bluuebunny/crossref_metadata_2025 huggingface dataset:
Inhibition of eIF2α dephosphorylation inhibits ErbB2-induced deregulation of mammary acinar morphogenesis
Authors: Sequeira Sharon J , Wen Huei Chi , Avivar-Valderas Alvaro , Farias Eduardo F , Aguirre-Ghiso Julio A
Published: September 2009

Background

The ErbB2/Her2/Neu receptor tyrosine kinase is amplified in ~30% of human breast cancers. Phosphorylation of the translation initiation factor, eIF2α inhibits global protein synthesis and activates a stress signaling and growth suppressive program. We have shown that forced phosphorylation of eIF2α can suppress head and neck, colorectal carcinoma and multiple myeloma tumor growth and/or survival. Here we explore whether ErbB2 modulates eIF2α phosphorylation and whether forced phosphorylation of the latter can antagonize ErbB2 deregulation of mammary acinar morphogenesis.

Results

We tested whether ErbB2 signaling influenced eIF2α signaling and whether enhanced phosphorylation of the latter affected ErbB2-deregulated mammary acinar development. We obtained stable MCF10A cells overexpressing wild-type (Wt) Neu/ErbB2 or a constitutively active (CA) variant via retroviral delivery or mammary tumor cells from MMTV-Neu tumors. Western blotting, RT-PCR and confocal microscopy were used to analyze the effects of ErbB2 activation on eIF2α signaling and the effect of the GADD34-PP1C inhibitor salubrinal. Wt- and MMTV-Neu cells formed aberrant acini structures resembling DCIS, while CA-ErbB2 overexpression induced invasive lesions. In these structures we found that CA-ErbB2 but not the Wt variant significantly down-regulated the pro-apoptotic gene CHOP. This occurred without apparent modulation of basal phosphorylation of PERK and eIF2α or induction of its downstream target ATF4. However, inhibition of eIF2α dephosphorylation with salubrinal was sufficient to inhibit Wt- and CA-ErbB2- as well as MMTV-Neu-induced deregulation of acinar growth. This was linked to enhanced CHOP expression, inhibition of proliferation, induction of apoptosis and luminal clearing in Wt-ErbB2 and to inhibition of cyclin D1 levels and subsequent proliferation in CA-ErbB2 cells.

Conclusion

Depending on the strength of ErbB2 signaling there is a differential regulation of CHOP and eIF2α phosphorylation. ErbB2 uncouples in basal conditions eIF2α phosphorylation from CHOP induction. However, this signal was restored by salubrinal treatment in Wt-ErbB2 expressing MCF10A cells as these DCIS-like structures underwent luminal clearing. In CA-ErbB2 structures apoptosis is not induced by salubrinal and instead a state of quiescence with reduced proliferation was achieved. Treatments that stabilize P-eIF2α levels may be effective in treating ErbB2 positive cancers without severely disrupting normal tissue function and structure.
Conserved repertoire of orthologous vomeronasal type 1 receptor genes in ruminant species
Authors: Ohara Hiromi , Nikaido Masato , Date-Ito Atsuko , Mogi Kazutaka , Okamura Hiroaki , Okada Norihiro , Takeuchi Yukari , Mori Yuji , Hagino-Yamagishi Kimiko
Published: September 2009

Background

In mammals, pheromones play an important role in social and innate reproductive behavior within species. In rodents, vomeronasal receptor type 1 (V1R), which is specifically expressed in the vomeronasal organ, is thought to detect pheromones. The V1R gene repertoire differs dramatically between mammalian species, and the presence of species-specific V1R subfamilies in mouse and rat suggests that V1R plays a profound role in species-specific recognition of pheromones. In ruminants, however, the molecular mechanism(s) for pheromone perception is not well understood. Interestingly, goat male pheromone, which can induce out-of-season ovulation in anestrous females, causes the same pheromone response in sheep, and vice versa, suggesting that there may be mechanisms for detecting "inter-species" pheromones among ruminant species.

Results

We isolated 23 goat and 21 sheep intact V1R genes based on sequence similarity with 32 cow V1R genes in the cow genome database. We found that all of the goat and sheep V1R genes have orthologs in their cross-species counterparts among these three ruminant species and that the sequence identity of V1R orthologous pairs among these ruminants is much higher than that of mouse-rat V1R orthologous pairs. Furthermore, all goat V1Rs examined thus far are expressed not only in the vomeronasal organ but also in the main olfactory epithelium.

Conclusion

Our results suggest that, compared with rodents, the repertoire of orthologous V1R genes is remarkably conserved among the ruminants cow, sheep and goat. We predict that these orthologous V1Rs can detect the same or closely related chemical compound(s) within each orthologous set/pair. Furthermore, all identified goat V1Rs are expressed in the vomeronasal organ and the main olfactory epithelium, suggesting that V1R-mediated ligand information can be detected and processed by both the main and accessory olfactory systems. The fact that ruminant and rodent V1Rs have distinct features suggests that ruminant and rodent V1Rs have evolved distinct functions.
Sequenced BAC anchored reference genetic map that reconciles the ten individual chromosomes of Brassica rapa
Authors: Kim HyeRan , Choi Su Ryun , Bae Jina , Hong Chang Pyo , Lee Seo Yeon , Hossain Md Jamil , Van Nguyen Dan , Jin Mina , Park Beom-Seok , Bang Jea-Wook , Bancroft Ian , Lim Yong Pyo
Published: September 2009

Background

In view of the immense value ofBrassica rapain the fields of agriculture and molecular biology, the multinationalBrassica rapaGenome Sequencing Project (BrGSP) was launched in 2003 by five countries. The developing BrGSP has valuable resources for the community, including a reference genetic map and seed BAC sequences. Although the initialB. rapalinkage map served as a reference for the BrGSP, there was ambiguity in reconciling the linkage groups with the ten chromosomes ofB. rapa. Consequently, the BrGSP assigned each of the linkage groups to the project members as chromosome substitutes for sequencing.

Results

We identified simple sequence repeat (SSR) motifs in theB. rapagenome with the sequences of seed BACs used for the BrGSP. By testing 749 amplicons containing SSR motifs, we identified polymorphisms that enabled the anchoring of 188 BACs onto theB. rapareference linkage map consisting of 719 loci in the 10 linkage groups with an average distance of 1.6 cM between adjacent loci. The anchored BAC sequences enabled the identification of 30 blocks of conserved synteny, totaling 534.9 cM in length, between the genomes ofB. rapaandArabidopsis thaliana. Most of these were consistent with previously reported duplication and rearrangement events that differentiate these genomes. However, we were able to identify the collinear regions for seven additional previously uncharacterized sections of the A genome. Integration of the linkage map with theB. rapacytogenetic map was accomplished by FISH with probes representing 20 BAC clones, along with probes for rDNA and centromeric repeat sequences. This integration enabled unambiguous alignment and orientation of the maps representing the 10B. rapachromosomes.

Conclusion

We developed a second generation reference linkage map forB. rapa, which was aligned unambiguously to theB. rapacytogenetic map. Furthermore, using our data, we confirmed and extended the comparative genome analysis betweenB. rapaandA. thaliana. This work will serve as a basis for integrating the genetic, physical, and chromosome maps of the BrGSP, as well as for studies on polyploidization, speciation, and genome duplication in the genusBrassica.
malT knockout mutation invokes a stringent type gene-expression profile in Actinobacillus pleuropneumoniae in bronchoalveolar fluid
Authors: Lone Abdul G , Deslandes Vincent , Nash John HE , Jacques Mario , MacInnes Janet I
Published: September 2009

Background

Actinobacillus pleuropneumoniaecauses contagious pleuropneumonia, an economically important disease of commercially reared pigs throughout the world. To cause this disease,A. pleuropneumoniaemust rapidly overcome porcine pulmonary innate immune defenses. Since bronchoalveolar fluid (BALF) contains many of the innate immune and other components found in the lungs, we examined the gene expression of a virulent serovar 1 strain ofA. pleuropneumoniaeafter exposure to concentrated BALF for 30 min.

Results

In reverse transcription PCR differential display (RT-PCR DD) experiments,A. pleuropneumoniaeCM5 exposed to BALF up-regulated, among other genes, a gene predicted to encode LamB, an outer-membrane transport protein of the maltose regulon. To determine the role of thelamBand other genes of the maltose regulon in the pathogenesis ofA. pleuropneumoniae, knockout mutations were created in thelamBandmalTgenes, the latter being the positive transcriptional regulator of the maltose regulon. Relative to thelamBmutant and the wild type, themalTmutant had a significant (P< 0.05) decrease in growth rate and an increased sensitivity to fresh porcine serum and high concentrations (more than 0.5 M) of sodium chloride. In DNA microarray experiments, the BALF-exposedmalTmutant exhibited a gene-expression profile resembling that of a stringent type gene-expression profile seen in bacteria facing amino acid or carbon starvation. Genes encoding proteins for protein synthesis, energy metabolism, and DNA replication were down-regulated, while genes involved in stringent response (e.g.,relA), amino acid and nucleotide biosynthesis, biofilm formation, DNA transformation, and stress response were up-regulated.

Conclusion

These results suggest that MalT may be involved in protection against some stressors and in the transport of one or more essential nutrients in BALF. Moreover, if MalT is directly or indirectly linked to the stringent response, an important global mechanism of bacterial persistence and virulence in many bacterial pathogens, it might play a role inA. pleuropneumoniaepathogenesis.
Expression analysis of E-cadherin, Slug and GSK3β in invasive ductal carcinoma of breast
Authors: Prasad Chandra P , Rath Gayatri , Mathur Sandeep , Bhatnagar Dinesh , Parshad Rajinder , Ralhan Ranju
Published: September 2009

Background

Cancer progression is linked to a partially dedifferentiated epithelial cell phenotype. The signaling pathways Wnt, Hedgehog, TGF-β and Notch have been implicated in experimental and developmental epithelial mesenchymal transition (EMT). Recent findings from our laboratory confirm that active Wnt/β-catenin signaling is critically involved in invasive ductal carcinomas (IDCs) of breast.

Methods

In the current study, we analyzed the expression patterns and relationships between the key Wnt/β-catenin signaling components- E-cadherin, Slug and GSK3β in IDCs of breast.

Results

Of the 98 IDCs analyzed, 53 (54%) showed loss/or reduced membranous staining of E-cadherin in tumor cells. Nuclear accumulation of Slug was observed in 33 (34%) IDCs examined. Loss or reduced level of cytoplasmic GSK3β expression was observed in 52/98 (53%) cases; while 34/98 (35%) tumors showed nuclear accumulation of GSK3β. Statistical analysis revealed associations of nuclear Slug expression with loss of membranous E-cadherin (p = 0.001); nuclear β-catenin (p = 0.001), and cytoplasmic β-catenin (p = 0.005), suggesting Slug mediated E-cadherin suppression via the activation of Wnt/β-catenin signaling pathway in IDCs. Our study also demonstrated significant correlation between GSK3β nuclear localization and tumor grade (p = 0.02), suggesting its association with tumor progression.

Conclusion

The present study for the first time provided the clinical evidence in support of Wnt/β-catenin signaling upregulation in IDCs and key components of this pathway - E-cadherin, Slug and GSK3β with β-catenin in implementing EMT in these cells.
Hemoglobin levels and anemia evaluation during pregnancy in the highlands of Tibet: a hospital-based study
Authors: Xing Yuan , Yan Hong , Dang Shaonong , Zhuoma Bianba , Zhou Xiaoyan , Wang Duolao
Published: September 2009

Background

Anemia is regarded as a major risk factor for unfavorable pregnancy outcomes, but there have been no previous studies describing the pattern of hemoglobin concentration during pregnancy in Tibet and the relationship between altitude and Hb concentration in the pregnant women living in Tibet still has not been clearly established. The main objectives of this study were to study the hemoglobin levels and prevalence of anemia among pregnant women living in the highlands of Tibet and to evaluate potential associations of hemoglobin and anemia with women's characteristics.

Methods

The hospital-based study was conducted in 380 pregnant women. Their blood samples were tested and related sociodemographic information was collected. Multiple linear regression model and multiple logistic regression model were used to assess the association of pregnant women's characteristics with hemoglobin level and the occurrence of anemia. Centers for Disease Control (CDC), Dirren et al. and Dallman et al. methods were used to adjust the hemoglobin measurements based on altitude for estimating the prevalence of anemia.

Results

The mean hemoglobin concentration was 127.6 g/L (range: 55.0-190.0 g/L). Prevalence rate of anemia in this study was 70.0%, 77.9% and 41.3%, respectively for three altitude-correction methods for hemoglobin (CDC method, Dirren et al. method, and Dallman et al. method). Gestational age, ethnicity, residence and income were significantly associated with the hemoglobin concentration and prevalence of anemia in the study population. Specially, the hemoglobin concentration of pregnant women decreased with increase in gestational age.

Conclusion

The hemoglobin level was low and prevalence rate of anemia was high among pregnant women in Lhasa, Tibet. Gestational age, ethnicity, residence and income were found to be significantly associated with the hemoglobin level and the occurrence of anemia in the study population.
Use of the slide positivity rate to estimate changes in malaria incidence in a cohort of Ugandan children
Authors: Jensen Trevor P , Bukirwa Hasifa , Njama-Meya Denise , Francis Damon , Kamya Moses R , Rosenthal Philip J , Dorsey Grant
Published: September 2009

Background

As malaria control efforts intensify, it is critical to monitor trends in disease burden and measure the impact of interventions. A key surveillance indicator is the incidence of malaria. Yet measurement of incidence is challenging. The slide positivity rate (SPR) has been used as a surrogate measure of malaria incidence, but limited data exist on the relationship between SPR and the incidence of malaria.

Methods

A cohort of 690 children aged 1-10 years at enrollment were followed for all their health care needs over a four-year period in Kampala, Uganda. All children with fever underwent laboratory testing, allowing us to measure the incidence of malaria and non-malaria fevers. A formula was derived to estimate relative changes in the incidence of malaria (rΔIm) based on changes in the SPR and the assumption that the incidence of non-malaria fevers was consistent over time. Observed and estimated values of rΔIm were compared over two, six, and 12 month time intervals after restricting the analysis to children contributing observation time between the ages of 4-10 years to control for aging of the cohort.

Results

Over the four-year observation period the incidence of malaria declined significantly from 0.93 episodes per person-year in 2005 to 0.39 episodes per person-year in 2008 (p < 0.0001) and the incidence of non-malaria fevers declined significantly from 2.31 episodes per person-year in 2005 to 1.31 episodes per person-year in 2008 (p < 0.0001). Younger age was associated with a significantly greater incidence of malaria and the incidence of malaria was significantly higher during seasonal peaks occurring each January-February and May-June. Changes in SPR produced reasonably accurate estimates of rΔIm over all time intervals. The average absolute difference in observed and estimated values of rΔIm was lower for six-month intervals (0.13) than it was for two-month (0.21) or 12 month intervals (0.21).

Conclusion

Changes in SPR provided a useful estimate of changes in the incidence of malaria in a well defined cohort; however, a gradual decline in the incidence of non-malaria fevers introduced some bias in these estimates.
Expression of cartilage-derived morphogenetic protein in human intervertebral discs and its effect on matrix synthesis in degenerate human nucleus pulposus cells
Authors: Le Maitre Christine L , Freemont Anthony J , Hoyland Judith A
Published: September 2009

Introduction

Loss of intervertebral disc (IVD) matrix and ultimately disc height as a result of 'degeneration' has been implicated as a major cause of low back pain (LBP). The use of anabolic growth factors as therapies to regenerate IVD matrix, hence restoring disc height and thus reversing degenerative disc disease, has been suggested. Cartilage-derived morphogenetic protein (CDMP) is a growth factor which stimulates proteoglycan production in chondrocyte-like cells and thus could be a useful growth factor for LBP therapies. However, little is known about the expression of CDMP or its receptor in human IVD, nor its effects on human disc cells.

Methods

Using immunohistochemistry we investigated the localisation of CDMP in non-degenerate and degenerate human IVDs. Additionally, we investigated the effect of CDMP on aggrecan and type II collagen gene expression and proteoglycan synthesis in nucleus pulposus (NP) cells derived from degenerate IVDs.

Results

We demonstrated that CDMP 1 and 2 were expressed in the non-degenerate and degenerate IVD, particularly in cells of the NP. A small decrease in the number of CDMP 1 and 2 immunopositive cells was seen with degeneration. Treatment of human NP cells, (derived from degenerate IVD), with CDMP showed an increase in aggrecan and type II collagen gene expression and increased production of proteoglycan (GAGs).

Conclusions

The data suggests that CDMP may be a useful growth factor to stimulate proteoglycan production in the human degenerate IVD and hence the repair of the extracellular matrix.
Perioperative indocyanine green clearance is predictive for prolonged intensive care unit stay after coronary artery bypass grafting - an observational study
Authors: Sander Michael , Spies Claudia D , Berger Katharina , Schröder Torsten , Grubitzsch Herko , Wernecke Klaus D , von Heymann Christian
Published: September 2009

Introduction

During cardiac surgery with cardiopulmonary bypass (CPB) haemodilution occurs. Hepatic dysfunction after CPB is a rare, but serious, complication. Clinical data have validated the plasma-disappearance rate of indocyanine green (PDR ICG) as a marker of hepatic function and perfusion. Primary objective of this analysis was to investigate the impact of haemodilutional anaemia on hepatic function and perfusion by the time course of PDR ICG and liver enzymes in elective CABG surgery. Secondary objective was to define predictors of prolonged ICU treatment like decreased PDR ICG after surgery.

Methods

60 Patients were subjected to normothermic CPB with predefined levels of haemodilution anaemia (haemotacrit (Hct) of 25% versus 20% during CPB). Hepatic function and perfusion was assessed by PDR ICG, plasma levels of aspartate aminotransferase (ASAT) and α-GST. Prolonged ICU treatment was defined as treatment ≥ 48 hours.

Results

Logistic regression analysis showed that all postoperative measurements of PDR ICG (P < 0.01), and the late postoperative ASAT (P < 0.01) measurement were independent risk factors for prolonged ICU treatment. The predictive capacity for prolonged ICU treatment was best of the PDR ICG one hour after admission to the ICU. Furthermore, the time course of PDR ICG as well as ASAT and α-GST did not differ between groups of haemodilutional anaemia.

Conclusions

Our study provides evidence that impaired PDR ICG as a marker of hepatic dysfunction and hypoperfusion may be a valid marker of prolonged ICU treatment. Additionally this study provides evidence that haemodilutional anaemia to a Hct of 20% does not impair hepatic function and perfusion.

Trial registration

[ISRCTN35655335]
Genome-wide deletion mutant analysis reveals genes required for respiratory growth, mitochondrial genome maintenance and mitochondrial protein synthesis in Saccharomyces cerevisiae
Authors: Merz Sandra , Westermann Benedikt
Published: September 2009

Background

The mitochondrial respiratory chain produces metabolic energy by oxidative phosphorylation. Biogenesis of the respiratory chain requires the coordinated expression of two genomes: the nuclear genome encoding the vast majority of mitochondrial proteins, and the mitochondrial genome encoding a handful of mitochondrial proteins. The understanding of the molecular processes contributing to respiratory chain assembly and maintenance requires the systematic identification and functional analysis of the genes involved.

Results

We pursued a systematic, genome-wide approach to define the sets of genes required for respiratory activity and maintenance and expression of the mitochondrial genome in yeast. By comparative gene deletion analysis we found an unexpected phenotypic plasticity among respiratory-deficient mutants, and we identified ten previously uncharacterized genes essential for respiratory growth (RRG1 through RRG10). Systematic functional analysis of 319 respiratory-deficient mutants revealed 16 genes essential for maintenance of the mitochondrial genome, 88 genes required for mitochondrial protein translation, and 10 genes required for expression of specific mitochondrial gene products. A group of mutants acquiring irreversible damage compromising respiratory capacity includes strains defective in assembly of the cytochrome c oxidase that were found to be particularly sensitive to aging.

Conclusions

These data advance the understanding of the molecular processes contributing to maintenance of the mitochondrial genome, mitochondrial protein translation, and assembly of the respiratory chain. They revealed a number of previously uncharacterized components, and provide a comprehensive picture of the molecular processes required for respiratory activity in a simple eukaryotic cell.
Reverse-engineering the Arabidopsis thaliana transcriptional network under changing environmental conditions
Authors: Carrera Javier , Rodrigo Guillermo , Jaramillo Alfonso , Elena Santiago F
Published: September 2009

Background

Understanding the molecular mechanisms plants have evolved to adapt their biological activities to a constantly changing environment is an intriguing question and one that requires a systems biology approach. Here we present a network analysis of genome-wide expression data combined with reverse-engineering network modeling to dissect the transcriptional control of Arabidopsis thaliana. The regulatory network is inferred by using an assembly of microarray data containing steady-state RNA expression levels from several growth conditions, developmental stages, biotic and abiotic stresses, and a variety of mutant genotypes.

Results

We show that the A. thaliana regulatory network has the characteristic properties of hierarchical networks. We successfully applied our quantitative network model to predict the full transcriptome of the plant for a set of microarray experiments not included in the training dataset. We also used our model to analyze the robustness in expression levels conferred by network motifs such as the coherent feed-forward loop. In addition, the meta-analysis presented here has allowed us to identify regulatory and robust genetic structures.

Conclusions

These data suggest that A. thaliana has evolved high connectivity in terms of transcriptional regulation among cellular functions involved in response and adaptation to changing environments, while gene networks constitutively expressed or less related to stress response are characterized by a lower connectivity. Taken together, these findings suggest conserved regulatory strategies that have been selected during the evolutionary history of this eukaryote.
Bridging the gap between systems biology and medicine
Authors: Clermont Gilles , Auffray Charles , Moreau Yves , Rocke David M , Dalevi Daniel , Dubhashi Devdatt , Marshall Dana R , Raasch Peter , Dehne Frank , Provero Paolo , Tegner Jesper , Aronow Bruce J , Langston Michael A , Benson Mikael
Published: September 2009

Systems biology has matured considerably as a discipline over the last decade, yet some of the key challenges separating current research efforts in systems biology and clinically useful results are only now becoming apparent. As these gaps are better defined, the new discipline of systems medicine is emerging as a translational extension of systems biology. How is systems medicine defined? What are relevant ontologies for systems medicine? What are the key theoretic and methodologic challenges facing computational disease modeling? How are inaccurate and incomplete data, and uncertain biologic knowledge best synthesized in useful computational models? Does network analysis provide clinically useful insight? We discuss the outstanding difficulties in translating a rapidly growing body of data into knowledge usable at the bedside. Although core-specific challenges are best met by specialized groups, it appears fundamental that such efforts should be guided by a roadmap for systems medicine drafted by a coalition of scientists from the clinical, experimental, computational, and theoretic domains.
Prevention of Thrombosis in Ambulatory Patients With Cancer
Authors: Rana Punam , Levine Mark N.
Published: September 2009

Cancer patients with solid tumors or hematologic malignancies receive most of their cancer treatment as outpatients. Thromboembolism, when it occurs, complicates the clinical care of these patients because of the associated morbidity and the need for anticoagulant treatment. It would seem that prevention of venous thromboembolism in these patients would be worthwhile. However, to date there are relatively few trials of anticoagulant prophylaxis in ambulatory patients with cancer and it is not possible to recommend prophylaxis for most patients. Research is needed to better define a population at high enough risk to warrant pharmacologic prophylaxis and to develop new antithrombotic agents for this indication.
Longitudinal Patterns of Chemotherapy Use in Metastatic Colorectal Cancer
Authors: Zafar S. Yousuf , Marcello Jennifer E. , Wheeler Jane L. , Rowe Krista L. , Morse Michael A. , Herndon James E. , Abernethy Amy P.
Published: September 2009

Multiple agents and combination therapies available to patients with advanced colorectal cancer have significantly improved survival and provided an opportunity for individualization of care, allowing clinicians and patients to prioritize risks and benefits of comparable regimens.
Safe Handling of Parenteral Cytotoxics: Recommendations for Ontario
Authors: Green Esther , Johnston Mary , Trudeau Maureen , Schwartz Lisa , Poirier Susan , Macartney Gail , Milliken Deborah
Published: September 2009

In caring for patients with cancer, health care workers may be exposed to cytotoxic agents. Recommendations are needed to mitigate potential risks for cancer and adverse reproductive outcomes associated with exposure.
Penny Wise, Dollar Foolish Approach to Antiemetic Use May Compromise Patient Care
Authors: Hesketh Paul J.
Published: September 2009

A recent coverage determination by National Government Services threatens to compromise the ability of patients to achieve complete control of chemotherapy-induced nausea and vomiting by limiting oncologist discretion in prescribing antiemetics.
Policy Update: Federal Incentives for the Adoption of Electronic Health Records
Authors: Worzala Chantal
Published: September 2009

The American Recovery and Reinvestment Act of 2009 provides financial incentives for physicians and hospitals to adopt electronic health records. Practices can take initial steps outlined here to receive bonus payments and avoid penalties.
Coordination of Outsourced Operations to Minimize Weighted Flow Time and Capacity Booking Costs
Authors: Aydinliyim Tolga , Vairaktarakis George L.
Published: September 2009

A set of manufacturers outsources certain operations to a single third party following the announcement of a booking price for each available day of production. Knowing these costs, manufacturers book available production days in a first-come-first-serve order to optimize their individual cost. The cost for each manufacturer consists of booking and work-in-progress costs, as expressed by the weighted flow time. When window booking is completed, the third party identifies a schedule that minimizes the total cost incurred by all manufacturers. This coordination reduces the total cost but may result in higher costs for a subset of manufacturers. For this reason, the third party devises a savings sharing scheme with which the monetary benefit for each manufacturer is greater. In this article we present algorithms for the problem considered, as well as savings-sharing schemes that make coordination a better alternative for all parties. The highlight of our experiments is that the costs of the production chain can be reduced by an average of 32% if one-third of the members let the third party cover their increased work-in-progress cost in exchange for 38%–53% of the total savings.
Ignition of Contaminated Aluminum by Impact in Liquid Oxygen—Influence of Oxygen Purity
Authors: Werlen Etienne , Crayssac Frédéric , Longuet Olivier , Willot Fabien
Published: September 2009

Impact tests in liquid oxygen and oxygen enriched liquids have been conducted on aluminum foils (0.2 mm thick) used for heat exchangers of air separation units (ASUs). Some adaptations to the ASTM Standard D2512, “Standard Test Method for Compatibility of Materials with Liquid Oxygen,” have been done to ensure the good control of oxygen content in the cryogenic liquid and to get reproducible results in aluminum ignition with hydrocarbon coating. Modified striker pins with a cavity on the contact surface have been used. The vertical guiding and the centering of the striker pins have been ensured by using two machined guides. Test samples were three layers of aluminum foil, two corrugated and one flat, contaminated by various quantities of hexadecane. The criteria for the identification of aluminum ignition (positive tests) have been validated by performing Scanning electron microscope surface analysis on residuals of a few impact tests performed in copper cups. Criteria have also been defined to check that hexadecane combustion took place in negative tests. A sufficient number of tests have been performed to plot the probability of ignition of the aluminum samples as a function of the average thickness of hexadecane coating and as a function of the oxygen content in the cryogenic liquid varying from 50 % to above 99.95 %. The remaining part in the cryogenic liquid was nitrogen and 2.3 % argon except for one series of tests where the influence of the absence of argon could be identified. The results of these tests can be used to assess the risk of ignition of some aluminum exchangers or structures used in ASU.
Test Methods for Characterizing Air Void Systems in Portland Cement Pervious Concrete
Authors: Kevern John T. , Wang Kejin , Schaefer Vernon R.
Published: September 2009

Portland cement pervious concrete is becoming a common tool for stormwater management across the United States. The air void system in pervious concrete is particularly important because of its effect on stormwater infiltration, concrete strength, and long-term durability. However, currently the concrete industry lacks standardized testing techniques for characterizing air void systems in pervious concrete. In this paper a series of air system characterization tests performed during a field placement of pervious concrete is detailed, and the test results are compared. Fresh pervious concrete samples from two delivered mixtures were evaluated using pressure, volumetric, Chace, and air void analyzer air test methods. The hardened concrete samples were tested for water-permeable void content, water permeability, air voids (using ASTM Standard C457 method), and freeze-thaw durability (using ASTM Standard C666A method). Based on the results of the study, determination of air systems for the freeze-thaw protection of pervious concrete is proposed.
Fracture Mechanics of Brittle Ceramics - 30 Years of Progress
Authors: Bradt RC
Published: September 2009

The application of fracture mechanics to advanced technical ceramics was initiated nearly 30 years ago. It was heralded by an international conference at the Pennsylvania State University in 1973. Unbridled optimism prevailed as many believed that the coupling of fracture mechanics with ceramics would enable high temperature advanced ceramics to find extensive structural applications. Unfortunately, there were a number of barriers to the use of ceramics as structural materials, even with the application of fracture mechanics.

The use of brittle ceramics in structural applications faced major challenges. These included: (1) the absence of a reliable data base of materials properties, (2) the lack of appropriate standards for the determination of the properties of these materials, (3) a lack of any rational, fracture mechanics based design methodology for brittle ceramics, and (4) the high costs of producing and utilizing structural parts from advanced ceramics. These were serious deficiencies that inhibited the achievement of successful applications of ceramics.

Fracture mechanics tests provided a basis for the design methodology and also provided understanding of the basics of the fracture process in brittle ceramics. It informed the engineering community that ceramic fracture toughnesses were low, < 10 MPa√m and that there were serious problems with slow crack growth and fatigue. The presence of rising R-curve behavior was observed and related to the crack tip's following wake region. Cyclic fatigue was confirmed to exist and related to the presence of a rising R-curve.

Today, the promise of structural ceramics remains mostly unfulfilled, except for a few niche applications that are nonetheless encouraging. In addition, there have been significant advances in the properties and integrity of structural ceramics over the past three decades. Advanced structural ceramics are better than ever. This can be attributed to the use of fracture mechanics concepts to identify the microstructural processing defects and then improve the processing methodology to eliminate those defects. There have also been major advances in the development of standards applied to ceramics in which ASTM has played a major role. Unfortunately, we still have not learned to design with brittle ceramics and the cost of their utilization in structural applications remains prohibitively high.
Stresses in Ceramic Plates Subjected to Loading Between Concentric Rings
Authors: Powers LM , Salem JA , Weaver AS
Published: September 2009

Plates of both square and round geometries are tested to determine the strength and fatigue properties of ceramics under multiaxial stresses. The necessary tolerances required for accurate testing are not well documented in published literature. The stresses in square and round plates subjected to loading between concentric rings were investigated via the finite element analysis method. In particular, the effects of load ring concentricity and the amount of the plate overhanging the support ring were investigated. Also, the errors generated by testing square plates between circular rings were investigated. The analyses were performed in support of an effort by the American Society for Testing and Materials Committee C28 on Advanced Ceramics to standardized multiaxial testing of ceramic plates.
Does Anyone Know The Real Fracture Toughness? SRM 2100: The World's First Ceramic Fracture Toughness Reference Material
Authors: Quinn GD , Xu K , Gettings RJ , Salem JA , Swab JJ
Published: September 2009

Standard Reference Material (SRM) 2100 is the first reference material in the world for the property fracture toughness. The SRM was developed in tandem with the new ASTM test method C 1421-99. The SRM also supports two International Standards Organization (ISO) draft standards now under development in ISO Committee TC 206, Fine Ceramics. The SRM is a set of five silicon nitride test specimens. The SRM may be used with any credible ceramic fracture toughness test method, but has been optimized for test methods that use beams in bending. Identical results are obtained with single-edge precracked beam, chevron-notched beam, and surface crack in flexure methods. SRM 2100 should dramatically improve fracture toughness testing and enhance data quality around the world. This paper describes SRM 2100 and its creation.
The Fracture Toughness Round Robins in VAMAS: What We Have Learned
Authors: Quinn GD
Published: September 2009

Over the last 13 years the Versailles project on Advanced Materials and Standards (VAMAS) has conducted five full fledged, international round robins on ceramic fracture toughness characterization. As many as forty laboratories have done thousands of experiments on silicon nitride, silicon carbide, zirconia, alumina, zirconiaalumina composite, and whisker-reinforced alumina. Test methods have included singleedged precracked beam, single-edged V-notched beam, chevron-notched beam, surface crack in flexure, indentation strength, and indentation crack length. Highlights of these projects are presented along with some lessons learned about round robins in general.
R-Curve Measurement of Silicon Nitride Based Ceramics at Elevated Temperatures with Single Edge Notched Beam Specimens
Authors: Sakaguchi S
Published: September 2009

In order to understand the fracture behavior of the structural ceramics at elevated temperatures, the R-curve behavior of silicon nitride based ceramics was measured by using single edge notched beam (SENB) specimens, at room and elevated temperatures. It is difficult to obtain stable fracture with the SENB method, but if we cut the straight notch deep enough, we can obtain the stable fracture in bending, even though the specimen is brittle and shows no rising R-curve behavior. This technique is easy to apply in high temperature testing. Three kinds of silicon nitride based ceramics were tested up to 1200 °C. We could measure the R-curve behavior, if the specimen did not show creep deformation. This technique is quite useful for discussing fracture behavior of ceramics at elevated temperatures.
Crack Deflection Toughening Mechanism in Brittle Materials
Authors: Awaji H , Ebisudani M , Choi S-M , Ohashi T
Published: September 2009

Toughening mechanisms in polycrystalline ceramics and ceramic-based composites were discussed based on Griffith's energy equilibrium and classified into three groups: (A) the frontal process-zone toughening mechanism, (B) the crack-bridging mechanism, and (C) the macroscopic crack-deflection mechanism. The increase in fracture toughness caused by enforced macroscopic crack-deflection was estimated using the energy equilibrium between the energy-release rate and the fracture-energy rate. The analytical results revealed that the fracture toughness under Mode I loading was enhanced by twice the normal value when the crack propagates in the direction 90° from its original plane. Under Mode II loading the fracture toughness is increased 1.2 times the normal value when the crack propagates in its original plane. Crack-deflection tests were carried out by using wooden, thin rectangular plates with a central crack. The increase in the fracture toughness caused by crack deflection was confirmed and the experimental data was coincident with the calculated results.
Application of Quantitative Fractography to the Characterization of R-Curve Behavior
Authors: Mecholsky JJ , Hill TJ , Chen Z
Published: September 2009

The objective of this work is to demonstrate the applicability of quantitative fractography and fractal analysis to fracture processes in materials that exhibit R-curve behavior. In-situ toughened silicon nitride and baria-silica glass ceramics are used as model materials to demonstrate the effect of changes in morphology on toughness. These two tools, i.e., quantitative fracture surface analysis and fractal geometry, provide a new way of quantitatively assessing the mechanisms of toughening due to elongated grains and changes in microstructure.

For example, in silicon nitride the R-curve behavior only has an effect when the crack sizes are larger than about 30 micrometers. In applications where small cracks are expected, i.e., in bearing applications and for other well-polished surface finishes, R-curve materials may not be desirable.

In another example, 3BaO•5SiO2 glass ceramics were fabricated with crystals of aspect ratios (AR) of 1.4, 3.6 and 8.1. Based on fractal analysis, fractography and other accumulated data, it was shown that there was a statistical difference in the toughening behavior between materials with AR = 1.4 & 3.6, as compared to the material with AR = 8.1. The fractal dimensional increment was used to provide a method for determining the amount of toughening increase over that due to crack deflections as 0.4-0.6 MPam1/2. The implication of these results for the fracture process of toughened materials and the role of microstructure are discussed and explained in terms of material design.
The Effect of Stress Rate on Slow Crack Growth Parameter Estimates
Authors: Salem JA , Jenkins MG
Published: September 2009

Dynamic fatigue or constant stress-rate testing is a convenient method for generating SCG (slow crack growth) data on ceramics and glasses. The tests are simple, inexpensive, and accomplished quickly. However, the use of dynamic fatigue testing to generate slow crack growth data for SCG parameter estimation assumes that the test specimen lifetime is dominated by a single region of the SCG curve. This assumption breaks down when excessive stressing rates are used and significant portions of the crack growth occurs in all three regions of the SCG curve. The resultant averaging of data representing all three regions of the SCG curve results in an error in the estimated SCG parameters n and D, and such data may not be accurate for predicting the lifetime of industrial components.

Dynamic fatigue tests covering five orders of magnitude well below the inert strength were performed on an alumina. The tests were performed using ASTM C 1161 “B” flexure specimens in accordance with ASTM Test Method for Determination of Slow Crack Growth Parameters of Advanced Ceramics by Constant Stress Rate Testing (C 1368-97). Statistical analysis of the experimental results indicates a statistically significant effect of stress rate on the SCG parameter n for stress rates above several MPa/s. The experimental results are in agreement with analytical results of Sudreau et al. [1] that show significant effects for rates greater than approximately one MPa/s. Recommendations for dynamic fatigue testing are given with regard to the current procedures in ASTM C 1368-97.
Comparison between various Field and Laboratory Measurements of the Hydraulic Conductivity of three Clay Liners
Authors: Cazaux D , Didier G
Published: September 2009

For waste facilities, field assessment of the hydraulic conductivity of fine- grained soils has been a real challenge for the past decades that has led to several types of test methods. Although standards (ASTM, NF, etc.) have been adopted in many countries, any test method needs careful application for constructing quality-control programs. The type of apparatus, its geometry, and even specimen preparation may be major sources of discrepancy. We compared hydraulic-conductivity values obtained from various field-testing methods (open, sealed, single and double infiltrometers, and borehole methods), and laboratory-testing methods such as oedometer cells or rigid and flexible-wall permeameters. Three materials were tested in this study: a compacted sandbentonite mixture, compacted clayey silt, and natural sandy clay. The field tests were run on soil-test pads whose characteristics were defined beforehand in the laboratory and the field. Comparison of the results shows a large range of hydraulic-conductivity values for a single soil sample. Such variability can commonly be explained by a scale effect, as demonstrated by the use of various types of diameter or geometry for the field or laboratory tests. Soil behavior (swelling or shrinkage) and test-analysis methods (saturated or unsaturated-flow analysis) are other important parameters. In conclusion, we identified the main problems affecting tests with infiltrometers and permeameters, and how they can be reduced or avoided by the improvement of current techniques.
Hydraulic Conductivity of a Fractured Aquitard
Authors: Abichou T , Benson CH , Friend M , Wang X
Published: September 2009

An investigation was conducted to characterize the hydraulic conductivity of a shallow clay till aquitard over which a municipal solid waste landfill was being sited. Hydraulic conductivity tests were conducted in the laboratory on specimens removed from the till in thin-wall sampling tubes (71 mm diameter) and as large hand-carved blocks (460 mm diameter). Field hydraulic conductivity was measured using a slug test. Tests on specimens from the sampling tubes indicated that the hydraulic conductivity of the till was very low (10−9 to 10-8 cm/s). The slug test and tests on large blocks containing fractures yielded much higher hydraulic conductivities, on the order of 10−6 cm/s. This difference in hydraulic conductivities is attributed to fractures, which were evident in the block specimens. Testing of the block specimens at higher overburden stresses showed that the hydraulic conductivity decreased by one order of magnitude as the overburden stress increased from 35 kPa to 175 kPa, apparently due to closure of the fractures.