bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic inactivation of
AKT1
,
AKT2
, and
PDPK1
in human colorectal cancer cells clarifies their roles in tumor growth regulation
Authors: Ericson Kajsa , Gan Christine , Cheong Ian , Rago Carlo , Samuels Yardena , Velculescu Victor E. , Kinzler Kenneth W. , Huso David L. , Vogelstein Bert , Papadopoulos Nickolas
Published: January 2010

Phosphotidylinositol-3-kinase (PI3K) signaling is altered in the majority of human cancers. To gain insight into the roles of members of this pathway in growth regulation, we inactivated
AKT1
,
AKT2
, or
PDPK1
genes by targeted homologous recombination in human colon cancer cell lines. Knockout of either
AKT1
or
AKT2
had minimum effects on cell growth or downstream signaling. In contrast, knockout of
both AKT1
and
AKT2
resulted in markedly reduced proliferation in vitro when growth factors were limiting and severely affected experimental metastasis in mice. Unexpectedly,
AKT1
and
AKT2
appeared to regulate growth through FOXO proteins, but not through either GSK3β or mTOR. In contrast, inactivation of
PDPK1
affected GSK3β and mTOR activation. These findings show that the PI3K signaling pathway is wired differently in human cancer cells than in other cell types or organisms, which has important implications for the design and testing of drugs that target this pathway.
Neutron emission generated by fast deuterons accelerated with ion cyclotron heating at JET
Authors: Hellesen C. , Johnson M. Gatu , Sundén E. Anderson , Conroy S. , Ericsson G. , Ronchi E , Sjöstrand H. , Weiszflog M. , Gorini G. , Tardocchi M. , Johnson T. , Kiptily V.G. , Pinches S.D. , Sharapov S.E.
Published: January 2010

For the first time, the neutron emission from JET plasmas heated with combined deuterium neutral beam injection and third harmonic ion cyclotron radio frequency heating have been studied with neutron emission spectroscopy (NES). Very high DD neutron rates were observed with only modest external heating powers, which was attributed to acceleration of deuterium beam ions to energies of about 2–3 MeV, where the DD reactivity is on a par of that of the DT reaction. Fast deuterium energy distributions were derived from analysis of NES data and confirm acceleration of deuterium beam ions up to energies around 3 MeV, in agreement with theoretical predictions. The high neutron rates allowed for observations of changes in the fast deuterium populations on a time scale of 50 ms. Correlations were seen between fast deuterium ions at different energies and magnetohydrodynamic activities, such as monster sawtooth crashes and toroidal Alfvén eigenmodes.
Effect of magnetic field ripple on electron cyclotron current drive in Heliotron J
Authors: Nagasaki K. , Motojima G. , Kobayashi S. , Yamamoto S. , Mizuuchi T. , Okada H. , Hanatani K. , Konoshima S. , Masuda K. , Nakamura Y. , Watanabe S. , Mukai K. , Hosaka K. , Kowada K. , Mihara S. , Yoshimura Y. , Suzuki Y. , Fernández A. , Cappa A. , Sano F.
Published: January 2010

Electron cyclotron current drive (ECCD) experiments have been conducted in the helical heliotron device, Heliotron J. A wide configuration scan shows that the electron cyclotron (EC) driven current is strongly dependent on the magnetic ripple structure where the EC power is deposited. As the EC power is deposited on the deeper ripple bottom, the EC current flowing in the Fisch–Boozer direction decreases, and the reversal of directly measured EC driven current is observed. Measurement results using electron cyclotron emission and soft-x ray spectrum diagnostics imply that high-energy electrons are generated for ripple top heating while they are suppressed for ripple bottom heating, indicating that the generation and confinement of trapped electrons have an important role on ECCD. For ripple top heating, the typical ECCD efficiency is estimated as γ = n
e
I
EC
R/P
EC = 0.8 × 1017 A W−1 m−2 and
, where n
e is in 1020 m−3, I
EC in A, R in m, P
EC in W and T
e in keV. The normalized ECCD efficiency is found to be independent of the absorbed EC power for both ripple top and bottom heating cases.
Interaction of nitrogen plasmas with tungsten
Authors: Schmid K. , Manhard A. , Linsmeier Ch. , Wiltner A. , Schwarz-Selinger T. , Jacob W. , Mändl S.
Published: January 2010

The use of nitrogen seeding to reduce the edge plasma temperature has recently been successfully applied in ASDEX Upgrade. While the plasma performance was significantly improved compared with other seeding species such as Ar or Ne, questions remained as to the interaction of nitrogen with a tungsten first wall. In particular the formation of thick tungsten nitride layers with reduced melting temperature and increased physical sputtering was a concern. Therefore dedicated laboratory experiments have been performed to investigate the interaction of W surfaces with N plasmas. Tungsten coated Si samples were exposed to N ions from plasma and ion gun sources at energies from 20 eV to 10 keV and W surface temperatures from 300 to 750 K. After exposure to the N plasma with fluences of up to several 1023 N m−2 the N content in the samples was measured by nuclear reaction analysis. The sputter erosion was determined by measuring the thickness change of the W layer by Rutherford backscattering. The formation of W-nitride phases was investigated in separate XPS experiments where the samples were implanted in situ with kiloelectronvolt N ions. It was found that only very small fractions of N are accumulated on the W surface and that N is bound in a nitride state. At temperatures above 600 K the nitrides are no longer stable which further reduces the N uptake into the W. Moreover the accumulation of N on the surface leads to a decrease in W physical sputtering due to the lower W concentration at the surface.
Self-consistent three-dimensional computations of non-axisymmetric ITER equilibria
Authors: Strumberger E. , Günter S. , Merkel P. , Schwarz E. , Tichmann C.
Published: January 2010

Three planned test blanket modules (TBMs) and 18 toroidal field coils break the axisymmetry of the ITER magnetic field. In this paper, the plasma response on these non-axisymmetric fields is studied quantitatively. For this purpose, self-consistent, three-dimensional, free-boundary equilibria of type ITER scenario 4 are computed. The resulting 3D equilibrium magnetic fields are then compared with the corresponding axisymmetric fields to which the vacuum perturbation fields are superimposed. The studies are performed for various normalized plasma pressures.
Linear and nonlinear stability of drift-tearing mode
Authors: Yu Q.
Published: January 2010

The drift-tearing mode stability is studied numerically using the (reduced) two fluid equations. With a set of experimental data as input, the mode is found to be driven unstable by the electron temperature gradient when the classical perpendicular electron heat conductivity is taken into account. In the nonlinear phase two saturation regimes are found, a small magnetic island regime existing for an intermediate electron diamagnetic drift frequency and a large island regime for a sufficiently high bootstrap current fraction.
Study of current decay time during disruption in JT-60U tokamak
Authors: Shibata Y. , Watanabe K.Y. , Okamoto M. , Ohno N. , Isayama A. , Kurihara K. , Nakano T. , Oyama N. , Kawano Y. , Matsunaga G. , Sakakibara S. , Sugihara M. , Kamada Y.
Published: January 2010

AnL/Rmodel that predicts the current decay time from the circuit equation is essentially used for the design of the International Thermonuclear Experimental Reactor. In order to verify the validity of theL/Rmodel in the determination of current decay time during disruption, the plasma current decay time in the JT-60U tokamak is studied using experimental plasma resistance and inductance. The plasma resistance during the initial phase of current quench is estimated from the electron temperature profile measured using the electron cyclotron emission diagnostic system and by measuring the He I line emission intensity ratios and plasma inductance is estimated by the Cauchy-Condition surface method using magnetic sensor signals. Further, the radiation-induced disruptive plasma discharges with massive neon gas puffing are also analysed. The observed area-normalized current decay times have a weak dependence on the electron temperature, particularly in a small decay time region (5–10 ms m−2). The observed decay times are lesser by one order of magnitude than the decay times estimated by theL/Rmodel. However, a novel model for decay time prediction, which takes into account the time derivative of the plasma inductance, wields results that are extremely consistent with the experimental decay time.
Equilibrium and global MHD stability study of KSTAR high beta plasmas under passive and active mode control
Authors: Katsuro-Hopkins O. , Sabbagh S.A. , Bialek J.M. , Park H.K. , Bak J.G. , Chung J. , Hahn S.H. , Kim J.Y. , Kwon M. , Lee S.G. , Yoon S.W. , You K.-I. , Glasser A.H. , Lao L.L.
Published: January 2010

The Korea Superconducting Tokamak Advanced Research, KSTAR, is designed to operate a steady-state, high beta plasma while retaining global magnetohydrodynamic (MHD) stability to establish the scientific and technological basis of an economically attractive fusion reactor. An equilibrium model is established for stability analysis of KSTAR. Reconstructions were performed for the experimental start-up scenario and experimental first plasma operation using the EFIT code. The VALEN code was used to determine the vacuum vessel current distribution. Theoretical high beta equilibria spanning the expected operational range are computed for various profiles including generic L-mode and DIII-D experimental H-mode pressure profiles. Ideal MHD stability calculations of toroidal mode number of unity using the DCON code shows a factor of 2 improvement in the wall-stabilized plasma beta limit at moderate to low plasma internal inductance. The planned stabilization system in KSTAR comprises passive stabilizing plates and actively cooled in-vessel control coils (IVCCs) designed for non-axisymmetric field error correction and stabilization of slow timescale MHD modes including resistive wall modes (RWMs). VALEN analysis using standard proportional gain shows that active stabilization near the ideal wall limit can be reached with feedback using the midplane segment of the IVCC. The RMS power required for control using both white noise and noise taken from NSTX active stabilization experiments is computed for beta near the ideal wall limit. Advanced state-space control algorithms yield a factor of 2 power reduction assuming white noise while remaining robust with respect to variations in plasma beta.
A Specific Form of Phospho Protein Phosphatase 2 Regulates Anaphase-promoting Complex/Cyclosome Association with Spindle Poles
Authors: Torres Jorge Z. , Ban Kenneth H. , Jackson Peter K.
Published: January 2010

In early mitosis, the END (Emi1/NuMA/Dynein-dynactin) network anchors the anaphase-promoting complex/cyclosome (APC/C) to the mitotic spindle and poles. Spindle anchoring restricts APC/C activity, thereby limiting the destruction of spindle-associated cyclin B and ensuring maintenance of spindle integrity. Emi1 binds directly to hypophosphorylated APC/C, linking the APC/C to the spindle via NuMA. However, whether the phosphorylation state of the APC/C is important for its association with the spindle and what kinases and phosphatases are necessary for regulating this event remain unknown. Here, we describe the regulation of APC/C-mitotic spindle pole association by phosphorylation. We find that only hypophosphorylated APC/C associates with microtubule asters, suggesting that phosphatases are important. Indeed, a specific form of PPP2 (CA/R1A/R2B) binds APC/C, and PPP2 activity is necessary for Cdc27 dephosphorylation. Screening by RNA interference, we find that inactivation of CA, R1A, or R2B leads to delocalization of APC/C from spindle poles, early mitotic spindle defects, a failure to congress chromosomes, and decreased levels of cyclin B on the spindle. Consistently, inhibition of cyclin B/Cdk1 activity increased APC/C binding to microtubules. Thus, cyclin B/Cdk1 and PPP2 regulate the dynamic association of APC/C with spindle poles in early mitosis, a step necessary for proper spindle formation.
Differential Localization and Dynamics of Class I Myosins in the Enterocyte Microvillus
Authors: Benesh Andrew E. , Nambiar Rajalakshmi , McConnell Russell E. , Mao Suli , Tabb David L. , Tyska Matthew J.
Published: January 2010

Epithelial cells lining the intestinal tract build an apical array of microvilli known as the brush border. Each microvillus is a cylindrical membrane protrusion that is linked to a supporting actin bundle by myosin-1a (Myo1a). Mice lacking Myo1a demonstrate no overt physiological symptoms, suggesting that other myosins may compensate for the loss of Myo1a in these animals. To investigate changes in the microvillar myosin population that may limit the Myo1a KO phenotype, we performed proteomic analysis on WT and Myo1a KO brush borders. These studies revealed that WT brush borders also contain the short-tailed class I myosin, myosin-1d (Myo1d). Myo1d localizes to the terminal web and striking puncta at the tips of microvilli. In the absence of Myo1a, Myo1d peptide counts increase twofold; this motor also redistributes along the length of microvilli, into compartments normally occupied by Myo1a. FRAP studies demonstrate that Myo1a is less dynamic than Myo1d, providing a mechanistic explanation for the observed differential localization. These data suggest that Myo1d may be the primary compensating class I myosin in the Myo1a KO model; they also suggest that dynamics govern the localization and function of different yet closely related myosins that target common actin structures.
Compartmentalized Cyclic Adenosine 3′,5′-Monophosphate at the Plasma Membrane Clusters PDE3A and Cystic Fibrosis Transmembrane Conductance Regulator into Microdomains
Authors: Penmatsa Himabindu , Zhang Weiqiang , Yarlagadda Sunitha , Li Chunying , Conoley Veronica G. , Yue Junming , Bahouth Suleiman W. , Buddington Randal K. , Zhang Guangping , Nelson Deborah J. , Sonecha Monal D. , Manganiello Vincent , Wine Jeffrey J. , Naren Anjaparavanda P.
Published: January 2010

Formation of multiple-protein macromolecular complexes at specialized subcellular microdomains increases the specificity and efficiency of signaling in cells. In this study, we demonstrate that phosphodiesterase type 3A (PDE3A) physically and functionally interacts with cystic fibrosis transmembrane conductance regulator (CFTR) channel. PDE3A inhibition generates compartmentalized cyclic adenosine 3′,5′-monophosphate (cAMP), which further clusters PDE3A and CFTR into microdomains at the plasma membrane and potentiates CFTR channel function. Actin skeleton disruption reduces PDE3A–CFTR interaction and segregates PDE3A from its interacting partners, thus compromising the integrity of the CFTR-PDE3A–containing macromolecular complex. Consequently, compartmentalized cAMP signaling is lost. PDE3A inhibition no longer activates CFTR channel function in a compartmentalized manner. The physiological relevance of PDE3A–CFTR interaction was investigated using pig trachea submucosal gland secretion model. Our data show that PDE3A inhibition augments CFTR-dependent submucosal gland secretion and actin skeleton disruption decreases secretion.
Mitochondrial Dysfunction Confers Resistance to Multiple Drugs inCaenorhabditis elegans
Authors: Zubovych Iryna O. , Straud Sarah , Roth Michael G.
Published: January 2010

In a previous genetic screen for Caenorhabditis elegans mutants that survive in the presence of an antimitotic drug, hemiasterlin, we identified eight strong mutants. Two of these were found to be resistant to multiple toxins, and in one of these we identified a missense mutation in phb-2, which encodes the mitochondrial protein prohibitin 2. Here we identify two additional mutations that confer drug resistance, spg-7 and har-1, also in genes encoding mitochondrial proteins. Other mitochondrial mutants, isp-1, eat-3, and clk-1, were also found to be drug-resistant. Respiratory complex inhibitors, FCCP and oligomycin, and a producer of reactive oxygen species (ROS), paraquat, all rescued wild-type worms from hemiasterlin toxicity. Worms lacking mitochondrial superoxide dismutase (MnSOD) were modestly drug-resistant, and elimination of MnSOD in the phb-2, har-1, and spg-7 mutants enhanced resistance. The antioxidant N-acetyl-l-cysteine prevented mitochondrial inhibitors from rescuing wild-type worms from hemiasterlin and sensitized mutants to the toxin, suggesting that a mechanism sensitive to ROS is necessary to trigger drug resistance in C. elegans. Using genetics, we show that this drug resistance requires pkc-1, the C. elegans ortholog of human PKCε.
Biological and Structural Basis for Aha1 Regulation of Hsp90 ATPase Activity in Maintaining Proteostasis in the Human Disease Cystic Fibrosis
Authors: Koulov Atanas V. , LaPointe Paul , Lu Bingwen , Razvi Abbas , Coppinger Judith , Dong Meng-Qiu , Matteson Jeanne , Laister Rob , Arrowsmith Cheryl , Yates John R. , Balch William E.
Published: January 2010

The activator of Hsp90 ATPase 1, Aha1, has been shown to participate in the Hsp90 chaperone cycle by stimulating the low intrinsic ATPase activity of Hsp90. To elucidate the structural basis for ATPase stimulation of human Hsp90 by human Aha1, we have developed novel mass spectrometry approaches that demonstrate that the N- and C-terminal domains of Aha1 cooperatively bind across the dimer interface of Hsp90 to modulate the ATP hydrolysis cycle and client activity in vivo. Mutations in both the N- and C-terminal domains of Aha1 impair its ability to bind Hsp90 and stimulate its ATPase activity in vitro and impair in vivo the ability of the Hsp90 system to modulate the folding and trafficking of wild-type and variant (ΔF508) cystic fibrosis transmembrane conductance regulator (CFTR) responsible for the inherited disease cystic fibrosis (CF). We now propose a general model for the role of Aha1 in the Hsp90 ATPase cycle in proteostasis whereby Aha1 regulates the dwell time of Hsp90 with client. We suggest that Aha1 activity integrates chaperone function with client folding energetics by modulating ATPase sensitive N-terminal dimer structural transitions, thereby protecting transient folding intermediates in vivo that could contribute to protein misfolding systems disorders such as CF when destabilized.
Impacts of Minimum Quality Standards Imposed Through Marketing Orders or Related Producer Organizations
Authors: Saitone Tina L. , Sexton Richard J.
Published: January 2010

We analyze the impacts of minimum quality standards (MQS) imposed by producers acting collectively through a producer organization, such as a marketing order. MQS imposed in a competitive market can never enhance social welfare because in general an MQS creates two deadweight losses—one due to inefficient enhancement of product quality and a second due to wastage of the low‐quality product. Any MQS that a competitive industry implements based upon a profit criterion causes all consumers in the market to be harmed. However, an MQS may be preferred relative to supply control as a second‐best instrument for transferring income to producers.
Do Economic Variables Follow Scale or Location‐Scale Distributions?
Authors: Antle John M.
Published: January 2010

Economics researchers often assume that random variables are drawn from distributions that are members of scale or location‐scale families of distributions. This article generalizes earlier results in the literature on the bias in least squares estimates of multiplicative error models, and uses those results to construct a test of the scale and location‐scale hypotheses. A Monte Carlo simulation shows that the test is powerful in large samples. The empirical relevance of these findings is illustrated with estimates of a supply function for U.S. wheat production. Implications for applied economics research are discussed.
Estimating Griliches' k‐Shifts
Authors: Fulginiti Lilyan E.
Published: January 2010

Griliches' k‐shift, a crucial parameter in the welfare evaluation of technological change, is shown to be equal to the radial rate of technological change plus a vector of commodity bias parameters obtained from the distance function. The analysis permits decomposition of sectoral productivity growth into productivity growth by commodity. The k‐shifts estimated for wheat, corn, soybeans, and beef in U.S. agriculture indicate a decrease in the marginal cost of production of corn, soybeans, and wheat during the 1950–1993 years.
Producer Protection Legislation and Termination Damages in the Presence of Contracting Frictions
Authors: Wu Steven Y.
Published: January 2010

This study models producer protection legislation (PPL) that would grant growers the right to claim damages if their contracts are prematurely terminated. In the absence of contracting frictions that prevent contractors from redesigning contracts to accommodate exogenous policy changes, producer protection legislation damages (PPLD) would not be distortionary or redistributive. If contracting frictions exist, then PPLD would have efficiency and redistributive effects, though the direction and magnitude depends on the size of PPL damages vis‐à‐vis expected damages under existing contract law. This study clarifies the conditions under which PPLD would decrease efficiency and protect growers.
Multifactor dimensionality reduction for graphics processing units enables genome-wide testing of epistasis in sporadic ALS
Authors: Greene Casey S. , Sinnott-Armstrong Nicholas A. , Himmelstein Daniel S. , Park Paul J. , Moore Jason H. , Harris Brent T.
Published: January 2010

Motivation: Epistasis, the presence of gene–gene interactions, has been hypothesized to be at the root of many common human diseases, but current genome-wide association studies largely ignore its role. Multifactor dimensionality reduction (MDR) is a powerful model-free method for detecting epistatic relationships between genes, but computational costs have made its application to genome-wide data difficult. Graphics processing units (GPUs), the hardware responsible for rendering computer games, are powerful parallel processors. Using GPUs to run MDR on a genome-wide dataset allows for statistically rigorous testing of epistasis.

Results: The implementation of MDR for GPUs (MDRGPU) includes core features of the widely used Java software package, MDR. This GPU implementation allows for large-scale analysis of epistasis at a dramatically lower cost than the standard CPU-based implementations. As a proof-of-concept, we applied this software to a genome-wide study of sporadic amyotrophic lateral sclerosis (ALS). We discovered a statistically significant two-SNP classifier and subsequently replicated the significance of these two SNPs in an independent study of ALS. MDRGPU makes the large-scale analysis of epistasis tractable and opens the door to statistically rigorous testing of interactions in genome-wide datasets.

Availability: MDRGPU is open source and available free of charge from http://www.sourceforge.net/projects/mdr.

Contact:  jason.h.moore@dartmouth.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
ProteinWorldDB: querying radical pairwise alignments among protein sets from complete genomes
Authors: Otto Thomas Dan , Catanho Marcos , Tristão Cristian , Bezerra Márcia , Fernandes Renan Mathias , Elias Guilherme Steinberger , Scaglia Alexandre Capeletto , Bovermann Bill , Berstis Viktors , Lifschitz Sergio , de Miranda Antonio Basílio , Degrave Wim
Published: January 2010

Motivation: Many analyses in modern biological research are based on comparisons between biological sequences, resulting in functional, evolutionary and structural inferences. When large numbers of sequences are compared, heuristics are often used resulting in a certain lack of accuracy. In order to improve and validate results of such comparisons, we have performed radical all-against-all comparisons of 4 million protein sequences belonging to the RefSeq database, using an implementation of the Smith–Waterman algorithm. This extremely intensive computational approach was made possible with the help of World Community Grid™, through the Genome Comparison Project. The resulting database, ProteinWorldDB, which contains coordinates of pairwise protein alignments and their respective scores, is now made available. Users can download, compare and analyze the results, filtered by genomes, protein functions or clusters. ProteinWorldDB is integrated with annotations derived from Swiss-Prot, Pfam, KEGG, NCBI Taxonomy database and gene ontology. The database is a unique and valuable asset, representing a major effort to create a reliable and consistent dataset of cross-comparisons of the whole protein content encoded in hundreds of completely sequenced genomes using a rigorous dynamic programming approach.

Availability: The database can be accessed through http://proteinworlddb.org

Contact:  otto@fiocruz.br
Protein secondary structure appears to be robust underin silicoevolution while protein disorder appears not to be
Authors: Schaefer Christian , Schlessinger Avner , Rost Burkhard
Published: January 2010

Motivation: The mutation of amino acids often impacts protein function and structure. Mutations without negative effect sustain evolutionary pressure. We study a particular aspect of structural robustness with respect to mutations: regular protein secondary structure and natively unstructured (intrinsically disordered) regions. Is the formation of regular secondary structure an intrinsic feature of amino acid sequences, or is it a feature that is lost upon mutation and is maintained by evolution against the odds? Similarly, is disorder an intrinsic sequence feature or is it difficult to maintain? To tackle these questions, we in silico mutated native protein sequences into random sequence-like ensembles and monitored the change in predicted secondary structure and disorder.

Results: We established that by our coarse-grained measures for change, predictions and observations were similar, suggesting that our results were not biased by prediction mistakes. Changes in secondary structure and disorder predictions were linearly proportional to the change in sequence. Surprisingly, neither the content nor the length distribution for the predicted secondary structure changed substantially. Regions with long disorder behaved differently in that significantly fewer such regions were predicted after a few mutation steps. Our findings suggest that the formation of regular secondary structure is an intrinsic feature of random amino acid sequences, while the formation of long-disordered regions is not an intrinsic feature of proteins with disordered regions. Put differently, helices and strands appear to be maintained easily by evolution, whereas maintaining disordered regions appears difficult. Neutral mutations with respect to disorder are therefore very unlikely.

Contact:  schaefer@rostlab.org

Supplementary Information:  Supplementary data are available at Bioinformatics online.
NEMO: a tool for analyzing gene and chromosome territory distributions from 3D-FISH experiments
Authors: Iannuccelli E. , Mompart F. , Gellin J. , Lahbib-Mansais Y. , Yerle M. , Boudier T.
Published: January 2010

Summary: Three-dimensional fluorescence in situ hybridization (3D-FISH) is used to study the organization and the positioning of chromosomes or specific sequences such as genes or RNA in cell nuclei. Many different programs (commercial or free) allow image analysis for 3D-FISH experiments. One of the more efficient open-source programs for automatically processing 3D-FISH microscopy images is Smart 3D-FISH, an ImageJ plug-in designed to automatically analyze distances between genes. One of the drawbacks of Smart 3D-FISH is that it has a rather basic user interface and produces its results in various text and image files thus making the data post-processing step time consuming. We developed a new Smart 3D-FISH graphical user interface, NEMO, which provides all information in the same place so that results can be checked and validated efficiently. NEMO gives users the ability to drive their experiments analysis in either automatic, semi-automatic or manual detection mode. We also tuned Smart 3D-FISH to better analyze chromosome territories.

Availability: NEMO is a stand-alone Java application available for Windows and Linux platforms. The program is distributed under the creative commons licence and can be freely downloaded from https://www-lgc.toulouse.inra.fr/nemo

Contact:  eddie.iannuccelli@toulouse.inra.fr
Random distance dependent attachment as a model for neural network generation in the Caenorhabditis elegans
Authors: Itzhack Royi , Louzoun Yoram
Published: January 2010

Motivation: The topology of the network induced by the neurons connectivity's in the Caenorhabditis elegans differs from most common random networks. The neurons positions of the C.elegans have been previously explained as being optimal to induce the required network wiring. We here propose a complementary explanation that the network wiring is the direct result of a local stochastic synapse formation process.

Results: We show that a model based on the physical distance between neurons can explain the C.elegans neural network structure, specifically, we demonstrate that a simple model based on a geometrical synapse formation probability and the inhibition of short coherent cycles can explain the properties of the C.elegans' neural network. We suggest this model as an initial framework to discuss neural network generation and as a first step toward the development of models for more advanced creatures. In order to measure the circle frequency in the network, a novel graph-theory circle length measurement algorithm is proposed.

Contact:  royi.its@gmail.com

Supplementary information:  Supplementary data are available at Bioinformatics online.
Next-generation bioinformatics: using many-core processor architecture to develop a web service for sequence alignment
Authors: Gálvez Sergio , Díaz David , Hernández Pilar , Esteban Francisco J. , Caballero Juan A. , Dorado Gabriel
Published: January 2010

Motivation: Bioinformatics algorithms and computing power are the main bottlenecks for analyzing huge amount of data generated by the current technologies, such as the ‘next-generation’ sequencing methodologies. At the same time, most powerful microprocessors are based on many-core chips, yet most applications cannot exploit such power, requiring parallelized algorithms. As an example of next-generation bioinformatics, we have developed from scratch a new parallelization of the Needleman–Wunsch (NW) sequence alignment algorithm for the 64-core Tile64 microprocessor. The unprecedented performance it offers for a standalone personal computer (PC) is discussed, optimally aligning sequences up to 20 times faster than the non-parallelized version, thus saving valuable time.

Availability: This algorithm is available as a free web service for the scientific community at http://www.sicuma.uma.es/multicore. The open source code is also available on such site.

Contact:  galvez@uma.es

Supplementary information: Supplementary data are available here.
iDBPs: a web server for the identification of DNA binding proteins
Authors: Nimrod Guy , Schushan Maya , Szilágyi András , Leslie Christina , Ben-Tal Nir
Published: January 2010

Summary: The iDBPs server uses the three-dimensional (3D) structure of a query protein to predict whether it binds DNA. First, the algorithm predicts the functional region of the protein based on its evolutionary profile; the assumption is that large clusters of conserved residues are good markers of functional regions. Next, various characteristics of the predicted functional region as well as global features of the protein are calculated, such as the average surface electrostatic potential, the dipole moment and cluster-based amino acid conservation patterns. Finally, a random forests classifier is used to predict whether the query protein is likely to bind DNA and to estimate the prediction confidence. We have trained and tested the classifier on various datasets and shown that it outperformed related methods. On a dataset that reflects the fraction of DNA binding proteins (DBPs) in a proteome, the area under the ROC curve was 0.90. The application of the server to an updated version of the N-Func database, which contains proteins of unknown function with solved 3D-structure, suggested new putative DBPs for experimental studies.

Availability:  http://idbps.tau.ac.il/

Contact:  NirB@tauex.tau.ac.il

Supplementary information:  Supplementary data are available at Bioinformatics online.
rMAT - an R/Bioconductor package for analyzing ChIP-chip experiments
Authors: Droit Arnaud , Cheung Charles , Gottardo Raphael
Published: January 2010

Summary: Chromatin immunoprecipitation combined with DNA microarrays (ChIP-chip) has evolved as a popular technique to study DNA–protein binding or post-translational chromatin/histone modifications at the genomic level. However, the raw microarray intensities generate a massive amount of data, creating a need for efficient analysis algorithms and statistical methods to identify enriched regions.

Results: We present a fast, free and powerful, open source R package, rMAT, that allows the identification of regions enriched for transcription factor binding sites in ChIP-chip experiments on Affymetrix tiling arrays.

Availability: The R-package rMAT is available from the Bioconductor web site at http://bioconductor.org and runs on Linux, MAC OS and MS-Windows. rMAT is distributed under the terms of the Artistic Licence 2.0.

Contact:  arnaud.droit@ircm.qc.ca; raphael.gottardo@ircm.qc.ca

Supplementary information:  Supplementary data are available at Bioinformatics online.
Multinational Corporations, Business Groups, and Economic Nationalism: Standard Oil (New Jersey), Royal Dutch-Shell, and Energy Politics in Chile 1913–2005
Authors: Bucheli Marcelo
Published: January 2010

This article analyzes the long-term strategies employed by multinational oil corporations in a late industrializing country with powerful business groups when faced with economic nationalism. I study the case of Royal Dutch-Shell in Chile from 1913 to 2005, where two oil multinationals controlled 100 percent of the Chilean market until forced by the government to accept a domestic private company, COPEC, into a new three-member cartel. The multinationals accepted this arrangement reluctantly, but in the long term it proved beneficial. COPEC's involvement in Chilean business groups protected the multinationals from hostile actions by the government and gave legitimacy to the cartel. These benefits ended when Chile abandoned its import substitution industrialization strategy in the 1970s.
Right ventricular dysfunction is an independent predictor for mortality in ST‐elevation myocardial infarction patients presenting with cardiogenic shock on admission
Authors: Engström Annemarie E. , Vis Marije M. , Bouma Berto J. , van den Brink Renée B.A. , Baan Jan , Claessen Bimmer E.P.M. , Kikkert Wouter J. , Sjauw Krischan D. , Meuwissen Martijn , Koch Karel T. , de Winter Robbert J. , Tijssen Jan G.P. , Piek Jan J. , Henriques José P.S.
Published: January 2010

Aims

Despite improvement in prognosis for ST‐elevation myocardial infarction (STEMI) patients, mortality remains high in STEMI patients presenting with cardiogenic shock (CS). Right ventricular (RV) dysfunction is an established independent predictor for adverse prognosis in STEMI patients without CS. The purpose of our study was to determine the prognostic value of RV dysfunction on admission in STEMI patients presenting in CS.

Methods and results

Two hundred and ninety‐two consecutive STEMI patients with CS on admission were treated by primary percutaneous coronary intervention (PCI) from January 1997 through March 2005. RV function was assessed by measurement of tricuspid annular plane systolic excursion (TAPSE) on early echocardiography in 184 of 292 patients. Right ventricular dysfunction was defined as a TAPSE of ≤14 mm. Right ventricular dysfunction was present on early echocardiography in 70 of 184 patients (38%). The Kaplan–Meier estimate for overall 4‐year survival was 57%. Kaplan–Meier estimates for 4‐year survival in patients with and without RV dysfunction were 33 and 73%, respectively (P< 0.001). Cox‐regression analysis revealed a hazard ratio of 2.1 (95% CI 1.3–3.4, P = 0.002) for RV dysfunction when adjusted for age, glucose on admission, and LVEF < 40%. In patients with and without RV dysfunction, the right coronary artery was the infarct‐related artery in 41 and 28% of patients, respectively (P = 0.06).

Conclusion

In STEMI patients presenting with CS on admission and treated with primary PCI, RV dysfunction as assessed by echocardiography is an independent predictor for long‐term mortality.
Getting a Better Grip on Research: The Organizational Dimension
Authors: Greenhalgh Trisha , Macfarlane Fraser , Maskrey Neal
Published: January 2010

This is the fourth paper in a series of five describing the use of evidence to support decisions made in clinical practice. The series covers large elements of statement 2: The general practice consultation, statement 3.5: Evidence-based practice of the GP curriculum.
Effects of Permissive Hypercapnia on Transient Global Cerebral Ischemia–Reperfusion Injury in Rats
Authors: Zhou Qiang , Cao Bo , Niu Li , Cui Xiaoguang , Yu Hongwei , Liu Jinfeng , Li Haibo , Li Wenzhi
Published: January 2010

Background

Permissive hypercapnia is a widely practiced protective ventilatory strategy that has significant protective effects on several models of in vitro and in vivo neuronal injury. However, conclusive effects of permissive hypercapnia on cerebral ischemia are still unknown.

Methods

One hundred sixty male Wistar rats were divided into five groups: S group (control), ischemia-reperfusion (I/R) group, P1 group, P2 group, and P3 group. I/R was induced by bilateral occlusion of the common carotid arteries, combined with controlled hypotension for 15 min. In groups P1, P2, and P3, the rats inhaled carbon dioxide for 2 h during reperfusion to keep Paco2 within the ranges of 60-80 mmHg, 80-100 mmHg, and 100-120 mmHg, respectively. After 24 and 72 h, neurologic deficit scores, ultrastructural changes, apoptotic neurons, and brain wet-to-dry weight ratios were observed. Caspase-3 and aquaporin-4 protein expression and caspase-3 activity were analyzed.

Results

Compared with groups I/R and P3, groups P1 and P2 had better neurologic deficit scores and fewer ultrastructural histopathologic changes. I/R-induced cerebral apoptosis was also significantly reduced. The neuroprotective effect was significantly increased in the P2 group compared with the P1 group. There was a significant increase of brain water content and of aquaporin-4 levels in the P3 group.

Conclusions

Mild to moderate hypercapnia (Paco2 60-100 mmHg) is neuroprotective after transient global cerebral I/R injury. Such a protection might be associated with apoptosis-regulating proteins. In contrast, severe hypercapnia (Paco2 100-120 mmHg) increased brain injury, which may be caused by increased brain edema.
Use of a Novel Acellular Xenograft as a Patch for Aortic Annular Enlargement during Aortic Valve Replacement
Authors: Gerdisch Marc W. , Akinwande Akindolapo O. , Matheny Robert G.
Published: January 2010

A patient with a history of aortic valve endocarditis and surgical debridement presented with acute congestive heart failure because of severe aortic stenosis. During valve replacement surgery, an aortic annular enlargement was required to overcome a potential patient-prosthesis mismatch. We describe the use of a novel, bioresorbable, acellular xenograft for the enlargement patch. This material is expected to remodel into native patient tissue over time. This case offers an alternative implant for left heart reconstruction using a regenerative patch.
Novel Techniques in Mitral Repair Extended and Rotational Chordal Transfer
Authors: Elwatidy Ahmed M.
Published: January 2010

Mitral valve repair is preferable to mitral valve replacement because of low rate of thromboembolism, resistance to endocarditis, excellent late durability, and no need for anticoagulation in the majority of patients. This article describes 2 novel techniques for repairing the anterior mitral leaflet prolapse. The extended chordal transfer is achieved by transferring an extended segment of posterior mitral leaflet and, rotational chordal transfer, by rotating the transferred segment either vertical or horizontal. Both techniques are simple and reproducible. It uses patient's own natural chorda and eliminates the problem of knotting and determination of appropriate chordal length faced with other techniques.
Impact of Subxiphoid Video Pericardioscopy with a Rigid Shaft on Cardiac Hemodynamics in a Porcine Model
Authors: Yokota Takenori , Ota Takeyoshi , Schwartzman David , Zenati Marco A.
Published: January 2010

Objective

Single-port subxiphoid videopericardioscopy with a rigid shaft is useful for left atrial exclusion, left ventricular (LV) pacing lead implantation, and epicardial mapping, but it may interfere with the cardiac rhythm and adversely alter hemodynamics. We examined the impact of this technique on hemodynamic indices in a porcine model.

Methods

The videopericardioscopy device was introduced into the pericardial space of five pigs (35–45 kg) via a subxiphoid approach and navigated to six anatomic targets [right atrial appendage, superior vena cava, ascending aorta, left atrial appendage (anterior and posterior approaches), transverse sinus, and atrioventricular (AV) groove]. After successful target acquisition, the device was withdrawn through the subxiphoid port. When the hemodynamics stabilized, the device was navigated to another target. The heart rate (HR), arterial blood pressure (BP), central venous pressure (CVP), pulmonary arterial pressure, and mixed venous oxygen saturation (SvO2) were measured at every pretarget (subxiphoid incision) and target point. After the navigation trials, the animals were killed and the mediastinum space was examined for procedure-related injuries.

Results

The device afforded a good view, and the navigation trials were successfully performed on the beating heart. Four animals tolerated the procedures, whereas one died of device-induced ventricular fibrillation after the trials. Hemodynamics was severely compromised at all anatomic targets except the left atrial appendage (anterior approach).

Conclusions

Subxiphoid videopericardioscopy significantly interferes with the cardiac rhythm, causing life-threatening arrhythmia and hemodynamic compromise, when the target is located deep and far from the pericardiotomy. A flexible or highly articulated device would enable intrapericardial navigation without hemodynamic compromise.
Minimally Invasive Direct Coronary Artery Bypass as a Primary Strategy for Reoperative Myocardial Revascularization
Authors: Balacumaraswami Lognathen , Patel Nirav C. , Gorki Hagen , Jennings Joan , Plestis Konstadinos A. , Subramanian Valavanur A.
Published: January 2010

Objective

Conventional reoperative coronary artery bypass grafting is associated with risk of sternal re-entry, injury to patent grafts, and embolization from diseased grafts. Sternal sparing minimally invasive direct coronary artery bypass (MIDCAB) avoids such risks in cases where it is technically feasible. We sought to examine in-hospital outcomes of reoperative MIDCAB surgery.

Methods

We recorded prospective standardized data from the New York Cardiac Surgical Reporting System database of 369 reoperative MIDCAB cases from 1996 to 2006 and compared with 822 primary MIDCAB patients in the same time period. We compared the preoperative risk profile and postoperative in-hospital outcomes and length of stay for both groups.

Results

There was a significantly higher risk profile typical of the reoperative patient population (P < 0.001 for stroke, peripheral/cerebrovascular disease, extensive aortic calcification, renal failure, and left ventricular ejection fraction <40%) compared with the primary MIDCAB group. Despite this fact, there was no difference in the in-hospital outcomes and length of hospital stay between the two groups.

Conclusions

Reoperative MIDCAB provides targeted coronary revascularization and avoids hazards of sternal re-entry, graft injury and manipulation, and deleterious effects of cardiopulmonary bypass. This hastens recovery and provides excellent early outcomes equivalent to primary MIDCAB procedures.
Cerebral Emboli Generation during Off-Pump Coronary Artery Bypass Grafting with a Clampless Device versus Partial Clamping of the Ascending Aorta
Authors: Eldaif Shady M. , Thourani Vinod H. , Puskas John D.
Published: January 2010

Objective

It is not known whether use of a clampless facilitating device during proximal graft anastamosis decreases intraoperative cerebral emboli in patients with mild atherosclerotic ascending aorta (AAA) having off-pump coronary artery bypass.

Methods

After intraoperative epiaortic ultrasound showed no more than mild (grade I–II) atherosclerotic ascending aorta, 20 patients were randomized to receive either partial clamping (PC, n = 10) or the HEARTSTRING clampless device (HS, n = 9) for proximal graft construction on the ascending aorta. Continuous transcranial Doppler monitoring, with capability to discern gaseous from solid particulates, was used intraoperatively to monitor high-intensity transient signals (HITS) in the middle cerebral arteries. Postoperative diffusion-weighted brain magnetic resonance imaging documented old and new ischemic brain lesions.

Results

There were no significant differences between the groups in the number of proximals (P = 0.14), distals (P = 0.4), or intraoperative cell saver transfusions (P = 0.69). The total number of HITS was not significantly different between the PC and HS groups (P = 0.2). However, the number of solid HITS was significantly lower in the HS than in the PC group (2.7 ± 2.6 versus 14.0 ± 8.1; P < 0.001). The number of gaseous emboli in the HS group was fourfold greater when a mister-blower rather than a suction device was used to clear blood away from the HS site. Postoperatively, there were no deaths, myocardial infarctions, or clinical strokes observed in either group. Diffusion-weighted cerebral magnetic resonance imaging revealed no statistical difference between groups for new infarct lesions.

Conclusions

Use of the HS device during off-pump coronary artery bypass was associated with significantly fewer intraoperative solid emboli in the middle cerebral artery than PC of the ascending aorta.