bluuebunny/crossref_metadata_2025 huggingface dataset:
Formation of Jets through Mixing and Forcing of Potential Vorticity: Analysis and Parameterization of Beta-Plane Turbulence
Authors: Nakamura Noboru , Zhu Da
Published: January 2010

Formation of multiple jets in forced beta-plane turbulence is studied from the perspective of nonuniform nonconservative arrangement of potential vorticity (PV). Numerical simulations are analyzed to show that mixing and forcing reinforce jets by concentrating PV gradients at the axes of prograde jets. Based on the formalism developed in the companion paper, the nonconservative driving of jets is diagnosed and parameterized through the diffusive flux of PV and the source of wave activity. It is found that the two terms nearly balance on a long time scale, and they are both strongly anticorrelated with the PV gradient, which suggests that PV controls the nonconservative processes and that these processes could be parameterized as functions of the PV gradient. The flux is modeled using the effective diffusivity formula recently obtained by Ferrari and Nikurashin. Consistent with the PV barrier concept, the nonlinear diffusivity is a decreasing function of the squared PV gradient and agrees well with the diffusivity diagnosed from the numerical simulation. The source term is assumed to be inversely proportional to the PV gradient. The parameterization gives rise to a nonlinear partial differential equation (PDE) for the mean flow. A finite-difference model of the PDE predicts formation of a piecewise linear PV (staircase) and piecewise parabolic jets from a near-uniform initial condition when anisotropy and mixing of the flow are sufficiently strong. The origin of the discontinuities is antidiffusive instability of PV gradients, and although nonlinearity allows the discrete model to integrate stably, the solution is sensitive to the initial condition and resolution. The emerging jets in the 1D model have similar characteristics to those in the numerical simulation, but the details of the transient behavior are distinct. Similar discrete models of ill-posed PDEs in which discontinuities form also appear in image processing and granular matter dynamics.
Validation of Surface Current Measurements in the Northern Adriatic Sea from High-Frequency Radars
Authors: Cosoli Simone , Mazzoldi Andrea , Gačić Miroslav
Published: January 2010

The performances of a shore-based high-frequency (HF) radar network deployed along the coast of the Venice lagoon (northern Adriatic Sea) are discussed based on a comparison with a single bottom-mounted ADCP deployed in the shallow-water area offshore of the lagoon for a 40-day period in August–September 2005.

The analyses, carried out using currents representative of the first meter for the HF radars and 2.5 m for the ADCP, gave rms differences of radial currents in the range of 8.7–14.7 cm s−1 (correlation 0.37– 0.82) for the ideal pattern and 8.4–20.5 cm s−1 (correlation 0.14–0.84) for the measured pattern. Good correlation was found between surface current vectors and moored data (scalar correlation up to R = 0.83, vector correlation ρ = 0.78, veering angle 6°). Comparison metrics were improved for the low-passed currents. Angular offsets ranged between +6° and +11°. Differences depended primarily on the geophysical variability within the water column. Bearing offsets also contributed because they lead to comparisons with radial velocities at erroneous angular sectors.

Radar performances were severely affected by strong northeasterly wind pulses in their early stages. An increased broadband noise, spread over the entire Doppler spectrum across all ranges to the antennas, masked the Bragg peaks and determined the loss in radar coverage, introducing gross underestimations of both radial velocities and total currents.
A Synoptic Weather Typing Approach to Simulate Daily Rainfall and Extremes in Ontario, Canada: Potential for Climate Change Projections
Authors: Cheng Chad Shouquan , Li Guilong , Li Qian , Auld Heather
Published: January 2010

An automated synoptic weather typing and stepwise cumulative logit/nonlinear regression analyses were employed to simulate the occurrence and quantity of daily rainfall events. The synoptic weather typing was developed using principal component analysis, an average linkage clustering procedure, and discriminant function analysis to identify the weather types most likely to be associated with daily rainfall events for the four selected river basins in Ontario. Within-weather-type daily rainfall simulation models comprise a two-step process: (i) cumulative logit regression to predict the occurrence of daily rainfall events, and (ii) using probability of the logit regression, a nonlinear regression procedure to simulate daily rainfall quantities. The rainfall simulation models were validated using an independent dataset, and the results showed that the models were successful at replicating the occurrence and quantity of daily rainfall events. For example, the relative operating characteristics score is greater than 0.97 for rainfall events with daily rainfall ≥10 or ≥25 mm, for both model development and validation. For evaluation of daily rainfall quantity simulation models, four correctness classifications of excellent, good, fair, and poor were defined, based on the difference between daily rainfall observations and model simulations. Across four selected river basins, the percentage of excellent and good simulations for model development ranged from 62% to 84% (of 20 individuals, 16 cases ≥ 70%, 7 cases ≥ 80%); the corresponding percentage for model validation ranged from 50% to 76% (of 20 individuals, 15 cases ≥ 60%, 6 cases ≥ 70%).
Snow Studies. Part I: A Study of Natural Variability of Snow Terminal Velocity
Authors: Zawadzki Isztar , Jung Eunsil , Lee Gyowon
Published: January 2010

The variability and the uncertainties in snowfall velocity measurements are addressed in this study. The authors consider (i) the instrumental uncertainty in the fall velocity measurement, (ii) the effect of unstable falling motion on the accuracy of velocity measurement, and (iii) the natural variability of homogeneous snow terminal fall velocity. It is shown that, when periods of homogeneous characteristics of snow are selected to minimize the mixture of particles of different origin, the standard deviation of snowfall velocity within each period tends to stabilize at a value between 0.1 and 0.2 m s−1.

In addition, the variability of snow terminal fall velocity is examined with three control variables: surface temperature Ts, echo-top temperature Tt, and the depth of precipitation system H. The results show that the exponent b in the power-law relationship V = aDb has little effect on the variability of snowfall velocity: the coefficient a correlates much better with the control variables (Ts, Tt, H) than the exponent b. Hence, snowfall velocity can be modeled with a varying coefficient a and a fixed exponent b = 0.18 (V = aD0.18) with good accuracy.
Observed Self-Similarity of Precipitation Regimes over the Tropical Oceans
Authors: Elsaesser Gregory S. , Kummerow Christian D. , L’Ecuyer Tristan S. , Takayabu Yukari N. , Shige Shoichi
Published: January 2010

A K-means clustering algorithm was used to classify Tropical Rainfall Measuring Mission (TRMM) Precipitation Radar (PR) scenes within 1° square patches over the tropical (15°S–15°N) oceans. Three cluster centroids or “regimes” that minimize the Euclidean distance metric in a five-dimensional space of standardized variables were sought [convective surface rainfall rate; ratio of convective rain to total rain; and fractions of convective echo profiles with tops in three fixed height ranges (<5, 5–9, and >9 km)]. Independent cluster computations in adjacent ocean basins return very similar clusters in terms of PR echo-top distributions, rainfall, and diabatic heating profiles. The clusters consist of shallow convection (SHAL cluster), with a unimodal distribution of PR echo tops and composite diabatic heating rates of ∼2 K day−1 below 3 km; midlevel convection (MID-LEV cluster), with a bimodal distribution of PR echo tops and ∼5 K day−1 heating up to about 7 km; and deeper convection (DEEP cluster), with a multimodal distribution of PR echo tops and >20 K day−1 heating from 5 to 10 km. Each contributes roughly 20%–40% in terms of total tropical rainfall, but with MID-LEV clusters especially enhanced in the Indian and Atlantic sectors, SHAL relatively enhanced in the central and east Pacific, and DEEP most prominent in the western Pacific. While the clusters themselves are quite similar in rainfall and heating, specific cloud types defined according to the PR echo top and surface rainfall rate are less similar and exhibit systematic differences from one cluster to another, implying that the degree to which precipitation structures are similar decreases when one considers individual precipitating clouds as repeating tropical structures instead of larger-scale cluster ensembles themselves.
Deep Equatorial Ocean Circulation Induced by a Forced–Dissipated Yanai Beam*
Authors: Ascani François , Firing Eric , Dutrieux Pierre , McCreary Julian P. , Ishida Akio
Published: January 2010

A complex pattern of zonal currents below the thermocline has been observed in the equatorial Pacific and Atlantic Oceans. The currents have typical speeds from 10 to 15 cm s−1 and extend as deep as 2500 m. Their structure can be divided into two overlapping parts: the equatorial deep jets (EDJs), centered on the equator and alternating in the vertical with a wavelength of several hundred meters, and the Equatorial Intermediate Current system (EICS), composed of currents with large vertical scale and alternating with latitude over several degrees on either side of the equator. The strongest EICS current is a westward flow on the equator flanked by eastward currents at 2°N and 2°S.

In the present study, the authors use idealized numerical simulations and analytical solutions to demonstrate that the EICS currents within 2.5° from the equator could result from the self-advection with dissipation of a downward-propagating beam of monthly periodic Yanai (Rossby gravity) waves. The zonally restricted beam is generated in the eastern part of the basin by instabilities of the swift near-surface equatorial currents. For a weak Yanai wave amplitude and no dissipation, mean Eulerian currents resembling the three strongest EICS currents are obtained but only within the beam; in this case, the Eulerian flow is balanced by the wave-induced Stokes drift, yielding a zero-mean Lagrangian flow, and the water parcels conserve their potential vorticity (PV) and are stationary over a wave cycle. For larger amplitudes, the Yanai waves break, losing their energy to small vertical scales where it is dissipated. This dissipation changes the mean (wave averaged) PV of a water parcel within the beam, allowing the parcel to have a persistent equatorward drift across PV contours. This can be viewed as a wave-induced Sverdrup transport; by continuity and by virtue of the westward group velocity of long Rossby waves, this Lagrangian-mean meridional flow requires a Lagrangian-mean zonal flow within and to the west of the beam, with a meridional structure consistent with the three strongest EICS currents. This mechanism of EICS formation is active in some ocean general circulation models; its importance in the ocean remains to be evaluated.
Simultaneous Observations of Thin Humidity Gradients in the Lower Troposphere with a Raman Lidar and the Very High-Frequency Middle- and Upper-Atmosphere Radar
Authors: Luce H. , Takai T. , Nakamura T. , Yamamoto M. , Fukao S.
Published: January 2010

Humidity is, among other things, a key parameter in the evolution of atmospheric dynamics and in the formation of clouds and precipitation through latent heat release. The continuous observation of its vertical distribution is thus important in meteorology. In the absence of convection, humidity in the lower troposphere is distributed into nearly horizontally stratified layers. The thin humidity gradients at the edges of these layers are known to be the main cause of very high-frequency (VHF) stratosphere–troposphere (ST) radar backscatter in the lower troposphere. This property has been experimentally demonstrated many times in the literature from comparisons between balloon measurements and low-resolution radar observations. In the present work, original results of comparisons between Raman lidar measurements of water vapor and middle- and upper-atmosphere (MU) radar measurements of echo power using a range-imaging technique are shown at high spatial and temporal resolutions (∼50 m, ∼20 s). Other tremendous advantages of such comparisons are the simultaneity, time continuity, and colocalization of the lidar and radar measurements. The results show that the radar can be used for continuously monitoring the thin positive and negative gradients of humidity when operated in range-imaging mode. With additional information from balloon measurements, it would be possible to retrieve humidity profiles in the lower troposphere at an unprecedented vertical and time resolution.
Operational Monitoring of Radar Differential Reflectivity Using the Sun
Authors: Holleman Iwan , Huuskonen Asko , Gill Rashpal , Tabary Pierre
Published: January 2010

A method for the daily monitoring of the differential reflectivity bias for polarimetric weather radars is presented. Sun signals detected in polar volume data produced during operational scanning of the radar are used. This method is an extension of that for monitoring the weather radar antenna pointing at low elevations and the radar receiving chain using the sun. This “online” method is ideally suited for routine application in networks of operational radars.

The online sun monitoring can be used to check the agreement between horizontal and vertical polarization lobes of the radar antenna, which is a prerequisite for high-quality polarimetric measurements. By performing both online sun monitoring and rain calibration at vertical incidence, the differential receiver bias and differential transmitter bias can be disentangled. Results from the polarimetric radars in Trappes (France) and Bornholm (Denmark), demonstrating the importance of regular monitoring of the differential reflectivity bias, are discussed.

It is recommended that the online sun-monitoring method, preferably in combination with rain calibration, is routinely performed on all polarimetric weather radars because accurate calibration is a prerequisite for most polarimetric algorithms.
Fixing Globalization Institutionally
Authors: Chorev Nitsan
Published: January 2010

What are the origins of neoliberal and globalizing policies? The most common sociological explanation for the emergence of neoliberalism draws on the importance of institutional legacies. This article focuses, instead, on the fundamental role of institutional innovations. Rather than extant institutions, it was a new institutional context, itself an outcome of political struggles between supporters and critics of neoliberalism, which allowed for the emergence of neoliberal policies. The article investigates the case of trade liberalization in the US, showing that supporters of liberal trade defeated protectionists by challenging extant legacies, replacing old institutions with new ones. Internationalists managed to change protectionist policies by shifting decision-making authority from US Congress to quasi-judicial bodies in the executive and to judicial proceedings at the World Trade Organization.
The Stability of Self-Employment
Authors: Park Hyunjoon
Published: January 2010

The persistent role of self-employment in the Japanese and Korean economies and its changing character under recent economic and industrial changes merit renewed attention to self-employment in the two countries. Using individuals’ job history data, the article compares the occupational heterogeneity of self-employment activities and stability in Japan and Korea. Korea shows a much higher prevalence of shop/restaurant owners among total self-employment than Japan, where skilled blue-collar self-employed occupy a relatively large share. The hazard models of exit from self-employment show that the overall likelihood of leaving self-employment is greater among Korean self-employed than their Japanese counterparts. In Korea, shop/restaurant owners not only comprise the majority of self-employed persons but also show a fairly high risk of exit, similar to unskilled self-employed. This pattern is contrasted to shop/restaurant owners in Japan, who show considerable stability. The study addresses how differences in the stability of self-employment between Japan and Korea are linked to different features of broader work arrangements in the two countries.
Just over the horizon — the surveillance society and the state in the EU
Authors: Bunyan Tony
Published: January 2010

In cold war times, the ‘West espoused liberal democracy and freedom from surveillance and control. It is thus ironic that with the cold war a distant memory — though it only ended less than twenty years ago — the EU and its member states are set on a path which will, in just a few years time, turn it into the most surveilled, monitored region in the world. The wider context for all this is increased state racism (both at the national and EU levels), combined with the emergence of the ‘policing state , engendered by a political and governmental authoritarianism that legitimises itself through the trappings of representative democracy.
Palestine: notes from the inside
Authors: Issa Shawqi
Published: January 2010

This article, based on a talk given at the Institute of Race Relations on 14 April 2009, gives an account of the failures of the Palestinian leadership to respond effectively to Israel s strategy, which, it is argued, aims ultimately at the complete occupation of Palestine.
Validity, Utilization and Evidence-Based Policy: The Development and Impact of Performance Improvement Regimes in Local Public Services
Authors: Martin Steve , Downe James , Grace Clive , Nutley Sandra
Published: January 2010

Over the last decade, external assessments of organizational effectiveness have played an increasingly pivotal role in the regulation of UK local authorities. Unlike most approaches to evaluation, which are concerned with the implementation and outcomes of policies, programmes or interventions, these assessments are concerned primarily with internal organizational processes. And in contrast to traditional forms of public services inspection, which focus on specific services, they seek to judge the capacity of an organization as a whole. Inspectors in England, Scotland and Wales have taken different approaches to assessments of local authorities, but in all three cases their judgements have excited considerable interest among policy-makers, achieving a much higher level of utilization than is usual for evaluative activities and being credited with leading to significant improvements in public service organizations. There are, however, important questions about the validity of the measures they use and the sustainability of this approach to driving public services improvement.
Identifying the functional part of heparin-binding protein (HBP) as a monocyte stimulator and the novel role of monocytes as HBP producers
Authors: Schou Morten , Djurup René , Norris Kjeld , Flodgaard Hans
Published: January 2010

Heparin-binding protein (HBP), an evolutionary ancient and biologically highly important molecule in inflammation, is an inactive serine protease due to mutations in the catalytic triad. The histidine (position 41) in the conserved sequence TAAHC is mutated to serine and this sequence (TAASC) plays a crucial role when HBP binds to monocytes. We synthesized a 20—44 HBP peptide, cyclicized by a sulphur bridge, which encompasses this amino acid and functions as full-length HBP. Using a human monocyte cell line, we have shown that lipopolysaccharide (LPS)-triggered secretion of IL-6 is enhanced up to 10-fold when full-length HBP or the peptide are present in low-to-moderate concentrations. A monoclonal antibody neutralizing HBP also neutralizes the peptide, indicating that the ligand for the HBP receptor is located near serine in position 41 on the HBP surface. A ‘back mutated’ 20—44 peptide (serine→histidine) has some, but not significant, stimulatory effect on monocytes. Normally, HBP production and release is ascribed to neutrophil granulocytes, but here we find that also monocytes secrete HBP when stimulated with LPS. Furthermore, a small amount of HBP can be demonstrated when monocytes are incubated in medium alone. Our efforts to identify a suggested HBP receptor on monocytes has failed so far.
CpG oligodeoxynucleotide and double-stranded RNA synergize to enhance nitric oxide production and mRNA expression of inducible nitric oxide synthase, pro-inflammatory cytokines and chemokines in chicken monocytes
Authors: Haiqi He  , MacKinnon Kathryn M. , Genovese Kenneth J. , Kogut Michael H.
Published: January 2010

Toll-like receptors (TLRs) recognize microbial components and initiate the innate immune responses that control microbial infections. The interaction between ligands of TLR3 and TLR9, poly I:C (an analog of viral double-stranded RNA) and CpG-ODN (a CpG-motif containing oligodeoxydinucleotide) on the inflammatory immune responses, including the production of nitric oxide (NO) and the expression of inducible NO synthase (iNOS), pro-inflammatory cytokines interleukin (IL)-1β and IL-6, and chemokines IL-8 and macrophage inflammatory protein (MIP)-1β, were investigated in chicken monocytes. The NO production was significantly higher when stimulated with a combination of CpG-ODN and poly I:C than with either CpG-ODN or poly I:C alone. Similarly, a significant synergistic effect by CpG-ODN and poly I:C was observed in the up-regulation of iNOS and IL-8 mRNA after 2 h and persisted up to 24 h. Although the combinatory treatment of CpG-ODN and poly I:C enhanced the expression of IL-1β, IL-6, and MIP-1β(3 after 2 h stimulation, the synergism in the up-regulation of IL-1β and IL-6 mRNA was observed after 8-h and 24-h stimulation, respectively, whereas there was no synergistic effect on MIP-1β. Our results demonstrate that CpG-ODN synergizes with poly I:C to induce pro-inflammatory immune response in chicken monocytes.
PostMod: sequence based prediction of kinase-specific phosphorylation sites with indirect relationship
Authors: Jung Inkyung , Matsuyama Akihisa , Yoshida Minoru , Kim Dongsup
Published: January 2010

Background

Post-translational modifications (PTMs) have a key role in regulating cell functions. Consequently, identification of PTM sites has a significant impact on understanding protein function and revealing cellular signal transductions. Especially, phosphorylation is a ubiquitous process with a large portion of proteins undergoing this modification. Experimental methods to identify phosphorylation sites are labor-intensive and of high-cost. With the exponentially growing protein sequence data, development of computational approaches to predict phosphorylation sites is highly desirable.

Results

Here, we present a simple and effective method to recognize phosphorylation sites by combining sequence patterns and evolutionary information and by applying a novel noise-reducing algorithm. We suggested that considering long-range region surrounding a phosphorylation site is important for recognizing phosphorylation peptides. Also, from compared results to AutoMotif in 36 different kinase families, new method outperforms AutoMotif. The mean accuracy, precision, and recall of our method are 0.93, 0.67, and 0.40, respectively, whereas those of AutoMotif with a polynomial kernel are 0.91, 0.47, and 0.17, respectively. Also our method shows better or comparable performance in four main kinase groups, CDK, CK2, PKA, and PKC compared to six existing predictors.

Conclusion

Our method is remarkable in that it is powerful and intuitive approach without need of a sophisticated training algorithm. Moreover, our method is generally applicable to other types of PTMs.
HORI: a web server to compute Higher Order Residue Interactions in protein structures
Authors: Sundaramurthy Pandurangan , Shameer Khader , Sreenivasan Raashi , Gakkhar Sunita , Sowdhamini Ramanathan
Published: January 2010

Background

Folding of a protein into its three dimensional structure is influenced by both local and global interactions within a protein. Higher order residue interactions, like pairwise, triplet and quadruplet ones, play a vital role in attaining the stable conformation of the protein structure. It is generally agreed that higher order interactions make significant contribution to the potential energy landscape of folded proteins and therefore it is important to identify them to estimate their contributions to overall stability of a protein structure.

Results

We developed HORI [Higher order residue interactions in proteins], a web server for the calculation of global and local higher order interactions in protein structures. The basic algorithm of HORI is designed based on the classical concept of four-body nearest-neighbour propensities of amino-acid residues. It has been proved that higher order residue interactions up to the level of quadruple interactions plays a major role in the three-dimensional structure of proteins and is an important feature that can be used in protein structure analysis.

Conclusion

HORI server will be a useful resource for the structural bioinformatics community to perform analysis on protein structures based on higher order residue interactions. HORI server is a highly interactive web server designed in three modules that enables the user to analyse higher order residue interactions in protein structures. HORI server is available from the URL: http://caps.ncbs.res.in/hori
A hub-attachment based method to detect functional modules from confidence-scored protein interactions and expression profiles
Authors: Chin Chia-Hao , Chen Shu-Hwa , Ho Chin-Wen , Ko Ming-Tat , Lin Chung-Yen
Published: January 2010

Background

Many research results show that the biological systems are composed of functional modules. Members in the same module usually have common functions. This is useful information to understand how biological systems work. Therefore, detecting functional modules is an important research topic in the post-genome era. One of functional module detecting methods is to find dense regions in Protein-Protein Interaction (PPI) networks. Most of current methods neglect confidence-scores of interactions, and pay little attention on using gene expression data to improve their results.

Results

In this paper, we propose a novel hu b-attachment based method to detect functional modules from confidence-scored protein inte ractions and expression pr ofiles, and we name it HUNTER. Our method not only can extract functional modules from a weighted PPI network, but also use gene expression data as optional input to increase the quality of outcomes. Using HUNTER on yeast data, we found it can discover more novel components related with RNA polymerase complex than those existed methods from yeast interactome. And these new components show the close relationship with polymerase after functional analysis on Gene Ontology.

Conclusion

A C++ implementation of our prediction method, dataset and supplementary material are available at http://hub.iis.sinica.edu.tw/Hunter/. Our proposed HUNTER method has been applied on yeast data, and the empirical results show that our method can accurately identify functional modules. Such useful application derived from our algorithm can reconstruct the biological machinery, identify undiscovered components and decipher common sub-modules inside these complexes like RNA polymerases I, II, III.
Prediction of novel precursor miRNAs using a context-sensitive hidden Markov model (CSHMM)
Authors: Agarwal Sumeet , Vaz Candida , Bhattacharya Alok , Srinivasan Ashwin
Published: January 2010

Background

It has been apparent in the last few years that small non coding RNAs (ncRNA) play a very significant role in biological regulation. Among these microRNAs (miRNAs), 22-23 nucleotide small regulatory RNAs, have been a major object of study as these have been found to be involved in some basic biological processes. So far about 706 miRNAs have been identified in humans alone. However, it is expected that there may be many more miRNAs encoded in the human genome. In this report, a "context-sensitive" Hidden Markov Model (CSHMM) to represent miRNA structures has been proposed and tested extensively. We also demonstrate how this model can be used in conjunction with filters as an ab initio method for miRNA identification.

Results

The probabilities of the CSHMM model were estimated using known human miRNA sequences. A classifier for miRNAs based on the likelihood score of this "trained" CSHMM was evaluated by: (a) cross-validation estimates using known human sequences, (b) predictions on a dataset of known miRNAs, and (c) prediction on a dataset of non coding RNAs. The CSHMM is compared with two recently developed methods, miPred and CID-miRNA. The results suggest that the CSHMM performs better than these methods. In addition, the CSHMM was used in a pipeline that includes filters that check for the presence of EST matches and the presence of Drosha cutting sites. This pipeline was used to scan and identify potential miRNAs from the human chromosome 19. It was also used to identify novel miRNAs from small RNA sequences of human normal leukocytes obtained by the Deep sequencing (Solexa) methodology. A total of 49 and 308 novel miRNAs were predicted from chromosome 19 and from the small RNA sequences respectively.

Conclusion

The results suggest that the CSHMM is likely to be a useful tool for miRNA discovery either for analysis of individual sequences or for genome scan. Our pipeline, consisting of a CSHMM and filters to reduce false positives shows promise as an approach for ab initio identification of novel miRNAs.
Active machine learning for transmembrane helix prediction
Authors: Osmanbeyoglu Hatice U , Wehner Jessica A , Carbonell Jaime G , Ganapathiraju Madhavi K
Published: January 2010

Background

About 30% of genes code for membrane proteins, which are involved in a wide variety of crucial biological functions. Despite their importance, experimentally determined structures correspond to only about 1.7% of protein structures deposited in the Protein Data Bank due to the difficulty in crystallizing membrane proteins. Algorithms that can identify proteins whose high-resolution structure can aid in predicting the structure of many previously unresolved proteins are therefore of potentially high value. Active machine learning is a supervised machine learning approach which is suitable for this domain where there are a large number of sequences but only very few have known corresponding structures. In essence, active learning seeks to identify proteins whose structure, if revealed experimentally, is maximally predictive of others.

Results

An active learning approach is presented for selection of a minimal set of proteins whose structures can aid in the determination of transmembrane helices for the remaining proteins. TMpro, an algorithm for high accuracy TM helix prediction we previously developed, is coupled with active learning. We show that with a well-designed selection procedure, high accuracy can be achieved with only few proteins. TMpro, trained with a single protein achieved an F-score of 94% on benchmark evaluation and 91% on MPtopo dataset, which correspond to the state-of-the-art accuracies on TM helix prediction that are achieved usually by training with over 100 training proteins.

Conclusion

Active learning is suitable for bioinformatics applications, where manually characterized data are not a comprehensive representation of all possible data, and in fact can be a very sparse subset thereof. It aids in selection of data instances which when characterized experimentally can improve the accuracy of computational characterization of remaining raw data. The results presented here also demonstrate that the feature extraction method of TMpro is well designed, achieving a very good separation between TM and non TM segments.
An integrative modular approach to systematically predict gene-phenotype associations
Authors: Mehan Michael R , Nunez-Iglesias Juan , Dai Chao , Waterman Michael S , Zhou Xianghong Jasmine
Published: January 2010

Background

Complex human diseases are often caused by multiple mutations, each of which contributes only a minor effect to the disease phenotype. To study the basis for these complex phenotypes, we developed a network-based approach to identify coexpression modules specifically activated in particular phenotypes. We integrated these modules, protein-protein interaction data, Gene Ontology annotations, and our database of gene-phenotype associations derived from literature to predict novel human gene-phenotype associations. Our systematic predictions provide us with the opportunity to perform a global analysis of human gene pleiotropy and its underlying regulatory mechanisms.

Results

We applied this method to 338 microarray datasets, covering 178 phenotype classes, and identified 193,145 phenotype-specific coexpression modules. We trained random forest classifiers for each phenotype and predicted a total of 6,558 gene-phenotype associations. We showed that 40.9% genes are pleiotropic, highlighting that pleiotropy is more prevalent than previously expected. We collected 77 ChIP-chip datasets studying 69 transcription factors binding over 16,000 targets under various phenotypic conditions. Utilizing this unique data source, we confirmed that dynamic transcriptional regulation is an important force driving the formation of phenotype specific gene modules.

Conclusion

We created a genome-wide gene to phenotype mapping that has many potential implications, including providing potential new drug targets and uncovering the basis for human disease phenotypes. Our analysis of these phenotype-specific coexpression modules reveals a high prevalence of gene pleiotropy, and suggests that phenotype-specific transcription factor binding may contribute to phenotypic diversity. All resources from our study are made freely available on our online Phenotype Prediction Database [1].
Proteomic analysis of peach fruit mesocarp softening and chilling injury using difference gel electrophoresis (DIGE)
Authors: Nilo Ricardo , Saffie Carlos , Lilley Kathryn , Baeza-Yates Ricardo , Cambiazo Verónica , Campos-Vargas Reinaldo , González Mauricio , Meisel Lee A , Retamales Julio , Silva Herman , Orellana Ariel
Published: January 2010

Background

Peach fruit undergoes a rapid softening process that involves a number of metabolic changes. Storing fruit at low temperatures has been widely used to extend its postharvest life. However, this leads to undesired changes, such as mealiness and browning, which affect the quality of the fruit. In this study, a 2-D DIGE approach was designed to screen for differentially accumulated proteins in peach fruit during normal softening as well as under conditions that led to fruit chilling injury.

Results

The analysis allowed us to identify 43 spots -representing about 18% of the total number analyzed- that show statistically significant changes. Thirty-nine of the proteins could be identified by mass spectrometry. Some of the proteins that changed during postharvest had been related to peach fruit ripening and cold stress in the past. However, we identified other proteins that had not been linked to these processes. A graphical display of the relationship between the differentially accumulated proteins was obtained using pairwise average-linkage cluster analysis and principal component analysis. Proteins such as endopolygalacturonase, catalase, NADP-dependent isocitrate dehydrogenase, pectin methylesterase and dehydrins were found to be very important for distinguishing between healthy and chill injured fruit. A categorization of the differentially accumulated proteins was performed using Gene Ontology annotation. The results showed that the 'response to stress', 'cellular homeostasis', 'metabolism of carbohydrates' and 'amino acid metabolism' biological processes were affected the most during the postharvest.

Conclusions

Using a comparative proteomic approach with 2-D DIGE allowed us to identify proteins that showed stage-specific changes in their accumulation pattern. Several proteins that are related to response to stress, cellular homeostasis, cellular component organization and carbohydrate metabolism were detected as being differentially accumulated. Finally, a significant proportion of the proteins identified had not been associated with softening, cold storage or chilling injury-altered fruit before; thus, comparative proteomics has proven to be a valuable tool for understanding fruit softening and postharvest.
Expression profiling of prospero in the Drosophila larval chemosensory organ: Between growth and outgrowth
Authors: Guenin Laure , Raharijaona Mahatsangy , Houlgatte Rémi , Baba-Aissa Fawzia
Published: January 2010

Background

The antenno-maxilary complex (AMC) forms the chemosensory system of theDrosophilalarva and is involved in gustatory and olfactory perception. We have previously shown that a mutant allele of the homeodomain transcription factor Prospero (prosVoila1,V1), presents several developmental defects including abnormal growth and altered taste responses. In addition, many neural tracts connecting the AMC to the central nervous system (CNS) were affected. Our earlier reports on larval AMC did not argue in favour of a role ofprosin cell fate decision, but strongly suggested thatproscould be involved in the control of other aspect of neuronal development. In order to identify these functions, we used microarray analysis of larval AMC and CNS tissue isolated from the wild type, and three other previously characterisedprosperoalleles, including theV1mutant, considered as a null allele for the AMC.

Results

A total of 17 samples were first analysed with hierarchical clustering. To determine those genes affected by loss ofprosfunction, we calculated a discriminating score reflecting the differential expression betweenV1mutant and otherprosalleles. We identified a total of 64 genes in the AMC. Additional manual annotation using all the computed information on the attributed role of these genes in theDrosophilalarvae nervous system, enabled us to identify one functional category of potential Prospero target genes known to be involved in neurite outgrowth, synaptic transmission and more specifically in neuronal connectivity remodelling. The second category of genes found to be differentially expressed between the null mutant AMC and the other alleles concerned the development of the sensory organs and more particularly the larval olfactory system. Surprisingly, a third category emerged from our analyses and suggests an association ofproswith the genes that regulate autophagy, growth and insulin pathways. Interestingly, EGFR and Notch pathways were represented in all of these three functional categories. We now propose that Pros could perform all of these different functions through the modulation of these two antagonistic and synergic pathways.

Conclusions

The current data contribute to the clarification of theprosperofunction in the larval AMC and show thatprosregulates different function in larvae as compared to those controlled by this gene in embryos. In the future, the possible mechanism by which Pros could achieve its function in the AMC will be explored in detail.
Expression profiling and cross-species RNA interference (RNAi) of desiccation-induced transcripts in the anhydrobiotic nematode Aphelenchus avenae
Authors: Reardon Wesley , Chakrabortee Sohini , Pereira Tiago Campos , Tyson Trevor , Banton Matthew C , Dolan Katharine M , Culleton Bridget A , Wise Michael J , Burnell Ann M , Tunnacliffe Alan
Published: January 2010

Background

Some organisms can survive extreme desiccation by entering a state of suspended animation known as anhydrobiosis. The free-living mycophagous nematodeAphelenchus avenaecan be induced to enter anhydrobiosis by pre-exposure to moderate reductions in relative humidity (RH) prior to extreme desiccation. This preconditioning phase is thought to allow modification of the transcriptome by activation of genes required for desiccation tolerance.

Results

To identify such genes, a panel of expressed sequence tags (ESTs) enriched for sequences upregulated inA. avenaeduring preconditioning was created. A subset of 30 genes with significant matches in databases, together with a number of apparently novel sequences, were chosen for further study. Several of the recognisable genes are associated with water stress, encoding, for example, two new hydrophilic proteins related to the late embryogenesis abundant (LEA) protein family. Expression studies confirmed EST panel members to be upregulated by evaporative water loss, and the majority of genes was also induced by osmotic stress and cold, but rather fewer by heat. We attempted to use RNA interference (RNAi) to demonstrate the importance of this gene set for anhydrobiosis, but foundA. avenaeto be recalcitrant with the techniques used. Instead, therefore, we developed a cross-species RNAi procedure usingA. avenaesequences in another anhydrobiotic nematode,Panagrolaimus superbus, which is amenable to gene silencing. Of 20A. avenaeESTs screened, a significant reduction in survival of desiccation in treatedP. superbuspopulations was observed with two sequences, one of which was novel, while the other encoded a glutathione peroxidase. To confirm a role for glutathione peroxidases in anhydrobiosis, RNAi with cognate sequences fromP. superbuswas performed and was also shown to reduce desiccation tolerance in this species.

Conclusions

This study has identified and characterised the expression profiles of members of the anhydrobiotic gene set inA. avenae. It also demonstrates the potential of RNAi for the analysis of anhydrobiosis and provides the first genetic data to underline the importance of effective antioxidant systems in metazoan desiccation tolerance.
Association between novel TARDBP mutations and Chinese patients with amyotrophic lateral sclerosis
Authors: Xiong Hui-Ling , Wang Jin-Yang , Sun Yi-Min , Wu Jian-Jun , Chen Yan , Qiao Kai , Zheng Qiao-Juan , Zhao Gui-xian , Wu Zhi-Ying
Published: January 2010

Background

TARDBP mutations have been reported in patients with amyotrophic lateral sclerosis (ALS) in different populations except Chinese. The present aim is to investigate the association between TARDBP mutations and Chinese patients with ALS.

Methods

71 SALS patients and 5 FALS families with non-SOD1 mutations were screened for TARDBP mutations via direct sequencing.

Results

A novel heterozygous variation, Ser292Asn (875G>A), was identified in the proband and 4 asymptomatic relatives including the children of the dead patient from a FALS family. Thus the dead patient, the proband's brother, was speculated to carry Ser292Asn though his sample was unavailable to the detection. This variation was not found in 200 unrelated control subjects. A homology search of the TDP-43 protein in different species demonstrated that it was highly conserved. Also, it was predicted to be deleterious to protein function with SIFT-calculated probabilities of 0.00. Therefore, Ser292Asn is predicted to be a pathogenic mutation. In addition, we have found two silent mutations (Gly40Gly and Ala366Ala) and one novel polymorphism (239-18t>c).

Conclusions

The present data have extended the spectrum of TARDBP mutations and polymorphisms, and supported the pathological role of TDP-43 in Chinese ALS patients.
Impact of gene variants on sex-specific regulation of human Scavenger receptor class B type 1 (SR-BI) expression in liver and association with lipid levels in a population-based study
Authors: Chiba-Falek Ornit , Nichols Marshall , Suchindran Sunil , Guyton John , Ginsburg Geoffrey S , Barrett-Connor Elizabeth , McCarthy Jeanette J
Published: January 2010

Background

Several studies have noted that genetic variants of SCARB1, a lipoprotein receptor involved in reverse cholesterol transport, are associated with serum lipid levels in a sex-dependent fashion. However, the mechanism underlying this gene by sex interaction has not been explored.

Methods

We utilized both epidemiological and molecular methods to study how estrogen and gene variants interact to influence SCARB1 expression and lipid levels. Interaction between 35 SCARB1 haplotype-tagged polymorphisms and endogenous estradiol levels was assessed in 498 postmenopausal Caucasian women from the population-based Rancho Bernardo Study. We further examined associated variants with overall and SCARB1 splice variant (SR-BI and SR-BII) expression in 91 human liver tissues using quantitative real-time PCR.

Results

Several variants on a haplotype block spanning intron 11 to intron 12 of SCARB1 showed significant gene by estradiol interaction affecting serum lipid levels, the strongest for rs838895 with HDL-cholesterol (p = 9.2 × 10-4) and triglycerides (p = 1.3 × 10-3) and the triglyceride:HDL cholesterol ratio (p = 2.7 × 10-4). These same variants were associated with expression of the SR-BI isoform in a sex-specific fashion, with the strongest association found among liver tissue from 52 young women <45 years old (p = 0.002).

Conclusions

Estrogen and SCARB1 genotype may act synergistically to regulate expression of SCARB1 isoforms and impact serum levels of HDL cholesterol and triglycerides. This work highlights the importance of considering sex-dependent effects of gene variants on serum lipid levels.
Training auscultatory skills: computer simulated heart sounds or additional bedside training? A randomized trial on third-year medical students
Authors: Sverdrup Øystein , Jensen Torstein , Solheim Svein , Gjesdal Knut
Published: January 2010

Background

The present study compares the value of additional use of computer simulated heart sounds, to conventional bedside auscultation training, on the cardiac auscultation skills of 3rd year medical students at Oslo University Medical School.

Methods

In addition to their usual curriculum courses, groups of seven students each were randomized to receive four hours of additional auscultation training either employing a computer simulator system or adding on more conventional bedside training. Cardiac auscultation skills were afterwards tested using live patients. Each student gave a written description of the auscultation findings in four selected patients, and was rewarded from 0-10 points for each patient. Differences between the two study groups were evaluated using student's t-test.

Results

At the auscultation test no significant difference in mean score was found between the students who had used additional computer based sound simulation compared to additional bedside training.

Conclusions

Students at an early stage of their cardiology training demonstrated equal performance of cardiac auscultation whether they had received an additional short auscultation course based on computer simulated training, or had had additional bedside training.