bluuebunny/crossref_metadata_2025_split huggingface dataset:
From MC/DC to RC/DC: formalization and analysis of control-flow testing criteria
Authors: Vilkomir Sergiy A. , Bowen Jonathan P. 
Published: January 2006

Abstract
This paper describes an approach to the formalization of existing criteria used in computer systems software testing and proposes a new Reinforced Condition/Decision Coverage (RC/DC) criterion. This new criterion has been developed from the well-known Modified Condition/Decision Coverage (MC/DC) criterion and is more suitable for the testing of safety-critical software where MC/DC may not provide adequate assurance. As a formal language for describing the criteria, the Z notation has been selected. Formal definitions in the Z notation for RC/DC, as well as MC/DC and other criteria, are presented. Specific examples of using these criteria for specification-based testing are considered and some features are formally proved. This characterization is helpful in the understanding of different types of testing and also the correct application of a desired testing regime.
Bayesian classifiers for detecting HGT using fixed and variable order markov models of genomic signatures
Authors: Dalevi Daniel , Dubhashi Devdatt , Hermansson Malte 
Published: January 2006

Abstract
Motivation: Analyses of genomic signatures are gaining attention as they allow studies of species-specific relationships without involving alignments of homologous sequences. A naïve Bayesian classifier was built to discriminate between different bacterial compositions of short oligomers, also known as DNA words. The classifier has proven successful in identifying foreign genes in Neisseria meningitis. In this study we extend the classifier approach using either a fixed higher order Markov model (Mk) or a variable length Markov model (VLMk).
Results: We propose a simple algorithm to lock a variable length Markov model to a certain number of parameters and show that the use of Markov models greatly increases the flexibility and accuracy in prediction to that of a naïve model. We also test the integrity of classifiers in terms of false-negatives and give estimates of the minimal sizes of training data. We end the report by proposing a method to reject a false hypothesis of horizontal gene transfer.
Availability: Software and Supplementary information available at
Contact: dalevi@cs.chalmers.se
IWoCS: analyzing ribosomal intergenic transcribed spacers configuration and taxonomic relationships
Authors: D'Auria Giuseppe , Pushker Ravindra , Rodriguez-Valera Francisco 
Published: January 2006

Abstract
Motivation: Lately the use of 16S–23S Intergenic Transcribed Spacer (ITS) sequences for bacterial typing purposes has increased. The presence of conserved regions like tRNA genes or boxes together with hypervariable regions allows performing intraspecific discrimination of very close bacterial strains. On the other hand this mosaic of variability makes the ITS a sequence difficult to analyze and compare.
Results: A software to study ITSs by a Word Count based System (IWoCS) is proposed. A large dataset of ITS was created (comprising 7355 sequences). A database indicating all the occurrences of possible n-mers (tags), describing each ITS sequence, was created (with n going from 5 to 13) including 32 061 819 entries. The database allows to analyze ITS sequences submitted by users using a web-based interface. The abundance in the database of each n-mer is given in a one-base sliding frame. A dominance plot reflects how common the tags are within different taxonomic levels. The obtained profile identifies highly repeated tags as evolutionarily conserved regions (like tRNA or boxes) or low frequency tags as regions specifically associated to taxonomic groups. The study of the dominance and abundance profiles combined with the taxonomy reports provides a novel tool for the use of the ITS in bacteria typing and identification.
Availability: The database is freely accessible at
Contact: gdauria@umh.es
A greedier approach for finding tag SNPs
Authors: Chang Chia-Jung , Huang Yao-Ting , Chao Kun-Mao 
Published: January 2006

Abstract
Motivation: Recent studies have shown that a small subset of Single Nucleotide Polymorphisms (SNPs) (called tag SNPs) is sufficient to capture the haplotype patterns in a high linkage disequilibrium region. To find the minimum set of tag SNPs, exact algorithms for finding the optimal solution could take exponential time. On the other hand, approximation algorithms are more efficient but may fail to find the optimal solution.
Results: We propose a hybrid method that combines the ideas of the branch-and-bound method and the greedy algorithm. This method explores larger solution space to obtain a better solution than a traditional greedy algorithm. It also allows the user to adjust the efficiency of the program and quality of solutions. This algorithm has been implemented and tested on a variety of simulated and biological data. The experimental results indicate that our program can find better solutions than previous methods. This approach is quite general since it can be used to adapt other greedy algorithms to solve their corresponding problems.
Availability: The program is available upon request.
Contact: kmchao@csie.ntu.edu.tw
MZmine: toolbox for processing and visualization of mass spectrometry based molecular profile data
Authors: Katajamaa Mikko , Miettinen Jarkko , Orešič Matej 
Published: January 2006

Abstract
Summary: New additional methods are presented for processing and visualizing mass spectrometry based molecular profile data, implemented as part of the recently introduced MZmine software. They include new features and extensions such as support for mzXML data format, capability to perform batch processing for large number of files, support for parallel processing, new methods for calculating peak areas using post-alignment peak picking algorithm and implementation of Sammon's mapping and curvilinear distance analysis for data visualization and exploratory analysis.
Availability: MZmine is available under GNU Public license from
Contact: matej.oresic@vtt.fi
GUUGle: a utility for fast exact matching under RNA complementary rules including G–U base pairing
Authors: Gerlach Wolfgang , Giegerich Robert 
Published: January 2006

Abstract
Motivation: RNA secondary structure analysis often requires searching for potential helices in large sequence data.
Results: We present a utility program GUUGle that efficiently locates potential helical regions under RNA base pairing rules, which include Watson–Crick as well as G–U pairs. It accepts a positive and a negative set of sequences, and determines all exact matches under RNA rules between positive and negative sequences that exceed a specified length. The GUUGle algorithm can also be adapted to use a precomputed suffix array of the positive sequence set. We show how this program can be effectively used as a filter preceding a more computationally expensive task such as miRNA target prediction.
Availability: GUUGle is available via the Bielefeld Bioinformatics Server at
Contact: robert@TechFak.Uni-Bielefeld.DE
Haloferax volcanii PitA: an example of functional interaction between the Pfam chlorite dismutase and antibiotic biosynthesis monooxygenase families?
Authors: Bab-Dinitz Elizabeta , Shmuely Hagay , Maupin-Furlow Julie , Eichler Jerry , Shaanan Boaz 
Published: January 2006

Abstract
A curious fusion between chlorite dismutase-like and antibiotic biosynthesis monooxygenase-like domains within a single open reading frame has been revealed by both sequence homology and structural modeling in Haloferax volcanii PitA and its homologues in other halophilic archaea. While this fusion may reflect an environmental adaptation to life in hypersaline environments and hence one specific to haloarchaea, PitA and its homologues may represent a paradigm of biologically-relevant interplay between these two distinct activities in accordance with the Rosetta Stone approach.
Contact: bshaanan@bgu.ac.il
The hairless guinea‐pig as a model for treatment of cumulative irritation in humans
Authors: Andersen F. , Hedegaard K. , Petersen T. K. , Bindslev‐Jensen C. , Fullerton A. , Andersen K. E. 
Published: January 2006

Background: The effect of six skin‐care formulations (SCFs) on experimentally induced cumulative irritation was studied in hairless guinea‐pigs (HLGPs) and in human volunteers (HVs). The formulations were a basic cream, a carbomer cream and four modifications of the carbomer cream, containing either 10% isopropyl palmitate (IPP cream), 10% glycerol (glycerol cream), 19.5% canola oil (canola oil cream) or 0.5% (‐)‐α‐bisabolol (bisabolol cream).Methods: In HLGP, irritant dermatitis was induced with 30 min daily exposure for 4 days to 0.5% sodium lauryl sulfate aq. (SLS). In HVs, irritant dermatitis was induced with 10 min daily exposure for 5+4 days (no irritation on weekends) to 3% SLS aq. on the right and 30% nonanoic acid (NON) in n‐propanol on the left volar forearm. Clinical scoring was performed daily; evaporimetry (total epidermal water loss (TEWL)), hydration and colorimetry were measured at baseline (day 0) in the middle and at the end of treatment. Treatments were applied twice daily. The basic cream and the IPP cream were excluded from testing in HLGP because they were known from previous studies to be irritant in HLGP, while all formulations were known to be equally and well tolerated locally in humans.Results: All formulations worsened the skin irritation in HLGP: the glycerol cream the least, the canola oil cream the most, while the bisabolol cream and the carbomer cream were indistinguishable. In humans, the glycerol cream was better than ‘No Treatment’ after cumulative irritation with both SLS and NON. The basic cream was better tolerated in humans than was expected from previous testing in HLGPs.Conclusion: In conclusion, the results from the studies in HLGPs and HVs are in agreement with regard to ranking of the SCFs. Further, the glycerol cream showed a positive treatment effect on both SLS‐ and NON‐irritated skin in HVs.
Towards targeted therapy for infant acute lymphoblastic leukaemia
Authors: Stam Ronald W. , den Boer Monique L. , Pieters Rob 
Published: January 2006

SummaryDespite the greatly improved treatment regimes for childhood acute lymphoblastic leukaemia (ALL) in general, resulting in long‐term survival in approximately 80% of cases, current therapies still fail in >50% of ALL cases diagnosed within the first year of life (i.e. in infants). Therefore, more adequate treatment strategies are urgently needed to also improve the prognosis for these very young patients with ALL. Here we review the current acquaintance with the biology of infant ALL and describe how this knowledge may lead to innovative therapeutic approaches.
Thalassaemia‐like carriers not linked to the β‐globin gene cluster
Authors: Faà Valeria , Meloni Alessandra , Moi Loredana , Ibba Giuseppe , Travi Maurizio , Vitucci Antonio , Cao Antonio , Rosatelli Maria Cristina 
Published: January 2006

SummaryThis study describes the largest series reported to date, of individuals belonging to unrelated families carrying a β‐thalassaemia‐like phenotype in whom the β‐globin gene was found to be structurally intact by sequence analysis. This genetic determinant appears haematologically heterogeneous, displaying either a silent β‐thalassaemia‐like phenotype or a typical β‐thalassaemia carrier‐like phenotype in different families. Compound heterozygosity for both β‐thalassaemia‐like determinant and typical β‐thalassaemia allele resulted either in thalassaemia intermedia or thalassaemia major. By linkage analysis both the silent and the typical β‐like determinants were found not to be linked to the β‐globin cluster. Sequence analysis of the hypersensitive site cores of locus control region and of the genes coding for the transcription factors erythroid Kruppel‐like factor and nuclear factor (erythroid‐derived 2) were normal. β‐globin mRNA levels determined by real‐time polymerase chain reaction were reduced in both types of β‐like carriers. These results indicate the existence of causative genetic determinants not yet molecularly defined, but most likely, resulting from either the reduction or loss of function of a gene coding for unknown transcriptional regulator(s) of the β‐globin gene. The knowledge of these rare β‐thalassaemia‐like determinants have implications for clinical and, especially, prenatal diagnosis of β‐thalassaemia.
Specific polymorphisms of cytokine genes are associated with different risks to develop single‐system or multi‐system childhood Langerhans cell histiocytosis
Authors: Filippi Paola De , Badulli Carla , Cuccia Mariaclara , Silvestri Annalisa De , Dametto Ennia , Pasi Annamaria , Garaventa Alberto , Prever Adalberto Brach del , Todesco Alessandra , Trizzino Antonino , Danesino Cesare , Martinetti Miryam , Aricò Maurizio 
Published: January 2006

SummaryCytokines and chemokines determine mobilisation of Langerhans cells and their dysregulation is implicated in the pathogenesis of Langerhans cell histiocytosis (LCH). Twenty point mutations of 12 different cytokine genes were studied in 41 Italian children, 15 with single‐system (SS) and 26 with multi‐system disease. The allele and genotype distributions of interleukin‐4 (IL‐4) and interferon‐γ (IFNγ) were significantly different in patients vs. 140 controls (P = 0.007, and P = 0.018). Older children with single‐system disease shared the ‘anti‐inflammatory profile’ determined by the intermediate producer genotype IFNγ +874A/T (P = 0.029) and the high‐producer genotypes IL‐4 –590C/T and T/T (P = 0.029). Our findings suggest that specific cytokine gene variants affect susceptibility to LCH and its clinical heterogeneity.
Triiodothyronine Expands the Lactotroph and Maintains the Lactosomatotroph Population, Whereas Thyrotrophin‐Releasing Hormone Augments Thyrotroph Abundance in Aggregate Cell Cultures of Postnatal Rat Pituitary Gland
Authors: Pals K. , Vankelecom H. , Denef C. 
Published: January 2006

AbstractIn the present study, we used a three‐dimensional pituitary cell culture system from early postnatal rats to examine the in vitro developmental potential of triiodothyronine (T3) and thyrotrophin‐releasing hormone (TRH). Cell types were identified at the hormone mRNA level by single‐cell reverse transcription‐polymerase chain reaction and any change in abundance was further examined by immunofluorescence staining of the corresponding hormone protein. In aggregates from 14‐day‐old rats, long‐term (12–16 days) treatment with T3 (0.5 nM) increased the abundance of cells expressing prolactin mRNA (PRLmRNA cells) by 2.5‐fold and lowered that of nonhormonal cells and thyroid‐stimulating hormone β (TSHβ)mRNA cells. The abundance of growth hormone (GH) mRNA cells decreased during culture compared to that in the freshly dispersed pituitary gland and T3 did not significantly affect this cell population. Cells coexpressing PRL mRNA and GH mRNA virtually disappeared during culture but reappeared in the presence of T3. T3 increased the abundance of PRL‐immunoreactive (ir) cells in aggregates from 14‐day‐old rats, as well as in aggregates from newborn and 1‐week‐old rats. As estimated by bromodeoxyuridine (BrdU) labelling, a 3‐day treatment with T3 enhanced the number of PRL‐ir cells that had incorporated BrdU, but did not yet expand the total population of PRL‐ir cells. Long‐term treatment with TRH (100 nM) did not affect the proportion of PRLmRNA or GHmRNA cells, but consistently increased the proportional number of TSHβmRNA and TSHβ‐ir cells. The present data confirm the findings obtained in recent in vivo loss of function genetic studies suggesting that T3 plays a prominent role in postnatal expansion of the lactotroph population and that TRH is important for thyrotroph development. The data suggest that the effect of T3 is brought about by a direct action on the pituitary gland through a cell proliferation mechanism. T3 also appears to support the lactosomatotroph population. In view of the established theory that lactotrophs develop from GH‐expressing progenitor cells and that this is a post mitotic event, we propose that T3 is mitogenic for GHmRNA cells that lack GH‐ir material and that transdifferentiate into PRL‐ir cells, but that a pathway of PRL cell development from mitotic nonhormonal cell progenitors may also be involved.
Clinical efficacy of local administration of ceftiofur in aStaphylococcus aureusinfection in tissue cages in ponies
Authors: BOSCH G. , VAN DUIJKEREN E. , BERGWERFF A. A. , RIJKENHUIZEN A. B. M. , ENSINK J. M. 
Published: January 2006

Ceftiofur concentrations in an infected and uninfected environment were compared and the efficacy of locally administered ceftiofur was evaluated in an experimental infection withStaphylococcus aureusin tissue cages.Eight ponies had tissue cages (TCs) implanted s.c. on each side of the neck. Into one of the cages 150 mg of ceftiofur was administered and fluid samples were taken to determine ceftiofur concentrations. After 1 week the other TC was infected withS. aureusand subsequently treated with 150 mg ceftiofur administered locally into the TC once daily for 21 days. Samples of fluid were taken to determine ceftiofur concentrations and for bacterial counts. Ceftiofur concentrations did not differ significantly in the infected and uninfected environments after single dose of 150 mg of ceftiofur. Concentrations were considerably in excess of the minimum inhibitory concentration (MIC) of theS. aureusstrain used. A marked decrease of viable bacteria in tissue cage fluid (TCF) occurred. In five of seven ponies; however, the infection was not eliminated and abscess formation occurred. Therefore, local application of ceftiofur alone is not advisable for infections withS. aureusin secluded sites in horses, but should be used only with adjunctive therapy.
Derived cleaved amplified polymorphic sequence, a simple method to detect a key point mutation conferring acetyl CoA carboxylase inhibitor herbicide resistance in grass weeds
Authors: KAUNDUN S S , WINDASS J D 
Published: January 2006

SummarySubstitution of isoleucine by leucine at the equivalent of residue 1781 of acetyl CoA carboxylase (ACCase) in Alopecurus myosuroides (I1781L) has been shown to be a key point mutation conferring resistance to most aryloxypropionate and cyclohexanedione herbicides in Lolium spp., A. myosuroides, Avena fatua and Setaria viridis. This substitution results from changing an adenine residue to either thymine or cytosine at position 5341 in the ACCase coding sequence of A. myosuroides and at the homologous position in the other species. The I1781L mutation can be detected by allele‐specific amplification assays. These are, however, very dependent on the conservation of the nucleotide sequences flanking the causative single nucleotide polymorphism. Moreover, such assays cannot distinguish between homozygous and heterozygous individuals in a single polymerase chain reaction reaction. Here we present an alternative derived Cleaved Amplified Polymorphic Sequence (dCAPS) method to define I1781L status in the ACCase enzyme of four grass weeds. This dCAPS approach is simple, economical, highly transferable between species and can readily distinguish homozygous Leu/Leu 1781 and heterozygous Ile/Leu 1781 resistant individuals, providing the basis for accurate measures of the frequency of the dominant Leu allele in a given population.
Malaria and blood transfusion
Authors: Kitchen A. D. , Chiodini P. L. 
Published: January 2006

The transmission of malaria by blood transfusion was one of the first recorded incidents of transfusion‐transmitted infection. Although a number of different infections have been reported to be transmitted by transfusion since then, on a global scale malaria remains one of the most common transfusion‐transmitted infections. Transfusion‐transmitted malaria can have serious consequences, as infection withPlasmodium falciparummay prove rapidly fatal. Ensuring that, in non‐endemic countries, the blood supply is free from malaria is problematical, especially as travel to malarious areas is increasing and there is some spread of the disease into new areas, as well as a resurgence of malaria in areas where previously it had been eradicated. In non‐endemic countries, donor deferral can be effective, but clear guidelines are needed. In endemic countries the problem is far greater as the majority of donors may be potentially infected with malaria parasites. In both situations, the simple deferral of donors may be wasteful and can eventually erode the donor base. Thus, other strategies are needed to ensure safety with sufficiency. However, the screening of donations for evidence of malaria is not without its problems. Although the examination of blood films is still the basis for diagnosing acute malaria, in most situations it is not sufficiently sensitive for blood bank screening. In non‐endemic countries, donor deferral in combination with screening for specific antimalarial immunoglobulin provides an effective means of minimizing the risk of transmission. In endemic countries, more specific donor questioning, consideration of seasonal variation and geographical distribution may help to identify the population of donors who are most likely to be infected. In addition, the administration of antimalarials to transfusion recipients may help to prevent transmission. Nonetheless, no matter what strategy is adopted, it is likely that cases of transfusion‐transmitted malaria may still occur, so malaria must always be considered in any patient with a febrile illness post‐transfusion.
Spatial and Temporal Definition of Weed Patches Using Quantitative Image Analysis
Authors: Krohmann P. , Gerhards R. , Kühbauch W. 
Published: January 2006

AbstractPopulations of Alopecurus myosuroides were studied in maize, sugar beet, winter wheat and winter barley over 5 years. Objective definitions for a ‘weed aggregation’ and a ‘weed patch’ within weed distribution maps were determined. Weedy areas in 1 year, whose distance to each other not exceeded a certain maximum value, are defined as ‘weed aggregation’. Field areas, which were defined as a weed aggregation in at least 1 year, were investigated for weed occurrence in the other years. Therefore, the resulting field area was determined by the spatial expansion of the aggregations of all years. Image analysis was a helpful tool for further investigation of the visually obtained information. With this method, marginal changes within the weed aggregations could be determined. The analysed weed populations were largely stable in their existence throughout the period of the study. Still, the aggregations varied in their size depending on the crop. ‘Weed patches’ were defined as weeds that appear in 4 of the 5 years at the same location and were limited themselves to very small field segments. Identification of the weed patches was enabled by image analysis. It is obvious that the field segments become smaller by increasing requirements on the repetition rate of a weed population at the same location.