Mohammad S. R.

    1996-04-01

    Thermochromic switching between a low-temperature and high-temperature less transparent state is possible in thin films based on vanadium dioxide (VO2). The critical temperature Tc at which the transition takes place in VO2 is on the order of 68 degrees Celsius which can be depressed towards a comfortable temperature by several techniques, including dopants. Dopants can be inserted by electrochemical means. This work is an exploratory study of the electrochromism of LixVO2 with a view to 'smart window' applications. Thin films of LixVO2 (0 less than or equal to x less than or equal to 0.43) were made by reactive sputtering and annealing electrolyte of LiClO4 and propylene carbonate. A maximum lithium content of x equals 0.43 was accomplished. Optical spectral response at wavelength pertinent to solar radiation was reported. Lithium insertion increased the transmittance gradually and reversibly i.e. LixVO2 showed electrochromism and bleached under Li insertion. LixVO2 also showed thermochroism, although to a smaller degree than VO2 and was most transparent at low temperature. Temperature- dependent electrical conductivity and thermoelectric power measurements were also performed. A conductivity transition by approximately 3 orders of magnitude was seen at approximately 60 degrees Celsius in VO2. This transition decreased in proportion with the amount of Li intercalation and was less than one order of magnitude in Li0.43VO2. Lithiation also decreased Tc by a few degrees Celsius. The thermoelectric power showed a well defined increase when Tc was exceeded.

  17. Ancient intron insertion sites and palindromic genomic duplication evolutionally shapes an elementally functioning membrane protein family

    PubMed Central

    Tanaka-Kunishima, Motoko; Ishida, Yoshihiro; Takahashi, Kunitaro; Honda, Motoo; Oonuma, Takashi

    2007-01-01

    Background In spite of the recent accumulation of genomic data, the evolutionary pathway in the individual genes of present-day living taxa is still elusive for most genes. Among ion channels, inward K+ rectifier (IRK) channels are the fundamental and well-defined protein group. We analyzed the genomic structures of this group and compared them among a phylogenetically wide range with our sequenced Halocynthia roretzi, a tunicate, IRK genomic genes. Results A total of 131 IRK genomic genes were analyzed. The phylogenic trees of amino acid sequences revealed a clear diversification of deuterostomic IRKs from protostomic IRKs and suggested that the tunicate IRKs are possibly representatives of the descendants of ancestor forms of three major groups of IRKs in the vertebrate. However, the exon-intron structures of the tunicate IRK genomes showed considerable similarities to those of Caenorhabditis. In the vertebrate clade, the members in each major group increased at least four times those in the tunicate by various types of global gene duplication. The generation of some major groups was inferred to be due to anti-tandem (palindromic) duplication in early history. The intron insertion points greatly decreased during the evolution of the vertebrates, remaining as a unique conservation of an intron insertion site in the portion of protein-protein interaction within the coding regions of all vertebrate G-protein-activated IRK genes. Conclusion From the genomic survey of a family of IRK genes, it was suggested that the ancient intron insertion sites and the unique palindromic genomic duplication evolutionally shaped this membrane protein family. PMID:17708769

  18. The genetic diversity and evolution of field pea (Pisum) studied by high throughput retrotransposon based insertion polymorphism (RBIP) marker analysis

    PubMed Central

    2010-01-01

    Background The genetic diversity of crop species is the result of natural selection on the wild progenitor and human intervention by ancient and modern farmers and breeders. The genomes of modern cultivars, old cultivated landraces, ecotypes and wild relatives reflect the effects of these forces and provide insights into germplasm structural diversity, the geographical dimension to species diversity and the process of domestication of wild organisms. This issue is also of great practical importance for crop improvement because wild germplasm represents a rich potential source of useful under-exploited alleles or allele combinations. The aim of the present study was to analyse a major Pisum germplasm collection to gain a broad understanding of the diversity and evolution of Pisum and provide a new rational framework for designing germplasm core collections of the genus. Results 3020 Pisum germplasm samples from the John Innes Pisum germplasm collection were genotyped for 45 retrotransposon based insertion polymorphism (RBIP) markers by the Tagged Array Marker (TAM) method. The data set was stored in a purpose-built Germinate relational database and analysed by both principal coordinate analysis and a nested application of the Structure program which yielded substantially similar but complementary views of the diversity of the genus Pisum. Structure revealed three Groups (1-3) corresponding approximately to landrace, cultivar and wild Pisum respectively, which were resolved by nested Structure analysis into 14 Sub-Groups, many of which correlate with taxonomic sub-divisions of Pisum, domestication related phenotypic traits and/or restricted geographical locations. Genetic distances calculated between these Sub-Groups are broadly supported by principal coordinate analysis and these, together with the trait and geographical data, were used to infer a detailed model for the domestication of Pisum. Conclusions These data provide a clear picture of the major distinct gene

  19. Filtering to match hearing aid insertion gain to individual ear acoustics.

    PubMed

    Bell, Steven L

    2009-09-01

    When hearing aid gain is prescribed by software, gain is calculated based on the average acoustics for the age of patient, gender, mold type, and so on. The acoustics of the individual's ear often vary from the average values, so there will be a mismatch between the prescribed gain and the real-ear gain. Real-ear measurement can be used to verify the gain and adjust it to meet targets, but the quality of the match will be limited by the number of channels and the flexibility of the hearing aid. A potential way to improve this process is to generate a filter that compensates for variations in real-ear insertion gain due to individual ear acoustics. Such a filter could be included in the processing path of a digital hearing aid. This article describes how such a filter can be generated using the windowing method, and the principle is demonstrated in a real ear. The approach requires communication between the real-ear measurement and hearing aid programming software. A finite impulse response filter with group delay just over 2 ms matched insertion gain to target values within the acceptable tolerance defined by British Society of Audiology guidelines. PMID:19713209

  20. Structure, dynamics, and insertion of a chloroplast targeting peptide in mixed micelles.

    PubMed

    Wienk, H L; Wechselberger, R W; Czisch, M; de Kruijff, B

    2000-07-18

    Nuclear-encoded, chloroplast-destined proteins are synthesized with transit sequences that contain all information to get them inside the organelle. Different proteins are imported via a general protein import machinery, but their transit sequences do not share amino acid homology. It has been suggested that interactions between transit sequence and chloroplast envelope membrane lipids give rise to recognizable, structural motifs. In this study a detailed investigation of the structural, dynamical, and topological features of an isolated transit peptide associated with mixed micelles is described. The structure of the preferredoxin transit peptide in these micelles was studied by circular dichroism (CD) and multidimensional NMR techniques. CD experiments indicated that the peptide, which is unstructured in aqueous solution, obtained helical structure in the presence of the micelles. By NMR it is shown that the micelles introduced ill-defined helical structures in the transit peptide. Heteronuclear relaxation experiments showed that the whole peptide backbone is very flexible. The least dynamic segments are two N- and C-terminal helical regions flanking an unstructured proline-rich amino acid stretch. Finally, the insertion of the peptide backbone in the hydrophobic interior of the micelle was investigated by use of hydrophobic spin-labels. The combined data result in a model of the transit peptide structure, backbone dynamics, and insertion upon its interaction with mixed micelles. PMID:10889029

  1. DNA transposon Hermes inserts into DNA in nucleosome-free regions in vivo.

    PubMed

    Gangadharan, Sunil; Mularoni, Loris; Fain-Thornton, Jennifer; Wheelan, Sarah J; Craig, Nancy L

    2010-12-21

    Transposons are mobile genetic elements that are an important source of genetic variation and are useful tools for genome engineering, mutagenesis screens, and vectors for transgenesis including gene therapy. We have used second-generation sequencing to analyze ≈2 × 10(5) unique de novo transposon insertion sites of the transposon Hermes in the Saccharomyces cerevisiae genome from both in vitro transposition reactions by using purified yeast genomic DNA, to better characterize intrinsic sequence specificity, and sites recovered from in vivo transposition events, to characterize the effect of intracellular factors such as chromatin on target site selection. We find that Hermes transposon targeting in vivo is profoundly affected by chromatin structure: The subset of genome-wide target sites used in vivo is strongly associated (P < 2e-16 by Fisher's exact test) with nucleosome-free chromatin. Our characterization of the insertion site preferences of Hermes not only assists in the future use of this transposon as a molecular biology tool but also establishes methods to more fully determine targeting mechanisms of other transposons. We have also discovered a long-range sequence motif that defines S. cerevisiae nucleosome-free regions. PMID:21131571

  2. DNA transposon Hermes inserts into DNA in nucleosome-free regions in vivo

    PubMed Central

    Gangadharan, Sunil; Mularoni, Loris; Fain-Thornton, Jennifer; Wheelan, Sarah J.; Craig, Nancy L.

    2010-01-01

    Transposons are mobile genetic elements that are an important source of genetic variation and are useful tools for genome engineering, mutagenesis screens, and vectors for transgenesis including gene therapy. We have used second-generation sequencing to analyze ≈2 × 105 unique de novo transposon insertion sites of the transposon Hermes in the Saccharomyces cerevisiae genome from both in vitro transposition reactions by using purified yeast genomic DNA, to better characterize intrinsic sequence specificity, and sites recovered from in vivo transposition events, to characterize the effect of intracellular factors such as chromatin on target site selection. We find that Hermes transposon targeting in vivo is profoundly affected by chromatin structure: The subset of genome-wide target sites used in vivo is strongly associated (P < 2e-16 by Fisher's exact test) with nucleosome-free chromatin. Our characterization of the insertion site preferences of Hermes not only assists in the future use of this transposon as a molecular biology tool but also establishes methods to more fully determine targeting mechanisms of other transposons. We have also discovered a long-range sequence motif that defines S. cerevisiae nucleosome-free regions. PMID:21131571

  3. Lesion insertion in the projection domain: Methods and initial results

    SciTech Connect

    Chen, Baiyu; Leng, Shuai; Yu, Lifeng; Yu, Zhicong; Ma, Chi; McCollough, Cynthia

    2015-12-15

    Purpose: To perform task-based image quality assessment in CT, it is desirable to have a large number of realistic patient images with known diagnostic truth. One effective way of achieving this objective is to create hybrid images that combine patient images with inserted lesions. Because conventional hybrid images generated in the image domain fails to reflect the impact of scan and reconstruction parameters on lesion appearance, this study explored a projection-domain approach. Methods: Lesions were segmented from patient images and forward projected to acquire lesion projections. The forward-projection geometry was designed according to a commercial CT scanner and accommodated both axial and helical modes with various focal spot movement patterns. The energy employed by the commercial CT scanner for beam hardening correction was measured and used for the forward projection. The lesion projections were inserted into patient projections decoded from commercial CT projection data. The combined projections were formatted to match those of commercial CT raw data, loaded onto a commercial CT scanner, and reconstructed to create the hybrid images. Two validations were performed. First, to validate the accuracy of the forward-projection geometry, images were reconstructed from the forward projections of a virtual ACR phantom and compared to physically acquired ACR phantom images in terms of CT number accuracy and high-contrast resolution. Second, to validate the realism of the lesion in hybrid images, liver lesions were segmented from patient images and inserted back into the same patients, each at a new location specified by a radiologist. The inserted lesions were compared to the original lesions and visually assessed for realism by two experienced radiologists in a blinded fashion. Results: For the validation of the forward-projection geometry, the images reconstructed from the forward projections of the virtual ACR phantom were consistent with the images physically

  4. One-pot synthesis of 2-amino-4(3H)-quinazolinones via ring-opening of isatoic anhydride and palladium-catalyzed oxidative isocyanide-insertion.

    PubMed

    Ji, Fei; Lv, Mei-Fang; Yi, Wen-Bin; Cai, Chun

    2014-08-14

    An efficient and practical two-step process has been developed for the synthesis of 2-amino-4(3H)-quinazolinones via ring-opening of isatoic anhydride and palladium-catalyzed oxidative isocyanide-insertion in one pot. This regioselective procedure could construct a wide range of 2-amino-4(3H)-quinazolinones in moderate to excellent yields. Furthermore, the methodology also had distinct advantages of easily accessible starting materials and operational simplicity. PMID:24968809

  5. Tensor distinction of domains in ferroic crystals

    NASA Astrophysics Data System (ADS)

    Litvin, D. B.

    2009-10-01

    Ferroic crystals contain two or more domains and may be distinguished by the values of components of tensorial physical properties of the domains. We have extended Aizu’s global tensor distinction by magnetization, polarization, and strain of all domains which arise in a ferroic phase transition to include distinction by toroidal moment, and from phases invariant under time reversal to domains which arise in transitions from all magnetic and non-magnetic phases. For determining possible switching of domains, a domain pair tensor distinction is also considered for all pairs of domains which arise in each ferroic phase transition.

  6. Competition for actin between two distinct F-actin networks defines a bistable switch for cell polarization.

    PubMed

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

    2015-11-01

    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 after 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. Under low-contractility regimes, epithelial cells polarize in a front-back manner owing to the 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

  7. Salinity stress in roots of contrasting barley genotypes reveals time-distinct and genotype-specific patterns for defined proteins.

    PubMed

    Witzel, Katja; Matros, Andrea; Strickert, Marc; Kaspar, Stephanie; Peukert, Manuela; Mühling, Karl H; Börner, Andreas; Mock, Hans-Peter

    2014-02-01

    Soil salinity is one of the most severe abiotic stress factors threatening agriculture worldwide. Hence, particular interest exists in unraveling mechanisms leading to salt tolerance and improved crop plant performance on saline soils. Barley is considered to be one of the most salinity-tolerant crops, but varying levels of tolerance are well characterized. A proteomic analysis of the roots of two contrasting cultivars (cv. Steptoe and cv. Morex) is presented. Young plants were exposed to a period of 1, 4, 7, or 10 d at 0, 100, or 150 mM NaCl. The root proteome was analyzed based on two-dimensional gel electrophoresis. A number of cultivar-specific and salinity stress-responsive proteins were identified. Mass spectrometry-based identification was successful for 74 proteins, and a hierarchical clustering analysis grouped these into five clusters based on similarity of expression profile. The rank product method was applied to statistically access the early and late responses, and this delivered a number of new candidate proteins underlying salinity tolerance in barley. Among these were some germin-like proteins, some pathogenesis-related proteins, and numerous as-yet uncharacterized proteins. Notably, proteins involved in detoxification pathways and terpenoid biosynthesis were detected as early responsive to salinity and may function as a means of modulating growth-regulating mechanisms and membrane stability via fine tuning of phytohormone and secondary metabolism in the root. PMID:24004485

  8. Structural Features and Functional Dependency on β-Clamp Define Distinct Subfamilies of Bacterial Mismatch Repair Endonuclease MutL.

    PubMed

    Fukui, Kenji; Baba, Seiki; Kumasaka, Takashi; Yano, Takato

    2016-08-12

    In early reactions of DNA mismatch repair, MutS recognizes mismatched bases and activates MutL endonuclease to incise the error-containing strand of the duplex. DNA sliding clamp is responsible for directing the MutL-dependent nicking to the newly synthesized/error-containing strand. In Bacillus subtilis MutL, the β-clamp-interacting motif (β motif) of the C-terminal domain (CTD) is essential for both in vitro direct interaction with β-clamp and in vivo repair activity. A large cluster of negatively charged residues on the B. subtilis MutL CTD prevents nonspecific DNA binding until β clamp interaction neutralizes the negative charge. We found that there are some bacterial phyla whose MutL endonucleases lack the β motif. For example, the region corresponding to the β motif is completely missing in Aquifex aeolicus MutL, and critical amino acid residues in the β motif are not conserved in Thermus thermophilus MutL. We then revealed the 1.35 Å-resolution crystal structure of A. aeolicus MutL CTD, which lacks the β motif but retains the metal-binding site for the endonuclease activity. Importantly, there was no negatively charged cluster on its surface. It was confirmed that CTDs of β motif-lacking MutLs, A. aeolicus MutL and T. thermophilus MutL, efficiently incise DNA even in the absence of β-clamp and that β-clamp shows no detectable enhancing effect on their activity. In contrast, CTD of Streptococcus mutans, a β motif-containing MutL, required β-clamp for the digestion of DNA. We propose that MutL endonucleases are divided into three subfamilies on the basis of their structural features and dependence on β-clamp. PMID:27369079

  9. Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site

    NASA Astrophysics Data System (ADS)

    Wang, Xizhuo; Wang, Youjun; Zhou, Yandong; Hendron, Eunan; Mancarella, Salvatore; Andrake, Mark D.; Rothberg, Brad S.; Soboloff, Jonathan; Gill, Donald L.

    2014-02-01

    STIM1 and STIM2 are widely expressed endoplasmic reticulum (ER) Ca2+ sensor proteins able to translocate within the ER membrane to physically couple with and gate plasma membrane Orai Ca2+ channels. Although they are structurally similar, we reveal critical differences in the function of the short STIM-Orai-activating regions (SOAR) of STIM1 and STIM2. We narrow these differences in Orai1 gating to a strategically exposed phenylalanine residue (Phe-394) in SOAR1, which in SOAR2 is substituted by a leucine residue. Remarkably, in full-length STIM1, replacement of Phe-394 with the dimensionally similar but polar histidine head group prevents both Orai1 binding and gating, creating an Orai1 non-agonist. Thus, this residue is critical in tuning the efficacy of Orai activation. While STIM1 is a full Orai1-agonist, leucine-replacement of this crucial residue in STIM2 endows it with partial agonist properties, which may be critical for limiting Orai1 activation stemming from its enhanced sensitivity to store-depletion.

  10. Distinct Orai-coupling domains in STIM1 and STIM2 define the Orai-activating site

    PubMed Central

    Wang, Xizhuo; Wang, Youjun; Zhou, Yandong; Hendron, Eunan; Mancarella, Salvatore; Andrake, Mark D.; Rothberg, Brad S.; Soboloff, Jonathan; Gill, Donald L.

    2014-01-01

    STIM1 and STIM2 are widely expressed endoplasmic reticulum (ER) Ca2+ sensor proteins able to translocate within the ER membrane to physically couple with and gate plasma membrane Orai Ca2+ channels. Although structurally similar, we reveal critical differences in the function of the short STIM-Orai activating regions (SOAR) from STIM1 and STIM2. We narrowed these differences in Orai1 gating to a strategically exposed phenylalanine residue (Phe-394) in SOAR1, which in SOAR2 is substituted by a leucine residue. Remarkably, in full-length STIM1, replacement of Phe-394 with the dimensionally similar but polar histidine headgroup, prevents both Orai1 binding and gating, creating an Orai1 non-agonist. Thus, this residue is critical in tuning the efficacy of Orai activation. While STIM1 is a full Orai1-agonist, leucine-replacement of this crucial residue in STIM2 endows it with partial agonist properties, which may be critical for limiting Orai1 activation stemming from its enhanced sensitivity to store-depletion. PMID:24492416

  11. Epigenetic Marks Define the Lineage and Differentiation Potential of Two Distinct Neural Crest-Derived Intermediate Odontogenic Progenitor Populations

    PubMed Central

    Gopinathan, Gokul; Kolokythas, Antonia

    2013-01-01

    Epigenetic mechanisms, such as histone modifications, play an active role in the differentiation and lineage commitment of mesenchymal stem cells. In the present study, epigenetic states and differentiation profiles of two odontogenic neural crest-derived intermediate progenitor populations were compared: dental pulp (DP) and dental follicle (DF). ChIP on chip assays revealed substantial H3K27me3-mediated repression of odontoblast lineage genes DSPP and dentin matrix protein 1 (DMP1) in DF cells, but not in DP cells. Mineralization inductive conditions caused steep increases of mineralization and patterning gene expression levels in DP cells when compared to DF cells. In contrast, mineralization induction resulted in a highly dynamic histone modification response in DF cells, while there was only a subdued effect in DP cells. Both DF and DP progenitors featured H3K4me3-active marks on the promoters of early mineralization genes RUNX2, MSX2, and DLX5, while OSX, IBSP, and BGLAP promoters were enriched for H3K9me3 or H3K27me3. Compared to DF cells, DP cells expressed higher levels of three pluripotency-associated genes, OCT4, NANOG, and SOX2. Finally, gene ontology comparison of bivalent marks unique for DP and DF cells highlighted cell–cell attachment genes in DP cells and neurogenesis genes in DF cells. In conclusion, the present study indicates that the DF intermediate odontogenic neural crest lineage is distinguished from its DP counterpart by epigenetic repression of DSPP and DMP1 genes and through dynamic histone enrichment responses to mineralization induction. Findings presented here highlight the crucial role of epigenetic regulatory mechanisms in the terminal differentiation of odontogenic neural crest lineages. PMID:23379639

  12. An Old Story Retold: Loss of G1 Control Defines A Distinct Genomic Subtype of Esophageal Squamous Cell Carcinoma

    PubMed Central

    Wang, Qiyan; Bai, Jian; Abliz, Amir; Liu, Ying; Gong, Kenan; Li, Jingjing; Shi, Wenjie; Pan, Yaqi; Liu, Fangfang; Lai, Shujuan; Yang, Haijun; Lu, Changdong; Zhang, Lixin; Chen, Wei; Xu, Ruiping; Cai, Hong; Ke, Yang; Zeng, Changqing

    2015-01-01

    Esophageal squamous cell carcinoma (ESCC) has a high mortality rate. To determine the molecular basis of ESCC development, this study sought to identify characteristic genome-wide alterations in ESCC, including exonic mutations and structural alterations. The clinical implications of these genetic alterations were also analyzed. Exome sequencing and verification were performed for nine pairs of ESCC and the matched blood samples, followed by validation with additional samples using Sanger sequencing. Whole-genome SNP arrays were employed to detect copy number alteration (CNA) and loss of heterozygosity (LOH) in 55 cases, including the nine ESCC samples subjected to exome sequencing. A total of 108 non-synonymous somatic mutations (NSSMs) in 102 genes were verified in nine patients. The chromatin modification process was found to be enriched in our gene ontology (GO) analysis. Tumor genomes with TP53 mutations were significantly more unstable than those without TP53 mutations. In terms of the landscape of genomic alterations, deletion of 9p21.3 covering CDKN2A/2B (30.9%), amplification of 11q13.3 covering CCND1 (30.9%), and TP53 point mutation (50.9%) occurred in two-thirds of the cases. These results suggest that the deregulation of the G1 phase during the cell cycle is a key event in ESCC. Furthermore, six minimal common regions were found to be significantly altered in ESCC samples and three of them, 9p21.3, 7p11.2, and 3p12.1, were associated with lymph node metastasis. With the high correlation of TP53 mutation and genomic instability in ESCC, the amplification of CCND1, the deletion of CDKN2A/2B, and the somatic mutation of TP53 appear to play pivotal roles via G1 deregulation and therefore helps to classify this cancer into different genomic subtypes. These findings provide clinical significance that could be useful in future molecular diagnoses and therapeutic targeting. PMID:26386145

  13. An Insertion Peptide in Yeast Glycyl-tRNA Synthetase Facilitates both Productive Docking and Catalysis of Cognate tRNAs

    PubMed Central

    Wu, Yi-Hua; Chang, Chia-Pei; Chien, Chin-I; Tseng, Yi-Kuan

    2013-01-01

    The yeast Saccharomyces cerevisiae possesses two distinct glycyl-tRNA synthetase (GlyRS) genes: GRS1 and GRS2. GRS1 is dually functional, encoding both cytoplasmic and mitochondrial activities, while GRS2 is dysfunctional and not required for growth. The protein products of these two genes, GlyRS1 and GlyRS2, are much alike but are distinguished by an insertion peptide of GlyRS1, which is absent from GlyRS2 and other eukaryotic homologues. We show that deletion or mutation of the insertion peptide modestly impaired the enzyme's catalytic efficiency in vitro (with a 2- to 3-fold increase in Km and a 5- to 8-fold decrease in kcat). Consistently, GRS2 can be conveniently converted to a functional gene via codon optimization, and the insertion peptide is dispensable for protein stability and the rescue activity of GRS1 at 30°C in vivo. A phylogenetic analysis further showed that GRS1 and GRS2 are paralogues that arose from a gene duplication event relatively recently, with GRS1 being the predecessor. These results indicate that GlyRS2 is an active enzyme essentially resembling the insertion peptide-deleted form of GlyRS1. Our study suggests that the insertion peptide represents a novel auxiliary domain, which facilitates both productive docking and catalysis of cognate tRNAs. PMID:23816885

  14. On the Reversibility of Parallel Insertion, and Its Relation to Comma Codes

    NASA Astrophysics Data System (ADS)

    Cui, Bo; Kari, Lila; Seki, Shinnosuke

    This paper studies conditions under which the operation of parallel insertion can be reversed by parallel deletion, i.e., when does the equality (L_1 Leftarrow L_2) Rightarrow L_2 = L_1 hold for languages L 1 and L 2. We obtain a complete characterization of the solutions in the special case when both languages involved are singleton words. We also define comma codes, a family of codes with the property that, if L 2 is a comma code, then the above equation holds for any language L_1 subseteq {Σ}^*. Lastly, we generalize the notion of comma codes to that of comma intercodes of index m. Besides several properties, we prove that the families of comma intercodes of index m form an infinite proper inclusion hierarchy, the first element which is a subset of the family of infix codes, and the last element of which is a subset of the family of bifix codes.

  15. Manufacturing microstructured tool inserts for the production of polymeric microfluidic devices

    NASA Astrophysics Data System (ADS)

    Zhang, Nan; Srivastava, Amit; Kirwan, Brendan; Byrne, Richard; Fang, Fengzhou; Browne, David J.; Gilchrist, Michael D.

    2015-09-01

    Tooling is critical in defining multi-scale patterns for mass production of polymeric microfluidic devices using the microinjection molding process. In the present work, fabrication of various microstructured tool inserts using stainless steel, nickel and bulk metallic glasses (BMGs) is discussed based on die-sinking EDM (electrical discharge machining), electroforming, focused ion beam milling and thermoplastic forming processes. Tool performance is evaluated in terms of surface roughness, hardness and tool life. Compared to stainless steel, nickel and BMGs are capable of integrating length scales from 100 to 10-8 m and are good candidates for producing polymeric microfluidics. Selection of tool materials and manufacturing technologies should consider the end-user requirements of actual applications.

  16. MassToMI-A Mathematica package for an automatic Mass Insertion expansion

    NASA Astrophysics Data System (ADS)

    Rosiek, Janusz

    2016-04-01

    We present a Mathematica package designed to automatize the expansion of transition amplitudes calculated in the mass eigenstates basis (i.e. expressed in terms of physical masses and mixing matrices) into series of "mass insertions", defined as off-diagonal entries of mass matrices in Lagrangian before diagonalization and identification of the physical states. The algorithm implemented in this package is based on the general "Flavor Expansion Theorem" proven in Dedes et al. (2015). The supplied routines are able to automatically analyze the structure of the amplitude, identify the parts which could be expanded and expand them to any required order. They are capable of dealing with amplitudes depending on both scalar or vector (Hermitian) and Dirac or Majorana fermion (complex) mass matrices. The package can be downloaded from the address www.fuw.edu.pl/masstomi.

  17. Feasibility Study of Free-Hand Technique for Pedicle Screw Insertion at C7 without Fluoroscopy-Guidance

    PubMed Central

    Lee, Gun Woo; Kim, Ho-Joong; Yeom, Jin S.; Uh, Jae-Hyung; Park, Jong-Ho; Lee, Ji-Hoon; Kim, Dong-Wook

    2016-01-01

    Study Design Retrospective interventional study. Purpose To introduce a free-hand pedicle screw (PS) insertion technique without fluoroscopic guidance in the C7 vertebra and evaluate the procedure's feasibility and radiologic outcomes. Overview of Literature Although PS insertion at C7 has been recognized as a critical procedure in posterior cervical fusion surgery, conventional techniques for C7 PS have several limitations. Methods Thirty two patients (64 screws) who underwent PS insertion in C7 with the novel technique were included in this study. Postoperative clinical and radiological outcomes were evaluated. Special attention was paid to the presence of any problems in the screw position including cortical breaches of the PS and encroachment of the PS into the spinal canal or the vertebral foramen. This novel technique for PS insertion in C7 without fluoroscopy guidance had three key elements. First, the ideal PS entry point was chosen near the C6–7 facet joint using preoperative images. Second, the convergent angle distance was measured at axial computed tomography (CT) imaging, which defined the distance between the tip of C7 spinous process and the extended line passing through the pedicle axis from the ideal entry point. Third, the cranial-caudal angle distance was measured in sagittal CT images, which defined the distance between the tip of the C7 spinous process and the extended line passing through the pedicle axis. Results Cortical breach on postoperative CT images was observed in three screws. All violated only the lateral wall of the affected pedicle. The breached screws occurred in the initial five cases. Postoperative neurologic deterioration was not observed in any patient, regardless of cortical breaching. Conclusions The novel technique successfully allows for C7 PS to be placed and is associated with a low rate of cortical breach. PMID:26949456

  18. Elicited versus emitted behavior: Time to abandon the distinction.

    PubMed

    Domjan, Michael

    2016-03-01

    The concept of emitted behavior was formulated as a part of the original argument for the validity of a new kind of learning called operant conditioning. The rationale for operant conditioning contrasted it with Pavlovian or classical conditioning, which was (and remains) fundamentally based on responses to conditioned and unconditioned stimuli. Classical conditioned responses were said to be elicited. In contrast, operant behavior was viewed as emitted and controlled primarily by response consequences rather than antecedents. I argue that the distinction between emitted and elicited behavior is no longer warranted for three major reasons. First, the distinction was based on a view of Pavlovian conditioning that is no longer viable. Second, the distinction is incompatible with both empirical data and contemporary conceptualizations of operant behavior. Third, the only way to overcome these problems is to define emitted and elicited in terms of the type of conditioning (operant and classical) that produces these behaviors, but that approach makes the definitions circular and does not avoid implications of the terms that are misleading and counterproductive in light of contemporary research and thinking. PMID:26872681

  19. Insertional mutagenesis by transposable elements in the mammalian genome.

    PubMed

    Amariglio, N; Rechavi, G

    1993-01-01

    Several mammalian repetitive transposable genetic elements were characterized in recent years, and their role in mutagenesis is delineated in this review. Two main groups have been described: elements with symmetrical termini such as the murine IAP sequences and the human THE 1 elements and elements characterized by a poly-A rich tail at the 3' end such as the SINE and LINE sequences. The characteristic property of such mobile elements to spread and integrate in the host genome leads to insertional mutagenesis. Both germline and somatic mutations have been documented resulting from the insertion of the various types of mammalian repetitive transposable genetic elements. As foreseen by Barbara McClintock, such genetic events can cause either the activation or the inactivation of specific genes, resulting in their identification via an altered phenotype. Several disease states, such as hemophilia and cancer, are the result of this apparent aspect of genome instability. PMID:8385004

  20. Construction of targeted insertion mutations in Francisella tularensis subsp. novicida.

    PubMed

    Liu, Jirong; Zogaj, Xhavit; Barker, Jeffrey R; Klose, Karl E

    2007-10-01

    Francisella tularensis is one of the most deadly bacterial agents, yet most of the genetic determinants of pathogenesis are still unknown. We have developed an efficient targeted mutagenesis strategy in the model organism F. tularensis subsp. novicida by utilizing universal priming of optimized antibiotic resistance cassettes and splicing by overlap extension (SOE). This process enables fast and efficient construction of targeted insertion mutations in F. tularensis subsp. novicida that have characteristics of nonpolar mutations; optimized targeted mutagenesis strategies will promote the study of this mysterious bacterium and facilitate vaccine development against tularemia. Moreover the general strategy of gene disruption by PCR-based antibiotic resistance cassette insertion is broadly applicable to many bacterial species. PMID:18019340