bluuebunny/crossref_metadata_2025 huggingface dataset:
Dietary Quality and Relationships With Health Indicators Among Early Adolescents
Authors: Adamson Katie A. , Daratha Kenneth B. , Bindler Ruth C.
Published: April 2010

Healthy eating patterns during adolescence support appropriate growth and development and influence eating habits later in life. Recent analyses of US adolescents’ diets have consistently demonstrated that significant numbers do not meet Institute of Medicine dietary reference intakes for macronutrients or micronutrients. The aims of this baseline study were to examine dietary intakes of a sample of seventh-graders and the associations between micronutrient and macro-nutrient intakes out of recommended range with health indicators. A total of 167 predominantly European American participants (54% female; mean age 12.6 years) completed a 24-hour diet recall with trained interviewers. Data were entered into the Food Processor computer program to assess dietary quality. Recommended intakes were calculated based on age, height, weight, and activity level (assessed by the previous day’s physical activity recall). Major findings were incongruence between dietary intake and recommendations among adolescents (eg, >70% failed to report recommended intake of calcium, vitamin D, folate, and vitamin A) and relationship of protein intakes greater than recommended with health indicators (eg, mean triglycerides 84 mg/dL in high-protein intake vs 108 mg/dL for lower intake). Further research regarding relationships between protein intake greater than the recommended range in early adolescents and health indicators is important.
Glucocorticoid-induced osteoporosis: how best to avoid fractures
Authors: Cooper Mark S.
Published: April 2010

Glucocorticoids are one of the most commonly prescribed medications and are used to treat a wide range of chronic inflammatory diseases. The main limitation of this therapy is the development of osteoporosis and bone fractures. Recent studies have given us insight into the epidemiology of glucocorticoid-induced fractures demonstrating both the magnitude of the problem and the types of patients who are likely to be most at risk. Additionally, several randomised trials have demonstrated beneficial effects of bone targeted medications in the setting of glucocorticoid-induced osteoporosis. This article will review these recent findings, will suggest when patients are likely to be at a significant risk of fracture and discuss how best to reduce this risk.
Endocrine and metabolic emergencies: hypocalcaemia
Authors: Carroll Richard , Matfin Glenn
Published: April 2010

Hypocalcaemia is a common electrolyte disturbance, especially in the inpatient setting. There are a wide variety of causes of hypocalcaemia and correct management depends on the underlying diagnosis. However, acute hypocalcaemia is associated with significant morbidity and mortality and should be managed as a medical emergency. Chronic care of the hypocalcaemic patient is also briefly described, as this is an important opportunity to reduce further admissions related to both hypocalcaemic and hypercalcaemic presentations.
Improved FE model for simulation of friction stir welding of different materials
Authors: Fratini L. , Buffa G. , Monaco L. Lo
Published: April 2010

One of the most relevant aspects of friction stir welding is the possibility to weld different materials. In the present paper, the authors present an improved continuum finite element model for the simulation of friction stir welding processes aimed to obtain T joints, made of a stringer in AA7175-T73511 and of a skin in AA2024-T4. The model, taking into account the thermomechanical behaviours of the two different materials, is utilised to study the occurring material flow and residual stress state. Numerical results are compared with experimental observations: the model is able to predict the material flow, obtaining important information on the joint failure mode.
Influence of cooling rate on microstructure and properties of high strength steel weld metal
Authors: Keehan E. , Zachrisson J. , Karlsson L.
Published: April 2010

Microstructures, and hence mechanical properties, of high strength steel weld metals are affected by cooling rate. Weld metal microstructures for a nominal composition of Fe–0·05C–0·3Si–2Mn–3Ni–0·5Cr–0·6Mo (wt-%) were therefore characterised for a range of cooling rates using high resolution scanning electron microscopy, and transformation behaviour, assessed from cooling curves, is presented as a continuous cooling transformation diagram. As deposited last bead microstructure changes gradually from lower bainite and martensite interspersed with coalesced bainite, via a mixture of relatively fine upper and lower bainite, to coarse upper bainite as cooling rate decreases. The microstructure of reheated beads follows the as deposited structure closely and becomes coarse with slower cooling. Mechanical properties correlate with observed microstructure and transformation behaviour. Results suggest high strength and good toughness for cooling rates between 800 and 500°C of about 3–13 s. A fine microstructure will then form with varying proportions of martensite, lower bainite, coalesced bainite and fine upper bainite.
New method for investigating material flow during friction stir spot welding
Authors: Sun N. , Zhou H. , North T. H. , Yin Y. H.
Published: April 2010

In this paper, an examination of dissimilar wrought and heat treated AZ31 spot welds (AZ31/AZ31HT) was conducted to allow visualisation of material flow based on their differing etching characteristics. The results indicated that dissimilar AZ31/AZ31HT welds could successfully mirror the material flow in friction stir spot welding. The upper sheet material moved downwards towards the rotational pin, whereas the lower sheet material displaced upwards and outwards during the penetrate stage, and then moved inwards towards the keyhole after reached the base of the shoulder.
BiGG: a Biochemical Genetic and Genomic knowledgebase of large scale metabolic reconstructions
Authors: Schellenberger Jan , Park Junyoung O , Conrad Tom M , Palsson Bernhard Ø
Published: April 2010

Background

Genome-scale metabolic reconstructions under the Constraint Based Reconstruction and Analysis (COBRA) framework are valuable tools for analyzing the metabolic capabilities of organisms and interpreting experimental data. As the number of such reconstructions and analysis methods increases, there is a greater need for data uniformity and ease of distribution and use.

Description

We describe BiGG, a knowledgebase of Biochemically, Genetically and Genomically structured genome-scale metabolic network reconstructions. BiGG integrates several published genome-scale metabolic networks into one resource with standard nomenclature which allows components to be compared across different organisms. BiGG can be used to browse model content, visualize metabolic pathway maps, and export SBML files of the models for further analysis by external software packages. Users may follow links from BiGG to several external databases to obtain additional information on genes, proteins, reactions, metabolites and citations of interest.

Conclusions

BiGG addresses a need in the systems biology community to have access to high quality curated metabolic models and reconstructions. It is freely available for academic use at http://bigg.ucsd.edu.
Bacillus anthracis genome organization in light of whole transcriptome sequencing
Authors: Martin Jeffrey , Zhu Wenhan , Passalacqua Karla D , Bergman Nicholas , Borodovsky Mark
Published: April 2010

Emerging knowledge of whole prokaryotic transcriptomes could validate a number of theoretical concepts introduced in the early days of genomics. What are the rules connecting gene expression levels with sequence determinants such as quantitative scores of promoters and terminators? Are translation efficiency measures, e.g. codon adaptation index and RBS score related to gene expression? We used the whole transcriptome shotgun sequencing of a bacterial pathogen Bacillus anthracis to assess correlation of gene expression level with promoter, terminator and RBS scores, codon adaptation index, as well as with a new measure of gene translational efficiency, average translation speed. We compared computational predictions of operon topologies with the transcript borders inferred from RNA-Seq reads. Transcriptome mapping may also improve existing gene annotation. Upon assessment of accuracy of current annotation of protein-coding genes in the B. anthracis genome we have shown that the transcriptome data indicate existence of more than a hundred genes missing in the annotation though predicted by an ab initio gene finder. Interestingly, we observed that many pseudogenes possess not only a sequence with detectable coding potential but also promoters that maintain transcriptional activity.
Quantitative polymerase chain reaction analysis by deconvolution of internal standard
Authors: Hirakawa Yasuko , Medh Rheem D , Metzenberg Stan
Published: April 2010

Background

Quantitative Polymerase Chain Reaction (qPCR) is a collection of methods for estimating the number of copies of a specific DNA template in a sample, but one that is not universally accepted because it can lead to highly inaccurate (albeit precise) results. The fundamental problem is that qPCR methods use mathematical models that explicitly or implicitly apply an estimate of amplification efficiency, the error of which is compounded in the analysis to unacceptable levels.

Results

We present a new method of qPCR analysis that is efficiency-independent and yields accurate and precise results in controlled experiments. The method depends on a computer-assisted deconvolution that finds the point of concordant amplification behavior between the "unknown" template and an admixed amplicon standard. We apply the method to demonstrate dexamethasone-induced changes in gene expression in lymphoblastic leukemia cell lines.

Conclusions

This method of qPCR analysis does not use any explicit or implicit measure of efficiency, and may therefore be immune to problems inherent in other qPCR approaches. It yields an estimate of absolute initial copy number of template, and controlled tests show it generates accurate results.
High-efficiency transfection of cultured primary motor neurons to study protein localization, trafficking, and function
Authors: Fallini Claudia , Bassell Gary J , Rossoll Wilfried
Published: April 2010

Background

Cultured spinal motor neurons are a valuable tool to study basic mechanisms of development, axon growth and pathfinding, and, importantly, to analyze the pathomechanisms underlying motor neuron diseases. However, the application of this cell culture model is limited by the lack of efficient gene transfer techniques which are available for other neurons. To address this problem, we have established magnetofection as a novel method for the simple and efficient transfection of mouse embryonic motor neurons. This technique allows for the study of the effects of gene expression and silencing on the development and survival of motor neurons.

Results

We found that magnetofection, a novel transfection technology based on the delivery of DNA-coated magnetic nanobeads, can be used to transfect primary motor neurons. Therefore, in order to use this method as a new tool for studying the localization and transport of axonal proteins, we optimized conditions and determined parameters for efficient transfection rates of >45% while minimizing toxic effects on survival and morphology. To demonstrate the potential of this method, we have used transfection with plasmids encoding fluorescent fusion-proteins to show for the first time that the spinal muscular atrophy-disease protein Smn is actively transported along axons of live primary motor neurons, supporting an axon-specific role for Smn that is different from its canonical function in mRNA splicing. We were also able to show the suitability of magnetofection for gene knockdown with shRNA-based constructs by significantly reducing Smn levels in both cell bodies and axons, opening new opportunities for the study of the function of axonal proteins in motor neurons.

Conclusions

In this study we have established an optimized magnetofection protocol as a novel transfection method for primary motor neurons that is simple, efficient and non-toxic. We anticipate that this novel approach will have a broad applicability in the study of motor neuron development, axonal trafficking, and molecular mechanisms of motor neuron diseases.
Dynamics and Control of the Central Carbon Metabolism in Hepatoma Cells
Authors: Maier Klaus , Hofmann Ute , Reuss Matthias , Mauch Klaus
Published: April 2010

Background

The liver plays a major role in metabolism and performs a number of vital functions in the body. Therefore, the determination of hepatic metabolite dynamics and the analysis of the control of the respective biochemical pathways are of great pharmacological and medical importance. Extra- and intracellular time-series data from stimulus-response experiments are gaining in importance in the identification of in vivo metabolite dynamics, while dynamic network models are excellent tools for analyzing complex metabolic control patterns. This is the first study that has been undertaken on the data-driven identification of a dynamic liver central carbon metabolism model and its application in the analysis of the distribution of metabolic control in hepatoma cells.

Results

Dynamic metabolite data were collected from HepG2 cells after they had been deprived of extracellular glucose. The concentration of 25 extra- and intracellular intermediates was quantified using HPLC, LC-MS-MS, and GC-MS. The in silico metabolite dynamics were in accordance with the experimental data. The central carbon metabolism of hepatomas was further analyzed with a particular focus on the control of metabolite concentrations and metabolic fluxes. It was observed that the enzyme glucose-6-phosphate dehydrogenase exerted substantial negative control over the glycolytic flux, whereas oxidative phosphorylation had a significant positive control. The control over the rate of NADPH consumption was found to be shared between the NADPH-demand itself (0.65) and the NADPH supply (0.38).

Conclusions

Based on time-series data, a dynamic central carbon metabolism model was developed for the investigation of new and complex metabolic control patterns in hepatoma cells. The control patterns found support the hypotheses that the glucose-6-phosphate dehydrogenase and the Warburg effect are promising targets for tumor treatment. The systems-oriented identification of metabolite dynamics is a first step towards the genome-based assessment of potential risks posed by nutrients and drugs.
Concomitant homozygosity for the prothrombin gene variant with mild deficiency of antithrombin III in a patient with multiple hepatic infarctions: a case report
Authors: Emmanuelle Theodore , Husein Belkys , Iqbal Javaid , Macheta M , Isaacs Peter
Published: April 2010

Introduction

Hereditary causes of visceral thrombosis or thrombosis should be sought among young patients. We present a case of a young man presenting with multiple hepatic infarctions resulting in portal hypertension due to homozygosity of the prothrombin gene mutation not previously described in literature.

Case presentation

A 42-year-old Caucasian man with a previous history of idiopathic deep vein thrombosis 11 years earlier presented with vague abdominal pains and mildly abnormal liver function tests. An ultrasound and computed tomography scan showed evidence of hepatic infarction and portal hypertension (splenic varices). A thrombophilia screen confirmed a homozygous mutation for the prothrombin gene mutation, with mildly reduced levels of anti-thrombin III (AT III). Subsequent testing of his father and brother revealed heterozygosity for the same gene mutation.

Conclusion

Hepatic infarction is unusual due to the rich dual arterial and venous blood supply to the liver. In the absence of an arterial or haemodynamic insult causing hepatic infarction, a thrombophilia should be considered. To our knowledge, this is the first reported case of a hepatic infarction due to homozygosity of the prothrombin gene mutation. It is unclear whether homozygotes have a higher risk of thrombosis than heterozygotes. In someone presenting with a first thrombosis with this mutation, the case for life-long anticoagulation is unclear, but it may be necessary to prevent a second and more severe second thrombotic event, as occurred in this case.
Influence of HLA DRB1 alleles in the susceptibility of rheumatoid arthritis and the regulation of antibodies against citrullinated proteins and rheumatoid factor
Authors: Balsa Alejandro , Cabezón Arancha , Orozco Gisela , Cobo Tatiana , Miranda-Carus Eugenia , López-Nevot Miguel Ángel , Vicario José Luis , Martín-Mola Emilio , Martín Javier , Pascual-Salcedo Dora
Published: April 2010

Introduction

The purpose of this study was to investigate the association between HLA-DRB1 alleles with susceptibility to rheumatoid arthritis (RA) and production of antibodies against citrullinated proteins (ACPA) and rheumatoid factor (RF).

Methods

We studied 408 patients (235 with RA, 173 non-RA) and 269 controls. ACPA, RF and HLA-DR typing were determined.

Results

We found an increased frequency of HLA DRB1 alleles with the shared epitope (SE) in ACPA-positive RA. Inversely, HLA DRB1 alleles encoding DERAA sequences were more frequent in controls than in ACPA-positive RA, and a similar trend was found for HLA DR3. However, these results could not be confirmed after stratification for the presence of the SE, probably due to the relatively low number of patients. These data may suggest that the presence of these alleles may confer a protective role for ACPA-positive RA. In RA patients we observed association between SE alleles and ACPA titers in a dose-dependent effect. The presence of HLA DR3 or DERAA-encoding alleles was associated with markedly reduced ACPA levels. No association between RF titers and HLA DR3 or DERAA-encoding alleles was found.

Conclusions

HLA DRB1 alleles with the SE are associated with production of ACPA. DERAA-encoding HLA-DR alleles and HLA DR3 may be protective for ACPA-positive RA.
Enhanced protein-energy provision via the enteral route in critically ill patients: a single center feasibility trial of the PEP uP protocol
Authors: Heyland Daren K , Cahill Naomi E , Dhaliwal Rupinder , Wang Miao , Day Andrew G , Alenzi Ahmed , Aris Fiona , Muscedere John , Drover John W , McClave Stephen A
Published: April 2010

Introduction

The purpose of this pilot study is to assess the feasibility, acceptability, and safety of a new feeding protocol designed to enhance the delivery of enteral nutrition (EN).

Methods

In a prospective before and after study, we evaluated a new protocol compared to our standard feeding protocol. Innovative elements of the new protocol included setting daily volume based goals instead of hourly rate targets, initiating motility agents and protein supplements on Day 1, liberalizing the gastric residual volume threshold, and the option to use trophic feeds. Bedside nurses filled out questionnaires to assess the acceptability of the new approach and we assessed patients' nutritional and clinical outcomes.

Results

We enrolled 20 mechanically ventilated patients who stayed in the Intensive Care Unit for more than three days in the before group and 30 such patients in the after group. On a scale where 1 = totally unacceptable and 10 = totally acceptable, 30 nurses rated the new protocol as 7.1 (range 1 to 10) and no incidents compromising patient safety were observed. In the before group, on average, patients received 58.8% of their energy and 61.2% of their protein requirements by EN compared to 67.9% and 73.6% in the after group (P = 0.33 and 0.13). When the subgroup of patients prescribed to receive full volume feeds in the after group were evaluated (n = 18), they received 83.2% and 89.4% of their energy and protein requirements by EN respectively (P = 0.02 for energy and 0.002 for protein compared to the before group). The rates of vomiting, regurgitation, aspiration, and pneumonia were similar between the two groups.

Conclusions

This new feeding protocol seems to be safe and acceptable to critical care nurses. The adoption of this protocol may be associated with enhanced delivery of EN but further trials are warranted to evaluate its effect on nutritional and clinical endpoints.

Trial registration

ClinicalTrials.gov NCT01102348
Optimized design and data analysis of tag-based cytosine methylation assays
Authors: Suzuki Masako , Jing Qiang , Lia Daniel , Pascual Marién , McLellan Andrew , Greally John M
Published: April 2010

Using the type III restriction-modification enzyme EcoP15I, we isolated sequences flanking sites digested by the methylation-sensitive HpaII enzyme or its methylation-insensitive MspI isoschizomer for massively parallel sequencing. A novel data transformation allows us to normalise HpaII by MspI counts, resulting in more accurate quantification of methylation at >1.8 million loci in the human genome. This HELP-tagging assay is not sensitive to sequence polymorphism or base composition and allows exploration of both CG-rich and depleted genomic contexts.
Insulin Sensitivity and Glucose Tolerance Are Altered by Maintenance on a Ketogenic Diet
Authors: Kinzig Kimberly P. , Honors Mary Ann , Hargrave Sara L.
Published: April 2010

Low-carbohydrate, ketogenic diets (KD) are frequently implemented in efforts to reduce or maintain body weight, although the metabolic effects of long-term exposure to this type of diet remain controversial. This study assessed the responsivity to peripheral and central insulin, glucose tolerance, and meal-induced effects of consuming a KD in the rat. After 8 wk of consuming chow or KD, caloric intake after peripheral or central insulin and insulin and glucose levels after a glucose challenge were assessed. In a separate group of rats, glucose and insulin responses to either a low- or high-carbohydrate test meal were measured. Finally, rats maintained on KD were switched back to a chow diet, and insulin sensitivity and glucose tolerance were evaluated to determine whether the effects of KD were reversible. Maintenance on KD resulted in decreased sensitivity to peripheral insulin and impaired glucose tolerance. Furthermore, consumption of a high-carbohydrate meal in rats that habitually consumed KD induced significantly greater insulin and glucose levels for an extended period of time, as compared with chow-fed controls. Responsivity to central insulin was heightened in KD rats and associated with increased expression levels of insulin receptor mRNA. Finally, returning to a chow diet rapidly reversed the effects of KD on insulin sensitivity and glucose tolerance. These data suggest that maintenance on KD negatively affects glucose homeostasis, an effect that is rapidly reversed upon cessation of the diet.
Progressive Osseous Heteroplasia: A Model for the Imprinting Effects of GNAS Inactivating Mutations in Humans
Authors: Lebrun M. , Richard N. , Abeguilé G. , David A. , Dieux A. Coëslier , Journel H. , Lacombe D. , Pinto G. , Odent S. , Salles J. P. , Taieb A. , Gandon-Laloum S. , Kottler M. L.
Published: April 2010

Context: Heterozygous GNAS inactivating mutations are known to induce pseudohypoparathyroidism type 1a when maternally inherited and pseudopseudohypoparathyroidism when paternally inherited. Progressive osseous heteroplasia (POH) is a rare disease of ectopic bone formation, and studies in different families have shown that POH is also caused by paternally inherited GNAS mutations.

Objective: Our purpose was to characterize parental origin of the mutated allele in de novo cases of POH and to draw phenotype/genotype correlations according to maternal or paternal transmission of a same GNAS mutation.

Design and Setting: We conducted a retrospective study on patients addressed to our referral center for the rare diseases of calcium and phosphorus metabolism.

Patients and Methods: We matched 10 cases of POH with cases of pseudohypoparathyroidism type 1a carrying the same GNAS mutations.

Main Outcome Measures: The parental origin of the mutated allele was studied using informative intragenic polymorphisms and subcloning of PCR products.

Results: Paternal origin of GNAS mutations was clearly demonstrated in eight POH cases including one patient with mutation in exon 1. Genotype/phenotype analyses suggest that there is no direct correlation between the ossifying process and the position of the inactivating GNAS mutation. It is, however, more severe in patients in whom origin of the mutation is paternal. Severe intrauterine growth retardation was clearly evidenced in paternally inherited mutations.

Conclusions: Clinical heterogeneity makes genetic counseling a delicate matter, especially in which paternal inheritance is concerned because it can lead to either a mild expression of pseudopseudohypoparathyroidism or a severe expression of POH.
Perchlorate and Thiocyanate Exposure and Thyroid Function in First-Trimester Pregnant Women
Authors: Pearce Elizabeth N. , Lazarus John H. , Smyth Peter P. A. , He Xuemei , Dall'Amico Daniela , Parkes Arthur B. , Burns Robert , Smith Derek F. , Maina Aldo , Bestwick Jonathan P. , Jooman Mohammed , Leung Angela M. , Braverman Lewis E.
Published: April 2010

Context: Thyroid hormone, requiring adequate maternal iodine intake, is critical for fetal neurodevelopment. Perchlorate decreases thyroidal iodine uptake by competitively inhibiting the sodium/iodide symporter. It is unclear whether environmental perchlorate exposure adversely affects thyroid function in pregnant women. Thiocyanate, derived from foods and cigarette smoke, is a less potent competitive sodium/iodide symporter inhibitor than perchlorate.

Objective: Our objective was to determine whether environmental perchlorate and/or thiocyanate exposure is associated with alterations in thyroid function in pregnancy.

Design and Setting: We conducted a cross-sectional study at health centers in Cardiff, Wales, and Turin, Italy.

Patients: During 2002–2006, 22,000 women at less than 16 wk gestation were enrolled in the Controlled Antenatal Thyroid Screening Study. Subsets of 261 hypothyroid/hypothyroxinemic and 526 euthyroid women from Turin and 374 hypothyroid/hypothyroxinemic and 480 euthyroid women from Cardiff were selected based on availability of stored urine samples and thyroid function data.

Main Outcome Measures: Urinary iodine, thiocyanate, and perchlorate and serum TSH, free T4 (FT4), and thyroperoxidase antibody were measured.

Results: Urinary iodine was low: median 98 μg/liter in Cardiff and 52 μg/liter in Turin. Urine perchlorate was detectable in all women. The median (range) urinary perchlorate concentration was 5 μg/liter (0.04–168 μg/liter) in Turin and 2 μg/liter (0.02–368 μg/liter) in Cardiff. There were no associations between urine perchlorate concentrations and serum TSH or FT4 in the individual euthyroid or hypothyroid/hypothyroxinemic cohorts. In multivariable linear analyses, log perchlorate was not a predictor of serum FT4 or TSH.

Conclusions: Low-level perchlorate exposure is ubiquitous but did not affect thyroid function in this cohort of iodine-deficient pregnant women.
The ciliary pocket: an endocytic membrane domain at the base of primary and motile cilia
Authors: Molla-Herman Anahi , Ghossoub Rania , Blisnick Thierry , Meunier Alice , Serres Catherine , Silbermann Flora , Emmerson Chris , Romeo Kelly , Bourdoncle Pierre , Schmitt Alain , Saunier Sophie , Spassky Nathalie , Bastin Philippe , Benmerah Alexandre
Published: April 2010

Cilia and flagella are eukaryotic organelles involved in multiple cellular functions. The primary cilium is generally non motile and found in numerous vertebrate cell types where it controls key signalling pathways. Despite a common architecture, ultrastructural data suggest some differences in their organisation. Here, we report the first detailed characterisation of the ciliary pocket, a depression of the plasma membrane in which the primary cilium is rooted. This structure is found at low frequency in kidney epithelial cells (IMCD3) but is associated with virtually all primary cilia in retinal pigment epithelial cells (RPE1). Transmission and scanning electron microscopy, immunofluorescence analysis and videomicroscopy revealed that the ciliary pocket establishes closed links with the actin-based cytoskeleton and that it is enriched in active and dynamic clathrin-coated pits. The existence of the ciliary pocket was confirmed in mouse tissues bearing primary cilia (cumulus), as well as motile cilia and flagella (ependymal cells and spermatids). The ciliary pocket shares striking morphological and functional similarities with the flagellar pocket of Trypanosomatids, a trafficking-specialised membrane domain at the base of the flagellum. Our data therefore highlight the conserved role of membrane trafficking in the vicinity of cilia.
Telomeric function of mammalian telomerases at short telomeres
Authors: Fakhoury Johans , Marie-Egyptienne Delphine Tamara , Londoño-Vallejo José-Arturo , Autexier Chantal
Published: April 2010

Telomerase synthesizes telomeric sequences and is minimally composed of a reverse transcriptase (RT) known as TERT and an RNA known as TR. We reconstituted heterologous mouse (m) and human (h) TERT-TR complexes and chimeric mTERT-hTERT-hTR complexes in vitro and in immortalized human alternative lengthening of telomere (ALT) cells. Our data suggest that species-specific determinants of activity, processivity and telomere function map not only to the TR but also to the TERT component. The presence of hTERT-hTR, but not heterologous TERT-TR complexes or chimeric mTERT-hTERT-hTR complexes, significantly reduced the percentage of chromosomes without telomeric signals in ALT cells. Moreover, heterologous and chimeric complexes were defective in recruitment to telomeres. Our results suggest a requirement for several hTERT domains and interaction with multiple proteins for proper recruitment of telomerase to the shortest telomeres in human ALT cells. Late-passage mTERT−/− mouse embryonic stem (ES) cells ectopically expressing hTERT or mTERT harboured fewer chromosome ends without telomeric signals and end-to-end fusions than typically observed in late-passage mTERT−/− ES cells. The ability of hTERT to function at mouse telomeres and the inability of mTERT to function at human telomeres suggest that mechanisms regulating the recruitment and activity of hTERT at mouse telomeres might be less stringent than the mechanisms regulating mTERT at human telomeres.
Multi-objective optimization of a centrifugal compressor impeller through evolutionary algorithms
Authors: Kim J-H , Choi J-H , Husain A , Kim K-Y
Published: April 2010

This paper presents the design optimization of a centrifugal compressor impeller with a hybrid multi-objective evolutionary algorithm. Reynolds-averaged Navier—Stokes (RANS) equations are solved with the shear stress transport turbulence model as a turbulence closure model. Flow analysis is performed on a hexahedral grid through a finite-volume solver. Two objectives, viz., the isentropic efficiency and the total pressure ratio (PR), are selected with four design variables that define the impeller hub and shroud contours in meridian terms for optimizing the system. The validation of numerical results was performed through experimental data for the total PR and the isentropic efficiency. Objective-function values are numerically evaluated through the RANS analysis at design points that are selected through the Latin hypercube sampling method. A fast and elitist non-dominated sorting genetic algorithm (NSGA-II) with an ε-constraint strategy for local search coupled with a surrogate model is used for multi-objective optimization. The surrogate model, the radial basis neural network, is trained on discrete numerical solutions by the execution of leave-one-out cross-validation for the dataset. The trade-off between the two objectives has been ascertained and discussed in the light of Pareto-optimal solutions. The optimization results show that the isentropic efficiency and the total PR are enhanced at both design and off-design conditions through multi-objective optimization.
Implementation and investigation of internet-based teleoperation of a mobile robot using wave variable approach
Authors: Hassanzadeh I , Moosapour S S , Mansouria S
Published: April 2010

In the present paper, the wave variable method is applied for internet-based teleoperation of a mobile robot in practice. In the proposed setup, a force feedback joystick is employed as a haptic device on the master side. In order to compensate for large time delays of transmitting data and have better transparency, a Virtual Reality Simulator (VRS) model was designed using VRML builder® embedded with Matlab®. An open architecture package was developed using Matlab, Simulink®, and xPC target® that handles real-time control of the mobile robot through the internet as well as simulation tasks. xPC target has hardware in-the-loop (HIL) property, providing advantages such as ease of use, reliability, and flexibility. With this open package various controllers for the system can easily be investigated. As a case study, a Khepera II mobile robot is considered and several experiments with diverse scenarios are carried out. Simulation and experimental results show that teleoperation of the mobile robot using the wave variable technique is not efficient in terms of internet delay compensation.
An identification-based state estimation method for a class of non-linear systems
Authors: Atam E , Hooker G
Published: April 2010

In this paper, an online state estimation method for unmeasured states appearing linearly in deterministic non-linear systems is developed. The method is based on a recursive least-squares identification algorithm. The proposed method possesses some superior properties, mainly its simplicity and better estimation performance, compared with other typical estimation methods. The effectiveness of the method is demonstrated on case studies with a comparison to the popular extended Kalman filter (EKF). Although the method is presented for state estimation, it can be easily modified for time-varying parameter estimation.
Delay-dependent global robust stability criterion for neural networks with neutral-type time-varying delays
Authors: Wang G , Chen W , Liu Y
Published: April 2010

The problem of global robust stability for neural networks with neutral-type time-varying delays is investigated in this paper. Neutral differential equations are used to construct this class of neural networks. The time-varying delay function is bounded, and it is not required to be continuously differentiable. A new delay-dependent global stability criterion is derived based on the Lyapunov-Krasovskii functional approach. The criterion is formulated in terms of a linear matrix inequality. Numerical examples are given to illustrate the validity of the proposed stability criterion.
Large eddy simulation analysis of engine steady intake flows using a mixed-time-scale subgrid-scale model
Authors: Inagaki M , Nagaoka M , Horinouchi N , Suga K
Published: April 2010

Large eddy simulation (LES) using a mixed-time-scale (MTS) subgrid-scale (SGS) model is applied to the intake flows in simplified internal combustion engine geometry. A modified colocated grid system is employed to obtain results as precise as possible and to perform calculations in a stable way with a central difference scheme for convective terms.

The results are compared with corresponding experimental data and the Reynolds averaged Navier—Stokes (RANS) equation model results obtained using the low-Reynolds-number linear k—

In addition, it is made clear that when the QUICK scheme is used in LES for the convective terms instead of the central difference scheme, the result obtained deteriorates owing to the numerical viscosity. The importance of the discretization method in practical LES is also confirmed.
Implementation of multi-objective optimization for vulnerability analysis of complex networks
Authors: Rocco C M , Ramirez-Marquez J E , Salazar D E , Hernandez I
Published: April 2010

This paper describes the vulnerability analysis of a complex network as the process of identifying the combination of component failures that provide maximum reduction of network performance. By way of a vulnerability analysis, the understanding of these failures can be related to the occurrence of a disruptive event, and also to the fundamental tasks for the protection of critical infrastructures. To describe vulnerability, the paper provides an analytical method to characterize completely the importance of network disruptions and identify a vulnerability set via the solution of a proposed multi-objective network vulnerability problem. This approach makes it possible to recognize that decision-makers (e.g. network managers) could benefit from understanding the relationship between different failure scenarios and network performance, for example, how the increase in protection resources would reduce the vulnerability of the network. Numerical examples, related to a medium-sized network and two complex networks, are solved using the evolutionary algorithm known as the multi-objective probabilistic solution discovery algorithm (MO-PSDA) and illustrate the proposed approach.
Some testimators for the scale parameter and reliability function of Weibull lifetime data
Authors: Al-Hemyari Z A
Published: April 2010

The Weibull failure model is considered in this paper. Some testimators are proposed of the scale parameter (β) and of the reliability function ( R( t)) using life-testing data when a prior value about the unknown parameter (β) is available. The expressions for the bias, mean squared error and relative efficiency are obtained and compared with existing estimators.
On the Importance of Lennard–Jones Parameter Calibration in QM/MM Framework: Reaction Path Tracing via Free Energy Gradient Method for Ammonia Ionization Process in Aqueous Solution
Authors: Koyano Yoshiyuki , Takenaka Norio , Nakagawa Yukinori , Nagaoka Masataka
Published: April 2010

The free energy gradient (FEG) method combined with the QM/MM–MD calculation has realized full-atomic structural optimization of the solute NH3–H2O molecule pair in aqueous solution, exploring successful tracing of the reaction path on the free energy surface from the neutral state (H3N–H2O) to the ionized (H4+N–O−H) through the transition state (H3N···H+···O−H). To reproduce accurately the structural change of the hydrated molecule pair, the LJ parameter calibration in the QM/MM nonelectrostatic interaction was essential for four kinds of QM solute species, i.e., OH−, H2O, NH3, and NH4+, treated in the NDDO-SSRP framework with the ab initio quality. Two linear interpolations of these calibrated LJ parameters optimized at the NSS and ISS were utilized in the path-dependent FEG calculation, as is common in the free energy perturbation treatment. After including the effects of the intramolecular entropic contribution and quantum tunneling, the free energies of activation and reaction were satisfactorily estimated to be 13.8 and 9.8 kcal mol−1 (1 kcal = 4.184 kJ), respectively. It is expected that far more agreement with the experimental values should be reasonably attained if the QM region were extended to three surrounding water molecules to take in the electron delocalization effect adequately.
Synthesis of π-Conjugated Polymers by Organometallic Polycondensation
Authors: Yamamoto Takakazu
Published: April 2010

Organometallic polycondensations give various π-conjugated polymers. For example, nickel complex-promoted dehalogenative polycondensation of dihaloaromatic compounds and dihalogenataed heterocyles, X–Ar–X (Ar = aromatic unit or heterocyclic unit), affords poly(arylene)s and poly(heterocycles), (Ar)n, such as poly(p-phenylene), poly(thiophene-2,5-diyl), poly(3-alkylthiophene-2,5-diyl), and poly(pyridine-2,5-diyl). Pd-catalyzed polycondensation gives poly(aryleneethynylene) type polymers and alternating copolymers of Ar and Ar′. These polymers have well defined bonds between the monomeric units, and they are electrochemically active, electrically conductive, and light-emitting. Their well-characterized linear structure brings about unique packing of the polymer molecules in the solid and alignment of the polymer molecules on the surface of substrates. In this paper, we describe synthesis of π-conjugated polymers by organometallic polycondensations. Basic chemical and physical properties of the synthesized π-conjugated polymers, as well as ordered structures in the solid and applications for electronic and optical devices of the π-conjugated polymers, are also described.
Preferences for limited versus no contact in SD rats
Authors: Sørensen Dorte , Hanse Helle , Krohn Thomas , Bertelsen Thomas
Published: April 2010

In biomedical research, single housing of rats is used in different test paradigms and the rats are traditionally group-housed prior to testing. Intuitively this separation may have a negative impact on animal welfare. The objective of this study was to assess the importance of non-tactile contact with a social partner. The hypothesis was that rats, previously housed in pairs, prefer non-tactile contact with a partner to single housing. Moreover, it was hypothesized that females show a higher preference for non-tactile contact than males. Animals were housed for 48 h in two-compartment cages, where the animal could choose either to spend time in the compartment, where only a perforated plexiglas wall separated it from its social partner, or to spend time in the compartment with no rat behind the plexiglas barrier. The proportion of time spent in the two compartments was evaluated. We found a significant effect on gender ( P = 0.0368) with females spending significantly more time close to the companion animal. During their inactive period, females spent approximately half their time close to their partner, whereas males preferred to stay in the cage next to the empty compartment. Female rats also demonstrated more activity compared with males ( P < 0.0001).
Local histories and local sensemaking: a case of policy implementation in the English National Health Service
Authors: Coleman Anna , Checkland Kath , Harrison Stephen , Hiroeh Urara
Published: April 2010

Central policies that are only loosely specified might be expected to result in local variations in interpretation and implementation, and practice-based commissioning in the English National Health Service (NHS) is no exception. We show how local ‘sensemaking’ in relation to this policy has been influenced by local histories and by conceptual schemata derived from earlier reorganisations of the NHS. Changes to organisational formalities do not necessarily, therefore, result in reappraisals of sensemaking on the part of local actors. We also employ our data to address issues raised by commentators critical of the way the concept of sensemaking has been previously employed.
The European Register of Specialists in Clinical Chemistry and Laboratory Medicine: Guide to the Register, Version 3-2010
Authors: McMurray Janet , Zérah Simone , Hallworth Michael , Schuff-Werner Peter , Haushofer Alexander , Szekeres Thomas , Wallemacq Pierre , Tzatchev Kamen , Charilaou Charis , Racek Jaroslav , Johnsen Anders , Tomberg Karel , Harmoinen Aimo , Baum Hannsjörg , Rizos Demetrios , Kappelmayer Janos , O'Mullane John , Nubile Giuseppe , Pupure Silvija , Kucinskiene Zita , Opp Matthias , Jansen Rob , Solnica Bogdan , Reguengo Henrique , Grigore Camelia , Ŝpaňár Július , Ŝtrakl Greta , Queralto Josep , Wallinder Hans , Wieringa Gijsbert
Published: April 2010

In 1997, the European Communities Confederation of Clinical Chemistry and Laboratory Medicine (EC4) set up a Register for European Specialists in Clinical Chemistry and Laboratory Medicine. The operation of the Register is undertaken by a Register Commission (EC4RC). During the last 12 years, more than 2200 specialists in Clinical Chemistry and Laboratory Medicine have joined the Register. In 2007, EC4 merged with the Forum of European Societies of Clinical Chemistry and Laboratory Medicine (FESCC) to form the European Federation of Clinical Chemistry and Laboratory Medicine (EFCC). Two previous Guides to the Register have been published, one in 1997 and another in 2003. The third version of the Guide is presented in this article and is based on the experience gained and development of the profession since the last revision. Registration is valid for 5 years and the procedure and criteria for re-registration are presented as an Appendix at the end of the article.

Clin Chem Lab Med 2010;48:999–1008.
An exercise in a posteriori language sampling
Authors: Dahl Östen
Published: April 2010

A central methodological issue in language typology is sampling  how to choose a representative set of languages for a typological investigation. Most proposed typological sampling methods are a priori in the sense that they are based on assumed, rather than observed, effects of biasing factors  such as genealogical and areal proximity. The advent of the World Atlas of Language Structures (WALS) creates for the first time a chance to attempt a posteriori sampling. The basic idea is to create a sample by removing from the set of available languages one member of each pair of languages whose typological distance  as defined in terms of the features in WALS  does not reach a predefined threshold. In this way, a sample of 101 languages was chosen from an initial set of the 222 languages that are best represented in WALS. The number of languages from different macroareas in this sample can be taken as an indication of the internal diversity of the area in question. Two issues are discussed in some detail: (i) the high diversity of the indigenous languages of the Americas and the tendency for these to be underrepresented by previous sampling methods; (ii) the extreme areal convergence of Mainland South East Asian languages. It is concluded that areal factors cannot be neglected in typological sampling, and that it must be questioned whether the creation of elaborate sampling algorithms makes sense.
Automated classification of the world′s languages: a description of the method and preliminary results
Authors: Brown Cecil H. , Holman Eric W. , Wichmann Søren , Velupillai Viveka
Published: April 2010

An approach to the classification of languages through automated lexical comparison is described. This method produces near-expert classifications. At the core of the approach is the Automated Similarity Judgment Program (ASJP). ASJP is applied to 100-item lists of core vocabulary from 245 globally distributed languages. The output is 29,890 lexical similarity percentages for the same number of paired languages. Percentages are used as a database in a program designed originally for generating phylogenetic trees in biology. This program yields branching structures (ASJP trees) reflecting the lexical similarity of languages. ASJP trees for languages of the sample spoken in Middle America and South America show that the method is capable of grouping together on distinct branches languages of non-controversial genetic groups. In addition, ASJP sub-branching for each of nine respective genetic groups  Mayan, Mixe-Zoque, Otomanguean, Huitotoan-Ocaina, Tacanan, Chocoan, Muskogean, Indo-European, and Austro-Asiatic  agrees substantially with subgrouping for those groups produced by expert historical linguists. ASJP can be applied, among many other uses, to search for possible relationships among languages heretofore not observed or only provisionally recognized. Preliminary ASJP analysis reveals several such possible relationships for languages of Middle America and South America. Expanding the ASJP database to all of the world′s languages for which 100-word lists can be assembled is a realistic goal that could be achieved in a relatively short period of time, maybe one year or even less.