bluuebunny/crossref_metadata_2025 huggingface dataset:
Femtosecond study on the isomerization dynamics of NK88. II. Excited-state dynamics
Authors: Vogt Gerhard , Nuernberger Patrick , Gerber Gustav , Improta Roberto , Santoro Fabrizio
Published: July 2006

The molecule 3,3′-diethyl-2,2′-thiacyanine isomerizes after irradiation with light of the proper wavelength. After excitation, it undergoes a transition, in which one or more conical intersections are involved, back to the ground state to form different product photoisomers. The dynamics before and directly after the transition back to the ground state is investigated by transient absorption spectroscopy in a wavelength region of 360–950nm, as well as by fluorescence upconversion. It is shown that the excited-state dynamics are governed by two time scales: a short one with a decay time of less than 2ps and a long one with about 9ps. A thorough comparison of the experimental results with those of configuration interaction singles and time-dependent density functional theory calculations suggests that these dynamics are related to two competing pathways differing in the molecular twisting on the excited surface after photoexcitation. From the experimental point of view this picture arises taking into account the time scales for ground-state bleach, excited-state absorption, stimulated emission, fluorescence, and assumed hot ground-state absorption both in the solvent methanol and ethylene glycol.
Principles of control for decoherence-free subsystems
Authors: Cappellaro P. , Hodges J. S. , Havel T. F. , Cory D. G.
Published: July 2006

Decoherence-free subsystems (DFSs) are a powerful means of protecting quantum information against noise with known symmetry properties. Although Hamiltonians that can implement a universal set of logic gates on DFS encoded qubits without ever leaving the protected subsystem theoretically exist, the natural Hamiltonians that are available in specific implementations do not necessarily have this property. Here we describe some of the principles that can be used in such cases to operate on encoded qubits without losing the protection offered by the DFSs. In particular, we show how dynamical decoupling can be used to control decoherence during the unavoidable excursions outside of the DFS. By means of cumulant expansions, we show how the fidelity of quantum gates implemented by this method on a simple two physical qubit DFS depends on the correlation time of the noise responsible for decoherence. We further show by means of numerical simulations how our previously introduced “strongly modulating pulses” for NMR quantum information processing can permit high-fidelity operations on multiple DFS encoded qubits in practice, provided that the rate at which the system can be modulated is fast compared to the correlation time of the noise. The principles thereby illustrated are expected to be broadly applicable to many implementations of quantum information processors based on DFS encoded qubits.
Molecular fractionation with conjugated caps density matrix with pairwise interaction correction for protein energy calculation
Authors: Chen X. H. , Zhang J. Z. H.
Published: July 2006

Pairwise interaction correction (PIC) is introduced to account for electron density polarization due to short-range interactions such as hydrogen bonding and close contact between molecular fragments in the molecular fractionation with conjugated caps density matrix (MFCC-DM) approach for energy calculation of protein and other polymers [Chen et al., J. Chem. Phys. 122, 184105 (2005)]. With this PIC, the accuracy of the calculated protein energy and other electronic properties are improved, and the MFCC approach can be applied to study real proteins with short-range structural complexity. In the present MFCC-DM-PIC approach, the short-range interresidual interactions are represented by a pair of small molecules (interacting units) which are made from the two residues that fall within a certain distance criterion. The density matrices of fragments, concaps, interacting units and pairs are calculated by conventional Hartree-Fock or density functional theory methods and are combined to construct the full density matrix which is finally employed to calculate the total energy, electron density, electrostatic potential, dipole moment, etc., of the protein. Numerical tests on seven conformationally varied peptides are presented to demonstrate the accuracy of the MFCC-DM-PIC method.
Adsorption of transition-metal atoms on boron nitride nanotube: A density-functional study
Authors: Wu Xiaojun , Zeng X. C.
Published: July 2006

Adsorption of transition atoms on a (8,0) zigzag single-walled boron nitride (BN) nanotube has been investigated using density-functional theory methods. Main focuses have been placed on configurations corresponding to the located minima of the adsorbates, the corresponding binding energies, and the modified electronic properties of the BN nanotubes due to the adsorbates. We have systemically studied a series of metal adsorbates including all 3d transition-metal elements (Sc, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, and Zn) and two group-VIIIA transition-metal elements (Pd and Pt). We found that many transition-metal atoms can be chemically adsorbed on the outer surface of the BN nanotubes and that the adsorption process is typically exothermic. Upon adsorption, the binding energies of the Sc, Ti, Ni, Pd, and Pt atoms are relatively high (>1.0eV), while those of V, Fe, and Co atoms are modest, ranging from 0.62to0.92eV. Mn atom forms a weak bond with the BN nanotube, while Zn atom cannot be chemically adsorbed on the BN nanotube. In most cases, the adsorption of transition-metal atoms can induce certain impurity states within the band gap of the pristine BN nanotube, thereby reducing the band gap. Most metal-adsorbed BN nanotubes exhibit nonzero magnetic moments, contributed largely by the transition-metal atoms.
Thermodynamics of polydomain ferroelectric bilayers and graded multilayers
Authors: Roytburd Alexander L. , Slutsker Julia
Published: July 2006

The equilibrium domain structure and its evolution under an electric field in ferroelectric bilayers and graded multilayers are considered. The equilibrium bilayer is self-poled and contains single-domain and polydomain (with 180° domains) layers. The polarization of a graded multilayer proceeds by movement of wedge-like domains as a result of progressive transformation of polydomain layers to a single-domain state. The theory provides the principal explanation of dielectric behavior of graded ferroelectric films.
Charge transport in melt-dispersed carbon nanotubes
Authors: Hobbie E. K. , Obrzut J. , Kharchenko S. B. , Grulke E. A.
Published: July 2006

We investigate the effect of interfacial stabilizer on charge transport in polymer-dispersed carbon nanotubes. Despite mechanical contact, samples with dispersant show poor conductivity, which we attribute to a robust interfacial layer between contacted nanotubes. In comparison, results obtained when nanotubes are mechanically mixed into polymer melts without dispersant show much better conductivity. The difference is striking; at comparable loading, neat melt composites have resistivities five orders of magnitude smaller than those containing interfacial stabilizer. Our results highlight a fundamental issue for the engineering of conducting carbon nanotube composites; dispersion stability will typically be achieved at the expense of conductivity.
The influence of chain length and ripening time on the self-assembly of alkylamines on mica
Authors: Benítez J. J. , Salmeron M.
Published: July 2006

The influence of chain length and ripening time on the self-assembly of tetradecyl (C14), hexadecyl (C16), and octadecylamine (C16) on mica has been studied by atomic force microscopy. The overall process can be described in three stages characterized by different time scales. First, alkylamine molecules adsorb in a process controlled by water mediated interactions of the NH2 head groups and mica. Second, surface diffusion and aggregation into islands takes place, driven by energy interactions between alkyl chains. The third stage consists of a progressive tilt of the self-assembled molecules towards the surface, driven by relaxation of the electrostatic repulsion between protonated amino groups due to water uptake from atmosphere.
Trapped whispering-gallery optical modes in white light-emitting diode lamps with remote phosphor
Authors: Luo Hong , Kim Jong Kyu , Xi Yangang Andrew , Schubert E. Fred , Cho Jaehee , Sone Cheolsoo , Park Yongjo
Published: July 2006

Three-dimensional ray tracing simulations show that a significant fraction of the phosphorescence emitted in high-power white light-emitting diode lamps with a remote phosphor is trapped as whispering-gallery modes propagating along the circumference of the encapsulant. The whispering-gallery modes, which are a significant optical loss mechanism and occur for multiple shapes of the encapsulation dome, are shown to be sensitively dependent on the diffusivity of the reflector cup employed in the lamp. By employing a diffuse reflector cup, up to 86% of the trapped modes is extracted out from the encapsulant. In addition, it is experimentally demonstrated that the phosphorescence efficiency is improved by up to 12.2% as the diffusivity of the reflector increases. The experimental results are consistent with theoretical ray tracing simulations.
Selective surface purification via crater eruption under pulsed electron beam irradiation
Authors: Zou Jianxin , Zhang Kemin , Dong Chuang , Qin Ying , Hao Shengzhi , Grosdidier Thierry
Published: July 2006

This letter reports an interesting phenomenon associated with the high-current pulsed electron beam treatment:selective surface purification. The treatment induces crater eruptions that preferentially occur at irregular composition and structure sites. The eruptions of second phase inclusions naturally lead to the purification and homogenization of the melted surface layer. This improves significantly the corrosion resistance of NiTi and 316L alloys.
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controlling photoluminescence of AWO4 (A=Ca,Sr,Ba) nanofilms
Authors: Jia Runping , Zhang Guoxin , Wu Qingsheng , Ding Yaping
Published: July 2006

A W O 4  (A=Ca,Sr,Ba) nanofilms are prepared by a self-inventive technique using collodion to disperse nanoparticles and form film, and their photoluminescence (PL) properties are controlled by a nano-TiO2 doping method. This cannot only reach the results of uniform film and PL enhancement, but also realize a PL increase/decrease shift effect. The PL behaviors of AWO4 nanofilms doped by TiO2 are in good agreement with Gaussion function relation. In addition, there is a positive correlation between the critical concentrations of TiO2 in AWO4–TiO2 nanofilm series and A’s ionic potential.
Low-temperature growth and blue luminescence of SnO2 nanoblades
Authors: Her Yung-Chiun , Wu Jer-Yau , Lin Yan-Ru , Tsai Song-Yeu
Published: July 2006

Large-scale SnO2 nanoblades have been synthesized on a glass substrate covered with a 100-nm-thick SnO2 buffer layer in a controlled aqueous solution at temperatures below 100°C. Typical widths of the nanoblades were about 100–300nm and the lengths were up to 10μm, depending on the growth temperature. The thicknesses were about a few tens of nanometers. Transmission electron microscopy data, x-ray diffraction patterns, and x-ray photoelectron spectroscopy spectral analyses confirmed that the as-grown nanoblades had the phase structure of the rutile form of SnO2 growing along the [110] direction. No other impurities, such as elemental Sn and tin oxides, were detected. An intense blue luminescence centered at a wavelength of 445nm with a full width at half maximum of 75nm was observed in the as-grown SnO2 nanoblades, which is different from the yellow-red light emission observed in SnO2 nanostructures prepared by other methods. It is believed that the strong blue luminescence from the as-grown SnO2 nanoblades is attributed to oxygen-related defects that have been introduced during the growth process.
GaN microcavity structure with dielectric distributed Bragg reflectors fabricated by using a wet-chemical etching of a (111) Si substrate
Authors: Kim T. K. , Yang S. S. , Son J. K. , Hong Y. G. , Yang G. M.
Published: July 2006

GaN microcavity structure with SiO2∕ZrO2 dielectric distributed Bragg reflectors was fabricated by means of transferring an InGaN∕GaN multiple quantum well (QW) structure from the (111) Si substrate onto a sapphire carrier and wet-chemical etching of the substrate. A dip in the reflectivity spectrum of the microcavity structure is observed at a wavelength of 411nm indicating the cavity resonance mode. Also, the strong influence of the cavity on the QW photoluminescence has been observed. A sharp emission spectrum, with a linewidth of 3.5nm, occurs at a wavelength of 411nm coincided with the position of the cavity resonance mode.
Anisotropic polarization characteristics of lasing and spontaneous surface and edge emissions from deep-ultraviolet (λ≈240nm) AlGaN multiple-quantum-well lasers
Authors: Kawanishi Hideo , Senuma Masanori , Nukui Takeaki
Published: July 2006

The authors report on their experimental discovery of a transverse-magnetic-field (TM)-mode polarization of lasing and spontaneous edge emissions (anisotropic polarization emissions) above and below the lasing threshold from the AlGaN multiple-quantum-well (MQW) laser at 240.8nm. The deep ultraviolet MQW emitted very weak or no surface emission (anisotropic polarization emission) below the threshold. On the other hand, the AlGaN multiple-quantum-well laser at 355.1nm operated in the transverse-electric-field (TE) mode above the threshold, and homogeneous high-intensity spontaneous surface emission and both TE- and TM-mode edge emissions (isotropic emissions) were observed below the threshold.
Red emission from poly(9,9-dioctylfluorene) doped with phosphorescent dye through maskless dye-diffusion technique
Authors: Tada Kazuya , Onoda Mitsuyoshi
Published: July 2006

A phosphorescent metal complex, iridium (III) bis[2-(2′-benzothienyl)pyridinato-N,C3′] (acetylacetonate) (BtpIr), was introduced in poly(9,9-dioctylfluorene) (PDOF) films through a dry process for local dye doping into a film, the maskless dye-diffusion technique. A light-emitting device with a PDOF film with BtpIr diffusion for 80s showed red emission originating from the dye with superior quantum efficiency compared to a device with a pristine PDOF film. The effect of heat treatment on PDOF films was also studied to confirm that the enhanced quantum efficiency was attributable not to the heat treatment effect but to that of the phosphorescent nature of BtpIr.
Wavelength and temperature dependence of photorefractive effect in quasi-phase-matched LiNbO3 waveguides
Authors: Chen Bo , Campos Jorge Fonseca , Liang Wanguo , Wang Yong , Xu Chang-Qing
Published: July 2006

The photorefractive effect (PRE) in quasi-phase-matched LiNbO3 waveguides is studied systematically by employing the pump-probe technique. It is found that the PRE is gradually eased with an increase of the device operation temperature. With increasing light irradiation power, the PRE becomes severe, the buildup (relaxation) time constant decreases (increases), while the second harmonic generation (SHG) efficiency is enhanced for the devices used in studies. The PRE under a shorter wavelength (980nm) light irradiation is much stronger than that at a longer wavelength one (1550nm), and the PRE for the latter is mainly caused by the SHG of the pump.
Measurement of the mean electron-hole pair ionization energy in 4H SiC
Authors: Chandrashekhar M. V. S. , Thomas Christopher I. , Spencer Michael G.
Published: July 2006

A measurement of the mean e-h pair creation energy ⟨Ee-h⟩ in SiC using a scanning electron microscope is presented. Uncertainties stemming from backscattering from high Z metal contacts, as well as from the semiconductor surface, are removed by explicit measurement through direct electron bombardment of the bare semiconductor surface. A reduced value of ⟨Ee-h⟩=5.05eV for 4H SiC is reported, which is significantly lower than previously reported values. Good correspondence with Monte Carlo simulations of impact ionization in 4H SiC was obtained.
Is the formation of cationic lipid-DNA complexes a thermodynamically driven phenomenon? Structure and phase behavior of DC-Chol/DNA complexes say not
Authors: Caracciolo Giulio , Pozzi Daniela , Caminiti Ruggero
Published: July 2006

The currently accepted mechanism of formation of cationic lipid-DNA complexes (lipoplexes) relies on the basic assumption that equilibrium structure of lipoplexes is regulated by thermodynamics. The main consequence is that neutral lipoplexes are one phase whereas positively (or negatively) charged ones coexist with excess lipid (or excess DNA). The authors report a small angle x-ray diffraction study on the structure of lipoplexes made of the cationic lipid 3β-[N-(N,N-dimethylaminoethane)-carbamoyl]cholesterol and calf thymus Na-DNA. Here the authors show that positively charged lipoplexes can coexist with unbound DNA and they claim that steric size effects are definitely important to determine the equilibrium structure of lipoplexes.
A configural effect in visual short-term memory for features from different parts of an object
Authors: Delvenne Jean-François , Bruyer Raymond
Published: July 2006

Previous studies have shown that change detection performance is improved when the visual display holds features (e.g., a colour and an orientation) that are grouped into different parts of the same object compared to when they are all spatially separated (Xu, 2002a, 2002b). These findings indicate that visual short-term memory (VSTM) encoding can be “object based”. Recently, however, it has been demonstrated that changing the orientation of an item could affect the spatial configuration of the display (Jiang, Chun, & Olson, 2004), which may have an important influence on change detection. The perceptual grouping of features into an object obviously reduces the amount of distinct spatial relations in a display and hence the complexity of the spatial configuration. In the present study, we ask whether the object-based encoding benefit observed in previous studies may reflect the use of configural coding rather than the outcome of a true object-based effect. The results show that when configural cues are removed, the object-based encoding benefit remains for features (i.e., colour and orientation) from different parts of an object, but is significantly reduced. These findings support the view that memory for features from different parts of an object can benefit from object-based encoding, but the use of configural coding significantly helps enlarge this effect.
Aging, Working Memory, and Discrimination Learning
Authors: Mutter Sharon A. , Haggbloom Steven J. , Plumlee Leslie F. , Schirmer Amy R.
Published: July 2006

Older adults easily learn probabilistic relationships between cues and outcomes when the predictive event is the occurrence of a cue, but have greater difficulty when the predictive event is the nonoccurrence of a cue (Mutter & Pliske, 1996; Mutter & Plumlee, 2004; Mutter & Williams, 2004). This study explored whether this age-related deficit occurs in a simpler learning context and whether it might be related to working memory (WM) decline. We gave younger and older adults simultaneous discrimination tasks that allowed us to compare their ability to learn deterministic relationships when either the occurrence (feature positive; FP) or the nonoccurrence (feature negative; FN) of a distinctive feature predicted reinforcement. We also included a group of younger adults who performed the discrimination tasks under a concurrent WM load. Both age and WM load had a detrimental effect on initial FP and FN discrimination; however, these effects persisted only in FN discrimination after additional learning experience. Learning predictive relationships requires inductive reasoning processes that apparently do not operate as efficiently in individuals with reduced WM capacity. The impact of WM decline may ultimately be greater for negative cue–outcome relationships because learning these relationships requires more difficult inductive reasoning processes, which place greater demands on WM.
Tyrosine Phosphatases ε and α Perform Specific and Overlapping Functions in Regulation of Voltage-gated Potassium Channels in Schwann Cells
Authors: Tiran Zohar , Peretz Asher , Sines Tal , Shinder Vera , Sap Jan , Attali Bernard , Elson Ari
Published: July 2006

Tyrosine phosphatases (PTPs) ε and α are closely related and share several molecular functions, such as regulation of Src family kinases and voltage-gated potassium (Kv) channels. Functional interrelationships between PTPε and PTPα and the mechanisms by which they regulate K+channels and Src were analyzed in vivo in mice lacking either or both PTPs. Lack of either PTP increases Kv channel activity and phosphorylation in Schwann cells, indicating these PTPs inhibit Kv current amplitude in vivo. Open probability and unitary conductance of Kv channels are unchanged, suggesting an effect on channel number or organization. PTPα inhibits Kv channels more strongly than PTPε; this correlates with constitutive association of PTPα with Kv2.1, driven by membranal localization of PTPα. PTPα, but not PTPε, activates Src in sciatic nerve extracts, suggesting Src deregulation is not responsible exclusively for the observed phenotypes and highlighting an unexpected difference between both PTPs. Developmentally, sciatic nerve myelination is reduced transiently in mice lacking either PTP and more so in mice lacking both PTPs, suggesting both PTPs support myelination but are not fully redundant. We conclude that PTPε and PTPα differ significantly in their regulation of Kv channels and Src in the system examined and that similarity between PTPs does not necessarily result in full functional redundancy in vivo.
Inhibition of Ribosome Recruitment Induces Stress Granule Formation Independently of Eukaryotic Initiation Factor 2α Phosphorylation
Authors: Mazroui Rachid , Sukarieh Rami , Bordeleau Marie-Eve , Kaufman Randal J. , Northcote Peter , Tanaka Junichi , Gallouzi Imed , Pelletier Jerry
Published: July 2006

Cytoplasmic aggregates known as stress granules (SGs) arise as a consequence of cellular stress and contain stalled translation preinitiation complexes. These foci are thought to serve as sites of mRNA storage or triage during the cell stress response. SG formation has been shown to require induction of eukaryotic initiation factor (eIF)2α phosphorylation. Herein, we investigate the potential role of other initiation factors in this process and demonstrate that interfering with eIF4A activity, an RNA helicase required for the ribosome recruitment phase of translation initiation, induces SG formation and that this event is not dependent on eIF2α phosphorylation. We also show that inhibition of eIF4A activity does not impair the ability of eIF2α to be phosphorylated under stress conditions. Furthermore, we observed SG assembly upon inhibition of cap-dependent translation after poliovirus infection. We propose that SG modeling can occur via both eIF2α phosphorylation-dependent and -independent pathways that target translation initiation.
Nonadaptive Regulation of ERK2 inDictyostelium: Implications for Mechanisms of cAMP Relay
Authors: Brzostowski Joseph A. , Kimmel Alan R.
Published: July 2006

It is assumed that ERK2 in Dictyostelium is subject to adaptive regulation in response to constant extracellular ligand stimulation. We now show, to the contrary, that ERK2 remains active under continuous stimulation, differing from most ligand-activated pathways in chemotactically competent Dictyostelium and other cells. We show that the upstream phosphorylation pathway, responsible for ERK2 activation, transiently responds to receptor stimulation, whereas ERK2 dephosphorylation (deactivation) is inhibited by continuous stimulation. We argue that the net result of these two regulatory actions is a persistently active ERK2 pathway when the extracellular ligand (i.e., cAMP) concentration is held constant and that oscillatory production/destruction of secreted cAMP in chemotaxing cells accounts for the observed oscillatory activity of ERK2. We also show that pathways controlling seven-transmembrane receptor (7-TMR) ERK2 activation/deactivation function independently of G proteins and ligand-induced production of intracellular cAMP and the consequent activation of PKA. Finally, we propose that this regulation enables ERK2 to function both in an oscillatory manner, critical for chemotaxis, and in a persistent manner, necessary for gene expression, as secreted ligand concentration increases during later development. This work redefines mechanisms of ERK2 regulation by 7-TMR signaling in Dictyostelium and establishes new implications for control of signal relay during chemotaxis.
Bistable switching and excitable behaviour in the activation of Src at mitosis
Authors: Fuß Hendrik , Dubitzky Werner , Downes Stephen , Kurth Mary Jo
Published: July 2006

Motivation: The protein tyrosine kinase Src is involved in a multitude of biochemical pathways and cellular functions. A complex network of interactions with other kinases and phosphatases obscures its precise mode of operation.

Results: We have constructed a semi-quantitative computational dynamic systems model of the activation of Src at mitosis based on protein interactions described in the literature. Through numerical simulation and bifurcation analysis we show that Src regulation involves a bistable switch, a pattern increasingly recognised as essential to biochemical signalling. The switch is operated by the tyrosine kinase CSK, which itself is involved in a negative feedback loop with Src. Negative feedback generates an excitable system, which produces transient activation of Src. One of the system parameters, which is linked to the cyclin dependent kinase cdc2, controls excitability via a second bistable switch. This topology allows for differentiated responses to a multitude of signals. The model offers explanations for the existence of the positive and negative feedback loops involving protein tyrosine phosphatase alpha (PTPα) and translocation of CSK and predicts a specific relationship between Src phosphorylation and activity.

Contact:  fuss-h@ulster.ac.uk
Identification of metabolic units induced by environmental signals
Authors: Nacher Jose C. , Schwartz Jean-Marc , Kanehisa Minoru , Akutsu Tatsuya
Published: July 2006

Motivation: Biological cells continually need to adapt the activity levels of metabolic functions to changes in their living environment. Although genome-wide transcriptional data have been gathered in a large variety of environmental conditions, the connections between the expression response to external changes and the induction or repression of specific metabolic functions have not been investigated at the genome scale.

Results: We present here a correlation-based analysis for identifying the expression response of genes involved in metabolism to specific external signals, and apply it to analyze the transcriptional response of Saccharomyces cerevisiae to different stress conditions. We show that this approach leads to new insights about the specificity of the genomic response to given environmental changes, and allows us to identify genes that are particularly sensitive to a unique condition. We then integrate these signal-induced expression data with structural data of the yeast metabolic network and analyze the topological properties of the induced or repressed subnetworks. They reveal significant discrepancies from random networks, and in particular exhibit a high connectivity, allowing them to be mapped back to complete metabolic routes.

Contact:  nacher@kuicr.kyoto-u.ac.jp, jean@kuicr.kyoto-u.ac.jp
An ontology for a Robot Scientist
Authors: Soldatova Larisa N. , Clare Amanda , Sparkes Andrew , King Ross D.
Published: July 2006

Motivation: A Robot Scientist is a physically implemented robotic system that can automatically carry out cycles of scientific experimentation. We are commissioning a new Robot Scientist designed to investigate gene function in S. cerevisiae. This Robot Scientist will be capable of initiating >1,000 experiments, and making >200,000 observations a day. Robot Scientists provide a unique test bed for the development of methodologies for the curation and annotation of scientific experiments: because the experiments are conceived and executed automatically by computer, it is possible to completely capture and digitally curate all aspects of the scientific process. This new ability brings with it significant technical challenges. To meet these we apply an ontology driven approach to the representation of all the Robot Scientist’s data and metadata.

Results: We demonstrate the utility of developing an ontology for our new Robot Scientist. This ontology is based on a general ontology of experiments. The ontology aids the curation and annotating of the experimental data and metadata, and the equipment metadata, and supports the design of database systems to hold the data and metadata.

Availability: EXPO in XML and OWL formats is at: . All materials about the Robot Scientist project are available at: .

Contact:  lss@aber.ac.uk
Dynamical analysis of a generic Boolean model for the control of the mammalian cell cycle
Authors: Fauré Adrien , Naldi Aurélien , Chaouiya Claudine , Thieffry Denis
Published: July 2006

Motivation: To understand the behaviour of complex biological regulatory networks, a proper integration of molecular data into a full-fledge formal dynamical model is ultimately required. As most available data on regulatory interactions are qualitative, logical modelling offers an interesting framework to delineate the main dynamical properties of the underlying networks.

Results: Transposing a generic model of the core network controlling the mammalian cell cycle into the logical framework, we compare different strategies to explore its dynamical properties. In particular, we assess the respective advantages and limits of synchronous versus asynchronous updating assumptions to delineate the asymptotical behaviour of regulatory networks. Furthermore, we propose several intermediate strategies to optimize the computation of asymptotical properties depending on available knowledge.

Availability: The mammalian cell cycle model is available in a dedicated XML format (GINML) on our website, along with our logical simulation software GINsim (). Higher resolution state transitions graphs are also found on this web site (Model Repository page).

Contact:  thieffry@ibdm.univ-mrs.fr
Relative contributions of structural designability and functional diversity in molecular evolution of duplicates
Authors: Shakhnovich Boris E.
Published: July 2006

Analysis of increasingly saturated sequence databases have shown that gene family sizes are highly skewed with many families being small and few containing many, far-diverged homologs. Additionally, recently published results have identified a structural determinant of mutational plasticity: designability that correlates strongly with gene family size. In this paper, we explore the possible links between the two observations, exploring the possible effect of designability on duplication and divergence.

We show that designability has an inverse of expected relationship with strength of selection. More designable domains that should have more mutational plasticity evolve slower. However, we also present evidence that recently duplicated genes have variable probability of locus fixation correlated with strength of selection. As expected, paralogs under stronger evolutionary pressure have a lower failure rate. Finally, we show that probability of pseudogene formation from gene duplication can be directly tied to designability and functional flexibility of the family.

We present evidence that gene families with higher designability have diverged farther because of lower probability of pseudogenization. Additionally, mutational plasticity may play an integral role by influencing pseudogenization rate. Either way, we show that considering the failure rate of duplications is integral in understanding the determinants and dynamics of molecular evolution.

Contact:  borya@acs.bu.edu
Semi-supervised LC/MS alignment for differential proteomics
Authors: Fischer Bernd , Grossmann Jonas , Roth Volker , Gruissem Wilhelm , Baginsky Sacha , Buhmann Joachim M.
Published: July 2006

Motivation: Mass spectrometry (MS) combined with high-performance liquid chromatography (LC) has received considerable attention for high-throughput analysis of proteomes. Isotopic labeling techniques such as ICAT [5,6] have been successfully applied to derive differential quantitative information for two protein samples, however at the price of significantly increased complexity of the experimental setup. To overcome these limitations, we consider a label-free setting where correspondences between elements of two samples have to be established prior to the comparative analysis. The alignment between samples is achieved by nonlinear robust ridge regression. The correspondence estimates are guided in a semi-supervised fashion by prior information which is derived from sequenced tandem mass spectra.

Results: The semi-supervised method for finding correspondences was successfully applied to aligning highly complex protein samples, even if they exhibit large variations due to different biological conditions. A large-scale experiment clearly demonstrates that the proposed method bridges the gap between statistical data analysis and label-free quantitative differential proteomics.

Availability: The software will be available on the website

Contact:  bernd.fischer@inf.ethz.ch
Improved Pruning algorithms and Divide-and-Conquer strategies for Dead-End Elimination, with application to protein design
Authors: Georgiev Ivelin , Lilien Ryan H. , Donald Bruce R.
Published: July 2006

Motivation: Structure-based protein redesign can help engineer proteins with desired novel function. Improving computational efficiency while still maintaining the accuracy of the design predictions has been a major goal for protein design algorithms. The combinatorial nature of protein design results both from allowing residue mutations and from the incorporation of protein side-chain flexibility. Under the assumption that a single conformation can model protein folding and binding, the goal of many algorithms is the identification of the Global Minimum Energy Conformation (GMEC). A dominant theorem for the identification of the GMEC is Dead-End Elimination (DEE). DEE-based algorithms have proven capable of eliminating the majority of candidate conformations, while guaranteeing that only rotamers not belonging to the GMEC are pruned. However, when the protein design process incorporates rotameric energy minimization, DEE is no longer provably-accurate. Hence, with energy minimization, the minimized-DEE (MinDEE) criterion must be used instead.

Results: In this paper, we present provably-accurate improvements to both the DEE and MinDEE criteria. We show that our novel enhancements result in a speedup of up to a factor of more than 1000 when applied in redesign for three different proteins: Gramicidin Synthetase A, plastocyanin, and protein G.

Availability: Contact authors for source code.

Contact:  Bruce.R.Donald@dartmouth.edu
Annotating proteins by mining protein interaction networks
Authors: Kirac Mustafa , Ozsoyoglu Gultekin , Yang Jiong
Published: July 2006

Motivation: In general, most accurate gene/protein annotations are provided by curators. Despite having lesser evidence strengths, it is inevitable to use computational methods for fast and a priori discovery of protein function annotations. This paper considers the problem of assigning Gene Ontology (GO) annotations to partially annotated or newly discovered proteins.

Results: We present a data mining technique that computes the probabilistic relationships between GO annotations of proteins on protein-protein interaction data, and assigns highly correlated GO terms of annotated proteins to non-annotated proteins in the target set. In comparison with other techniques, probabilistic suffix tree and correlation mining techniques produce the highest prediction accuracy of 81% precision with the recall at 45%.

Availability: Code is available upon request. Results and used materials are available online at

Contact:  kirac@case.edu
BaCelLo: a balanced subcellular localization predictor
Authors: Pierleoni Andrea , Martelli Pier Luigi , Fariselli Piero , Casadio Rita
Published: July 2006

Motivation. The knowledge of the subcellular localization of a protein is fundamental for elucidating its function. It is difficult to determine the subcellular location for eukaryotic cells with experimental high-throughput procedures. Computational procedures are then needed for annotating the subcellular location of proteins in large scale genomic projects.

Results. BaCelLo is a predictor for five classes of subcellular localization (secretory pathway, cytoplasm, nucleus, mitochondrion and chloroplast) and it is based on different SVMs organized in a decision tree. The system exploits the information derived from the residue sequence and from the evolutionary information contained in alignment profiles. It analyzes the whole sequence composition and the compositions of both the N- and C-termini. The training set is curated in order to avoid redundancy. For the first time a balancing procedure is introduced in order to mitigate the effect of biased training sets. Three kingdom-specific predictors are implemented: for animals, plants and fungi, respectively. When distributing the proteins from animals and fungi into four classes, accuracy of BaCelLo reach 74% and 76%, respectively; a score of 67% is obtained when proteins from plants are distributed into five classes. BaCelLo outperforms the other presently available methods for the same task and gives more balanced accuracy and coverage values for each class. We also predict the subcellular localization of five whole proteomes, Homo sapiens, Mus musculus, Caenorhabditis elegans, Saccharomyces cerevisiae and Arabidopsis thaliana, comparing the protein content in each different compartment.

Availability. BaCelLo can be accessed at

Contact.  casadio@alma.unibo.it, andrea@biocomp.unibo.it, gigi@biocomp.unibo.it, piero@biocomp.unibo.it
A model-based approach for mining membrane protein crystallization trials
Authors: Asur Sitaram , Raman Pichai , Otey Matthew Eric , Parthasarathy Srinivasan
Published: July 2006

Motivation: Membrane proteins are known to play crucial roles in various cellular functions. Information about their function can be derived from their structure, but knowledge of these proteins is limited, as their structures are difficult to obtain. Crystallization has proved to be an essential step in the determination of macromolecular structure. Unfortunately, the bottleneck is that the crystallization process is quite complex and extremely sensitive to experimental conditions, the selection of which is largely a matter of trial and error. Even under the best conditions, it can take a large amount of time, from weeks to years, to obtain diffraction-quality crystals. Other issues include the time and cost involved in taking multiple trials and the presence of very few positive samples in a wide and largely undetermined parameter space. Therefore, any help in directing scientists’ attention to the hot spots in the conceptual crystallization space would lead to increased efficiency in crystallization trials.

Results: This work is an application case study on mining membrane protein crystallization trials to predict novel conditions that have a high likelihood of leading to crystallization. We use suitable supervised learning algorithms to model the data-space and predict a novel set of crystallization conditions. Our preliminary wet laboratory results are very encouraging and we believe this work shows great promise. We conclude with a view of the crystallization space that is based on our results, which should prove useful for future studies in this area.

Contact: Srinivasan Parthasarathy, 693 Dreese Lab, 2015 Neil Ave, Columbus, OH-43210, USA, Email: srini@cse.ohio-state.edu
Peptide sequence tag-based blind identification of post-translational modifications with point process model
Authors: Liu Chunmei , Yan Bo , Song Yinglei , Xu Ying , Cai Liming
Published: July 2006

An important but difficult problem in proteomics is the identification of post-translational modifications (PTMs) in a protein. In general, the process of PTM identification by aligning experimental spectra with theoretical spectra from peptides in a peptide database is very time consuming and may lead to high false positive rate. In this paper, we introduce a new approach that is both efficient and effective for blind PTM identification. Our work consists of the following phases. First, we develop a novel tree decomposition based algorithm that can efficiently generate peptide sequence tags (PSTs) from an extended spectrum graph. Sequence tags are selected from all maximum weighted antisymmetric paths in the graph and their reliabilities are evaluated with a score function. An efficient deterministic finite automaton (DFA) based model is then developed to search a peptide database for candidate peptides by using the generated sequence tags. Finally, a point process model—an efficient blind search approach for PTM identification, is applied to report the correct peptide and PTMs if there are any. Our tests on 2657 experimental tandem mass spectra and 2620 experimental spectra with one artificially added PTM show that, in addition to high efficiency, our ab-initio sequence tag selection algorithm achieves better or comparable accuracy to other approaches. Database search results show that the sequence tags of lengths 3 and 4 filter out more than 98.3% and 99.8% peptides respectively when applied to a yeast peptide database. With the dramatically reduced search space, the point process model achieves significant improvement in accuracy as well.

Availability: The software is available upon request.

Contact: {chunmei,cai}@cs.uga.edu
An integrative approach for causal gene identification and gene regulatory pathway inference
Authors: Tu Zhidong , Wang Li , Arbeitman Michelle N. , Chen Ting , Sun Fengzhu
Published: July 2006

Motivation: Gene expression variation can often be linked to certain chromosomal regions and are tightly associated with phenotypic variation such as disease conditions. Inferring the causal genes for the expression variation is of great importance but rather challenging as the linked region generally contains multiple genes. Even when a single candidate gene is proposed, the underlying biological mechanism by which the regulation is enforced remains unknown. Novel approaches are needed to both infer the causal genes and generate hypothesis on the underlying regulatory mechanisms.

Results: We propose a new approach which aims at achieving the above objectives by integrating genotype information, gene expression, protein-protein interaction, protein phosphorylation, and transcription factor (TF)–DNA binding information. A network based stochastic algorithm is designed to infer the causal genes and identify the underlying regulatory pathways. We first quantitatively verified our method by a test using data generated by yeast knock-out experiments. Over 40% of inferred causal genes are correct, which is significantly better than 10% by random guess. We then applied our method to a recent genome-wide expression variation study in yeast. We show that our method can correctly identify the causal genes and effectively output experimentally verified pathways. New potential gene regulatory pathways are generated and presented as a global network.

Availability: Source code is available upon request.

Contacts:  fsun@usc.edu
Integrating structured biological data by Kernel Maximum Mean Discrepancy
Authors: Borgwardt Karsten M. , Gretton Arthur , Rasch Malte J. , Kriegel Hans-Peter , Schölkopf Bernhard , Smola Alex J.
Published: July 2006

Motivation: Many problems in data integration in bioinformatics can be posed as one common question: Are two sets of observations generated by the same distribution? We propose a kernel-based statistical test for this problem, based on the fact that two distributions are different if and only if there exists at least one function having different expectation on the two distributions. Consequently we use the maximum discrepancy between function means as the basis of a test statistic.

The Maximum Mean Discrepancy (MMD) can take advantage of the kernel trick, which allows us to apply it not only to vectors, but strings, sequences, graphs, and other common structured data types arising in molecular biology.

Results: We study the practical feasibility of an MMD-based test on three central data integration tasks: Testing cross-platform comparability of microarray data, cancer diagnosis, and data-content based schema matching for two different protein function classification schemas. In all of these experiments, including high-dimensional ones, MMD is very accurate in finding samples that were generated from the same distribution, and outperforms its best competitors.

Conclusions: We have defined a novel statistical test of whether two samples are from the same distribution, compatible with both multivariate and structured data, that is fast, easy to implement, and works well, as confirmed by our experiments.

Availability:  

Contact:  kb@dbs.ifi.lmu.de
A probabilistic approach to protein backbone tracing in electron density maps
Authors: DiMaio Frank , Shavlik Jude , Phillips George N.
Published: July 2006

One particularly time-consuming step in protein crystallography is interpreting the electron density map; that is, fitting a complete molecular model of the protein into a 3D image of the protein produced by the crystallographic process. In poor-quality electron density maps, the interpretation may require a significant amount of a crystallographer's time. Our work investigates automating the time-consuming initial backbone trace in poor-quality density maps. We describe ACMI (Automatic Crystallographic Map Interpreter), which uses a probabilistic model known as a Markov field to represent the protein. Residues of the protein are modeled as nodes in a graph, while edges model pairwise structural interactions. Modeling the protein in this manner allows the model to be flexible, considering an almost infinite number of possible conformations, while rejecting any that are physically impossible. Using an efficient algorithm for approximate inference—belief propagation—allows the most probable trace of the protein's backbone through the density map to be determined. We test ACMI on a set of ten protein density maps (at 2.5 to 4.0 Å resolution), and compare our results to alternative approaches. At these resolutions, ACMI offers a more accurate backbone trace than current approaches.

Contact:  dimaio@cs.wisc.edu