bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of the SpeechEasy on Objective and Perceived Aspects of Stuttering: A 6-Month, Phase I Clinical Trial in Naturalistic Environments
Authors: Pollard Ryan , Ellis John B. , Finan Don , Ramig Peter R.
Published: August 2008

Purpose

Effects of the SpeechEasy when used under extraclinical conditions over several months were investigated. Primary purposes were to help establish Phase I level information about the therapeutic utility of the SpeechEasy and to compare those results with previous findings obtained in laboratory and clinical settings.

Method

Eleven adults who stutter participated. A nonrandomized ABA group design was utilized. Speech samples were collected every 2 weeks in extraclinical environments. Qualitative data were collected through weekly written logs and an exit questionnaire.

Results

Group analyses revealed a statistically significant effect of the SpeechEasy immediately postfitting but no treatment effect across 4 months' time. Individual responses varied greatly with regard to stuttering frequency and subjective impressions. Relatively more stuttering reduction occurred during oral reading than during formulated speech.

Conclusions

Based on this protocol, Phase II trials are not indicated. However, positive individual responses and self-reports suggest some clinical utility for the SpeechEasy. The use of more challenging sampling procedures strengthened external validity and captured more modest altered auditory feedback effects compared with those previously reported in laboratory settings. Device use coincided more so with positive subjective impressions than with measurable fluency improvement, highlighting challenges facing clinicians when implementing principles of evidence-based practice, including client-based preferences.
Aerodynamic and Acoustic Effects of Abrupt Frequency Changes in Excised Larynges
Authors: Alipour Fariborz , Finnegan Eileen M. , Scherer Ronald C.
Published: August 2008

Purpose

To determine the aerodynamic and acoustic effects due to a sudden change from chest to falsetto register or vice versa. It was hypothesized that the continuous change in subglottal pressure and flow rate alone (pressure-flow sweep [PFS]) can trigger a mode change in the canine larynx.

Method

Ten canine larynges were each mounted over a tapered tube that supplied pressurized, heated, and humidified air. Glottographic signals were recorded during each PFS experiment, during which airflow was increased in a gradual manner for a period of 20–30 s.

Results

Abrupt changes in fundamental frequency (F
0
) and mode of vibration occurred during the PFS in the passive larynx without any change in adduction or elongation. The lower frequency mode of oscillation of the vocal folds, perceptually identified as the chest register, had relatively large amplitude oscillation, significant vocal fold contact, a rich spectral content, and a relatively loud audio signal. The higher frequency mode of oscillation, perceptually identified as falsetto, had little or no vocal fold contact and a dominant first partial. Relatively abrupt F
0
changes also occurred for gradual adduction changes, with the chest register corresponding to greater adduction, falsetto to less adduction.
Argon cluster-mediated isolation and vibrational spectra of peroxy and nominally D3h isomers of CO3− and NO3−
Authors: Relph Rachael A. , Bopp Joseph C. , Johnson Mark A. , Viggiano A. A.
Published: August 2008

Vibrational predissociation spectra are reported for two isomeric forms of the gas-phase ions, CO3− and NO3−. The peroxy forms, (OOCO− and OONO−) were isolated using an Ar-mediated synthetic scheme involving exchange of CO and NO for the more weakly bound Ar ligands in O2−⋅Arm clusters, while the forms based on a central heteroatom (CO3− and NO3−) were generated by electron impact on CO2 and HNO3 vapor. The simple two-band spectrum of OOCO− indicates that it is best described as the O2−⋅CO ion-molecule complex, whereas the covalently bound CO3− form yields a much more complicated vibrational spectrum with bands extending out to 4000cm−1. In contrast, the NO3− ion yields a simple spectrum with only one transition as expected for the antisymmetric NO stretching fundamental of a species with D3h structure. The spectrum of the peroxynitrite isomer, OONO−, displays intermediate complexity that can be largely understood in the context of fundamentals associated with its cis and trans structures previously characterized in an Ar matrix.
Energy-enstrophy stability of β-plane Kolmogorov flow with drag
Authors: Tsang Yue-Kin , Young William R.
Published: August 2008

We develop a nonlinear stability method, the energy-enstrophy (EZ) method, that is specialized to two-dimensional hydrodynamics and basic state flows consisting of a single Helmholtz eigenmode. The method is applied to a β-plane flow driven by a sinusoidal body force and retarded by drag with damping time scale μ−1. The standard energy method [H. Fukuta and Y. Murakami, J. Phys. Soc. Jpn. 64, 3725 (1995)] shows that the laminar solution is monotonically and globally stable in a certain portion of the (μ,β)-parameter space. The EZ method proves nonlinear stability in a larger portion of the (μ,β)-parameter space than does the energy method. Moreover, by penalizing high wavenumbers, the EZ method identifies a most strongly amplifying disturbance that is more physically realistic than that delivered by the energy method. Linear instability calculations are used to determine the region of the (μ,β)-parameter space where the flow is unstable to infinitesimal perturbations. There is only a small gap between the linearly unstable region and the nonlinearly stable region, and full numerical solutions show only small transient amplification in that gap.
X-ray induced damage in DNA monitored by X-ray photoelectron spectroscopy
Authors: Ptasińska Sylwia , Stypczyńska Agnieszka , Nixon Tony , Mason Nigel J. , Klyachko Dimitri V. , Sanche Léon
Published: August 2008

In this work, the chemical changes in calf thymus DNA samples were analyzed by X-ray photoelectron spectroscopy (XPS). The DNA samples were irradiated for over 5h and spectra were taken repeatedly every 30min. In this approach the X-ray beam both damages and probes the samples. In most cases, XPS spectra have complex shapes due to contributions of C, N, and O atoms bonded at several different sites. We show that from a comparative analysis of the modification in XPS line shapes of the C 1s, O 1s, N 1s, and P 2p peaks, one can gain insight into a number of reaction pathways leading to radiation damage to DNA.
Bremsstrahlung target optimization for reflex triodes
Authors: Swanekamp S. B. , Weber B. V. , Stephanakis S. J. , Mosher D. , Commisso R. J.
Published: August 2008

The anode (tantalum) foil thickness in a reflex triode was varied from 2.5 to 250μm to maximize the dose from bremsstrahlung produced by a 1MV, 1MA, 100ns electron beam. Experiments and computer simulations show that the dose is maximized for a foil thickness of about 25μm, 1∕18th of the electron range computed from the continuous slowing down approximation. For foils thicker than optimum, self-absorption in the foil attenuates 10–100keV photons, reducing the dose. For foils thinner than optimum, the dose decreases as a result of electron migration to large radius. A simple formula that predicts the optimum thickness as a function of the beam current and voltage is derived that should be applicable to a large range of experimental parameters.
Homogeneous fractional embeddings
Authors: Inizan Pierre
Published: August 2008

Fractional equations appear in the description of the dynamics of various physical systems. For Lagrangian systems, the embedding theory developed by Cresson [“Fractional embedding of differential operators and Lagrangian systems,” J. Math. Phys. 48, 033504 (2007)] provides a univocal way to obtain such equations, stemming from a least action principle. However, no matter how equations are obtained, the dimension of the fractional derivative differs from the classical one and may induce problems of temporal homogeneity in fractional objects. In this paper, we show that it is necessary to introduce an extrinsic constant of time. Then, we use it to construct two equivalent fractional embeddings which retains homogeneity. The notion of fractional constant is also discussed through this formalism. Finally, an illustration is given with natural Lagrangian systems, and the case of the harmonic oscillator is entirely treated.
Nucleation and growth of cobalt disilicide precipitates during in situ transmission electron microscopy implantation
Authors: Ruault M.-O. , Fortuna F. , Borodin V. A. , Ganchenkova M. G. , Kirk M. A.
Published: August 2008

The paper is aimed at getting deeper insight into the fundamental mechanisms that govern CoSi2 precipitate nucleation and growth during Co ion implantation at high temperatures (500–650 °C). Information about nucleation and growth of metal silicides as a function of temperature and implantation flux is provided by experiments on cobalt implantation in silicon, performed directly by in situ transmission electron microscopy. The main attention is paid to the nucleation of B-type precipitates, which dominate under ion implantation conditions. The obtained quantitative behavior of precipitate number density and size and the scaling of these values with implantation flux are discussed and rationalized in terms of analytical and simulation approaches. An atomistic model of B-type precipitate nucleation based on the first-principles calculations of relative energetic efficiency of different Co clusters is proposed.
Linear variation of aluminum nitride capacitance versus voltage induced by a piezoelectric-electrostrictive coupling
Authors: Ben Hassine Nizar , Mercier Denis , Renaux Philippe , Chappaz Cédrick , Basrour Skandar , Defay Emmanuel
Published: August 2008

We report here the physical explanation of the unusual observed linear variation of AlN capacitance versus voltage bias: a third order coupling between piezoelectricity and electrostriction. A phenomenological model based on free energy consideration is proposed in order to implement the electrostrictive effect together with the piezoelectric one. This model allows the accurate determination of the electrostrictive coefficient of interest by two independent ways (Q13=0.094 m4 C−2), giving high confidence in the physical explanation proposed.
Effect of antenna capacitance on the plasma characteristics of an internal linear inductively coupled plasma system
Authors: Lim Jong Hyeuk , Kim Kyong Nam , Park Jung Kyun , Yeom Geun Young
Published: August 2008

This study examined the effect of the antenna capacitance of an inductively coupled plasma (ICP) source, which was varied using an internal linear antenna, on the electrical and plasma characteristics of the ICP source. The inductive coupling at a given rf current increased with decreasing antenna capacitance. This was caused by a decrease in the inner copper diameter of the antenna made from coaxial copper/quartz tubing, which resulted in a higher plasma density and lower plasma potential. By decreasing the diameter of the copper tube from 25to10mm, the plasma density of a plasma source size of 2750×2350mm2 was increased from approximately 8×1010∕cm3to1.5×1011∕cm3 at 15mTorr Ar and 9kW of rf power.
Origin of enhanced field emission characteristics postplasma treatment of multiwalled carbon nanotube array
Authors: Lee Kyu , Lim Seong Chu , Choi Young Chul , Lee Young Hee
Published: August 2008

Field emission properties of chemical-vapor-deposition-grown multiwalled carbon nanotubes (MWCNTs) with plasma treatment have been investigated. Origin of the enhanced field emission current was interpreted in terms of surface morphology of MWCNTs, work function, field enhancement factor, and emission area. Contrary to the general belief, the change in the work function increased slightly with the plasma treatment time, whereas the field enhancement factor decreased. We found that the number of emittable MWCNTs played a dominant role in the current enhancement.
Southern Ocean frontal structure and sea-ice formation rates revealed by elephant seals
Authors: Charrassin J.-B. , Hindell M. , Rintoul S. R. , Roquet F. , Sokolov S. , Biuw M. , Costa D. , Boehme L. , Lovell P. , Coleman R. , Timmermann R. , Meijers A. , Meredith M. , Park Y.-H. , Bailleul F. , Goebel M. , Tremblay Y. , Bost C.-A. , McMahon C. R. , Field I. C. , Fedak M. A. , Guinet C.
Published: August 2008

Polar regions are particularly sensitive to climate change, with the potential for significant feedbacks between ocean circulation, sea ice, and the ocean carbon cycle. However, the difficulty in obtaining
in situ
data means that our ability to detect and interpret change is very limited, especially in the Southern Ocean, where the ocean beneath the sea ice remains almost entirely unobserved and the rate of sea-ice formation is poorly known. Here, we show that southern elephant seals (
Mirounga leonina
) equipped with oceanographic sensors can measure ocean structure and water mass changes in regions and seasons rarely observed with traditional oceanographic platforms. In particular, seals provided a 30-fold increase in hydrographic profiles from the sea-ice zone, allowing the major fronts to be mapped south of 60°S and sea-ice formation rates to be inferred from changes in upper ocean salinity. Sea-ice production rates peaked in early winter (April–May) during the rapid northward expansion of the pack ice and declined by a factor of 2 to 3 between May and August, in agreement with a three-dimensional coupled ocean–sea-ice model. By measuring the high-latitude ocean during winter, elephant seals fill a “blind spot” in our sampling coverage, enabling the establishment of a truly global ocean-observing system.
Impact of enhanced tuberculosis diagnosis in South Africa: A mathematical model of expanded culture and drug susceptibility testing
Authors: Dowdy David W. , Chaisson Richard E. , Maartens Gary , Corbett Elizabeth L. , Dorman Susan E.
Published: August 2008

South Africa has high rates of tuberculosis (TB), including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Expanding access to culture and drug susceptibility testing (DST) for TB diagnosis may help control this epidemic, but the potential impact of existing and novel TB diagnostics is uncertain. By fitting to World Health Organization epidemiological estimates, we developed a compartmental difference-equation model of the TB/HIV epidemic among South African adults. Performing culture and DST in 37% of new cases and 85% of previously treated cases was projected to save 47,955 lives (17.2% reduction in TB mortality, 95% simulation interval (S.I.) 8.9−24.4%), avert 7,721 MDR-TB cases (14.1% reduction, 95% S.I. 5.3–23.8%), and prevent 46.6% of MDR-TB deaths (95% S.I. 32.6–56.0%) in South Africa over 10 years. Used alone, expanded culture and DST did not reduce XDR-TB incidence, but they enhanced the impact of transmission-reduction strategies, such as respiratory isolation. In South Africa, expanding TB culture and DST could substantially reduce TB, and particularly MDR-TB, mortality. Control of XDR-TB will require additional interventions, the impact of which may be enhanced by improved TB diagnosis.
PAI-1 inhibits neutrophil efferocytosis
Authors: Park Young-Jun , Liu Gang , Lorne Emmanuel F. , Zhao Xia , Wang Jing , Tsuruta Yuko , Zmijewski Jaroslaw , Abraham Edward
Published: August 2008

Phagocytosis of apoptotic cells, also called efferocytosis, is an essential feature of immune responses and critical for the resolution of inflammation. Plasma and tissue levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, are elevated in inflammatory conditions, including sepsis and acute lung injury, in which activated neutrophils accumulate in tissues and contribute to organ dysfunction. In this study, we explored the potential involvement of PAI-1 in modulating neutrophil efferocytosis. We found enhanced phagocytosis of viable PAI-1 deficient (PAI-1
−/−
) and of wild-type neutrophils treated with anti-PAI-1 antibodies. PAI-1 levels were decreased on the surface of apoptotic neutrophils and the enhanced phagocytosis of apoptotic wild-type neutrophils or of viable PAI-1
−/−
neutrophils was diminished by preincubation with PAI-1. The increased phagocytosis associated with PAI-1 deficiency or blockade depended on both the lipoprotein receptor-related protein (LRP) and its ligand, calreticulin (CRT), because the LRP-mediated increase in phagocytosis of viable neutrophils induced by blockade of CD 47 was abrogated by PAI-1. CRT levels are increased on viable PAI-1
−/−
neutrophils. While CRT colocalizes with PAI-1 on viable neutrophils, markedly diminished colocalization of PAI-1 and CRT was present on apoptotic neutrophils. Our data therefore indicate that PAI-1 serves as a novel “don't eat me” signal for viable and apoptotic neutrophils.
Megafauna biomass tradeoff as a driver of Quaternary and future extinctions
Authors: Barnosky Anthony D.
Published: August 2008

Earth's most recent major extinction episode, the Quaternary Megafauna Extinction, claimed two-thirds of mammal genera and one-half of species that weighed >44 kg between ≈50,000 and 3,000 years ago. Estimates of megafauna biomass (including humans as a megafauna species) for before, during, and after the extinction episode suggest that growth of human biomass largely matched the loss of non-human megafauna biomass until ≈12,000 years ago. Then, total megafauna biomass crashed, because many non-human megafauna species suddenly disappeared, whereas human biomass continued to rise. After the crash, the global ecosystem gradually recovered into a new state where megafauna biomass was concentrated around one species, humans, instead of being distributed across many species. Precrash biomass levels were finally reached just before the Industrial Revolution began, then skyrocketed above the precrash baseline as humans augmented the energy available to the global ecosystem by mining fossil fuels. Implications include (
i
) an increase in human biomass (with attendant hunting and other impacts) intersected with climate change to cause the Quaternary Megafauna Extinction and an ecological threshold event, after which humans became dominant in the global ecosystem; (
ii
) with continued growth of human biomass and today's unprecedented global warming, only extraordinary and stepped-up conservation efforts will prevent a new round of extinctions in most body-size and taxonomic spectra; and (
iii
) a near-future biomass crash that will unfavorably impact humans and their domesticates and other species is unavoidable unless alternative energy sources are developed to replace dwindling supplies of fossil fuels.
Microbes on mountainsides: Contrasting elevational patterns of bacterial and plant diversity
Authors: Bryant Jessica A. , Lamanna Christine , Morlon Hélène , Kerkhoff Andrew J. , Enquist Brian J. , Green Jessica L.
Published: August 2008

The study of elevational diversity gradients dates back to the foundation of biogeography. Although elevational patterns of plant and animal diversity have been studied for centuries, such patterns have not been reported for microorganisms and remain poorly understood. Here, in an effort to assess the generality of elevational diversity patterns, we examined soil bacterial and plant diversity along an elevation gradient. To gain insight into the forces that structure these patterns, we adopted a multifaceted approach to incorporate information about the structure, diversity, and spatial turnover of montane communities in a phylogenetic context. We found that observed patterns of plant and bacterial diversity were fundamentally different. While bacterial taxon richness and phylogenetic diversity decreased monotonically from the lowest to highest elevations, plants followed a unimodal pattern, with a peak in richness and phylogenetic diversity at mid-elevations. At all elevations bacterial communities had a tendency to be phylogenetically clustered, containing closely related taxa. In contrast, plant communities did not exhibit a uniform phylogenetic structure across the gradient: they became more overdispersed with increasing elevation, containing distantly related taxa. Finally, a metric of phylogenetic beta-diversity showed that bacterial lineages were not randomly distributed, but rather exhibited significant spatial structure across the gradient, whereas plant lineages did not exhibit a significant phylogenetic signal. Quantifying the influence of sample scale in intertaxonomic comparisons remains a challenge. Nevertheless, our findings suggest that the forces structuring microorganism and macroorganism communities along elevational gradients differ.
Epsin 1 is a cargo-specific adaptor for the clathrin-mediated endocytosis of the influenza virus
Authors: Chen Chen , Zhuang Xiaowei
Published: August 2008

During clathrin-mediated endocytosis, adaptor proteins recognize specific internalization signals on cargo receptors, either recruiting cargos into clathrin-coated pits (CCPs) or initiating clathrin-coat assembly around the cargo molecules. Here, we identify epsin 1, a clathrin-, ubiquitin-, and phospholipid-interacting protein, as a cargo-specific adaptor for influenza virus entry through the clathrin-mediated pathway. Using live-cell imaging to monitor the entry of individual virus particles, we observed recruitment of epsin 1 to the binding sites of influenza viruses in synchrony with the assembly of CCPs. Epsin 1 knockdown by siRNA significantly inhibited the clathrin-mediated endocytosis of the influenza virus and caused the majority of the virus particles to enter through a clathrin-independent pathway. The same treatment did not affect the entry of several classical ligands for clathrin-mediated endocytosis, including transferrin, LDL, and EGF. Overexpression of the dominant-negative epsin 1 mutant lacking the ubiquitin-interaction motifs nearly completely blocked the clathrin-mediated entry of the influenza virus without affecting transferrin uptake. These results suggest that epsin 1 functions as a cargo-specific adaptor for the clathrin-mediated entry of the influenza virus.
Attitudes to taboo phenomenon among Yoruba–English bilinguals
Authors: Adeyanju Dele
Published: August 2008

In most sociolinguistic environments, taboo phenomena exert a considerable influence on people’s linguistic usage. In modern times however, people’s attitudes to taboos vary depending on sex, age, occupation, literacy level and geographical location. Using a questionnaire for data elicitation, this study examines attitudes to taboos among Yoruba–English bilinguals in Nigeria. The study discovers that most of our subjects are favourably disposed to the existence of taboos and that this results in the preponderance of euphemisms and circumlocutions in Yoruba–English usage.
Coping with racism in Hebrew literary translation
Authors: Weissbrod Rachel
Published: August 2008

This article examines the treatment of racism in Hebrew literary translation. It relies on culture theorists such as Foucault, Said, Fanon and Bhabha who have analyzed the relations of a society with individuals and groups whom it regards as “others”. The texts discussed have been selected because they can illustrate critical arguments made by these theorists. They include texts which are openly racist (Henryk Sienkiewicz’s W pustyni i w puszczy [In Desert and Wilderness], Margaret Mitchell’s Gone with the Wind, Edgar Wallace’s The People of the River) and others that criticize racism but fall into the trap against which they warn (Mark Twain’s Adventures of Huckleberry Finn, Harriet Beecher Stowe’s Uncle Tom’s Cabin). The article also refers to “Geschichte von den schwarzen Buben” (in English, “The Story of the Inky Boys”), one of the stories included in Heinrich Hoffmann’s Struwwelpeter (The Slovenly Peter). In the latter, the Hebrew translations (rather than the German source) make use of racist stereotypes.

Inspired by translation researchers who regard translation as the meeting place of a culture with “others” (Venuti, Tymoczco, Cronin), the article also makes use of the concept of norms as elaborated by Toury. In line with his theoretical approach, it is assumed that the treatment of racism in translation depends not only on the overall attitude to racism in the receiving culture but also on its translation norms.
Does the taxman need a face? Effects of including photographs and examples in a tax form; a field experiment with senior citizens in The Netherlands
Authors: van Wijk Carel , Arts Anja
Published: August 2008

Due to changes in legislation, the Dutch tax department has become responsible for several allowances as well. This forces the department to improve the affective and motivational responses to its forms. In an attempt to do so, the department has included photographs and examples in a form for reimbursement of medical care costs. This form was tested in a field experiment by comparing it with three versions from which either photographs, examples or both were removed. 242 senior citizens gave their evaluations after working with one of these form versions. The inclusion of photos and examples appeared to make the form more attractive, less discouraging, and a bit more favourable for the image of the tax department. It also led to more self-confidence, but only among false optimists, i.e., those who actually had their answers wrong became more certain about their performance. A post-hoc analysis revealed that the scores on affective and motivational aspects correlated strongly, and almost exclusively, with the perceived intelligibility of a form. The addition of feelgood elements seems to be of limited relevance.
Role of the chemokine decoy receptor D6 in balancing inflammation, immune activation, and antimicrobial resistance in Mycobacterium tuberculosis infection
Authors: Di Liberto Diana , Locati Massimo , Caccamo Nadia , Vecchi Annunciata , Meraviglia Serena , Salerno Alfredo , Sireci Guido , Nebuloni Manuela , Caceres Neus , Cardona Pere-Joan , Dieli Francesco , Mantovani Alberto
Published: August 2008

D6 is a decoy and scavenger receptor for inflammatory CC chemokines. D6-deficient mice were rapidly killed by intranasal administration of low doses of Mycobacterium tuberculosis. The death of D6−/− mice was associated with a dramatic local and systemic inflammatory response with levels of M. tuberculosis colony-forming units similar to control D6-proficient mice. D6-deficient mice showed an increased numbers of mononuclear cells (macrophages, dendritic cells, and CD4 and CD8 T lymphocytes) infiltrating inflamed tissues and lymph nodes, as well as abnormal increased concentrations of CC chemokines (CCL2, CCL3, CCL4, and CCL5) and proinflammatory cytokines (tumor necrosis factor α, interleukin 1β, and interferon γ) in bronchoalveolar lavage and serum. High levels of inflammatory cytokines in D6−/− infected mice were associated with liver and kidney damage, resulting in both liver and renal failure. Blocking inflammatory CC chemokines with a cocktail of antibodies reversed the inflammatory phenotype of D6−/− mice but led to less controlled growth of M. tuberculosis. Thus, the D6 decoy receptor plays a key role in setting the balance between antimicrobial resistance, immune activation, and inflammation in M. tuberculosis infection.
Fusing time series expression data through hybrid aggregation and hierarchical merge
Authors: Tsiporkova Elena , Boeva Veselka
Published: August 2008

Summary: A novel integration approach targeting the combination of multi-experiment time series expression data is proposed. A recursive hybrid aggregation algorithm is initially employed to extract a set of genes, which are eventually of interest for the biological phenomenon under study. Next, a hierarchical merge procedure is specifically developed for the purpose of fusing together the multiple-experiment expression profiles of the selected genes. This employs dynamic time warping alignment techniques in order to account adequately for the potential phase shift between the different experiments. We subsequently demonstrate that the resulting gene expression profiles consistently reflect the behavior of the original expression profiles in the different experiments.

Contact:  vboeva@tu-plovdiv.bg

Supplementary information: Supplementary data are available at http://www.tu-plovdiv.bg/Container/bi/DataIntegration/
A fast and flexible method for the segmentation of aCGH data
Authors: Ben-Yaacov Erez , Eldar Yonina C.
Published: August 2008

Motivation: Array Comparative Genomic Hybridization (aCGH) is used to scan the entire genome for variations in DNA copy number. A central task in the analysis of aCGH data is the segmentation into groups of probes sharing the same DNA copy number. Some well known segmentation methods suffer from very long running times, preventing interactive data analysis.

Results: We suggest a new segmentation method based on wavelet decomposition and thresholding, which detects significant breakpoints in the data. Our algorithm is over 1000 times faster than leading approaches, with similar performance. Another key advantage of the proposed method is its simplicity and flexibility. Due to its intuitive structure, it can be easily generalized to incorporate several types of side information. Here, we consider two extensions which include side information indicating the reliability of each measurement, and compensating for a changing variability in the measurement noise. The resulting algorithm outperforms existing methods, both in terms of speed and performance, when applied on real high density CGH data.

Availability: Implementation is available under software tab at: http://www.ee.technion.ac.il/Sites/People/YoninaEldar/

Contact:  yonina@ee.technion.ac.il
Automatic decomposition of kinetic models of signaling networks minimizing the retroactivity among modules
Authors: Saez-Rodriguez Julio , Gayer Stefan , Ginkel Martin , Gilles Ernst Dieter
Published: August 2008

Motivation: The modularity of biochemical networks in general, and signaling networks in particular, has been extensively studied over the past few years. It has been proposed to be a useful property to analyze signaling networks: by decomposing the network into subsystems, more manageable units are obtained that are easier to analyze. While many powerful algorithms are available to identify modules in protein interaction networks, less attention has been paid to signaling networks defined as chemical systems. Such a decomposition would be very useful as most quantitative models are defined using the latter, more detailed formalism.

Results: Here, we introduce a novel method to decompose biochemical networks into modules so that the bidirectional (retroactive) couplings among the modules are minimized. Our approach adapts a method to detect community structures, and applies it to the so-called retroactivity matrix that characterizes the couplings of the network. Only the structure of the network, e.g. in SBML format, is required. Furthermore, the modularized models can be loaded into ProMoT, a modeling tool which supports modular modeling. This allows visualization of the models, exploiting their modularity and easy generation of models of one or several modules for further analysis. The method is applied to several relevant cases, including an entangled model of the EGF-induced MAPK cascade and a comprehensive model of EGF signaling, demonstrating its ability to uncover meaningful modules. Our approach can thus help to analyze large networks, especially when little a priori knowledge on the structure of the network is available.

Availability: The decomposition algorithms implemented in MATLAB (Mathworks, Inc.) are freely available upon request. ProMoT is freely available at http://www.mpi-magdeburg.mpg.de/projects/promot

Contact:  gayers@mpi-magdeburg.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
Poisson adjacency distributions in genome comparison: multichromosomal, circular, signed and unsigned cases
Authors: Xu Wei , Alain Benoît , Sankoff David
Published: August 2008

The number of common adjacencies of genetic markers, as a measure of the similarity of two genomes, has been widely used as indicator of evolutionary relatedness and as the basis for inferring phylogenetic relationships. Its probability distribution enables statistical tests in detecting whether significant evolutionary signal remains in the marker order. In this article, we derive the probability distributions of the number of adjacencies for a number of types of genome—signed or unsigned, circular or linear, single-chromosome or multichromosomal. Generating functions are found for singlechromosome cases, from which exact counts can be calculated. Probability approaches are adopted for multichromosomal cases, where we find the exact values for expectations and variances. In both cases, the limiting distributions are derived in term of numbers of adjacencies. For all unsigned cases, the limiting distribution is Poisson with parameter 2; for all signed cases, the limiting distribution is Poisson with parameter ½.

Contact:  wxu060@uottawa.ca
Connect the dots: exposing hidden protein family connections from the entire sequence tree
Authors: Loewenstein Yaniv , Linial Michal
Published: August 2008

Motivation: Mapping of remote evolutionary links is a classic computational problem of much interest. Relating protein families allows for functional and structural inference on uncharacterized families. Since sequences have diverged beyond reliable alignment, these are too remote to identify by conventional methods.

Approach: We present a method to systematically identify remote evolutionary relations between protein families, leveraging a novel evolutionary-driven tree of all protein sequences and families. A global approach which considers the entire volume of similarities while clustering sequences, leads to a robust tree that allows tracing of very faint evolutionary links. The method systematically scans the tree for clusters which partition exceptionally well into extant protein families, thus suggesting an evolutionary breakpoint in a putative ancient superfamily. Our method does not require family profiles (or HMMs), or multiple alignment.

Results: Considering the entire Pfam database, we are able to suggest 710 links between protein families, 125 of which are confirmed by existence of Pfam clans. The quality of our predictions is also validated by structural assignments. We further provide an intrinsic characterization of the validity of our results and provide examples for new biological findings, from our systematic scan. For example, we are able to relate several bacterial pore-forming toxin families, and then link them with a novel family of eukaryotic toxins expressed in plants,.sh venom and notably also uncharacterized proteins from human pathogens.

Availability: A detailed list of putative homologous superfamilies, including 210 families of unknown function, has been made available online: http://www.protonet.cs.huji.ac.il/dots

Contact:  lonshy@cs.huji.ac.il
On the frequency of copy number variants
Authors: Ionita-Laza Iuliana , Laird Nan M. , Raby Benjamin A. , Weiss Scott T. , Lange Christoph
Published: August 2008

Motivation: Estimating the frequency distribution of copy number variants (CNVs) is an important aspect of the effort to characterize this new type of genetic variation. Currently, most studies report a strong skew toward low-frequency CNVs. In this article, our goal is to investigate the frequencies of CNVs. We employ a two-step procedure for the CNV frequency estimation process. We use family information a posteriori to select only the most reliable CNV regions, i.e. those showing high rates of Mendelian transmission.

Results: Our results suggest that the current skew toward low-frequency CNVs may not be representative of the true frequency distribution, but may be due, among other reasons, to the non-negligible false negative rates that characterize CNV detection methods. Moreover, false positives are also likely, as low-frequency CNVs are hard to detect with small sample sizes and technologies that are not ideally suited for their detection. Without appropriate validation methods, such as incorporation of biologically relevant information (for example, in our case, the transmission of heritable CNVs from parents to offspring), it is difficult to assess the validity of specific CNVs, and even harder to obtain reliable frequency estimates.

Availability: Software implementing the methods described in this article is available for download at the following address: http://www.isites.harvard.edu/icb/icb.do?keyword=k36162

Contact:  iionita@hsph.harvard.edu

Supplementary informantion:  Supplementary data are available at Bioinformatics online.
Limitations of population models in predicting climate change effects: a simulation study of sociable weavers in southern Africa
Authors: Schwager Monika , Covas Rita , Blaum Niels , Jeltsch Florian
Published: August 2008

Current approaches for predicting climate change effects on populations comprise static models based on the geographical distribution of species, and dynamic population models based on the relationship between population processes and the recent variation in climate. Population models have the inherent advantage of considering a species’ response to climate as resulting from distinct mechanisms. However, they may have the disadvantage of considering only short‐term processes as they occur under the current climate, disregarding slowly adapting mechanisms. It would be important, however, to know whether slowly adapting processes occur, and whether they will respond to climate change. A way of testing for a discrepancy between short‐term and long‐term mechanisms in the response to climate is contrasting a population model with the current distribution and abundance in different climates. We demonstrate this idea for the sociable weaverPhiletairussocius, a passerine bird of semiarid southern Africa. We develop a dynamic population model that predicts the species’ response to mean annual precipitation (MAP) and tests whether the model can reproduce the occurrence of sociable weavers in their current range of MAP as well as realistic abundances in two study locations with different MAP. The model predicts a decreased abundance under a scenario of decreased MAP and it can reproduce realistic populations in a single location. However it cannot explain the occurrence of sociable weavers across their entire distribution nor does it produce realistic abundances in the two areas when they were tested simultaneously. The results imply that the sensitive short‐term response to MAP is buffered by long‐term processes such as adaptation or plasticity in life history, shifts in interspecific interactions or changes in habitat structure. We suggest that this result is common for animals in semi‐arid and arid regions and discuss implications for static and dynamic modelling approaches in climate change research.
Habitat choice precedes host plant choice – niche separation in a species pair of a generalist and a specialist butterfly
Authors: Friberg Magne , Olofsson Martin , Berger David , Karlsson Bengt , Wiklund Christer
Published: August 2008

The sister species Leptidea reali and L. sinapis have partitioned their niches differently in different parts of their sympatric distribution. In Spain and France L. sinapis is a widespread generalist whereas L. reali is specialized on high altitude open areas. Interestingly, the reverse is true in Ireland and the Czech Republic where L. reali is widespread and L. sinapis specialized on meadows. In Sweden, L. reali is a habitat specialist confined to meadows, whereas L. sinapis is a habitat generalist also inhabiting forests. Ultimately, the geographic mosaic of niche separation is the result of local processes in each contact zone or a secondary effect of the host plant distribution, if L. sinapis and L. reali prefer different legume host plants. Hence, in Sweden L. sinapis might utilize the forest habitat either due to a wider habitat preference or due to a wider host plant preference than L. reali. Studies of wild butterflies showed that L. sinapis laid 26% of their eggs on forest‐associated legumes compared to 6% in L. reali, although laboratory experiments showed that both species had virtually identical host plant preferences strongly preferring the meadow‐associated legume Lathyrus pratensis. Furthermore, flight duration tests in a variety of temperatures demonstrated a between‐species difference; L. sinapis females reached their flight optimum at a lower temperature than L. reali females. The lower L. sinapis flight temperature optimum is most probably a secondary effect due to habitat‐specific selection, and therefore a consequence rather than the cause of the habitat partitioning. The finding that habitat choice precedes host plant choice suggests that the European geographic mosaic of niche separation, with L. sinapis and L. reali shifting habitat specialist/generalist roles, is not caused by rigid between‐species differences in a related niche parameter, but instead is a result of local processes within each secondary contact zone.
Caspase‐3 activation as a key factor for HBx‐transformed cell death
Authors: Kim A. , Kwon O. S. , Kim S. O. , He L. , Bae E. Y. , Lee M. S. , Jeong S. J. , Shim J. H. , Yoon D. Y. , Kim C. H. , Moon A. , Kim K. E. , Ahn J. S. , Kim B. Y.
Published: August 2008

Abstract.  Objectives: Nuclear factor‐kappa B (NF‐κB) activation has been associated with the tumorigenic growth of hepatitis B virus X protein (HBx)‐transformed cells. This study was aimed to find a key target for treatment of HBx‐mediated cancers. Materials and methods: NF‐κB activation, endoplasmic reticulum‐stress (ER‐stress), caspase‐3 activation, and cell proliferation were evaluated after Chang/HBx cells permanently expressing HBx viral protein were treated with inhibitors of NF‐κB, proteasome and DNA topoisomerase. Results: Inhibition of NF‐κB transcriptional activity by transient transfection with mutant plasmids encoding Akt1 and glycogen synthase kinase‐3β (GSK‐3β), or by treatment with chemical inhibitors, wortmannin and LY294002, showed little effect on the survival of Chang/HBx cells. Furthermore, IκBα (S32/36A) mutant plasmid or other NF‐κB inhibitors, 1‐pyrrolidinecarbonidithioic acid and sulphasalazine, were also shown to have little effect on the cell proliferation. By contrast, proteasome inhibitor‐1 (Pro1) and MG132 enhanced the HBx‐induced ER‐stress response and the subsequent activation of caspase‐12, ‐9 and ‐3 and reduced cell proliferation. Camptothecin (CPT), however, triggered activation of caspase‐3 without induction of caspase‐12, and reduced cell proliferation. In addition, CPT‐induced cell death was reversed by pre‐treatment with z‐DEVD, a caspase‐3‐specific inhibitor. Conclusions: Detailed exploitation of the regulators of caspase‐3 activation could open the gate for finding an efficient target for development of anticancer therapeutics against HBx‐transformed hepatocellular carcinoma.
Current situation of regular replacement therapy (prophylaxis) for haemophilia in Japan
Authors: TAKI M. , SHIRAHATA A. ,   FOR THE FOURTH SEMINAR ON REGULAR REPLACEMENT THERAPY
Published: August 2008

Summary.  We conducted a questionnaire survey of haemophilia treaters participating in the Fourth Seminar on Regular Replacement Therapy (sponsored by Baxter Bioscience, 4 March 2006) to clarify the current status (up to January 2006) of replacement therapy for haemophilia. The haemophilia treaters including medical doctor, nurse belonged to 48 institutions located in the 23 prefectures of Japan. Topics included age at the initiation of regular replacement therapy (prophylaxis), and expected future situation of patients who are currently receiving prophylaxis. Data were collected from 1267 patients with haemophilia A and 273 patients with haemophilia B who had been treated at the represented institutions. Of these haemophilia A and B patients, 23% and 16% had received a prophylactic treatment regimen respectively. A breakdown of each disease by severity demonstrated that of the patients with severe haemophilia A and B patients, 27% and 18% of patients received a prophylaxis treatment, compared to 17% and 19% of patients with moderate type, and 1% and 3% of patients with mild type respectively. Of those severe haemophilia A and B patients receiving prophylaxis, the percentage of primary prophylaxis, which means prophylaxis begins under 2 years of age, was still small for 24% and 29% respectively. However, approximately half of the patients received prophylaxis during the age of 2–14 years, which suggests that secondary prophylaxis is widely spread in the age group in Japan. Problems in introduction of prophylaxis include difficulty in peripheral venous access, a lack of understanding of the therapy by the caregiver. In addition, the fear of inhibitor development, as well as the psychological anxiety in paediatric patients, was also mentioned as barriers to initiating and continuing prophylaxis.
An investigation into the relationship between apical root Impedance and canal anatomy
Authors: Ardeshna S. M. , Flanagan M. , Ng Y.‐L. , Gulabivala K.
Published: August 2008

Aim  To investigate a possible relationship between apical root impedance and canal anatomy.

Methodology  Twenty‐three roots from human extracted teeth (mostly single rooted but also from molars) with different apical anatomy were selected. The apical anatomy was initially classified by staining the root tip to identify number of canal exits; after impedance measurements, the anatomy was confirmed by staining and clearing the dentine. The roots were divided into two groups; 12 had simple (S) anatomy (Vertucci type 1 with a single exit) and 11 had complex (C) anatomy (various Vertucci canal types with multiple exist). Impedance measurements were taken using a frequency response analyser at seven levels in the root (0.0, 0.5, 1.0, 2.0, 3.0, 4.0 and 5.0 mm short of the apical terminus) at 14 frequencies ranging from 1120 to 100 000 Hz. Care was taken to control the temperature and other variables that could confound measurement accuracy. The impedance characteristics of individual roots were compared with 37 equivalent circuits (based on a pool created from a previous study); the best fitting equivalent circuit was selected. The equivalent circuits were used as the single outcome measure describing the impedance characteristics and correlated with the canal anatomy (S/C). Generalized estimating equations were used to perform logistic regression to analyse the data.

Results  Canal anatomy had a significant (P = 0.046) effect on the equivalent circuit model. One circuit (model 10) was found to be the commonest and occurred significantly more commonly in the simple canals. The odds of prevalence of circuit model 10 were 2.2 times (odds ratio 2.17, 95% confidence interval 1.01–4.63) higher in canals with simple anatomy compared with canals with complex anatomy.

Conclusions  Canal anatomy had a significant effect on the equivalent circuit describing its impedance characteristics. It should be possible to use impedance spectroscopy to clinically predict and image apical canal complexities.