bluuebunny/crossref_metadata_2025 huggingface dataset:
SPACE-CHARGE LAYER, INTRINSIC "BULK" AND SURFACE COMPLEX DEFECTS IN ZnO NANOPARTICLES — A HIGH-FIELD ELECTRON PARAMAGNETIC RESONANCE ANALYSIS
Authors: EICHEL RÜDIGER-A. , ERDEM EMRE , JAKES PETER , OZAROWSKI ANDREW , VAN TOL JOHAN , HOFFMANN RUDOLF C. , SCHNEIDER JÖRG J.
Published: June 2013

The defect structure of ZnO nanoparticles is characterized by means of high-field electron paramagnetic resonance (EPR) spectroscopy. Different point and complex defects could be identified, located at the "bulk" or the surface region of the nanoparticles. In particular, by exploiting the enhanced g-value resolution at a Larmor frequency of 406.4 GHz, it could be shown that the resonance commonly observed at g = 1.96 is comprised of several overlapping resonances from different defects. Based on the high-field EPR analysis, the development of a space-charge layer could be monitored that consists of (shallow) donor-type [Formula: see text] defects at the "bulk" and acceptor-type [Formula: see text] and complex [Formula: see text] defects at the surface. Application of a core-shell model allows to determine the thickness of the depletion layer to 1.0 nm for the here studied compounds [J.J. Schneider et al., Chem. Mater.22, 2203 (2010)].
IMPROVED AND UNUSUAL MAGNETIC PROPERTIES OF ZnO NANORINGS
Authors: MONDAL OINDRILA , THANH NGUYEN TK , GREEN LUKE AW , PAL MRINAL
Published: June 2013

We report the novel result regarding the observation of unusual magnetic behavior with high magnetic moment (higher than reported so far) at room temperature in highly pure ZnO nanorings synthesized by a simple chemical route using cetyltrimethyl ammonium bromide. The enhanced magnetization is attributed to the huge number of surface spins associated with defects created due to the larger surface to volume ratio of nanorings. The present study demonstrates that ZnO samples can be made highly magnetic just by tailoring the nanostructure even without doping transition-metal. Some new magnetic features have been observed and possible explanations are delineated here.
First-Order Logic on Higher-Order Nested Pushdown Trees
Authors: Kartzow Alexander
Published: June 2013

We introduce a new hierarchy of
higher-order nested pushdown trees
generalising Alur et al.’s concept of nested pushdown trees. Nested pushdown trees are useful representations of control flows in the verification of programs with recursive calls of first-order functions. Higher-order nested pushdown trees are expansions of unfoldings of graphs generated by higher-order pushdown systems. Moreover, the class of nested pushdown trees of level
n
is uniformly first-order interpretable in the class of collapsible pushdown graphs of level
n
 + 1. The relationship between the class of higher-order pushdown graphs and the class of collapsible higher-order pushdown graphs is not very well understood. We hope that the further study of the nested pushdown tree hierarchy leads to a better understanding of these two hierarchies. In this article, we are concerned with the first-order model checking problem on higher-order nested pushdown trees. We show that the first-order model checking on the first two levels of this hierarchy is decidable. Moreover, we obtain an alternating 2-EXPTIME algorithm for the class of nested pushdown trees of level 1. The proof technique involves a pseudo-local analysis of strategies in the Ehrenfeucht-Fraïssé games on two identical copies of a nested pushdown tree. Ordinary locality arguments in the spirit of Gaifman’s lemma do not apply here because nested pushdown trees tend to have small diameters. We introduce the notion of relevant ancestors which provide a sufficient description of the
FO
k
-type of each element in a higher-order nested pushdown tree. The local analysis of these ancestors allows us to prove the existence of restricted winning strategies in the Ehrenfeucht-Fraïssé game. These strategies are then used to create a first-order model checking algorithm.
Instantiation Schemes for Nested Theories
Authors: Echenim Mnacho , Peltier Nicolas
Published: June 2013

This article investigates under which conditions instantiation-based proof procedures can be combined in a
nested
way, in order to mechanically construct new instantiation procedures for richer theories. Interesting applications in the field of verification are emphasized, particularly for handling extensions of the theory of arrays.
Statutory damages as a threat to innovation
Authors: Samuelson Pamela
Published: June 2013

Considering the negative influence of U.S. statutory damage rules on technology innovation.
The business of professionals
Authors: Sako Mari
Published: June 2013

Expertise and service ethics are just two of the many components comprising a modern professional.
Future Tense: Where the cross-platform bends
Authors: McClelland Mark
Published: June 2013

From the intersection of computational science and technological speculation, with boundaries limited only by our ability to imagine what could be.
Towards adaptive GPU resource management for embedded real-time systems
Authors: Kim Junsung , Rajkumar Ragunathan (Raj) , Kato Shinpei
Published: June 2013

In this paper, we present two conceptual frameworks for GPU applications to adjust their task execution times based on total workload. These frameworks enable smart GPU resource management when many applications share GPU resources while the workloads of those applications vary. Application developers can explicitly adjust the number of GPU cores depending on their needs. An implicit adjustment will be supported by a run-time framework, which dynamically allocates the number of cores to tasks based on the total workload. The runtime support of the proposed system can be realized using functions which measure the execution times of the tasks on GPU and change the number of GPU cores. We motivate the necessity of this framework in the context of self-driving technologies, and we believe that our frameworks for GPU programming are useful contributions given the increasing emphasis on parallel heterogeneous computing.
Model-driven development of SOA-based driver assistance systems
Authors: Wagner Marco , Zöbel Dieter , Meroth Ansgar
Published: June 2013

This paper describes an approach towards model-driven development of SOA-based Driver Assistance Systems. In the field of assistance systems for truck and trailer combinations Service-oriented Architecture (SOA) is a promising approach to handle the heterogeneity and the high degree of distribution of these systems. Through connecting or disconnecting trailers the system is very likely to change at runtime which sets up the demand of runtime adaption. This paper illustrates a process model to use SoaML for modeling the components and architectures of these systems. Based on these models, model-driven runtime adaption can be carried out.
Adsorption and Assembly of Ions and Organic Molecules at Electrochemical Interfaces: Nanoscale Aspects
Authors: Yoshimoto Soichiro , Itaya Kingo
Published: June 2013

We describe the history of electrochemical scanning tunneling microscopy (STM) and advances made in this field during the past 20 years. In situ STM allows one to monitor various electrode processes, such as the underpotential deposition of copper and silver ions; the specific adsorption of iodine and sulfate/bisulfate ions; electrochemical dissolution processes of silicon and gold single-crystal surfaces in electrolyte solutions; and the molecular assembly of metalloporphyrins, metallophthalocyanines, and fullerenes, at atomic and/or molecular resolution. Furthermore, a laser confocal microscope, combined with a differential interference contrast microscope, enables investigation of the dynamics of electrochemical processes at atomic resolution.
Modern Raman Imaging: Vibrational Spectroscopy on the Micrometer and Nanometer Scales
Authors: Opilik Lothar , Schmid Thomas , Zenobi Renato
Published: June 2013

Raman microscopes are currently used in various fields of research because they allow for label-free sample investigation. Moreover, the inherently low scattering cross section of Raman spectroscopy, as well as its diffraction-limited lateral resolution, has been overcome by new Raman microscopy techniques. Nonlinear methods such as coherent anti-Stokes Raman spectroscopy and stimulated Raman spectroscopy reduce measurement times and improve z resolution, allowing for three-dimensional spectroscopic imaging of biological samples. Moreover, tip-enhanced Raman spectroscopy, a near-field optical technique that combines scanning-probe microscopy with the enhancement offered by surface-enhanced Raman scattering, enables Raman spectroscopic imaging far below the optical diffraction limit. We cover the theoretical and technical aspects of Raman microscopy and related new imaging techniques and review some very recent applications in graphene research and cell biology.
Real-Time Clinical Monitoring of Biomolecules
Authors: Rogers Michelle L. , Boutelle Martyn G.
Published: June 2013

Continuous monitoring of clinical biomarkers offers the exciting possibility of new therapies that use biomarker levels to guide treatment in real time. This review explores recent progress toward this goal. We initially consider measurements in body fluids by a range of analytical methods. We then discuss direct tissue measurements performed by implanted sensors; sampling techniques, including microdialysis and ultrafiltration; and noninvasive methods. A future directions section considers analytical methods at the cusp of clinical use.
Clues to the Function of the Tumour Susceptibility Gene BRCA2
Authors: Gayther Simon A. , Ponder Bruce A. J.
Published: June 2013

The breast cancer susceptibility gene BRCA2 was isolated in 1995. BRCA2 is a large gene comprising 10,254 nucleotides and 26 coding exons. Neither the nucleotide nor the predicted protein sequences (comprising 3,418 amino acids) have provided substantial clues about its function. As a result, researchers have been trying to elucidate the function using a combination of cell biological and biochemical methods and the construction of animal models using gene targeting in mice. Recent data suggest that BRCA2 may participate in pathways associated with recombination or double‐strand DNA break repair and may act by either sensing or responding to DNA damage. In addition, there is evidence to suggest that BRCA2 functions in a manner similar to the previously isolated breast cancer susceptibility gene BRCA1.
Implication of HLA‐DMA Alleles in Corsican IDDM
Authors: Cucchi-Mouillot P. , Lai S. , Carcassi C. , Sorba P. , Stuart-Simoni M. , Amoros J.-P. , Genetet B. , Haras D. , Contu L.
Published: June 2013

The HLA‐DM molecule catalyses the CLIP/antigen peptide exchange in the classical class II peptide‐binding groove. As such, DM is an antigen presentation regulator and may be linked to autoimmune diseases. Using PCR derived methods, a relationship was revealed between DM gene polymorphism and IDDM, in a Corsican population. The DMA*0101 allele was observed to confer a significant predisposition to this autoimmune disease while the DMA*0102 allele protected significantly. Experiments examining polymorphism of the HLA‐DRB1 gene established that these relationships are not a consequence of linkage disequilibrium with HLA‐DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore be an additional tool for early IDDM diagnosis in the Corsican population.
Inflammatory Bowel Disease: Are There Gender Differences in the Genetics of Signal Transduction? A Preliminary Study of Cytosolic Low Molecular Weight Protein Tyrosine Phosphatase
Authors: Bottini Nunzio , Gloria-Bottini Fulvia , Lucarini Nazzareno , Ronchetti Pier Giulio , Fontana Luigi
Published: June 2013

The phenotype of cytosolic Low Molecular Weight Protein Tyrosine Phosphatase (cLMWPTP or ACP1), an enzyme involved in signal transduction of insulin, PDGF and T‐cell receptors, has been determined in 71 patients with Crohn′s Disease (CD: 37 males and 34 females), 49 patients with Ulcerative Colitis (UC: 27 males and 22 females) and 358 consecutive newborns (194 males and 164 females). cLMWPTP phenotypes showing a high concentration of F isoforms are associated with CD in females and with UC in males. Since PTPases counteract the effects of protein tyrosines kinases, a high concentration of F isoform of cLMWPTP may influence the mucosal response to pathogenic factors, increasing susceptibility to CD in females and to UC in males.
HLA‐Association in Patients with Intolerance to Mercury and Other Metals in Dental Materials
Authors: Procházková J. , Bártová J. , Ivašková E. , Kupková L. , Šterzl I. , Stejskal V. D. M.
Published: June 2013

A group of selected 25 patients with serious intolerance to heavy metals used for dental restoration were examined for HLA antigens. A significant increase for HLA – B37, B47 and DR4 was found. The value of the relative risk is not significant after correction for the number of antigens tested and therefore further studies of more patients are needed.
Sex Steroid Hormones in Serum and Tissue of Benign and Malignant Breast Tumor Patients
Authors: Mady Essam A. , Ramadan Ezz El-Din H. , Ossman Alaa A.
Published: June 2013

The ability of breast tumors to synthesize sex steroid hormones is well recognized and their local production is thought to play a role in breast cancer development and growth. The aim of this study was to estimate local intra‐tumoral and circulating levels of Estrone (E1), Estrone Sulfate (E1S), Estradiol (E2), Estriol (E3), and Testosterone (T) in 33 pre‐ and postmenopausal women with primary breast cancer in comparison to 12 pre‐ and postmenopausal women with benign breast tumors. The mean levels of the studied sex hormones were higher in serum and tumor tissue of breast cancer women than those with benign breast tumors apart from Testosterone which showed a significant decrease in pre‐ and postmenopausal women with breast cancer (P < 0.001 for follicular phase, P < 0.001 for luteal phase, and P < 0.001 for postmenopausal). The levels of the five hormones were significantly higher intra‐tumoral than in serum of both benign and malignant breast tumor women with E1S as the predominant estrogen. There was only a positive significant correlation between serum and tumor tissue levels of E1 (rs = 0.52, P < 0.05 for follicular; rs = 0.63, P < 0.05 for luteal and rs = 0.58, P < 0.05 for postmenopausal) and a significant correlation between serum and tumor tissue of T (rs = 0.64, P < 0.05 for follicular; rs = ‐0.51, P < 0.05 for luteal and rs = ‐0.81, P < 0.04 for postmenopausal).
Association between the Endogenous Retrovirus HRES‐1 and Multiple Sclerosis in the United Kingdom – Evidence of Genetically Different Disease Subsets?
Authors: Rasmussen H. B. , Kelly M. A. , Francis D. A. , Clausen J.
Published: June 2013

In the present study we determined the frequencies of four haplotypes of the human T‐cell lymphotropic virus‐related endogenous sequence, HRES‐1, in 110 multiple sclerosis (MS) patients and 100 healthy control subjects from the United Kingdom. We found evidence of an association between this endogenous retrovirus and MS (p < 0.01), in particular reflecting an increased frequency of HRES‐1 haplotype 1 in the group of patients. There was no significant difference in the distribution of HRES‐1 haplotypes between relapsing‐remitting MS and the primary progressive form of the disease. The odds ratio for HRES‐1 haplotype 1 and MS did not differ significantly between individuals positive for HLA‐DR2 and DR2‐negative individuals. Comparison of the observations from the present study with previous results implicated HRES‐1 as a marker of genetic heterogeneity in MS.
Creating Hybrid Genes by Homologous Recombination
Authors: Wang Peter L.
Published: June 2013

Recombination of homologous genes is a powerful mechanism for generating sequence diversity, and can be applied to protein analysis and directed evolution. In vitro recombination methods such as DNA shuffling are very flexible and can give hybrid genes with multiple crossovers; they have been used extensively to evolve proteins with improved and novel properties. In vivo recombination in both E. coli and yeast is greatly enhanced by double‐strand breaks; for E. coli, mutant strains are often necessary to obtain high efficiency. Intra‐ and inter‐molecular recombination In vivo have distinct features; both give hybrids with one or two crossovers, and have been used to study structure‐function relationships of many proteins. Recently in vivo recombination has been used to generate diversity for directed evolution, creating a large phage display antibody library. Recombination methods will become increasingly useful in light of the explosion in genomic sequence data and potential for engineered proteins.
Rh System and Intrauterine Growth. Interaction with Season of Birth
Authors: Gloria-Bottini F. , Meloni G. F. , Finocchi A. , Porcu S. , Amante A. , Bottini E.
Published: June 2013

Based on the hypothesis that maternal‐fetal genetic differences in membrane transport and signal transduction may influence intrauterine development, the recent acquisition on transport function of Rh protein prompted us to study the relationship between joint maternal‐fetal Rh phenotype and birth weight. Considering that metabolic effect of maternal‐fetal competition could be amplified by environmental conditions, we have investigated possible seasonal effects on such relationship. We have studied 5291 infants born in Sardinia in the period January 1993–December 1996 and 984 infants born in Rome during 1996. In Rh(–) mothers there is a significant association between season of birth and birth weight that shows the highest mean value in infants born in autumn (i.e. conceived in winter). The association is much more evident in male than in female infants. In male infants from Rh(–) mothers, the association between birth weight and season is significant in Rh(+) male newborns only. Recent observations by our group in NIDDM suggest that glucose transport in RBC may be related to D protein, thus we propose an interpretation of the present observation in terms of transport function. When the density of D protein in the infant is greater than in the mother, the balance is in favour of the infant who may attain a significant developmental advantage when conceived in the cold season.
The Significance of PSA/IGF‐1 Ratio in Differentiating Benign Prostate Hyperplasia from Prostate Cancer
Authors: Koliakos G. , Chatzivasiliou D. , Dimopoulos Th. , Trachana V. , Paschalidou K. , Galiamoutsas V. , Triantos A. , Chitas G. , Dimopoulos A. , Vlatsas G.
Published: June 2013

The importance of insulin‐like growth factor 1 (IGF‐1) in human serum for the early diagnosis of prostate cancer is controversial. The IGF‐1/PSA ratio may improve the performance of prostate specific antigen (PSA) as a prostate cancer marker. IGF‐1, along with PSA and free PSA concentration, was measured in the serum of 34 patients with prostate cancer and in 131 patients with benign prostatic hyperplasia (BPH). Although IGF‐1 concentration did not significantly differ between the groups, PSA/IGF‐1 ratio could clearly distinguish the two groups. In patients with cancer but not in patients with BPH, IGF‐1 concentration correlated with PSA and free PSA. The values of PSA and free PSA correlated with each other for both groups. Receivers Operating Curve (ROC) analysis indicated a better sensitivity to specificity ratio for PSA/IGF‐1 than for PSA or Free/Total (F/T) PSA.
Contribution of Flow Cytometry to Acute Leukemia Classification in Tunisia
Authors: Feki S. , El Omri H. , Laatiri M. A. , Ennabli S. , Boukef K. , Jenhani F.
Published: June 2013

The precision of immunological characterization of leukemias was improved by a certain number of technical innovations, particularly hybridoma production and standardization, resulting in monoclonal antibodies and definition of recognised cellular antigens (designated by CD: Cluster of Differentiation).

The aim of this work was to determine the immunophenotyping profile of patients with leukemia, by means of a flow cytometric method: 66 blood samples coming from leukemic persons in the Sahel region were studied by flow cytometry, using about thirty monoclonal antibodies all marked with a fluorochrome, in one or two colour systems to assess their distribution according to type (lymphoid B or T / myeloid) and age, and to search for possible co‐expressions of markers of different lineages.

The marked preponderance of childhood B‐ALL in our series is, at least partly, attributable to the age distribution of the Tunisian population. In agreement with studies from other countries, the majority of AML cases occurred among adults. A high proportion of AML cases in our series co‐expressed markers of other lineages. Overall, accurate classification of acute leukemias was possible from a simple peripheral blood sample in 62 of 66 cases (93.9%).
Use of Phage Antibodies to Distinguish Closely Related Species of Protozoan Parasites
Authors: Paget Timothy , Khan Naveed , Temple Graham , Hough Victoria , Greenman John
Published: June 2013

Acanthamoeba are typically identified in the laboratory using culture and microscopic observation. In this paper we describe the isolation and specificity of antibody fragments that can be used for the identification of Acanthamoeba. A phage library expressing a large repertoire (approx. 5×109) of antibody fragments was used to generate two libraries one enriched for bacteriophage that exhibit genus specific binding and the other containing bacteriophage that bind specifically to pathogenic Acanthamoeba. Individual clones were isolated on the basis of binding by ELISA, and then flowcytometry and immunofluorescence were used for further characterisation. Four monoclonal antibodies were isolated, specific for Acanthamoeba at the generic level with clone HPPG6 exhibiting the highest level of binding. Furthermore clone HPPG55 was specific for pathogenic species of Acanthamoeba.
Proteome Analysis—A Novel Approach to Understand the Pathogenesis of Type 1 Diabetes Mellitus
Authors: Karlsen Allan E. , Sparre Thomas , Nielsen Karin , Nerup Jørn , Pociot Flemming
Published: June 2013

Type 1 (insulin‐dependent) diabetes mellitus (T1DM) is associated with a specific destruction of the insulin‐producing beta‐cells in the islets of Langerhans. Several factors, e.g. genetic, environmental and immunologial, may be involved in the etiology and pathogenesis of T1DM. Autoreactive Tand B‐lymphocytes, together with macrophages infiltrate the islets during the pathogenesis, releasing a mixture of cytokines, demonstrated to be specifically toxic to the beta‐cells within the islets. Our goal is to understand the molecular mechanisms responsible for the beta‐cell specific toxicity enabling us to design novel intervention strategies in T1DM. The proteome approach allows us to get a detailed picture of the beta‐cell proteins, which change expression level or are post‐translationally modified in different in vitro and in vivo models of T1DM‐associated beta‐cell destruction. Combining the information obtained from this extended proteome approach, with that of genetic‐, transcriptome‐ and candidategene approaches, we believe that it is possible to reach this goal.
Proteomic‐Based Approach for the Identification of Tumor Markers Associated with Hepatocellular Carcinoma
Authors: Shalhoub Philip , Kern Sarah , Girard Sophie , Beretta Laura
Published: June 2013

There is increasing evidence for an immune response to cancer in humans, demonstrated in part by the identification of autoantibodies to tumor antigens. The identification of panels of tumor antigens that elicit a humoral response may have utility in cancer screening, diagnosis or in establishing prognosis. Several approaches are currently available for the identification of tumor antigens. We have used a proteomic‐based approach for the identification of tumor antigens that induce an antibody response which we have applied to hepatocellular carcinoma, a major type of cancer worldwide. Two‐dimensional gel electrophoresis allows simultaneous separation of several thousand individual proteins from tumor tissue or tumor cell lines. Proteins eliciting a humoral response in HCC were identified by 2‐D Western blotting using sera from patients with hepatocellular carcinoma, followed by mass spectrometry analysis and database search. The common occurrence of autoantibodies to specific proteins may have utility for HCC screening and diagnosis.
ANX7 as a Bio‐Marker in Prostate and Breast Cancer Progression
Authors: Srivastava Meera , Bubendorf Lukas , Nolan Lisa , Glasman Mirta , Leighton Ximena , Miller Georgina , Fehrle Wilfred , Raffeld Mark , Eidelman Ofer , Kallioniemi Olli P. , Srivastava Shiv , Pollard Harvey B.
Published: June 2013

The ANX7 gene codes for a Ca2+‐activated GTPase, which has been implicated in both exocytotic secretion in cells and control of growth. In this review, we summarize information regarding increased tumor frequency in the Anx7 knockout mice, ANX7 growth suppression of human cancer cell lines, and ANX7 expression in human tumor tissue micro‐arrays. The loss of ANX7 is significant in metastatic and hormone refractory prostate cancer compared to benign prostatic hyperplasia. In addition, ANX7 expression has prognostic value for predicting survival of breast cancer patients.
C282Y and H63D Mutation Frequencies in a Population from Central Spain
Authors: Alvarez S. , Mesa M. S. , Bandrés F. , Arroyo E.
Published: June 2013

Objectives: To determine the frequency of hereditary hemochromatosis gene mutations, C282Y and H63D, from 125 autochthonous blood donors originating from a Central region of Spain, to provide epidemiological data about HFE gene in the Iberian Peninsula.

Methods: DNA extracted from blood samples was analyzed by PCR‐RFLP. Restriction enzimes were Snab I and Bcl I for C282Y and H63D, respectively. Results were visualized with Ethidium Bromide staining after gel electrophoresis.

Results and discussion: C282Y frequency was 0.02 and that of H63D was 0.16. Result for C282Y mutation falls within the range of variation of the Mediterranean populations. H63D frequency agrees with those reported for other European populations. In both cases frequencies obtained are the lowest of compared Spanish data.

Conclusions: This study is useful to compare expected versus presented C282Y and H63D frequencies in Spanish populations and to contribute to the knowledge of Spanish variability, rarely analyzed until now for HFE gene mutations.
Protein Expression Analysis: From ‘Tip of the Iceberg’ to a Global Method
Authors: James Peter
Published: June 2013

In this review I will describe the advances that have recently been made in ‘traditional’ two‐dimensional gel based protein expression analysis. A major jump has been made toward the automation of gel image analysis and comparison, one of the major bottlenecks in the analysis chain as well as the automation of spot excision and preparation for mass spectrometric analysis. Currently the gel‐based ‘proteome mapping’ approach is highly effective and 300 gels and over 10,000 spots a week can be analysed. Very recently, viable alternatives to the use of two‐dimensional gel electrophoresis have emerged and these approaches are discussed here. In combination with the recently developed stable isotopic tagging methods for peptide quantitation and new mass spectrometers, this emerging technology will be a rapid and highly effective alternative to gel‐based methods with few of the latter′s shortcomings.
Analysis of the Proteomic Profiling of Brain Tissue in Alzheimer′s Disease
Authors: Tsuji T. , Shimohama S.
Published: June 2013

In proteome analysis, it is necessary to separate proteins as a first step prior to characterization. Thus, the overall performance of the analysis depends strongly on the separation tool, which is usually two‐dimensional electrophoresis (2DE). We have utilized 2DE to begin characterization of the complex pathologic processes in Alzheimer′s disease (AD). In the present study, we show how a reliable 2‐DE database of brain proteins in Alzheimer′s disease was created, improving reproducibility by using an immobilized pH gradient (IPG) for the first dimension gel electrophoresis. The recent progress in this field, and future prospects in this area are also discussed. Preparation of brain proteins into a suitable solubilized state enabled us to separate over 1000 well‐defined protein spots in each 2‐DE. A comparison of the density of the spots identified on the reference map between the AD and control group, showed that 5 protein spots were significantly increased, 28 spots were significantly decreased and 7 spots were specifically detected in AD. Two spots among those significantly increased and one spot among those significantly decreased were identified as GFAP related. It is hoped that comparative studies to identify, quantitate, and characterize the proteins differentially expressed in normal brain versus diseased brain will give insight into the mechanisms of pathogenesis and allow the development of a strategy to control both the etiology and course of the diseases.
Pseudomonas aeruginosa and a Proteomic Approach to Bacterial Pathogenesis
Authors: Sherman Nicholas E. , Stefansson Bjarki , Fox Jay W. , Goldberg Joanna B.
Published: June 2013

Pseudomonas aeruginosa is a Gram‐negative bacterium that is ubiquitous in the environment and can cause a variety of diseases in compromised patients. The genome of P. aeruginosa strain PAO1 has been reported to contain 5570 potential proteins. The value of this genomic database is that new proteins can be recognized to use as diagnostic markers, novel drug targets, and to better understand the physiology of this organism. However, similar to what has been observed in other sequenced bacterial genomes, approximately one third of the potential proteins have no known function. This is somewhat surprising given the long‐standing interest in P. aeruginosa as an opportunistic pathogen. Obviously new tools, in addition to sequence similarity analysis, are needed to determine the role of these proteins. Proteomics using two‐dimensional gel electrophoresis followed by mass spectrometry to detect and identify P. aeruginosa proteins represents a novel approach to address this gap.
A Proteomic Approach to the Identification of Lung Cancer Markers
Authors: Hanash Samir , Brichory Franck , Beer David
Published: June 2013

We have developed a comprehensive approach to the identification of protein markers in lung cancer that includes profiling of tumor tissue and cell lines as well as the analysis of serum for autoantibodies to lung tumor antigens. A large number of proteins that are differentially expressed in the major subtypes of lung cancer have been identified by mass spectrometry. A database of protein expression in lung cancer and other types of cancer has been constructed that integrates two‐dimensional gel profiles, mass spectrometry data, quantitative protein data and gene expression data at the RNA level, that serves as a resource for biomarker identification. Analysis of the serological response in lung cancer has led to the identification of novel markers detectable in serum of lung cancer patients at the time of diagnosis. The proteomic approach is likely to yield novel classification schemes and novel markers for early diagnosis of lung cancer.
Proteomic Patterns of Nipple Aspirate Fluids Obtained by SELDI‐TOF: Potential for New Biomarkers to Aid in the Diagnosis of Breast Cancer
Authors: Paweletz Cloud P. , Trock Bruce , Pennanen Marie , Tsangaris Theodore , Magnant Collette , Liotta Lance A. , Petricoin Emanuel F.
Published: June 2013

Nipple aspirate fluid (NAF) has been used for many years as a potential non‐invasive method to identify markers for breast cancer risk or early detection. Because individual markers have not been optimal, we are exploring the use of surface enhanced laser desorption and ionization time of flight (SELDI‐TOF) mass spectrometry to identify patterns of proteins that might define a proteomic signature for breast cancer. SELDI‐TOF was used to analyze a study set of NAF samples that included 12 women with breast cancer and 15 healthy controls (the latter included three women with an abnormal mammogram but subsequent normal biopsy). In this preliminary report, we present data showing that SELDI analysis of NAF is rapid, reproducible, and capable of identifying protein signatures that appear to differentiate NAF samples from breast cancer patients and healthy controls, including those with an abnormal mammogram who were later proven to be biopsy normal.
Analysis of Expression Patterns: The Scope of the Problem, the Problem of Scope
Authors: Chen Yidong , Yakhini Zohar , Ben-Dor Amir , Dougherty Edward , Trent Jeffrey M. , Bittner Michael
Published: June 2013

Studies of the expression patterns of many genes simultaneously lead to the observation that even in closely related pathologies, there are numerous genes that are differentially expressed in consistent patterns correlated to each sample type. The early uses of the enabling technology, microarrays, was focused on gathering mechanistic biological insights. The early findings now pose another clear challenge, finding ways to effectively use this kind of information to develop diagnostics.
A Comparison of Gene Expression Signatures from Breast Tumors and Breast Tissue Derived Cell Lines
Authors: Ross Douglas T. , Perou Charles M.
Published: June 2013

Cell lines derived from human tumors have historically served as the primary experimental model system for exploration of tumor cell biology and pharmacology. Cell line studies, however, must be interpreted in the context of artifacts introduced by selection and establishment of cell lines in vitro. This complication has led to difficulty in the extrapolation of biology observed in cell lines to tumor biology in vivo. Modern genomic analysis tool like DNA microarrays and gene expression profiling now provide a platform for the systematic characterization and classification of both cell lines and tumor samples. Studies using clinical samples have begun to identify classes of tumors that appear both biologically and clinically unique as inferred from their distinctive patterns of expressed genes. In this review, we explore the relationships between patterns of gene expression in breast tumor derived cell lines to those from clinical tumor specimens. This analysis demonstrates that cell lines and tumor samples have distinctive gene expression patterns in common and underscores the need for careful assessment of the appropriateness of any given cell line as a model for a given tumor subtype.
A Study of Wavelet Analysis and Data Extraction from Second-Order Self-Similar Time Series
Authors: Estrada Vargas Leopoldo , Torres Roman Deni , Toral Cruz Homero
Published: June 2013

Statistical analysis and synthesis of self-similar discrete time signals are presented. The analysis equation is formally defined through a special family of basis functions of which the simplest case matches the Haar wavelet. The original discrete time series is synthesized without loss by a linear combination of the basis functions after some scaling, displacement, and phase shift. The decomposition is then used to synthesize a new second-order self-similar signal with a different Hurst index than the original. The components are also used to describe the behavior of the estimated mean and variance of self-similar discrete time series. It is shown that the sample mean, although it is unbiased, provides less information about the process mean as its Hurst index is higher. It is also demonstrated that the classical variance estimator is biased and that the widely accepted aggregated variance-based estimator of the Hurst index results biased not due to its nature (which is being unbiased and has minimal variance) but to flaws in its implementation. Using the proposed decomposition, the correct estimation of theVariance Plotis described, as well as its close association with the popularLogscale Diagram.
Update on Anticytokine Treatment for Asthma
Authors: Gallelli Luca , Busceti Maria Teresa , Vatrella Alessandro , Maselli Rosario , Pelaia Girolamo
Published: June 2013

Current advances in the knowledge of asthma pathobiology suggest that anticytokine therapies can be potentially useful for the treatment of this complex and heterogeneous airway disease. Recent evidence is accumulating in support of the efficacy of anti-IL-4, anti-IL-5, and anti-IL-13 drugs. Therefore, these new developments are now changing the global scenario of antiasthma therapies, especially with regard to more severe disease. Current findings referring to variability of individual therapeutic responses highlight that the different asthma subtypes need to be well characterized, in order to implement phenotype-targeted treatments which in the near future will hopefully be mainly based on cytokine-directed biologics.
Impact of Cardiovascular Organ Damage on Cortical Renal Perfusion in Patients with Chronic Renal Failure
Authors: Lubas Arkadiusz , Ryczek Robert , Kade Grzegorz , Smoszna Jerzy , Niemczyk Stanisław
Published: June 2013

Introduction. Properly preserved renal perfusion is the basic determinant of oxygenation, vitality, nutrition, and organ function and its structure. Perfusion disorders are functional changes and are ahead of the appearance of biochemical markers of organ damage. The aim of this study was to evaluate a relationship between the renal cortex perfusion and markers of cardiovascular organ damage in patients with stable chronic renal failure (CKD).Methods. Seventeen patients (2 F; 15 M; age47±16) with stable CKD at 2–4 stages and hypertension or signs of heart failure were enrolled in this study. Blood tests with an estimation of renal and cardiac functions, echocardiographic parameters, intima-media thickness (IMT), renal resistance index (RRI), and total (TPI), proximal (PPI), and distal (DPI) renal cortical perfusion intensity measurements were collected.Results. DPI was significantly lower than PPI. TPI significantly correlated with age, Cys, CKD-EPI (cystatin), and IMT, whereas DPI significantly depended on Cystain, CKD-EPI (cystatin; cystatin-creatinine), IMT, NT-proBNP, and troponin I. In multiple stepwise regression analysis model only CKD-EPI (cystatin) independently influenced DPI.Conclusions. Cardiovascular and kidney damage significantly influences renal cortical perfusion. Ultrasound measurement of renal perfusion could be a sensitive method for early investigation of cardiovascular and renal injuries.
Ventricular Dyssynchrony and Function Improve following Catheter Ablation of Nonseptal Accessory Pathways in Children
Authors: Abadir Sylvia , Fournier Anne , Dubuc Marc , Sarquella-Brugada Georgia , Garceau Patrick , Khairy Paul
Published: June 2013

Introduction. Paradoxical or hypokinetic interventricular septal motion has been described in patients with septal or paraseptal accessory pathways. Data regarding nonseptal pathways is limited.Methods and Results. We quantified left ventricular dyssynchrony and function in 16 consecutive children,14.2±3.7years, weighing53 ± 17 kg, prior to and following catheter ablation of bidirectional septal (N=6) and nonseptal (N=10) accessory pathways. Following ablation, the left ventricular ejection fraction increased by4.9±2.1% (P=0.038) from a baseline value of57.0%±7.8%. By tissue Doppler imaging, the interval between QRS onset and peak systolic velocity (Ts) decreased from a median of 33.0 ms to 18.0 ms (P=0.013). The left ventricular ejection fraction increased to a greater extent following catheter ablation of nonseptal (5.9%±2.6%,P=0.023) versus septal (2.5%±4.1%,P=0.461) pathways. The four patients with an ejection fraction <50%, two of whom had left lateral pathways, improved to >50% after ablation. Similarly, the improvement in dyssynchrony was more marked in patients with nonseptal versus septal pathways (difference between septal and lateral wall motion delay before and after ablation20.6±7.1 ms (P=0.015) versus1.4±11.4 ms (P=0.655)).Conclusion. Left ventricular systolic function and dyssynchrony improve after ablation of antegrade-conducting accessory pathways in children, with more pronounced changes noted for nonseptal pathways.
Radiation Hardness of Flash Memory Fabricated in Deep-Submicron Technology
Authors: Cavrić Bojan , Dolićanin Edin , Petronijević Predrag , Pejović Milić , Stanković Koviljka
Published: June 2013

This paper discusses the current problem of the electronic memory reliability in terms of the ionizing radiation effects. The topic is actual since the high degree of components' miniaturization integrated into the flash memory causes the extreme sensitivity of this memory type to the ionizing radiation effects. The effects of ionizing radiation may cause changes in stored data, or even the physical destruction of the components. At the end, the experimentally and numerically obtained effects of radiation on specific flash memories are shown and discussed. The results obtained by laboratory and numerical experiments showed good agreement with each other and with the theoretically expected results.
Early Changes in mRNA and Protein Expression Related to Cancer Treatment by Modulated Electrohyperthermia
Authors: Meggyesházi Nóra , Andócs Gábor , Spisák Sándor , Krenács Tibor
Published: June 2013

Modulated electrohyperthermia (mEHT), generated by capacitive coupled, modulated 13.56 MHz radiofrequency, is a noninvasive technique for targeted tumor treatment based on elevated ion concentration and electric admittance in malignant tumors. In this study, we tested early changes in protein expression related to tumor destruction upon a single shot of 30-minute mEHT treatment of xenografted human colorectal cell line (HT29) implanted into the femoral region of Balb/c nu/nu mice. Treatment-related mRNA expression profiling was done using the human genome U133 Plus 2.0 Arrays. Apoptosis protein arrays and immunohistochemistry were performed for validating changes at the protein level. The mEHT treatment resulted in major expression changes in 48 genes including several heat-shock proteins. Apoptosis protein arrays revealed the upregulation of death receptors, Bcl-2 superfamily mitochondrial apoptosis regulatory proteins, and heat-shock proteins, which were also confirmed in situ. Within 24-hour post-treatment, mEHT resulted in the upregulation apoptosis induction and heat-shock-related gene and protein expression in HT29 colorectal cancer xenografts contributing to tumor destruction.
Spatiotemporal Dynamic Simulation of Acute Perfusion/Diffusion Ischemic Stroke Lesions Evolution: A Pilot Study Derived from Longitudinal MR Patient Data
Authors: Rekik Islem , Allassonnière Stéphanie , Durrleman Stanley , Carpenter Trevor , Wardlaw Joanna
Published: June 2013

The spatiotemporal evolution of stroke lesions, from acute injury to final tissue damage, is complex. Diffusion-weighted (DWI) and perfusion-weighted (PWI) imaging is commonly used to detect early ischemic changes and attempts to distinguish between permanently damaged and salvageable tissues. To date, 2D and 3D measures of diffusion/perfusion regions at individual timepoints have been widely used but may underestimate the true lesion spatio-temporal dynamics. Currently there is no spatio-temporal 4D dynamic model that simulates the continuous evolution of ischemic stroke from MR images. We determined whether a 4D current-based diffeomorphic model, developed in the field of statistical modeling for measuring the variability of anatomical surfaces, could estimate patient-specific spatio-temporal continuous evolution for MR PWI (measured as mean transit time, (MTT)) and DWI lesions. In our representative pilot sample, the model fitted the data well. Our dynamic analysis of lesion evolution showed different patterns; for example, some DWI/PWI dynamic changes corresponded with DWI lesion expansion into PWI lesions, but other patterns were much more complex and diverse. There was wide variation in the time when the final tissue damage was reached after stroke for DWI and MTT.
Delay-Partitioning Approach to Stability of Linear Discrete-Time Systems with Interval-Like Time-Varying Delay
Authors: Kokil Priyanka , Kandanvli V. Krishna Rao , Kar Haranath
Published: June 2013

This paper is concerned with the problem of global asymptotic stability of linear discrete-time systems with interval-like time-varying delay in the state. By utilizing the concept of delay partitioning, a new linear-matrix-inequality-(LMI-) based criterion for the global asymptotic stability of such systems is proposed. The proposed criterion does not involve any free weighting matrices but depends on both the size of delay and partition size. The developed approach is extended to address the problem of global asymptotic stability of state-delayed discrete-time systems with norm-bounded uncertainties. The proposed results are compared with several existing results.
Experimental Characterisation and Modelling of Homogeneous Solid Suspension in an Industrial Stirred Tank
Authors: Calvo Sébastien , Delafosse Angélique , Collignon Marie-Laure , Crine Michel , Toye Dominique
Published: June 2013

In this work, we study the conditions needed to reach homogeneous distribution of aluminium salts particles in water inside a torispherical bottom shaped stirred tank of 70 L equipped with a Pfaudler RCI type impeller and three equispaced vertical baffles. The aim of the present study is to develop a CFD model describing the quality of particle distribution in industrial scale tanks. This model, validated with experimental data, is used afterwards to develop scale-up and scale-down correlations to predict the minimum impeller speed needed to reach homogeneous solid distribution Nhs. The commercial CFD software Fluent 14 is used to model the fluid flow and the solid particle distribution in the tank. Sliding Mesh approach is used to take the impeller motion into account. Assuming that the discrete solid phase has no influence on the continuous liquid phase behaviour, the fluid flow dynamics is simulated independently using the well-known k-∊ turbulence model. The liquid-solid mixture behaviour is then described by implementing the Eulerian Mixture model. Computed liquid velocity fields are validated by comparison with PIV measurements. Computed Nhs were found to be in good agreement with experimental measurements. Results from different scales allowed correlating Nhs values to the volumetric power consumption.
Identification, Selection, and Enrichment of Cardiomyocyte Precursors
Authors: Zanetti Bianca Ferrarini , Gomes Walter José , Han Sang Won
Published: June 2013

The large-scale production of cardiomyocytes is a key step in the development of cell therapy and tissue engineering to treat cardiovascular diseases, particularly those caused by ischemia. The main objective of this study was to establish a procedure for the efficient production of cardiomyocytes by reprogramming mesenchymal stem cells from adipose tissue. First, lentiviral vectors expressing neoR and GFP under the control of promoters expressed specifically during cardiomyogenesis were constructed to monitor cell reprogramming into precardiomyocytes and to select cells for amplification and characterization. Cellular reprogramming was performed using 5′-azacytidine followed by electroporation with plasmid pOKS2a, which expressed Oct4, Sox2, and Klf4. Under these conditions, GFP expression began only after transfection with pOKS2a, and less than 0.015% of cells were GFP+. These GFP+cells were selected for G418 resistance to find molecular markers of cardiomyocytes by RT-PCR and immunocytochemistry. Both genetic and protein markers of cardiomyocytes were present in the selected cells, with some variations among them. Cell doubling time did not change after selection. Together, these results indicate that enrichment with vectors expressing GFP and neoR under cardiomyocyte-specific promoters can produce large numbers of cardiomyocyte precursors (CMPs), which can then be differentiated terminally for cell therapy and tissue engineering.