bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rediscovering secondary structures as network motifs—an unsupervised learning approach
Authors: Raveh Barak , Rahat Ofer , Basri Ronen , Schreiber Gideon 
Published: January 2007

AbstractMotivation: Secondary structures are key descriptors of a protein fold and its topology. In recent years, they facilitated intensive computational tasks for finding structural homologues, fold prediction and protein design. Their popularity stems from an appealing regularity in patterns of geometry and chemistry. However, the definition of secondary structures is of subjective nature. An unsupervised de-novo discovery of these structures would shed light on their nature, and improve the way we use these structures in algorithms of structural bioinformatics.Methods: We developed a new method for unsupervised partitioning of undirected graphs, based on patterns of small recurring network motifs. Our input was the network of all H-bonds and covalent interactions of protein backbones. This method can be also used for other biological and non-biological networks.Results: In a fully unsupervised manner, and without assuming any explicit prior knowledge, we were able to rediscover the existence of conventional α-helices, parallel β-sheets, anti-parallel sheets and loops, as well as various non-conventional hybrid structures. The relation between connectivity and crystallographic temperature factors establishes the existence of novel secondary structures.Contact: barak.raveh@weizmann.ac.il; gideon.schreiber@weizmann.ac.il
Analysis of binding site similarity, small-molecule similarity and experimental binding profiles in the human cytosolic sulfotransferase family
Authors: Najmanovich Rafael J. , Allali-Hassani Abdellah , Morris Richard J. , Dombrovsky Ludmila , Pan Patricia W. , Vedadi Masoud , Plotnikov Alexander N. , Edwards Aled , Arrowsmith Cheryl , Thornton Janet M. 
Published: January 2007

AbstractMotivation: In the present work we combine computational analysis and experimental data to explore the extent to which binding site similarities between members of the human cytosolic sulfotransferase family correlate with small-molecule binding profiles. Conversely, from a small-molecule point of view, we explore the extent to which structural similarities between small molecules correlate to protein binding profiles.Results: The comparison of binding site structural similarities and small-molecule binding profiles shows that proteins with similar small-molecule binding profiles tend to have a higher degree of binding site similarity but the latter is not sufficient to predict small-molecule binding patterns, highlighting the difficulty of predicting small-molecule binding patterns from sequence or structure. Likewise, from a small-molecule perspective, small molecules with similar protein binding profiles tend to be topologically similar but topological similarity is not sufficient to predict their protein binding patterns. These observations have important consequences for function prediction and drug design.Contact: rafael.najmanovich@ebi.ac.uk
Vorolign—fast structural alignment using Voronoi contacts
Authors: Birzele Fabian , Gewehr Jan E. , Csaba Gergely , Zimmer Ralf 
Published: January 2007

AbstractSummary: Vorolign, a fast and flexible structural alignment method for two or more protein structures is introduced. The method aligns protein structures using double dynamic programming and measures the similarity of two residues based on the evolutionary conservation of their corresponding Voronoi-contacts in the protein structure. This similarity function allows aligning protein structures even in cases where structural flexibilities exist. Multiple structural alignments are generated from a set of pairwise alignments using a consistency-based, progressive multiple alignment strategy.Results: The performance of Vorolign is evaluated for different applications of protein structure comparison, including automatic family detection as well as pairwise and multiple structure alignment. Vorolign accurately detects the correct family, superfamily or fold of a protein with respect to the SCOP classification on a set of difficult target structures. A scan against a database of &gt;4000 proteins takes on average 1 min per target. The performance of Vorolign in calculating pairwise and multiple alignments is found to be comparable with other pairwise and multiple protein structure alignment methods.Availability: Vorolign is freely available for academic users as a web server atContact: fabian.birzele@ifi.lmu.deSupplementary information: Datasets used throughout the article are available at
Identification of conserved protein complexes based on a model of protein network evolution
Authors: Hirsh Eitan , Sharan Roded 
Published: January 2007

AbstractMotivation: Data on protein–protein interactions (PPIs) are increasing exponentially. To date, large-scale protein interaction networks are available for human and most model species. The arising challenge is to organize these networks into models of cellular machinery. As in other biological domains, a comparative approach provides a powerful basis for addressing this challenge.Results: We develop a probabilistic model for protein complexes that are conserved across two species. The model describes the evolution of conserved protein complexes from an ancestral species by protein interaction attachment and detachment and gene duplication events. We apply our model to search for conserved protein complexes within the PPI networks of yeast and fly, which are the largest networks in public databases. We detect 150 conserved complexes that match well-known complexes in yeast and are coherent in their functional annotations both in yeast and in fly. In comparison with two previous approaches, our model yields higher specificity and sensitivity levels in protein complex detection.Availability: The program is available upon request.Contact: roded@tau.ac.il
A comparative genome approach to marker ordering
Authors: Faraut T. , de Givry S. , Chabrier P. , Derrien T. , Galibert F. , Hitte C. , Schiex T. 
Published: January 2007

AbstractMotivation: Genome maps are fundamental to the study of an organism and essential in the process of genome sequencing which in turn provides the ultimate map of the genome. The increased number of genomes being sequenced offers new opportunities for the mapping of closely related organisms. We propose here an algorithmic formalization of a genome comparison approach to marker ordering.Results: In order to integrate a comparative mapping approach in the algorithmic process of map construction and selection, we propose to extend the usual statistical model describing the experimental data, here radiation hybrids (RH) data, in a statistical framework that models additionally the evolutionary relationships between a proposed map and a reference map: an existing map of the corresponding orthologous genes or markers in a closely related organism. This has concretely the effect of exploiting, in the process of map selection, the information of marker adjacencies in the related genome when the information provided by the experimental data is not conclusive for the purpose of ordering. In order to compute efficiently the map, we proceed to a reduction of the maximum likelihood estimation to the Traveling Salesman Problem. Experiments on simulated RH datasets as well as on a real RH dataset from the canine RH project show that maps produced using the likelihood defined by the new model are significantly better than maps built using the traditional RH model.Availability: The comparative mapping approach is available in the last version of de Givry,S. et al. [(2004) Bioinformatics, 21, 1703–1704, ], a free (the LKH part is free for academic use only) mapping software in C++, including LKH (Helsgaun,K. (2000) Eur. J. Oper. Res., 126, 106–130, ) for maximum likelihood computation.Contact: thomas.faraut@toulouse.inra.fr
Difference detection in LC-MS data for protein biomarker discovery
Authors: Listgarten Jennifer , Neal Radford M. , Roweis Sam T. , Wong Peter , Emili Andrew 
Published: January 2007

AbstractMotivation: There is a pressing need for improved proteomic screening methods allowing for earlier diagnosis of disease, systematic monitoring of physiological responses and the uncovering of fundamental mechanisms of drug action. The combined platform of LC-MS (Liquid-Chromatography-Mass-Spectrometry) has shown promise in moving toward a solution in these areas. In this paper we present atechnique for discovering differences in protein signal between two classes of samples of LC-MS serum proteomic data without use of tandem mass spectrometry, gels or labeling. This method works on data from a lower-precision MS instrument, the type routinely used by and available to the community at large today. We test our technique on a controlled (spike-in) but realistic (serum biomarker discovery) experiment which is therefore verifiable. We also develop a new method for helping to assess the difficulty of a given spike-in problem. Lastly, we show that the problem of class prediction, sometimes mistaken as a solution to biomarker discovery, is actually a much simpler problem.Results: Using precision–recall curves with experimentally extracted ground truth, we show that (1) our technique has good performance using seven replicates from each class, (2) performance degrades with decreasing number of replicates, (3) the signal that we are teasing out is not trivially available (i.e. the differences are not so large that the task is easy). Lastly, we easily obtain perfect classification results for data in which the problem of extracting differences does not produce absolutely perfect results. This emphasizes the different nature of the two problems and also their relative difficulties.Availability: Our data are publicly available as a benchmark for further studies of this nature atSupplementary Information: Contact: jenn@cs.toronto.edu
Nested Containment List (NCList): a new algorithm for accelerating interval query of genome alignment and interval databases
Authors: Alekseyenko Alexander V. , Lee Christopher J. 
Published: January 2007

AbstractMotivation: The exponential growth of sequence databases poses a major challenge to bioinformatics tools for querying alignment and annotation databases. There is a pressing need for methods for finding overlapping sequence intervals that are highly scalable to database size, query interval size, result size and construction/updating of the interval database.Results: We have developed a new interval database representation, the Nested Containment List (NCList), whose query time is O(n + log N), where N is the database size and n is the size of the result set. In all cases tested, this query algorithm is 5–500-fold faster than other indexing methods tested in this study, such as MySQL multi-column indexing, MySQL binning and R-Tree indexing. We provide performance comparisons both in simulated datasets and real-world genome alignment databases, across a wide range of database sizes and query interval widths. We also present an in-place NCList construction algorithm that yields database construction times that are ∼100-fold faster than other methods available. The NCList data structure appears to provide a useful foundation for highly scalable interval database applications.Availability: NCList data structure is part of Pygr, a bioinformatics graph database library, available at http://sourceforge.net/projects/pygrContact: leec@chem.ucla.eduSupplementary information: Supplementary data are available at Bioinformatics online.
What are we learning from simulating wall turbulence?
Authors: Jiménez Javier , Moser Robert D 
Published: January 2007

The study of turbulence near walls has experienced a renaissance in the last decade, largely owing to the availability of high-quality numerical simulations. The viscous and buffer layers over smooth walls are essentially independent of the outer flow, and there is a family of numerically exact nonlinear structures that account for about half of the energy production and dissipation. The rest can be modelled by their unsteady bursting. Many characteristics of the wall layer, such as the dimensions of the dominant structures, are well predicted by those models, which were essentially completed in the 1990s after the increase in computer power made the kinematic simulations of the late 1980s cheap enough to undertake dynamic experiments.Today, we are at the early stages of simulating the logarithmic (or overlap) layer, and a number of details regarding its global properties are becoming clear. For instance, a finite Reynolds number correction to the logarithmic law has been validated in turbulent channels. This has allowed upper and lower limits of the overlap region to be clarified, with both upper and lower bounds occurring at much larger distances from the wall than commonly assumed. A kinematic picture of the various cascades present in this part of the flow is also beginning to emerge. Dynamical understanding can be expected in the next decade.
CONFIDENCE INTERVALS FOR POLICY REFORMS IN BEHAVIOURAL TAX MICROSIMULATION MODELLING
Authors: Creedy John , Kalb Guyonne , Kew Hsein 
Published: January 2007

ABSTRACTThis paper addresses the need for a measure of the uncertainty that is associated with the results calculated using tax policy behavioural microsimulation models. Deriving the analytical measure would be extremely complicated. Therefore, a simulated approach is proposed, which approximates the sampling distribution of aggregate measures based on the sampling distribution of the estimated labour supply parameters. This approach, which is very computer intensive, is compared with a more time‐efficient approach where the functional form of the sampling distribution is assumed to be normal. The results show that in many instances the results from the two approaches are quite similar. The exception is when aggregate measures for minor types of payments, involving relatively small groups of the population, are examined.
Depression of T cell‐mediated immunity reduces sulfadimethoxine‐induced capsular inflammation and inhibits associated development of invasive thyroid follicular cell carcinomas in rats
Authors: Imai Toshio , Hasumura Mai , Cho Young‐Man , Onose Jun‐ichi , Hirose Masao 
Published: January 2007

We previously demonstrated that thyroid capsular inflammation induced by continuous treatment with the antithyroidal agent sulfadimethoxine is associated with development of invasive follicular cell carcinomas in rats initiated with N‐bis(2‐hydroxypropyl)nitrosamine (DHPN). The inflammatory changes are characterized by large numbers of macrophages and lymphocytes as well as fibroblasts and we hypothesized that it might be enhanced by interplay between macrophages and T cells. To clarify this hypothesis, a comparative study was conducted between athymic nude (rnu/rnu) rats and euthymic (rnu/+) littermates initiated with DHPN (2800 mg/kg, s.c.) followed by sulfadimethoxine treatment in drinking water (0.1%) for 10 weeks. In rnu/+rats, marked capsular thickening with inflammation was induced along with invasive follicular cell carcinomas (2.8 ± 1.3/rat). In rnu/rnu rats, limited fibrous capsular thickening was noted with or without minimal inflammatory change, and the multiplicity of invasive carcinomas was significantly lower (1.1 ± 1.0/rat, P < 0.01). Inducible nitric oxide synthase expression in the inflamed lesions was detected in three of 10 rnu/+rats but in none of the rnu/rnu animals. The results thus suggest that development of invasive carcinomas is enhanced by capsular inflammation mediated by T cells, and inducible nitric oxide synthase induction may play a role in tumor progression. (Cancer Sci 2007; 98: 294–298)
Local interferon‐α gene therapy elicits systemic immunity in a syngeneic pancreatic cancer model in hamster
Authors: Hara Hidehiko , Kobayashi Akihiko , Yoshida Kimiko , Ohashi Masaki , Ohnami Shumpei , Uchida Eiji , Higashihara Eiji , Yoshida Teruhiko , Aoki Kazunori 
Published: January 2007

The interferon (IFN) protein is a cytokine with pleiotropic biological functions that include induction of apoptosis, inhibition of angiogenesis and immunomodulation. We previously examined the two antitumor mechanisms, taking advantage of the fact that IFN‐α did not show cross‐species activity in its in vivo effect. In a nude mouse subcutaneous xenograft model using human pancreatic cancer cells, the expression of human IFN‐α effectively induced cell death of human pancreatic cancer cells, whereas mouse IFN‐α augmented antitumor immunity by stimulation of natural killer cells. Here, we extended our investigation to a syngeneic pancreatic cancer model, so that the integrated antitumor activity of local IFN‐α gene therapy, including the antiproliferative, proapoptotic, antiangiogeneic and immunomodulatory effects, can be evaluated rigorously. When a recombinant hamster IFN‐α adenovirus was injected into syngeneic subcutaneous tumors of hamster pancreatic cancer (PGHAM‐1) cells in Syrian hamster, tumor growth was significantly suppressed due to cell death and T cell‐ and natural killer cell‐mediated antitumor immunity. Moreover, in this case, tumor regression was observed not only for the injected subcutaneous tumors but also for the untreated tumors both in the peritoneal cavity and at distant sites. No significant systemic toxicity was observed in the treated hamsters. Moreover, the subcutaneous rechallenge of PGHAM‐1 cells was rejected in three of four cured hamsters from the initial tumor challenge. This study further demonstrated that local IFN‐α gene therapy is a promising therapeutic strategy for pancreatic cancer, due to its multiple mechanisms of antitumor activity and its lack of significant toxicity. (Cancer Sci 2007; 98: 455–463))
Significance of error‐avoiding mechanisms for oxidative DNA damage in carcinogenesis
Authors: Tsuzuki Teruhisa , Nakatsu Yoshimichi , Nakabeppu Yusaku 
Published: January 2007

Reactive oxygen species (ROS) are produced through normal cellular metabolism, and their formation is further enhanced by exposure to ionizing radiation and various chemicals. ROS attack DNA, and the resulting oxidative DNA damage is considered to contribute to aging, carcinogenesis and neurodegeneration. Among various types of oxidative DNA damage, 8‐oxo‐7,8‐dihydroguanine (8‐oxoguanine or 8‐oxoG) is the most abundant, and plays significant roles in mutagenesis because of its ability to pair with adenine as well as cytosine. Enzymatic activities that may be responsible for preventing 8‐oxoG‐evoked mutations were identified in mammalian cells. We have focused on the following three enzymes: MTH1, OGG1 and MUTYH. MTH1 is a mammalian ortholog of Escherichia coli MutT, which hydrolyzes 8‐oxo‐dGTP to its monophosphate form in nucleotide pools, thereby preventing incorporation of the mutagenic substrate into DNA. OGG1, a functional counterpart of E. coli MutM, has an 8‐oxoG DNA glycosylase activity. MUTYH, a mammalian ortholog of E. coli MutY, excises an adenine paired with 8‐oxoG. These three enzymes are thought to prevent mutagenesis caused by 8‐oxoG in mammals. To analyze the functions of mammalian MTH1 (Mth1), OGG1 (Ogg1) and MUTYH (Mutyh) in vivo, we established mutant mice for these three enzymes by targeted mutagenesis, and investigated spontaneous tumorigenesis as well as mutagenesis. Here we discuss our recent investigation of mutagenesis and carcinogenesis in these mutant mice. (Cancer Sci 2007; 98: 465–470)
Perceived freedom in leisure and physical co‐ordination ability: impact on out‐of‐school activity participation and life satisfaction
Authors: Poulsen A. A. , Ziviani J. M. , Cuskelly M. 
Published: January 2007

AbstractBackground  Perceived freedom in leisure (PFL) is explored as a potential mechanism mediating relationships between physical co‐ordination ability and both global life satisfaction and leisure‐time physical activity participation for boys with differing levels of physical co‐ordination ability. Understanding psychological mechanisms contributing to low rates of participation in physical activities for boys with developmental co‐ordination disorder (DCD) is a clinical and research priority with potential to inform clinical interventions and preventive health initiatives.Method  Sixty boys aged 10–13 years with DCD and 113 boys without DCD completed self‐report measures of PFL and life satisfaction. Seven‐day leisure‐time activity diaries and 12‐month retrospective recall questionnaires were completed by parents.Results  Lower self‐appraisals of PFL and overall life satisfaction were found for boys with DCD compared with boys without DCD. PFL mediated relationships between physical ability and both life satisfaction and team sport participation.Conclusion  Perceived freedom in leisure, comprising self‐appraisals of leisure needs satisfaction and competence, depth of involvement and perceived control over leisure outcomes, was a significant mechanism influencing leisure‐time participation and life satisfaction for boys. The implications for effective intervention and preventive health programmes are discussed.
Corrosive poisoning mimicking cicatricial pemphigoid: Munchausen by proxy
Authors: Tamay Z. , Akcay A. , Kilic G. , Peykerli G. , Devecioglu E. , Ones U. , Guler N. 
Published: January 2007

AbstractBackground  Munchausen by proxy (MBP) is a severe form of abuse in which a caregiver simulates or fabricates illness in another person, primarily the elderly and children, which can even result in death.Case  We report two siblings who were victims of MBP, one of whom died. A very rare diagnosis, cicatricial pemphigoid was suspected in the 2‐year‐old girl who was first abused. She was hospitalized twice, for 3 and 4 months, respectively. Her second hospitalization ended with her death. MBP was diagnosed after the second sibling's admission with similar atypical signs and symptoms. It was realized that a household‐cleaning product, sodium hydroxide, was administered repeatedly by oral route to the children by their own mother.Conclusions  Physicians must consider the diagnosis of MBP whenever they are confronted with unusual, persistent or recurrent signs and symptoms in a child.
Performance on the Movement Assessment Battery for Children by Australian 3‐ to 5‐year‐old children
Authors: Livesey D. , Coleman R. , Piek J. 
Published: January 2007

AbstractBackground  The Movement Assessment Battery for Children (Movement ABC) was developed as a means of identifying those at risk of motor impairment. This test has been widely adopted as a means of assessing Australian children, but no attempt has been made to test the validity of its normative data for Australian samples. This study examines the 4‐ and 5‐year‐old Australian data in comparison with the Movement ABC age norms. Additionally, a 3‐year‐old sample was tested to determine if the test is suitable for discriminating motor performance in this age group.Methods  Representative samples of 3‐, 4‐ and 5‐year‐old children from two Australian cities (Sydney and Perth) were tested on the Movement ABC band‐one tests and the results compared with 4‐ and 5‐year norms.Results  There was significant age‐related change in performance across the Australian samples with significant gender effects on some tasks. The Australian 4‐year‐old children performed better than the American sample on most tests, but this difference had disappeared by 5 years.Conclusion  The results indicate that the Movement ABC is a useful tool in discriminating among pre‐school Australian children as young as 3 years of age. The differences between Australian and American children indicate that further studies comparing other age groups are warranted, but the differences did not appear to be sufficiently large to have clinical significance.