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Sample records for deletion network derived

  1. Determining protein complex connectivity using a probabilistic deletion network derived from quantitative proteomics.

    Science.gov (United States)

    Sardiu, Mihaela E; Gilmore, Joshua M; Carrozza, Michael J; Li, Bing; Workman, Jerry L; Florens, Laurence; Washburn, Michael P

    2009-10-06

    Protein complexes are key molecular machines executing a variety of essential cellular processes. Despite the availability of genome-wide protein-protein interaction studies, determining the connectivity between proteins within a complex remains a major challenge. Here we demonstrate a method that is able to predict the relationship of proteins within a stable protein complex. We employed a combination of computational approaches and a systematic collection of quantitative proteomics data from wild-type and deletion strain purifications to build a quantitative deletion-interaction network map and subsequently convert the resulting data into an interdependency-interaction model of a complex. We applied this approach to a data set generated from components of the Saccharomyces cerevisiae Rpd3 histone deacetylase complexes, which consists of two distinct small and large complexes that are held together by a module consisting of Rpd3, Sin3 and Ume1. The resulting representation reveals new protein-protein interactions and new submodule relationships, providing novel information for mapping the functional organization of a complex.

  2. Determining protein complex connectivity using a probabilistic deletion network derived from quantitative proteomics.

    Directory of Open Access Journals (Sweden)

    Mihaela E Sardiu

    2009-10-01

    Full Text Available Protein complexes are key molecular machines executing a variety of essential cellular processes. Despite the availability of genome-wide protein-protein interaction studies, determining the connectivity between proteins within a complex remains a major challenge. Here we demonstrate a method that is able to predict the relationship of proteins within a stable protein complex. We employed a combination of computational approaches and a systematic collection of quantitative proteomics data from wild-type and deletion strain purifications to build a quantitative deletion-interaction network map and subsequently convert the resulting data into an interdependency-interaction model of a complex. We applied this approach to a data set generated from components of the Saccharomyces cerevisiae Rpd3 histone deacetylase complexes, which consists of two distinct small and large complexes that are held together by a module consisting of Rpd3, Sin3 and Ume1. The resulting representation reveals new protein-protein interactions and new submodule relationships, providing novel information for mapping the functional organization of a complex.

  3. A local-world node deleting evolving network model

    International Nuclear Information System (INIS)

    Gu Yuying; Sun Jitao

    2008-01-01

    A new type network growth rule which comprises node addition with the concept of local-world connectivity and node deleting is studied. A series of theoretical analysis and numerical simulation to the LWD network are conducted in this Letter. Firstly, the degree distribution p(k) of this network changes no longer pure scale free but truncates by an exponential tail and the truncation in p(k) increases as p a decreases. Secondly, the connectivity is tighter, as the local-world size M increases. Thirdly, the average path length L increases and the clustering coefficient decreases as generally node deleting increases. Finally, trends up when the local-world size M increases, so as to k max . Hence, the expanding local-world can compensate the infection of the node deleting

  4. A local-world node deleting evolving network model

    Energy Technology Data Exchange (ETDEWEB)

    Gu Yuying [Department of Mathematics, Tongji University, Shanghai 200092 (China); Sun Jitao [Department of Mathematics, Tongji University, Shanghai 200092 (China)], E-mail: sunjt@sh163.net

    2008-06-16

    A new type network growth rule which comprises node addition with the concept of local-world connectivity and node deleting is studied. A series of theoretical analysis and numerical simulation to the LWD network are conducted in this Letter. Firstly, the degree distribution p(k) of this network changes no longer pure scale free but truncates by an exponential tail and the truncation in p(k) increases as p{sub a} decreases. Secondly, the connectivity is tighter, as the local-world size M increases. Thirdly, the average path length L increases and the clustering coefficient decreases as generally node deleting increases. Finally, trends up when the local-world size M increases, so as to k{sub max}. Hence, the expanding local-world can compensate the infection of the node deleting.

  5. Detection of three-base deletion by exciplex formation with perylene derivatives.

    Science.gov (United States)

    Kashida, Hiromu; Kondo, Nobuyo; Sekiguchi, Koji; Asanuma, Hiroyuki

    2011-06-14

    Here, we synthesized fluorescent DNA probes labeled with two perylene derivatives for the detection of a three-base deletion mutant. One such probe discriminated the three-base deletion mutant from the wild-type sequence by exciplex emission, and the deletion mutant was identifiable even by the naked eye. This journal is © The Royal Society of Chemistry 2011

  6. Network topologies and convergent aetiologies arising from deletions and duplications observed in individuals with autism.

    Science.gov (United States)

    Noh, Hyun Ji; Ponting, Chris P; Boulding, Hannah C; Meader, Stephen; Betancur, Catalina; Buxbaum, Joseph D; Pinto, Dalila; Marshall, Christian R; Lionel, Anath C; Scherer, Stephen W; Webber, Caleb

    2013-06-01

    Autism Spectrum Disorders (ASD) are highly heritable and characterised by impairments in social interaction and communication, and restricted and repetitive behaviours. Considering four sets of de novo copy number variants (CNVs) identified in 181 individuals with autism and exploiting mouse functional genomics and known protein-protein interactions, we identified a large and significantly interconnected interaction network. This network contains 187 genes affected by CNVs drawn from 45% of the patients we considered and 22 genes previously implicated in ASD, of which 192 form a single interconnected cluster. On average, those patients with copy number changed genes from this network possess changes in 3 network genes, suggesting that epistasis mediated through the network is extensive. Correspondingly, genes that are highly connected within the network, and thus whose copy number change is predicted by the network to be more phenotypically consequential, are significantly enriched among patients that possess only a single ASD-associated network copy number changed gene (p = 0.002). Strikingly, deleted or disrupted genes from the network are significantly enriched in GO-annotated positive regulators (2.3-fold enrichment, corrected p = 2×10(-5)), whereas duplicated genes are significantly enriched in GO-annotated negative regulators (2.2-fold enrichment, corrected p = 0.005). The direction of copy change is highly informative in the context of the network, providing the means through which perturbations arising from distinct deletions or duplications can yield a common outcome. These findings reveal an extensive ASD-associated molecular network, whose topology indicates ASD-relevant mutational deleteriousness and that mechanistically details how convergent aetiologies can result extensively from CNVs affecting pathways causally implicated in ASD.

  7. Quantitative proteomics and network analysis of SSA1 and SSB1 deletion mutants reveals robustness of chaperone HSP70 network in Saccharomyces cerevisiae.

    Science.gov (United States)

    Jarnuczak, Andrew F; Eyers, Claire E; Schwartz, Jean-Marc; Grant, Christopher M; Hubbard, Simon J

    2015-09-01

    Molecular chaperones play an important role in protein homeostasis and the cellular response to stress. In particular, the HSP70 chaperones in yeast mediate a large volume of protein folding through transient associations with their substrates. This chaperone interaction network can be disturbed by various perturbations, such as environmental stress or a gene deletion. Here, we consider deletions of two major chaperone proteins, SSA1 and SSB1, from the chaperone network in Sacchromyces cerevisiae. We employ a SILAC-based approach to examine changes in global and local protein abundance and rationalise our results via network analysis and graph theoretical approaches. Although the deletions result in an overall increase in intracellular protein content, correlated with an increase in cell size, this is not matched by substantial changes in individual protein concentrations. Despite the phenotypic robustness to deletion of these major hub proteins, it cannot be simply explained by the presence of paralogues. Instead, network analysis and a theoretical consideration of folding workload suggest that the robustness to perturbation is a product of the overall network structure. This highlights how quantitative proteomics and systems modelling can be used to rationalise emergent network properties, and how the HSP70 system can accommodate the loss of major hubs. © 2015 The Authors. PROTEOMICS published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. MicroRNA Dysregulation, Gene Networks, and Risk for Schizophrenia in 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Merico, Daniele; Costain, Gregory; Butcher, Nancy J.; Warnica, William; Ogura, Lucas; Alfred, Simon E.; Brzustowicz, Linda M.; Bassett, Anne S.

    2014-01-01

    The role of microRNAs (miRNAs) in the etiology of schizophrenia is increasingly recognized. Microdeletions at chromosome 22q11.2 are recurrent structural variants that impart a high risk for schizophrenia and are found in up to 1% of all patients with schizophrenia. The 22q11.2 deletion region overlaps gene DGCR8, encoding a subunit of the miRNA microprocessor complex. We identified miRNAs overlapped by the 22q11.2 microdeletion and for the first time investigated their predicted target genes, and those implicated by DGCR8, to identify targets that may be involved in the risk for schizophrenia. The 22q11.2 region encompasses seven validated or putative miRNA genes. Employing two standard prediction tools, we generated sets of predicted target genes. Functional enrichment profiles of the 22q11.2 region miRNA target genes suggested a role in neuronal processes and broader developmental pathways. We then constructed a protein interaction network of schizophrenia candidate genes and interaction partners relevant to brain function, independent of the 22q11.2 region miRNA mechanisms. We found that the predicted gene targets of the 22q11.2 deletion miRNAs, and targets of the genome-wide miRNAs predicted to be dysregulated by DGCR8 hemizygosity, were significantly represented in this schizophrenia network. The findings provide new insights into the pathway from 22q11.2 deletion to expression of schizophrenia, and suggest that hemizygosity of the 22q11.2 region may have downstream effects implicating genes elsewhere in the genome that are relevant to the general schizophrenia population. These data also provide further support for the notion that robust genetic findings in schizophrenia may converge on a reasonable number of final pathways. PMID:25484875

  9. ReacKnock: identifying reaction deletion strategies for microbial strain optimization based on genome-scale metabolic network.

    Directory of Open Access Journals (Sweden)

    Zixiang Xu

    Full Text Available Gene knockout has been used as a common strategy to improve microbial strains for producing chemicals. Several algorithms are available to predict the target reactions to be deleted. Most of them apply mixed integer bi-level linear programming (MIBLP based on metabolic networks, and use duality theory to transform bi-level optimization problem of large-scale MIBLP to single-level programming. However, the validity of the transformation was not proved. Solution of MIBLP depends on the structure of inner problem. If the inner problem is continuous, Karush-Kuhn-Tucker (KKT method can be used to reformulate the MIBLP to a single-level one. We adopt KKT technique in our algorithm ReacKnock to attack the intractable problem of the solution of MIBLP, demonstrated with the genome-scale metabolic network model of E. coli for producing various chemicals such as succinate, ethanol, threonine and etc. Compared to the previous methods, our algorithm is fast, stable and reliable to find the optimal solutions for all the chemical products tested, and able to provide all the alternative deletion strategies which lead to the same industrial objective.

  10. Energy-Aware Topology Evolution Model with Link and Node Deletion in Wireless Sensor Networks

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    Xiaojuan Luo

    2012-01-01

    Full Text Available Based on the complex network theory, a new topological evolving model is proposed. In the evolution of the topology of sensor networks, the energy-aware mechanism is taken into account, and the phenomenon of change of the link and node in the network is discussed. Theoretical analysis and numerical simulation are conducted to explore the topology characteristics and network performance with different node energy distribution. We find that node energy distribution has the weak effect on the degree distribution P(k that evolves into the scale-free state, nodes with more energy carry more connections, and degree correlation is nontrivial disassortative. Moreover, the results show that, when nodes energy is more heterogeneous, the network is better clustered and enjoys higher performance in terms of the network efficiency and the average path length for transmitting data.

  11. Adaptive synchronization of the complex dynamical network with non-derivative and derivative coupling

    Energy Technology Data Exchange (ETDEWEB)

    Xu Yuhua, E-mail: yuhuaxu2004@163.co [College of Information Science and Technology, Donghua University, Shanghai 201620 (China) and Department of Maths, Yunyang Teachers' College, Hubei 442000 (China); Zhou Wuneng, E-mail: wnzhou@163.co [College of Information Science and Technology, Donghua University, Shanghai 201620 (China); Fang Jian' an [College of Information Science and Technology, Donghua University, Shanghai 201620 (China); Sun Wen [School of Mathematics and Information, Yangtze University, Hubei Jingzhou 434023 (China)

    2010-04-05

    This Letter investigates the synchronization of a general complex dynamical network with non-derivative and derivative coupling. Based on LaSalle's invariance principle, adaptive synchronization criteria are obtained. Analytical result shows that under the designed adaptive controllers, a general complex dynamical network with non-derivative and derivative coupling can asymptotically synchronize to a given trajectory, and several useful criteria for synchronization are given. What is more, the coupling matrix is not assumed to be symmetric or irreducible. Finally, simulations results show the method is effective.

  12. An affected core drives network integration deficits of the structural connectome in 22q11.2 deletion syndrome

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    František Váša

    2016-01-01

    Full Text Available Chromosome 22q11.2 deletion syndrome (22q11DS is a genetic disease known to lead to cerebral structural alterations, which we study using the framework of the macroscopic white-matter connectome. We create weighted connectomes of 44 patients with 22q11DS and 44 healthy controls using diffusion tensor magnetic resonance imaging, and perform a weighted graph theoretical analysis. After confirming global network integration deficits in 22q11DS (previously identified using binary connectomes, we identify the spatial distribution of regions responsible for global deficits. Next, we further characterize the dysconnectivity of the deficient regions in terms of sub-network properties, and investigate their relevance with respect to clinical profiles. We define the subset of regions with decreased nodal integration (evaluated using the closeness centrality measure as the affected core (A-core of the 22q11DS structural connectome. A-core regions are broadly bilaterally symmetric and consist of numerous network hubs — chiefly parietal and frontal cortical, as well as subcortical regions. Using a simulated lesion approach, we demonstrate that these core regions and their connections are particularly important to efficient network communication. Moreover, these regions are generally densely connected, but less so in 22q11DS. These specific disturbances are associated to a rerouting of shortest network paths that circumvent the A-core in 22q11DS, “de-centralizing” the network. Finally, the efficiency and mean connectivity strength of an orbito-frontal/cingulate circuit, included in the affected regions, correlate negatively with the extent of negative symptoms in 22q11DS patients, revealing the clinical relevance of present findings. The identified A-core overlaps numerous regions previously identified as affected in 22q11DS as well as in schizophrenia, which approximately 30–40% of 22q11DS patients develop.

  13. Homozygous deletion of the α- and β1-interferon genes in human leukemia and derived cell lines

    International Nuclear Information System (INIS)

    Diaz, M.O.; Ziemin, S.; Le Beau, M.M.; Pitha, P.; Smith, S.D.; Chilcote, R.R.; Rowley, J.D.

    1988-01-01

    The loss of bands p21-22 from one chromosome 9 homologue as a consequence of a deletion of the short arm [del(9p)], unbalanced translocation, or monosomy 9 is frequently observed in the malignant cells of patients with lymphoid neoplasias, including acute lymphoblastic leukemia and non-Hodgkin lymphoma. The α- and β 1 -interferon genes have been assigned to this chromosome region (9p21-22). The authors now present evidence of the homozygous deletion of the interferon genes in neoplastic hematopoietic cell lines and primary leukemia cells in the presence or absence of chromosomal deletions that are detectable at the level of the light microscope. In these cell lines, the deletion of the interferon genes is accompanied by a deficiency of 5'-methylthioadenosine phosphorylase, an enzyme of purine metabolism. These homozygous deletions may be associated with the loss of a tumor-suppressor gene that is involved in the development of these neoplasias. The relevant genes may be either the interferon genes themselves or a gene that has a tumor-suppressor function and is closely linked to them

  14. Myeloid Malignancies with Chromosome 5q Deletions Acquire a Dependency on an Intrachromosomal NF-κB Gene Network

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    Jing Fang

    2014-09-01

    Full Text Available Chromosome 5q deletions (del[5q] are common in high-risk (HR myelodysplastic syndrome (MDS and acute myeloid leukemia (AML; however, the gene regulatory networks that sustain these aggressive diseases are unknown. Reduced miR-146a expression in del(5q HR MDS/AML and miR-146a−/− hematopoietic stem/progenitor cells (HSPCs results in TRAF6/NF-κB activation. Increased survival and proliferation of HSPCs from miR-146alow HR MDS/AML is sustained by a neighboring haploid gene, SQSTM1 (p62, expressed from the intact 5q allele. Overexpression of p62 from the intact allele occurs through NF-κB-dependent feedforward signaling mediated by miR-146a deficiency. p62 is necessary for TRAF6-mediated NF-κB signaling, as disrupting the p62-TRAF6 signaling complex results in cell-cycle arrest and apoptosis of MDS/AML cells. Thus, del(5q HR MDS/AML employs an intrachromosomal gene network involving loss of miR-146a and haploid overexpression of p62 via NF-κB to sustain TRAF6/NF-κB signaling for cell survival and proliferation. Interfering with the p62-TRAF6 signaling complex represents a therapeutic option in miR-146a-deficient and aggressive del(5q MDS/AML.

  15. What value do users derive from social networking applications?

    OpenAIRE

    Neale, Larry; Russell-Bennett, Rebekah

    2009-01-01

    Why do users of social networking sites recommend some applications to their friends while rejecting others? What value do they obtain from applications? This exploratory study investigates the value users derive from ‘cool’ Facebook applications, and explores the features that either encourage or discourage users to recommend applications to their friends. Our qualitative data reveal consumers derive a combination of functional value along with either social or emotional value from the app...

  16. Neural network representation and learning of mappings and their derivatives

    Science.gov (United States)

    White, Halbert; Hornik, Kurt; Stinchcombe, Maxwell; Gallant, A. Ronald

    1991-01-01

    Discussed here are recent theorems proving that artificial neural networks are capable of approximating an arbitrary mapping and its derivatives as accurately as desired. This fact forms the basis for further results establishing the learnability of the desired approximations, using results from non-parametric statistics. These results have potential applications in robotics, chaotic dynamics, control, and sensitivity analysis. An example involving learning the transfer function and its derivatives for a chaotic map is discussed.

  17. Strategies for state-dependent quantum deleting

    International Nuclear Information System (INIS)

    Song Wei; Yang Ming; Cao Zhuoliang

    2004-01-01

    A quantum state-dependent quantum deleting machine is constructed. We obtain a upper bound of the global fidelity on N-to-M quantum deleting from a set of K non-orthogonal states. Quantum networks are constructed for the above state-dependent quantum deleting machine when K=2. Our deleting protocol only involves a unitary interaction among the initial copies, with no ancilla. We also present some analogies between quantum cloning and deleting

  18. NT2 derived neuronal and astrocytic network signalling.

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    Eric J Hill

    Full Text Available A major focus of stem cell research is the generation of neurons that may then be implanted to treat neurodegenerative diseases. However, a picture is emerging where astrocytes are partners to neurons in sustaining and modulating brain function. We therefore investigated the functional properties of NT2 derived astrocytes and neurons using electrophysiological and calcium imaging approaches. NT2 neurons (NT2Ns expressed sodium dependent action potentials, as well as responses to depolarisation and the neurotransmitter glutamate. NT2Ns exhibited spontaneous and coordinated calcium elevations in clusters and in extended processes, indicating local and long distance signalling. Tetrodotoxin sensitive network activity could also be evoked by electrical stimulation. Similarly, NT2 astrocytes (NT2As exhibited morphology and functional properties consistent with this glial cell type. NT2As responded to neuronal activity and to exogenously applied neurotransmitters with calcium elevations, and in contrast to neurons, also exhibited spontaneous rhythmic calcium oscillations. NT2As also generated propagating calcium waves that were gap junction and purinergic signalling dependent. Our results show that NT2 derived astrocytes exhibit appropriate functionality and that NT2N networks interact with NT2A networks in co-culture. These findings underline the utility of such cultures to investigate human brain cell type signalling under controlled conditions. Furthermore, since stem cell derived neuron function and survival is of great importance therapeutically, our findings suggest that the presence of complementary astrocytes may be valuable in supporting stem cell derived neuronal networks. Indeed, this also supports the intriguing possibility of selective therapeutic replacement of astrocytes in diseases where these cells are either lost or lose functionality.

  19. Efficient Minimax Design of Networks without Using Derivatives

    DEFF Research Database (Denmark)

    Madsen, Kaj; Nielsen, Niels Ole; Schjær-Jacobsen, Hans

    1975-01-01

    ., which makes the gradient computation by the adjoint network method or related methods rather complicated, and often numerical errors are introduced in the gradients. Consequently, the algorithm is found to be of particular relevance in optimum design of practical microwave networks. The relative...... design results. Finally, optimum broad-band design of a practical coaxial transferred-electron reflection-type amplilier is carried out by means of the proposed method. The results are supported by experimental verification.......A new minimax network optimization algorithm not requiring derivatives has been developed. It is based on successive linear approximations to the nonlinear functions defining the problem. Adequate modeling of distributed parameter circuits for optimization purposes often involves parasitic, etc...

  20. The Network of Counterparty Risk: Analysing Correlations in OTC Derivatives.

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    Nanumyan, Vahan; Garas, Antonios; Schweitzer, Frank

    2015-01-01

    Counterparty risk denotes the risk that a party defaults in a bilateral contract. This risk not only depends on the two parties involved, but also on the risk from various other contracts each of these parties holds. In rather informal markets, such as the OTC (over-the-counter) derivative market, institutions only report their aggregated quarterly risk exposure, but no details about their counterparties. Hence, little is known about the diversification of counterparty risk. In this paper, we reconstruct the weighted and time-dependent network of counterparty risk in the OTC derivatives market of the United States between 1998 and 2012. To proxy unknown bilateral exposures, we first study the co-occurrence patterns of institutions based on their quarterly activity and ranking in the official report. The network obtained this way is further analysed by a weighted k-core decomposition, to reveal a core-periphery structure. This allows us to compare the activity-based ranking with a topology-based ranking, to identify the most important institutions and their mutual dependencies. We also analyse correlations in these activities, to show strong similarities in the behavior of the core institutions. Our analysis clearly demonstrates the clustering of counterparty risk in a small set of about a dozen US banks. This not only increases the default risk of the central institutions, but also the default risk of peripheral institutions which have contracts with the central ones. Hence, all institutions indirectly have to bear (part of) the counterparty risk of all others, which needs to be better reflected in the price of OTC derivatives.

  1. Association of brain-derived neurotrophic factor (BDNF) haploinsufficiency with lower adaptive behaviour and reduced cognitive functioning in WAGR/11p13 deletion syndrome.

    Science.gov (United States)

    Han, Joan C; Thurm, Audrey; Golden Williams, Christine; Joseph, Lisa A; Zein, Wadih M; Brooks, Brian P; Butman, John A; Brady, Sheila M; Fuhr, Shannon R; Hicks, Melanie D; Huey, Amanda E; Hanish, Alyson E; Danley, Kristen M; Raygada, Margarita J; Rennert, Owen M; Martinowich, Keri; Sharp, Stephen J; Tsao, Jack W; Swedo, Susan E

    2013-01-01

    In animal studies, brain-derived neurotrophic factor (BDNF) is an important regulator of central nervous system development and synaptic plasticity. WAGR (Wilms tumour, Aniridia, Genitourinary anomalies, and mental Retardation) syndrome is caused by 11p13 deletions of variable size near the BDNF locus and can serve as a model for studying human BDNF haploinsufficiency (+/-). We hypothesized that BDNF+/- would be associated with more severe cognitive impairment in subjects with WAGR syndrome. Twenty-eight subjects with WAGR syndrome (6-28 years), 12 subjects with isolated aniridia due to PAX6 mutations/microdeletions (7-54 years), and 20 healthy controls (4-32 years) received neurocognitive assessments. Deletion boundaries for the subjects in the WAGR group were determined by high-resolution oligonucleotide array comparative genomic hybridization. Within the WAGR group, BDNF+/- subjects (n = 15), compared with BDNF intact (+/+) subjects (n = 13), had lower adaptive behaviour (p = .02), reduced cognitive functioning (p = .04), higher levels of reported historical (p = .02) and current (p = .02) social impairment, and higher percentage meeting cut-off score for autism (p = .047) on Autism Diagnostic Interview-Revised. These differences remained nominally significant after adjusting for visual acuity. Using diagnostic measures and clinical judgement, 3 subjects (2 BDNF+/- and 1 BDNF+/+) in the WAGR group (10.7%) were classified with autism spectrum disorder. A comparison group of visually impaired subjects with isolated aniridia had cognitive functioning comparable to that of healthy controls. In summary, among subjects with WAGR syndrome, BDNF+/- subjects had a mean Vineland Adaptive Behaviour Compose score that was 14-points lower and a mean intelligence quotient (IQ) that was 20-points lower than BDNF+/+ subjects. Our findings support the hypothesis that BDNF plays an important role in human neurocognitive development. Published by Elsevier Ltd.

  2. MicroRNA Dysregulation, Gene Networks, and Risk for Schizophrenia in 22q11.2 Deletion Syndrome

    OpenAIRE

    Merico, Daniele; Costain, Gregory; Butcher, Nancy J.; Warnica, William; Ogura, Lucas; Alfred, Simon E.; Brzustowicz, Linda M.; Bassett, Anne S.

    2014-01-01

    The role of microRNAs (miRNAs) in the etiology of schizophrenia is increasingly recognized. Microdeletions at chromosome 22q11.2 are recurrent structural variants that impart a high risk for schizophrenia and are found in up to 1% of all patients with schizophrenia. The 22q11.2 deletion region overlaps gene DGCR8, encoding a subunit of the miRNA microprocessor complex. We identified miRNAs overlapped by the 22q11.2 microdeletion and for the first time investigated their predicted target genes...

  3. Microclones derived from the mouse chromosome 7 D-E bands map within the proximal region of the c14CoS deletion in albino mutant mice

    International Nuclear Information System (INIS)

    Toenjes, R.R.W.; Weith, A.; Rinchik, E.M.; Winking, H.; Carnwath, J.W.; Kaliner, B.; Paul, D.

    1991-01-01

    A group of radiation-induced perinatal-lethal deletions that include the albino (c) locus on mouse chromosome 7 causes failure of expression of various hepatocyte-specific genes when homozygous. The transcription of such genes could be controlled in trans by a regulatory gene(s) located within the proximal region of the C14CoS deletion. To identify this potential regulatory gene, a microclone library was established from microdissected D and E bands of chromosome 7. Three nonoverlapping microclones (E305, E336B, and E453B) hybridizing with wildtype but not with C14CoS/C14CoS DNA were isolated. E336B represents a single-copy DNA fragment, whereas E305 and E453B hybridized with 3 and 10 EcoRI DNA restriction fragments, respectively. All fragments map exclusively within the deletion. The microclones hybridized to DNA of viable C6H/C14CoS deletion heterozygotes but not to DNA of homozygotes for the lethal mutation c10R75M, which belongs to the same complementation group as c14CoS. DNA of viable homozygous mutant C62DSD, which carries a deletion breakpoint proximal to that of c6H, hybridized only with E453B. This microclone identified 6 EcoRI restriction fragments in C62DSD/C62DSD DNA. The results demonstrate that of the isolated microclones, E453B identifies a locus (D7RT453B) that maps closest to the hsdr-1 (hepatocyte-specific developmental regulation) locus, which maps between the proximal breakpoints of deletions c10R75M and c62DSD

  4. pn: A Tool for Improved Derivation of Process Networks

    Directory of Open Access Journals (Sweden)

    Sven Verdoolaege

    2007-04-01

    Full Text Available Current emerging embedded System-on-Chip platforms are increasingly becoming multiprocessor architectures. System designers experience significant difficulties in programming these platforms. The applications are typically specified as sequential programs that do not reveal the available parallelism in an application, thereby hindering the efficient mapping of an application onto a parallel multiprocessor platform. In this paper, we present our compiler techniques for facilitating the migration from a sequential application specification to a parallel application specification using the process network model of computation. Our work is inspired by a previous research project called Compaan. With our techniques we address optimization issues such as the generation of process networks with simplified topology and communication without sacrificing the process networks' performance. Moreover, we describe a technique for compile-time memory requirement estimation which we consider as an important contribution of this paper. We demonstrate the usefulness of our techniques on several examples.

  5. Clinical, cytogenetic and molecular investigation in a fetus with Wolf-Hirschhorn syndrome with paternally derived 4p deletion. Case report and review of the literature.

    Science.gov (United States)

    Dietze, Ilona; Fritz, Barbara; Huhle, Dagmar; Simoens, Wouter; Piecha, Ernestine; Rehder, Helga

    2004-01-01

    Wolf-Hirschhorn (4p-) syndrome (WHS), caused by partial deletion of the short arm of chromosome 4, has been extensively described in children and young adults. Knowledge on fetuses with WHS is still limited due to the small number of published cases. We report on a fetus with prenatally diagnosed severe intrauterine growth retardation, reduced thoracal diameter, clubfeet deformity and midface hypoplasia including slight microretrognathia indicative for fetal karyotyping. Chromosome analysis after amniocentesis revealed a de novo terminal deletion of chromosome 4p [karyotype: 46,XX,del(4) (p16)] which was confirmed by FISH. Analyses of a set of polymorphic markers mapping in 4pter->4p15.3 showed absence of paternal haplotypes. These observations corroborate the preferential paternal origin of the de novo 4p deletion in WHS patients. Furthermore, the distal breakpoint could be narrowed to band 4p16.1. At autopsy, the fetus showed typical craniofacial dysmorphic signs of WHS, severe IUGR and delayed bone age. This report suggests the possibility of recognising the particular phenotype of WHS in utero by prenatal ultrasound and emphasises the importance of karyotyping fetuses with severe IUGR, especially when the amount of amniotic fluid is normal. Copyright 2004 S. Karger AG, Basel

  6. Establishment and antitumor effects of dasatinib and PKI-587 in BD-138T, a patient-derived muscle invasive bladder cancer preclinical platform with concomitant EGFR amplification and PTEN deletion.

    Science.gov (United States)

    Chang, Nakho; Lee, Hye Won; Lim, Joung Eun; Jeong, Da Eun; Song, Hye Jin; Kim, Sudong; Nam, Do-Hyun; Sung, Hyun Hwan; Jeong, Byong Chang; Seo, Seong Il; Jeon, Seong Soo; Lee, Hyun Moo; Choi, Han-Yong; Jeon, Hwang Gyun

    2016-08-09

    Muscle-invasive bladder cancer (MIBC) consists of a heterogeneous group of tumors with a high rate of metastasis and mortality. To facilitate the in-depth investigation and validation of tailored strategies for MIBC treatment, we have developed an integrated approach using advanced high-throughput drug screening and a clinically relevant patient-derived preclinical platform. We isolated patient-derived tumor cells (PDCs) from a rare MIBC case (BD-138T) that harbors concomitant epidermal growth factor receptor (EGFR) amplification and phosphatase and tensin homolog (PTEN) deletion. High-throughput in vitro drug screening demonstrated that dasatinib, a SRC inhibitor, and PKI-587, a dual PI3K/mTOR inhibitor, exhibited targeted anti-proliferative and pro-apoptotic effects against BD-138T PDCs. Using established patient-derived xenograft models that successfully retain the genomic and molecular characteristics of the parental tumor, we confirmed that these anti-tumor responses occurred through the inhibition of SRC and PI3K/AKT/mTOR signaling pathways. Taken together, these experimental results demonstrate that dasatinib and PKI-587 might serve as promising anticancer drug candidates for treating MIBC with combined EGFR gene amplification and PTEN deletion.

  7. PROFEAT Update: A Protein Features Web Server with Added Facility to Compute Network Descriptors for Studying Omics-Derived Networks.

    Science.gov (United States)

    Zhang, P; Tao, L; Zeng, X; Qin, C; Chen, S Y; Zhu, F; Yang, S Y; Li, Z R; Chen, W P; Chen, Y Z

    2017-02-03

    The studies of biological, disease, and pharmacological networks are facilitated by the systems-level investigations using computational tools. In particular, the network descriptors developed in other disciplines have found increasing applications in the study of the protein, gene regulatory, metabolic, disease, and drug-targeted networks. Facilities are provided by the public web servers for computing network descriptors, but many descriptors are not covered, including those used or useful for biological studies. We upgraded the PROFEAT web server http://bidd2.nus.edu.sg/cgi-bin/profeat2016/main.cgi for computing up to 329 network descriptors and protein-protein interaction descriptors. PROFEAT network descriptors comprehensively describe the topological and connectivity characteristics of unweighted (uniform binding constants and molecular levels), edge-weighted (varying binding constants), node-weighted (varying molecular levels), edge-node-weighted (varying binding constants and molecular levels), and directed (oriented processes) networks. The usefulness of the network descriptors is illustrated by the literature-reported studies of the biological networks derived from the genome, interactome, transcriptome, metabolome, and diseasome profiles. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Deriving frequency-dependent spatial patterns in MEG-derived resting state sensorimotor network: A novel multiband ICA technique.

    Science.gov (United States)

    Nugent, Allison C; Luber, Bruce; Carver, Frederick W; Robinson, Stephen E; Coppola, Richard; Zarate, Carlos A

    2017-02-01

    Recently, independent components analysis (ICA) of resting state magnetoencephalography (MEG) recordings has revealed resting state networks (RSNs) that exhibit fluctuations of band-limited power envelopes. Most of the work in this area has concentrated on networks derived from the power envelope of beta bandpass-filtered data. Although research has demonstrated that most networks show maximal correlation in the beta band, little is known about how spatial patterns of correlations may differ across frequencies. This study analyzed MEG data from 18 healthy subjects to determine if the spatial patterns of RSNs differed between delta, theta, alpha, beta, gamma, and high gamma frequency bands. To validate our method, we focused on the sensorimotor network, which is well-characterized and robust in both MEG and functional magnetic resonance imaging (fMRI) resting state data. Synthetic aperture magnetometry (SAM) was used to project signals into anatomical source space separately in each band before a group temporal ICA was performed over all subjects and bands. This method preserved the inherent correlation structure of the data and reflected connectivity derived from single-band ICA, but also allowed identification of spatial spectral modes that are consistent across subjects. The implications of these results on our understanding of sensorimotor function are discussed, as are the potential applications of this technique. Hum Brain Mapp 38:779-791, 2017. © 2016 Wiley Periodicals, Inc. Published 2016. This article is a U.S. Government work and is in the public domain in the USA.

  9. Some analogies between quantum cloning and quantum deleting

    International Nuclear Information System (INIS)

    Qiu Daowen

    2002-01-01

    We further verify the impossibility of deleting an arbitrary unknown quantum state, and also show it is impossible to delete two nonorthogonal quantum states as a consequence of unitarity of quantum mechanics. A quantum approximate (deterministic) deleting machine and a probabilistic (exact) deleting machine are constructed. The estimation for the global fidelity characterizing the efficiency of the quantum approximate deleting is given. We then demonstrate that unknown nonorthogonal states chosen from a set with their multiple copies can evolve into a linear superposition of multiple deletions and failure branches by a unitary process if and only if the states are linearly independent. It is notable that the proof for necessity is somewhat different from Pati's [Phys. Rev. Lett. 83, 2849 (1999)]. Another deleting machine for the input states that are unnecessarily linearly independent is also presented. The bounds on the success probabilities of these deleting machines are derived. So we expound some preliminary analogies between quantum cloning and deleting

  10. Image-guided, Laser-based Fabrication of Vascular-derived Microfluidic Networks

    OpenAIRE

    Heintz, Keely A.; Mayerich, David; Slater, John H.

    2017-01-01

    This detailed protocol outlines the implementation of image-guided, laser-based hydrogel degradation for the fabrication of vascular-derived microfluidic networks embedded in PEGDA hydrogels. Here, we describe the creation of virtual masks that allow for image-guided laser control; the photopolymerization of a micromolded PEGDA hydrogel, suitable for microfluidic network fabrication and pressure head-driven flow; the setup and use of a commercially available laser scanning confocal microscope...

  11. Probabilistic deletion of copies of linearly independent quantum states

    International Nuclear Information System (INIS)

    Feng Jian; Gao Yunfeng; Wang Jisuo; Zhan Mingsheng

    2002-01-01

    We show that each of two copies of the nonorthogonal states randomly selected from a certain set S can be probabilistically deleted by a general unitary-reduction operation if and only if the states are linearly independent. We derive a tight bound on the best possible deleting efficiencies. These results for 2→1 probabilistic deleting are also generalized into the case of N→M deleting (N,M positive integers and N>M)

  12. Large photonic band gaps and strong attenuations of two-segment-connected Peano derivative networks

    International Nuclear Information System (INIS)

    Lu, Jian; Yang, Xiangbo; Zhang, Guogang; Cai, Lianzhang

    2011-01-01

    In this Letter, based on ancient Peano curves we construct four kinds of interesting Peano derivative networks composed of one-dimensional (1D) waveguides and investigate the optical transmission spectra and photonic attenuation behavior of electromagnetic (EM) waves in one- and two-segment-connected networks. It is found that for some two-segment-connected networks large photonic band gaps (PBGs) can be created and the widths of large PBGs can be controlled by adjusting the matching ratio of waveguide length and are insensitive to generation number. Diamond- and hexagon-Peano networks are good selectable structures for the designing of optical devices with large PBG(s) and strong attenuation(s). -- Highlights: → Peano and Peano derivative networks composed of 1D waveguides are designed. → Large PBGs with strong attenuations have been created by these fractal networks. → New approach for designing optical devices with large PBGs is proposed. → Diamond- and hexagon-Peano networks with d2:d1=2:1 are good selectable structures.

  13. Probabilistic cloning and deleting of quantum states

    International Nuclear Information System (INIS)

    Feng Yuan; Zhang Shengyu; Ying Mingsheng

    2002-01-01

    We construct a probabilistic cloning and deleting machine which, taking several copies of an input quantum state, can output a linear superposition of multiple cloning and deleting states. Since the machine can perform cloning and deleting in a single unitary evolution, the probabilistic cloning and other cloning machines proposed in the previous literature can be thought of as special cases of our machine. A sufficient and necessary condition for successful cloning and deleting is presented, and it requires that the copies of an arbitrarily presumed number of the input states are linearly independent. This simply generalizes some results for cloning. We also derive an upper bound for the success probability of the cloning and deleting machine

  14. Unified Framework for Deriving Simultaneous Equation Algorithms for Water Distribution Networks

    Science.gov (United States)

    The known formulations for steady state hydraulics within looped water distribution networks are re-derived in terms of linear and non-linear transformations of the original set of partly linear and partly non-linear equations that express conservation of mass and energy. All of ...

  15. Widely Used Herpes Simplex Virus 1 ICP0 Deletion Mutant Strain dl1403 and Its Derivative Viruses Do Not Express Glycoprotein C Due to a Secondary Mutation in the gC Gene.

    Directory of Open Access Journals (Sweden)

    Cristina W Cunha

    Full Text Available Herpes simplex virus 1 (HSV-1 ICP0 is a multi-functional phosphoprotein expressed with immediate early kinetics. An ICP0 deletion mutant, HSV-1 dl1403, has been widely used to study the roles of ICP0 in the HSV-1 replication cycle including gene expression, latency, entry and assembly. We show that HSV-1 dl1403 virions lack detectable levels of envelope protein gC, and that gC is not synthesized in infected cells. Sequencing of the gC gene from HSV-1 dl1403 revealed a single amino acid deletion that results in a frameshift mutation. The HSV-1 dl1403 gC gene is predicted to encode a polypeptide consisting of the original 62 N-terminal amino acids of the gC protein followed by 112 irrelevant, non-gC residues. The mutation was also present in a rescuant virus and in two dl1403-derived viruses, D8 and FXE, but absent from the parental 17+, suggesting that the mutation was introduced during the construction of the dl1403 virus, and not as a result of passage in culture.

  16. multi scale analysis of a function by neural networks elementary derivatives functions

    International Nuclear Information System (INIS)

    Chikhi, A.; Gougam, A.; Chafa, F.

    2006-01-01

    Recently, the wavelet network has been introduced as a special neural network supported by the wavelet theory . Such networks constitute a tool for function approximation problems as it has been already proved in reference . Our present work deals with this model, treating a multi scale analysis of a function. We have then used a linear expansion of a given function in wavelets, neglecting the usual translation parameters. We investigate two training operations. The first one consists on an optimization of the output synaptic layer, the second one, optimizing the output function with respect to scale parameters. We notice a temporary merging of the scale parameters leading to some interesting results : new elementary derivatives units emerge, representing a new elementary task, which is the derivative of the output task

  17. Niche-dependent development of functional neuronal networks from embryonic stem cell-derived neural populations

    Directory of Open Access Journals (Sweden)

    Siebler Mario

    2009-08-01

    Full Text Available Abstract Background The present work was performed to investigate the ability of two different embryonic stem (ES cell-derived neural precursor populations to generate functional neuronal networks in vitro. The first ES cell-derived neural precursor population was cultivated as free-floating neural aggregates which are known to form a developmental niche comprising different types of neural cells, including neural precursor cells (NPCs, progenitor cells and even further matured cells. This niche provides by itself a variety of different growth factors and extracellular matrix proteins that influence the proliferation and differentiation of neural precursor and progenitor cells. The second population was cultivated adherently in monolayer cultures to control most stringently the extracellular environment. This population comprises highly homogeneous NPCs which are supposed to represent an attractive way to provide well-defined neuronal progeny. However, the ability of these different ES cell-derived immature neural cell populations to generate functional neuronal networks has not been assessed so far. Results While both precursor populations were shown to differentiate into sufficient quantities of mature NeuN+ neurons that also express GABA or vesicular-glutamate-transporter-2 (vGlut2, only aggregate-derived neuronal populations exhibited a synchronously oscillating network activity 2–4 weeks after initiating the differentiation as detected by the microelectrode array technology. Neurons derived from homogeneous NPCs within monolayer cultures did merely show uncorrelated spiking activity even when differentiated for up to 12 weeks. We demonstrated that these neurons exhibited sparsely ramified neurites and an embryonic vGlut2 distribution suggesting an inhibited terminal neuronal maturation. In comparison, neurons derived from heterogeneous populations within neural aggregates appeared as fully mature with a dense neurite network and punctuated

  18. Potential of commercial microwave link network derived rainfall for river runoff simulations

    Science.gov (United States)

    Smiatek, Gerhard; Keis, Felix; Chwala, Christian; Fersch, Benjamin; Kunstmann, Harald

    2017-03-01

    Commercial microwave link networks allow for the quantification of path integrated precipitation because the attenuation by hydrometeors correlates with rainfall between transmitter and receiver stations. The networks, operated and maintained by cellphone companies, thereby provide completely new and country wide precipitation measurements. As the density of traditional precipitation station networks worldwide is significantly decreasing, microwave link derived precipitation estimates receive increasing attention not only by hydrologists but also by meteorological and hydrological services. We investigate the potential of microwave derived precipitation estimates for streamflow prediction and water balance analyses, exemplarily shown for an orographically complex region in the German Alps (River Ammer). We investigate the additional value of link derived rainfall estimations combined with station observations compared to station and weather radar derived values. Our river runoff simulation system employs a distributed hydrological model at 100 × 100 m grid resolution. We analyze the potential of microwave link derived precipitation estimates for two episodes of 30 days with typically moderate river flow and an episode of extreme flooding. The simulation results indicate the potential of this novel precipitation monitoring method: a significant improvement in hydrograph reproduction has been achieved in the extreme flooding period that was characterized by a large number of local strong precipitation events. The present rainfall monitoring gauges alone were not able to correctly capture these events.

  19. Three-Dimensional Vascular Network Assembly From Diabetic Patient-Derived Induced Pluripotent Stem Cells.

    Science.gov (United States)

    Chan, Xin Yi; Black, Rebecca; Dickerman, Kayla; Federico, Joseph; Lévesque, Mathieu; Mumm, Jeff; Gerecht, Sharon

    2015-12-01

    In diabetics, hyperglycemia results in deficient endothelial progenitors and cells, leading to cardiovascular complications. We aim to engineer 3-dimensional (3D) vascular networks in synthetic hydrogels from type 1 diabetes mellitus (T1D) patient-derived human-induced pluripotent stem cells (hiPSCs), to serve as a transformative autologous vascular therapy for diabetic patients. We validated and optimized an adherent, feeder-free differentiation procedure to derive early vascular cells (EVCs) with high portions of vascular endothelial cadherin-positive cells from hiPSCs. We demonstrate similar differentiation efficiency from hiPSCs derived from healthy donor and patients with T1D. T1D-hiPSC-derived vascular endothelial cadherin-positive cells can mature to functional endothelial cells-expressing mature markers: von Willebrand factor and endothelial nitric oxide synthase are capable of lectin binding and acetylated low-density lipoprotein uptake, form cords in Matrigel and respond to tumor necrosis factor-α. When embedded in engineered hyaluronic acid hydrogels, T1D-EVCs undergo morphogenesis and assemble into 3D networks. When encapsulated in a novel hypoxia-inducible hydrogel, T1D-EVCs respond to low oxygen and form 3D networks. As xenografts, T1D-EVCs incorporate into developing zebrafish vasculature. Using our robust protocol, we can direct efficient differentiation of T1D-hiPSC to EVCs. Early endothelial cells derived from T1D-hiPSC are functional when mature. T1D-EVCs self-assembled into 3D networks when embedded in hyaluronic acid and hypoxia-inducible hydrogels. The capability of T1D-EVCs to assemble into 3D networks in engineered matrices and to respond to a hypoxic microenvironment is a significant advancement for autologous vascular therapy in diabetic patients and has broad importance for tissue engineering. © 2015 American Heart Association, Inc.

  20. Phenotypic stability and plasticity in GMP-derived cells as determined by their underlying regulatory network.

    Science.gov (United States)

    Ramírez, Carlos; Mendoza, Luis

    2018-04-01

    Blood cell formation has been recognized as a suitable system to study celular differentiation mainly because of its experimental accessibility, and because it shows characteristics such as hierarchical and gradual bifurcated patterns of commitment, which are present in several developmental processes. Although hematopoiesis has been extensively studied and there is a wealth of molecular and cellular data about it, it is not clear how the underlying molecular regulatory networks define or restrict cellular differentiation processes. Here, we infer the molecular regulatory network that controls the differentiation of a blood cell subpopulation derived from the granulocyte-monocyte precursor (GMP), comprising monocytes, neutrophils, eosinophils, basophils and mast cells. We integrate published qualitative experimental data into a model to describe temporal expression patterns observed in GMP-derived cells. The model is implemented as a Boolean network, and its dynamical behavior is studied. Steady states of the network can be clearly identified with the expression profiles of monocytes, mast cells, neutrophils, basophils, and eosinophils, under wild-type and mutant backgrounds. All scripts are publicly available at https://github.com/caramirezal/RegulatoryNetworkGMPModel. lmendoza@biomedicas.unam.mx. Supplementary data are available at Bioinformatics online.

  1. Human embryonic stem cell-derived neurons adopt and regulate the activity of an established neural network

    Science.gov (United States)

    Weick, Jason P.; Liu, Yan; Zhang, Su-Chun

    2011-01-01

    Whether hESC-derived neurons can fully integrate with and functionally regulate an existing neural network remains unknown. Here, we demonstrate that hESC-derived neurons receive unitary postsynaptic currents both in vitro and in vivo and adopt the rhythmic firing behavior of mouse cortical networks via synaptic integration. Optical stimulation of hESC-derived neurons expressing Channelrhodopsin-2 elicited both inhibitory and excitatory postsynaptic currents and triggered network bursting in mouse neurons. Furthermore, light stimulation of hESC-derived neurons transplanted to the hippocampus of adult mice triggered postsynaptic currents in host pyramidal neurons in acute slice preparations. Thus, hESC-derived neurons can participate in and modulate neural network activity through functional synaptic integration, suggesting they are capable of contributing to neural network information processing both in vitro and in vivo. PMID:22106298

  2. The Relation between Degree and Strength in the Complex Network Derived from an Individual Stock

    Directory of Open Access Journals (Sweden)

    Zelin Zhang

    2016-01-01

    Full Text Available A method based on coarse-graining to construct a directed weighted complex network which models the transformation of the trading data of an individual stock is introduced. The degree (strength distribution of derived network follows a power-law. A moderated regression equation with interaction effects of average return and out-degree (in-degree on out-strength (in-strength is established. Moreover, we found that the differences of nodes affect the network’s structure and average return level impacts nodes’ eigenvector centrality and pagerank, significantly.

  3. Calculating degree-based topological indices of dominating David derived networks

    Science.gov (United States)

    Ahmad, Muhammad Saeed; Nazeer, Waqas; Kang, Shin Min; Imran, Muhammad; Gao, Wei

    2017-12-01

    An important area of applied mathematics is the Chemical reaction network theory. The behavior of real world problems can be modeled by using this theory. Due to applications in theoretical chemistry and biochemistry, it has attracted researchers since its foundation. It also attracts pure mathematicians because it involves interesting mathematical structures. In this report, we compute newly defined topological indices, namely, Arithmetic-Geometric index (AG1 index), SK index, SK1 index, and SK2 index of the dominating David derived networks [1, 2, 3, 4, 5].

  4. Partial deletion 11q

    DEFF Research Database (Denmark)

    Hertz, Jens Michael; Tommerup, N; Sørensen, F B

    1995-01-01

    We describe the cytogenetic findings and the dysmorphic features in a stillborn girl with a large de novo terminal deletion of the long arm of chromosome 11. The karyotype was 46,XX,del(11)(q21qter). By reviewing previous reports of deletion 11q, we found that cleft lip and palate are most...

  5. Topological derivatives of eigenvalues and neural networks in identification of imperfections

    International Nuclear Information System (INIS)

    Grzanek, M; Nowakowski, A; Sokolowski, J

    2008-01-01

    Numerical method for identification of imperfections is devised for elliptic spectral problems. The neural networks are employed for numerical solution. The topological derivatives of eigenvalues are used in the learning procedure of the neural networks. The topological derivatives of eigenvalues are determined by the methods of asymptotic analysis in singularly perturbed geometrical domains. The convergence of the numerical method in a probabilistic setting is analysed. The method is presented for the identification of small singular perturbations of the boundary of geometrical domain, however the framework is general and can be used for numerical solutions of inverse problems in the presence of small imperfections in the interior of the domain. Some numerical results are given for elliptic spectral problem in two spatial dimensions.

  6. Deletion mutations of bacteriophage

    International Nuclear Information System (INIS)

    Ryo, Yeikou

    1975-01-01

    Resolution of mutation mechanism with structural changes of DNA was discussed through the studies using bacteriophage lambda. One of deletion mutations inductions of phage lambda is the irradiation of ultraviolet ray. It is not clear if the inductions are caused by errors in reparation of ultraviolet-induced damage or by the activation of int gene. Because the effective site of int gene lies within the regions unnecessary for existing, it is considered that int gene is connected to deletion mutations induction. A certain system using prophage complementarity enables to detect deletion mutations at essential hereditary sites and to solve the relations of deletion mutations with other recombination system, DNA reproduction and repairment system. Duplication and multiplication of hereditary elements were discussed. If lambda deletion mutations of the system, which can control recombination, reproduction and repairment of added DNA, are constructed, mutations mechanism with great changes of DNA structure can be solved by phage lambda. (Ichikawa, K.)

  7. Schizophrenia and chromosomal deletions

    Energy Technology Data Exchange (ETDEWEB)

    Lindsay, E.A.; Baldini, A. [Baylor College of Medicine, Houston, TX (United States); Morris, M. A. [Univ. of Geneva School of Medicine, NY (United States)] [and others

    1995-06-01

    Recent genetic linkage analysis studies have suggested the presence of a schizophrenia locus on the chromosomal region 22q11-q13. Schizophrenia has also been frequently observed in patients affected with velo-cardio-facial syndrome (VCFS), a disorder frequently associated with deletions within 22q11.1. It has been hypothesized that psychosis in VCFS may be due to deletion of the catechol-o-methyl transferase gene. Prompted by these observations, we screened for 22q11 deletions in a population of 100 schizophrenics selected from the Maryland Epidemiological Sample. Our results show that there are schizophrenic patients carrying a deletion of 22q11.1 and a mild VCFS phenotype that might remain unrecognized. These findings should encourage a search for a schizophrenia-susceptibility gene within the deleted region and alert those in clinical practice to the possible presence of a mild VCFS phenotype associated with schizophrenia. 9 refs.

  8. A unified software framework for deriving, visualizing, and exploring abstraction networks for ontologies

    Science.gov (United States)

    Ochs, Christopher; Geller, James; Perl, Yehoshua; Musen, Mark A.

    2016-01-01

    Software tools play a critical role in the development and maintenance of biomedical ontologies. One important task that is difficult without software tools is ontology quality assurance. In previous work, we have introduced different kinds of abstraction networks to provide a theoretical foundation for ontology quality assurance tools. Abstraction networks summarize the structure and content of ontologies. One kind of abstraction network that we have used repeatedly to support ontology quality assurance is the partial-area taxonomy. It summarizes structurally and semantically similar concepts within an ontology. However, the use of partial-area taxonomies was ad hoc and not generalizable. In this paper, we describe the Ontology Abstraction Framework (OAF), a unified framework and software system for deriving, visualizing, and exploring partial-area taxonomy abstraction networks. The OAF includes support for various ontology representations (e.g., OWL and SNOMED CT's relational format). A Protégé plugin for deriving “live partial-area taxonomies” is demonstrated. PMID:27345947

  9. Quantum deletion: Beyond the no-deletion principle

    International Nuclear Information System (INIS)

    Adhikari, Satyabrata

    2005-01-01

    Suppose we are given two identical copies of an unknown quantum state and we wish to delete one copy from among the given two copies. The quantum no-deletion principle restricts us from perfectly deleting a copy but it does not prohibit us from deleting a copy approximately. Here we construct two types of a 'universal quantum deletion machine' which approximately deletes a copy such that the fidelity of deletion does not depend on the input state. The two types of universal quantum deletion machines are (1) a conventional deletion machine described by one unitary operator and (2) a modified deletion machine described by two unitary operators. Here it is shown that the modified deletion machine deletes a qubit with fidelity 3/4, which is the maximum limit for deleting an unknown quantum state. In addition to this we also show that the modified deletion machine retains the qubit in the first mode with average fidelity 0.77 (approx.) which is slightly greater than the fidelity of measurement for two given identical states, showing how precisely one can determine its state [S. Massar and S. Popescu, Phys. Rev. Lett. 74, 1259 (1995)]. We also show that the deletion machine itself is input state independent, i.e., the information is not hidden in the deleting machine, and hence we can delete the information completely from the deletion machine

  10. On the Mass Fractal Character of Si-Based Structural Networks in Amorphous Polymer Derived Ceramics

    Directory of Open Access Journals (Sweden)

    Sabyasachi Sen

    2015-03-01

    Full Text Available The intermediate-range packing of SiNxC4−x (0 ≤ x ≤ 4 tetrahedra in polysilycarbodiimide and polysilazane-derived amorphous SiCN ceramics is investigated using 29Si spin-lattice relaxation nuclear magnetic resonance (SLR NMR spectroscopy. The SiCN network in the polysilylcarbodiimide-derived ceramic consists predominantly of SiN4 tetrahedra that are characterized by a 3-dimensional spatial distribution signifying compact packing of such units to form amorphous Si3N4 clusters. On the other hand, the SiCN network of the polysilazane-derived ceramic is characterized by mixed bonded SiNxC4−x tetrahedra that are inefficiently packed with a mass fractal dimension of Df ~2.5 that is significantly lower than the embedding Euclidean dimension (D = 3. This result unequivocally confirms the hypothesis that the presence of dissimilar atoms, namely, 4-coordinated C and 3-coordinated N, in the nearest neighbor environment of Si along with some exclusion in connectivity between SiCxN4−x tetrahedra with widely different N:C ratios and the absence of bonding between C and N result in steric hindrance to an efficient packing of these structural units. It is noted that similar inefficiencies in packing are observed in polymer-derived amorphous SiOC ceramics as well as in proteins and binary hard sphere systems.

  11. On the Mass Fractal Character of Si-Based Structural Networks in Amorphous Polymer Derived Ceramics.

    Science.gov (United States)

    Sen, Sabyasachi; Widgeon, Scarlett

    2015-03-17

    The intermediate-range packing of SiN x C 4- x (0 ≤ x ≤ 4) tetrahedra in polysilycarbodiimide and polysilazane-derived amorphous SiCN ceramics is investigated using 29 Si spin-lattice relaxation nuclear magnetic resonance (SLR NMR) spectroscopy. The SiCN network in the polysilylcarbodiimide-derived ceramic consists predominantly of SiN₄ tetrahedra that are characterized by a 3-dimensional spatial distribution signifying compact packing of such units to form amorphous Si₃N₄ clusters. On the other hand, the SiCN network of the polysilazane-derived ceramic is characterized by mixed bonded SiN x C 4- x tetrahedra that are inefficiently packed with a mass fractal dimension of D f ~2.5 that is significantly lower than the embedding Euclidean dimension ( D = 3). This result unequivocally confirms the hypothesis that the presence of dissimilar atoms, namely, 4-coordinated C and 3-coordinated N, in the nearest neighbor environment of Si along with some exclusion in connectivity between SiC x N 4- x tetrahedra with widely different N:C ratios and the absence of bonding between C and N result in steric hindrance to an efficient packing of these structural units. It is noted that similar inefficiencies in packing are observed in polymer-derived amorphous SiOC ceramics as well as in proteins and binary hard sphere systems.

  12. Extending Topological Approaches to Microseismic-Derived 3D Fracture Networks

    Science.gov (United States)

    Urbancic, T.; Bosman, K.; Baig, A.; Ardakani, E. P.

    2017-12-01

    for the 3D case to provide a meaningful measurement of fracture network connectivity. We have developed an approach to analyze the topology of 3D fracture networks derived from microseismic moment tensors. We illustrate the utility of the approach with applications to example datasets from hydraulic fracturing completions.

  13. The fate of deleted DNA produced during programmed genomic deletion events in Tetrahymena thermophila.

    Science.gov (United States)

    Saveliev, S V; Cox, M M

    1994-01-01

    Thousands of DNA deletion events occur during macronuclear development in the ciliate Tetrahymena thermophila. In two deleted genomic regions, designated M and R, the eliminated sequences form circles that can be detected by PCR. However, the circles are not normal products of the reaction pathway. The circular forms occur at very low levels in conjugating cells, but are stable. Sequencing analysis showed that many of the circles (as many as 50% of those examined) reflected a precise deletion in the M and R regions. The remaining circles were either smaller or larger and contained varying lengths of sequences derived from the chromosomal DNA surrounding the eliminated region. The chromosomal junctions left behind after deletion were more precise, although deletions in either the M or R regions can generate any of several alternative junctions (1). Some new chromosomal junctions were detected in the present study. The results suggest that the deleted segment is released as a linear DNA species that is degraded rapidly. The species is only rarely converted to the stable circles we detect. The deletion mechanism is different from those proposed for deletion events in hypotrichous ciliates (2-4), and does not reflect a conservative site-specific recombination process such as that promoted by the bacteriophage lambda integrase (5). Images PMID:7838724

  14. Design of a universal two-layered neural network derived from the PLI theory

    Science.gov (United States)

    Hu, Chia-Lun J.

    2004-05-01

    The if-and-only-if (IFF) condition that a set of M analog-to-digital vector-mapping relations can be learned by a one-layered-feed-forward neural network (OLNN) is that all the input analog vectors dichotomized by the i-th output bit must be positively, linearly independent, or PLI. If they are not PLI, then the OLNN just cannot learn no matter what learning rules is employed because the solution of the connection matrix does not exist mathematically. However, in this case, one can still design a parallel-cascaded, two-layered, perceptron (PCTLP) to acheive this general mapping goal. The design principle of this "universal" neural network is derived from the major mathematical properties of the PLI theory - changing the output bits of the dependent relations existing among the dichotomized input vectors to make the PLD relations PLI. Then with a vector concatenation technique, the required mapping can still be learned by this PCTLP system with very high efficiency. This paper will report in detail the mathematical derivation of the general design principle and the design procedures of the PCTLP neural network system. It then will be verified in general by a practical numerical example.

  15. Cross-Domain Analogies as Relating Derived Relations among Two Separate Relational Networks

    Science.gov (United States)

    Ruiz, Francisco J; Luciano, Carmen

    2011-01-01

    Contemporary behavior analytic research is making headway in analyzing analogy as the establishment of a relation of coordination among common types of trained or derived relations. Previous studies have been focused on within-domain analogy. The current study expands previous research by analyzing cross-domain analogy as relating relations among separate relational networks and by correlating participants' performance with a standard measure of analogical reasoning. In two experiments, adult participants first completed general intelligence and analogical reasoning tests. Subsequently, they were exposed to a computerized conditional discrimination training procedure designed to create two relational networks, each consisting of two 3-member equivalence classes. The critical test was a two-part analogical test in which participants had to relate combinatorial relations of coordination and distinction between the two relational networks. In Experiment 1, combinatorial relations for each network were individually tested prior to analogical testing, but in Experiment 2 they were not. Across both experiments, 65% of participants passed the analogical test on the first attempt. Moreover, results from the training procedure were strongly correlated with the standard measure of analogical reasoning. PMID:21547072

  16. Network-derived inhomogeneity in monthly rainfall analyses over western Tasmania

    International Nuclear Information System (INIS)

    Fawcett, Robert; Trewin, Blair; Barnes-Keoghan, Ian

    2010-01-01

    Monthly rainfall in the wetter western half of Tasmania was relatively poorly observed in the early to middle parts of the 20th century, and this causes a marked inhomogeneity in the operational gridded monthly rainfall analyses generated by the Australian Bureau of Meteorology up until the end of 2009. These monthly rainfall analyses were generated for the period 1900 to 2009 in two forms; a national analysis at 0.25 0 latitude-longitude resolution, and a southeastern Australia regional analysis at 0.1 0 resolution. For any given month, they used all the monthly data from the standard Bureau rainfall gauge network available in the Australian Data Archive for Meteorology. Since this network has changed markedly since Federation (1901), there is obvious scope for network-derived inhomogeneities in the analyses. In this study, we show that the topography-resolving techniques of the new Australian Water Availability Project analyses, adopted as the official operational analyses from the start of 2010, substantially diminish those inhomogeneities, while using largely the same observation network. One result is an improved characterisation of recent rainfall declines across Tasmania. The new analyses are available at two resolutions, 0.25 0 and 0.05 0 .

  17. Influence of degree correlations on network structure and stability in protein-protein interaction networks

    Directory of Open Access Journals (Sweden)

    Zimmer Ralf

    2007-08-01

    Full Text Available Abstract Background The existence of negative correlations between degrees of interacting proteins is being discussed since such negative degree correlations were found for the large-scale yeast protein-protein interaction (PPI network of Ito et al. More recent studies observed no such negative correlations for high-confidence interaction sets. In this article, we analyzed a range of experimentally derived interaction networks to understand the role and prevalence of degree correlations in PPI networks. We investigated how degree correlations influence the structure of networks and their tolerance against perturbations such as the targeted deletion of hubs. Results For each PPI network, we simulated uncorrelated, positively and negatively correlated reference networks. Here, a simple model was developed which can create different types of degree correlations in a network without changing the degree distribution. Differences in static properties associated with degree correlations were compared by analyzing the network characteristics of the original PPI and reference networks. Dynamics were compared by simulating the effect of a selective deletion of hubs in all networks. Conclusion Considerable differences between the network types were found for the number of components in the original networks. Negatively correlated networks are fragmented into significantly less components than observed for positively correlated networks. On the other hand, the selective deletion of hubs showed an increased structural tolerance to these deletions for the positively correlated networks. This results in a lower rate of interaction loss in these networks compared to the negatively correlated networks and a decreased disintegration rate. Interestingly, real PPI networks are most similar to the randomly correlated references with respect to all properties analyzed. Thus, although structural properties of networks can be modified considerably by degree

  18. In Vitro Reconstruction of Neuronal Networks Derived from Human iPS Cells Using Microfabricated Devices.

    Directory of Open Access Journals (Sweden)

    Yuzo Takayama

    Full Text Available Morphology and function of the nervous system is maintained via well-coordinated processes both in central and peripheral nervous tissues, which govern the homeostasis of organs/tissues. Impairments of the nervous system induce neuronal disorders such as peripheral neuropathy or cardiac arrhythmia. Although further investigation is warranted to reveal the molecular mechanisms of progression in such diseases, appropriate model systems mimicking the patient-specific communication between neurons and organs are not established yet. In this study, we reconstructed the neuronal network in vitro either between neurons of the human induced pluripotent stem (iPS cell derived peripheral nervous system (PNS and central nervous system (CNS, or between PNS neurons and cardiac cells in a morphologically and functionally compartmentalized manner. Networks were constructed in photolithographically microfabricated devices with two culture compartments connected by 20 microtunnels. We confirmed that PNS and CNS neurons connected via synapses and formed a network. Additionally, calcium-imaging experiments showed that the bundles originating from the PNS neurons were functionally active and responded reproducibly to external stimuli. Next, we confirmed that CNS neurons showed an increase in calcium activity during electrical stimulation of networked bundles from PNS neurons in order to demonstrate the formation of functional cell-cell interactions. We also confirmed the formation of synapses between PNS neurons and mature cardiac cells. These results indicate that compartmentalized culture devices are promising tools for reconstructing network-wide connections between PNS neurons and various organs, and might help to understand patient-specific molecular and functional mechanisms under normal and pathological conditions.

  19. Enhanced growth of neural networks on conductive cellulose-derived nanofibrous scaffolds

    International Nuclear Information System (INIS)

    Kuzmenko, Volodymyr; Kalogeropoulos, Theodoros; Thunberg, Johannes; Johannesson, Sara; Hägg, Daniel; Enoksson, Peter; Gatenholm, Paul

    2016-01-01

    The problem of recovery from neurodegeneration needs new effective solutions. Tissue engineering is viewed as a prospective approach for solving this problem since it can help to develop healthy neural tissue using supportive scaffolds. This study presents effective and sustainable tissue engineering methods for creating biomaterials from cellulose that can be used either as scaffolds for the growth of neural tissue in vitro or as drug screening models. To reach this goal, nanofibrous electrospun cellulose mats were made conductive via two different procedures: carbonization and addition of multi-walled carbon nanotubes. The resulting scaffolds were much more conductive than untreated cellulose material and were used to support growth and differentiation of SH-SY5Y neuroblastoma cells. The cells were evaluated by scanning electron microscopy and confocal microscopy methods over a period of 15 days at different time points. The results showed that the cellulose-derived conductive scaffolds can provide support for good cell attachment, growth and differentiation. The formation of a neural network occurred within 10 days of differentiation, which is a promising length of time for SH-SY5Y neuroblastoma cells. - Highlights: • The conductive scaffolds for neural tissue engineering are derived from cellulose. • The scaffolds are used to support growth and differentiation of SH-SY5Y cells. • Distinctive cell differentiation occurs within 10 days on conductive scaffolds. • Electrical conductivity and nanotopography improve neural network formation.

  20. Differential reconstructed gene interaction networks for deriving toxicity threshold in chemical risk assessment.

    Science.gov (United States)

    Yang, Yi; Maxwell, Andrew; Zhang, Xiaowei; Wang, Nan; Perkins, Edward J; Zhang, Chaoyang; Gong, Ping

    2013-01-01

    Pathway alterations reflected as changes in gene expression regulation and gene interaction can result from cellular exposure to toxicants. Such information is often used to elucidate toxicological modes of action. From a risk assessment perspective, alterations in biological pathways are a rich resource for setting toxicant thresholds, which may be more sensitive and mechanism-informed than traditional toxicity endpoints. Here we developed a novel differential networks (DNs) approach to connect pathway perturbation with toxicity threshold setting. Our DNs approach consists of 6 steps: time-series gene expression data collection, identification of altered genes, gene interaction network reconstruction, differential edge inference, mapping of genes with differential edges to pathways, and establishment of causal relationships between chemical concentration and perturbed pathways. A one-sample Gaussian process model and a linear regression model were used to identify genes that exhibited significant profile changes across an entire time course and between treatments, respectively. Interaction networks of differentially expressed (DE) genes were reconstructed for different treatments using a state space model and then compared to infer differential edges/interactions. DE genes possessing differential edges were mapped to biological pathways in databases such as KEGG pathways. Using the DNs approach, we analyzed a time-series Escherichia coli live cell gene expression dataset consisting of 4 treatments (control, 10, 100, 1000 mg/L naphthenic acids, NAs) and 18 time points. Through comparison of reconstructed networks and construction of differential networks, 80 genes were identified as DE genes with a significant number of differential edges, and 22 KEGG pathways were altered in a concentration-dependent manner. Some of these pathways were perturbed to a degree as high as 70% even at the lowest exposure concentration, implying a high sensitivity of our DNs approach

  1. Geographic patterns of networks derived from extreme precipitation over the Indian subcontinent

    Science.gov (United States)

    Stolbova, Veronika; Bookhagen, Bodo; Marwan, Norbert; Kurths, Juergen

    2014-05-01

    Complex networks (CN) and event synchronization (ES) methods have been applied to study a number of climate phenomena such as Indian Summer Monsoon (ISM), South-American Monsoon, and African Monsoon. These methods proved to be powerful tools to infer interdependencies in climate dynamics between geographical sites, spatial structures, and key regions of the considered climate phenomenon. Here, we use these methods to study the spatial temporal variability of the extreme rainfall over the Indian subcontinent, in order to filter the data by coarse-graining the network, and to identify geographic patterns that are signature features (spatial signatures) of the ISM. We find four main geographic patterns of networks derived from extreme precipitation over the Indian subcontinent using up-to-date satellite-derived, and high temporal and spatial resolution rain-gauge interpolated daily rainfall datasets. In order to prove that our results are also relevant for other climatic variables like pressure and temperature, we use re-analysis data provided by the National Center for Environmental Prediction and National Center for Atmospheric Research (NCEP/NCAR). We find that two of the patterns revealed from the CN extreme rainfall analysis coincide with those obtained for the pressure and temperature fields, and all four above mentioned patterns can be explained by topography, winds, and monsoon circulation. CN and ES enable to select the most informative regions for the ISM, providing realistic description of the ISM dynamics with fewer data, and also help to infer geographic pattern that are spatial signatures of the ISM. These patterns deserve a special attention for the meteorologists and can be used as markers of the ISM variability.

  2. Comparing land surface phenology derived from satellite and GPS network microwave remote sensing.

    Science.gov (United States)

    Jones, Matthew O; Kimball, John S; Small, Eric E; Larson, Kristine M

    2014-08-01

    The land surface phenology (LSP) start of season (SOS) metric signals the seasonal onset of vegetation activity, including canopy growth and associated increases in land-atmosphere water, energy and carbon (CO2) exchanges influencing weather and climate variability. The vegetation optical depth (VOD) parameter determined from satellite passive microwave remote sensing provides for global LSP monitoring that is sensitive to changes in vegetation canopy water content and biomass, and insensitive to atmosphere and solar illumination constraints. Direct field measures of canopy water content and biomass changes desired for LSP validation are generally lacking due to the prohibitive costs of maintaining regional monitoring networks. Alternatively, a normalized microwave reflectance index (NMRI) derived from GPS base station measurements is sensitive to daily vegetation water content changes and may provide for effective microwave LSP validation. We compared multiyear (2007-2011) NMRI and satellite VOD records at over 300 GPS sites in North America, and their derived SOS metrics for a subset of 24 homogenous land cover sites to investigate VOD and NMRI correspondence, and potential NMRI utility for LSP validation. Significant correlations (P<0.05) were found at 276 of 305 sites (90.5 %), with generally favorable correspondence in the resulting SOS metrics (r (2)=0.73, P<0.001, RMSE=36.8 days). This study is the first attempt to compare satellite microwave LSP metrics to a GPS network derived reflectance index and highlights both the utility and limitations of the NMRI data for LSP validation, including spatial scale discrepancies between local NMRI measurements and relatively coarse satellite VOD retrievals.

  3. GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

    Directory of Open Access Journals (Sweden)

    Meeri Eeva-Liisa Mäkinen

    2018-03-01

    Full Text Available The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging and temporal resolution microelectrode array (MEA. We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling.

  4. GABA and Gap Junctions in the Development of Synchronized Activity in Human Pluripotent Stem Cell-Derived Neural Networks

    Science.gov (United States)

    Mäkinen, Meeri Eeva-Liisa; Ylä-Outinen, Laura; Narkilahti, Susanna

    2018-01-01

    The electrical activity of the brain arises from single neurons communicating with each other. However, how single neurons interact during early development to give rise to neural network activity remains poorly understood. We studied the emergence of synchronous neural activity in human pluripotent stem cell (hPSC)-derived neural networks simultaneously on a single-neuron level and network level. The contribution of gamma-aminobutyric acid (GABA) and gap junctions to the development of synchronous activity in hPSC-derived neural networks was studied with GABA agonist and antagonist and by blocking gap junctional communication, respectively. We characterized the dynamics of the network-wide synchrony in hPSC-derived neural networks with high spatial resolution (calcium imaging) and temporal resolution microelectrode array (MEA). We found that the emergence of synchrony correlates with a decrease in very strong GABA excitation. However, the synchronous network was found to consist of a heterogeneous mixture of synchronously active cells with variable responses to GABA, GABA agonists and gap junction blockers. Furthermore, we show how single-cell distributions give rise to the network effect of GABA, GABA agonists and gap junction blockers. Finally, based on our observations, we suggest that the earliest form of synchronous neuronal activity depends on gap junctions and a decrease in GABA induced depolarization but not on GABAA mediated signaling. PMID:29559893

  5. Altered structural network architecture is predictive of the presence of psychotic symptoms in patients with 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Maria C. Padula

    2017-01-01

    Our results point to alterations in structural network architecture and white matter microstructure in patients with 22q11DS with attenuated positive symptoms, mainly involving connections of the limbic system. These alterations may therefore represent a potential biomarker for an increased risk of psychosis that should be further tested in longitudinal studies.

  6. Fractional-order gradient descent learning of BP neural networks with Caputo derivative.

    Science.gov (United States)

    Wang, Jian; Wen, Yanqing; Gou, Yida; Ye, Zhenyun; Chen, Hua

    2017-05-01

    Fractional calculus has been found to be a promising area of research for information processing and modeling of some physical systems. In this paper, we propose a fractional gradient descent method for the backpropagation (BP) training of neural networks. In particular, the Caputo derivative is employed to evaluate the fractional-order gradient of the error defined as the traditional quadratic energy function. The monotonicity and weak (strong) convergence of the proposed approach are proved in detail. Two simulations have been implemented to illustrate the performance of presented fractional-order BP algorithm on three small datasets and one large dataset. The numerical simulations effectively verify the theoretical observations of this paper as well. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. M-Polynomials and Topological Indices of Dominating David Derived Networks

    Directory of Open Access Journals (Sweden)

    Kang Shin Min

    2018-03-01

    Full Text Available There is a strong relationship between the chemical characteristics of chemical compounds and their molecular structures. Topological indices are numerical values associated with the chemical molecular graphs that help to understand the physical features, chemical reactivity, and biological activity of chemical compound. Thus, the study of the topological indices is important. M-polynomial helps to recover many degree-based topological indices for example Zagreb indices, Randic index, symmetric division idex, inverse sum index etc. In this article we compute M-polynomials of dominating David derived networks of the first type, second type and third type of dimension n and find some topological properties by using these M-polynomials. The results are plotted using Maple to see the dependence of topological indices on the involved parameters.

  8. Plasmid-derived DNA Strand Displacement Gates for Implementing Chemical Reaction Networks.

    Science.gov (United States)

    Chen, Yuan-Jyue; Rao, Sundipta D; Seelig, Georg

    2015-11-25

    DNA nanotechnology requires large amounts of highly pure DNA as an engineering material. Plasmid DNA could meet this need since it is replicated with high fidelity, is readily amplified through bacterial culture and can be stored indefinitely in the form of bacterial glycerol stocks. However, the double-stranded nature of plasmid DNA has so far hindered its efficient use for construction of DNA nanostructures or devices that typically contain single-stranded or branched domains. In recent work, it was found that nicked double stranded DNA (ndsDNA) strand displacement gates could be sourced from plasmid DNA. The following is a protocol that details how these ndsDNA gates can be efficiently encoded in plasmids and can be derived from the plasmids through a small number of enzymatic processing steps. Also given is a protocol for testing ndsDNA gates using fluorescence kinetics measurements. NdsDNA gates can be used to implement arbitrary chemical reaction networks (CRNs) and thus provide a pathway towards the use of the CRN formalism as a prescriptive molecular programming language. To demonstrate this technology, a multi-step reaction cascade with catalytic kinetics is constructed. Further it is shown that plasmid-derived components perform better than identical components assembled from synthetic DNA.

  9. Pricing and hedging derivative securities with neural networks: Bayesian regularization, early stopping, and bagging.

    Science.gov (United States)

    Gençay, R; Qi, M

    2001-01-01

    We study the effectiveness of cross validation, Bayesian regularization, early stopping, and bagging to mitigate overfitting and improving generalization for pricing and hedging derivative securities with daily S&P 500 index daily call options from January 1988 to December 1993. Our results indicate that Bayesian regularization can generate significantly smaller pricing and delta-hedging errors than the baseline neural-network (NN) model and the Black-Scholes model for some years. While early stopping does not affect the pricing errors, it significantly reduces the hedging error (HE) in four of the six years we investigated. Although computationally most demanding, bagging seems to provide the most accurate pricing and delta hedging. Furthermore, the standard deviation of the MSPE of bagging is far less than that of the baseline model in all six years, and the standard deviation of the average HE of bagging is far less than that of the baseline model in five out of six years. We conclude that they be used at least in cases when no appropriate hints are available.

  10. Artificial Neural Network for Production of Antioxidant Peptides Derived from Bighead Carp Muscles with Alcalase

    Directory of Open Access Journals (Sweden)

    Lin Li

    2006-01-01

    Full Text Available Controlled enzymatic modification proteins are currently being used as good sources of bioactive protein ingredients, and hydrolysates derived from bighead carp muscles may serve as antioxidants through the control of the processing-related parameters. The antioxidant ability was evaluated with regard to the scavenging effect on free radical DPPH·, OH· and O2 ·–. Due to the robustness, fault tolerance, high computational speed and self--learning ability, artificial neural network (ANN can be employed to build a predictive model for hydrolysis and optimize the hydrolysis variables: pH, temperature, hydrolysis time, muscle/water ratio and enzyme/substrate ratio (E/S for the production of antioxidant peptides. Optimum conditions to achieve the maximum antioxidant ability were obtained. The hydrolysates, which scavenged most effectively the DPPH·, OH· and O2 ·–, were hydrolyzed for 4.8 h with an activity of alcalase of 4.8 AU/kg, for 6 h with 3.84 AU/kg and for 4.3 h with 4.8 AU/kg, at pH=7.5 and 60 °C. Their respective muscle/water ratio was 1:1.9, 1:1.4 and 1:1. The present study confirmed that ANN could be used to simulate the hydrolysis process and predict hydrolysis conditions under which the hydrolysates could show the most effective scavenging ability on DPPH·, OH· and O2 ·–.

  11. The hematopoietic chemokine CXCL12 promotes integration of human endothelial colony forming cell-derived cells into immature vessel networks.

    Science.gov (United States)

    Newey, Sarah E; Tsaknakis, Grigorios; Khoo, Cheen P; Athanassopoulos, Thanassi; Camicia, Rosalba; Zhang, Youyi; Grabowska, Rita; Harris, Adrian L; Roubelakis, Maria G; Watt, Suzanne M

    2014-11-15

    Proangiogenic factors, vascular endothelial growth factor (VEGF), and fibroblast growth factor-2 (FGF-2) prime endothelial cells to respond to "hematopoietic" chemokines and cytokines by inducing/upregulating expression of the respective chemokine/cytokine receptors. Coculture of human endothelial colony forming cell (ECFC)-derived cells with human stromal cells in the presence of VEGF and FGF-2 for 14 days resulted in upregulation of the "hematopoietic" chemokine CXCL12 and its CXCR4 receptor by day 3 of coculture. Chronic exposure to the CXCR4 antagonist AMD3100 in this vasculo/angiogenesis assay significantly reduced vascular tubule formation, an observation recapitulated by delayed AMD3100 addition. While AMD3100 did not affect ECFC-derived cell proliferation, it did demonstrate a dual action. First, over the later stages of the 14-day cocultures, AMD3100 delayed tubule organization into maturing vessel networks, resulting in enhanced endothelial cell retraction and loss of complexity as defined by live cell imaging. Second, at earlier stages of cocultures, we observed that AMD3100 significantly inhibited the integration of exogenous ECFC-derived cells into established, but immature, vascular networks. Comparative proteome profiler array analyses of ECFC-derived cells treated with AMD3100 identified changes in expression of potential candidate molecules involved in adhesion and/or migration. Blocking antibodies to CD31, but not CD146 or CD166, reduced the ECFC-derived cell integration into these extant vascular networks. Thus, CXCL12 plays a key role not only in endothelial cell sensing and guidance, but also in promoting the integration of ECFC-derived cells into developing vascular networks.

  12. Erythropoietin promotes network formation of transplanted adipose tissue-derived microvascular fragments

    Directory of Open Access Journals (Sweden)

    P Karschnia

    2018-05-01

    Full Text Available The seeding of tissue constructs with adipose tissue-derived microvascular fragments (ad-MVF is an emerging pre-vascularisation strategy. Ad-MVF rapidly reassemble into new microvascular networks after in vivo implantation. Herein it was analysed whether this process was improved by erythropoietin (EPO. Ad-MVF were isolated from green fluorescent protein (GFP+ as well as wild-type C57BL/6 mice and cultivated for 24 h in medium supplemented with EPO (20 IU/mL or vehicle. Freshly isolated, non-cultivated ad-MVF served as controls. Protein expression, cell viability and proliferation of ad-MVF were assessed by proteome profiler array and fluorescence microscopy. GFP+ ad-MVF were seeded on collagen-glycosaminoglycan matrices, which were implanted into dorsal skinfold chambers of C57BL/6 mice, to analyse their vascularisation over 14 d by intravital fluorescence microscopy, histology and immunohistochemistry. Cultivation up-regulated the expression of pro- and anti-angiogenic factors within both vehicle- and EPO-treated ad-MVF when compared with non-cultivated controls. Moreover, EPO treatment suppressed cultivation-associated apoptosis and significantly increased the number of proliferating endothelial cells in ad-MVF when compared with vehicle-treated and non-cultivated ad-MVF. Accordingly, implanted matrices seeded with EPO-treated ad-MVF exhibited an improved vascularisation, as indicated by a significantly higher functional microvessel density. The matrices of the three groups contained a comparably large fraction of GFP+ microvessels originating from the ad-MVF, whereas the tissue surrounding the matrices seeded with EPO-treated ad-MVF exhibited a significantly increased microvessel density when compared with the other two groups. These findings indicated that EPO represents a promising cytokine to further boost the excellent vascularisation properties of ad-MVF in tissue-engineering applications.

  13. The Reference Ability Neural Network Study: Life-time stability of reference-ability neural networks derived from task maps of young adults.

    Science.gov (United States)

    Habeck, C; Gazes, Y; Razlighi, Q; Steffener, J; Brickman, A; Barulli, D; Salthouse, T; Stern, Y

    2016-01-15

    Analyses of large test batteries administered to individuals ranging from young to old have consistently yielded a set of latent variables representing reference abilities (RAs) that capture the majority of the variance in age-related cognitive change: Episodic Memory, Fluid Reasoning, Perceptual Processing Speed, and Vocabulary. In a previous paper (Stern et al., 2014), we introduced the Reference Ability Neural Network Study, which administers 12 cognitive neuroimaging tasks (3 for each RA) to healthy adults age 20-80 in order to derive unique neural networks underlying these 4 RAs and investigate how these networks may be affected by aging. We used a multivariate approach, linear indicator regression, to derive a unique covariance pattern or Reference Ability Neural Network (RANN) for each of the 4 RAs. The RANNs were derived from the neural task data of 64 younger adults of age 30 and below. We then prospectively applied the RANNs to fMRI data from the remaining sample of 227 adults of age 31 and above in order to classify each subject-task map into one of the 4 possible reference domains. Overall classification accuracy across subjects in the sample age 31 and above was 0.80±0.18. Classification accuracy by RA domain was also good, but variable; memory: 0.72±0.32; reasoning: 0.75±0.35; speed: 0.79±0.31; vocabulary: 0.94±0.16. Classification accuracy was not associated with cross-sectional age, suggesting that these networks, and their specificity to the respective reference domain, might remain intact throughout the age range. Higher mean brain volume was correlated with increased overall classification accuracy; better overall performance on the tasks in the scanner was also associated with classification accuracy. For the RANN network scores, we observed for each RANN that a higher score was associated with a higher corresponding classification accuracy for that reference ability. Despite the absence of behavioral performance information in the

  14. DERIVAÇÃO DE REDE DE DRENAGEM A PARTIR DE DADOS DO SRTM / DERIVING DRAINAGE NETWORK FROM SRTM DATA

    Directory of Open Access Journals (Sweden)

    Walter Collischonn

    2008-08-01

    Full Text Available The development and improvement of Geographic Information Systems and geoprocessing algorithms,together with the increase in computational capacity and data availability from remote sensing, becamepossible to prepare information for hydrologic studies of large areas with relative low cost and incrediblespeed. This paper describes the use of SRTM data to derive drainage network and related products, suchas accumulated drainage areas and river lengths, with application to the Uruguay river basin. Six distinctDigital Elevation Models (DEMs were used, varying the spatial resolution and applying the stream burningpre-processing technique. The main limitations of the DEM-derived drainage network refer to the incapacityof representing river meanders that are smaller than the pixel size and the problem of artificial sinuosity thatoccurs when the width of the river is larger than pixel side.

  15. Photo-cross-linked poly(thioether-co-carbonate) networks derived from the natural product quinic acid.

    Science.gov (United States)

    Link, Lauren A; Lonnecker, Alexander T; Hearon, Keith; Maher, Cameron A; Raymond, Jeffery E; Wooley, Karen L

    2014-10-22

    Polycarbonate networks derived from the natural product quinic acid that can potentially return to their natural building blocks upon hydrolytic degradation are described herein. Solvent-free thiol-ene chemistry was utilized in the copolymerization of tris(alloc)quinic acid and a variety of multifunctional thiol monomers to obtain poly(thioether-co-carbonate) networks with a wide range of achievable thermomechanical properties including glass transition temperatures from -18 to +65 °C and rubbery moduli from 3.8 to 20 MPa. The network containing 1,2-ethanedithiol expressed an average toughness at 25 and 63 °C of 1.08 and 2.35 MJ/m(3), respectively, and an order-of-magnitude increase in the average toughness at 37 °C of 15.56 MJ/m(3).

  16. Sox17-Mediated XEN Cell Conversion Identifies Dynamic Networks Controlling Cell-Fate Decisions in Embryo-Derived Stem Cells

    Directory of Open Access Journals (Sweden)

    Angela C.H. McDonald

    2014-10-01

    Full Text Available Little is known about the gene regulatory networks (GRNs distinguishing extraembryonic endoderm (ExEn stem (XEN cells from those that maintain the extensively characterized embryonic stem cell (ESC. An intriguing network candidate is Sox17, an essential transcription factor for XEN derivation and self-renewal. Here, we show that forced Sox17 expression drives ESCs toward ExEn, generating XEN cells that contribute to ExEn when placed back into early mouse embryos. Transient Sox17 expression is sufficient to drive this fate change during which time cells transit through distinct intermediate states prior to the generation of functional XEN-like cells. To orchestrate this conversion process, Sox17 acts in autoregulatory and feedforward network motifs, regulating dynamic GRNs directing cell fate. Sox17-mediated XEN conversion helps to explain the regulation of cell-fate changes and reveals GRNs regulating lineage decisions in the mouse embryo.

  17. Identifying Typhoon Tracks based on Event Synchronization derived Spatially Embedded Climate Networks

    Science.gov (United States)

    Ozturk, Ugur; Marwan, Norbert; Kurths, Jürgen

    2017-04-01

    Complex networks are commonly used for investigating spatiotemporal dynamics of complex systems, e.g. extreme rainfall. Especially directed networks are very effective tools in identifying climatic patterns on spatially embedded networks. They can capture the network flux, so as the principal dynamics of spreading significant phenomena. Network measures, such as network divergence, bare the source-receptor relation of the directed networks. However, it is still a challenge how to catch fast evolving atmospheric events, i.e. typhoons. In this study, we propose a new technique, namely Radial Ranks, to detect the general pattern of typhoons forward direction based on the strength parameter of the event synchronization over Japan. We suggest to subset a circular zone of high correlation around the selected grid based on the strength parameter. Radial sums of the strength parameter along vectors within this zone, radial ranks are measured for potential directions, which allows us to trace the network flux over long distances. We employed also the delay parameter of event synchronization to identify and separate the frontal storms' and typhoons' individual behaviors.

  18. Validation of Networks Derived from Snowball Sampling of Municipal Science Education Actors

    Science.gov (United States)

    von der Fehr, Ane; Sølberg, Jan; Bruun, Jesper

    2018-01-01

    Social network analysis (SNA) has been used in many educational studies in the past decade, but what these studies have in common is that the populations in question in most cases are defined and known to the researchers studying the networks. Snowball sampling is an SNA methodology most often used to study hidden populations, for example, groups…

  19. Photometric Properties of Network and Faculae Derived from HMI Data Compensated for Scattered Light

    Energy Technology Data Exchange (ETDEWEB)

    Criscuoli, Serena; Whitney, Taylor [National Solar Observatory, 3665 Discovery Drive, Boulder, CO 80303 (United States); Norton, Aimee [Hansen Experimental Physics Laboratory, Stanford University, Stanford, CA, 94305 (United States)

    2017-10-01

    We report on the photometric properties of faculae and network, as observed in full-disk, scattered-light-corrected images from the Helioseismic Magnetic Imager. We use a Lucy–Richardson deconvolution routine that corrects an image in less than one second. Faculae are distinguished from network through proximity to active regions. This is the first report that full-disk observations, including center-to-limb variations, reproduce the photometric properties of faculae and network observed previously only in sub-arcsecond-resolution; small field-of-view studies, i.e. that network, as defined by distance from active regions, exhibit higher photometric contrasts. Specifically, for magnetic flux values larger than approximately 300 G, the network is brighter than faculae and the contrast differences increase toward the limb, where the network contrast is about twice the facular one. For lower magnetic flux values, network appear darker than faculae. Contrary to reports from previous full-disk observations, we also found that network exhibits a higher center-to-limb variation. Our results are in agreement with reports from simulations that indicate magnetic flux alone is a poor proxy of the photometric properties of magnetic features. We estimate that the contribution of faculae and network to Total Solar Irradiance variability of the current Cycle 24 is overestimated by at least 11%, due to the photometric properties of network and faculae not being recognized as different. This estimate is specific to the method employed in this study to reconstruct irradiance variations, so caution should be paid when extending it to other techniques.

  20. Photometric Properties of Network and Faculae Derived from HMI Data Compensated for Scattered Light

    International Nuclear Information System (INIS)

    Criscuoli, Serena; Whitney, Taylor; Norton, Aimee

    2017-01-01

    We report on the photometric properties of faculae and network, as observed in full-disk, scattered-light-corrected images from the Helioseismic Magnetic Imager. We use a Lucy–Richardson deconvolution routine that corrects an image in less than one second. Faculae are distinguished from network through proximity to active regions. This is the first report that full-disk observations, including center-to-limb variations, reproduce the photometric properties of faculae and network observed previously only in sub-arcsecond-resolution; small field-of-view studies, i.e. that network, as defined by distance from active regions, exhibit higher photometric contrasts. Specifically, for magnetic flux values larger than approximately 300 G, the network is brighter than faculae and the contrast differences increase toward the limb, where the network contrast is about twice the facular one. For lower magnetic flux values, network appear darker than faculae. Contrary to reports from previous full-disk observations, we also found that network exhibits a higher center-to-limb variation. Our results are in agreement with reports from simulations that indicate magnetic flux alone is a poor proxy of the photometric properties of magnetic features. We estimate that the contribution of faculae and network to Total Solar Irradiance variability of the current Cycle 24 is overestimated by at least 11%, due to the photometric properties of network and faculae not being recognized as different. This estimate is specific to the method employed in this study to reconstruct irradiance variations, so caution should be paid when extending it to other techniques.

  1. Analysis of spontaneous deletions and gene amplification in the lac region of Escherichia coli

    International Nuclear Information System (INIS)

    Albertini, A.M.; Hofer, M.; Calos, M.P.; Tlsty, T.D.; Miller, J.H.

    1983-01-01

    Spontaneous rearrangements, such as large deletions and duplications, have important implications for the structure of the genome. It is therefore of great interest to analyze these events at the molecular level. We have constructed derivatives of a lacI-Z fusion strain, which allow us to study deletions in a more systematic manner than was previously possible. These derivatives have been used to investigate how frequently larger deletions (> 700 bp) occur between short homologies on both recA and recA - strains and to determine the effect of the lengths of the short homologies and of the distance between homologies on the frequency of deletion formation. 38 references, 11 figures

  2. The quest for EEG power band correlation with ICA derived fMRI resting state networks

    NARCIS (Netherlands)

    Meyer, M.C.; Janssen, R.J.; van Oort, E.S.B.; Beckmann, Christian; Barth, M.

    2013-01-01

    The neuronal underpinnings of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI) resting state networks (RSNs) are still unclear. To investigate the underlying mechanisms, specifically the relation to the electrophysiological signal, we used simultaneous recordings of

  3. On Deletion of Sutra Translation

    Institute of Scientific and Technical Information of China (English)

    CHEN Shu-juan

    2017-01-01

    Dao An's the metaphor of translation "wine diluted with water' ' expressed a view about translation that had been abridged.Later Kumarajiva provided metaphor "rice chewed—tasteless and downright disgusting".Both of them felt regretted at the weakening of taste,sometimes even the complete loss of flavor caused by deletion in translation of Buddhist sutras.In early sutra translation,deletion is unavoidable which made many sutra translators felt confused and drove them to study it further and some even managed to give their understanding to this issue.This thesis will discuss the definition,and what causes deletion and the measures adopted by the sutra translators.

  4. Transcription Factor Networks derived from Breast Cancer Stem Cells control the immune response in the Basal subtype

    DEFF Research Database (Denmark)

    da Silveira, W A; Palma, P V B; Sicchieri, R D

    2017-01-01

    Breast cancer is the most common cancer in women worldwide and metastatic dissemination is the principal factor related to death by this disease. Breast cancer stem cells (bCSC) are thought to be responsible for metastasis and chemoresistance. In this study, based on whole transcriptome analysis...... of these networks in patient tumours is predictive of engraftment success. Our findings point out a potential molecular mechanism underlying the balance between immune surveillance and EMT activation in breast cancer. This molecular mechanism may be useful to the development of new target therapies....... and IKZF3 transcription factors which correspond to immune response modulators. Immune response network expression is correlated with pathological response to chemotherapy, and in the Basal subtype is related to better recurrence-free survival. In patient-derived xenografts, the expression...

  5. Establishing the resting state default mode network derived from functional magnetic resonance imaging tasks as an endophenotype: A twins study.

    Science.gov (United States)

    Korgaonkar, Mayuresh S; Ram, Kaushik; Williams, Leanne M; Gatt, Justine M; Grieve, Stuart M

    2014-08-01

    The resting state default mode network (DMN) has been shown to characterize a number of neurological and psychiatric disorders. Evidence suggests an underlying genetic basis for this network and hence could serve as potential endophenotype for these disorders. Heritability is a defining criterion for endophenotypes. The DMN is measured either using a resting-state functional magnetic resonance imaging (fMRI) scan or by extracting resting state activity from task-based fMRI. The current study is the first to evaluate heritability of this task-derived resting activity. 250 healthy adult twins (79 monozygotic and 46 dizygotic same sex twin pairs) completed five cognitive and emotion processing fMRI tasks. Resting state DMN functional connectivity was derived from these five fMRI tasks. We validated this approach by comparing connectivity estimates from task-derived resting activity for all five fMRI tasks, with those obtained using a dedicated task-free resting state scan in an independent cohort of 27 healthy individuals. Structural equation modeling using the classic twin design was used to estimate the genetic and environmental contributions to variance for the resting-state DMN functional connectivity. About 9-41% of the variance in functional connectivity between the DMN nodes was attributed to genetic contribution with the greatest heritability found for functional connectivity between the posterior cingulate and right inferior parietal nodes (P<0.001). Our data provide new evidence that functional connectivity measures from the intrinsic DMN derived from task-based fMRI datasets are under genetic control and have the potential to serve as endophenotypes for genetically predisposed psychiatric and neurological disorders. Copyright © 2014 Wiley Periodicals, Inc.

  6. Calibration of GOES-derived solar radiation data using a distributed network of surface measurements in Florida, USA

    Science.gov (United States)

    Sumner, David M.; Pathak, Chandra S.; Mecikalski, John R.; Paech, Simon J.; Wu, Qinglong; Sangoyomi, Taiye; Babcock, Roger W.; Walton, Raymond

    2008-01-01

    Solar radiation data are critically important for the estimation of evapotranspiration. Analysis of visible-channel data derived from Geostationary Operational Environmental Satellites (GOES) using radiative transfer modeling has been used to produce spatially- and temporally-distributed datasets of solar radiation. An extensive network of (pyranometer) surface measurements of solar radiation in the State of Florida has allowed refined calibration of a GOES-derived daily integrated radiation data product. This refinement of radiation data allowed for corrections of satellite sensor drift, satellite generational change, and consideration of the highly-variable cloudy conditions that are typical of Florida. To aid in calibration of a GOES-derived radiation product, solar radiation data for the period 1995–2004 from 58 field stations that are located throughout the State were compiled. The GOES radiation product was calibrated by way of a three-step process: 1) comparison with ground-based pyranometer measurements on clear reference days, 2) correcting for a bias related to cloud cover, and 3) deriving month-by-month bias correction factors. Pre-calibration results indicated good model performance, with a station-averaged model error of 2.2 MJ m–2 day–1 (13 percent). Calibration reduced errors to 1.7 MJ m–2 day–1 (10 percent) and also removed time- and cloudiness-related biases. The final dataset has been used to produce Statewide evapotranspiration estimates.

  7. Ionic networks derived from the protonation of dendritic amines with carboxylic acid end‐functionalized PEGs

    DEFF Research Database (Denmark)

    Gonzalez, Lidia; Skov, Anne Ladegaard; Hvilsted, Søren

    2013-01-01

    The synthesis and characterization of novel ionic networks linked by the ammonium salts of poly(propylene imine) (PPI) dendrimers of the first (PPI G1) and second (PPI G2) generation and two short bis carboxymethyl ether terminated poly(ethylene glycol)s (DiCOOH‐PEG) with different molecular...... weights (Mn ∼ 250 and Mn ∼ 600) are reported. Likewise, an ionic network based on PPI G1 and a long αω‐dicarboxylic acid functionalized PEG (Mn ∼ 4800) were evaluated. Simpler ionic structures based on tris(2‐aminoethyl)amine or hexamethylene diamine and the short DiCOOH‐PEGs are also investigated....... The ionic structures formed were confirmed by differential scanning calorimetry, Fourier Transform Infrared spectroscopy in the attenuated‐total‐reflection mode, and 1H‐13C NMR spectroscopy. A comprehensive 1H NMR analysis revealed that only the primary amines of the PPI G1 dendrimer residing...

  8. Differential reconstructed gene interaction networks for deriving toxicity threshold in chemical risk assessment

    OpenAIRE

    Yang, Yi; Maxwell, Andrew; Zhang, Xiaowei; Wang, Nan; Perkins, Edward J; Zhang, Chaoyang; Gong, Ping

    2013-01-01

    Background Pathway alterations reflected as changes in gene expression regulation and gene interaction can result from cellular exposure to toxicants. Such information is often used to elucidate toxicological modes of action. From a risk assessment perspective, alterations in biological pathways are a rich resource for setting toxicant thresholds, which may be more sensitive and mechanism-informed than traditional toxicity endpoints. Here we developed a novel differential networks (DNs) appro...

  9. Development of a neutral network model to predict the excretion of purine derivatives in the urine of cows

    International Nuclear Information System (INIS)

    Volpe, V.; Stefanon, B.; Moscardini, S.; Susmel, P.; Gruber, L.

    1999-01-01

    A Neural Network Model to predict the urinary excretion of purine derivative nitrogen (UPDN) in cows is presented. The input variables of the model are dry matter intake (DMINT), NDF intake (NDFINT), total soluble nitrogen (SP), total soluble non-protein dry matter (SNPDM), total degradable nitrogen (DCP), total degradable non-protein dry matter (DNPDM), hourly available CP in the rumen (HACP), hourly available non-protein dry matter (HANPDM), three different gross indexes of synchronization, namely SYNCA (SP/SNPDM), SYNCB (DCP/DNPDM) and SYNCK (HACP/HANPDM) and two variables describing some metabolic aspects of purine derivative excretion such as live weight of the cow (LW) and milk yield (MILKY). The Model developed uses the Multi Layer Perceptron (MLP) utility, with 13 nodes in the input layer, 8 nodes in the hidden layer and 1 node in the output layer. The Model performances have been tested over 24 observations not previously used to train the model. When compared to a linear regression approach, the Neural Network model showed better performance but under predicted the daily excretion of UPDN for values around 20 g/day. When evaluated in terms of behaviour and depicted scenario the model responded to changes of live weight (LW) and milk yield (MILKY) and to modifications of the pattern of nutrients supplied to rumen microbes. (author)

  10. Development of a neutral network model to predict the excretion of purine derivatives in the urine of cows

    Energy Technology Data Exchange (ETDEWEB)

    Volpe, V; Stefanon, B; Moscardini, S; Susmel, P [University of Udine, Department of Animal Production Science, Pagnacco, UD (Italy); Gruber, L [Federal Research Institute for Agriculture in the Alpine Regions, Irdning (Austria)

    1999-06-01

    A Neural Network Model to predict the urinary excretion of purine derivative nitrogen (UPDN) in cows is presented. The input variables of the model are dry matter intake (DMINT), NDF intake (NDFINT), total soluble nitrogen (SP), total soluble non-protein dry matter (SNPDM), total degradable nitrogen (DCP), total degradable non-protein dry matter (DNPDM), hourly available CP in the rumen (HACP), hourly available non-protein dry matter (HANPDM), three different gross indexes of synchronization, namely SYNCA (SP/SNPDM), SYNCB (DCP/DNPDM) and SYNCK (HACP/HANPDM) and two variables describing some metabolic aspects of purine derivative excretion such as live weight of the cow (LW) and milk yield (MILKY). The Model developed uses the Multi Layer Perceptron (MLP) utility, with 13 nodes in the input layer, 8 nodes in the hidden layer and 1 node in the output layer. The Model performances have been tested over 24 observations not previously used to train the model. When compared to a linear regression approach, the Neural Network model showed better performance but under predicted the daily excretion of UPDN for values around 20 g/day. When evaluated in terms of behaviour and depicted scenario the model responded to changes of live weight (LW) and milk yield (MILKY) and to modifications of the pattern of nutrients supplied to rumen microbes. (author) 16 refs, 11 figs, 1 tab

  11. ATLAS DQ2 Deletion Service

    International Nuclear Information System (INIS)

    Oleynik, Danila; Petrosyan, Artem; Garonne, Vincent; Campana, Simone

    2012-01-01

    The ATLAS Distributed Data Management project DQ2 is responsible for the replication, access and bookkeeping of ATLAS data across more than 100 distributed grid sites. It also enforces data management policies decided on by the collaboration and defined in the ATLAS computing model. The DQ2 Deletion Service is one of the most important DDM services. This distributed service interacts with 3rd party grid middleware and the DQ2 catalogues to serve data deletion requests on the grid. Furthermore, it also takes care of retry strategies, check-pointing transactions, load management and fault tolerance. In this paper special attention is paid to the technical details which are used to achieve the high performance of service, accomplished without overloading either site storage, catalogues or other DQ2 components. Special attention is also paid to the deletion monitoring service that allows operators a detailed view of the working system.

  12. A rapid approach for automated comparison of independently derived stream networks

    Science.gov (United States)

    Stanislawski, Larry V.; Buttenfield, Barbara P.; Doumbouya, Ariel T.

    2015-01-01

    This paper presents an improved coefficient of line correspondence (CLC) metric for automatically assessing the similarity of two different sets of linear features. Elevation-derived channels at 1:24,000 scale (24K) are generated from a weighted flow-accumulation model and compared to 24K National Hydrography Dataset (NHD) flowlines. The CLC process conflates two vector datasets through a raster line-density differencing approach that is faster and more reliable than earlier methods. Methods are tested on 30 subbasins distributed across different terrain and climate conditions of the conterminous United States. CLC values for the 30 subbasins indicate 44–83% of the features match between the two datasets, with the majority of the mismatching features comprised of first-order features. Relatively lower CLC values result from subbasins with less than about 1.5 degrees of slope. The primary difference between the two datasets may be explained by different data capture criteria. First-order, headwater tributaries derived from the flow-accumulation model are captured more comprehensively through drainage area and terrain conditions, whereas capture of headwater features in the NHD is cartographically constrained by tributary length. The addition of missing headwaters to the NHD, as guided by the elevation-derived channels, can substantially improve the scientific value of the NHD.

  13. DESIGN OF LOW CYTOTOXICITY DIARYLANILINE DERIVATIVES BASED ON QSAR RESULTS: AN APPLICATION OF ARTIFICIAL NEURAL NETWORK MODELLING

    Directory of Open Access Journals (Sweden)

    Ihsanul Arief

    2016-11-01

    Full Text Available Study on cytotoxicity of diarylaniline derivatives by using quantitative structure-activity relationship (QSAR has been done. The structures and cytotoxicities of  diarylaniline derivatives were obtained from the literature. Calculation of molecular and electronic parameters was conducted using Austin Model 1 (AM1, Parameterized Model 3 (PM3, Hartree-Fock (HF, and density functional theory (DFT methods.  Artificial neural networks (ANN analysis used to produce the best equation with configuration of input data-hidden node-output data = 5-8-1, value of r2 = 0.913; PRESS = 0.069. The best equation used to design and predict new diarylaniline derivatives.  The result shows that compound N1-(4′-Cyanophenyl-5-(4″-cyanovinyl-2″,6″-dimethyl-phenoxy-4-dimethylether benzene-1,2-diamine is the best-proposed compound with cytotoxicity value (CC50 of 93.037 μM.

  14. Three-dimensional tetranuclear Cd(II) coordination network based on a 1,3-alternate calix[4]arene derivative

    International Nuclear Information System (INIS)

    Lee, Eun Ji; Ju, Hui Yeong; Park, Ki Min; Moon, ASuk Hee; Kang, Young Jin

    2015-01-01

    Polynuclear coordination polymers can exhibit more intriguing network topologies and better functionalities than those of common complexes because they have metal-cluster nodes for the construction of multidimensional frameworks and the potential applications induced by collaborative activities between metal ions. New tetranuclear Cd(II) coordination polymer 1 based on 1,3-alternate calix arene derivative (H_4 CTA) with four carboxyl pendant arms has been synthesized by the solvo thermal reaction at 110 .deg. C for 2 days. Compound 1 shows a 3-D framework consisting of tetranuclear Cd(II) cluster core as a metal-cluster node and 1,3-alternate H_4CTA as a multidentate linker. The coordination polymer 1 displays intense blue emission, implying that this tetranuclear Cd(II) coordination polymer could be a suitable material in the area of luminescence research

  15. A Liver Capsular Network of Monocyte-Derived Macrophages Restricts Hepatic Dissemination of Intraperitoneal Bacteria by Neutrophil Recruitment.

    Science.gov (United States)

    Sierro, Frederic; Evrard, Maximilien; Rizzetto, Simone; Melino, Michelle; Mitchell, Andrew J; Florido, Manuela; Beattie, Lynette; Walters, Shaun B; Tay, Szun Szun; Lu, Bo; Holz, Lauren E; Roediger, Ben; Wong, Yik Chun; Warren, Alessandra; Ritchie, William; McGuffog, Claire; Weninger, Wolfgang; Le Couteur, David G; Ginhoux, Florent; Britton, Warwick J; Heath, William R; Saunders, Bernadette M; McCaughan, Geoffrey W; Luciani, Fabio; MacDonald, Kelli P A; Ng, Lai Guan; Bowen, David G; Bertolino, Patrick

    2017-08-15

    The liver is positioned at the interface between two routes traversed by pathogens in disseminating infection. Whereas blood-borne pathogens are efficiently cleared in hepatic sinusoids by Kupffer cells (KCs), it is unknown how the liver prevents dissemination of peritoneal pathogens accessing its outer membrane. We report here that the hepatic capsule harbors a contiguous cellular network of liver-resident macrophages phenotypically distinct from KCs. These liver capsular macrophages (LCMs) were replenished in the steady state from blood monocytes, unlike KCs that are embryonically derived and self-renewing. LCM numbers increased after weaning in a microbiota-dependent process. LCMs sensed peritoneal bacteria and promoted neutrophil recruitment to the capsule, and their specific ablation resulted in decreased neutrophil recruitment and increased intrahepatic bacterial burden. Thus, the liver contains two separate and non-overlapping niches occupied by distinct resident macrophage populations mediating immunosurveillance at these two pathogen entry points to the liver. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Three-dimensional tetranuclear Cd(II) coordination network based on a 1,3-alternate calix[4]arene derivative

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ji; Ju, Hui Yeong; Park, Ki Min [Dept. of Chemistry and Research Institute of Natural Science, Gyeongsang National University, Jinju (Korea, Republic of); Moon, ASuk Hee [Dept. of Food and Nutrition, Kyungnam College of Inform ation and Technology, Busan (Korea, Republic of); Kang, Young Jin [Div. of cience Education, Kangwon National University, Chuncheon (Korea, Republic of)

    2015-08-15

    Polynuclear coordination polymers can exhibit more intriguing network topologies and better functionalities than those of common complexes because they have metal-cluster nodes for the construction of multidimensional frameworks and the potential applications induced by collaborative activities between metal ions. New tetranuclear Cd(II) coordination polymer 1 based on 1,3-alternate calix arene derivative (H{sub 4} CTA) with four carboxyl pendant arms has been synthesized by the solvo thermal reaction at 110 .deg. C for 2 days. Compound 1 shows a 3-D framework consisting of tetranuclear Cd(II) cluster core as a metal-cluster node and 1,3-alternate H{sub 4}CTA as a multidentate linker. The coordination polymer 1 displays intense blue emission, implying that this tetranuclear Cd(II) coordination polymer could be a suitable material in the area of luminescence research.

  17. Prediction of biopore- and matrix-dominated flow from X-ray CT-derived macropore network characteristics

    DEFF Research Database (Denmark)

    Naveed, Muhammad; Møldrup, Per; Schaap, Marcel G

    2016-01-01

    was to investigate the predictive performance of previously developed empirical models for both water and air flow and to explore the potential applicability of X-ray computed tomography (CT)-derived macropore network characteristics. For this purpose, 65 cylindrical soil columns (6 cm diameter and 3.5 cm height......Prediction and modeling of localized flow processes in macropores is of crucial importance for sustaining both soil and water quality. However, currently there are no reliable means to predict preferential flow due to its inherently large spatial variability. The aim of this study......) were extracted from the topsoil (5 cm to 8.5 cm depth) in a 15m15m grid from an agricultural field located in Silstrup, Denmark. All soil columns were scanned with an industrial X-ray CT scanner (129 μm resolution) and later employed for measurement of saturated hydraulic conductivity, air permeability...

  18. QSAR Study of Insecticides of Phthalamide Derivatives Using Multiple Linear Regression and Artificial Neural Network Methods

    Directory of Open Access Journals (Sweden)

    Adi Syahputra

    2014-03-01

    Full Text Available Quantitative structure activity relationship (QSAR for 21 insecticides of phthalamides containing hydrazone (PCH was studied using multiple linear regression (MLR, principle component regression (PCR and artificial neural network (ANN. Five descriptors were included in the model for MLR and ANN analysis, and five latent variables obtained from principle component analysis (PCA were used in PCR analysis. Calculation of descriptors was performed using semi-empirical PM6 method. ANN analysis was found to be superior statistical technique compared to the other methods and gave a good correlation between descriptors and activity (r2 = 0.84. Based on the obtained model, we have successfully designed some new insecticides with higher predicted activity than those of previously synthesized compounds, e.g.2-(decalinecarbamoyl-5-chloro-N’-((5-methylthiophen-2-ylmethylene benzohydrazide, 2-(decalinecarbamoyl-5-chloro-N’-((thiophen-2-yl-methylene benzohydrazide and 2-(decaline carbamoyl-N’-(4-fluorobenzylidene-5-chlorobenzohydrazide with predicted log LC50 of 1.640, 1.672, and 1.769 respectively.

  19. Electrical responses and spontaneous activity of human iPS-derived neuronal networks characterized for three-month culture with 4096-electrode arrays

    Directory of Open Access Journals (Sweden)

    Hayder eAmin

    2016-03-01

    Full Text Available The recent availability of human induced pluripotent stem cells (hiPSCs holds great promise as a novel source of human-derived neurons for cell and tissue therapies as well as for in vitro drug screenings that might replace the use of animal models. However, there is still a considerable lack of knowledge on the functional properties of hiPSC-derived neuronal networks, thus limiting their application. Here, upon optimization of cell culture protocols, we demonstrate that both spontaneous and evoked electrical spiking activities of these networks can be characterized on-chip by taking advantage of the resolution provided by CMOS multielectrode arrays (CMOS-MEAs. These devices feature a large and closely-spaced array of 4096 simultaneously recording electrodes and multi-site on-chip electrical stimulation. Our results show that networks of human-derived neurons can respond to electrical stimulation with a physiological repertoire of spike waveforms after three months of cell culture, a period of time during which the network undergoes the expression of developing patterns of spontaneous spiking activity. To achieve this, we have investigated the impact on the network formation and on the emerging network-wide functional properties induced by different biochemical substrates, i.e. poly-dl-ornithine (PDLO, poly-l-ornithine (PLO, and polyethylenimine (PEI, that were used as adhesion promoters for the cell culture. Interestingly, we found that neuronal networks grown on PDLO coated substrates show significantly higher spontaneous firing activity, reliable responses to low-frequency electrical stimuli, and an appropriate level of PSD-95 that may denote a physiological neuronal maturation profile and synapse stabilization. However, our results also suggest that even three-month culture might not be sufficient for human-derived neuronal network maturation. Taken together, our results highlight the tight relationship existing between substrate coatings

  20. Protecting Neural Structures and Cognitive Function During Prolonged Space Flight by Targeting the Brain Derived Neurotrophic Factor Molecular Network

    Science.gov (United States)

    Schmidt, M. A.; Goodwin, T. J.

    2014-01-01

    Brain derived neurotrophic factor (BDNF) is the main activity-dependent neurotrophin in the human nervous system. BDNF is implicated in production of new neurons from dentate gyrus stem cells (hippocampal neurogenesis), synapse formation, sprouting of new axons, growth of new axons, sprouting of new dendrites, and neuron survival. Alterations in the amount or activity of BDNF can produce significant detrimental changes to cortical function and synaptic transmission in the human brain. This can result in glial and neuronal dysfunction, which may contribute to a range of clinical conditions, spanning a number of learning, behavioral, and neurological disorders. There is an extensive body of work surrounding the BDNF molecular network, including BDNF gene polymorphisms, methylated BDNF gene promoters, multiple gene transcripts, varied BDNF functional proteins, and different BDNF receptors (whose activation differentially drive the neuron to neurogenesis or apoptosis). BDNF is also closely linked to mitochondrial biogenesis through PGC-1alpha, which can influence brain and muscle metabolic efficiency. BDNF AS A HUMAN SPACE FLIGHT COUNTERMEASURE TARGET Earth-based studies reveal that BDNF is negatively impacted by many of the conditions encountered in the space environment, including oxidative stress, radiation, psychological stressors, sleep deprivation, and many others. A growing body of work suggests that the BDNF network is responsive to a range of diet, nutrition, exercise, drug, and other types of influences. This section explores the BDNF network in the context of 1) protecting the brain and nervous system in the space environment, 2) optimizing neurobehavioral performance in space, and 3) reducing the residual effects of space flight on the nervous system on return to Earth

  1. Human iPSC-Derived Cerebellar Neurons from a Patient with Ataxia-Telangiectasia Reveal Disrupted Gene Regulatory Networks

    Directory of Open Access Journals (Sweden)

    Sam P. Nayler

    2017-10-01

    Full Text Available Ataxia-telangiectasia (A-T is a rare genetic disorder caused by loss of function of the ataxia-telangiectasia-mutated kinase and is characterized by a predisposition to cancer, pulmonary disease, immune deficiency and progressive degeneration of the cerebellum. As animal models do not faithfully recapitulate the neurological aspects, it remains unclear whether cerebellar degeneration is a neurodevelopmental or neurodegenerative phenotype. To address the necessity for a human model, we first assessed a previously published protocol for the ability to generate cerebellar neuronal cells, finding it gave rise to a population of precursors highly enriched for markers of the early hindbrain such as EN1 and GBX2, and later more mature cerebellar markers including PTF1α, MATH1, HOXB4, ZIC3, PAX6, and TUJ1. RNA sequencing was used to classify differentiated cerebellar neurons generated from integration-free A-T and control induced pluripotent stem cells. Comparison of RNA sequencing data with datasets from the Allen Brain Atlas reveals in vitro-derived cerebellar neurons are transcriptionally similar to discrete regions of the human cerebellum, and most closely resemble the cerebellum at 22 weeks post-conception. We show that patient-derived cerebellar neurons exhibit disrupted gene regulatory networks associated with synaptic vesicle dynamics and oxidative stress, offering the first molecular insights into early cerebellar pathogenesis of ataxia-telangiectasia.

  2. The rates and patterns of deletions in the human factor IX gene

    Energy Technology Data Exchange (ETDEWEB)

    Ketterling, R.P.; Vielhaber, E.L.; Lind, T.J.; Thorland, E.C.; Sommer S.S. (Mayo Clinic/Foundation, Rochester, MN (United States))

    1994-02-01

    Deletions are commonly observed in genes with either segments of highly homologous sequences or excessive gene length. However, in the factor IX gene and in most genes, deletions (of [ge]21 bp) are uncommon. The authors have analyzed DNA from 290 families with hemophilia B (203 independent mutations) and have found 12 deletions >20 bp. Eleven of these are >2 kb (range >3-163 kb), and one is 1.1 kb. The junctions of the four deletions that are completely contained within the factor IX gene have been determined. A novel mutation occurred in patient HB128: the data suggest that a 26.8-kb deletion occurred between two segments of alternating purines and pyrimidines and that a 2.3-kb sense strand segment derived from the deleted region was inserted. For a sample of 203 independent mutations, the authors estimate the [open quotes]baseline[close quotes] rates of deletional mutation per base pair per generation as a function of size. The rate for large (>2 kb)I deletions is exceedingly low. For every mutational event in which a given base is at the junction of a large deletion, there are an estimated 58 microdeletions (<20 bp) and 985 single-base substitutions at that base. Analysis of the nine reported deletion junctions in the factor IX gene literature reveals that (i) five are associated with inversion, orphan sequences, or sense strand insertions; (ii) four are simple deletions that display an excess of short direct repeats at their junctions; (iii) there is no dramatic clustering of junctions within the gene; and (iv) with the exception of alternating purines and pyrimidines, deletion junctions are not preferentially associated with repetitive DNA. 58 refs., 5 figs., 5 tabs.

  3. Characterization of transcription factor networks involved in umbilical cord blood CD34+ stem cells-derived erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Biaoru Li

    Full Text Available Fetal stem cells isolated from umbilical cord blood (UCB possess a great capacity for proliferation and differentiation and serve as a valuable model system to study gene regulation. Expanded knowledge of the molecular control of hemoglobin synthesis will provide a basis for rational design of therapies for β-hemoglobinopathies. Transcriptome data are available for erythroid progenitors derived from adult stem cells, however studies to define molecular mechanisms controlling globin gene regulation during fetal erythropoiesis are limited. Here, we utilize UCB-CD34+ stem cells induced to undergo erythroid differentiation to characterize the transcriptome and transcription factor networks (TFNs associated with the γ/β-globin switch during fetal erythropoiesis. UCB-CD34+ stem cells grown in the one-phase liquid culture system displayed a higher proliferative capacity than adult CD34+ stem cells. The γ/β-globin switch was observed after day 42 during fetal erythropoiesis in contrast to adult progenitors where the switch occurred around day 21. To gain insights into transcription factors involved in globin gene regulation, microarray analysis was performed on RNA isolated from UCB-CD34+ cell-derived erythroid progenitors harvested on day 21, 42, 49 and 56 using the HumanHT-12 Expression BeadChip. After data normalization, Gene Set Enrichment Analysis identified transcription factors (TFs with significant changes in expression during the γ/β-globin switch. Forty-five TFs were silenced by day 56 (Profile-1 and 30 TFs were activated by day 56 (Profile-2. Both GSEA datasets were analyzed using the MIMI Cytoscape platform, which discovered TFNs centered on KLF4 and GATA2 (Profile-1 and KLF1 and GATA1 for Profile-2 genes. Subsequent shRNA studies in KU812 leukemia cells and human erythroid progenitors generated from UCB-CD34+ cells supported a negative role of MAFB in γ-globin regulation. The characteristics of erythroblasts derived from UCB-CD34

  4. A recurrent neural network approach to quantitatively studying solar wind effects on TEC derived from GPS; preliminary results

    Directory of Open Access Journals (Sweden)

    J. B. Habarulema

    2009-05-01

    Full Text Available This paper attempts to describe the search for the parameter(s to represent solar wind effects in Global Positioning System total electron content (GPS TEC modelling using the technique of neural networks (NNs. A study is carried out by including solar wind velocity (Vsw, proton number density (Np and the Bz component of the interplanetary magnetic field (IMF Bz obtained from the Advanced Composition Explorer (ACE satellite as separate inputs to the NN each along with day number of the year (DN, hour (HR, a 4-month running mean of the daily sunspot number (R4 and the running mean of the previous eight 3-hourly magnetic A index values (A8. Hourly GPS TEC values derived from a dual frequency receiver located at Sutherland (32.38° S, 20.81° E, South Africa for 8 years (2000–2007 have been used to train the Elman neural network (ENN and the result has been used to predict TEC variations for a GPS station located at Cape Town (33.95° S, 18.47° E. Quantitative results indicate that each of the parameters considered may have some degree of influence on GPS TEC at certain periods although a decrease in prediction accuracy is also observed for some parameters for different days and seasons. It is also evident that there is still a difficulty in predicting TEC values during disturbed conditions. The improvements and degradation in prediction accuracies are both close to the benchmark values which lends weight to the belief that diurnal, seasonal, solar and magnetic variabilities may be the major determinants of TEC variability.

  5. Eribulin regresses a doxorubicin-resistant Ewing's sarcoma with a FUS-ERG fusion and CDKN2A-deletion in a patient-derived orthotopic xenograft (PDOX) nude mouse model.

    Science.gov (United States)

    Miyake, Kentaro; Murakami, Takashi; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Li, Yunfeng; Singh, Arun S; Dry, Sarah M; Eckardt, Mark A; Hiroshima, Yukihiko; Momiyama, Masashi; Matsuyama, Ryusei; Chishima, Takashi; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2018-01-01

    Ewing's sarcoma is a recalcitrant tumor greatly in need of more effective therapy. The aim of this study was to determine the efficacy of eribulin on a doxorubicin (DOX)-resistant Ewing's sarcoma patient derived orthotopic xenograft (PDOX) model. The Ewing's sarcoma PDOX model was previously established in the right chest wall of nude mice from tumor resected form the patient's right chest wall. In the previous study, the Ewing's sarcoma PDOX was resistant to doxorubicin (DOX) and sensitive to palbociclib and linsitinib. In the present study, the PDOX models were randomized into three groups when the tumor volume reached 60 mm 3 : G1, untreated control (n = 6); G2, DOX treated (n = 6), intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, Eribulin treated (n = 6, intravenous (i.v.) injection, weekly for 2 weeks). All mice were sacrificed on day 15. Changes in body weight and tumor volume were assessed two times per week. Tumor weight was measured after sacrifice. DOX did not suppress tumor growth compared to the control group (P = 0.589), consistent with the previous results in the patient and PDOX. Eribulin regressed tumor size significantly compared to G1 and G2 (P = 0.006, P = 0.017) respectively. No significant difference was observed in body weight among any group. Our results demonstrate that eribulin is a promising novel therapeutic agent for Ewing's sarcoma. © 2017 Wiley Periodicals, Inc.

  6. Effective molecular targeting of CDK4/6 and IGF-1R in a rare FUS-ERG fusion CDKN2A-deletion doxorubicin-resistant Ewing's sarcoma patient-derived orthotopic xenograft (PDOX) nude-mouse model.

    Science.gov (United States)

    Murakami, Takashi; Singh, Arun S; Kiyuna, Tasuku; Dry, Sarah M; Li, Yunfeng; James, Aaron W; Igarashi, Kentaro; Kawaguchi, Kei; DeLong, Jonathan C; Zhang, Yong; Hiroshima, Yukihiko; Russell, Tara; Eckardt, Mark A; Yanagawa, Jane; Federman, Noah; Matsuyama, Ryusei; Chishima, Takashi; Tanaka, Kuniya; Bouvet, Michael; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2016-07-26

    Ewing's sarcoma is a rare and aggressive malignancy. In the present study, tumor from a patient with a Ewing's sarcoma with cyclin-dependent kinase inhibitor 2A/B (CDKN2A/B) loss and FUS-ERG fusion was implanted in the right chest wall of nude mice to establish a patient-derived orthotopic xenograft (PDOX) model. The aim of the present study was to determine efficacy of cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors on the Ewing's sarcoma PDOX. The PDOX models were randomized into the following groups when tumor volume reached 50 mm3: G1, untreated control; G2, doxorubicin (DOX) (intraperitoneal (i.p.) injection, weekly, for 2 weeks); G3, CDK4/6 inhibitor (palbociclib, PD0332991, per oral (p.o.), daily, for 14 days); G4, IGF-1R inhibitor (linsitinib, OSI-906, p.o., daily, for 14 days). Tumor growth was significantly suppressed both in G3 (palbociclib) and in G4 (linsitinib) compared to G1 (untreated control) at all measured time points. In contrast, DOX did not inhibit tumor growth at any time point, which is consistent with the failure of DOX to control tumor growth in the patient. The results of the present study demonstrate the power of the PDOX model to identify effective targeted molecular therapy of a recalcitrant DOX-resistant Ewing's sarcoma with specific genetic alterations. The results of this study suggest the potential of PDOX models for individually-tailored, effective targeted therapy for recalcitrant cancer.

  7. Neural network modelling of antifungal activity of a series of oxazole derivatives based on in silico pharmacokinetic parameters

    Directory of Open Access Journals (Sweden)

    Kovačević Strahinja Z.

    2013-01-01

    Full Text Available In the present paper, the antifungal activity of a series of benzoxazole and oxazolo[ 4,5-b]pyridine derivatives was evaluated against Candida albicans by using quantitative structure-activity relationships chemometric methodology with artificial neural network (ANN regression approach. In vitro antifungal activity of the tested compounds was presented by minimum inhibitory concentration expressed as log(1/cMIC. In silico pharmacokinetic parameters related to absorption, distribution, metabolism and excretion (ADME were calculated for all studied compounds by using PreADMET software. A feedforward back-propagation ANN with gradient descent learning algorithm was applied for modelling of the relationship between ADME descriptors (blood-brain barrier penetration, plasma protein binding, Madin-Darby cell permeability and Caco-2 cell permeability and experimental log(1/cMIC values. A 4-6-1 ANN was developed with the optimum momentum and learning rates of 0.3 and 0.05, respectively. An excellent correlation between experimental antifungal activity and values predicted by the ANN was obtained with a correlation coefficient of 0.9536. [Projekat Ministarstva nauke Republike Srbije, br. 172012 i br. 172014

  8. Derivation of a correlation for Drag coefficient in two-dimensional bounded supercavitating flows, using artificial neural networks

    Energy Technology Data Exchange (ETDEWEB)

    Shafaghat, R.; Hosseinalipour, S.M.; Derakhshani, S.M.E. [Iran University of Science and Technology, Department of Mechanical Engineering, Tehran (Iran)

    2010-07-15

    Artificial neural networks (ANNs) are used as a new approach for the determination of the relations between drag coefficient and Cavitation Number with cavity geometry in supercavitating flows which have been most widely used in the hydrodynamics researches. Also the result of the ANNs as a cost function potentially will be used in an optimization algorithm. Instead of complex differential equations and limited experimental data, faster and simpler solutions were obtained using equations derived from the ANN model. For training of the ANN the numerical results are used that are obtained from a boundary element method (BEM). At this problem, a two-dimensional supercavitation potential inviscid flow pasts a symmetric two-dimensional cavitator, which is placed perpendicular to the flow in a channel of infinite width and immediately a cavity is formed behind the cavitator. It was found that the coefficient of multiple determination (R{sup 2}-value) between the actual and ANN predicted data is equal to about 0.9998 for the drag coefficient and Cavitation number. As seen from the obtained results, the calculated cavity geometry for all drag coefficients and Cavitation Numbers are obviously within acceptable limits. (orig.)

  9. Induced pluripotent stem cells with a pathological mitochondrial DNA deletion

    Science.gov (United States)

    Cherry, Anne B. C.; Gagne, Katelyn E.; McLoughlin, Erin M.; Baccei, Anna; Gorman, Bryan; Hartung, Odelya; Miller, Justine D.; Zhang, Jin; Zon, Rebecca L.; Ince, Tan A.; Neufeld, Ellis J.; Lerou, Paul H.; Fleming, Mark D.; Daley, George Q.; Agarwal, Suneet

    2013-01-01

    In congenital mitochondrial DNA (mtDNA) disorders, a mixture of normal and mutated mtDNA (termed heteroplasmy) exists at varying levels in different tissues, which determines the severity and phenotypic expression of disease. Pearson marrow pancreas syndrome (PS) is a congenital bone marrow failure disorder caused by heteroplasmic deletions in mtDNA. The cause of the hematopoietic failure in PS is unknown, and adequate cellular and animal models are lacking. Induced pluripotent stem (iPS) cells are particularly amenable for studying mtDNA disorders, as cytoplasmic genetic material is retained during direct reprogramming. Here we derive and characterize iPS cells from a patient with PS. Taking advantage of the tendency for heteroplasmy to change with cell passage, we isolated isogenic PS-iPS cells without detectable levels of deleted mtDNA. We found that PS-iPS cells carrying a high burden of deleted mtDNA displayed differences in growth, mitochondrial function, and hematopoietic phenotype when differentiated in vitro, compared to isogenic iPS cells without deleted mtDNA. Our results demonstrate that reprogramming somatic cells from patients with mtDNA disorders can yield pluripotent stem cells with varying burdens of heteroplasmy that might be useful in the study and treatment of mitochondrial diseases. PMID:23400930

  10. Neuronal activity in the isolated mouse spinal cord during spontaneous deletions in fictive locomotion: insights into locomotor central pattern generator organization

    Science.gov (United States)

    Zhong, Guisheng; Shevtsova, Natalia A; Rybak, Ilya A; Harris-Warrick, Ronald M

    2012-01-01

    We explored the organization of the spinal central pattern generator (CPG) for locomotion by analysing the activity of spinal interneurons and motoneurons during spontaneous deletions occurring during fictive locomotion in the isolated neonatal mouse spinal cord, following earlier work on locomotor deletions in the cat. In the isolated mouse spinal cord, most spontaneous deletions were non-resetting, with rhythmic activity resuming after an integer number of cycles. Flexor and extensor deletions showed marked asymmetry: flexor deletions were accompanied by sustained ipsilateral extensor activity, whereas rhythmic flexor bursting was not perturbed during extensor deletions. Rhythmic activity on one side of the cord was not perturbed during non-resetting spontaneous deletions on the other side, and these deletions could occur with no input from the other side of the cord. These results suggest that the locomotor CPG has a two-level organization with rhythm-generating (RG) and pattern-forming (PF) networks, in which only the flexor RG network is intrinsically rhythmic. To further explore the neuronal organization of the CPG, we monitored activity of motoneurons and selected identified interneurons during spontaneous non-resetting deletions. Motoneurons lost rhythmic synaptic drive during ipsilateral deletions. Flexor-related commissural interneurons continued to fire rhythmically during non-resetting ipsilateral flexor deletions. Deletion analysis revealed two classes of rhythmic V2a interneurons. Type I V2a interneurons retained rhythmic synaptic drive and firing during ipsilateral motor deletions, while type II V2a interneurons lost rhythmic synaptic input and fell silent during deletions. This suggests that the type I neurons are components of the RG, whereas the type II neurons are components of the PF network. We propose a computational model of the spinal locomotor CPG that reproduces our experimental results. The results may provide novel insights into the

  11. Exploration of methods to localize DNA sequences missing from c-locus deletions

    International Nuclear Information System (INIS)

    Albritton, L.M.; Russell, L.B.; Montgomery, C.S.

    1987-01-01

    The authors have earlier characterized a large number of radiation-induced mutations at the c locus (on Chromosome 7) through genetic analysis, including extensive complementation tests. Based on this work, they have postulated that many of these mutations are deletions of various lengths, overlapping at c (the marker used in the mutation-rate experiments that generated the mutants). It was possible to apportion these deletions among 13 complementation groups and to fit them to a linear map of 8 functional units. Collectively, the deletions extend from a point between tp and c to one between sh-1 and Hbb, i.e., a genetic distance of from 6 to 10 cM, corresponding to at least 10 4 Kb of DNA. This year, the authors completed a pilot study designed to explore methods for finding DNA sequences that map to the region covered by the various c-deletions. The general plan was to probe DNA with clones derived from Chromosome-7-enriched libraries or with sequences known (or suspected) to reside in Chromosome 7. Three methods were explored for deriving the c-region-deficient DNA: (a) from mouse-hamster somatic-cell hydrids retaining a deleted mouse Chromosome 7, but no homologue; (b) from F 1 hybrids of M. musculus domesticus (carrying a c-locus deletion) by M. spretus; and (c) from F 1 hybrids of M. domesticus stocks carrying complementing deletions

  12. Skin fibroblasts from a D-deletion type retinoblastoma patient are abnormally X-ray sensitive

    International Nuclear Information System (INIS)

    Weichselbaum, R.R.; Nove, J.; Little, J.B.

    1977-01-01

    Retinoblastoma is a rare malignant eye tumour that appears either spontaneously or in genetically predisposed persons. The latter group is composed of persons who inherit the tumour with a dominant mode of transmission (the familial type) and those who have a deletion in the long arm of chromosome 13 referred to as the D-deletion type. When this deletion is present it is observed in many somatic cells and is often associated with structural defects. Survivors of the genetic forms of retinoblastoma have an increased risk of the development of cancers at other sites. A single genetic locus is unlikely to predispose many somatic cells to tumour formation unless a fundamental molecular defect, possibly related to DNA repair, is present. In order to investigate this hypothesis a study was made of the in vitro X-ray sensitivity of skin fibroblasts derived from three retinoblastoma patients, comprising a pair of twins with the familial type accompanied by no gross chromosome abnormalities, and a patient with the D-deletion type. It was found that fibroblasts derived from the D-deletion patient were significantly more radiosensitive than those from the other two patients. X-ray survival curves are shown. It is concluded that skin fibroblasts derived from a patient with the D-deletion variant of retinoblastoma are abnormally radiosensitive. Future investigations may indicate a specific defect in molecular repair of DNA that will explain the predisposition of these patients to the development of other tumours. (U.K.)

  13. Combinations of probabilistic and approximate quantum cloning and deleting

    International Nuclear Information System (INIS)

    Qiu Daowen

    2002-01-01

    We first construct a probabilistic and approximate quantum cloning machine (PACM) and then clarify the relation between the PACM and other cloning machines. After that, we estimate the global fidelity of the approximate cloning that improves the previous estimation for the deterministic cloning machine; and also derive a bound on the success probability of producing perfect multiple clones. Afterwards, we further establish a more generalized probabilistic and approximate cloning and deleting machine (PACDM) and discuss the connections of the PACDM to some of the existing quantum cloning and deleting machines. Finally the global fidelity and a bound on the success probability of the PACDM are obtained. Summarily, the quantum devices established in this paper improve and also greatly generalize some of the existing machines

  14. Network Biomarkers of Bladder Cancer Based on a Genome-Wide Genetic and Epigenetic Network Derived from Next-Generation Sequencing Data.

    Science.gov (United States)

    Li, Cheng-Wei; Chen, Bor-Sen

    2016-01-01

    Epigenetic and microRNA (miRNA) regulation are associated with carcinogenesis and the development of cancer. By using the available omics data, including those from next-generation sequencing (NGS), genome-wide methylation profiling, candidate integrated genetic and epigenetic network (IGEN) analysis, and drug response genome-wide microarray analysis, we constructed an IGEN system based on three coupling regression models that characterize protein-protein interaction networks (PPINs), gene regulatory networks (GRNs), miRNA regulatory networks (MRNs), and epigenetic regulatory networks (ERNs). By applying system identification method and principal genome-wide network projection (PGNP) to IGEN analysis, we identified the core network biomarkers to investigate bladder carcinogenic mechanisms and design multiple drug combinations for treating bladder cancer with minimal side-effects. The progression of DNA repair and cell proliferation in stage 1 bladder cancer ultimately results not only in the derepression of miR-200a and miR-200b but also in the regulation of the TNF pathway to metastasis-related genes or proteins, cell proliferation, and DNA repair in stage 4 bladder cancer. We designed a multiple drug combination comprising gefitinib, estradiol, yohimbine, and fulvestrant for treating stage 1 bladder cancer with minimal side-effects, and another multiple drug combination comprising gefitinib, estradiol, chlorpromazine, and LY294002 for treating stage 4 bladder cancer with minimal side-effects.

  15. Healthy human CSF promotes glial differentiation of hESC-derived neural cells while retaining spontaneous activity in existing neuronal networks

    Directory of Open Access Journals (Sweden)

    Heikki Kiiski

    2013-05-01

    The possibilities of human pluripotent stem cell-derived neural cells from the basic research tool to a treatment option in regenerative medicine have been well recognized. These cells also offer an interesting tool for in vitro models of neuronal networks to be used for drug screening and neurotoxicological studies and for patient/disease specific in vitro models. Here, as aiming to develop a reductionistic in vitro human neuronal network model, we tested whether human embryonic stem cell (hESC-derived neural cells could be cultured in human cerebrospinal fluid (CSF in order to better mimic the in vivo conditions. Our results showed that CSF altered the differentiation of hESC-derived neural cells towards glial cells at the expense of neuronal differentiation. The proliferation rate was reduced in CSF cultures. However, even though the use of CSF as the culture medium altered the glial vs. neuronal differentiation rate, the pre-existing spontaneous activity of the neuronal networks persisted throughout the study. These results suggest that it is possible to develop fully human cell and culture-based environments that can further be modified for various in vitro modeling purposes.

  16. The combination of temozolomide-irinotecan regresses a doxorubicin-resistant patient-derived orthotopic xenograft (PDOX) nude-mouse model of recurrent Ewing's sarcoma with a FUS-ERG fusion and CDKN2A deletion: Direction for third-line patient therapy.

    Science.gov (United States)

    Miyake, Kentaro; Murakami, Takashi; Kiyuna, Tasuku; Igarashi, Kentaro; Kawaguchi, Kei; Miyake, Masuyo; Li, Yunfeng; Nelson, Scott D; Dry, Sarah M; Bouvet, Michael; Elliott, Irmina A; Russell, Tara A; Singh, Arun S; Eckardt, Mark A; Hiroshima, Yukihiko; Momiyama, Masashi; Matsuyama, Ryusei; Chishima, Takashi; Endo, Itaru; Eilber, Fritz C; Hoffman, Robert M

    2017-11-28

    The aim of the present study was to determine the usefulness of a patient-derived orthotopic xenograft (PDOX) nude-mouse model of a doxorubicin-resistant metastatic Ewing's sarcoma, with a unique combination of a FUS-ERG fusion and CDKN2A deletion, to identify effective drugs for third-line chemotherapy of the patient. Our previous study showed that cyclin-dependent kinase 4/6 (CDK4/6) and insulin-like growth factor-1 receptor (IGF-1R) inhibitors were effective on the Ewing's sarcoma PDOX, but not doxorubicin, similar to the patient's resistance to doxorubicin. The results of the previous PDOX study were successfully used for second-line therapy of the patiend. In the present study, the PDOX mice established with the Ewing's sarcoma in the right chest wall were randomized into 5 groups when the tumor volume reached 60 mm 3 : untreated control; gemcitabine combined with docetaxel (intraperitoneal [i.p.] injection, weekly, for 2 weeks); irinotecan combined with temozolomide (irinotecan: i.p. injection; temozolomide: oral administration, daily, for 2 weeks); pazopanib (oral administration, daily, for 2 weeks); yondelis (intravenous injection, weekly, for 2 weeks). All mice were sacrificed on day 15. Body weight and tumor volume were assessed 2 times per week. Tumor weight was measured after sacrifice. Irinotecan combined with temozolomide was the most effective regimen compared to the untreated control group (p=0.022). Gemcitabine combined with docetaxel was also effective (p=0.026). Pazopanib and yondelis did not have significant efficacy compared to the untreated control (p=0.130, p=0.818). These results could be obtained within two months after the physician's request and were used for third-line therapy of the patient.

  17. The shareholding similarity of the shareholders of the worldwide listed energy companies based on a two-mode primitive network and a one-mode derivative holding-based network

    Science.gov (United States)

    Li, Huajiao; Fang, Wei; An, Haizhong; Yan, LiLi

    2014-12-01

    Two-mode and multi-mode networks represent new directions of simulating a complex network that can simulate the relationships among the entities more precisely. In this paper, we constructed two different levels of networks: one is the two-mode primitive networks of the energy listed companies and their shareholders on the basis of the two-mode method of complex theory, and the other is the derivative one-mode holding-based network based on the equivalence network theory. We calculated two different topological characteristics of the two networks, that is, the out-degree of the actor nodes of the two-mode network (9003 nodes) and the weights of the edges of the one-mode network (619,766 edges), and we analyzed the distribution features of both of the two topological characteristics. In this paper, we define both the weighted and un-weighted Shareholding Similarity Coefficient, and using the data of the worldwide listed energy companies and their shareholders as empirical study subjects, we calculated and compared both the weighted and un-weighted shareholding similarity coefficient of the worldwide listed energy companies. The result of the analysis indicates that (1) both the out-degree of the actor nodes of the two-mode network and the weights of the edges of the one-mode network follow a power-law distribution; (2) there are significant differences between the weighted and un-weighted shareholding similarity coefficient of the worldwide listed energy companies, and the weighted shareholding similarity coefficient is of greater regularity than the un-weighted one; (3) there are a vast majority of shareholders who hold stock in only one or a few of the listed energy companies; and (4) the shareholders hold stock in the same listed energy companies when the value of the un-weighted shareholding similarity coefficient is between 0.4 and 0.8. The study will be a helpful tool to analyze the relationships of the nodes of the one-mode network, which is constructed based

  18. Networking

    OpenAIRE

    Rauno Lindholm, Daniel; Boisen Devantier, Lykke; Nyborg, Karoline Lykke; Høgsbro, Andreas; Fries, de; Skovlund, Louise

    2016-01-01

    The purpose of this project was to examine what influencing factor that has had an impact on the presumed increasement of the use of networking among academics on the labour market and how it is expressed. On the basis of the influence from globalization on the labour market it can be concluded that the globalization has transformed the labour market into a market based on the organization of networks. In this new organization there is a greater emphasis on employees having social qualificati...

  19. A network-based classification model for deriving novel drug-disease associations and assessing their molecular actions.

    Directory of Open Access Journals (Sweden)

    Min Oh

    Full Text Available The growing number and variety of genetic network datasets increases the feasibility of understanding how drugs and diseases are associated at the molecular level. Properly selected features of the network representations of existing drug-disease associations can be used to infer novel indications of existing drugs. To find new drug-disease associations, we generated an integrative genetic network using combinations of interactions, including protein-protein interactions and gene regulatory network datasets. Within this network, network adjacencies of drug-drug and disease-disease were quantified using a scored path between target sets of them. Furthermore, the common topological module of drugs or diseases was extracted, and thereby the distance between topological drug-module and disease (or disease-module and drug was quantified. These quantified scores were used as features for the prediction of novel drug-disease associations. Our classifiers using Random Forest, Multilayer Perceptron and C4.5 showed a high specificity and sensitivity (AUC score of 0.855, 0.828 and 0.797 respectively in predicting novel drug indications, and displayed a better performance than other methods with limited drug and disease properties. Our predictions and current clinical trials overlap significantly across the different phases of drug development. We also identified and visualized the topological modules of predicted drug indications for certain types of cancers, and for Alzheimer's disease. Within the network, those modules show potential pathways that illustrate the mechanisms of new drug indications, including propranolol as a potential anticancer agent and telmisartan as treatment for Alzheimer's disease.

  20. Seven gene deletions in seven days

    DEFF Research Database (Denmark)

    Ingemann Jensen, Sheila; Lennen, Rebecca; Herrgard, Markus

    2015-01-01

    Generation of multiple genomic alterations is currently a time consuming process. Here, a method was established that enables highly efficient and simultaneous deletion of multiple genes in Escherichia coli. A temperature sensitive plasmid containing arabinose inducible lambda Red recombineering ...

  1. Conditional Deletion of Pten Causes Bronchiolar Hyperplasia

    OpenAIRE

    Davé, Vrushank; Wert, Susan E.; Tanner, Tiffany; Thitoff, Angela R.; Loudy, Dave E.; Whitsett, Jeffrey A.

    2007-01-01

    Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that regulates multiple cellular processes including cell polarity, migration, proliferation, and carcinogenesis. In this work, we demonstrate that conditional deletion of Pten (PtenΔ/Δ) in the respiratory epithelial cells of the developing mouse lung caused epithelial cell proliferation and hyperplasia as early as 4 to 6 weeks of age. While bronchiolar cell differentiation was normal, as in...

  2. Preparation and wear behavior of polymer matrix composites with an interpenetrating network structure derived from natural sponge

    International Nuclear Information System (INIS)

    Wang Tianchi; Zhou Tianle; Xiong Dangsheng

    2010-01-01

    Natural sponge was used as a template to produce carbon/epoxy resin and (carbon+silicon carbide)/epoxy resin composites with interpenetrating network structures. Carbon with a network structure was first obtained by pyrolysis of the natural sponge. The composites were then obtained by injecting epoxy resin and silicone resin into the carbon. Their microstructures and wear properties were analyzed. The results show that the natural structure of sponge controlled the interpenetrating network structures of the composites. The netlike carbon in the composites reduced the wear rate of the epoxy resin. Compared with the carbon/epoxy resin composite, the (carbon+silicon carbide)/epoxy resin composite shows better wear resistance.

  3. 46 CFR 67.171 - Deletion; requirement and procedure.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Deletion; requirement and procedure. 67.171 Section 67...; Requirement for Exchange, Replacement, Deletion, Cancellation § 67.171 Deletion; requirement and procedure. (a... provided in § 67.161, and the vessel is subject to deletion from the roll of actively documented vessels...

  4. 19 CFR 142.49 - Deletion of C-4 Code.

    Science.gov (United States)

    2010-04-01

    .... Entry filers may delete C-4 Codes from Line Release by notifying the port director in writing on a Deletion Data Loading Sheet. Such notification shall state the C-4 Code which is to be deleted, the port... TREASURY (CONTINUED) ENTRY PROCESS Line Release § 142.49 Deletion of C-4 Code. (a) By Customs. A port...

  5. US emissions of HFC-134a derived for 2008-2012 from an extensive flask-air sampling network

    NARCIS (Netherlands)

    Hu, Lei; Montzka, Stephen A.; Miller, John B.; Andrews, Aryln E.; Lehman, Scott J.; Miller, Benjamin R.; Thoning, Kirk; Sweeney, Colm; Chen, Huilin; Godwin, David S.; Masarie, Kenneth; Bruhwiler, Lori; Fischer, Marc L.; Biraud, Sebastien C.; Torn, Margaret S.; Mountain, Marikate; Nehrkorn, Thomas; Eluszkiewicz, Janusz; Miller, Scot; Draxler, Roland R.; Stein, Ariel F.; Hall, Bradley D.; Elkins, James W.; Tans, Pieter P.

    2015-01-01

    U.S. national and regional emissions of HFC-134a are derived for 2008-2012 based on atmospheric observations from ground and aircraft sites across the U.S. and a newly developed regional inverse model. Synthetic data experiments were first conducted to optimize the model assimilation design and to

  6. Batch sequencing of oil derivates in pipeline networks; Sequenciamento de bateladas de derivados leves de petroleo numa rede dutoviaria

    Energy Technology Data Exchange (ETDEWEB)

    Bonacin, Mario Vicente; Oliveira, Daniel Rossato de; Czaikowski, Daniel Irineu; Polli, Helton Luis; Magatao, Leandro; Stebel, Sergio Leandro; Neves Junior, Flavio [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil); Ribas, Paulo Cesar [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil). Centro de Pesquisas (CENPES)

    2008-07-01

    This work presents a computational tool to assist the operational scheduling of a pipeline network. In this network, transfer of products is carried out by batches, from a source to a destination. This tool implements a proposal to determine priorities of the outgoing batches as well as alternatives for sequencing them fulfilling the stated periods stipulated. This proposal uses an analysis of production and demand plans, stockage, products draining in terminals, as well as operational restrictions of the pipeline network, looking for optimizing the use of resources such as pipes, bombs and tanks. The scenario in study is composed by 14 areas (4 refineries, 2 harbours, 6 distribution centres and 2 costumers) and 29 pipes. Prioritizing the attendance to the areas of source or demand, the algorithm carries choices between routes and possible batches volumes, considering calculations of time windows, that determine the limited interval when transference operations must occur. Moreover, operations called 'lung' are also treated, which involve flow changes during the movement. (author)

  7. Application of adaptive boosting to EP-derived multilayer feed-forward neural networks (MLFN) to improve benign/malignant breast cancer classification

    Science.gov (United States)

    Land, Walker H., Jr.; Masters, Timothy D.; Lo, Joseph Y.; McKee, Dan

    2001-07-01

    A new neural network technology was developed for improving the benign/malignant diagnosis of breast cancer using mammogram findings. A new paradigm, Adaptive Boosting (AB), uses a markedly different theory in solutioning Computational Intelligence (CI) problems. AB, a new machine learning paradigm, focuses on finding weak learning algorithm(s) that initially need to provide slightly better than random performance (i.e., approximately 55%) when processing a mammogram training set. Then, by successive development of additional architectures (using the mammogram training set), the adaptive boosting process improves the performance of the basic Evolutionary Programming derived neural network architectures. The results of these several EP-derived hybrid architectures are then intelligently combined and tested using a similar validation mammogram data set. Optimization focused on improving specificity and positive predictive value at very high sensitivities, where an analysis of the performance of the hybrid would be most meaningful. Using the DUKE mammogram database of 500 biopsy proven samples, on average this hybrid was able to achieve (under statistical 5-fold cross-validation) a specificity of 48.3% and a positive predictive value (PPV) of 51.8% while maintaining 100% sensitivity. At 97% sensitivity, a specificity of 56.6% and a PPV of 55.8% were obtained.

  8. Rapid deletion production in fungi via Agrobacterium mediated transformation of OSCAR deletion contructs.

    Science.gov (United States)

    Precise deletion of gene(s) of interest, while leaving the rest of the genome unchanged, provides the ideal product to determine that particular gene’s function in the living organism. In this protocol we describe the OSCAR method of precise and rapid deletion plasmid construction. OSCAR relies on t...

  9. An Aerosol Extinction-to-Backscatter Ratio Database Derived from the NASA Micro-Pulse Lidar Network: Applications for Space-based Lidar Observations

    Science.gov (United States)

    Welton, Ellsworth J.; Campbell, James R.; Spinhime, James D.; Berkoff, Timothy A.; Holben, Brent; Tsay, Si-Chee; Bucholtz, Anthony

    2004-01-01

    Backscatter lidar signals are a function of both backscatter and extinction. Hence, these lidar observations alone cannot separate the two quantities. The aerosol extinction-to-backscatter ratio, S, is the key parameter required to accurately retrieve extinction and optical depth from backscatter lidar observations of aerosol layers. S is commonly defined as 4*pi divided by the product of the single scatter albedo and the phase function at 180-degree scattering angle. Values of S for different aerosol types are not well known, and are even more difficult to determine when aerosols become mixed. Here we present a new lidar-sunphotometer S database derived from Observations of the NASA Micro-Pulse Lidar Network (MPLNET). MPLNET is a growing worldwide network of eye-safe backscatter lidars co-located with sunphotometers in the NASA Aerosol Robotic Network (AERONET). Values of S for different aerosol species and geographic regions will be presented. A framework for constructing an S look-up table will be shown. Look-up tables of S are needed to calculate aerosol extinction and optical depth from space-based lidar observations in the absence of co-located AOD data. Applications for using the new S look-up table to reprocess aerosol products from NASA's Geoscience Laser Altimeter System (GLAS) will be discussed.

  10. Integration of donor mesenchymal stem cell-derived neuron-like cells into host neural network after rat spinal cord transection.

    Science.gov (United States)

    Zeng, Xiang; Qiu, Xue-Cheng; Ma, Yuan-Huan; Duan, Jing-Jing; Chen, Yuan-Feng; Gu, Huai-Yu; Wang, Jun-Mei; Ling, Eng-Ang; Wu, Jin-Lang; Wu, Wutian; Zeng, Yuan-Shan

    2015-06-01

    Functional deficits following spinal cord injury (SCI) primarily attribute to loss of neural connectivity. We therefore tested if novel tissue engineering approaches could enable neural network repair that facilitates functional recovery after spinal cord transection (SCT). Rat bone marrow-derived mesenchymal stem cells (MSCs), genetically engineered to overexpress TrkC, receptor of neurotrophin-3 (NT-3), were pre-differentiated into cells carrying neuronal features via co-culture with NT-3 overproducing Schwann cells in 3-dimensional gelatin sponge (GS) scaffold for 14 days in vitro. Intra-GS formation of MSC assemblies emulating neural network (MSC-GS) were verified morphologically via electron microscopy (EM) and functionally by whole-cell patch clamp recording of spontaneous post-synaptic currents. The differentiated MSCs still partially maintained prototypic property with the expression of some mesodermal cytokines. MSC-GS or GS was then grafted acutely into a 2 mm-wide transection gap in the T9-T10 spinal cord segments of adult rats. Eight weeks later, hindlimb function of the MSC-GS-treated SCT rats was significantly improved relative to controls receiving the GS or lesion only as indicated by BBB score. The MSC-GS transplantation also significantly recovered cortical motor evoked potential (CMEP). Histologically, MSC-derived neuron-like cells maintained their synapse-like structures in vivo; they additionally formed similar connections with host neurites (i.e., mostly serotonergic fibers plus a few corticospinal axons; validated by double-labeled immuno-EM). Moreover, motor cortex electrical stimulation triggered c-fos expression in the grafted and lumbar spinal cord cells of the treated rats only. Our data suggest that MSC-derived neuron-like cells resulting from NT-3-TrkC-induced differentiation can partially integrate into transected spinal cord and this strategy should be further investigated for reconstructing disrupted neural circuits. Copyright

  11. Consistent individual differences and population plasticity in network-derived sociality: An experimental manipulation of density in a gregarious ungulate

    Science.gov (United States)

    O’Brien, Paul P.; Vander Wal, Eric

    2018-01-01

    In many taxa, individual social traits appear to be consistent across time and context, thus meeting the criteria for animal personality. How these differences are maintained in response to changes in population density is unknown, particularly in large mammals, such as ungulates. Using a behavioral reaction norm (BRN) framework, we examined how among- and within-individual variation in social connectedness, measured using social network analyses, change as a function of population density. We studied a captive herd of elk (Cervus canadensis) separated into a group of male elk and a group of female elk. Males and females were exposed to three different density treatments and we recorded social associations between individuals with proximity-detecting radio-collars fitted to elk. We constructed social networks using dyadic association data and calculated three social network metrics reflective of social connectedness: eigenvector centrality, graph strength, and degree. Elk exhibited consistent individual differences in social connectedness across densities; however, they showed little individual variation in their response to changes in density, i.e., individuals oftentimes responded plastically, but in the same manner to changes in density. Female elk had highest connectedness at an intermediate density. In contrast, male elk increased connectedness with increasing density. Whereas this may suggest that the benefits of social connectedness outweigh the costs of increased competition at higher density for males, females appear to exhibit a threshold in social benefits (e.g. predator detection and forage information). Our study illustrates the importance of viewing social connectedness as a density-dependent trait, particularly in the context of plasticity. Moreover, we highlight the need to revisit our understanding of density dependence as a population-level phenomenon by accounting for consistent individual differences not only in social connectedness, but likely

  12. 9q22 Deletion - First Familial Case

    Directory of Open Access Journals (Sweden)

    Yamamoto Toshiyuki

    2011-06-01

    Full Text Available Abstract Background Only 29 cases of constitutional 9q22 deletions have been published and all have been sporadic. Most associate with Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS, MIM #109400 due to haploinsufficiency of the PTCH1 gene (MIM *601309. Methods and Results We report two mentally retarded female siblings and their cognitively normal father, all carrying a similar 5.3 Mb microdeletion at 9q22.2q22.32, detected by array CGH (244 K. The deletion does not involve the PTCH1 gene, but instead 30 other gene,s including the ROR2 gene (MIM *602337 which causing both brachydactyly type 1 (MIM #113000 and Robinow syndrome (MIM #268310, and the immunologically active SYK gene (MIM *600085. The deletion in the father was de novo and FISH analysis of blood lymphocytes did not suggest mosaicism. All three patients share similar mild dysmorphic features with downslanting palpebral fissures, narrow, high bridged nose with small nares, long, deeply grooved philtrum, ears with broad helix and uplifted lobuli, and small toenails. All have significant dysarthria and suffer from continuous middle ear and upper respiratory infections. The father also has a funnel chest and unilateral hypoplastic kidney but the daughters have no malformations. Conclusions This is the first report of a familial constitutional 9q22 deletion and the first deletion studied by array-CGH which does not involve the PTCH1 gene. The phenotype and penetrance are variable and the deletion found in the cognitively normal normal father poses a challenge in genetic counseling.

  13. The Nature and Variability of Automated Practice Alerts Derived from Electronic Health Records in a U.S. Nationwide Critical Care Research Network.

    Science.gov (United States)

    Benthin, Cody; Pannu, Sonal; Khan, Akram; Gong, Michelle

    2016-10-01

    The nature, variability, and extent of early warning clinical practice alerts derived from automated query of electronic health records (e-alerts) currently used in acute care settings for clinical care or research is unknown. To describe e-alerts in current use in acute care settings at medical centers participating in a nationwide critical care research network. We surveyed investigators at 38 institutions involved in the National Institutes of Health-funded Clinical Trials Network for the Prevention and Early Treatment of Acute Lung Injury (PETAL) for quantitative and qualitative analysis. Thirty sites completed the survey (79% response rate). All sites used electronic health record systems. Epic Systems was used at 56% of sites; the others used alternate commercially available vendors or homegrown systems. Respondents at 57% of sites represented in this survey used e-alerts. All but 1 of these 17 sites used an e-alert for early detection of sepsis-related syndromes, and 35% used an e-alert for pneumonia. E-alerts were triggered by abnormal laboratory values (37%), vital signs (37%), or radiology reports (15%) and were used about equally for clinical decision support and research. Only 59% of sites with e-alerts have evaluated them either for accuracy or for validity. A majority of the research network sites participating in this survey use e-alerts for early notification of potential threats to hospitalized patients; however, there was significant variability in the nature of e-alerts between institutions. Use of one common electronic health record vendor at more than half of the participating sites suggests that it may be possible to standardize e-alerts across multiple sites in research networks, particularly among sites using the same medical record platform.

  14. Pumping propagation and influence of oil derivatives transport in a pipeline network; Propagacao e influencia de bombeamento no transporte de derivados de petroleo em uma rede de dutos

    Energy Technology Data Exchange (ETDEWEB)

    Borba, Camila Baldissera de [Petroleo Brasileiro S.A. (PETROBRAS), Rio de Janeiro, RJ (Brazil); Kluppel, Liege Bauer; Neves Junior, Flavio [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil); Ribas, Paulo Cesar [Petroleo Brasileiro S.A (CENPES/PETROBRAS), Rio de Janeiro, RJ (Brazil). Centro de Pesquisa e Desenvolvimento

    2012-07-01

    This paper presents the work developed on a pipeline network that transports oil derivatives. The transport occurs in batches of a specific product, each one having a defined route: the pumping origin, a destination for its receipt and the pipelines which the product is moved through. The network studied has a total of thirty pipelines connected by fourteen possible areas of pumping and/or receiving, this makes it not trivial to obtain the batches order in the pipeline. In order to obtain the passage of batches ordered list in the pipeline network, was developed an algorithm capable of propagating a batches list that only have route, start time and end time of pumping in the origin. This algorithm is part of a larger project whose goal is to obtain a tool to aid the process of operational decision making in a real pipeline network. The developed module can also generate the entry and exit times of each batch for each pipe through which it passes. With this information, analysis and/or validations can be made. At the end of the process, the result is a list of all the pumped batches in all pipes where it must go by. Thus, it is made a small pos-processing where the list is sorted, first by pipeline and then by start time of entry into the duct, which naturally causes the passage of the batches list in the ducts to be obtained. This work is based on the development presented by Czaikowski et al (2008). (author)

  15. Dynamical processes and epidemic threshold on nonlinear coupled multiplex networks

    Science.gov (United States)

    Gao, Chao; Tang, Shaoting; Li, Weihua; Yang, Yaqian; Zheng, Zhiming

    2018-04-01

    Recently, the interplay between epidemic spreading and awareness diffusion has aroused the interest of many researchers, who have studied models mainly based on linear coupling relations between information and epidemic layers. However, in real-world networks the relation between two layers may be closely correlated with the property of individual nodes and exhibits nonlinear dynamical features. Here we propose a nonlinear coupled information-epidemic model (I-E model) and present a comprehensive analysis in a more generalized scenario where the upload rate differs from node to node, deletion rate varies between susceptible and infected states, and infection rate changes between unaware and aware states. In particular, we develop a theoretical framework of the intra- and inter-layer dynamical processes with a microscopic Markov chain approach (MMCA), and derive an analytic epidemic threshold. Our results suggest that the change of upload and deletion rate has little effect on the diffusion dynamics in the epidemic layer.

  16. Deletion 22q13.3 syndrome

    Directory of Open Access Journals (Sweden)

    Phelan Mary C

    2008-05-01

    Full Text Available Abstract The deletion 22q13.3 syndrome (deletion 22q13 syndrome or Phelan-McDermid syndrome is a chromosome microdeletion syndrome characterized by neonatal hypotonia, global developmental delay, normal to accelerated growth, absent to severely delayed speech, and minor dysmorphic features. The deletion occurs with equal frequency in males and females and has been reported in mosaic and non-mosaic forms. Due to lack of clinical recognition and often insufficient laboratory testing, the syndrome is under-diagnosed and its true incidence remains unknown. Common physical traits include long eye lashes, large or unusual ears, relatively large hands, dysplastic toenails, full brow, dolicocephaly, full cheeks, bulbous nose, and pointed chin. Behavior is autistic-like with decreased perception of pain and habitual chewing or mouthing. The loss of 22q13.3 can result from simple deletion, translocation, ring chromosome formation and less common structural changes affecting the long arm of chromosome 22, specifically the region containing the SHANK3 gene. The diagnosis of deletion 22q13 syndrome should be considered in all cases of hypotonia of unknown etiology and in individuals with absent speech. Although the deletion can sometimes be detected by high resolution chromosome analysis, fluorescence in situ hybridization (FISH or array comparative genomic hybridization (CGH is recommended for confirmation. Differential diagnosis includes syndromes associated with hypotonia, developmental delay, speech delay and/or autistic-like affect (Prader-Willi, Angelman, Williams, Smith-Magenis, Fragile X, Sotos, FG, trichorhinophalangeal and velocardiofacial syndromes, autism spectrum disorders, cerebral palsy. Genetic counseling is recommended and parental laboratory studies should be considered to identify cryptic rearrangements and detect parental mosaicism. Prenatal diagnosis should be offered for future pregnancies in those families with inherited rearrangements

  17. The deeper structure of the southern Dead Sea basin derived from neural network analysis of velocity and attenuation tomography

    Science.gov (United States)

    Braeuer, Benjamin; Haberland, Christian; Bauer, Klaus; Weber, Michael

    2014-05-01

    The Dead Sea basin is a pull-apart basin at the Dead Sea transform fault, the boundary between the African and the Arabian plates. Though the DSB has been studied for a long time, the available knowledge - based mainly on surface geology, drilling and seismic reflection surveys - gives only a partial picture of its shallow structure. Therefore, within the framework of the international DESIRE (DEad Sea Integrated REsearch) project, a dense temporary local seismological network was operated in the southern Dead Sea area. Within 18 month of recording 650 events were detected. In addition to an already published tomography study revealing the distribution of P velocities and the Vp/Vs ratios a 2D P-wave attenuation tomography (parameter Qp) was performed. The neural network technique of Self-organizing maps (SOM) is used for the joint interpretation of these three parameters (Vp, Vp/Vs, Qp). The resulting clusters in the petrophysical parameter space are assigned to the main lithological units below the southern part of the Dead Sea basin: (1) The basin sediments characterized by strong attenuation, high vp/vs ratios and low P velocities. (2) The pre-basin sediments characterized by medium to strong attenuation, low Vp/Vs ratios and medium P velocities. (3) The basement characterized by low to moderate attenuation, medium vp/vs ratios and high P velocities. Thus, the asymmetric southern Dead Sea basin is filled with basin sediments down to depth of 7 to 12 km. Below the basin sediments, the pre-basin sediments are extending to a depth between 13 and 18 km.

  18. Familial deletion 18p syndrome: case report

    Directory of Open Access Journals (Sweden)

    Lemyre Emmanuelle

    2006-07-01

    Full Text Available Abstract Background Deletion 18p is a frequent deletion syndrome characterized by dysmorphic features, growth deficiencies, and mental retardation with a poorer verbal performance. Until now, five families have been described with limited clinical description. We report transmission of deletion 18p from a mother to her two daughters and review the previous cases. Case presentation The proband is 12 years old and has short stature, dysmorphic features and moderate mental retardation. Her sister is 9 years old and also has short stature and similar dysmorphic features. Her cognitive performance is within the borderline to mild mental retardation range. The mother also presents short stature. Psychological evaluation showed moderate mental retardation. Chromosome analysis from the sisters and their mother revealed the same chromosomal deletion: 46, XX, del(18(p11.2. Previous familial cases were consistent regarding the transmission of mental retardation. Our family differs in this regard with variable cognitive impairment and does not display poorer verbal than non-verbal abilities. An exclusive maternal transmission is observed throughout those families. Women with del(18p are fertile and seem to have a normal miscarriage rate. Conclusion Genetic counseling for these patients should take into account a greater range of cognitive outcome than previously reported.

  19. 78 FR 37525 - Procurement List; Deletions

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    2013-06-21

    .... Contracting Activity: Dept of the Air Force, FA7014 AFDW A7KI, Andrews AFB, MD. Service Type/Location: Laundry... Procurement List. SUMMARY: This action deletes products and services from the Procurement List that were... products and services listed below are no longer suitable for procurement by the Federal Government under...

  20. Sequence analysis of 17 NRXN1 deletions

    DEFF Research Database (Denmark)

    Hoeffding, Louise Kristine Enggaard; Hansen, Thomas; Ingason, Andrés

    2014-01-01

    into the molecular mechanisms governing such genomic rearrangements may increase our understanding of disease pathology and evolutionary processes. Here we analyse 17 carriers of non-recurrent deletions in the NRXN1 gene, which have been associated with neurodevelopmental disorders, e.g. schizophrenia, autism...

  1. Angiotensin Converting Enzyme Insertion/Deletion Gene ...

    African Journals Online (AJOL)

    Angiotensin Converting Enzyme Insertion/Deletion Gene Polymorphism: An Observational Study among Diabetic Hypertensive Subjects in Malaysia. ... Methods: The pharmacological effect of ACE inhibition on mean arterial pressure (MAP) and glomerular filtration rate (GFR) were observed among a total of 62 subjects for ...

  2. Obtaining a Proportional Allocation by Deleting Items

    NARCIS (Netherlands)

    Dorn, B.; de Haan, R.; Schlotter, I.; Röthe, J.

    2017-01-01

    We consider the following control problem on fair allocation of indivisible goods. Given a set I of items and a set of agents, each having strict linear preference over the items, we ask for a minimum subset of the items whose deletion guarantees the existence of a proportional allocation in the

  3. Union-Find with Constant Time Deletions

    DEFF Research Database (Denmark)

    Alstrup, Stephen; Thorup, Mikkel; Gørtz, Inge Li

    2014-01-01

    operations performed, and α_M/N_(n) is a functional inverse of Ackermann’s function. They left open the question whether delete operations can be implemented more efficiently than find operations, for example, in o(log n) worst-case time. We resolve this open problem by presenting a relatively simple...

  4. Mapping genomic deletions down to the base

    DEFF Research Database (Denmark)

    Dunø, Morten; Hove, Hanne; Kirchhoff, Maria

    2004-01-01

    the breakpoint of the third patient was mapped to a region previously predicted to be prone for rearrangements. One patient also harboured an inversion in connection with the deletion that disrupted the HDAC9 gene. All three patients showed clinical characteristics reminiscent of the hand-foot-genital syndrome...

  5. Delayed chromosomal instability caused by large deletion

    International Nuclear Information System (INIS)

    Ojima, M.; Suzuki, K.; Kodama, S.; Watanabe, M.

    2003-01-01

    Full text: There is accumulating evidence that genomic instability, manifested by the expression of delayed phenotypes, is induced by X-irradiation but not by ultraviolet (UV) light. It is well known that ionizing radiation, such as X-rays, induces DNA double strand breaks, but UV-light mainly causes base damage like pyrimidine dimers and (6-4) photoproducts. Although the mechanism of radiation-induced genomic instability has not been thoroughly explained, it is suggested that DNA double strand breaks contribute the induction of genomic instability. We examined here whether X-ray induced gene deletion at the hprt locus induces delayed instability in chromosome X. SV40-immortalized normal human fibroblasts, GM638, were irradiated with X-rays (3, 6 Gy), and the hprt mutants were isolated in the presence of 6-thioguanine (6-TG). A 2-fold and a 60-fold increase in mutation frequency were found by 3 Gy and 6 Gy irradiation, respectively. The molecular structure of the hprt mutations was determined by multiplex polymerase chain reaction of nine exons. Approximately 60% of 3 Gy mutants lost a part or the entire hprt gene, and the other mutants showed point mutations like spontaneous mutants. All 6 Gy mutants show total gene deletion. The chromosomes of the hprt mutants were analyzed by Whole Human Chromosome X Paint FISH or Xq telomere FISH. None of the point or partial gene deletion mutants showed aberrations of X-chromosome, however total gene deletion mutants induced translocations and dicentrics involving chromosome X. These results suggest that large deletion caused by DNA double strand breaks destabilizes chromosome structure, which may be involved in an induction of radiation-induced genomic instability

  6. N-Doped Carbon Nanofibrous Network Derived from Bacterial Cellulose for the Loading of Pt Nanoparticles for Methanol Oxidation Reaction.

    Science.gov (United States)

    Yuan, Fanshu; Huang, Yang; Fan, Mengmeng; Chen, Chuntao; Qian, Jieshu; Hao, Qingli; Yang, Jiazhi; Sun, Dongping

    2018-02-06

    The large-scale, low-cost preparation of Pt-based catalysts with high activity and durability for the methanol oxidation reaction is still challenging. The key to achieving this aim is finding suitable supporting materials. In this paper, N-doped carbon nanofibrous networks are prepared by annealing a gel containing two inexpensive and ecofriendly precursors, that is, bacterial cellulose and urea, for the loading of Pt nanoparticles. An undoped analogue is also prepared for comparison. Meanwhile, the effect of the annealing temperature on the performance of the catalysts is evaluated. The results show that the N doping and higher annealing temperature can improve the electron conductivity of the catalyst and provide more active sites for the loading of ultrafine Pt nanoparticles with a narrow size distribution. The best catalyst exhibits a remarkably high electrocatalytic activity (627 mA mg -1 ), excellent poison tolerance, and high durability. This work demonstrates an ideal Pt supporting material for the methanol oxidation reaction. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Evaluating nonindigenous species management in a Bayesian networks derived relative risk framework for Padilla Bay, WA, USA.

    Science.gov (United States)

    Herring, Carlie E; Stinson, Jonah; Landis, Wayne G

    2015-10-01

    Many coastal regions are encountering issues with the spread of nonindigenous species (NIS). In this study, we conducted a regional risk assessment using a Bayesian network relative risk model (BN-RRM) to analyze multiple vectors of NIS introductions to Padilla Bay, Washington, a National Estuarine Research Reserve. We had 3 objectives in this study. The 1st objective was to determine whether the BN-RRM could be used to calculate risk from NIS introductions for Padilla Bay. Our 2nd objective was to determine which regions and endpoints were at greatest risk from NIS introductions. Our 3rd objective was to incorporate a management option into the model and predict endpoint risk if it were to be implemented. Eradication can occur at different stages of NIS invasions, such as the elimination of these species before being introduced to the habitat or removal of the species after settlement. We incorporated the ballast water treatment management scenario into the model, observed the risk to the endpoints, and compared this risk with the initial risk estimates. The model results indicated that the southern portion of the bay was at greatest risk because of NIS. Changes in community composition, Dungeness crab, and eelgrass were the endpoints most at risk from NIS introductions. The currents node, which controls the exposure of NIS to the bay from the surrounding marine environment, was the parameter that had the greatest influence on risk. The ballast water management scenario displayed an approximate 1% reduction in risk in this Padilla Bay case study. The models we developed provide an adaptable template for decision makers interested in managing NIS in other coastal regions and large bodies of water. © 2015 SETAC.

  8. Genetics Home Reference: 17q12 deletion syndrome

    Science.gov (United States)

    ... with 17q12 deletion syndrome have delayed development (particularly speech and language delays), intellectual disability, or behavioral or psychiatric disorders. Behavioral and psychiatric conditions that have been reported in people with 17q12 deletion syndrome include autism ...

  9. ZNF804A Transcriptional Networks in Differentiating Neurons Derived from Induced Pluripotent Stem Cells of Human Origin.

    Directory of Open Access Journals (Sweden)

    Jian Chen

    Full Text Available ZNF804A (Zinc Finger Protein 804A has been identified as a candidate gene for schizophrenia (SZ, autism spectrum disorders (ASD, and bipolar disorder (BD in replicated genome wide association studies (GWAS and by copy number variation (CNV analysis. Although its function has not been well-characterized, ZNF804A contains a C2H2-type zinc-finger domain, suggesting that it has DNA binding properties, and consequently, a role in regulating gene expression. To further explore the role of ZNF804A on gene expression and its downstream targets, we used a gene knockdown (KD approach to reduce its expression in neural progenitor cells (NPCs derived from induced pluripotent stem cells (iPSCs. KD was accomplished by RNA interference (RNAi using lentiviral particles containing shRNAs that target ZNF804A mRNA. Stable transduced NPC lines were generated after puromycin selection. A control cell line expressing a random (scrambled shRNA was also generated. Neuronal differentiation was induced, RNA was harvested after 14 days and transcriptome analysis was carried out using RNA-seq. 1815 genes were found to be differentially expressed at a nominally significant level (p<0.05; 809 decreased in expression in the KD samples, while 1106 increased. Of these, 370 achieved genome wide significance (FDR<0.05; 125 were lower in the KD samples, 245 were higher. Pathway analysis showed that genes involved in interferon-signaling were enriched among those that were down-regulated in the KD samples. Correspondingly, ZNF804A KD was found to affect interferon-alpha 2 (IFNA2-mediated gene expression. The findings suggest that ZNF804A may affect a differentiating neuron's response to inflammatory cytokines, which is consistent with models of SZ and ASD that support a role for infectious disease, and/or autoimmunity in a subgroup of patients.

  10. Derivation of suspended sediment data for Al-Adhiam watershed-Iraq using artificial neural network model

    Directory of Open Access Journals (Sweden)

    Al-Khafaji Mahmoud Saleh

    2018-01-01

    Full Text Available The mean part of river sediments is suspended sediment load, its prediction and simulation has important significance to manage the water resources and environments. In Iraq, most researchers avoid to fighting in sediment researches when related with hydrological models spatially with that need enough observed sediment data for calibration and validation because the sediment data very limitation or scars. The aim of this study is employing the Artificial Neural Network (ANN model to estimate the suspended sediment load of Al-Adhaim watershed in Iraq from available measured sediment data, identify the suitable pattern of input and target data sampling and obtaining the best nonlinear equation between the river discharge and suspended sediment load. To this end, the ANN model was training and tested with the available sediment data, which was for water year (1983-1984. Two modes were applied for input and target data sampling each mode has two cases, where in the first mode the time series data sampling was used with flow as an input for case one while flow and average precipitation in case two with used suspended sediment as a target variable. For second mode the supervise data sampling was used with the same input and target division in first mode. The performance of the model was evaluated by using Coefficient of determination (R2 and the Nash- Sutcliffe efficiency (NS and standardization of root mean square error (RSR, the statistical analysis model testing for Al-Adhiam watershed showed satisfactory agreement between observed and estimated daily values for Mode2- Case2. R2, NS and RSR of the testing period were 0.99 and 0.8and 0.2 respectively. The result shows that the conducted ANN model can be used with the best net as a predictor for sediment yield in this watershed. The model was used to predict daily sediment load data for period from 1Oct. 1984 to 31Spt 1985. The predicted daily sediment data was plotted against daily measured flow

  11. Deriving amplification factors from simple site parameters using generalized regression neural networks: implications for relevant site proxies

    Science.gov (United States)

    Boudghene Stambouli, Ahmed; Zendagui, Djawad; Bard, Pierre-Yves; Derras, Boumédiène

    2017-07-01

    Most modern seismic codes account for site effects using an amplification factor (AF) that modifies the rock acceleration response spectra in relation to a "site condition proxy," i.e., a parameter related to the velocity profile at the site under consideration. Therefore, for practical purposes, it is interesting to identify the site parameters that best control the frequency-dependent shape of the AF. The goal of the present study is to provide a quantitative assessment of the performance of various site condition proxies to predict the main AF features, including the often used short- and mid-period amplification factors, Fa and Fv, proposed by Borcherdt (in Earthq Spectra 10:617-653, 1994). In this context, the linear, viscoelastic responses of a set of 858 actual soil columns from Japan, the USA, and Europe are computed for a set of 14 real accelerograms with varying frequency contents. The correlation between the corresponding site-specific average amplification factors and several site proxies (considered alone or as multiple combinations) is analyzed using the generalized regression neural network (GRNN). The performance of each site proxy combination is assessed through the variance reduction with respect to the initial amplification factor variability of the 858 profiles. Both the whole period range and specific short- and mid-period ranges associated with the Borcherdt factors Fa and Fv are considered. The actual amplification factor of an arbitrary soil profile is found to be satisfactorily approximated with a limited number of site proxies (4-6). As the usual code practice implies a lower number of site proxies (generally one, sometimes two), a sensitivity analysis is conducted to identify the "best performing" site parameters. The best one is the overall velocity contrast between underlying bedrock and minimum velocity in the soil column. Because these are the most difficult and expensive parameters to measure, especially for thick deposits, other

  12. 78 FR 29119 - Procurement List; Additions and Deletion

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  13. 5 CFR 1631.17 - Deletion of exempted information.

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  1. 75 FR 69638 - Procurement List; Additions and Deletion

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    ... Additions and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Proposed Additions to and Deletion from the Procurement List. SUMMARY: The Committee is proposing to add... Activity: Department of Energy, Idaho Operations Office, Idaho Falls, ID. DELETION Regulatory Flexibility...

  3. 44 CFR 5.27 - Deletion of identifying details.

    Science.gov (United States)

    2010-10-01

    ... 44 Emergency Management and Assistance 1 2010-10-01 2010-10-01 false Deletion of identifying... Availability of General Agency Information, Rules, Orders, Policies, and Similar Material § 5.27 Deletion of..., interpretation, or staff manual or instruction. However, the justification for each deletion will be explained...

  4. 29 CFR 1610.20 - Deletion of exempted matters.

    Science.gov (United States)

    2010-07-01

    ... 29 Labor 4 2010-07-01 2010-07-01 false Deletion of exempted matters. 1610.20 Section 1610.20 Labor... Production or Disclosure Under 5 U.S.C. 552 § 1610.20 Deletion of exempted matters. Where requested records... the remainder of the records, they shall be disclosed by the Commission with deletions. To each such...

  5. 49 CFR 7.6 - Deletion of identifying detail.

    Science.gov (United States)

    2010-10-01

    ... 49 Transportation 1 2010-10-01 2010-10-01 false Deletion of identifying detail. 7.6 Section 7.6... To Be Made Public by DOT § 7.6 Deletion of identifying detail. Whenever it is determined to be... the deletion will accompany the record published or made available for inspection. ...

  6. 76 FR 5142 - Procurement List; Additions and Deletion

    Science.gov (United States)

    2011-01-28

    ... and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Additions to and deletion from the Procurement List. SUMMARY: This action adds services to the Procurement.... Contracting Activity: Department of Transportation, Federal Aviation Administration, Jamaica, NY. Deletion On...

  7. Genetics Home Reference: proximal 18q deletion syndrome

    Science.gov (United States)

    ... characteristic features. Most cases of proximal 18q deletion syndrome are the result of a new (de novo) deletion and are not inherited from a ... J, Fox PT, Stratton RF, Perry B, Hale DE. Recurrent interstitial deletions of proximal 18q: a new syndrome involving expressive speech delay. Am J Med Genet ...

  8. Characterization of five partial deletions of the factor VIII gene

    International Nuclear Information System (INIS)

    Youssoufian, H.; Antonarakis, S.E.; Aronis, S.; Tsiftis, G.; Phillips, D.G.; Kazazian, H.H. Jr.

    1987-01-01

    Hemophilia A is an X-linked disorder of coagulation caused by a deficiency of factor VIII. By using cloned DNA probes, the authors have characterized the following five different partial deletions of the factor VIII gene from a panel of 83 patients with hemophilia A: (i) a 7-kilobase (kb) deletion that eliminates exon 6; (ii) a 2.5-kb deletion that eliminates 5' sequences of exon 14; (iii) a deletion of at least 7 kb that eliminates exons 24 and 25; (iv) a deletion of at least 16 kb that eliminates exons 23-25; and (v) a 5.5-kb deletion that eliminates exon 22. The first four deletions are associated with severe hemophilia A. By contrast, the last deletion is associated with moderate disease, possibly because of in-frame splicing from adjacent exons. None of those patients with partial gene deletions had circulating inhibitors to factor VIII. One deletion occurred de novo in a germ cell of the maternal grandmother, while a second deletion occurred in a germ cell of the maternal grandfather. These observations demonstrate that de novo deletions of X-linked genes can occur in either male or female gametes

  9. Global high-resolution monthly pCO2 climatology for the coastal ocean derived from neural network interpolation

    Directory of Open Access Journals (Sweden)

    G. G. Laruelle

    2017-10-01

    Full Text Available In spite of the recent strong increase in the number of measurements of the partial pressure of CO2 in the surface ocean (pCO2, the air–sea CO2 balance of the continental shelf seas remains poorly quantified. This is a consequence of these regions remaining strongly under-sampled in both time and space and of surface pCO2 exhibiting much higher temporal and spatial variability in these regions compared to the open ocean. Here, we use a modified version of a two-step artificial neural network method (SOM-FFN; Landschützer et al., 2013 to interpolate the pCO2 data along the continental margins with a spatial resolution of 0.25° and with monthly resolution from 1998 to 2015. The most important modifications compared to the original SOM-FFN method are (i the much higher spatial resolution and (ii the inclusion of sea ice and wind speed as predictors of pCO2. The SOM-FFN is first trained with pCO2 measurements extracted from the SOCATv4 database. Then, the validity of our interpolation, in both space and time, is assessed by comparing the generated pCO2 field with independent data extracted from the LDVEO2015 database. The new coastal pCO2 product confirms a previously suggested general meridional trend of the annual mean pCO2 in all the continental shelves with high values in the tropics and dropping to values beneath those of the atmosphere at higher latitudes. The monthly resolution of our data product permits us to reveal significant differences in the seasonality of pCO2 across the ocean basins. The shelves of the western and northern Pacific, as well as the shelves in the temperate northern Atlantic, display particularly pronounced seasonal variations in pCO2,  while the shelves in the southeastern Atlantic and in the southern Pacific reveal a much smaller seasonality. The calculation of temperature normalized pCO2 for several latitudes in different oceanic basins confirms that the seasonality in shelf pCO2 cannot solely be explained by

  10. An environment-mediated quantum deleter

    International Nuclear Information System (INIS)

    Srikanth, R.; Banerjee, Subhashish

    2007-01-01

    Environment-induced decoherence presents a great challenge to realizing a quantum computer. We point out the somewhat surprising fact that decoherence can be useful, indeed necessary, for practical quantum computation, in particular, for the effective erasure of quantum memory in order to initialize the state of the quantum computer. The essential point behind the deleter is that the environment, by means of a dissipative interaction, furnishes a contractive map towards a pure state. We present a specific example of an amplitude damping channel provided by a two-level system's interaction with its environment in the weak Born-Markov approximation. This is contrasted with a purely dephasing, non-dissipative channel provided by a two-level system's interaction with its environment by means of a quantum nondemolition interaction. We point out that currently used state preparation techniques, for example using optical pumping, essentially perform as quantum deleters

  11. Conditional deletion of Pten causes bronchiolar hyperplasia.

    Science.gov (United States)

    Davé, Vrushank; Wert, Susan E; Tanner, Tiffany; Thitoff, Angela R; Loudy, Dave E; Whitsett, Jeffrey A

    2008-03-01

    Tumor suppressor phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that regulates multiple cellular processes including cell polarity, migration, proliferation, and carcinogenesis. In this work, we demonstrate that conditional deletion of Pten (Pten(Delta/Delta)) in the respiratory epithelial cells of the developing mouse lung caused epithelial cell proliferation and hyperplasia as early as 4 to 6 weeks of age. While bronchiolar cell differentiation was normal, as indicated by beta-tubulin and FOXJ1 expression in ciliated cells and by CCSP expression in nonciliated cells, cell proliferation (detected by expression of Ki-67, phospho-histone-H3, and cyclin D1) was increased and associated with activation of the AKT/mTOR survival pathway. Deletion of Pten caused papillary epithelial hyperplasia characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protruded into the airway lumens. Cell polarity, as assessed by subcellular localization of cadherin, beta-catenin, and zonula occludens-1, was unaltered. PTEN is required for regulation of epithelial cell proliferation in the lung and for the maintenance of the normal simple columnar epithelium characteristics of bronchi and bronchioles.

  12. Sequential computation of elementary modes and minimal cut sets in genome-scale metabolic networks using alternate integer linear programming

    Energy Technology Data Exchange (ETDEWEB)

    Song, Hyun-Seob; Goldberg, Noam; Mahajan, Ashutosh; Ramkrishna, Doraiswami

    2017-03-27

    Elementary (flux) modes (EMs) have served as a valuable tool for investigating structural and functional properties of metabolic networks. Identification of the full set of EMs in genome-scale networks remains challenging due to combinatorial explosion of EMs in complex networks. It is often, however, that only a small subset of relevant EMs needs to be known, for which optimization-based sequential computation is a useful alternative. Most of the currently available methods along this line are based on the iterative use of mixed integer linear programming (MILP), the effectiveness of which significantly deteriorates as the number of iterations builds up. To alleviate the computational burden associated with the MILP implementation, we here present a novel optimization algorithm termed alternate integer linear programming (AILP). Results: Our algorithm was designed to iteratively solve a pair of integer programming (IP) and linear programming (LP) to compute EMs in a sequential manner. In each step, the IP identifies a minimal subset of reactions, the deletion of which disables all previously identified EMs. Thus, a subsequent LP solution subject to this reaction deletion constraint becomes a distinct EM. In cases where no feasible LP solution is available, IP-derived reaction deletion sets represent minimal cut sets (MCSs). Despite the additional computation of MCSs, AILP achieved significant time reduction in computing EMs by orders of magnitude. The proposed AILP algorithm not only offers a computational advantage in the EM analysis of genome-scale networks, but also improves the understanding of the linkage between EMs and MCSs.

  13. Chromosomal deletion unmasking a recessive disease: 22q13 deletion syndrome and metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    Bisgaard, A-M; Kirchhoff, M; Nielsen, J E

    2008-01-01

    A deletion on one chromosome and a mutant allele on the other may cause an autosomal recessive disease. We report on two patients with mental retardation, dysmorphic features and low catalytic activity of arylsulfatase A. One patient had a pathogenic mutation in the arylsulfatase A gene (ARSA......) and succumbed to metachromatic leukodystrophy (MLD). The other patient had a pseudoallele, which does not lead to MLD. The presenting clinical features and low arylsulfatase A activity were explained, in each patients, by a deletion of 22q13 and, thereby, of one allele of ARSA....

  14. Ground-state transcriptional requirements for skin-derived precursors.

    Science.gov (United States)

    Suflita, Michael T; Pfaltzgraff, Elise R; Mundell, Nathan A; Pevny, Larysa H; Labosky, Patricia A

    2013-06-15

    Skin-derived precursors (SKPs) are an attractive stem cell model for cell-based therapies. SKPs can be readily generated from embryonic and adult mice and adult humans, exhibit a high degree of multipotency, and have the potential to serve as a patient autologous stem cell. The advancement of these cells toward therapeutic use depends on the ability to control precisely the self-renewal and differentiation of SKPs. Here we show that two well-known stem cell factors, Foxd3 and Sox2, are critical regulators of the stem cell properties of SKPs. Deletion of Foxd3 completely abolishes the sphere-forming potential of these cells. In the absence of Sox2, SKP spheres can be formed, but with reduced size and frequency. Our results provide entry points into the gene regulatory networks dictating SKP behavior, and pave the way for future studies on a therapeutically relevant stem cell.

  15. Sex-specific aspects of endogenous retroviral insertion and deletion.

    Science.gov (United States)

    Gemmell, Patrick; Hein, Jotun; Katzourakis, Aris

    2013-11-07

    We wish to understand how sex and recombination affect endogenous retroviral insertion and deletion. While theory suggests that the risk of ectopic recombination will limit the accumulation of repetitive DNA in areas of high meiotic recombination, the experimental evidence so far has been inconsistent. Under the assumption of neutrality, we examine the genomes of eighteen species of animal in order to compute the ratio of solo-LTRs that derive from insertions occurring down the male germ line as opposed to the female one (male bias). We also extend the simple idea of comparing autosome to allosome in order to predict the ratio of full-length proviruses we would expect to see under conditions of recombination linked deletion or otherwise. Using our model, we predict the ratio of allosomal to autosomal full-length proviruses to lie between32 and 23 under increasing male bias in mammals and between 1 and 2 under increasing male bias in birds. In contrast to our expectations, we find that a pattern of male bias is not universal across species and that there is a frequent overabundance of full-length proviruses on the allosome beyond the ratios predicted by our model. We use our data as a whole to argue that full-length proviruses should be treated as deleterious mutations or as effectively neutral mutations whose persistence in a full-length state is linked to the rate of meiotic recombination and whose origin is not universally male biased. These conclusions suggest that retroviral insertions on the allosome may be more prolific and that it might be possible to identify mechanisms of replication that are enhanced in the female sex.

  16. Writing and deleting single magnetic skyrmions.

    Science.gov (United States)

    Romming, Niklas; Hanneken, Christian; Menzel, Matthias; Bickel, Jessica E; Wolter, Boris; von Bergmann, Kirsten; Kubetzka, André; Wiesendanger, Roland

    2013-08-09

    Topologically nontrivial spin textures have recently been investigated for spintronic applications. Here, we report on an ultrathin magnetic film in which individual skyrmions can be written and deleted in a controlled fashion with local spin-polarized currents from a scanning tunneling microscope. An external magnetic field is used to tune the energy landscape, and the temperature is adjusted to prevent thermally activated switching between topologically distinct states. Switching rate and direction can then be controlled by the parameters used for current injection. The creation and annihilation of individual magnetic skyrmions demonstrates the potential for topological charge in future information-storage concepts.

  17. SNORD116 deletions cause Prader-Willi syndrome with a mild phenotype and macrocephaly.

    Science.gov (United States)

    Fontana, P; Grasso, M; Acquaviva, F; Gennaro, E; Galli, M L; Falco, M; Scarano, F; Scarano, G; Lonardo, F

    2017-10-01

    Prader-Willi syndrome is a complex condition caused by lack of expression of imprinted genes in the paternally derived region of chromosome 15 (15q11q13). A small number of patients with Prader-Willi phenotype have been discovered to have narrow deletions, not encompassing the whole critical region, but only the SNORD116 cluster, which includes genes codifying for small nucleolar RNAs. This kind of deletion usually is not detected by the classic DNA methylation analysis test. We present the case of a male patient with a mild Prader-Willi phenotype and a small deletion including SNORD116, diagnosed by methylation-sensitive multiplex ligation-dependent probe amplification (MLPA. The patient showed neonatal hypotonia, hyperphagia, obesity, central hypogonadism, hypothyroidism, strabismus. Stature and intellectual development are within the normal range. The presence of macrocephaly, observed in other cases of SNORD116 deletions as well, is uncommon for the classic phenotype of the syndrome. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Whole genome HBV deletion profiles and the accumulation of preS deletion mutant during antiviral treatment

    Science.gov (United States)

    2012-01-01

    Background Hepatitis B virus (HBV), because of its error-prone viral polymerase, has a high mutation rate leading to widespread substitutions, deletions, and insertions in the HBV genome. Deletions may significantly change viral biological features complicating the progression of liver diseases. However, the clinical conditions correlating to the accumulation of deleted mutants remain unclear. In this study, we explored HBV deletion patterns and their association with disease status and antiviral treatment by performing whole genome sequencing on samples from 51 hepatitis B patients and by monitoring changes in deletion variants during treatment. Clone sequencing was used to analyze preS regions in another cohort of 52 patients. Results Among the core, preS, and basic core promoter (BCP) deletion hotspots, we identified preS to have the highest frequency and the most complex deletion pattern using whole genome sequencing. Further clone sequencing analysis on preS identified 70 deletions which were classified into 4 types, the most common being preS2. Also, in contrast to the core and BCP regions, most preS deletions were in-frame. Most deletions interrupted viral surface epitopes, and are possibly involved in evading immuno-surveillance. Among various clinical factors examined, logistic regression showed that antiviral medication affected the accumulation of deletion mutants (OR = 6.81, 95% CI = 1.296 ~ 35.817, P = 0.023). In chronic carriers of the virus, and individuals with chronic hepatitis, the deletion rate was significantly higher in the antiviral treatment group (Fisher exact test, P = 0.007). Particularly, preS2 deletions were associated with the usage of nucleos(t)ide analog therapy (Fisher exact test, P = 0.023). Dynamic increases in preS1 or preS2 deletions were also observed in quasispecies from samples taken from patients before and after three months of ADV therapy. In vitro experiments demonstrated that preS2 deletions alone

  19. Selection Shapes Transcriptional Logic and Regulatory Specialization in Genetic Networks.

    Science.gov (United States)

    Fogelmark, Karl; Peterson, Carsten; Troein, Carl

    2016-01-01

    Living organisms need to regulate their gene expression in response to environmental signals and internal cues. This is a computational task where genes act as logic gates that connect to form transcriptional networks, which are shaped at all scales by evolution. Large-scale mutations such as gene duplications and deletions add and remove network components, whereas smaller mutations alter the connections between them. Selection determines what mutations are accepted, but its importance for shaping the resulting networks has been debated. To investigate the effects of selection in the shaping of transcriptional networks, we derive transcriptional logic from a combinatorially powerful yet tractable model of the binding between DNA and transcription factors. By evolving the resulting networks based on their ability to function as either a simple decision system or a circadian clock, we obtain information on the regulation and logic rules encoded in functional transcriptional networks. Comparisons are made between networks evolved for different functions, as well as with structurally equivalent but non-functional (neutrally evolved) networks, and predictions are validated against the transcriptional network of E. coli. We find that the logic rules governing gene expression depend on the function performed by the network. Unlike the decision systems, the circadian clocks show strong cooperative binding and negative regulation, which achieves tight temporal control of gene expression. Furthermore, we find that transcription factors act preferentially as either activators or repressors, both when binding multiple sites for a single target gene and globally in the transcriptional networks. This separation into positive and negative regulators requires gene duplications, which highlights the interplay between mutation and selection in shaping the transcriptional networks.

  20. Deletion of ultraconserved elements yields viable mice

    Energy Technology Data Exchange (ETDEWEB)

    Ahituv, Nadav; Zhu, Yiwen; Visel, Axel; Holt, Amy; Afzal, Veena; Pennacchio, Len A.; Rubin, Edward M.

    2007-07-15

    Ultraconserved elements have been suggested to retainextended perfect sequence identity between the human, mouse, and ratgenomes due to essential functional properties. To investigate thenecessities of these elements in vivo, we removed four non-codingultraconserved elements (ranging in length from 222 to 731 base pairs)from the mouse genome. To maximize the likelihood of observing aphenotype, we chose to delete elements that function as enhancers in amouse transgenic assay and that are near genes that exhibit markedphenotypes both when completely inactivated in the mouse as well as whentheir expression is altered due to other genomic modifications.Remarkably, all four resulting lines of mice lacking these ultraconservedelements were viable and fertile, and failed to reveal any criticalabnormalities when assayed for a variety of phenotypes including growth,longevity, pathology and metabolism. In addition more targeted screens,informed by the abnormalities observed in mice where genes in proximityto the investigated elements had been altered, also failed to revealnotable abnormalities. These results, while not inclusive of all thepossible phenotypic impact of the deleted sequences, indicate thatextreme sequence constraint does not necessarily reflect crucialfunctions required for viability.

  1. Method for introducing unidirectional nested deletions

    Science.gov (United States)

    Dunn, J.J.; Quesada, M.A.; Randesi, M.

    1999-07-27

    Disclosed is a method for the introduction of unidirectional deletions in a cloned DNA segment. More specifically, the method comprises providing a recombinant DNA construct comprising a DNA segment of interest inserted in a cloning vector. The cloning vector has an f1 endonuclease recognition sequence adjacent to the insertion site of the DNA segment of interest. The recombinant DNA construct is then contacted with the protein pII encoded by gene II of phage f1 thereby generating a single-stranded nick. The nicked DNA is then contacted with E. coli Exonuclease III thereby expanding the single-stranded nick into a single-stranded gap. The single-stranded gapped DNA is then contacted with a single-strand-specific endonuclease thereby producing a linearized DNA molecule containing a double-stranded deletion corresponding in size to the single-stranded gap. The DNA treated in this manner is then incubated with DNA ligase under conditions appropriate for ligation. Also disclosed is a method for producing single-stranded DNA probes. In this embodiment, single-stranded gapped DNA, produced as described above, is contacted with a DNA polymerase in the presence of labeled nucleotides to fill in the gap. This DNA is then linearized by digestion with a restriction enzyme which cuts outside the DNA segment of interest. The product of this digestion is then denatured to produce a labeled single-stranded nucleic acid probe. 1 fig.

  2. Rare human diseases: 9p deletion syndrome

    Directory of Open Access Journals (Sweden)

    Galagan V.O.

    2014-09-01

    Full Text Available Objective of the study was to review the anamnesis, pheno - and genotype in patients with rare chromosome disorders such as 9p deletion syndrome. Genetic methods of investigation (clinical and genealogical, cytogenetic, FISH- method, paraclinical and instrumental methods of examination were used. Karyotyping was performed by the G-method of differential staining of chromosomes. Only three cases of pathology were diagnosed in the Medical Genetics Center over the last 10 years. By anamnesis data nobody in the probands’ families had bad habits, was exposed to occupational hazards, took part in the elimination of the Chernobyl accident or lived in contaminated areas. Clinical signs of diseases have not been identified in probands’ parents. All probands had trigonocephaly, bilateral epicanthal folds, ocular hypertelorism, downslanting palpebral fissures, long philtrum, flat face and nasal bridge, low set ears with malformed auricles. Two patients of three ones had exophthalmos, contracture of the second and third fingers, abnormal external genitalia. In all three cases there was monosomy of chromosome 9 of critical segment p 24. Normal karyotypes were seen in all parents, so there were three cases of new mutations of 9p deletion syndrome. Retardation of physical, psycho-spech, mental development in proband with or without congenital anomalies requires medical genetic counseling in a specialized institution. Cases of reproductive loss in anamnesis require cytogenetic investigation of fetal membranes and amniotic fluid.

  3. Are there ethnic differences in deletions in the dystrophin gene?

    Energy Technology Data Exchange (ETDEWEB)

    Banerjee, M.; Verma, I.C. [All India Inst. of Medical Sciences, New Delhi (India)

    1997-01-20

    We studied 160 cases of Duchenne muscular dystrophy (DMD) drawn from all parts of India, using multiplex PCR of 27 exons. Of these, 103 (64.4%) showed intragenic deletions. Most (69.7%) of the deletions involved exons 45-51. The phenotype of cases with deletion of single exons did not differ significantly from those with deletion of multiple exons. The distribution of deletions in studies from different countries was variable, but this was accounted for either by the small number of cases studied, or by fewer exons analyzed. It is concluded that there is likely to be no ethnic difference with respect to deletions in the DMD gene. 38 refs., 2 figs., 3 tabs.

  4. Panchromatic cooperative hyperspectral adaptive wide band deletion repair method

    Science.gov (United States)

    Jiang, Bitao; Shi, Chunyu

    2018-02-01

    In the hyperspectral data, the phenomenon of stripe deletion often occurs, which seriously affects the efficiency and accuracy of data analysis and application. Narrow band deletion can be directly repaired by interpolation, and this method is not ideal for wide band deletion repair. In this paper, an adaptive spectral wide band missing restoration method based on panchromatic information is proposed, and the effectiveness of the algorithm is verified by experiments.

  5. NPL deletion policy for RCRA-regulated TSD facilities finalized

    International Nuclear Information System (INIS)

    Anon.

    1995-01-01

    Under a new policy published by EPA on March 20, 1995, certain sites may be deleted from the National Priorities List (NPL) and deferred to RCRA corrective action. To be deleted from the NPL, a site must (1) be regulated under RCRA as a treatment, storage, or disposal (TSD) facility and (2) meet the four criteria specified by EPA. The new NPL deletion policy, which does not pertain to federal TSD facilities, became effective on April 19, 1995. 1 tab

  6. Clival encephalocele and 5q15 deletion: a case report.

    Science.gov (United States)

    Puvabanditsin, Surasak; Malik, Imran; Garrow, Eugene; Francois, Lissa; Mehta, Rajeev

    2015-03-01

    A preterm neonate presenting with respiratory distress after birth was found to have a clival encephalocele, which is a variant of a basal encephalocele, and hypoplasia of the cerebellum. Genetic studies revealed a small deletion of the long arm of chromosome 5: 5q15 deletion. We report a rare variant of a basal encephalocele with a cerebellar malformation and 5q15 deletion. © The Author(s) 2014.

  7. Male gametophytic sterility. 1 - Gametic sterilities and deletions in petunia

    Energy Technology Data Exchange (ETDEWEB)

    Cornu, A.; Maizonnier, D. (Station d' Amelioration des Plantes de l' I.N.R.A., Dijon (France))

    1982-01-01

    Terminal deletions induced by ionizing radiations in Petunia are not sexually transmitted. Cytogenetic study of plants with a heterozygous deletion and their progenies shows that this lack of transmission is accompanied by a gametic semi-sterility due to the fact that gametes carrying the deleted chromosome are not viable. The interest of such a male sterility with a gametophytic determinism for the study of sporophyte-gametophyte relationships is underlined.

  8. HOXA genes cluster: clinical implications of the smallest deletion

    OpenAIRE

    Pezzani, Lidia; Milani, Donatella; Manzoni, Francesca; Baccarin, Marco; Silipigni, Rosamaria; Guerneri, Silvana; Esposito, Susanna

    2015-01-01

    Background HOXA genes cluster plays a fundamental role in embryologic development. Deletion of the entire cluster is known to cause a clinically recognizable syndrome with mild developmental delay, characteristic facies, small feet with unusually short and big halluces, abnormal thumbs, and urogenital malformations. The clinical manifestations may vary with different ranges of deletions of HOXA cluster and flanking regions. Case presentation We report a girl with the smallest deletion reporte...

  9. A Comparative Study of Quantum and Classical Deletion

    International Nuclear Information System (INIS)

    Shen Yao; Hao Liang; Long Guilu

    2010-01-01

    Here in this letter, we study the difference between quantum and classical deletion. We point out that the linear mapping deletion operation used in the impossibility proof for quantum systems applies also to classical system. The general classical deletion operation is a combined operation of measurement and transformation, i.e., first read the state and then transfer the state to the standard blank state. Though both quantum information and classical information can be deleted in an open system, quantum information cannot be recovered while classical information can be recovered. (general)

  10. Comprehensive analysis of pathogenic deletion variants in Fanconi anemia genes.

    Science.gov (United States)

    Flynn, Elizabeth K; Kamat, Aparna; Lach, Francis P; Donovan, Frank X; Kimble, Danielle C; Narisu, Narisu; Sanborn, Erica; Boulad, Farid; Davies, Stella M; Gillio, Alfred P; Harris, Richard E; MacMillan, Margaret L; Wagner, John E; Smogorzewska, Agata; Auerbach, Arleen D; Ostrander, Elaine A; Chandrasekharappa, Settara C

    2014-11-01

    Fanconi anemia (FA) is a rare recessive disease resulting from mutations in one of at least 16 different genes. Mutation types and phenotypic manifestations of FA are highly heterogeneous and influence the clinical management of the disease. We analyzed 202 FA families for large deletions, using high-resolution comparative genome hybridization arrays, single-nucleotide polymorphism arrays, and DNA sequencing. We found pathogenic deletions in 88 FANCA, seven FANCC, two FANCD2, and one FANCB families. We find 35% of FA families carry large deletions, accounting for 18% of all FA pathogenic variants. Cloning and sequencing across the deletion breakpoints revealed that 52 FANCA deletion ends, and one FANCC deletion end extended beyond the gene boundaries, potentially affecting neighboring genes with phenotypic consequences. Seventy-five percent of the FANCA deletions are Alu-Alu mediated, predominantly by AluY elements, and appear to be caused by nonallelic homologous recombination. Individual Alu hotspots were identified. Defining the haplotypes of four FANCA deletions shared by multiple families revealed that three share a common ancestry. Knowing the exact molecular changes that lead to the disease may be critical for a better understanding of the FA phenotype, and to gain insight into the mechanisms driving these pathogenic deletion variants. © 2014 WILEY PERIODICALS, INC.

  11. 75 FR 1355 - Procurement List Additions and Deletions

    Science.gov (United States)

    2010-01-11

    .../Location: Janitorial Services, Jamestown Service Center, 8430 Country Club Street, Jamestown, ND. NPA..., the following products and services are deleted from the Procurement List: Products Business Cards NSN...

  12. Architecture of a corporate system to aid the scheduling of a oil derivatives transport in a pipeline network; Arquitetura de um sistema corporativo para auxilio a programacao do transporte de derivados de petroleo em redes dutoviarias

    Energy Technology Data Exchange (ETDEWEB)

    Lara, Guilherme R.; Polli, Helton L.; Esser, Eduardo M.; Lueders, Ricardo; Neves Junior, Flavio; Magatao, Leandro; Stebel, Sergio L. [Universidade Tecnologica Federal do Parana (UTFPR), Curitiba, PR (Brazil); Ribas, Paulo C. [PETROBRAS S.A., Rio de Janeiro, RJ (Brazil). Centro de Pesquisas (CENPES)

    2008-07-01

    This paper addresses the development and the architecture of a corporative package to aid the operational decision-making of the scheduling activities in a real-world pipeline network for oil derivatives. The system was developed based on a service-oriented architecture, allowing the development of Web applications to define the network scheduling, as well as graphic display of the movements. The solution of the scheduling is generated by an optimization block as a service of this application. However, this paper emphasizes the description of the architecture and its functionalities, which was defined with the help of experienced programmers. (author)

  13. Klf5 deletion promotes Pten deletion-initiated luminal-type mouse prostate tumors through multiple oncogenic signaling pathways.

    Science.gov (United States)

    Xing, Changsheng; Ci, Xinpei; Sun, Xiaodong; Fu, Xiaoying; Zhang, Zhiqian; Dong, Eric N; Hao, Zhao-Zhe; Dong, Jin-Tang

    2014-11-01

    Krüppel-like factor 5 (KLF5) regulates multiple biologic processes. Its function in tumorigenesis appears contradictory though, showing both tumor suppressor and tumor promoting activities. In this study, we examined whether and how Klf5 functions in prostatic tumorigenesis using mice with prostate-specific deletion of Klf5 and phosphatase and tensin homolog (Pten), both of which are frequently inactivated in human prostate cancer. Histologic analysis demonstrated that when one Pten allele was deleted, which causes mouse prostatic intraepithelial neoplasia (mPIN), Klf5 deletion accelerated the emergence and progression of mPIN. When both Pten alleles were deleted, which causes prostate cancer, Klf5 deletion promoted tumor growth, increased cell proliferation, and caused more severe morphologic and molecular alterations. Homozygous deletion of Klf5 was more effective than hemizygous deletion. Unexpectedly, while Pten deletion alone expanded basal cell population in a tumor as reported, Klf5 deletion in the Pten-null background clearly reduced basal cell population while expanding luminal cell population. Global gene expression profiling, pathway analysis, and experimental validation indicate that multiple mechanisms could mediate the tumor-promoting effect of Klf5 deletion, including the up-regulation of epidermal growth factor and its downstream signaling molecules AKT and ERK and the inactivation of the p15 cell cycle inhibitor. KLF5 also appears to cooperate with several transcription factors, including CREB1, Sp1, Myc, ER and AR, to regulate gene expression. These findings validate the tumor suppressor function of KLF5. They also yield a mouse model that shares two common genetic alterations with human prostate cancer-mutation/deletion of Pten and deletion of Klf5.

  14. Adaptation to diverse nitrogen-limited environments by deletion or extrachromosomal element formation of the GAP1 locus

    DEFF Research Database (Denmark)

    Gresham, D.; Usaite, Renata; Germann, S.M.

    2010-01-01

    and deletions at the GAP1 locus. GAP1 encodes the general amino acid permease, which transports amino acids across the plasma membrane. We identified a self-propagating extrachromosomal circular DNA molecule that results from intrachromosomal recombination between long terminal repeats (LTRs) flanking GAP1....... Extrachromosomal DNA circles (GAP1(circle)) contain GAP1, the replication origin ARS1116, and a single hybrid LTR derived from recombination between the two flanking LTRs. Formation of the GAP1(circle) is associated with deletion of chromosomal GAP1 (gap1 Delta) and production of a single hybrid LTR at the GAP1...

  15. Network science

    CERN Document Server

    Barabasi, Albert-Laszlo

    2016-01-01

    Networks are everywhere, from the Internet, to social networks, and the genetic networks that determine our biological existence. Illustrated throughout in full colour, this pioneering textbook, spanning a wide range of topics from physics to computer science, engineering, economics and the social sciences, introduces network science to an interdisciplinary audience. From the origins of the six degrees of separation to explaining why networks are robust to random failures, the author explores how viruses like Ebola and H1N1 spread, and why it is that our friends have more friends than we do. Using numerous real-world examples, this innovatively designed text includes clear delineation between undergraduate and graduate level material. The mathematical formulas and derivations are included within Advanced Topics sections, enabling use at a range of levels. Extensive online resources, including films and software for network analysis, make this a multifaceted companion for anyone with an interest in network sci...

  16. Bottlenecks and Hubs in Inferred Networks Are Important for Virulence in Salmonella typhimurium

    Energy Technology Data Exchange (ETDEWEB)

    McDermott, Jason E.; Taylor, Ronald C.; Yoon, Hyunjin; Heffron, Fred

    2009-02-01

    Recent advances in experimental methods have provided sufficient data to consider systems as large networks of interconnected components. High-throughput determination of protein-protein interaction networks has led to the observation that topological bottlenecks, that is proteins defined by high centrality in the network, are enriched in proteins with systems-level phenotypes such as essentiality. Global transcriptional profiling by microarray analysis has been used extensively to characterize systems, for example, cellular response to environmental conditions and genetic mutations. These transcriptomic datasets have been used to infer regulatory and functional relationship networks based on co-regulation. We use the context likelihood of relatedness (CLR) method to infer networks from two datasets gathered from the pathogen Salmonella typhimurium; one under a range of environmental culture conditions and the other from deletions of 15 regulators found to be essential in virulence. Bottleneck nodes were identified from these inferred networks and we show that these nodes are significantly more likely to be essential for virulence than their non-bottleneck counterparts. A network generated using Pearson correlation did not display this behavior. Overall this study demonstrates that topology of networks inferred from global transcriptional profiles provides information about the systems-level roles of bottleneck genes. Analysis of the differences between the two CLR-derived networks suggests that the bottleneck nodes are either mediators of transitions between system states or sentinels that reflect the dynamics of these transitions.

  17. Brand deletion: How the decision-making approach affects deletion success

    Directory of Open Access Journals (Sweden)

    Víctor Temprano-García

    2018-04-01

    Full Text Available Literature on brand deletion (BD, a critical and topical decision within a firm's marketing strategy, is extremely scarce. The present research is concerned with the decision-making process and examines the effect on BD success of three different approaches to decision-making – rational, intuitive and political – and of the interaction between the rational and political approaches. The moderating effect of the type of BD – i.e., total brand killing or disposal vs. brand name change – is also analyzed. The model is tested on a sample of 155 cases of BD. Results point to positive effects on BD success of both rationality and intuition, and a negative effect of politics. Findings also indicate that the negative impact of political behavior on BD success is minimized in the absence of evidence and objective information and when the BD is undertaken through a brand name change. JEL classification: L10, M31, Keywords: Brand deletion, Rational decision-making, Intuitive decision-making, Political decision-making, Brand deletion success

  18. Phosphatase and tensin homologue deleted on chromosome 10 ...

    African Journals Online (AJOL)

    Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) is a tumor suppressor gene deleted or mutated in many human cancers such as glioblastoma, spinal tumors, prostate, bladder, adrenals, thyroid, breast, endometrium, and colon cancers. They result from loss of heterozygosity (LOH) for the PTEN ...

  19. Generalised deletion designs | Gachii | African Journal of Science ...

    African Journals Online (AJOL)

    In this paper asymmetrical single replicate factorial designs are constructed from symmetrical single replicate factorial designs using the deletion technique. The study is along the lines of Voss(1986), Chauhan(1989) and Gachii and Odhiambo(1997). We give results for the general order deletion designs of the form sn-m1(s ...

  20. 24 CFR 990.155 - Addition and deletion of units.

    Science.gov (United States)

    2010-04-01

    ... 24 Housing and Urban Development 4 2010-04-01 2010-04-01 false Addition and deletion of units. 990.155 Section 990.155 Housing and Urban Development Regulations Relating to Housing and Urban...; Computation of Eligible Unit Months § 990.155 Addition and deletion of units. (a) Changes in public housing...

  1. 4977-bp mitochondrial DNA deletion in infertile patients with varicocele.

    Science.gov (United States)

    Gashti, N G; Salehi, Z; Madani, A H; Dalivandan, S T

    2014-04-01

    Varicocele is the abnormal inflexion and distension of veins of the pampiniform plexus within spermatic cord and is one of the amendable causes of male infertility. It can increase reactive oxygen species (ROS) production in semen and cause oxidative stress. The purpose of this study was to analyse spermatozoa mtDNA 4977-bp deletion in infertile men with varicocele. To detect 4977-bp deletion in spermatozoa mtDNA, semen samples of 60 infertile patients with clinical varicocele and 90 normal men from northern Iran were prepared. After extraction of spermatozoa total DNA, Gap polymerase chain reaction (Gap PCR) was performed. 4977-bp deletion was observed in 81.66% of patients with varicocele, while approximately 15.55% of controls had this deletion. As spermatozoa from patients with varicocele had a high frequency of occurrence of 4977-bp deletion in mtDNA [OR = 24.18, 95% confidence interval (CI) = 10.15-57.57, P deletion in spermatozoa and cause infertility in north Iranian men. However, to determine the relation between sperm mtDNA 4977-bp deletion and varicocele-induced infertility, larger population-based studies are needed. It is concluded that there is an association between sperm mtDNA 4977-bp deletion and varicocele-induced infertility in the population studied. © 2013 Blackwell Verlag GmbH.

  2. 34 CFR 5.16 - Deletion of identifying details.

    Science.gov (United States)

    2010-07-01

    ... 34 Education 1 2010-07-01 2010-07-01 false Deletion of identifying details. 5.16 Section 5.16 Education Office of the Secretary, Department of Education AVAILABILITY OF INFORMATION TO THE PUBLIC PURSUANT TO PUB. L. 90-23 (Eff. until 7-14-10) What Records Are Available § 5.16 Deletion of identifying...

  3. 42 CFR 401.118 - Deletion of identifying details.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Deletion of identifying details. 401.118 Section 401.118 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN... Deletion of identifying details. When CMS publishes or otherwise makes available an opinion or order...

  4. Coexistence of 9p Deletion Syndrome and Autism Spectrum Disorder

    Science.gov (United States)

    Günes, Serkan; Ekinci, Özalp; Ekinci, Nuran; Toros, Fevziye

    2017-01-01

    Deletion or duplication of the short arm of chromosome 9 may lead to a variety of clinical conditions including craniofacial and limb abnormalities, skeletal malformations, mental retardation, and autism spectrum disorder. Here, we present a case report of 5-year-old boy with 9p deletion syndrome and autism spectrum disorder.

  5. Linguistic and Psychomotor Development in Children with Chromosome 14 Deletions

    Science.gov (United States)

    Zampini, Laura; D'Odorico, Laura; Zanchi, Paola; Zollino, Marcella; Neri, Giovanni

    2012-01-01

    The present study focussed on a specific type of rare genetic condition: chromosome 14 deletions. Children with this genetic condition often show developmental delays and brain and neurological problems, although the type and severity of symptoms varies depending on the size and location of the deleted genetic material. The specific aim of the…

  6. 76 FR 78248 - Procurement List; Addition and Deletions

    Science.gov (United States)

    2011-12-16

    .... Service Type/Location: Laundry Service, Stratton Medical Center, 113 Holland Ave, Albany, NY. [[Page 78249...: Addition to and Deletions from the Procurement List. SUMMARY: This action adds a service to the Procurement... disabilities, and deletes products and services from the Procurement List previously furnished by such agencies...

  7. 75 FR 49481 - Procurement List; Additions and Deletion

    Science.gov (United States)

    2010-08-13

    ... added to the Procurement List: Services Service Type/Locations: Laundry Service, Atlanta VA Medical...: Additions to and deletion from the Procurement List. SUMMARY: This action adds services to the Procurement... disabilities and deletes a service from the Procurement List previously furnished by such agency. DATES...

  8. 78 FR 21916 - Procurement List; Addition And Deletions

    Science.gov (United States)

    2013-04-12

    ..., the following service is added to the Procurement List: Service Service Type/Location: Laundry Service...: Addition to and Deletions from the Procurement List. SUMMARY: This action adds a service to the Procurement... disabilities, and deletes products and services from the Procurement List previously furnished by such agencies...

  9. 78 FR 53733 - Procurement List Additions and Deletions

    Science.gov (United States)

    2013-08-30

    .../Location: Industrial Laundry Service, Bureau of Engraving and Printing, 9000 Blue Mound Road, Fort Worth...: Additions to and Deletions from the Procurement List. SUMMARY: This action adds products and services to the... severe disabilities, and deletes services from the Procurement List previously provided by such agencies...

  10. Recurrence and Variability of Germline EPCAM Deletions in Lynch Syndrome

    NARCIS (Netherlands)

    Kuiper, Roland P.; Vissers, Lisenka E. L. M.; Venkatachalam, Ramprasath; Bodmer, Danielle; Hoenselaar, Eveline; Goossens, Monique; Haufe, Aline; Kamping, Eveline; Niessen, Renee C.; Hogervorst, Frans B. L.; Gille, Johan J. P.; Redeker, Bert; Tops, Carli M. J.; van Gijn, Marielle E.; van den Ouweland, Ans M. W.; Rahner, Nils; Steinke, Verena; Kahl, Philip; Holinski-Feder, Elke; Morak, Monika; Kloor, Matthias; Stemmler, Susanne; Betz, Beate; Hutter, Pierre; Bunyan, David J.; Syngal, Sapna; Culver, Julie O.; Graham, Tracy; Chan, Tsun L.; Nagtegaal, Iris D.; van Krieken, J. Han J. M.; Schackert, Hans K.; Hoogerbrugge, Nicoline; van Kessel, Ad Geurts; Ligtenberg, Marjolijn J. L.

    Recently, we identified 3' end deletions in the EPCAM gene as a novel cause of Lynch syndrome. These truncating EPCAM deletions cause allele-specific epigenetic silencing of the neighboring DNA mismatch repair gene MSH2 in tissues expressing EPCAM. Here we screened a cohort of unexplained Lynch-like

  11. SLUG (SNAI2) deletions in patients with Waardenburg disease.

    Science.gov (United States)

    Sánchez-Martín, Manuel; Rodríguez-García, Arancha; Pérez-Losada, Jesús; Sagrera, Ana; Read, Andrew P; Sánchez-García, Isidro

    2002-12-01

    Waardenburg syndrome (WS; deafness with pigmentary abnormalities) is a congenital disorder caused by defective function of the embryonic neural crest. Depending on additional symptoms, WS is classified into four types: WS1, WS2, WS3 and WS4. WS1 and WS3 are caused by mutations in PAX3, whereas WS2 is heterogenous, being caused by mutations in the microphthalmia (MITF) gene in some but not all affected families. The identification of Slugh, a zinc-finger transcription factor expressed in migratory neural crest cells, as the gene responsible for pigmentary disturbances in mice prompted us to analyse the role of its human homologue SLUG in neural crest defects. Here we show that two unrelated patients with WS2 have homozygous deletions in SLUG which result in absence of the SLUG product. We further show that Mitf is present in Slug-deficient cells and transactivates the SLUG promoter, and that Slugh and Kit genetically interact in vivo. Our findings further define the locus heterogeneity of WS2 and point to an essential role of SLUG in the development of neural crest-derived human cell lineages: its absence causes the auditory-pigmentary symptoms in at least some individuals with WS2.

  12. Attenuation of monkeypox virus by deletion of genomic regions

    Science.gov (United States)

    Lopera, Juan G.; Falendysz, Elizabeth A.; Rocke, Tonie E.; Osorio, Jorge E.

    2015-01-01

    Monkeypox virus (MPXV) is an emerging pathogen from Africa that causes disease similar to smallpox. Two clades with different geographic distributions and virulence have been described. Here, we utilized bioinformatic tools to identify genomic regions in MPXV containing multiple virulence genes and explored their roles in pathogenicity; two selected regions were then deleted singularly or in combination. In vitro and in vivostudies indicated that these regions play a significant role in MPXV replication, tissue spread, and mortality in mice. Interestingly, while deletion of either region led to decreased virulence in mice, one region had no effect on in vitro replication. Deletion of both regions simultaneously also reduced cell culture replication and significantly increased the attenuation in vivo over either single deletion. Attenuated MPXV with genomic deletions present a safe and efficacious tool in the study of MPX pathogenesis and in the identification of genetic factors associated with virulence.

  13. Role of DNA deletion length in mutation and cell survival

    International Nuclear Information System (INIS)

    Braby, L.A.; Morgan, T.L.

    1992-01-01

    A model is presented which is based on the assumption that malignant transformation, mutation, chromosome aberration, and reproductive death of cells are all manifestations of radiation induced deletions in the DNA of the cell, and that the size of the deletion in relation to the spacing of essential genes determines the consequences of that deletion. It is assumed that two independent types of potentially lethal lesions can result in DNA deletions, and that the relative numbers of these types of damage is dependent on radiation quality. The repair of the damage reduces the length of a deletion, but does not always eliminate it. The predictions of this model are in good agreement with a wide variety of experimental evidence. (author)

  14. Ku80-deleted cells are defective at base excision repair

    International Nuclear Information System (INIS)

    Li, Han; Marple, Teresa; Hasty, Paul

    2013-01-01

    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H 2 O 2 and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs

  15. Ku80-deleted cells are defective at base excision repair

    Energy Technology Data Exchange (ETDEWEB)

    Li, Han [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain); Marple, Teresa [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Hasty, Paul, E-mail: hastye@uthscsa.edu [The University of Texas Health Science Center at San Antonio, The Institute of Biotechnology, The Department of Molecular Medicine, 15355 Lambda Drive, San Antonio, TX 78245-3207 (United States); Tumor Suppression Group, Spanish National Cancer Research Centre (CNIO), Madrid 28029 (Spain)

    2013-05-15

    Graphical abstract: - Highlights: • Ku80-deleted cells are hypersensitive to ROS and alkylating agents. • Cells deleted for Ku80, but not Ku70 or Lig4, have reduced BER capacity. • OGG1 rescues hypersensitivity to H{sub 2}O{sub 2} and paraquat in Ku80-mutant cells. • Cells deleted for Ku80, but not Lig4, are defective at repairing AP sites. • Cells deleted for Ku80, but not Lig4 or Brca2 exon 27, exhibit increased PAR. - Abstract: Ku80 forms a heterodimer with Ku70, called Ku, that repairs DNA double-strand breaks (DSBs) via the nonhomologous end joining (NHEJ) pathway. As a consequence of deleting NHEJ, Ku80-mutant cells are hypersensitive to agents that cause DNA DSBs like ionizing radiation. Here we show that Ku80 deletion also decreased resistance to ROS and alkylating agents that typically cause base lesions and single-strand breaks (SSBs). This is unusual since base excision repair (BER), not NHEJ, typically repairs these types of lesions. However, we show that deletion of another NHEJ protein, DNA ligase IV (Lig4), did not cause hypersensitivity to these agents. In addition, the ROS and alkylating agents did not induce γ-H2AX foci that are diagnostic of DSBs. Furthermore, deletion of Ku80, but not Lig4 or Ku70, reduced BER capacity. Ku80 deletion also impaired BER at the initial lesion recognition/strand scission step; thus, involvement of a DSB is unlikely. Therefore, our data suggests that Ku80 deletion impairs BER via a mechanism that does not repair DSBs.

  16. Pathological mechanisms underlying single large‐scale mitochondrial DNA deletions

    Science.gov (United States)

    Rocha, Mariana C.; Rosa, Hannah S.; Grady, John P.; Blakely, Emma L.; He, Langping; Romain, Nadine; Haller, Ronald G.; Newman, Jane; McFarland, Robert; Ng, Yi Shiau; Gorman, Grainne S.; Schaefer, Andrew M.; Tuppen, Helen A.; Taylor, Robert W.

    2018-01-01

    Objective Single, large‐scale deletions in mitochondrial DNA (mtDNA) are a common cause of mitochondrial disease. This study aimed to investigate the relationship between the genetic defect and molecular phenotype to improve understanding of pathogenic mechanisms associated with single, large‐scale mtDNA deletions in skeletal muscle. Methods We investigated 23 muscle biopsies taken from adult patients (6 males/17 females with a mean age of 43 years) with characterized single, large‐scale mtDNA deletions. Mitochondrial respiratory chain deficiency in skeletal muscle biopsies was quantified by immunoreactivity levels for complex I and complex IV proteins. Single muscle fibers with varying degrees of deficiency were selected from 6 patient biopsies for determination of mtDNA deletion level and copy number by quantitative polymerase chain reaction. Results We have defined 3 “classes” of single, large‐scale deletion with distinct patterns of mitochondrial deficiency, determined by the size and location of the deletion. Single fiber analyses showed that fibers with greater respiratory chain deficiency harbored higher levels of mtDNA deletion with an increase in total mtDNA copy number. For the first time, we have demonstrated that threshold levels for complex I and complex IV deficiency differ based on deletion class. Interpretation Combining genetic and immunofluorescent assays, we conclude that thresholds for complex I and complex IV deficiency are modulated by the deletion of complex‐specific protein‐encoding genes. Furthermore, removal of mt‐tRNA genes impacts specific complexes only at high deletion levels, when complex‐specific protein‐encoding genes remain. These novel findings provide valuable insight into the pathogenic mechanisms associated with these mutations. Ann Neurol 2018;83:115–130 PMID:29283441

  17. Detection of genomic deletions in rice using oligonucleotide microarrays

    Directory of Open Access Journals (Sweden)

    Bordeos Alicia

    2009-03-01

    Full Text Available Abstract Background The induction of genomic deletions by physical- or chemical- agents is an easy and inexpensive means to generate a genome-saturating collection of mutations. Different mutagens can be selected to ensure a mutant collection with a range of deletion sizes. This would allow identification of mutations in single genes or, alternatively, a deleted group of genes that might collectively govern a trait (e.g., quantitative trait loci, QTL. However, deletion mutants have not been widely used in functional genomics, because the mutated genes are not tagged and therefore, difficult to identify. Here, we present a microarray-based approach to identify deleted genomic regions in rice mutants selected from a large collection generated by gamma ray or fast neutron treatment. Our study focuses not only on the utility of this method for forward genetics, but also its potential as a reverse genetics tool through accumulation of hybridization data for a collection of deletion mutants harboring multiple genetic lesions. Results We demonstrate that hybridization of labeled genomic DNA directly onto the Affymetrix Rice GeneChip® allows rapid localization of deleted regions in rice mutants. Deletions ranged in size from one gene model to ~500 kb and were predicted on all 12 rice chromosomes. The utility of the technique as a tool in forward genetics was demonstrated in combination with an allelic series of mutants to rapidly narrow the genomic region, and eventually identify a candidate gene responsible for a lesion mimic phenotype. Finally, the positions of mutations in 14 mutants were aligned onto the rice pseudomolecules in a user-friendly genome browser to allow for rapid identification of untagged mutations http://irfgc.irri.org/cgi-bin/gbrowse/IR64_deletion_mutants/. Conclusion We demonstrate the utility of oligonucleotide arrays to discover deleted genes in rice. The density and distribution of deletions suggests the feasibility of a

  18. Transcriptional response to deletion of the phosphatidylserine decarboxylase Psd1p in the yeast Saccharomyces cerevisiae.

    Science.gov (United States)

    Gsell, Martina; Mascher, Gerald; Schuiki, Irmgard; Ploier, Birgit; Hrastnik, Claudia; Daum, Günther

    2013-01-01

    In the yeast, Saccharomyces cerevisiae, the synthesis of the essential phospholipid phosphatidylethanolamine (PE) is accomplished by a network of reactions which comprises four different pathways. The enzyme contributing most to PE formation is the mitochondrial phosphatidylserine decarboxylase 1 (Psd1p) which catalyzes conversion of phosphatidylserine (PS) to PE. To study the genome wide effect of an unbalanced cellular and mitochondrial PE level and in particular the contribution of Psd1p to this depletion we performed a DNA microarray analysis with a ∆psd1 deletion mutant. This approach revealed that 54 yeast genes were significantly up-regulated in the absence of PSD1 compared to wild type. Surprisingly, marked down-regulation of genes was not observed. A number of different cellular processes in different subcellular compartments were affected in a ∆psd1 mutant. Deletion mutants bearing defects in all 54 candidate genes, respectively, were analyzed for their growth phenotype and their phospholipid profile. Only three mutants, namely ∆gpm2, ∆gph1 and ∆rsb1, were affected in one of these parameters. The possible link of these mutations to PE deficiency and PSD1 deletion is discussed.

  19. A High-Performance Recycling Solution for Polystyrene Achieved by the Synthesis of Renewable Poly(thioether) Networks Derived from d-Limonene

    Science.gov (United States)

    Nash, Landon D.; Rodriguez, Jennifer N.; Lonnecker, Alexander T.; Raymond, Jeffery E.; Wilson, Thomas S.; Wooley, Karen L.; Maitland, Duncan J.

    2014-01-01

    Nanocomposite polymers have been prepared using a new sustainable materials synthesis process in which d-Limonene functions simultaneously both as a solvent for recycling polystyrene (PS) waste and as a monomer that undergoes UV-catalyzed thiol-ene polymerization reactions with polythiol co-monomers to afford polymeric products comprised of precipitated PS phases dispersed throughout elastomeric poly(thioether) networks. These blended networks exhibit mechanical properties that greatly exceed those of either polystyrene or the poly(thioether) network homopolymers alone. PMID:24249666

  20. Metabolic responses to pyruvate kinase deletion in lysine producing Corynebacterium glutamicum

    Directory of Open Access Journals (Sweden)

    Wittmann Christoph

    2008-03-01

    flux analysis performed illustrates the high flexibility of the metabolic network of C. glutamicum to compensate for external perturbation. The organism could almost maintain its growth and production performance through a local redirection of the metabolic flux, thereby fulfilling all anabolic and catabolic needs. The formation of the undesired overflow metabolites dihydroxyacetone and glycerol, in the deletion mutant, however, indicates a limiting capacity of the metabolism down-stream of their common precursor glyceraldehyde 3-phosphate and opens possibilities for further strain engineering.

  1. Tau deletion promotes brain insulin resistance.

    Science.gov (United States)

    Marciniak, Elodie; Leboucher, Antoine; Caron, Emilie; Ahmed, Tariq; Tailleux, Anne; Dumont, Julie; Issad, Tarik; Gerhardt, Ellen; Pagesy, Patrick; Vileno, Margaux; Bournonville, Clément; Hamdane, Malika; Bantubungi, Kadiombo; Lancel, Steve; Demeyer, Dominique; Eddarkaoui, Sabiha; Vallez, Emmanuelle; Vieau, Didier; Humez, Sandrine; Faivre, Emilie; Grenier-Boley, Benjamin; Outeiro, Tiago F; Staels, Bart; Amouyel, Philippe; Balschun, Detlef; Buee, Luc; Blum, David

    2017-08-07

    The molecular pathways underlying tau pathology-induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological tau functions, which are largely unknown but could contribute to neuronal dysfunction. In the present study, we uncovered a novel function of tau in its ability to regulate brain insulin signaling. We found that tau deletion leads to an impaired hippocampal response to insulin, caused by altered IRS-1 and PTEN (phosphatase and tensin homologue on chromosome 10) activities. Our data also demonstrate that tau knockout mice exhibit an impaired hypothalamic anorexigenic effect of insulin that is associated with energy metabolism alterations. Consistently, we found that tau haplotypes are associated with glycemic traits in humans. The present data have far-reaching clinical implications and raise the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which is instrumental for cognitive and metabolic impairments in Alzheimer's disease patients. © 2017 Marciniak et al.

  2. Usefulness of MLPA in the detection of SHOX deletions.

    Science.gov (United States)

    Funari, Mariana F A; Jorge, Alexander A L; Souza, Silvia C A L; Billerbeck, Ana E C; Arnhold, Ivo J P; Mendonca, Berenice B; Nishi, Mirian Y

    2010-01-01

    SHOX haploinsufficiency causes a wide spectrum of short stature phenotypes, such as Leri-Weill dyschondrosteosis (LWD) and disproportionate short stature (DSS). SHOX deletions are responsible for approximately two thirds of isolated haploinsufficiency; therefore, it is important to determine the most appropriate methodology for detection of gene deletion. In this study, three methodologies for the detection of SHOX deletions were compared: the fluorescence in situ hybridization (FISH), microsatellite analysis and multiplex ligation-dependent probe amplification (MLPA). Forty-four patients (8 LWD and 36 DSS) were analyzed. The cosmid LLNOYCO3'M'34F5 was used as a probe for the FISH analysis and microsatellite analysis were performed using three intragenic microsatellite markers. MLPA was performed using commercial kits. Twelve patients (8 LWD and 4 DSS) had deletions in SHOX area detected by MLPA and 2 patients generated discordant results with the other methodologies. In the first case, the deletion was not detected by FISH. In the second case, both FISH and microsatellite analyses were unable to identify the intragenic deletion. In conclusion, MLPA was more sensitive, less expensive and less laborious; therefore, it should be used as the initial molecular method for the detection of SHOX gene deletion. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

  3. Conversion of Deletions during Recombination in Pneumococcal Transformation

    Science.gov (United States)

    Lefevre, J. C.; Mostachfi, P.; Gasc, A. M.; Guillot, E.; Pasta, F.; Sicard, M.

    1989-01-01

    Genetic analysis of 16 deletions obtained in the amiA locus of pneumococcus is described. When present on donor DNA, all deletions increased drastically the frequency of wild-type recombinants in two-point crosses. This effect was maximal for deletions longer than 200 bases. It was reduced for heterologies shorter than 76 bases and did not exist for very short deletions. In three-point crosses in which the deletion was localized between two point mutations, we demonstrated that this excess of wild-type recombinants was the result of a genetic conversion. This conversion extended over several scores of bases outside the deletion. Conversion takes place during the heteroduplex stage of recombination. Therefore, in pneumococcal transformation, long heterologies participated in this heteroduplex configuration. As this conversion did not require an active DNA polymerase A gene it is proposed that the mechanism of conversion is not a DNA repair synthesis but involves breakage and ligation between DNA molecules. Conversion of deletions did not require the Hex system of correction of mismatched bases. It differs also from localized conversion. It appears that it is a process that evolved to correct errors of replication which lead to long heterologies and which are not eliminated by other systems. PMID:2599365

  4. A strong deletion bias in nonallelic gene conversion.

    Directory of Open Access Journals (Sweden)

    Raquel Assis

    Full Text Available Gene conversion is the unidirectional transfer of genetic information between orthologous (allelic or paralogous (nonallelic genomic segments. Though a number of studies have examined nucleotide replacements, little is known about length difference mutations produced by gene conversion. Here, we investigate insertions and deletions produced by nonallelic gene conversion in 338 Drosophila and 10,149 primate paralogs. Using a direct phylogenetic approach, we identify 179 insertions and 614 deletions in Drosophila paralogs, and 132 insertions and 455 deletions in primate paralogs. Thus, nonallelic gene conversion is strongly deletion-biased in both lineages, with almost 3.5 times as many conversion-induced deletions as insertions. In primates, the deletion bias is considerably stronger for long indels and, in both lineages, the per-site rate of gene conversion is orders of magnitudes higher than that of ordinary mutation. Due to this high rate, deletion-biased nonallelic gene conversion plays a key role in genome size evolution, leading to the cooperative shrinkage and eventual disappearance of selectively neutral paralogs.

  5. Performance of quantum cloning and deleting machines over coherence

    Science.gov (United States)

    Karmakar, Sumana; Sen, Ajoy; Sarkar, Debasis

    2017-10-01

    Coherence, being at the heart of interference phenomena, is found to be an useful resource in quantum information theory. Here we want to understand quantum coherence under the combination of two fundamentally dual processes, viz., cloning and deleting. We found the role of quantum cloning and deletion machines with the consumption and generation of quantum coherence. We establish cloning as a cohering process and deletion as a decohering process. Fidelity of the process will be shown to have connection with coherence generation and consumption of the processes.

  6. Brand deletion: How the decision-making approach affects deletion success

    OpenAIRE

    Víctor Temprano-García; Ana Isabel Rodríguez-Escudero; Javier Rodríguez-Pinto

    2018-01-01

    Literature on brand deletion (BD), a critical and topical decision within a firm's marketing strategy, is extremely scarce. The present research is concerned with the decision-making process and examines the effect on BD success of three different approaches to decision-making – rational, intuitive and political – and of the interaction between the rational and political approaches. The moderating effect of the type of BD – i.e., total brand killing or disposal vs. brand name change – is also...

  7. Molecular and cellular pathways associated with chromosome 1p deletions during colon carcinogenesis

    Directory of Open Access Journals (Sweden)

    Payne CM

    2011-05-01

    Full Text Available Claire M Payne, Cheray Crowley-Skillicorn, Carol Bernstein, Hana Holubec, Harris BernsteinDepartment of Cell Biology and Anatomy, College of Medicine, University of Arizona Tucson, AZ, USAAbstract: Chromosomal instability is a major pathway of sporadic colon carcinogenesis. Chromosome arm 1p appears to be one of the “hot spots” in the non-neoplastic mucosa that, when deleted, is associated with the initiation of carcinogenesis. Chromosome arm 1p contains genes associated with DNA repair, spindle checkpoint function, apoptosis, multiple microRNAs, the Wnt signaling pathway, tumor suppression, antioxidant activities, and defense against environmental toxins. Loss of 1p is dangerous since it would likely contribute to genomic instability leading to tumorigenesis. The 1p deletion-associated colon carcinogenesis pathways are reviewed at the molecular and cellular levels. Sporadic colon cancer is strongly linked to a high-fat/low-vegetable/low-micronutrient, Western-style diet. We also consider how selected dietary-related compounds (eg, excess hydrophobic bile acids, and low levels of folic acid, niacin, plant-derived antioxidants, and other modulatory compounds might affect processes leading to chromosomal deletions, and to the molecular and cellular pathways specifically altered by chromosome 1p loss.Keywords: chromosome 1p, colon carcinogenesis, molecular pathways, cellular pathways

  8. 22q11.2 deletion syndrome

    Science.gov (United States)

    McDonald-McGinn, Donna M.; Sullivan, Kathleen E.; Marino, Bruno; Philip, Nicole; Swillen, Ann; Vorstman, Jacob A. S.; Zackai, Elaine H.; Emanuel, Beverly S.; Vermeesch, Joris R.; Morrow, Bernice E.; Scambler, Peter J.; Bassett, Anne S.

    2016-01-01

    22q11.2 deletion syndrome (22q11.2DS) is the most common chromosomal microdeletion disorder, estimated to result mainly from de novo non-homologous meiotic recombination events occurring in approximately 1 in every 1,000 fetuses. The first description in the English language of the constellation of findings now known to be due to this chromosomal difference was made in the 1960s in children with DiGeorge syndrome, who presented with the clinical triad of immunodeficiency, hypoparathyroidism and congenital heart disease. The syndrome is now known to have a heterogeneous presentation that includes multiple additional congenital anomalies and later-onset conditions, such as palatal, gastrointestinal and renal abnormalities, autoimmune disease, variable cognitive delays, behavioural phenotypes and psychiatric illness — all far extending the original description of DiGeorge syndrome. Management requires a multidisciplinary approach involving paediatrics, general medicine, surgery, psychiatry, psychology, interventional therapies (physical, occupational, speech, language and behavioural) and genetic counselling. Although common, lack of recognition of the condition and/or lack of familiarity with genetic testing methods, together with the wide variability of clinical presentation, delays diagnosis. Early diagnosis, preferably prenatally or neonatally, could improve outcomes, thus stressing the importance of universal screening. Equally important, 22q11.2DS has become a model for understanding rare and frequent congenital anomalies, medical conditions, psychiatric and developmental disorders, and may provide a platform to better understand these disorders while affording opportunities for translational strategies across the lifespan for both patients with 22q11.2DS and those with these associated features in the general population. PMID:27189754

  9. Heme oxygenase-1 deletion affects stress erythropoiesis.

    Directory of Open Access Journals (Sweden)

    Yu-An Cao

    Full Text Available Homeostatic erythropoiesis leads to the formation of mature red blood cells under non-stress conditions, and the production of new erythrocytes occurs as the need arises. In response to environmental stimuli, such as bone marrow transplantation, myelosuppression, or anemia, erythroid progenitors proliferate rapidly in a process referred to as stress erythropoiesis. We have previously demonstrated that heme oxygenase-1 (HO-1 deficiency leads to disrupted stress hematopoiesis. Here, we describe the specific effects of HO-1 deficiency on stress erythropoiesis.We used a transplant model to induce stress conditions. In irradiated recipients that received hmox(+/- or hmox(+/+ bone marrow cells, we evaluated (i the erythrocyte parameters in the peripheral blood; (ii the staining intensity of CD71-, Ter119-, and CD49d-specific surface markers during erythroblast differentiation; (iii the patterns of histological iron staining; and (iv the number of Mac-1(+-cells expressing TNF-α. In the spleens of mice that received hmox(+/- cells, we show (i decreases in the proerythroblast, basophilic, and polychromatophilic erythroblast populations; (ii increases in the insoluble iron levels and decreases in the soluble iron levels; (iii increased numbers of Mac-1(+-cells expressing TNF-α; and (iv decreased levels of CD49d expression in the basophilic and polychromatophilic erythroblast populations.As reflected by effects on secreted and cell surface proteins, HO-1 deletion likely affects stress erythropoiesis through the retention of erythroblasts in the erythroblastic islands of the spleen. Thus, HO-1 may serve as a therapeutic target for controlling erythropoiesis, and the dysregulation of HO-1 may be a predisposing condition for hematologic diseases.

  10. SNX27 Deletion Causes Hydrocephalus by Impairing Ependymal Cell Differentiation and Ciliogenesis.

    Science.gov (United States)

    Wang, Xin; Zhou, Ying; Wang, Jian; Tseng, I-Chu; Huang, Timothy; Zhao, Yingjun; Zheng, Qiuyang; Gao, Yue; Luo, Hong; Zhang, Xian; Bu, Guojun; Hong, Wanjin; Xu, Huaxi

    2016-12-14

    Hydrocephalus is a brain disorder derived from CSF accumulation due to defects in CSF clearance. Although dysfunctional apical cilia in the ependymal cell layer are causal to the onset of hydrocephalus, mechanisms underlying proper ependymal cell differentiation are largely unclear. SNX27 is a trafficking component required for normal brain function and was shown previously to suppress γ-secretase-dependent amyloid precursor protein and Notch cleavage. However, it was unclear how SNX27-dependent γ-secretase inhibition could contribute to brain development and pathophysiology. Here, we describe and characterize an Snx27-deleted mouse model for the ependymal layer defects of deciliation and hydrocephalus. SNX27 deficiency results in reductions in ependymal cells and cilia density, as well as severe postnatal hydrocephalus. Inhibition of Notch intracellular domain signaling with γ-secretase inhibitors reversed ependymal cells/cilia loss and dilation of lateral ventricles in Snx27-deficient mice, giving strong indication that Snx27 deletion triggers defects in ependymal layer formation and ciliogenesis through Notch hyperactivation. Together, these results suggest that SNX27 is essential for ependymal cell differentiation and ciliogenesis, and its deletion can promote hydrocephalus pathogenesis. Down's syndrome (DS) in humans and mouse models has been shown previously to confer a high risk for the development of pathological hydrocephalus. Because we have previously described SNX27 as a component that is consistently downregulated in DS, we present here a robust Snx27-deleted mouse model that produces hydrocephalus and associated ciliary defects with complete penetrance. In addition, we find that γ-secretase/Notch modulation may be a candidate drug target in SNX27-associated hydrocephalus such as that observed in DS. Based on these findings, we anticipate that future study will determine whether modulation of a SNX27/Notch/γ-secretase pathway can also be of

  11. Multigene deletions in lung adenocarcinomas from irradiated and control mice

    International Nuclear Information System (INIS)

    Zhang, Y.; Woloschak, G.E.

    1996-01-01

    K-ras codon 12 point mutations mRb and p53 gene deletions were examined in tissues from 120 normal lungs and lung adenocarcinomas that were Formalin-treated and paraffin-embedded 25 years ago. The results showed that 12 of 60 (20%) lung adenocarcinomas had mRb deletions. All lung adenocarcinomas that were initially found bearing deleted mRb had p53 deletions (15 of 15; 100%). A significantly higher mutation frequency for K-ras codon 12 point mutations was also found in the lung adenocarcinomas from mice exposed to 24 once-weekly neutron irradiation (10 of 10; 100%) compared with those exposed to 24 or 60 once-weekly γ-ray doses (5 of 10; 50%). The data suggested that p53 and K-ras gene alterations were two contributory factors responsible for the increased incidence of lung adenocarcinoma in B6CF 1 male mice exposed to protracted neutron radiation

  12. Additions and deletions to the known cerambycidae (Coleoptera) of Bolivia

    Science.gov (United States)

    An additional 137 species and two tribes are added to the known cerambycid fauna of Bolivia while 12 species are deleted. Comments and statistics regarding the growth of knowledge on the Bolivian Cerambycid fauna and species endemicity are included....

  13. 78 FR 75911 - Procurement List; Proposed Additions and Deletions

    Science.gov (United States)

    2013-12-13

    ... persons who are blind or have other severe disabilities and to delete products and a service previously...: General Services Administration, New York, NY NSN: 8955-01-E61-3689--Coffee, Roasted, Ground, 39 oz. bag...

  14. 76 FR 37069 - Procurement List; Proposed Additions and Deletion

    Science.gov (United States)

    2011-06-24

    ... Certification The following products and service are proposed for addition to Procurement List for production by... following product is proposed for deletion from the Procurement List: Product Detergent, Laundry NSN: 7930...

  15. Markerless deletion of putative alanine dehydrogenase genes in Bacillus licheniformis using a codBA-based counterselection technique.

    Science.gov (United States)

    Kostner, David; Rachinger, Michael; Liebl, Wolfgang; Ehrenreich, Armin

    2017-11-01

    Bacillus licheniformis strains are used for the large-scale production of industrial exoenzymes from proteinaceous substrates, but details of the amino acid metabolism involved are largely unknown. In this study, two chromosomal genes putatively involved in amino acid metabolism of B. licheniformis were deleted to clarify their role. For this, a convenient counterselection system for markerless in-frame deletions was developed for B. licheniformis. A deletion plasmid containing up- and downstream DNA segments of the chromosomal deletion target was conjugated to B. licheniformis and integrated into the genome by homologous recombination. Thereafter, the counterselection was done by using a codBA cassette. The presence of cytosine deaminase and cytosine permease exerted a conditionally lethal phenotype on B. licheniformis cells in the presence of the cytosine analogue 5-fluorocytosine. Thereby clones were selected that lost the integrated vector sequence and the anticipated deletion target after a second recombination step. This method allows the construction of markerless mutants in Bacillus strains in iterative cycles. B. licheniformis MW3 derivatives lacking either one of the ORFs BL03009 or BL00190, encoding a putative alanine dehydrogenase and a similar putative enzyme, respectively, retained the ability to grow in minimal medium supplemented with alanine as the carbon source. In the double deletion mutant MW3 ΔBL03009 ΔBL00190, however, growth on alanine was completely abolished. These data indicate that the two encoded enzymes are paralogues fulfilling mutually replaceable functions in alanine utilization, and suggest that in B. licheniformis MW3 alanine utilization is initiated by direct oxidative transamination to pyruvate and ammonium.

  16. The effect of the CCR5-delta32 deletion on global gene expression considering immune response and inflammation

    Directory of Open Access Journals (Sweden)

    Hütter Gero

    2011-10-01

    Full Text Available Abstract Background The natural function of the C-C chemokine receptor type 5 (CCR5 is poorly understood. A 32 base pair deletion in the CCR5 gene (CCR5-delta32 located on chromosome 3 results in a non-functional protein. It is supposed that this deletion causes an alteration in T-cell response to inflammation. For example, the presence of the CCR5-delta32 allele in recipients of allografts constitutes as an independent and protective factor associated with a decreased risk of graft-versus-host disease (GVHD and graft rejection. However, the mechanism of this beneficial effect of the deletion regarding GVHD is unknown. In this survey we searched for a CCR5-delta32 associated regulation of critical genes involved in the immune response and the development of GVHD. Methods We examined CD34+ hematopoietic progenitor cells derived from bone marrow samples from 19 healthy volunteers for the CCR5-delta32 deletion with a genomic PCR using primers flanking the site of the deletion. Results 12 individuals were found to be homozygous for CCR5 WT and 7 carried the CCR5-delta32 deletion heterozygously. Global gene expression analysis led to the identification of 11 differentially regulated genes. Six of them are connected with mechanisms of immune response and control: LRG1, CXCR2, CCRL2, CD6, CD7, WD repeat domain, and CD30L. Conclusions Our data indicate that the CCR5-delta32 mutation may be associated with differential gene expression. Some of these genes are critical for immune response, in the case of CD30L probably protective in terms of GVHD.

  17. The significance of chromosome deletions in atomic-bomb survivors

    International Nuclear Information System (INIS)

    Tanaka, Kimio; Shigeta, Chiharu; Oguma, Nobuo; Kamada, Nanao; Deng, Z.; Niimi, Masanobu; Aisaka, Tadaichi.

    1986-01-01

    In 39 A-bomb survivors 40 years after exposure at ≤ 1,000 m from ground zero, the frequency and features of chromosome deletions in peripheral lymphocytes were examined using a differential staining technique. Simultaneously, in vitro irradiation experiment with Cf-252 was made to infer chromosome aberrations occuring immediately after exposure. Californium-252 with 100 rad induced dicentric and ring chromosomes in 40 % of the cells and acentric fragments in 44 %. Among the A-bomb survivors, chromosome aberrations were observed in 651 (21 %) of the total 3,136 cells. There were 146 cells with deletions (22 % of abnormal cells; 5 % of the total cells), and 10 cells with acentric fragment (0.3 % of the total cells). The figure for deletions was far higher than that reported in the literature. A large number of deletions were seen in chromosomes no.4, no.21, and no.22, and a few deletions in chromosomes no.7 and no.20. Significance of chromosome deletions is discussed. (Namekawa, K.)

  18. Fast detection of deletion breakpoints using quantitative PCR

    Directory of Open Access Journals (Sweden)

    Gulshara Abildinova

    2016-01-01

    Full Text Available Abstract The routine detection of large and medium copy number variants (CNVs is well established. Hemizygotic deletions or duplications in the large Duchenne muscular dystrophy DMD gene responsible for Duchenne and Becker muscular dystrophies are routinely identified using multiple ligation probe amplification and array-based comparative genomic hybridization. These methods only map deleted or duplicated exons, without providing the exact location of breakpoints. Commonly used methods for the detection of CNV breakpoints include long-range PCR and primer walking, their success being limited by the deletion size, GC content and presence of DNA repeats. Here, we present a strategy for detecting the breakpoints of medium and large CNVs regardless of their size. The hemizygous deletion of exons 45-50 in the DMD gene and the large autosomal heterozygous PARK2 deletion were used to demonstrate the workflow that relies on real-time quantitative PCR to narrow down the deletion region and Sanger sequencing for breakpoint confirmation. The strategy is fast, reliable and cost-efficient, making it amenable to widespread use in genetic laboratories.

  19. Overexpression and deletion of phospholipid transfer protein reduce HDL mass and cholesterol efflux capacity but not macrophage reverse cholesterol transport[S

    Science.gov (United States)

    Kuwano, Takashi; Bi, Xin; Cipollari, Eleonora; Yasuda, Tomoyuki; Lagor, William R.; Szapary, Hannah J.; Tohyama, Junichiro; Millar, John S.; Billheimer, Jeffrey T.; Lyssenko, Nicholas N.; Rader, Daniel J.

    2017-01-01

    Phospholipid transfer protein (PLTP) may affect macrophage reverse cholesterol transport (mRCT) through its role in the metabolism of HDL. Ex vivo cholesterol efflux capacity and in vivo mRCT were assessed in PLTP deletion and PLTP overexpression mice. PLTP deletion mice had reduced HDL mass and cholesterol efflux capacity, but unchanged in vivo mRCT. To directly compare the effects of PLTP overexpression and deletion on mRCT, human PLTP was overexpressed in the liver of wild-type animals using an adeno-associated viral (AAV) vector, and control and PLTP deletion animals were injected with AAV-null. PLTP overexpression and deletion reduced plasma HDL mass and cholesterol efflux capacity. Both substantially decreased ABCA1-independent cholesterol efflux, whereas ABCA1-dependent cholesterol efflux remained the same or increased, even though preβ HDL levels were lower. Neither PLTP overexpression nor deletion affected excretion of macrophage-derived radiocholesterol in the in vivo mRCT assay. The ex vivo and in vivo assays were modified to gauge the rate of cholesterol efflux from macrophages to plasma. PLTP activity did not affect this metric. Thus, deviations in PLTP activity from the wild-type level reduce HDL mass and ex vivo cholesterol efflux capacity, but not the rate of macrophage cholesterol efflux to plasma or in vivo mRCT. PMID:28137768

  20. Association between BIM deletion polymorphism and clinical outcome of EGFR-mutated NSCLC patient with EGFR-TKI therapy: A meta-analysis.

    Science.gov (United States)

    Ma, Ji-Yong; Yan, Hai-Jun; Gu, Wei

    2015-01-01

    BIM deletion polymorphism was deemed to be associated with downregulation of BIM, resulting in a decreased apoptosis induced by epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC). However, accumulating evidences concerning the association between BIM deletion polymorphism and efficacy of EGFR-TKI and survival in EGFR-mutation-driven NSCLC patient reported contradictory results. A meta-analysis was conducted by combing six original eligible studies including 871 NSCLC patients. Our study showed that BIM deletion polymorphism was significantly associated with poor response to EGFR-TKI therapy in mutant EGFRNSCLC patients (P(h) = 0.309, P(z) = 0.001, OR = 0.39, 95% confidence interval (CI) = 0.23-0.67). Disease control rate (DCR) in mutant EGFRNSCLC patient with treatment of EGFR-TKI was significantly decreased in patients with BIM deletion polymorphism comparing to patients harbored BIM wild variant (P(h) = 0.583, P(Z) = 0.007, OR = 0.46, 95%CI = 0.25-0.85). EGFR mutation-derived NSCLC patient carrying BIM deletion polymorphism had a shorter progression-free survival (PFS; P(h) deletion polymorphism might be a cause that contributes to primary EGFR-TKI resistance, and it could be used as a genetic predictor for EGFR-TKI outcome and an independent prognostic factor of EGFR mutation-driven NSCLC patient.

  1. 41 CFR 51-2.3 - Notice of proposed addition or deletion.

    Science.gov (United States)

    2010-07-01

    ... addition or deletion. 51-2.3 Section 51-2.3 Public Contracts and Property Management Other Provisions... or deletion. At least 30 days prior to the Committee's consideration of the addition or deletion of a... Register announcing the proposed addition or deletion and providing interested persons an opportunity to...

  2. 10 CFR 9.19 - Segregation of exempt information and deletion of identifying details.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Segregation of exempt information and deletion of... Information Act Regulations § 9.19 Segregation of exempt information and deletion of identifying details. (a... deletions are made from parts of the record by computer, the amount of information deleted will be indicated...

  3. Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru

    Science.gov (United States)

    Akinyi, Sheila; Hayden, Tonya; Gamboa, Dionicia; Torres, Katherine; Bendezu, Jorge; Abdallah, Joseph F.; Griffing, Sean M.; Quezada, Wilmer Marquiño; Arrospide, Nancy; De Oliveira, Alexandre Macedo; Lucas, Carmen; Magill, Alan J.; Bacon, David J.; Barnwell, John W.; Udhayakumar, Venkatachalam

    2013-01-01

    The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times. PMID:24077522

  4. Optimal in-feed amino acid ratio for broiler breeder hens based on deletion studies.

    Science.gov (United States)

    Dorigam, J C P; Sakomura, N K; Sarcinelli, M F; Gonçalves, C A; de Lima, M B; Peruzzi, N J

    2017-12-01

    An ideal amino acid ratio (IAAR) for breeder hens is needed for maximum nitrogen retention (NR) taking into account nitrogen deposition in body (ND B ), feathers (ND F ) and egg mass (NEM) to improve dietary protein efficiency. Thus, the aim of this study was to apply the deletion method to derive the IAAR for broiler breeder hens. The nitrogen balance trials were performed from 31 to 35 weeks and from 46 to 50 weeks. Twelve treatments with eight replicates and one hen per cage were used. A balanced diet (BD) was formulated to meet the requirement of all nutrients. The other diets were formulated diluting 55% of BD with corn starch and refilled with amino acids (AAs) and other ingredients, except the AA tested. Each trial lasted 25 days. Feather losses, egg production and egg weight were recorded daily, and the samples were stored to further determine NEM and nitrogen in feather losses (ND FL ). At the start and the end of each period, a group of birds were slaughtered to further determine ND B and ND F . The NR was calculated as the sum of ND B , ND F , ND FL , NEM and the nitrogen maintenance requirement (NMR). The deletion of valine greatly depressed the NR in peak production (31 to 35 weeks) while the deletion of the isoleucine greatly depressed the NR of the hens from 46 to 50 weeks of age. The percentual reduction in NR and the per cent of the AA to delete from the BD were used to calculate the AA requirement. The average IAAR was Lys 100, Met+Cys 86, Trp 23, Thr 80, Arg 113, Val 90, Ile 91, Leu 133, Phe+Tyr 108, Gly+Ser 94 and His 35. The IAAR was in line with the recommendation from the literature, validating deletion method with the advantages from a rapid and low-cost procedure. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  5. Account Deletion Prediction on RuNet: A Case Study of Suspicious Twitter Accounts Active During the Russian-Ukrainian Crisis

    Energy Technology Data Exchange (ETDEWEB)

    Volkova, Svitlana; Bell, Eric B.

    2016-06-17

    Social networks are dynamically changing over time e.g., some accounts are being created and some are being deleted or become private. This ephemerality at both an account level and content level results from a combination of privacy concerns, spam, and deceptive behaviors. In this study we analyze a large dataset of 180,340 accounts active during the Russian-Ukrainian crisis to discover a series of predictive features for the removal or shutdown of a suspicious account. We find that unlike previously reported profile and net- work features, lexical features form the basis for highly accurate prediction of the deletion of an account.

  6. Amino-acid composition after loop deletion drives domain swapping.

    Science.gov (United States)

    Nandwani, Neha; Surana, Parag; Udgaonkar, Jayant B; Das, Ranabir; Gosavi, Shachi

    2017-10-01

    Rational engineering of a protein to enable domain swapping requires an understanding of the sequence, structural and energetic factors that favor the domain-swapped oligomer over the monomer. While it is known that the deletion of loops between β-strands can promote domain swapping, the spliced sequence at the position of the loop deletion is thought to have a minimal role to play in such domain swapping. Here, two loop-deletion mutants of the non-domain-swapping protein monellin, frame-shifted by a single residue, were designed. Although the spliced sequence in the two mutants differed by only one residue at the site of the deletion, only one of them (YEIKG) promoted domain swapping. The mutant containing the spliced sequence YENKG was entirely monomeric. This new understanding that the domain swapping propensity after loop deletion may depend critically on the chemical composition of the shortened loop will facilitate the rational design of domain swapping. © 2017 The Protein Society.

  7. The Yeast Deletion Collection: A Decade of Functional Genomics

    Science.gov (United States)

    Giaever, Guri; Nislow, Corey

    2014-01-01

    The yeast deletion collections comprise >21,000 mutant strains that carry precise start-to-stop deletions of ∼6000 open reading frames. This collection includes heterozygous and homozygous diploids, and haploids of both MATa and MATα mating types. The yeast deletion collection, or yeast knockout (YKO) set, represents the first and only complete, systematically constructed deletion collection available for any organism. Conceived during the Saccharomyces cerevisiae sequencing project, work on the project began in 1998 and was completed in 2002. The YKO strains have been used in numerous laboratories in >1000 genome-wide screens. This landmark genome project has inspired development of numerous genome-wide technologies in organisms from yeast to man. Notable spinoff technologies include synthetic genetic array and HIPHOP chemogenomics. In this retrospective, we briefly describe the yeast deletion project and some of its most noteworthy biological contributions and the impact that these collections have had on the yeast research community and on genomics in general. PMID:24939991

  8. Molecular studies of deletions at the human steroid sulfatase locus

    International Nuclear Information System (INIS)

    Shapiro, L.J.; Yen, P.; Pomerantz, D.; Martin, E.; Rolewic, L.; Mohandas, T.

    1989-01-01

    The human steroid sulfatase gene (STS) is located on the distal X chromosome short arm close to the pseudoautosomal region but in a segment of DNA that is unique to the X chromosome. In contrast to most X chromosome-encoded genes, STS expression is not extinguished during the process of X chromosome inactivation. Deficiency of STS activity produced the syndrome of X chromosome-linked ichthyosis, which is one of the most common inborn errors of metabolism in man. Approximately 90% of STS - individuals have large deletions at the STS locus. The authors and others have found that the end points of such deletions are heterogeneous in their location. One recently ascertained subject was observed to have a 40-kilobase deletion that is entirely intragenic, permitting the cloning and sequencing of the deletion junction. Studies of this patient and of other X chromosome sequences in other subjects permit some insight into the mechanism(s) responsible for generating frequent deletions on the short arm of the X chromosome

  9. Sorting genomes by reciprocal translocations, insertions, and deletions.

    Science.gov (United States)

    Qi, Xingqin; Li, Guojun; Li, Shuguang; Xu, Ying

    2010-01-01

    The problem of sorting by reciprocal translocations (abbreviated as SBT) arises from the field of comparative genomics, which is to find a shortest sequence of reciprocal translocations that transforms one genome Pi into another genome Gamma, with the restriction that Pi and Gamma contain the same genes. SBT has been proved to be polynomial-time solvable, and several polynomial algorithms have been developed. In this paper, we show how to extend Bergeron's SBT algorithm to include insertions and deletions, allowing to compare genomes containing different genes. In particular, if the gene set of Pi is a subset (or superset, respectively) of the gene set of Gamma, we present an approximation algorithm for transforming Pi into Gamma by reciprocal translocations and deletions (insertions, respectively), providing a sorting sequence with length at most OPT + 2, where OPT is the minimum number of translocations and deletions (insertions, respectively) needed to transform Pi into Gamma; if Pi and Gamma have different genes but not containing each other, we give a heuristic to transform Pi into Gamma by a shortest sequence of reciprocal translocations, insertions, and deletions, with bounds for the length of the sorting sequence it outputs. At a conceptual level, there is some similarity between our algorithm and the algorithm developed by El Mabrouk which is used to sort two chromosomes with different gene contents by reversals, insertions, and deletions.

  10. Actor-Network Procedures

    NARCIS (Netherlands)

    Pavlovic, Dusko; Meadows, Catherine; Ramanujam, R.; Ramaswamy, Srini

    2012-01-01

    In this paper we propose actor-networks as a formal model of computation in heterogenous networks of computers, humans and their devices, where these new procedures run; and we introduce Procedure Derivation Logic (PDL) as a framework for reasoning about security in actor-networks, as an extension

  11. Learning conditional Gaussian networks

    DEFF Research Database (Denmark)

    Bøttcher, Susanne Gammelgaard

    This paper considers conditional Gaussian networks. The parameters in the network are learned by using conjugate Bayesian analysis. As conjugate local priors, we apply the Dirichlet distribution for discrete variables and the Gaussian-inverse gamma distribution for continuous variables, given...... a configuration of the discrete parents. We assume parameter independence and complete data. Further, to learn the structure of the network, the network score is deduced. We then develop a local master prior procedure, for deriving parameter priors in these networks. This procedure satisfies parameter...... independence, parameter modularity and likelihood equivalence. Bayes factors to be used in model search are introduced. Finally the methods derived are illustrated by a simple example....

  12. Umbilical Cord Blood-Derived Mononuclear Cells Exhibit Pericyte-Like Phenotype and Support Network Formation of Endothelial Progenitor Cells In Vitro.

    Science.gov (United States)

    Peters, Erica B; Liu, Betty; Christoforou, Nicolas; West, Jennifer L; Truskey, George A

    2015-10-01

    Umbilical cord blood represents a promising cell source for pro-angiogenic therapies. The present study examined the potential of mononuclear cells (MNCs) from umbilical cord blood to support endothelial progenitor cell (EPC) microvessel formation. MNCs were isolated from the cord blood of 20 separate donors and selected for further characterization based upon their proliferation potential and morphological resemblance to human vascular pericytes (HVPs). MNCs were screened for their ability to support EPC network formation using an in vitro assay (Matrigel™) as well as a reductionist, coculture system consisting of no additional angiogenic cytokines beyond those present in serum. In less than 15% of the isolations, we identified a population of highly proliferative MNCs that phenotypically resembled HVPs as assessed by expression of PDGFR-β, NG2, α-SMA, and ephrin-B2. Within a Matrigel™ system, MNCs demonstrated pericyte-like function through colocalization to EPC networks and similar effects as HVPs upon total EPC tubule length (p = 0.95) and number of branch points (p = 0.93). In a reductionist coculture system, MNCs served as pro-angiogenic mural cells by supporting EPC network formation to a significantly greater extent than HVP cocultures, by day 14 of coculture, as evidenced through EPC total tubule length (p < 0.0001) and number of branch points (p < 0.0001). Our findings are significant as we demonstrate mural cell progenitors can be isolated from umbilical cord blood and develop culture conditions to support their use in microvascular tissue engineering applications.

  13. Sequential computation of elementary modes and minimal cut sets in genome-scale metabolic networks using alternate integer linear programming.

    Science.gov (United States)

    Song, Hyun-Seob; Goldberg, Noam; Mahajan, Ashutosh; Ramkrishna, Doraiswami

    2017-08-01

    Elementary (flux) modes (EMs) have served as a valuable tool for investigating structural and functional properties of metabolic networks. Identification of the full set of EMs in genome-scale networks remains challenging due to combinatorial explosion of EMs in complex networks. It is often, however, that only a small subset of relevant EMs needs to be known, for which optimization-based sequential computation is a useful alternative. Most of the currently available methods along this line are based on the iterative use of mixed integer linear programming (MILP), the effectiveness of which significantly deteriorates as the number of iterations builds up. To alleviate the computational burden associated with the MILP implementation, we here present a novel optimization algorithm termed alternate integer linear programming (AILP). Our algorithm was designed to iteratively solve a pair of integer programming (IP) and linear programming (LP) to compute EMs in a sequential manner. In each step, the IP identifies a minimal subset of reactions, the deletion of which disables all previously identified EMs. Thus, a subsequent LP solution subject to this reaction deletion constraint becomes a distinct EM. In cases where no feasible LP solution is available, IP-derived reaction deletion sets represent minimal cut sets (MCSs). Despite the additional computation of MCSs, AILP achieved significant time reduction in computing EMs by orders of magnitude. The proposed AILP algorithm not only offers a computational advantage in the EM analysis of genome-scale networks, but also improves the understanding of the linkage between EMs and MCSs. The software is implemented in Matlab, and is provided as supplementary information . hyunseob.song@pnnl.gov. Supplementary data are available at Bioinformatics online. Published by Oxford University Press 2017. This work is written by US Government employees and are in the public domain in the US.

  14. A Rare Syndrome of Deletion in 2 Siblings

    Directory of Open Access Journals (Sweden)

    Aravindhan Veerapandiyan MBBS

    2017-08-01

    Full Text Available The Glutamate receptor, ionotropic, delta 2 gene codes for an ionotropic glutamate delta-2 receptor, which is selectively expressed in cerebellar Purkinje cells, and facilitates cerebellar synapse organization and transmission. The phenotype associated with the deletion of Glutamate receptor, ionotropic, delta 2 gene in humans was initially defined in 2013. In this case report, the authors describe 2 brothers who presented with developmental delay, tonic upward gaze, nystagmus, oculomotor apraxia, hypotonia, hyperreflexia, and ataxia. They were found to have a homozygous intragenic deletion within the Glutamate receptor, ionotropic, delta 2 gene at exon 2. Our patients serve as an addition to the literature of previously reported children with this rare clinical syndrome associated with Glutamate receptor, ionotropic, delta 2 deletion.

  15. Monoamine oxidase deficiency in males with an X chromosome deletion.

    Science.gov (United States)

    Sims, K B; de la Chapelle, A; Norio, R; Sankila, E M; Hsu, Y P; Rinehart, W B; Corey, T J; Ozelius, L; Powell, J F; Bruns, G

    1989-01-01

    Mapping of the human MAOA gene to chromosomal region Xp21-p11 prompted our study of two affected males in a family previously reported to have Norrie disease resulting from a submicroscopic deletion in this chromosomal region. In this investigation we demonstrate in these cousins deletion of the MAOA gene, undetectable levels of MAO-A and MAO-B activities in their fibroblasts and platelets, respectively, loss of mRNA for MAO-A in fibroblasts, and substantial alterations in urinary catecholamine metabolites. The present study documents that a marked deficiency of MAO activity is compatible with life and that genes for MAO-A and MAO-B are near each other in this Xp chromosomal region. Some of the clinical features of these MAO deletion patients may help to identify X-linked MAO deficiency diseases in humans.

  16. Bacterial-cellulose-derived interconnected meso-microporous carbon nanofiber networks as binder-free electrodes for high-performance supercapacitors

    Science.gov (United States)

    Hao, Xiaodong; Wang, Jie; Ding, Bing; Wang, Ya; Chang, Zhi; Dou, Hui; Zhang, Xiaogang

    2017-06-01

    Bacterial cellulose (BC), a typical biomass prepared from the microbial fermentation process, has been proved that it can be an ideal platform for design of three-dimensional (3D) multifunctional nanomaterials in energy storage and conversion field. Here we developed a simple and general silica-assisted strategy for fabrication of interconnected 3D meso-microporous carbon nanofiber networks by confine nanospace pyrolysis of sustainable BC, which can be used as binder-free electrodes for high-performance supercapacitors. The synthesized carbon nanofibers exhibited the features of interconnected 3D networks architecture, large surface area (624 m2 g-1), mesopores-dominated hierarchical porosity, and high graphitization degree. The as-prepared electrode (CN-BC) displayed a maximum specific capacitance of 302 F g-1 at a current density of 0.5 A g-1, high-rate capability and good cyclicity in 6 M KOH electrolyte. This work, together with cost-effective preparation strategy to make high-value utilization of cheap biomass, should have significant implications in the green and mass-producible energy storage.

  17. Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation.

    Science.gov (United States)

    Staines, Katherine A; Javaheri, Behzad; Hohenstein, Peter; Fleming, Robert; Ikpegbu, Ekele; Unger, Erin; Hopkinson, Mark; Buttle, David J; Pitsillides, Andrew A; Farquharson, Colin

    2017-11-01

    The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the initial stages of osteocyte differentiation. However, its precise function and regulatory mechanisms are still unknown. Due to the known embryonic lethality induced by global Pdpn deletion, we have herein explored the effect of bone-specific Pdpn knockdown on osteocyte form and function in the post-natal mouse. Extensive skeletal phenotyping of male and female 6-week-old Oc-cre;Pdpn flox/flox (cKO) mice and their Pdpn flox/flox controls (fl/fl) has revealed that Pdpn deletion significantly compromises tibial cortical bone microarchitecture in both sexes, albeit to different extents (p < 0.05). Consistent with this, we observed an increase in stiffness in female cKO mice in comparison to fl/fl mice (p < 0.01). Moreover, analysis of the osteocyte phenotype by phalloidin staining revealed a significant decrease in the dendrite volume (p < 0.001) and length (p < 0.001) in cKO mice in which deletion of Pdpn also modifies the bone anabolic loading response (p < 0.05) in comparison to age-matched fl/fl mice. Together, these data confirm a regulatory role for Pdpn in osteocyte dendrite formation and as such, in the control of osteocyte function. As the osteocyte dendritic network is known to play vital roles in regulating bone modeling/remodeling, this highlights an essential role for Pdpn in bone homeostasis. © 2017 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

  18. The diagnosis and molecular analysis of a novel 21.9kb deletion (Qinzhou type deletion) causing α+ thalassemia.

    Science.gov (United States)

    Long, Ju; Yan, Shanhuo; Lao, Kegan; Pang, Wanrong; Ye, Xuehe; Sun, Lei

    2014-04-01

    α-Thalassemia is a common single-gene genetic disease that can cause Hb Bart's hydrops fetalis and Hb H disease in tropical and subtropical regions. When examining conventional thalassemia genes, an only detected --(SEA) genotype sample needs further analysis. In doing so, we found a novel 21.9kb deletion (Qinzhou type deletion). The deletion position of the novel 21.9kb deletion is from 14373bp to 36299bp of the α-globin gene cluster (NG_000006.1); thus, there exists a 21927bp sequence deletion, into which a 29bp sequence is added. After sequence analysis, a group of Gap-PCR primers were synthesized to diagnose this novel thalassemia genotype. Through pedigree analysis, we deduced that the propositus obtained the novel alleles from her mother. The genotype of this propositus is --(SEA)/-α(21.9) and its phenotype conforms to the characteristics of Hb H disease, establishing that the combination between -α(21.9) genotype and α(0) genotype can lead to Hb H disease. By molecular analysis, we established that this case fits the characteristic of an α(+) thalassemia genotype. © 2013.

  19. Global Derivatives

    DEFF Research Database (Denmark)

    Andersen, Torben Juul

    approaches to dealing in the global business environment." - Sharon Brown-Hruska, Commissioner, Commodity Futures Trading Commission, USA. "This comprehensive survey of modern risk management using derivative securities is a fine demonstration of the practical relevance of modern derivatives theory to risk......" provides comprehensive coverage of different types of derivatives, including exchange traded contracts and over-the-counter instruments as well as real options. There is an equal emphasis on the practical application of derivatives and their actual uses in business transactions and corporate risk...... management situations. Its key features include: derivatives are introduced in a global market perspective; describes major derivative pricing models for practical use, extending these principles to valuation of real options; practical applications of derivative instruments are richly illustrated...

  20. Pseudotumor of the pituitary due to PROP-1 deletion.

    Science.gov (United States)

    Teinturier, C; Vallette, S; Adamsbaum, C; Bendaoud, M; Brue, T; Bougnères, P F

    2002-01-01

    Hypopituitarism associated with pituitary mass in childhood is most frequently the consequence of craniopharyngioma or Rathke's cleft cyst. We report a patient with an intrasellar pseudotumor associated with hypopituitarism, which led us to a misdiagnosis of intrasellar craniopharyngioma. After spontaneous involution of the mass, diagnosis was revised. DNA analysis showed a deletion in the Prophet of Pit-1 (PROP-1) gene, a pituitary transcription factor. It is important to recognize that a PROP-1 deletion can cause pituitary pseudotumor that can be mistaken for a craniopharyngioma or Rathke's pouch cyst.

  1. Internally deleted WNV genomes isolated from exotic birds in New Mexico: function in cells, mosquitoes, and mice.

    Science.gov (United States)

    Pesko, Kendra N; Fitzpatrick, Kelly A; Ryan, Elizabeth M; Shi, Pei-Yong; Zhang, Bo; Lennon, Niall J; Newman, Ruchi M; Henn, Matthew R; Ebel, Gregory D

    2012-05-25

    Most RNA viruses exist in their hosts as a heterogeneous population of related variants. Due to error prone replication, mutants are constantly generated which may differ in individual fitness from the population as a whole. Here we characterize three WNV isolates that contain, along with full-length genomes, mutants with large internal deletions to structural and nonstructural protein-coding regions. The isolates were all obtained from lorikeets that died from WNV at the Rio Grande Zoo in Albuquerque, NM between 2005 and 2007. The deletions are approximately 2kb, in frame, and result in the elimination of the complete envelope, and portions of the prM and NS-1 proteins. In Vero cell culture, these internally deleted WNV genomes function as defective interfering particles, reducing the production of full-length virus when introduced at high multiplicities of infection. In mosquitoes, the shortened WNV genomes reduced infection and dissemination rates, and virus titers overall, and were not detected in legs or salivary secretions at 14 or 21 days post-infection. In mice, inoculation with internally deleted genomes did not attenuate pathogenesis relative to full-length or infectious clone derived virus, and shortened genomes were not detected in mice at the time of death. These observations provide evidence that large deletions may occur within flavivirus populations more frequently than has generally been appreciated and suggest that they impact population phenotype minimally. Additionally, our findings suggest that highly similar mutants may frequently occur in particular vertebrate hosts. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Decreased DGCR8 expression and miRNA dysregulation in individuals with 22q11.2 deletion syndrome.

    Directory of Open Access Journals (Sweden)

    Chantal Sellier

    Full Text Available Deletion of the 1.5-3 Mb region of chromosome 22 at locus 11.2 gives rise to the chromosome 22q11.2 deletion syndrome (22q11DS, also known as DiGeorge and Velocardiofacial Syndromes. It is the most common micro-deletion disorder in humans and one of the most common multiple malformation syndromes. The syndrome is characterized by a broad phenotype, whose characterization has expanded considerably within the last decade and includes many associated findings such as craniofacial anomalies (40%, conotruncal defects of the heart (CHD; 70-80%, hypocalcemia (20-60%, and a range of neurocognitive anomalies with high risk of schizophrenia, all with a broad phenotypic variability. These phenotypic features are believed to be the result of a change in the copy number or dosage of the genes located in the deleted region. Despite this relatively clear genetic etiology, very little is known about which genes modulate phenotypic variations in humans or if they are due to combinatorial effects of reduced dosage of multiple genes acting in concert. Here, we report on decreased expression levels of genes within the deletion region of chromosome 22, including DGCR8, in peripheral leukocytes derived from individuals with 22q11DS compared to healthy controls. Furthermore, we found dysregulated miRNA expression in individuals with 22q11DS, including miR-150, miR-194 and miR-185. We postulate this to be related to DGCR8 haploinsufficiency as DGCR8 regulates miRNA biogenesis. Importantly we demonstrate that the level of some miRNAs correlates with brain measures, CHD and thyroid abnormalities, suggesting that the dysregulated miRNAs may contribute to these phenotypes and/or represent relevant blood biomarkers of the disease in individuals with 22q11DS.

  3. Chassis organism from Corynebacterium glutamicum--a top-down approach to identify and delete irrelevant gene clusters.

    Science.gov (United States)

    Unthan, Simon; Baumgart, Meike; Radek, Andreas; Herbst, Marius; Siebert, Daniel; Brühl, Natalie; Bartsch, Anna; Bott, Michael; Wiechert, Wolfgang; Marin, Kay; Hans, Stephan; Krämer, Reinhard; Seibold, Gerd; Frunzke, Julia; Kalinowski, Jörn; Rückert, Christian; Wendisch, Volker F; Noack, Stephan

    2015-02-01

    For synthetic biology applications, a robust structural basis is required, which can be constructed either from scratch or in a top-down approach starting from any existing organism. In this study, we initiated the top-down construction of a chassis organism from Corynebacterium glutamicum ATCC 13032, aiming for the relevant gene set to maintain its fast growth on defined medium. We evaluated each native gene for its essentiality considering expression levels, phylogenetic conservation, and knockout data. Based on this classification, we determined 41 gene clusters ranging from 3.7 to 49.7 kbp as target sites for deletion. 36 deletions were successful and 10 genome-reduced strains showed impaired growth rates, indicating that genes were hit, which are relevant to maintain biological fitness at wild-type level. In contrast, 26 deleted clusters were found to include exclusively irrelevant genes for growth on defined medium. A combinatory deletion of all irrelevant gene clusters would, in a prophage-free strain, decrease the size of the native genome by about 722 kbp (22%) to 2561 kbp. Finally, five combinatory deletions of irrelevant gene clusters were investigated. The study introduces the novel concept of relevant genes and demonstrates general strategies to construct a chassis suitable for biotechnological application. © 2014 The Authors. Biotechnology Journal published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim. This is an open access article under the terms of the Creative Commons Attribution-Non-Commercial-NoDerivs Licence, which permits use and distribution in any medium, provided the original work is properly cited, the use is non- commercial and no modifications or adaptations are made.

  4. Transplantation of motoneurons derived from MASH1-transfected mouse ES cells reconstitutes neural networks and improves motor function in hemiplegic mice.

    Science.gov (United States)

    Ikeda, Ritsuko; Kurokawa, Manae S; Chiba, Shunmei; Yoshikawa, Hideshi; Hashimoto, Takuo; Tadokoro, Mamoru; Suzuki, Noboru

    2004-10-01

    Mouse embryonic stem (ES) cells were transfected with a MASH1 expression vector and G418-resistant cells were selected. The MASH1-transfected cells became neuron-like appearance and expressed betaIIItubulin and panNCAM. Glial fibrillary acidic protein (GFAP) and galactocerebroside (GalC)-expressing cells were rarely detected. Half of the neural cells differentiated into the Islet1+ motoneuron lineage. Thus, we obtained motoneuron lineage-enriched neuronal cells by transfection of ES cells with MASH1. A hemiplegic model of mice was developed by cryogenic injury of the motor cortex, and motoneuron lineage-enriched neuronal cells were transplanted underneath the injured motor cortex neighboring the periventricular region. The motor function of the recipients was assessed by a beam walking and rotarod tests, whereby the results gradually improved, but little improvement was observed in vehicle injected control mice. We found that the grafted cells not only remained close to the implantation site, but also exhibited substantial migration, penetrating into the damaged lesion in a directed manner up to the cortical region. Grafted neuronal cells that had migrated into the cortex were elongated axon-positive for neurofilament middle chain (NFM). Synaptophysin immunostaining showed a positive staining pattern around the graft, suggesting that the transplanted neurons interacted with the recipient neurons to form a neural network. Our study suggests that the motoneuron lineage can be induced from ES cells, and grafted cells adapt to the host environment and can reconstitute a neural network to improve motor function of a paralyzed limb.

  5. A comparison of extreme rainfall characteristics in the Brazilian Amazon derived from two gridded data sets and a national rain gauge network

    Science.gov (United States)

    Clarke, Robin T.; Bulhoes Mendes, Carlos Andre; Costa Buarque, Diogo

    2010-07-01

    Two issues of particular importance for the Amazon watershed are: whether annual maxima obtained from reanalysis and raingauge records agree well enough for the former to be useful in extending records of the latter; and whether reported trends in Amazon annual rainfall are reflected in the behavior of annual extremes in precipitation estimated from reanalyses and raingauge records. To explore these issues, three sets of daily precipitation data (1979-2001) from the Brazilian Amazon were analyzed (NCEP/NCAR and ERA-40 reanalyses, and records from the raingauge network of the Brazilian water resources agency - ANA), using the following variables: (1) mean annual maximum precipitation totals, accumulated over one, two, three and five days; (2) linear trends in these variables; (3) mean length of longest within-year "dry" spell; (4) linear trends in these variables. Comparisons between variables obtained from all three data sources showed that reanalyses underestimated time-trends and mean annual maximum precipitation (over durations of one to five days), and the correlations between reanalysis and spatially-interpolated raingauge estimates were small for these two variables. Both reanalyses over-estimated mean lengths of dry period relative to the mean length recorded by the raingauge network. Correlations between the trends calculated from all three data sources were small. Time-trends averaged over the reanalysis grid-squares, and spatially-interpolated time trends from raingauge data, were all clustered around zero. In conclusion, although the NCEP/NCAR and ERA-40 gridded data-sets may be valuable for studies of inter-annual variability in precipitation totals, they were found to be inappropriate for analysis of precipitation extremes.

  6. Systematic deletion of homeobox genes in Podospora anserina uncovers their roles in shaping the fruiting body.

    Directory of Open Access Journals (Sweden)

    Evelyne Coppin

    Full Text Available Higher fungi, which comprise ascomycetes and basidiomycetes, play major roles in the biosphere. Their evolutionary success may be due to the extended dikaryotic stage of their life cycle, which is the basis for their scientific name: the Dikarya. Dikaryosis is maintained by similar structures, the clamp in basidiomycetes and the crozier in ascomycetes. Homeodomain transcription factors are required for clamp formation in all basidiomycetes studied. We identified all the homeobox genes in the filamentous ascomycete fungus Podospora anserina and constructed deletion mutants for each of these genes and for a number of gene combinations. Croziers developed normally in these mutants, including those with up to six deleted homeogenes. However, some mutants had defects in maturation of the fruiting body, an effect that could be rescued by providing wild-type maternal hyphae. Analysis of mutants deficient in multiple homeogenes revealed interactions between the genes, suggesting that they operate as a complex network. Similar to their role in animals and plants, homeodomain transcription factors in ascomycetes are involved in shaping multicellular structures.

  7. Systematic deletion of homeobox genes in Podospora anserina uncovers their roles in shaping the fruiting body.

    Science.gov (United States)

    Coppin, Evelyne; Berteaux-Lecellier, Véronique; Bidard, Frédérique; Brun, Sylvain; Ruprich-Robert, Gwenaël; Espagne, Eric; Aït-Benkhali, Jinane; Goarin, Anne; Nesseir, Audrey; Planamente, Sara; Debuchy, Robert; Silar, Philippe

    2012-01-01

    Higher fungi, which comprise ascomycetes and basidiomycetes, play major roles in the biosphere. Their evolutionary success may be due to the extended dikaryotic stage of their life cycle, which is the basis for their scientific name: the Dikarya. Dikaryosis is maintained by similar structures, the clamp in basidiomycetes and the crozier in ascomycetes. Homeodomain transcription factors are required for clamp formation in all basidiomycetes studied. We identified all the homeobox genes in the filamentous ascomycete fungus Podospora anserina and constructed deletion mutants for each of these genes and for a number of gene combinations. Croziers developed normally in these mutants, including those with up to six deleted homeogenes. However, some mutants had defects in maturation of the fruiting body, an effect that could be rescued by providing wild-type maternal hyphae. Analysis of mutants deficient in multiple homeogenes revealed interactions between the genes, suggesting that they operate as a complex network. Similar to their role in animals and plants, homeodomain transcription factors in ascomycetes are involved in shaping multicellular structures.

  8. Epidemics on interconnected networks

    Science.gov (United States)

    Dickison, Mark; Havlin, S.; Stanley, H. E.

    2012-06-01

    Populations are seldom completely isolated from their environment. Individuals in a particular geographic or social region may be considered a distinct network due to strong local ties but will also interact with individuals in other networks. We study the susceptible-infected-recovered process on interconnected network systems and find two distinct regimes. In strongly coupled network systems, epidemics occur simultaneously across the entire system at a critical infection strength βc, below which the disease does not spread. In contrast, in weakly coupled network systems, a mixed phase exists below βc of the coupled network system, where an epidemic occurs in one network but does not spread to the coupled network. We derive an expression for the network and disease parameters that allow this mixed phase and verify it numerically. Public health implications of communities comprising these two classes of network systems are also mentioned.

  9. Parameters affecting the resilience of scale-free networks to random failures.

    Energy Technology Data Exchange (ETDEWEB)

    Link, Hamilton E.; LaViolette, Randall A.; Lane, Terran (University of New Mexico, Albuquerque, NM); Saia, Jared (University of New Mexico, Albuquerque, NM)

    2005-09-01

    It is commonly believed that scale-free networks are robust to massive numbers of random node deletions. For example, Cohen et al. in (1) study scale-free networks including some which approximate the measured degree distribution of the Internet. Their results suggest that if each node in this network failed independently with probability 0.99, most of the remaining nodes would still be connected in a giant component. In this paper, we show that a large and important subclass of scale-free networks are not robust to massive numbers of random node deletions. In particular, we study scale-free networks which have minimum node degree of 1 and a power-law degree distribution beginning with nodes of degree 1 (power-law networks). We show that, in a power-law network approximating the Internet's reported distribution, when the probability of deletion of each node is 0.5 only about 25% of the surviving nodes in the network remain connected in a giant component, and the giant component does not persist beyond a critical failure rate of 0.9. The new result is partially due to improved analytical accommodation of the large number of degree-0 nodes that result after node deletions. Our results apply to power-law networks with a wide range of power-law exponents, including Internet-like networks. We give both analytical and empirical evidence that such networks are not generally robust to massive random node deletions.

  10. Financial Derivatives

    DEFF Research Database (Denmark)

    Wigan, Duncan

    2013-01-01

    Contemporary derivatives mark the development of capital and constitute a novel form of ownership. By reconfiguring the temporal, spatial and legal character of ownership derivatives present a substantive challenge to the tax collecting state. While fiscal systems are nationally bounded...... and inherently static, capital itself is unprecedentedly mobile, fluid and fungible. As such derivatives raise the specter of ‘financial weapons of mass destruction’....

  11. Financial Derivatives

    OpenAIRE

    Janečková, Alena

    2011-01-01

    1 Abstract/ Financial derivatives The purpose of this thesis is to provide an introduction to financial derivatives which has been, from the legal perspective, described in a not satisfactory manner as quite little literature that can be found about this topic. The main objectives of this thesis are to define the term "financial derivatives" and its particular types and to analyse legal nature of these financial instruments. The last objective is to try to draft future law regulation of finan...

  12. Sugar sensing by ChREBP/Mondo-Mlx-new insight into downstream regulatory networks and integration of nutrient-derived signals.

    Science.gov (United States)

    Havula, Essi; Hietakangas, Ville

    2018-04-01

    Animals regulate their physiology with respect to nutrient status, which requires nutrient sensing pathways. Simple carbohydrates, sugars, are sensed by the basic-helix-loop-helix leucine zipper transcription factors ChREBP/Mondo, together with their heterodimerization partner Mlx, which are well-established activators of sugar-induced lipogenesis. Loss of ChREBP/Mondo-Mlx in mouse and Drosophila leads to sugar intolerance, that is, inability to survive on sugar containing diet. Recent evidence has revealed that ChREBP/Mondo-Mlx responds to sugar and fatty acid-derived metabolites through several mechanisms and cross-connects with other nutrient sensing pathways. ChREBP/Mondo-Mlx controls several downstream transcription factors and hormones, which mediate not only readjustment of metabolic pathways, but also control feeding behavior, intestinal digestion, and circadian rhythm. Copyright © 2017. Published by Elsevier Ltd.

  13. Rapid generation of sub-type, region-specific neurons and neural networks from human pluripotent stem cell-derived neurospheres

    Directory of Open Access Journals (Sweden)

    Aynun N. Begum

    2015-11-01

    Full Text Available Stem cell-based neuronal differentiation has provided a unique opportunity for disease modeling and regenerative medicine. Neurospheres are the most commonly used neuroprogenitors for neuronal differentiation, but they often clump in culture, which has always represented a challenge for neurodifferentiation. In this study, we report a novel method and defined culture conditions for generating sub-type or region-specific neurons from human embryonic and induced pluripotent stem cells derived neurosphere without any genetic manipulation. Round and bright-edged neurospheres were generated in a supplemented knockout serum replacement medium (SKSRM with 10% CO2, which doubled the expression of the NESTIN, PAX6 and FOXG1 genes compared with those cultured with 5% CO2. Furthermore, an additional step (AdSTEP was introduced to fragment the neurospheres and facilitate the formation of a neuroepithelial-type monolayer that we termed the “neurosphederm”. The large neural tube-type rosette (NTTR structure formed from the neurosphederm, and the NTTR expressed higher levels of the PAX6, SOX2 and NESTIN genes compared with the neuroectoderm-derived neuroprogenitors. Different layers of cortical, pyramidal, GABAergic, glutamatergic, cholinergic neurons appeared within 27 days using the neurosphederm, which is a shorter period than in traditional neurodifferentiation-protocols (42–60 days. With additional supplements and timeline dopaminergic and Purkinje neurons were also generated in culture too. Furthermore, our in vivo results indicated that the fragmented neurospheres facilitated significantly better neurogenesis in severe combined immunodeficiency (SCID mouse brains compared with the non-fragmented neurospheres. Therefore, this neurosphere-based neurodifferentiation protocol is a valuable tool for studies of neurodifferentiation, neuronal transplantation and high throughput screening assays.

  14. Deletion Mutagenesis and Identification of Causative Mutations in Maize.

    Science.gov (United States)

    Jia, Shangang; Li, Aixia; Zhang, Chi; Holding, David

    2018-01-01

    We describe a method for gamma-irradiation of mature maize seeds to generate mutants with opaque endosperm and reduced kernel fill phenotypes. We also describe methods for mapping mutants and identifying causal gene mutations. Using this method, a population of 1788M2 families and 47 Mo17 × F2s showing stable, segregating, and viable kernel phenotypes was developed. For molecular characterization of the mutants, we utilized a novel functional genomics platform that combines separate Bulked Segregant RNA and exome sequencing data sets (BSREx-seq) to map causative mutations and identify candidate genes within mapping intervals. We also describe the use of exome capture sequencing of F2 mutant and normal pools to perform mapping and candidate gene identification without the need for separate RNA-seq (BSEx-seq). To exemplify the utility of the deletion mutants for functional genomics and provide proof-of-concept for the bioinformatics platform, we summarize the identification of the causative deletion in two mutants. Mutant 937, which was characterized by BSREx-seq, harbors a 6203-bp in-frame deletion covering six exons within the Opaque-1 gene on chromosome 4. Preliminary investigation of opaque mutant 1486 with BSEx-seq shows a tight mapping interval and associated deletion on chromosome 10.

  15. Genetics Home Reference: 22q13.3 deletion syndrome

    Science.gov (United States)

    ... 5 links) Diagnostic Tests Drug Therapy Genetic Counseling Palliative Care Surgery and Rehabilitation Related Information How are genetic ... Veltman JA, de Vries BB. Molecular characterisation of patients with subtelomeric 22q ... L, Enns GM, Hoyme HE. Terminal 22q deletion syndrome: a newly recognized cause of ...

  16. 78 FR 21348 - Procurement List; Additions and Deletions; Recissions

    Science.gov (United States)

    2013-04-10

    ... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Additions and Deletions; Recissions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION: Rescission of Previous Procurement List Decision. SUMMARY: The Committee for Purchase...

  17. Genetics Home Reference: 2q37 deletion syndrome

    Science.gov (United States)

    ... on PubMed or Free article on PubMed Central Casas KA, Mononen TK, Mikail CN, Hassed SJ, Li S, ... 2005 Aug 18. Citation on PubMed Falk RE, Casas KA. Chromosome 2q37 deletion: clinical and molecular aspects. ...

  18. The detection of large deletions or duplications in genomic DNA.

    Science.gov (United States)

    Armour, J A L; Barton, D E; Cockburn, D J; Taylor, G R

    2002-11-01

    While methods for the detection of point mutations and small insertions or deletions in genomic DNA are well established, the detection of larger (>100 bp) genomic duplications or deletions can be more difficult. Most mutation scanning methods use PCR as a first step, but the subsequent analyses are usually qualitative rather than quantitative. Gene dosage methods based on PCR need to be quantitative (i.e., they should report molar quantities of starting material) or semi-quantitative (i.e., they should report gene dosage relative to an internal standard). Without some sort of quantitation, heterozygous deletions and duplications may be overlooked and therefore be under-ascertained. Gene dosage methods provide the additional benefit of reporting allele drop-out in the PCR. This could impact on SNP surveys, where large-scale genotyping may miss null alleles. Here we review recent developments in techniques for the detection of this type of mutation and compare their relative strengths and weaknesses. We emphasize that comprehensive mutation analysis should include scanning for large insertions and deletions and duplications. Copyright 2002 Wiley-Liss, Inc.

  19. 78 FR 24733 - Procurement List, Additions and Deletions

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    2013-04-26

    ... Purchase From People Who Are Blind or Severely Disabled published notices of proposed additions to the... Services Administration. Portable Desktop Clipboard, 9\\1/2\\ W x 1\\1/2\\ D x 13\\1/2\\ H NSN: 7510-00-NIB-2133... for Purchase From People Who Are Blind or Severely Disabled published notices of proposed deletions...

  20. 76 FR 35415 - Procurement List; Proposed Additions and Deletions

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    2011-06-17

    ... Command, Natick, MA. SERVICE: Service Type/Location: Laundry Services, Department of Veterans Affairs... proposing to add products and a service to the Procurement List that will be furnished by nonprofit agencies employing persons who are blind or have other severe disabilities, and deletes products and a service...

  1. 76 FR 14942 - Procurement List; Additions and Deletions

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    2011-03-18

    ... DFAC. Service Type/Location: Laundry & Dry Cleaning Service, F.E. Warren, AFB, WY. NPA: Goodwill... Service Type/Location: Laundry Service, Atlanta VA Medical Center, Decatur, GA. NPA: GINFL Services, Inc...: Additions to and deletions from the Procurement List. SUMMARY: This action adds services to the Procurement...

  2. 75 FR 41449 - Procurement List Additions and Deletion

    Science.gov (United States)

    2010-07-16

    ... Customs and Border Protection, Office of Procurement, Washington, DC Service Type/Locations: Laundry.../Locations: Laundry Service, Naval Hospital System, 2800 Child Street, Jacksonville, FL NPA: GINFL Services...: Additions to and deletion from the Procurement List. SUMMARY: This action adds products and services to the...

  3. 77 FR 31335 - Procurement List; Proposed Additions and Deletion

    Science.gov (United States)

    2012-05-25

    .... Services Service Type/Location: Laundry and Dry Cleaning Service, Buckley Air Force Base Lodging & Medical... products and services to the Procurement List that will be furnished by nonprofit agencies employing persons who are blind or have other severe disabilities, and deletes a service previously provided by such...

  4. 76 FR 62391 - Procurement List; Proposed Additions and Deletions

    Science.gov (United States)

    2011-10-07

    ... Investigation, Washington, DC Service Type/Location: Laundry Service, Stratton Medical Center, 113 Holland Ave... persons who are blind or have other severe disabilities, and deletes services previously furnished by such... entities to furnish the services to the Government. 3. There are no known regulatory alternatives which...

  5. 78 FR 17641 - Procurement List; Proposed Addition and Deletion

    Science.gov (United States)

    2013-03-22

    ... People Who Are Blind or Severely Disabled, 1401 S. Clarke Street, Suite 10800, Arlington, Virginia 22202... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Addition and Deletion AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled. ACTION...

  6. 78 FR 45183 - Procurement List; Proposed Addition and Deletions

    Science.gov (United States)

    2013-07-26

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  7. 78 FR 68823 - Procurement List Proposed Additions and Deletions

    Science.gov (United States)

    2013-11-15

    ... for Purchase From People Who Are Blind or Severely Disabled, 1401 S. Clark Street, Suite 10800... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List Proposed Additions and Deletions AGENCY: Committee for Purchase From People Who Are Blind or Severely Disabled...

  8. 78 FR 32631 - Procurement List; Proposed Additions and Deletions

    Science.gov (United States)

    2013-05-31

    ... People Who Are Blind or Severely Disabled, 1401 S. Clark Street, Suite 10800, Arlington, Virginia 22202... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions and Deletions AGENCY: Committee for Purchase from People Who are Blind or Severely Disabled...

  9. 78 FR 43180 - Procurement List; Proposed Additions and Deletions

    Science.gov (United States)

    2013-07-19

    ... for Purchase From People Who Are Blind or Severely Disabled, 1401 S. Clark Street, Suite 10800... COMMITTEE FOR PURCHASE FROM PEOPLE WHO ARE BLIND OR SEVERELY DISABLED Procurement List; Proposed Additions and Deletions AGENCY: Committee for Purchase from People Who Are Blind or Severely Disabled...

  10. Angiotensin-converting enzyme insertion/deletion gene ...

    Indian Academy of Sciences (India)

    Angiotensin-converting enzyme insertion/deletion gene polymorphism in cystic fibrosis patients. Sabrine Oueslati Sondess Hadj Fredj Hajer Siala Amina Bibi Hajer Aloulou Lamia Boughamoura Khadija Boussetta Sihem Barsaoui Taieb Messaoud. Research Note Volume 95 Issue 1 March 2016 pp 193-196 ...

  11. The insertion/deletion polymorphism of angiotensin-converting ...

    African Journals Online (AJOL)

    The association between type 2 diabetes mellitus (T2DM) and essential hypertension (EH) is not well understood. Both conditions result from an interaction of multiple genetic (ethnic) and environmental (geographical) factors. One possible genetic determinant is the angiotensin-converting enzyme (ACE) insertion/deletion ...

  12. Oncolytic Replication of E1b-Deleted Adenoviruses

    Directory of Open Access Journals (Sweden)

    Pei-Hsin Cheng

    2015-11-01

    Full Text Available Various viruses have been studied and developed for oncolytic virotherapies. In virotherapy, a relatively small amount of viruses used in an intratumoral injection preferentially replicate in and lyse cancer cells, leading to the release of amplified viral particles that spread the infection to the surrounding tumor cells and reduce the tumor mass. Adenoviruses (Ads are most commonly used for oncolytic virotherapy due to their infection efficacy, high titer production, safety, easy genetic modification, and well-studied replication characteristics. Ads with deletion of E1b55K preferentially replicate in and destroy cancer cells and have been used in multiple clinical trials. H101, one of the E1b55K-deleted Ads, has been used for the treatment of late-stage cancers as the first approved virotherapy agent. However, the mechanism of selective replication of E1b-deleted Ads in cancer cells is still not well characterized. This review will focus on three potential molecular mechanisms of oncolytic replication of E1b55K-deleted Ads. These mechanisms are based upon the functions of the viral E1B55K protein that are associated with p53 inhibition, late viralmRNAexport, and cell cycle disruption.

  13. Remarks on Causative Verbs and Object Deletion in English

    Science.gov (United States)

    Onozuka, Hiromi

    2007-01-01

    Rappaport Hovav and Levin [Rappaport Hovav, M., Levin, B., 1998. "Building verb meanings." In: Butt, M., Geuder, W. (Eds.), "The Projection of Arguments: Lexical and Compositional Factors." CSLI Publications, Stanford, pp. 97-134] contend that result verbs disallow object deletion because of their lexical semantic properties. Their point is that…

  14. [An updated review of 1p36 deletion (monosomy) syndrome].

    Science.gov (United States)

    Bello, Sabina; Rodríguez-Moreno, Antonio

    The Monosomy 1p36 deletion syndrome is part of the group of diseases known as Rare Diseases. The objective of the present work is to review the characteristics of Monosomy 1p36 deletion syndrome. The monosomy 1p36 deletion syndrome phenotype includes: dysmorphic craniofacial features; large anterior fontanelle, unibrow, deep-set eyes, epicanthus, wide nasal root/bridge, mandible hypoplasia, abnormal location of the pinna, philtrum and pointed chin; neurological alterations: seizures and hydrocephalus (in some cases). Cerebral malformations: ventricular hypertrophy, increased subarachnoid space, morphological alterations of corpus callosum, cortical atrophy, delays in myelinisation, periventricular leukomalacia and periventricular heterotopia. These alterations produce intellectual disability and delays in motor growth, communication skills, language, social and adaptive behaviour. It is Hearing and vision impairments are also observed in subjects with this syndrome, as well as alterations of cardiac, endocrine and urinary systems and alterations at skin and skeletal level. Approximately 100 cases have been documented since 1981. This rare disease is the most common subtelomeric-micro-deletion syndrome. In situ hybridization with fluorescence (FISH) and array-comparative genomic hybridization (CGH-array) are at present the two best diagnostic techniques. There is currently no effective medical treatment for this disease. Copyright © 2016 Sociedad Chilena de Pediatría. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. 78 FR 73503 - Procurement List Additions and Deletions

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    2013-12-06

    ... by the General Services Administration. NSN: MR 376--Resealable Bags, Holiday, 6.5'' x 5.875''. NSN..., Holiday, 24PC. NPA: Winston-Salem Industries for the Blind, Inc., Winston-Salem, NC. Contracting Activity... disabilities, and deletes a product and services from the Procurement List previously furnished by such...

  16. Genetics Home Reference: distal 18q deletion syndrome

    Science.gov (United States)

    ... 18q deletion syndrome chromosome 18q monosomy chromosome 18q- syndrome De Grouchy syndrome del(18q) syndrome monosomy 18q Related Information How ... MS, Tienari PJ, Wirtavuori KO, Valanne LK. 18q-syndrome: brain MRI shows poor differentiation of gray and white matter on ... RL, Hale DE, Rose SR, Leach RJ, Cody JD. The spectrum ...

  17. Construction of a psb C deletion strain in Synechocystis 6803.

    Science.gov (United States)

    Goldfarb, N; Knoepfle, N; Putnam-Evans, C

    1997-01-01

    Synechocystis 6803 is a cyanobacterium that carries out-oxygenic photosynthesis. We are interested in the introduction of mutations in the large extrinsic loop region of the CP43 protein of Photosystem II (PSII). CP43 appears to be required for the stable assembly of the PSII complex and also appears to play a role in photosynthetic oxygen evolution. Deletion of short segments of the large extrinsic loop results in mutants incapable of evolving oxygen. Alterations in psbC, the gene encoding CP43, are introduced into Synechocystis 6803 by transformation and homologous recombination. Specifically, plasmid constructs bearing the site-directed mutations are introduced into a deletion strain where the portion of the gene encoding the area of mutation has been deleted and replaced by a gene conferring antibiotic resistance. We have constructed a deletion strain of Synechocystis appropriate for the introduction of mutations in the large extrinsic loop of CP43 and have used it successfully to produce site-directed mutants.

  18. 77 FR 60969 - Procurement List; Proposed Additions and Deletions

    Science.gov (United States)

    2012-10-05

    ...., Wichita, KS. Contracting Activity: Defense Logistics Agency Troop Support, Philadelphia, PA. Coverage: C-List for 100% of the requirement of the Department of Defense, as aggregated by the Defense Logistics...., Portsmouth, VA. Contracting Activity: Dept. of the Army, W071 Endist Kansas City, Kansas City, MO. Deletions...

  19. Frequency of heterozygous TET2 deletions in myeloproliferative neoplasms

    Directory of Open Access Journals (Sweden)

    Joseph Tripodi

    2010-09-01

    Full Text Available Joseph Tripodi1, Ronald Hoffman1, Vesna Najfeld2, Rona Weinberg31The Myeloproliferative Disorders Program, Tisch Cancer Institute, Department of Medicine and 2Department of Medicine and Pathology, Mount Sinai School of Medicine, 3The Myeloproliferative Disorders Program, Cellular Therapy Laboratory, The New York Blood Center, New York, NY, USAAbstract: The Philadelphia chromosome (Ph-negative myeloproliferative neoplasms (MPNs, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis, are a group of clonal hematopoietic stem cell disorders with overlapping clinical and cytogenetic features and a variable tendency to evolve into acute leukemia. These diseases not only share overlapping chromosomal abnormalities but also a number of acquired somatic mutations. Recently, mutations in a putative tumor suppressor gene, ten-eleven translocation 2 (TET2 on chromosome 4q24 have been identified in 12% of patients with MPN. Additionally 4q24 chromosomal rearrangements in MPN, including TET2 deletions, have also been observed using conventional cytogenetics. The goal of this study was to investigate the frequency of genomic TET2 rearrangements in MPN using fluorescence in situ hybridization as a more sensitive method for screening and identifying genomic deletions. Among 146 MPN patients, we identified two patients (1.4% who showed a common 4q24 deletion, including TET2. Our observations also indicated that the frequency of TET2 deletion is increased in patients with an abnormal karyotype (5%.Keywords: TET2, myeloproliferative neoplasms, fluorescence in situ hybridization, cytogenetics

  20. Complementary Information Derived from CRISPR Cas9 Mediated Gene Deletion and Suppression. | Office of Cancer Genomics

    Science.gov (United States)

    CRISPR-Cas9 provides the means to perform genome editing and facilitates loss-of-function screens. However, we and others demonstrated that expression of the Cas9 endonuclease induces a gene-independent response that correlates with the number of target sequences in the genome. An alternative approach to suppressing gene expression is to block transcription using a catalytically inactive Cas9 (dCas9). Here we directly compare genome editing by CRISPR-Cas9 (cutting, CRISPRc) and gene suppression using KRAB-dCas9 (CRISPRi) in loss-of-function screens to identify cell essential genes.

  1. Dysfunctional p53 deletion mutants in cell lines derived from Hodgkin's lymphoma

    DEFF Research Database (Denmark)

    Feuerborn, Alexander; Moritz, Constanze; von Bonin, Frederike

    2006-01-01

    Classical Hodgkin's lymphoma (cHL) is a distinct malignancy of the immune system. Despite the progress made in the understanding of the pathology of cHL, the transforming events remain to be elucidated. It has been proposed that mutations in the TP53 gene in biopsy material as well as cell lines ...

  2. Design of a decoupled AP1000 reactor core control system using digital proportional–integral–derivative (PID) control based on a quasi-diagonal recurrent neural network (QDRNN)

    International Nuclear Information System (INIS)

    Wei, Xinyu; Wang, Pengfei; Zhao, Fuyu

    2016-01-01

    Highlights: • We establish a disperse dynamic model for AP1000 reactor core. • A digital PID control based on QDRNN is used to design a decoupling control system. • The decoupling performance is verified and discussed. • The decoupling control system is simulated under the load following operation. - Abstract: The control system of the AP1000 reactor core uses the mechanical shim (MSHIM) strategy, which includes a power control subsystem and an axial power distribution control subsystem. To address the strong coupling between the two subsystems, an interlock between the two subsystems is used, which can only alleviate but not eliminate the coupling. Therefore, sometimes the axial offset (AO) cannot be controlled tightly, and the flexibility of load-following operation is limited. Thus, the decoupling of the original AP1000 reactor core control system is the focus of this paper. First, a two-node disperse dynamic model is established for the AP1000 reactor core to use PID control. Then, a digital PID control system based on a quasi-diagonal recurrent neural network (QDRNN) is designed to decouple the original system. Finally, the decoupling of the control system is verified by the step signal and load-following condition. The results show that the designed control system can decouple the original system as expected and the AO can be controlled much more tightly. Moreover, the flexibility of the load following is increased.

  3. Predictive lethal proarrhythmic risk evaluation using a closed-loop-circuit cell network with human induced pluripotent stem cells derived cardiomyocytes

    Science.gov (United States)

    Nomura, Fumimasa; Hattori, Akihiro; Terazono, Hideyuki; Kim, Hyonchol; Odaka, Masao; Sugio, Yoshihiro; Yasuda, Kenji

    2016-06-01

    For the prediction of lethal arrhythmia occurrence caused by abnormality of cell-to-cell conduction, we have developed a next-generation in vitro cell-to-cell conduction assay, i.e., a quasi in vivo assay, in which the change in spatial cell-to-cell conduction is quantitatively evaluated from the change in waveforms of the convoluted electrophysiological signals from lined-up cardiomyocytes on a single closed loop of a microelectrode of 1 mm diameter and 20 µm width in a cultivation chip. To evaluate the importance of the closed-loop arrangement of cardiomyocytes for prediction, we compared the change in waveforms of convoluted signals of the responses in the closed-loop circuit arrangement with that of the response of cardiomyocyte clusters using a typical human ether a go-go related gene (hERG) ion channel blocker, E-4031. The results showed that (1) waveform prolongation and fluctuation both in the closed loops and clusters increased depending on the E-4031 concentration increase. However, (2) only the waveform signals in closed loops showed an apparent temporal change in waveforms from ventricular tachycardia (VT) to ventricular fibrillation (VF), which is similar to the most typical cell-to-cell conductance abnormality. The results indicated the usefulness of convoluted waveform signals of a closed-loop cell network for acquiring reproducible results acquisition and more detailed temporal information on cell-to-cell conduction.

  4. Design of a decoupled AP1000 reactor core control system using digital proportional–integral–derivative (PID) control based on a quasi-diagonal recurrent neural network (QDRNN)

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Xinyu, E-mail: xyuwei@mail.xjtu.edu.cn; Wang, Pengfei, E-mail: pengfeixiaoli@yahoo.cn; Zhao, Fuyu, E-mail: fuyuzhao_xj@163.com

    2016-08-01

    Highlights: • We establish a disperse dynamic model for AP1000 reactor core. • A digital PID control based on QDRNN is used to design a decoupling control system. • The decoupling performance is verified and discussed. • The decoupling control system is simulated under the load following operation. - Abstract: The control system of the AP1000 reactor core uses the mechanical shim (MSHIM) strategy, which includes a power control subsystem and an axial power distribution control subsystem. To address the strong coupling between the two subsystems, an interlock between the two subsystems is used, which can only alleviate but not eliminate the coupling. Therefore, sometimes the axial offset (AO) cannot be controlled tightly, and the flexibility of load-following operation is limited. Thus, the decoupling of the original AP1000 reactor core control system is the focus of this paper. First, a two-node disperse dynamic model is established for the AP1000 reactor core to use PID control. Then, a digital PID control system based on a quasi-diagonal recurrent neural network (QDRNN) is designed to decouple the original system. Finally, the decoupling of the control system is verified by the step signal and load-following condition. The results show that the designed control system can decouple the original system as expected and the AO can be controlled much more tightly. Moreover, the flexibility of the load following is increased.

  5. Increasing aridity threats to Himalayan alpine ecosystems? A millenial history of hydroclimate from the Tibetan plateau derived from a δ18O tree-ring network

    Science.gov (United States)

    Griessinger, J.

    2015-12-01

    The Tibetan plateau (TP) plays an important role as an elevated heat source responsible for the establishment of the Asias monsoonal systems. Besides the Indian Summer Monsoon (ISM), also the East Asian Summer Monsoon (EASM) is triggering the regional precipitation regimes during the vegetation period from May to September. Within recent decades, fundamental climate changes on the southeastern part of the TP were detected leading to substantial changes within the regional hydrological budget and affecting local ecosystems. By using a spatial network of multicentennial to 1.5 millenial year old tree-ring δ18O time-series from the southeastern part of the TP, the regional climate history as well as the late Holocene monsoonal variability will be presented. Since the main climatically sensitive periods like the Medieval Warm Period and the Little Ice Age are displayed in all chronologies, their typical hydroclimatological characteristics and impacts will be discussed especially in regard to the recent warming trend on the TP and the responsible climatic triggers. Arising from these results, regional impacts and differences of the proposed hydrological changes will be discussed. In addition, first results of a comparison between proxy-based (δ18O) and model-based (re-analysis datasets) trajectory calculations will be presented, trying to give insights in the origin and impact of air masses for the most striking last three decades on the southeastern part of the TP.

  6. Application of Tempered-Stable Time Fractional-Derivative Model to Upscale Subdiffusion for Pollutant Transport in Field-Scale Discrete Fracture Networks

    Directory of Open Access Journals (Sweden)

    Bingqing Lu

    2018-01-01

    Full Text Available Fractional calculus provides efficient physical models to quantify non-Fickian dynamics broadly observed within the Earth system. The potential advantages of using fractional partial differential equations (fPDEs for real-world problems are often limited by the current lack of understanding of how earth system properties influence observed non-Fickian dynamics. This study explores non-Fickian dynamics for pollutant transport in field-scale discrete fracture networks (DFNs, by investigating how fracture and rock matrix properties influence the leading and tailing edges of pollutant breakthrough curves (BTCs. Fractured reservoirs exhibit erratic internal structures and multi-scale heterogeneity, resulting in complex non-Fickian dynamics. A Monte Carlo approach is used to simulate pollutant transport through DFNs with a systematic variation of system properties, and the resultant non-Fickian transport is upscaled using a tempered-stable fractional in time advection–dispersion equation. Numerical results serve as a basis for determining both qualitative and quantitative relationships between BTC characteristics and model parameters, in addition to the impacts of fracture density, orientation, and rock matrix permeability on non-Fickian dynamics. The observed impacts of medium heterogeneity on tracer transport at late times tend to enhance the applicability of fPDEs that may be parameterized using measurable fracture–matrix characteristics.

  7. Sustained release of stem cell factor in a double network hydrogel for ex vivo culture of cord blood-derived CD34+ cells.

    Science.gov (United States)

    Zhang, Yuanhao; Pan, Xiuwei; Shi, Zhen; Cai, Haibo; Gao, Yun; Zhang, Weian

    2018-04-01

    Stem cell factor (SCF) is considered as a commonly indispensable cytokine for proliferation of haematopoietic stem cells (HSCs), which is used in large dosages during ex vivo culture. The work presented here aimed to reduce the consumption of SCF by sustained release but still support cells proliferation and maintain the multipotency of HSCs. Stem cell factor was physically encapsulated within a hyaluronic acid/gelatin double network (HGDN) hydrogel to achieve a slow release rate. CD34 + cells were cultured within the SCF-loaded HGDN hydrogel for 14 days. The cell number, phenotype and functional capacity were investigated after culture. The HGDN hydrogels had desirable properties and encapsulated SCF kept being released for more than 6 days. SCF remained the native bioactivity, and the proliferation of HSCs within the SCF-loaded HGDN hydrogel was not affected, although the consumption of SCF was only a quarter in comparison with the conventional culture. Moreover, CD34 + cells harvested from the SCF-loaded HGDN hydrogels generated more multipotent colony-forming units (CFU-GEMM). The data suggested that the SCF-loaded HGDN hydrogel could support ex vivo culture of HSCs, thus providing a cost-effective culture protocol for HSCs. © 2017 John Wiley & Sons Ltd.

  8. Coastal 'Big Data' and nature-inspired computation: Prediction potentials, uncertainties, and knowledge derivation of neural networks for an algal metric

    Science.gov (United States)

    Millie, David F.; Weckman, Gary R.; Young, William A.; Ivey, James E.; Fries, David P.; Ardjmand, Ehsan; Fahnenstiel, Gary L.

    2013-07-01

    Coastal monitoring has become reliant upon automated sensors for data acquisition. Such a technical commitment comes with a cost; particularly, the generation of large, high-dimensional data streams ('Big Data') that personnel must search through to identify data structures. Nature-inspired computation, inclusive of artificial neural networks (ANNs), affords the unearthing of complex, recurring patterns within sizable data volumes. In 2009, select meteorological and hydrological data were acquired via autonomous instruments in Sarasota Bay, Florida (USA). ANNs estimated continuous chlorophyll (CHL) a concentrations from abiotic predictors, with correlations between measured:modeled concentrations >0.90 and model efficiencies ranging from 0.80 to 0.90. Salinity and water temperature were the principal influences for modeled CHL within the Bay; concentrations steadily increased at temperatures >28° C and were greatest at salinities 6.1 μg CHL L-1 maximized at a salinity of ca. 36.3 and a temperature of ca. 29.5 °C. A 10th-order Chebyshev bivariate polynomial equation was fit (adj. r2 = 0.99, p turbidity, temperature, and salinity (and to lesser degrees, wind speed, wind/current direction, irradiance, and urea-nitrogen) were key variables for quantitative rules in tree formalisms. Taken together, computations enabled knowledge provision for and quantifiable representations of the non-linear relationships between environmental variables and CHL a.

  9. Comprehensive profiling of proteome changes upon sequential deletion of deubiquitylating enzymes

    DEFF Research Database (Denmark)

    Poulsen, Jon W; Madsen, Christian Toft; Young, Clifford

    2012-01-01

    Deubiquitylating enzymes (DUBs) are a large group of proteases that regulate ubiquitin-dependent metabolic pathways by cleaving ubiquitin-protein bonds. Here we present a global study aimed at elucidating the effects DUBs have on protein abundance changes in eukaryotic cells. To this end we compare...... wild-type Saccharomyces cerevisiae to 20 DUB knock-out strains using quantitative proteomics to measure proteome-wide expression of isotope labeled proteins, and analyze the data in the context of known transcription-factor regulatory networks. Overall we find that protein abundances differ widely...... between individual deletion strains, demonstrating that removing just a single component from the complex ubiquitin system causes major changes in cellular protein expression. The outcome of our analysis confirms many of the known biological roles for characterized DUBs such as Ubp3p and Ubp8p, and we...

  10. LEDGF/p75 Deficiency Increases Deletions at the HIV-1 cDNA Ends.

    Science.gov (United States)

    Bueno, Murilo T D; Reyes, Daniel; Llano, Manuel

    2017-09-15

    Processing of unintegrated linear HIV-1 cDNA by the host DNA repair system results in its degradation and/or circularization. As a consequence, deficient viral cDNA integration generally leads to an increase in the levels of HIV-1 cDNA circles containing one or two long terminal repeats (LTRs). Intriguingly, impaired HIV-1 integration in LEDGF/p75-deficient cells does not result in a correspondent increase in viral cDNA circles. We postulate that increased degradation of unintegrated linear viral cDNA in cells lacking the lens epithelium-derived growth factor (LEDGF/p75) account for this inconsistency. To evaluate this hypothesis, we characterized the nucleotide sequence spanning 2-LTR junctions isolated from LEDGF/p75-deficient and control cells. LEDGF/p75 deficiency resulted in a significant increase in the frequency of 2-LTRs harboring large deletions. Of note, these deletions were dependent on the 3' processing activity of integrase and were not originated by aberrant reverse transcription. Our findings suggest a novel role of LEDGF/p75 in protecting the unintegrated 3' processed linear HIV-1 cDNA from exonucleolytic degradation.

  11. Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesis

    Science.gov (United States)

    Xuan, Shouhong; Borok, Matthew J.; Decker, Kimberly J.; Battle, Michele A.; Duncan, Stephen A.; Hale, Michael A.; Macdonald, Raymond J.; Sussel, Lori

    2012-01-01

    Pancreatic agenesis is a human disorder caused by defects in pancreas development. To date, only a few genes have been linked to pancreatic agenesis in humans, with mutations in pancreatic and duodenal homeobox 1 (PDX1) and pancreas-specific transcription factor 1a (PTF1A) reported in only 5 families with described cases. Recently, mutations in GATA6 have been identified in a large percentage of human cases, and a GATA4 mutant allele has been implicated in a single case. In the mouse, Gata4 and Gata6 are expressed in several endoderm-derived tissues, including the pancreas. To analyze the functions of GATA4 and/or GATA6 during mouse pancreatic development, we generated pancreas-specific deletions of Gata4 and Gata6. Surprisingly, loss of either Gata4 or Gata6 in the pancreas resulted in only mild pancreatic defects, which resolved postnatally. However, simultaneous deletion of both Gata4 and Gata6 in the pancreas caused severe pancreatic agenesis due to disruption of pancreatic progenitor cell proliferation, defects in branching morphogenesis, and a subsequent failure to induce the differentiation of progenitor cells expressing carboxypeptidase A1 (CPA1) and neurogenin 3 (NEUROG3). These studies address the conserved and nonconserved mechanisms underlying GATA4 and GATA6 function during pancreas development and provide a new mouse model to characterize the underlying developmental defects associated with pancreatic agenesis. PMID:23006325

  12. Deletion affecting band 7q36 not associated with holoprosencephaly

    Energy Technology Data Exchange (ETDEWEB)

    Ebrahim, S.A.D.; Krivchenia, E.; Mohamed, A.N. [Wayne State Univ., Detroit, MI (United States)] [and others

    1994-09-01

    Although the appearance of 7q36 aberrations have been postulated to be responsible for holoprosencephaly (HPE), the presence of a de novo 7q36 deletion in fetus without HPE has not been reported. We report the first case of a fetus with 7q36 deletion but lacking HPE. Ultrasound examination of a 25-year-old G3P1 Caucasian female showed small head circumference with microcephaly at 28 weeks. Decreased amniotic fluid volume, bilateral renal dilatation and abnormal facial features were also noted. Chromosome analysis after cordocentesis showed an abnormal female karyotype with a deletion involving the chromosome band 7q36, 46,XX,del(7)(q36). Chromosome studies on the biological parents were normal. In view of the chromosome finding and after extensive counseling, the couple elected to terminate the pregnancy. The chromosome findings were confirmed by fetal blood chromosome analysis at termination. Post-mortem examination confirmed dysmorphic features including a depressed nasal bridge and large flat ears with no lobules, but no cleft lip or palate was noted. Internal abnormalities included a bicuspid pulmonary valve and abnormally located lungs. The brain weighed 190g (249 {plus_minus} 64g expected) and had symmetric cerebral hemispheres without evidence of HPE or other gross or microscopic malformation, except focal cerebellar cortical dysplasia. In summary, our patient showed a deletion of the same chromosomal band implicated in HPE but lacked HPE. This finding indicates that 7q36 deletion may be seen in the absence of HPE and suggests that other genetic mechanisms may be responsible for HPE in this setting.

  13. Rare copy number deletions predict individual variation in intelligence.

    Directory of Open Access Journals (Sweden)

    Ronald A Yeo

    2011-01-01

    Full Text Available Phenotypic variation in human intellectual functioning shows substantial heritability, as demonstrated by a long history of behavior genetic studies. Many recent molecular genetic studies have attempted to uncover specific genetic variations responsible for this heritability, but identified effects capture little variance and have proven difficult to replicate. The present study, motivated an interest in "mutation load" emerging from evolutionary perspectives, examined the importance of the number of rare (or infrequent copy number variations (CNVs, and the total number of base pairs included in such deletions, for psychometric intelligence. Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77 had been administered the Wechsler Abbreviated Scale of Intelligence (WASI. After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = -.30, p = .01. As prior studies have indicated greater heritability in individuals with relatively higher parental socioeconomic status (SES, we also examined the impact of ethnicity (Anglo/White vs. Other, as a proxy measure of SES; these groups did not differ on any genetic variable. This categorical variable significantly moderated the effect of length of deletions on intelligence, with larger effects being noted in the Anglo/White group. Overall, these results suggest that rare deletions (between 5% and 1% population frequency or less adversely affect intellectual functioning, and that pleotropic effects might partly account for the association of intelligence with health and mental health status. Significant limitations of this research, including issues of generalizability and CNV measurement, are discussed.

  14. Rare Copy Number Deletions Predict Individual Variation in Intelligence

    Science.gov (United States)

    Yeo, Ronald A.; Gangestad, Steven W.; Liu, Jingyu; Calhoun, Vince D.; Hutchison, Kent E.

    2011-01-01

    Phenotypic variation in human intellectual functioning shows substantial heritability, as demonstrated by a long history of behavior genetic studies. Many recent molecular genetic studies have attempted to uncover specific genetic variations responsible for this heritability, but identified effects capture little variance and have proven difficult to replicate. The present study, motivated an interest in “mutation load” emerging from evolutionary perspectives, examined the importance of the number of rare (or infrequent) copy number variations (CNVs), and the total number of base pairs included in such deletions, for psychometric intelligence. Genetic data was collected using the Illumina 1MDuoBeadChip Array from a sample of 202 adult individuals with alcohol dependence, and a subset of these (N = 77) had been administered the Wechsler Abbreviated Scale of Intelligence (WASI). After removing CNV outliers, the impact of rare genetic deletions on psychometric intelligence was investigated in 74 individuals. The total length of the rare deletions significantly and negatively predicted intelligence (r = −.30, p = .01). As prior studies have indicated greater heritability in individuals with relatively higher parental socioeconomic status (SES), we also examined the impact of ethnicity (Anglo/White vs. Other), as a proxy measure of SES; these groups did not differ on any genetic variable. This categorical variable significantly moderated the effect of length of deletions on intelligence, with larger effects being noted in the Anglo/White group. Overall, these results suggest that rare deletions (between 5% and 1% population frequency or less) adversely affect intellectual functioning, and that pleotropic effects might partly account for the association of intelligence with health and mental health status. Significant limitations of this research, including issues of generalizability and CNV measurement, are discussed. PMID:21298096

  15. A VNTR element associated with steroid sulfatase gene deletions stimulates recombination in cultured cells

    Energy Technology Data Exchange (ETDEWEB)

    Gong, Y.; Li, X.M.; Shapiro, L.J. [UCSF School of Medicine, San Francisco, CA (United States)] [and others

    1994-09-01

    Steroid sulfatase deficiency is a common genetic disorder, with a prevalence of approximately one in every 3500 males world wide. About 90% of these patients have complete gene deletions, which appear to result from recombination between members of a low-copy repeat family (CRI-232 is the prototype) that flank the gene. RU1 and RU2 are two VNTR elements found within each of these family members. RU1 consists of 30 bp repeating units and its length shows minimal variation among individuals. The RU2 element consists of repeating sequences which are highly asymmetric, with about 90% purines and no C`s on one strand, and range from 0.6 kb to over 23 kb among different individuals. We conducted a study to determine if the RU1 or RU2 elements can promote recombination in an in vivo test system. We inserted these elements adjacent to the neo gene in each of two pSV2neo derivatives, one of which has a deletion in the 5{prime} portion of the neo gene and the other having a deletion in the 3{prime} portion. These plasmids were combined and used to transfect EJ cells. Survival of cells in G418 indicates restoration of a functional neo gene by recombination between two deletion constructs. Thus counting G418 resistant colonies gives a quantitative measure of the enhancement of recombination by the inserted VNTR elements. The results showed no effect on recombination by the inserted RU1 element (compared to the insertion of a nonspecific sequence), while the RU2 element stimulated recombination by 3.5-fold (P<0.01). A separate set of constructs placed RU1 or RU2 within the intron of an exon trapping vector. Following tranfection of cells, recombination events were monitored by a PCR assay that detected the approximation of primer binding sites (as a result of recombination). These studies showed that, as in the first set of experiments, the highly variable RU2 element is capable of stimulating somatic recombination in mammalian cells.

  16. A programming language study and an implementation of a simulation system with formal derivation. Application to nuclear reactors, control systems and elecronic networks

    International Nuclear Information System (INIS)

    Nakhle, Michel.

    1979-06-01

    Physical systems simulation requires a lot of information about the controlled process, and the mathematical approach must be appropriate. On the other hand, the parameters describing most systems components are nonlinear and time dependent. Moreover the differential equations describing them are 'stiff' equations of high order. The scope of the study is the description of the NEPTUNIX language and the differential equations. Most of the algorithms used, and the programs implementing these algorithms, are dealt with. Examples of nuclear reactors and mechanical processes simulation are investigated. NEPTUNIX handles a given mathematical description of a continuous system such as: f (x, x(.), t) = 0. Even more, symbolic derivation is performed automatically in order to compute the jacobian associated with the system, requisite for the numerical integration. So, for large systems the manual method for computer the jacobian and the classical method of differentiation are avoided, the former being tiresome and consuming of human time and the latter being costly in run time. The jacobian evaluated in this way is dealt with, by the approach of sparse matrices. Every element of this matrix is assigned a type attribute to improve time execution. Moreover, this is done only once, for a physical system which is described by a mathematical model which topology is invariant. The results of this process are sayed on a suitable device ready for performing repeated simulations [fr

  17. Restoration of half the normal dystrophin sequence in a double-deletion Duchenne muscular dystrophy family

    Energy Technology Data Exchange (ETDEWEB)

    Hoop, R.C.; Schwartz, L.S.; Hoffman, E.P. [Univ. of Pittsburgh School of Medicine, Pittsburgh, PA (United States); Russo, L.S. [Univ. of Florida, Jacksonville, FL (United States); Riconda, D.L. [Orlando Regional Medical Center, Orlando, FL (United States)

    1994-02-01

    Two male cousins with Duchenne muscular dystrophy were found to have different maternal dystrophin gene haplotypes and different deletion mutations. One propositus showed two noncontiguous deletions-one in the 5{prime}, proximal deletional hotspot region, and the other in the 3{prime}, more distal deletional hotspot region. The second propositus showed only the 5{prime} deletion. Using multiple fluorescent exon dosage and fluorescent multiplex CA repeat linkage analyses, the authors show that the mother of each propositus carries both deletions on the same grandmaternal X chromosome. This paradox is explained by a single recombinational event between the 2 deleted regions of one of the carrier`s dystrophin genes, giving rise to a son with a partially {open_quotes}repaired{close_quotes} gene retaining only the 5{prime} deletion. 20 refs., 4 figs.

  18. Sequence homology at the breakpoint and clinical phenotype of mitochondrial DNA deletion syndromes.

    Science.gov (United States)

    Sadikovic, Bekim; Wang, Jing; El-Hattab, Ayman W; Landsverk, Megan; Douglas, Ganka; Brundage, Ellen K; Craigen, William J; Schmitt, Eric S; Wong, Lee-Jun C

    2010-12-20

    Mitochondrial DNA (mtDNA) deletions are a common cause of mitochondrial disorders. Large mtDNA deletions can lead to a broad spectrum of clinical features with different age of onset, ranging from mild mitochondrial myopathies (MM), progressive external ophthalmoplegia (PEO), and Kearns-Sayre syndrome (KSS), to severe Pearson syndrome. The aim of this study is to investigate the molecular signatures surrounding the deletion breakpoints and their association with the clinical phenotype and age at onset. MtDNA deletions in 67 patients were characterized using array comparative genomic hybridization (aCGH) followed by PCR-sequencing of the deletion junctions. Sequence homology including both perfect and imperfect short repeats flanking the deletion regions were analyzed and correlated with clinical features and patients' age group. In all age groups, there was a significant increase in sequence homology flanking the deletion compared to mtDNA background. The youngest patient group (deletion distribution in size and locations, with a significantly lower sequence homology flanking the deletion, and the highest percentage of deletion mutant heteroplasmy. The older age groups showed rather discrete pattern of deletions with 44% of all patients over 6 years old carrying the most common 5 kb mtDNA deletion, which was found mostly in muscle specimens (22/41). Only 15% (3/20) of the young patients (deletion, which is usually present in blood rather than muscle. This group of patients predominantly (16 out of 17) exhibit multisystem disorder and/or Pearson syndrome, while older patients had predominantly neuromuscular manifestations including KSS, PEO, and MM. In conclusion, sequence homology at the deletion flanking regions is a consistent feature of mtDNA deletions. Decreased levels of sequence homology and increased levels of deletion mutant heteroplasmy appear to correlate with earlier onset and more severe disease with multisystem involvement.

  19. Exonic deletion of OPHN1 resulting in seizures, intellectual disability, and brain malformations

    Directory of Open Access Journals (Sweden)

    Larson A

    2014-07-01

    Full Text Available Austin Larson,1 Jamie LeRoux,2 Ellen Roy Elias11Department of Pediatrics, University of Colorado Denver Anschutz Medical Campus, Aurora, CO, USA; 2Colorado Genetics Laboratory, Denver, CO, USAAbstract: We report the case of a 9-year-old boy with autism, intellectual disability, and complex partial seizures as well as cerebellar vermian hypoplasia, caudate nucleus hypoplasia, and ventriculomegaly. He was found to have a deletion within the oligophrenin 1 gene (OPHN1, affecting exons 2–5. OPHN1 mutations result in a rare but well-characterized syndrome of neuroanatomical anomalies, epilepsy, and intellectual disability. This is a novel mutation in OPHN1 that adds to the spectrum of pathogenic variants of the gene. Additionally, the case illustrates the significant benefit that patients and families can derive from a definitive genetic diagnosis, even in the absence of direct therapeutic interventions.Keywords: X-linked intellectual disability, autism, cerebellar hypoplasia, chromosomal microarray, oligophrenin 1

  20. Differentiated psychopharmacological treatment in three genetic subtypes of 22q11.2 deletion syndrome

    NARCIS (Netherlands)

    Verhoeven, W.M.A.; Egger, J.I.M.; Leeuw, N. de

    2017-01-01

    Introduction: The 22q11.2 deletion syndrome (22q11DS), mostly caused by the common deletion including the TBX- and COMT-genes (LCR22A-D), is highly associated with somatic anomalies. The distal deletion (distal of LCR22D) comprises the MAPK1-gene and is associated with specific heart defects. The

  1. 41 CFR 51-6.8 - Deletion of items from the Procurement List.

    Science.gov (United States)

    2010-07-01

    ... 41 Public Contracts and Property Management 1 2010-07-01 2010-07-01 true Deletion of items from...-PROCUREMENT PROCEDURES § 51-6.8 Deletion of items from the Procurement List. (a) When a central nonprofit... shall notify the Committee staff immediately. Before reaching a decision to request a deletion of an...

  2. 36 CFR 902.14 - Deletion of nondiscloseable information from requested records.

    Science.gov (United States)

    2010-07-01

    ... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Deletion of nondiscloseable... AVENUE DEVELOPMENT CORPORATION FREEDOM OF INFORMATION ACT General Administration § 902.14 Deletion of... segregable after deletion of the nondiscloseable portions, will be released. If the information in the...

  3. 46 CFR 67.513 - Application for evidence of deletion from documentation.

    Science.gov (United States)

    2010-10-01

    ... 46 Shipping 2 2010-10-01 2010-10-01 false Application for evidence of deletion from documentation... AND MEASUREMENT OF VESSELS DOCUMENTATION OF VESSELS Fees § 67.513 Application for evidence of deletion from documentation. An application fee is charged for evidence of deletion from documentation in...

  4. 14 CFR 1206.202 - Deletion of segregable portions of a record.

    Science.gov (United States)

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Deletion of segregable portions of a record... AVAILABILITY OF AGENCY RECORDS TO MEMBERS OF THE PUBLIC Records Available § 1206.202 Deletion of segregable... that indication would harm an interest protected by the exemption in Subpart 3 under which the deletion...

  5. 32 CFR 310.34 - Amendment and deletion of system notices.

    Science.gov (United States)

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Amendment and deletion of system notices. 310.34... (CONTINUED) PRIVACY PROGRAM DOD PRIVACY PROGRAM Publication Requirements § 310.34 Amendment and deletion of... system. (see § 310.32(q)). (c) Deletion of system notices. (1) Whenever a system is discontinued...

  6. 19 CFR 176.22 - Deletion of protest or entry number.

    Science.gov (United States)

    2010-04-01

    ... 19 Customs Duties 2 2010-04-01 2010-04-01 false Deletion of protest or entry number. 176.22... Facts § 176.22 Deletion of protest or entry number. If any protest number or entry number is to be... authorized official making and approving the deletion. [T.D. 70-181, 35 FR 13433, Aug. 22, 1970] ...

  7. 47 CFR 76.1601 - Deletion or repositioning of broadcast signals.

    Science.gov (United States)

    2010-10-01

    ... 47 Telecommunication 4 2010-10-01 2010-10-01 false Deletion or repositioning of broadcast signals... RADIO SERVICES MULTICHANNEL VIDEO AND CABLE TELEVISION SERVICE Notices § 76.1601 Deletion or... to § 76.1601: No deletion or repositioning of a local commercial television station shall occur...

  8. Partial USH2A deletions contribute to Usher syndrome in Denmark

    DEFF Research Database (Denmark)

    Dad, Shzeena; Rendtorff, Nanna Dahl; Kann, Erik

    2015-01-01

    deletions identified in USH2A. Our results suggest that USH2 is caused by USH2A exon deletions in a small fraction of the patients, whereas deletions or duplications in PCDH15 might be rare in Danish Usher patients.European Journal of Human Genetics advance online publication, 25 March 2015; doi:10.1038...

  9. Mitochondrial DNA deletion mutations in adult mouse cardiac side population cells

    International Nuclear Information System (INIS)

    Lushaj, Entela B.; Lozonschi, Lucian; Barnes, Maria; Anstadt, Emily; Kohmoto, Takushi

    2012-01-01

    We investigated the presence and potential role of mitochondrial DNA (mtDNA) deletion mutations in adult cardiac stem cells. Cardiac side population (SP) cells were isolated from 12-week-old mice. Standard polymerase chain reaction (PCR) was used to screen for the presence of mtDNA deletion mutations in (a) freshly isolated SP cells and (b) SP cells cultured to passage 10. When present, the abundance of mtDNA deletion mutation was analyzed in single cell colonies. The effect of different levels of deletion mutations on SP cell growth and differentiation was determined. MtDNA deletion mutations were found in both freshly isolated and cultured cells from 12-week-old mice. While there was no significant difference in the number of single cell colonies with mtDNA deletion mutations from any of the groups mentioned above, the abundance of mtDNA deletion mutations was significantly higher in the cultured cells, as determined by quantitative PCR. Within a single clonal cell population, the detectable mtDNA deletion mutations were the same in all cells and unique when compared to deletions of other colonies. We also found that cells harboring high levels of mtDNA deletion mutations (i.e. where deleted mtDNA comprised more than 60% of total mtDNA) had slower proliferation rates and decreased differentiation capacities. Screening cultured adult stem cells for mtDNA deletion mutations as a routine assessment will benefit the biomedical application of adult stem cells.

  10. 31 CFR 363.144 - May I delete a pending transaction involving a certificate of indebtedness?

    Science.gov (United States)

    2010-07-01

    ... 31 Money and Finance: Treasury 2 2010-07-01 2010-07-01 false May I delete a pending transaction... I delete a pending transaction involving a certificate of indebtedness? (a) You may delete a pending... a pending purchase of a security using a certificate of indebtedness as payment. (c) You may not...

  11. Common Deletion (CD) in mitochondrial DNA of irradiated rat heart

    Energy Technology Data Exchange (ETDEWEB)

    Siqueira, Raquel Gomes; Ferreira-Machado, Samara C.; Almeida, Carlos E.V. de, E-mail: raquelgsiqueira@gmail.com [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biologia Roberto Alcanatara Gomes. Lab. de Ciencias Radiologicas; Silva, Dayse A. da; Carvalho, Elizeu F. de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biologia Roberto Alcanatara Gomes. Lab. de Diagnosticos por DNA; Melo, Luiz D.B. de [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Instituto de Biofisica Carlos Chagas Filho. Lab. de Parasitologia Molecular

    2014-05-15

    The purpose of this study was to map the common deletion (CD) area in mtDNA and investigate the levels of this deletion in irradiated heart. The assays were developed in male Wistar rats that were irradiated with three different single doses (5, 10 or 15 Gy) delivered directly to the heart and the analyses were performed at various times post-irradiation (3, 15 or 120 days). The CDs area were sequenced and the CD quantified by real-time PCR. Our study demonstrated that the CD levels progressively decreased from the 3rd until the 15th day after irradiation, and then increased thereafter. Additionally, it was observed that the levels of CD are modulated differently according to the different categories of doses (moderate and high). This study demonstrated an immediate response to ionizing radiation, measured by the presence of mutations in the CD area and a decrease in the CD levels. (author)

  12. Two novel deletions (array CGH findings) in pigment dispersion syndrome.

    Science.gov (United States)

    Mikelsaar, Ruth; Molder, Harras; Bartsch, Oliver; Punab, Margus

    2007-12-01

    We report the first male with pigment dispersion syndrome and a balanced translocation t(10;15)(p11.1;q11.1). Cytogenetic analyses using Giemsa banding and FISH methods, and array CGH were performed. Array CGH analyses did not show altered DNA sequences in the breakpoints of the translocation, but revealed two novel deletions in 2q22.1 and 18q22.1. We suppose that the coexistence of t(10;15) and pigment dispersion syndrome in our patient is a coincidence. The deletion in 2q22.1, where the gene LRP1B has been located, may play a major role in the dysembryogenesis of the eye and cause the disorder.

  13. Detection of mitochondrial DNA deletions in human cells induced by ionizing radiation

    International Nuclear Information System (INIS)

    Liu, Qing-Jie; Feng, Jiang-Bin; Lu, Xue; Li, Yu-Wen; Chen, De-Qing

    2008-01-01

    Full text: Purpose: To screen the novel mitochondrial DNA (mt DNA) deletions induced by ionizing radiation, and analyze the several kinds of mt DNA deletions, known as 3895 bp, 889 bp, 7436 bp or 4934 bp deletions. Methods: Long-range PCR with two pairs of primers, which could amplify the whole human mitochondrial genome, was used to analyze the lymphoblastoid cell line before and after exposed to 10 Gy 60 Co γ-rays. The limited condition PCR was used to certify the possible mt DNA deletion showed by long-range PCR. The PCR products were purified, cloned, sequenced and the sequence result were BLASTed. Regular PCR or nest-PCR were used to analyze the 3895 bp, 889 bp, 7436 bp or 4934 bp deletions before and after radiation exposure. The final PCR products were purified, sequenced and BALSTed on standard human mitochondrial genome sequence database. Results: (1) The predicted bands of mt DNA were observed on the control cell lines, and the possible mt DNA deletions were also detected on the irradiated cell lines. The deletions were certified by the limited condition PCR. The sequence BLAST results of the cloned PCR products showed that two kinds of deletions, 7455 bp deletion (nt 475-7929 in heavy strand) and 9225 bp deletion (nt 7714-369 in heavy strand), which were between two 8 bp direct repeats. Further bioinformatics analysis showed that the two deletions were novel deletions. (2) The 889 bp and 3895 bp deletion were not detected for the cell line samples not exposed to 60 Co γ-rays. The 889 bp and 3895 bp deletions were detected on samples exposed to 10 Gy 60 Co γ-rays. The BALST results showed that the 889 bp and 3895 deletions flanked nt 11688 bp-12576, nt 548 bp-4443, respectively. The 7436 bp deletion levels were not changed much before and after irradiation. (3) The 4934 bp deletions had the same pattern as 7436 bp deletion, but it could induced by radiation. Conclusions: Ionizing radiation could induce the human lymphoblastoid two novel mt DNA

  14. Remarks on Causative Verbs and Object Deletion in English

    OpenAIRE

    Onozuka, Hiromi

    2007-01-01

    Rappaport Hovav and Levin (1998) contend that result verbs disallow object deletion becauseof their lexical semantic properties. Their point is that the distinction between result verbs andmanner verbs with their different event structure representation constitutes the important factorwhich dictates the possibility of the variation of argument realization, of which object deletionrepresents one instance. Responding to their claim, Goldberg (2001) presents the evidencewhich mainly concerns the...

  15. Novel deletion alleles carrying CYP21A1P/A2 chimeric genes in Brazilian patients with 21-hydroxylase deficiency

    Directory of Open Access Journals (Sweden)

    Guerra-Júnior Gil

    2010-06-01

    Full Text Available Abstract Background Congenital adrenal hyperplasia due to 21-hydroxylase deficiency is caused by deletions, large gene conversions or mutations in CYP21A2 gene. The human gene is located at 6p21.3 within a locus containing the genes for putative serine/threonine Kinase RP, complement C4, steroid 21-hydroxylase CYP21 tenascin TNX, normally, in a duplicated cluster known as RCCX module. The CYP21 extra copy is a pseudogene (CYP21A1P. In Brazil, 30-kb deletion forming monomodular alleles that carry chimeric CYP21A1P/A2 genes corresponds to ~9% of disease-causing alleles. Such alleles are considered to result from unequal crossovers within the bimodular C4/CYP21 locus. Depending on the localization of recombination breakpoint, different alleles can be generated conferring the locus high degree of allelic variability. The purpose of the study was to investigate the variability of deleted alleles in patients with 21-hydroxylase deficiency. Methods We used different techniques to investigate the variability of 30-kb deletion alleles in patients with 21-hydroxylase deficiency. Alleles were first selected after Southern blotting. The composition of CYP21A1P/A2 chimeric genes was investigated by ASO-PCR and MLPA analyses followed by sequencing to refine the location of recombination breakpoints. Twenty patients carrying at least one allele with C4/CYP21 30-kb deletion were included in the study. Results An allele carrying a CYP21A1P/A2 chimeric gene was found unusually associated to a C4B/C4A Taq I 6.4-kb fragment, generally associated to C4B and CYP21A1P deletions. A novel haplotype bearing both p.P34L and p.H62L, novel and rare mutations, respectively, was identified in exon 1, however p.P30L, the most frequent pseudogene-derived mutation in this exon, was absent. Four unrelated patients showed this haplotype. Absence of p.P34L in CYP21A1P of normal controls indicated that it is not derived from pseudogene. In addition, the combination of different

  16. SHANK1 Deletions in Males with Autism Spectrum Disorder.

    Science.gov (United States)

    Sato, Daisuke; Lionel, Anath C; Leblond, Claire S; Prasad, Aparna; Pinto, Dalila; Walker, Susan; O'Connor, Irene; Russell, Carolyn; Drmic, Irene E; Hamdan, Fadi F; Michaud, Jacques L; Endris, Volker; Roeth, Ralph; Delorme, Richard; Huguet, Guillaume; Leboyer, Marion; Rastam, Maria; Gillberg, Christopher; Lathrop, Mark; Stavropoulos, Dimitri J; Anagnostou, Evdokia; Weksberg, Rosanna; Fombonne, Eric; Zwaigenbaum, Lonnie; Fernandez, Bridget A; Roberts, Wendy; Rappold, Gudrun A; Marshall, Christian R; Bourgeron, Thomas; Szatmari, Peter; Scherer, Stephen W

    2012-05-04

    Recent studies have highlighted the involvement of rare (number variations and point mutations in the genetic etiology of autism spectrum disorder (ASD); these variants particularly affect genes involved in the neuronal synaptic complex. The SHANK gene family consists of three members (SHANK1, SHANK2, and SHANK3), which encode scaffolding proteins required for the proper formation and function of neuronal synapses. Although SHANK2 and SHANK3 mutations have been implicated in ASD and intellectual disability, the involvement of SHANK1 is unknown. Here, we assess microarray data from 1,158 Canadian and 456 European individuals with ASD to discover microdeletions at the SHANK1 locus on chromosome 19. We identify a hemizygous SHANK1 deletion that segregates in a four-generation family in which male carriers--but not female carriers--have ASD with higher functioning. A de novo SHANK1 deletion was also detected in an unrelated male individual with ASD with higher functioning, and no equivalent SHANK1 mutations were found in >15,000 controls (p = 0.009). The discovery of apparent reduced penetrance of ASD in females bearing inherited autosomal SHANK1 deletions provides a possible contributory model for the male gender bias in autism. The data are also informative for clinical-genetics interpretations of both inherited and sporadic forms of ASD involving SHANK1. Copyright © 2012 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

  17. A Large PROP1 Gene Deletion in a Turkish Pedigree

    Directory of Open Access Journals (Sweden)

    Suheyla Gorar

    2018-01-01

    Full Text Available Pituitary-specific paired-like homeodomain transcription factor, PROP1, is associated with multiple pituitary hormone deficiency. Alteration of the gene encoding the PROP1 may affect somatotropes, thyrotropes, and lactotropes, as well as gonadotropes and corticotropes. We performed genetic analysis of PROP1 gene in a Turkish pedigree with three siblings who presented with short stature. Parents were first degree cousins. Index case, a boy, had somatotrope, gonadotrope, thyrotrope, and corticotrope deficiency. However, two elder sisters had somatotroph, gonadotroph, and thyrotroph deficiency and no corticotroph deficiency. On pituitary magnetic resonance, partial empty sella was detected with normal bright spot in all siblings. In genetic analysis, we found a gross deletion involving PROP1 coding region. In conclusion, we report three Turkish siblings with a gross deletion in PROP1 gene. Interestingly, although little boy with combined pituitary hormone deficiency has adrenocorticotropic hormone (ACTH deficiency, his elder sisters with the same gross PROP1 deletion have no ACTH deficiency. This finding is in line with the fact that patients with PROP1 mutations may have different phenotype/genotype correlation.

  18. A case of 18p deletion syndrome after blepharoplasty

    Directory of Open Access Journals (Sweden)

    Xu LJ

    2017-01-01

    Full Text Available Li-juan Xu,1 Lv-xian Wu,2 Qing Yuan,3 Zhi-gang Lv,1 Xue-yan Jiang2 1Department of Opthalmology, 2Department of Pediatrics, 3Department of Clinical Laboratory, Jinhua Central Hospital, Jinhua, Zhejiang, People’s Republic of China Objective: The deletion of the short arm of chromosome 18 is thought to be one of the rare chromosomal aberrations. Here, we report a case to review this disease.Case report: The proband is a five-and-a-half-year-old girl who has had phenotypes manifested mainly by ptosis, broad face, broad neck with low posterior hairline, mental retardation, short stature, and other malformations. Chromosomal analysis for her mother showed a normal karyotype. Her father and younger brother were phenotypically normal.Result: Phenotypical features were quite similar throughout other cases and in accordance with the usual phenotype of del(18p suggested within the same cases and among the del(18p cases described. She underwent blepharoplasty, which improved her appearance.Conclusion: 18p deletion syndrome is diagnosed by gene analysis. Plastic surgeries for improving the appearance might be an option for these patients. Keywords: chromosome, deletion, blepharoplasty

  19. Distinct phenotype of PHF6 deletions in females.

    Science.gov (United States)

    Di Donato, N; Isidor, B; Lopez Cazaux, S; Le Caignec, C; Klink, B; Kraus, C; Schrock, E; Hackmann, K

    2014-02-01

    We report on two female patients carrying small overlapping Xq26.2 deletions of 100 kb and 270 kb involving the PHF6 gene. Mutations in PHF6 have been reported in individuals with Borjeson-Forssman-Lehmann syndrome, a condition present almost exclusively in males. Two very recent papers revealed de novo PHF6 defects in seven female patients with intellectual disability and a phenotype resembling Coffin-Siris syndrome (sparse hair, bitemporal narrowing, arched eyebrows, synophrys, high nasal root, bulbous nasal tip, marked clinodactyly with the hypoplastic terminal phalanges of the fifth fingers and cutaneous syndactyly of the toes, Blaschkoid linear skin hyperpigmentation, dental anomalies and occasional major malformations). The clinical presentation of these patients overlaps completely with our first patient, who carries a germline deletion involving PHF6. The second patient has a mosaic deletion and presented with a very mild phenotype of PHF6 loss in females. Our report confirms that PHF6 loss in females results in a recognizable phenotype overlapping with Coffin-Siris syndrome and distinct from Borjeson-Forssman-Lehmann syndrome. We expand the clinical spectrum and provide the first summary of the recommended medical evaluation. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  20. Deletion of ameloblastin exon 6 is associated with amelogenesis imperfecta.

    Science.gov (United States)

    Poulter, James A; Murillo, Gina; Brookes, Steven J; Smith, Claire E L; Parry, David A; Silva, Sandra; Kirkham, Jennifer; Inglehearn, Chris F; Mighell, Alan J

    2014-10-15

    Amelogenesis imperfecta (AI) describes a heterogeneous group of inherited dental enamel defects reflecting failure of normal amelogenesis. Ameloblastin (AMBN) is the second most abundant enamel matrix protein expressed during amelogenesis. The pivotal role of AMBN in amelogenesis has been confirmed experimentally using mouse models. However, no AMBN mutations have been associated with human AI. Using autozygosity mapping and exome sequencing, we identified genomic deletion of AMBN exon 6 in a second cousin consanguineous family with three of the six children having hypoplastic AI. The genomic deletion corresponds to an in-frame deletion of 79 amino acids, shortening the protein from 447 to 368 residues. Exfoliated primary teeth (unmatched to genotype) were available from family members. The most severely affected had thin, aprismatic enamel (similar to that reported in mice homozygous for Ambn lacking exons 5 and 6). Other teeth exhibited thicker but largely aprismatic enamel. One tooth had apparently normal enamel. It has been suggested that AMBN may function in bone development. No clinically obvious bone or other co-segregating health problems were identified in the family investigated. This study confirms for the first time that AMBN mutations cause non-syndromic human AI and that mouse models with disrupted Ambn function are valid. © The Author 2014. Published by Oxford University Press.

  1. Derivative chameleons

    International Nuclear Information System (INIS)

    Noller, Johannes

    2012-01-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂ μ φ∂ μ φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂ μ φ∂ μ φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type

  2. Derivative chameleons

    Energy Technology Data Exchange (ETDEWEB)

    Noller, Johannes, E-mail: johannes.noller08@imperial.ac.uk [Theoretical Physics, Blackett Laboratory, Imperial College London, Prince Consort Road, London, SW7 2BZ (United Kingdom)

    2012-07-01

    We consider generalized chameleon models where the conformal coupling between matter and gravitational geometries is not only a function of the chameleon field φ, but also of its derivatives via higher order co-ordinate invariants (such as ∂{sub μ}φ∂{sup μ}φ,□φ,...). Specifically we consider the first such non-trivial conformal factor A(φ,∂{sub μ}φ∂{sup μ}φ). The associated phenomenology is investigated and we show that such theories have a new generic mass-altering mechanism, potentially assisting the generation of a sufficiently large chameleon mass in dense environments. The most general effective potential is derived for such derivative chameleon setups and explicit examples are given. Interestingly this points us to the existence of a purely derivative chameleon protected by a shift symmetry for φ → φ+c. We also discuss potential ghost-like instabilities associated with mass-lifting mechanisms and find another, mass-lowering and instability-free, branch of solutions. This suggests that, barring fine-tuning, stable derivative models are in fact typically anti-chameleons that suppress the field's mass in dense environments. Furthermore we investigate modifications to the thin-shell regime and prove a no-go theorem for chameleon effects in non-conformal geometries of the disformal type.

  3. Electricity derivatives

    CERN Document Server

    Aïd, René

    2015-01-01

    Offering a concise but complete survey of the common features of the microstructure of electricity markets, this book describes the state of the art in the different proposed electricity price models for pricing derivatives and in the numerical methods used to price and hedge the most prominent derivatives in electricity markets, namely power plants and swings. The mathematical content of the book has intentionally been made light in order to concentrate on the main subject matter, avoiding fastidious computations. Wherever possible, the models are illustrated by diagrams. The book should allow prospective researchers in the field of electricity derivatives to focus on the actual difficulties associated with the subject. It should also offer a brief but exhaustive overview of the latest techniques used by financial engineers in energy utilities and energy trading desks.

  4. Generating Bona Fide Mammalian Prions with Internal Deletions.

    Science.gov (United States)

    Munoz-Montesino, Carola; Sizun, Christina; Moudjou, Mohammed; Herzog, Laetitia; Reine, Fabienne; Chapuis, Jérôme; Ciric, Danica; Igel-Egalon, Angelique; Laude, Hubert; Béringue, Vincent; Rezaei, Human; Dron, Michel

    2016-08-01

    Mammalian prions are PrP proteins with altered structures causing transmissible fatal neurodegenerative diseases. They are self-perpetuating through formation of beta-sheet-rich assemblies that seed conformational change of cellular PrP. Pathological PrP usually forms an insoluble protease-resistant core exhibiting beta-sheet structures but no more alpha-helical content, loosing the three alpha-helices contained in the correctly folded PrP. The lack of a high-resolution prion structure makes it difficult to understand the dynamics of conversion and to identify elements of the protein involved in this process. To determine whether completeness of residues within the protease-resistant domain is required for prions, we performed serial deletions in the helix H2 C terminus of ovine PrP, since this region has previously shown some tolerance to sequence changes without preventing prion replication. Deletions of either four or five residues essentially preserved the overall PrP structure and mutant PrP expressed in RK13 cells were efficiently converted into bona fide prions upon challenge by three different prion strains. Remarkably, deletions in PrP facilitated the replication of two strains that otherwise do not replicate in this cellular context. Prions with internal deletion were self-propagating and de novo infectious for naive homologous and wild-type PrP-expressing cells. Moreover, they caused transmissible spongiform encephalopathies in mice, with similar biochemical signatures and neuropathologies other than the original strains. Prion convertibility and transfer of strain-specific information are thus preserved despite shortening of an alpha-helix in PrP and removal of residues within prions. These findings provide new insights into sequence/structure/infectivity relationship for prions. Prions are misfolded PrP proteins that convert the normal protein into a replicate of their own abnormal form. They are responsible for invariably fatal neurodegenerative

  5. Characterization of genetic deletions in Becker muscular dystrophy using monoclonal antibodies against a deletion-prone region of dystrophin

    Energy Technology Data Exchange (ETDEWEB)

    Thanh, L.T.; Man, Nguyen Thi; Morris, G.E. [Wales Institute, Clwyd (United Kingdom)] [and others

    1995-08-28

    We have produced a new panel of 20 monoclonal antibodies (mAbs) against a region of the dystrophin protein corresponding to a deletion-prone region of the Duchenne muscular dystrophy gene (exons 45-50). We show that immunohistochemistry or Western blotting with these {open_quotes}exon-specific{close_quotes} mAbs can provide a valuable addition to Southern blotting or PCR methods for the accurate identification of genetic deletions in Becker muscular dystrophy patients. The antibodies were mapped to the following exons: exon 45 (2 mAbs), exon 46 (6), exon 47 (1), exons 47/48 (4), exons 48-50 (6), and exon 50 (1). PCR amplification of single exons or groups of exons was used both to produce specific dystrophin immunogens and to map the mAbs obtained. PCR-mediated mutagenesis was also used to identify regions of dystrophin important for mAb binding. Because the mAbs can be used to characterize the dystrophin produced by individual muscle fibres, they will also be useful for studying {open_quotes}revertant{close_quotes} fibres in Duchenne muscle and for monitoring the results of myoblast therapy trials in MD patients with deletions in this region of the dystrophin gene. 27 refs., 7 figs., 3 tabs.

  6. Molecular and cytogenetic investigation of Y chromosome deletions over three generations facilitated by intracytoplasmic sperm injection.

    Science.gov (United States)

    Minor, Agata; Wong, Edgar Chan; Harmer, Karynn; Ma, Sai

    2007-08-01

    The azoospermic factor (AZF) region is critical for normal spermatogenesis since microdeletions and partial deletions have been associated with infertility. We investigate the diagnostic ability of karyotyping in detecting clinically relevant Y chromosome deletions. The clinical significance of heterochromatin deletions, microdeletions and partial AZFc deletions is also evaluated. A patient with a Yq deletion, affected by severe oligoasthenoteratozoospermia, underwent intracytoplasmic sperm injection (ICSI) which resulted in the birth of a healthy baby boy. The patient, his father and his son underwent Y chromosome microdeletion and partial AZFc deletion screening. We also studied the aneuploidy rate in the sperm of the patient by fluorescent in situ hybridization. AZF microdeletions were absent in the family. However, microdeletion analysis confirmed that the Yq deletion was limited to the heterochromatin. We found a partial AZFc gr/gr deletion in all three family members. We observed an increased rate of sex chromosome aneuploidy in the infertile patient. Cytogenetic analysis was misleading in identifying the Yq breakpoint. Infertility observed in the patient was associated with the gr/gr partial deletion. However, because of the incomplete penetrance of gr/gr deletions, the consequence of the vertical transmission of the deletion through ICSI remains unknown. Copyright (c) 2007 John Wiley & Sons, Ltd.

  7. DNA-based detection of chromosome deletion and amplification: diagnostic and mechanistic significance

    International Nuclear Information System (INIS)

    Latt, S.A.; Lalande, M.; Donlon, T.

    1986-01-01

    This paper describes a few of the many possible examples in which application of a molecular cytogenetic approach can ultimately lead to a new, important understanding about the statics and dynamics of human chromosome structure. In the case of retinoblastoma, cytological observations of deletions and linkage analysis have positioned the retinoblastoma locus to bank 13q14. This locus is grossly deleted in some spontaneous tumors. It is still necessary to locate more precisely and characterize the nature of the retinoblastoma locus, as well as the basis for the heterogeneity in deletions removing one copy of this locus. One is left with the possibility that those deletions that may be observed cytologically reflect but the tip of the iceberg of deletions; detection of others may require molecular probes. A related question is the nature of the DNA sequences at the deletion boundaries and the role they play in promoting these deletions

  8. Conditional deletion of Cadherin 13 perturbs Golgi cells and disrupts social and cognitive behaviors.

    Science.gov (United States)

    Tantra, M; Guo, L; Kim, J; Zainolabidin, N; Eulenburg, V; Augustine, G J; Chen, A I

    2018-02-15

    Inhibitory interneurons mediate the gating of synaptic transmission and modulate the activities of neural circuits. Disruption of the function of inhibitory networks in the forebrain is linked to impairment of social and cognitive behaviors, but the involvement of inhibitory interneurons in the cerebellum has not been assessed. We found that Cadherin 13 (Cdh13), a gene implicated in autism spectrum disorder and attention-deficit hyperactivity disorder, is specifically expressed in Golgi cells within the cerebellar cortex. To assess the function of Cdh13 and utilize the manipulation of Cdh13 expression in Golgi cells as an entry point to examine cerebellar-mediated function, we generated mice carrying Cdh13-floxed alleles and conditionally deleted Cdh13 with GlyT2::Cre mice. Loss of Cdh13 results in a decrease in the expression/localization of GAD67 and reduces spontaneous inhibitory postsynaptic current (IPSC) in cerebellar Golgi cells without disrupting spontaneous excitatory postsynaptic current (EPSC). At the behavioral level, loss of Cdh13 in the cerebellum, piriform cortex and endopiriform claustrum have no impact on gross motor coordination or general locomotor behaviors, but leads to deficits in cognitive and social abilities. Mice lacking Cdh13 exhibit reduced cognitive flexibility and loss of preference for contact region concomitant with increased reciprocal social interactions. Together, our findings show that Cdh13 is critical for inhibitory function of Golgi cells, and that GlyT2::Cre-mediated deletion of Cdh13 in non-executive centers of the brain, such as the cerebellum, may contribute to cognitive and social behavioral deficits linked to neurological disorders. © 2018 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd.

  9. Neural Networks

    International Nuclear Information System (INIS)

    Smith, Patrick I.

    2003-01-01

    Physicists use large detectors to measure particles created in high-energy collisions at particle accelerators. These detectors typically produce signals indicating either where ionization occurs along the path of the particle, or where energy is deposited by the particle. The data produced by these signals is fed into pattern recognition programs to try to identify what particles were produced, and to measure the energy and direction of these particles. Ideally, there are many techniques used in this pattern recognition software. One technique, neural networks, is particularly suitable for identifying what type of particle caused by a set of energy deposits. Neural networks can derive meaning from complicated or imprecise data, extract patterns, and detect trends that are too complex to be noticed by either humans or other computer related processes. To assist in the advancement of this technology, Physicists use a tool kit to experiment with several neural network techniques. The goal of this research is interface a neural network tool kit into Java Analysis Studio (JAS3), an application that allows data to be analyzed from any experiment. As the final result, a physicist will have the ability to train, test, and implement a neural network with the desired output while using JAS3 to analyze the results or output. Before an implementation of a neural network can take place, a firm understanding of what a neural network is and how it works is beneficial. A neural network is an artificial representation of the human brain that tries to simulate the learning process [5]. It is also important to think of the word artificial in that definition as computer programs that use calculations during the learning process. In short, a neural network learns by representative examples. Perhaps the easiest way to describe the way neural networks learn is to explain how the human brain functions. The human brain contains billions of neural cells that are responsible for processing

  10. PP2A: The Achilles Heal in MDS with 5q Deletion

    Directory of Open Access Journals (Sweden)

    David eSallman

    2014-09-01

    Full Text Available Myelodysplastic syndromes (MDS represent a hematologically diverse group of myeloid neoplasms, however, one subtype characterized by an isolated deletion of chromosome 5q (del(5q is pathologically and clinically distinct. Patients with del(5q MDS share biological features that account for the profound hypoplastic anemia and unique sensitivity to treatment with lenalidomide. Ineffective erythropoiesis in del(5q MDS arises from allelic deletion of the ribosomal processing S-14 (RPS14 gene, which leads to MDM2 sequestration with consequent p53 activation and erythroid cell death. Since its approval in 2005, lenalidomide has changed the natural course of the disease. Patients who achieve transfusion independence and/or a cytogenetic response with lenalidomide have a decreased risk of progression to AML and an improved overall survival compared to non-responders. Elucidation of the mechanisms of action of lenalidomide in del(5q MDS has advanced therapeutic strategies for this disease. The selective cytotoxicity of lenalidomide in del(5q clones derives from inhibition of a haplodeficient phosphatase whose catalytic domain is encoded within the common deleted region on chromosome 5q, i.e., protein phosphatase 2A (PP2Acα. PP2A is a highly conserved, dual specificity phosphatase that plays an essential role in regulation of the G2/M checkpoint. Inhibition of PP2Acα results in cell cycle arrest and apoptosis in del(5q cells. Targeted knockdown of PP2Acα using siRNA is sufficient to sensitize non-del(5q clones to lenalidomide. Through its inhibitory effect on PP2A, lenalidomide stabilizes MDM2 to restore p53 degradation in erythroid precursors, with subsequent arrest in G2/M. Unfortunately, the majority of patients with del(5q MDS develop resistance to lenalidomide over time associated with PP2Acα overexpression. Targeted inhibition of PP2A with a more potent inhibitor has emerged as an attractive therapeutic approach for patients with del(5q MDS.

  11. Network Completion for Static Gene Expression Data

    Directory of Open Access Journals (Sweden)

    Natsu Nakajima

    2014-01-01

    Full Text Available We tackle the problem of completing and inferring genetic networks under stationary conditions from static data, where network completion is to make the minimum amount of modifications to an initial network so that the completed network is most consistent with the expression data in which addition of edges and deletion of edges are basic modification operations. For this problem, we present a new method for network completion using dynamic programming and least-squares fitting. This method can find an optimal solution in polynomial time if the maximum indegree of the network is bounded by a constant. We evaluate the effectiveness of our method through computational experiments using synthetic data. Furthermore, we demonstrate that our proposed method can distinguish the differences between two types of genetic networks under stationary conditions from lung cancer and normal gene expression data.

  12. The dimensional structure of psychopathology in 22q11.2 Deletion Syndrome.

    Science.gov (United States)

    Niarchou, Maria; Moore, Tyler M; Tang, Sunny X; Calkins, Monica E; McDonald-McGuinn, Donna M; Zackai, Elaine H; Emanuel, Beverly S; Gur, Ruben C; Gur, Raquel E

    2017-09-01

    22q11.2 Deletion Syndrome (22q11.2DS) is one of the strongest known genetic risk factors for developing schizophrenia. Individuals with 22q11.2DS have high rates of neurodevelopmental disorders in childhood, while in adulthood ∼25% develop schizophrenia. Similar to the general population, high rates of comorbidity are common in 22q11.2DS. Employing a dimensional approach where psychopathology is examined at the symptom-level as complementary to diagnostic categories in a population at such high genetic risk for schizophrenia can help gain a better understanding of how psychopathology is structured as well as its genetic underpinnings. This is the first study to examine the dimensional structure of a wide spectrum of psychopathology in the context of a homogeneous genetic etiology like 22q11.2DS. We evaluated 331 individuals with 22q11.2DS, mean age (SD) = 16.9(8.7); 51% males, who underwent prospective comprehensive phenotyping. We sought to replicate previous findings by examining a bi-factor model that derives a general factor of psychopathology in addition to more specific dimensions of psychopathology (i.e., internalizing, externalizing and thought disorder). Psychopathology in 22q11.2DS was divided into one 'general psychopathology' factor and four specific dimensions (i.e., 'anxiety', 'mood', 'ADHD' and 'psychosis'). The 'psychosis' symptoms loaded strongly on the 'general psychopathology' factor. The similarity of the symptom structure of psychopathology between 22q11.2DS and community and clinical populations without the deletion indicate that 22q11.2DS can provide a model to explore alternative approaches to our current nosology. Our findings add to a growing literature indicating the need to reorganize current diagnostic classification systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Homozygous Deletions and Recurrent Amplifications Implicate New Genes Involved in Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Wennuan Liu

    2008-08-01

    Full Text Available Prostate cancer cell lines provide ideal in vitro systems for the identification and analysis of prostate tumor suppressors and oncogenes. A detailed characterization of the architecture of prostate cancer cell line genomes would facilitate the study of precise roles of various genes in prostate tumorigenesis in general. To contribute to such a characterization, we used the GeneChip 500K single nucleotide polymorphic (SNP array for analysis of genotypes and relative DNA copy number changes across the genome of 11 cell lines derived from both normal and cancerous prostate tissues. For comparison purposes, we also examined the alterations observed in the cell lines in tumor/normal pairs of clinical samples from 72 patients. Along with genome-wide maps of DNA copy number changes and loss of heterozygosity for these cell lines, we report previously unreported homozygous deletions and recurrent amplifications in prostate cancers in this study. The homozygous deletions affected a number of biologically important genes, including PPP2R2A and BNIP3L identified in this study and CDKN2A/CDKN2B reported previously. Although most amplified genomic regions tended to be large, amplifications at 8q24.21 were of particular interest because the affected regions are relatively small, are found in multiple cell lines, are located near MYC, an oncogene strongly implicated in prostate tumorigenesis, and are known to harbor SNPs that are associated with inherited susceptibility for prostate cancer. The genomic alterations revealed in this study provide an important catalog of positional information relevant to efforts aimed at deciphering the molecular genetic basis of prostate cancer.

  14. Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

    Energy Technology Data Exchange (ETDEWEB)

    Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Martinelli, Diego [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Dionisi-Vici, Carlo [Division of Metabolism, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Nobili, Valerio [Gastroenterology and Liver Unit, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Francalanci, Paola; Boldrini, Renata; Callea, Francesco [Dept. Pathology, ' Bambino Gesu' Children' s Hospital, Rome (Italy); Santorelli, Filippo Maria [UOC Neurogenetica e Malattie Neuromuscolari, Fondazione Stella Maris, Pisa (Italy); Bertini, Enrico [Unit of Molecular Medicine for Neuromuscular and Neurodegenerative Diseases, ' Bambino Gesu' Children' s Hospital, Rome (Italy); and others

    2011-11-18

    Highlights: Black-Right-Pointing-Pointer Expanded array of mtDNA deletions. Black-Right-Pointing-Pointer Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. Black-Right-Pointing-Pointer Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. Black-Right-Pointing-Pointer Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.

  15. Novel large-range mitochondrial DNA deletions and fatal multisystemic disorder with prominent hepatopathy

    International Nuclear Information System (INIS)

    Bianchi, Marzia; Rizza, Teresa; Verrigni, Daniela; Martinelli, Diego; Tozzi, Giulia; Torraco, Alessandra; Piemonte, Fiorella; Dionisi-Vici, Carlo; Nobili, Valerio; Francalanci, Paola; Boldrini, Renata; Callea, Francesco; Santorelli, Filippo Maria; Bertini, Enrico

    2011-01-01

    Highlights: ► Expanded array of mtDNA deletions. ► Pearson syndrome with prominent hepatopathy associated with single mtDNA deletions. ► Detection of deletions in fibroblasts and blood avoids muscle and liver biopsy. ► Look for mtDNA deletions before to study nuclear genes related to mtDNA depletion. -- Abstract: Hepatic involvement in mitochondrial cytopathies rarely manifests in adulthood, but is a common feature in children. Multiple OXPHOS enzyme defects in children with liver involvement are often associated with dramatically reduced amounts of mtDNA. We investigated two novel large scale deletions in two infants with a multisystem disorder and prominent hepatopathy. Amount of mtDNA deletions and protein content were measured in different post-mortem tissues. The highest levels of deleted mtDNA were in liver, kidney, pancreas of both patients. Moreover, mtDNA deletions were detected in cultured skin fibroblasts in both patients and in blood of one during life. Biochemical analysis showed impairment of mainly complex I enzyme activity. Patients manifesting multisystem disorders in childhood may harbour rare mtDNA deletions in multiple tissues. For these patients, less invasive blood specimens or cultured fibroblasts can be used for molecular diagnosis. Our data further expand the array of deletions in the mitochondrial genomes in association with liver failure. Thus analysis of mtDNA should be considered in the diagnosis of childhood-onset hepatopathies.

  16. Learning Networks, Networked Learning

    NARCIS (Netherlands)

    Sloep, Peter; Berlanga, Adriana

    2010-01-01

    Sloep, P. B., & Berlanga, A. J. (2011). Learning Networks, Networked Learning [Redes de Aprendizaje, Aprendizaje en Red]. Comunicar, XIX(37), 55-63. Retrieved from http://dx.doi.org/10.3916/C37-2011-02-05

  17. The generation of chromosomal deletions to provide extensive coverage and subdivision of the Drosophila melanogaster genome.

    Science.gov (United States)

    Cook, R Kimberley; Christensen, Stacey J; Deal, Jennifer A; Coburn, Rachel A; Deal, Megan E; Gresens, Jill M; Kaufman, Thomas C; Cook, Kevin R

    2012-01-01

    Chromosomal deletions are used extensively in Drosophila melanogaster genetics research. Deletion mapping is the primary method used for fine-scale gene localization. Effective and efficient deletion mapping requires both extensive genomic coverage and a high density of molecularly defined breakpoints across the genome. A large-scale resource development project at the Bloomington Drosophila Stock Center has improved the choice of deletions beyond that provided by previous projects. FLP-mediated recombination between FRT-bearing transposon insertions was used to generate deletions, because it is efficient and provides single-nucleotide resolution in planning deletion screens. The 793 deletions generated pushed coverage of the euchromatic genome to 98.4%. Gaps in coverage contain haplolethal and haplosterile genes, but the sizes of these gaps were minimized by flanking these genes as closely as possible with deletions. In improving coverage, a complete inventory of haplolethal and haplosterile genes was generated and extensive information on other haploinsufficient genes was compiled. To aid mapping experiments, a subset of deletions was organized into a Deficiency Kit to provide maximal coverage efficiently. To improve the resolution of deletion mapping, screens were planned to distribute deletion breakpoints evenly across the genome. The median chromosomal interval between breakpoints now contains only nine genes and 377 intervals contain only single genes. Drosophila melanogaster now has the most extensive genomic deletion coverage and breakpoint subdivision as well as the most comprehensive inventory of haploinsufficient genes of any multicellular organism. The improved selection of chromosomal deletion strains will be useful to nearly all Drosophila researchers.

  18. Round Spermatid Injection Rescues Female Lethality of a Paternally Inherited Xist Deletion in Mouse.

    Directory of Open Access Journals (Sweden)

    Federica Federici

    2016-10-01

    Full Text Available In mouse female preimplantation embryos, the paternal X chromosome (Xp is silenced by imprinted X chromosome inactivation (iXCI. This requires production of the noncoding Xist RNA in cis, from the Xp. The Xist locus on the maternally inherited X chromosome (Xm is refractory to activation due to the presence of an imprint. Paternal inheritance of an Xist deletion (XpΔXist is embryonic lethal to female embryos, due to iXCI abolishment. Here, we circumvented the histone-to-protamine and protamine-to-histone transitions of the paternal genome, by fertilization of oocytes via injection of round spermatids (ROSI. This did not affect initiation of XCI in wild type female embryos. Surprisingly, ROSI using ΔXist round spermatids allowed survival of female embryos. This was accompanied by activation of the intact maternal Xist gene, initiated with delayed kinetics, around the morula stage, resulting in Xm silencing. Maternal Xist gene activation was not observed in ROSI-derived males. In addition, no Xist expression was detected in male and female morulas that developed from oocytes fertilized with mature ΔXist sperm. Finally, the expression of the X-encoded XCI-activator RNF12 was enhanced in both male (wild type and female (wild type as well as XpΔXist ROSI derived embryos, compared to in vivo fertilized embryos. Thus, high RNF12 levels may contribute to the specific activation of maternal Xist in XpΔXist female ROSI embryos, but upregulation of additional Xp derived factors and/or the specific epigenetic constitution of the round spermatid-derived Xp are expected to be more critical. These results illustrate the profound impact of a dysregulated paternal epigenome on embryo development, and we propose that mouse ROSI can be used as a model to study the effects of intergenerational inheritance of epigenetic marks.

  19. The htpAB operon of Legionella pneumophila cannot be deleted in the presence of the groE chaperonin operon of Escherichia coli.

    Science.gov (United States)

    Nasrallah, Gheyath K; Gagnon, Elizabeth; Orton, Dennis J; Garduño, Rafael A

    2011-11-01

    HtpB, the chaperonin of the intracellular bacterial pathogen Legionella pneumophila , displays several virulence-related functions in vitro. To confirm HtpB's role in vivo, host infections with an htpB deletion mutant would be required. However, we previously reported that the htpAB operon (encoding co-chaperonin and chaperonin) is essential. We attempted here to delete htpAB in a L. pneumophila strain carrying the groE operon (encoding the Escherichia coli co-chaperonin and chaperonin). The groE operon was inserted into the chromosome of L. pneumophila Lp02, and then allelic replacement of htpAB with a gentamicin resistance cassette was attempted. Although numerous potential postallelic replacement transformants showed a correct selection phenotype, we still detected htpAB by PCR and full-size HtpB by immunoblot. Southern blot and PCR analysis indicated that the gentamicin resistance cassette had apparently integrated in a duplicated htpAB region. However, we showed by Southern blot that strain Lp02, and the Lp02 derivative carrying the groE operon, have only one copy of htpAB. These results confirmed that the htpAB operon cannot be deleted, not even in the presence of the groE operon, and suggested that attempts to delete htpAB under strong phenotypic selection result in aberrant genetic recombinations that could involve duplication of the htpAB locus.

  20. Hematological abnormalities and 22q11.2 deletion syndrome

    Directory of Open Access Journals (Sweden)

    Rafael Fabiano Machado Rosa

    2011-01-01

    Full Text Available The 22q11.2 deletion syndrome (22q11DS is a common genetic disease characterized by broad phenotypic variability. Despite the small number of studies describing hematological alterations in individuals with 22q11DS, it appears that these abnormalities are more frequent than previously imagined. Thus, the objective of our study was to report on a patient with 22q11DS presenting thrombocytopenia and large platelets and to review the literature. The patient, a 13-year-old boy, was originally evaluated due to craniofacial dysmorphia and speech delay. He also had a history of behavioral changes, neuropsychomotor delay and recurrent otitis/sinusitis. The identification of a 22q11.2 microdeletion by fluorescent in situ hybridization diagnosed the syndrome. Despite his hematological alterations, he only had a history of epistaxis and bruising of the upper and lower limbs. Assessments of the prothrombin time, thrombin time, partial thromboplastin time, bleeding time, fibrinogen levels and platelet aggregation (including the ristocetin induced platelet aggregation test were all normal. Hematological alterations observed in 22q11DS are directly related to the genetic disorder itself (especially in respect to deletion of the GPIb gene and secondary to some clinical findings, such as immunodeficiency. Macrothrombocytopenia is increasingly being considered a feature of the broad spectrum of 22q11DS and may potentially be a clinical marker for the syndrome.

  1. Deletion Mutations in an Australian Series of HNPCC Patients

    Directory of Open Access Journals (Sweden)

    McPhillips Mary

    2005-11-01

    Full Text Available Abstract Hereditary non polyposis colorectal cancer (HNPCC is characterized by the presence of early onset colorectal cancer and other epithelial malignancies. The genetic basis of HNPCC is a deficiency in DNA mismatch repair, which manifests itself as DNA microsatellite instability in tumours. There are four genes involved in DNA mismatch repair that have been linked to HNPCC; these include hMSH2, hMLH1, hMSH6 and hPMS2. Of these four genes hMLH1 and hMSH2 account for the majority of families diagnosed with the disease. Notwithstanding, up to 40 percent of families do not appear to harbour a change in either hMSH2 or hMLH1 that can be detected using standard screening procedures such as direct DNA sequencing or a variety of methods all based on a heteroduplex analysis. In this report we have screened a series of 118 probands that all have the clinical diagnosis of HNPCC for medium to large deletions by the Multiplex Ligation-Dependent Probe Amplification assay (MLPA to determine the frequency of this type of mutation. The results indicate that a significant proportion of Australian HNPCC patients harbour deletion or duplication mutations primarily in hMSH2 but also in hMLH1.

  2. Files synchronization from a large number of insertions and deletions

    Science.gov (United States)

    Ellappan, Vijayan; Kumari, Savera

    2017-11-01

    Synchronization between different versions of files is becoming a major issue that most of the applications are facing. To make the applications more efficient a economical algorithm is developed from the previously used algorithm of “File Loading Algorithm”. I am extending this algorithm in three ways: First, dealing with non-binary files, Second backup is generated for uploaded files and lastly each files are synchronized with insertions and deletions. User can reconstruct file from the former file with minimizing the error and also provides interactive communication by eliminating the frequency without any disturbance. The drawback of previous system is overcome by using synchronization, in which multiple copies of each file/record is created and stored in backup database and is efficiently restored in case of any unwanted deletion or loss of data. That is, to introduce a protocol that user B may use to reconstruct file X from file Y with suitably low probability of error. Synchronization algorithms find numerous areas of use, including data storage, file sharing, source code control systems, and cloud applications. For example, cloud storage services such as Drop box synchronize between local copies and cloud backups each time users make changes to local versions. Similarly, synchronization tools are necessary in mobile devices. Specialized synchronization algorithms are used for video and sound editing. Synchronization tools are also capable of performing data duplication.

  3. Rag Deletion in Peripheral T Cells Blocks TCR Revision

    Science.gov (United States)

    Hale, J. Scott; Ames, Kristina T.; Boursalian, Tamar E.; Fink, Pamela J.

    2010-01-01

    Mature CD4+Vβ5+ T cells that recognize a peripherally expressed endogenous superantigen are tolerized either by deletion or T cell receptor (TCR) revision. In Vβ5 transgenic mice, this latter tolerance pathway results in the appearance of CD4+Vβ5−TCRβ+ T cells, coinciding with Rag1, Rag2, and TdT expression and the accumulation of Vβ-DJβ recombination intermediates in peripheral CD4+ T cells. Because post-thymic RAG-dependent TCR rearrangement has remained controversial, we sought to definitively determine whether TCR revision is an extrathymic process that occurs in mature peripheral T cells. We now show that Rag deletion in post-positive selection T cells in Vβ5 transgenic mice blocks TCR revision in vivo, and that mature peripheral T cells sorted to remove cells bearing endogenous TCRβ chains can express newly generated TCRβ molecules in adoptive hosts. These findings unambiguously demonstrate post-thymic, RAG-dependent TCR rearrangement and define TCR revision as a tolerance pathway that targets mature peripheral CD4+ T cells. PMID:20435935

  4. Deletion of Fanca or Fancd2 dysregulates Treg in mice

    Science.gov (United States)

    Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M.; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C.; Steinbrecher, Kris A.; Davies, Stella M.

    2014-01-01

    Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca−/− or Fancd2−/− BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca−/− or Fancd2−/− mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25+Foxp3+ Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25+Foxp3+ Tregs of Fanca−/− or Fancd2−/− mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients. PMID:24501220

  5. Dystrophin in frameshift deletion patients with Becker Muscular Dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Gangopadhyay, S.B.; Ray, P.N.; Worton, R.G.; Sherratt, T.G.; Heckmatt, J.Z.; Dubowitz, V.; Strong, P.N.; Miller, G. (Penn State College of Medicine, Hershey, PA (United States)); Shokeir, M. (Univ. Hospital, Saskatchewan (Canada))

    1992-09-01

    In a previous study the authors identified 14 cases with Duchenne muscular dystrophy (DMD) or its milder variant, Becker muscular dystrophy (BMD), with a deletion of exons 3-7, a deletion that would be expected to shift the translational reading frame of the mRNA and give a severe phenotype. They have examined dystrophin and its mRNA from muscle biopsies of seven cases with either mild or intermediate phenotypes. In all cases they detected slightly lower-molecular-weight dystrophin in 12%-15% abundance relative to the normal. By sequencing amplified mRNA they have found that exon 2 is spliced to exon 8, a splice that produces a frameshifted mRNA, and have found no evidence for alternate splicing that might be involved in restoration of dystrophin mRNA reading frame in the patients with a mild phenotype. Other transcriptional and posttranscriptional mechanisms such as cryptic promoter, ribosomal frameshifting, and reinitiation are suggested that might play some role in restoring the reading frame. 34 refs., 5 figs. 1 tab.

  6. Targeted deletion of hepatocyte Ikkβ confers growth advantages

    International Nuclear Information System (INIS)

    Koch, Katherine S.; Maeda, Shin; He, Guobin; Karin, Michael; Leffert, Hyam L.

    2009-01-01

    Mice lacking hepatocyte IKKβ (Ikkβ Δhep ) are defective in TNFα-activation of hepatocellular transcription factor NF-κB, and highly susceptible to hepatotoxicity. Following diethylnitrosamine (DEN) exposure, Ikkβ Δhep mice develop more hepatocellular carcinoma (HCC) than control mice due partly to enhanced DEN-induced hepatocyte death. Here we show that Ikkβ Δhep hepatocytes display growth advantages over normal hepatocytes consisting of precocious PCNA and cyclin D1 expression during liver regeneration (shortened hepatocyte G 0 → G 1 transitions), and enhanced recovery efficiency, cyclin D1 expression and cell proliferation after plating. Ex vivo deletion of Ikkβ also accelerates hepatocyte growth. Ikkβ Δhep hepatocyte proliferative responses show heightened sensitivity to TGFα and TNFα, and heightened expression of fibronectin, collagens I/III, nidogen, β-actin and integrin β1 mRNAs. These findings suggest that altered mitogen signaling and expression of extracellular matrix and its associated components underlie growth advantages. Increased HCC development in Ikkβ Δhep mice may also be caused by growth advantages of surviving Ikkβ-deleted hepatocytes.

  7. Deletion of Fanca or Fancd2 dysregulates Treg in mice.

    Science.gov (United States)

    Du, Wei; Erden, Ozlem; Wilson, Andrew; Sipple, Jared M; Schick, Jonathan; Mehta, Parinda; Myers, Kasiani C; Steinbrecher, Kris A; Davies, Stella M; Pang, Qishen

    2014-03-20

    Fanconi anemia (FA) is a genetic disorder associated with bone marrow (BM) failure and leukemia. Recent studies demonstrate variable immune defects in FA. However, the cause for FA immunodeficiency is unknown. Here we report that deletion of Fanca or Fancd2 dysregulates the suppressive activity of regulatory T cells (Tregs), shown functionally as exacerbation of graft-vs-host disease (GVHD) in mice. Recipient mice of Fanca(-/-) or Fancd2(-/-) BM chimeras exhibited severe acute GVHD after allogeneic BM transplantation (BMT). T cells from Fanca(-/-) or Fancd2(-/-) mice induced higher GVHD lethality than those from wild-type (WT) littermates. FA Tregs possessed lower proliferative suppression potential compared with WT Tregs, as demonstrated by in vitro proliferation assay and BMT. Analysis of CD25(+)Foxp3(+) Tregs indicated that loss of Fanca or Fancd2 dysregulated Foxp3 target gene expression. Additionally, CD25(+)Foxp3(+) Tregs of Fanca(-/-) or Fancd2(-/-) mice were less efficient in suppressing the production of GVHD-associated inflammatory cytokines. Consistently, aberrant NF-κB activity was observed in infiltrated T cells from FA GVHD mice. Conditional deletion of p65 in FA Tregs decreased GVHD mortality. Our study uncovers an essential role for FA proteins in maintaining Treg homeostasis, possibly explaining, at least in part, the immune deficiency reported in some FA patients.

  8. Production planning and coronal stop deletion in spontaneous speech

    Directory of Open Access Journals (Sweden)

    James Tanner

    2017-06-01

    Full Text Available Many phonological processes can be affected by segmental context spanning word boundaries, which often lead to variable outcomes. This paper tests the idea that some of this variability can be explained by reference to production planning. We examine coronal stop deletion (CSD, a variable process conditioned by preceding and upcoming phonological context, in a corpus of spontaneous British English speech, as a means of investigating a number of variables associated with planning: Prosodic boundary strength, word frequency, conditional probability of the following word, and speech rate. From the perspective of production planning, (1 prosodic boundaries should affect deletion rate independently of following context; (2 given the locality of production planning, the effect of the following context should decrease at stronger prosodic boundaries; and (3 other factors affecting planning scope should modulate the effect of upcoming phonological material above and beyond the modulating effect of prosodic boundaries. We build a statistical model of CSD realization, using pause length as a quantitative proxy for boundary strength, and find support for these predictions. These findings are compatible with the hypothesis that the locality of production planning constrains variability in speech production, and have practical implications for work on CSD and other variable processes.

  9. Meta-Analysis of Transcriptome Data Related to Hippocampus Biopsies and iPSC-Derived Neuronal Cells from Alzheimer's Disease Patients Reveals an Association with FOXA1 and FOXA2 Gene Regulatory Networks.

    Science.gov (United States)

    Wruck, Wasco; Schröter, Friederike; Adjaye, James

    2016-01-01

    Although the incidence of Alzheimer's disease (AD) is continuously increasing in the aging population worldwide, effective therapies are not available. The interplay between causative genetic and environmental factors is partially understood. Meta-analyses have been performed on aspects such as polymorphisms, cytokines, and cognitive training. Here, we propose a meta-analysis approach based on hierarchical clustering analysis of a reliable training set of hippocampus biopsies, which is condensed to a gene expression signature. This gene expression signature was applied to various test sets of brain biopsies and iPSC-derived neuronal cell models to demonstrate its ability to distinguish AD samples from control. Thus, our identified AD-gene signature may form the basis for determination of biomarkers that are urgently needed to overcome current diagnostic shortfalls. Intriguingly, the well-described AD-related genes APP and APOE are not within the signature because their gene expression profiles show a lower correlation to the disease phenotype than genes from the signature. This is in line with the differing characteristics of the disease as early-/late-onset or with/without genetic predisposition. To investigate the gene signature's systemic role(s), signaling pathways, gene ontologies, and transcription factors were analyzed which revealed over-representation of response to stress, regulation of cellular metabolic processes, and reactive oxygen species. Additionally, our results clearly point to an important role of FOXA1 and FOXA2 gene regulatory networks in the etiology of AD. This finding is in corroboration with the recently reported major role of the dopaminergic system in the development of AD and its regulation by FOXA1 and FOXA2.

  10. ASYMMETRIC EFFECTS OF ADDED VERSUS DELETED FEATURE OF STIMULUS ON RECOGNITION MEMORY

    OpenAIRE

    内野, 八潮; 箱田, 裕司

    2000-01-01

    This article reviewed a number of studies which revealed superiority of addition over deletion. Such an asymmetric effect was found in picture recognitioa memory, discrimination learning, proofreading for misspellings and so on. However, few studies have controlled typicality of original stimulus or the effect of addition and deletion on typicality of changed stimulus. Therefore this article focussed particularly on the studies in which addition and deletion applied to original stimulus was d...

  11. Submicroscopic deletions at the WAGR locus, revealed by nonradioactive in situ hybridization.

    OpenAIRE

    Fantes, J A; Bickmore, W A; Fletcher, J M; Ballesta, F; Hanson, I M; van Heyningen, V

    1992-01-01

    Fluorescence in situ hybridization (FISH) with biotin-labeled probes mapping to 11p13 has been used for the molecular analysis of deletions of the WAGR (Wilms tumor, aniridia, genitourinary abnormalities, and mental retardation) locus. We have detected a submicroscopic 11p13 deletion in a child with inherited aniridia who subsequently presented with Wilms tumor in a horseshoe kidney, only revealed at surgery. The mother, who has aniridia, was also found to carry a deletion including both the ...

  12. The male gametophytic sterility. 1 - Gametic sterilities and deletions in petunia

    International Nuclear Information System (INIS)

    Cornu, A.; Maizonnier, D.

    1982-01-01

    Terminal deletions induced by ionizing radiations in Petunia are not sexually transmitted. Cytogenetic study of plants with a heterozygous deletion and their progenies shows that this lack of transmission is accompanied by a gametic semi-sterility due to the fact that gametes carrying the deleted chromosome are not viable. The interest of such a male sterility with a gametophytic determinism for the study of sporophyte-gametophyte relationships is underlined [fr

  13. [Grave's disease in children with 22q11 deletion. Report of three cases].

    Science.gov (United States)

    Gosselin, J; Lebon-Labich, B; Lucron, H; Marçon, F; Leheup, B

    2004-12-01

    Hypothyroidism is a well recognized complication of 22q11.2 deletion syndrome. Auto-immune hyperthyroidism is less common. We report three patients with a 22q11.2 deletion and Graves' disease diagnosed at age 17, 14 and 11 years, respectively. The clinical and biological presentation was typical for auto-immune hyperthyroidism. Graves' disease should be periodically sought during the follow-up program of patients with 22q11.2 deletion syndrome.

  14. Topological isomorphisms of human brain and financial market networks

    Directory of Open Access Journals (Sweden)

    Petra E Vértes

    2011-09-01

    Full Text Available Although metaphorical and conceptual connections between the human brain and the financial markets have often been drawn, rigorous physical or mathematical underpinnings of this analogy remain largely unexplored. Here, we apply a statistical and graph theoretic approach to the study of two datasets - the timeseries of 90 stocks from the New York Stock Exchange over a three-year period, and the fMRI-derived timeseries acquired from 90 brain regions over the course of a 10 min-long functional MRI scan of resting brain function in healthy volunteers. Despite the many obvious substantive differences between these two datasets, graphical analysis demonstrated striking commonalities in terms of global network topological properties. Both the human brain and the market networks were non-random, small-world, modular, hierarchical systems with fat-tailed degree distributions indicating the presence of highly connected hubs. These properties could not be trivially explained by the univariate time series statistics of stock price returns. This degree of topological isomorphism suggests that brains and markets can be regarded broadly as members of the same family of networks. The two systems, however, were not topologically identical. The financial market was more efficient and more modular - more highly optimised for information processing - than the brain networks; but also less robust to systemic disintegration as a result of hub deletion. We conclude that the conceptual connections between brains and markets are not merely metaphorical; rather these two information processing systems can be rigorously compared in the same mathematical language and turn out often to share important topological properties in common to some degree. There will be interesting scientific arbitrage opportunities in further work at the graph theoretically-mediated interface between systems neuroscience and the statistical physics of financial markets.

  15. Topological isomorphisms of human brain and financial market networks.

    Science.gov (United States)

    Vértes, Petra E; Nicol, Ruth M; Chapman, Sandra C; Watkins, Nicholas W; Robertson, Duncan A; Bullmore, Edward T

    2011-01-01

    Although metaphorical and conceptual connections between the human brain and the financial markets have often been drawn, rigorous physical or mathematical underpinnings of this analogy remain largely unexplored. Here, we apply a statistical and graph theoretic approach to the study of two datasets - the time series of 90 stocks from the New York stock exchange over a 3-year period, and the fMRI-derived time series acquired from 90 brain regions over the course of a 10-min-long functional MRI scan of resting brain function in healthy volunteers. Despite the many obvious substantive differences between these two datasets, graphical analysis demonstrated striking commonalities in terms of global network topological properties. Both the human brain and the market networks were non-random, small-world, modular, hierarchical systems with fat-tailed degree distributions indicating the presence of highly connected hubs. These properties could not be trivially explained by the univariate time series statistics of stock price returns. This degree of topological isomorphism suggests that brains and markets can be regarded broadly as members of the same family of networks. The two systems, however, were not topologically identical. The financial market was more efficient and more modular - more highly optimized for information processing - than the brain networks; but also less robust to systemic disintegration as a result of hub deletion. We conclude that the conceptual connections between brains and markets are not merely metaphorical; rather these two information processing systems can be rigorously compared in the same mathematical language and turn out often to share important topological properties in common to some degree. There will be interesting scientific arbitrage opportunities in further work at the graph-theoretically mediated interface between systems neuroscience and the statistical physics of financial markets.

  16. Mosaic deletion of 20pter due to rescue by somatic recombination.

    Science.gov (United States)

    Martin, Megan M; Vanzo, Rena J; Sdano, Mallory R; Baxter, Adrianne L; South, Sarah T

    2016-01-01

    We report on a unique case of a mosaic 20pter-p13 deletion due to a somatic repair event identified by allele differentiating single nucleotide polymorphism (SNP) probes on chromosomal microarray. Small terminal deletions of 20p have been reported in a few individuals and appear to result in a variable phenotype. This patient was a 24-month-old female who presented with failure to thrive and speech delay. Chromosomal microarray analysis (CMA) performed on peripheral blood showed a 1.6 Mb deletion involving the terminus of 20p (20pter-20p13). This deletion appeared mosaic by CMA and this suspicion was confirmed by fluorescence in situ hybridization (FISH) analysis. Additionally, the deletion interval at 20p was directly adjacent to 15 Mb of mosaic copy-neutral loss of heterozygosity (LOH). The pattern of SNP probes was highly suggestive of a somatic repair event that resulted in rescue of the deleted region using the non-deleted homologue as a template. Structural mosaicism is rare and most often believed to be due to a postzygotic mechanism. This case demonstrates the additional utility of allele patterns to help distinguish mechanisms and in this case identified the possibility of either a post-zygotic repair of a germline deletion or a post-zygotic deletion with somatic recombination repair in a single step. © 2015 Wiley Periodicals, Inc.

  17. Concurrent deletion of 16q23 and PTEN is an independent prognostic feature in prostate cancer.

    Science.gov (United States)

    Kluth, Martina; Runte, Frederic; Barow, Philipp; Omari, Jazan; Abdelaziz, Zaid M; Paustian, Lisa; Steurer, Stefan; Christina Tsourlakis, Maria; Fisch, Margit; Graefen, Markus; Tennstedt, Pierre; Huland, Hartwig; Michl, Uwe; Minner, Sarah; Sauter, Guido; Simon, Ronald; Adam, Meike; Schlomm, Thorsten

    2015-11-15

    The deletion of 16q23-q24 belongs to the most frequent chromosomal changes in prostate cancer, but the clinical consequences of this alteration have not been studied in detail. We performed fluorescence in situ hybridization analysis using a 16q23 probe in more than 7,400 prostate cancers with clinical follow-up data assembled in a tissue microarray format. Chromosome 16q deletion was found in 21% of cancers, and was linked to advanced tumor stage, high Gleason grade, accelerated cell proliferation, the presence of lymph node metastases (p Deletion was more frequent in ERG fusion-positive (27%) as compared to ERG fusion-negative cancers (16%, p deletions including phosphatase and tensin homolog (PTEN) (p deletion of 16q was linked to early biochemical recurrence independently from the ERG status (p deletion of 16q alone. Multivariate modeling revealed that the prognostic value of 16q/PTEN deletion patterns was independent from the established prognostic factors. In summary, the results of our study demonstrate that the deletion of 16q and PTEN cooperatively drives prostate cancer progression, and suggests that deletion analysis of 16q and PTEN could be of important clinical value particularly for preoperative risk assessment of the clinically most challenging group of low- and intermediated grade prostate cancers. © 2015 UICC.

  18. Risk of Psychiatric Disorders Among Individuals With the 22q11.2 Deletion or Duplication

    DEFF Research Database (Denmark)

    Hoeffding, Louise K; Trabjerg, Betina B; Olsen, Line

    2017-01-01

    ) age at diagnosis of any psychiatric disorder was 12.5 (8.3) years for individuals with deletions and 6.1 (0.9) years for duplication carriers. A parental diagnosis of schizophrenia-but not of other psychiatric diagnoses-was associated with a 22q11.2 deletion, and parental psychiatric diagnoses other.......2 deletion or duplicationwas performed. A total of 3 768 943 individuals born in Denmark from 1955 to 2012 were followed up during the study period (total follow-up, 57.1 million person-years). Indicators of 22q11.2 deletion or duplication and cumulative incidenceswere estimated using a nested case...

  19. The DrosDel Deletion Collection: A Drosophila Genomewide Chromosomal Deficiency Resource

    OpenAIRE

    Ryder, Edward; Ashburner, Michael; Bautista-Llacer, Rosa; Drummond, Jenny; Webster, Jane; Johnson, Glynnis; Morley, Terri; Chan, Yuk Sang; Blows, Fiona; Coulson, Darin; Reuter, Gunter; Baisch, Heiko; Apelt, Christian; Kauk, Andreas; Rudolph, Thomas

    2007-01-01

    We describe a second-generation deficiency kit for Drosophila melanogaster composed of molecularly mapped deletions on an isogenic background, covering ∼77% of the Release 5.1 genome. Using a previously reported collection of FRT-bearing P-element insertions, we have generated 655 new deletions and verified a set of 209 deletion-bearing fly stocks. In addition to deletions, we demonstrate how the P elements may also be used to generate a set of custom inversions and duplications, particularly...

  20. A Case With Short Stature, Growth Hormone Deficiency and 46, XX, Xq27-qter Deletion.

    Science.gov (United States)

    Yıldırım, Şule; Topaloğlu, Naci; Tekin, Mustafa; Sılan, Fatma

    2017-10-01

    We report a case of 11-year-old girl with growth retardation and 46, XX, Xq27-qter deletion. The endocrinologic evaluation revealed growth hormone deficiency. In karyotype analysis  46, XX, Xq27-qter deletion was determined. The deletion of terminal region of chromosome 27 is most commonly being detected during the evaluation of infertility, premature ovarian insufficiency or in screening for fragile X carrier status. To our knowledge, this is the first reported case with 46, XX, Xq27-qter deletion and growth hormone deficiency. Furthermore, this case might facilitate future search for candidate genes involved in growth hormone deficiency.

  1. Genomic rearrangements by LINE-1 insertion-mediated deletion in the human and chimpanzee lineages.

    Science.gov (United States)

    Han, Kyudong; Sen, Shurjo K; Wang, Jianxin; Callinan, Pauline A; Lee, Jungnam; Cordaux, Richard; Liang, Ping; Batzer, Mark A

    2005-01-01

    Long INterspersed Elements (LINE-1s or L1s) are abundant non-LTR retrotransposons in mammalian genomes that are capable of insertional mutagenesis. They have been associated with target site deletions upon insertion in cell culture studies of retrotransposition. Here, we report 50 deletion events in the human and chimpanzee genomes directly linked to the insertion of L1 elements, resulting in the loss of approximately 18 kb of sequence from the human genome and approximately 15 kb from the chimpanzee genome. Our data suggest that during the primate radiation, L1 insertions may have deleted up to 7.5 Mb of target genomic sequences. While the results of our in vivo analysis differ from those of previous cell culture assays of L1 insertion-mediated deletions in terms of the size and rate of sequence deletion, evolutionary factors can reconcile the differences. We report a pattern of genomic deletion sizes similar to those created during the retrotransposition of Alu elements. Our study provides support for the existence of different mechanisms for small and large L1-mediated deletions, and we present a model for the correlation of L1 element size and the corresponding deletion size. In addition, we show that internal rearrangements can modify L1 structure during retrotransposition events associated with large deletions.

  2. Association between the CCR5 32-bp deletion allele and late onset of schizophrenia

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Timm, Sally; Wang, August G

    2006-01-01

    OBJECTIVE: The 32-bp deletion allele in chemokine receptor CCR5 has been associated with several immune-mediated diseases and might be implicated in schizophrenia as well. METHOD: The authors genotyped DNA samples from 268 schizophrenia patients and 323 healthy subjects. Age at first admission...... of the deletion allele in the latter subgroup of patients. CONCLUSIONS: These findings suggest that the CCR5 32-bp deletion allele is a susceptibility factor for schizophrenia with late onset. Alternatively, the CCR5 32-bp deletion allele may act as a modifier by delaying the onset of schizophrenia without...

  3. Novel and differential accumulation of mitochondrial DNA deletions in Swedish and vietnamese patients with colorectal cancer.

    Science.gov (United States)

    Dimberg, Jan; Hong, Thai Trinh; Skarstedt, Marita; Löfgren, Sture; Zar, Niklas; Matussek, Andreas

    2014-01-01

    Mitochondrial DNA (mtDNA) has been proposed to be involved in carcinogenesis and aging. The mtDNA 4977 bp deletion is one of the most frequently observed mtDNA mutations in human tissues and may play a role in colorectal cancer (CRC). In the present study, we aimed to evaluate the frequency of mtDNA 4977 bp deletion in CRC tissues and its association with clinical factors. We determined the presence of the 4977 bp common deletion in cancer and normal paired tissue samples from 105 Swedish and 88 Vietnamese patients with CRC using polymerase chain reaction (PCR) assays. The mtDNA 4977 bp deletion was shown to be significantly more frequent in normal tissues in comparison with paired cancer tissues in both Swedish and Vietnamese patients. The 4977 bp common deletion was significantly more frequent in cancer tissues of the Vietnamese patients compared to the Swedish patients, and in Vietnamese cancer tissues, the 4977 bp deletion was significantly over represented in those with localized disease compared to those with disseminated disease. Moreover, we detected nine novel mtDNA deletions and found a significantly higher rate of these in CRC tissues in Swedish in comparison to Vietnamese patients. The mtDNA 4977 bp deletion seems to have an impact on the clinical outcome of CRC in Vietnamese patients, that the Swedish patients accumulate more of the detected novel deletions in CRC tissue compared to Vietnamese patients probably indicates divergent mechanisms in colorectal carcinogenesis.

  4. Induction of Mitochondrial DNA Deletion by Ionizing Radiation in Human Lung Fibroblast IMR-90 Cells

    International Nuclear Information System (INIS)

    Eom, Hyeon Soo; Jung, U Hee; Park, Hae Ran; Jo, Sung Kee

    2009-01-01

    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging and also contributes to their unfavorable effects in cultured cells and animal tissues. This study was conducted to investigate the effect of ionizing radiation (IR) on mtDNA deletion and the involvement of reactive oxygen species (ROS) in this process in human lung fibroblast (IMR-90) cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated with 137 Cs -rays and the intracellular ROS level was determined by 2',7'-dichlorofluorescein diacetate (DCFH-DA) and mtDNA common deletion (4977bp) was detected by nested PCR. Old cells at PD 55 and H 2 O 2 -treated young cells were compared as the positive control. IR increased the intracellular ROS level and mtDNA 4977 bp deletion in IMR-90 cells dose-dependently. The increases of ROS level and mtDNA deletion were also observed in old cells and H 2 O 2 -treated young cells. To confirm the increased ROS level is essential for mtDNA deletion in irradiated cells, the effects of N-acetylcysteine (NAC) on IRinduced ROS and mtDNA deletion were examined. 5 mM NAC significantly attenuated the IR-induced ROS increase and mtDNA deletion. These results suggest that IR induces the mtDNA deletion and this process is mediated by ROS in IMR-90 cells

  5. Induction of Mitochondrial DNA Deletion by Ionizing Radiation in Human Lung Fibroblast IMR-90 Cells

    Energy Technology Data Exchange (ETDEWEB)

    Eom, Hyeon Soo; Jung, U Hee; Park, Hae Ran; Jo, Sung Kee [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of)

    2009-06-15

    Mitochondrial DNA (mtDNA) deletion is a well-known marker for oxidative stress and aging and also contributes to their unfavorable effects in cultured cells and animal tissues. This study was conducted to investigate the effect of ionizing radiation (IR) on mtDNA deletion and the involvement of reactive oxygen species (ROS) in this process in human lung fibroblast (IMR-90) cells. Young IMR-90 cells at population doubling (PD) 39 were irradiated with {sup 137}Cs -rays and the intracellular ROS level was determined by 2',7'-dichlorofluorescein diacetate (DCFH-DA) and mtDNA common deletion (4977bp) was detected by nested PCR. Old cells at PD 55 and H{sub 2}O{sub 2}-treated young cells were compared as the positive control. IR increased the intracellular ROS level and mtDNA 4977 bp deletion in IMR-90 cells dose-dependently. The increases of ROS level and mtDNA deletion were also observed in old cells and H{sub 2}O{sub 2}-treated young cells. To confirm the increased ROS level is essential for mtDNA deletion in irradiated cells, the effects of N-acetylcysteine (NAC) on IRinduced ROS and mtDNA deletion were examined. 5 mM NAC significantly attenuated the IR-induced ROS increase and mtDNA deletion. These results suggest that IR induces the mtDNA deletion and this process is mediated by ROS in IMR-90 cells.

  6. Transcriptome Profiling of Peripheral Blood in 22q11.2 Deletion Syndrome Reveals Functional Pathways Related to Psychosis and Autism Spectrum Disorder.

    Directory of Open Access Journals (Sweden)

    Maria Jalbrzikowski

    Full Text Available 22q11.2 Deletion Syndrome (22q11DS represents one of the greatest known genetic risk factors for the development of psychotic illness, and is also associated with high rates of autistic spectrum disorders (ASD in childhood. We performed integrated genomic analyses of 22q11DS to identify genes and pathways related to specific phenotypes.We used a high-resolution aCGH array to precisely characterize deletion breakpoints. Using peripheral blood, we examined differential expression (DE and networks of co-expressed genes related to phenotypic variation within 22q11DS patients. Whole-genome transcriptional profiling was performed using Illumina Human HT-12 microarrays. Data mining techniques were used to validate our results against independent samples of both peripheral blood and brain tissue from idiopathic psychosis and ASD cases.Eighty-five percent of 22q11DS individuals (N = 39 carried the typical 3 Mb deletion, with significant variability in deletion characteristics in the remainder of the sample (N = 7. DE analysis and weighted gene co-expression network analysis (WGCNA identified expression changes related to psychotic symptoms in patients, including a module of co-expressed genes which was associated with psychosis in 22q11DS and involved in pathways associated with transcriptional regulation. This module was enriched for brain-expressed genes, was not related to antipsychotic medication use, and significantly overlapped with transcriptional changes in idiopathic schizophrenia. In 22q11DS-ASD, both DE and WGCNA analyses implicated dysregulation of immune response pathways. The ASD-associated module showed significant overlap with genes previously associated with idiopathic ASD.These findings further support the use of peripheral tissue in the study of major mutational models of diseases affecting the brain, and point towards specific pathways dysregulated in 22q11DS carriers with psychosis and ASD.

  7. Deletion of intragenic tandem repeats in unit C of FLO1 of Saccharomyces cerevisiae increases the conformational stability of flocculin under acidic and alkaline conditions.

    Directory of Open Access Journals (Sweden)

    Ee Li

    Full Text Available Flocculation is an attractive property for Saccaromyces cerevisiae, which plays important roles in fermentation industry and environmental remediation. The process of flocculation is mediated by a family of cell surface flocculins. As one member of flocculins, Flo1 is characterized by four families of repeats (designated as repeat units A, B, C and D in the central domain. It is generally accepted that variation of repeat unit A in length in Flo1 influences the degree of flocculation or specificity for sugar recognization. However, no reports were observed for other repeat units. Here, we compared the flocculation ability and its sensitivity to environmental factors between yeast strain YSF1 carrying the intact FLO1 gene and yeast strains carrying the derived forms of FLO1 with partial or complete deletion of repeats in unit C. No obvious differences in flocculation ability and specificity of carbohydrate recognition were observed among these yeast strains, which indicates the truncated flocculins can stride across the cell wall and cluster the N-terminal domain on the surface of yeast cells as the intact Flo1 thereby improving intercellular binding. However, yeast strains with the truncated flocculins required more mannose to inhibit completely the flocculation, displayed broad tolerance of flocculation to pH fluctuation, and the fewer the repeats in unit C, the stronger adaptability of flocculation to pH change, which was not relevant to the position of deletion. This suggests that more stable active conformation is obtained for flocculin by deletion the repeat unit C in the central domain of Flo1, which was validated further by the higher hydrophobicity on the surface of cells of YSF1c with complete deletion of unit C under neutral and alkaline conditions and the stabilization of GFP conformation by fusion with flocculin with complete deletion of unit C in the central domain.

  8. SVA retrotransposon insertion-associated deletion represents a novel mutational mechanism underlying large genomic copy number changes with non-recurrent breakpoints

    Science.gov (United States)

    2014-01-01

    Background Genomic disorders are caused by copy number changes that may exhibit recurrent breakpoints processed by nonallelic homologous recombination. However, region-specific disease-associated copy number changes have also been observed which exhibit non-recurrent breakpoints. The mechanisms underlying these non-recurrent copy number changes have not yet been fully elucidated. Results We analyze large NF1 deletions with non-recurrent breakpoints as a model to investigate the full spectrum of causative mechanisms, and observe that they are mediated by various DNA double strand break repair mechanisms, as well as aberrant replication. Further, two of the 17 NF1 deletions with non-recurrent breakpoints, identified in unrelated patients, occur in association with the concomitant insertion of SINE/variable number of tandem repeats/Alu (SVA) retrotransposons at the deletion breakpoints. The respective breakpoints are refractory to analysis by standard breakpoint-spanning PCRs and are only identified by means of optimized PCR protocols designed to amplify across GC-rich sequences. The SVA elements are integrated within SUZ12P intron 8 in both patients, and were mediated by target-primed reverse transcription of SVA mRNA intermediates derived from retrotranspositionally active source elements. Both SVA insertions occurred during early postzygotic development and are uniquely associated with large deletions of 1 Mb and 867 kb, respectively, at the insertion sites. Conclusions Since active SVA elements are abundant in the human genome and the retrotranspositional activity of many SVA source elements is high, SVA insertion-associated large genomic deletions encompassing many hundreds of kilobases could constitute a novel and as yet under-appreciated mechanism underlying large-scale copy number changes in the human genome. PMID:24958239

  9. Delimitation of the Earliness per se D1 (Eps-D1) flowering gene to a subtelomeric chromosomal deletion in bread wheat (Triticum aestivum)

    Science.gov (United States)

    Zikhali, Meluleki; Wingen, Luzie U.; Griffiths, Simon

    2016-01-01

    Earliness per se (Eps) genes account for the variation in flowering time when vernalization and photoperiod requirements are satisfied. Genomics and bioinformatics approaches were used to describe allelic variation for 40 Triticum aestivum genes predicted, by synteny with Brachypodium distachyon, to be in the 1DL Eps region. Re-sequencing 1DL genes revealed that varieties carrying early heading alleles at this locus, Spark and Cadenza, carry a subtelomeric deletion including several genes. The equivalent region in Rialto and Avalon is intact. A bimodal distribution in the segregating Spark X Rialto single seed descent (SSD) populations enabled the 1DL QTL to be defined as a discrete Mendelian factor, which we named Eps-D1. Near isogenic lines (NILs) and NIL derived key recombinants between markers flanking Eps-D1 suggest that the 1DL deletion contains the gene(s) underlying Eps-D1. The deletion spans the equivalent of the Triticum monoccocum Eps-A m 1 locus, and hence includes MODIFIER OF TRANSCRIPTION 1 (MOT1) and FTSH PROTEASE 4 (FTSH4), the candidates for Eps-A m 1. The deletion also contains T. aestivum EARLY FLOWERING 3-D1 (TaELF3-D1) a homologue of the Arabidopsis thaliana circadian clock gene EARLY FLOWERING 3. Eps-D1 is possibly a homologue of Eps-B1 on chromosome 1BL. NILs carrying the Eps-D1 deletion have significantly reduced total TaELF3 expression and altered TaGIGANTEA (TaGI) expression compared with wild type. Altered TaGI expression is consistent with an ELF3 mutant, hence we propose TaELF3-D1 as the more likely candidate for Eps-D1. This is the first direct fine mapping of Eps effect in bread wheat. PMID:26476691

  10. Paracentric inversion of chromosome 2 associated with cryptic duplication of 2q14 and deletion of 2q37 in a patient with autism.

    Science.gov (United States)

    Devillard, Françoise; Guinchat, Vincent; Moreno-De-Luca, Daniel; Tabet, Anne-Claude; Gruchy, Nicolas; Guillem, Pascale; Nguyen Morel, Marie-Ange; Leporrier, Nathalie; Leboyer, Marion; Jouk, Pierre-Simon; Lespinasse, James; Betancur, Catalina

    2010-09-01

    We describe a patient with autism and a paracentric inversion of chromosome 2q14.2q37.3, with a concurrent duplication of the proximal breakpoint at 2q14.1q14.2 and a deletion of the distal breakpoint at 2q37.3. The abnormality was derived from his mother with a balanced paracentric inversion. The inversion in the child appeared to be cytogenetically balanced but subtelomere FISH revealed a cryptic deletion at the 2q37.3 breakpoint. High-resolution single nucleotide polymorphism array confirmed the presence of a 3.5 Mb deletion that extended to the telomere, and showed a 4.2 Mb duplication at 2q14.1q14.2. FISH studies using a 2q14.2 probe showed that the duplicated segment was located at the telomeric end of chromosome 2q. This recombinant probably resulted from breakage of a dicentric chromosome. The child had autism, mental retardation, speech and language delay, hyperactivity, growth retardation with growth hormone deficiency, insulin-dependent diabetes, and mild facial dysmorphism. Most of these features have been previously described in individuals with simple terminal deletion of 2q37. Pure duplications of the proximal chromosome 2q are rare and no specific syndrome has been defined yet, so the contribution of the 2q14.1q14.2 duplication to the phenotype of the patient is unknown. These findings underscore the need to explore apparently balanced chromosomal rearrangements inherited from a phenotypically normal parent in subjects with autism and/or developmental delay. In addition, they provide further evidence indicating that chromosome 2q terminal deletions are among the most frequently reported cytogenetic abnormalities in individuals with autism.

  11. Delimitation of the Earliness per se D1 (Eps-D1) flowering gene to a subtelomeric chromosomal deletion in bread wheat (Triticum aestivum).

    Science.gov (United States)

    Zikhali, Meluleki; Wingen, Luzie U; Griffiths, Simon

    2016-01-01

    Earliness per se (Eps) genes account for the variation in flowering time when vernalization and photoperiod requirements are satisfied. Genomics and bioinformatics approaches were used to describe allelic variation for 40 Triticum aestivum genes predicted, by synteny with Brachypodium distachyon, to be in the 1DL Eps region. Re-sequencing 1DL genes revealed that varieties carrying early heading alleles at this locus, Spark and Cadenza, carry a subtelomeric deletion including several genes. The equivalent region in Rialto and Avalon is intact. A bimodal distribution in the segregating Spark X Rialto single seed descent (SSD) populations enabled the 1DL QTL to be defined as a discrete Mendelian factor, which we named Eps-D1. Near isogenic lines (NILs) and NIL derived key recombinants between markers flanking Eps-D1 suggest that the 1DL deletion contains the gene(s) underlying Eps-D1. The deletion spans the equivalent of the Triticum monoccocum Eps-A (m) 1 locus, and hence includes MODIFIER OF TRANSCRIPTION 1 (MOT1) and FTSH PROTEASE 4 (FTSH4), the candidates for Eps-A (m) 1. The deletion also contains T. aestivum EARLY FLOWERING 3-D1 (TaELF3-D1) a homologue of the Arabidopsis thaliana circadian clock gene EARLY FLOWERING 3. Eps-D1 is possibly a homologue of Eps-B1 on chromosome 1BL. NILs carrying the Eps-D1 deletion have significantly reduced total TaELF3 expression and altered TaGIGANTEA (TaGI) expression compared with wild type. Altered TaGI expression is consistent with an ELF3 mutant, hence we propose TaELF3-D1 as the more likely candidate for Eps-D1. This is the first direct fine mapping of Eps effect in bread wheat. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

  12. A 54 Mb 11qter duplication and 0.9 Mb 1q44 deletion in a child with laryngomalacia and agenesis of corpus callosum

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    Lall Meena

    2011-09-01

    Full Text Available Abstract Background Partial Trisomy 11q syndrome (or Duplication 11q has defined clinical features and is documented as a rare syndrome by National Organization of Rare Disorders (NORD. Deletion 1q44 (or Monosomy 1q44 is a well-defined syndrome, but there is controversy about the genes lying in 1q44 region, responsible for agenesis of the corpus callosum. We report a female child with the rare Partial Trisomy 11q syndrome and Deletion 1q44 syndrome. The genomic imbalance in the proband was used for molecular characterization of the critical genes in 1q44 region for agenesis of corpus callosum. Some genes in 11q14q25 may be responsible for laryngomalacia. Results We report a female child with dysmorphic features, microcephaly, growth retardation, seizures, acyanotic heart disease, and hand and foot deformities. She had agenesis of corpus callosum, laryngomalacia, anterior ectopic anus, esophageal reflux and respiratory distress. Chromosome analysis revealed a derivative chromosome 1. Her karyotype was 46,XX,der(1t(1;11(q44;q14pat. The mother had a normal karyotype and the karyotype of the father was 46,XY,t(1;11(q44;q14. SNP array analysis showed that the proband had a 54 Mb duplication of 11q14q25 and a 0.9 Mb deletion of the submicroscopic subtelomeric 1q44 region. Fluorescence Insitu Hybridisation confirmed the duplication of 11qter and deletion of 1qter. Conclusion Laryngomalacia or obstruction of the upper airway is the outcome of increased dosage of some genes due to Partial Trisomy 11q Syndrome. In association with other phenotypic features, agenesis of corpus callosum appears to be a landmark phenotype for Deletion 1q44 syndrome, the critical genes lying proximal to SMYD3 in 1q44 region.

  13. Indirect presentation in the thymus limits naive and regulatory T-cell differentiation by promoting deletion of self-reactive thymocytes.

    Science.gov (United States)

    Yap, Jin Yan; Wirasinha, Rushika C; Chan, Anna; Howard, Debbie R; Goodnow, Christopher C; Daley, Stephen R

    2018-02-07

    Acquisition of T-cell central tolerance involves distinct pathways of self-antigen presentation to thymocytes. One pathway termed indirect presentation requires a self-antigen transfer step from thymic epithelial cells (TECs) to bone marrow-derived cells before the self-antigen is presented to thymocytes. The role of indirect presentation in central tolerance is context-dependent, potentially due to variation in self-antigen expression, processing and presentation in the thymus. Here, we report experiments in mice in which TECs expressed a membrane-bound transgenic self-antigen, hen egg lysozyme (HEL), from either the insulin (insHEL) or thyroglobulin (thyroHEL) promoter. Intrathymic HEL expression was less abundant and more confined to the medulla in insHEL mice compared with thyroHEL mice. When indirect presentation was impaired by generating mice lacking MHC class II expression in bone marrow-derived antigen-presenting cells, insHEL-mediated thymocyte deletion was abolished, whereas thyroHEL-mediated deletion occurred at a later stage of thymocyte development and Foxp3 + regulatory T-cell differentiation increased. Indirect presentation increased the strength of T-cell receptor signalling that both self-antigens induced in thymocytes, as assessed by Helios expression. Hence, indirect presentation limits the differentiation of naive and regulatory T cells by promoting deletion of self-reactive thymocytes. © 2018 John Wiley & Sons Ltd.

  14. Physiological characterisation of acuB deletion in Aspergillus niger

    DEFF Research Database (Denmark)

    Meijer, Susan Lisette; De Jongh, Willem Adriaan; Olsson, Lisbeth

    2009-01-01

    The acuB gene of Aspergillus niger is an ortholog of facB in Aspergillus nidulans. Under carbon-repression conditions, facB is repressed, thereby preventing acetate metabolism when the repressing carbon source is present. Even though facB is reported to be repressed directly by CreA, it is believed...... that a basal level of FacB activity exists under glucose-repressive conditions. In the present study, the effect of deletion of acuB on the physiology of A. niger was assessed. Differences in organic acid and acetate production, enzyme activities and extracellular amino and non-amino organic acid production...... were determined under glucose-repressing and -derepressing conditions. Furthermore, consumption of alternative carbon sources (e.g. xylose, citrate, lactate and succinate) was investigated. It was shown that AcuB has pleiotropic effects on the physiology of A. niger. The results indicate that metabolic...

  15. Syndrome of proximal interstitial deletion 4p15

    Energy Technology Data Exchange (ETDEWEB)

    Fryns, J.P. [Univ. of Leuven (Belgium)

    1995-09-11

    In this journal, Chitayat et al. reported on 2 boys and a girl with interstitial deletion in the short arm of chromosome 4, including p15.2p15.33. All 3 patients had a characteristic face distinct from that of Wolf-Hirschhorn syndrome and multiple minor congenital anomalies. One patient had a congenitally enlarged penis. The authors noted that all had normal growth, and all had moderate psychomotor retardation (patient 1, developmental age of 4-6 years at age 9 years; patient 2, mental age 6 years at age 25 years; and patient 3, global delay with hypotonia, difficulties in both gross and fine motor development, and persistent delay in language skills). 5 refs., 1 fig.

  16. Catalytic properties of ADAM12 and its domain deletion mutants

    DEFF Research Database (Denmark)

    Jacobsen, Jonas; Visse, Robert; Sørensen, Hans Peter

    2008-01-01

    of pro, catalytic, disintegrin, cysteine-rich, and EGF domains. Here we present a novel activity of recombinant ADAM12-S and its domain deletion mutants on S-carboxymethylated transferrin (Cm-Tf). Cleavage of Cm-Tf occurred at multiple sites, and N-terminal sequencing showed that the enzyme exhibits...... restricted specificity but a consensus sequence could not be defined as its subsite requirements are promiscuous. Kinetic analysis revealed that the noncatalytic C-terminal domains are important regulators of Cm-Tf activity and that ADAM12-PC consisting of the pro domain and catalytic domain is the most...... active on this substrate. It was also observed that NaCl inhibits ADAM12. Among the tissue inhibitors of metalloproteinases (TIMP) examined, the N-terminal domain of TIMP-3 (N-TIMP-3) inhibits ADAM12-S and ADAM12-PC with low nanomolar Ki(app) values while TIMP-2 inhibits them with a slightly lower...

  17. Kcne4 Deletion Sex-Dependently Alters Vascular Reactivity

    DEFF Research Database (Denmark)

    Abbott, Geoffrey W; Jepps, Thomas A

    2016-01-01

    transcripts, with no striking sex-specific differences. However, Kv7.4 protein expression in females was twice that in males, and was reduced in both sexes by Kcne4 deletion. Our findings confirm a crucial role for KCNE4 in regulation of Kv7 channel activity to modulate vascular tone, and provide the first......Voltage-gated potassium (Kv) channels formed by Kv7 (KCNQ) α-subunits are recognized as crucial for vascular smooth muscle function, in addition to their established roles in the heart (Kv7.1) and the brain (Kv7.2-5). In vivo, Kv7 α-subunits are often regulated by KCNE subfamily ancillary (β...... known molecular mechanism for sex-specificity of this modulation that has important implications for vascular reactivity and may underlie sex-specific susceptibility to cardiovascular diseases....

  18. Deletion of the Mitochondrial Chaperone TRAP-1 Uncovers Global Reprogramming of Metabolic Networks

    Directory of Open Access Journals (Sweden)

    Sofia Lisanti

    2014-08-01

    Full Text Available Reprogramming of metabolic pathways contributes to human disease, especially cancer, but the regulators of this process are unknown. Here, we have generated a mouse knockout for the mitochondrial chaperone TRAP-1, a regulator of bioenergetics in tumors. TRAP-1−/− mice are viable and showed reduced incidence of age-associated pathologies, including obesity, inflammatory tissue degeneration, dysplasia, and spontaneous tumor formation. This was accompanied by global upregulation of oxidative phosphorylation and glycolysis transcriptomes, causing deregulated mitochondrial respiration, oxidative stress, impaired cell proliferation, and a switch to glycolytic metabolism in vivo. These data identify TRAP-1 as a central regulator of mitochondrial bioenergetics, and this pathway could contribute to metabolic rewiring in tumors.

  19. Metabolic flux balance analysis and the in silico analysis of Escherichia coli K-12 gene deletions

    Directory of Open Access Journals (Sweden)

    Edwards Jeremy S

    2000-07-01

    Full Text Available Abstract Background Genome sequencing and bioinformatics are producing detailed lists of the molecular components contained in many prokaryotic organisms. From this 'parts catalogue' of a microbial cell, in silico representations of integrated metabolic functions can be constructed and analyzed using flux balance analysis (FBA. FBA is particularly well-suited to study metabolic networks based on genomic, biochemical, and strain specific information. Results Herein, we have utilized FBA to interpret and analyze the metabolic capabilities of Escherichia coli. We have computationally mapped the metabolic capabilities of E. coli using FBA and examined the optimal utilization of the E. coli metabolic pathways as a function of environmental variables. We have used an in silico analysis to identify seven gene products of central metabolism (glycolysis, pentose phosphate pathway, TCA cycle, electron transport system essential for aerobic growth of E. coli on glucose minimal media, and 15 gene products essential for anaerobic growth on glucose minimal media. The in silico tpi-, zwf, and pta- mutant strains were examined in more detail by mapping the capabilities of these in silico isogenic strains. Conclusions We found that computational models of E. coli metabolism based on physicochemical constraints can be used to interpret mutant behavior. These in silica results lead to a further understanding of the complex genotype-phenotype relation. Supplementary information: http://gcrg.ucsd.edu/supplementary_data/DeletionAnalysis/main.htm

  20. Construction and Analysis of Two Genome-Scale Deletion Libraries for Bacillus subtilis.

    Science.gov (United States)

    Koo, Byoung-Mo; Kritikos, George; Farelli, Jeremiah D; Todor, Horia; Tong, Kenneth; Kimsey, Harvey; Wapinski, Ilan; Galardini, Marco; Cabal, Angelo; Peters, Jason M; Hachmann, Anna-Barbara; Rudner, David Z; Allen, Karen N; Typas, Athanasios; Gross, Carol A

    2017-03-22

    A systems-level understanding of Gram-positive bacteria is important from both an environmental and health perspective and is most easily obtained when high-quality, validated genomic resources are available. To this end, we constructed two ordered, barcoded, erythromycin-resistance- and kanamycin-resistance-marked single-gene deletion libraries of the Gram-positive model organism, Bacillus subtilis. The libraries comprise 3,968 and 3,970 genes, respectively, and overlap in all but four genes. Using these libraries, we update the set of essential genes known for this organism, provide a comprehensive compendium of B. subtilis auxotrophic genes, and identify genes required for utilizing specific carbon and nitrogen sources, as well as those required for growth at low temperature. We report the identification of enzymes catalyzing several missing steps in amino acid biosynthesis. Finally, we describe a suite of high-throughput phenotyping methodologies and apply them to provide a genome-wide analysis of competence and sporulation. Altogether, we provide versatile resources for studying gene function and pathway and network architecture in Gram-positive bacteria. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  1. Glucose-dependent insulinotropic polypeptide (GIP) receptor deletion leads to reduced bone strength and quality.

    Science.gov (United States)

    Mieczkowska, Aleksandra; Irwin, Nigel; Flatt, Peter R; Chappard, Daniel; Mabilleau, Guillaume

    2013-10-01

    Bone is permanently remodeled by a complex network of local, hormonal and neuronal factors that affect osteoclast and osteoblast biology. In this context, a role for gastro-intestinal hormones has been proposed based on evidence that bone resorption dramatically falls after a meal. Glucose-dependent insulinotropic polypeptide (GIP) is one of the candidate hormones as its receptor, glucose-dependent insulinotropic polypeptide receptor (GIPR), is expressed in bone. In the present study we investigated bone strength and quality by three-point bending, quantitative x-ray microradiography, microCT, qBEI and FTIR in a GIPR knockout (GIPR KO) mouse model and compared with control wild-type (WT) animals. Animals with a deletion of the GIPR presented with a significant reduction in ultimate load (--11%), stiffness (-16%), total absorbed (-28%) and post-yield energies (-27%) as compared with WT animals. Furthermore, despite no change in bone outer diameter, the bone marrow diameter was significantly increased and as a result cortical thickness was significantly decreased by 20% in GIPR deficient animals. Bone resorption at the endosteal surface was significantly increased whilst bone formation was unchanged in GIPR deficient animals. Deficient animals also presented with a pronounced reduction in the degree of mineralization of bone matrix. Furthermore, the amount of mature cross-links of collagen matrix was significantly reduced in GIPR deficient animals and was associated with lowered intrinsic material properties. Taken together, these data support a positive effect of the GIPR on bone strength and quality. © 2013.

  2. Potential complications when developing gene deletion clones in Xylella fastidiosa.

    Science.gov (United States)

    Johnson, Kameka L; Cursino, Luciana; Athinuwat, Dusit; Burr, Thomas J; Mowery, Patricia

    2015-04-16

    The Gram-negative xylem-limited bacterium, Xylella fastidiosa, is an important plant pathogen that infects a number of high value crops. The Temecula 1 strain infects grapevines and induces Pierce's disease, which causes symptoms such as scorching on leaves, cluster collapse, and eventual plant death. In order to understand the pathogenesis of X. fastidiosa, researchers routinely perform gene deletion studies and select mutants via antibiotic markers. Site-directed pilJ mutant of X. fastidiosa were generated and selected on antibiotic media. Mutant cultures were assessed by PCR to determine if they were composed of purely transformant cells or included mixtures of non-transformants cells. Then pure pilJ mutant and wildtype cells were mixed in PD2 medium and following incubation and exposure to kanamycin were assessed by PCR for presence of mutant and wildtype populations. We have discovered that when creating clones of targeted mutants of X. fastidiosa Temecula 1 with selection on antibiotic plates, X. fastidiosa lacking the gene deletion often persist in association with targeted mutant cells. We believe this phenomenon is due to spontaneous antibiotic resistance and/or X. fastidiosa characteristically forming aggregates that can be comprised of transformed and non-transformed cells. A combined population was confirmed by PCR, which showed that targeted mutant clones were mixed with non-transformed cells. After repeated transfer and storage the non-transformed cells became the dominant clone present. We have discovered that special precautions are warranted when developing a targeted gene mutation in X. fastidiosa because colonies that arise following transformation and selection are often comprised of transformed and non-transformed cells. Following transfer and storage the cells can consist primarily of the non-transformed strain. As a result, careful monitoring of targeted mutant strains must be performed to avoid mixed populations and confounding results.

  3. Bad Clade Deletion Supertrees: A Fast and Accurate Supertree Algorithm.

    Science.gov (United States)

    Fleischauer, Markus; Böcker, Sebastian

    2017-09-01

    Supertree methods merge a set of overlapping phylogenetic trees into a supertree containing all taxa of the input trees. The challenge in supertree reconstruction is the way of dealing with conflicting information in the input trees. Many different algorithms for different objective functions have been suggested to resolve these conflicts. In particular, there exist methods based on encoding the source trees in a matrix, where the supertree is constructed applying a local search heuristic to optimize the respective objective function. We present a novel heuristic supertree algorithm called Bad Clade Deletion (BCD) supertrees. It uses minimum cuts to delete a locally minimal number of columns from such a matrix representation so that it is compatible. This is the complement problem to Matrix Representation with Compatibility (Maximum Split Fit). Our algorithm has guaranteed polynomial worst-case running time and performs swiftly in practice. Different from local search heuristics, it guarantees to return the directed perfect phylogeny for the input matrix, corresponding to the parent tree of the input trees, if one exists. Comparing supertrees to model trees for simulated data, BCD shows a better accuracy (F1 score) than the state-of-the-art algorithms SuperFine (up to 3%) and Matrix Representation with Parsimony (up to 7%); at the same time, BCD is up to 7 times faster than SuperFine, and up to 600 times faster than Matrix Representation with Parsimony. Finally, using the BCD supertree as a starting tree for a combined Maximum Likelihood analysis using RAxML, we reach significantly improved accuracy (1% higher F1 score) and running time (1.7-fold speedup). © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  4. Deletion of 7q33-q35 in a Patient with Intellectual Disability and Dysmorphic Features: Further Characterization of 7q Interstitial Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Kristen Dilzell

    2015-01-01

    Full Text Available This case report concerns a 16-year-old girl with a 9.92 Mb, heterozygous interstitial chromosome deletion at 7q33-q35, identified using array comparative genomic hybridization. The patient has dysmorphic facial features, intellectual disability, recurrent infections, self-injurious behavior, obesity, and recent onset of hemihypertrophy. This patient has overlapping features with previously reported individuals who have similar deletions spanning the 7q32-q36 region. It has been difficult to describe an interstitial 7q deletion syndrome due to variations in the sizes and regions in the few patients reported in the literature. This case contributes to the further characterization of an interstitial distal 7q deletion syndrome.

  5. Do all roads lead to Rome? A comparison of brain networks derived from inter-subject volumetric and metabolic covariance and moment-to-moment hemodynamic correlations in old individuals.

    Science.gov (United States)

    Di, Xin; Gohel, Suril; Thielcke, Andre; Wehrl, Hans F; Biswal, Bharat B

    2017-11-01

    Relationships between spatially remote brain regions in human have typically been estimated by moment-to-moment correlations of blood-oxygen-level dependent signals in resting-state using functional MRI (fMRI). Recently, studies using subject-to-subject covariance of anatomical volumes, cortical thickness, and metabolic activity are becoming increasingly popular. However, question remains on whether these measures reflect the same inter-region connectivity and brain network organizations. In the current study, we systematically analyzed inter-subject volumetric covariance from anatomical MRI images, metabolic covariance from fluorodeoxyglucose positron emission tomography images from 193 healthy subjects, and resting-state moment-to-moment correlations from fMRI images of a subset of 44 subjects. The correlation matrices calculated from the three methods were found to be minimally correlated, with higher correlation in the range of 0.31, as well as limited proportion of overlapping connections. The volumetric network showed the highest global efficiency and lowest mean clustering coefficient, leaning toward random-like network, while the metabolic and resting-state networks conveyed properties more resembling small-world networks. Community structures of the volumetric and metabolic networks did not reflect known functional organizations, which could be observed in resting-state network. The current results suggested that inter-subject volumetric and metabolic covariance do not necessarily reflect the inter-regional relationships and network organizations as resting-state correlations, thus calling for cautions on interpreting results of inter-subject covariance networks.

  6. Impaired spermatogenesis and gr/gr deletions related to Y chromosome haplogroups in Korean men.

    Directory of Open Access Journals (Sweden)

    Jin Choi

    Full Text Available Microdeletion of the Azoospermia Factor (AZF regions in Y chromosome is a well-known genetic cause of male infertility resulting from spermatogenetic impairment. However, the partial deletions of AZFc region related to spermatogenetic impairment are controversial. In this study, we characterized partial deletion of AZFc region in Korean patients with spermatogenetic impairment and assessed whether the DAZ and CDY1 contributes to the phenotype in patients with gr/gr deletions. Total of 377 patients with azoo-/oligozoospermia and 217 controls were analyzed using multiplex polymerase chain reaction (PCR, analysis of DAZ-CDY1 sequence family variants (SFVs, and quantitative fluorescent (QF-PCR. Of the 377 men with impaired spermatogenesis, 59 cases (15.6% had partial AZFc deletions, including 32 gr/gr (8.5%, 22 b2/b3 (5.8%, four b1/b3 (1.1% and one b3/b4 (0.3% deletion. In comparison, 14 of 217 normozoospermic controls (6.5% had partial AZFc deletions, including five gr/gr (2.3% and nine b2/b3 (4.1% deletions. The frequency of gr/gr deletions was significantly higher in the azoo-/oligozoospermic group than in the normozoospermic control group (p = 0.003; OR = 3.933; 95% CI = 1.509-10.250. Concerning Y haplogroup, we observed no significant differences in the frequency of gr/gr deletions between the case and the control groups in the YAP+ lineages, while gr/gr deletion were significantly higher in azoo-/oligozoospermia than normozoospermia in the YAP- lineage (p = 0.004; OR = 6.341; 95% CI = 1.472-27.312. Our data suggested that gr/gr deletion is associated with impaired spermatogenesis in Koreans with YAP- lineage, regardless of the gr/gr subtypes.

  7. Comparative genome analysis identifies two large deletions in the genome of highly-passaged attenuated Streptococcus agalactiae strain YM001 compared to the parental pathogenic strain HN016.

    Science.gov (United States)

    Wang, Rui; Li, Liping; Huang, Yan; Luo, Fuguang; Liang, Wanwen; Gan, Xi; Huang, Ting; Lei, Aiying; Chen, Ming; Chen, Lianfu

    2015-11-04

    Streptococcus agalactiae (S. agalactiae), also known as group B Streptococcus (GBS), is an important pathogen for neonatal pneumonia, meningitis, bovine mastitis, and fish meningoencephalitis. The global outbreaks of Streptococcus disease in tilapia cause huge economic losses and threaten human food hygiene safety as well. To investigate the mechanism of S. agalactiae pathogenesis in tilapia and develop attenuated S. agalactiae vaccine, this study sequenced and comparatively analyzed the whole genomes of virulent wild-type S. agalactiae strain HN016 and its highly-passaged attenuated strain YM001 derived from tilapia. We performed Illumina sequencing of DNA prepared from strain HN016 and YM001. Sequencedreads were assembled and nucleotide comparisons, single nucleotide polymorphism (SNP) , indels were analyzed between the draft genomes of HN016 and YM001. Clustered regularly interspaced short palindromic repeats (CRISPRs) and prophage were detected and analyzed in different S. agalactiae strains. The genome of S. agalactiae YM001 was 2,047,957 bp with a GC content of 35.61 %; it contained 2044 genes and 88 RNAs. Meanwhile, the genome of S. agalactiae HN016 was 2,064,722 bp with a GC content of 35.66 %; it had 2063 genes and 101 RNAs. Comparative genome analysis indicated that compared with HN016, YM001 genome had two significant large deletions, at the sizes of 5832 and 11,116 bp respectively, resulting in the deletion of three rRNA and ten tRNA genes, as well as the deletion and functional damage of ten genes related to metabolism, transport, growth, anti-stress, etc. Besides these two large deletions, other ten deletions and 28 single nucleotide variations (SNVs) were also identified, mainly affecting the metabolism- and growth-related genes. The genome of attenuated S. agalactiae YM001 showed significant variations, resulting in the deletion of 10 functional genes, compared to the parental pathogenic strain HN016. The deleted and mutated functional genes all

  8. Deletion of the Saccharomyces cerevisiae ARO8 gene, encoding an aromatic amino acid transaminase, enhances phenylethanol production from glucose.

    Science.gov (United States)

    Romagnoli, Gabriele; Knijnenburg, Theo A; Liti, Gianni; Louis, Edward J; Pronk, Jack T; Daran, Jean-Marc

    2015-01-01

    Phenylethanol has a characteristic rose-like aroma that makes it a popular ingredient in foods, beverages and cosmetics. Microbial production of phenylethanol currently relies on whole-cell bioconversion of phenylalanine with yeasts that harbour an Ehrlich pathway for phenylalanine catabolism. Complete biosynthesis of phenylethanol from a cheap carbon source, such as glucose, provides an economically attractive alternative for phenylalanine bioconversion. In this study, synthetic genetic array (SGA) screening was applied to identify genes involved in regulation of phenylethanol synthesis in Saccharomyces cerevisiae. The screen focused on transcriptional regulation of ARO10, which encodes the major decarboxylase involved in conversion of phenylpyruvate to phenylethanol. A deletion in ARO8, which encodes an aromatic amino acid transaminase, was found to underlie the transcriptional upregulation of ARO10 during growth, with ammonium sulphate as the sole nitrogen source. Physiological characterization revealed that the aro8Δ mutation led to substantial changes in the absolute and relative intracellular concentrations of amino acids. Moreover, deletion of ARO8 led to de novo production of phenylethanol during growth on a glucose synthetic medium with ammonium as the sole nitrogen source. The aro8Δ mutation also stimulated phenylethanol production when combined with other, previously documented, mutations that deregulate aromatic amino acid biosynthesis in S. cerevisiae. The resulting engineered S. cerevisiae strain produced >3 mm phenylethanol from glucose during growth on a simple synthetic medium. The strong impact of a transaminase deletion on intracellular amino acid concentrations opens new possibilities for yeast-based production of amino acid-derived products. Copyright © 2014 John Wiley & Sons, Ltd.

  9. SnoRNA Snord116 (Pwcr1/MBII-85 deletion causes growth deficiency and hyperphagia in mice.

    Directory of Open Access Journals (Sweden)

    Feng Ding

    Full Text Available Prader-Willi syndrome (PWS is the leading genetic cause of obesity. After initial severe hypotonia, PWS children become hyperphagic and morbidly obese, if intake is not restricted. Short stature with abnormal growth hormone secretion, hypogonadism, cognitive impairment, anxiety and behavior problems are other features. PWS is caused by lack of expression of imprinted genes in a approximately 4 mb region of chromosome band 15q11.2. Our previous translocation studies predicted a major role for the C/D box small nucleolar RNA cluster SNORD116 (PWCR1/HBII-85 in PWS. To test this hypothesis, we created a approximately 150 kb deletion of the > 40 copies of Snord116 (Pwcr1/MBII-85 in C57BL/6 mice. Snord116del mice with paternally derived deletion lack expression of this snoRNA. They have early-onset postnatal growth deficiency, but normal fertility and lifespan. While pituitary structure and somatotrophs are normal, liver Igf1 mRNA is decreased. In cognitive and behavior tests, Snord116del mice are deficient in motor learning and have increased anxiety. Around three months of age, they develop hyperphagia, but stay lean on regular and high-fat diet. On reduced caloric intake, Snord116del mice maintain their weight better than wild-type littermates, excluding increased energy requirement as a cause of hyperphagia. Normal compensatory feeding after fasting, and ability to maintain body temperature in the cold indicate normal energy homeostasis regulation. Metabolic chamber studies reveal that Snord116del mice maintain energy homeostasis by altered fuel usage. Prolonged mealtime and increased circulating ghrelin indicate a defect in meal termination mechanism. Snord116del mice, the first snoRNA deletion animal model, reveal a novel role for a non-coding RNA in growth and feeding regulation.

  10. Current approaches to gene regulatory network modelling

    Directory of Open Access Journals (Sweden)

    Brazma Alvis

    2007-09-01

    Full Text Available Abstract Many different approaches have been developed to model and simulate gene regulatory networks. We proposed the following categories for gene regulatory network models: network parts lists, network topology models, network control logic models, and dynamic models. Here we will describe some examples for each of these categories. We will study the topology of gene regulatory networks in yeast in more detail, comparing a direct network derived from transcription factor binding data and an indirect network derived from genome-wide expression data in mutants. Regarding the network dynamics we briefly describe discrete and continuous approaches to network modelling, then describe a hybrid model called Finite State Linear Model and demonstrate that some simple network dynamics can be simulated in this model.

  11. Combined Heuristic Attack Strategy on Complex Networks

    Directory of Open Access Journals (Sweden)

    Marek Šimon

    2017-01-01

    Full Text Available Usually, the existence of a complex network is considered an advantage feature and efforts are made to increase its robustness against an attack. However, there exist also harmful and/or malicious networks, from social ones like spreading hoax, corruption, phishing, extremist ideology, and terrorist support up to computer networks spreading computer viruses or DDoS attack software or even biological networks of carriers or transport centers spreading disease among the population. New attack strategy can be therefore used against malicious networks, as well as in a worst-case scenario test for robustness of a useful network. A common measure of robustness of networks is their disintegration level after removal of a fraction of nodes. This robustness can be calculated as a ratio of the number of nodes of the greatest remaining network component against the number of nodes in the original network. Our paper presents a combination of heuristics optimized for an attack on a complex network to achieve its greatest disintegration. Nodes are deleted sequentially based on a heuristic criterion. Efficiency of classical attack approaches is compared to the proposed approach on Barabási-Albert, scale-free with tunable power-law exponent, and Erdős-Rényi models of complex networks and on real-world networks. Our attack strategy results in a faster disintegration, which is counterbalanced by its slightly increased computational demands.

  12. Rapid deletion plasmid construction methods for protoplast and Agrobacterium based fungal transformation systems

    Science.gov (United States)

    Increasing availability of genomic data and sophistication of analytical methodology in fungi has elevated the need for functional genomics tools in these organisms. Gene deletion is a critical tool for functional analysis. The targeted deletion of genes requires both a suitable method for the trans...

  13. Deletion of /T, D/ and the Acquisition of Linguistic Variation by Second Language Learners of English

    Science.gov (United States)

    Edwards, Jette G. Hansen

    2011-01-01

    This study investigated second language (L2) learners' acquisition of English /t, d/ deletion patterns in word-final consonant clusters, (a) focusing on how constraints such as grammatical conditioning and phonological environment affect deletion of /t, d/ in L2 acquisition and (b) determining the extent to which these L2 learners had acquired…

  14. Multiple Patterns of FHIT Gene Homozygous Deletion in Egyptian Breast Cancer Patients

    International Nuclear Information System (INIS)

    Ismail, H.M.S.; Zakhary, N.I.; Medhat, A.M.; Karim, A.M.

    2011-01-01

    Fragile histidine triad (FHIT) gene encodes a putative tumour suppressor protein. Loss of Fhit protein in cancer is attributed to different genetic alterations that affect the FHIT gene structure. In this study, we investigated the pattern of homozygous deletion that target the FHIT gene exons 3 to 9 genomic structure in Egyptian breast cancer patients. We have found that 65% (40 out of 62) of the cases exhibited homozygous deletion in at least one FHIT exon. The incidence of homozygous deletion was not associated with patients clinico pathological parameters including patients age, tumour grade, tumour type, and lymph node involvement. Using correlation analysis, we have observed a strong correlation between homozygous deletions of exon 3 and exon 4 (P<0.0001). Deletions in exon 5 were positively correlated with deletions in exon 7 (P<0.0001), Exon 8 (P<0.027), and exon 9 (P=0.04). Additionally, a strong correlation was observed between exons 8 and exon 9 (P<0.0001).We conclude that FHIT gene exons are homozygously deleted at high frequency in Egyptian women population diagnosed with breast cancer. Three different patterns of homozygous deletion were observed in this population indicating different mechanisms of targeting FHIT gene genomic structure.

  15. 40 CFR 63.60 - Deletion of caprolactam from the list of hazardous air pollutants.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 9 2010-07-01 2010-07-01 false Deletion of caprolactam from the list of hazardous air pollutants. 63.60 Section 63.60 Protection of Environment ENVIRONMENTAL PROTECTION..., Source Category List § 63.60 Deletion of caprolactam from the list of hazardous air pollutants. The...

  16. Autism, ADHD, Mental Retardation and Behavior Problems in 100 Individuals with 22q11 Deletion Syndrome

    Science.gov (United States)

    Niklasson, Lena; Rasmussen, Peder; Oskarsdottir, Solveig; Gillberg, Christopher

    2009-01-01

    This study assessed the prevalence and type of associated neuropsychiatric problems in children and adults with 22q11 deletion syndrome. One-hundred consecutively referred individuals with 22q11 deletion syndrome were given in-depth neuropsychiatric assessments and questionnaires screens. Autism spectrum disorders (ASDs) and/or attention…

  17. Prenatal Diagnosis and Molecular Analysis of a Large Novel Deletion (- -JS) Causing α0-Thalassemia.

    Science.gov (United States)

    Cao, Jinru; He, Shuzhen; Pu, Yudong; Liu, Jingjing; Liu, Fuping; Feng, Jun

    α-Thalassemia (α-thal) is a very common single gene hereditary disease caused by large deletions or point mutations of the α-globin gene cluster in tropical and subtropical regions of the world. Here, we report for the first time, a novel large α-thal deletion in a Chinese family from Jiangsu Province, People's Republic of China (PRC), which removes almost the entire α2 and α1 genes from the α-globin gene cluster. Thus, it was named the Jiangsu deletion (- - JS ) on the α-globin gene cluster causing α 0 -thal. Heterozygotes for this deletion showed an α-thal trait phenotype with reduced mean corpuscular volume (MCV) and mean corpuscular hemoglobin (Hb) (MCH) levels. The sequencing results showed that a 2538 bp deletion (NG_000006.1: g.35801_38338) existed in this novel genotype on the basis of -α 4.2 (leftward), indicating a deletion of about 6.8 kb from the α-globin cluster. In addition, a 29 bp sequence was inserted into the deletion during the recombination events that led to this deletion. Through pedigree analysis, we knew that the proband inherited the novel allele from his mother.

  18. UCP2 and 3 deletion screening and distribution in 15 pig breeds.

    Science.gov (United States)

    Li, Yanhua; Li, Hanjie; Zhao, Xingbo; Li, Ning; Wu, Changxin

    2007-02-01

    The uncoupling protein family is a mitochondrial anion carrier family. It plays an important role in the biological traits of animal body weight, basal metabolic rate and energy conversion. Using PCR and PCR-SSCP, we scanned the porcine uncoupling protein 2 gene (UCP2) and uncoupling protein 3 gene (UCP3) and found seven deletion sites, three in UCP2 and four in UCP3. The deletions in 15 pig breeds showed that deletion influenced weight. The genotype compounding of seven deletion sites in 15 pig breeds had significant effects on performance traits of the pig, such as body weight. We predicted the potential protein factor binding sites using the transcription factor analysis tool TFSearch version 1.3 online. Two deletions (1830 nt and 3219 nt) in UCP3 were found to change the transcriptional factor sites. The 16 bp deletion in 1830 nt added a SP1 site and a 6 bp deletion in 3219 nt removed two MZF1 sites. Seven deletion polymorphisms were covered in introns of linkage genes of UCP2 and UCP3, showing that UCPs have conservation and genetic reliability.

  19. Genotype call for chromosomal deletions using read-depth from whole genome sequence variants in cattle

    DEFF Research Database (Denmark)

    Mesbah-Uddin, Md; Guldbrandtsen, Bernt; Lund, Mogens Sandø

    2018-01-01

    We presented a deletion genotyping (copy-number estimation) method that leverages population-scale whole genome sequence variants data from 1K bull genomes project (1KBGP) to build reference panel for imputation. To estimate deletion-genotype likelihood, we extracted read-depth (RD) data of all...

  20. Oncogenic activation of FOXR1 by 11q23 intrachromosomal deletion-fusions in neuroblastoma

    NARCIS (Netherlands)

    Santo, E. E.; Ebus, M. E.; Koster, J.; Schulte, J. H.; Lakeman, A.; van Sluis, P.; Vermeulen, J.; Gisselsson, D.; Øra, I.; Lindner, S.; Buckley, P. G.; Stallings, R. L.; Vandesompele, J.; Eggert, A.; Caron, H. N.; Versteeg, R.; Molenaar, J. J.

    2012-01-01

    Neuroblastoma tumors frequently show loss of heterozygosity of chromosome 11q with a shortest region of overlap in the 11q23 region. These deletions are thought to cause inactivation of tumor suppressor genes leading to haploinsufficiency. Alternatively, micro-deletions could lead to gene fusion

  1. 77 FR 17055 - Sunshine Act Meeting; Deletion of Agenda Items From March 21, 2012 Open Meeting

    Science.gov (United States)

    2012-03-23

    ... FEDERAL COMMUNICATIONS COMMISSION Sunshine Act Meeting; Deletion of Agenda Items From March 21, 2012 Open Meeting March 20, 2012. The following items have been deleted from the list of Agenda items scheduled for consideration at the Wednesday, March 21, 2012, Open Meeting and previously listed in the...

  2. New recurrent deletions in the PPARgamma and TP53 genes are associated with childhood myelodysplastic syndrome

    DEFF Research Database (Denmark)

    Silveira, Cássia G T; Oliveira, Fábio M; Valera, Elvis T

    2009-01-01

    Myelodysplastic syndrome (MDS) is a rare hematological malignancy in children. It was performed FISH analysis in 19 pediatric MDS patients to investigate deletions involving the PPARgamma and TP53 genes. Significant losses in the PPARgamma gene and deletions in the tumor suppressor gene TP53 were...

  3. A new alpha(0)-thalassemia deletion found in a Dutch family (--(AW)).

    NARCIS (Netherlands)

    Phylipsen, M.; Vogelaar, I.P.; Schaap, R.A.; Arkesteijn, S.G.; Boxma, G.L.; Helden, W.C. van; Wildschut, I.C.; Bruin-Roest, A.C. de; Giordano, P.C.; Harteveld, C.L.

    2010-01-01

    Alpha-thalassemia is an inherited hemoglobin disorder characterized by a microcytic hypochromic anemia caused by a quantitative reduction of the alpha-globin chain. The majority of the alpha-thalassemias is caused by deletions in the alpha-globin gene cluster. A deletion in the alpha-globin gene

  4. The smt-0 mutation which abolishes mating-type switching in fission yeast is a deletion

    DEFF Research Database (Denmark)

    Styrkársdóttir, U; Egel, R; Nielsen, O

    1993-01-01

    Mating-type switching in the fission yeast, S. pombe, is initiated by a DNA double-strand break (DSB) between the mat1 cassette and the H1 homology box. The mat1-cis-acting mutant, smt-0, abolishes mating-type switching and is shown here to be a 263-bp deletion. This deletion starts in the middle...

  5. Neural correlates of reward processing in adults with 22q11 deletion syndrome

    NARCIS (Netherlands)

    van Duin, Esther D. A.; Goossens, Liesbet; Hernaus, Dennis; da Silva Alves, Fabiana; Schmitz, Nicole; Schruers, Koen; van Amelsvoort, Therese

    2016-01-01

    Background: 22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic

  6. Y chromosome gr/gr deletions are a risk factor for low semen quality

    NARCIS (Netherlands)

    Visser, L.; Westerveld, G. H.; Korver, C. M.; van Daalen, S. K. M.; Hovingh, S. E.; Rozen, S.; van der Veen, F.; Repping, S.

    2009-01-01

    Subfertility affects one in eight couples. In up to 50% of cases, the male partner has low semen quality. Four Y chromosome deletions, i.e. Azoospermia factor a (AZFa), P5/proximal-P1 (AZFb), P5/distal-P1 and AZFc deletions, are established causes of low semen quality. Whether a recently identified

  7. 78 FR 2363 - Notification of Deletion of a System of Records; Automated Trust Funds Database

    Science.gov (United States)

    2013-01-11

    ... [Docket No. APHIS-2012-0041] Notification of Deletion of a System of Records; Automated Trust Funds Database AGENCY: Animal and Plant Health Inspection Service, USDA. ACTION: Notice of deletion of a system... establishing the Automated Trust Funds (ATF) database system of records. The Federal Information Security...

  8. Maladaptive Behavior Differences in Prader-Willi Syndrome Due to Paternal Deletion versus Maternal Uniparental Disomy.

    Science.gov (United States)

    Dykens, Elisabeth M.; King, Bryan H.; Cassidy, Suzanne B.

    1999-01-01

    This study compared maladaptive behavior in 23 people with Prader-Willi syndrome due to paternal deletion and in 23 age- and gender-matched subjects with maternal uniparental disomy. Controlling for IQs, the deletion cases showed significantly higher maladaptive ratings, more symptom-related distress, and more behavior problems. Findings suggest a…

  9. Neural correlates of reward processing in adults with 22q11 deletion syndrome.

    Science.gov (United States)

    van Duin, Esther D A; Goossens, Liesbet; Hernaus, Dennis; da Silva Alves, Fabiana; Schmitz, Nicole; Schruers, Koen; van Amelsvoort, Therese

    2016-01-01

    22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission. The functional anatomy of the brain reward circuitry has not yet been investigated in 22q11DS. This study aims to investigate neural activity during anticipation of reward and loss in adult patients with 22q11DS. We measured blood-oxygen-level dependent (BOLD) activity in 16 patients with 22q11DS and 12 healthy controls during a monetary incentive delay task using a 3T Philips Intera MRI system. Data were analysed using SPM8. During anticipation of reward, the 22q11DS group alone displayed significant activation in bilateral middle frontal and temporal brain regions. Compared to healthy controls, significantly less activation in bilateral cingulate gyrus extending to premotor, primary motor and somatosensory areas was found. During anticipation of loss, the 22q11DS group displayed activity in the left middle frontal gyrus and anterior cingulate cortex, and relative to controls, they showed reduced brain activation in bilateral (pre)cuneus and left posterior cingulate. Within the 22q11DS group, COMT Val hemizygotes displayed more activation compared to Met hemizygotes in right posterior cingulate and bilateral parietal regions during anticipation of reward. During anticipation of loss, COMT Met hemizygotes compared to Val hemizygotes showed more activation in bilateral insula, striatum and left anterior cingulate. This is the first study to investigate reward processing in 22q11DS. Our preliminary results suggest that people with 22q11DS

  10. The Role of Middlemen inEfficient and Strongly Pairwise Stable Networks

    NARCIS (Netherlands)

    Gilles, R.P.; Chakrabarti, S.; Sarangi, S.; Badasyan, N.

    2004-01-01

    We examine the strong pairwise stability concept in network formation theory under collective network benefits.Strong pairwise stability considers a pair of players to add a link through mutual consent while permitting them to unilaterally delete any subset of links under their control.We examine

  11. Transcriptomic profile of aguR deletion mutant of Lactococcus lactis subsp. cremoris CECT 8666

    Science.gov (United States)

    del Rio, Beatriz; Linares, Daniel M.; Redruello, Begoña; Martin, Maria Cruz; Fernandez, Maria; de Jong, Anne; Kuipers, Oscar P.; Ladero, Victor; Alvarez, Miguel A.

    2015-01-01

    Lactococcus lactis subsp. cremoris CECT 8666 (formerly GE2-14) is a dairy strain that catabolizes agmatine (a decarboxylated derivative of arginine) into the biogenic amine putrescine by the agmatine deiminase (AGDI) pathway [1]. The AGDI cluster of L. lactis is composed by five genes aguR, aguB, aguD, aguA and aguC. The last four genes are responsible for the deamination of agmatine to putrescine and are co-transcribed as a single policistronic mRNA forming the catabolic operon aguBDAC[1]. aguR encodes a transmembrane protein that functions as a one-component signal transduction system that senses the agmatine concentration of the medium and accordingly regulates the transcription of aguBDAC[2], which is also transcriptionally regulated by carbon catabolic repression (CCR) via glucose, but not by other sugars such as lactose and galactose [1], [3]. Here we report the transcriptional profiling of the aguR gene deletion mutant (L. lactis subsp. cremoris CECT 8666 ∆aguR) [2] compared to the wild type strain, both grown in M17 medium with galactose as carbon source and supplemented with agmatine. The transcriptional profiling data of AguR-regulated genes were deposited in the Gene Expression Omnibus (GEO) database under accession no. GSE59514. PMID:26697381

  12. Transcriptomic profile of aguR deletion mutant of Lactococcus lactis subsp. cremoris CECT 8666

    Directory of Open Access Journals (Sweden)

    Beatriz del Rio

    2015-12-01

    Full Text Available Lactococcus lactis subsp. cremoris CECT 8666 (formerly GE2-14 is a dairy strain that catabolizes agmatine (a decarboxylated derivative of arginine into the biogenic amine putrescine by the agmatine deiminase (AGDI pathway [1]. The AGDI cluster of L. lactis is composed by five genes aguR, aguB, aguD, aguA and aguC. The last four genes are responsible for the deamination of agmatine to putrescine and are co-transcribed as a single policistronic mRNA forming the catabolic operon aguBDAC [1]. aguR encodes a transmembrane protein that functions as a one-component signal transduction system that senses the agmatine concentration of the medium and accordingly regulates the transcription of aguBDAC [2], which is also transcriptionally regulated by carbon catabolic repression (CCR via glucose, but not by other sugars such as lactose and galactose [1,3]. Here we report the transcriptional profiling of the aguR gene deletion mutant (L. lactis subsp. cremoris CECT 8666 ∆aguR [2] compared to the wild type strain, both grown in M17 medium with galactose as carbon source and supplemented with agmatine. The transcriptional profiling data of AguR-regulated genes were deposited in the Gene Expression Omnibus (GEO database under accession no. GSE59514.

  13. Deletion of an X-inactivation boundary disrupts adjacent gene silencing.

    Directory of Open Access Journals (Sweden)

    Lindsay M Horvath

    2013-11-01

    Full Text Available In mammalian females, genes on one X are largely silenced by X-chromosome inactivation (XCI, although some "escape" XCI and are expressed from both Xs. Escapees can closely juxtapose X-inactivated genes and provide a tractable model for assessing boundary function at epigenetically regulated loci. To delimit sequences at an XCI boundary, we examined female mouse embryonic stem cells carrying X-linked BAC transgenes derived from an endogenous escape locus. Previously we determined that large BACs carrying escapee Kdm5c and flanking X-inactivated transcripts are properly regulated. Here we identify two lines with truncated BACs that partially and completely delete the distal Kdm5c XCI boundary. This boundary is not required for escape, since despite integrating into regions that are normally X inactivated, transgenic Kdm5c escapes XCI, as determined by RNA FISH and by structurally adopting an active conformation that facilitates long-range preferential association with other escapees. Yet, XCI regulation is disrupted in the transgene fully lacking the distal boundary; integration site genes up to 350 kb downstream of the transgene now inappropriately escape XCI. Altogether, these results reveal two genetically separable XCI regulatory activities at Kdm5c. XCI escape is driven by a dominant element(s retained in the shortest transgene that therefore lies within or upstream of the Kdm5c locus. Additionally, the distal XCI boundary normally plays an essential role in preventing nearby genes from escaping XCI.

  14. Deletion Analysis Of The Duchenne/Becker Muscular Dystrophy Gene Using Multiplex Polymerase Chain Reaction

    Directory of Open Access Journals (Sweden)

    Dastur P

    2004-01-01

    Full Text Available The diagnosis of Duchenna Muscular Dystrophy (DMD and Becker Muscular Dystorphy (BMD is mainly based on clinical profile, serum CPK values, muscle biopsy and immunostaining for dystrophin. This was done in 100 unrelated patients using 19 exons including the promoter region in two sets of multiplex polymerase chain reaction (PCR. These primers amplify most of the exons in the deletion prone ′hot spot′ regions allowing determinations of deletion end points. Intragenic deletions were detected in 74 patients indicating that the use of PCR- based assays will allow deletion detection help in prenatal diagnosis for most of the DMD/BMD patients. The frequency of deletions observed in the present study was 74%.

  15. Deletion Analysis Of The Duchenne/Becker Muscular Dystrophy Gene Using Multiplex Polymerase Chain Reaction

    Directory of Open Access Journals (Sweden)

    Dastur R

    2003-01-01

    Full Text Available The diagnosis of Duchenne Muscular Dystrophy (DMD and Becker Muscular Dystrophy (BMD is mainly based on clinical profile, serum CPK values, muscle biopsy and immunostaining for dystrophin. Most recent and accurate method for diagnosing DMD/BMD is by detection of mutations in the DMD gene. This was done in 100 unrelated patients using 19 exons including the promoter region in two sets of multiplex polymerase chain reaction (PCR. These primers amplify most of the exons in the deletion prone ′hotspot′ regions allowing determination of deletion end point. Intragenic deletions were detected in 74 patients indicating that the use of PCR-based assays will allow deletion detection help in prenatal diagnosis for most of the DMD/BMD patients. The frequency of deletions observed in the present study was 74%.

  16. Heart defects and other features of the 22q11 distal deletion syndrome

    DEFF Research Database (Denmark)

    Fagerberg, Christina Ringmann; Graakjaer, Jesper; Heinl, Ulrike D

    2013-01-01

    patients with 22q11 distal deletions, of whom two have complex congenital heart malformation, thus broadening the phenotypic spectrum. We compare cardiac malformations reported in 22q11 distal deletion to those reported in the common 22q11 deletion syndrome. We also review the literature for patients...... with 22q11 distal deletions, and discuss the possible roles of haploinsufficiency of the MAPK1 gene. We find the most frequent features in 22q11 distal deletion to be developmental delay or learning disability, short stature, microcephalus, premature birth with low birth weight, and congenital heart...... malformation ranging from minor anomalies to complex malformations. Behavioral problems are also seen in a substantial portion of patients. The following dysmorphic features are relatively common: smooth philtrum, abnormally structured ears, cleft palate/bifid uvula, micro-/retrognathia, upslanting palpebral...

  17. 22q13.3 Deletion Syndrome: An Underdiagnosed Cause of Mental Retardation

    Directory of Open Access Journals (Sweden)

    ilknur Erol

    2015-03-01

    Full Text Available Phelan-McDermid syndrome, also known as 22q13.3 deletion syndrome, is characterized by global developmental delay, absent or delayed speech, generalized hypotonia, and minor physical anomalies. The deletion typically involves the terminal band 22q13.3 and has been associated with both familial and de-novo translocations. We report the case of an 11-year-old Turkish girl with 22q13.3 deletion syndrome presenting with repeated seizures during the course of a rubella infection. We also review the clinical features of 22q13.3 deletion syndrome and emphasize the importance of considering a rare microdeletion syndrome for idiopathic mental retardation when results of a routine karyotype analysis are normal. To the best of our knowledge, this is the first reported case of a Turkish patient with isolated 22q13.3 deletion syndrome. [Cukurova Med J 2015; 40(1.000: 169-173

  18. Relatively low proportion of dystrophin gene deletions in Israeili Duchenne and Becker muscular dystrophy patients

    Energy Technology Data Exchange (ETDEWEB)

    Shomrat, R.; Gluck, E.; Legum, C.; Shiloh, Y. [Tel Aviv Univ. (Israel)

    1994-02-15

    Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) are allelic disorders caused by mutations in the X-linked dystrophin gene. The most common mutations in western populations are deletions that are spread non-randomly throughout the gene. Molecular analysis of the dystrophin gene structure by hybridization of the full length cDNA to Southern blots and by PCR in 62 unrelated Israeli male DMD/BMD patients showed deletions in 23 (37%). This proportion is significantly lower than that found in European and North American populations (55-65%). Seventy-eight percent of the deletions were confined to exons 44-52, half of these exons 44-45, and the remaining 22% to exons 1 and 19. There was no correlation between the size of the deletion and the severity of the disease. All the deletions causing frameshift resulted in the DMD phenotypes. 43 refs., 1 fig., 1 tab.

  19. A deletion affecting an LRR-RLK gene co-segregates with the fruit flat shape trait in peach.

    Science.gov (United States)

    López-Girona, Elena; Zhang, Yu; Eduardo, Iban; Mora, José Ramón Hernández; Alexiou, Konstantinos G; Arús, Pere; Aranzana, María José

    2017-07-27

    In peach, the flat phenotype is caused by a partially dominant allele in heterozygosis (Ss), fruits from homozygous trees (SS) abort a few weeks after fruit setting. Previous research has identified a SSR marker (UDP98-412) highly associated with the trait, found suitable for marker assisted selection (MAS). Here we report a ∼10 Kb deletion affecting the gene PRUPE.6G281100, 400 Kb upstream of UDP98-412, co-segregating with the trait. This gene is a leucine-rich repeat receptor-like kinase (LRR-RLK) orthologous to the Brassinosteroid insensitive 1-associated receptor kinase 1 (BAK1) group. PCR markers suitable for MAS confirmed its strong association with the trait in a collection of 246 cultivars. They were used to evaluate the DNA from a round fruit derived from a somatic mutation of the flat variety 'UFO-4', revealing that the mutation affected the flat associated allele (S). Protein BLAST alignment identified significant hits with genes involved in different biological processes. Best protein hit occurred with AtRLP12, which may functionally complement CLAVATA2, a key regulator that controls the stem cell population size. RT-PCR analysis revealed the absence of transcription of the partially deleted allele. The data support PRUPE.6G281100 as a candidate gene for flat shape in peach.

  20. Subtelomeric deletion of chromosome 10p15.3: clinical findings and molecular cytogenetic characterization.

    Science.gov (United States)

    DeScipio, Cheryl; Conlin, Laura; Rosenfeld, Jill; Tepperberg, James; Pasion, Romela; Patel, Ankita; McDonald, Marie T; Aradhya, Swaroop; Ho, Darlene; Goldstein, Jennifer; McGuire, Marianne; Mulchandani, Surabhi; Medne, Livija; Rupps, Rosemarie; Serrano, Alvaro H; Thorland, Erik C; Tsai, Anne C-H; Hilhorst-Hofstee, Yvonne; Ruivenkamp, Claudia A L; Van Esch, Hilde; Addor, Marie-Claude; Martinet, Danielle; Mason, Thornton B A; Clark, Dinah; Spinner, Nancy B; Krantz, Ian D

    2012-09-01

    We describe 19 unrelated individuals with submicroscopic deletions involving 10p15.3 characterized by chromosomal microarray (CMA). Interestingly, to our knowledge, only two individuals with isolated, submicroscopic 10p15.3 deletion have been reported to date; however, only limited clinical information is available for these probands and the deleted region has not been molecularly mapped. Comprehensive clinical history was obtained for 12 of the 19 individuals described in this study. Common features among these 12 individuals include: cognitive/behavioral/developmental differences (11/11), speech delay/language disorder (10/10), motor delay (10/10), craniofacial dysmorphism (9/12), hypotonia (7/11), brain anomalies (4/6) and seizures (3/7). Parental studies were performed for nine of the 19 individuals; the 10p15.3 deletion was de novo in seven of the probands, not maternally inherited in one proband and inherited from an apparently affected mother in one proband. Molecular mapping of the 19 individuals reported in this study has identified two genes, ZMYND11 (OMIM 608668) and DIP2C (OMIM 611380; UCSC Genome Browser), mapping within 10p15.3 which are most commonly deleted. Although no single gene has been identified which is deleted in all 19 individuals studied, the deleted region in all but one individual includes ZMYND11 and the deleted region in all but one other individual includes DIP2C. There is not a clearly identifiable phenotypic difference between these two individuals and the size of the deleted region does not generally predict clinical features. Little is currently known about these genes complicating a direct genotype/phenotype correlation at this time. These data however, suggest that ZMYND11 and/or DIP2C haploinsufficiency contributes to the clinical features associated with 10p15 deletions in probands described in this study. Copyright © 2012 Wiley Periodicals, Inc.

  1. Analysis of human HPRT- deletion mutants by the microarray-CGH (comparative genomic hybridization)

    International Nuclear Information System (INIS)

    Kodaira, M.; Sasaki, K.; Tagawa, H.; Omine, H.; Kushiro, J.; Takahashi, N.; Katayama, H.

    2003-01-01

    We are trying to evaluate genetic effects of radiation on human using mutation frequency as an indicator. For the efficient detection of mutations, it is important to understand the mechanism and the characteristics of radiation-induced mutations. We have started the analysis of hypoxanthine-guanine phosphoribosyl transferase (HPRT) mutants induced by X-ray in order to clarify the deletion size and the mutation-distribution. We analyzed 39 human X-ray induced HPRT-deletion mutants by using the microarray-CGH. The array for this analysis contains 57 BAC clones covering as much as possible of the 4Mb of the 5' side and 10Mb of the 3' side of the HPRT gene based on the NCBI genome database. DNA from parent strain and each HPRT-mutant strain are labeled with Cy5 and Cy3 respectively, and were mixed and hybridized on the array. Fluorescent intensity ratio of the obtained spots was analyzed using software we developed to identify clones corresponding to the deletion region. The deletion in these strains ranged up to 3.5 Mb on the 5' side and 6 Mb on the 3' side of the HPRT gene. Deletions in 13 strains ended around BAC clones located at about 3 Mb on the 5' side. On the 3' side, deletions extended up to the specific clones located at 1.5 Mb in 11 strains. The mutations seem to be complex on the 3' end of deletion; some accompanied duplications with deletions and others could not be explained by one mutation event. We need to confirm these results, taking into account the experimental reproducibility and the accuracy of the published genetic map. The results of the research using the microarray-CGH help us to search the regions where deletions are easily induced and to identify the factors affecting the range of deletions

  2. TTY2 genes deletions as genetic risk factor of male infertility.

    Science.gov (United States)

    Shaveisi-Zadeh, F; Alibakhshi, R; Asgari, R; Rostami-Far, Z; Bakhtiari, M; Abdi, H; Movafagh, A; Mirfakhraie, R

    2017-02-28

    Y chromosome has a number of genes that are expressed in testis and have a role in spermatogenesis. TTY2L12A and TTY2L2A are the members of testis transcript Y2 (TTY2) that are Y linked multi-copy gene families, located on Yp11 and Yq11 loci respectively. The aim of this study was to investigate frequency of TTY2L12A and TTY2L2A deletions in azoospermic patients compared with fertile males. This study was performed on 45 infertile males with idiopathic azoospermia without any AZF micro deletions (group A), 33 infertile males with azoospermia which do not screened for AZF micro deletions (group B) and 65 fertile males (group C), from October 2013 to April 2015 in west of Iran. Polymerase chain reaction (PCR) method was used for detection of TTY2L12A and TTY2L2A gene deletions in studied groups. No deletions were detected in normal fertile males of group C. 1 out of 45 azoospermic males of group A (2.22%) and 3 out of 33 azoospermic males of group B (9.09%) had TTY2L2A deletion (p= 0.409 and p= 0.036 respectively), also 1 out of 45 azoospermic males of group A (2.22%) and 4 out of 33 azoospermic males of group B (12.12%) had TTY2L12A deletion (p= 0.409 and p= 0.011 respectively).  None of azoospermic males in Group A and B had deletions in both genes. Our data showed significant correlation between non-obstructive azoospermia and TTY2L12A and TTY2L2A deletions. Thus, it seems that TTY2L12A and TTY2L2A deletions can consider as one of the genetic risk factors for non-obstructive azoospermia.

  3. Spontaneous and mutagen-induced deletions: mechanistic studies in Salmonella tester strain TA102

    International Nuclear Information System (INIS)

    Levin, D.E.; Marnett, L.J.; Ames, B.N.

    1984-01-01

    Salmonella tester strain TA102 carries the hisG428 ochre mutation on the multicopy plasmid pAQ1. DNA sequence analysis of 45 spontaneous revertants of hisG428 on the chromosome in the presence of pKM101 (strain TA103) indicates that hisG428 revertants fall into three major categories: (i) small, in-frame deletions (3 or 6 base pairs) that remove part or all of the ochre triplet; (ii) base substitution mutations at the ochre site; (iii) extragenic ochre suppressors. Deletion revertants are identified in a simple phenotypic screen by their resistance to the inhibitory histidine analog thiazolealanine, which feedback inhibits the wild-type hisG enzyme but not the enzyme resulting from the deletions. The effect of various genetic backgrounds on the generation of spontaneous deletion revertants was examined. The presence of a uvrB mutation or a recA mutation suppressed the generation of spontaneous deletion revertants to approximately 1/2.5. When hisG428 was in multiple copies on pAQ1, the frequency of spontaneous deletion revertants increased by 40-fold, which is the approximate copy number of pAQ1. Mutagenic agents that induce single-strand breaks in DNA (e.g., x-rays, bleomycin, and nalidixic acid) induced deletion revertants in TA102. These agents induced deletion revertants only in hisG428 on pAQ1 and only in the presence of pKM101. Deletion revertants were not induced by frameshift mutagens (i.e., ICR-191 and 9aminoacridine). These results indicate that different pathways exist for the generation of spontaneous and mutagen-induced deletion revertants of hisG428. 41 references, 2 figures, 3 tables

  4. Characterization of novel RS1 exonic deletions in juvenile X-linked retinoschisis.

    Science.gov (United States)

    D'Souza, Leera; Cukras, Catherine; Antolik, Christian; Craig, Candice; Lee, Ji-Yun; He, Hong; Li, Shibo; Smaoui, Nizar; Hejtmancik, James F; Sieving, Paul A; Wang, Xinjing

    2013-01-01

    X-linked juvenile retinoschisis (XLRS) is a vitreoretinal dystrophy characterized by schisis (splitting) of the inner layers of the neuroretina. Mutations within the retinoschisis (RS1) gene are responsible for this disease. The mutation spectrum consists of amino acid substitutions, splice site variations, small indels, and larger genomic deletions. Clinically, genomic deletions are rarely reported. Here, we characterize two novel full exonic deletions: one encompassing exon 1 and the other spanning exons 4-5 of the RS1 gene. We also report the clinical findings in these patients with XLRS with two different exonic deletions. Unrelated XLRS men and boys and their mothers (if available) were enrolled for molecular genetics evaluation. The patients also underwent ophthalmologic examination and in some cases electroretinogram (ERG) recording. All the exons and the flanking intronic regions of the RS1 gene were analyzed with direct sequencing. Two patients with exonic deletions were further evaluated with array comparative genomic hybridization to define the scope of the genomic aberrations. After the deleted genomic region was identified, primer walking followed by direct sequencing was used to determine the exact breakpoints. Two novel exonic deletions of the RS1 gene were identified: one including exon 1 and the other spanning exons 4 and 5. The exon 1 deletion extends from the 5' region of the RS1 gene (including the promoter) through intron 1 (c.(-35)-1723_c.51+2664del4472). The exon 4-5 deletion spans introns 3 to intron 5 (c.185-1020_c.522+1844del5764). Here we report two novel exonic deletions within the RS1 gene locus. We have also described the clinical presentations and hypothesized the genomic mechanisms underlying these schisis phenotypes.

  5. Molecular cytogenetic characterization of the first reported case of an inv dup (4p)(p15.1-pter) with a concomitant 4q35.1-qter deletion and normal parents.

    Science.gov (United States)

    Tassano, E; Alpigiani, M G; Salvati, P; Gimelli, S; Lorini, R; Gimelli, G

    2012-12-15

    Inverted duplications associated with terminal deletions are complex anomalies described in an increasing of chromosome ends. We report on the cytogenetic characterization of the first de novo inv dup del(4) with partial 4p duplication and 4q deletion in a girl with clinical signs consistent with "recombinant 4 syndrome". This abnormality was suspected by banding, but high-resolution molecular cytogenetic investigations allowed us to define the breakpoints of the rearrangement. The terminal duplicated region extending from 4p15.1 to the telomere was estimated to be 29.27 Mb, while the size of the terminal deletion was 3.114 Mb in the 4q35.1 region. Until now, 10 patients with duplicated 4p14-p15 and deleted 4q35 chromosome 4 have been described. In all cases the abnormal chromosome 4 was derived from a pericentric inversion inherited from one of the parents. In conclusion, we have identified the first case of inv dup del(4) with normal parents suggesting that, often, terminal duplications or terminal deletions mask complex rearrangements. Copyright © 2012 Elsevier B.V. All rights reserved.

  6. An internal deletion in MTH1 enables growth on glucose of pyruvate-decarboxylase negative, non-fermentative Saccharomyces cerevisiae.

    Science.gov (United States)

    Oud, Bart; Flores, Carmen-Lisset; Gancedo, Carlos; Zhang, Xiuying; Trueheart, Joshua; Daran, Jean-Marc; Pronk, Jack T; van Maris, Antonius J A

    2012-09-15

    Pyruvate-decarboxylase negative (Pdc⁻) strains of Saccharomyces cerevisiae combine the robustness and high glycolytic capacity of this yeast with the absence of alcoholic fermentation. This makes Pdc⁻S. cerevisiae an interesting platform for efficient conversion of glucose towards pyruvate-derived products without formation of ethanol as a by-product. However, Pdc⁻ strains cannot grow on high glucose concentrations and require C₂-compounds (ethanol or acetate) for growth under conditions with low glucose concentrations, which hitherto has limited application in industry. Genetic analysis of a Pdc⁻ strain previously evolved to overcome these deficiencies revealed a 225 p in-frame internal deletion in MTH1, encoding a transcriptional regulator involved in glucose sensing. This internal deletion contains a phosphorylation site required for degradation, thereby hypothetically resulting in increased stability of the protein. Reverse engineering of this alternative MTH1 allele into a non-evolved Pdc⁻ strain enabled growth on 20 g l⁻¹ glucose and 0.3% (v/v) ethanol at a maximum specific growth rate (0.24 h⁻¹) similar to that of the evolved Pdc⁻ strain (0.23 h⁻¹). Furthermore, the reverse engineered Pdc⁻ strain grew on glucose as sole carbon source, albeit at a lower specific growth rate (0.10 h⁻¹) than the evolved strain (0.20 h⁻¹). The observation that overexpression of the wild-type MTH1 allele also restored growth of Pdc⁻S. cerevisiae on glucose is consistent with the hypothesis that the internal deletion results in decreased degradation of Mth1. Reduced degradation of Mth1 has been shown to result in deregulation of hexose transport. In Pdc⁻ strains, reduced glucose uptake may prevent intracellular accumulation of pyruvate and/or redox problems, while release of glucose repression due to the MTH1 internal deletion may contribute to alleviation of the C₂-compound auxotrophy. In this study we have discovered and characterised a

  7. An internal deletion in MTH1 enables growth on glucose of pyruvate-decarboxylase negative, non-fermentative Saccharomyces cerevisiae

    Directory of Open Access Journals (Sweden)

    Oud Bart

    2012-09-01

    Full Text Available Abstract Background Pyruvate-decarboxylase negative (Pdc- strains of Saccharomyces cerevisiae combine the robustness and high glycolytic capacity of this yeast with the absence of alcoholic fermentation. This makes Pdc-S. cerevisiae an interesting platform for efficient conversion of glucose towards pyruvate-derived products without formation of ethanol as a by-product. However, Pdc- strains cannot grow on high glucose concentrations and require C2-compounds (ethanol or acetate for growth under conditions with low glucose concentrations, which hitherto has limited application in industry. Results Genetic analysis of a Pdc- strain previously evolved to overcome these deficiencies revealed a 225bp in-frame internal deletion in MTH1, encoding a transcriptional regulator involved in glucose sensing. This internal deletion contains a phosphorylation site required for degradation, thereby hypothetically resulting in increased stability of the protein. Reverse engineering of this alternative MTH1 allele into a non-evolved Pdc- strain enabled growth on 20 g l-1 glucose and 0.3% (v/v ethanol at a maximum specific growth rate (0.24 h-1 similar to that of the evolved Pdc- strain (0.23 h-1. Furthermore, the reverse engineered Pdc- strain grew on glucose as sole carbon source, albeit at a lower specific growth rate (0.10 h-1 than the evolved strain (0.20 h-1. The observation that overexpression of the wild-type MTH1 allele also restored growth of Pdc-S. cerevisiae on glucose is consistent with the hypothesis that the internal deletion results in decreased degradation of Mth1. Reduced degradation of Mth1 has been shown to result in deregulation of hexose transport. In Pdc- strains, reduced glucose uptake may prevent intracellular accumulation of pyruvate and/or redox problems, while release of glucose repression due to the MTH1 internal deletion may contribute to alleviation of the C2-compound auxotrophy. Conclusions In this study we have discovered and

  8. Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes.

    Science.gov (United States)

    Dorin, Julia R

    2015-01-01

    β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.

  9. Novel phenotype of mouse spermatozoa following deletion of nine β-defensin genes

    Directory of Open Access Journals (Sweden)

    Julia R Dorin

    2015-01-01

    Full Text Available β-defensin peptides are a large family of antimicrobial peptides. Although they kill microbes in vitro and interact with immune cells, the precise role of these genes in vivo remains uncertain. Despite their inducible presence at mucosal surfaces, their main site of expression is the epididymis. Recent evidence suggests that a major function of these peptides is in sperm maturation. In addition to previous work suggesting this, work at the MRC Human Genetics Unit, Edinburgh, has shown that homozygous deletion of a cluster of nine β-defensin genes in the mouse results in profound male sterility. The spermatozoa derived from the mutants had reduced motility and increased fragility. Epididymal spermatozoa isolated from the cauda region of the homozygous mutants demonstrated precocious capacitation and increased spontaneous acrosome reactions compared with those from wild-types. Despite this, these mutant spermatozoa had reduced ability to bind to the zona pellucida of oocytes. Ultrastructural examination revealed a disintegration of the microtubule structure of mutant-derived spermatozoa isolated from the epididymal cauda region, but not from the caput. Consistent with premature acrosome reaction and hyperactivation, spermatozoa from mutant animals had significantly increased intracellular calcium content. This work demonstrates that in vivo β-defensins are essential for successful sperm maturation, and that their disruption alters intracellular calcium levels, which most likely leads to premature activation and spontaneous acrosome reactions that result in hyperactivation and loss of microtubule structure of the axoneme. Determining which of the nine genes are responsible for the phenotype and the relevance to human sperm function is important for future work on male infertility.

  10. Conditional IL-2 gene deletion: consequences for T cell proliferation

    Directory of Open Access Journals (Sweden)

    Kendall A Smith

    2012-05-01

    Full Text Available To explore the role of interleukin-2 (IL-2 in T cell proliferation, and to circumvent the IL-2 deficiency autoimmune syndrome of conventional il2 gene deletion, mice were created to allow conditional il2 gene deletion when treated with the estrogen analogue, tamoxifen (TAM as adults. Splenocytes from four different mouse strains, C57Bl/6 wild type (WT, conventional IL-2 (-/-, TAM-treated Cre recombinase negative (Cre-/IL2fl/fl, and Cre+/IL-2fl/fl (Cre+, were activated with anti-CD3 and anti-CD28, and monitored for CD4+ and CD8+ T cell lymphocyte blastogenesis, aerobic glycolysis, BrdU incorporation into newly synthesized DNA, and CFSE dye dilution to monitor cell division. IL-2 production was monitored by quantitative ELISA and multiple additional cytokines were monitored by protein-bead arrays. Splenocytes from conventional IL-2 (-/- and TAM-treated Cre+ mice resulted in undetectable IL-2 production, so that both strains were IL-2 deficient. As monitored by flow cytometry, activated CD4+ and CD8+ T cells from WT, Cre+ and Cre- mice all underwent blastogenesis, whereas far fewer cells from conventional IL-2 (-/- mice did so. By comparison, only cells from IL-2 sufficient WT and Cre- switched to aerobic glycolysis as evidenced by a drop in media pH. Blastogenesis was mirrored by BrdU incorporation and CFSE dye dilution by CD4+ and CD8+ T cells from WT, Cre+ and Cre- mice, which were all equivalent, while proliferation of cells from conventional IL-2 (-/- mice was compromised. Splenocytes from IL-2 deficient conventional IL-2 (-/- mice produced low or undetectable other γc-chain cytokines (IL-4, IL-7, IL-9, IL-13, IL-15, and IL-21, whereas production of these γc-chain cytokines from IL-2-deficient conditional IL-2 (-/- Cre+ mice were comparable with WT and Cre- mice. These results indicate that CD4+ and CD8+ T cell blastogenesis cannot be attributable to IL-2 alone, but a switch to aerobic glycolysis is attributable to IL-2, and proliferation

  11. Activating and inhibiting connections in biological network dynamics

    Directory of Open Access Journals (Sweden)

    Knight Rob

    2008-12-01

    Full Text Available Abstract Background Many studies of biochemical networks have analyzed network topology. Such work has suggested that specific types of network wiring may increase network robustness and therefore confer a selective advantage. However, knowledge of network topology does not allow one to predict network dynamical behavior – for example, whether deleting a protein from a signaling network would maintain the network's dynamical behavior, or induce oscillations or chaos. Results Here we report that the balance between activating and inhibiting connections is important in determining whether network dynamics reach steady state or oscillate. We use a simple dynamical model of a network of interacting genes or proteins. Using the model, we study random networks, networks selected for robust dynamics, and examples of biological network topologies. The fraction of activating connections influences whether the network dynamics reach steady state or oscillate. Conclusion The activating fraction may predispose a network to oscillate or reach steady state, and neutral evolution or selection of this parameter may affect the behavior of biological networks. This principle may unify the dynamics of a wide range of cellular networks. Reviewers Reviewed by Sergei Maslov, Eugene Koonin, and Yu (Brandon Xia (nominated by Mark Gerstein. For the full reviews, please go to the Reviewers' comments section.

  12. Declarative Networking

    CERN Document Server

    Loo, Boon Thau

    2012-01-01

    Declarative Networking is a programming methodology that enables developers to concisely specify network protocols and services, which are directly compiled to a dataflow framework that executes the specifications. Declarative networking proposes the use of a declarative query language for specifying and implementing network protocols, and employs a dataflow framework at runtime for communication and maintenance of network state. The primary goal of declarative networking is to greatly simplify the process of specifying, implementing, deploying and evolving a network design. In addition, decla

  13. Brain Network Modelling

    DEFF Research Database (Denmark)

    Andersen, Kasper Winther

    Three main topics are presented in this thesis. The first and largest topic concerns network modelling of functional Magnetic Resonance Imaging (fMRI) and Diffusion Weighted Imaging (DWI). In particular nonparametric Bayesian methods are used to model brain networks derived from resting state f...... for their ability to reproduce node clustering and predict unseen data. Comparing the models on whole brain networks, BCD and IRM showed better reproducibility and predictability than IDM, suggesting that resting state networks exhibit community structure. This also points to the importance of using models, which...... allow for complex interactions between all pairs of clusters. In addition, it is demonstrated how the IRM can be used for segmenting brain structures into functionally coherent clusters. A new nonparametric Bayesian network model is presented. The model builds upon the IRM and can be used to infer...

  14. Deletion of Pr130 Interrupts Cardiac Development in Zebrafish

    Directory of Open Access Journals (Sweden)

    Jie Yang

    2016-11-01

    Full Text Available Protein phosphatase 2 regulatory subunit B, alpha (PPP2R3A, a regulatory subunit of protein phosphatase 2A (PP2A, is a major serine/threonine phosphatase that regulates crucial function in development and growth. Previous research has implied that PPP2R3A was involved in heart failure, and PR130, the largest transcription of PPP2R3A, functioning in the calcium release of sarcoplasmic reticulum (SR, plays an important role in the excitation-contraction (EC coupling. To obtain a better understanding of PR130 functions in myocardium and cardiac development, two pr130-deletion zebrafish lines were generated using clustered regularly interspaced short palindromic repeats (CRISPR/CRISPR-associated proteins (Cas system. Pr130-knockout zebrafish exhibited cardiac looping defects and decreased cardiac function (decreased fractional area and fractional shortening. Hematoxylin and eosin (H&E staining demonstrated reduced cardiomyocytes. Subsequent transmission electron microscopy revealed that the bright and dark bands were narrowed and blurred, the Z- and M-lines were fogged, and the gaps between longitudinal myocardial fibers were increased. Additionally, increased apoptosis was observed in cardiomyocyte in pr130-knockout zebrafish compared to wild-type (WT. Taken together, our results suggest that pr130 is required for normal myocardium formation and efficient cardiac contractile function.

  15. Remote Wiping and Secure Deletion on Mobile Devices: A Review.

    Science.gov (United States)

    Leom, Ming Di; Choo, Kim-Kwang Raymond; Hunt, Ray

    2016-11-01

    Mobile devices have become ubiquitous in almost every sector of both private and commercial endeavors. As a result of such widespread use in everyday life, many users knowingly and unknowingly save significant amounts of personal and/or commercial data on these mobile devices. Thus, loss of mobile devices through accident or theft can expose users-and their businesses-to significant personal and corporate cost. To mitigate this data leakage issue, remote wiping features have been introduced to modern mobile devices. Given the destructive nature of such a feature, however, it may be subject to criminal exploitation (e.g., a criminal exploiting one or more vulnerabilities to issue a remote wiping command to the victim's device). To obtain a better understanding of remote wiping, we survey the literature, focusing on existing approaches to secure flash storage deletion and provide a critical analysis and comparison of a variety of published research in this area. In support of our analysis, we further provide prototype experimental results for three Android devices, thus providing both a theoretical and applied focus to this article as well as providing directions for further research. © 2016 American Academy of Forensic Sciences.

  16. Stage specific requirement of platelet-derived growth factor receptor-α in embryonic development.

    Directory of Open Access Journals (Sweden)

    Chen Qian

    Full Text Available Platelet-derived growth factor receptor alpha (PDGFRα is a cell-surface receptor tyrosine kinase for platelet-derived growth factors. Correct timing and level of Pdgfra expression is crucial for embryo development, and deletion of Pdgfra caused developmental defects of multiple endoderm and mesoderm derived structures, resulting in a complex phenotypes including orofacial cleft, spina bifida, rib deformities, and omphalocele in mice. However, it is not clear if deletion of Pdgfra at different embryonic stages differentially affects these structures.To address the temporal requirement of Pdgfra in embryonic development.We have deleted the Pdgfra in Pdgfra-expressing tissues at different embryonic stages in mice, examined and quantified the developmental anomalies.Current study showed that (i conditional deletion of Pdgfra at different embryonic days (between E7.5 and E10.5 resulted in orofacial cleft, spina bifida, rib cage deformities, and omphalocele, and (ii the day of Pdgfra deletion influenced the combinations, incidence and severities of these anomalies. Deletion of Pdgfra caused apoptosis of Pdgfra-expressing tissues, and developmental defects of their derivatives.Orofacial cleft, spina bifida and omphalocele are among the commonest skeletal and abdominal wall defects of newborns, but their genetic etiologies are largely unknown. The remarkable resemblance of our conditional Pdgfra knockout embryos to theses human congenital anomalies, suggesting that dysregulated PDGFRA expression could cause these anomalies in human. Future work should aim at defining (a the regulatory elements for the expression of the human PDGFRA during embryonic development, and (b if mutations / sequence variations of these regulatory elements cause these anomalies.

  17. Introduction to neural networks

    International Nuclear Information System (INIS)

    Pavlopoulos, P.

    1996-01-01

    This lecture is a presentation of today's research in neural computation. Neural computation is inspired by knowledge from neuro-science. It draws its methods in large degree from statistical physics and its potential applications lie mainly in computer science and engineering. Neural networks models are algorithms for cognitive tasks, such as learning and optimization, which are based on concepts derived from research into the nature of the brain. The lecture first gives an historical presentation of neural networks development and interest in performing complex tasks. Then, an exhaustive overview of data management and networks computation methods is given: the supervised learning and the associative memory problem, the capacity of networks, the Perceptron networks, the functional link networks, the Madaline (Multiple Adalines) networks, the back-propagation networks, the reduced coulomb energy (RCE) networks, the unsupervised learning and the competitive learning and vector quantization. An example of application in high energy physics is given with the trigger systems and track recognition system (track parametrization, event selection and particle identification) developed for the CPLEAR experiment detectors from the LEAR at CERN. (J.S.). 56 refs., 20 figs., 1 tab., 1 appendix

  18. Value Creation in Knowledge Networks

    DEFF Research Database (Denmark)

    Hansen, Magnus Rotvit Perlt; Pries-Heje, Jan

    2017-01-01

    Knowledge networks enable businesses to enhance their levels of innovation and market competitiveness. In this paper, we propose five principles for designing IT tools that can support the facilitation and improvement of knowledge networks. We also introduce a new value proposition that constitutes...... a nascent design theory in the domain of knowledge network improvement. The design principles are derived from an iterative process applied in three different case settings. In each case, we apply and evaluate the network nexus tool to determine whether the knowledge network provides value to its...

  19. Association of BIM Deletion Polymorphism and BIM-γ RNA Expression in NSCLC with EGFR Mutation.

    Science.gov (United States)

    Isobe, Kazutoshi; Kakimoto, Atsushi; Mikami, Tetsuo; Kaburaki, Kyohei; Kobayashi, Hiroshi; Yoshizawa, Takahiro; Makino, Takashi; Otsuka, Hajime; Sano, G O; Sugino, Keishi; Sakamoto, Susumu; Takai, Yujiro; Tochigi, Naobumi; Iyoda, Akira; Homma, Sakae

    This pilot study assessed the association of BIM deletion polymorphism and BIM RNA isoform in patients with EGFR-positive non-small cell lung cancer (NSCLC). The study included 33 patients with EGFR-positive NSCLC treated with gefitinib. BIM deletion polymorphism and BIM RNA isoform (EL/L/S/γ) were determined by polymerase chain reaction (PCR). BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism inside tumors (p=0.038) and around tumors (p=0.0024). Relative BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism (p=0.0017). Patients with BIM-γ had significantly shorter progression-free survival than those without BIM-γ (median: 304 vs. 732 days; p=0.023). Expression of BIM-γ mRNA and BIM deletion polymorphism were strongly associated. BIM-γ overexpression may have a role in apoptosis related to EGFR-tyrosine kinase inhibitor. Copyright© 2016, International Institute of Anticancer Research (Dr. John G. Delinasios), All rights reserved.

  20. Microarray-based ultra-high resolution discovery of genomic deletion mutations

    Science.gov (United States)

    2014-01-01

    Background Oligonucleotide microarray-based comparative genomic hybridization (CGH) offers an attractive possible route for the rapid and cost-effective genome-wide discovery of deletion mutations. CGH typically involves comparison of the hybridization intensities of genomic DNA samples with microarray chip representations of entire genomes, and has widespread potential application in experimental research and medical diagnostics. However, the power to detect small deletions is low. Results Here we use a graduated series of Arabidopsis thaliana genomic deletion mutations (of sizes ranging from 4 bp to ~5 kb) to optimize CGH-based genomic deletion detection. We show that the power to detect smaller deletions (4, 28 and 104 bp) depends upon oligonucleotide density (essentially the number of genome-representative oligonucleotides on the microarray chip), and determine the oligonucleotide spacings necessary to guarantee detection of deletions of specified size. Conclusions Our findings will enhance a wide range of research and clinical applications, and in particular will aid in the discovery of genomic deletions in the absence of a priori knowledge of their existence. PMID:24655320

  1. Dual entanglement measures based on no local cloning and no local deleting

    International Nuclear Information System (INIS)

    Horodecki, Michal; Sen, Aditi; Sen, Ujjwal

    2004-01-01

    The impossibility of cloning and deleting of unknown states constitute important restrictions on processing of information in the quantum world. On the other hand, a known quantum state can always be cloned or deleted. However, if we restrict the class of allowed operations, there will arise restrictions on the ability of cloning and deleting machines. We have shown that cloning and deleting of known states is in general not possible by local operations. This impossibility hints at quantum correlation in the state. We propose dual measures of quantum correlation based on the dual restrictions of no local cloning and no local deleting. The measures are relative entropy distances of the desired states in a (generally impossible) perfect local cloning or local deleting process from the best approximate state that is actually obtained by imperfect local cloning or deleting machines. Just like the dual measures of entanglement cost and distillable entanglement, the proposed measures are based on important processes in quantum information. We discuss their properties. For the case of pure states, estimations of these two measures are also provided. Interestingly, the entanglement of cloning for a maximally entangled state of two two-level systems is not unity

  2. Analysis of Dystrophin Gene Deletions by Multiplex PCR in Moroccan Patients

    Directory of Open Access Journals (Sweden)

    Aziza Sbiti

    2002-01-01

    Full Text Available Duchenne and Becker muscular dystrophy (DMD and BMD are X-linked diseases resulting from a defect in the dystrophin gene located on Xp21. DMD is the most frequent neuromuscular disease in humans (1/3500 male newborn. Deletions in the dystrophin gene represent 65% of mutations in DMD/BMD patients. We have analyzed DNA from 72 Moroccan patients with DMD/BMD using the multiplex polymerase chain reaction (PCR to screen for exon deletions within the dystrophin gene, and to estimate the frequency of these abnormalities. We found dystrophin gene deletions in 37 cases. Therefore the frequency in Moroccan DMD/BMD patients is about 51.3%. All deletions were clustered in the two known hot-spots regions, and in 81% of cases deletions were detected in the region from exon 43 to exon 52. These findings are comparable to those reported in other studies. It is important to note that in our population, we can first search for deletions of DMD gene in the most frequently deleted exons determined by this study. This may facilitate the molecular diagnosis of DMD and BMD in our country.

  3. Spectrum of phenotypic anomalies in four families with deletion of the SHOX enhancer region.

    Science.gov (United States)

    Gatta, Valentina; Palka, Chiara; Chiavaroli, Valentina; Franchi, Sara; Cannataro, Giovanni; Savastano, Massimo; Cotroneo, Antonio Raffaele; Chiarelli, Francesco; Mohn, Angelika; Stuppia, Liborio

    2014-07-23

    SHOX alterations have been reported in 67% of patients affected by Léri-Weill dyschondrosteosis (LWD), with a larger prevalence of gene deletions than point mutations. It has been recently demonstrated that these deletions can involve the SHOX enhancer region, rather that the coding region, with variable phenotype of the affected patients.Here, we report a SHOX gene analysis carried out by MLPA in 14 LWD patients from 4 families with variable phenotype. All patients presented a SHOX enhancer deletion. In particular, a patient with a severe bilateral Madelung deformity without short stature showed a homozygous alteration identical to the recently described 47.5 kb PAR1 deletion. Moreover, we identified, for the first time, in three related patients with a severe bilateral Madelung deformity, a smaller deletion than the 47.5 kb PAR1 deletion encompassing the same enhancer region (ECR1/CNE7). Data reported in this study provide new information about the spectrum of phenotypic alterations showed by LWD patients with different deletions of the SHOX enhancer region.

  4. Clinical and molecuar characterization of Brazilian patients with growth hormone gene deletions

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    I.J.P. Arnhold

    1998-04-01

    Full Text Available Genomic DNA from 23 patients with isolated growth hormone (GH deficiency (12 males and 11 females: heights -4.9 ± 1.4 SDS was screened for GH gene deletions by restriction endonuclease analysis of polymerase chain reaction amplification products. Three unrelated patients had typical features of severe GH deficiency and deletions (6.7 kb in two and 7.6 kb in one of the GH gene. The two patients with 6.7-kb deletions developed growth-attenuating anti-GH antibodies whereas the patient with the 7.6-kb deletion continued to grow with GH replacement therapy. Our finding that 3/23 (~13% Brazilian subjects had GH gene deletions agrees with previous studies of severe isolated GH deficiency subjects in other populations. Two of three subjects (67% with deletions developed blocking antibodies despite administration of exogenous GH at low doses. Interestingly, only 1/10 of cases with affected relatives or parental consanguinity had GH-1 gene deletions

  5. The role of mitochondrial DNA large deletion for the development of presbycusis in Fischer 344 rats.

    Science.gov (United States)

    Yin, Shankai; Yu, Zhiping; Sockalingam, Ravi; Bance, Manohar; Sun, Genlou; Wang, Jian

    2007-09-01

    Age-related hearing loss, or presbycusis, has been associated with large-scale mitochondrial DNA (mtDNA) deletion in previous studies. However, the role of this mtDNA damage in presbycusis is still not clear because the deletion in inner ears has not been measured quantitatively and analyzed in parallel with the time course of presbycusis. In the present study, the deletion was quantified using quantitative real-time PCR (qRT-PCR) in male Fischer 344 rats of different ages. It was found that the deletion increased quickly during young adulthood and reached over 60% at 6 months of age. However, a significant hearing loss was not seen until after 12 months of age. The results suggest that the existence of the deletion per se does not necessarily imply cochlear damage, but rather a critical level of the accumulated deletion seems to precede the hearing loss. The long delay may indicate the involvement of mechanisms other than mtDNA deletion in the development of presbycusis.

  6. Sequence characterisation of deletion breakpoints in the dystrophin gene by PCR

    Energy Technology Data Exchange (ETDEWEB)

    Abbs, S.; Sandhu, S.; Bobrow, M. [Guy`s Hospital, London (United Kingdom)

    1994-09-01

    Partial deletions of the dystrophin gene account for 65% of cases of Duchenne muscular dystrophy. A high proportion of these structural changes are generated by new mutational events, and lie predominantly within two `hotspot` regions, yet the underlying reasons for this are not known. We are characterizing and sequencing the regions surrounding deletion breakpoints in order to: (i) investigate the mechanisms of deletion mutation, and (ii) enable the design of PCR assays to specifically amplify mutant and normal sequences, allowing us to search for the presence of somatic mosaicism in appropriate family members. Using this approach we have been able to demonstrate the presence of somatic mosaicism in a maternal grandfather of a DMD-affected male, deleted for exons 49-50. Three deletions, namely of exons 48-49, 49-50, and 50, have been characterized using a PCR approach that avoids any cloning procedures. Breakpoints were initially localized to within regions of a few kilobases using Southern blot restriction analyses with exon-specific probes and PCR amplification of exonic and intronic loci. Sequencing was performed directly on PCR products: (i) mutant sequences were obtained from long-range or inverse-PCR across the deletion junction fragments, and (ii) normal sequences were obtained from the products of standard PCR, vectorette PCR, or inverse-PCR performed on YACs. Further characterization of intronic sequences will allow us to amplify and sequence across other deletion breakpoints and increase our knowledge of the mechanisms of mutation in the dystophin gene.

  7. Partial USH2A deletions contribute to Usher syndrome in Denmark.

    Science.gov (United States)

    Dad, Shzeena; Rendtorff, Nanna D; Kann, Erik; Albrechtsen, Anders; Mehrjouy, Mana M; Bak, Mads; Tommerup, Niels; Tranebjærg, Lisbeth; Rosenberg, Thomas; Jensen, Hanne; Møller, Lisbeth B

    2015-12-01

    Usher syndrome is an autosomal recessive disorder characterized by congenital hearing impairment, progressive visual loss owing to retinitis pigmentosa and in some cases vestibular dysfunction. Usher syndrome is divided into three subtypes, USH1, USH2 and USH3. Twelve loci and eleven genes have so far been identified. Duplications and deletions in PCDH15 and USH2A that lead to USH1 and USH2, respectively, have previously been identified in patients from United Kingdom, Spain and Italy. In this study, we investigate the proportion of exon deletions and duplications in PCDH15 and USH2A in 20 USH1 and 30 USH2 patients from Denmark using multiplex ligation-dependent probe amplification (MLPA). Two heterozygous deletions were identified in USH2A, but no deletions or duplications were identified in PCDH15. Next-generation mate-pair sequencing was used to identify the exact breakpoints of the two deletions identified in USH2A. Our results suggest that USH2 is caused by USH2A exon deletions in a small fraction of the patients, whereas deletions or duplications in PCDH15 might be rare in Danish Usher patients.

  8. A novel 3q29 deletion associated with autism, intellectual disability, psychiatric disorders, and obesity.

    Science.gov (United States)

    Biamino, Elisa; Di Gregorio, Eleonora; Belligni, Elga Fabia; Keller, Roberto; Riberi, Evelise; Gandione, Marina; Calcia, Alessandro; Mancini, Cecilia; Giorgio, Elisa; Cavalieri, Simona; Pappi, Patrizia; Talarico, Flavia; Fea, Antonio M; De Rubeis, Silvia; Cirillo Silengo, Margherita; Ferrero, Giovanni Battista; Brusco, Alfredo

    2016-03-01

    Copy number variation (CNV) has been associated with a variety of neuropsychiatric disorders, including intellectual disability/developmental delay (ID/DD), autism spectrum disorder (ASD), and schizophrenia (SCZ). Often, individuals carrying the same pathogenic CNV display high clinical variability. By array-CGH analysis, we identified a novel familial 3q29 deletion (1.36 Mb), centromeric to the 3q29 deletion region, which manifests with variable expressivity. The deletion was identified in a 3-year-old girl diagnosed with ID/DD and autism and segregated in six family members, all affected by severe psychiatric disorders including schizophrenia, major depression, anxiety disorder, and personality disorder. All individuals carrying the deletion were overweight or obese, and anomalies compatible with optic atrophy were observed in three out of four cases examined. Amongst the 10 genes encompassed by the deletion, the haploinsufficiency of Optic Atrophy 1 (OPA1), associated with autosomal dominant optic atrophy, is likely responsible for the ophthalmological anomalies. We hypothesize that the haploinsufficiency of ATPase type 13A4 (ATP13A4) and/or Hairy/Enhancer of Split Drosophila homolog 1 (HES1) contribute to the neuropsychiatric phenotype, while HES1 deletion might underlie the overweight/obesity. In conclusion, we propose a novel contiguous gene syndrome due to a proximal 3q29 deletion variably associated with autism, ID/DD, psychiatric traits and overweight/obesity. © 2015 Wiley Periodicals, Inc.

  9. Selection of Mycoplasma hominis PG21 deletion mutants by cultivation in the presence of monoclonal antibody 552

    DEFF Research Database (Denmark)

    Jensen, L T; Ladefoged, S; Birkelund, S

    1995-01-01

    characterized. The mutants showed deletions of a various number of repeats. The deletions were accompanied by a decrease in size of the proteins. With increasing size of deletions, agglutination and growth inhibition by MAb 552 became less pronounced. Spontaneous aggregation of the mutant M. hominis cells...

  10. Construction and characterization of a glycoprotein E deletion mutant of bovine herpesvirus type 1.2 strain isolated in Brazil

    NARCIS (Netherlands)

    Franco, A.C.; Rijsewijk, F.A.M.; Flores, E.F.; Weiblen, R.; Roehe, P.M.

    2002-01-01

    This paper describes the construction and characterization of a Brazilian strain of bovine herpesvirus type 1.2a (BoHV-1.2a) with a deletion of the glycoprotein E (gE) gene. The deletion was introduced by co-transfection of a deletion fragment containing the 5´and 3´gE flanking regions and genomic

  11. A 3-base pair deletion, c.9711_9713del, in DMD results in intellectual disability without muscular dystrophy

    NARCIS (Netherlands)

    Brouwer, A.P.M. de; Nabuurs, S.B.; Verhaart, I.E.; Oudakker, A.R.; Hordijk, R.; Yntema, H.G.; Hordijk-Hos, J.M.; Voesenek, K.E.; Vries, B. de; Essen, T. van; Chen, W.; Hu, H; Chelly, J.; Dunnen, J.T. den; Kalscheuer, V.M.M.; Aartsma-Rus, A.M.; Hamel, B.C.J.; Bokhoven, H. van; Kleefstra, T.

    2014-01-01

    We have identified a deletion of 3 base pairs in the dystrophin gene (DMD), c.9711_9713del, in a family with nonspecific X-linked intellectual disability (ID) by sequencing of the exons of 86 known X-linked ID genes. This in-frame deletion results in the deletion of a single-amino-acid residue,

  12. Phenotypic and molecular assessment of seven patients with 6p25 deletion syndrome: Relevance to ocular dysgenesis and hearing impairment

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    Ritch Robert

    2004-06-01

    Full Text Available Abstract Background Thirty-nine patients have been described with deletions involving chromosome 6p25. However, relatively few of these deletions have had molecular characterization. Common phenotypes of 6p25 deletion syndrome patients include hydrocephalus, hearing loss, and ocular, craniofacial, skeletal, cardiac, and renal malformations. Molecular characterization of deletions can identify genes that are responsible for these phenotypes. Methods We report the clinical phenotype of seven patients with terminal deletions of chromosome 6p25 and compare them to previously reported patients. Molecular characterization of the deletions was performed using polymorphic marker analysis to determine the extents of the deletions in these seven 6p25 deletion syndrome patients. Results Our results, and previous data, show that ocular dysgenesis and hearing impairment are the two most highly penetrant phenotypes of the 6p25 deletion syndrome. While deletion of the forkhead box C1 gene (FOXC1 probably underlies the ocular dysgenesis, no gene in this region is known to be involved in hearing impairment. Conclusions Ocular dysgenesis and hearing impairment are the two most common phenotypes of 6p25 deletion syndrome. We conclude that a locus for dominant hearing loss is present at 6p25 and that this locus is restricted to a region distal to D6S1617. Molecular characterization of more 6p25 deletion patients will aid in refinement of this locus and the identification of a gene involved in dominant hearing loss.

  13. Novel 31.2 kb α0 Deletion in a Palestinian Family with α-Thalassemia

    DEFF Research Database (Denmark)

    Brieghel, Christian; Birgens, Henrik; Frederiksen, Henrik

    2015-01-01

    A previously unknown α(0) deletion, designated - -(DANE), was found in three generations of a Danish family of Palestinian origin. Six patients were heterozygous and three patients had deletional Hb H (β4) disease with a compound heterozygosity for the common -α(3.7) (rightward) deletion. Multipl...

  14. Impaired intervertebral disc development and premature disc degeneration in mice with notochord-specific deletion of CCN2.

    Science.gov (United States)

    Bedore, Jake; Sha, Wei; McCann, Matthew R; Liu, Shangxi; Leask, Andrew; Séguin, Cheryle A

    2013-10-01

    Currently, our ability to treat intervertebral disc (IVD) degeneration is hampered by an incomplete understanding of disc development and aging. The specific function of matricellular proteins, including CCN2, during these processes remains an enigma. The aim of this study was to determine the tissue-specific localization of CCN proteins and to characterize their role in IVD tissues during embryonic development and age-related degeneration by using a mouse model of notochord-specific CCN2 deletion. Expression of CCN proteins was assessed in IVD tissues from wild-type mice beginning on embryonic day 15.5 to 17 months of age. Given the enrichment of CCN2 in notochord-derived tissues, we generated notochord-specific CCN2-null mice to assess the impact on the IVD structure and extracellular matrix composition. Using a combination of histologic evaluation and magnetic resonance imaging (MRI), IVD health was assessed. Loss of the CCN2 gene in notochord-derived cells disrupted the formation of IVDs in embryonic and newborn mice, resulting in decreased levels of aggrecan and type II collagen and concomitantly increased levels of type I collagen within the nucleus pulposus. CCN2-knockout mice also had altered expression of CCN1 (Cyr61) and CCN3 (Nov). Mirroring its role during early development, notochord-specific CCN2 deletion accelerated age-associated degeneration of IVDs. Using a notochord-specific gene targeting strategy, this study demonstrates that CCN2 expression by nucleus pulposus cells is essential to the regulation of IVD development and age-associated tissue maintenance. The ability of CCN2 to regulate the composition of the intervertebral disc suggests that it may represent an intriguing clinical target for the treatment of disc degeneration. Copyright © 2013 by the American College of Rheumatology.

  15. Targeted deletion of Sox10 by Wnt1-cre defects neuronal migration and projection in the mouse inner ear.

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    YanYan Mao

    Full Text Available Sensory nerves of the brainstem are mostly composed of placode-derived neurons, neural crest-derived neurons and neural crest-derived Schwann cells. This mixed origin of cells has made it difficult to dissect interdependence for fiber guidance. Inner ear-derived neurons are known to connect to the brain after delayed loss of Schwann cells in ErbB2 mutants. However, the ErbB2 mutant related alterations in the ear and the brain compound interpretation of the data. We present here a new model to evaluate exclusively the effect of Schwann cell loss on inner ear innervation. Conditional deletion of the neural crest specific transcription factor, Sox10, using the rhombic lip/neural crest specific Wnt1-cre driver spares Sox10 expression in the ear. We confirm that neural crest-derived cells provide a stop signal for migrating spiral ganglion neurons. In the absence of Schwann cells, spiral ganglion neurons migrate into the center of the cochlea and even out of the ear toward the brain. Spiral ganglion neuron afferent processes reach the organ of Corti, but many afferent fibers bypass the organ of Corti to enter the lateral wall of the cochlea. In contrast to this peripheral disorganization, the central projection to cochlear nuclei is normal. Compared to ErbB2 mutants, conditional Sox10 mutants have limited cell death in spiral ganglion neurons, indicating that the absence of Schwann cells alone contributes little to the embryonic survival of neurons. These data suggest that neural crest-derived cells are dispensable for all central and some peripheral targeting of inner ear neurons. However, Schwann cells provide a stop signal for migratory spiral ganglion neurons and facilitate proper targeting of the organ of Corti by spiral ganglion afferents.

  16. Targeted Deletion of Sox10 by Wnt1-cre Defects Neuronal Migration and Projection in the Mouse Inner Ear

    Science.gov (United States)

    Mao, YanYan; Reiprich, Simone; Wegner, Michael; Fritzsch, Bernd

    2014-01-01

    Sensory nerves of the brainstem are mostly composed of placode-derived neurons, neural crest-derived neurons and neural crest-derived Schwann cells. This mixed origin of cells has made it difficult to dissect interdependence for fiber guidance. Inner ear-derived neurons are known to connect to the brain after delayed loss of Schwann cells in ErbB2 mutants. However, the ErbB2 mutant related alterations in the ear and the brain compound interpretation of the data. We present here a new model to evaluate exclusively the effect of Schwann cell loss on inner ear innervation. Conditional deletion of the neural crest specific transcription factor, Sox10, using the rhombic lip/neural crest specific Wnt1-cre driver spares Sox10 expression in the ear. We confirm that neural crest-derived cells provide a stop signal for migrating spiral ganglion neurons. In the absence of Schwann cells, spiral ganglion neurons migrate into the center of the cochlea and even out of the ear toward the brain. Spiral ganglion neuron afferent processes reach the organ of Corti, but many afferent fibers bypass the organ of Corti to enter the lateral wall of the cochlea. In contrast to this peripheral disorganization, the central projection to cochlear nuclei is normal. Compared to ErbB2 mutants, conditional Sox10 mutants have limited cell death in spiral ganglion neurons, indicating that the absence of Schwann cells alone contributes little to the embryonic survival of neurons. These data suggest that neural crest-derived cells are dispensable for all central and some peripheral targeting of inner ear neurons. However, Schwann cells provide a stop signal for migratory spiral ganglion neurons and facilitate proper targeting of the organ of Corti by spiral ganglion afferents. PMID:24718611

  17. Correlation between chromosome 9p21 locus deletion and prognosis in clinically localized prostate cancer.

    Science.gov (United States)

    Barros, Érika Aparecida Felix de; Pontes-Junior, José; Reis, Sabrina Thalita; Lima, Amanda Eunice Ramos; Souza, Isida C; Salgueiro, Jose Lucas; Fontes, Douglas; Dellê, Humberto; Coelho, Rafael Ferreira; Viana, Nayara Izabel; Leite, Kátia Ramos Moreira; Nahas, William C; Srougi, Miguel

    2017-05-04

    Some studies have reported that deletions at chromosome arm 9p occur frequently and represent a critical step in carcinogenesis of some neoplasms. Our aim was to evaluate the deletion of locus 9p21 and chromosomes 3, 7 and 17 in localized prostate cancer (PC) and correlate these alterations with prognostic factors and biochemical recurrence after surgery. We retrospectively evaluated surgical specimens from 111 patients with localized PC who underwent radical prostatectomy. Biochemical recurrence was defined as a prostate-specific antigen (PSA) >0.2 ng/mL and the mean postoperative follow-up was 123 months. The deletions were evaluated using fluorescence in situ hybridization with centromeric and locus-specific probes in a tissue microarray containing 2 samples from each patient. We correlated the occurrence of any deletion with pathological stage, Gleason score, ISUP grade group, PSA and biochemical recurrence. We observed a loss of any probe in only 8 patients (7.2%). The most common deletion was the loss of locus 9p21, which occurred in 6.4% of cases. Deletions of chromosomes 3, 7 and 17 were observed in 2.3%, 1.2% and 1.8% patients, respectively. There was no correlation between chromosome loss and Gleason score, ISUP, PSA or stage. Biochemical recurrence occurred in 83% cases involving 9p21 deletions. Loss of 9p21 locus was significantly associated with time to recurrence (p = 0.038). We found low rates of deletion in chromosomes 3, 7 and 17 and 9p21 locus. We observed that 9p21 locus deletion was associated with worse prognosis in localized PC treated by radical prostatectomy.

  18. Thorough analysis of unorthodox ABO deletions called by the 1000 Genomes project.

    Science.gov (United States)

    Möller, M; Hellberg, Å; Olsson, M L

    2018-02-01

    ABO remains the clinically most important blood group system, but despite earlier extensive research, significant findings are still being made. The vast majority of catalogued ABO null alleles are based on the c.261delG polymorphism. Apart from c.802G>A, other mechanisms for O alleles are rare. While analysing the data set from the 1000 Genomes (1000G) project, we encountered two previously uncharacterized deletions, which needed further exploration. The Erythrogene database, complemented with bioinformatics software, was used to analyse ABO in 2504 individuals from 1000G. DNA samples from selected 1000G donors and African blood donors were examined by allele-specific PCR and Sanger sequencing to characterize predicted deletions. A 5821-bp deletion encompassing exons 5-7 was called in twenty 1000G individuals, predominantly Africans. This allele was confirmed and its exact deletion point defined by bioinformatic analyses and in vitro experiments. A PCR assay was developed, and screening of African samples revealed three donors heterozygous for this deletion, which was thereby phenotypically established as an O allele. Analysis of upstream genetic markers indicated an ancestral origin from ABO*O.01.02. We estimate this deletion as the 3rd most common mechanism behind O alleles. A 24-bp deletion was called in nine individuals and showed greater diversity regarding ethnic distribution and allelic background. It could neither be confirmed by in silico nor in vitro experiments. A previously uncharacterized ABO deletion among Africans was comprehensively mapped and a genotyping strategy devised. The false prediction of another deletion emphasizes the need for cautious interpretation of NGS data and calls for strict validation routines. © 2017 International Society of Blood Transfusion.

  19. The frequency of previously undetectable deletions involving 3' Exons of the PMS2 gene.

    Science.gov (United States)

    Vaughn, Cecily P; Baker, Christine L; Samowitz, Wade S; Swensen, Jeffrey J

    2013-01-01

    Lynch syndrome is characterized by mutations in one of four mismatch repair genes, MLH1, MSH2, MSH6, or PMS2. Clinical mutation analysis of these genes includes sequencing of exonic regions and deletion/duplication analysis. However, detection of deletions and duplications in PMS2 has previously been confined to Exons 1-11 due to gene conversion between PMS2 and the pseudogene PMS2CL in the remaining 3' exons (Exons 12-15). We have recently described an MLPA-based method that permits detection of deletions of PMS2 Exons 12-15; however, the frequency of such deletions has not yet been determined. To address this question, we tested for 3' deletions in 58 samples that were reported to be negative for PMS2 mutations using previously available methods. All samples were from individuals whose tumors exhibited loss of PMS2 immunohistochemical staining without concomitant loss of MLH1 immunostaining. We identified seven samples in this cohort with deletions in the 3' region of PMS2, including three previously reported samples with deletions of Exons 13-15 (two samples) and Exons 14-15. Also detected were deletions of Exons 12-15, Exon 13, and Exon 14 (two samples). Breakpoint analysis of the intragenic deletions suggests they occurred through Alu-mediated recombination. Our results indicate that ∼12% of samples suspected of harboring a PMS2 mutation based on immunohistochemical staining, for which mutations have not yet been identified, would benefit from testing using the new methodology. Copyright © 2012 Wiley Periodicals, Inc.

  20. Novel features of 3q29 deletion syndrome: Results from the 3q29 registry

    Science.gov (United States)

    Glassford, Megan R.; Rosenfeld, Jill A.; Freedman, Alexa A.; Zwick, Michael E.

    2016-01-01

    3q29 deletion syndrome is caused by a recurrent, typically de novo heterozygous 1.6 Mb deletion, but because incidence of the deletion is rare (1 in 30,000 births) the phenotype is not well described. To characterize the range of phenotypic manifestations associated with 3q29 deletion syndrome, we have developed an online registry (3q29deletion.org) for ascertainment of study subjects and phenotypic data collection via Internet‐based survey instruments. We report here on data collected during the first 18 months of registry operation, from 44 patients. This is the largest cohort of 3q29 deletion carriers ever assembled and surveyed in a systematic way. Our data reveal that 28% of registry participants report neuropsychiatric phenotypes, including anxiety disorder, panic attacks, depression, bipolar disorder, and schizophrenia. Other novel findings include a high prevalence (64%) of feeding problems in infancy and reduced weight at birth for 3q29 deletion carriers (average reduction 13.9 oz (394 g), adjusted for gestational age and sex, P = 6.5e‐07). We further report on the frequency of heart defects, autism, recurrent ear infections, gastrointestinal phenotypes, and dental phenotypes, among others. We also report on the expected timing of delayed developmental milestones. This is the most comprehensive description of the 3q29 deletion phenotype to date. These results are clinically actionable toward improving patient care for 3q29 deletion carriers, and can guide the expectations of physicians and parents. These data also demonstrate the value of patient‐reported outcomes to reveal the full phenotypic spectrum of rare genomic disorders. © 2016 The Authors. American Journal of Medical Genetics Part A Published by Wiley Periodicals, Inc. PMID:26738761

  1. A persistent mitochondrial deletion reduces fitness and sperm performance in heteroplasmic populations of C. elegans

    Directory of Open Access Journals (Sweden)

    Chin Kara

    2007-03-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA mutations are of increasing interest due to their involvement in aging, disease, fertility, and their role in the evolution of the mitochondrial genome. The presence of reactive oxygen species and the near lack of repair mechanisms cause mtDNA to mutate at a faster rate than nuclear DNA, and mtDNA deletions are not uncommon in the tissues of individuals, although germ-line mtDNA is largely lesion-free. Large-scale deletions in mtDNA may disrupt multiple genes, and curiously, some large-scale deletions persist over many generations in a heteroplasmic state. Here we examine the phenotypic effects of one such deletion, uaDf5, in Caenorhabditis elegans (C. elegans. Our study investigates the phenotypic effects of this 3 kbp deletion. Results The proportion of uaDf5 chromosomes in worms was highly heritable, although uaDf5 content varied from worm to worm and within tissues of individual worms. We also found an impact of the uaDf5 deletion on metabolism. The deletion significantly reduced egg laying rate, defecation rate, and lifespan. Examination of sperm bearing the uaDf5 deletion revealed that sperm crawled more slowly, both in vitro and in vivo. Conclusion Worms harboring uaDf5 are at a selective disadvantage compared to worms with wild-type mtDNA. These effects should lead to the rapid extinction of the deleted chromosome, but it persists indefinitely. We discuss both the implications of this phenomenon and the possible causes of a shortened lifespan for uaDf5 mutant worms.

  2. When Is Network Lasso Accurate?

    Directory of Open Access Journals (Sweden)

    Alexander Jung

    2018-01-01

    Full Text Available The “least absolute shrinkage and selection operator” (Lasso method has been adapted recently for network-structured datasets. In particular, this network Lasso method allows to learn graph signals from a small number of noisy signal samples by using the total variation of a graph signal for regularization. While efficient and scalable implementations of the network Lasso are available, only little is known about the conditions on the underlying network structure which ensure network Lasso to be accurate. By leveraging concepts of compressed sensing, we address this gap and derive precise conditions on the underlying network topology and sampling set which guarantee the network Lasso for a particular loss function to deliver an accurate estimate of the entire underlying graph signal. We also quantify the error incurred by network Lasso in terms of two constants which reflect the connectivity of the sampled nodes.

  3. System xC- is a mediator of microglial function and its deletion slows symptoms in amyotrophic lateral sclerosis mice.

    Science.gov (United States)

    Mesci, Pinar; Zaïdi, Sakina; Lobsiger, Christian S; Millecamps, Stéphanie; Escartin, Carole; Seilhean, Danielle; Sato, Hideyo; Mallat, Michel; Boillée, Séverine

    2015-01-01

    Amyotrophic lateral sclerosis is the most common adult-onset motor neuron disease and evidence from mice expressing amyotrophic lateral sclerosis-causing SOD1 mutations suggest that neurodegeneration is a non-cell autonomous process where microglial cells influence disease progression. However, microglial-derived neurotoxic factors still remain largely unidentified in amyotrophic lateral sclerosis. With excitotoxicity being a major mechanism proposed to cause motor neuron death in amyotrophic lateral sclerosis, our hypothesis was that excessive glutamate release by activated microglia through their system [Formula: see text] (a cystine/glutamate antiporter with the specific subunit xCT/Slc7a11) could contribute to neurodegeneration. Here we show that xCT expression is enriched in microglia compared to total mouse spinal cord and absent from motor neurons. Activated microglia induced xCT expression and during disease, xCT levels were increased in both spinal cord and isolated microglia from mutant SOD1 amyotrophic lateral sclerosis mice. Expression of xCT was also detectable in spinal cord post-mortem tissues of patients with amyotrophic lateral sclerosis and correlated with increased inflammation. Genetic deletion of xCT in mice demonstrated that activated microglia released glutamate mainly through system [Formula: see text]. Interestingly, xCT deletion also led to decreased production of specific microglial pro-inflammatory/neurotoxic factors including nitric oxide, TNFa and IL6, whereas expression of anti-inflammatory/neuroprotective markers such as Ym1/Chil3 were increased, indicating that xCT regulates microglial functions. In amyotrophic lateral sclerosis mice, xCT deletion surprisingly led to earlier symptom onset but, importantly, this was followed by a significantly slowed progressive disease phase, which resulted in more surviving motor neurons. These results are consistent with a deleterious contribution of microglial-derived glutamate during symptomatic

  4. [Polymorphisms of KITLG, SPRY4, and BAK1 genes in patients with testicular germ cell tumors and individuals with infertility associated with AZFc deletion of the Y chromosome].

    Science.gov (United States)

    Nemtsova, M V; Ivkin, E V; Simonova, O A; Rudenko, V V; Chernykh, V B; Mikhaylenko, D S; Loran, O B

    2016-01-01

    Testicular cancer is the most common form of solid cancer in young men. Testicular cancer is represented by testicular germ cell tumors (TGCTs) derived from embryonic stem cells with different degrees of differentiation in about 95% of cases. The development of these tumors is related to the formation of a pool of male germ cells and gametogenesis. Clinical factors that are predisposed to the development of germ-cell tumors include cryptorchidism and testicular microlithiasis, as well as infertility associated with the gr/gr deletion within the AZFс locus. KITLG, SPRY4, and BAK1 genes affect the development of the testes and gametogenesis; mutations and polymorphisms of these genes lead to a significant increase in the risk of the TGCT development. To determine the relationship between gene polymorphisms and the development of TGCTs, we developed a system for detection and studied the allele and genotype frequencies of the KITLG (rs995030, rs1508595), SPRY4 (rs4624820, rs6897876), and BAK1 (rs210138) genes in fertile men, patients with TGCTs, and patients with infertility that have the AZFс deletion. A significant association of rs995030 of the KITLG gene with the development of TGCTs (p = 0.029 for the allele G, p = 0.0124 for the genotype GG) was revealed. Significant differences in the frequencies of the studied polymorphisms in patients with the AZFc deletion and the control group of fertile men were not found. We showed significant differences in the frequencies for the combination of all high-risk polymorphisms in the control group, patients with the AZFc deletion and patients with TGCTs (p (TGCTs-AZF-control) = 0.0207). A fivefold increase in the frequency of the combination of all genotypes in the TGCT group (p = 0.0116; OR = 5.25 [1.44-19.15]) and 3.7-fold increase was identified in patients with the AZFc deletion (p = 0.045; OR = 3.69 [1.11-12.29]) were revealed. The genotyping of patients with infertility caused by the AZFc deletion can be used to

  5. Schizophrenia with the 22q11.2 deletion and additional genetic defects: case history.

    Science.gov (United States)

    Toyosima, M; Maekawa, M; Toyota, T; Iwayama, Y; Arai, M; Ichikawa, T; Miyashita, M; Arinami, T; Itokawa, M; Yoshikawa, T

    2011-09-01

    The 22q11.2 deletion is the most prominent known genetic risk factor for schizophrenia, but its penetrance is at most approximately 50% suggesting that additional risk factors are required for disease progression. We examined a woman with schizophrenia with this deletion for such risk factors. She had high plasma pentosidine levels ('carbonyl stress') and a frameshift mutation in the responsible gene, GLO1. She also had a constant exotropia, so we examined the PHOX2B gene associated with both schizophrenia and strabismus, and detected a 5-alanine deletion. We propose that the combination of these genetic defects may have exceeded the threshold for the manifestation of schizophrenia.

  6. A novel large deletion of the ICR1 region including H19 and putative enhancer elements.

    Science.gov (United States)

    Fryssira, Helen; Amenta, Stella; Kanber, Deniz; Sofocleous, Christalena; Lykopoulou, Evangelia; Kanaka-Gantenbein, Christina; Cerrato, Flavia; Lüdecke, Hermann-Josef; Bens, Susanne; Riccio, Andrea; Buiting, Karin

    2015-05-06

    Beckwith-Wiedemann syndrome (BWS) is a rare pediatric overgrowth disorder with a variable clinical phenotype caused by deregulation affecting imprinted genes in the chromosomal region 11p15. Alterations of the imprinting control region 1 (ICR1) at the IGF2/H19 locus resulting in biallelic expression of IGF2 and biallelic silencing of H19 account for approximately 10% of patients with BWS. The majority of these patients have epimutations of the ICR1 without detectable DNA sequence changes. Only a few patients were found to have deletions. Most of these deletions are small affecting different parts of the ICR1 differentially methylated region (ICR1-DMR) removing target sequences for CTCF. Only a very few deletions reported so far include the H19 gene in addition to the CTCF binding sites. None of these deletions include IGF2. A male patient was born with hypotonia, facial dysmorphisms and hypoglycemia suggestive of Beckwith-Wiedemann syndrome. Using methylation-specific (MS)-MLPA (Multiplex ligation-dependent probe amplification) we have identified a maternally inherited large deletion of the ICR1 region in a patient and his mother. The deletion results in a variable clinical expression with a classical BWS in the mother and a more severe presentation of BWS in her son. By genome-wide SNP array analysis the deletion was found to span ~100 kb genomic DNA including the ICR1DMR, H19, two adjacent non-imprinted genes and two of three predicted enhancer elements downstream to H19. Methylation analysis by deep bisulfite next generation sequencing revealed hypermethylation of the maternal allele at the IGF2 locus in both, mother and child, although IGF2 is not affected by the deletion. We here report on a novel large familial deletion of the ICR1 region in a BWS family. Due to the deletion of the ICR1-DMR CTCF binding cannot take place and the residual enhancer elements have access to the IGF2 promoters. The aberrant methylation (hypermethylation) of the maternal IGF2

  7. Fluorescence in situ hybridization evaluation of chromosome deletion patterns in prostate cancer.

    Science.gov (United States)

    Huang, S F; Xiao, S; Renshaw, A A; Loughlin, K R; Hudson, T J; Fletcher, J A

    1996-11-01

    Various nonrandom chromosomal aberrations have been identified in prostate carcinoma. These aberrations include deletions of several chromosome regions, particularly the chromosome 8 short arm. Large-scale numerical aberrations, reflected in aberrant DNA ploidy, are also found in a minority of cases. However, it is unclear whether prostate carcinomas contain aberrations of certain chromosome regions that are deleted frequently in other common types of cancer. In this study, we performed dual-color fluorescence in situ hybridization on intact nuclei from touch preparations of 16 prostate cancers. Chromosome copy number was determined using pericentromeric probes, whereas potential chromosome arm deletions were evaluated using yeast artificial chromosome (YAC) and P1 probes. Two YAC probes targeted chromosome 8 short arm regions known to be deleted frequently in prostate cancer. Other YACs and P1s were for chromosome regions, including 1p22, 3p14, 6q21, 9p21, and 22q12, that are deletion targets in a variety of cancers although not extensively studied in prostate cancer. Hybridization efficiencies and signal intensities were excellent for both repeat sequence (alpha-satellite) and single, copy (YAC and P1) fluorescence in situ hybridization probes. Of 16 prostate cancers, 11 had clonal aberrations of 1 or more of the 13 chromosome regions evaluated, and 10 cases (62.5%) had 8p deletions, including 4 cases with 8p deletion in virtually all cells and aneuploidy in only a subset of those deleted cells. Deletions at 3p14, 6q21, and 22q12 were identified in 2, 1, and 1 case, respectively, and each of those cases had a similarly sized cell population with 8p deletion. These studies confirm 8p deletion in the majority of prostate carcinomas. 8p deletions appear to be early events in prostate tumorigenesis, often antedating aneuploidy. Fluorescence in situ hybridization strategies incorporating pericentromeric and single-copy regional chromosome probes offer a powerful and

  8. Do mtDNA Deletions Play a Role in the Development of Nasal Polyposis?

    Directory of Open Access Journals (Sweden)

    Arzu Tatar

    2014-04-01

    Full Text Available Objective:Nasal polyposis (NP is an inflammatory disease of the nasal mucosa and paranasal sinuses. Mitochondria are the cellular organelles which produce cellular energy by Oxidative Phosphorylation (OXPHOS, and they have own inheritance material, mtDNA. mtDNA is affected by reactive oxygen samples (ROS which are produced by both OXPHOS and the inflammatory process. The aim of this study was to investigate the 4977 bp and 7400 bp deletions of mtDNA in nasal polyposis tissue, and to indicate the possible association of mtDNA deletions with NP. Methods:Thirty-three patients, aged 15 to 65 years, with nasal polyposis were selected to be assessed for mitochondrial DNA deletions. The patients with possible mtDNA mutations due to mitochondrial disease, being treated with radiotherapy, of advanced age, with a familiar history, aspirin hypersensitivity, or a history of asthma, were excluded. Polyp excision surgery was applied to the treatment of the NP, and after histopathological diagnosis 1x1 cm of polyp tissue samples were used to isolate mtDNA. The 4977 bp and 7400 bp deletion regions, and two control regions of mtDNA were assessed by using four pairs of primers. DNA extractions from the NP tissues and peripheral blood samples of the patients were made, and then Polymerase Chain Reactions (PCR were made. PCR products were separated in 2% agarose gel.Results:No patient had either the 4977 bp deletion or the 7400 bp deletion in their NP tissue, and neither were these deletions evident in their peripheral blood. Two control sequences, one of them from a non-deleted region, and the other from a possible deletion region, were detected in the NP tissues and peripheral blood of all the patients.Conclusions:We had anticipated that some mtDNA deletion might have occurred in NP tissue due to the increased ROS levels caused by chronic inflammation, but we did not detect any deletion. Probably, the duration of inflammation in NP is insufficient to form mt

  9. ErasuCrypto: A Light-weight Secure Data Deletion Scheme for Solid State Drives

    Directory of Open Access Journals (Sweden)

    Liu Chen

    2017-01-01

    Full Text Available Securely deleting invalid data from secondary storage is critical to protect users’ data privacy against unauthorized accesses. However, secure deletion is very costly for solid state drives (SSDs, which unlike hard disks do not support in-place update. When applied to SSDs, both erasure-based and cryptography-based secure deletion methods inevitably incur large amount of valid data migrations and/or block erasures, which not only introduce extra latency and energy consumption, but also harm SSD lifetime.

  10. Occurrence of two different intragenic deletions in two male relatives affected with Duchenne muscular dystrophy

    Energy Technology Data Exchange (ETDEWEB)

    Mostacciuolo, M.L.; Miorin, M.; Vitiello, L.; Rampazzo, A.; Fanin, M.; Angelini, C.; Danieli, G.A. [Univ. of Padua (Italy)

    1994-03-01

    The occurrence of 2 different intragenic deletions (exons 10-44 and exon 45, respectively) is reported in 2 male relatives affected with Duchenne muscular dystrophy, both showing the same haplotype for DNA markers not included in the deleted segment. The 2 different deletions seem to have occurred independently in the same X chromosome. This finding, together with other reports, suggests possibly an increased predisposition to mutations within the DMD locus in some families. Therefore, when dealing with prenatal diagnosis, the investigation on fetal DNA cannot be restricted only to the region in which a mutation was previously identified in the family. 14 refs., 1 fig.

  11. Computing with Spiking Neuron Networks

    NARCIS (Netherlands)

    H. Paugam-Moisy; S.M. Bohte (Sander); G. Rozenberg; T.H.W. Baeck (Thomas); J.N. Kok (Joost)

    2012-01-01

    htmlabstractAbstract Spiking Neuron Networks (SNNs) are often referred to as the 3rd gener- ation of neural networks. Highly inspired from natural computing in the brain and recent advances in neurosciences, they derive their strength and interest from an ac- curate modeling of synaptic interactions

  12. 75 FR 10223 - Procurement List Proposed Additions and Deletions

    Science.gov (United States)

    2010-03-05

    ....gov . SUPPLEMENTARY INFORMATION: This notice is published pursuant to 41 U.S.C. 47(a)(2) and 41 CFR 51... Services, Alaska VA Healthcare System and Regional Office, Anchorage, AK NPA: MQC Enterprises, Inc., Anchorage, AK Contracting Activity: Department of Veterans Affairs, Network Business Office (10N20VBO...

  13. Mapping the end points of large deletions affecting the hprt locus in human peripheral blood cells and cell lines

    International Nuclear Information System (INIS)

    Nelson, S.L.; Grosovsky, A.J.; Jones, I.M.; Burkhart-Schultz, K.; Fuscoe, J.C.

    1995-01-01

    We have examined the extent of of HPRT - total gene deletions in three mutant collections: spontaneous and X-ray-induced deletions in TK6 human B lymphoblasts, and HPRT - deletions arising in vivo in T cells. A set of 13 Xq26 STS markers surrounding hprt and spanning approximately 3.3 Mb was used. Each marker used was observed to be missing in at least one of the hprt deletion mutants analyzed. The largest deletion observed encompassed at least 3 Mb. Nine deletions extended outside of the mapped region in the centromeric direction (>1.7 Mb). In contrast, only two telomeric deletions extended to marker 342R (1.26 Mb), and both exhibited slowed or limited cell growth. These data suggest the existence of a gene, within the vicinity of 342R, which establishes the telomeric limit of recoverable deletions. Most (25/41) X-ray-induced total gene deletion mutants exhibited marker loss, but only 1/8 of the spontaneous deletions encompassed any Xq26 markers (P = 0.0187). Furthermore, nearly half (3/8) of the spontaneous 3' total deletion breakpoints were within 14 kb of the hprt coding sequence. In contrast, 40/41 X-ray-induced HPRT - total deletions extended beyond this point (P = 0.011). Although the overall representation of total gene deletions in the in vivo spectrum is low, 4/5 encompass Xq26 markers flanking hprt. This pattern differs significantly from spontaneous HPRT - large deletions occurring in vitro (P = 0.032) but resembles the spectrum of X-ray-induced deletions. 24 refs., 6 figs., 1 tab

  14. Discrimination of Deletion and Duplication Subtypes of the Deleted in Azoospermia Gene Family in the Context of Frequent Interloci Gene Conversion

    Science.gov (United States)

    Vaszkó, Tibor; Papp, János; Krausz, Csilla; Casamonti, Elena; Géczi, Lajos; Olah, Edith

    2016-01-01

    Due to its palindromic setup, AZFc (Azoospermia Factor c) region of chromosome Y is one of the most unstable regions of the human genome. It contains eight gene families expressed mainly in the testes. Several types of rearrangement resulting in changes in the cumulative copy number of the gene families were reported to be associated with diseases such as male infertility and testicular germ cell tumors. The best studied AZFc rearrangement is gr/gr deletion. Its carriers show widespread phenotypic variation from azoospermia to normospermia. This phenomenon was initially attributed to different gr/gr subtypes that would eliminate distinct members of the affected gene families. However, studies conducted to confirm this hypothesis have brought controversial results, perhaps, in part, due to the shortcomings of the utilized subtyping methodology. This proof-of-concept paper is meant to introduce here a novel method aimed at subtyping AZFc rearrangements. It is able to differentiate the partial deletion and partial duplication subtypes of the Deleted in Azoospermia (DAZ) gene family. The keystone of the method is the determination of the copy number of the gene family member-specific variant(s) in a series of sequence family variant (SFV) positions. Most importantly, we present a novel approach for the correct interpretation of the variant copy number data to determine the copy number of the individual DAZ family members in the context of frequent interloci gene conversion.Besides DAZ1/DAZ2 and DAZ3/DAZ4 deletions, not yet described rearrangements such as DAZ2/DAZ4 deletion and three duplication subtypes were also found by the utilization of the novel approach. A striking feature is the extremely high concordance among the individual data pointing to a certain type of rearrangement. In addition to being able to identify DAZ deletion subtypes more reliably than the methods used previously, this approach is the first that can discriminate DAZ duplication subtypes as well

  15. Protein kinase Cα deletion causes hypotension and decreased vascular contractility.

    Science.gov (United States)

    Wynne, Brandi M; McCarthy, Cameron G; Szasz, Theodora; Molina, Patrick A; Chapman, Arlene B; Webb, R Clinton; Klein, Janet D; Hoover, Robert S

    2018-03-01

    Protein kinase Cα (PKCα) is a critical regulator of multiple cell signaling pathways including gene transcription, posttranslation modifications and activation/inhibition of many signaling kinases. In regards to the control of blood pressure, PKCα causes increased vascular smooth muscle contractility, while reducing cardiac contractility. In addition, PKCα has been shown to modulate nephron ion transport. However, the role of PKCα in modulating mean arterial pressure (MAP) has not been investigated. In this study, we used a whole animal PKCα knock out (PKC KO) to test the hypothesis that global PKCα deficiency would reduce MAP, by a reduction in vascular contractility. Radiotelemetry measurements of ambulatory blood pressure (day/night) were obtained for 18 h/day during both normal chow and high-salt (4%) diet feedings. PKCα mice had a reduced MAP, as compared with control, which was not normalized with high-salt diet (14 days). Metabolic cage studies were performed to determine urinary sodium excretion. PKC KO mice had a significantly lower diastolic, systolic and MAP as compared with control. No significant differences in urinary sodium excretion were observed between the PKC KO and control mice, whether fed normal chow or high-salt diet. Western blot analysis showed a compensatory increase in renal sodium chloride cotransporter expression. Both aorta and mesenteric vessels were removed for vascular reactivity studies. Aorta and mesenteric arteries from PKC KO mice had a reduced receptor-independent relaxation response, as compared with vessels from control. Vessels from PKC KO mice exhibited a decrease in maximal contraction, compared with controls. Together, these data suggest that global deletion of PKCα results in reduced MAP due to decreased vascular contractility.

  16. Quantification of the mitochondrial DNA common deletion in presbycusis.

    Science.gov (United States)

    Markaryan, Adam; Nelson, Erik G; Hinojosa, Raul

    2009-06-01

    This study was conducted to evaluate the association between the mitochondrial DNA (mtDNA) common deletion (CD) level in cochlear tissue and the severity of hearing loss in individuals with presbycusis. Nineteen individuals with presbycusis, ranging from 60 to 87 years of age, who met strict audiometric criteria were compared with four age frequency-matched normal hearing controls ranging from 51 to 76 years of age. Five additional normal hearing individuals, ranging from 9 to 50 years of age, were also studied. A duplex real time polymerase chain reaction assay was used to quantify the mtDNA in archival cochlear tissue samples. Linear regression models were used for comparison of the CD level between groups. The presbycusis group had a mean CD level of 32% with a standard deviation of 14%, and the normal hearing age matched control group had a mean CD level of 12% with a standard deviation of 2%. This difference in CD levels reached statistical significance (P = .011) and remained significant after adjusting for any differences in age between the two groups (age-adjusted P = .007). Furthermore, there was evidence for a significant association between the CD level and the severity of hearing loss based on audiometric thresholds at 8 kHz (r = 0.44, P = .034; age-adjusted partial correlation = 0.55, P = .007). For the first time, to our knowledge, these results demonstrate a relationship between quantitatively measured levels of the CD in human cochlear tissue and the severity of hearing loss in individuals with presbycusis. Laryngoscope, 2009.

  17. Network cohesion

    OpenAIRE

    Cavalcanti, Tiago Vanderlei; Giannitsarou, Chrysi; Johnson, CR

    2017-01-01

    We define a measure of network cohesion and show how it arises naturally in a broad class of dynamic models of endogenous perpetual growth with network externalities. Via a standard growth model, we show why network cohesion is crucial for conditional convergence and explain that as cohesion increases, convergence is faster. We prove properties of network cohesion and define a network aggregator that preserves network cohesion.

  18. The network researchers' network

    DEFF Research Database (Denmark)

    Henneberg, Stephan C.; Jiang, Zhizhong; Naudé, Peter

    2009-01-01

    The Industrial Marketing and Purchasing (IMP) Group is a network of academic researchers working in the area of business-to-business marketing. The group meets every year to discuss and exchange ideas, with a conference having been held every year since 1984 (there was no meeting in 1987). In thi......The Industrial Marketing and Purchasing (IMP) Group is a network of academic researchers working in the area of business-to-business marketing. The group meets every year to discuss and exchange ideas, with a conference having been held every year since 1984 (there was no meeting in 1987......). In this paper, based upon the papers presented at the 22 conferences held to date, we undertake a Social Network Analysis in order to examine the degree of co-publishing that has taken place between this group of researchers. We identify the different components in this database, and examine the large main...

  19. Effect of partial and complete variable loop deletions of the human immunodeficiency virus type 1 envelope glycoprotein on the breadth of gp160-specific immune responses

    International Nuclear Information System (INIS)

    Gzyl, Jaroslaw; Bolesta, Elizabeth; Wierzbicki, Andrew; Kmieciak, Dariusz; Naito, Toshio; Honda, Mitsuo; Komuro, Katsutoshi; Kaneko, Yutaro; Kozbor, Danuta

    2004-01-01

    Induction of cross-reactive cellular and humoral responses to the HIV-1 envelope (env) glycoprotein was examined after DNA immunization of BALB/c mice with gp140 89.6 -derived constructs exhibiting partial or complete deletions of the V1, V2, and V3 domains. It was demonstrated that specific modification of the V3 loop (mV3) in combination with the V2-modified (mV2) or V1/V2-deleted (ΔV1/V2) region elicited increased levels of cross-reactive CD8 + T cell responses. Mice immunized with the mV2/mV3 or ΔV1/V2/mV3 gp140 89.6 plasmid DNA were greater than 50-fold more resistant to challenge with recombinant vaccinia virus (rVV) expressing heterologous env gene products than animals immunized with the wild-type (WT) counterpart. Sera from mV2/mV3- and ΔV1/V2/mV3-immunized mice exhibited the highest cross-neutralizing activity and displayed intermediate antibody avidity values which were further enhanced by challenge with rVV expressing the homologous gp160 glycoprotein. In contrast, complete deletion of the variable regions had little or no effect on the cross-reactive antibody responses. The results of these experiments indicate that the breadth of antibody responses to the HIV-1 env glycoprotein may not be increased by removal of the variable domains. Instead, partial deletions within these regions may redirect specific responses toward conserved epitopes and facilitate approaches for boosting cross-reactive cellular and antibody responses to the env glycoprotein

  20. Antigenicity and Immunogenicity of RV144 Vaccine AIDSVAX Clade E Envelope Immunogen Is Enhanced by a gp120 N-Terminal Deletion

    Science.gov (United States)

    Liao, Hua-Xin; Tomaras, Georgia D.; Bonsignori, Mattia; Tsao, Chun-Yen; Hwang, Kwan-Ki; Chen, Haiyan; Lloyd, Krissey E.; Bowman, Cindy; Sutherland, Laura; Jeffries, Thomas L.; Kozink, Daniel M.; Stewart, Shelley; Anasti, Kara; Jaeger, Frederick H.; Parks, Robert; Yates, Nicole L.; Overman, R. Glenn; Sinangil, Faruk; Berman, Phillip W.; Pitisuttithum, Punnee; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Karasavva, Nicos; Rerks-Ngarm, Supachai; Kim, Jerome H.; Michael, Nelson L.; Zolla-Pazner, Susan; Santra, Sampa; Letvin, Norman L.; Harrison, Stephen C.

    2013-01-01

    An immune correlates analysis of the RV144 HIV-1 vaccine trial revealed that antibody responses to the gp120 V1/V2 region correlated inversely with infection risk. The RV144 protein immunogens (A244-rp120 and MN-rgp120) were modified by an N-terminal 11-amino-acid deletion (Δ11) and addition of a herpes simplex virus (HSV) gD protein-derived tag (gD). We investigated the effects of these modifications on gp120 expression, antigenicity, and immunogenicity by comparing unmodified A244 gp120 with both Δ11 deletion and gD tag and with Δ11 only. Analysis of A244 gp120, with or without Δ11 or gD, demonstrated that the Δ11 deletion, without the addition of gD, was sufficient for enhanced antigenicity to gp120 C1 region, conformational V2, and V1/V2 gp120 conformational epitopes. RV144 vaccinee serum IgGs bound more avidly to A244 gp120 Δ11 than to the unmodified gp120, and their binding was blocked by C1, V2, and V1/V2 antibodies. Rhesus macaques immunized with the three different forms of A244 gp120 proteins gave similar levels of gp120 antibody titers, although higher antibody titers developed earlier in A244 Δ11 gp120-immunized animals. Conformational V1/V2 monoclonal antibodies (MAbs) gave significantly higher levels of blocking of plasma IgG from A244 Δ11 gp120-immunized animals than IgG from animals immunized with unmodified A244 gp120, thus indicating a qualitative difference in the V1/V2 antibodies induced by A244 Δ11 gp120. These results demonstrate that deletion of N-terminal residues in the RV144 A244 gp120 immunogen improves both envelope antigenicity and immunogenicity. PMID:23175357