bluuebunny/crossref_metadata_2025_split huggingface dataset:
An investigation of manual transmission drive rattle
Authors: De la Cruz M , Theodossiades S , Rahnejat H 
Published: November 2009

Manual transmission gear rattle is an NVH (noise, vibration, and harshness) concern in the automotive industry. It is induced by repetitive impacts on loose (unselected) gear wheel teeth by their corresponding driving pinions. This phenomenon occurs under various loading conditions and is classified accordingly, including ‘idle rattle’ when the transmission is in neutral and ‘creep and drive rattle’ when the transmission is in a gear with a widely open or a partially open throttle. The phenomenon is also present from drive to coast conditions, referred to as overrun rattle. Engine order fluctuations on the input shaft are considered to be the underlying cause for rattle of loose gears. However, the mechanism of transmission of vibration through lubricated contacts is not fundamentally understood. It is surmised that changes in lubricated contact conditions at different bulk oil temperatures may play a key role and, therefore, offer an opportunity to deal with rattle by a root-cause fundamental solution. This means that a detailed multi-physics approach (including dynamics, vibration, and tribology) is needed. This article provides detailed analytical models of lubricated conjunctions in a multi-body dynamics model of a transaxle seven-speed transmission system under creep rattle conditions. The results show the important role of the regime of lubrication in lightly loaded conjunctions, increasing the propensity to rattle at higher temperatures. It is also revealed that the effect of engine order vibration as an initiating source for rattle becomes significant with reduced hydrodynamic contact stiffness at rising temperatures.
Controlled Synthesis of Pd Clusters in Subnanometer Range Using Poly(propylene imine) Dendrimers
Authors: Mizugaki Tomoo , Kibata Takayuki , Ota Kazuya , Mitsudome Takato , Ebitani Kohki , Jitsukawa Koichiro , Kaneda Kiyotomi 
Published: November 2009

Abstract
Tailor-made synthesis of Pd clusters in the subnanometer range was achieved using dendrimers as tunable host materials. The subnano Pd clusters consisting of a specific number of Pd atoms of Pd4, Pd8, and Pd16 were obtained by preorganization of Pd ions within the PPI dendrimers and subsequent reduction.
Alternative Splicing and Molecular Characterization of Splice Site Variants: BRCA1 c.591C&gt;T as a Case Study
Authors: Dosil Vanesa , Tosar Alicia , Cañadas Carmen , Pérez-Segura Pedro , Díaz-Rubio Eduardo , Caldés Trinidad , de la Hoya Miguel 
Published: November 2009

Abstract
Background: Deleterious mutations in BRCA1 (breast cancer 1, early onset; MIM 113705) increase breast and ovarian cancer [B(O)C] risk; however, many variants cannot be readily classified as deleterious or neutral. Unclassified variants (UVs) pose serious problems in genetic counseling. RNA-splicing analysis is essential for the assessment of many UVs.
Methods: Denaturing gradient gel electrophoresis was used to genotype the BRCA1 c.591C&gt;T variant in 685 index cases of B(O)C families, 326 sporadic breast cancer cases, and 450 healthy controls from Spain. In silico tools were used to predict the effect of the c.591C&gt;T variant on splicing. In vitro splicing analysis was performed in 7 c.591C&gt;T carriers and 10 noncarriers. cDNAs were PCR-amplified with primers designed to detect BRCA1 alternative splicing isoforms. The products were analyzed by capillary electrophoresis. Peak areas were used to quantify the relative abundance of each isoform. Sequencing through exonic single-nucleotide polymorphisms (SNPs) enabled us to discriminate wild-type and variant transcripts.
Results: c.591C&gt;T was detected in B(O)C families (1.5%), breast cancer cases (0.3%), and controls (0.9%). c.591C&gt;T induced BRCA1 exon 9 skipping and modified the relative expression of Δ(9,10), Δ(9,10,11B), Δ11B, and full-length isoforms. The mean ratio of Δ(9,10) to the full-length isoform increased from 0.25 in noncarriers to 1.5 in carriers. The mean Δ(9,10,11B)/Δ11B ratio increased from 0.2 to 4. Overall expression levels of c.591C&gt;T and wild-type alleles were similar.
Conclusions: Our data support a nonpathogenic role for the BRCA1 c.591C&gt;T variant. Naturally occurring alternative splicing isoforms need to be considered when assessing the role of BRCA1 UVs on splicing.
Is there a Consensus in the Management of Distal Radial Fractures?
Authors: Nazar M.A. , Mansingh R. , Bassi R.S. , Waseem M. 
Published: November 2009

This unique postal survey was setup to assess the agreement on treatment options in displaced distal radius fractures and whether or not there existed a consensus amongst the surgeons contacted. With this in view we contacted 244 surgeons and 166 completed answers were received.We chose two common examples of displaced distal radius fractures. Case one was a 38 year old teacher with a closed, displaced extra-articular fracture (Frykman type II) of her left non-dominant hand and case two was a 42 year old carer, with a closed, displaced intra-articular fracture (Frykman type VII) of her right dominant wrist. There was a questionnaire included with these radiographs.In the first case, 82 (49%) surgeons favoured MUA + K-wiring, 47 (28%) favoured volar plating and 14 (8%) an external fixator. In the second case, 28 (17%) surgeons favoured MUA + K-wiring, 53 (32%) advocated volar plating and 33 (20%) an external fixator. Furthermore surgeons with specialist Upper limb interest were more likely to apply a volar plate (63% in either case) whilst the surgeons with general or other areas of expertise (18% in first case and 23% for second case).In conclusion there is no consensus among the Orthopaedic surgeons in treating displaced distal radial fractures. A multicentered randomized clinical trial would help elucidate the best treatment options.
Tobacco Use as Response to Economic Insecurity: Evidence from the National Longitudinal Survey of Youth
Authors: Barnes Michael G , Smith Trenton G. 
Published: November 2009

Abstract
Emerging evidence from neuroscience and clinical research suggests a novel hypothesis about tobacco use: consumers may choose to smoke, in part, as a "self-medicating" response to the presence of economic insecurity. To test this hypothesis, we examine the effect of economic insecurity (roughly, the risk of catastrophic income loss) on the smoking behavior of a sample of male working-age smokers from the 1979 National Longitudinal Survey of Youth (NLSY79). Using instrumental variables to control for unobserved heterogeneity, we find that economic insecurity has a large and statistically significant positive effect on the decision to continue or resume smoking. Our results indicate, for example, that a 1 percent increase in the probability of becoming unemployed causes an individual to be 2.4 percent more likely to continue smoking. We find that the explanatory power of economic insecurity in predicting tobacco use is comparable to (but distinct from) household income, a more commonly used metric.
Urinary Proteome Analysis using Capillary Electrophoresis Coupled to Mass Spectrometry: A Powerful Tool in Clinical Diagnosis, Prognosis and Therapy Evaluation
Authors: Mischak Harald , Schiffer Eric , Zürbig Petra , Dakna Mohammed , Metzger Jochen 
Published: November 2009

Urinary Proteome Analysis using Capillary Electrophoresis Coupled to Mass Spectrometry: A Powerful Tool in Clinical Diagnosis, Prognosis and Therapy EvaluationProteome analysis has emerged as a powerful tool to decipher (patho) physiological processes, resulting in the establishment of the field of clinical proteomics. One of the main goals is to discover biomarkers for diseases from tissues and body fluids. Due to the enormous complexity of the proteome, a separation step is required for mass spectrometry (MS)-based proteome analysis. In this review, the advantages and limitations of protein separation by two-dimensional gel electrophoresis, liquid chromatography, surface-enhanced laser desorption/ionization and capillary electrophoresis (CE) for proteomic analysis are described, focusing on CE-MS. CE-MS enables separation and detection of the small molecular weight proteome in biological fluids with high reproducibility and accuracy in one single processing step and in a short time. As sensitive and specific single biomarkers generally may not exist, a strategy to overcome this diagnostic void is shifting from single analyte detection to simultaneous analysis of multiple analytes that together form a disease-specific pattern. Such approaches, however, are accompanied with additional challenges, which we will outline in this review. Besides the choice of adequate technological platforms, a high level of standardization of proteomic measurements and data processing is also necessary to establish proteomic profiling. In this regard, demands concerning study design, choice of specimens, sample preparation, proteomic data mining, and clinical evaluation should be considered before performing a proteomic study.
Glucocorticoid Receptor in Health and Disease
Authors: Dunđerski Jadranka , Matić Gordana 
Published: November 2009

Glucocorticoid Receptor in Health and DiseaseGlucocorticoid hormones are essential for life, have a vital place in the treatment of inflammatory and autoimmune diseases and are increasingly implicated in the pathogenesis of a number of common disorders. Their action is mediated by an intracellular receptor protein, the glucocorticoid receptor (GR), functioning as a ligand-inducible transcription factor. Multiple synthetic glucocorticoids are used as potent antiinflammatory and immunosuppressive agents, but their therapeutic usefulness is limited by a wide range and severity of side-effects. One of the most important pharmaceutical goals has been to design steroidal and non-steroidal GR ligands with profound therapeutic efficacy and reduced unwanted effects. The therapeutic benefit of glucocorticoid agonists is frequently compromised by resistance to glucocorticoids, which may depend on: access of the hormones to target cells, steroid metabolism, expression level and isoform composition of the GR protein, mutations and polymorphisms in the GR gene and association of the receptor with chaperone proteins. The major breakthrough into the critical role of glucocorticoid signaling in the maintenance of homeostasis and pathogenesis of diseases, as well as into the molecular mechanisms underlying the therapeutic usefulness of antiinflammatory drugs acting through the GR is expected to result from the current progress in large-scale gene expression profiling technologies and computational biology.
From Research to Clinical Application Multi-Parameter Testing: Marker Panels for the Early Detection of Complex Diseases
Authors: Wild Norbert , Karl Johann , Risse Bernhard 
Published: November 2009

From Research to Clinical Application Multi-Parameter Testing: Marker Panels for the Early Detection of Complex DiseasesMulti Parameter Analysis can open novel diagnostic opportunities for the early diagnosis and screening of multimodal diseases like cancer. Single proteins have so far failed to describe such complex diseases. Being able to screen with a set of analytes is one promising way to overcome the present limitations. Various marker identification tools including proteomics approaches have been successfully applied to identify new screening markers for early detection of colorectal cancer (CRC). CRC is one of the most incident cancers worldwide and early detection is clearly a key factor in reducing mortality from CRC. Several screening methods are recommended, including colonoscopy, fecal occult blood testing (FOBT) and fecal DNA analysis. Of these annual stool testing with the guaiac based FOBT is most often applied, in spite of limitations such as low sensitivity and dietary influences. Though proce dures with improved performance eg. immunolo gical FOBT are available, a screening assay for CRC in serum that could easily be integrated in any health check-up would be highly welcome. A positive result of such a test would trigger a follow-up colonoscopy for an exact diagnosis. In this review we will cover aspects of marker identification strategies and describe a well structured marker validation process that is based on clinically characterized sample materials. Finally the value of analytical multi-parameter platforms enabling the combination of multi markers in routine diagnostics settings is outlined. An appropriate multi-parameter immunochemistry platform concept, currently developed under the working name »IMPACT« will be introduced.
The Use of Biochip Cardiac Array Technology for Early Diagnosis of Acute Coronary Syndromes
Authors: Sypniewska Grazyna , Sawicki Marcin , Krintus Magdalena , Kozinski Marek , Kubica Jacek 
Published: November 2009

The Use of Biochip Cardiac Array Technology for Early Diagnosis of Acute Coronary SyndromesSerum troponin is the best biomarker for the diagnosis of acute coronary syndrome, but it takes considerable time before a definitive diagnosis is available. The purpose of this study was to evaluate whether a multimarker approach, using the biochip cardiac array, would facilitate the early diagnosis. Serum biomarkers were determined on admission (≤6 hrs) and after 6 hours in 42 patients suspected for ACS. Cardiac troponin I was measured by a sensitive assay (STATcTnI) and cardiac markers (H-FABP, myoglobin, cTnI, CK-MB mass, carbonic anhydrase III) were assayed with the use of Biochip Array Technology.STATcTnI concentrations, within the first 6 hours, were elevated >99thpercentile for the reference population in 83.3% of subjects, but none reached the cut-off for AMI. On admission H-FABP was the only marker with 90.5% sensitivity in all ACS cases and 100% sensitivity in STEMI/NSTEMI patients. The sensitivity of myoglobin at presentation was 71.4% in ACS, however, combined sensitivity of myoglobin and H-FABP reached 95.2%. Lowering the cut-off for cTnI allowed early diagnosis (≤6 hrs) in only 26.2% of ACS patients and 95.2% after the next 6 hours. In unstable angina the cardiac panel was not sufficiently accurate for early risk stratification. In conclusion, testing for both markers, H-FABP and sensitive cardiac troponin, available with the cardiac array may facilitate the early detection of myocardial injury in clinical practice.
Advanced Techniques in Clinical Practice: Use of Lab-on-a-Chip Electrophoresis and Other Methods in Protein Profiling
Authors: Trenčevska Olgica , Aleksovski Vasko , Stojanoski Kiro 
Published: November 2009

Advanced Techniques in Clinical Practice: Use of Lab-on-a-Chip Electrophoresis and Other Methods in Protein ProfilingProteins in clinical practice are analyzed as important parameters in the determination and treatment of different diseases. The scopes of the analyses are mainly concentrated in two levels - analyses of the complete protein profile, or determination of an isolated protein. In this work, despite of the use of conventional methods, mainly electrophoresis, new techniques have been implemented in protein analyses. Lab-on-a-chip is an electrophoretic technique that, when optimized, provides analyses of the total protein profile. When normal samples are compared to samples obtained from patients with different neurological diseases, characteristic patterns can be noted. Also, correlation and comparison can be made between the newly developed microchip electrophoresis method and the results obtained using the conventional techniques. When an analysis of a specific protein is necessary, mass spectrometry has proven to give best results, in both the se lectivity and specificity of analyses. It is believed that cystatin C is a potential biomarker in neurological diseases; therefore, the mass spectrometry method has been developed in order to obtain qualitative and quantitative analyses of biological fluids. Using the developed method of mass spectrometry immunoassay (MSIA), cystatin C was easily isolated and analyzed, obtaining complete analysis within minutes. The resulting mass spectra revealed various levels of cystatin C isoforms in serum and CSF samples.
Application of Preparative Electrophoresis for Clinical Proteomics in Urine: Is it Feasible?
Authors: Zoidakis Jérôme , Dimitraki Ploumisti , Zerefos Panagiotis , Vlahou Antonia 
Published: November 2009

Application of Preparative Electrophoresis for Clinical Proteomics in Urine: Is it Feasible?Urine samples are easily attainable which makes them ideal substrates for biomarker research. Various techniques have been employed to unravel the urine proteome and identify disease biomarkers. Even though the presence of high abundance proteins in urine is not so pronounced as in the case of plasma, the presence of proteolytic products, many of which at low abundance, along with numerous frequently random chemical modifications, makes the analysis of urinary proteins challenging. To facilitate the detection of low abundance urinary proteins, in the study presented herein we applied two different electrophoretic techniques, preparative Lithium Dodecyl Sulfate (LDS)-PAGE in combination with 2-DE for urinary protein separation and enrichment. Our results indicate the effectiveness of this approach for the enrichment of low abundance and low molecular weight proteins and peptides in urine, and contribute towards the establishment of a urinary proteomic database. The application of this technique as a biomarker discovery tool faces several challenges: these include down-scaling of the technique, possible recompensation for the consequent expected decrease in protein resolution, by optimizing steps of the experimental workflow as well as getting a good understanding of the technical variability of the technique. Under these conditions, preparative electrophoresis can become an effective tool for clinical proteomics applications.
Simultaneous Detection of Colorectal Cancer Mutations in Stool Samples with Biochip Arrays
Authors: Murray Helena , Latten Mark , Cartwright Andrew , McAleer Damien , Fitzgerald Stephen 
Published: November 2009

Simultaneous Detection of Colorectal Cancer Mutations in Stool Samples with Biochip ArraysColorectal cancer (CRC) is the second main cause of cancer-related death in the Western world and like many other tumours is curable if detected at an early stage. Current detection options include faecal occult blood testing and invasive direct visualisation techniques such as flexible sigmoidoscopy, colonoscopy and barium enema. The availability of a more simple, non-invasive test that detects tumour specific products with optimal analytical performance might overcome barriers among patients who are not willing to undergo more sensitive but invasive tests. One such emerging technology, which has shown promise in recent years, is the analysis of DNA alterations exfoliated from tumour cells into stool. Here we report an analytical platform for non-invasive detection of 28 common mutations within CRC-related genesAPC, TP53, K-rasandBRAFin stool samples based on biochip array technology and applied to the semi-automated Evidence Investigator analyser. Mutation detection was possible in 1000-fold excess of wildtype DNA and analysis of 10 CRC-positive patient samples showed presence of targeted mutations with equivalent mutations also identified by an alternative method. This application represents an excellent tool for the multiplex detection of CRC-specific mutations using a single platform.
Madge - Microplate Array Diagonal Gel Electrophoresis
Authors: Stanković Sanja , Alavantić Dragan , Majkić-Singh Nada 
Published: November 2009

Madge - Microplate Array Diagonal Gel ElectrophoresisMicroplate array diagonal gel electrophoresis (MADGE) was invented for molecular genetic epidemio-logical studies. MADGE is a highly flexible, cost effective, microplate compatible solution to high throughput electrophoresis needs. It enables several thousands to million gel lines per day for direct assay of single-base variation in different capacity laboratories. Variants of the standard 96-well MADGE include: 96-well stretch-MADGE, 192-well MADGE, 384-well MADGE, and 768-well MADGE. Melt-MADGE combines the temporal thermal ramp apparatus to achieve similar throughput for de novo mutation scanning. Basic MADGE principles and procedures, preparation of MADGE gels, electrophoresis, visualization and analysis of these gels, as well as modifications of the basic 96-well MADGE will be discussed in detail. For the first time in our country, this revolutionary polyacrylamid electrophoresis was done in 1998. We shortly review our studies which used MADGE for high throughput genotyping of the apolipoprotein E. MADGE and melt-MADGE will have an important role in the future genetic research of complex diseases and especially in pharmacogenomics.
Long-Term Quality Control of the Cytokine & Growth Factors and Cell Adhesion Molecule Arrays at the Randox Evidence Investigator
Authors: van Pelt Johannes , Romijn Fred 
Published: November 2009

Long-Term Quality Control of the Cytokine & Growth Factors and Cell Adhesion Molecule Arrays at the Randox Evidence InvestigatorMulti component assays are a promising development in laboratory medicine. Reproducibility and standardization of the used technology is crucial for the quality of the results. In our laboratory several studies were carried out in a period of more than two years using the Randox Evidence Investigator. We applied the Cytokine & Growth Factors and Cell Adhesion Molecule Array from which reference values could be obtained. Cytokines are not useful in low grade inflammation or in normal persons as the levels are too low to detect. However growth factors and cell adhesion molecules could be determined in those studies. Outcomes with the arrays were compared with conventional assays such as ELISA. The correlations of IL-6 and IL-10 were very good and that of s-ICAM acceptable. Inter-assay coefficients of variation could be calculated by using the same control level material during those years. The system turned out to be easy to handle and very stable over a long period of time with CV's of about 8-12%. The results obtained are not dependent of the lot number of the arrays or apparatus as two different apparatus gave same outcomes.