bluuebunny/crossref_metadata_2025 huggingface dataset:
The diversity of cyanobacterial metabolism: genome analysis of multiple phototrophic microorganisms
Authors: Beck Christian , Knoop Henning , Axmann Ilka M , Steuer Ralf
Published: February 2012

Background

Cyanobacteria are among the most abundant organisms on Earth and represent one of the oldest and most widespread clades known in modern phylogenetics. As the only known prokaryotes capable of oxygenic photosynthesis, cyanobacteria are considered to be a promising resource for renewable fuels and natural products. Our efforts to harness the sun's energy using cyanobacteria would greatly benefit from an increased understanding of the genomic diversity across multiple cyanobacterial strains. In this respect, the advent of novel sequencing techniques and the availability of several cyanobacterial genomes offers new opportunities for understanding microbial diversity and metabolic organization and evolution in diverse environments.

Results

Here, we report a whole genome comparison of multiple phototrophic cyanobacteria. We describe genetic diversity found within cyanobacterial genomes, specifically with respect to metabolic functionality. Our results are based on pair-wise comparison of protein sequences and concomitant construction of clusters of likely ortholog genes. We differentiate between core, shared and unique genes and show that the majority of genes are associated with a single genome. In contrast, genes with metabolic function are strongly overrepresented within the core genome that is common to all considered strains. The analysis of metabolic diversity within core carbon metabolism reveals parts of the metabolic networks that are highly conserved, as well as highly fragmented pathways.

Conclusions

Our results have direct implications for resource allocation and further sequencing projects. It can be extrapolated that the number of newly identified genes still significantly increases with increasing number of new sequenced genomes. Furthermore, genome analysis of multiple phototrophic strains allows us to obtain a detailed picture of metabolic diversity that can serve as a starting point for biotechnological applications and automated metabolic reconstructions.
Medicago truncatula transporter database: a comprehensive database resource for M. truncatula transporters
Authors: Miao Zhenyan , Li Daofeng , Zhang Zhenhai , Dong Jiangli , Su Zhen , Wang Tao
Published: February 2012

Background

Medicago truncatula has been chosen as a model species for genomic studies. It is closely related to an important legume, alfalfa. Transporters are a large group of membrane-spanning proteins. They deliver essential nutrients, eject waste products, and assist the cell in sensing environmental conditions by forming a complex system of pumps and channels. Although studies have effectively characterized individual M. truncatula transporters in several databases, until now there has been no available systematic database that includes all transporters in M. truncatula.

Description

The M. truncatula transporter database (MTDB) contains comprehensive information on the transporters in M. truncatula. Based on the TransportTP method, we have presented a novel prediction pipeline. A total of 3,665 putative transporters have been annotated based on International Medicago Genome Annotated Group (IMGAG) V3.5 V3 and the M. truncatula Gene Index (MTGI) V10.0 releases and assigned to 162 families according to the transporter classification system. These families were further classified into seven types according to their transport mode and energy coupling mechanism. Extensive annotations referring to each protein were generated, including basic protein function, expressed sequence tag (EST) mapping, genome locus, three-dimensional template prediction, transmembrane segment, and domain annotation. A chromosome distribution map and text-based Basic Local Alignment Search Tools were also created. In addition, we have provided a way to explore the expression of putative M. truncatula transporter genes under stress treatments.

Conclusions

In summary, the MTDB enables the exploration and comparative analysis of putative transporters in M. truncatula. A user-friendly web interface and regular updates make MTDB valuable to researchers in related fields. The MTDB is freely available now to all users at http://bioinformatics.cau.edu.cn/MtTransporter/.
In vitro and in vivo safety evaluation of Dipteryx alata Vogel extract
Authors: Esteves-Pedro Natália Mencacci , Borim Thaisa , Nazato Virginia Sbrugnera , Silva Magali Glauzer , Lopes Patricia Santos , dos Santos Márcio Galdino , Dal Belo Cháriston André , Primila Cardoso Cássia Regina , Varanda Eliana Aparecida , Groppo Francisco Carlos , Gerenutti Marli , Oshima-Franco Yoko
Published: February 2012

Background

Dipteryx alata Vogel popularly known as "baru" is an important commercial leguminous tree species from the Brazilian Cerrado, which possess medicinal properties, besides its fruits consumption by animals and humans. The use of the "naturally occurring plants" as herbal remedies and foods mainly from leaves, seeds, flowers and roots of plants or extracts require precautions before ensuring these are safe and efficacious. The objective of this study was to evaluate the safety of D. alata barks extract.

Methods

Vegetal drugs of D. alata barks were submitted to quality control assays and further to the safety assays under 1) in vitro parameter by Salmonella (Ames) mutagenicity, and 2) in vivo parameter on the pregnancy of rats.

Results

The extract was non-mutagenic to any of the assessed strains TA97a, TA98, TA100 and TA102 even after metabolic activation (+S9). All in vivo parameters (reproductive ability evaluation, physical development of rat offsprings, and neurobehavioral development assays) showed no changes related to control group.

Conclusion

D. alata barks extract is neither mutagenic by the Ames test nor toxic in the pregnancy of rats, with no physical-neurobehavioral consequences on the rat offsprings development.
Mechanisms for an effect of acetylcysteine on renal function after exposure to radio-graphic contrast material: study protocol
Authors: Sandilands Euan A , Cameron Sharon , Paterson Frances , Donaldson Sam , Briody Lesley , Crowe Jane , Donnelly Julie , Thompson Adrian , Johnston Neil R , Mackenzie Ivor , Uren Neal , Goddard Jane , Webb David J , Megson Ian L , Bateman Nicholas , Eddleston Michael
Published: February 2012

Background

Contrast-induced nephropathy is a common complication of contrast administration in patients with chronic kidney disease and diabetes. Its pathophysiology is not well understood; similarly the role of intravenous or oral acetylcysteine is unclear. Randomized controlled trials to date have been conducted without detailed knowledge of the effect of acetylcysteine on renal function. We are conducting a detailed mechanistic study of acetylcysteine on normal and impaired kidneys, both with and without contrast. This information would guide the choice of dose, route, and appropriate outcome measure for future clinical trials in patients with chronic kidney disease.

Methods/Design

We designed a 4-part study. We have set up randomised controlled cross-over studies to assess the effect of intravenous (50 mg/kg/hr for 2 hrs before contrast exposure, then 20 mg/kg/hr for 5 hrs) or oral acetylcysteine (1200 mg twice daily for 2 days, starting the day before contrast exposure) on renal function in normal and diseased kidneys, and normal kidneys exposed to contrast. We have also set up a parallel-group randomized controlled trial to assess the effect of intravenous or oral acetylcysteine on patients with chronic kidney disease stage III undergoing elective coronary angiography. The primary outcome is change in renal blood flow; secondary outcomes include change in glomerular filtration rate, tubular function, urinary proteins, and oxidative balance.

Discussion

Contrast-induced nephropathy represents a significant source of hospital morbidity and mortality. Over the last ten years, acetylcysteine has been administered prior to contrast to reduce the risk of contrast-induced nephropathy. Randomized controlled trials, however, have not reliably demonstrated renoprotection; a recent large randomized controlled trial assessing a dose of oral acetylcysteine selected without mechanistic insight did not reduce the incidence of contrast-induced nephropathy. Our study should reveal the mechanism of effect of acetylcysteine on renal function and identify an appropriate route for future dose response studies and in time randomized controlled trials.

Trial registration

Clinical Trials.gov: NCT00558142; EudraCT: 2006-003509-18.
Deciphering the role of Paenibacillus strain Q8 in the organic matter recycling in the acid mine drainage of Carnoulès
Authors: Delavat François , Phalip Vincent , Forster Anne , Lett Marie-Claire , Lièvremont Didier
Published: February 2012

Background

The recycling of the organic matter is a crucial function in any environment, especially in oligotrophic environments such as Acid Mine Drainages (AMDs). Polymer-degrading bacteria might play an important role in such ecosystem, at least by releasing by-products useful for the rest of the community. In this study, physiological, molecular and biochemical experiments were performed to decipher the role of aPaenibacillusstrain isolated from the sediment of Carnoulès AMD.

Results

Even thoughPaenibacillussp. strain Q8 was isolated from an oligotrophic AMD showing an acidic pH, it developed under both acidic and alkaline conditions and showed a heterotrophic metabolism based on the utilization of a broad range of organic compounds. It resisted to numerous metallic stresses, particularly high arsenite (As(III)) concentrations (> 1,800 mg/L). Q8 was also able to efficiently degrade polymers such as cellulose, xylan and starch. Function-based screening of a Q8 DNA-library allowed the detection of 15 clones with starch-degrading activity and 3 clones with xylan-degrading activity. One clone positive for starch degradation carried a single gene encoding a "protein of unknown function". Amylolytic and xylanolytic activities were measured both in growing cells and with acellular extracts of Q8. The results showed the ability of Q8 to degrade both polymers under a broad pH range and high As(III) and As(V) concentrations. Activity measurements allowed to point out the constitutive expression of the amylase genes and the mainly inducible expression of the xylanase genes. PACE demonstrated the endo-acting activity of the amylases and the exo-acting activity of the xylanases.

Conclusions

AMDs have been studied for years especially with regard to interactions between bacteria and the inorganic compartment hosting them. To date, no study reported the role of microorganisms in the recycling of the organic matter. The present work suggests that the strain Q8 might play an important role in the community by recycling the scarce organic matter (cellulose, hemicellulose, starch...), especially when the conditions change. Furthermore, function-based screening of a Q8 DNA library allowed to assign an amylolytic function to a gene previously unknown. AMDs could be considered as a reservoir of genes with potential biotechnological properties.
Protein tyrosine phosphatase receptor delta acts as a neuroblastoma tumor suppressor by destabilizing the aurora kinase a oncogene
Authors: Meehan Maria , Parthasarathi Laavanya , Moran Niamh , Jefferies Caroline A , Foley Niamh , Lazzari Elisa , Murphy Derek , Ryan Jacqueline , Ortiz Berenice , Fabius Armida W M , Chan Timothy A , Stallings Raymond L
Published: February 2012

Background

Protein tyrosine phosphatase receptor delta (PTPRD) is a member of a large family of protein tyrosine phosphatases which negatively regulate tyrosine phosphorylation. Neuroblastoma is a major childhood cancer arising from precursor cells of the sympathetic nervous system which is known to acquire deletions and alterations in the expression patterns ofPTPRD, indicating a potential tumor suppressor function for this gene. The molecular mechanism, however, by which PTPRD renders a tumor suppressor effect in neuroblastoma is unknown.

Results

As a molecular mechanism, we demonstrate that PTPRD interacts with aurora kinase A (AURKA), an oncogenic protein that is over-expressed in multiple forms of cancer, including neuroblastoma. Ectopic up-regulation of PTPRD in neuroblastoma dephosphorylates tyrosine residues in AURKA resulting in a destabilization of this protein culminating in interfering with one of AURKA's primary functions in neuroblastoma, the stabilization of MYCN protein, the gene of which is amplified in approximately 25 to 30% of high risk neuroblastoma.

Conclusions

PTPRD has a tumor suppressor function in neuroblastoma through AURKA dephosphorylation and destabilization and a downstream destabilization of MYCN protein, representing a novel mechanism for the function of PTPRD in neuroblastoma.
Clinicopathologic study of E-cadherin/beta-catenin complex, and topoisomerase-II in a series of 71 liposarcoma cases
Authors: Gogou Pinelopi , Pakos Emilios , Batistatou Anna , Panelos Ioannis , Briasoulis Evangelos , Stefanou Dimitrios , Apostolikas Nikoforos , Tsekeris Periclis
Published: February 2012

Background

To investigate the expression of E-cadherin, beta-catenin and topoisomerase-II alpha and examine their clinical relevance in liposarcomas.

Materials and methods

The expression of E-cadherin, beta-catenin and topoisomerase II alpha was examined immunohistochemically on formalin-fixed paraffin-embedded tissue specimens from 71 patients who underwent surgical treatment for liposarcomas of the extremities or the retroperitoneum in two major cancer reference centres between 1990 and 2000. Detailed medical notes were available for all patients who were followed for median 82 months (range 5 to 215 months). Obtained expression data were weighted against clinical and pathology parameters of clinical relevance.

Results

Patients were mostly male (59%), median age was 56 years for the liposarcomas of the extremities and 60 years for the retroperitoneal liposarcomas. The tumours were of diverse histology, grade and size (median diameters 7 and 17 cm for tumours of the extremities and retroperitoneum respectively). Expression of β-catenin protein was weakly detected in 15 cases (21.1%). Similarly weak expression of topoisomerase II-alpha was detected in 14 (19.7%) cases of which only two had more than 20% of tumor cells stained positive. E-cadherin was not detected in the studied cohort of liposarcomas. We did not detect associations between the expression of the above proteins by liposarcoma cells and clinical outcome.

Conclusions

Liposarcomas do not express E-cadherin, which matches the absence of epithelioid differentiation in this sarcoma subtype, and have low topoisomerase II-alpha expression, which justifies to some extend their resistance to anthracycline-based chemotherapy.
PhosphoRice: a meta-predictor of rice-specific phosphorylation sites
Authors: Que Shufu , Li Kuan , Chen Min , Wang Yongfei , Yang Qiaobin , Zhang Wenfeng , Zhang Baoqian , Xiong Bangshu , He Huaqin
Published: February 2012

Background

As a result of the growing body of protein phosphorylation sites data, the number of phosphoprotein databases is constantly increasing, and dozens of tools are available for predicting protein phosphorylation sites to achieve fast automatic results. However, none of the existing tools has been developed to predict protein phosphorylation sites in rice.

Results

In this paper, the phosphorylation site predictors, NetPhos 2.0, NetPhosK, Kinasephos, Scansite, Disphos and Predphosphos, were integrated to construct meta-predictors of rice-specific phosphorylation sites using several methods, including unweighted voting, unreduced weighted voting, reduced unweighted voting and weighted voting strategies. PhosphoRice, the meta-predictor produced by using weighted voting strategy with parameters selected by restricted grid search and conditional random search, performed the best at predicting phosphorylation sites in rice. Its Matthew's Correlation Coefficient (MCC) and Accuracy (ACC) reached to 0.474 and 73.8%, respectively. Compared to the best individual element predictor (Disphos_default), PhosphoRice archieved a significant increase in MCC of 0.071 (P < 0.01), and an increase in ACC of 4.6%.

Conclusions

PhosphoRice is a powerful tool for predicting unidentified phosphorylation sites in rice. Compared to the existing methods, we found that our tool showed greater robustness in ACC and MCC. PhosphoRice is available to the public at http://bioinformatics.fafu.edu.cn/PhosphoRice.
Differences and discrepancies between 2005 and 2008 Abbreviated Injury Scale versions - time to standardise
Authors: Ringdal Kjetil G , Hestnes Morten , Palmer Cameron S
Published: February 2012

The aim of this letter is to facilitate the standardisation of Abbreviated Injury Scale (AIS) codesets used to code injuries in trauma registries. We have compiled a definitive list of the changes which have been implemented between the AIS 2005 and Update 2008 versions. While the AIS 2008 codeset appears to have remained consistent since its release, we have identified discrepancies between the codesets in copies of AIS 2005 dictionaries. As a result, we recommend that use of the AIS 2005 should be discontinued in favour of the Update 2008 version.
Petro-electric modeling for CSEM reservoir characterization and monitoring
Authors: Shahin Alireza , Key Kerry , Stoffa Paul , Tatham Robert
Published: February 2012

The controlled-source electromagnetic (CSEM) method has been successfully applied to petroleum exploration; however, less effort has been made to highlight the applicability of this technique for reservoir monitoring. This work appraises the ability of time-lapse CSEM data to detect the changes in fluid saturation during water flooding into an oil reservoir. We simulated a poorly consolidated shaly sandstone reservoir based on a prograding near-shore depositional environment. Starting with an effective porosity model simulated by Gaussian geostatistics, dispersed clay and dual water models were efficiently combined with other well-known theoretical and experimental petrophysical correlations to consistently simulate reservoir properties. The constructed reservoir model was subjected to numerical simulation of multiphase fluid flow to predict the spatial distributions of fluid pressure and saturation. A geologically consistent rock physics model and a modified Archie’s equation for shaly sandstones were then used to simulate the electrical resistivity, showing up to 60% decreases in electrical resistivity due to changes in water saturation during 10 years of production. Time-lapse CSEM data were simulated at three production time steps (zero, five, and ten years) using a 2.5D parallel adaptive finite element algorithm. Analysis of the time-lapse signal in the simulated multicomponent and multifrequency data set demonstrates that a detectable time-lapse signal after five years and a strong time-lapse signal after ten years of water flooding are attainable using current CSEM technology.
Waveform tomography of field vibroseis data using an approximate 2D geometry leads to improved velocity models
Authors: Smithyman Brendan R. , Clowes Ronald M.
Published: February 2012

Waveform tomography, a combination of traveltime tomography (or inversion) and waveform inversion, is applied to vibroseis first-arrival data to generate an interpretable model of P-wave velocity for a site in the Nechako Basin, south-central British Columbia, Canada. We use constrained 3D traveltime inversion followed by 2D full-waveform inversion to process long-offset (14.4 km) first-arrival refraction waveforms, resulting in a velocity model of significantly higher detail than a conventional refraction-statics model generated for a processing workflow. The crooked-line acquisition of the data set makes 2D full-waveform inversion difficult. Thus, a procedure that improves the tractability of waveform tomography processing of vibroseis data recorded on crooked roads is developed to generate a near-surface ([Formula: see text]) velocity model for the study area. The data waveforms are first static corrected using a time shift determined by 3D raytracing, which accounts for the crossline offsets produced by the crooked-line acquisition. The velocity model generated from waveform tomography exhibits substantial improvement when compared with a conventional refraction-statics model. It also shows improved resolution of sharp discontinuities and low-velocity regions when compared to the model from traveltime tomography alone, especially in regions where the geometry errors are moderate. Interpretation of the near-surface velocity model indicates possible subbasins in the Nechako Basin and delineates the Eocene volcanic rocks of the study area. This approach limits the ability of the full-waveform inversion to fit some propagation modes; however, the tractability of the inversion in the near-surface region is improved. This new development is especially useful in studies that do not warrant 3D seismic acquisition and processing.
Nonexponential decay of the surface-NMR signal and implications for water content estimation
Authors: Grunewald Elliot , Knight Rosemary
Published: February 2012

Noninvasive surface nuclear magnetic resonance (SNMR) measurements can yield direct and quantitative estimates of water content in the near surface. A fundamental assumption that is always made in the analysis of SNMR data is that the measured signal exhibits an exponential decay. Although the assumption of exponential decay is frequently valid, it can be shown that in the presence of an inhomogeneous magnetic field, the decay may be nonexponential in form. Simulated SNMR data were used to explore how the decay shape will vary with certain environmental and measurement conditions and to assess how nonexponential decay will affect SNMR-based estimates of water content. Results derived from analytical and pore-scale modeling demonstrated that the shape of the decay depends strongly on both pore geometry and the statistics of the regional or pore-scale magnetic field. In particular, the decay is most likely to be nonexponential when pores are large and when a strongly inhomogeneous magnetic field is present. For conditions in which the SNMR signal cannot be accurately modeled as exponential, standard processing approaches were found to result in significant errors in estimated water content—specifically, water content tends to be overestimated. Analysis of data misfits suggests that, in practice, it will be difficult to directly identify errors associated with nonexponential decay based only on the measured signal. Therefore, a description of the conditions leading to nonexponential decay and the implications for water content estimates is useful to support improved interpretation of SNMR measurements.
Continual and partial MEK inhibition ameliorates cardio-facio-cutaneous phenotypes in zebrafish
Authors: Anastasaki Corina , Rauen Katherine A. , Patton E. Elizabeth
Published: February 2012

Cardio-facio-cutaneous (CFC) syndrome is caused by germ-line mutations in RAS, BRAF and MEK. The highly selective and potent MEK inhibitors that have been developed as anti-cancer agents hold potential as therapeutics for CFC syndrome. We have previously shown that the effects of CFC mutations on zebrafish gastrulation can be prevented by a one-hour treatment with MEK inhibitors within a specific developmental time-window. However, MEK activity is essential for normal development and PD0325901 treatment outside this treatment window leads to additional developmental defects in MEK dependent tissues. We now test 10 different doses of PD0325901 at six developmental time points and assess the effects on body axis length, heart development, and craniofacial structures in zebrafish embryos. Notably, we find that a continuous, partial dose of PD0325901 that has only minor inhibition of MEK activity can prevent the action of both the common CFC BRAFQ257R kinase-active allele and the BRAFG596V kinase-impaired mutant allele through the first five days of development. These results provide a detailed study of the effects of PD0325901 in development and show that, unlike in cancer that requires robust inhibition of MAPK signalling, a partial reduction in phospho-ERK activity treatment is sufficient to moderate the developmental effects BRAFCFC mutations.
Tiam1-regulated osteopontin in senescent fibroblasts contributes to the migration and invasion of associated epithelial cells
Authors: Liu Jiewei , Xu Kun , Chase Maya , Ji Yuxin , Logan Jennifer K. , Buchsbaum Rachel J.
Published: February 2012

The tumor microenvironment undergoes changes concurrent with neoplastic progression. Cancer incidence increases with aging and is associated with tissue accumulation of senescent cells. Senescent fibroblasts are thought to contribute to tumor development in aging tissues. We have shown that fibroblasts deficient in the Rac exchange factor Tiam1 promote invasion and metastasis of associated epithelial tumor cells. Here, we use a three-dimensional culture model of cellular invasiveness to outline several steps underlying this effect. We find that stress-induced senescence induces decreased fibroblast Tiam1 protein levels and increased osteopontin levels, and that senescent fibroblast lysates induce Tiam1 protein degradation in a calcium- and calpain-dependent fashion. Changes in fibroblast Tiam1 protein levels induce converse changes in osteopontin mRNA and protein. Senescent fibroblasts induce increased invasion and migration in co-cultured mammary epithelial cells. These effects in epithelial cells are ameliorated by either increasing fibroblast Tiam1 or decreasing fibroblast osteopontin. Finally, in seeded cell migration assays we find that either senescent or Tiam1-deficient fibroblasts induce increased epithelial cell migration that is dependent on fibroblast secretion of osteopontin. These findings indicate that one mechanism by which senescent fibroblasts promote neoplastic progression in associated tumors is through degradation of fibroblast Tiam1 protein and the consequent increase in secretion of osteopontin by fibroblasts.
A dual role for Rac1 GTPases in the regulation of cell motility
Authors: Filić Vedrana , Marinović Maja , Faix Jan , Weber Igor
Published: February 2012

Rac proteins are the only canonical Rho family GTPases in Dictyostelium, where they act as key regulators of the actin cytoskeleton. To monitor the dynamics of activated Rac1 in Dictyostelium cells, a fluorescent probe was developed that specifically binds to the GTP-bound form of Rac1. The probe is based on the GTPase-binding domain (GBD) from PAK1 kinase, and was selected on the basis of yeast two-hybrid, GST pull-down and fluorescence resonance energy transfer assays. The PAK1 GBD localizes to leading edges of migrating cells and to endocytotic cups. Similarly to its role in vertebrates, activated Rac1 therefore appears to control de novo actin polymerization at protruding regions of the Dictyostelium cell. Additionally, we found that the IQGAP-related protein DGAP1, which sequesters active Rac1 into a quaternary complex with actin-binding proteins cortexillin I and cortexillin II, localizes to the trailing regions of migrating cells. Notably, PAK1 GBD and DGAP1, which both bind to Rac1-GTP, display mutually exclusive localizations in cell migration, phagocytosis and cytokinesis, and opposite dynamics of recruitment to the cell cortex upon stimulation with chemoattractants. Moreover, cortical localization of the PAK1 GBD depends on the integrity of the actin cytoskeleton, whereas cortical localization of DGAP1 does not. Taken together, these results imply that Rac1 GTPases play a dual role in regulation of cell motility and polarity in Dictyostelium.
GCP6 is a substrate of Plk4 and required for centriole duplication
Authors: Bahtz Ramona , Seidler Joerg , Arnold Marc , Haselmann-Weiss Uta , Antony Claude , Lehmann Wolf D. , Hoffmann Ingrid
Published: February 2012

Centriole duplication occurs once per cell cycle and requires Plk4, a member of the Polo-like kinase family. A key component of the centrosome is the γ-tubulin ring complex (γ-TuRC) that nucleates microtubules. GCP6 is a member of the γ-TuRC, but its role in human cells and the regulation of its functions remain unclear. Here we report that depletion of human GCP6 prevents assembly of the γ-TuRC and induces a high percentage of monopolar spindles. These spindles are characterized by a loss of centrosomal γ-tubulin and reduced centriole numbers. We found that GCP6 is localized in the pericentriolar material but also at distal portions of centrioles. In addition, GCP6 is required for centriole duplication and Plk4-induced centriole overduplication. GCP6 interacts with and is phosphorylated by Plk4. Moreover, we find that Plk4-dependent phosphorylation of GCP6 regulates centriole duplication. These data suggest that GCP6 is a target of Plk4 in centriole biogenesis.
E-cadherin inhibits nuclear accumulation of Nrf2: implications for chemoresistance of cancer cells
Authors: Kim Won Dong , Kim Young Woo , Cho Il Je , Lee Chang Ho , Kim Sang Geon
Published: February 2012

Nrf2 has an anti-carcinogenic effect. However, an increase in Nrf2 activity is also implicated in cancer chemoresistance. A switch from E-cadherin to N-cadherin affects the transdifferentiation and metastasis of cancer cells. In view of the key role of this switch in cancer malignancy, we investigated the regulatory effect of E-cadherin on Nrf2. In HEK293 cells, overexpression of E-cadherin inhibited the nuclear accumulation of Nrf2, and prevented Nrf2-dependent gene induction. GST pull-down and immunocytochemical assays verified the interaction between E-cadherin and Nrf2: E-cadherin bound the C-terminus of Nrf2, but not its N-terminus, which comprises the Neh2 domain responsible for phosphorylation of Ser40. Our finding that the mutation of Ser40 to alanine in Nrf2 did not affect the ability of E-cadherin to bind Nrf2 and repress target gene transactivation suggests that E-cadherin might not disturb the phosphorylation. Studies using mutant constructs of E-cadherin suggested that the β-catenin-binding domain contributes to the inhibitory effect of E-cadherin on Nrf2. Consistently, knockdown of β-catenin attenuated not only the effect of E-cadherin binding to Nrf2, but also Keap1-dependent ubiquitylation of Nrf2, and thereby increased Nrf2 activity, supporting the involvement of β-catenin in the interactions. Collectively, E-cadherin recruits Nrf2 through β-catenin, and assists the function of Keap1 for the inhibition of nuclear localization and transcriptional activity of Nrf2. In HepG2 cells, the loss of E-cadherin by either siRNA knockdown or treatment with TGFβ1 enhanced the constitutive or inducible activity of Nrf2, implying that chemoresistance of cancer cells upon the loss of E-cadherin might be associated with Nrf2.
Suitability of epididymal and testicular ultrasonography and computerized image analysis for assessment of current and future semen quality in the ram
Authors: Ahmadi Bahareh , Lau Cathy Pik-Shan , Giffin Jennifer , Santos Natalia , Hahnel Ann , Raeside James , Christie Heather , Bartlewski Pawel
Published: February 2012

Breeding soundness evaluation (BSE) is the primary assessment for determining the reproductive potential of male animals. This method, however, cannot be used to evaluate semen frequently or to predict future semen quality. Computerized analysis of ultrasonographic images provides information on histophysiological changes in male reproductive organs. We hypothesized that: (i) semen parameters would correlate with ultrasonographic characteristics of the distal region (cauda) of the epididymis and (ii) testicular ultrasound images and/or circulating testosterone concentration would predict future semen quality in the ram. Six adult rams underwent BSE and scrotal ultrasonography approximately 60 d apart (average duration of the spermatogenic cycle) both during the breeding (December and February) and non-breeding (June and August) seasons. An inverse correlation was found between pixel intensity (numerical pixel values) of the epididymes and percentage of sperm in semen with normal morphology ( r = −0.46, P < 0.05). Pixel heterogeneity (standard deviation of pixel values) correlated negatively with percentage of sperm with normal morphology ( r = −0.42, P < 0.05) and directly with percentage of spermatozoa with abnormal tails ( r = 0.43, P < 0.05). Pixel heterogeneity of testicular parenchyma obtained approximately 60 d prior to semen evaluation inversely correlated with percentage of sperm with normal morphology ( r = −0.73, P < 0.01) and sperm progressive motility ( r = −0.76, P < 0.01), and directly with percentage of sperm with abnormal tails ( r = 0.72, P < 0.01) and loose heads ( r = 0.79, P < 0.01). We concluded that scrotal ultrasonography combined with computer-assisted analyses of epididymal and testicular echotexture in the ram was a valuable method for determining certain current and future semen parameters, respectively.
Robust Adversarial Risk Analysis: A Level-k Approach
Authors: McLay Laura , Rothschild Casey , Guikema Seth
Published: February 2012

Adversarial risk analysis is an active and important area of decision analytic research. Both single-actor decision analysis and multiple-actor game theory have been applied to this problem, with game theoretic methods being particularly popular. Although game theory models do explicitly capture strategic interactions between attackers and defenders, two of the key assumptions—decision making based on subjective expected utility maximization and common knowledge of rationality—are known to be descriptively inaccurate in some situations. This paper addresses these shortcomings by proposing, formulating, and illustrating the application of robust optimization methodologies to a level-k game theory model for adversarial risk analysis. Level-k game theory provides a practical method for modeling bounded rationality. Robust optimization provides an alternative way to model the actions of conservative players facing “deep” uncertainties about their environment—uncertainties that are possible to bound but that are difficult or impossible to represent using probability distributions. Our approach thus combines level-k and robust optimization insights to provide a computationally tractable model of boundedly rational players who are faced with significant and difficult to quantify uncertainties.
Dynamic Purchase Decisions Under Regret: Price and Availability
Authors: Diecidue Enrico , Rudi Nils , Tang Wenjie
Published: February 2012

We model a dynamic purchase context in which a consumer is uncertain about the product's valuation. The consumer has two purchase opportunities for the product: forward purchase in Period 1 or spot purchase in Period 2. Two forms of regret are considered: buyer's regret over the money paid in excess of his valuation of the product when buying forward and hesitater's regret for the lost opportunity of an increased surplus when not buying forward. We illustrate how regrets affect the purchase decision: a consumer is more likely to buy forward when more averse to hesitater's regret but more likely to delay the decision when more averse to buyer's regret. We also consider alternative consumer types to characterize how regret affects their spot purchase decisions as well as what triggers the regret. We show that type inconsistency—that is, a consumer's incorrect anticipation of his future type—induces an inferior Period 1 purchase decision and thereby reduces the consumer's expected surplus.
A Decision Support System for Scheduling the Canadian Football League
Authors: Kostuk Kent J. , Willoughby Keith A.
Published: February 2012

The eight-team Canadian Football League (CFL) features an 18-game regular season played between late June and early November. The regular-season schedule is manually created using an iterative process involving league management, teams, and a television sports broadcaster. We developed a mixed-integer program-driven decision support system that provided league officials with multiple schedule versions relatively quickly. Our approach informed the development of the regular-season schedule by offering league management a neighborhood of potentially solid solutions. We demonstrated the impact of specific schedule requests to decision makers. Such sensitivity analysis was impossible under the previous manual creation method.
On Randomized Approximation for Finding a Level Ideal of a Poset and the Generalized Median Stable Matchings
Authors: Kijima Shuji , Nemoto Toshio
Published: February 2012

This study is concerned with finding a level ideal (LI) of a partially ordered set (poset). Given a finite poset P, the level of each element p ∈ P is defined as the number of ideals that do not include p, then the problem is to find the ith LI–the ideal consisting of elements whose levels are less than a given integer i. The concept of a level ideal is naturally derived from the generalized median stable matchings, introduced by Teo and Sethuraman [Teo, C. P., J. Sethuraman. 1998. The geometry of fractional stable matchings and its applications. Math. Oper. Res. 23(4) 874–891] in the context of “fairness” of matchings in a stable marriage problem. Cheng [Cheng, C. T. 2010. Understanding the generalized median stable matchings. Algorithmica 58(1) 34–51] showed that finding the ith LI is #P-hard when i = Θ(N), where N is the total number of ideals of P. This paper shows that finding the ith LI is #P-hard even if i = Θ(N1/c), where c is an arbitrary constant at least one. Meanwhile, we present a polynomial time exact algorithm when i = O((log N)c′), where c′ is an arbitrary positive constant. We also devise two randomized approximation schemes for the ideals of a poset, by using an oracle of an almost-uniform sampler.
Capacity Planning in the Semiconductor Industry: Dual-Mode Procurement with Options
Authors: Peng Chen , Erhun Feryal , Hertzler Erik F. , Kempf Karl G.
Published: February 2012

To help a firm reduce inefficiencies associated with equipment capacity planning, we propose a dual-mode equipment procurement (DMEP) framework. DMEP combines dual-source (i.e., a less-expensive-but-slower base mode and a faster-but-more-expensive flexible mode) procurement with option contracts in three layers: a contract negotiation layer, where the firm chooses the best combination of lead time and price for each mode from the supply contract menu; a capacity reservation layer, where the firm reserves total equipment procurement quantities from the two supply modes before the planning horizon starts; and an execution layer, where the firm orders equipment from the two supply modes based on the updated demand information. We first investigate the execution layer as a dynamic dual-source capacity expansion problem with demand backlogging and demonstrate that the optimal policy lacks structure even under the simplest setting. Thus, we propose a heuristic solution for the execution-layer problem, which also serves as a building block for the other two layers. Through numerical analysis, we quantify the value of the added flexibility of DMEP for the firm. The DMEP framework has been implemented at Intel Corporation and has resulted in savings of tens of millions of dollars for one process technology.
Hydro-Mechanical and Chemical-Mineralogical Analyses of the Bentonite Buffer from A Full-Scale Field Experiment Simulating a High-Level Waste Repository
Authors: Dueck Ann , Johannesson Lars-Erik , Kristensson Ola , Olsson Siv , Sjöland Anders
Published: February 2012

The effect of exposure to repository-like conditions on compacted Wyoming bentonite was determined by comparing the hydraulic, mechanical, and mineralogical properties of samples from the bentonite buffer of the Canister Retrieval Test (CRT) with those of reference material. The CRT, located at the Swedish Äspö Hard Rock Laboratory (HRL), was a full-scale field experiment simulating conditions relevant for the Swedish, so called KBS-3, concept for disposal of high-level radioactive waste in crystalline host rock. The compacted bentonite, surrounding a copper canister equipped with heaters, had been subjected to heating at temperatures up to 95°C and hydration by natural Na-Ca-Cl type groundwater for almost 5 y at the time of retrieval.

Under the thermal and hydration gradients that prevailed during the test, sulfate in the bentonite was redistributed and accumulated as anhydrite close to the canister. The major change in the exchangeable cation pool was a loss in Mg in the outer parts of the blocks, suggesting replacement of Mg mainly by Ca along with the hydration with groundwater. Close to the Cu canister, small amounts of Cu were incorporated into the bentonite. A reduction of strain at failure was observed in the innermost part of the bentonite buffer, but no influence was noted on the shear strength. No change in swelling pressure was observed, while a modest decrease in hydraulic conductivity was found for the samples with the highest densities. No coupling was found between these changes in the hydro-mechanical properties and the montmorillonite — the X-ray diffraction characteristics, the cation exchange properties, and the average crystal chemistry of the Na-converted <1 μm fractions provided no evidence of any chemical/structural changes in the montmorillonite after the 5 y hydrothermal test.
Polymer Model of Zeolite Thermochemical Stability
Authors: Arthur Randolph , Sasamoto Hiroshi , Walker Colin , Yui Mikazu
Published: February 2012

The polymer model provides a relatively simple and robust basis for estimating the standard Gibbs free energies of formation (ΔGfo) and standard enthalpies of formation (ΔHfo) of clay minerals and other aluminosilicates with an accuracy that is comparable to or better than can be obtained using alternative techniques. The model developed in the present study for zeolites entailed the selection of internally consistent standard thermodynamic properties for model components, calibration of adjustable model parameters using a linear regression technique constrained by ΔGfo and ΔHfo values retrieved from calorimetric, solubility, and phase-equilibrium experiments, and assessments of model accuracy based on comparisons of predicted values with experimental counterparts not included in the calibration dataset. The ΔGfo and ΔHfo predictions were found to average within ±0.2% and ±0.3%, respectively, of experimental values at 298.15 K and 1 bar. The latter result is comparable to the good accuracy that has been obtained by others using a more rigorous electronegativity-based model for ΔHfo that accounts explicitly for differences in zeolite structure based on differences in framework density and unit-cell volume. This observation is consistent with recent calorimetric studies indicating that enthalpies of transition from quartz to various pure-silica zeolite frameworks (zeosils) are small and only weakly dependent on framework type, and suggests that the effects on ΔHfo of differences in framework topology can be ignored for estimation purposes without incurring a significant loss of accuracy. The relative simplicity of the polymer model, together with its applicability to both zeolites and clay minerals, is based on a common set of experimentally determined and internally consistent thermodynamic properties for model components. These attributes are particularly well suited for studies of the effects of water-rock-barrier interactions on the long-term safety of geologic repositories for high-level nuclear waste (HLW).
Cost, Delay and Justice: The High Court of Australia Recognizes the Importance of Case Management in Civil Litigation— Aon Risk Services Australia Limited v Australian National University
Authors: Boniface Dorne , Legg Michael
Published: February 2012

‘Justice’ in civil litigation has traditionally meant justice as between the parties. However, pressure on public resources and delay resulting from traditional civil procedures has precipitated reform that now requires judges to case manage proceedings. ‘Justice’ has been broadened by such reform to include taking into account cost, delay and prejudice to other users of the civil litigation system as a central consideration when determining whether to grant leave to amend. The High Court in Queensland v J L Holdings Pty Ltd appeared to maintain the traditional narrow concept of ‘justice’. Recently, however, the High Court appears to have, in part, resiled from that view when considering court rules concerning amendment.

This article examines the High Court's interpretation of the court rules for amendment at issue in Aon Risk Services, the impact of that reasoning on the scope of J L Holdings and case management.
Is Debtor-in-Possession Viable in Hong Kong?
Authors: Ho John Kong Shan , Chan Raymond Siu Yeung
Published: February 2012

In October 2009, the Financial Services and the Treasury Bureau of the Hong Kong Government published a consultation paper to review corporate rescue procedure with the aim of reforming key issues relating to corporate rescue. This paper compares the proposed reform in Hong Kong and the debtor-in-possession concept of the United States of America in Chapter 11 corporate rescue, and seeks to identify the reasoning behind the differences.
Clone Wars? The Challenges of Cloned Food in EU, US and WTO Law
Authors: Petetin Ludivine
Published: February 2012

Following the recent ‘green light’ from the FDA in the US and from the EFSA in the EU, cloned meat and milk may soon arrive on food shelves. Yet evidence suggests that consumers remain apprehensive about eating such food, for reasons which stand outside the scientific community (including ethical and moral issues). These consumer concerns may be hard to accommodate. Not least, in the US no labelling will be required. Although a more restrictive legislative approach is envisaged in the EU, this could trigger a WTO dispute. If the Dispute Settlement Body of the WTO declared cloned and conventional foods to be ‘like products’, commercial advantages for the US would ensue, as cloned products would be allowed to be sold onto the markets with no labelling, creating one market combining conventional and cloned foods. In particular, the application of the principle of non-discrimination could oblige the EU to remove any labelling of cloned products. On the other hand, consumer preferences are a factor to be considered in any ‘like product’ determination and it may be that the consumer hostility towards cloned food in the EU may prove decisive.
European Union Agricultural Policy and Practice: The New Challenge of Climate Change
Authors: Cardwell Michael
Published: February 2012

Climate change has been identified as a new challenge for EU agricultural policy which must be addressed as a matter of priority. The importance of climate-friendly agricultural practices in mitigating greenhouse gas emissions already receives some recognition under the current legislative framework; and the proposed regulations for the period 2014–2020, issued in October 2011, indicate that this importance will be considerably enhanced. Such practices will be examined with specific reference to: cross-compliance obligations attached to direct payments to farmers (under Pillar I of the CAP); more targeted rural development measures (under Pillar II of the CAP); and sustainability criteria in respect of feedstock for biofuels and bioliquids, as laid down by the Renewable Energy Directive. In addition, the article will consider two broader issues which each present an obstacle to any regulation in this area. The first issue is the inherent difficulty in creating a regime that is sensitive to the complexities and uncertainties which pervade the climate change debate, yet, at the same time, can be effective in practice. A second issue is the further inherent difficulty of finding in this context the appropriate balance between measures implemented under respectively Pillar I and Pillar II of the CAP, both Pillars having their apparent strengths and weaknesses.