bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyanine dyes in biophysical research: the photophysics of polymethine fluorescent dyes in biomolecular environments
Authors: Levitus Marcia , Ranjit Suman 
Published: November 2010

AbstractThe breakthroughs in single molecule spectroscopy of the last decade and the recent advances in super resolution microscopy have boosted the popularity of cyanine dyes in biophysical research. These applications have motivated the investigation of the reactions and relaxation processes that cyanines undergo in their electronically excited states. Studies show that the triplet state is a key intermediate in the photochemical reactions that limit the photostability of cyanine dyes. The removal of oxygen greatly reduces photobleaching, but induces rapid intensity fluctuations (blinking). The existence of non-fluorescent states lasting from milliseconds to seconds was early identified as a limitation in single-molecule spectroscopy and a potential source of artifacts. Recent studies demonstrate that a combination of oxidizing and reducing agents is the most efficient way of guaranteeing that the ground state is recovered rapidly and efficiently. Thiol-containing reducing agents have been identified as the source of long-lived dark states in some cyanines that can be photochemically switched back to the emissive state. The mechanism of this process is the reversible addition of the thiol-containing compound to a double bond in the polymethine chain resulting in a non-fluorescent molecule. This process can be reverted by irradiation at shorter wavelengths. Another mechanism that leads to non-fluorescent states in cyanine dyes is cis–trans isomerization from the singlet-excited state. This process, which competes with fluorescence, involves the rotation of one-half of the molecule with respect to the other with an efficiency that depends strongly on steric effects. The efficiency of fluorescence of most cyanine dyes has been shown to depend dramatically on their molecular environment within the biomolecule. For example, the fluorescence quantum yield of Cy3 linked covalently to DNA depends on the type of linkage used for attachment, DNA sequence and secondary structure. Cyanines linked to the DNA termini have been shown to be mostly stacked at the end of the helix, while cyanines linked to the DNA internally are believed to partially bind to the minor or major grooves. These interactions not only affect the photophysical properties of the probes but also create a large uncertainty in their orientation.
Role-based software agent interaction models: a survey
Authors: Cabri Giacomo , Leonardi Letizia , Ferrari Luca , Zambonelli Franco 
Published: November 2010

AbstractThe role concept represents a useful approach that has been exploited in different agent-based systems, in particular applied to interactions between agents. There are some requirements that are important for the development of agent-based applications using roles, for instance the support for the analysis, the design and the implementation phases. We have considered and compared different role-based proposals in the literature, and this paper presents a survey of the most spread ones. We explain each proposal and point out if and how it meets the identified requirements. Far from deciding the best proposal, our aim is to present the advantages and drawbacks of several proposals to designers and developers, so that they can make the best choice with regard to their needs.
Discretization as the enabling technique for the Naïve Bayes and semi-Naïve Bayes-based classification
Authors: Mizianty Marcin J. , Kurgan Lukasz A. , Ogiela Marek R. 
Published: November 2010

AbstractCurrent classification problems that concern data sets of large and increasing size require scalable classification algorithms. In this study, we concentrate on several scalable, linear complexity classifiers that include one of the top 10 voted data mining methods, Naïve Bayes (NB), and several recently proposed semi-NB classifiers. These algorithms perform front-end discretization of the continuous features since by design they work only with nominal or discrete features. We address the lack of studies that investigate the benefits and drawbacks of discretization in the context of the subsequent classification. Our comprehensive empirical study considers 12 discretizers (two unsupervised and 10 supervised), seven classifiers (two classical NB and five semi-NB), and 16 data sets. We investigate the scalability of the discretizers and show that the fastest supervised discretizers fast class-attribute interdependency maximization (FCAIM), class-attribute interdependency maximization (CAIM), and information entropy maximization (IEM) provide discretization schemes with the highest overall quality. We show that discretization improves the classification accuracy when compared against the two classical methods, NB and Flexible Naïve Bayes (FNB), executed on the raw data. The choice of the discretization algorithm impacts the significance of the improvements. The MODL, FCAIM, and CAIM methods provide statistically significant improvements, while the IEM, Class-attribute contingency coefficient (CACC), and Khiops discretizers provide moderate improvements. The most accurate classification models are generated by the Averaged one-dependence estimators (AODEsr) classifier followed by AODE and HNB (Hidden Naïve Bayes). AODEsr run on data discretized with MODL, FCAIM, and CAIM provides statistically significantly better accuracies than both the classical NB methods. The worst results are obtained with the NB, FNB, and LBR (Lazy Bayes rule) classifiers. We show that although the time to build the discretization scheme could be longer than the time to train the classifier, the completion of the entire process (to discretize data, compute the classifier, and predict test instances) is often faster than the NB-based classification of the continuous instances. This is because the time to classify test instances is an important factor that is positively influenced by discretization. The biggest positive influence, both on the accuracy and the classification time, is associated with the MODL, FCAIM, and CAIM algorithms.
The role of perceptual availability and discourse context in young children's question answering
Authors: SALOMO DOROTHÉ , GRAF EILEEN , LIEVEN ELENA , TOMASELLO MICHAEL 
Published: November 2010

ABSTRACTThree- and four-year-old children were asked predicate-focus questions (‘What's X doing?’) about a scene in which an agent performed an action on a patient. We varied: (i) whether (or not) the preceding discourse context, which established the patient as given information, was available for the questioner; and (ii) whether (or not) the patient was perceptually available to the questioner when she asked the question. The main finding in our study differs from those of previous studies since it suggests that children are sensitive to the perceptual context at an earlier age than they are to previous discourse context if they need to take the questioner's perspective into account. Our finding indicates that, while children are in principle sensitive to both factors, young children rely on perceptual availability when a conflict arises.
Syndromic surveillance of acute gastroenteritis based on drug consumption
Authors: BOUNOURE F. , BEAUDEAU P. , MOULY D. , SKIBA M. , LAHIANI-SKIBA M. 
Published: November 2010

SUMMARYSince 1998, the French Health Insurance (NHI) system had established a national database in order to reimburse drug prescriptions. These electronical data are a considerable potential source for syndromic surveillance because of their exhaustive and regular updates. The aim of this study was to develop a method to identify acute gastroenteritis (AG) cases from drug reimbursements of the NHI database. The algorithm aimed at discriminating AG from other pathologies was determined from a sample of 206 AG prescriptions and 351 non-AG prescriptions collected in five pharmacies. The AG case identification was mainly based on the lag time between the prescription and delivery day, the occurrence of non-AG case-specific drugs, AG case-specific drug associations and treatment duration. The discriminant algorithm led to a sensitive and specific indicator of medically treated cases of AG with a time–spatial resolution power which met the need for waterborne AG surveillance.
Wide range of point prevalences of healthcare-associated infections in Western Greece
Authors: ALEXOPOULOS E. C. , BATZI E. , MESSOLORA F. , JELASTOPULU E. 
Published: November 2010

SUMMARYThe purpose of this study was to estimate the prevalence of healthcare-associated infections (HAIs) in the region of Western Greece and its relationship with possible predisposing factors. Two 1-day prevalence studies were performed in all hospitals of the region. The average HAI prevalence was 2·9% (range 0–6·8%) in the hospitals and 0–22·7% between different medical wards. Overall, 90% of HAI patients had predisposing factors. The most frequently isolated microorganism was Escherichia coli (14·3%). The study revealed a relatively low overall point prevalence of HAI, but remarkable discrepancies between the hospitals and wards. This may be due to the presence of confounding medical conditions and/or underreporting of HAIs from certain hospital wards. Local point-prevalence surveys may increase the awareness of HAIs in hospital staff and contribute to the establishment of effective infection control.
Rabies virus strains circulating in Bhutan: implications for control
Authors: TENZIN  , WACHARAPLUESADEE S. , DENDUANGBORIPANT J. , DHAND N. K. , DORJI R. , TSHERING D. , RINZIN K. , RAIKA V. , DAHAL N. , WARD M. P. 
Published: November 2010

SUMMARYWe report a molecular epidemiological study of rabies virus (RABV) strains circulating in animal populations in Bhutan, and investigate potential origins of these viruses. Twenty-three RABV isolates originating from dogs and other domestic animals were characterized by sequencing the partial nucleoprotein (N) gene (395 bp). Phylogenetic analysis was conducted and the Bhutanese isolates were compared with rabies viruses originating from other parts of the world. Phylogenetic analysis showed that Bhutanese isolates were highly similar and were closely related to Indian strains and South Asian Arctic-like-1 viruses. Our study suggests that the rabies viruses spreading in southern parts of Bhutan have originated from a common ancestor, perhaps from the Indian virus strain.
A review and meta-analysis of red and processed meat consumption and breast cancer
Authors: Alexander Dominik D. , Morimoto Libby M. , Mink Pamela J. , Cushing Colleen A. 
Published: November 2010

The relationship between meat consumption and breast cancer has been the focus of several epidemiological investigations, yet there has been no clear scientific consensus as to whether red or processed meat intake increases the risk of breast cancer. We conducted a comprehensive meta-analysis incorporating data from several recently published prospective studies of red or processed meat intake and breast cancer. In the meta-analysis utilising data from the Pooling Project publication (includes data from eight cohorts) combined with data from nine studies published between 2004 and 2009 and one study published in 1996, the fixed-effect summary relative risk estimate (SRRE) for red meat intake (highv.low) and breast cancer was 1·02 (95 % CI 0·98, 1·07;Pvalue for heterogeneity = 0·001) and the random-effects SRRE was 1·07 (95 % CI 0·98, 1·17). The SRRE for each 100 g increment of red meat was 1·04 (95 % CI 1·00, 1·07), based on a fixed-effects model, and 1·12 (95 % CI 1·03, 1·23) based on a random-effects model. No association was observed for each 100 g increment of red meat among premenopausal women (SRRE 1·01; 95 % CI 0·92, 1·11) but a statistically significant SRRE of 1·22 (95 % CI 1·04, 1·44) was observed among postmenopausal women using a random-effects model. However, the association for postmenopausal women was attenuated and non-significant when using a fixed-effects model (SRRE 1·03; 95 % CI 0·98, 1·08). The fixed- and random-effect SRRE for high (v.low) processed meat intake and breast cancer were 1·00 (95 % CI 0·98, 1·01;Pvalue for heterogeneity = 0·005) and 1·08 (95 % CI 1·01, 1·16), respectively. The fixed- and random-effect SRRE for each 30 g increment of processed meat were 1·03 (95 % CI 1·00, 1·06) and 1·06 (95 % CI 0·99, 1·14), respectively. Overall, weak positive summary associations were observed across all meta-analysis models, with the majority being non-statistically significant. Heterogeneity was evident in most analyses, summary associations were sensitive to the choice of analytical model (fixedv.random effects), and publication bias appeared to have produced slightly elevated summary associations. On the basis of this quantitative assessment, red meat and processed meat intake does not appear to be independently associated with increasing the risk of breast cancer, although further investigations of potential effect modifiers, such as analyses by hormone receptor status, may provide valuable insight to potential patterns of associations.
A performance enhanced PSI-BLAST based on hybrid alignment
Authors: Li Yuheng , Chia Nicholas , Lauria Mario , Bundschuh Ralf 
Published: November 2010

Abstract
Motivation: Sequence alignment is one of the most popular tools of modern biology. NCBI's PSI-BLAST utilizes iterative model building in order to better detect distant homologs with greater sensitivity than non-iterative BLAST. However, PSI-BLAST's performance is limited by the fact that it relies on deterministic alignments. Using a semi-probabilistic alignment scheme such as Hybrid alignment should allow for better informed model building and improved identification of homologous sequences, particularly remote homologs.
Results: We have built a new version of the tool in which the Smith-Waterman alignment algorithm core is replaced by the hybrid alignment algorithm. The favorable statistical properties of the hybrid algorithm allow the introduction of position-specific gap penalties in Hybrid PSI-BLAST. This improves the position-specific modeling of protein families and results in an overall improvement of performance.
Availability: Source code is freely available for download at http://bioserv.mps.ohio-state.edu/HybridPSI, implemented in C and supported on linux.
Contact: bundschuh@mps.ohio-state.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Modification of recombinant maize ChitA chitinase by fungal chitinase‐modifying proteins
Authors: NAUMANN TODD A. 
Published: November 2010

SUMMARYIn commercial maize, there are at least two different alleles of the chiA gene that encode alloforms of ChitA chitinase, a protein that is abundant in developing seed. Both known alloforms are modified by Bz‐cmp, a chitinase‐modifying protein (cmp) secreted by the fungal pathogen Bipolaris zeicola. One alloform (ChitA‐B73) is also modified by Stm‐cmp, a protein secreted by the fungal pathogen Stenocarpella maydis, whereas the other (ChitA‐LH82) is resistant. The two ChitA alloforms possess six differences or polymorphisms (P1–P6). To determine whether the P2 polymorphism in the chitin‐binding domain is responsible for resistance or susceptibility to modification by Stm‐cmp, and to determine whether Stm‐cmp and Bz‐cmp are proteases, heterologous expression strains of the yeast Pichia pastoris that produce recombinant maize ChitA (rChitA) alloforms and mutant rChitAs were created. rChitA alloforms and mutant rChitAs were purified from yeast cultures and used as substrates in assays with Stm‐cmp and Bz‐cmp. As with native protein, Bz‐cmp modified both rChitA‐LH82 and rChitA‐B73, whereas Stm‐cmp modified rChitA‐B73 only. Mutant rChitAs, in which the P2 amino acids were changed to those of the other alloform, resulted in a significant exchange in Stm‐cmp susceptibility. Amino‐terminal sequencing of unmodified and modified rChitA‐B73 demonstrated that Stm‐cmp cleaves the peptide bond on the amino‐terminal side of the P2 alanine, whereas Bz‐cmp cleaves in the poly‐glycine hinge region, the site of P3. The results demonstrate that Stm‐cmp and Bz‐cmp are proteases that truncate ChitA chitinase at the amino terminus, but at different sites. Both sites correspond to polymorphisms in the two alloforms, suggesting that the sequence diversity at P2 and P3 is the result of selective pressure to prevent truncation by fungal proteases.
Determinants of mercaptopurine toxicity in paediatric acute lymphoblastic leukemia maintenance therapy
Authors: Adam de Beaumais Tiphaine , Fakhoury May , Medard Yves , Azougagh Said , Zhang Daolun , Yakouben Karima , Jacqz‐Aigrain Evelyne 
Published: November 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The pharmacogenetic polymorphisms of both TPMT and ITPA are associated with individual variability in 6‐mercaptopurine (6‐MP) intracellular metabolism.• The balance between red blood cell (RBC) 6‐thioguanine nucleotide (6TGN) and 6‐methylated metabolite (6‐MMPN) concentrations has an important impact on efficacy in children treated for acute lymphoblastic leukemia.• Hepatotoxicity is a frequent complication of the association 6‐MP and methotrexate during maintenance therapy.WHAT THIS STUDY ADDS• RBC 6‐TGN concentrations are dependant on TPMT genotype and age, while RBC 6‐MMPN concentrations depend on TPMT and ITPA polymorphisms.• Children aged 6 years or less had lower RBC 6‐TGN concentrations during maintenance therapy, demonstrating an age effect on 6‐MP intracellular metabolism.• Hepatotoxicity is a frequent complication of the association of 6‐MP and methotrexate. A 6‐MMPN threshold of 5000 pmol/8 × 108RBC was associated with an increased risk of hepatotoxicity.AIMS6‐mercaptopurine (6‐MP) is used in the treatment of childhood acute lymphoblastic leukaemia (ALL). Its red blood cell (RBC) metabolite concentrations (6‐thioguanine [6‐TGN] and 6‐methylmercaptopurine nucleotides [6‐MMPN]) are related to drug response. We investigated the impact of non‐genetic covariates and pharmacogenetic polymorphisms affecting thiopurine methyltransferase (TPMT) and inosine triphosphate pyrophosphatase (ITPA) on 6‐MP metabolism and response.METHODSSixty‐six children with ALL treated according to EORTC 58951 protocol were included in this study. Six patients had a heterozygous genotype for the most commonTPMTpolymorphisms, nine forITPA 94 C>Aand 17 forITPA IVS2+21 A>C. 6‐MP metabolites concentrations were analyzed by mixed model analysis.RESULTSDuring maintenance, steady‐state RBC 6‐TGN concentrations were lower in patients aged 6 years or younger (493 pmol/8 × 108RBC) than in older children (600 pmol/8 × 108RBC). 6‐MMPN concentrations were low in patients withTPMTvariant/wild‐typeITPA(1862 pmol/8 × 108RBC), intermediate in wild‐type patients and high (16468 pmol/8 × 108RBC) in patients wild‐typeTPMT/variantITPA. A 6‐MMPN threshold of 5000 pmol/8 × 108RBC was associated with an increased risk of hepatotoxicity.CONCLUSIONIn this study, age and bothTPMTandITPAgenotypes influenced 6‐MP metabolism. High 6‐MMPN was associated with hepatotoxicity. These pharmacological tools should be used to monitor ALL treatment in children.
Tamsulosin shows a higher unbound drug fraction in human prostate than in plasma: a basis for uroselectivity?
Authors: Korstanje Cees , Krauwinkel Walter , van Doesum‐Wolters Francisca L. C. 
Published: November 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• The efficacy‐tolerability profile of tamsulosin in patients with benign prostatic hyperplasia (BPH) is assumed to be associated both with the α1‐adrenoceptor selectivity profile of the drug and a small peak : trough ratio in the plasma pharmacokinetic (PK) profile. Tamsulosin is highly bound to plasma proteins, notably α1‐acid glycoprotein (AGP). This protein is a high‐affinity binding protein and AGP plasma concentration was found to influence the therapeutic (unbound) plasma concentrations for high‐AGP‐binding drugs.WHAT THIS STUDY ADDS• The study actually assessed unbound tamsulosin concentrations in both blood plasma and prostate tissue and reported that the unbound tamsulosin concentrations after multiple dosing in men with BPH, were much higher in prostate than in blood plasma. The assumption is put forward that differential free drug concentrations in prostate and blood plasma may contribute to the relative ‘uroselectivity’ of tamsulosin.AIMThe aim of this small patient study was to investigate tamsulosin concentrations in prostate and plasma samples in order to identify potential differences in the pharmacokinetics (PK) in plasma and prostate contributing to its pharmacodynamic activity profile in patients.METHODSForty‐one patients with benign prostatic hyperplasia (BPH) scheduled for open prostatectomy were given tamsulosin 0.4 mg for 6–21 days in order to reach steady‐state PK. Patients were randomized over four groups to allow collection of plasma and tissue samples at different time points after last dose administration. Samples were collected during surgery and assayed for tamsulosin HCl. The free fraction (fu) of tamsulosin was determined by ultracentrifugation of plasma and prostate tissue spiked with14C‐tamsulosin.RESULTSCmaxin plasma at 4.4 h for total tamsulosin was 15.2 ng ml−1and AUC(0,24 h) was 282 ng ml−1 h, while for prostateCmaxat 11.4 h post‐dose was 5.4 ng ml−1and AUC(0,24 h) was 120 ng ml−1 h. AUC(0,24 h) for total tamsulosin in prostate was 43% of the plasma AUC(0,24 h).fuwas 0.4 % for plasma and 59.1% for prostate. Therefore calculated on unbound tamsulosin, a ratio of 63 resulted for prostatevs.plasmaCmaxconcentrations.CONCLUSIONSThese data indicate that in patients with confirmed BPH the amount of tamsulosin freely available in the target tissue (prostate) is much higher than in plasma.