CiteULike: Author Hunter

OpenDMAP: An open-source, ontology-driven concept analysis engine, with applications to capturing knowledge regarding protein transport, protein interactions and cell-specific gene expression

Lawrence Hunter — 2008-02-02T00:42:17-00:00

BMC Bioinformatics, Vol. 9 (31 January 2008), 78.

Population Substructure and Control Selection in Genome-Wide Association Studies

Kai Yu — 2008-07-25T01:12:58-00:00

PLoS ONE, Vol. 3, No. 7. (2 July 2008), e2551.

Determination of the relevance of both demanding classical epidemiologic criteria for control selection and robust handling of population stratification (PS) represents a major challenge in the design and analysis of genome-wide association studies (GWAS). Empirical data from two GWAS in European Americans of the Cancer Genetic Markers of Susceptibility (CGEMS) project were used to evaluate the impact of PS in studies with different control selection strategies. In each of the two original case-control studies nested in corresponding prospective cohorts, a minor confounding effect due to PS (inflation factor λ of 1.025 and 1.005) was observed. In contrast, when the control groups were exchanged to mimic a cost-effective but theoretically less desirable control selection strategy, the confounding effects were larger (λ of 1.090 and 1.062). A panel of 12,898 autosomal SNPs common to both the Illumina and Affymetrix commercial platforms and with low local background linkage disequilibrium (pair-wise r2<0.004) was selected to infer population substructure with principal component analysis. A novel permutation procedure was developed for the correction of PS that identified a smaller set of principal components and achieved a better control of type I error (to λ of 1.032 and 1.006, respectively) than currently used methods. The overlap between sets of SNPs in the bottom 5% of p-values based on the new test and the test without PS correction was about 80%, with the majority of discordant SNPs having both ranks close to the threshold. Thus, for the CGEMS GWAS of prostate and breast cancer conducted in European Americans, PS does not appear to be a major problem in well-designed studies. A study using suboptimal controls can have acceptable type I error when an effective strategy for the correction of PS is employed.

Recent developments in the electroacoustic characterisation of colloidal suspensions and emulsions

Robert Hunter — 2008-07-24T20:43:50-00:00

Colloids and Surfaces A: Physicochemical and Engineering Aspects, Vol. 141, No. 1. (15 October 1998), pp. 37-66.

Manual curation is not sufficient for annotation of genomic databases

William Baumgartner — 2007-09-10T13:28:05-00:00

Bioinformatics, Vol. 23, No. 13. (1 July 2007), pp. i41-48.

Motivation: Knowledge base construction has been an area of intense activity and great importance in the growth of computational biology. However, there is little or no history of work on the subject of evaluation of knowledge bases, either with respect to their contents or with respect to the processes by which they are constructed. This article proposes the application of a metric from software engineering known as the found/fixed graph to the problem of evaluating the processes by which genomic knowledge bases are built, as well as the completeness of their contents. Results: Well-understood patterns of change in the found/fixed graph are found to occur in two large publicly available knowledge bases. These patterns suggest that the current manual curation processes will take far too long to complete the annotations of even just the most important model organisms, and that at their current rate of production, they will never be sufficient for completing the annotation of all currently available proteomes. Contact: larry.hunter@uchsc.edu 10.1093/bioinformatics/btm229

Biomedical Language Processing: What's Beyond PubMed?

L Hunter — 2006-03-14T04:37:05-00:00

Mol Cell, Vol. 21, No. 5. (3 March 2006), pp. 589-594.

Effects of RU 486 and tamoxifen on cocaine-induced behavioral and endocrinologic activations in male and female Fischer rats.

HB Wu — 2008-07-23T15:35:09-00:00

Ethnicity & disease, Vol. 18, No. 2 Suppl 2. (2008)

Evidence suggests that sex differences in response to cocaine administration may be regulated by activation of progesterone and estrogen receptors. To test this hypothesis, rats were pretreated with either RU 486 (progesterone antagonist; 0, 3, or 25 mg/kg), tamoxifen (estrogen antagonist; 0, 1, or 3 mg/kg), or vehicle followed by saline or cocaine administration (15 mg/kg). Although RU 486 did not affect cocaine-induced locomotor activity in female rats, it dose-dependently decreased such activity in males (3 mg/kg significantly attenuated locomotor responses in cocaine-treated rats as compared with vehicle treatment or 25 mg/kg of RU 486). RU 486 also affected baseline serum levels of corticosterone. Males treated with 3 mg/kg of RU 486 plus cocaine had higher progesterone and corticosterone serum levels than vehicle-treated groups. In females, both doses (3 and 25 mg/kg) of RU 486 significantly attenuated corticosterone serum levels compared with vehicle treatment. For both sexes overall, tamoxifen neither significantly influenced cocaine-induced ambulatory and rearing responses nor altered cocaine-induced progesterone and corticosterone serum levels. Taken together, our results suggest that progesterone receptors have a sexually dimorphic role in cocaine-induced effects, but estrogen receptors have only a limited role. Moreover, both receptor antagonists modulate neurochemical responses differentially.

What Does It Mean to Be Globally Competent?

Bill Hunter — 2008-07-23T01:53:40-00:00

Journal of Studies in International Education, Vol. 10, No. 3. (1 September 2006), pp. 267-285.

To contribute to the valuable and ongoing debate regarding the definition of global citizenship and global competency, this study proposes a definition developed through the use of a Delphi Technique involving human resource managers at top transnational corporations, senior international educators, United Nations officials, inter-cultural trainers, and foreign government officers. This definition is used as the foundation for the development of a survey to determine the knowledge, skills, and attitudes and experiences necessary to be considered globally competent. The survey was sent to 133 representatives from universities that self-nominated for recognition in the "Profiles of Success at Colleges and Universities--Internationalizing the Campus 2003" (NAFSA: Association of International Educators publication) and the transnational corporation human resource officials serving as members of the National Foreign Trade Council's Expatriate Management Committee and Global Mobility Roundtable. Results are reported and discussed, and a proposed curricular plan is presented based on the findings. 10.1177/1028315306286930

Somatic mutations of the protein kinase gene family in human lung cancer.

H Davies — 2008-04-29T19:30:38-00:00

Cancer research, Vol. 65, No. 17. (1 September 2005), pp. 7591-7595.

Protein kinases are frequently mutated in human cancer and inhibitors of mutant protein kinases have proven to be effective anticancer drugs. We screened the coding sequences of 518 protein kinases (approximately 1.3 Mb of DNA per sample) for somatic mutations in 26 primary lung neoplasms and seven lung cancer cell lines. One hundred eighty-eight somatic mutations were detected in 141 genes. Of these, 35 were synonymous (silent) changes. This result indicates that most of the 188 mutations were "passenger" mutations that are not causally implicated in oncogenesis. However, an excess of approximately 40 nonsynonymous substitutions compared with that expected by chance (P = 0.07) suggests that some nonsynonymous mutations have been selected and are contributing to oncogenesis. There was considerable variation between individual lung cancers in the number of mutations observed and no mutations were found in lung carcinoids. The mutational spectra of most lung cancers were characterized by a high proportion of C:G > A:T transversions, compatible with the mutagenic effects of tobacco carcinogens. However, one neuroendocrine cancer cell line had a distinctive mutational spectrum reminiscent of UV-induced DNA damage. The results suggest that several mutated protein kinases may be contributing to lung cancer development, but that mutations in each one are infrequent.

A screen of the complete protein kinase gene family identifies diverse patterns of somatic mutations in human breast cancer

Philip Stephens — 2005-05-26T19:59:26-00:00

Nature Genetics, Vol. 37, No. 6. (22 May 2005), pp. 590-592.

Thucydides: The Artful Reporter

Virginia Hunter — 2008-07-18T16:01:22-00:00

Predicting Aircraft Pilot- Training Success: A Meta-Analysis of Published Research

David Hunter — 2008-07-18T00:12:01-00:00

International Journal of Aviation Psychology, Vol. 4, No. 4. (1994), pp. 297-313.

Results are given from a meta-analysis of validities for aircraft pilot-selection measures. Sixty-eight published studies were identified for the 1940-to-1990 period, from which 468 correlations were extracted for a cumulated sample of 437,258 cases. The method proposed by Hunter and Schmidt (1990b) was applied to produce a bare-bones analysis. Mean sample-weighted correlations, estimates of true variance, and confidence intervals were computed. Several classes of predictors were found to have confidence intervals that did not include zero, indicating possible generalizability of validities. For the most part, however, the variance accounted for by sampling error alone was small. The effects of moderator variables (including nationality, service, decade of publication, and aircraft type) were evaluated. Of these, decade of publication was most consistently correlated with obtained validities and was associated with a decline in average validities over the five decades of studies examined. Limitations on interpretation of the results and problems associated with the analysis and interpretation of data from the published reports are discussed, and the range of correlations that might be expected from a composite of the groups of predictors that were examined is reported.

TarO: a target optimisation system for structural biology

Ian Overton — 2008-07-09T08:06:31-00:00

Nucl. Acids Res., Vol. 36, No. suppl_2. (1 July 2008), pp. W190-196.

TarO (http://www.compbio.dundee.ac.uk/taro) offers a single point of reference for key bioinformatics analyses relevant to selecting proteins or domains for study by structural biology techniques. The protein sequence is analysed by 17 algorithms and compared to 8 databases. TarO gathers putative homologues, including orthologues, and then obtains predictions of properties for these sequences including crystallisation propensity, protein disorder and post-translational modifications. Analyses are run on a high-performance computing cluster, the results integrated, stored in a database and accessed through a web-based user interface. Output is in tabulated format and in the form of an annotated multiple sequence alignment (MSA) that may be edited interactively in the program Jalview. TarO also simplifies the gathering of additional annotations via the Distributed Annotation System, both from the MSA in Jalview and through links to Dasty2. Routes to other information gateways are included, for example to relevant pages from UniProt, COG and the Conserved Domains Database. Open access to TarO is available from a guest account with private accounts for academic use available on request. Future development of TarO will include further analysis steps and integration with the Protein Information Management System (PIMS), a sister project in the BBSRC Structural Proteomics of Rational Targets' initiative 10.1093/nar/gkn141

Measuring the Quality of Uncertain Information Using Possibilistic Logic

Anthony Hunter — 2008-07-07T14:02:12-00:00

Symbolic and Quantitative Approaches to Reasoning with Uncertainty (2005), pp. 415-426.

In previous papers, we have presented a framework for merging structured information in XML involving uncertainty in the form of probabilities, degrees of beliefs and necessity measures [HL04,HL05a,HL05b]. In this paper, we focus on the quality of uncertain information before merging. We first provide two definitions for measuring information quality of individually inconsistent possibilistic XML documents, and they complement the commonly used concept of inconsistency degree. These definitions enable us to identify if an XML document is of good or lower quality when it is inconsistent, as well as enable us to differentiate between documents that have the same degree of inconsistency. We then propose a more general method to measure the quality of an inconsistent possibilistic XML document in terms of a pair of coherence measures.

CellML and associated tools and techniques.

Alan Garny — 2008-07-05T00:25:36-00:00

Philosophical transactions. Series A, Mathematical, physical, and engineering sciences (25 June 2008)

We have, in the last few years, witnessed the development and availability of an ever increasing number of computer models that describe complex biological structures and processes. The multi-scale and multi-physics nature of these models makes their development particularly challenging, not only from a biological or biophysical viewpoint but also from a mathematical and computational perspective. In addition, the issue of sharing and reusing such models has proved to be particularly problematic, with the published models often lacking information that is required to accurately reproduce the published results.The International Union of Physiological Sciences Physiome Project was launched in 1997 with the aim of tackling the aforementioned issues by providing a framework for the modelling of the human body. As part of this initiative, the specifications of the CellML mark-up language were released in 2001.Now, more than 7 years later, the time has come to assess the situation, in particular with regard to the tools and techniques that are now available to the modelling community. Thus, after introducing CellML, we review and discuss existing editors, validators, online repository, code generators and simulation environments, as well as the CellML Application Program Interface. We also address possible future directions including the need for additional mark-up languages.

A systematic review and meta-analysis of the effectiveness and safety of atovaquone proguanil (Malarone) for chemoprophylaxis against malaria

Halima Nakato — 2008-07-03T19:17:29-00:00

J. Antimicrob. Chemother., Vol. 60, No. 5. (1 November 2007), pp. 929-936.

ObjectivesA systematic review and meta-analysis of the effectiveness of atovaquone-proguanil (Malarone) as a chemoprophylactic agent against malaria. MethodsThe data sources searched for this study included Cochrane systematic reviews (on infectious diseases), MEDLINE and EMBASE, Web of Knowledge and Annals of Tropical Medicine. All unconfounded randomized controlled trials assessing the chemoprophylaxis against malaria with atovaquone-proguanil were included in the review. Data on study design, study sample, inclusion and exclusion criteria, allocation, blinding, primary and secondary study end points were all extracted by one reviewer and independently rechecked by the second reviewer. ResultsIn general, all 10 studies identified had excellent quality with total scores of [≥]4 using the Jadad criteria. Ten controlled trials comprising 4539 participants were included for this review. A meta-analysis of six of the ten studies found chemoprophylaxis with atovaquone-proguanil, with a prophylaxis efficacy of 95.8% (95% CI = 91.5-97.9), to be superior to placebo. It was also considered safe and better tolerated with fewer treatment-related adverse events that could lead to premature discontinuation of prophylaxis than in controls. Comparison with alternative chemoprophylaxis also showed atovaquone-proguanil to be better tolerated with fewer treatment-related self-reported adverse events (RR = 0.8234; 95% CI = 0.673164-1.01) or severe adverse events (RR = 0.6140; 95% CI = 0.420055-0.8975). Atovaquone-proguanil is well tolerated with no difference in non-compliance with placebo (RR = 0.8804; 95% CI = 0.6964-1.113; I2 = 31.4%). ConclusionsEvidence from this review shows that atovaquone-proguanil is highly efficacious as a prophylactic agent against malaria infection and is very well tolerated compared with other antimalarial agents. 10.1093/jac/dkm337

Improving protein function prediction methods with integrated literature data

Aaron Gabow — 2008-04-17T06:42:51-00:00

BMC Bioinformatics, Vol. 9 (15 April 2008), 198.

Vision based hand gesture interpretation using recursive estimation

J Schlenzig — 2008-07-02T04:30:44-00:00

Signals, Systems and Computers, 1994. 1994 Conference Record of the Twenty-Eighth Asilomar Conference on, Vol. 2 (1994), pp. 1267-1271 vol.2.

Gesture recognition requires spatio-temporal image sequence analysis. The actual length of the sequence varies with each instantiation of the gesture, and can be quite long in the case of a multiple gesture sequence. To achieve adequate system response we introduce the concept of recursive estimation of the gesture state. This consists of modeling the gestures as a sequence of static hand poses. Using a hidden Markov model where the unobservable state is the spatio-temporal gesture and the hand poses are the observations allows us to determine the current probabilities of each gesture with a finite state estimator. This decomposes the gesture recognition process into two stages: identification of the hand pose within the current image frame and incorporation of the new information into the probability estimates. We illustrate the performance of the estimator by describing the implementation of a telerobotic application

From Darwin's Finches to Canaries in the Coal Mine -- Mining the Genome for New Biology

David Hunter — 2008-06-26T01:17:22-00:00

N Engl J Med, Vol. 358, No. 26. (26 June 2008), pp. 2760-2763.

10.1056/NEJMp0804318

The topology of the bacterial co-conserved protein network and its implications for predicting protein function

Anis Fard — 2008-06-30T23:31:49-00:00

BMC Genomics, Vol. 9, No. 1. (2008)

BACKGROUND:Protein-protein interactions networks are most often generated from physical protein-protein interaction data. Co-conservation, also known as phylogenetic profiles, is an alternative source of information for generating protein interaction networks. Co-conservation methods generate interaction networks among proteins that are gained or lost together through evolution. Co-conservation is a particularly useful technique in the compact bacteria genomes. Prior studies in yeast suggest that the topology of protein-protein interaction networks generated from physical interaction assays can offer important insight into protein function. Here, we hypothesize that in bacteria, the topology of protein interaction networks derived via co-conservation information could similarly improve methods for predicting protein function. Since the topology of bacteria co-conservation protein-protein interaction networks has not previously been studied in depth, we first perform such an analysis for co-conservation networks in E. coli K12. Next, we demonstrate one way in which network connectivity measures and global and local function distribution can be exploited to predict protein function for previously uncharacterized proteins. RESULTS:Our results showed, like most biological networks, our bacteria co-conserved protein-protein interaction networks had scale-free topologies. Our results indicated that some properties of the physical yeast interaction network hold in our bacteria co-conservation networks, such as high connectivity for essential proteins. However, the high connectivity among protein complexes in the yeast physical network was not seen in the co-conservation network which uses all bacteria as the reference set. We found that the distribution of node connectivity varied by functional category and could be informative for function prediction. By integrating of functional information from different annotation sources and using the network topology, we were able to infer function for uncharacterized proteins.CONCLUSIONS:Interactions networks based on co-conservation can contain information distinct from networks based on physical or other interaction types. Our study has shown co-conservation based networks to exhibit a scale free topology, as expected for biological networks. We also revealed ways that connectivity in our networks can be informative for the functional characterization of proteins.

Comparison of Image Quality Between Conventional and Low-Dose Nonenhanced Head CT

Mark Mullins — 2008-06-30T17:52:17-00:00

AJNR Am J Neuroradiol, Vol. 25, No. 4. (1 April 2004), pp. 533-538.

BACKGROUND AND PURPOSE: Increasing use of CT for evaluating neurologic disease may expose patients to considerable levels of ionizing radiation. We compared the image quality of low-mAs head CT scans with that of conventional nonenhanced scans. METHODS: Conventional head CT scans were obtained in 20 patients (all >65 years with history of non-CNS malignancy) by using a multidetector technique: 170 mA and 1-second scanning time (ie, 170 mAs), 140 kVp, table speed of 7.5 mm per rotation, pitch of 0.75, section thickness of 5 mm, and field of view of 25 mm. A limited volume helical data acquisition covering four 5-mm-thick images was obtained by using 90 mAs but otherwise the same parameters. Three neuroradiologists visually rated the resulting images for quality in a blinded comparison. Representative 1- to 4-mm2 regions of interest were chosen in gray matter and white matter locations. Conspicuity and the contrast-to-noise ratio were analyzed. Statistical comparisons were done by using the Student t test. RESULTS: Mean gray matter conspicuity was not significantly different between the 170- and 90-mAs groups (0.39 +/- 0.19 vs 0.41 +/- 0.03, P = .32). Mean gray matter contrast-to-noise ratio was approximately 22% higher with 170 mAs than with 90 mAs (1.77 +/- 0.52 vs 1.39 +/- 0.38, P = .005). All 90-mAs images were rated as having slightly greater image noise than the 170-mAs scans but with sufficient perceived resolution. CONCLUSION: Although 90-mAs head CT images were moderately noisier than 170-mAs images, they were rated as having acceptable diagnostic quality.

Peripherally inserted central catheter placement @ the speed of sound.

M Hunter — 2008-06-28T12:27:16-00:00

Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition, Vol. 22, No. 4. (August 2007), pp. 406-411.

Over the past few years, one of the major advancements in bedside peripherally inserted central catheter (PICC) placement has been the addition of portable ultrasound for vascular access. Traditional bedside PICC insertion success rates varied from 65% to 75% due to the limited visualized area of access available for PICC placement (1.5 inches above to 1.5 inches below the antecubital fossa). With the implementation of ultrasound, success rates have climbed to 91%-94% for bed-side-placed PICC. This article reviews the dynamics of ultrasound, provides practical tips to use image visualization, and illustrates the important key functions of this technology.

CCR2 modulates inflammatory and metabolic effects of high-fat feeding.

SP Weisberg — 2008-04-17T23:20:15-00:00

The Journal of clinical investigation, Vol. 116, No. 1. (January 2006), pp. 115-124.

The C-C motif chemokine receptor-2 (CCR2) regulates monocyte and macrophage recruitment and is necessary for macrophage-dependent inflammatory responses and the development of atherosclerosis. Although adipose tissue expression and circulating concentrations of CCL2 (also known as MCP1), a high-affinity ligand for CCR2, are elevated in obesity, the role of CCR2 in metabolic disorders, including insulin resistance, hepatic steatosis, and inflammation associated with obesity, has not been studied. To determine what role CCR2 plays in the development of metabolic phenotypes, we studied the effects of Ccr2 genotype on the development of obesity and its associated phenotypes. Genetic deficiency in Ccr2 reduced food intake and attenuated the development of obesity in mice fed a high-fat diet. In obese mice matched for adiposity, Ccr2 deficiency reduced macrophage content and the inflammatory profile of adipose tissue, increased adiponectin expression, ameliorated hepatic steatosis, and improved systemic glucose homeostasis and insulin sensitivity. In mice with established obesity, short-term treatment with a pharmacological antagonist of CCR2 lowered macrophage content of adipose tissue and improved insulin sensitivity without significantly altering body mass or improving hepatic steatosis. These data suggest that CCR2 influences the development of obesity and associated adipose tissue inflammation and systemic insulin resistance and plays a role in the maintenance of adipose tissue macrophages and insulin resistance once obesity and its metabolic consequences are established.

A critical review of PASBio's argument structures for biomedical verbs

Bretonnel Cohen — 2008-06-02T06:48:16-00:00

BMC Bioinformatics, Vol. 7, No. Suppl 3. (2006)

BACKGROUND:Propositional representations of biomedical knowledge are a critical component of most aspects of semantic mining in biomedicine. However, the proper set of propositions has yet to be determined. Recently, the PASBio project proposed a set of propositions and argument structures for biomedical verbs. This initial set of representations presents an opportunity for evaluating the suitability of predicate-argument structures as a scheme for representing verbal semantics in the biomedical domain. Here, we quantitatively evaluate several dimensions of the initial PASBio propositional structure repository.RESULTS:We propose a number of metrics and heuristics related to arity, role labelling, argument realization, and corpus coverage for evaluating large-scale predicate-argument structure proposals. We evaluate the metrics and heuristics by applying them to PASBio 1.0.CONCLUSION:PASBio demonstrates the suitability of predicate-argument structures for representing aspects of the semantics of biomedical verbs. Metrics related to theta-criterion violations and to the distribution of arguments are able to detect flaws in semantic representations, given a set of predicate-argument structures and a relatively small corpus annotated with them.

Evolution of protein kinase signaling from yeast to man

Gerard Manning — 2008-04-23T15:32:06-00:00

Trends in Biochemical Sciences, Vol. 27, No. 10. (1 October 2002), pp. 514-520.

Protein phosphorylation controls many cellular processes, especially those involved in intercellular communication and coordination of complex functions. To explore the evolution of protein phosphorylation, we compared the protein kinase complements ([`]kinomes') of budding yeast, worm and fly, with known human kinases. We classify kinases into putative orthologous groups with conserved functions and discuss kinase families and pathways that are unique, expanded or lost in each lineage. Fly and human share several kinase families involved in immunity, neurobiology, cell cycle and morphogenesis that are absent from worm, suggesting that these functions might have evolved after the divergence of nematodes from the main metazoan lineage.

Charge-transfer-to-solvent Spectra

MF Fox — 2008-06-23T20:51:45-00:00

Nature, Vol. 223, No. 5202. (12 July 1969), pp. 177-178.

Patterns of somatic mutation in human cancer genomes

Christopher Greenman — 2007-03-08T11:23:13-00:00

Nature, Vol. 446, No. 7132., pp. 153-158.

Drinking from the fire hose--statistical issues in genomewide association studies.

DJ Hunter — 2007-08-16T19:44:21-00:00

N Engl J Med, Vol. 357, No. 5. (2 August 2007), pp. 436-439.

Experimental and bioinformatic approaches for interrogating protein-protein interactions to determine protein function

Arnaud Droit — 2008-06-20T18:14:56-00:00

J Mol Endocrinol, Vol. 34, No. 2. (1 April 2005), pp. 263-280.

An ambitious goal of proteomics is to elucidate the structure, interactions and functions of all proteins within cells and organisms. One strategy to determine protein function is to identify the protein-protein interactions. The increasing use of high-throughput and large-scale bioinformatics-based studies has generated a massive amount of data stored in a number of different databases. A challenge for bioinformatics is to explore this disparate data and to uncover biologically relevant interactions and pathways. In parallel, there is clearly a need for the development of approaches that can predict novel protein-protein interaction networks in silico. Here, we present an overview of different experimental and bioinformatic methods to elucidate protein-protein interactions. 10.1677/jme.1.01693

Kinomics: methods for deciphering the kinome

Sam Johnson — 2004-12-23T14:17:46-00:00

Nature Methods, Vol. 2, No. 1. (21 December 2004), 17.

The mouse kinome: discovery and comparative genomics of all mouse protein kinases.

S Caenepeel — 2005-02-08T22:19:26-00:00

Proc Natl Acad Sci U S A, Vol. 101, No. 32. (10 August 2004), pp. 11707-11712.

We have determined the full protein kinase (PK) complement (kinome) of mouse. This set of 540 genes includes many novel kinases and corrections or extensions to >150 published sequences. The mouse has orthologs for 510 of the 518 human PKs. Nonorthologous kinases arise only by retrotransposition and gene decay. Orthologous kinase pairs vary in sequence conservation along their length, creating a map of functionally important regions for every kinase pair. Many species-specific sequence inserts exist and are frequently alternatively spliced, allowing for the creation of evolutionary lineage-specific functions. Ninety-seven kinase pseudogenes were found, all distinct from the 107 human kinase pseudogenes. Chromosomal mapping links 163 kinases to mutant phenotypes and unlocks the use of mouse genetics to determine functions of orthologous human kinases.

The protein kinase complement of the human genome.

G Manning — 2005-02-08T22:21:15-00:00

Science, Vol. 298, No. 5600. (6 December 2002), pp. 1912-1934.

We have catalogued the protein kinase complement of the human genome (the "kinome") using public and proprietary genomic, complementary DNA, and expressed sequence tag (EST) sequences. This provides a starting point for comprehensive analysis of protein phosphorylation in normal and disease states, as well as a detailed view of the current state of human genome analysis through a focus on one large gene family. We identify 518 putative protein kinase genes, of which 71 have not previously been reported or described as kinases, and we extend or correct the protein sequences of 56 more kinases. New genes include members of well-studied families as well as previously unidentified families, some of which are conserved in model organisms. Classification and comparison with model organism kinomes identified orthologous groups and highlighted expansions specific to human and other lineages. We also identified 106 protein kinase pseudogenes. Chromosomal mapping revealed several small clusters of kinase genes and revealed that 244 kinases map to disease loci or cancer amplicons.

Temporal Interpolation of Spatially Dynamic Object

Wei Zhang — 2008-06-18T14:07:37-00:00

Geoinformatica, Vol. 4, No. 4. (December 2000), pp. 403-418.

Statistics for Experimenters: Design, Innovation, and Discovery , 2nd Edition

George Box — 2008-06-18T10:37:57-00:00

(14 June 2005)

**A Classic adapted to modern times** Rewritten and updated, this new edition of Statistics for Experimenters adopts the same approaches as the landmark First Edition by teaching with examples, readily understood graphics, and the appropriate use of computers. Catalyzing innovation, problem solving, and discovery, the Second Edition provides experimenters with the scientific and statistical tools needed to maximize the knowledge gained from research data, illustrating how these tools may best be utilized during all stages of the investigative process. The authors’ practical approach starts with a problem that needs to be solved and then examines the appropriate statistical methods of design and analysis. Providing even greater accessibility for its users, the Second Edition is thoroughly revised and updated to reflect the changes in techniques and technologies since the publication of the classic First Edition. Among the new topics included are: * Graphical Analysis of Variance * Computer Analysis of Complex Designs * Simplification by transformation * Hands-on experimentation using Response Service Methods * Further development of robust product and process design using split plot arrangements and minimization of error transmission * Introduction to Process Control, Forecasting and Time Series * Illustrations demonstrating how multi-response problems can be solved using the concepts of active and inert factor spaces and canonical spaces * Bayesian approaches to model selection and sequential experimentation An appendix featuring Quaquaversal quotes from a variety of sources including noted statisticians and scientists to famous philosophers is provided to illustrate key concepts and enliven the learning process. All the computations in the Second Edition can be done utilizing the statistical language R. Functions for displaying ANOVA and lamba plots, Bayesian screening, and model building are all included and R packages are available online. All theses topics can also be applied utilizing easy-to-use commercial software packages. Complete with applications covering the physical, engineering, biological, and social sciences, Statistics for Experimenters is designed for individuals who must use statistical approaches to conduct an experiment, but do not necessarily have formal training in statistics. Experimenters need only a basic understanding of mathematics to master all the statistical methods presented. This text is an essential reference for all researchers and is a highly recommended course book for undergraduate and graduate students.

Getting Started in Text Mining

Bretonnel Cohen — 2008-01-25T23:39:38-00:00

PLoS Computational Biology, Vol. 4, No. 1. (1 January 2008), e20.

The systems biology markup language (SBML): a medium for representation and exchange of biochemical network models.

M Hucka — 2004-11-22T00:17:30-00:00

Bioinformatics, Vol. 19, No. 4. (1 March 2003), pp. 524-531.

MOTIVATION: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. RESULTS: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. AVAILABILITY: The specification of SBML Level 1 is freely available from http://www.sbml.org/

Harvana: harvesting community tags to enrich collection metadata

Jane Hunter — 2008-06-17T02:35:31-00:00

(2008), pp. 147-156.

Collaborative, social tagging and annotation systems have exploded on the Internet as part of the Web 2.0 phenomenon. Systems such as Flickr, Del.icio.us, Technorati, Connotea and LibraryThing, provide a community-driven approach to classifying information and resources on the Web, so that they can be browsed, discovered and re-used. Although social tagging sites provide simple, user-relevant tags, there are issues associated with the quality of the metadata and the scalability compared with conventional indexing systems. In this paper we propose a hybrid approach that enables authoritative metadata generated by traditional cataloguing methods to be merged with community annotations and tags. The HarvANA (Harvesting and Aggregating Networked Annotations) system uses a standardized but extensible RDF model for representing the annotations/tags and OAI-PMH to harvest the annotations/tags from distributed community servers. The harvested annotations are aggregated with the authoritative metadata in a centralized metadata store. This streamlined, interoperable, scalable approach enables libraries, archives and repositories to leverage community enthusiasm for tagging and annotation, augment their metadata and enhance their discovery services. This paper describes the HarvANA system and its evaluation through a collaborative testbed with the National Library of Australia using architectural images from PictureAustralia.

Automated measurement of myofiber disarray in transgenic mice with ventricular expression of <I>ras</I>

William Karlon — 2008-06-17T02:18:35-00:00

The Anatomical Record, Vol. 252, No. 4. (1998), pp. 612-625.

Quantitative assessment of myofiber disarray associated with diseases such as familial hypertrophic cardiomyopathy (FHC) can be performed by estimating local angular deviation of fiber orientation in histologic sections. The large number of measurements required to estimate angular deviation prohibits manual measurement. We describe methods for automated measurement of local orientation and angular deviation in tissue sections from transgenic mice with ventricular expression of ras, proposed as a model of FHC.Images of histologic tissue sections from normal and transgenic mice were analyzed using image processing techniques to estimate local orientation of myofibers. Results from the automated methods were compared with manual measurements.Automated methods estimated differing mean orientation in 7-20% of normal sections and 17-29% of transgenic tissue sections with differing dispersions in 23-30% of normal sections and 25% of transgenic tissue sections. Automated methods estimate 24.47 ± 13.03% of total ventricular mass affected by disarray that is comparable to a previous estimate of 21.7% in the same mouse model.Automated methods are a rapid and accurate alternative to manual measurement for estimation of mean orientation and angular deviation in myocardial tissue sections. Differences between manual and automated methods may be attributed to the substantially larger number of measurements made by automated methods. Automated methods are particularly appropriate for use in determining local variation in orientation such as focal myofiber disarray associated with FHC. The generality of these methods suggests they may have use in other biological fields such as quantifying cellular alignment. Anat Rec. 252:612-625, 1998. © 1998 Wiley-Liss, Inc.

Reversal of rocuronium-induced neuromuscular block with sugammadex is faster than reversal of cisatracurium-induced block with neostigmine.

EA Flockton — 2008-06-14T15:47:16-00:00

British journal of anaesthesia, Vol. 100, No. 5. (May 2008), pp. 622-630.

BACKGROUND: Reversal of the residual effect of rocuronium or cisatracurium by neostigmine may be slow and associated with side-effects. This randomized, safety-assessor-blinded study compared the efficacy of sugammadex, a selective relaxant binding agent for reversal of rocuronium-induced neuromuscular block, with that of neostigmine for reversal of cisatracurium-induced neuromuscular block. The safety of sugammadex and neostigmine was also evaluated. METHODS: Adult surgical patients (ASA class I-III) were randomized to sugammadex 2.0 mg kg(-1) for reversal of block induced by rocuronium 0.6 mg kg(-1), or neostigmine 50 microg kg(-1) for reversal of block induced by cisatracurium 0.15 mg kg(-1). Anaesthesia was induced and maintained using i.v. propofol and remifentanil, fentanyl, or sufentanil. Neuromuscular function was monitored using acceleromyography (TOF-Watch SX). Sugammadex or neostigmine was administered at reappearance of T(2). The primary efficacy variable was time for recovery of the train-of-four (TOF) ratio to 0.9. RESULTS: Eighty-four patients were randomized, 73 of whom received sugammadex (n=34) or neostigmine (n=39). Time from start of administration of reversal agent to recovery of the TOF ratio to 0.9 was 4.7 times faster with sugammadex than with neostigmine (geometric mean=1.9 vs 9.0 min, P<0.0001). Reversal of block was sustained in all patients. There were no serious adverse effects from either reversal agent and no significant changes in any measure of safety, except for similar elevations in urinary N-acetyl glucosaminidase in both groups. CONCLUSIONS: Sugammadex 2.0 mg kg(-1) administered at reappearance of T(2) was significantly faster in reversing rocuronium-induced blockade than neostigmine was in reversing cisatracurium-induced block.

Pharmacokinetic studies of neuromuscular blocking agents: good clinical research practice (GCRP).

J Viby-Mogensen — 2008-06-14T15:43:40-00:00

Acta anaesthesiologica Scandinavica, Vol. 44, No. 10. (November 2000), pp. 1169-1190.

In September 1997, an international consensus conference on standardization of studies of neuromuscular blocking agents was held in Copenhagen, Denmark. Based on the conference, a set of guidelines for good clinical research practice (GCRP) in pharmacokinetic studies of neuromuscular blocking agents is presented. Guidelines include: design of the study; relevant patient groups to investigate; test drug administration, sampling and analysis; pharmacokinetic analysis; pharmacokinetic/pharmacodynamic modeling; population pharmacokinetics; statistics; and presentation of pharmacokinetic data. The guidelines are intended to aid those working in this research area; it is hoped that they will assist researchers, editors of scientific papers, and pharmaceutical companies in improving the quality of pharmacokinetic studies.

Histamine release and neuromuscular blocking drugs.

JM Hunter — 2008-06-14T04:18:18-00:00

Anaesthesia, Vol. 48, No. 7. (July 1993), pp. 561-563.

Land-use effects on fluxes of suspended sediment, nitrogen and phosphorus from a river catchment of the Great Barrier Reef, Australia

Heather Hunter — 2008-06-13T18:24:08-00:00

Journal of Hydrology, Vol. 356, No. 1-2. (1 July 2008), pp. 131-146.

Summary A 6-year study was conducted in the Johnstone River system in the wet tropics of north-eastern Australia, to address concerns that the Great Barrier Reef is at risk from elevated levels of suspended sediment (SS) and nutrients discharged from its river catchments. Aims were to quantify: (i) fluxes of SS, phosphorus (P) and nitrogen (N) exported annually from the catchment and (ii) the influence of rural land uses on these fluxes. Around 55% of the 1602 km2 catchment was native rainforest, with the reminder developed mainly for livestock and crop production. Water quality and stream flow were monitored at 16 sites, with the emphasis on sampling major runoff events. Monitoring data were used to calibrate a water quality model for the catchment (HSPF), which was run with 39 years of historical precipitation and evaporation data. Modelled specific fluxes from the catchment of 1.2 ± 1.1 t SS ha-1 y-1, 2.2 ± 1.8 kg P ha-1 y-1 and 11.4 ± 7.3 kg N ha-1 y-1 were highly variable between and within years. Fluxes of SS and P were strongly dominated by major events, with 91% of SS and 84% of P exported during the highest 10% of daily flows. On average, sediment P comprised 81% of the total P flux. The N flux was less strongly dominated by major events and sediment N comprised 46% of total N exports. Specific fluxes of SS, N and P from areas receiving precipitation of 3545 mm y-1 were around 3-4 times those from areas receiving 1673 mm y-1. For a given mean annual precipitation, specific fluxes of SS and P from beef pastures, dairy pastures and unsewered residential areas were similar to those from rainforest, while fluxes from areas of sugar cane and bananas were 3-4 times higher. Specific fluxes of N from areas with an annual precipitation of 3545 mm ranged from 8.9 ± 6.5 kg N ha-1 y-1 (rainforest) to 72 ± 50 kg N ha-1 y-1 (unsewered residential). Aggregated across the entire catchment, disproportionately large fluxes of SS, total P and total N were derived from areas of sugar cane and banana production. Fluxes of nitrate N comprised 32% of mean annual total N flux and were disproportionately high from unsewered residential areas and from areas used for sugar cane and banana production. Notably, 60% of the total catchment flux of nitrate came from areas of sugar cane, which comprised only 12% of the total land area. Modelled scenarios suggest contemporary nitrate fluxes were nearly six times those under natural conditions (pre-development), a much greater increase than estimated for SS, total P and total N. These elevated nitrate fluxes are of particular concern for the protection of aquatic ecosystems, since nitrate is a readily bio-available form of N. Results of the study suggest management practices associated with certain land uses may need further investigation and improvement. To reduce nitrate fluxes, this includes a need to address fertiliser management in the sugar cane and banana industries and wastewater disposal practices in unsewered residential areas.

Oncogenic kinase signalling.

P Blume-Jensen — 2006-07-03T14:27:23-00:00

Nature, Vol. 411, No. 6835. (17 May 2001), pp. 355-365.

Protein-tyrosine kinases (PTKs) are important regulators of intracellular signal-transduction pathways mediating development and multicellular communication in metazoans. Their activity is normally tightly controlled and regulated. Perturbation of PTK signalling by mutations and other genetic alterations results in deregulated kinase activity and malignant transformation. The lipid kinase phosphoinositide 3-OH kinase (PI(3)K) and some of its downstream targets, such as the protein-serine/threonine kinases Akt and p70 S6 kinase (p70S6K), are crucial effectors in oncogenic PTK signalling. This review emphasizes how oncogenic conversion of protein kinases results from perturbation of the normal autoinhibitory constraints on kinase activity and provides an update on our knowledge about the role of deregulated PI(3)K/Akt and mammalian target of rapamycin/p70S6K signalling in human malignancies.

Coded cooperation in wireless communications: space-time transmission and iterative decoding

M Janani — 2008-06-11T20:21:52-00:00

Signal Processing, IEEE Transactions on [see also Acoustics, Speech, and Signal Processing, IEEE Transactions on], Vol. 52, No. 2. (2004), pp. 362-371.

When mobiles cannot support multiple antennas due to size or other constraints, conventional space-time coding cannot be used to provide uplink transmit diversity. To address this limitation, the concept of cooperation diversity has been introduced, where mobiles achieve uplink transmit diversity by relaying each other's messages. A particularly powerful variation of this principle is coded cooperation. Instead of a simple repetition relay, coded cooperation partitions the codewords of each mobile and transmits portions of each codeword through independent fading channels. This paper presents two extensions to the coded cooperation framework. First, we increase the diversity of coded cooperation in the fast-fading scenario via ideas borrowed from space-time codes. We calculate bounds for the bit- and block-error rates to demonstrate the resulting gains. Second, since cooperative coding contains two code components, it is natural to apply turbo codes to this framework. We investigate the application of turbo codes in coded cooperation and demonstrate the resulting gains via error bounds and simulations.

Negotiating the global Internet rating and filtering system: opposing views of the Bertelsmann foundation's self-regulation of Internet content proposal

Christopher Hunter — 2008-06-11T18:55:44-00:00

(2000), pp. 235-238.

Laminar structure of the heart: a mathematical model.

IJ Legrice — 2008-06-11T11:27:44-00:00

The American journal of physiology, Vol. 272, No. 5 Pt 2. (May 1997)

A mathematical description of cardiac anatomy is presented for use with finite element models of the electrical activation and mechanical function of the heart. The geometry of the heart is given in terms of prolate spheroidal coordinates defined at the nodes of a finite element mesh and interpolated within elements by a combination of linear Lagrange and cubic Hermite basis functions. Cardiac microstructure is assumed to have three axes of symmetry: one aligned with the muscle fiber orientation (the fiber axis); a second set orthogonal to the fiber direction and lying in the newly identified myocardial sheet plane (the sheet axis); and a third set orthogonal to the first two, in the sheet-normal direction. The geometry, fiber-axis direction, and sheet-axis direction of a dog heart are fitted with parameters defined at the nodes of the finite element mesh. The fiber and sheet orientation parameters are defined with respect to the ventricular geometry such that 1) they can be applied to any heart of known dimensions, and 2) they can be used for the same heart at various states of deformation, as is needed, for example, in continuum models of ventricular contraction.

Getting Started in Text Mining

Bretonnel Cohen — 2008-01-30T03:27:37-00:00

PLoS Computational Biology, Vol. 4, No. 1. (1 January 2008), e20.

A Conserved Tryptophan-Rich Motif in the Membrane-Proximal Region of the Human Immunodeficiency Virus Type 1 gp41 Ectodomain Is Important for Env-Mediated Fusion and Virus Infectivity

Karl Salzwedel — 2008-06-09T09:35:51-00:00

J. Virol., Vol. 73, No. 3. (1 March 1999), pp. 2469-2480.

Mutations were introduced into the ectodomain of the human immunodeficiency virus type 1 (HIV-1) transmembrane envelope glycoprotein, gp41, within a region immediately adjacent to the membrane-spanning domain. This region, which is predicted to form an [alpha]-helix, contains highly conserved hydrophobic residues and is unusually rich in tryptophan residues. In addition, this domain overlaps the epitope of a neutralizing monoclonal antibody, 2F5, as well as the sequence corresponding to a peptide, DP-178, shown to potently neutralize virus. Site-directed mutagenesis was used to create deletions, substitutions, and insertions centered around a stretch of 17 hydrophobic and uncharged amino acids (residues 666 to 682 of the HXB2 strain of HIV-1) in order to determine the role of this region in the maturation and function of the envelope glycoprotein. Deletion of the entire stretch of 17 amino acids abrogated the ability of the envelope glycoprotein to mediate both cell-cell fusion and virus entry without affecting the normal maturation, transport, or CD4-binding ability of the protein. This phenotype was also demonstrated by substituting alanine residues for three of the five tryptophan residues within this sequence. Smaller deletions, as well as multiple amino acid substitutions, were also found to inhibit but not block cell-cell fusion. These results demonstrate the crucial role of a tryptophan-rich motif in gp41 during a post-CD4-binding step of glycoprotein-mediated fusion. The basis for the invariant nature of the tryptophans, however, appears to be at the level of glycoprotein incorporation into virions. Even the substitution of phenylalanine for a single tryptophan residue was sufficient to reduce Env incorporation and drop the efficiency of virus entry approximately 10-fold, despite the fact that the same mutation had no significant effect on syncytium formation.

Corpus Refactoring: a Feasibility Study

Helen Johnson — 2007-09-14T15:11:16-00:00

Journal of Biomedical Discovery and Collaboration, Vol. 2 (13 September 2007), 4.

Temporal organization of phytoplankton communities linked to physical forcing

Monika Winder — 2008-05-16T06:00:47-00:00

Oecologia, Vol. 156, No. 1. (May 2008), pp. 179-192.

The performance of individual phytoplankton species is strongly governed by the thermal stratification’s impact on vertical mixing within the water column, which alters the position of phytoplankton relative to nutrients and light. The present study documents shifts in phytoplankton structure and vertical positioning that have accompanied intensified long-term stratification in a natural ecosystem. Ordination analysis is used to extract gradients in phytoplankton composition in Lake Tahoe, an extremely nutrient-poor lake, over a 23-year period of records. Community structure in the 1980s was associated most strongly with resource availability (low nitrogen to phosphorus ratios, deeper euphotic zone depth), while intensified stratification dominated the phytoplankton structure since the late 1990s. Within diatoms, small-sized cells increased with reduced mixing, suggesting that suppressed turbulence provides them with a competitive advantage over large-sized cells. Among the morphologically diverse chlorophytes, filamentous and coenobial forms were favored under intensified stratification. The selection for small-sized diatoms is accompanied by a shoaling trend in their vertical position in the water column. In contrast, the motile flagellates displayed a deeper vertical positioning in recent years, indicating that optimal growth conditions shifted likely due to reduced upwelling of nutrients. As the thermal stratification of lakes and oceans is strongly linked to climate variables, the present study confirms that climate warming will alter phytoplankton structure and dynamics largely through effects on nutrient availability and sinking velocities. Intensified stratification should favor the expansion of small-sized species and species with the capability of buoyancy regulation, which may alter primary productivity, nutrient recycling, and higher trophic productivity.

Dependence of cyclin E-CDK2 kinase activity on cell anchorage.

F Fang — 2008-05-27T20:44:45-00:00

Science (New York, N.Y.), Vol. 271, No. 5248. (26 January 1996), pp. 499-502.

Most nonmalignant cells are anchorage-dependent; they require substrate attachment for growth and, in some instances, survival. This requirement is lost on oncogenic transformation. The cyclin E-CDK2 complex, which is required for the G1-S transition of the cell cycle, was activated in late G1 phase in attached human fibroblasts, but not in fibroblasts maintained in suspension. In transformed fibroblasts the complex was active regardless of attachment. The lack of cyclin E-CDK2 activity in suspended cells appeared to result from increased expression of CDK2 inhibitors and a concomitant decrease in phosphorylation of CDK2 on threonine-160. Suppression of cyclin E-CDK2 activity may thus underlie the anchorage dependence of cell growth.