CiteULike: Author Andrews

Otogenic pneumocephalus.

JC Andrews — 2008-07-24T03:15:44-00:00

The Laryngoscope, Vol. 96, No. 5. (May 1986), pp. 521-528.

Fifty-four previously reported cases of otogenic pneumocephalus were analyzed in addition to five new cases which are presented in detail. Forty-one males and 18 females were included with 95% of the patients being over 12 years of age. The most common presenting symptom was headache, and the ventricular system was the intracranial space most commonly involved. Tension pneumocephalus was present in 40 (66%) cases. Trauma (36%) was the most common etiologic factor, while otitis media (30%), otologic surgery (30%), and congenital defects (2%) accounted for the rest. The overall mortality was 12% with all patients succumbing to causes other than pneumocephalus. Because of its lack of specific symptoms, pneumocephalus was usually unsuspected and the diagnosis made only after radiographic evaluation. Despite its rarity, pneumocephalus has to be considered whenever the dura is violated, especially if associated with a CSF leak. Management depends on the degree of tension, symptomatology, and underlying cause. When associated with trauma or surgery, bedrest and close monitoring may suffice, although needle aspiration or re-exploration may be needed. When secondary to otitis media or a congenital defect, control of any infection and repair of the defect are mandatory.

Global Mapping of DNA Methylation in Mouse Promoters Reveals Epigenetic Reprogramming of Pluripotency Genes

Cassandra Farthing — 2008-06-27T18:47:56-00:00

PLoS Genet, Vol. 4, No. 6. (27 June 2008), e1000116.

DNA methylation patterns are reprogrammed in primordial germ cells and in preimplantation embryos by demethylation and subsequent de novo methylation. It has been suggested that epigenetic reprogramming may be necessary for the embryonic genome to return to a pluripotent state. We have carried out a genome-wide promoter analysis of DNA methylation in mouse embryonic stem (ES) cells, embryonic germ (EG) cells, sperm, trophoblast stem (TS) cells, and primary embryonic fibroblasts (pMEFs). Global clustering analysis shows that methylation patterns of ES cells, EG cells, and sperm are surprisingly similar, suggesting that while the sperm is a highly specialized cell type, its promoter epigenome is already largely reprogrammed and resembles a pluripotent state. Comparisons between pluripotent tissues and pMEFs reveal that a number of pluripotency related genes, including Nanog, Lefty1 and Tdgf1, as well as the nucleosome remodeller Smarcd1, are hypomethylated in stem cells and hypermethylated in differentiated cells. Differences in promoter methylation are associated with significant differences in transcription levels in more than 60% of genes analysed. Our comparative approach to promoter methylation thus identifies gene candidates for the regulation of pluripotency and epigenetic reprogramming. While the sperm genome is, overall, similarly methylated to that of ES and EG cells, there are some key exceptions, including Nanog and Lefty1, that are highly methylated in sperm. Nanog promoter methylation is erased by active and passive demethylation after fertilisation before expression commences in the morula. In ES cells the normally active Nanog promoter is silenced when targeted by de novo methylation. Our study suggests that reprogramming of promoter methylation is one of the key determinants of the epigenetic regulation of pluripotency genes. Epigenetic reprogramming in the germline prior to fertilisation and the reprogramming of key pluripotency genes in the early embryo is thus crucial for transmission of pluripotency.

A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice

Naoko Shima — 2006-12-28T00:50:00-00:00

Nature Genetics, Vol. 39, No. 1. (03 December 2006), pp. 93-98.

Simulated diffusion of phosphorylated CheY through the cytoplasm of Escherichia coli.

K Lipkow — 2007-04-26T19:28:39-00:00

J Bacteriol, Vol. 187, No. 1. (January 2005), pp. 45-53.

We describe the use of a computational model to study the effects of cellular architecture and macromolecular crowding on signal transduction in Escherichia coli chemotaxis. A newly developed program, Smoldyn, allows the movement and interaction of a large number of individual molecules in a structured environment to be simulated (S. S. Andrews and D. Bray, Phys. Biol., in press). With Smoldyn, we constructed a three-dimensional model of an E. coli cell and examined the diffusion of CheYp from the cluster of receptors to the flagellar motors under control conditions and in response to attractant and repellent stimuli. Our simulations agree well with experimental observations of cell swimming responses and are consistent with the diffusive behavior expected in wild-type and mutant cells. The high resolution available to us in the new program allows us to calculate the loci of individual CheYp molecules in a cell and the distribution of their lifetimes under different cellular conditions. We find that the time delay between stimulus and response differs for flagellar motors located at different positions in the cell. We explore different possible locations for the phosphatase CheZ and show conditions under which a gradient of CheYp exists in the cell. The introduction of inert blocks into the cytoplasm, representing impenetrable structures such as the nucleoid and large protein complexes, produces a fall in the apparent diffusion coefficient of CheYp and enhances the differences between motors. These and other results are left as predictions for future experiments.

Stochastic simulation of chemical reactions with spatial resolution and single molecule detail.

SS Andrews — 2007-05-13T15:51:46-00:00

Phys Biol, Vol. 1, No. 3-4. (December 2004), pp. 137-151.

Methods are presented for simulating chemical reaction networks with a spatial resolution that is accurate to nearly the size scale of individual molecules. Using an intuitive picture of chemical reaction systems, each molecule is treated as a point-like particle that diffuses freely in three-dimensional space. When a pair of reactive molecules collide, such as an enzyme and its substrate, a reaction occurs and the simulated reactants are replaced by products. Achieving accurate bimolecular reaction kinetics is surprisingly difficult, requiring a careful consideration of reaction processes that are often overlooked. This includes whether the rate of a reaction is at steady-state and the probability that multiple reaction products collide with each other to yield a back reaction. Inputs to the simulation are experimental reaction rates, diffusion coefficients and the simulation time step. From these are calculated the simulation parameters, including the 'binding radius' and the 'unbinding radius', where the former defines the separation for a molecular collision and the latter is the initial separation between a pair of reaction products. Analytic solutions are presented for some simulation parameters while others are calculated using look-up tables. Capabilities of these methods are demonstrated with simulations of a simple bimolecular reaction and the Lotka-Volterra system.

Structure/function analysis of the phosphatidylinositol-3-kinase domain of yeast tra1.

AI Mutiu — 2008-07-19T18:24:27-00:00

Genetics, Vol. 177, No. 1. (September 2007), pp. 151-166.

Tra1 is an essential component of the Saccharomyces cerevisiae SAGA and NuA4 complexes. Using targeted mutagenesis, we identified residues within its C-terminal phosphatidylinositol-3-kinase (PI3K) domain that are required for function. The phenotypes of tra1-P3408A, S3463A, and SRR3413-3415AAA included temperature sensitivity and reduced growth in media containing 6% ethanol or calcofluor white or depleted of phosphate. These alleles resulted in a twofold or greater change in expression of approximately 7% of yeast genes in rich media and reduced activation of PHO5 and ADH2 promoters. Tra1-SRR3413 associated with components of both the NuA4 and SAGA complexes and with the Gal4 transcriptional activation domain similar to wild-type protein. Tra1-SRR3413 was recruited to the PHO5 promoter in vivo but gave rise to decreased relative amounts of acetylated histone H3 and histone H4 at SAGA and NuA4 regulated promoters. Distinct from other components of these complexes, tra1-SRR3413 resulted in generation-dependent telomere shortening and synthetic slow growth in combination with deletions of a number of genes with roles in membrane-related processes. While the tra1 alleles have some phenotypic similarities with deletions of SAGA and NuA4 components, their distinct nature may arise from the simultaneous alteration of SAGA and NuA4 functions.

Intellectual property. Patents on human genes: an analysis of scope and claims.

J Paradise — 2005-04-29T19:48:07-00:00

Science, Vol. 307, No. 5715. (11 March 2005), pp. 1566-1567.

GroupBar: The TaskBar Evolved

G Smith — 2008-07-17T12:30:44-00:00

(2003)

Our studies have shown that as displays become larger, users leave more windows open for easy multitasking. A larger number of windows, however, may increase the time that users spend arranging and switching between tasks. We introduce GroupBar, a task management system for dealing with the profusion of windows on the PC desktop. Designed to offer the same basic form and function as the existing Microsoft Windows^TM TaskBar, GroupBar additionally allows users to group windows into higher-level...

New Directions in Cognitive Information Retrieval. Edited by Amanda Spink and Charles Cole. Netherlands: Springer, 2005. 250 pp. $99.00. ISBN: 1-4020-4013-X (hardcover) (The Information Retrieval Series, v. 19).

James Andrews — 2008-07-17T10:00:01-00:00

Library & Information Science Research, Vol. 29, No. 1. (March 2007), pp. 146-147.

Introduction to Mathematical Logic and Type Theory (Computer Science & Applied Mathematics)

Peter Andrews — 2008-07-17T04:54:56-00:00

This introduction to mathematical logic starts with propositional calculus and first-order logic. Topics covered include syntax, semantics, soundness, completeness, independence, normal forms, vertical paths through negation normal formulas, compactness, Smullyan's Unifying Principle, natural deduction, cut-elimination, semantic tableaux, Skolemization, Herbrand's Theorem, unification, duality, interpolation, and definability. The last three chapters of the book provide an introduction to type theory (higher-order logic). It is shown how various mathematical concepts can be formalized in this very expressive formal language. This expressive notation facilitates proofs of the classical incompleteness and undecidability theorems which are very elegant and easy to understand. The discussion of semantics makes clear the important distinction between standard and nonstandard models which is so important in understanding puzzling phenomena such as the incompleteness theorems and Skolem's Paradox about countable models of set theory. Some of the numerous exercises require giving formal proofs. A computer program called ETPS which is available from the web facilitates doing and checking such exercises. _Audience:_ This volume will be of interest to mathematicians, computer scientists, and philosophers in universities, as well as to computer scientists in industry who wish to use higher-order logic for hardware and software specification and verification.

Indexing consistency in Information Science Abstracts

Maryellen Sievert — 2008-07-15T18:57:18-00:00

Journal of the American Society for Information Science, Vol. 42, No. 1. (1991), pp. 1-6.

Duplicate entries in Information Science Abstracts allowed for a study of the consistency of the indexing of this file. The results showed a bipolar distribution: indexing matched completely almost half of the time and did not match at all almost half of the time. The indexing policies of ISA require one mainheading and one or two subheadings per document. This restriction in the number of terms and the fact that ISA has a very small vocabulary from which to draw these terms may be the reason for this bipolar distribution. The indexing consistency was highest for the descriptors, drawn from a small controlled vocabulary, and lowest for identifiers, drawn from natural language or the controlled vocabulary. The data suggested that as the number of terms assigned per article increased indexing consistency decreased. © 1991 John Wiley & Sons, Inc.

Global analysis of protein phosphorylation in yeast

Jason Ptacek — 2005-11-30T19:42:56-00:00

Nature, Vol. 438, No. 7068., pp. 679-684.

The landscape of histone modifications across 1% of the human genome in five human cell lines

Christoph Koch — 2007-06-13T23:52:52-00:00

Genome Res., Vol. 17, No. 6. (1 June 2007), pp. 691-707.

We generated high-resolution maps of histone H3 lysine 9/14 acetylation (H3ac), histone H4 lysine 5/8/12/16 acetylation (H4ac), and histone H3 at lysine 4 mono-, di-, and trimethylation (H3K4me1, H3K4me2, H3K4me3, respectively) across the ENCODE regions. Studying each modification in five human cell lines including the ENCODE Consortium common cell lines GM06990 (lymphoblastoid) and HeLa-S3, as well as K562, HFL-1, and MOLT4, we identified clear patterns of histone modification profiles with respect to genomic features. H3K4me3, H3K4me2, and H3ac modifications are tightly associated with the transcriptional start sites (TSSs) of genes, while H3K4me1 and H4ac have more widespread distributions. TSSs reveal characteristic patterns of both types of modification present and the position relative to TSSs. These patterns differ between active and inactive genes and in particular the state of H3K4me3 and H3ac modifications is highly predictive of gene activity. Away from TSSs, modification sites are enriched in H3K4me1 and relatively depleted in H3K4me3 and H3ac. Comparison between cell lines identified differences in the histone modification profiles associated with transcriptional differences between the cell lines. These results provide an overview of the functional relationship among histone modifications and gene expression in human cells. 10.1101/gr.5704207

Separating cognitive capacity from knowledge: a new hypothesis.

GS Halford — 2008-07-11T15:06:17-00:00

Trends in cognitive sciences, Vol. 11, No. 6. (June 2007), pp. 236-242.

We propose that working memory and reasoning share related capacity limits. These limits are quantified in terms of the number of items that can be kept active in working memory, and the number of interrelationships between elements that can be kept active in reasoning. The latter defines the complexity of reasoning problems and the processing loads they impose. Principled procedures for measuring, controlling or limiting recoding and other strategies for reducing memory and processing loads have opened up new research opportunities, and yielded orderly quantification of capacity limits in both memory and reasoning. We argue that both types of limit might be based on the limited ability to form and preserve bindings between elements in memory.

Pax6 Regulates the Identity of Embryonic Diencephalic Neurons

Grant Mastick — 2008-07-09T20:06:53-00:00

Molecular and Cellular Neuroscience, Vol. 17, No. 1. (January 2001), pp. 190-207.

The transcription factor Pax6 is expressed in discrete domains in the developing brain, generally limited to progenitor populations. However, in the embryonic mouse diencephalon, Pax6 is not only expressed in neuroepithelial progenitors, but also at high levels in a specific set of initial neurons. These neurons first appeared on embryonic day 9.5 (E9.5) in the presumptive ventral thalamus and were fated to become A13 dopaminergic neurons of the medial zona incerta. To further characterize the initial differentiation of these neurons, and the function of Pax6 in their formation, the expression patterns of a number of transcription factors were described. The progenitor population was defined by reciprocal overlapping expression gradients of Pax6 and Nkx2.2, and a subset of proliferating progenitors were labeled with an antibody against DLX transcription factors. The initial neurons expressed combinations of transcription factors, including Pax6, DLX, and the LIM-domain proteins islet-1, Lhx1 (Lim1), and Lhx5 (Lim-2). Bromo-deoxyuridine (BrdU) labeling was used to follow the fate of a cohort of proliferating cells, defining a step-wise sequence of gene activation during differentiation. Pax6 up-regulation occurred only several hours postdifferentiation. The loss of Pax6 altered progenitor specification, and the Lhx1 neuronal marker was lost, indicating a role for Pax6 in the specification of forebrain neuron identity.

Global Mapping of the Yeast Genetic Interaction Network

Amy Tong — 2005-02-21T20:30:21-00:00

Science, Vol. 303, No. 5659. (06 February 2004), pp. 808-813.

A genetic interaction network containing [~]1000 genes and [~]4000 interactions was mapped by crossing mutations in 132 different query genes into a set of [~]4700 viable gene yeast deletion mutants and scoring the double mutant progeny for fitness defects. Network connectivity was predictive of function because interactions often occurred among functionally related genes, and similar patterns of interactions tended to identify components of the same pathway. The genetic network exhibited dense local neighborhoods; therefore, the position of a gene on a partially mapped network is predictive of other genetic interactions. Because digenic interactions are common in yeast, similar networks may underlie the complex genetics associated with inherited phenotypes in other organisms.

Bandwidth Partitioning in Decentralized Wireless Networks

Nihar Jindal — 2008-07-07T14:05:49-00:00

(2 Apr 2008)

This paper addresses the following question, which is of interest in the design of a multiuser decentralized network. Given a total system bandwidth of W Hz and a fixed data rate constraint of R bps for each transmission, how many frequency slots N of size W/N should the band be partitioned into in order to maximize the number of simultaneous links in the network? Dividing the available spectrum results in two competing effects. On the positive side, a larger N allows for more parallel, noninterfering communications to take place in the same area. On the negative side, a larger N increases the SINR requirement for each link because the same information rate must be achieved over less bandwidth. Exploring this tradeoff and determining the optimum value of N in terms of the system parameters is the focus of the paper. Using stochastic geometry, the optimal SINR threshold - which directly corresponds to the optimal spectral efficiency - is derived for both the low SNR (power-limited) and high SNR (interference-limited) regimes. This leads to the optimum choice of the number of frequency bands N in terms of the path loss exponent, power and noise spectral density, desired rate, and total bandwidth.

The Political Economy of Hope and Fear: Capitalism and the Black Condition in America

Marcellus Andrews — 2008-07-06T06:55:06-00:00

(31 May 1999)

"Andrews does a superb job in offering solutions to familiar problems for African Americans. Complete with charts, graphs, facts and figures, the author provides readers with a vivid display of how the scales of equality, wealth and power are tipped against people of color." --Upscale "Andrews' aim is to paint an intellectually defensible and decidedly anti- conservative picture of the complicated tie between race and economic wellbeing." --Booklist "Fiery, passionate, and provocative, but also unflinchingly rigorous in its argument. It is rare for an economist to write with such fire bolstered by such a commitment to logical reasoning." --William A. Darity, Jr "Marcellus Andrews has written a fascinating and theoretically grounded account of the relationship between America's market economy and the prospects faced by African Americans."—_The Journal of Economic Issues_ Popular liberal writing on race has relied on appeals to the value of "diversity" and the fading memory of the Civil Rights movement to counter the aggressive conservative assault on liberal racial reform generally, and on black well-being, in particular. Yet appeals to fairness and justice, no matter how heartfelt, are bound to fail, Marcellus Andrews argues, since the economic foundations of the Civil Rights movement have been destroyed by the combined forces of globalization, technology, and tight government budgets. **The Political Economy of Hope and Fear** fills an important intellectual gap in writing on race by developing a hard-nosed economic analysis of the links between competitive capitalism, racial hostility, and persistent racial inequality in post-Civil Rights America. Andrews speaks to the anger and frustration that blacks feel in the face of the nation's abandonment of racial equality as a worthy objective by showing how the considerable difficulties that black Americans face are related to fundamental changes in the economic fortunes of the U.S. **The Political Economy of Hope and Fear** is an economist's plea for unsentimental thinking on matters of race to replace the mixture of liberal hand wringing and conservative mythmaking that currently passes for serious analysis about the nation's racial predicament.

Protein purification using chromatography: selection of type, modelling and optimization of operating conditions.

J A Asenjo — 2008-07-03T08:28:49-00:00

Journal of molecular recognition : JMR (10 June 2008)

To achieve a high level of purity in the purification of recombinant proteins for therapeutic or analytical application, it is necessary to use several chromatographic steps. There is a range of techniques available including anion and cation exchange, which can be carried out at different pHs, hydrophobic interaction chromatography, gel filtration and affinity chromatography. In the case of a complex mixture of partially unknown proteins or a clarified cell extract, there are many different routes one can take in order to choose the minimum and most efficient number of purification steps to achieve a desired level of purity (e.g. 98%, 99.5% or 99.9%).This review shows how an initial 'proteomic' characterization of the complex mixture of target protein and protein contaminants can be used to select the most efficient chromatographic separation steps in order to achieve a specific level of purity with a minimum number of steps. The chosen methodology was implemented in a computer- based Expert System. Two algorithms were developed, the first algorithm was used to select the most efficient purification method to separate a protein from its contaminants based on the physicochemical properties of the protein product and the protein contaminants and the second algorithm was used to predict the number and concentration of contaminants after each separation as well as protein product purity.The application of the Expert System approach was experimentally tested and validated with a mixture of four proteins and the experimental validation was also carried out with a supernatant of Bacillus subtilis producing a recombinant beta-1,3-glucanase.Once the type of chromatography is chosen, optimization of the operating conditions is essential. Chromatographic elution curves for a three-protein mixture (alpha-lactoalbumin, ovalbumin and beta-lactoglobulin), carried out under different flow rates and ionic strength conditions, were simulated using two different mathematical models. These models were the Plate Model and the more fundamentally based Rate Model. Simulated elution curves were compared with experimental data not used for parameter identification. Deviation between experimental data and the simulated curves using the Plate Model was less than 0.0189 (absorbance units); a slightly higher deviation [0.0252 (absorbance units)] was obtained when the Rate Model was used. In order to optimize operating conditions, a cost function was built that included the effect of the different production stages, namely fermentation, purification and concentration. This cost function was also successfully used for the determination of the fraction of product to be collected (peak cutting) in chromatography. It can be used for protein products with different characteristics and qualities, such as purity and yield, by choosing the appropriate parameters. Copyright (c) 2008 John Wiley & Sons, Ltd.

Organic antigen-induced interstitial lung disease: diagnosis and management.

RL Jacobs — 2008-07-03T05:29:58-00:00

Annals of allergy, asthma & immunology : official publication of the American College of Allergy, Asthma, & Immunology, Vol. 88, No. 1. (January 2002), pp. 30-41.

BACKGROUND: Traditionally, chronic idiopathic interstitial pneumonia/fibrosis (IIP/F) had included usual interstitial pneumonia, desquamative interstitial pneumonia, and nonspecific interstitial pneumonia (NSIP). More recent classifications have included bronchiolitis obliterans-organizing pneumonia (BOOP), respiratory bronchiolitis-associated interstitial lung disease, and acute interstitial pneumonia. Some chronic eosinophilic pneumonias (CEP)/pulmonary infiltrate with eosinophilia (PIE) have obvious causes, but many lack an identifiable etiology. We felt that hypersensitivity pneumonitis (HP) was being underdiagnosed and was hidden within this large heterogeneous group of interstitial lung disorders of unrecognized cause. OBJECTIVE: We sought to prove that detailed environmental histories and investigations would reveal causative contaminations in the home or workplace of some patients with idiopathic interstitial lung disease and remediation of the contamination would stabilize the disorder. METHODS: Consecutive cases of IIP/F were investigated. Patients were identified by compatible signs and symptoms, roentgenographic studies, pulmonary function tests, and lung biopsies. They were further evaluated with detailed environmental histories, serologic tests, and investigation into the suspected causative environment. Environmental and specific antigen challenges were done in some cases. Remediation of contaminations or moving into another environment were the methods used as therapy. RESULTS: Eighty-six consecutive patients with IIP/F were evaluated. Twelve patients were subsequently diagnosed with specific causes for interstitial lung disease. Fifty-seven of 74 patients were identified by clinical evaluation and lung biopsy with HP, CEP/PIE, NSIP, BOOP, UIP, and nonclassifiable morphologic patterns. Seventeen patients were not biopsied or had an inadequate transbronchial biopsy but had consistent findings radiographically and clinically of idiopathic interstitial lung disease. Contamination of the home was causative in 69 of 74 and the workplace in 3 of 74 cases. There were 9 positive and 33 negative environmental challenges with 4 positive and 1 negative specific challenges. Fifty of 74 (67%) patients are receiving no treatment and are free of active disease after remediation of the environmental contamination, with a mean survival of 8.2 years. CONCLUSIONS: Our data show that UIP, BOOP, NSIP, CEP/PIE, and nonclassifiable morphologic patterns represent a spectrum of interstitial lung disease that may be caused by inhalation of organic dusts in the home or workplace as described with HP. Remediation of, or moving from the contamination, can lead to arrest of the active inflammatory process and stability of the lung disorder.

Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.

AJ Moss — 2008-05-30T07:54:39-00:00

The New England journal of medicine, Vol. 346, No. 12. (21 March 2002), pp. 877-883.

BACKGROUND: Patients with reduced left ventricular function after myocardial infarction are at risk for life-threatening ventricular arrhythmias. This randomized trial was designed to evaluate the effect of an implantable defibrillator on survival in such patients. METHODS: Over the course of four years, we enrolled 1232 patients with a prior myocardial infarction and a left ventricular ejection fraction of 0.30 or less. Patients were randomly assigned in a 3:2 ratio to receive an implantable defibrillator (742 patients) or conventional medical therapy (490 patients). Invasive electrophysiological testing for risk stratification was not required. Death from any cause was the end point. RESULTS: The clinical characteristics at base line and the prevalence of medication use at the time of the last follow-up visit were similar in the two treatment groups. During an average follow-up of 20 months, the mortality rates were 19.8 percent in the conventional-therapy group and 14.2 percent in the defibrillator group. The hazard ratio for the risk of death from any cause in the defibrillator group as compared with the conventional-therapy group was 0.69 (95 percent confidence interval, 0.51 to 0.93; P=0.016). The effect of defibrillator therapy on survival was similar in subgroup analyses stratified according to age, sex, ejection fraction, New York Heart Association class, and the QRS interval. CONCLUSIONS: In patients with a prior myocardial infarction and advanced left ventricular dysfunction, prophylactic implantation of a defibrillator improves survival and should be considered as a recommended therapy.

Combining biological networks to predict genetic interactions.

SL Wong — 2005-02-27T22:54:06-00:00

Proc Natl Acad Sci U S A, Vol. 101, No. 44. (2 November 2004), pp. 15682-15687.

Genetic interactions define overlapping functions and compensatory pathways. In particular, synthetic sick or lethal (SSL) genetic interactions are important for understanding how an organism tolerates random mutation, i.e., genetic robustness. Comprehensive identification of SSL relationships remains far from complete in any organism, because mapping these networks is highly labor intensive. The ability to predict SSL interactions, however, could efficiently guide further SSL discovery. Toward this end, we predicted pairs of SSL genes in Saccharomyces cerevisiae by using probabilistic decision trees to integrate multiple types of data, including localization, mRNA expression, physical interaction, protein function, and characteristics of network topology. Experimental evidence demonstrated the reliability of this strategy, which, when extended to human SSL interactions, may prove valuable in discovering drug targets for cancer therapy and in identifying genes responsible for multigenic diseases.

Motifs, themes and thematic maps of an integrated Saccharomyces cerevisiae interaction network.

LV Zhang — 2005-08-29T23:42:08-00:00

J Biol, Vol. 4, No. 2. (2005)

BACKGROUND: Large-scale studies have revealed networks of various biological interaction types, such as protein-protein interaction, genetic interaction, transcriptional regulation, sequence homology, and expression correlation. Recurring patterns of interconnection, or 'network motifs', have revealed biological insights for networks containing either one or two types of interaction. RESULTS: To study more complex relationships involving multiple biological interaction types, we assembled an integrated Saccharomyces cerevisiae network in which nodes represent genes (or their protein products) and differently colored links represent the aforementioned five biological interaction types. We examined three- and four-node interconnection patterns containing multiple interaction types and found many enriched multi-color network motifs. Furthermore, we showed that most of the motifs form 'network themes' -- classes of higher-order recurring interconnection patterns that encompass multiple occurrences of network motifs. Network themes can be tied to specific biological phenomena and may represent more fundamental network design principles. Examples of network themes include a pair of protein complexes with many inter-complex genetic interactions -- the 'compensatory complexes' theme. Thematic maps -- networks rendered in terms of such themes -- can simplify an otherwise confusing tangle of biological relationships. We show this by mapping the S. cerevisiae network in terms of two specific network themes. CONCLUSION: Significantly enriched motifs in an integrated S. cerevisiae interaction network are often signatures of network themes, higher-order network structures that correspond to biological phenomena. Representing networks in terms of network themes provides a useful simplification of complex biological relationships.

Special Functions

George Andrews — 2005-03-08T18:02:51-00:00

(15 February 2001)

Special functions, which include the trigonometric functions, have been used for centuries. Their role in the solution of differential equations was exploited by Newton and Leibniz, and the subject of special functions has been in continuous development ever since. In just the past thirty years several new special functions and applications have been discovered. This treatise presents an overview of the area of special functions, focusing primarily on the hypergeometric functions and the associated hypergeometric series. It includes both important historical results and recent developments and shows how these arise from several areas of mathematics and mathematical physics. Particular emphasis is placed on formulas that can be used in computation. The book begins with a thorough treatment of the gamma and beta functions that are essential to understanding hypergeometric functions. Later chapters discuss Bessel functions, orthogonal polynomials and transformations, the Selberg integral and its applications, spherical harmonics, q-series, partitions, and Bailey chains. This clear, authoritative work will be a lasting reference for students and researchers in number theory, algebra, combinatorics, differential equations, applied mathematics, mathematical computing, and mathematical physics.

Global variation in copy number in the human genome

Richard Redon — 2006-11-22T18:14:00-00:00

Nature, Vol. 444, No. 7118. (23 November 2006), pp. 444-454.

Exploring genetic interactions and networks with yeast

Charles Boone — 2007-05-19T03:15:41-00:00

Nature Reviews Genetics, Vol. 8, No. 6., pp. 437-449.

Admissibility of the Likelihood Ratio Test When a Nuisance Parameter is Present Only Under the Alternative

Donald Andrews — 2008-06-30T15:12:50-00:00

The Annals of Statistics, Vol. 23, No. 5. (1995), pp. 1609-1629.

This paper establishes the asymptotic admissibility of the likelihood ratio (LR) test for a general class of testing problems in which a nuisance parameter is present only under the alternative hypothesis. The paper also establishes the finite sample admissibility of the LR test for testing problems of this sort that arise in Gaussian linear regression models with known variance.

Medium scale integration of molecular logic gates in an automaton.

J Macdonald — 2008-06-29T00:34:37-00:00

Nano letters, Vol. 6, No. 11. (November 2006), pp. 2598-2603.

The assembly of molecular automata that perform increasingly complex tasks, such as game playing, presents an unbiased test of molecular computation. We now report a second-generation deoxyribozyme-based automaton, MAYA-II, which plays a complete game of tic-tac-toe according to a perfect strategy. In silicon terminology, MAYA-II represents the first "medium-scale integrated molecular circuit", integrating 128 deoxyribozyme-based logic gates, 32 input DNA molecules, and 8 two-channel fluorescent outputs across 8 wells.

Remotely piloted vehicles in civil airspace: requirements and analysis methods for the traffic alert and collision avoidance system (TCAS) and see-and-avoid systems

AC Drumm — 2008-06-26T21:06:37-00:00

Digital Avionics Systems Conference, 2004. DASC 04. The 23rd, Vol. 2 (2004), pp. 12.D.1-121-14 Vol.2.

The integration of remotely piloted vehicles (RPVs) into civil airspace requires new methods of ensuring aircraft separation. This work discusses issues affecting requirements for RPV traffic avoidance systems and for performing the safety evaluations that are necessary to certify such systems. The paper outlines current ways in which traffic avoidance is assured depending on the type of airspace and type of traffic that is encountered. Alternative methods for RPVs to perform traffic avoidance are discussed, including the potential use of new see-and-avoid sensors or the traffic alert and collision avoidance system (TCAS). Finally, the paper outlines an established safety evaluation process that can be adapted to assure regulatory authorities that RPVs meet level of safety requirements.

Comprehensive curation and analysis of global interaction networks in Saccharomyces cerevisiae

Teresa Reguly — 2006-06-13T14:14:14-00:00

Journal of Biology, Vol. 5, No. 4. (08 June 2006), 11.

BACKGROUND:The study of complex biological networks and prediction of gene function has been enabled by high-throughput (HTP) methods for detection of genetic and protein interactions. Sparse coverage in HTP datasets may, however, distort network properties and confound predictions. Although a vast number of well substantiated interactions are recorded in the scientific literature, these data have not yet been distilled into networks that enable system-level inference.RESULTS:We describe here a comprehensive database of genetic and protein interactions, and associated experimental evidence, for the budding yeast Saccharomyces cerevisiae, as manually curated from over 31,793 abstracts and online publications. This literature-curated (LC) dataset contains 33,311 interactions, on the order of all extant HTP datasets combined. Surprisingly, HTP protein-interaction datasets currently achieve only around 14% coverage of the interactions in the literature. The LC network nevertheless shares attributes with HTP networks, including scale-free connectivity and correlations between interactions, abundance, localization, and expression. We find that essential genes or proteins are enriched for interactions with other essential genes or proteins, suggesting that the global network may be functionally unified. This interconnectivity is supported by a substantial overlap of protein and genetic interactions in the LC dataset. We show that the LC dataset considerably improves the predictive power of network-analysis approaches. The full LC dataset is available at the BioGRID (http://www.thebiogrid.org) and SGD (http://www.yeastgenome.org/) databases.CONCLUSION:Comprehensive datasets of biological interactions derived from the primary literature provide critical benchmarks for HTP methods, augment functional prediction, and reveal system-level attributes of biological networks.

Output Coupler for Bose-Einstein Condensed Atoms

MO Mewes — 2008-06-26T16:28:47-00:00

Physical Review Letters, Vol. 78, No. 4. (27 January 1997), 582.

A machine-learning approach to combined evidence validation of genome assemblies

Jeong-Hyeon Choi — 2008-03-13T19:52:49-00:00

Bioinformatics, Vol. 24, No. 6. (15 March 2008), pp. 744-750.

Motivation: While it is common to refer to the genome sequence' as if it were a single, complete and contiguous DNA string, it is in fact an assembly of millions of small, partially overlapping DNA fragments. Sophisticated computer algorithms (assemblers and scaffolders) merge these DNA fragments into contigs, and place these contigs into sequence scaffolds using the paired-end sequences derived from large-insert DNA libraries. Each step in this automated process is susceptible to producing errors; hence, the resulting draft assembly represents (in practice) only a likely assembly that requires further validation. Knowing which parts of the draft assembly are likely free of errors is critical if researchers are to draw reliable conclusions from the assembled sequence data. Results: We develop a machine-learning method to detect assembly errors in sequence assemblies. Several in silico measures for assembly validation have been proposed by various researchers. Using three benchmarking Drosophila draft genomes, we evaluate these techniques along with some new measures that we propose, including the good-minus-bad coverage (GMB), the good-to-bad-ratio (RGB), the average Z-score (AZ) and the average absolute Z-score (ASZ). Our results show that the GMB measure performs better than the others in both its sensitivity and its specificity for assembly error detection. Nevertheless, no single method performs sufficiently well to reliably detect genomic regions requiring attention for further experimental verification. To utilize the advantages of all these measures, we develop a novel machine learning approach that combines these individual measures to achieve a higher prediction accuracy (i.e. greater than 90%). Our combined evidence approach avoids the difficult and often ad hoc selection of many parameters the individual measures require, and significantly improves the overall precisions on the benchmarking data sets. Availability: http://people.cgb.indiana.edu/jeochoi/gav/ Contact: jeochoi@indiana.edu Supplementary information: Supplementary data are available at Bioinformatics online. 10.1093/bioinformatics/btm608

An interdisciplinary perspective on artificial immune systems

J Timmis — 2008-04-09T18:21:39-00:00

Evolutionary Intelligence, Vol. 1, No. 1. (19 March 2008), pp. 5-26.

Abstract This review paper attempts to position the area of Artificial Immune Systems (AIS) in a broader context of interdisciplinary research. We review AIS based on an established conceptual framework that encapsulates mathematical and computational modelling of immunology, abstraction and then development of engineered systems. We argue that AIS are much more than engineered systems inspired by the immune system and that there is a great deal for both immunology and engineering to learn from each other through working in an interdisciplinary manner.

Ventricular arrhythmia storms in postinfarction patients with implantable defibrillators for primary prevention indications: a MADIT-II substudy.

HW Sesselberg — 2008-06-23T13:02:33-00:00

Heart rhythm : the official journal of the Heart Rhythm Society, Vol. 4, No. 11. (November 2007), pp. 1395-1402.

BACKGROUND: Much of prognostic implications of ventricular arrhythmia storms remain unclear. OBJECTIVE: We evaluated the risk associated with electrical storm in patients with defibrillators in the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) study. METHODS: Electrical storm was defined as > or =3 episodes of ventricular tachycardia (VT) or ventricular fibrillation (VF) in 24 hours. RESULTS: Of the 719 patients who received internal cardiac defibrillator (ICD) implants and had follow-up in the MADIT-II, 27 patients (4%) had electrical storm, 142 (20%) had isolated episodes of VT/VF, and the remaining 550 patients had no ICD-recorded VT events. Baseline clinical characteristics among the groups were similar. Patients who experienced electrical storm had a significantly higher risk of death. After adjustments for relevant clinical covariates, the hazard ratio (HR) for death in the first 3 months after the storm event was 17.8 (95% confidence interval [CI] 8.0 to 39.5, P <.01) in comparison with those with no VT/VF. This risk continued even after 3 months for those with electrical storm (HR of 3.5, 95% CI 1.2 to 9.8, P = .02). Study patients with isolated VT/VF episodes also were at an increased risk of dying (HR = 2.5, 95% CI 1.5 to 4.0, P <.01) when compared with patients without VT/VF episodes. Statistically significant predictors of electrical storm were interim postenrollment coronary events (myocardial infarction or angina) HR 3.1 (95% CI 1.2 to 8.1, P = .02) and isolated VT or VF HR 9.2 (95% CI 4.0 to 20.9, P <.01). CONCLUSION: Postinfarction patients with severe left ventricular dysfunction in whom electrical storm developed have significantly higher mortality than patients with only isolated VT/VF as well as those without any episodes of VT/VF. Patients who experienced postenrollment ventricular arrhythmias and/or interim coronary events during follow-up were at higher risk for VT/VF storms.

Compact 2.5-W 10-kHz Nd:YLF-Pumped Dye Laser

Andrew Mcgonigle — 2008-06-20T20:25:20-00:00

Appl. Opt., Vol. 41, No. 9. (20 March 2002), pp. 1714-1717.

A 10-kHz pulse repetition frequency dye laser, end pumped by a Nd:YLF laser, is reported. This laser was tunable from 590 to 655 nm, and up to 2.55 W of output power was obtained at the 609-nm peak tuning wavelength. By inserting an etalon into the dye laser cavity and frequency doubling using a β-barium borate crystal, we obtained up to 125 mW of 308-nm single-etalon-mode output, which shows potential for the performance of airborne measurements of tropospheric hydroxyl radical concentrations.

Exploration of essential gene functions via titratable promoter alleles.

S Mnaimneh — 2005-05-16T12:32:20-00:00

Cell, Vol. 118, No. 1. (9 July 2004), pp. 31-44.

Nearly 20% of yeast genes are required for viability, hindering genetic analysis with knockouts. We created promoter-shutoff strains for over two-thirds of all essential yeast genes and subjected them to morphological analysis, size profiling, drug sensitivity screening, and microarray expression profiling. We then used this compendium of data to ask which phenotypic features characterized different functional classes and used these to infer potential functions for uncharacterized genes. We identified genes involved in ribosome biogenesis (HAS1, URB1, and URB2), protein secretion (SEC39), mitochondrial import (MIM1), and tRNA charging (GSN1). In addition, apparent negative feedback transcriptional regulation of both ribosome biogenesis and the proteasome was observed. We furthermore show that these strains are compatible with automated genetic analysis. This study underscores the importance of analyzing mutant phenotypes and provides a resource to complement the yeast knockout collection.

Visualising cyberspace: information visualisation in the Harmony Internet browser

Keith Andrews — 2008-06-18T14:11:42-00:00

(1999), pp. 493-502.

Functional dissection of protein complexes involved in yeast chromosome biology using a genetic interaction map

Sean Collins — 2007-02-22T10:11:12-00:00

Nature (21 February 2007)

Highly sensitive assays for SUMOylation and small ubiquitin-like modifier-dependent protein-protein interactions.

N Rouleau — 2008-06-17T03:48:31-00:00

Analytical biochemistry, Vol. 375, No. 2. (15 April 2008), pp. 364-366.

Small ubiquitin-like proteins (SUMO) are recently discovered post-translational modifiers that regulate protein functions and intracellular trafficking. In this study, we are describing two chemoluminescence-based assays, one for SUMOylation and another one for SUMO-mediated protein-protein interactions. These assays can be used to characterize the activity and kinetics of the enzymes that catalyze SUMOylation, and in high-throughput screening for inhibitors of SUMOylation and SUMO-dependent protein-protein interactions. These novel assays represent the most sensitive assays for ubiquitin-like systems published to date. Similar strategies can be used to develop assays for other ubiquitin-like modification systems.

alpha2-Noradrenergic receptors activation enhances excitability and synaptic integration in rat prefrontal cortex pyramidal neurons via inhibition of HCN currents

Carr — 2007-10-20T19:42:19-00:00

The Journal of Physiology, Vol. 584, No. 2. (October 2007), pp. 437-450.

Use of the Timeout Ribbon Procedure during Community-Based Instruction

Paul Alberto — 2008-06-16T01:07:14-00:00

Behav Modif, Vol. 26, No. 2. (1 April 2002), pp. 297-311.

Involvement in community-based instruction can be adversely affected when students engage in behavior that interferes with participation in instruction.Amultiple probe across settings design with an embedded reversalwas used to investigate the effectiveness of the nonseclusionary timeout ribbon procedure for two middle-school students with moderate mental retardation in community and school settings. An athletic wristband served as the timeout ribbon, which functioned as the stimulus for the availability of reinforcement. When the student was wearing the wristband, he could earn reinforcers. On occurrence of inappropriate behavior, the wristband was removed and the student was placed in nonseclusionary timeout. Implementation of the timeout ribbon procedure resulted in target behaviors reduced to zero occurrences for both youths. This was maintained at a 2-week follow-up, even as the reinforcement schedule was thinned. The timeout ribbon procedure provided an efficient, effective, and socially valid means of supporting positive behavior across settings for these students. 10.1177/0145445502026002008

A large simple randomized trial of rocuronium versus succinylcholine in rapid-sequence induction of anaesthesia along with propofol.

JI Andrews — 2008-06-14T15:35:01-00:00

Acta anaesthesiologica Scandinavica, Vol. 43, No. 1. (January 1999), pp. 4-8.

BACKGROUND: Rocuronium has an onset of action more rapid than other non-depolarizing neuromuscular blocking agents, but it is unclear whether it and succinylcholine give equivalent intubating conditions during rapid-sequence induction of anaesthesia. We performed this study to answer the question--are there clinically relevant differences between the use of rocuronium and succinylcholine to secure acceptable intubating conditions during rapid-sequence induction of anaesthesia with propofol? METHODS: Anaesthesia was induced using propofol 2.5 mg/kg in 349 ASA physical status grade I-IV patients who were undergoing either elective or emergency surgery. Propofol was followed immediately by either rocuronium 0.6 or 1 mg/kg or succinylcholine 1.0 mg/kg (randomly selected). Fifty seconds after the end of muscle relaxant injection laryngoscopy was performed and intubating conditions were graded by an experienced anaesthetist blind to the muscle relaxant allocation. This study design was selected so that a 10% difference in clinically acceptable intubating conditions between drugs would be detectable. RESULTS: In this setting rocuronium 1.0 mg/kg provided superior intubating conditions compared with rocuronium 0.6 mg/kg. The incidence of clinically acceptable intubating conditions with rocuronium 1.0 mg/kg and succinylcholine 1.0 mg/kg was 93.2% and 97.1% respectively, the difference being -3.9% (95% C.I. -9.7% to 1.9%). CONCLUSION: Rocuronium 1.0 mg/kg given along with propofol in a rapid-sequence induction of anaesthesia is clinically equivalent to succinylcholine 1.0 mg/kg.

Critical care in the emergency department: introduction

P Nee — 2008-06-13T20:09:39-00:00

Emerg Med J, Vol. 23, No. 7. (1 July 2006), 560.

10.1136/emj.2005.029942

Critical care in the emergency department: monitoring the critically ill patient.

FJ Andrews — 2007-03-22T14:42:40-00:00

Emerg Med J, Vol. 23, No. 7. (July 2006), pp. 561-564.

The aim of monitoring patients is to detect organ dysfunction and guide the restoration and maintenance of tissue oxygen delivery. Monitoring is a crucial part of the care of the critically ill patient in the emergency department as the physiological response to critical illness is linked strongly to outcome. As it is important to appreciate the limitations of monitoring systems and monitored data, and to understand that invasive monitoring may be hazardous, this review concentrates on the techniques used to monitor critically ill patients in the emergency department. End tidal carbon dioxide monitoring, pulse oximetry, arterial blood pressure monitoring, central venous pressure monitoring, continuous central venous oxygenation saturation monitoring, temperature monitoring, and urine output are discussed. Practitioners should be familiar with the physiology and technology underlying these monitoring techniques and be aware of the pitfalls in interpretation of monitored data.

A wide range of protein isoforms in serum and plasma uncovered by a quantitative intact protein analysis system

David e — 2008-06-13T16:14:09-00:00

PROTEOMICS, Vol. 5, No. 13. (2005), pp. 3343-3352.

We have implemented an orthogonal 3-D intact protein analysis system (IPAS) to quantitatively profile protein differences between human serum and plasma. Reference specimens consisting of pooled Caucasian-American serum, citrate-anticoagulated plasma, and EDTA-anticoagulated plasma were each depleted of six highly abundant proteins, concentrated, and labeled with a different Cy dye (Cy5, Cy3, or Cy2). A mixture consisting of each of the labeled samples was subjected to three dimensions of separation based on charge, hydrophobicity, and molecular mass. Differences in the abundance of proteins between each of the three samples were determined. More than 5000 bands were found to have greater than two-fold difference in intensity between any pair of labeled specimens by quantitative imaging. As expected, some of the differences in band intensities between serum and plasma were attributable to proteins related to coagulation. Interestingly, many proteins were identified in multiple fractions, each exhibiting different pI, hydrophobicity, or molecular mass. This is likely reflective of the expression of different protein isoforms or specific protein cleavage products, as illustrated by complement component 3 precursor and clusterin. IPAS provides a high resolution, high sensitivity, and quantitative approach for the analysis of serum and plasma proteins, and allows assessment of PTMs as a potential source of biomarkers.

Bcl-XL Inhibits Membrane Permeabilization by Competing with Bax

Lieven Billen — 2008-06-10T14:46:54-00:00

PLoS Biology, Vol. 6, No. 6. (1 June 2008), e147.

Although Bcl-XL and Bax are structurally similar, activated Bax forms large oligomers that permeabilize the outer mitochondrial membrane, thereby committing cells to apoptosis, whereas Bcl-XL inhibits this process. Two different models of Bcl-XL function have been proposed. In one, Bcl-XL binds to an activator, thereby preventing Bax activation. In the other, Bcl-XL binds directly to activated Bax. It has been difficult to sort out which interaction is important in cells, as all three proteins are present simultaneously. We examined the mechanism of Bax activation by tBid and its inhibition by Bcl-XL using full-length recombinant proteins and measuring permeabilization of liposomes and mitochondria in vitro. Our results demonstrate that Bcl-XL and Bax are functionally similar. Neither protein bound to membranes alone. However, the addition of tBid recruited molar excesses of either protein to membranes, indicating that tBid activates both pro- and antiapoptotic members of the Bcl-2 family. Bcl-XL competes with Bax for the activation of soluble, monomeric Bax through interaction with membranes, tBid, or t-Bid-activated Bax, thereby inhibiting Bax binding to membranes, oligomerization, and membrane permeabilization. Experiments in which individual interactions were abolished by mutagenesis indicate that both Bcl-XL–tBid and Bcl-XL–Bax binding contribute to the antiapoptotic function of Bcl-XL. By out-competing Bax for the interactions leading to membrane permeabilization, Bcl-XL ties up both tBid and Bax in nonproductive interactions and inhibits Bax binding to membranes. We propose that because Bcl-XL does not oligomerize it functions like a dominant-negative Bax in the membrane permeabilization process.

Rethinking Canadian and American Nationality: Indigeneity and the 49th Parallel in Thomas King

Andrews — 2006-09-17T07:22:47-00:00

American Literary History, Vol. 18, No. 3. (2006), pp. 600-617.

Direct Activation of Human Endothelial Cells by Plasmodium falciparum-Infected Erythrocytes

Nicola Viebig — 2008-06-04T15:10:32-00:00

Infect. Immun., Vol. 73, No. 6. (1 June 2005), pp. 3271-3277.

Cytoadherence of Plasmodium falciparum-infected erythrocytes (PRBC) to endothelial cells causes severe clinical disease, presumably as a of result perfusion failure and tissue hypoxia. Cytoadherence to endothelial cells is increased by endothelial cell activation, which is believed to occur in a paracrine fashion by mediators such as tumor necrosis factor alpha (TNF-alpha) released from macrophages that initially recognize PRBC. Here we provide evidence that PRBC directly stimulate human endothelial cells in the absence of macrophages, leading to increased expression of adhesion-promoting molecules, such as intercellular adhesion molecule 1. Endothelial cell stimulation by PRBC required direct physical contact for a short time (30 to 60 min) and was correlated with parasitemia. Gene expression profiling of endothelial cells stimulated by PRBC revealed increased expression levels of chemokine and adhesion molecule genes. PRBC-stimulated endothelial cells especially showed increased expression of molecules involved in parasite adhesion but failed to express molecules promoting leukocyte adhesion, such as E-selectin and vascular cell adhesion molecule 1, even after challenge with TNF-alpha. Collectively, our data suggest that stimulation of endothelial cells by PRBC may have two effects: prevention of parasite clearance through increased cytoadherence and attenuation of leukocyte binding to endothelial cells, thereby preventing deleterious immune reactivity. 10.1128/IAI.73.6.3271-3277.2005

On SWNT reinforced composites from a continuous mixing process

Gopinath Subramanian — 2008-02-22T19:03:14-00:00

Nanotechnology, Vol. 18, No. 34. (2007), 345703.

A new continuous impingement mixing process has been used to disperse unpurified single-walled carbon nanotubes (SWNTs) in a Shell EPON-862/EpiCURE system. Composites with up to 0.2 wt% loading of SWNTs were prepared by this process. The hydrodynamic dispersion of SWNTs was found to depend on the non-dimensional Curtet number (Ct). Dispersion was evaluated by analyzing SEM images of the fracture surface using an image processing technique based on the concept of Shannon entropy. Electrical conductivity of these composites was greatly enhanced when compared with the plain material. The behavior of electrical conductivity as a function of dispersion was found to be in accordance with results from the image processing technique, and was also used to estimate the sedimentation of SWNTs.

Predictive Value of Ventricular Arrhythmia Inducibility for Subsequent Ventricular Tachycardia or Ventricular Fibrillation in Multicenter Automatic Defibrillator Implantation Trial (MADIT) II Patients

James Daubert — 2008-05-30T21:47:57-00:00

J Am Coll Cardiol, Vol. 47, No. 1. (3 January 2006), pp. 98-107.

OBJECTIVES: We correlated electrophysiologic inducibility with spontaneous ventricular tachycardia (VT) or ventricular fibrillation (VF) in the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II. BACKGROUND: In the MADIT II study, 593 (82%) of 720 implantable cardioverter-defibrillator (ICD) randomized patients underwent electrophysiologic testing. Patients received an ICD whether they were inducible or not. METHODS: A "standard" inducibility definition included sustained monomorphic or polymorphic VT induced with three or fewer extrastimuli or VF induced with two or fewer extrastimuli. We compared a narrow inducibility definition (only monomorphic VT) and a broad definition (standard definition plus VF with three extrastimuli). We used ICD-stored electrograms to categorize spontaneous VT or VF. RESULTS: Inducible patients (standard definition) had a greater likelihood of experiencing ICD therapy for VT than noninducible patients (p = 0.023). Unexpectedly, ICD therapy for spontaneous VF was less common (p = 0.021) in inducible patients than in noninducible patients. The two-year Kaplan-Meier event rate for VT or VF was 29.4% for inducible patients and 25.5% for noninducible patients. Standard inducibility did not predict the combined end point of VT or VF (p = 0.280, by log-rank analysis). The narrow inducibility definition outperformed the standard definition, whereas the broad definition appeared inferior to the standard definition. CONCLUSIONS: In the MADIT II study patients, inducibility was associated with an increased likelihood of VT. Noninducible MADIT II study subjects using this electrophysiologic protocol had a considerable VT event rate and a higher VF event rate than inducible patients. Induction of polymorphic VT or VF, even with double extrastimuli, appears less relevant than induction of monomorphic VT. 10.1016/j.jacc.2005.08.049