bluuebunny/crossref_metadata_2025 huggingface dataset:
Mathematical modelling and experimental study of a solar distillation system
Authors: Mahian O , Kianifar A
Published: April 2011

The production of potable water from saltwater or brackish water using solar distillation has been practised for many years in different parts of the world. However, little attention has been paid to the feasibility of this technique in Iran. In this work, a solar still with a basin area of 0.9 m2 and a glass cover in the form of a pyramid has been designed and constructed, and its performance is studied experimentally in Mashhad, Iran. Also, the performance of the solar still is modelled where a small fan was utilized to enhance the daily productivity of freshwater. In addition to the effect of forced convection caused by a fan, the effects of the water depth, the insulation thickness of the basin base, and the wind velocity have been investigated. The empirical results have been compared with the results obtained from the mathematical model and good agreement has been obtained. The results show that the use of a low-cost fan with negligible power can be an effective and economical way of enhancing the evaporation rate and hence freshwater production. Based on the mathematical model, the daily productivity of freshwater increases up to ∼ 56 per cent at a Reynolds number of 35 000. Finally, an effective range for the wind velocity as well as insulation thickness is presented in order to optimize the production rate of freshwater.
On the kinematics and synthesis of a geared five-bar slider–crank mechanism
Authors: Sultan I A , Kalim A
Published: April 2011

The geared five-bar mechanism possesses kinematic abilities that qualify its utility in various industrial applications. Small changes to the mechanism topology or dimensions create new designs with different motion characteristics. This article presents design-orientated kinematical insights and mathematical treatments for the embodiment of the mechanism in which the end gear is eccentrically pivoted to a sliding element. For its synthesis, a kinematic classification is introduced and approximate curves are used to guide the motion of the slider. A gradient-based Levenberg–Marquardt formulation is employed for the optimization procedure. Geometric, mobility, and dimensional constraints are utilized together with numerical position equations for the analysis. Two case studies are presented at the end of this article to highlight the versatility of the mechanism and prove the validity of the presented mathematical model.
Robust and precision control for a directly-driven XY table
Authors: Wang F , Zhao X , Zhang D , Ma Z , Jing X
Published: April 2011

To provide faster, more repeatable, and stronger microelectronics bonding technology, this article presents the design and implementation of a robust and precision controller for a high-speed linear voice-coil motor, direct-drive, XY positioning table. Moreover, the dynamic design methodology of the control system for the positioning table is proposed based on electromechanical co-simulation. Using the finite-element method and dynamic analysis, the rigid–flexible coupled mechanical model of the XY table is established. With the aid of the system identification approach, the open-loop model of the control system for the X-axis table is obtained. On this basis, the proportion integration differentiation controller with incomplete derivation and the sliding mode controller (SMC) with the exponential reaching law are designed to control the X-axis table. The performances of the controllers are investigated using electromechanical co-simulations and experimental tests, and the results show that the motion overshoot and settling time are reduced using the SMC with an exponential reaching law. The SMC with the exponential reaching law also shows strong robustness against external disturbances. The experiment and co-simulation results are in good agreement, which confirms the validity and feasibility of the dynamic design methodology for a high-speed and high-accuracy positioning table based on electromechanical co-simulation.
Guided tail modelling for efficient and accurate reliability estimation of highly safe mechanical systems
Authors: Acar E
Published: April 2011

Classical tail modelling is based on performing a relatively small number of limit-state calculations through Monte Carlo sampling, and then fitting a generalized Pareto distribution to the tail part of the data. The limit-state calculations that do not belong to the tail part are discarded. To reduce the amount of discarded data, this article proposes an efficient tail modelling procedure based on guiding the limit-state evaluations towards the sampling points that have high chances of yielding limit-state values falling into the tail region. The guidance of the limit-state evaluations is achieved through a procedure that utilizes limit-state approximation and distribution fitting. The accuracy of the proposed method is tested through a mathematical problem and four structural mechanics problems, and it is found that the accuracy of reliability estimations can be significantly increased compared to classical tail modelling techniques for the same number of limit-state function evaluations. In addition, it is also found that the improvement in accuracy can be traded off for reducing the number of limit-state evaluations.
Uniaxial tensile fracture of stainless steel–aluminium bi-metals
Authors: Zhang D-H , Guo C , Du X-P
Published: April 2011

The mechanical behaviour of aluminium 1A30–stainless steel 1Cr18Ni9Ti bi-metals, made by the explosive welding method, is investigated under uniaxial tension conditions. The mechanical parameters of the bi-metal calculated using the mixture rule theory under uniaxial tension conditions are compared with measured parameters. It is found that the mixture rule theory is suitable for the calculation of the mechanical parameters except for ultimate tensile strength. Experimental data show that yield stress and ultimate tensile strength have an exponential relationship with the relative thickness ratio of stainless steel, respectively. A mathematical model is introduced to describe the relationships of yield stress and ultimate tensile strength to the relative thickness ratio of stainless steel. It is also found that elastic modulus, hardening coefficient, and hardening exponent basically have a linear relationship with the absolute thickness ratio of stainless steel, respectively. All the relationships show a monotonically increasing tendency. Fracture behaviour under uniaxial tensile conditions mainly take the form of fracture on the stainless steel side of the bi-metal and detachment in the interface.
A numerical study of the effect of radial confinement on the characteristics of laminar co-flow methane–oxygen diffusion flames
Authors: Bhadraiah K , Raghavan V
Published: April 2011

A numerical investigation of the characteristics of laminar co-flow methane–oxygen diffusion flames has been carried out. The temperature and nitric oxide (NO) distributions in unconfined and partly confined flames are studied in detail. Radial confinements of different diameters and with a length of 150 times the fuel jet diameter have been considered to allow atmospheric nitrogen entry only from the top. A numerical model with a 43-step chemical kinetics mechanism and an optically thin radiation sub-model is employed to carry out simulations. The numerical model has been validated using the experimental data available in the literature. The effect of oxygen flowrate on temperature distributions is studied thoroughly. Confined flame extents are compared with the corresponding unconfined flame extents with the help of OH contours. The effect of confinement diameter on temperature and NO distributions is analysed in detail. At low oxygen flowrates, the extents of confined flames are higher than those of an unconfined flame. At a higher oxygen flowrate, the extent of unconfined flame becomes higher. The confined flames are in general hotter than the unconfined flames. However, at the highest oxygen flowrate and for an intermediate confinement diameter, the flame has the lowest maximum temperature. The amount of NO produced in confined flames is higher than the unconfined flames, due to air entrainment from the top of the confining tube, which increases the residence time for nitrogen transport and its oxidation. At the highest oxygen flowrate considered, numerical predictions show that for a given confinement length, there is an optimum confinement diameter which results in a minimum net production of NO among all the flames.
A Transformative Collegiate Discourse
Authors: Ortlieb Evan
Published: April 2011

The languages, attitudes, experiences, and interests of groups of people are often interconnected through discourses. Within collegiate courses, systems of connected individuals progress through learning opportunities, often led by their professors. During one graduate course at Louisiana State University, two students acted as research investigators studying the unique characteristics of a collegiate discourse. The findings indicate that authors of the study were members of the discourse, topics of discussion were guided by only those students in attendance, and there was reciprocity in teaching and learning between active members of the discourse.
Lars and the Real Girl
Authors: Remington Ted
Published: April 2011

The 2007 film Lars and the Real Girl challenged viewer’s expectations, not simply through its unusual premise (a man having a relationship with a doll), through its consistent refusal to resolve the plot’s various conflicts through verbal or physical violence. Instead, the plot resolves in a way consistent with what peace researcher Johan Galtung has termed positive transcendence, a means of coming to a resolution that meets the needs of all parties. Although the film’s far-fetched plot makes direct practical application of the characters’ actions unlikely, the film performs a more important role in helping to expand moviegoers’ “horizons of expectation.” By prompting its audience to accept an utterly nonviolent, nonconfrontational resolution to the central conflict of the plot, Lars and the Real Girl subverts the notion that satisfying cinematic endings must involve winners and losers. It helps make room for a greater acceptance of nonviolent resolution of problems in popular film.
Constitutive Notch pathway activation in murine ZMYM2-FGFR1–induced T-cell lymphomas associated with atypical myeloproliferative disease
Authors: Ren MingQiang , Cowell John K.
Published: April 2011

The ZMYM2-FGFR1 (formerly known as ZNF198-FGFR1) fusion kinase induces stem cell leukemia–lymphoma syndrome (SCLL), a hematologic malignancy characterized by rapid transformation to acute myeloid leukemia and T-lymphoblastic lymphoma. In the present study, we demonstrate frequent, constitutive activation of Notch1 and its downstream target genes in T-cell lymphomas that arose in a murine model of ZMYM2-FGFR1 SCLL. Notch up-regulation was also demonstrated in human SCLL- and FGFR1OP2-FGFR1-expressing KG-1 cells. To study the role of Notch in T-cell lymphomagenesis, we developed a highly tumorigenic cell line from ZMYM2-FGFR1–expressing cells. Pharmacologic inhibition of Notch signaling in these cells using γ-secretase inhibitors significantly delayed leukemogenesis in vivo. shRNA targeting of Notch1, as well as c-promoter–binding factor 1 (CBF1) and mastermind-like 1 (MAML1), 2 essential cofactors involved in transcriptional activation of Notch target genes, also significantly delayed or inhibited tumorigenesis in vivo. Mutation analysis demonstrated that 5′ promoter deletions and alternative promoter usage were responsible for constitutive activation of Notch1 in all T-cell lymphomas. These data demonstrate the importance of Notch signaling in the etiology of SCLL, and suggest that targeting this pathway could provide a novel strategy for molecular therapies to treat SCLL patients.
Overexpression of microRNA-16-2 contributes to the abnormal erythropoiesis in polycythemia vera
Authors: Guglielmelli Paola , Tozzi Lorenzo , Bogani Costanza , Iacobucci Ilaria , Ponziani Vanessa , Martinelli Giovanni , Bosi Alberto , Vannucchi Alessandro M.
Published: April 2011

Deregulated expression of microRNAs is associated with neoplasia. Here, we show that mature miR-16 levels are abnormally increased in CD34+ cells of patients with polycythemia vera as a consequence of preferential expression of miR-16-2 on chromosome 3 rather than of miR-16-1 on chromosome 13. Forced expression of miRNA-16 in normal CD34+ cells stimulated erythroid cell proliferation and maturation. Conversely, exposure of polycythemia vera CD34+ cells to small interfering RNA against pre-miR-16-2 reduced erythroid colonies and largely prevented formation of erythropoietin-independent colonies; myeloid progenitors remained unaffected. Experiments with knock down of JAK2 indicated that overexpression of miR-16 was independent of JAK/STAT pathway activation. Mice injected with an miR-16 antagomir showed a blunted erythroid response to exogenous erythropoietin, which indicates a role of miR-16 in normal erythropoiesis. These data suggest that deregulation of miR-16-2 contributes to abnormal expansion of erythroid lineage in polycythemia vera. However, the mechanisms for miR-16-2 overexpression remain to be elucidated, because no genetic abnormalities at the miR-16-2 locus were discovered.
Discovering time-lagged rules from microarray data using gene profile classifiers
Authors: Gallo Cristian A , Carballido Jessica A , Ponzoni Ignacio
Published: April 2011

Background

Gene regulatory networks have an essential role in every process of life. In this regard, the amount of genome-wide time series data is becoming increasingly available, providing the opportunity to discover the time-delayed gene regulatory networks that govern the majority of these molecular processes.

Results

This paper aims at reconstructing gene regulatory networks from multiple genome-wide microarray time series datasets. In this sense, a new model-free algorithm called GRNCOP2 (G ene R egulatory N etwork inference by C ombinatorial OP timization 2), which is a significant evolution of the GRNCOP algorithm, was developed using combinatorial optimization of gene profile classifiers. The method is capable of inferring potential time-delay relationships with any span of time between genes from various time series datasets given as input. The proposed algorithm was applied to time series data composed of twenty yeast genes that are highly relevant for the cell-cycle study, and the results were compared against several related approaches. The outcomes have shown that GRNCOP2 outperforms the contrasted methods in terms of the proposed metrics, and that the results are consistent with previous biological knowledge. Additionally, a genome-wide study on multiple publicly available time series data was performed. In this case, the experimentation has exhibited the soundness and scalability of the new method which inferred highly-related statistically-significant gene associations.

Conclusions

A novel method for inferring time-delayed gene regulatory networks from genome-wide time series datasets is proposed in this paper. The method was carefully validated with several publicly available data sets. The results have demonstrated that the algorithm constitutes a usable model-free approach capable of predicting meaningful relationships between genes, revealing the time-trends of gene regulation.
PEX11β induces peroxisomal gene expression and alters peroxisome number during early Xenopus laevis development
Authors: Fox Mark A , Walsh Logan A , Nieuwesteeg Michelle , Damjanovski Sashko
Published: April 2011

Background

Peroxisomes are organelles whose roles in fatty acid metabolism and reactive oxygen species elimination have contributed much attention in understanding their origin and biogenesis. Many studies have shown that de novo peroxisome biogenesis is an important regulatory process, while yeast studies suggest that total peroxisome numbers are in part regulated by proteins such as Pex11, which can facilitate the division of existing peroxisomes. Although de novo biogenesis and divisions are likely important mechanisms, the regulation of peroxisome numbers during embryonic development is poorly understood. Peroxisome number and function are particularly crucial in oviparous animals such as frogs where large embryonic yolk and fatty acid stores must be quickly metabolized, and resulting reactive oxygen species eliminated. Here we elucidate the role of Pex11β in regulating peroxisomal gene expression and number in Xenopus laevis embryogenesis.

Results

Microinjecting haemagglutinin (HA) tagged Pex11β in early embryos resulted in increased RNA levels for peroxisome related genes PMP70 and catalase at developmental stages 10 and 20, versus uninjected embryos. Catalase and PMP70 proteins were found in punctate structures at stage 20 in control embryos, whereas the injection of ectopic HA-Pex11β induced their earlier localization in punctate structures at stage 10. Furthermore, the peroxisomal marker GFP-SKL, which was found localized as peroxisome-like structures at stage 20, was similarly found at stage 10 when co-microinjected with HA-Pex11β.

Conclusions

Overexpressed Pex11β altered peroxisomal gene levels and induced the early formation of peroxisomes-like structures during development, both of which demonstrate that Pex11β may be a key regulator of peroxisome number in early Xenopus embryos.
Identification and characterisation of a novel adhesin Ifp in Yersinia pseudotuberculosis
Authors: Strong Philippa CR , Hinchliffe Stewart J , Patrick Hannah , Atkinson Steve , Champion Olivia L , Wren Brendan W
Published: April 2011

Background

In order to identify new virulence determinants in Y. pseudotuberculosis a comparison between its genome and that of Yersinia pestis was undertaken. This reveals dozens of pseudogenes in Y. pestis, which are still putatively functional in Y. pseudotuberculosis and may be important in the enteric lifestyle. One such gene, YPTB1572 in the Y. pseudotuberculosis IP32953 genome sequence, encodes a protein with similarity to invasin, a classic adhesion/invasion protein, and to intimin, the attaching and effacing protein from enteropathogenic (EPEC) and enterohaemorraghic (EHEC) Escherichia coli.

Results

We termed YPTB1572 Ifp (Intimin family protein) and show that it is able to bind directly to human HEp-2 epithelial cells. Cysteine and tryptophan residues in the C-terminal region of intimin that are essential for function in EPEC and EHEC are conserved in Ifp. Protein binding occurred at distinct foci on the HEp-2 cell surface and can be disrupted by mutation of a single cysteine residue at the C-terminus of the protein. Temporal expression analysis using lux reporter constructs revealed that ifp is expressed at late log phase at 37°C in contrast to invasin, suggesting that Ifp is a late stage adhesin. An ifp defined mutant showed a reduction in adhesion to HEp-2 cells and was attenuated in the Galleria mellonella infection model.

Conclusion

A new Y. pseudotuberculosis adhesin has been identified and characterised. This Ifp is a new member in the family of invasin/intimin outer membrane adhesins.
The analysis of para-cresol production and tolerance in Clostridium difficile 027 and 012 strains
Authors: Dawson Lisa F , Donahue Elizabeth H , Cartman Stephen T , Barton Richard H , Bundy Jake , McNerney Ruth , Minton Nigel P , Wren Brendan W
Published: April 2011

Background

Clostridium difficile is the major cause of antibiotic associated diarrhoea and in recent years its increased prevalence has been linked to the emergence of hypervirulent clones such as the PCR-ribotype 027. Characteristically, C. difficile infection (CDI) occurs after treatment with broad-spectrum antibiotics, which disrupt the normal gut microflora and allow C. difficile to flourish. One of the relatively unique features of C. difficile is its ability to ferment tyrosine to para-cresol via the intermediate para-hydroxyphenylacetate (p-HPA). P-cresol is a phenolic compound with bacteriostatic properties which C. difficile can tolerate and may provide the organism with a competitive advantage over other gut microflora, enabling it to proliferate and cause CDI. It has been proposed that the hpdBCA operon, rarely found in other gut microflora, encodes the enzymes responsible for the conversion of p-HPA to p-cresol.

Results

We show that the PCR-ribotype 027 strain R20291 quantitatively produced more p-cresol in-vitro and was significantly more tolerant to p-cresol than the sequenced strain 630 (PCR-ribotype 012). Tyrosine conversion to p-HPA was only observed under certain conditions. We constructed gene inactivation mutants in the hpdBCA operon in strains R20291 and 630Δerm which curtails their ability to produce p-cresol, confirming the role of these genes in p-cresol production. The mutants were equally able to tolerate p-cresol compared to the respective parent strains, suggesting that tolerance to p-cresol is not linked to its production.

Conclusions

C. difficile converts tyrosine to p-cresol, utilising the hpdBCA operon in C. difficile strains 630 and R20291. The hypervirulent strain R20291 exhibits increased production of and tolerance to p-cresol, which may be a contributory factor to the virulence of this strain and other hypervirulent PCR-ribotype 027 strains.
Growth of breast cancer recurrences assessed by consecutive MRI
Authors: Millet Ingrid , Bouic-Pages Emmanuelle , Hoa Denis , Azria David , Taourel Patrice
Published: April 2011

Background

Women with a personal history of breast cancer have a high risk of developing an ipsi- or contralateral recurrence. We aimed to compare the growth rate of primary breast cancer and recurrences in women who had undergone prior breast magnetic resonance imaging (MRI).

Methods

Three hundred and sixty-two women were diagnosed with breast cancer and had undergone breast MRI at the time of diagnosis in our institution (2005 - 2009). Among them, 37 had at least one prior breast MRI with the lesion being visible but not diagnosed as cancer. A linear regression of tumour volume measured on MRI scans and time data was performed using a generalized logistic model to calculate growth rates. The primary objective was to compare the tumour growth rate of patients with either primary breast cancer (no history of breast cancer) or ipsi- or contralateral recurrences of breast cancer.

Results

Twenty women had no history of breast cancer and 17 patients were diagnosed as recurrences (7 and 10 were ipsi- and contralateral, respectively). The tumour growth rate was higher in contralateral recurrences than in ipsilateral recurrences (growth rate [10-3 days-1] 3.56 vs 1.38, p < .001) or primary cancer (3.56 vs 2.09, p = 0.01). Differences in tumour growth were not significant for other patient-, tumour- or treatment-related characteristics.

Conclusions

These findings suggest that contralateral breast cancer presents accelerated growth compared to ipsilateral recurrences or primary breast events.
In vivo monitoring of fetoplacental Vegfr2 gene activity in a murine pregnancy model using a Vegfr2-luc reporter gene and bioluminescent imaging
Authors: Greene Jonathan M , Dunaway Chad W , Bowers Susan D , Rude Brian J , Feugang Jean M , Ryan Peter L
Published: April 2011

Background

Vascular endothelial growth factor receptor-2 (VEGFR2) plays a pivotal role in angiogenesis by eliciting vascular endothelial cell growth when bound to VEGF, a powerful pro-angiogenic ligand. While Vegf and Vegfr2 are expressed throughout gestation, the latter third of gestation in mice is characterized by a marked increase in fetoplacental angiogenesis. Thus, the objective of this study was to determine the feasibility of monitoring fetoplacental Vegfr2 gene activity non-invasively using a Vegfr2-luc reporter transgenic mouse and bioluminescent imaging.

Methods

Imaging parameters were optimized using two wild-type (WT) females, bearing Vegfr2-luc fetuses. Then, seven WT females, bred to Vegfr2-luc males, were imaged from gestational day (GD) 12 to 18 to determine the usefulness of the Vegfr2-luc mouse as a model for studying fetoplacental Vegfr2 activity during pregnancy. Semi-quantitative RT-PCR of Vegfr2 was also performed on whole fetoplacental units during this time. Additionally, resultant neonates were imaged at postnatal day (PND) 7, 14 and 21 to monitor Vegfr2 activity during post-natal development.

Results

Fetoplacental Vegfr2 gene activity was detected as light emissions beginning on GD 12 of gestation and increased throughout the imaging period (P < 0.05), and this paralleled the Vegfr2 mRNA data obtained from RT-PCR analysis. A decline in fetoplacental light emissions was associated with a poor pregnancy outcome in one pregnancy, indicating that this approach has potential use for studies monitoring pregnancy well being. Additionally, neonatal Vegfr2 activity was detected at PND 7, 14 and 21 but declined with time (P < 0.0001).

Conclusions

In utero fetoplacental Vegfr2 gene activity was monitored longitudinally in a quantitative manner using a luciferase reporter gene and bioluminescent imaging during the latter third of gestation. This study demonstrates the feasibility of using the Vegfr2-luc mouse to monitor late gestation fetoplacental angiogenic activity under normal and experimental conditions. Additionally, neonatal Vegfr2 gene activity was monitored for three weeks postpartum, allowing continuous monitoring of Vegfr2 activity during the latter third of gestation and postnatal development within the same animals.
Architectures of archaeal GINS complexes, essential DNA replication initiation factors
Authors: Oyama Takuji , Ishino Sonoko , Fujino Seiji , Ogino Hiromi , Shirai Tsuyoshi , Mayanagi Kouta , Saito Mihoko , Nagasawa Naoko , Ishino Yoshizumi , Morikawa Kosuke
Published: April 2011

Background

In the early stage of eukaryotic DNA replication, the template DNA is unwound by the MCM helicase, which is activated by forming a complex with the Cdc45 and GINS proteins. The eukaryotic GINS forms a heterotetramer, comprising four types of subunits. On the other hand, the archaeal GINS appears to be either a tetramer formed by two types of subunits in a 2:2 ratio (α2β2) or a homotetramer of a single subunit (α4). Due to the low sequence similarity between the archaeal and eukaryotic GINS subunits, the atomic structures of the archaeal GINS complexes are attracting interest for comparisons of their subunit architectures and organization.

Results

We determined the crystal structure of the α2β2 GINS tetramer from Thermococcus kodakaraensis (TkoGINS), comprising Gins51 and Gins23, and compared it with the reported human GINS structures. The backbone structure of each subunit and the tetrameric assembly are similar to those of human GINS. However, the location of the C-terminal small domain of Gins51 is remarkably different between the archaeal and human GINS structures. In addition, TkoGINS exhibits different subunit contacts from those in human GINS, as a consequence of the different relative locations and orientations between the domains. Based on the GINS crystal structures, we built a homology model of the putative homotetrameric GINS from Thermoplasma acidophilum (TacGINS). Importantly, we propose that a long insertion loop allows the differential positioning of the C-terminal domains and, as a consequence, exclusively leads to the formation of an asymmetric homotetramer rather than a symmetrical one.

Conclusions

The DNA metabolizing proteins from archaea are similar to those from eukaryotes, and the archaeal multi-subunit complexes are occasionally simplified versions of the eukaryotic ones. The overall similarity in the architectures between the archaeal and eukaryotic GINS complexes suggests that the GINS function, directed through interactions with other protein components, is basically conserved. On the other hand, the different subunit contacts, including the locations and contributions of the C-terminal domains to the tetramer formation, imply the possibility that the archaeal and eukaryotic GINS complexes contribute to DNA unwinding reactions by significantly different mechanisms in terms of the atomic details.
TRESK Channel Contribution to Nociceptive Sensory Neurons Excitability: Modulation by Nerve Injury
Authors: Tulleuda Astrid , Cokic Barbara , Callejo Gerard , Saiani Barbara , Serra Jordi , Gasull Xavier
Published: April 2011

Background:

Neuronal hyperexcitability is a crucial phenomenon underlying spontaneous and evoked pain. In invertebrate nociceptors, the S-type leak K+ channel (analogous to TREK-1 in mammals) plays a critical role of in determining neuronal excitability following nerve injury. Few data are available on the role of leak K2P channels after peripheral axotomy in mammals.

Results:

Here we describe that rat sciatic nerve axotomy induces hyperexcitability of L4-L5 DRG sensory neurons and decreases TRESK (K2P18.1) expression, a channel with a major contribution to total leak current in DRGs. While the expression of other channels from the same family did not significantly change, injury markers ATF3 and Cacna2d1 were highly upregulated. Similarly, acute sensory neuron dissociation ( in vitro axotomy) produced marked hyperexcitability and similar total background currents compared with neurons injured in vivo. In addition, the sanshool derivative IBA, which blocked TRESK currents in transfected HEK293 cells and DRGs, increased intracellular calcium in 49% of DRG neurons in culture. Most IBA-responding neurons (71%) also responded to the TRPV1 agonist capsaicin, indicating that they were nociceptors. Additional evidence of a biological role of TRESK channels was provided by behavioral evidence of pain (flinching and licking), in vivo electrophysiological evidence of C-nociceptor activation following IBA injection in the rat hindpaw, and increased sensitivity to painful pressure after TRESK knockdown in vivo.

Conclusions:

In summary, our results clearly support an important role of TRESK channels in determining neuronal excitability in specific DRG neurons subpopulations, and show that axonal injury down-regulates TRESK channels, therefore contributing to neuronal hyperexcitability.
Enhancing genome assemblies by integrating non-sequence based data
Authors: Heider Thomas N , Lindsay James , Wang Chenwei , O’Neill Rachel J , Pask Andrew J
Published: April 2011

Introduction

Many genome projects were underway before the advent of high-throughput sequencing and have thus been supported by a wealth of genome information from other technologies. Such information frequently takes the form of linkage and physical maps, both of which can provide a substantial amount of data useful in de novo sequencing projects. Furthermore, the recent abundance of genome resources enables the use of conserved synteny maps identified in related species to further enhance genome assemblies.

Methods

The tammar wallaby (Macropus eugenii) is a model marsupial mammal with a low coverage genome. However, we have access to extensive comparative maps containing over 14,000 markers constructed through the physical mapping of conserved loci, chromosome painting and comprehensive linkage maps. Using a custom Bioperl pipeline, information from the maps was aligned to assembled tammar wallaby contigs using BLAT. This data was used to construct pseudo paired-end libraries with intervals ranging from 5-10 MB. We then used Bambus (a program designed to scaffold eukaryotic genomes by ordering and orienting contigs through the use of paired-end data) to scaffold our libraries. To determine how map data compares to sequence based approaches to enhance assemblies, we repeated the experiment using a 0.5× coverage of unique reads from 4 KB and 8 KB Illumina paired-end libraries. Finally, we combined both the sequence and non-sequence-based data to determine how a combined approach could further enhance the quality of the low coverage de novo reconstruction of the tammar wallaby genome.

Results

Using the map data alone, we were able order 2.2% of the initial contigs into scaffolds, and increase the N50 scaffold size to 39 KB (36 KB in the original assembly). Using only the 0.5× paired-end sequence based data, 53% of the initial contigs were assigned to scaffolds. Combining both data sets resulted in a further 2% increase in the number of initial contigs integrated into a scaffold (55% total) but a 35% increase in N50 scaffold size over the use of sequence-based data alone.

Conclusions

We provide a relatively simple pipeline utilizing existing bioinformatics tools to integrate map data into a genome assembly which is available at http://www.mcb.uconn.edu/fac.php?name=paska. While the map data only contributed minimally to assigning the initial contigs to scaffolds in the new assembly, it greatly increased the N50 size. This process added structure to our low coverage assembly, greatly increasing its utility in further analyses.
Deciphering transcription factor binding patterns from genome-wide high density ChIP-chip tiling array data
Authors: Li Juntao , Zhu Lei , Eshaghi Majid , Liu Jianhua , Karuturi Krishna Murthy R
Published: April 2011

Background

The binding events of DNA-interacting proteins and their patterns can be extensively characterized by high density ChIP-chip tiling array data. The characteristics of the binding events could be different for different transcription factors. They may even vary for a given transcription factor among different interaction loci. The knowledge of binding sites and binding occupancy patterns are all very useful to understand the DNA-protein interaction and its role in the transcriptional regulation of genes.

Results

In the view of the complexity of the DNA-protein interaction and the opportunity offered by high density tiled ChIP-chip data, we present a statistical procedure which focuses on identifying the interaction signal regions instead of signal peaks using moving window binomial testing method and deconvolving the patterns of interaction using peakedness and skewness scores. We analyzed ChIP-chip data of 4 different DNA interacting proteins including transcription factors and RNA polymerase in fission yeast using our procedure. Our analysis revealed the variation of binding patterns within and across different DNA interacting proteins. We present their utility in understanding transcriptional regulation from ChIP-chip data.

Conclusions

Our method can successfully detect the signal regions and characterize the binding patterns in ChIP-chip data which help appropriate analysis of the ChIP-chip data.
Poroelastic analysis of frequency-dependent amplitude-versus-offset variations
Authors: Liu Lanfeng , Cao Siyuan , Wang Lu
Published: April 2011

Using analytic equations and numerical modeling, we have investigated characteristics of the frequency-dependent amplitude versus incident angle at an interface between a nondispersive medium and a patchy-saturated dispersive medium. For acoustically hard rocks, at normal incidence and smaller incident angles, the reflection magnitude increases when frequency increases, whereas in the amplitude versus incident-angle domain, the amplitude decreases with increasing incident angle (offset). For acoustically moderate to slightly hard rocks, phase reversal may occur when frequency increases from low to high. This type of response can happen in traditional amplitude-versus-offset class I and II reservoirs, but the frequency-domain phase reversal will be in different incident-angle ranges. For acoustically soft reservoirs, in amplitude versus incident-angle domain, the reflection magnitude increases with increasing incident angle. However, in amplitude-versus-frequency domain, the reflection magnitude increases when frequency decreases, which occurs in all investigated frequencies.
Simultaneous seismic data denoising and reconstruction via multichannel singular spectrum analysis
Authors: Oropeza Vicente , Sacchi Mauricio
Published: April 2011

We present a rank reduction algorithm that permits simultaneous reconstruction and random noise attenuation of seismic records. We based our technique on multichannel singular spectrum analysis (MSSA). The technique entails organizing spatial data at a given temporal frequency into a block Hankel matrix that in ideal conditions is a matrix of rank [Formula: see text], where [Formula: see text] is the number of plane waves in the window of analysis. Additive noise and missing samples will increase the rank of the block Hankel matrix of the data. Consequently, rank reduction is proposed as a means to attenuate noise and recover missing traces. We present an iterative algorithm that resembles seismic data reconstruction with the method of projection onto convex sets. In addition, we propose to adopt a randomized singular value decomposition to accelerate the rank reduction stage of the algorithm. We apply MSSA reconstruction to synthetic examples and a field data set. Synthetic examples were used to assess the performance of the method in two reconstruction scenarios: a noise-free case and data contaminated with noise. In both cases, we found extremely low reconstructions errors that are indicative of an optimal recovery. The field data example consists of a 2D prestack volume that depends on common midpoint and offset. We use the MSSA reconstruction method to complete missing offsets and, at the same time, increase the signal-to-noise ratio of the seismic volume.
Wavefield simulation and data-acquisition-scheme analysis for LWD acoustic tools in very slow formations
Authors: Wang Hua , Tao Guo
Published: April 2011

Propagating wavefields from monopole, dipole, and quadrupole acoustic logging-while-drilling (LWD) tools in very slow formations have been studied using the discrete wavenumber integration method. These studies examine the responses of monopole and dipole systems at different source frequencies in a very slow surrounding formation, and the responses of a quadrupole system operating at a low source frequency in a slow formation with different S-wave velocities. Analyses are conducted of coherence-velocity/slowness relationships (semblance spectra) in the time domain and of the dispersion characteristics of these waveform signals from acoustic LWD array receivers. These analyses demonstrate that, if the acoustic LWD tool is centralized properly and is operating at low frequencies (below 3 kHz), a monopole system can measure P-wave velocity by means of a “leaky” P-wave for very slow formations. Also, for very slow formations a dipole system can measure the P-wave velocity via a leaky P-wave and can measure the S-wave velocity from a formation flexural wave. With a quadrupole system, however, the lower frequency limit (cutoff frequency) of the drill-collar interference wave would decrease to 5 kHz and might no longer be neglected if the surrounding formation becomes a very slow formation, with S-wave velocities at approximately 500 m/s.
Phase and amplitude inversion of crosswell radar data
Authors: Ellefsen Karl J. , Mazzella Aldo T. , Horton Robert J. , McKenna Jason R.
Published: April 2011

Phase and amplitude inversion of crosswell radar data estimates the logarithm of complex slowness for a 2.5D heterogeneous model. The inversion is formulated in the frequency domain using the vector Helmholtz equation. The objective function is minimized using a back-propagation method that is suitable for a 2.5D model and that accounts for the near-, intermediate-, and far-field regions of the antennas. The inversion is tested with crosswell radar data collected in a laboratory tank. The model anomalies are consistent with the known heterogeneity in the tank; the model’s relative dielectric permittivity, which is calculated from the real part of the estimated complex slowness, is consistent with independent laboratory measurements. The methodologies developed for this inversion can be adapted readily to inversions of seismic data (e.g., crosswell seismic and vertical seismic profiling data).
Wave-equation global datuming based on the double square root operator
Authors: Liu Wenge , Zhao Bo , Zhou Hua-wei , He Zhenhua , Liu Hui , Du Zengli
Published: April 2011

Current schemes for removing near-surface effects in seismic data processing use either static corrections or wave-equation datuming (WED). In the presence of rough topography and strong lateral velocity variations in the near surface, the WED scheme is the only option available. However, the traditional procedure of WED downward continues the sources and receivers in different domains. A new wave-equation global-datuming method is based on the double-square-root operator, implementing the wavefield continuation in a single domain following the survey sinking concept. This method has fewer approximations and therefore is more robust and convenient than the traditional WED methods. This method is compared with the traditional methods using a synthetic data example.
Adaptive learning 3D gravity inversion for salt-body imaging
Authors: Silva Dias Fernando J. S. , Barbosa Valéria C. F. , Silva João B. C.
Published: April 2011

We have developed an iterative scheme for inverting gravity data produced by salt bodies with density contrasts relative to the sediments varying from positive to negative, crossing, in this way, the nil zone. Our inversion method estimates a 3D density-contrast distribution, through a piecewise constant function defined on a user-specified grid of cells. It consists of two nested iterative loops. The outer loop uses an adaptive learning strategy that starts with a coarse grid of cells, a set of first-guess geometric elements (axes and points) and the corresponding assigned density contrasts. From the second iteration on, this strategy refines the grid and automatically creates a new set of geometric elements (points only) and associated density contrasts. Each geometric element operates as the first-guess skeletal outline of a section of the salt body to be imaged. The inner loop estimates the 3D density-contrast distribution for the grid of cells and for the set of geometric elements defined in the outer loop. The outer loop allows for easy incorporation of prior geologic information about the lithologic units and automatic evolution of the prior information. The inner loop forces the estimated density contrast of each cell to be close either to a null or to a non-null prespecified value. The iteration stops when the geometries of the estimated salt bodies are invariant along successive iterations. We apply our method to synthetic gravity data produced by a homogeneous salt body embedded in heterogeneous sediments. We tested two geologic hypotheses about the real gravity data from Galveston Island salt dome, USA. In the first, the estimated salt body attains a maximum bottom depth of 5 km, whereas in the second hypothesis, it is shallower and discloses an overhang. Both solutions fit the data and are feasible geologically, so both hypotheses are acceptable.
The DEAD-box RNA helicase Vasa functions in embryonic mitotic progression in the sea urchin
Authors: Yajima Mamiko , Wessel Gary M.
Published: April 2011

Vasa is a broadly conserved ATP-dependent RNA helicase that functions in the germ line of organisms from cnidarians to mammals. Curiously, Vasa is also present in the somatic cells of many animals and functions as a regulator of multipotent cells. Here, we report a mitotic function of Vasa revealed in the sea urchin embryo. We found that Vasa protein is present in all blastomeres of the early embryo and that its abundance oscillates with the cell cycle. Vasa associates with the spindle and the separating sister chromatids at metaphase, and then quickly disappears after telophase. Inhibition of Vasa protein synthesis interferes with proper chromosome segregation, arrests cells at M-phase, and delays overall cell cycle progression. Cdk activity is necessary for the proper localization of Vasa, implying that Vasa is involved in the cyclin-dependent cell cycle network, and Vasa is required for the efficient translation of cyclinB mRNA. Our results suggest an evolutionarily conserved role of Vasa that is independent of its function in germ line determination.
Emerin inhibits Lmo7 binding to thePax3andMyoDpromoters and expression of myoblast proliferation genes
Authors: Dedeic Zinaida , Cetera Maureen , Cohen Tatiana V. , Holaska James M.
Published: April 2011

X-linked Emery–Dreifuss muscular dystrophy (X-EDMD) is caused by mutations in the inner nuclear membrane protein emerin. Previous studies have shown that emerin binds to and inhibits the activity of LIM domain only 7 (Lmo7), a transcription factor that regulates the expression of genes implicated in X-EDMD. Here, we analyzed Lmo7 function in C2C12 myoblast differentiation and its regulation by emerin. We found that Lmo7 was required for proper myoblast differentiation. Lmo7-downregulated myoblasts exhibited reduced expression of Pax3, Pax7, Myf5 and MyoD, whereas overexpression of GFP–Lmo7 increased the expression of MyoD and Myf5. Upon myotube formation, Lmo7 shuttled from the nucleus to the cytoplasm, concomitant with reduced expression of MyoD, Pax3 and Myf5. Importantly, we show that Lmo7 bound the Pax3, MyoD and Myf5 promoters both in C2C12 myoblasts and in vitro. Because emerin inhibited Lmo7 activity, we tested whether emerin competed with the MyoD promoter for binding to Lmo7 or whether emerin sequestered promoter-bound Lmo7 to the nuclear periphery. Supporting the competition model, emerin binding to Lmo7 inhibited Lmo7 binding to and activation of the MyoD and Pax3 promoters. These findings support the hypothesis that the functional interaction between emerin and Lmo7 is crucial for temporally regulating the expression of key myogenic differentiation genes.
Formation and stability of eisosomes in the filamentous fungus Ashbya gossypii
Authors: Seger Shanon , Rischatsch Riccarda , Philippsen Peter
Published: April 2011

One hallmark of the rapid expansion of the polar surface of fungal hyphae is the spatial separation of regions of exocytosis and endocytosis at hyphal tips, as recently shown for Ashbya gossypii and Aspergillus nidulans. To determine where cortex-associated eisosomes form with respect to these two regions, we monitored fluorescently marked eisosomes in A. gossypii. Each minute, 1.6±0.5 eisosomes form within the first 30 μm of each hypha and are exclusively subapical of the endocytosis region. This spatial separation of the processes of eisosome formation and endocytosis, and the much lower frequency of eisosome formation compared with that of endocytic vesicle production do not support a recently proposed role for eisosomes in endocytosis. Levels of mRNA encoding eisosome components are tenfold higher in spores than in hyphae, explaining the observed higher eisosome density at the cortex of germ bubbles. As in Saccharomyces cerevisiae, eisosomes in A. gossypii are very stable. In contrast to S. cerevisiae, however, the A. gossypii homologue of Pil1, one of the main eisosome subunits, is very important for polar growth, whereas the homologue of Nce102, which colocalizes with eisosomes, is not needed for eisosome stability. By testing partial deletions of the A. gossypii homologue of Ymr086w, another component of the eisosome, we identified a novel protein domain essential for eisosome stability. We also compare our results with recent findings about eisosomes in A. nidulans.