bluuebunny/crossref_metadata_2025 huggingface dataset:
A predictive model for respiratory syncytial virus (RSV) hospitalisation of premature infants born at 33–35 weeks of gestational age, based on data from the Spanish FLIP study
Authors: Simões Eric AF , Carbonell-Estrany Xavier , Fullarton John R , Liese Johannes G , Figueras-Aloy Jose , Doering Gunther , Guzman Juana ,   European RSV Risk Factor Study Group
Published: December 2008

Background

The aim of this study, conducted in Europe, was to develop a validated risk factor based model to predict RSV-related hospitalisation in premature infants born 33–35 weeks' gestational age (GA).

Methods

The predictive model was developed using risk factors captured in the Spanish FLIP dataset, a case-control study of 183 premature infants born between 33–35 weeks' GA who were hospitalised with RSV, and 371 age-matched controls. The model was validated internally by 100-fold bootstrapping. Discriminant function analysis was used to analyse combinations of risk factors to predict RSV hospitalisation. Successive models were chosen that had the highest probability for discriminating between hospitalised and non-hospitalised infants. Receiver operating characteristic (ROC) curves were plotted.

Results

An initial 15 variable model was produced with a discriminant function of 72% and an area under the ROC curve of 0.795. A step-wise reduction exercise, alongside recalculations of some variables, produced a final model consisting of 7 variables: birth ± 10 weeks of start of season, birth weight, breast feeding for ≤ 2 months, siblings ≥ 2 years, family members with atopy, family members with wheeze, and gender. The discrimination of this model was 71% and the area under the ROC curve was 0.791. At the 0.75 sensitivity intercept, the false positive fraction was 0.33. The 100-fold bootstrapping resulted in a mean discriminant function of 72% (standard deviation: 2.18) and a median area under the ROC curve of 0.785 (range: 0.768–0.790), indicating a good internal validation. The calculated NNT for intervention to treat all at risk patients with a 75% level of protection was 11.7 (95% confidence interval: 9.5–13.6).

Conclusion

A robust model based on seven risk factors was developed, which is able to predict which premature infants born between 33–35 weeks' GA are at highest risk of hospitalisation from RSV. The model could be used to optimise prophylaxis with palivizumab across Europe.
Magnetic gradients produced by a 2D homogeneous polygonal source
Authors: Jia Zhen , Meng Lingshun
Published: December 2008

We use a set of analytic equations for calculating horizontal and vertical gradients of the magnetic anomaly produced by a 2D homogeneous magnetic source with a polygonal cross section. The magnetization vector of the source is assumed to be constant and known, and the anomalous field is assumed to be much smaller than the ambient geomagnetic field in magnitude. The derivation begins from an expression of the magnetic potential; then we evaluate clockwise integrations to establish the equations. A comparison between this analytic approach and a numerical approach using the finite-difference method to compute gradients indicates the reliability of the equations. The proposed method is numerically efficient and does not present singularity on the edges of the polygon prism, except at the vertices where the gradients approach to infinity.
Equivalent viscoelastic solids for heterogeneous fluid-saturated porous rocks
Authors: Rubino J. Germán , Ravazzoli Claudia L. , Santos Juan E.
Published: December 2008

Different theoretical and laboratory studies on the propagation of elastic waves in real rocks have shown that the presence of heterogeneities larger than the pore size but smaller than the predominant wavelengths (mesoscopic-scale heterogeneities) may produce significant attenuation and velocity dispersion effects on seismic waves. Such phenomena are known as “mesoscopic effects” and are caused by equilibration of wave-induced fluid pressure gradients. We propose a numerical upscaling procedure to obtain equivalent viscoelastic solids for heterogeneous fluid-saturated rocks. It consists in simulating oscillatory compressibility and shear tests in the space-frequency domain, which enable us to obtain the equivalent complex undrained plane wave and shear moduli of the rock sample. We assume that the behavior of the porous media obeys Biot’s equations and use a finite-element procedure to approximate the solutions of the associated boundary value problems. Also, because at mesoscopic scales rock parameter distributions are generally uncertain and of stochastic nature, we propose applying the compressibility and shear tests in a Monte Carlo fashion. This facilitates the definition of average equivalent viscoelastic media by computing the moments of the equivalent phase velocities and inverse quality factors over a set of realizations of stochastic rock parameters described by a given spectral density distribution. We analyzed the sensitivity of the mesoscopic effects to different kinds of heterogeneities in the rock and fluid properties using numerical examples. Also, the application of the Monte Carlo procedure allowed us to determine the statistical properties of phase velocities and inverse quality factors for the particular case of quasi-fractal heterogeneities.
Phosphorylated ERα, HIF-1α, and MAPK Signaling As Predictors of Primary Endocrine Treatment Response and Resistance in Patients With Breast Cancer
Authors: Generali Daniele , Buffa Francesca M. , Berruti Alfredo , Brizzi Maria P. , Campo Leticia , Bonardi Simone , Bersiga Alessandra , Allevi Giovanni , Milani Manuela , Aguggini Sergio , Papotti Mauro , Dogliotti Luigi , Bottini Alberto , Harris Adrian L. , Fox Stephen B.
Published: December 2008

Purpose

We aimed to identify signaling pathways involved in the response and resistance to aromatase inhibitor therapy in patients with breast cancer.

Patients and Methods

One hundred fourteen women with T2-4 N0-1, estrogen receptor (ER) α–positive tumors were randomly assigned to neoadjuvant letrozole or letrozole plus metronomic cyclophosphamide. Twenty-four tumor proteins involved in apoptosis, cell survival, hypoxia, angiogenesis, growth factor, and hormone signaling were assessed by immunohistochemistry in pretreatment samples (eg, caspase 3, phospho- mammalian target of rapamycin, hypoxia-inducible factor 1α [HIF-1α], vascular endothelial growth factor, mitogen-activated protein kinase [MAPK], phosphorylated epidermal growth factor receptor, phosphorylated ERα [pERα]). A multivariate generalized linear regression approach was applied using a penalized least-square minimization to perform variable selection and regularization. Ten-fold cross-validation and iterative leave-one-out were employed to validate and test the model, respectively. Tumor size, nodal status, age, tumor grade, histological type, and treatment were included in the analysis.

Results

Ninety-one patients (81%) attained a disease response, 48 achieved a complete clinical response (43%) whereas 22 did not respond (19%). Increased pERα and decreased p44/42 MAPK were significant factors for complete response to treatment in all leave-one-out iterations. Increased p44/42 MAPK and HIF-1α were significant factors for treatment resistance in all leave-one-out iterations. There was no significant interaction between these variables and treatment.

Conclusion

Activated ERα form was an independent factor for sensitivity to chemoendocrine treatment, whereas HIF-1α and p44/42 MAPK were independent factors for resistance. Although further confirmatory analyses are needed, these findings have clear potential implications for future strategies in the management of clinical trials with aromatase inhibitors in the breast cancer.
Increased Incidence of Transformation and Myelodysplasia/Acute Leukemia in Patients With Waldenström Macroglobulinemia Treated With Nucleoside Analogs
Authors: Leleu Xavier , Soumerai Jacob , Roccaro Aldo , Hatjiharissi Evdoxia , Hunter Zachary R. , Manning Robert , Ciccarelli Bryan T. , Sacco Antonio , Ioakimidis Leukothea , Adamia Sophia , Moreau Anne-Sophie , Patterson Christopher J. , Ghobrial Irene M. , Treon Steven P.
Published: December 2008

Purpose

Nucleoside analogs (NAs) are considered as appropriate agents in the treatment of Waldenström macroglobulinemia (WM), a lymphoplasmacytic lymphoma. Sporadic reports on increased incidence of transformation to high-grade non-Hodgkin's lymphoma and development of therapy-related myelodysplasia/acute leukemia (t-MDS/AML) among patients with WM treated with NAs prompted us to examine the incidence of such events in a large population of patients with WM.

Patients and Methods

We examined the incidence of these events in 439 patients with WM, 193 and 136 of whom were previously treated with and without an NA, respectively, and 110 of whom had similar long-term follow-up without treatment. The median follow-up for all patients was 5 years.

Results

Overall, 12 patients (6.2%) either developed transformation (n = 9; 4.7%) or developed t-MDS/AML (n = 3; 1.6%) among NA-treated patients, compared with one patient (0.4%) who developed transformation in the non-NA treated group (P < .001); no such events occurred among untreated patients. Transformation and t-MDS/AML occurred at a median of 5 years from onset of NA therapy. The median survival of NA-treated patients who developed transformation did not differ from other NA-treated patients as a result of effective salvage treatment used for transformed disease. However, all NA-treated patients who developed t-MDS/AML died at a median of 5 months.

Conclusion

These data demonstrate an increased incidence of disease transformation to high-grade NHL and the development of t-MDS/AML among patients with WM treated with NAs.
Favorable Long-Term Survival After Reduced-Intensity Allogeneic Transplantation for Multiple-Relapse Aggressive Non-Hodgkin's Lymphoma
Authors: Thomson Kirsty J. , Morris Emma C. , Bloor Adrian , Cook Gordon , Milligan Don , Parker Anne , Clark Fiona , Yung Lynny , Linch David C. , Chakraverty Ronjon , Peggs Karl S. , Mackinnon Stephen
Published: December 2008

Purpose

The role of allogeneic transplantation with reduced-intensity conditioning in diffuse large B-cell lymphoma (DLBCL) is currently unclear, with relatively little published data. We report the outcome of reduced-intensity transplantation (RIT) in a cohort of 48 consecutive patients with relapsed/refractory DLBCL (30 patients with de novo disease and 18 patients with transformed follicular lymphoma) who underwent transplantation with an alemtuzumab-containing regimen, with a median follow-up of 52 months.

Patients and Methods

Patients had experienced treatment failure with a median of five lines of prior therapy, including autologous transplantation in 69%, and 17% of patients were chemotherapy refractory at transplantation. Median age was 46 years, and 38% of patients had matched/mismatched unrelated donors. Conditioning was with alemtuzumab, fludarabine, and melphalan, and additional graft-versus-host disease (GVHD) prophylaxis was with cyclosporine.

Results

All patients were successfully engrafted. Only 17% of patients developed grade 2 to 4 acute GVHD, with 13% experiencing extensive chronic GVHD. Four-year estimated nonrelapse mortality was 32%, and relapse risk was 33%. Twelve patients received donor lymphocyte infusions ± chemoimmunotherapy for relapse, and five patients obtained durable remissions, giving current progression-free survival (PFS) and overall survival (OS) rates at 4 years of 48% and 47%, respectively. Patients who had chemotherapy-sensitive disease before RIT had current PFS and OS rates at 4 years of 55% and 54%, respectively. Chemotherapy-refractory patients had a poor outcome.

Conclusion

The encouraging survival rates with extended follow-up suggest a role for RIT in chemotherapy-sensitive relapsed DLBCL, even in patients who have previously experienced treatment failure with autologous transplantation. Future studies will be required to determine whether any subset of patients with relapsed DLBCL should be considered for RIT versus autologous transplantation.
Insulin, the Insulin-Like Growth Factor Axis, and Mortality in Patients With Nonmetastatic Colorectal Cancer
Authors: Wolpin Brian M. , Meyerhardt Jeffrey A. , Chan Andrew T. , Ng Kimmie , Chan Jennifer A. , Wu Kana , Pollak Michael N. , Giovannucci Edward L. , Fuchs Charles S.
Published: December 2008

Purpose

Obesity, sedentary lifestyle, and Western dietary pattern have been linked to increased risk of cancer recurrence and mortality among patients with surgically resected colorectal cancer. Excess energy balance leads to increased circulating insulin and depressed levels of circulating insulin-like growth factor binding protein (IGFBP) -1, which promote cancer cell growth in preclinical models.

Patients and Methods

Among 373 patients diagnosed with nonmetastatic colorectal cancer between 1991 and 2004, we performed a prospective observational study nested within two large US cohorts to evaluate the association between mortality and prediagnosis circulating C-peptide (a marker of insulin secretion), IGFBP-1, insulin-like growth factor-I (IGF-I), and IGFBP-3.

Results

Compared with patients in the bottom quartile, patients in the top quartile of plasma C-peptide had an age-adjusted hazard ratio (HR) for death of 1.87 (95% CI, 1.04 to 3.36; P = .03 for trend), whereas those in the top quartile of circulating IGFBP-1 had a significant reduction in mortality (HR = 0.48; 95% CI, 0.28 to 0.84; P = .02 for trend). Little change in these estimates was noted after adjusting for other covariates known or suspected to influence survival. No associations were noted between mortality and IGF-I or IGFBP-3, which are two components of the IGF axis not closely correlated with lifestyle factors.

Conclusion

Among patients with surgically resected colorectal cancer, higher levels of prediagnosis plasma C-peptide and lower levels of prediagnosis plasma IGFBP-1 were associated with increased mortality. Circulating insulin and IGFBP-1 are potential mediators of the association between lifestyle factors and mortality after colorectal cancer resection.
Inertia friction welds between nickel superalloy components: Analysis of residual stress by eigenstrain distributions
Authors: Korsunsky A M , Regino G M , Nowell D , Karadge M , Grant B , Withers P J , Preuss M , Baxter G
Published: December 2008

Machining, surface treatment, plastic forming and stretching, welding, and other manufacturing processes introduce residual stresses and distortion into work pieces and engineering components. These phenomena exert a significant influence on the behaviour of components affecting the response to thermal/mechanical in-service loading, e.g. in terms of crack initiation and propagation under the conditions of creep and fatigue, thus ultimately affecting their durability. In the present study, the inertia friction welding process is considered that is used for butt joining of hollow cylindrical components, such as shafts and drums. An inverse eigenstrain framework is used for the interpretation of neutron diffraction measurements in terms of the underlying eigenstrain distributions. Eigenstrain distributions that describe the nature of permanent inelastic deformation are found by minimizing the sum-of-squares measure of the disagreement between model prediction and experimental measurements of residual elastic strains. Experimental data obtained from neutron diffraction measurements are used in an inverse solution scheme in order to determine the underlying eigenstrain (strains permanently ‘locked in’) that give rise to the residual stress state. Once these are found, approximate reconstruction of the complete stress tensor within the entire component becomes straightforward. Eigenstrain distributions are first obtained for reduced size test specimens which have been characterized in detail using neutron diffraction. Subsequently, the eigenstrain distributions are scaled and applied to more complex, full-size real engine components, with scaling factors adjusted to match surface hole drilling measurements.
Genetic algorithm optimization of the hole-drilling method for non-uniform residual stress fields
Authors: Beghini M , Bertini L , Mori L F , Rosellini W
Published: December 2008

The hole-drilling method, coupled with the influence functions method, is a versatile technique for measuring residual stresses. The latter determines a relationship between residual stress and measured relaxed strains for any experimental configuration and material. However, several parameters which describe the functional basis for the residual stress must be defined. This paper presents a procedure, based on the least squares method and genetic algorithms, optimally to choose these parameters to reduce the effects of noise and uncertainty in experimental measurements. The performance of the method was tested against finite element simulations for typical applications such as shot peening, showing that the method is flexible and accurate and allows the reconstruction of residual stress at deeper positions than other techniques.
Architecture for machining process and production monitoring based in open computer numerical control
Authors: Oliveira J F G , Ferraz Júnior F , Coelho R T , Silva E J
Published: December 2008

This paper proposes an architecture for machining process and production monitoring to be applied in machine tools with open computer numerical control (CNC). A brief description of the advantages of using open CNC for machining process and production monitoring is presented with an emphasis on the CNC architecture using a personal computer (PC)-based human—machine interface. The proposed architecture uses the CNC data and sensors to gather information about the machining process and production. It allows the development of different levels of monitoring systems with minimum investment, minimum need for sensor installation, and low intrusiveness to the process. Successful examples of the utilization of this architecture in a laboratory environment are briefly described. As a conclusion, it is shown that a wide range of monitoring solutions can be implemented in production processes using the proposed architecture.
Estimation of Gurson material parameters in bimetallic weldments for the nuclear reactor heat transport piping system
Authors: Chhibber R , Arora N , Gupta S R , Dutta B K
Published: December 2008

Bimetallic welds (BMWs) play a critical and indispensable role in the primary heat transport piping system of nuclear reactors. The primary heat transport system itself is the critical part of a nuclear reactor. Any failure of this system can lead to very grave consequences, not only speaking of huge monetary losses resulting from non-utilization of the reactor setup, but also immensely valuable and irreparable loss of human life. This paper describes the experimental efforts towards estimation of Gurson material parameters of base metal and weld metal regions of a BMW so as to use the micromechanical modelling approach for addressing the structural integrity issues in BMWs.
Flexural stiffness of leaf springs for compliant micromechanisms
Authors: Angeli P , De Bona F , Munteanu M G
Published: December 2008

Von Kármán equations have been used to evaluate the flexural behaviour of rectangular leaf springs with constant thickness. A closed form solution is obtained, showing that flexural stiffness varies continuously from that obtained by considering a beam model to the value given by the linear plate theory. This behaviour depends on section geometry, Poisson's ratio, and main curvature. A new characterizing parameter, whose relation with flexural stiffness allows a typical non-linear behaviour to be emphasized, is introduced in this work. In particular, for a given geometry and material, the flexural stiffness increases with the deflection and consequently with the load.
Type determination and analysis of mobility region for bimodal linkages
Authors: Chung W-Y
Published: December 2008

A bimodal linkage has two potential output angles for any given input angle and vice versa. The analysis treats all bimodal linkages as a common problem. A conic curve is derived from the general input—output equation. The mobility regions of any concerned link are then attained from the intersection points between the conic curve and a unit circle with the aid of corresponding differentiation. The linkages with one axis of the conic curve passing through the origin are classified as a selective group. The concise criteria for type determination exist for this group, and the strategies to derive them straightforwardly are developed. Unlike Grashof's rule, which is only applicable to planar four-bar, the criteria developed can be used to determine the type efficiently for all linkages belonging to this selective group and are certainly preferable. The linkages with prismatic output are also considered. Several examples including RPSPR, RPSC, RSSR, and RSSP linkages are given for illustration.
Testing and analysis of fatigue behaviour in edge details: A comparative study using hot spot and structural stresses
Authors: Kim M-H , Kang S-W
Published: December 2008

At present, the fatigue design of welded structures is primarily based on a nominal stress or hot spot stress (HSS) approach with a series of classified weld S-N curves. Although well accepted by major industries, the nominal stress-based fatigue design approach is relatively cumbersome in terms of securing a series of S-N curves corresponding to each class of joint types and loading modes. Moreover, it is very difficult, if not impossible, to determine the nominal stress at each structural component, particularly in complex ship structures. The HSS-based fatigue design is based on the stress at the weld toes obtained by linear or quadratic extrapolation of stresses over two or three points in front of the weld toe. Finite-element analysis is mostly applied. However, this method has a difficulty of finding a proper stress through the global model, the medium size model and the detail model of ship structure. Besides, the calculated HSS values may vary depending on the extrapolation technique used. Recently, a mesh-size insensitive structural stress (SS) definition that gives a stress state at the weld toe with a relatively large mesh size has been proposed. The SS definition is based on the elementary structural mechanics theory and provides an effective measure of a stress state in front of the weld toe. As an experimental validation of the Battelle SS method in obtaining the fatigue strength of weldments, a series of experiments are carried out for various sizes of weldments. Based on the results from this study, it is expected to achieve the development of a more precise fatigue strength evaluation technique and saving on the time required in the fatigue design of ship and offshore structures.
Modelling and optimizing automotive assembly plant flash-programming time
Authors: Shi J , Rosa C H
Published: December 2008

As automotive companies standardize their electronic control units (ECUs) on a common electrical architecture across all vehicle platforms, more and more software-enabled features will be delivered using assembly plant flash programming. Assembly plant flash programming is the process by which software or calibration data sets are downloaded to vehicle electronic control units using an off-board programming tool during the final vehicle assembly process, thus postponing vehicle product differentiation and customization, reducing the rate of growth in the number of unique ECU part numbers, and reducing manufacturing complexity. As vehicle electronic control modules and their software content or calibration data sets increase, the demand on manufacturing time and space increases significantly. This paper identifies and examines all factors that impact the assembly plant flash-programming time, develops simple and accurate analytical models, and describes an innovative optimization-based approach for determining the parallel flash-programming time for the in-vehicle communication buses that are capable of interleaving packets. The optimization approach can be used to identify the optimal scheme for the parallel flash programming of all vehicle ECUs. By following the suggested scheme, it can dramatically increase the amount of calibration data that can be flash programmed within the same process time constraint, thus increasing manufacturing flexibility and more fully utilizing limited manufacturing production capacity.
Effect of an electromagnetically optimized magnetorheological damper on vehicle suspension control performance
Authors: Sung K-G , Choi S-B
Published: December 2008

This paper examines the effect of an electromagnetically optimized magnetorheological (MR) damper for vehicle suspension on vibration control performance. In order to achieve this goal, a cylindrical MR damper that satisfies design specifications for a middle-sized commercial passenger vehicle is designed using an optimization methodology. The optimization problem is to find the optimal geometric dimensions of the electromagnetic circuit for the MR damper in order to maximize the damping force. A first-order optimization method using commercial finite element method (FEM) software is adopted for the constrained optimization algorithm. After manufacturing the MR damper with optimally obtained design parameters, its field-dependent characteristics are experimentally evaluated. The effect of the optimal MR damper on suspension control is then investigated using a quarter-vehicle test facility. Control performances such as vertical acceleration, suspension travel, and power consumption are evaluated and compared between the initial and optimal dampers. In addition, vibration control performances of the optimal MR damper are experimentally evaluated under bump and random road conditions and presented in both time and frequency domains.
An experimental study on the performance and exhaust emissions of a diesel engine fuelled with soybean oil methyl ester
Authors: Song J-T , Zhang C-H
Published: December 2008

In order to optimize the application of biodiesel for diesel engines, the emissions, fuel economies, and power performances of diesel, soybean oil methyl ester, and its blends with diesel from 10 to 80wt% were compared and analysed by bench tests of a supercharged direct injection (DI) diesel engine. The exhaust emissions (smoke density, NO x, CO, and HC), the brake specific fuel consumption rate, the specific energy consumption rate, and the brake power and torque were investigated under different engine loads and speeds. Experimental results show that, compared with diesel fuel, with increase in the soybean oil methyl ester percentage in the blends, smoke density and HC decrease while NO x emissions increase, CO increases under full load at 2000r/min but decreases at 3000r/min, specific energy consumption decreases and brake specific fuel consumption increases under different loads at 2200r/min, and brake power and torque increase at different speeds under full load. A biodiesel content of 20wt% is an optimum compromise between increased NO x and reduction in smoke density.
Metallurgical aspects of induction-bending thick-walled super duplex pipework
Authors: Collie G J , Black I
Published: December 2008

In this article, the authors' present findings indicate that the induction-bending process can have a severe detrimental effect on the mechanical properties and the corrosion resistance of super duplex stainless steel. After outlining the parametric testing of the pipe that produced reduction in properties, the article presents comparative data from mechanical testing, corrosion analysis, and micrographic analysis before and after induction bending and after post-bend heat treatment. An explanation for the deterioration of properties is provided in terms of metallurgical characteristics; the root cause of deterioration is discussed; a method of restoring the mechanical and corrosion resistant properties is provided; and finally, process improvements are suggested which might, if adopted, prevent the re-occurrence of this phenomenon in the future.
Attempts to enhance the differential coefficients method for reconstruction of transient emissions from heavy-duty vehicles
Authors: Madireddy M R , Clark N N
Published: December 2008

Engine tailpipe emissions as measured by a sampling system and analyser do not clearly reflect the actual transient emissions from the engine at the tailpipe of the vehicle exhaust. With increasing demand for accurate emissions measurements, several research efforts are being made to compensate for the measurement distortions of the analyser system. The differential coefficients method is one such approach which reconstructs the input signal by approximating the analyser input as a linear combination of the output and the first two derivatives of the output. While the results with this approach were found to be acceptable, this paper focuses on the possibilities of improving the accuracy of the reconstruction by altering the ways in which the numerical derivatives are computed and by considering higher order derivatives in the linear combination. It was found that the use of backward differences in computing the numerical derivatives proved more effective than forward differences. Using higher order derivatives has shown improvement of about 10 per cent over using just the first two derivatives, but this margin may be important for model accuracy or for assessing pass/fail emissions criteria.
Selection of condition monitoring techniques using discrete probability distributions: A case study
Authors: Carnero M C
Published: December 2008

The setting up of a condition monitoring program is considered a strategic decision owing to its influence on cost, safety, quality, and availability in an industrial plant. However, no previous structured analysis of the selection of condition monitoring techniques and their characteristics has been made, so further analysis is needed. This paper proposes a model for the selection of the most suitable condition monitoring technique to be set up in a subsidiary of a petrochemical plant. For this purpose, different criteria, indicators, and utility functions are defined; nine alternatives are proposed depending on the technological level of the condition monitoring program. The model applies the analytic hierarchy process to obtain a ranking of alternatives. Owing to the special characteristics of the decision, discrete probability distributions are defined. The final ranking is computed by applying the Monte Carlo method considering 2000 simulation trials. Finally, a sensitivity analysis is applied.
Challenges to metallomics and analytical chemistry solutions
Authors: Mounicou Sandra , Lobinski Ryszard
Published: December 2008

Metal ions play a fundamental role in the chemistry of life. The understanding of the molecular bases of the living process requires the knowledge of the correlations existing between metal ions and the genome and the derived -omes: transcriptome, proteome, and metabolome. An indispensable step on this way is the characterization of the coordination environment of metal ions present and the identification and quantification of metal-containing chemical species. The ensemble of research activities related to metal ions in biological systems has been recently referred to as "metallomics" [1]. The progress in this field is largely dependent on the high-throughput acquisition of multielement and -species analytical data in biological samples. The paper gives a brief overview of the state of the art of analytical techniques and methods for the multielement quantitative analysis of biological microsamples, and for the detection, identification, and quantitation of metal-containing proteins and low-molecular-weight metabolites. The potential contribution of molecular biology techniques in terms of linking information on metals and metal-species to the genome of an organism is highlighted.
Metallomics, elementomics, and analytical techniques
Authors: Li Yu-Feng , Chen Chunying , Qu Ying , Gao Yuxi , Li Bai , Zhao Yuliang , Chai Zhifang
Published: December 2008

Metallomics is an emerging and promising research field which has attracted more and more attention. However, the term itself might be restrictive. Therefore, the term "elementomics" is suggested to encompass the study of nonmetals as well. In this paper, the application of state-of-the-art analytical techniques with the capabilities of high-throughput quantification, distribution, speciation, identification, and structural characterization for metallomics and elementomics is critically reviewed. High-throughput quantification of multielements can be achieved by inductively coupled plasma-mass spectrometry (ICP-MS) and neutron activation analysis (NAA). High-throughput multielement distribution mapping can be performed by fluorescence-detecting techniques such as synchrotron radiation X-ray fluorescence (SR-XRF), XRF tomography, energy-dispersive X-ray (EDX), proton-induced X-ray emission (PIXE), laser ablation (LA)-ICP-MS, and ion-detecting-based, secondary-ion mass spectrometry (SIMS), while Fourier transform-infrared (FT-IR) and Raman microspectroscopy are excellent tools for molecular mapping. All the techniques for metallome and elementome structural characterization are generally low-throughput, such as X-ray absorption spectroscopy (XAS), NMR, and small-angle X-ray spectroscopy (SAXS). If automation of arraying small samples, rapid data collection of multiple low-volume and -concentration samples together with data reduction and analysis are developed, high-throughput techniques will be available and in fact have partially been achieved.
Metallomics study on all-elements analysis of salmon egg cells and fractionation analysis of metals in cell cytoplasm
Authors: Haraguchi Hiroki , Ishii Atsushi , Hasegawa Takuya , Matsuura Hirotaka , Umemura Tomonari
Published: December 2008

Salmon egg cells were the subject of investigation for all-elements analysis in a single biological cell, where the elements in egg cells were simultaneously determined by inductively coupled plasma atomic emission spectrometry (ICP-AES) and inductively coupled plasma mass spectrometry (ICP-MS) after microwave-assisted acid digestion. As a result, 74 elements among 78 stable isotope elements were determined or detected, although H, C, N, and O were determined separately by conventional CHN elemental analysis. In addition, the survey of protein-binding metallic elements as well as metalloid elements in salmon egg cell cytoplasm was performed by the fractionation analysis with a hyphenated system of high-performance liquid chromatography (HPLC)/ICP-MS using a 3-[(3-cholamidopropyl)-dimethylammonio]-1-propane sulfonate (CHAPS)-coated octadecylsilyl silica (ODS) column and a size exclusion chromatography (SEC) column.
Integrated application of transcriptomics, proteomics, and metallomics in environmental studies
Authors: González-Fernández Macarena , García-Barrera Tamara , Jurado Juan , Prieto-Álamo María J. , Pueyo Carmen , López-Barea Juan , Gómez-Ariza José Luis
Published: December 2008

Here we report a preliminary working scheme for the integrative application of transcriptomic, proteomic, and metallomic methodologies in environmental monitoring, by using as sentinel the wildlife species Mus spretus and as reference the gene/protein sequence databases from the key model species Mus musculus. We have demonstrated that the absolute transcript expression signatures quantified by reverse transcription (RT) and real-time polymerase chain reaction (PCR) of selected key genes (e.g., those coding for biotransformation enzymes) in M. spretus is a useful and reliable novel biomonitoring end-point. The suitability of commercial M. musculus oligonucleotide arrays for genome-wide transcriptional profiling in M. spretus has been also shown. Transcriptomic studies indicate considerable gene sequence similarities between both mouse species. Based on these similarities, we have demonstrated the applicability in free-living M. spretus of high-throughput proteomic methods, based on matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry (MALDI-TOFMS) analysis of tryptic 2D electrophoresis (2-DE) spot digest and peptide matching with M. musculus database. A metallomic approach based on size exclusion chromatography inductively coupled plasma-mass spectrometry (SEC-ICP-MS) was applied to trace metal-biomolecule profiles. A preliminary integration of these three -omics has been addressed to M. musculus/M. spretus couple, two rodent species that separated 3 million years ago. The integrated application of transcriptomic and proteomic data and the bidirectional use of metallomics and proteomics for selective isolation of metal-biomolecules are covered in the working scheme MEPROTRANS-triple-OMIC reported in this study.
Development of multielemental imaging on semiconductor Compton telescope
Authors: Motomura Shinji , Kanayama Yousuke , Haba Hiromitsu , Igarashi Kaori , Watanabe Yasuyoshi , Enomoto Shuichi
Published: December 2008

The feasibility of using a Compton camera for multitracer imaging has been demonstrated with the results of two biological sample imaging experiments. The distribution of the multitracer administered to a soybean sample and a tumor-bearing mouse has been visualized for each nuclide simultaneously. 3D images of the multitracer have been obtained even though the samples were measured from a fixed direction.
Simultaneous tracing of multiple precursors each labeled with a different homo-elemental isotope by speciation analysis: Distribution and metabolism of four parenteral selenium sources
Authors: Suzuki Kazuo T. , Doi Chiaki , Suzuki Noriyuki
Published: December 2008

The availability, distribution, and metabolism of four typical selenium sources [inorganic selenite and selenate, and organic selenomethionine (SeMet) and methylselenocysteine (MeSeCys)] were compared by administering them simultaneously through a parenteral route. The four selenium sources were each labeled with a different enriched selenium isotope (82Se, 78Se, 77Se, and 76Se, respectively), and administered intravenously at the dose of 25 μg Se/kg body weight each to rats that had been depleted of natural abundance selenium with a single isotope, 80Se, by feeding 80Se-selenite in drinking water and a selenium-deficient diet. At 1 h post-injection, the amounts of the four tracers recovered from major organs and blood comprised around 70, 55, and 50 % of the doses for selenite, MeSeCys and SeMet, and selenate, respectively, being most abundant in the liver. The intact precursors, except for selenite, were recovered from all organs. 77Se and 76Se of SeMet and MeSeCys origin, respectively, were much more efficiently recovered from the pancreas than selenite and selenate, in forms mostly bound to proteins together with intact forms, suggesting that SeMet and MeSeCys are preferentially distributed directly to the pancreas. The incorporations of selenium into selenoprotein P (Sel P) and selenosugars were most efficient from selenite and less efficient from SeMet, suggesting that selenite was most efficiently utilized for the syntheses of selenoproteins and selenosugars. Although selenate was partly excreted into the urine in its intact form, it was retained longer in the plasma in its intact form than the other selenium sources. The advantage of simultaneous administration of multiple precursors each labeled with a different enriched isotope to depleted hosts followed by simultaneous tracing of the labeled isotopes over the conventional method with a single tracer is emphasized together with cautions that may occur with the new multiple tracer method.
Monads and vector bundles on quadrics
Authors: Malaspina Francesco
Published: December 2008

We improve Ottaviani's splitting criterion for vector bundles on a quadric hypersurface and obtain the equivalent of the result by Rao, Mohan Kumar and Peterson. Then we give the classification of rank 2 bundles without “inner” cohomology on 𝒬
n
(n > 3). It surprisingly exactly agrees with the classification by Ancona, Peternell and Wisniewski of rank 2 Fano bundles.
A Targeted Gain-of-Function Screen Identifies Genes Affecting Salivary Gland Morphogenesis/Tubulogenesis in Drosophila
Authors: Maybeck Vanessa , Röper Katja
Published: December 2008

During development individual cells in tissues undergo complex cell-shape changes to drive the morphogenetic movements required to form tissues. Cell shape is determined by the cytoskeleton and cell-shape changes critically depend on a tight spatial and temporal control of cytoskeletal behavior. We have used the formation of the salivary glands in the Drosophila embryo, a process of tubulogenesis, as an assay for identifying factors that impinge on cell shape and the cytoskeleton. To this end we have performed a gain-of-function screen in the salivary glands, using a collection of fly lines carrying EP-element insertions that allow the overexpression of downstream-located genes using the UAS-Gal4 system. We used a salivary-gland-specific fork head-Gal4 line to restrict expression to the salivary glands, in combination with reporters of cell shape and the cytoskeleton. We identified a number of genes known to affect salivary gland formation, confirming the effectiveness of the screen. In addition, we found many genes not implicated previously in this process, some having known functions in other tissues. We report the initial characterization of a subset of genes, including chickadee, rhomboid1, egalitarian, bitesize, and capricious, through comparison of gain- and loss-of-function phenotypes.
Genomic Consequences of Background Effects onscallopedMutant Expressivity in the Wing ofDrosophila melanogaster
Authors: Dworkin Ian , Kennerly Erin , Tack David , Hutchinson Jennifer , Brown Julie , Mahaffey James , Gibson Greg
Published: December 2008

Genetic background effects contribute to the phenotypic consequences of mutations and are pervasive across all domains of life that have been examined, yet little is known about how they modify genetic systems. In part this is due to the lack of tractable model systems that have been explicitly developed to study the genetic and evolutionary consequences of background effects. In this study we demonstrate that phenotypic expressivity of the scallopedE3 (sdE3) mutation of Drosophila melanogaster is background dependent and is the result of at least one major modifier segregating between two standard lab wild-type strains. We provide evidence that at least one of the modifiers is linked to the vestigial region and demonstrate that the background effects modify the spatial distribution of known sd target genes in a genotype-dependent manner. In addition, microarrays were used to examine the consequences of genetic background effects on the global transcriptome. Expression differences between wild-type strains were found to be as large as or larger than the effects of mutations with substantial phenotypic effects, and expression differences between wild type and mutant varied significantly between genetic backgrounds. Significantly, we demonstrate that the epistatic interaction between sdE3 and an optomotor blind mutation is background dependent. The results are discussed within the context of developing a complex but more realistic view of the consequences of genetic background effects with respect to mutational analysis and studies of epistasis and cryptic genetic variation segregating in natural populations.
The PP2C Alphabet Is a Negative Regulator of Stress-Activated Protein Kinase Signaling in Drosophila
Authors: Baril Caroline , Sahmi Malha , Ashton-Beaucage Dariel , Stronach Beth , Therrien Marc
Published: December 2008

The Jun N-terminal kinase and p38 pathways, also known as stress-activated protein kinase (SAPK) pathways, are signaling conduits reiteratively used throughout the development and adult life of metazoans where they play central roles in the control of apoptosis, immune function, and environmental stress responses. We recently identified a Drosophila Ser/Thr phosphatase of the PP2C family, named Alphabet (Alph), which acts as a negative regulator of the Ras/ERK pathway. Here we show that Alph also plays an inhibitory role with respect to Drosophila SAPK signaling during development as well as under stress conditions such as oxidative or genotoxic stresses. Epistasis experiments suggest that Alph acts at a step upstream of the MAPKKs Hep and Lic. Consistent with this interpretation, biochemical experiments identify the upstream MAPKKKs Slpr, Tak1, and Wnd as putative substrates. Together with previous findings, this work identifies Alph as a general attenuator of MAPK signaling in Drosophila.
Arabidopsis thaliana Genes Encoding Defense Signaling and Recognition Proteins Exhibit Contrasting Evolutionary Dynamics
Authors: Caldwell Katherine S , Michelmore Richard W
Published: December 2008

The interplay between pathogen effectors, their host targets, and cognate recognition proteins provides various opportunities for antagonistic cycles of selection acting on plant and pathogen to achieve or abrogate resistance, respectively. Selection has previously been shown to maintain diversity in plant proteins involved in pathogen recognition and some of their cognate pathogen effectors. We analyzed the signatures of selection on 10 Arabidopsis thaliana genes encoding defense signal transduction proteins in plants, which are potential targets of pathogen effectors. There was insufficient evidence to reject neutral evolution for 6 genes encoding signaling components consistent with these proteins not being targets of effectors and/or indicative of constraints on their ability to coevolve with pathogen effectors. Functional constraints on effector targets may have provided the driving selective force for the evolution of guard proteins. PBS1, a known target of an effector, showed little variation but is known to be monitored by a variable guard protein. Evidence of selection maintaining diversity was present at NPR1, PAD4, and EDS1. Differences in the signatures of selection observed may reflect the numbers of effectors that target a particular protein, the presence or absence of a cognate guard protein, as well as functional constraints imposed by biochemical activities or interactions with plant proteins.