bluuebunny/crossref_metadata_2025 huggingface dataset:
Erythroid dysplasia, megaloblastic anemia, and impaired lymphopoiesis arising from mitochondrial dysfunction
Authors: Chen Michael L. , Logan T. Daniel , Hochberg Maryann L. , Shelat Suresh G. , Yu Xiang , Wilding Gregory E. , Tan Wei , Kujoth Gregory C. , Prolla Tomas A. , Selak Mary A. , Kundu Mondira , Carroll Martin , Thompson James E.
Published: September 2009

Recent reports describe hematopoietic abnormalities in mice with targeted instability of the mitochondrial genome. However, these abnormalities have not been fully described. We demonstrate that mutant animals develop an age-dependent, macrocytic anemia with abnormal erythroid maturation and megaloblastic changes, as well as profound defects in lymphopoiesis. Mice die of severe fatal anemia at 15 months of age. Bone-marrow transplantation studies demonstrate that these abnormalities are intrinsic to the hematopoietic compartment and dependent upon the age of donor hematopoietic stem cells. These abnormalities are phenotypically similar to those found in patients with refractory anemia, suggesting that, in some cases, the myelodysplastic syndromes are caused by abnormalities of mitochondrial function.
Pim kinase inhibitor, SGI-1776, induces apoptosis in chronic lymphocytic leukemia cells
Authors: Chen Lisa S. , Redkar Sanjeev , Bearss David , Wierda William G. , Gandhi Varsha
Published: September 2009

Pim kinases are involved in B-cell development and are overexpressed in B-cell chronic lymphocytic leukemia (CLL). We hypothesized that Pim kinase inhibition would affect B-cell survival. Identified from a screen of imidazo[1,2-b]pyridazine compounds, SGI-1776 inhibits Pim-1, Pim-2, and Pim-3. Treatment of CLL cells with SGI-1776 results in a concentration-dependent induction of apoptosis. To elucidate its mechanism of action, we evaluated the effect of SGI-1776 on Pim kinase function. Unlike in replicating cells, phosphorylation of traditional Pim-1 kinase targets, phospho-Bad (Ser112) and histone H3 (Ser10), and cell-cycle proteins were unaffected by SGI-1776, suggesting an alternative mechanism in CLL. Protein levels of total c-Myc as well as phospho-c-Myc(Ser62), a Pim-1 target site, were decreased after SGI-1776 treatment. Levels of antiapoptotic proteins Bcl-2, Bcl-XL, XIAP, and proapoptotic Bak and Bax were unchanged; however, a significant reduction in Mcl-1 was observed that was not caused by caspase-mediated cleavage of Mcl-1 protein. The mechanism of decline in Mcl-1 was at the RNA level and was correlated with inhibition of global RNA synthesis. Consistent with a decline in new RNA synthesis, MCL-1 transcript levels were decreased after treatment with SGI-1776. These data suggest that SGI-1776 induces apoptosis in CLL and that the mechanism involves Mcl-1 reduction.
Inactivating SOCS1 mutations are caused by aberrant somatic hypermutation and restricted to a subset of B-cell lymphoma entities
Authors: Mottok Anja , Renné Christoph , Seifert Marc , Oppermann Elsie , Bechstein Wolf , Hansmann Martin-Leo , Küppers Ralf , Bräuninger Andreas
Published: September 2009

STATs are constitutively activated in several malignancies. In primary mediastinal large B-cell lymphoma and Hodgkin lymphoma (HL), inactivating mutations in SOCS1, an inhibitor of JAK/STAT signaling, contribute to deregulated STAT activity. Based on indications that the SOCS1 mutations are caused by the B cell–specific somatic hypermutation (SHM) process, we analyzed B-cell non-HL and normal B cells for mutations in SOCS1. One-fourth of diffuse large B-cell lymphoma and follicular lymphomas carried SOCS1 mutations, which were preferentially targeted to SHM hotspot motifs and frequently obviously inactivating. Rare mutations were observed in Burkitt lymphoma, plasmacytoma, and mantle cell lymphoma but not in tumors of a non–B-cell origin. Mutations in single-sorted germinal center B cells were infrequent relative to other genes mutated as byproducts of normal SHM, indicating that SOCS1 inactivation in primary mediastinal large B-cell lymphoma, HL, diffuse large B-cell lymphoma, and follicular lymphoma is frequently the result of aberrant SHM.
EDGE3: A web-based solution for management and analysis of Agilent two color microarray experiments
Authors: Vollrath Aaron L , Smith Adam A , Craven Mark , Bradfield Christopher A
Published: September 2009

Background

The ability to generate transcriptional data on the scale of entire genomes has been a boon both in the improvement of biological understanding and in the amount of data generated. The latter, the amount of data generated, has implications when it comes to effective storage, analysis and sharing of these data. A number of software tools have been developed to store, analyze, and share microarray data. However, a majority of these tools do not offer all of these features nor do they specifically target the commonly used two color Agilent DNA microarray platform. Thus, the motivating factor for the development of EDGE3 was to incorporate the storage, analysis and sharing of microarray data in a manner that would provide a means for research groups to collaborate on Agilent-based microarray experiments without a large investment in software-related expenditures or extensive training of end-users.

Results

EDGE3 has been developed with two major functions in mind. The first function is to provide a workflow process for the generation of microarray data by a research laboratory or a microarray facility. The second is to store, analyze, and share microarray data in a manner that doesn't require complicated software. To satisfy the first function, EDGE3 has been developed as a means to establish a well defined experimental workflow and information system for microarray generation. To satisfy the second function, the software application utilized as the user interface of EDGE3 is a web browser. Within the web browser, a user is able to access the entire functionality, including, but not limited to, the ability to perform a number of bioinformatics based analyses, collaborate between research groups through a user-based security model, and access to the raw data files and quality control files generated by the software used to extract the signals from an array image.

Conclusion

Here, we present EDGE3, an open-source, web-based application that allows for the storage, analysis, and controlled sharing of transcription-based microarray data generated on the Agilent DNA platform. In addition, EDGE3 provides a means for managing RNA samples and arrays during the hybridization process. EDGE3 is freely available for download at http://edge.oncology.wisc.edu/.
SNP@Evolution: a hierarchical database of positive selection on the human genome
Authors: Cheng Feng , Chen Wei , Richards Elliott , Deng Libin , Zeng Changqing
Published: September 2009

Background

Positive selection is a driving force that has shaped the modern human. Recent developments in high throughput technologies and corresponding statistics tools have made it possible to conduct whole genome surveys at a population scale, and a variety of measurements, such as heterozygosity (HET), F

ST
, and Tajima's D, have been applied to multiple datasets to identify signals of positive selection. However, great effort has been required to combine various types of data from individual sources, and incompatibility among datasets has been a common problem. SNP@Evolution, a new database which integrates multiple datasets, will greatly assist future work in this area.

Description

As part of our research scanning for evolutionary signals in HapMap Phase II and Phase III datasets, we built SNP@Evolution as a multi-aspect database focused on positive selection. Among its many features, SNP@Evolution provides computed F

ST
and HET of all HapMap SNPs, 5+ HapMap SNPs per qualified gene, and all autosome regions detected from whole genome window scanning. In an attempt to capture multiple selection signals across the genome, selection-signal enrichment strength (ES) values of HET, F

ST
, and P-values of iHS of most annotated genes have been calculated and integrated within one frame for users to search for outliers. Genes with significant ES or P-values (with thresholds of 0.95 and 0.05, respectively) have been highlighted in color. Low diversity chromosome regions have been detected by sliding a 100 kb window in a 10 kb step. To allow this information to be easily disseminated, a graphical user interface (GBrowser) was constructed with the Generic Model Organism Database toolkit.

Conclusion

Available at http://bighapmap.big.ac.cn, SNP@Evolution is a hierarchical database focused on positive selection of the human genome. Based on HapMap Phase II and III data, SNP@Evolution includes 3,619,226/1,389,498 SNPs with their computed HET and F

ST
, as well as qualified genes of 21,859/21,099 with ES values of HET and F

ST
. In at least one HapMap population group, window scanning for selection signals has resulted in 1,606/10,138 large low HET regions. Among Phase II and III geographical groups, 660 and 464 regions show strong differentiation.
Comparative analyses of genotype dependent expressed sequence tags and stress-responsive transcriptome of chickpea wilt illustrate predicted and unexpected genes and novel regulators of plant immunity
Authors: Ashraf Nasheeman , Ghai Deepali , Barman Pranjan , Basu Swaraj , Gangisetty Nagaraju , Mandal Mihir K , Chakraborty Niranjan , Datta Asis , Chakraborty Subhra
Published: September 2009

Background

The ultimate phenome of any organism is modulated by regulated transcription of many genes. Characterization of genetic makeup is thus crucial for understanding the molecular basis of phenotypic diversity, evolution and response to intra- and extra-cellular stimuli. Chickpea is the world's third most important food legume grown in over 40 countries representing all the continents. Despite its importance in plant evolution, role in human nutrition and stress adaptation, very little ESTs and differential transcriptome data is available, let alone genotype-specific gene signatures. Present study focuses onFusariumwilt responsive gene expression in chickpea.

Results

We report 6272 gene sequences of immune-response pathway that would provide genotype-dependent spatial information on the presence and relative abundance of each gene. The sequence assembly led to the identification of aCaUnigene set of 2013 transcripts comprising of 973 contigs and 1040 singletons, two-third of which represent new chickpea genes hitherto undiscovered. We identified 209 gene families and 262 genotype-specific SNPs. Further, several novel transcription regulators were identified indicating their possible role in immune response. The transcriptomic analysis revealed 649 non-cannonical genes besides many unexpected candidates with known biochemical functions, which have never been associated with pathostress-responsive transcriptome.

Conclusion

Our study establishes a comprehensive catalogue of the immune-responsive root transcriptome with insight into their identity and function. The development, detailed analysis ofCaEST datasets and global gene expression by microarray provide new insight into the commonality and diversity of organ-specific immune-responsive transcript signatures and their regulated expression shaping the species specificity at genotype level. This is the first report on differential transcriptome of an unsequenced genome during vascular wilt.
Reversal of oncogene transformation and suppression of tumor growth by the novel IGF1R kinase inhibitor A-928605
Authors: Pappano William N , Jung Paul M , Meulbroek Jonathan A , Wang Yi-Chun , Hubbard Robert D , Zhang Qian , Grudzien Meagan M , Soni Niru B , Johnson Eric F , Sheppard George S , Donawho Cherrie , Buchanan Fritz G , Davidsen Steven K , Bell Randy L , Wang Jieyi
Published: September 2009

Background

The insulin-like growth factor (IGF) axis is an important signaling pathway in the growth and survival of many cell and tissue types. This pathway has also been implicated in many aspects of cancer progression from tumorigenesis to metastasis. The multiple roles of IGF signaling in cancer suggest that inhibition of the pathway might yield clinically effective therapeutics.

Methods

We describe A-928605, a novel pyrazolo [3,4-d]pyrimidine small molecule inhibitor of the receptor tyrosine kinases (IGF1R and IR) responsible for IGF signal transduction. This compound was first tested for its activity and selectivity via conventionalin vitrokinome profiling and cellular IGF1R autophosphorylation. Additionally, cellular selectivity and efficacy of A-928605 were analyzed in an IGF1R oncogene-addicted cell line by proliferation, signaling and microarray studies. Finally,in vivoefficacy of A-928605 was assessed in the oncogene-addicted cell line and in a neuroblastoma model as a single agent as well as in combination with clinically approved therapeutics targeting EGFR in models of pancreatic and non-small cell lung cancers.

Results

A-928605 is a selective IGF1R inhibitor that is able to abrogate activation of the pathway bothin vitroandin vivo. This novel compound dosed as a single agent is able to produce significant growth inhibition of neuroblastoma xenograftsin vivo. A-928605 is also able to provide additive effects when used in combination with clinically approved agents directed against EGFR in non-small cell lung and human pancreatic tumor models.

Conclusion

These results suggest that a selective IGF1R inhibitor such as A-928605 may provide a useful clinical therapeutic for IGF pathway affected tumors and warrants further investigation.
Meta-analysis of glioblastoma multiforme versus anaplastic astrocytoma identifies robust gene markers
Authors: Dreyfuss Jonathan M , Johnson Mark D , Park Peter J
Published: September 2009

Background

Anaplastic astrocytoma (AA) and its more aggressive counterpart, glioblastoma multiforme (GBM), are the most common intrinsic brain tumors in adults and are almost universally fatal. A deeper understanding of the molecular relationship of these tumor types is necessary to derive insights into the diagnosis, prognosis, and treatment of gliomas. Although genomewide profiling of expression levels with microarrays can be used to identify differentially expressed genes between these tumor types, comparative studies so far have resulted in gene lists that show little overlap.

Results

To achieve a more accurate and stable list of the differentially expressed genes and pathways between primary GBM and AA, we performed a meta-analysis using publicly available genome-scale mRNA data sets. There were four data sets with sufficiently large sample sizes of both GBMs and AAs, all of which coincidentally used human U133 platforms from Affymetrix, allowing for easier and more precise integration of data. After scoring genes and pathways within each data set, we combined the statistics across studies using the nonparametric rank sum method to identify the features that differentiate GBMs and AAs. We found >900 statistically significant probe sets after correction for multiple testing from the >22,000 tested. We also used the rank sum approach to select >20 significant Biocarta pathways after correction for multiple testing out of >175 pathways examined. The most significant pathway was the hypoxia-inducible factor (HIF) pathway. Our analysis suggests that many of the most statistically significant genes work together in aHIF1A/VEGF-regulated network to increase angiogenesis and invasion in GBM when compared to AA.

Conclusion

We have performed a meta-analysis of genome-scale mRNA expression data for 289 human malignant gliomas and have identified a list of >900 probe sets and >20 pathways that are significantly different between GBM and AA. These feature lists could be utilized to aid in diagnosis, prognosis, and grade reduction of high-grade gliomas and to identify genes that were not previously suspected of playing an important role in glioma biology. More generally, this approach suggests that combined analysis of existing data sets can reveal new insights and that the large amount of publicly available cancer data sets should be further utilized in a similar manner.
Innate immune response during Yersinia infection: critical modulation of cell death mechanisms through phagocyte activation
Authors: Bergsbaken Tessa , Cookson Brad T
Published: September 2009

Review of infected macrophages undergoing pyroptosis as a host-healthy alternative to apoptosis.

Yersinia pestis, the etiological agent of plague, is one of the most deadly pathogens on our planet. This organism shares important attributes with its ancestral progenitor, Yersinia pseudotuberculosis, including a 70-kb virulence plasmid, lymphotropism during growth in the mammalian host, and killing of host macrophages. Infections with both organisms are biphasic, where bacterial replication occurs initially with little inflammation, followed by phagocyte influx, inflammatory cytokine production, and tissue necrosis. During infection, plasmid-encoded attributes facilitate bacterial-induced macrophage death, which results from two distinct processes and corresponds to the inflammatory crescendo observed in vivo: Naïve cells die by apoptosis (noninflammatory), and later in infection, activated macrophages die by pyroptosis (inflammatory). The significance of this redirected cell death for the host is underscored by the importance of phagocyte activation for immunity to Yersinia and the protective role of pyroptosis during host responses to anthrax lethal toxin and infections with Francisella, Legionella, Pseudomonas, and Salmonella. The similarities of Y. pestis and Y. pseudotuberculosis, including conserved, plasmid-encoded functions inducing at least two distinct mechanisms of cell death, indicate that comparative studies are revealing about their critical pathogenic mechanism(s) and host innate immune responses during infection. Validation of this idea and evidence of similar interactions with the host immune system are provided by Y. pseudotuberculosis-priming, cross-protective immunity against Y. pestis. Despite these insights, additional studies indicate much remains to be understood concerning effective host responses against Yersinia, including chromosomally encoded attributes that also contribute to bacterial evasion and modulation of innate and adaptive immune responses.
Activity of Human Pregnancy Insulin-Like Growth Factor Binding Protein-3: Determination by Reconstituting Recombinant Complexes
Authors: Yan Xiaolang , Payet Louis D. , Baxter Robert C. , Firth Sue M.
Published: September 2009

During pregnancy, IGF binding protein-3 (IGFBP-3) is completely proteolyzed to fragments with low affinities for IGFs but appears to transport IGFs normally in high-molecular-mass complexes. We previously reported that synthetic isolated amino- and carboxyl-terminal domains of IGFBP-3 cooperate to bind IGFs, and we investigated whether this is the mechanism whereby proteolyzed IGFBP-3 fragments bind IGFs normally in pregnancy serum. Two fragments of IGFBP-3 have been isolated from pregnancy serum, one with the same N-terminal sequence as intact IGFBP-3 (GASSG) and the other with an N-terminal sequence 160KVDYE. Recombinant forms of these proteins, IGFBP-31-159 and IGFBP-3160-264, have been synthesized and characterized, demonstrating that although the fragments individually have greatly reduced affinity for IGF complex formation, when combined they cooperate to form complexes with IGF with or without the acid-labile subunit, inhibit IGF transport across endothelial cell monolayers and inhibit IGF-I-induced IGF type I receptor phosphorylation. It is proposed that proteolysis of IGFBP-3 into two discrete complementary fragments does not significantly increase IGF bioavailability, consistent with previous findings that proteolyzed IGFBP-3 in pregnancy serum is functionally normal and circulates as part of the IGF ternary complexes.
The Mammalian Target of Rapamycin as Novel Central Regulator of Puberty Onset via Modulation of Hypothalamic Kiss1 System
Authors: Roa J. , Garcia-Galiano D. , Varela L. , Sánchez-Garrido M. A. , Pineda R. , Castellano J. M. , Ruiz-Pino F. , Romero M. , Aguilar E. , López M. , Gaytan F. , Diéguez C. , Pinilla L. , Tena-Sempere M.
Published: September 2009

The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that operates as sensor of cellular energy status and effector for its coupling to cell growth and proliferation. At the hypothalamic arcuate nucleus, mTOR signaling has been recently proposed as transducer for leptin effects on energy homeostasis and food intake. However, whether central mTOR also participates in metabolic regulation of fertility remains unexplored. We provide herein evidence for the involvement of mTOR in the control of puberty onset and LH secretion, likely via modulation of hypothalamic expression of Kiss1. Acute activation of mTOR by l-leucine stimulated LH secretion in pubertal female rats, whereas chronic l-leucine infusion partially rescued the state of hypogonadotropism induced by food restriction. Conversely, blockade of central mTOR signaling by rapamycin caused inhibition of the gonadotropic axis at puberty, with significantly delayed vaginal opening, decreased LH and estradiol levels, and ovarian and uterine atrophy. Inactivation of mTOR also blunted the positive effects of leptin on puberty onset in food-restricted females. Yet the GnRH/LH system retained their ability to respond to ovariectomy and kisspeptin-10 after sustained blockade of mTOR, ruling out the possibility of unspecific disruption of GnRH function by rapamycin. Finally, mTOR inactivation evoked a significant decrease of Kiss1 expression at the hypothalamus, with dramatic suppression of Kiss1 mRNA levels at the arcuate nucleus. Altogether our results unveil the role of central mTOR signaling in the control of puberty onset and gonadotropin secretion, a phenomenon that involves the regulation of Kiss1 and may contribute to the functional coupling between energy balance and gonadal activation and function.
The zebrafish dystrophic mutantsoftymaintains muscle fibre viability despite basement membrane rupture and muscle detachment
Authors: Jacoby Arie S. , Busch-Nentwich Elisabeth , Bryson-Richardson Robert J. , Hall Thomas E. , Berger Joachim , Berger Silke , Sonntag Carmen , Sachs Caroline , Geisler Robert , Stemple Derek L. , Currie Peter D.
Published: September 2009

The skeletal muscle basement membrane fulfils several crucial functions during development and in the mature myotome and defects in its composition underlie certain forms of muscular dystrophy. A major component of this extracellular structure is the laminin polymer, which assembles into a resilient meshwork that protects the sarcolemma during contraction. Here we describe a zebrafish mutant, softy, which displays severe embryonic muscle degeneration as a result of initial basement membrane failure. The softy phenotype is caused by a mutation in the lamb2 gene,identifying laminin β2 as an essential component of this basement membrane. Uniquely, softy homozygotes are able to recover and survive to adulthood despite the loss of myofibre adhesion. We identify the formation of ectopic, stable basement membrane attachments as a novel means by which detached fibres are able to maintain viability. This demonstration of a muscular dystrophy model possessing innate fibre viability following muscle detachment suggests basement membrane augmentation as a therapeutic strategy to inhibit myofibre loss.
The cell adhesion molecules Echinoid and Friend of Echinoid coordinate cell adhesion and cell signaling to regulate the fidelity of ommatidial rotation in theDrosophilaeye
Authors: Fetting Jennifer L. , Spencer Susan A. , Wolff Tanya
Published: September 2009

Directed cellular movements are a universal feature of morphogenesis in multicellular organisms. Differential adhesion between the stationary and motile cells promotes these cellular movements to effect spatial patterning of cells. A prominent feature of Drosophila eye development is the 90° rotational movement of the multicellular ommatidial precursors within a matrix of stationary cells. We demonstrate that the cell adhesion molecules Echinoid (Ed) and Friend of Echinoid (Fred) act throughout ommatidial rotation to modulate the degree of ommatidial precursor movement. We propose that differential levels of Ed and Fred between stationary and rotating cells at the initiation of rotation create a permissive environment for cell movement,and that uniform levels in these two populations later contribute to stopping the movement. Based on genetic data, we propose that ed and fred impart a second, independent, `brake-like' contribution to this process via Egfr signaling. Ed and Fred are localized in largely distinct and dynamic patterns throughout rotation. However, ed and fredare required in only a subset of cells - photoreceptors R1, R7 and R6 - for normal rotation, cells that have only recently been linked to a role in planar cell polarity (PCP). This work also provides the first demonstration of a requirement for cone cells in the ommatidial rotation aspect of PCP. ed and fred also genetically interact with the PCP genes,but affect only the degree-of-rotation aspect of the PCP phenotype. Significantly, we demonstrate that at least one PCP protein, Stbm, is required in R7 to control the degree of ommatidial rotation.
Disruption of the pollen-expressedFERONIAhomologsANXUR1andANXUR2triggers pollen tube discharge
Authors: Boisson-Dernier Aurélien , Roy Sucharita , Kritsas Konstantinos , Grobei Monica A. , Jaciubek Miloslawa , Schroeder Julian I. , Grossniklaus Ueli
Published: September 2009

The precise delivery of male to female gametes during reproduction in eukaryotes requires complex signal exchanges and a flawless communication between male and female tissues. In angiosperms, molecular mechanisms have recently been revealed that are crucial for the dialog between male (pollen tube) and female gametophytes required for successful sperm delivery. When pollen tubes reach the female gametophyte, they arrest growth, burst and discharge their sperm cells. These processes are under the control of the female gametophyte via the receptor-like serine-threonine kinase (RLK) FERONIA(FER). However, the male signaling components that control the sperm delivery remain elusive. Here, we show that ANXUR1 and ANXUR2(ANX1, ANX2), which encode the closest homologs of the FER-RLK in Arabidopsis, are preferentially expressed in pollen. Moreover,ANX1-YFP and ANX2-YFP fusion proteins display polar localization to the plasma membrane at the tip of the pollen tube. Finally, genetic analyses demonstrate that ANX1 and ANX2 function redundantly to control the timing of pollen tube discharge as anx1 anx2 double-mutant pollen tubes cease their growth and burst in vitro and fail to reach the female gametophytes in vivo. We propose that ANX-RLKs constitutively inhibit pollen tube rupture and sperm discharge at the tip of growing pollen tubes to sustain their growth within maternal tissues until they reach the female gametophytes. Upon arrival, the female FER-dependent signaling cascade is activated to mediate pollen tube reception and fertilization, while male ANX-dependent signaling is deactivated, enabling the pollen tube to rupture and deliver its sperm cells to effect fertilization.
Hedgehog activation is required upstream of Wnt signalling to control neural progenitor proliferation
Authors: Alvarez-Medina Roberto , Le Dreau Gwenvael , Ros Marian , Martí Elisa
Published: September 2009

The canonical Wnt and sonic hedgehog (Shh) pathways have been independently linked to cell proliferation in a variety of tissues and systems. However,interaction of these signals in the control of cell cycle progression has not been studied. Here, we demonstrate that in the developing vertebrate nervous system these pathways genetically interact to control progression of the G1 phase of the cell cycle. By in vivo loss-of-function experiments, we demonstrate the absolute requirement of an upstream Shh activity for the regulation of Tcf3/4 expression. In the absence of Tcf3/4, the canonical Wnt pathway cannot activate target gene expression, including that of cyclin D1,and the cell cycle is necessarily arrested at G1. In addition to the control of G1 progression, Shh activity controls the G2 phase through the regulation of cyclin E, cyclin A and cyclin B expression, and this is achieved independently of Wnt. Thus, in neural progenitors, cell cycle progression is co-ordinately regulated by Wnt and Shh activities.
Scheduling for deadlock avoidance operation in robotic manufacturing cells
Authors: Yoon H J
Published: September 2009

This paper addresses a scheduling and control method for deadlock avoidance operation in robotic manufacturing cells with flexible job sequences. The proposed scheduling method generates an optimal or near-optimal schedule avoiding deadlock even when an unexpected event such as machine failure happens. The proposed deadlock-free scheduling approach consists of two components: deadlock manager, and dynamic scheduler. The deadlock manager builds and manages deadlock in a robotic manufacturing cell. The resources or machines in the robotic manufacturing cell are classified into two categories: potential deadlock set and deadlock-safe set. This paper presents an efficient method to obtain a minimal potential deadlock set using a genetic algorithm. Scheduling with deadlock avoidance policy is applied to the potential deadlock set, and scheduling only is applied to the deadlock-safe set. The dynamic scheduler generates a deadlock-free schedule using piecewise shifting operations in a real-time operation phase. The proposed scheduling approach is shown by simulation to be efficient in managing deadlock inherent to the robotic manufacturing cells.
Autonomous three-dimensional tracking for reconfigurable active-vision-based object recognition
Authors: de Ruiter H , Mackay M , Benhabib B
Published: September 2009

Recognition algorithms would significantly benefit from object images acquired from preferential view points, e.g. unobstructed frontal views or complementary views. Active-vision systems, which are dynamically reconfigurable in an online mode, have been suggested in the literature as effective solutions for achieving this objective, namely, relocating cameras to obtain optimal visibility for a given situation.

To obtain optimal visibility of an object of interest (OI), however, that OI's three-dimensional (3D) position and orientation (i.e. six degree-of-freedom pose) must be tracked in real time. Thus, this paper presents such an autonomous, real-time, six degree-of-freedom pose tracking system for a priori unknown objects. The proposed tracking method autonomously (a) selects the OI, (b) builds its approximate 3D model and uses this model to (c) track it in real time.

As will be shown in this paper, via experimental results, the output of the proposed modeller can be effectively used by an active-vision system to relocate its cameras for effective preferential image acquisition. In the examples included herein, it will be noted that object visibility data obtained via camera reconfiguration based on the authors' ‘approximate’ tracking method are comparable with those obtainable based on ‘perfect’ OI tracking.
Process value analysis for business process re-engineering
Authors: Borgianni Y , Cascini G , Rotini F
Published: September 2009

Two decades of studies about business process re-engineering have proposed several strategies for the reorganization of a production process aimed at costs saving and waste reduction. Nevertheless, there is still a substantial lack of suitable means to measure if and how much the production phases contribute to deliver value, i.e. satisfaction, to the end user. The present paper proposes a methodology aimed at supporting business process re-engineering activities by taking into account the impact each phase of a process has on the value perceived by the customers. The methodology swivels on process value analysis, that is performed through the evaluation of both the customer perceived benefits originated from the process phases, and the resources spent in the same phases. On the basis of customer satisfaction requirements, guidelines are defined in order to identify both process evolution strategies and resource reorganization activities allowing the market competitiveness of products and/or services that the process sells to be preserved and improved.

The methodology has been applied to a case study in the field of the Italian footwear industry in order to assess its efficiency.
Sequential metamodelling application to improve porthole die design
Authors: Pandey M K , Singh R K , Venkataramanaiah S , Tiwari M K
Published: September 2009

The conventional trial—error method and empirical approaches are time consuming for the design of complex shaped products like porthole dies. These methods are associated with higher production costs, lower efficiency, and design inaccuracies pertaining to ambiguity and uncertainty. Owing to these deficiencies, there is a need for a more reliable and better design approach. In this article, a Kriging metamodel and differential evolution-based random simulation design methodology is proposed in order to reduce the cognitive load on the designer. The proposed methodology helps in selecting the set of parameters to be used to perform a simulation such that an improved design is delivered with reduced time and effort. The combination of the input parameters and their probable effect on the final design is evaluated and provided to the designer beforehand. This information, when juxtaposed with the designer's knowledge, gives greater opportunities to produce an optimal design. The sequential sampling strategy is used to select this set of parameters. It depends on the confidence value: a function of the design variables and the desired performance parameter. A Kriging metamodel is employed for modelling a random simulation of porthole extrusion with different influencing parameters. It converts the black-box region (no information zone in the design space) into a grey region (design space with some available information). Differential evolution (an evolutionary algorithm) is used to search for the black-box region carrying the least information in the design space. Three-dimensional extrusion of aluminium is considered in this article for designing a porthole die. The effect of variation of the design parameters is described, sampling points are generated, and the effective set of parameters are evaluated. The results obtained with the proposed sequential methodology are comparable with the simulation results presented in the literature for porthole extrusion.
Study on the manufacture of a thermal management mould with three different materials using a direct metal tooling rapid tooling process
Authors: Ahn D-G , Kim H-W
Published: September 2009

The objective of this paper is to manufacture a thermal management mould with three different materials and conformal cooling channels using a laser-aided direct metal tooling process to obtain both rapid and uniform cooling characteristics. The geometry of the thermal management mould is decomposed into three parts, including a moulding part consisting of P21 injection tool steel, a mid-layer consisting of Monel 400 material, and a base part consisting of Ampcoloy 940 material, according to the functionality of each part. The base part is designed as a heat sink and the midlayer is adopted to reduce the thermal stress in the joined regions. In this paper, the features of the design and a rapid tooling process for the thermal management mould as well as the characteristics of the mould are discussed. Several injection-moulding experiments are performed to investigate the practical applicability of the fabricated mould and the effects of the cooling time on the quality of the moulded product. The results of the experiments show that the cooling time of the thermal management mould can be shortened to 3 s. Through comparison of the product from the thermal management mould with that of a previously designed mould, it is shown that the designed mould can improve both the cycle time and the quality of the product.
Grey-data envelopment analysis approach for solving the multi-response problem in the Taguchi method
Authors: Al-Refaie A
Published: September 2009

In practice, a product or process possesses multiple quality responses of main interest. The Taguchi method has been found only efficient for optimizing a single quality response. This research, therefore, proposes an approach for solving the multi-response problem in the Taguchi method by integrating the grey relational analysis and super efficiency technique in data envelopment analysis (DEA). The quadratic loss is calculated for each response. The grey relational analysis is used to normalize the quality losses and to obtain grey relational coefficients. Each experiment in the Taguchi's orthogonal array (OA) is then treated as a decision-making unit (DMU) with grey relational coefficients set as the inputs for all DMUs. The super efficiency model is then adopted to estimate the efficiency of each DMU. Finally, the level efficiency, i.e. the average of efficiencies for DMUs at each factor level, is calculated and used to determine the optimal factor levels for the multi-response problem. Four real case studies, which were investigated previously in literature, are provided for illustration; in all of which the proposed approach provides lowest total quality loss. In conclusion, the grey-DEA approach proposed in this research shall provide great assistance to practitioners in solving the multi-response problem in a wide range of manufacturing applications on the Taguchi method.
Effect of fluid application conditions on grinding behaviour
Authors: Parthasarathy A , Malkin S
Published: September 2009

Applying copious amounts of fluid to ensure adequate lubrication and cooling during grinding creates environmental and safety hazards. The present investigation was undertaken to explore the prospects for reducing the amount of applied fluid without having a deleterious effect on grinding performance. Straight surface grinding experiments were conducted to determine the effect of fluid flowrate and nozzle set-up conditions on the grinding behaviour for both up grinding and down grinding. A high-speed camera was used to observe fluid access to the grinding zone. For up grinding at low flowrates, lack of fluid reaching the wheel and workpiece caused an increase in the forces and surface roughness. The effect of a low flowrate was much less pronounced for down grinding due to the presence of residual fluid, which had collected on the workpiece top surface. A simple fluid mechanics model was developed to determine the flowrate and nozzle set-up condition required for the fluid to reach the wheel and the workpiece.
High strain-rate bulge forming of sheet metals using a solid bulging medium
Authors: Ramezani M , Ripin Z M , Ahmad R , Akil H M , Damghani-Nouri M
Published: September 2009

The biaxial bulge-forming of sheet metals is a standard test to evaluate the formability and mechanical behaviour of materials. A new dynamic bulge-testing method is simulated and analysed in this study that can be performed on a conventional split Hopkinson pressure bar (SHPB) system. The aim of this work is to develop a numerical and theoretical technique for the analysis of materials and structures, which are dynamically loaded and subjected to the different levels of strain rates. The commercial finite element code ABAQUS/Explicit has been selected as the numerical test bed for the simulation of the dynamic bulging test. In the new bulge-forming technique, flexible rubber is used as the pressure-carrying medium instead of hydraulic fluid. The theoretical analysis is based on conventional hydraulic bulge test principles and SHPB relations. To verify the accuracy of the developed technique, analytical and finite element methods are compared and show good correlation with each other.
Mechanical, micro-, and macrostructural analysis of AA7075–T6 fabricated by friction stir butt welding with different rotational speeds and tool pin profiles
Authors: Bahemmat P , Besharati M K , Haghpanahi M , Rahbari A , Salekrostam R
Published: September 2009

Friction stir welding (FSW) is a solid state welding process for joining aluminium alloys, has been employed in different industries, and is a new and promising welding process that can produce low-cost and high-quality joints of heat-treatable aluminium alloys because this process uses a non-consumable tool to generate frictional heat in the abutting surfaces and can eliminate some welding defects such as crack and porosity. The various parameters such as rotational speed, welding speed, axial force, and attack angle play vital roles in the FSW process in order to analyse the weld quality. In this research, the impact of processing parameters such as different rotational speed and tool pin profiles on the mechanical, micro-, and macrostructural properties during the FSW process involving the butt jointing of AA7075 T6 is investigated. It is important to note that four-flute and taper threaded pin profiles are utilized and the mechanical characteristics are determined by comparing the ultimate strength, percentage of elongation, and microhardness profiles for different rotational speeds and tool pin profiles.
Construction of a dynamic cutting force model for oblique cutting
Authors: Lin S-Y , Chen C-K
Published: September 2009

This work presents a dynamic cutting force model of oblique cutting by considering the oblique cutting operation, the relationship among cutting angles, the effects of wave removal and wave cutting on the fluctuation of shear angle, the variation of the instantaneous uncut chip thickness, and the variation of the chip flow angle. An equivalent orthogonal cutting plane that contains both the cutting velocity and the chip flow velocity vectors is defined for the oblique cutting operation whose cutting behaviour may be treated simply as a modified plane strain problem. The dynamic cutting force model is constructed initially from the fluctuation of the shear angle, in which the critical width of cut in the cutting system is estimated in terms of the consequent damping energy. The predicted critical width of cut is consistent with the results of the oblique cutting experiments.
Rapid coupling optimization method for a tube hydroforming process
Authors: Chebbah M S , Naceur H , Hecini M
Published: September 2009

This paper deals with the optimization of tube hydroforming parameters in order to reduce defects that may occur at the end of the forming process such as necking and wrinkling. A specific methodology is proposed based on the coupling between an inverse finite element model for the rapid simulation of the tube hydroforming process, and a response surface method based on diffuse approximation. The response surfaces are built using moving least-squares approximations and constructed within a moving region of interest, which moves across a predefined discrete grid of authorized experimental designs. An application of hydroforming of a bulge from aluminium alloy 6061-T6 tubing has been utilized to validate the methodology. The final design is validated with ABAQUS Explicit Dynamic commercial code.
Direct fabrication of an integral ceramic mould by stereolithography
Authors: Zhou W Z , Li D , Chen Z W , Chen S
Published: September 2009

The purpose of this study was to develop a novel direct fabrication of an integral ceramic mould by stereolithography (SL). An aqueous ceramic suspension suitable for SL was prepared and its photosensitive parameters were measured to optimize its formula. For a thin-walled aerospace component, the whole process of designing, building, drying, binder removing, and sintering of an integral ceramic casting mould was carried out. Finally, to verify whether this casting mould could meet the requirements of the casting process, an aluminium casting part was cast with the anti-gravity casting method. Compared with traditional fabrication of a multi-layer ceramic shell for investment casting, this novel direct fabrication of an integral ceramic casting mould would meet the needs of not only research but also other small batch products with lower costs and shorter lead time.
Feature recognition technology for aircraft structural parts based on a holistic attribute adjacency graph
Authors: Li Y G , Ding Y F , Mou W P , Guo H
Published: September 2009

A feature-recognition method based on an holistic attribute adjacency graph is put forward to solve the problems that complex features of aircraft structural parts find difficult to recognize by traditional feature-recognition methods. Extending the attribute's information and adding node types based on a traditional attribute adjacency graph, the method not only represents freeform surfaces and edge features, but also describes geometric information of topology elements precisely and completely. Combining feature recognition based on a graph with that based on hint, the method can deal with feature recognition of freeform surfaces, edge features, intersecting features, and convex features by a uniform algorithm, which virtually performs hint search, hint extension, and feature combination with hints of seed faces. According to the research, an original system has been used in a numerically controlled machining process of integer frame parts in certain large aviation enterprises.
Novel combined standard hydromechanical sheet hydroforming process
Authors: Hosseinzade M , Mostajeran H , Bakhshi-Jooybari M , Gorji A H , Nourouzi S , Hosseinipour S J
Published: September 2009

Sheet hydroforming techniques are widely used in industries for the production of different components with specific characteristics. Despite the advantages of the conventional sheet hydroforming techniques, they have their own limitations. In this paper, to increase the application and to overcome the limitations of conventional deep drawing, a new sheet hydroforming technique is proposed that is a combination of the standard and the hydromechanical sheet hydroforming processes. The proposed method has the advantages of conventional processes but eliminates their limitations. This technique is used in forming a cylindrical cup and a complex industrial part. After applying the appropriate pressure path, the products are formed successfully in one stage without any defects. It is also shown that the required forming pressure in the proposed process is low compared with other sheet hydroforming processes. It is demonstrated that because of the low internal pressure required in the present method, pre-bulging does not have any significant effect on the thickness distribution of the product. It is concluded that in this process increasing the friction coefficient between punch and blank can reduce the sheet thinning.
Morphological signal processing and computational intelligence for engineering system prognostics
Authors: Samanta B , Nataraj C
Published: September 2009

A computational intelligence (CI)-based approach is presented for prognostics of machine conditions using morphological signal processing (MSP). The machine vibration signals are processed using MSP to extract a novel entropy-based health index (HI) characterizing the signal shape-size complexity for system prognostics. The progression of HI is predicted using CI techniques, namely, recursive neural network (RNN), adaptive neuro-fuzzy inference system (ANFIS), and support vector regression (SVR). Both single- and multi-step ahead predictions were evaluated through benchmark datasets of non-linear, non-stationary, and chaotic time series solutions of Mackey-Glass and Lorenz equations. The prognostic effectiveness of the CI techniques was illustrated using a vibration dataset of a helicopter drive-train system gearbox. For each CI predictor, both training datasets gave almost similar prediction performance. In training, the performance of ANFIS was the best, followed by SVR and RNN. In test, the best performance was obtained with SVR for both single- and multi-step ahead predictions. The results are helpful in understanding the relationship between the system conditions, the corresponding indicating feature, the level of degradation, and their progression.