bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolutionary dynamics of U12-type spliceosomal introns
Authors: Lin Chiao-Feng , Mount Stephen M , Jarmołowski Artur , Makałowski Wojciech
Published: February 2010

Background

Many multicellular eukaryotes have two types of spliceosomes for the removal of introns from messenger RNA precursors. The major (U2) spliceosome processes the vast majority of introns, referred to as U2-type introns, while the minor (U12) spliceosome removes a small fraction (less than 0.5%) of introns, referred to as U12-type introns. U12-type introns have distinct sequence elements and usually occur together in genes with U2-type introns. A phylogenetic distribution of U12-type introns shows that the minor splicing pathway appeared very early in eukaryotic evolution and has been lost repeatedly.

Results

We have investigated the evolution of U12-type introns among eighteen metazoan genomes by analyzing orthologous U12-type intron clusters. Examination of gain, loss, and type switching shows that intron type is remarkably conserved among vertebrates. Among 180 intron clusters, only eight show intron loss in any vertebrate species and only five show conversion between the U12 and the U2-type. Although there are only nineteen U12-type introns in Drosophila melanogaster, we found one case of U2 to U12-type conversion, apparently mediated by the activation of cryptic U12 splice sites early in the dipteran lineage. Overall, loss of U12-type introns is more common than conversion to U2-type and the U12 to U2 conversion occurs more frequently among introns of the GT-AG subtype than among introns of the AT-AC subtype. We also found support for natural U12-type introns with non-canonical terminal dinucleotides (CT-AC, GG-AG, and GA-AG) that have not been previously reported.

Conclusions

Although complete loss of the U12-type spliceosome has occurred repeatedly, U12 introns are extremely stable in some taxa, including eutheria. Loss of U12 introns or the genes containing them is more common than conversion to the U2-type. The degeneracy of U12-type terminal dinucleotides among natural U12-type introns is higher than previously thought.
SoyTEdb: a comprehensive database of transposable elements in the soybean genome
Authors: Du Jianchang , Grant David , Tian Zhixi , Nelson Rex T , Zhu Liucun , Shoemaker Randy C , Ma Jianxin
Published: February 2010

Background

Transposable elements are the most abundant components of all characterized genomes of higher eukaryotes. It has been documented that these elements not only contribute to the shaping and reshaping of their host genomes, but also play significant roles in regulating gene expression, altering gene function, and creating new genes. Thus, complete identification of transposable elements in sequenced genomes and construction of comprehensive transposable element databases are essential for accurate annotation of genes and other genomic components, for investigation of potential functional interaction between transposable elements and genes, and for study of genome evolution. The recent availability of the soybean genome sequence has provided an unprecedented opportunity for discovery, and structural and functional characterization of transposable elements in this economically important legume crop.

Description

Using a combination of structure-based and homology-based approaches, a total of 32,552 retrotransposons (Class I) and 6,029 DNA transposons (Class II) with clear boundaries and insertion sites were structurally annotated and clearly categorized, and a soybean transposable element database, SoyTEdb, was established. These transposable elements have been anchored in and integrated with the soybean physical map and genetic map, and are browsable and visualizable at any scale along the 20 soybean chromosomes, along with predicted genes and other sequence annotations. BLAST search and other infrastracture tools were implemented to facilitate annotation of transposable elements or fragments from soybean and other related legume species. The majority (> 95%) of these elements (particularly a few hundred low-copy-number families) are first described in this study.

Conclusion

SoyTEdb provides resources and information related to transposable elements in the soybean genome, representing the most comprehensive and the largest manually curated transposable element database for any individual plant genome completely sequenced to date. Transposable elements previously identified in legumes, the third largest family of flowering plants, are relatively scarce. Thus this database will facilitate structural, evolutionary, functional, and epigenetic analyses of transposable elements in soybean and other legume species.
Broad spectrum microarray for fingerprint-based bacterial species identification
Authors: Pasquer Frédérique , Pelludat Cosima , Duffy Brion , Frey Jürg E
Published: February 2010

Background

Microarrays are powerful tools for DNA-based molecular diagnostics and identification of pathogens. Most target a limited range of organisms and are based on only one or a very few genes for specific identification. Such microarrays are limited to organisms for which specific probes are available, and often have difficulty discriminating closely related taxa. We have developed an alternative broad-spectrum microarray that employs hybridisation fingerprints generated by high-density anonymous markers distributed over the entire genome for identification based on comparison to a reference database.

Results

A high-density microarray carrying 95,000 unique 13-mer probes was designed. Optimized methods were developed to deliver reproducible hybridisation patterns that enabled confident discrimination of bacteria at the species, subspecies, and strain levels. High correlation coefficients were achieved between replicates. A sub-selection of 12,071 probes, determined by ANOVA and class prediction analysis, enabled the discrimination of all samples in our panel. Mismatch probe hybridisation was observed but was found to have no effect on the discriminatory capacity of our system.

Conclusions

These results indicate the potential of our genome chip for reliable identification of a wide range of bacterial taxa at the subspecies level without laborious prior sequencing and probe design. With its high resolution capacity, our proof-of-principle chip demonstrates great potential as a tool for molecular diagnostics of broad taxonomic groups.
High-level expression and purification of soluble recombinant FGF21 protein by SUMO fusion in Escherichia coli
Authors: Wang Huiyan , Xiao Yechen , Fu Lianjun , Zhao Hongxin , Zhang Yaofang , Wan Xiaoshan , Qin Yuxia , Huang Yadong , Gao Hongchang , Li Xiaokun
Published: February 2010

Background

Fibroblast growth factor 21 (FGF21) is a promising drug candidate to combat metabolic diseases. However, high-level expression and purification of recombinant FGF21 (rFGF21) in Escherichia coli (E. coli) is difficult because rFGF21 forms inclusion bodies in the bacteria making it difficult to purify and obtain high concentrations of bioactive rFGF21. To overcome this problem, we fused the FGF21 with SUMO (Small ubiquitin-related modifier) by polymerase chain reaction (PCR), and expressed the fused gene in E. coli BL21(DE3).

Results

By inducing with IPTG, SUMO-FGF21 was expressed at a high level. Its concentration reached 30% of total protein, and exceeded 95% of all soluble proteins. The fused protein was purified by DEAE sepharose FF and Ni-NTA affinity chromatography. Once cleaved by the SUMO protease, the purity of rFGF21 by high performance liquid chromatography (HPLC) was shown to be higher than 96% with low endotoxin level (<1.0 EU/ml). The results of in vivo animal experiments showed that rFGF21 produced by using this method, could decrease the concentration of plasma glucose in diabetic rats by streptozotocin (STZ) injection.

Conclusions

This study demonstrated that SUMO, when fused with FGF21, was able to promote its soluble expression of the latter in E. coli, making it more convenient to purify rFGF21 than previously. This may be a better method to produce rFGF21 for pharmaceutical research and development.
Culture independent molecular analysis of bacterial communities in the mangrove sediment of Sundarban, India
Authors: Ghosh Abhrajyoti , Dey Nirmalya , Bera Amit , Tiwari Amit , Sathyaniranjan KB , Chakrabarti Kalyan , Chattopadhyay Dhrubajyoti
Published: February 2010

Background

Sundarban is the world's largest coastal sediment comprising of mangrove forest which covers about one million hectares in the south-eastern parts of India and southern parts of Bangladesh. The microbial diversity in this sediment is largely unknown till date. In the present study an attempt has been made to understand the microbial diversity in this sediment using a cultivation-independent molecular approach.

Results

Two 16 S rRNA gene libraries were constructed and partial sequencing of the selected clones was carried out to identify bacterial strains present in the sediment. Phylogenetic analysis of partially sequenced 16 S rRNA gene sequences revealed the diversity of bacterial strains in the Sundarban sediment. At least 8 different bacterial phyla were detected. The major divisions of detected bacterial phyla were Proteobacteria (alpha, beta, gamma, and delta), Flexibacteria (CFB group), Actinobacteria, Acidobacteria, Chloroflexi, Firmicutes, Planctomycetes and Gammatimonadates.

Conclusion

The gammaproteobacteria were found to be the most abundant bacterial group in Sundarban sediment. Many clones showed similarity with previously reported bacterial lineages recovered from various marine sediments. The present study indicates a probable hydrocarbon and oil contamination in this sediment. In the present study, a number of clones were identified that have shown similarity with bacterial clones or isolates responsible for the maintenance of the S-cycle in the saline environment.
Phase I Clinical Trial of the CYP17 Inhibitor Abiraterone Acetate Demonstrating Clinical Activity in Patients With Castration-Resistant Prostate Cancer Who Received Prior Ketoconazole Therapy
Authors: Ryan Charles J. , Smith Matthew R. , Fong Lawrence , Rosenberg Jonathan E. , Kantoff Philip , Raynaud Florence , Martins Vanessa , Lee Gloria , Kheoh Thian , Kim Jennifer , Molina Arturo , Small Eric J.
Published: February 2010

Purpose

Abiraterone acetate is a prodrug of abiraterone, a selective inhibitor of CYP17, the enzyme catalyst for two essential steps in androgen biosynthesis. In castration-resistant prostate cancers (CRPCs), extragonadal androgen sources may sustain tumor growth despite a castrate environment. This phase I dose-escalation study of abiraterone acetate evaluated safety, pharmacokinetics, and effects on steroidogenesis and prostate-specific antigen (PSA) levels in men with CPRC with or without prior ketoconazole therapy.

Patients and Methods

Thirty-three men with chemotherapy-naïve progressive CRPC were enrolled. Nineteen patients (58%) had previously received ketoconazole for CRPC. Bone metastases were present in 70% of patients, and visceral involvement was present in 18%. Three patients (9%) had locally advanced disease without distant metastases. Fasted or fed cohorts received abiraterone acetate doses of 250, 500, 750, or 1,000 mg daily. Single-dose pharmacokinetic analyses were performed before continuous daily dosing.

Results

Adverse events were predominantly grade 1 or 2. No dose-limiting toxicities were observed. Hypertension (grade 3, 12%) and hypokalemia (grade 3, 6%; grade 4, 3%) were the most frequent serious toxicities and responded to medical management. Confirmed ≥ 50% PSA declines at week 12 were seen in 18 (55%) of 33 patients, including nine (47%) of 19 patients with prior ketoconazole therapy and nine (64%) of 14 patients without prior ketoconazole therapy. Substantial declines in circulating androgens and increases in mineralocorticoids were seen with all doses.

Conclusion

Abiraterone acetate was well tolerated and demonstrated activity in CRPC, including in patients previously treated with ketoconazole. Continued clinical study is warranted.
Alberta Physical Activity and Breast Cancer Prevention Trial: Sex Hormone Changes in a Year-Long Exercise Intervention Among Postmenopausal Women
Authors: Friedenreich Christine M. , Woolcott Christy G. , McTiernan Anne , Ballard-Barbash Rachel , Brant Rollin F. , Stanczyk Frank Z. , Terry Tim , Boyd Norman F. , Yaffe Martin J. , Irwin Melinda L. , Jones Charlotte A. , Yasui Yutaka , Campbell Kristin L. , McNeely Margaret L. , Karvinen Kristina H. , Wang Qinggang , Courneya Kerry S.
Published: February 2010

Purpose

We examined how an aerobic exercise intervention influenced circulating estradiol, estrone, sex hormone–binding globulin (SHBG), androstenedione, and testosterone levels, which may be involved in the association between physical activity and breast cancer risk.

Methods

A two-center, two-arm randomized controlled trial of exercise was conducted in 320 postmenopausal, sedentary women age 50 to 74 years. Participants were randomly assigned to a 1-year aerobic exercise intervention of 225 min/wk (n = 160) or to a control group who maintained their usual level of activity (n = 160). Baseline, 6-month, and 12-month assessments of estrone, estradiol, androstenedione, and testosterone were quantified by radioimmunoassay after extraction, and SHBG was quantified by an immunometric assay. Intent-to-treat analyses were performed using linear mixed models.

Results

Blood data were available on 309 women (96.6%) at 12 months. Women in the intervention group exercised an average of 3.6 d/wk for 178 min/wk. At 12 months, statistically significant reductions in estradiol (treatment effect ratio [TER] = 0.93; 95% CI, 0.88 to 0.98) and free estradiol (TER = 0.91; 95% CI, 0.87 to 0.96) and increases in SHBG (TER = 1.04; 95% CI, 1.02 to 1.07) were observed in the exercise group compared with the control group. No significant differences in estrone, androstenedione, and testosterone levels were observed between exercisers and controls at 12 months.

Conclusion

This trial found that previously sedentary postmenopausal women can adhere to a moderate- to vigorous-intensity exercise program that results in changes in estradiol and SHBG concentrations that are consistent with a lower risk for postmenopausal breast cancer.
Treatment of Favorable, Limited-Stage Hodgkin's Lymphoma With Chemotherapy Without Consolidation by Radiation Therapy
Authors: Canellos George P. , Abramson Jeremy S. , Fisher David C. , LaCasce Ann S.
Published: February 2010

Purpose

Limited-stage Hodgkin's lymphoma (HL) has been treated with radiation alone or radiation combined with chemotherapy. Although results in progression-free survival and overall survival have been excellent, the long-term, radiation-induced, toxic cardiac and secondary oncologic complications occurring in succeeding decades have compromised survival of young patients. This study examines the impact of chemotherapy alone in treatment of limited-stage, nonbulky HL, radiation therapy eliminated from primary treatment.

Patients and Methods

From 1992 to May 2008, 71 patients with a median age of 29 years (range, 17-44 years) with stages I and II HL without bulky nodes were treated with six cycles of classic combination doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD). Two patients received six cycles of ABVD-like modification. Two patients received four cycles of ABVD. The ABVD regimen was known to be curative in more advanced disease without radiation therapy.

Results

All patients achieved a clinical complete response (CR) or CR unconfirmed. After a median follow-up of at least 60 months (range, at least 12 to at least 204 months), six patients experienced relapse at 6, 10, 11, 16, 20, and 58 months. All relapses occurred at site of presenting disease. No patients have died. Salvage therapy was successful with second-line chemotherapy/radiation and autologous stem-cell transplantation.

Conclusion

Six cycles of ABVD is an effective and safe treatment for limited-stage, nonbulky HL and would spare young patients radiation toxicity. Interim positron emission tomography/computed tomography scans in current and future trials may identify those patients who require less than six cycles of chemotherapy.
Phase 1b Study of Dulanermin (recombinant human Apo2L/TRAIL) in Combination With Paclitaxel, Carboplatin, and Bevacizumab in Patients With Advanced Non-Squamous Non–Small-Cell Lung Cancer
Authors: Soria Jean-Charles , Smit Egbert , Khayat David , Besse Benjamin , Yang Xinqun , Hsu Cheng-Pang , Reese David , Wiezorek Jeffrey , Blackhall Fiona
Published: February 2010

Purpose

To determine the safety, pharmacokinetics (PK), and maximum-tolerated dose (MTD) up to a prespecified target dose of dulanermin in combination with paclitaxel, carboplatin, and bevacizumab (PCB) in patients with previously untreated, nonsquamous, stage IIIb (with pleural effusion)/IV or recurrent non–small-cell lung cancer (NSCLC).

Patients and Methods

In this phase 1b study, patients (n = 24) received PCB on day 1 of each 21-day cycle then dulanermin at 4 or 8 mg/kg/d for 5 consecutive days or 15 or 20 mg/kg/d for 2 consecutive days per assigned treatment cohort. Incidence of dose-limiting toxicities (DLTs), adverse events, and antidulanermin antibodies were assessed. PK parameters were recorded for each agent. Tumor response was measured by modified Response Evaluation Criteria in Solid Tumors.

Results

Twenty-four patients received at least one dose of dulanermin plus PCB, six in each treatment cohort. There were no DLTs. An MTD was not reached, and the drug combination was well tolerated. Treatment-emergent adverse events were generally as expected for the PCB regimen. Adverse events attributed to dulanermin were grade 1/2; no significant hepatotoxicity occurred. There was minimal impact of PCB on the PK of dulanermin. There was one confirmed complete response and 13 confirmed partial responses. The overall response rate was 58% (95% CI, 37 to 78). Median progression-free survival was 7.2 months (95% CI, 4.7 to 10.3).

Conclusion

Dulanermin plus PCB was well tolerated with no occurrence of DLTs and demonstrated antitumor activity in this patient population. Dulanermin at 8 mg/kg/d for 5 days and 20 mg/kg/d for 2 days every 3 weeks in combination with PCB is being studied in a phase II trial.
Phase II Multicenter Study of Abiraterone Acetate Plus Prednisone Therapy in Patients With Docetaxel-Treated Castration-Resistant Prostate Cancer
Authors: Danila Daniel C. , Morris Michael J. , de Bono Johann S. , Ryan Charles J. , Denmeade Samuel R. , Smith Matthew R. , Taplin Mary-Ellen , Bubley Glenn J. , Kheoh Thian , Haqq Christopher , Molina Arturo , Anand Aseem , Koscuiszka Michael , Larson Steve M. , Schwartz Lawrence H. , Fleisher Martin , Scher Howard I.
Published: February 2010

Purpose

Persistence of ligand-mediated androgen receptor signaling has been documented in castration-resistant prostate cancers (CRPCs). Abiraterone acetate (AA) is a potent and selective inhibitor of CYP17, which is required for androgen biosynthesis in the testes, adrenal glands, and prostate tissue. This trial evaluated the efficacy and safety of AA in combination with prednisone to reduce the symptoms of secondary hyperaldosteronism that can occur with AA monotherapy.

Patients and Methods

Fifty-eight men with progressive metastatic CRPC who experienced treatment failure with docetaxel-based chemotherapy received AA (1,000 mg daily) with prednisone (5 mg twice daily). Twenty-seven (47%) patients had received prior ketoconazole. The primary outcome was ≥ 50% prostate-specific antigen (PSA) decline, with objective response by Response Evaluation Criteria in Solid Tumors (RECIST) criteria, and changes in Eastern Cooperative Oncology Group (ECOG) performance status (PS) and circulating tumor cell (CTC) numbers. Safety was also evaluated.

Results

A ≥ 50% decline in PSA was confirmed in 22 (36%) patients, including 14 (45%) of 31 ketoconazole-naïve and seven (26%) of 27 ketoconazole-pretreated patients. Partial responses were seen in four (18%) of 22 patients with RECIST-evaluable target lesions. Improved ECOG PS was seen in 28% of patients. Median time to PSA progression was 169 days (95% CI, 82 to 200 days). CTC conversions with treatment from ≥ 5 to < 5 were noted in 10 (34%) of 29 patients. The majority of AA-related adverse events were grade 1 to 2, and no AA-related grade 4 events were seen.

Conclusion

AA plus prednisone was well tolerated, with encouraging antitumor activity in heavily pretreated CRPC patients. The incidence of mineralocorticoid-related toxicities (hypertension or hypokalemia) was reduced by adding low-dose prednisone. The combination of AA plus prednisone is recommended for phase III investigations.
Protein Malnutrition during Pregnancy in C57BL/6J Mice Results in Offspring with Altered Circadian Physiology before Obesity
Authors: Sutton Gregory M. , Centanni Armand V. , Butler Andrew A.
Published: February 2010

The mechanisms linking intrauterine growth retardation (IUGR) with adulthood obesity and diabetes are unclear. These studies investigated energy homeostasis in 8- and 20-wk-old male and female mice subjected to protein deficiency in utero. Pregnant C57BL/6J female mice were fed a protein-deficient diet (6% protein). Undernourished offspring (UO) and controls (CO) were cross-fostered to lactating dams fed a 20% control diet. The 24-h profiles of energy expenditure, feeding behavior, physical activity, and whole-body substrate preference was assessed using 8-wk UO and CO weaned onto control diet. Blood chemistries, glucose tolerance, and expression of genes involved in hepatic lipid and glucose metabolism were analyzed in 8- and 20-wk-old CO and UO fed control or a high-fat diet. UO exhibited IUGR with catch-up growth at 8 wk of age and increased severity of diet-induced obesity and insulin resistance by 20 wk of age. Therefore, fetal malnutrition in the C57BL/6J mouse increases sensitivity to diet-induced obesity. Abnormal daily rhythms in food intake and metabolism, increased lipogenesis, and inflammation preceded obesity in the UO group. Arrhythmic expression of circadian oscillator genes was evident in brain, liver, and muscle of UO at 8 and 20 wk of age. Expression of the clock-associated nuclear receptor and transcription repressor Rev-erbα was reduced in liver and muscle of UO. Altered circadian physiology may be symptomatic of the metabolic dysregulation associated with IUGR, and altered feeding behavior and substrate metabolism may contribute to the obese phenotype.
Inhibin-A Antagonizes TGFβ2 Signaling by Down-Regulating Cell Surface Expression of the TGFβ Coreceptor Betaglycan
Authors: Looyenga Brendan D. , Wiater Ezra , Vale Wylie , Hammer Gary D.
Published: February 2010

Inhibin is an atypical member of the TGFβ family of signaling ligands and is classically understood to function via competitive antagonism of activin ligand binding. Inhibin-null (Inha−/−) mice develop both gonadal and adrenocortical tumors, the latter of which depend upon gonadectomy for initiation. We have previously shown that gonadectomy initiates adrenal tumorigenesis in Inha−/− mice by elevating production of LH, which drives aberrant proliferation and differentiation of subcapsular adrenocortical progenitor cells. In this study, we demonstrate that LH signaling specifically up-regulates expression of TGFβ2 in the subcapsular region of the adrenal cortex, which coincides with regions of aberrant Smad3 activation in Inha−/− adrenal glands. Consistent with a functional interaction between inhibin and TGFβ2, we further demonstrate that recombinant inhibin-A antagonizes signaling by TGFβ2 in cultured adrenocortical cells. The mechanism of this antagonism depends upon the mutual affinity of inhibin-A and TGFβ2 for the signaling coreceptor betaglycan. Although inhibin-A cannot physically displace TGFβ2 from its binding sites on betaglycan, binding of inhibin-A to the cell surface causes endocytic internalization of betaglycan, thereby reducing the number of available binding sites for TGFβ2 on the cell surface. The mechanism by which inhibin-A induces betaglycan internalization is clathrin independent, making it distinct from the mechanism by which TGFβ ligands themselves induce betaglycan internalization. These data indicate that inhibin can specifically antagonize TGFβ2 signaling in cellular contexts where surface expression of betaglycan is limiting and provide a novel mechanism for activin-independent phenotypes in Inha−/− mice.
MAPK/Erk-dependent phosphorylation of synapsin mediates formation of functional synapses and short-term homosynaptic plasticity
Authors: Giachello Carlo Natale Giuseppe , Fiumara Ferdinando , Giacomini Caterina , Corradi Anna , Milanese Chiara , Ghirardi Mirella , Benfenati Fabio , Montarolo Pier Giorgio
Published: February 2010

MAPK/Erk is a protein kinase activated by neurotrophic factors involved in synapse formation and plasticity, which acts at both the nuclear and cytoplasmic level. Synapsin proteins are synaptic-vesicle-associated proteins that are well known to be MAPK/Erk substrates at phylogenetically conserved sites. However, the physiological role of MAPK/Erk-dependent synapsin phosphorylation in regulating synaptic formation and function is poorly understood. Here, we examined whether synapsin acts as a physiological effector of MAPK/Erk in synaptogenesis and plasticity. To this aim, we developed an in vitro model of soma-to-soma paired Helix B2 neurons, that establish bidirectional excitatory synapses. We found that the formation and activity-dependent short-term plasticity of these synapses is dependent on the MAPK/Erk pathway. To address the role of synapsin in this pathway, we generated non-phosphorylatable and pseudo-phosphorylated Helix synapsin mutants at the MAPK/Erk sites. Overexpression experiments revealed that both mutants interfere with presynaptic differentiation, synapsin clustering, and severely impair post-tetanic potentiation, a form of short-term homosynaptic plasticity. Our findings show that MAPK/Erk-dependent synapsin phosphorylation has a dual role both in the establishment of functional synaptic connections and their short-term plasticity, indicating that some of the multiple extranuclear functions of MAPK/Erk in neurons can be mediated by the same multifunctional presynaptic target.
GSK-3β promotes cell survival by modulating Bif-1-dependent autophagy and cell death
Authors: Yang Jun , Takahashi Yoshinori , Cheng Erdong , Liu Jihong , Terranova Paul F. , Zhao Bin , Thrasher J. Brantley , Wang Hong-Gang , Li Benyi
Published: February 2010

Glycogen synthase kinase 3 beta (GSK-3β) is constantly active in cells and its activity increases after serum deprivation, indicating that GSK-3β might play a major role in cell survival under serum starvation. In this study, we attempted to determine how GSK-3β promotes cell survival after serum depletion. Under full culture conditions (10% FBS), GSK-3β inhibition with chemical inhibitors or siRNAs failed to induce cell death in human prostate cancer cells. By contrast, under conditions of serum starvation, a profound necrotic cell death was observed as evidenced by cellular morphologic features and biochemical markers. Further analysis revealed that GSK-3β-inhibition-induced cell death was in parallel with an extensive autophagic response. Interestingly, blocking the autophagic response switched GSK-3β-inhibition-induced necrosis to apoptotic cell death. Finally, GSK-3β inhibition resulted in a remarkable elevation of Bif-1 protein levels, and silencing Bif-1 expression abrogated GSK-3β-inhibition-induced autophagic response and cell death. Taken together, our study suggests that GSK-3β promotes cell survival by modulating Bif-1-dependent autophagic response and cell death.
Dynamic pull-in instability of electrostatically actuated beams incorporating Casimir and van der Waals forces
Authors: Moghimi Zand M , Ahmadian M T
Published: February 2010

In this study, influences of intermolecular forces on the dynamic pull-in instability of electrostatically actuated beams are investigated. The effects of midplane stretching, electrostatic actuation, fringing fields, and intermolecular forces are considered. The boundary conditions of the beams are clamped—free and clamped—clamped. A finite-element model is developed to discretize the governing equations, and Newmark time discretization is then employed to solve the discretized equations. The static pull-in instability is investigated to validate the model. Finally, dynamic pull-in instability of cantilevers and double-clamped beams are studied considering the Casimir and van der Waals effects. The results indicate that by increasing the Casimir and van der Waals effects, the effect of inertia on pull-in values considerably increases.
Transonic Moist Air Flow around a Symmetric Disc Butterfly Valve with Non-Equilibrium Condensation
Authors: Hasan A B M T , Matsuo S , Setoguchi T , Kim H-D
Published: February 2010

Transonic flow around a symmetric disc butterfly valve is associated with the appearance of shock waves on valve surfaces. In this case, the interaction between shock waves and boundary layers becomes complex and thus generates the flow-induced aerodynamic instability. In the transonic or supersonic flow where vapour is contained in the main flow, the rapid expansion of the flow may give rise to non-equilibrium condensation. In the present study, the effect of non-equilibrium condensation of moist air on the shock-induced flow field oscillation around a butterfly valve was investigated numerically. The results showed that in cases with non-equilibrium condensation, the flow field aerodynamic instabilities such as root mean square of pressure oscillation and shock-induced oscillation frequency are reduced significantly compared with those without the non-equilibrium condensation. Moreover, the total pressure loss increases and the vortex shedding frequency is reduced with non-equilibrium condensation.
A vibration and buckling investigation of two-layered functionally graded cylindrical structures
Authors: Sepiani H A , Rastgoo A , Karimipour H , Naei M H
Published: February 2010

This work investigates the free vibration and buckling of a two-layered cylindrical shell structure made of an elastic embedded functionally graded (FG) shell subjected to combined static and periodic axial forces. Such structures are widely used in chemical and nuclear reactors, space and aerial industries, and so on. Material properties of an FG cylindrical shell are considered to be temperature dependent and graded in the thickness direction according to a power-law distribution in terms of the volume fractions of the constituents. Theoretical formulations are presented based on two different methods of the first-order shear deformation theory considering the transverse shear strains and the rotary inertias and the classical shell theory. The results obtained show that the effect of transverse shear and rotary inertias on free vibration of an FG cylindrical shell is dependent on the material composition, deformation mode, and geometry parameters of the shells. It is concluded that the application of an outer elastic layer increases elastic stability.
The bifurcation and chaos of a gear pair system based on a strongly non-linear rotor—bearing system
Authors: Chang-Jian C-W
Published: February 2010

A systematic analysis of the dynamic behaviours of a gear pair system based on a rotor—bearing system under strongly non-linear effects (i.e. non-linear suspension effect, non-linear oil-film force, non-linear rub-impact force, and non-linear gear mesh force) is presented in this study. The dynamic orbits of the system are observed using bifurcation diagrams plotted using the dimensionless unbalance coefficient, the dimensionless damping coefficient, and the dimensionless rotational speed ratio as control parameters. The onset of chaotic motion is specified from the phase diagrams, power spectra, Poincaré maps, Lyapunov exponents, and fractal dimension of the system. There exists various forms of periodic, quasi-periodic, and chaotic motions at different bifurcation parameters. The simulation results also found that highly non-periodic motions do exist in gear—rotor—bearing systems under those non-linear effects. The results presented in this study provide a better understanding of the operating conditions under which undesirable dynamic motion takes place in a gear—bearing system; they would therefore serve as a useful source of reference for engineers in designing and controlling such systems.
Research on the Order Selection of the Autoregressive Modelling for Rolling Bearing Diagnosis
Authors: Cong F , Chen J , Dong G
Published: February 2010

The article does a research on the order selection of the autoregressive (AR) model for the rolling element bearings. First, the model of the signal that matches the one introduced by McFadden is considered. To clearly describe it, here it is called the resonance damping model. It is shown that the impulses generated by a fault will cause structure resonance and soon decay with a periodic mode. As the AR process based on the prediction theory has an ability to recognize the periodic (quasi-periodic) part, it is possible to pick out the damping part that is a quasi-periodic component. Because of the background noise, the damping part cannot be recognized if the component decays to be buried into noise absolutely. Hence the optimal order should be the number of points contained by the process, which is the maximum length of the periodic damping part that the AR model can recognize. That is to say, the process should last until the resonance damping part is buried into noise completely. Then an experiment to validate the method is carried out and success is achieved in the fault diagnosis of real rolling bearings. In the end, it is concluded that the optimal order has a high ability for noise cancellation for rolling element bearing diagnosis.
Investigation on the Effects of Various Swirl Generators on Heat Transfer and Fluid Flow in Decaying Swirling Flows
Authors: Ahmadvand M , Najafi A F , Shahidinejad S
Published: February 2010

Influences of three typical vortex generators on flow pattern and ensuing heat transfer augmentation were investigated and compared at similar Re and swirl numbers inlet conditions. Studied swirlers such as propeller swirlers, jet-type swirlers, and rotating honeycombs were installed at the pipe inlet. Reynolds number ranges from 10000 to 30000. Swirlers were set on the swirl numbers 1.4, 0.89, and 0.52, which were obtained by propellers. This study has been carried out under uniform heat flux condition and air was employed as the working fluid. The obtained results provide the individual effects of each swirler configuration on mean flow and turbulence distribution as well as on enhancement of heat transfer. Considering S=1.4, jet-type swirlers pointed 133 per cent Nu enhancement compared to axial flow, whereas propellers and rotating honeycombs approached 105 per cent and 79 per cent, respectively. For S=0.89, relative treatment has been changed and propellers with 70 per cent Nu augmentation demonstrated tip-top performance behind of which other swirlers lined. By decreasing the swirl number, approximately closer heat performances were represented from all swirler configurations. Comparison of the results of various swirlers exhibited that Re and swirl numbers are not generally sufficient to determine the swirling flow characteristics and each swirler confirms an individual flow quality.
A numerical study using Hermitian cubic spline wavelets for the analysis of shafts
Authors: Xiang J W , Long J Q , Jiang Z S
Published: February 2010

Shafts are the main component of rotating machinery. The key problem for designing this kind of machine is how to accurately compute its dynamic characteristic. By using Hermite cubic spline wavelets on the interval, a multi-scale wavelet-based numerical method is proposed. For the orthogonal characteristic of the wavelet bases with respect to the given inner product, the corresponding multi-scale equations will be decoupled across scales partially and suit for nesting approximation using the lifting scheme of the wavelet numerical method. The present method is verified by some examples in the literatures. It shows that the proposed method has high precision and can be applied to analyse dynamic characteristic of shafts.
Robotic colorectal surgery: Where are we right now?
Authors: Kang J , Lee K Y
Published: February 2010

Minimally invasive surgery has become mainstream in surgical management of colorectal disease. Based on evidence of oncologic safety and benefit to patients, laparoscopic colorectal surgery is regarded as a successful alternative to open surgery. Since the introduction of the da Vinci® system as another tool for minimally invasive surgery, there have been several reports regarding the feasibility and safety of the system. The authors looked at their experience with 412 robotic colorectal surgeries and found that it was feasible and safe. Incidence of operation-related morbidity was around 11 per cent and system-related problems were 2.4 per cent. There was no operation-related or system-related mortality. From a technological perspective, robotic surgery has several advantages over laparoscopic surgery, including a magnifying view with a three-dimensional image, a stable camera platform, and instruments with Endowrist® technology that allow for seven degrees of freedom of movement. However, there is still room for improvement. The revolution of robotic technology can aid in the realization of a dream: a smaller, cheaper, and more sophisticated robotic system, which will further facilitate the widespread application of robotic surgery to colorectal disease.
Dependence of the dynamic properties of elastohydrodynamic liquids on temperature and pressure (volume)
Authors: Bair S
Published: February 2010

Shear viscosity is an essential property of elastohydrodynamic lubrication (EHL) liquids. Relaxation times that govern shear dependence of viscosity, time-dependent shear response, and time-dependent bulk behaviour all scale with temperature and pressure in the same way as does the low-shear viscosity. An accurate description of the temperature, pressure, and shear dependence of viscosity has, however, been missing from EHL analysis since the very beginning of the field resulting in many invalid conclusions. In this article, a generalized version of the Stickel plot is introduced and many empirical models are placed in their relevant region of the temperature and pressure domains by showing where they belong on the Stickel plot. The models that are capable of predicting both temperature and pressure responses are discussed in terms of scaling parameters and an example of a mineral oil from the 1953 ASME viscosity report is used to demonstrate the utility of the scaling parameter models. The Stickel analysis is shown to be extremely useful in identifying the appropriate scaling function.
Design and construction of large-area flexible printed-circuit automotive electrical interconnection harnesses
Authors: Webb D P , Jaggernauth W A , Cottrill M C W , Palmer P J , West A A , Conway P P
Published: February 2010

The replacement of automotive wiring harnesses with large-area flexible printed circuits (FPCs) would help to reduce the vehicle weight and emissions. To help clarify what a future large-area FPC interconnection harness should be capable of, a detailed design exercise to meet the engineering specification of the instrument panel wiring harness of a specific midrange passenger car was carried out. To demonstrate the added value of using an FPC, intelligence in the form of active circuitry was incorporated in the designs.

Two generic architectural concepts were pursued. The first, a single large-area FPC, supported the wire harness geometry, all point-to-point interconnections, and current ratings up to 4 A. However, the panel size was too large to be manufactured on existing automotive FPC process lines. The second, intended to be a collection of smaller FPCs that could be manufactured on existing automotive FPC process lines, was found not to be practical as originally conceived.

A physical implementation of the single large-area FPC design was made in stages at different company sites using various pieces of equipment, some of which are not normally used for FPC or electrical circuit manufacture. Modified versions of the equipment could be used to create a large-area automotive FPC manufacturing line.
Performance evaluation of high-contact-ratio gearing for combat tracked vehicles ― A case study
Authors: Sivakumar P , Gopinath K , Sundaresh S
Published: February 2010

To enhance the mobility of combat tracked vehicles, a high-powered compact power pack is crucial. To achieve this goal, it is planned to apply the concept of high-contact-ratio (HCR) gearing to an independent final-drive planetary gear assembly of the tracked vehicle transmission. Before applying the concept to the final-drive, the performances of both normal-contact-ratio (NCR) and HCR conventional parallel shaft spur gearing systems are evaluated and compared. The results show that, for the same torque, HCR gears are subjected to lower loads and endure almost double the life of NCR gears. This reveals that an HCR gear can transmit more power for the same size. Furthermore, the power loss, vibration, and noise level of the HCR gearing are significantly lower than those of the NCR gearing. The proven results of the case study have encouraged the replacement of the existing NCR gearing with the HCR gearing for the final-drive planetary assembly of the combat tracked vehicle for evaluation.
Non-linear dynamic response structural optimization of an automobile frontal structure using equivalent static loads
Authors: Jeong S-B , Yoon S , Xu S , Park G-J
Published: February 2010

Although the capability of the computer has been developed and numerical algorithms have been advanced, automobile crash optimization is still quite difficult owing to high non-linearity and numerical cost. Therefore, metamodel-based optimization methods have been frequently utilized in crashworthiness optimization. However, the methods have various limits on the number of design variables and precision. The equivalent-static-loads (ESLs) method has been proposed to overcome the limitations. ESLs are static loads which generate the same displacement field in static analysis as the displacement field at each time step in non-linear dynamic analysis; they are used as the external loads for linear static response optimization. The results of linear static response optimization are utilized to update the design, and non-linear dynamic analysis is performed again with the updated design. The process proceeds in an iterative manner until the convergence criteria are satisfied. From various research studies on the ESLs method, it has been demonstrated that the ESLs method is fairly useful. An automobile frontal structure is optimized for the pendulum test. The optimization problem is formulated with many design variables including displacement, velocity, and acceleration constraints. A method is proposed for handling the velocity and acceleration constraints by using the finite difference method. In a numerical analysis of the pendulum test, the velocity and acceleration are extremely non-linear and noisy. Thus, a filtering technique is utilized for the displacement, velocity, and acceleration curves. LS-DYNA is used for non-linear dynamic analysis, and NASTRAN is used for linear static response optimization and generation of ESLs. The SAE 60 filter in LS-PRE/POST is used to filter the displacement response. A program is developed for interfacing the two systems.
New efficient methods for powertrain vibration analysis
Authors: Novotny P , Pistek V
Published: February 2010

The paper presents new efficient computational and experimental approaches to a powertrain vibration analysis. A complex computational model of a powertrain (a virtual engine) is a powerful tool for the solution of structural, thermal, and fatigue problems. The virtual engine results have to provide answers to different questions, mainly those concerning the area of noise, vibration, and fatigue components. The paper also includes a description of a fast algorithm for hydrodynamic solution of a slide bearing incorporating pin tilting influences. The main contribution is the fact that all models, namely those of the cranktrain, valvetrain, gear timing mechanism and fuel injection pump, are solved simultaneously, using a complex computational model. Synchronous solutions can have a fundamental effect on the results of powertrain dynamics solutions. Additionally, it might help influences between powertrain parts to be understood. The virtual engine is assembled as well as numerically solved as a multi-body system. Virtual engine results are validated by measurements on a diesel in-line six-cylinder engine.
Optimal vehicle dynamics controller design using a four-degrees-of-freedom model
Authors: Mashadi B , Majidi M , Pourabdollah Dizaji H
Published: February 2010

A yaw moment control system is developed for a front-wheel-drive vehicle utilizing two brushless d.c. electric motors embedded in the rear wheels. An optimal linear quadratic regulator (LQR) controller is employed by using a four-degrees-of-freedom (4DOF) linear vehicle model. The objective is to include important effects of roll and steering into the controller design. A two-degrees-of-freedom (2DOF) optimal LQR model is also used for comparison purposes. For the simulation of system at different conditions, a non-linear eight-degrees-of-freedom vehicle model is used. The performances of the controlled vehicle have been compared with those of the uncontrolled vehicle in order to investigate the effectiveness of the proposed controllers. Simulation results indicate that, in normal situations where the uncontrolled vehicle becomes unstable, the controlled vehicles with both 2DOF and 4DOF controllers show stable responses. In severe conditions, however, even the 2DOF controller fails to stabilize the vehicle, whereas the 4DOF controller is successful in maintaining the stability of vehicle.
Integrated control of braking energy regeneration and pneumatic anti-lock braking
Authors: Zhang J-Z , Chen X , Zhang P-J
Published: February 2010

This paper mainly focuses on integrated control of the brake system of a hybrid electric vehicle, i.e. the integration of friction braking and regenerative braking during anti-lock braking control and series brake blending during normal deceleration. Based on a series regenerative braking system, the structure of an integrated brake system is proposed. The models of each part of a hybrid electric bus are built in MATLABÆ Simulink, taking authorized articles as references. A test bench with the original pneumatic brake system of a bus is also built to carry out hardware-in-the-loop (HIL) tests of the integrated brake system and to study the characteristics of the system better. The integrated control strategy is proposed on the basis of a pneumatic anti-lock braking strategy. Simulation results show that the participation of regenerative braking in the anti-lock braking control can be beneficial to both the ride comfort and the braking performance of the vehicle. HIL test results validate the results of the simulations. An integrated brake controller is designed and made to carry out the control strategies on board. A field in which further research could be carried out is also proposed.