bluuebunny/crossref_metadata_2025 huggingface dataset:
Usefulness and limitations of dK random graph models to predict interactions and functional homogeneity in biological networks under a pseudo-likelihood parameter estimation approach
Authors: Wang Wenhui , Nunez-Iglesias Juan , Luan Yihui , Sun Fengzhu
Published: September 2009

Background

Many aspects of biological functions can be modeled by biological networks, such as protein interaction networks, metabolic networks, and gene coexpression networks. Studying the statistical properties of these networks in turn allows us to infer biological function. Complex statistical network models can potentially more accurately describe the networks, but it is not clear whether such complex models are better suited to find biologically meaningful subnetworks.

Results

Recent studies have shown that the degree distribution of the nodes is not an adequate statistic in many molecular networks. We sought to extend this statistic with 2nd and 3rd order degree correlations and developed a pseudo-likelihood approach to estimate the parameters. The approach was used to analyze the MIPS and BIOGRID yeast protein interaction networks, and two yeast coexpression networks. We showed that 2nd order degree correlation information gave better predictions of gene interactions in both protein interaction and gene coexpression networks. However, in the biologically important task of predicting functionally homogeneous modules, degree correlation information performs marginally better in the case of the MIPS and BIOGRID protein interaction networks, but worse in the case of gene coexpression networks.

Conclusion

Our use of dK models showed that incorporation of degree correlations could increase predictive power in some contexts, albeit sometimes marginally, but, in all contexts, the use of third-order degree correlations decreased accuracy. However, it is possible that other parameter estimation methods, such as maximum likelihood, will show the usefulness of incorporating 2nd and 3rd degree correlations in predicting functionally homogeneous modules.
Arginine methyltransferase CARM1/PRMT4 regulates endochondral ossification
Authors: Ito Tatsuo , Yadav Neelu , Lee Jaeho , Furumatsu Takayuki , Yamashita Satoshi , Yoshida Kenji , Taniguchi Noboru , Hashimoto Megumi , Tsuchiya Megumi , Ozaki Toshifumi , Lotz Martin , Bedford Mark T , Asahara Hiroshi
Published: September 2009

Background

Chondrogenesis and subsequent endochondral ossification are processes tightly regulated by the transcription factor Sox9 (SRY-related high mobility group-Box gene 9), but molecular mechanisms underlying this activity remain unclear. Here we report that coactivator-associated arginine methyltransferase 1 (CARM1) regulates chondrocyte proliferation via arginine methylation of Sox9.

Results

CARM1-null mice display delayed endochondral ossification and decreased chondrocyte proliferation. Conversely, cartilage development of CARM1 transgenic mice was accelerated. CARM1 specifically methylates Sox9 at its HMG domain in vivo and in vitro. Arg-methylation of Sox9 by CARM1 disrupts interaction of Sox9 with beta-catenin, regulating Cyclin D1 expression and cell cycle progression of chondrocytes.

Conclusion

These results establish a role for CARM1 as an important regulator of chondrocyte proliferation during embryogenesis.
Differential transcriptional modulation of duplicated fatty acid-binding protein genes by dietary fatty acids in zebrafish (Danio rerio): evidence for subfunctionalization or neofunctionalization of duplicated genes
Authors: Karanth Santhosh , Lall Santosh P , Denovan-Wright Eileen M , Wright Jonathan M
Published: September 2009

Background

In the Duplication-Degeneration-Complementation (DDC) model, subfunctionalization and neofunctionalization have been proposed as important processes driving the retention of duplicated genes in the genome. These processes are thought to occur by gain or loss of regulatory elements in the promoters of duplicated genes. We tested the DDC model by determining the transcriptional induction of fatty acid-binding proteins (Fabps) genes by dietary fatty acids (FAs) in zebrafish. We chose zebrafish for this study for two reasons: extensive bioinformatics resources are available for zebrafish at zfin.org and zebrafish contains many duplicated genes owing to a whole genome duplication event that occurred early in the ray-finned fish lineage approximately 230-400 million years ago. Adult zebrafish were fed diets containing either fish oil (12% lipid, rich in highly unsaturated fatty acid), sunflower oil (12% lipid, rich in linoleic acid), linseed oil (12% lipid, rich in linolenic acid), or low fat (4% lipid, low fat diet) for 10 weeks. FA profiles and the steady-state levels offabpmRNA and heterogeneous nuclear RNA in intestine, liver, muscle and brain of zebrafish were determined.

Result

FA profiles assayed by gas chromatography differed in the intestine, brain, muscle and liver depending on diet. The steady-state level of mRNA for three sets of duplicated genes,fabp1a/fabp1b.1/fabp1b.2,fabp7a/fabp7b, andfabp11a/fabp11b, was determined by reverse transcription, quantitative polymerase chain reaction (RT-qPCR). In brain, the steady-state level offabp7bmRNAs was induced in fish fed the linoleic acid-rich diet; in intestine, the transcript level offabp1b.1andfabp7bwere elevated in fish fed the linolenic acid-rich diet; in liver, the level offabp7amRNAs was elevated in fish fed the low fat diet; and in muscle, the level offabp7aandfabp11amRNAs were elevated in fish fed the linolenic acid-rich or the low fat diets. In all cases, induction of the steady-state level offabpmRNAs by dietary FAs correlated with induced levels of hnRNA for a givenfabpgene. As such, up-regulation of the steady-state level offabpmRNAs by FAs occurred at the level of initiation of transcription. None of the sister duplicates of thesefabpgenes exhibited an increase in their steady-state transcript levels in a specific tissue following feeding zebrafish any of the four experimental diets.

Conclusion

Differential induction of only one of the sister pair of duplicatedfabpgenes by FAs provides evidence to support the DDC model for retention of duplicated genes in the zebrafish genome by either subfunctionalization or neofunctionalization.
Transcriptional response of the model planctomycete Rhodopirellula baltica SH1T to changing environmental conditions
Authors: Wecker Patricia , Klockow Christine , Ellrott Andreas , Quast Christian , Langhammer Philipp , Harder Jens , Glöckner Frank Oliver
Published: September 2009

Background

The marine model organismRhodopirellula balticaSH1Twas the firstPlanctomyceteto have its genome completely sequenced. The genome analysis predicted a complex lifestyle and a variety of genetic opportunities to adapt to the marine environment. Its adaptation to environmental stressors was studied by transcriptional profiling using a whole genome microarray.

Results

Stress responses to salinity and temperature shifts were monitored in time series experiments. Chemostat cultures grown in mineral medium at 28°C were compared to cultures that were shifted to either elevated (37°C) or reduced (6°C) temperatures as well as high salinity (59.5‰) and observed over 300 min. Heat shock showed the induction of several known chaperone genes. Cold shock altered the expression of genes in lipid metabolism and stress proteins. High salinity resulted in the modulation of genes coding for compatible solutes, ion transporters and morphology. In summary, over 3000 of the 7325 genes were affected by temperature and/or salinity changes.

Conclusion

Transcriptional profiling confirmed thatR. balticais highly responsive to its environment. The distinct responses identified here have provided new insights into the complex adaptation machinery of this environmentally relevant marine bacterium. Our transcriptome study and previous proteome data suggest a set of genes of unknown functions that are most probably involved in the global stress response. This work lays the foundation for further bioinformatic and genetic studies which will lead to a comprehensive understanding of the biology of a marinePlanctomycete.
Transcriptome and proteome analyses of adaptive responses to methyl methanesulfonate in Escherichia coli K-12 and ada mutant strains
Authors: Baek Jong Hwan , Han Mee-Jung , Lee Sang Yup , Yoo Jong-Shin
Published: September 2009

Background

The Ada-dependent adaptive response system inEscherichia coliis important for increasing resistance to alkylation damage. However, the global transcriptional and translational changes during this response have not been reported. Here we present time-dependent global gene and protein expression profiles following treatment with methyl methanesulfonate (MMS) inE. coliW3110 and itsadamutant strains.

Results

Transcriptome profiling showed that 1138 and 2177 genes were differentially expressed in response to MMS treatment in the wild-type and mutant strains, respectively. A total of 81 protein spots representing 76 nonredundant proteins differentially expressed were identified using 2-DE and LC-MS/MS. In the wild-type strain, many genes were differentially expressed upon long-exposure to MMS, due to both adaptive responses and stationary phase responses. In theadamutant strain, the genes involved in DNA replication, recombination, modification and repair were up-regulated 0.5 h after MMS treatment, indicating its connection to the SOS and other DNA repair systems. Interestingly, expression of the genes involved in flagellar biosynthesis, chemotaxis, and two-component regulatory systems related to drug or antibiotic resistance, was found to be controlled by Ada.

Conclusion

These results show in detail the regulatory components and pathways controlling adaptive response and how the related genes including the Ada regulon are expressed with this response.
Neuroprotective effects of compounds with antioxidant and anti-inflammatory properties in a Drosophila model of Parkinson's disease
Authors: Faust Katharina , Gehrke Stephan , Yang Yufeng , Yang Lichuan , Beal M Flint , Lu Bingwei
Published: September 2009

Background

Parkinson's disease (PD) is the most common movement disorder. Extrapyramidal motor symptoms stem from the degeneration of the dopaminergic pathways in patient brain. Current treatments for PD are symptomatic, alleviating disease symptoms without reversing or retarding disease progression. Although the cause of PD remains unknown, several pathogenic factors have been identified, which cause dopaminergic neuron (DN) death in the substantia nigra (SN). These include oxidative stress, mitochondrial dysfunction, inflammation and excitotoxicity. Manipulation of these factors may allow the development of disease-modifying treatment strategies to slow neuronal death. Inhibition of DJ-1A, theDrosophilahomologue of the familial PD gene DJ-1, leads to oxidative stress, mitochondrial dysfunction, and DN loss, making fly DJ-1A model an excellentin vivosystem to test for compounds with therapeutic potential.

Results

In the present study, aDrosophilaDJ-1A model of PD was used to test potential neuroprotective drugs. The drugs applied are the Chinese herb celastrol, the antibiotic minocycline, the bioenergetic amine coenzyme Q10 (coQ10), and the glutamate antagonist 2,3-dihydroxy-6-nitro-7-sulphamoylbenzo[f]-quinoxaline (NBQX). All of these drugs target pathogenic processes implicated in PD, thus constitute mechanism-based treatment strategies. We show that celastrol and minocycline, both having antioxidant and anti-inflammatory properties, confer potent dopaminergic neuroprotection inDrosophilaDJ-1A model, while coQ10 shows no protective effect. NBQX exerts differential effects on cell survival and brain dopamine content: it protects against DN loss but fails to restore brain dopamine level.

Conclusion

The present study further validatesDrosophilaas a valuable model for preclinical testing of drugs with therapeutic potential for neurodegenerative diseases. The lower cost and amenability to high throughput testing makeDrosophilaPD models effectivein vivotools for screening novel therapeutic compounds. If our findings can be further validated in mammalian PD models, they would implicate drugs combining antioxidant and anti-inflammatory properties as strong therapeutic candidates for mechanism-based PD treatment.
A MANBAmutation resulting in residual beta-mannosidase activity associated with severe leukoencephalopathy: a possible pseudodeficiency variant
Authors: Sabourdy Frédérique , Labauge Pierre , Stensland Hilde Monica Frostad Riise , Nieto Michèle , Garcés Violeta Latorre , Renard Dimitri , Castelnovo Giovanni , de Champfleur Nicolas , Levade Thierry
Published: September 2009

Background

β-Mannosidosis (OMIM 248510) is a rare inborn lysosomal storage disorder caused by the deficient activity of β-mannosidase, an enzyme encoded by a single gene (MANBA) located on chromosome 4q22-25. To date, only 20 cases of this autosomal recessive disorder have been described and 14 differentMANBAmutations were incriminated in the disease. These are all null mutations or missense mutations that abolish β-mannosidase activity. In this study, we characterized the molecular defect of a new case of β-mannosidosis, presenting with a severe neurological disorder.

Methods

Genomic DNA was isolated from peripheral blood leukocytes of the patient to allowMANBAsequencing. The identified mutation was engineered by site-directed mutagenesis and the mutant protein was expressed through transient transfection in HEK293T cells. The β-mannosidase expression and activity were respectively assessed by Western blot and fluorometric assay in both leukocytes and HEK293T cells.

Results

A missense disease-associated mutation, c.1922G>A (p.Arg641His), was identified for which the patient was homozygous. In contrast to previously described missense mutations, this substitution does not totally abrogate the enzyme activity but led to a residual activity of about 7% in the patient's leukocytes, 11% in lymphoblasts and 14% in plasma. Expression studies in transfected cells also resulted in 7% residual activity.

Conclusion

Correlations between MANBA mutations, residual activity of β-mannosidase and the severity of the ensuing neurological disorder are discussed. Whether the c.1922G>A mutation is responsible for a yet undescribed pseudodeficiency of β-mannosidase is also discussed.
RNOP-09: Pegylated liposomal doxorubicine and prolonged temozolomide in addition to radiotherapy in newly diagnosed glioblastoma - a phase II study
Authors: Beier Christoph P , Schmid Christina , Gorlia Thierry , Kleinletzenberger Christine , Beier Dagmar , Grauer Oliver , Steinbrecher Andreas , Hirschmann Birgit , Brawanski Alexander , Dietmaier Christopher , Jauch-Worley Tanja , Kölbl Oliver , Pietsch Torsten , Proescholdt Martin , Rümmele Petra , Muigg Armin , Stockhammer Günther , Hegi Monika , Bogdahn Ulrich , Hau Peter
Published: September 2009

Background

Although Temozolomide is effective against glioblastoma, the prognosis remains dismal and new regimens with synergistic activity are sought for.

Methods

In this phase-I/II trial, pegylated liposomal doxorubicin (Caelyx™, PEG-Dox) and prolonged administration of Temozolomide in addition to radiotherapy was investigated in 63 patients with newly diagnosed glioblastoma. In phase-I, PEG-Dox was administered in a 3-by-3 dose-escalation regimen. In phase-II, 20 mg/m2 PEG-Dox was given once prior to radiotherapy and on days 1 and 15 of each 28-day cycle starting 4 weeks after radiotherapy. Temozolomide was given in a dose of 75 mg/m2 daily during radiotherapy (60 Gy) and 150-200 mg/m2 on days 1-5 of each 28-day cycle for 12 cycles or until disease progression.

Results

The toxicity of the combination of PEG-Dox, prolonged administration of Temozolomide, and radiotherapy was tolerable. The progression free survival after 12 months (PFS-12) was 30.2%, the median overall survival was 17.6 months in all patients including the ones from Phase-I. None of the endpoints differed significantly from the EORTC26981/NCIC-CE.3 data in a post-hoc statistical comparison.

Conclusion

Together, the investigated combination is tolerable and feasible. Neither the addition of PEG-Dox nor the prolonged administration of Temozolomide resulted in a meaningful improvement of the patient's outcome as compared to the EORTC26981/NCIC-CE.3 data

Trial registration

clinicaltrials.gov NCT00944801.
A protein-based set of reference markers for liver tissues and hepatocellular carcinoma
Authors: Sun Stella , Yi Xin , Poon Ronnie TP , Yeung Chun , Day Philip JR , Luk John M
Published: September 2009

Background

During the last decade, investigations have focused on revealing genes or proteins that are involved in HCC carcinogenesis using either genetic or proteomic techniques. However, these studies are overshadowed by a lack of good internal reference standards. The need to identify "housekeeping" markers, whose expression is stable in various experimental and clinical conditions, is therefore of the utmost clinical relevance in quantitative studies. This is the first study employed 2-DE analysis to screen for potential reference markers and aims to correlate the abundance of these proteins with their level of transcript expression.

Methods

A Chinese cohort of 224 liver tissues samples (105 cancerous, 103 non-tumourous cirrhotic, and 16 normal) was profiled using 2-DE analysis. Expression of the potential reference markers was confirmed by western blot, immunohistochemistry and real-time quantitative PCR. geNorm algorithm was employed for gene stability measure of the identified reference markers.

Results

The expression levels of three protein markers beta-actin (ACTB), heat shock protein 60 (HSP60), and protein disulphide isomerase (PDI) were found to be stable using p-values (p > 0.99) as a ranking tool in all 224 human liver tissues examined by 2-DE analysis. Of high importance, ACTB and HSP 60 were successfully validated at both protein and mRNA levels in human hepatic tissues by western blot, immunohistochemistry and real-time quantitative PCR. In addition, no significant correlation of these markers with any clinicopathological features of HCC and cirrhosis was found. Gene stability measure of these two markers with other conventionally applied housekeeping genes was assessed by the geNorm algorithm, which ranked ACTB and HSP60 as the most stable genes among this cohort of clinical samples.

Conclusion

Our findings identified 2 reference markers that exhibited stable expression across human liver tissues with different conditions thus should be regarded as reliable reference moieties for normalisation of gene and protein expression in clinical research employing human hepatic tissues.
Loss of Programmed cell death 4 (Pdcd4) associates with the progression of ovarian cancer
Authors: Wei Na , Liu Stephanie S , Leung Thomas HY , Tam Kar F , Liao Xiao Y , Cheung Annie NY , Chan Karen KL , Ngan Hextan YS
Published: September 2009

Background

Programmed cell death 4 (Pdcd4) is a novel tumour suppressor and originally identified as a neoplastic transformation inhibitor. The aim of this study was to investigate the expression, prognostic significance and potential function of Pdcd4 in ovarian cancer.

Results

The expression of Pdcd4 was examined in 30 normal ovarian tissues, 16 borderline and 93 malignant ovarian tissues. A continuous down regulation of Pdcd4 expression in the sequence of normal, borderline and malignant tissues was observed. The expressions of Pdcd4 in both ovarian borderline tissues and carcinomas were significantly lower than the expression in normal ovarian tissues (p < 0.001). Furthermore, patients with lower Pdcd4 expressions were found to have shorter disease-free survival (p = 0.037). The expression of Pdcd4 was also assessed by immunohistochemical analysis in 13 ovarian normal tissues and 44 carcinomas. Different subcellular localization of Pdcd4 was observed in normal compared to malignant cells. Predominant nuclear localization of Pdcd4 was found in normal ovarian tissues while ovarian carcinomas showed mainly cytoplasmic localization of Pdcd4.

Conclusion

Our study demonstrated that the loss of Pdcd4 was a common abnormality at molecular level in ovarian cancer and it might be a potential prognostic factor in ovarian cancer patients.
Modulation Peroxisome Proliferators Activated Receptor alpha (PPAR α) and Acyl Coenzyme A: Cholesterol Acyltransferase1 (ACAT1) Gene expression by Fatty Acids in Foam cell
Authors: Zavvar Reza Javad , Doosti Mahmoud , salehipour Masoud , PackneJad Malehieh , Mojarrad Majed , Heidari Mansour , Emamian Effat S
Published: September 2009

Background

One of the most important factors in the initiation and progression of atherosclerosis is the default in macrophage cholesterol homeostasis. Many genes and transcription factors such as Peroxisome Proliferators Activated Receptors (PPARs) and Acyl Coenzyme A: Cholesterol Acyltransferase1 (ACAT1) are involved in cholesterol homeostasis. Fatty Acids are important ligands of PPARα and the concentration of them can effect expression of ACAT1. So this study designed to clarified on the role of these genes and fatty acids on the lipid metabolism in foam cells.

Methods

This study examined effects of c9, t11-Conjugated Linoleic Acid(c9, t11-CLA), Alpha Linolenic Acid (LA), Eicosapentaenoic Acid (EPA) on the PPARα and ACAT1 genes expression by using Real time PCR and cholesterol homeostasis in THP-1 macrophages derived foam cells.

Results

Incubation of c9, t11-CLA, LA cause a significant reduction in intracellular Total Cholesterol, Free Cholesterol, cellular and Estrified Cholesterol concentrations (P ≤ 0.05). CLA and LA had no significant effect on the mRNA levels of ACAT1, but EPA increased ACAT1 mRNA expression (P = 0.003). Treatment with EPA increased PPARα mRNA levels (P ≤ 0.001), although CLA, LA had no significant effect on PPARα mRNA expression.

Conclusion

In conclusion, it seems that different fatty acids have different effects on gene expression and lipid metabolism and for complete conception study of the genes involved in lipid metabolism in foam cell all at once maybe is benefit.
Light-dependent roles of the G-protein α subunit GNA1 of Hypocrea jecorina (anamorph Trichoderma reesei)
Authors: Seibel Christian , Gremel Gabriela , do Nascimento Silva Roberto , Schuster André , Kubicek Christian P , Schmoll Monika
Published: September 2009

Background

The filamentous ascomycete Hypocrea jecorina (anamorph Trichoderma reesei) is primarily known for its efficient enzymatic machinery that it utilizes to decompose cellulosic substrates. Nevertheless, the nature and transmission of the signals initiating and modulating this machinery are largely unknown. Heterotrimeric G-protein signaling represents one of the best studied signal transduction pathways in fungi.

Results

Analysis of the regulatory targets of the G-protein α subunit GNA1 in H. jecorina revealed a carbon source and light-dependent role in signal transduction. Deletion of gna1 led to significantly decreased biomass formation in darkness in submersed culture but had only minor effects on morphology and hyphal apical extension rates on solid medium. Cellulase gene transcription was abolished in Δgna1 on cellulose in light and enhanced in darkness. However, analysis of strains expressing a constitutively activated GNA1 revealed that GNA1 does not transmit the essential inducing signal. Instead, it relates a modulating signal with light-dependent significance, since induction still required the presence of an inducer. We show that regulation of transcription and activity of GNA1 involves a carbon source-dependent feedback cycle. Additionally we found a function of GNA1 in hydrophobin regulation as well as effects on conidiation and tolerance of osmotic and oxidative stress.

Conclusion

We conclude that GNA1 transmits a signal the physiological relevance of which is dependent on both the carbon source as well as the light status. The widespread consequences of mutations in GNA1 indicate a broad function of this Gα subunit in appropriation of intracellular resources to environmental (especially nutritional) conditions.
Large-scale analysis of Arabidopsis transcription reveals a basal co-regulation network
Authors: Atias Osnat , Chor Benny , Chamovitz Daniel A
Published: September 2009

Background

Analyses of gene expression data from microarray experiments has become a central tool for identifying co-regulated, functional gene modules. A crucial aspect of such analysis is the integration of data from different experiments and different laboratories. How to weigh the contribution of different experiments is an important point influencing the final outcomes. We have developed a novel method for this integration, and applied it to genome-wide data from multiple Arabidopsis microarray experiments performed under a variety of experimental conditions. The goal of this study is to identify functional globally co-regulated gene modules in the Arabidopsis genome.

Results

Following the analysis of 21,000 Arabidopsis genes in 43 datasets and about 2 × 108gene pairs, we identified a globally co-expressed gene network. We found clusters of globally co-expressed Arabidopsis genes that are enriched for known Gene Ontology annotations. Two types of modules were identified in the regulatory network that differed in their sensitivity to the node-scoring parameter; we further showed these two pertain to general and specialized modules. Some of these modules were further investigated using theGenevestigatorcompendium of microarray experiments. Analyses of smaller subsets of data lead to the identification of condition-specific modules.

Conclusion

Our method for identification of gene clusters allows the integration of diverse microarray experiments from many sources. The analysis reveals that part of theArabidopsistranscriptome is globally co-expressed, and can be further divided into known as well as novel functional gene modules. Our methodology is general enough to apply to any set of microarray experiments, using any scoring function.
Emerging role of Garcinol, the antioxidant chalcone from Garcinia indica Choisy and its synthetic analogs
Authors: Padhye Subhash , Ahmad Aamir , Oswal Nikhil , Sarkar Fazlul H
Published: September 2009

Garcinol, harvested fromGarcinia indica, has traditionally been used in tropical regions and appreciated for centuries; however its biological properties are only beginning to be elucidated. There is ample data to suggest potent antioxidant properties of this compound which have been used to explain most of its observed biological activities. However, emerging evidence suggests that garcinol could be useful as an anti-cancer agent, and it is increasingly being realized that garcinol is a pleiotropic agent capable of modulating key regulatory cell signaling pathways. Here we have summarized the progress of our current research knowledge on garcinol and its observed biological activities. We have also provided an explanation of observed properties based on its chemical structure and provided an insight into the structure and properties of chalcones, the precursors of garcinol. The available data is promising but more detailed investigations into the various properties of this compound, particularly its anti-cancer activity are urgently needed, and it is our hope that this review will stimulate further research for elucidating and appreciating the value of this nature's wonder agent.
Exploring trends in microcrack properties of sedimentary rocks: An audit of dry-core velocity-stress measurements
Authors: Angus Doug A. , Verdon James P. , Fisher Quentin J. , Kendall J.-M.
Published: September 2009

Rock-physics models are used increasingly to link fluid and mechanical deformation parameters for dynamic elastic modeling. We explore the input parameters of an analytical stress-dependent rock-physics model. To do this, we invert for the stress-dependent microcrack parameters of more than 150 sedimentary rock velocity-stress core measurements taken from a literature survey. The inversion scheme is based on a microstructural effective-medium formulation defined by a second-rank crack-density tensor (scalar crack model) or by a second- and fourth-rank crack-density tensor (joint inversion model). Then the inversion results are used to explore and predict the stress-dependent elastic behavior of various sedimentary rock lithologies using an analytical microstructural rock-physics model via the initial modelinput parameters: initial crack aspect ratio and initial crack density. Estimates of initial crack aspect ratio are consistent among most lithologies with a mean of 0.0004, but for shales they differ up to several times in magnitude with a mean of 0.001. Estimates of initial aspect ratio are relatively insensitive to the inversion method, although the scalar crack inversion becomes less reliable at low values of normal-to-tangential crack compliance ratio [Formula: see text]. Initial crack density is sensitive to the degree of damage as well as the inversion procedure. An important implication is that the fourth-rank crack-density term is not necessarily negligible for most sedimentary rocks and evaluation of this term or [Formula: see text] is necessary for accurate prediction of initial crack density. This is especially important because recent studies suggest that [Formula: see text] can indicate fluid content in cracks.
Randomized, Placebo-Controlled, Phase II Study of Sequential Erlotinib and Chemotherapy As First-Line Treatment for Advanced Non–Small-Cell Lung Cancer
Authors: Mok Tony S.K. , Wu Yi-Long , Yu Chong-Jen , Zhou Caicun , Chen Yuh-Min , Zhang Li , Ignacio Jorge , Liao Meilin , Srimuninnimit Vichien , Boyer Michael J. , Chua-Tan Marina , Sriuranpong Virote , Sudoyo Aru W. , Jin Kate , Johnston Michael , Chui Winsome , Lee Jin-Soo
Published: September 2009

Purpose

This study investigated whether sequential administration of erlotinib and chemotherapy improves clinical outcomes versus chemotherapy alone in unselected, chemotherapy-naïve patients with advanced non–small-cell lung cancer (NSCLC).

Patients and Methods

Previously untreated patients (n = 154) with stage IIIB or IV NSCLC and Eastern Cooperative Oncology Group performance status of 0 or 1 were randomly assigned to receive erlotinib (150 mg/d) or placebo on days 15 to 28 of a 4-week cycle that included gemcitabine (1,250 mg/m2 days 1 and 8) and either cisplatin (75 mg/m2 day 1) or carboplatin (5 × area under the serum concentration-time curve, day 1). The primary end point was nonprogression rate (NPR) at 8 weeks. Secondary end points included tumor response rate, NPR at 16 weeks, duration of response, progression-free survival (PFS), overall survival (OS), and safety.

Results

The NPR at 8 weeks was 80.3% in the gemcitabine plus cisplatin or carboplatin (GC) -erlotinib arm (n = 76) and 76.9% in the GC-placebo arm (n = 78). At 16 weeks, the NPR was 64.5% for GC-erlotinib versus 53.8% for GC-placebo. The response rate was 35.5% for GC-erlotinib versus 24.4% for GC-placebo. PFS was significantly longer with GC-erlotinib than with GC-placebo (adjusted hazard ratio, 0.47; log-rank P = .0002; median, 29.4 v 23.4 weeks); this benefit was consistent across all clinical subgroups. There was no significant difference in OS. The addition of erlotinib to chemotherapy was well tolerated, with no increase in hematologic toxicity, and no treatment-related interstitial lung disease.

Conclusion

Sequential administration of erlotinib following gemcitabine/platinum chemotherapy led to a significant improvement in PFS. This treatment approach warrants further investigation in a phase III study.
Prevalence, Natural Course, and Risk Factors of Insomnia Comorbid With Cancer Over a 2-Month Period
Authors: Savard Josée , Villa Julie , Ivers Hans , Simard Sébastien , Morin Charles M.
Published: September 2009

Purpose

This study aimed to assess the prevalence, natural course, and risk factors of insomnia comorbid with cancer over a 2-month period.

Patients and Methods

All patients scheduled to receive a curative surgery for a first diagnosis of nonmetastatic cancer were approached to participate in the study on the day of their preoperative visit. As part of a larger population-based longitudinal study, 991 cancer patients completed various self-report scales and an insomnia diagnostic interview at the perioperative phase (T1) and 2 months later (T2).

Results

At T1, 28.5% of the patients met the diagnostic criteria for an insomnia syndrome, and 31.0% had insomnia symptoms; these rates decreased to 26.2% and 22.2%, respectively, at T2. The highest rates of insomnia were found in breast cancer patients, whereas the lowest rates were obtained in prostate cancer patients. Findings indicated an incidence rate of 18.6%, a persistence rate of 68.0%, and a remission rate of 32.0%. Female sex and the presence of an arousability trait (predisposing factors), a diagnosis of head and neck cancer, the administration of surgery, and an increase in anxiety symptoms between T1 and T2 (precipitating factors), and higher baseline levels and increases between T1 and T2 in dysfunctional beliefs about sleep, sleep monitoring, and maladaptive sleep behaviors (maintenance factors) were all associated with an increased risk for insomnia incidence.

Conclusion

This study confirms the high prevalence of insomnia comorbid with cancer during the 2 months after the perioperative visit and identifies several factors that might be involved in its development.
Role of Tissue Factor in Cancer
Authors: Kasthuri Raj S. , Taubman Mark B. , Mackman Nigel
Published: September 2009

Tissue factor (TF) is a transmembrane glycoprotein that localizes the coagulation serine protease factor VII/VIIa (FVII/VIIa) to the cell surface. The primary function of TF is to activate the clotting cascade. The TF:FVIIa complex also activates cells by cleavage of a G-protein coupled receptor called protease-activated receptor 2 (PAR2). TF is expressed by tumor cells and contributes to a variety of pathologic processes, such as thrombosis, metastasis, tumor growth, and tumor angiogenesis. For instance, tumor cells release TF-positive procoagulant microparticles into the circulation and these may trigger venous thromboembolism in patients with cancer. TF on circulating tumor cells also leads to the coating of the cells with fibrin that traps them within the microvasculature and facilitates hematogenous metastasis. In addition, TF:FVIIa-dependent activation of PAR2 on tumor cells increases tumor growth via an undefined mechanism. One possibility is that PAR2-dependent signaling increases the expression of proangiogenic proteins. Other studies have reported that endothelial cells in the tumor vasculature express TF and this may enhance angiogenesis. These results suggest that inhibition of TF should reduce several pathologic pathways that increase tumor growth and metastasis. This would represent a novel approach to anticancer therapy. Initial studies using inhibitors of the TF:FVIIa complex in mouse tumor models have produced encouraging results. Nevertheless, additional studies are needed to determine if this strategy can be successfully translated to the treatment of cancer patients.
A finite difference solution of a steel plate with an internal hole using the displacement potential approach
Authors: Deb Nath S K , Salam Akanda M A
Published: September 2009

The finite difference technique based on a displacement potential formulation is extended to solve an elastic plane stress problem with geometric perturbations such as holes, arbitrary defects, notches, etc. An elastic steel plate having an internal hole is constrained at one edge and a shear load is applied to the opposite edge. The present problem is solved by using the extended finite difference technique based on displacement potential approach. The different displacement and stress components at different sections of the plate are shown graphically and discussed; from the analysis of stress and displacement components at different sections of the plate, critical regions of the plate are identified. The superiority of the finite difference method (FDM) based on the displacement potential formulation over the finite element method (FEM) is verified by the comparison between the solutions of the present problem by the FDM and FEM. From the comparison between the solutions of the FEM and FDM, it is concluded that the present finite difference technique based on the displacement potential formulation is reliable and can be used to solve the structural elements having internal defects.
An artificial neural network for prediction of the friction coefficient of multi-layer polymeric composites in three different orientations
Authors: Nasir T , Yousif B F , McWilliam S , Salih N D , Hui L T
Published: September 2009

In the present work, an artificial neural network (ANN) model was developed to predict frictional performance of a polymeric composite. The experimental dataset at different applied loads (30–100 N), sliding speeds (300–700 r/min), and up to 10 min of sliding duration was used to train the model. The ANN model was trained with a large volume of experimental data (7389 sets). In addition to that, fibre mat orientation was considered in ANN development. Various configurations with different functions of training were used to find the optimal model. As a result of this work, single-layered models with large number of neurons showed high accuracy, up to 90 per cent in prediction, when trained with the Levenberg—Marqurdt function.
Sonoporation, drug delivery, and gene therapy
Authors: Liang H-D , Tang J , Halliwell M
Published: September 2009

Ultrasound is a very effective modality for drug delivery and gene therapy because energy that is non-invasively transmitted through the skin can be focused deeply into the human body in a specific location and employed to release drugs at that site. Ultrasound cavitation, enhanced by injected microbubbles, perturbs cell membrane structures to cause sonoporation and increases the permeability to bioactive materials. Cavitation events also increase the rate of drug transport in general by augmenting the slow diffusion process with convective transport processes. Drugs and genes can be incorporated into microbubbles, which in turn can target a specific disease site using ligands such as the antibody. Drugs can be released ultrasonically from microbubbles that are sufficiently robust to circulate in the blood and retain their cargo of drugs until they enter an insonated volume of tissue. Local drug delivery ensures sufficient drug concentration at the diseased region while limiting toxicity for healthy tissues. Ultrasound-mediated gene delivery has been applied to heart, blood vessel, lung, kidney, muscle, brain, and tumour with enhanced gene transfection efficiency, which depends on the ultrasonic parameters such as acoustic pressure, pulse length, duty cycle, repetition rate, and exposure duration, as well as microbubble properties such as size, gas species, shell material, interfacial tension, and surface rigidity. Microbubble-augmented sonothrombolysis can be enhanced further by using targeting microbubbles.
Polycrystalline coating of hydroxyapatite on TiAl6V4 implant material grown at lower substrate temperatures by hydrothermal annealing after pulsed laser deposition
Authors: Saju K K , Reshmi R , Jayadas N H , James J , Jayaraj M K
Published: September 2009

Hydroxyapatite (HA) is a bioactive ceramic material that mimics the mineral composition of natural bone. This material does not possess acceptable mechanical properties for use as a bulk biomaterial; however, it does demonstrate significant potential for use as a coating on metallic orthopaedic and dental prostheses. Pulsed laser deposition (PLD) of thin films of HA on TiAl6V4 have shown crystalline coatings to be obtained at temperatures of the order of 350—500 °C. This condition of high substrate temperature promoted the oxidation of the substrate surface prior to the growth of the HA layer and the oxidation layer degraded the adhesion of the coating to the substrate. In this study, thin films of HA were deposited on TiAl6V4 alloy at a lower temperature of 200 °C by PLD and crystallized by a hydrothermal treatment at 100 °C. The film was subjected to mechanical as well as cell viability tests in vitro. The thickness, roughness, crystallanity, composition ratio, adhesive strength, and cell adhesion of the film suggest the application of this technique for producing bioactive implants.
The role of registration in accurate surgical guidance
Authors: Fitzpatrick J M
Published: September 2009

Registration is presented as the central issue of surgical guidance. The focus is on the accuracy of approaches employed today, all of which use pre-operative images to guide surgery on rigid anatomy. The three most well-established approaches to guidance, namely the stereotactic frame, point fiducials, and surface matching, are examined in detail, together with two new approaches based on microstereotactic frames. It is shown that each method relies on the registration of points in the image to corresponding points in the operating room, and therefore that the error patterns associated with point registration are similar for all of them. Three types of registration error, namely fiducial localization error (FLE), fiducial registration error (FRE), and target registration error (TRE), are highlighted, as well as two additional guidance errors, namely target localization error and total targeting error, the latter of which is the overall error of the guidance system. Statistical relationships between TRE and FLE, between FRE and FLE, and between TRE, TLE, and TTE are given. Finally some myths concerning fiducial registration are highlighted.
STING: a soft-tissue intervention and neurosurgical guide to access deep brain lesions through curved trajectories
Authors: Frasson L , Ko S Y , Turner A , Parittotokkaporn T , Vincent J F , Rodriguez y Baena F
Published: September 2009

Current trends in surgical intervention favour a minimally invasive approach, in which complex procedures are performed through very small incisions. Specifically, in neurosurgery there is a need for minimally invasive keyhole access, which conflicts with the lack of manoeuvrability of conventional rigid instruments. In an attempt to address this shortcoming, the current state of progress is reported on a soft-tissue intervention and neurosurgical guide (STING) to access deep brain lesions through curved trajectories. The underlying mechanism of motion, based on the reciprocal movement of interlocked probe segments, is biologically inspired and was designed around the unique features of the ovipositor of certain parasitic wasps. Work to date has focused on probe development, low- and high-level control, and trajectory planning. These aspects are described, together with results on each aspect of the work, including biomimetic microtexturing of the probe surface. Progress is very encouraging and demonstrates that forward motion into soft tissue through a reciprocating mechanism is indeed viable and can be achieved through a suitable combination of microtexturing and microfabrication techniques.
Analysis of pressure oscillations in a Francis hydraulic turbine with misaligned guide vanes
Authors: Qian Z D , Zheng B , Huai W X , Lee Y H
Published: September 2009

Three-dimensional unsteady turbulent flow in the entire flow passage of a model Francis turbine is simulated by adopting the realizable k-ε turbulence model. Using experimental data, the validity of the mathematical model is verified. Pressure oscillations are calculated for a model turbine attached with a misaligned guide vanes (MGV) device. Two MGV with five different MGV opening angles are selected for analysing the influence of MGV on pressure oscillations in the spiral case, guide vanes, runner, and draft tube. The computational results show that (a) the rotational frequency of the vortex rope remains unchanged despite different MGV openings, (b) the MGV device changes the peak-to-peak amplitude in a similar way as aligned guide vanes, (c) with increasing MGV opening, the amplitude of various frequency components in the draft tube vary in different ways, (d) a new frequency that is the product of the runner frequency and the number of MGV appears in the runner, and (e) with increasing difference between the MGV opening and the other guide vane openings, the amplitude of this new pressure oscillation increased.
Numerical investigation of the unsteady behaviour of tip clearance flow and its possible link to stall inception
Authors: Wu Y , Li Q , Chu W , Zhang H , Su Z
Published: September 2009

Three-dimensional unsteady calculations were performed to explore the unsteady nature of tip clearance flow and its possible linking with the spike stall inception. It was found that the interaction of the broken-down leakage vortex with the tip clearance flow formed another distinctive vortex, denoted as the tip separation vortex. It formed below the rotor blade tip section and propagated diagonally inward. This vortex propagated across the rotor passage from the pressure side to the suction side with its vortex core filled with low-energy fluid. The spike emergence during stall inception included the breakdown of the tip leakage vortex and the formation and movement of the tip separation vortex.
Effect of ingredients in slurry containing alumina on chemical mechanical polishing of hard disc substrates
Authors: Sun J Z , Pan G S , Zhou Y , Zhu Y H , Luo J B , Lu X C , Liu Y
Published: September 2009

In this article, new slurry containing alumina abrasives, oxidants, and surface modifiers is developed for the primary polishing of Ni—P-plated hard disc substrates. Compared with commercial slurry, the developed one improves the surface quality drastically by relieving cold weld (CW) and scratch. A fairly high material removal rate (MRR) is obtained when the pH value of the slurry is 3.0. D50 (mean particle diameter) of the alumina abrasive is decreased by using a ball mill, which is effective in alleviating deep scratches and CW. Scanning electronic microscope and X-ray diffractometer are used to study the formation mechanism of CW. The oxidant hydrogen peroxide H2O2 is proved to be helpful in eliminating CW and improving the MRR largely. Lauroyl monoethanolamide sulfate C11H23CONHC2H4OSO3H as a surface modifier is added to the slurry to improve the surface quality further.
The influence of natural frequency of the experimental set-up on the friction coefficient of copper
Authors: Chowdhury M A , Karim S Md I , Ali M L
Published: September 2009

The present article investigates experimentally the effect of natural frequency of the experimental set-up on the friction property of copper. To do so, a pin-on-disc apparatus having the facility of vibrating the test samples at different directions, amplitudes, and frequencies was designed and fabricated. The natural frequency of the set-up was varied by adding dead loads of the set-up from 0 kg to 490.33 N. At each added load the friction coefficient has been measured. Results show that both the natural frequency and friction coefficient decrease with the increase of added loads. It has also been observed that the coefficient of friction increases with the increase of natural frequency of the experimental set-up. The experimental results are also compared with those available in literature and simple physical explanations are provided.