bluuebunny/crossref_metadata_2025 huggingface dataset:
On interfacial instability as a cause of transverse subcritical bed forms
Authors: Venditti Jeremy G. , Church Michael , Bennett Sean J.
Published: July 2006

Recent experimental results suggest there are at least two distinct bed form initiation processes. Bed forms may be generated from local bed defects that are propagated down and across stream by flow separation processes when sediment transport is patchy and sporadic. Alternatively, bed form development may occur over the whole bed at once when sediment transport is general and widespread. Herein, we critically test a simple model for this latter bed form initiation mode that was originally presented by H.‐K. Liu in 1957 but not tested because of the complex nature of the measurements required. The theory is based on the idea that a moving sand bed might be likened to a dense fluid and that a hydrodynamic instability develops at the interface between the sediment transport layer and the near‐bed fluid, leading to the organization of the transport system into laterally extended, discrete bed forms. Our predicted initial bed form lengths are within 10% of the lengths observed in a series of flume experiments, suggesting that transverse waveforms on sand beds sheared by unidirectional currents can be initiated as an interfacial hydrodynamic instability of Kelvin‐Helmholtz type when the current is sufficiently vigorous to produce general sediment movement, that is, to create a sediment transport layer that acts as a pseudofluid with density composed of solid and fluid components.
Biological carbon pump revisited: Feedback mechanisms between climate and the Redfield ratio
Authors: Omta Anne Willem , Bruggeman Jorn , Kooijman S. A. L. M. , Dijkstra Henk A.
Published: July 2006

Biological activity gives rise to a difference in carbon concentration between the ocean surface and the deep waters. This difference is determined by the carbon:nutrient ratio of the sinking organic material and it is crucial in determining the distribution of CO2 between the atmosphere and the ocean. For this reason, it is interesting to determine whether the physical environment affects the carbon:nitrogen ratio of phytoplankton. Using a model with a novel representation of the effect of temperature on phytoplankton stoichiometry, we have investigated the influence of mixed‐layer depth and water temperature on the elemental composition of an algal community. In the light‐limited regime, the carbon:nutrient ratio turns out to decrease with increasing mixed‐layer depth and temperature. Hence our model suggests the existence of a positive feedback between temperature and atmospheric CO2 content through the stoichiometry of phytoplankton. This feedback may have contributed to the glacial/interglacial cycles in the atmospheric CO2 concentration.
Recent western South Atlantic bottom water warming
Authors: Johnson Gregory C. , Doney Scott C.
Published: July 2006

Potential temperature differences are computed from hydrographic sections transiting the western basins of the South Atlantic Ocean from 60°S to the equator in 2005/2003 and 1989/1995. While warming is observed throughout much of the water column, the most statistically significant warming is about +0.04°C in the bottom 1500 dbar of the Brazil Basin, with similar (but less statistically significant) warming signals in the abyssal Argentine Basin and Scotia Sea. These abyssal waters of Antarctic origin spread northward in the South Atlantic. The observed abyssal Argentine Basin warming is of a similar magnitude to that previously reported between 1980 and 1989. The Brazil Basin abyssal warming is similar in size to and consistent in timing with previously reported changes in abyssal southern inflow and northern outflow. The temperature changes reported here, if they were to hold throughout the abyssal world ocean, would contribute substantially to global ocean heat budgets.
Localization of volcanic activity: Topographic effects on dike propagation, eruption and conduit formation
Authors: Gaffney Edward S. , Damjanac Branko
Published: July 2006

Magma flow in a dike rising in a crack whose strike runs from a highland or a ridge to an adjacent lowland has been modelled to determine the effect of topography on the flow. It is found that there is a distinct tendency for the flow to be diverted away from the highland end of the strike toward the lowland. Separation of the geometric effect of the topography from its effect on lateral confining stresses on the crack indicates that both contribute to the effect but that the effect of stress is less important. Although this analysis explains a tendency for volcanic eruptions to occur in low lands, it does not preclude eruptions on highlands. The particular configuration modelled mimics topography around the proposed nuclear waste repository at Yucca Mountain, Nevada, so that the results may indicate some reduction in the volcanic hazard to the site.
Surface-enhanced Raman scattering of silver-gold bimetallic nanostructures with hollow interiors
Authors: Wang Yuling , Chen Hongjun , Dong Shaojun , Wang Erkang
Published: July 2006

Surface-enhanced Raman scattering (SERS) activity of silver-gold bimetallic nanostructures (a mean diameter of ∼100nm) with hollow interiors was checked using p-aminothiophenol (p-ATP) as a probe molecule at both visible light (514.5nm) and near-infrared (1064nm) excitation. Evident Raman peaks of p-ATP were clearly observed, indicating the enhancement Raman scattering activity of the hollow nanostructure to p-ATP. The enhancement factors (EF) at the hollow nanostructures were obtained to be as large as (0.8±0.3)×106 and (2.7±0.5)×108 for 7a and 19b (b2) vibration mode, respectively, which was 30–40 times larger than that at silver nanoparticles with solid interiors at 514.5nm excitation. EF values were also obtained at 1064nm excitation for 7a and b2-type vibration mode, which were estimated to be as large as (1.0±0.3)×106 and (0.9±0.2)×107, respectively. The additional EF values by a factor of ∼10 for b2-type band were assumed to be due to the chemical effect. Large electromagnetic EF values were presumed to derive from a strong localized plasmas electromagnetic field existed at the hollow nanostructures. SERS activity of hollow nanostructures with another size (a mean diameter of ∼80nm) was also investigated and large EF for 7a and b2-type band are obtained to be (0.6±0.3)×106 and (1.7±0.7)×108, respectively, at 514.5nm excitation and (0.2±0.1)×106 and (0.6±0.2)×107, respectively, at 1064nm excitation. Although the optical properties of the hollow nanostructures have not yet been well studied, high SERS activities of the nanostructures with hollow interiors have been exhibited in our report.
Rotationally resolved infrared spectrum of the Li+–D2 cation complex
Authors: Thompson C. D. , Emmeluth C. , Poad B. L. J. , Weddle G. H. , Bieske E. J.
Published: July 2006

The infrared spectrum of mass selected Li+–D2 cations is recorded in the D–D stretch region (2860–2950cm−1) in a tandem mass spectrometer by monitoring Li+ photofragments. The D–D stretch vibration of Li+–D2 is shifted by −79cm−1 from that of the free D2 molecule indicating that the vibrational excitation of the D2 subunit strengthens the effective Li+⋯D2 intermolecular interaction. Around 100 rovibrational transitions, belonging to parallel Ka=0-0, 1-1, and 2-2 subbands, are fitted to a Watson A-reduced Hamiltonian to yield effective molecular parameters. The infrared spectrum shows that the complex consists of a Li+ ion attached to a slightly perturbed D2 molecule with a T-shaped equilibrium configuration and a 2.035Å vibrationally averaged intermolecular separation. Comparisons are made between the spectroscopic data and data obtained from rovibrational calculations using a recent three dimensional Li+–D2 potential energy surface [R. Martinazzo, G. Tantardini, E. Bodo, and F. Gianturco, J. Chem. Phys. 119, 11241 (2003)].
Symmetry of quantum torus with crossed product algebra
Authors: Chang-Young Ee , Kim Hoil
Published: July 2006

In this paper, we study the symmetry of quantum torus with the concept of crossed product algebra. As a classical counterpart, we consider the orbifold of classical torus with complex structure and investigate the transformation property of classical theta function. An invariant function under the group action is constructed as a variant of the classical theta function. Then our main issue, the crossed product algebra representation of a quantum torus with complex structure under the symplectic group, is analyzed as a quantum version of orbifolding. We perform this analysis with Manin’s so-called model II quantum theta function approach. The symplectic group Sp(2n,Z) satisfies the consistency condition of a crossed product algebra representation of quantum torus times the algebra of functions on the Siegel space. However, only a subgroup of Sp(2n,Z) satisfies the consistency condition for orbifolding of the quantum torus.
Controlling photoinduced degradation in plastic photovoltaic cells: A time-resolved energy dispersive x-ray reflectometry study
Authors: Paci Barbara , Generosi Amanda , Rossi Albertini Valerio , Perfetti Paolo , de Bettignies Remi , Leroy Joceline , Firon Muriel , Sentein Carole
Published: July 2006

The electrode-active layer interface of organic photovoltaic cells, a critical point in the development of organic devices, was studied by the energy dispersive x-ray reflectivity (EDXR) technique applied in situ. An EDXR-based protocol allowing discrimination between the possible mechanisms that produce the aging process at the interface was established. The study detects photoinduced oxidation of the electrode at the buried interface, to which fading of the device performances could be attributed. This conclusion was further confirmed by results obtained on a new cell, of selectively modified architecture, whose performances turned out to be stable in time.
Photoinduced piezo-optical effect in Er doped ZnO films
Authors: Williams T. M. , Hunter D. , Pradhan A. K. , Kityk I. V.
Published: July 2006

A large increase of diagonal piezo-optic coefficient (up to 3.7×10−13m2∕N at λ=633nm) was observed in Er doped ZnO films under photoinduced treatment by two laser beams with frequencies of 1,060 and 530nm originating from the same Nd:YAG pulsed laser. It was demonstrated that piezo-optic effect is enhanced with increasing film thickness. This may be a consequence of the disturbance of the long range ordering in the nanocrystallites for the film with larger film thickness. The observed effect is explained due to Er ions creating additional local polarizability.
Singlet excimer electroluminescence within N,N′-di-1-naphthalenyl-N,N′-diphenyl-[1,1′-biphenyl]-4,4′-diamine based diodes
Authors: Losio Paolo A. , Khan Rizwan U. A. , Günter Peter , Yap Boon Kar , Wilson Jo S. , Bradley Donal D. C.
Published: July 2006

The authors report the fabrication of organic light-emitting diodes based on N,N′-di-1-naphthalenyl-N,N′-diphenyl-[1,1′-biphenyl]-4,4′-diamine (NPB) that emit via singlet excimer states. When the film deposition rate of NPB is reduced from 17to1nm∕min, they observe a reduction in intensity of the photoluminescence peak at 437nm and the evolution of a new, broader peak at 503nm. From optical absorption and time resolved photoluminescence data the authors attribute this new peak to singlet excimer emission. The authors demonstrate green electroluminescence from organic diodes that utilize this effect. The possible morphological variations resulting in the monomer to excimer transition are discussed.
Strong cotunneling suppression in a single-electron transistor with granulated metal film island
Authors: Luo Xiangning , Tomcsanyi Miklos , Orlov Alexei O. , Kosel Thomas H. , Snider Gregory L.
Published: July 2006

Macroscopic quantum tunneling (cotunneling) is a major source of errors in single-electron devices that require the transfer of a precise number of electrons. The authors present a single-electron transistor (SET) where the suppression of cotunneling is achieved by using a granulated metal film as the material of the SET island. In this device a characteristic charging energy is defined by the Al∕AlOx junctions while the cotunneling is suppressed by electron scattering in the granulated metal island. The authors discuss possible applications of this solution for single-electron latches and pumps.
Low density InAs quantum dots grown on GaAs nanoholes
Authors: Liang B. L. , Wang Zh. M. , Lee J. H. , Sablon K. , Mazur Yu. I. , Salamo G. J.
Published: July 2006

A growth technique combining droplet epitaxy and molecular beam epitaxy (MBE) is developed to obtain a low density of InAs quantum dots (QDs) on GaAs nanoholes. This growth technique is simple, flexible, and does not require additional substrate processing. It makes possible separate control of the QD density via droplet epitaxy and the QD quality via MBE growth. In this letter the authors report the use of this technique to produce InAs QDs with a low density of 2.7×108cm−2 as well as good photoluminescence properties. The resulting samples are suitable for single QD device fabrication and applications.
Magnetic properties of Sm–Fe–N thick films produced by compression shearing
Authors: Saito Tetsuji , Sato Hisanobu
Published: July 2006

Sm–Fe–N powders were deposited onto an aluminum substrate at room temperature in ambient atmosphere by compression shearing. In contrast to other film processing techniques, a thick film was produced at an extremely high production rate of 180μm∕min. The resultant thick film retained the original Sm2Fe17N3 phase structure without any appreciable decomposition of the Sm2Fe17N3 phase. The thick films exhibited magnetic properties matching the original Sm–Fe–N powder.
Improved tunneling magnetoresistance in interface engineered (La,Sr)MnO3 junctions
Authors: Ishii Y. , Yamada H. , Sato H. , Akoh H. , Ogawa Y. , Kawasaki M. , Tokura Y.
Published: July 2006

Spin tunnel junctions were fabricated and characterized with various insulating barriers and interface structures employing (La,Sr)MnO3 (LSMO) as the ferromagnetic electrodes. Junctions with LaAlO3 barriers exhibited systematically larger tunnel magnetoresistance (TMR) (TMR ratio ∼230% at 10K) than those with SrTiO3 barriers (∼50%). When two unit cells of nondoped LaMnO3 are inserted between LSMO and SrTiO3 at both interfaces in the SrTiO3-barrier junction, the TMR was also significantly enhanced to ∼170%. These results, including the temperature dependence of TMR, qualitatively agree with the characteristics of the local magnetization at the interface that was evaluated by magnetization-induced second harmonic generation (MSHG) for the corresponding interface structures. However, slight deviations appear as a systematic suppression of TMR for all the junctions at high temperatures compared with MSHG results. Also, TMR results appear to be more degraded than MSHG results for the SrTiO3-barrier junctions. The barrier thickness dependence of the TMR response revealed that a spin-independent and inelastic conduction channel is a possible origin for the apparent suppression of TMR compared with MSHG.
Olefin metathesis and quadruple hydrogen bonding: A powerful combination in multistep supramolecular synthesis
Authors: Scherman Oren A. , Ligthart G. B. W. L. , Ohkawa Haruki , Sijbesma Rint P. , Meijer E. W.
Published: July 2006

We show that combining concepts generally used in covalent organic synthesis such as retrosynthetic analysis and the use of protecting groups, and applying them to the self-assembly of polymeric building blocks in multiple steps, results in a powerful strategy for the self-assembly of dynamic materials with a high level of architectural control. We present a highly efficient synthesis of bifunctional telechelic polymers by ring-opening metathesis polymerization (ROMP) with complementary quadruple hydrogen-bonding motifs. Because the degree of functionality for the polymers is 2.0, the formation of alternating, blocky copolymers was demonstrated in both solution and the bulk leading to stable, microphase-separated copolymer morphologies.
Reading comprehension in children with specific language impairment: an examination of two subgroups
Authors: Kelso Katrina , Fletcher Janet , Lee Penny
Published: July 2006

Background: In reading research, children with specific language impairment (SLI) have tended to be included in groups of children expected to have difficulties with both decoding and reading comprehension (generally poor readers). This is because generally children with specific language impairment display difficulties with phonology as well as syntax and/or semantics. However, children with specific language impairment are a heterogeneous group. Many children with specific language impairment have oral comprehension difficulties that are likely to limit reading comprehension. A subgroup of these children may exhibit intact phonological and decoding skills. If so, they would resemble the children with specific reading comprehension difficulties (poor comprehenders) reported in the literature.

Aims: This study sought to identify a group of children with a poor comprehender reading profile amongst children with specific language impairment. It then compared the phonological and oral comprehension skills of the group of 15 poor comprehenders with a group of 15 generally poor readers with specific language impairment, to identify any differences in language skills. Secondarily, the study wanted to determine which of the language tasks best predicted group membership.

Methods & Procedures: The study was carried out in two phases. In Phase 1, children with specific language impairment were assessed on the Woodcock Word Attack to identify a group with adequate decoding skills. These children had poor reading comprehension on the Neale Analysis of Reading Ability. From the poor decoders on the Word Attack, a second group of children, matched for age and gender, was selected to form the generally poor reader group. In Phase 2, the participants were assessed on a battery of phonological and oral comprehension tasks.

Outcomes & Results: A group of children exhibiting a poor comprehender reading profile was found to exist amongst children with specific language impairment. As expected, the poor comprehenders performed significantly better than the generally poor readers on phonological awareness tasks. On the oral comprehension tasks, the two groups did not differ at the word and sentence level; however, the poor comprehenders had significantly weaker oral comprehension skills at the paragraph level.

Conclusions: This study found that children with specific language impairment, who have equally poor reading comprehension but which differ in their decoding ability, differ not only in their performance on phonological tasks, but also on oral comprehension at the paragraph level. This indicates a need for paragraph‐level oral comprehension to be included in assessment. In addition, educational and clinical intervention programmes for children with specific language impairment should ensure that they are meeting individual needs.
Short Article: Lexically Guided Retuning of Letter Perception
Authors: Norris Dennis , Butterfield Sally , McQueen James M. , Cutler Anne
Published: July 2006

Participants made visual lexical decisions to upper-case words and nonwords, and then categorized an ambiguous N–H letter continuum. The lexical decision phase included different exposure conditions: Some participants saw an ambiguous letter “?”, midway between N and H, in N-biased lexical contexts (e.g., REIG?), plus words with unambiguous H (e.g., WEIGH); others saw the reverse (e.g., WEIG?, REIGN). The first group categorized more of the test continuum as N than did the second group. Control groups, who saw “?” in nonword contexts (e.g., SMIG?), plus either of the unambiguous word sets (e.g., WEIGH or REIGN), showed no such subsequent effects. Perceptual learning about ambiguous letters therefore appears to be based on lexical knowledge, just as in an analogous speech experiment (Norris, McQueen, & Cutler, 2003) which showed similar lexical influence in learning about ambiguous phonemes. We argue that lexically guided learning is an efficient general strategy available for exploitation by different specific perceptual tasks.
Short Article: Preference Reversals are Diminished when Gambles are Presented as Relative Frequencies
Authors: Tunney Richard J.
Published: July 2006

Preference reversals are a well-documented example of suboptimal decision making. Typical preference reversals experiments have involved monetary bets presented in probability format. Research on other examples of decision making have shown that irrational or suboptimal choices are diminished or eliminated entirely when the probabilities are presented as relative frequencies (e.g., Gigerenzer & Hoffrage, 1995). The aim of the present experiment was to determine if the way in which information is presented to participants affects participants’ preferences. When the options were presented in the standard probability format 59% of participants’ preferences were reversed. However, reversals were significantly decreased in the frequency format group, with only 40% of participants’ responses being inconsistent. Although preference reversals were not eliminated when the gambles were presented as frequencies they were significantly diminished and may not be such a robust example of irrational decision making after all.
Spirals in the boundary of slices of quasi-Fuchsian space
Authors: Goodman Dan
Published: July 2006

We prove that the Bers and Maskit slices of the quasi-Fuchsian space of a once-punctured torus have a dense, uncountable set of points in their boundaries about which the boundary spirals infinitely.
Role of Insulin-dependent Cortical Fodrin/Spectrin Remodeling in Glucose Transporter 4 Translocation in Rat Adipocytes
Authors: Liu Libin , Jedrychowski Mark P. , Gygi Steven P. , Pilch Paul F.
Published: July 2006

Fodrin or nonerythroid spectrin is an abundant component of the cortical cytoskeletal network in rat adipocytes. Fodrin has a highly punctate distribution in resting cells, and insulin causes a dramatic remodeling of fodrin to a more diffuse pattern. Insulin-mediated remodeling of actin occurs to a lesser extent than does that of fodrin. We show that fodrin interacts with the t-soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) syntaxin 4, and this interaction is increased by insulin stimulation and decreased by prior latrunculin A treatment. Latrunculin A disrupts all actin filaments, inhibits glucose transporter 4 (GLUT4) translocation, and causes fodrin to partially redistribute from the plasma membrane to the cytosol. In contrast, cytochalasin D disrupts only the short actin filament signal, and cytochalasin D neither inhibits GLUT4 translocation nor fodrin redistribution in adipocytes. Together, our data suggest that insulin induces remodeling of the fodrin–actin network, which is required for the fusion of GLUT4 storage vesicles with the plasma membrane by permitting their access to the t-SNARE syntaxin 4.
A Single Common Portal for Clathrin-mediated Endocytosis of Distinct Cargo Governed by Cargo-selective Adaptors
Authors: Keyel Peter A. , Mishra Sanjay K. , Roth Robyn , Heuser John E. , Watkins Simon C. , Traub Linton M.
Published: July 2006

Sorting of transmembrane cargo into clathrin-coated vesicles requires endocytic adaptors, yet RNA interference (RNAi)-mediated gene silencing of the AP-2 adaptor complex only disrupts internalization of a subset of clathrin-dependent cargo. This suggests alternate clathrin-associated sorting proteins participate in cargo capture at the cell surface, and a provocative recent proposal is that discrete endocytic cargo are sorted into compositionally and functionally distinct clathrin coats. We show here that the FXNPXY-type internalization signal within cytosolic domain of the LDL receptor is recognized redundantly by two phosphotyrosine-binding domain proteins, Dab2 and ARH; diminishing both proteins by RNAi leads to conspicuous LDL receptor accumulation at the cell surface. AP-2–dependent uptake of transferrin ensues relatively normally in the absence of Dab2 and ARH, clearly revealing delegation of sorting operations at the bud site. AP-2, Dab2, ARH, transferrin, and LDL receptors are all present within the vast majority of clathrin structures at the surface, challenging the general existence of specialized clathrin coats for segregated internalization of constitutively internalized cargo. However, Dab2 expression is exceptionally low in hepatocytes, likely accounting for the pathological hypercholesterolemia that accompanies ARH loss.
Novel Function of Clathrin Light Chain in Promoting Endocytic Vesicle Formation
Authors: Newpher Thomas M. , Idrissi Fatima-Zahra , Geli Maria Isabel , Lemmon Sandra K.
Published: July 2006

Clathrin-mediated endocytosis is a major pathway for uptake of lipid and protein cargo at the plasma membrane. The lattices of clathrin-coated pits and vesicles are comprised of triskelions, each consisting of three oligomerized heavy chains (HC) bound by a light chain (LC). In addition to binding HC, LC interacts with members of the Hip1/R family of endocytic proteins, including the budding yeast homologue, Sla2p. Here, using in vivo analysis in yeast, we provide novel insight into the role of this interaction. We find that overexpression of LC partially restores endocytosis to cells lacking clathrin HC. This suppression is dependent on the Sla2p binding region of LC. Using live cell imaging techniques to visualize endocytic vesicle formation, we find that the N-terminal Sla2p binding region of LC promotes the progression of arrested Sla2p patches that form in the absence of HC. We propose that LC binding to Sla2p positively regulates Sla2p for efficient endocytic vesicle formation.
Inferring Functional Pathways from Multi-Perturbation Data
Authors: Yosef Nir , Kaufman Alon , Ruppin Eytan
Published: July 2006

Background: Recently, a conceptually new approach for analyzing gene networks, the Functional Influence Network (FIN) was presented. The FIN approach uses the measured performance of a given cellular function under different multi-perturbations, to identify the main functional pathways and interactions underlying its processing. Here we present and study an iterative, extended version of FIN, the Functional Influence Network Extractor (FINE), which is specifically geared towards the accurate analysis of sparse cellular systems. We employ it to study a conceptually fundamental question of practical importance—how well should we know the system studied (such that we can predict its performance) so that we can understand its workings (i.e., chart its underlying functional network)?

Results and Conclusions: The performance of FINE is studied in both simulated and biological sparse systems. It successfully obtains an accurate and compact description of the underlying functional network even with limited data, and outperforms FIN. We show that prior estimates of a system's functional complexity are instrumental in determining how much predictive knowledge is required to accurately chart its underlying functional network.

Availability: The FINE software is available for download at

Contact:  niryosef@post.tau.ac.il
ZPRED: Predicting the distance to the membrane center for residues in α-helical membrane proteins
Authors: Granseth Erik , Viklund Håkan , Elofsson Arne
Published: July 2006

Motivation: Prediction methods are of great importance for membrane proteins as experimental information is harder to obtain than for globular proteins. As more membrane protein structures are solved it is clear that topology information only provides a simplified picture of a membrane protein.

Here, we describe a novel challenge for the prediction of α-helical membrane proteins: to predict the distance between a residue and the center of the membrane, a measure we define as the Z–coordinate.

Even though the traditional way of depicting membrane protein topology is useful, it is advantageous to have a measure that is based on a more “physical” property such as the Z–coordinate, since it implicitly contains information about re-entrant helices, interfacial helices, the tilt of a transmembrane helix and loop lengths.

Results: We show that the Z–coordinate can be predicted using either artificial neural networks, hidden Markov models or combinations of both. The best method, ZPRED, uses the output from a hidden Markov model together with a neural network. The average error of ZPRED is 2.55Å and 68.6% of the residues are predicted within 3Å of the target Z–coordinate in the 5–25Å region. ZPRED is also able to predict the maximum protrusion of a loop to within 3Å for 78% of the loops in the dataset.

Availability: Supplementary information and training data is available at

Contact:  arne@bioinfo.se
Protein classification using ontology classification
Authors: Wolstencroft K. , Lord P. , Tabernero L. , Brass A. , Stevens R.
Published: July 2006

Motivation: The classification of proteins expressed by an organism is an important step in understanding the molecular biology of that organism. Traditionally, this classification has been performed by human experts. Human knowledge can recognise the functional properties that are sufficient to place an individual gene product into a particular protein family group. Automation of this task usually fails to meet the ‘gold standard’ of the human annotator because of the difficult recognition stage. The growing number of genomes, the rapid changes in knowledge and the central role of classification in the annotation process, however, motivates the need to automate this process.

Results: We capture human understanding of how to recognise members of the protein phosphatases family by domain architecture as an ontology. By describing protein instances in terms of the domains they contain, it is possible to use description logic reasoners and our ontology to assign those proteins to a protein family class.

We have tested our system on classifying the protein phosphatases of the human and Aspergillus fumigatus genomes and found that our knowledge-based, automatic classification matches, and sometimes surpasses, that of the human annotators. We have made the classification process fast and reproducible and, where appropriate knowledge is available, the method can potentially be generalised for use with any protein family.

Availability: All components described in this paper are freely available.

OWL ontology

myGrid

Instance Store

Contact:  KWolstencroft@cs.man.ac.uk
AClAP, Autonomous hierarchical agglomerative Cluster Analysis based protocol to partition conformational datasets
Authors: Bottegoni Giovanni , Rocchia Walter , Recanatini Maurizio , Cavalli Andrea
Published: July 2006

Motivation: Sampling the conformational space is a fundamental step for both ligand- and structure-based drug design. However, the rational organization of different molecular conformations still remains a challenge. In fact, for drug design applications, the sampling process provides a redundant conformation set whose thorough analysis can be intensive, or even prohibitive. We propose a statistical approach based on cluster analysis aimed at rationalizing the output of methods such as Monte Carlo, genetic, and reconstruction algorithms. Although some software already implements clustering procedures, at present, a universally accepted protocol is still missing.

Results: We integrated hierarchical agglomerative cluster analysis with a clusterability assessment method and a user independent cutting rule, to form a global protocol that we implemented in a MATLAB metalanguage program (AClAP). We tested it on the conformational space of a quite diverse set of drugs generated via Metropolis Monte Carlo simulation, and on the poses we obtained by reiterated docking runs performed by four widespread programs. In our tests, AClAP proved to remarkably reduce the dimensionality of the original datasets at a negligible computational cost. Moreover, when applied to the outcomes of many docking programs together, it was able to point to the crystallographic pose.

Availability: AClAP is available at the “AClAP” section of the website .

Contact: E-mail: andrea.cavalli@unibo.it.

Supplementary Information: The complete series of AClAP results is available in the “services” section of the website .
Automatic clustering of orthologs and inparalogs shared by multiple proteomes
Authors: Alexeyenko Andrey , Tamas Ivica , Liu Gang , Sonnhammer Erik L.L.
Published: July 2006

Motivation: The complete sequencing of many genomes has made it possible to identify orthologous genes descending from a common ancestor. However, reconstruction of evolutionary history over long time periods faces many challenges due to gene duplications and losses. Identification of orthologous groups shared by multiple proteomes therefore becomes a clustering problem in which an optimal compromise between conflicting evidences needs to be found.

Results: Here we present a new proteome-scale analysis program called MultiParanoid that can automatically find orthology relationships between proteins in multiple proteomes. The software is an extension of the InParanoid program that identifies orthologs and inparalogs in pairwise proteome comparisons. MultiParanoid applies a clustering algorithm to merge multiple pairwise ortholog groups from InParanoid into multi-species ortholog groups. To avoid outparalogs in the same cluster, MultiParanoid only combines species that share the same last ancestor.

To validate the clustering technique, we compared the results to a reference set obtained by manual phylogenetic analysis. We further compared the results to ortholog groups in KOGs and OrthoMCL, which revealed that MultiParanoid produces substantially fewer outparalogs than these resources.

Availability: MultiParanoid is a freely available standalone program that enables efficient orthology analysis much needed in the post-genomic era. A web-based service providing access to the original datasets, the resulting groups of orthologs, and the source code of the program can be found at .

Contact:  Erik.Sonnhammer@sbc.su.se

Supplementary information:
Computational inference of the molecular logic for synaptic connectivity in C. elegans
Authors: Varadan Vinay , Miller David M. , Anastassiou Dimitris
Published: July 2006

Motivation: The nematode C. elegans is an ideal model organism in which to investigate the biomolecular mechanisms underlying the connectivity of neurons, because synaptic connections are described in a comprehensive wiring diagram and methods for defining gene expression profiles of individual neurons are now available.

Results: Here we present computational techniques linking these two types of information. A systems-based approach (EMBP: Entropy Minimization and Boolean Parsimony) identifies sets of synergistically interacting genes whose joint expression predicts neural connectivity. We introduce an information theoretic measure of the multivariate synergy, a fundamental concept in systems biology, connecting the members of these gene sets. We present and validate our preliminary results based on publicly available information, and demonstrate that their synergy is exceptionally high indicating joint involvement in pathways. Our strategy provides a robust methodology that will yield increasingly more accurate results as more neuron-specific gene expression data emerge. Ultimately, we expect our approach to provide important clues for universal mechanisms of neural interconnectivity.

Contact:  anastas@ee.columbia.edu

Supplementary Information: Expression and connectivity data will be available and maintained in the future as new results become available, together with software and additional clarifying descriptions of our techniques, on
Quantification of transcription factor expression from Arabidopsis images
Authors: Mace Daniel L. , Lee Ji-Young , Twigg Richard W. , Colinas Juliette , Benfey Philip N. , Ohler Uwe
Published: July 2006

Motivation: Confocal microscopy has long provided qualitative information for a variety of applications in molecular biology. Recent advances have led to extensive image datasets, which can now serve as new data sources to obtain quantitative gene expression information. In contrast to microarrays, which usually provide data for many genes at one time point, these image data provide us with expression information for only one gene, but with the advantage of high spatial and/or temporal resolution, which is often lostin microarray samples.

Results: We have developed a prototype for the automatic analysis of Arabidopsis confocal images, which show the expression of a single transcription factor by means of GFP reporter constructs. Using techniques from image registration, we are able to address inherent problems of non-rigid transformation and partial mapping, and obtain relative expression values for 13 different tissues in Arabidopsis roots. This provides quantitative information with high spatial resolution, which accurately represents the underlying expression values within the organism. We validate our approach on a data set of 122 images depicting expression patterns of 30 transcription factors, both in terms of registration accuracy, as well as correlation with cell-sorted microarray data. Approaches like this will be useful to lay the groundwork to reconstruct regulatory networks on the level of tissues or even individual cells.

Contact:  uwe.ohler@duke.edu

Availability: Upon request from the authors.

Supplementary Data:
Identifying cycling genes by combining sequence homology and expression data
Authors: Lu Yong , Rosenfeld Roni , Bar-Joseph Ziv
Published: July 2006

Motivation: The expression of genes during the cell division process has now been studied in many different species. An important goal of these studies is to identify the set of cycling genes. To date, this was done independently for each of the species studied. Due to noise and other data analysis problems, accurately deriving a set of cycling genes from expression data is a hard problem. This is especially true for some of the multicellular organisms, including humans.

Results: Here we present the first algorithm that combines microarray expression data from multiple species for identifying cycling genes. Our algorithm represents genes from multiple species as nodes in a graph. Edges between genes represent sequence similarity. Starting with the measured expression values for each species we use Belief Propagation to determine a posterior score for genes. This posterior is used to determine a new set of cycling genes for each species.

We applied our algorithm to improve the identification of the set of cell cycle genes in budding yeast and humans. As we show, by incorporating sequence similarity information we were able to obtain a more accurate set of genes compared to methods that rely on expression data alone. Our method was especially successful for the human dataset indicating that it can use a high quality dataset from one species to overcome noise problems in another.

Availability: C implementation is available from the supporting website:

Contact:  zivbj@cs.cmu.edu
Predicting the prognosis of breast cancer by integrating clinical and microarray data with Bayesian networks
Authors: Gevaert Olivier , Smet Frank De , Timmerman Dirk , Moreau Yves , Moor Bart De
Published: July 2006

Motivation: Clinical data, such as patient history, laboratory analysis, ultrasound parameters—which are the basis of day-to-day clinical decision support—are often underused to guide the clinical management of cancer in the presence of microarray data. We propose a strategy based on Bayesian networks to treat clinical and microarray data on an equal footing. The main advantage of this probabilistic model is that it allows to integrate these data sources in several ways and that it allows to investigate and understand the model structure and parameters. Furthermore using the concept of a Markov Blanket we can identify all the variables that shield off the class variable from the influence of the remaining network. Therefore Bayesian networks automatically perform feature selection by identifying the (in)dependency relationships with the class variable.

Results: We evaluated three methods for integrating clinical and microarray data: decision integration, partial integration and full integration and used them to classify publicly available data on breast cancer patients into a poor and a good prognosis group. The partial integration method is most promising and has an independent test set area under the ROC curve of 0.845. After choosing an operating point the classification performance is better than frequently used indices.

Contact:  olivier.gevaert@esat.kuleuven.be
BNTagger: improved tagging SNP selection using Bayesian networks
Authors: Lee Phil Hyoun , Shatkay Hagit
Published: July 2006

Genetic variation analysis holds much promise as a basis for disease-gene association. However, due to the tremendous number of candidate single nucleotide polymorphisms (SNPs), there is a clear need to expedite genotyping by selecting and considering only a subset of all SNPs. This process is known as tagging SNP selection. Several methods for tagging SNP selection have been proposed, and have shown promising results. However, most of them rely on strong assumptions such as prior block-partitioning, bi-allelic SNPs, or a fixed number or location of tagging SNPs.

We introduce BNTagger, a new method for tagging SNP selection, based on conditional independence among SNPs. Using the formalism of Bayesian networks (BNs), our system aims to select a subset of independent and highly predictive SNPs. Similar to previous prediction-based methods, we aim to maximize the prediction accuracy of tagging SNPs, but unlike them, we neither fix the number nor the location of predictive tagging SNPs, nor require SNPs to be bi-allelic. In addition, for newly-genotyped samples, BNTagger directly uses genotype data as input, while producing as output haplotype data of all SNPs.

Using three public data sets, we compare the prediction performance of our method to that of three state-of-the-art tagging SNP selection methods. The results demonstrate that our method consistently improves upon previous methods in terms of prediction accuracy. Moreover, our method retains its good performance even when a very small number of tagging SNPs are used.

Contact:  lee@cs.queensu.ca, shatkay@cs.queensu.ca
Integrating image data into biomedical text categorization
Authors: Shatkay Hagit , Chen Nawei , Blostein Dorothea
Published: July 2006

Categorization of biomedical articles is a central task for supporting various curation efforts. It can also form the basis for effective biomedical text mining. Automatic text classification in the biomedical domain is thus an active research area. Contests organized by the KDD Cup (2002) and the TREC Genomics track (since 2003) defined several annotation tasks that involved document classification, and provided training and test data sets. So far, these efforts focused on analyzing only the text content of documents. However, as was noted in the KDD'02 text mining contest—where figure-captions proved to be an invaluable feature for identifying documents of interest—images often provide curators with critical information. We examine the possibility of using information derived directly from image data, and of integrating it with text-based classification, for biomedical document categorization. We present a method for obtaining features from images and for using them—both alone and in combination with text—to perform the triage task introduced in the TREC Genomics track 2004. The task was to determine which documents are relevant to a given annotation task performed by the Mouse Genome Database curators. We show preliminary results, demonstrating that the method has a strong potential to enhance and complement traditional text-based categorization methods.

Contact:  shatkay@cs.queensu.ca
Rapid knot detection and application to protein structure prediction
Authors: Khatib Firas , Weirauch Matthew T. , Rohl Carol A.
Published: July 2006

Motivation: Knots in polypeptide chains have been found in very few proteins, and consequently should be generally avoided in protein structure prediction methods. Most effective structure prediction methods do not model the protein folding process itself, but rather seek only to correctly obtain the final native state. Consequently, the mechanisms that prevent knots from occurring in native proteins are not relevant to the modeling process, and as a result, knots can occur with significantly higher frequency in protein models. Here we describe Knotfind, a simple algorithm for knot detection that is fast enough for structure prediction, where tens or hundreds of thousands of conformations may be sampled during the course of a prediction. We have used this algorithm to characterize knots in large populations of model structures generated for targets in CASP 5 and CASP 6 using the Rosetta homology-based modeling method.

Results: Analysis of CASP5 models suggested several possible avenues for introduction of knots into these models, and these insights were applied to structure prediction in CASP 6, resulting in a significant decrease in the proportion of knotted models generated. Additionally, using the knot detection algorithm on structures in the Protein Data Bank, a previously unreported deep trefoil knot was found in acetylornithine transcarbamylase.

Availability: The Knotfind algorithm is available in the Rosetta structure prediction program at

Contact:  bort@soe.ucsc.edu
Efficient identification of DNA hybridization partners in a sequence database
Authors: Mann Tobias P. , Noble William Stafford
Published: July 2006

Motivation: The specific hybridization of complementary DNA molecules underlies many widely used molecular biology assays, including the polymerase chain reaction and various types of microarray analysis. In order for such an assay to work well, the primer or probe must bind to its intended target, without also binding to additional sequences in the reaction mixture. For any given probe or primer, potential non-specific binding partners can be identified using state-of-the-art models of DNA binding stability. Unfortunately, these models rely on dynamic programming algorithms that are too slow to apply on a genomic scale.

Results: We present an algorithm that efficiently scans a DNA database for short (approximately 20–30 base) sequences that will bind to a query sequence. We use a filtering approach, in which a series of increasingly stringent filters is applied to a set of candidate k-mers. The k-mers that pass all filters are then located in the sequence database using a precomputed index, and an accurate model of DNA binding stability is applied to the sequence surrounding each of the k-mer occurrences. This approach reduces the time to identify all binding partners for a given DNA sequence in human genomic DNA by approximately three orders of magnitude, from two days for the ENCODE regions to less than one minute for typical queries. Our approach is scalable to large DNA sequences. Our method can scan the human genome for medium strength binding sites to a candidate PCR primer in an average of 34.5 minutes.

Availability: Software implementing the algorithms described here is available at

Contact:  mann@gs.washington.edu