bluuebunny/crossref_metadata_2025 huggingface dataset:
GEM-TREND: a web tool for gene expression data mining toward relevant network discovery
Authors: Feng Chunlai , Araki Michihiro , Kunimoto Ryo , Tamon Akiko , Makiguchi Hiroki , Niijima Satoshi , Tsujimoto Gozoh , Okuno Yasushi
Published: September 2009

Background

DNA microarray technology provides us with a first step toward the goal of uncovering gene functions on a genomic scale. In recent years, vast amounts of gene expression data have been collected, much of which are available in public databases, such as the Gene Expression Omnibus (GEO). To date, most researchers have been manually retrieving data from databases through web browsers using accession numbers (IDs) or keywords, but gene-expression patterns are not considered when retrieving such data. The Connectivity Map was recently introduced to compare gene expression data by introducing gene-expression signatures (represented by a set of genes with up- or down-regulated labels according to their biological states) and is available as a web tool for detecting similar gene-expression signatures from a limited data set (approximately 7,000 expression profiles representing 1,309 compounds). In order to support researchers to utilize the public gene expression data more effectively, we developed a web tool for finding similar gene expression data and generating its co-expression networks from a publicly available database.

Results

GEM-TREND, a web tool for searching gene expression data, allows users to search data from GEO using gene-expression signatures or gene expression ratio data as a query and retrieve gene expression data by comparing gene-expression pattern between the query and GEO gene expression data. The comparison methods are based on the nonparametric, rank-based pattern matching approach of Lamb et al. (Science 2006) with the additional calculation of statistical significance. The web tool was tested using gene expression ratio data randomly extracted from the GEO and with in-house microarray data, respectively. The results validated the ability of GEM-TREND to retrieve gene expression entries biologically related to a query from GEO. For further analysis, a network visualization interface is also provided, whereby genes and gene annotations are dynamically linked to external data repositories.

Conclusion

GEM-TREND was developed to retrieve gene expression data by comparing query gene-expression pattern with those of GEO gene expression data. It could be a very useful resource for finding similar gene expression profiles and constructing its gene co-expression networks from a publicly available database. GEM-TREND was designed to be user-friendly and is expected to support knowledge discovery. GEM-TREND is freely available at http://cgs.pharm.kyoto-u.ac.jp/services/network.
Multigene expression of protein complexes by iterative modification of genomic Bacmid DNA
Authors: Noad Rob J , Stewart Meredith , Boyce Mark , Celma Cristina C , Willison Keith R , Roy Polly
Published: September 2009

Background

Many cellular multi-protein complexes are naturally present in cells at low abundance. Baculovirus expression offers one approach to produce milligram quantities of correctly folded and processed eukaryotic protein complexes. However, current strategies suffer from the need to produce large transfer vectors, and the use of repeated promoter sequences in baculovirus, which itself produces proteins that promote homologous recombination. One possible solution to these problems is to construct baculovirus genomes that express each protein in a complex from a separate locus within the viral DNA. However current methods for selecting such recombinant genomes are too inefficient to routinely modify the virus in this way.

Results

This paper reports a method which combines the lambda red and bacteriophage P1 Cre-recombinase systems to efficiently generate baculoviruses in which protein complexes are expressed from multiple, single-locus insertions of foreign genes. This method is based on an 88 fold improvement in the selection of recombinant viruses generated by red recombination techniques through use of a bipartite selection cassette. Using this system, seven new genetic loci were identified in the AcMNPV genome suitable for the high level expression of recombinant proteins. These loci were used to allow the recovery two recombinant virus-like particles with potential biotechnological applications (influenza A virus HA/M1 particles and bluetongue virus VP2/VP3/VP5/VP7 particles) and the mammalian chaperone and cancer drug target CCT (16 subunits formed from 8 proteins).

Conclusion

1. Use of bipartite selections can significantly improve selection of modified bacterial artificial chromosomes carrying baculovirus DNA. Furthermore this approach is sufficiently robust to allow routine modification of the virus genome. 2. In addition to the commonly used p10 and polyhedrin loci, the ctx, egt, 39k, orf51, gp37, iap2 and odv-e56 loci in AcMNPV are all suitable for the high level expression of heterologous genes. 3. Two protein, four protein and eight protein complexes including virus-like particles and cellular chaperone complexes can be produced using the new approach.
Protective effect of transgenic expression of porcine heat shock protein 70 on hypothalamic ischemic and oxidative damage in a mouse model of heatstroke
Authors: Chen Zhih-Cherng , Wu Wen-Shian , Lin Mao-Tsun , Hsu Chuan-Chih
Published: September 2009

Background

Transgenic mice have been used to examine the role of heat shock protein (HSP)72 in experimental heatstroke. Transgenic mice that were heterozygous for a porcine HSP70β gene ([+] HSP72) and transgene-negative littermate controls ([-] HSP72), under pentobarbital sodium anesthesia, were subjected to heat stress to induce heatstroke. It was found that the overexpression of HSP72 in multiple organs improved survival during heatstroke by reducing hypotension and cerebral ischemia and damage in mice. Herein we attempted to further assess the effect of heat exposure on thermoregulatory function, hypothalamic integration, and survival in unrestrained, unanesthetized [+]HSP72 and compare with those of [-]HSP72. In this research with the transgenic mice, we first conducted several biochemical, physiologic and histological determinations and then investigated the beneficial effects of HSP72 overexpression on the identified hypothalamic deficits, thermoregulatory dysfunction, and mortality during heatstroke.

Results

We report here that when [-]HSP72 mice underwent heat stress (ambient temperature 42.4°C for 1 h), the fraction survival and core temperature at 4 h after heat stress were found to be 0 of 12 and 34.2°C ± 0.4°C, respectively. Mice that survived to day 4 after heat stress were considered as survivors. In [+]HSP72 mice, when exposed to the same heat treatment, both fraction survival and core temperature values were significantly increased to new values of 12/12 and 37.4°C ± 0.3°C, respectively. Compared to [-]HSP mice, [+]HSP72 mice displayed lower hypothalamic values of cellular ischemia (e.g., glutamate and lactate-to-pyruvate ratio) and damage (e.g., glycerol) markers, pro-oxidant enzymes (e.g., lipid peroxidation and glutathione oxidation), pro-inflammatory cytokines (e.g., interleukin-1beta and tumor necrosis factor-alpha), and neuronal damage score evaluated 4 h after heat stress. In contrast, [+]HSP72 mice had higher hypothalamic values of antioxidant defences (e.g., glutathione peroxidase and glutathione reductase), ATP, and HSP72 expression.

Conclusion

This study indicates that HSP72 overexpression appears to be critical to the development of thermotolerance and protection from heat-induced hypothalamic ischemic and oxidative damage.
Otitis media: a genome-wide linkage scan with evidence of susceptibility loci within the 17q12 and 10q22.3 regions
Authors: Casselbrant Margaretha L , Mandel Ellen M , Jung Jeesun , Ferrell Robert E , Tekely Kathleen , Szatkiewicz Jin P , Ray Amrita , Weeks Daniel E
Published: September 2009

Background

Otitis media (OM) is a common worldwide pediatric health care problem that is known to be influenced by genetics. The objective of our study was to use linkage analysis to map possible OM susceptibility genes.

Methods

Using a stringent diagnostic model in which only those who underwent tympanostomy tube insertion at least once for recurrent/persistent OM are considered affected, we have carried out a genome-wide linkage scan using the 10K Affymetrix SNP panel. We genotyped 403 Caucasian families containing 1,431 genotyped individuals and 377 genotyped affected sib pairs, and 26 African American families containing 75 genotyped individuals and 27 genotyped affected sib pairs. After careful quality control, non-parametric linkage analysis was carried out using 8,802 SNPs.

Results

In the Caucasian-only data set, our most significant linkage peak is on chromosome 17q12 at rs226088 with a p-value of 0.00007. Other peaks of potential interest are on 10q22.3 (0.00181 at rs1878001), 7q33 (0.00105 at rs958408), 6p25.1 (0.00261 at rs554653), and 4p15.2 (0.00301 at rs2133507). In the combined Caucasian and African American dataset, the 10q22.3 peak becomes more significant, with a minimal p-value of 0.00026 at rs719871. Family-based association testing reveals signals near previously implicated genes: 513 kb from SFTPA2 (10q22.3), 48 kb from IFNG (12q14), and 870 kb from TNF (6p21.3).

Conclusion

Our scan does not provide evidence for linkage in the previously reported regions of 10q26.3 and 19q13.43. Our best-supported linkage regions may contain susceptibility genes that influence the risk for recurrent/persistent OM. Plausible candidates in 17q12 include AP2B1, CCL5, and a cluster of other CCL genes, and in 10q22.3, SFTPA2.
Biomarkers of apoptosis and survival in esophageal squamous cell carcinoma
Authors: Takikita Mikiko , Hu Nan , Shou Jian-zhong , Wang Quan-Hong , Giffen Carol , Taylor Philip R , Hewitt Stephen M
Published: September 2009

Background

Cancer of the esophagus is a deadly malignancy, and development of biomarkers that predict survival is an urgent need. The apoptotic pathways have been hypothesized as important in progression of esophageal squamous cell carcinoma (ESCC). We investigated a panel of proteins that regulate apoptosis as candidate of biomarkers of prognosis in ESCC.

Methods

Tissue microarray (TMA) including 313 surgically-resected cases of ESCC specimens was built for immunohistochemical interrogation. We evaluated seven genes in the FasL-Fas apoptotic pathway - FasL, Fas, FAS-associated death domain protein (FADD), phosphorylated-FADD, and caspase 8 and 10, and the antiapoptotic protein bcl-2. We studied pathway integrity and relations to risk and clinical factors, and determined the prognostic significance of each marker.

Results

Five markers showed strong inter-marker correlations (r ≥ 0.28, p < 0.001), including FasL, Fas, FADD, and caspases 8 and 10. FasL and FADD also showed modest correlations with one or more cancer risk factors, but none of the markers was significantly associated with either tumor stage or lymph node metastasis, the only two clinical factors that predicted survival in these ESCC cases. Multivariate-adjusted proportional hazard regression models showed no association between protein expression and risk of death for any of the seven markers examined.

Conclusion

Individual biomarkers in the apoptosis pathway do not appear to predict survival of patients with ESCC.
Adaptation and evaluation of the bottle assay for monitoring insecticide resistance in disease vector mosquitoes in the Peruvian Amazon
Authors: Zamora Perea Elvira , Balta León Rosario , Palomino Salcedo Miriam , Brogdon William G , Devine Gregor J
Published: September 2009

Background

The purpose of this study was to establish whether the "bottle assay", a tool for monitoring insecticide resistance in mosquitoes, can complement and augment the capabilities of the established WHO assay, particularly in resource-poor, logistically challenging environments.

Methods

Laboratory reared Aedes aegypti and field collected Anopheles darlingi and Anopheles albimanus were used to assess the suitability of locally sourced solvents and formulated insecticides for use with the bottle assay. Using these adapted protocols, the ability of the bottle assay and the WHO assay to discriminate between deltamethrin-resistant Anopheles albimanus populations was compared. The diagnostic dose of deltamethrin that would identify resistance in currently susceptible populations of An. darlingi and Ae. aegypti was defined. The robustness of the bottle assay during a surveillance exercise in the Amazon was assessed.

Results

The bottle assay (using technical or formulated material) and the WHO assay were equally able to differentiate deltamethrin-resistant and susceptible An. albimanus populations. A diagnostic dose of 10 μg a.i./bottle was identified as the most sensitive discriminating dose for characterizing resistance in An. darlingi and Ae. aegypti. Treated bottles, prepared using locally sourced solvents and insecticide formulations, can be stored for > 14 days and used three times. Bottles can be stored and transported under local conditions and field-assays can be completed in a single evening.

Conclusion

The flexible and portable nature of the bottle assay and the ready availability of its components make it a potentially robust and useful tool for monitoring insecticide resistance and efficacy in remote areas that require minimal cost tools.
Modelling the progression of pandemic influenza A (H1N1) in Vietnam and the opportunities for reassortment with other influenza viruses
Authors: Boni Maciej F , Manh Bui Huu , Thai Pham Quang , Farrar Jeremy , Hien Tran Tinh , Hien Nguyen Tran , Van Kinh Nguyen , Horby Peter
Published: September 2009

Background

A novel variant of influenza A (H1N1) is causing a pandemic and, although the illness is usually mild, there are concerns that its virulence could change through reassortment with other influenza viruses. This is of greater concern in parts of Southeast Asia, where the population density is high, influenza is less seasonal, human-animal contact is common and avian influenza is still endemic.

Methods

We developed an age- and spatially-structured mathematical model in order to estimate the potential impact of pandemic H1N1 in Vietnam and the opportunities for reassortment with animal influenza viruses. The model tracks human infection among domestic animal owners and non-owners and also estimates the numbers of animals may be exposed to infected humans.

Results

In the absence of effective interventions, the model predicts that the introduction of pandemic H1N1 will result in an epidemic that spreads to half of Vietnam's provinces within 57 days (interquartile range (IQR): 45-86.5) and peaks 81 days after introduction (IQR: 62.5-121 days). For the current published range of the 2009 H1N1 influenza's basic reproductive number (1.2-3.1), we estimate a median of 410,000 cases among swine owners (IQR: 220,000-670,000) with 460,000 exposed swine (IQR: 260,000-740,000), 350,000 cases among chicken owners (IQR: 170,000-630,000) with 3.7 million exposed chickens (IQR: 1.9 M-6.4 M), and 51,000 cases among duck owners (IQR: 24,000 - 96,000), with 1.2 million exposed ducks (IQR: 0.6 M-2.1 M). The median number of overall human infections in Vietnam for this range of the basic reproductive number is 6.4 million (IQR: 4.4 M-8.0 M).

Conclusion

It is likely that, in the absence of effective interventions, the introduction of a novel H1N1 into a densely populated country such as Vietnam will result in a widespread epidemic. A large epidemic in a country with intense human-animal interaction and continued co-circulation of other seasonal and avian viruses would provide substantial opportunities for H1N1 to acquire new genes.
Identification of a high incidence region for retroviral vector integration near exon 1 of the LMO2locus
Authors: Yamada Koichiro , Tsukahara Tomonori , Yoshino Kazuhisa , Kojima Katsuhiko , Agawa Hideyuki , Yamashita Yuki , Amano Yuji , Hatta Mariko , Matsuzaki Yasunori , Kurotori Naoki , Wakui Keiko , Fukushima Yoshimitsu , Osada Ryosuke , Shiozawa Tanri , Sakashita Kazuo , Koike Kenichi , Kumaki Satoru , Tanaka Nobuyuki , Takeshita Toshikazu
Published: September 2009

Therapeutic retroviral vector integration near the oncogene LMO2 is thought to be a cause of leukemia in X-SCID gene therapy trials. However, no published studies have evaluated the frequency of vector integrations near exon 1 of the LMO2 locus. We identified a high incidence region (HIR) of vector integration using PCR techniques in the upstream region close to the LMO2 transcription start site in the TPA-Mat T cell line. The integration frequency of the HIR was one per 4.46 × 104 cells. This HIR was also found in Jurkat T cells but was absent from HeLa cells. Furthermore, using human cord blood-derived CD34+ cells we identified a HIR in a similar region as the TPA-Mat T cell line. One of the X-linked severe combined immunodeficiency (X-SCID) patients that developed leukemia after gene therapy had a vector integration site in this HIR. Therefore, the descriptions of the location and the integration frequency of the HIR presented here may help us to better understand vector-induced leukemogenesis.
Chondrogenic differentiation potential of osteoarthritic chondrocytes and their possible use in matrix-associated autologous chondrocyte transplantation
Authors: Dehne Tilo , Karlsson Camilla , Ringe Jochen , Sittinger Michael , Lindahl Anders
Published: September 2009

Introduction

Autologous chondrocyte transplantation (ACT) is a routine technique to regenerate focal cartilage lesions. However, patients with osteoarthritis (OA) are lacking an appropriate long-lasting treatment alternative, partly since it is not known if chondrocytes from OA patients have the same chondrogenic differentiation potential as chondrocytes from donors not affected by OA.

Methods

Articular chondrocytes from patients with OA undergoing total knee replacement (Mankin Score > 3, Ahlbäck Score > 2) and from patients undergoing ACT, here referred to as normal donors (ND), were isolated applying protocols used for ACT. Their chondrogenic differentiation potential was evaluated both in high-density pellet and scaffold (Hyaff-11) cultures by histological proteoglycan assessment (Bern Score) and immunohistochemistry for collagen types I and II. Chondrocytes cultured in monolayer and scaffolds were subjected to gene expression profiling using genome-wide oligonucleotide microarrays. Expression data were verified by using real-time PCR.

Results

Chondrocytes from ND and OA donors demonstrated accumulation of comparable amounts of cartilage matrix components, including sulphated proteoglycans and collagen types I and II. The mRNA expression of cartilage markers (ACAN, COL2A1, COMP, CRTL1, SOX9) and genes involved in matrix synthesis (BGN, CILP2, COL9A2, COL11A1, TIMP4) was highly induced in 3D cultures of chondrocytes from both donor groups. Genes associated with hypertrophic or OA cartilage (ALPL, COL1A1, COL3A1, COL10A1, MMP13, POSTN, PTH1R, RUNX2) were not significantly regulated between the two groups of donors. The expression of 661 genes, including COMP, FN1, and SOX9, was differentially regulated between OA and ND chondrocytes cultured in monolayer. During scaffold culture, the differences diminished between the OA and ND chondrocytes, and only 184 genes were differentially regulated.

Conclusions

Only few genes were differentially expressed between OA and ND chondrocytes in Hyaff-11 culture. The risk of differentiation into hypertrophic cartilage does not seem to be increased for OA chondrocytes. Our findings suggest that the chondrogenic capacity is not significantly affected by OA, and OA chondrocytes fulfill the requirements for matrix-associated ACT.
Mechanical effects of surgical procedures on osteochondral grafts elucidated by osmotic loading and real-time ultrasound
Authors: Hattori Koji , Uematsu Kota , Matsumoto Tomohiro , Ohgushi Hajime
Published: September 2009

Introduction

Osteochondral grafts have become popular for treating small, isolated and full-thickness cartilage lesions. It is recommended that a slightly oversized, rather than an exact-sized, osteochondral plug is transplanted to achieve a tight fit. Consequently, impacting forces are required to insert the osteochondral plug into the recipient site. However, it remains controversial whether these impacting forces affect the biomechanical condition of the grafted articular cartilage. The present study aimed to investigate the mechanical effects of osteochondral plug implantation using osmotic loading and real-time ultrasound.

Methods

A full-thickness cylindrical osteochondral defect (diameter, 3.5 mm; depth, 5 mm) was created in the lateral lower quarter of the patella. Using graft-harvesting instruments, an osteochondral plug (diameter, 3.5 mm as exact-size or 4.5 mm as oversize; depth, 5 mm) was harvested from the lateral upper quarter of the patella and transplanted into the defect. Intact patella was used as a control. The samples were monitored by real-time ultrasound during sequential changes of the bathing solution from 0.15 M to 2 M saline (shrinkage phase) and back to 0.15 M saline (swelling phase). For cartilage sample assessment, three indices were selected, namely the change in amplitude from the cartilage surface (amplitude recovery rate: ARR) and the maximum echo shifts from the cartilage surface and the cartilage-bone interface.

Results

The ARR is closely related to the cartilage surface integrity, while the echo shifts from the cartilage surface and the cartilage-bone interface are closely related to tissue deformation and NaCl diffusion, respectively. The ARR values of the oversized plugs were significantly lower than those of the control and exact-sized plugs. Regarding the maximum echo shifts from the cartilage surface and the cartilage-bone interface, no significant differences were observed among the three groups.

Conclusions

These findings demonstrated that osmotic loading and real-time ultrasound were able to assess the mechanical condition of cartilage plugs after osteochondral grafting. In particular, the ARR was able to detect damage to the superficial collagen network in a non-destructive manner. Therefore, osmotic loading and real-time ultrasound are promising as minimally invasive methods for evaluating cartilage damage in the superficial zone after trauma or impact loading for osteochondral grafting.
Brachial artery peak velocity variation to predict fluid responsiveness in mechanically ventilated patients
Authors: Monge García Manuel Ignacio , Gil Cano Anselmo , Díaz Monrové Juan Carlos
Published: September 2009

Introduction

Although several parameters have been proposed to predict the hemodynamic response to fluid expansion in critically ill patients, most of them are invasive or require the use of special monitoring devices. The aim of this study is to determine whether noninvasive evaluation of respiratory variation of brachial artery peak velocity flow measured using Doppler ultrasound could predict fluid responsiveness in mechanically ventilated patients.

Methods

We conducted a prospective clinical research in a 17-bed multidisciplinary ICU and included 38 mechanically ventilated patients for whom fluid administration was planned due to the presence of acute circulatory failure. Volume expansion (VE) was performed with 500 mL of a synthetic colloid. Patients were classified as responders if stroke volume index (SVi) increased ≥ 15% after VE. The respiratory variation in Vpeakbrach (ΔVpeakbrach) was calculated as the difference between maximum and minimum values of Vpeakbrach over a single respiratory cycle, divided by the mean of the two values and expressed as a percentage. Radial arterial pressure variation (ΔPPrad) and stroke volume variation measured using the FloTrac/Vigileo system (ΔSVVigileo), were also calculated.

Results

VE increased SVi by ≥ 15% in 19 patients (responders). At baseline, ΔVpeakbrach, ΔPPrad and ΔSVVigileo were significantly higher in responder than nonresponder patients [14 vs 8%; 18 vs. 5%; 13 vs 8%; P < 0.0001, respectively). A ΔVpeakbrach value >10% predicted fluid responsiveness with a sensitivity of 74% and a specificity of 95%. A ΔPPrad value >10% and a ΔSVVigileo >11% predicted volume responsiveness with a sensitivity of 95% and 79%, and a specificity of 95% and 89%, respectively.

Conclusions

Respiratory variations in brachial artery peak velocity could be a feasible tool for the noninvasive assessment of fluid responsiveness in patients with mechanical ventilatory support and acute circulatory failure.

Trial Registration

ClinicalTrials.gov ID: NCT00890071
Effects on management and outcome of severe sepsis and septic shock patients admitted to the intensive care unit after implementation of a sepsis program: a pilot study
Authors: Girardis Massimo , Rinaldi Laura , Donno Lara , Marietta Marco , Codeluppi Mauro , Marchegiano Patrizia , Venturelli Claudia ,   the 'Sopravvivere alla Sepsi 'group of the Modena-University Hospital
Published: September 2009

Introduction

The application in clinical practice of evidence-based guidelines for the management of patients with severe sepsis/septic shock is still poor in the emergency department, while little data are available for patients admitted to the intensive care unit (ICU). The aim of this study was to evaluate the effect of an in-hospital sepsis program on the adherence to evidence-based guidelines and outcome of patients with severe sepsis/septic shock admitted to the ICU.

Methods

This prospective observational cohort study included 67 patients with severe sepsis/septic shock admitted to a multidisciplinary ICU at a University Hospital from January 2005 to June 2007. Compliance to 5 resuscitation and 4 management sepsis interventions and in-hospital mortality were measured following an educational program on sepsis for physician and nurses of all hospital departments and hospital implementation of a specific protocol for recognition and management of patients with severe sepsis/septic shock, including an early consultation by a skilled 'sepsis team'.

Results

During the study period, the compliance to all 9 interventions increased from 8% to 35% of the patients (P < 0.01). The implementation of resuscitation and management interventions was associated with a lower risk of in-hospital mortality (23% vs 68% and 27% vs 68%, P < 0.01). In the latter 2 semesters, after activation of the 'sepsis team', in-hospital mortality of ICU septic shock patients decreased by about 40% compared with the previous period (32% vs 79%, P < 0.01).

Conclusions

In our experience, an in-hospital sepsis program, including education of health-care personnel and process-changes, improved the adherence to guidelines and the survival rate of patients with severe sepsis/septic shock admitted to the ICU.
mRNA expression profiles show differential regulatory effects of microRNAs between estrogen receptor-positive and estrogen receptor-negative breast cancer
Authors: Cheng Chao , Fu Xuping , Alves Pedro , Gerstein Mark
Published: September 2009

Background

Recent studies have shown that the regulatory effect of microRNAs can be investigated by examining expression changes of their target genes. Given this, it is useful to define an overall metric of regulatory effect for a specific microRNA and see how this changes across different conditions.

Results

Here, we define a regulatory effect score (RE-score) to measure the inhibitory effect of a microRNA in a sample, essentially the average difference in expression of its targets versus non-targets. Then we compare the RE-scores of various microRNAs between two breast cancer subtypes: estrogen receptor positive (ER+) and negative (ER-). We applied this approach to five microarray breast cancer datasets and found that the expression of target genes of most microRNAs was more repressed in ER- than ER+; that is, microRNAs appear to have higher RE-scores in ER- breast cancer. These results are robust to the microRNA target prediction method. To interpret these findings, we analyzed the level of microRNA expression in previous studies and found that higher microRNA expression was not always accompanied by higher inhibitory effects. However, several key microRNA processing genes, especially Ago2 and Dicer, were differentially expressed between ER- and ER+ breast cancer, which may explain the different regulatory effects of microRNAs in these two breast cancer subtypes.

Conclusions

The RE-score is a promising indicator to measure microRNAs' inhibitory effects. Most microRNAs exhibit higher RE-scores in ER- than in ER+ samples, suggesting that they have stronger inhibitory effects in ER- breast cancers.
Effect of strain ageing on the mechanical properties of interstitial-free steels under as-received, heat-treated, and spot-welded conditions for automotive applications
Authors: Bak A , Gündüz S
Published: September 2009

In this study, the artificial ageing behaviour of interstitial-free steels is investigated under as-received, heat-treated, and spot-welded conditions. All the test specimens except those in the as-received condition were austenitized at 950°C for 15min followed by water cooling. Both as-received test pieces and heat-treated test pieces were prestrained by 8 per cent in tension, and then aged at 170°C for 10min, 20min, 40min, 60min, 80min, and 120min. The experimental work revealed that strain ageing takes place in as-received, heat-treated, and spot-welded test pieces. However, strain ageing is more pronounced in heat-treated test pieces and spot-welded heat-treated test pieces, compared with the as-received test pieces and spot-welded as-received test pieces. This is due to the nature of heat treatment and spot welding.
Analysis of the roll properties of a tubular-type torsion beam suspension
Authors: Mun K-J , Kim T-J , Kim Y-S
Published: September 2009

Tubular-type torsion beam rear-suspension systems are widely used in small passenger cars owing to their compactness, light weight, and cost efficiency. It is already known that the roll behaviour of a torsion beam suspension system can be approximated to that of a semitrailing arm suspension system. By this kinematic assumption, analytical equations to obtain the roll centre height, roll steer, and roll camber have already been developed in terms of geometry points. Therefore, this paper proposes an analytical method to calculate the torsional stiffness of a tubular beam from its cross-section area based on the assumption that a tubular beam is a series connection of finite lengths with a constant cross-section. In addition, a potential energy method is proposed to calculate the roll stiffness of a tubular torsion beam suspension system based on considering the bushing stiffness and torsional stiffness of the tubular beam without the use of any commercial computer-aided engineering (CAE) software. The torsional stiffness and roll stiffness predicted using the proposed method showed errors of about 4 per cent and 3.3 per cent respectively, when compared with results from commercial CAE software.
Railway point mechanisms: Condition monitoring and fault detection
Authors: García Márquez F P , Roberts C , Tobias A M
Published: September 2009

Early attempts at monitoring the condition of railway point mechanisms employed simple thresholding techniques to detect faults, but success was limited and there were large numbers of false alarms and missed failures in the field. More recent research using data collected from line-side equipment and lab-based test rigs, though, is suggesting that it should indeed be possible to predict failures with sufficient accuracy and notice to be of genuine use to infrastructure maintainers and owners. This review into state-of-the-art predictive fault detection and diagnosis methods shows how some very different generic models have been tailored to the various types of mechanisms that are in use worldwide. In any specific case, the most appropriate combination of quantitative and qualitative techniques will be determined by the inherent failure modes of the system and the particular conditions under which it operates. Furthermore, it is vital to have a priori knowledge of the symptoms that are observable under fault conditions if diagnosis is to be reliable.
Optimal design of an aeroelastic wing structure with seamless control surfaces
Authors: Perera M , Guo S
Published: September 2009

This article presents an investigation into the concept and optimal design of a lightweight seamless aeroelastic wing (SAW) structure for small air vehicles. Attention has been first focused on the design of a hingeless flexible trailing edge (TE) control surface. Two innovative design features have been created in the SAW TE section: an open sliding TE and a curved beam and disc actuation mechanism. This type of actuated TE section allows for the SAW having a camber change in a desirable shape and minimum control power demand. This design concept has been simulated numerically and demonstrated by a test model. For a small air vehicle of large sweep back wing, it is noted that significant structural weight saving can be achieved. However, further weight saving is mainly restricted by the aeroelastic stability and minimum number of carbon/epoxy plies in a symmetric layup rather than the structural strength. Therefore, subsequent effort was made to optimize the primary wing box structure. The results show that an initial structural weight can be reduced significantly under the strength criterion. The resulting reduction of the wing box stiffness and aeroelastic stability and control effectiveness can be improved by applying the aeroelastic tailoring. Because of the large swept angle and resulting lightweight and highly flexible SAW, geometrical non-linearity and large bending—torsion aeroelastic coupling have been considered in the analysis.
Design, analysis, and manufacturing of a carbon-fibre-reinforced polyetheretherketone slat
Authors: Keck R , Machunze W , Dudenhausen W , Middendorf P
Published: September 2009

Regarding aircrafts, the application of composites within impact endangered areas is unusual. Therefore, an advanced thermoplastic composite slat had been developed with the aim of minimizing weight and manufacturing costs in scheduled series production. The investigation of many manufacturing techniques had been performed as well as integration of new materials. Several generic and full-scale thermoplastic demonstrators were manufactured, using endless fibre-reinforced carbon-fibre-reinforced polyetheretherketone tapes. The critical point, concerning the casting of thick and highly tapered, single curved thermoplastic shells, was identified and new manufacturing methods had been developed. Additionally, the thermoplastic welding process was improved, resulting in a low-cost assembly technique as an alternative to state-of-the-art joining methods. In addition to conventional linear static analysis, dynamic high-velocity impact simulations were carried out. A numerical approach for high-velocity bird strike impact had been developed. The results were used to dimension the residual strength of a damaged slat. Furthermore, a good compliance between the dynamic analysis and the performed tests has been reached. It has been shown that a significant weight reduction is possible by numerical optimization, even if composites are used for impact-sensitive areas.
Fuzzy state noise-driven Kalman filter for sensor fusion
Authors: Chauhan S , Patil C , Sinha M , Halder A
Published: September 2009

This article proposes a fuzzy state noise-driven Kalman filter for sensor fusion to estimate the instantaneous position and attitude of an unmanned air vehicle for navigation purpose. The formulation of the state noise covariance matrix has been carried out using the fuzzy regression method applied to the state residuals. This algorithm has been embedded in the real-time hardware and tested for performance on ground and not in real flight. A comparative study between the proposed and conventional algorithm illustrates its efficacy.
Robust target tracking using distributed unmanned aerial vehicle networks
Authors: Kim Y , Gu D-W , Postlethwaite I
Published: September 2009

In this article, a target tracking scheme for operation in distributed unmanned aerial vehicle (UAV) networks in which sensors may read the target position incorrectly is proposed. The proposed scheme operates two algorithms concurrently: semi-decentralized dynamic data fusion and fault detection. The semi-decentralized dynamic data fusion algorithm employs a median-consensus algorithm using extended non-faulty neighbours (whose sensor readings for the target position are within a prescribed tolerance level) and subsequently makes local estimates of the target position converge to nearly the actual target position. Meanwhile, the fault detection algorithm first asks each UAV to find the global median of the local target position through extended neighbours, and then diffuses the determined global median to all the UAVs in the network. As a result, the fault detection algorithm allows UAVs to detect and isolate faulty sensors quickly and to carry on target tracking in the semi-decentralized dynamic data fusion mode. As opposed to existing target tracking schemes, the proposed scheme is deterministic and guarantees the complete detection and isolation of faulty sensors on UAVs and thus successful target tracking. Numerical examples as well as experimental results are provided to support the developed ideas.
Correlation- and covariance-supported normalization method for estimating orthodontic trainer treatment for clenching activity
Authors: Akdemır B , Okkesım S , Kara S , Günes S
Published: September 2009

In this study, electromyography signals sampled from children undergoing orthodontic treatment were used to estimate the effect of an orthodontic trainer on the anterior temporal muscle. A novel data normalization method, called the correlation- and covariance-supported normalization method (CCSNM), based on correlation and covariance between features in a data set, is proposed to provide predictive guidance to the orthodontic technique. The method was tested in two stages: first, data normalization using the CCSNM; second, prediction of normalized values of anterior temporal muscles using an artificial neural network (ANN) with a Levenberg—Marquardt learning algorithm. The data set consists of electromyography signals from right anterior temporal muscles, recorded from 20 children aged 8—13 years with class II malocclusion. The signals were recorded at the start and end of a 6-month treatment. In order to train and test the ANN, two-fold cross-validation was used. The CCSNM was compared with four normalization methods: minimum—maximum normalization, z score, decimal scaling, and line base normalization. In order to demonstrate the performance of the proposed method, prevalent performance-measuring methods, and the mean square error and mean absolute error as mathematical methods, the statistical relation factor R2 and the average deviation have been examined. The results show that the CCSNM was the best normalization method among other normalization methods for estimating the effect of the trainer.
On the squeeze film lubrication of rough short porous partial journal bearings with micropolar fluids
Authors: Naduvinamani N B , Santosh S , Siddanagouda A
Published: September 2009

In this article, a theoretical study of the effect of surface roughness on the squeeze film characteristics of short porous partial journal bearing lubricated with micropolar fluids is made. The modified averaged Reynolds equation accounting for the randomized surface roughness structure is mathematically derived. The Christensen stochastic theory of hydrodynamic lubrication of a rough surface is used to study the effect of two types of one-dimensional (1D) surface roughness on the squeeze film characteristics of a short porous partial journal bearing with micropolar fluid. It is assumed that the roughness asperity heights are small compared to the film thickness. It is observed that the transverse surface roughness pattern improves the squeeze film characteristics, whereas the squeeze film bearing performance is affected due to the presence of 1D longitudinal surface roughness. These effects are more pronounced for the micropolar fluids.
Whole crankshaft beam-element finite-element method for calculating crankshaft deformation and bearing load of an engine
Authors: Sun J , Wang J , Gui C
Published: September 2009

Crankshaft deformation and bearing load are very important for the lubrication ana-lyses of crankshaft bearings of an engine. The calculating methods of crankshaft deformation and bearing load will affect the results. There were some problems in the current methods used for calculating crankshaft deformation and bearing load, such as complicated model, more time taken for calculation, and error brought by simplification. In this article, the crankshaft of a four-cylinder engine was taken as the object of study, and the whole crankshaft beam-element finite-element method to calculate crankshaft bearing load and crankshaft deformation of a multi-cylinder engine was studied. The results show that this method is closer to the actual condition and can calculate the loads of all main bearings simultaneously compared with traditional methods used for calculating the crankshaft bearing load of a multi-cylinder engine. Meanwhile, this method is a simple, convenient, time-saving method used for calculating crankshaft deformation compared to the whole crankshaft solid-element finite-element method, and its calculating precision can meet engineering demands.
Exact confidence intervals for Weibull parameters and percentiles
Authors: Phan L D , McCool J I
Published: September 2009

Simple estimators of the Weibull shape parameter and any quantile in uncensored samples are shown to share the pivotal function properties of maximum likelihood estimators. This allows interval estimation of the Weibull parameters and quantiles once the distributions of the necessary pivotal functions are determined by Monte Carlo sampling for a given sample size and quantile of interest. Free software for this purpose is made available for download. It is shown that the quantile and shape parameter estimates may be readily corrected so as to be median unbiased. The shape parameter estimator is shown to be less precise than the corresponding maximum likelihood estimator. However, the precision of the estimator of the pth quantile is quite comparable to that of the maximum likelihood method over the range from 0.4≤ p≤0.7.
A review of propulsive mechanisms in rowing
Authors: Caplan N , Coppel A , Gardner T
Published: September 2009

This paper reviews the fluid dynamic mechanisms that are fundamental to the rowing stroke. Complex interactions occur between the oar blade and water, and over the last 30 years our understanding of the mechanisms that govern rowing propulsion has developed significantly.

The oar blade was once believed to rip through the water, generating a drag force acting normal to the blade. Current research indicates that the oar blade acts as an aerofoil making use of lift forces to propel the boat through the water early and late in the stroke, with drag being the dominant propulsive force when the oar is perpendicular to the boat. Early on-water research showed variations in the fluid dynamic behaviour of different oar blades. Recently, more controlled laboratory tests have isolated the oar blade from the rower—boat—water system to obtain blade characteristics.

The isolated nature of recent oar blade studies and the complex nature of the oar blade—water interaction have led to suggestions that computational fluid dynamics (CFD) may be used to advance understanding of oar blade behaviour as a precursor to a more informed design process. By integrating a dynamic CFD model with a mathematical model of rowing mechanics, a full optimization of rower technique, boat rigging, and equipment design could be performed.
Design and development of a novel, integrated bowling machine for cricket
Authors: Justham L , West A
Published: September 2009

Bowling machines are used in cricket training to improve a batsman's technique and prevent injury or fatigue to the bowler through overuse; however, existing bowling machines do not provide a realistic training environment that compares to the experience of facing a real bowler. This paper presents the design process undertaken to specify a novel bowling machine which is capable of recreating all common types of technically correct bowling deliveries. The design was implemented based on the requirements and specifications outlined by cricket coaches and players. A prototype was then manufactured and tested thoroughly in the laboratory and at the England and Wales Cricket Board's National Cricket Centre at Loughborough University. Results obtained have shown that the novel bowling machine is capable of recreating realistic bowling deliveries with the correct spin and speed characteristics.
Serum total cortisol and free cortisol index give different information regarding the hypothalamus–pituitary–adrenal axis reserve in patients with liver impairment
Authors: Vincent Royce P , Etogo-Asse Frédérique E , Dew Tracy , Bernal William , Alaghband-Zadeh Jamshid , le Roux Carel W
Published: September 2009

Background

The short synacthen test (SST) is used to investigate patients with suspected hypothalamus–pituitary–adrenal (HPA) axis pathology. A rise of serum total cortisol (total cortisol) above 550 nmol/L is accepted as sufficient adrenal reserve. In total, 80% of cortisol is bound to cortisol-binding globulin (CBG) and 10% to albumin. In the acute phase responses CBG concentrations decrease and can influence the interpretation of SST. The free cortisol index (FCI) is a surrogate marker for free cortisol and is defined as total cortisol (nmol/L)/CBG (mg/L) with an FCI > 12 representing sufficient adrenal reserve. The aim of this study was to compare total cortisol and FCI in the interpretation of SST in patients with liver impairment.

Method

SST was done on 26 patients with liver impairment. Total cortisol was measured on Advia Centaur; serum CBG by radioimmunoassay and FCI calculated.

Results

Eleven (42%) patients had a total cortisol >550 nmol/L (range 555–2070) and FCI > 12 (12.0–68.9) suggesting sufficient cortisol reserve. Three patients (13%) had total cortisol <550 nmol/L (268–413) and FCI < 12 (3.5–11.6) consistent with cortisol deficiency. Twelve patients (46%) had a total cortisol <550 nmol/L (144–529), but an FCI > 12 (12.0–52.9). None of the patients had a total cortisol >550 nmol/L and FCI < 12.

Conclusion

When total cortisol alone is used to interpret SST in patients with liver impairment, 46% may have been classified as having adrenal insufficiency because of low CBG. FCI may be better for the evaluation of HPA axis insufficiency in patients with liver impairment.
Facility Location Modeling and Inventory Management with Multisourcing
Authors: Ozsen Leyla , Daskin Mark S. , Coullard Collette R.
Published: September 2009

In this paper we consider a centralized logistics system in which a single company owns the production facility and the set of retailers and establishes warehouses that will replenish the retailers' inventories. We analyze the potential savings that the company will achieve by allowing its retailers to be sourced by more than one warehouse probabilistically, through the use of information technology. We facilitate the discussion on the impact of multisourcing by introducing a capacitated location-inventory model that minimizes the sum of the fixed warehouse location costs, the transportation costs, and the inventory costs. The model is formulated as a nonlinear integer-programming problem that has a cost term that is neither concave nor convex. We propose a Lagrangian relaxation solution algorithm to solve the model and successfully test the algorithm on problems with 88 and 150 retailers. Based on the model properties and the sensitivity analysis results, we conclude that multisourcing becomes a more valuable option as transportation costs increase, i.e., constitute a larger portion of the total logistics cost. In addition, we show that in practice only a small portion of the retailers need to be multisourced to achieve significant cost savings.