bluuebunny/crossref_metadata_2025_split huggingface dataset:
DACTAL: divide-and-conquer trees (almost) without alignments
Authors: Nelesen Serita , Liu Kevin , Wang Li-San , Linder C. Randal , Warnow Tandy 
Published: June 2012

AbstractMotivation: While phylogenetic analyses of datasets containing 1000–5000 sequences are challenging for existing methods, the estimation of substantially larger phylogenies poses a problem of much greater complexity and scale.Methods: We present DACTAL, a method for phylogeny estimation that produces trees from unaligned sequence datasets without ever needing to estimate an alignment on the entire dataset. DACTAL combines iteration with a novel divide-and-conquer approach, so that each iteration begins with a tree produced in the prior iteration, decomposes the taxon set into overlapping subsets, estimates trees on each subset, and then combines the smaller trees into a tree on the full taxon set using a new supertree method. We prove that DACTAL is guaranteed to produce the true tree under certain conditions. We compare DACTAL to SATé and maximum likelihood trees on estimated alignments using simulated and real datasets with 1000–27 643 taxa.Results: Our studies show that on average DACTAL yields more accurate trees than the two-phase methods we studied on very large datasets that are difficult to align, and has approximately the same accuracy on the easier datasets. The comparison to SATé shows that both have the same accuracy, but that DACTAL achieves this accuracy in a fraction of the time. Furthermore, DACTAL can analyze larger datasets than SATé, including a dataset with almost 28 000 sequences.Availability: DACTAL source code and results of dataset analyses are available at www.cs.utexas.edu/users/phylo/software/dactal.Contact: tandy@cs.utexas.edu
Nonparametric Bayesian inference for perturbed and orthologous gene regulatory networks
Authors: Penfold Christopher A. , Buchanan-Wollaston Vicky , Denby Katherine J. , Wild David L. 
Published: June 2012

Abstract
Motivation: The generation of time series transcriptomic datasets collected under multiple experimental conditions has proven to be a powerful approach for disentangling complex biological processes, allowing for the reverse engineering of gene regulatory networks (GRNs). Most methods for reverse engineering GRNs from multiple datasets assume that each of the time series were generated from networks with identical topology. In this study, we outline a hierarchical, non-parametric Bayesian approach for reverse engineering GRNs using multiple time series that can be applied in a number of novel situations including: (i) where different, but overlapping sets of transcription factors are expected to bind in the different experimental conditions; that is, where switching events could potentially arise under the different treatments and (ii) for inference in evolutionary related species in which orthologous GRNs exist. More generally, the method can be used to identify context-specific regulation by leveraging time series gene expression data alongside methods that can identify putative lists of transcription factors or transcription factor targets.
Results: The hierarchical inference outperforms related (but non-hierarchical) approaches when the networks used to generate the data were identical, and performs comparably even when the networks used to generate data were independent. The method was subsequently used alongside yeast one hybrid and microarray time series data to infer potential transcriptional switches in Arabidopsis thaliana response to stress. The results confirm previous biological studies and allow for additional insights into gene regulation under various abiotic stresses.
Availability: The methods outlined in this article have been implemented in Matlab and are available on request.
Contact: d.l.wild@warwick.ac.uk
Supplementary Information: Supplementary data is available for this article.
GraphClust: alignment-free structural clustering of local RNA secondary structures
Authors: Heyne Steffen , Costa Fabrizio , Rose Dominic , Backofen Rolf 
Published: June 2012

Abstract
Motivation: Clustering according to sequence–structure similarity has now become a generally accepted scheme for ncRNA annotation. Its application to complete genomic sequences as well as whole transcriptomes is therefore desirable but hindered by extremely high computational costs.
Results: We present a novel linear-time, alignment-free method for comparing and clustering RNAs according to sequence and structure. The approach scales to datasets of hundreds of thousands of sequences. The quality of the retrieved clusters has been benchmarked against known ncRNA datasets and is comparable to state-of-the-art sequence–structure methods although achieving speedups of several orders of magnitude. A selection of applications aiming at the detection of novel structural ncRNAs are presented. Exemplarily, we predicted local structural elements specific to lincRNAs likely functionally associating involved transcripts to vital processes of the human nervous system. In total, we predicted 349 local structural RNA elements.
Availability: The GraphClust pipeline is available on request.
Contact: backofen@informatik.uni-freiburg.de
Supplementary information: Supplementary data are available at Bioinformatics online.
Ranking models of transmembrane β-barrel proteins using Z-coordinate predictions
Authors: Hayat Sikander , Elofsson Arne 
Published: June 2012

Abstract
Motivation: Transmembrane β-barrels exist in the outer membrane of gram-negative bacteria as well as in chloroplast and mitochondria. They are often involved in transport processes and are promising antimicrobial drug targets. Structures of only a few β-barrel protein families are known. Therefore, a method that could automatically generate such models would be valuable. The symmetrical arrangement of the barrels suggests that an approach based on idealized geometries may be successful.
Results: Here, we present tobmodel; a method for generating 3D models of β-barrel transmembrane proteins. First, alternative topologies are obtained from the BOCTOPUS topology predictor. Thereafter, several 3D models are constructed by using different angles of the β-sheets. Finally, the best model is selected based on agreement with a novel predictor, ZPRED3, which predicts the distance from the center of the membrane for each residue, i.e. the Z-coordinate. The Z-coordinate prediction has an average error of 1.61 Å. Tobmodel predicts the correct topology for 75% of the proteins in the dataset which is a slight improvement over BOCTOPUS alone. More importantly, however, tobmodel provides a Cα template with an average RMSD of 7.24 Å from the native structure.
Availability: Tobmodel is freely available as a web server at: http://tobmodel.cbr.su.se/. The datasets used for training and evaluations are also available from this site.
Contact: arne@bioinfo.se
Neoproterozoic–Devonian stratigraphic evolution of the eastern Murzuq Basin, Libya: a tale of tilting in the central Sahara
Authors: Le Heron Daniel Paul , Meinhold Guido , Bergig Khalid A. 
Published: June 2012

AbstractThe Murzuq Basin is one of the most petroliferous basins of North Africa. Its remote eastern flank has been largely ignored since early reconnaissance work in the 1950s and 1960s. This article presents new stratigraphic and sedimentological data on the Neoproterozoic through Devonian succession from the Mourizidie and Dor el Gussa regions. The Neoproterozoic to Cambrian Mourizidie and Hasawnah formations in the eastern part of the Mourizidie region dip to the east and north‐east, resting directly on late Precambrian metasediments and granitoids. These strata record the initial progradation of sand‐dominated braidplain systems upon peneplained Precambrian basement. Rhyolite clasts in the Hasawnah Formation may record tectonically driven uplift and unroofing in the southern Tibesti Massif or tectonomagmatic rejuvenation to the south of this massif. In the western part of the Mourizidie region, Late Ordovician through Silurian strata (Mamuniyat and Tanezzuft–Akakus formations) directly overlie late Precambrian metasediments and granitoids, and dip at a low angle towards the west into the Murzuq Basin. Elsewhere at the eastern Murzuq Basin flank, in Dor el Gussa, Late Ordovician glaciogenic sediments rest with angular unconformity upon shallow marine sandstones of Cambrian–Ordovician age. This angular unconformity may also occur in the Mourizidie region and indicates widespread tectonism, either as a result of a Middle–Late Ordovician orogenic event, far‐field tectonism related to the opening of the Rheic Ocean along the northern margin of Gondwana or alternatively crustal depression associated with the growth of Late Ordovician ice sheets. Unconformity development was also probably associated with glacial incision. Following ice sheet retreat, isostatic rebound during deglaciation resulted in uplift of tens to hundreds of metres, locally removing all Cambrian and Ordovician formations. Rising sea levels in the Silurian led to deposition of the Tanezzuft Formation on Precambrian basement in the northwestern Mourizidie region.
Pilot study of rosiglitazone as an in vivo probe of paclitaxel exposure
Authors: Hertz Daniel L. , Walko Christine M. , Bridges Arlene S. , Hull J. Heyward , Herendeen Jill , Rollins Kristan , Watkins Paul B. , Dees E. Claire 
Published: June 2012

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Paclitaxel and rosiglitazone are primarily metabolized by CYP2C8 and their in vitro metabolism by human liver microsomes is correlated. Probe assays that quantify the in vivo activity of CYP enzymes which are important in drug metabolism have been developed for use in clinical pharmacology research. A probe of CYP2C8 that is easy to administer and interpret may be valuable for individualized dosing of paclitaxel.WHAT THIS STUDY ADDS• This pilot study demonstrates for the first time that there is an in vivo correlation between paclitaxel and rosiglitazone exposure. The finding, that a single rosiglitazone plasma concentration after oral dosing may explain significant variance in paclitaxel exposure, suggests that rosiglitazone may satisfy the requirements of a clinically useful in vivo probe. However, it is acknowledged that there is a need for further studies evaluating the use of rosiglitazone as a CYP2C8 probe and quantifying the relationship, in order to guide dosing of narrow therapeutic index drugs metabolized primarily by CYP2C8, such as paclitaxel.AIMS To evaluate the use of rosiglitazone and the erythromycin breath test (ERMBT), as probes of CYP2C8 and CYP3A4, respectively, to explain inter‐individual variability in paclitaxel exposure.METHODS The concentration of rosiglitazone at 3 h and ERMBT results were included in a regression model to explain the variability in paclitaxel exposure in 14 subjects.RESULTS Rosiglitazone concentration was significantly correlated with paclitaxel exposure (P= 0.018) while ERMBT had no predictive value (P= 0.47).CONCLUSIONS The correlation between the exposure of rosiglitazone and paclitaxel likely reflects mutual dependence on the activity of CYP2C8. Rosiglitazone or similar agents may have value as in vivo probes of CYP2C8 activity.
Peripheral quantitative computed tomography (pQCT) reveals alterations in the three‐dimensional bone structure in children with haemophilia
Authors: Ranta S. , Viljakainen H. , Mäkipernaa A. , Mäkitie O. 
Published: June 2012

SummaryChildren with haemophilia are at risk of suboptimal bone mass accrual and low bone mineral density (BMD). We recently demonstrated that although BMD in Finnish children with haemophilia was within the normal range, their whole body BMD was significantly lower and hypercalciuria more prevalent than in controls. This study sought to determine the bone structure and strength in physically active children with haemophilia. To investigate the underlying mechanisms in this group, we conducted a case–control study to assess bone structure and strength by peripheral quantitative computed tomography (pQCT) at the radius. The study group comprised 29 patients (mean age 12.2 years) and 46 age‐matched controls. Children with haemophilia had decreased total BMD Z‐score at the distal radius (P ≤ 0.001), but increased cortical bone density at the proximal radius (P ≤ 0.001). Total bone area at the proximal radius was significantly lower in children with haemophilia (P = 0.002), whereas there were no differences in cortical bone area or in polar Strength‐Strain Index, a parameter of bone strength, between the patients and controls. Patients with mild to moderate haemophilia and on‐demand treatment had inferior bone strength compared to those with moderate to severe haemophilia and prophylaxis. Our findings suggest altered skeletal development in patients with haemophilia in the radius, resulting in smaller bone size and higher cortical bone density. Importantly, bone strength at the radius appears equal to healthy children. Prophylactic treatment seems to have a beneficial effect on bone health.
The development of a patient partnership programme and its impact on quality improvements in a comprehensive haemophilia care service
Authors: Grogan A. , Coughlan M. , O' Mahony B. , McKee G. 
Published: June 2012

SummaryIt has long been advocated that patient input in service quality development is essential. We have developed a model of quality evaluation and improvement within a comprehensive haemophilia service, and describe the issues and improvements that resulted from the process. The project utilized an action research methodology. Seven patients were recruited from the haemophilia service for the initial focus groups. The main themes initially explored were as follows: patient experience of the outpatient, inpatient and weekend services and provision of information. The focus group data were analysed using basic content analysis. The main themes the initial focus group identified were the need to optimize the annual review, emergency care and inpatient facilities. Following this, the haemophilia care team worked on improving these issues. At the second focus group the patients contributed at a higher level – patient participation. Patients assisted in addressing outstanding issues such as ID alert card content and the algorithm of care for emergency services. Finally, a patient panel was developed and the relationship became one of direct negotiation and partnership with the haemophilia team to address issues within the service. The expectations and needs of patients attending the haemophilia comprehensive care service are complex. The process of including patients as partners at the highest level of patient involvement evolved and proved an effective method of service evaluation and development, facilitating lateral decision‐making, not only improving care directly, but also improving the user experience.
SMARCB1/INI1 inactivation in renal medullary carcinoma
Authors: Calderaro Julien , Moroch Julien , Pierron Gaelle , Pedeutour Florence , Grison Camille , Maillé Pascale , Soyeux Pascale , de la Taille Alexandre , Couturier Jérome , Vieillefond Annick , Rousselet Marie Christine , Delattre Olivier , Allory Yves 
Published: June 2012

Calderaro J, Moroch J, Pierron G, Pedeutour F, Grison C, Maillé P, Soyeux P, de la Taille A, Couturier J, Vieillefond A, Rousselet M C, Delattre O & Allory Y  (2012) Histopathology 61, 428–435
SMARCB1/INI1 inactivation in renal medullary carcinomaAims:  Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle‐cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC. The aim of our study was to investigate if such loss of expression is specific for RMC. SMARCB1/INI1 genetic alterations and cyclin D1 expression were also studied.Methods and results:  Using immunochemistry, neoplastic cells showed complete loss of SMARCB1/INI1 expression in all six cases of RMC but in only one of 22 cases of CDC. In two RMC cases investigated, comparative genomic hybridization demonstrated complete loss of one SMARCB1/INI1 allele, with no other genomic imbalances, and no mutations were found on the remaining allele. Cyclin D1 was expressed in all RMCs, suggesting that SMARCB1/INI1 inactivation may result in increased cyclin D1 transcription.Conclusions:  The specific SMARCB1/INI1 inactivation observed in RMCs suggests that RMC and CDC are different entities.
Image and statistical analysis of melanocytic histology
Authors: Miedema Jayson , Marron James Stephen , Niethammer Marc , Borland David , Woosley John , Coposky Jason , Wei Susan , Reisner Howard , Thomas Nancy E 
Published: June 2012

Miedema J, Marron J S, Niethammer M, Borland D, Woosley J, Coposky J, Wei S, Reisner H & Thomas N E  (2012) Histopathology 61, 436–444Image and statistical analysis of melanocytic histologyAims:  We applied digital image analysis techniques to study selected types of melanocytic lesions.Methods and results:  We used advanced digital image analysis to compare melanocytic lesions as follows: (i) melanoma to nevi, (ii) melanoma subtypes to nevi, (iii) severely dysplastic nevi to other nevi and (iv) melanoma to severely dysplastic nevi. We were successful in differentiating melanoma from nevi [receiver operating characteristic area (ROC) 0.95] using image‐derived features, among which those related to nuclear size and shape and distance between nuclei were most important. Dividing melanoma into subtypes, even greater separation was obtained (ROC area 0.98 for superficial spreading melanoma; 0.95 for lentigo maligna melanoma; and 0.99 for unclassified). Severely dysplastic nevi were best differentiated from conventional and mildly dysplastic nevi by differences in cellular staining qualities (ROC area 0.84). We found that melanomas were separated from severely dysplastic nevi by features related to shape and staining qualities (ROC area 0.95). All comparisons were statistically significant (P < 0.0001).Conclusions:  We offer a unique perspective into the evaluation of melanocytic lesions and demonstrate a technological application with increasing prevalence, and with potential use as an adjunct to traditional diagnosis in the future.
LPS induces IL‐8 expression through TLR4, MyD88, NF‐kappaB and MAPK pathways in human dental pulp stem cells
Authors: He W. , Qu T. , Yu Q. , Wang Z. , Lv H. , Zhang J. , Zhao X. , Wang P. 
Published: June 2012

AbstractAimTo evaluate the effects of lipopolysaccharide (LPS) on interleukin‐8 (IL‐8) and related intracellular signalling pathways in human dental pulp stem cells (hDPSCs).MethodologyHuman pulp tissues were isolated from human impacted third molars, and the hDPSCs were cultured and characterized. The effects of LPS on IL‐8 and Toll‐like receptor 4 (TLR4) gene expression in hDPSCs were investigated using real‐time quantitative RT‐PCR and ELISA. Whether TLR4/MyD88/NF‐кB was involved in the LPS‐induced up‐regulation of IL‐8 in hDPSCs was determined using transient transfection, luciferase assay and ELISA. The involvement of MAPKs in the LPS‐induced up‐regulation of IL‐8 in hDPSCs was investigated via transient transfection, luciferase assay, ELISA and western blot. The data were statistically analysed using Student's t‐test or one‐way anova followed by the Student–Neumann–Keuls test.ResultsCells exposed to LPS not only displayed an enhanced expression of TLR4 but also showed an elevated IL‐8 gene expression; exposure to LPS also resulted in the induction of IL‐8 gene transcription via promoter activation. The LPS‐induced IL‐8 promoter activation was inhibited through dominant‐negative mutations in TLR4 and MyD88, but not in TLR2. The LPS‐induced IL‐8 protein release was attenuated through the administration of TLR4‐neutralizing antibody or MyD88 inhibitory peptide and a dominant‐negative mutation in IκBα. In contrast, IL‐8 protein release was enhanced through the expression of NF‐κB p65. Treatment with PDTC, TPCK or Bay117082 effectively antagonized LPS‐induced IL‐8 protein release. Moreover, both the promoter activity and the LPS‐induced release of IL‐8 were diminished upon the administration of U0126 and SB203580, but not SP600125. Moreover, the exposure to LPS activated ERK1/2 and p38 MAPK phosphorylation in cells.ConclusionsThis study reports the LPS‐mediated transcriptional and post‐translational up‐regulation of IL‐8, which is a process that also involves TLR4, MyD88, NF‐κB and MAPK.
Functional, biochemical and pasting properties of extruded bean (Phaseolus vulgaris) cotyledons
Authors: Lopes Lilian Cristian Mattos , de Aleluia Batista Karla , Fernandes Kátia Flávia , de Andrade Cardoso Santiago Raquel 
Published: June 2012

SummaryResponse surface methodology was used to investigate the effects of extrusion conditions – namely moisture content (12.3–23.7 g 100 g−1) and temperature (150–178 °C) – on physicochemical, antinutritional compounds, functional and pasting properties of extruded bean cotyledons. Results indicated that extrusion cooking did not change the chemical composition of bean flours, but completely eliminated the activity of the trypsin and α‐amylase inhibitors and haemagglutinins. The extrusion significantly improved starch and protein digestibility, water solubility and absorption of bean cotyledon. In addition, extrusion conditions significantly affected pasting properties, resulting in extrudate flours with different peaks and final viscosity values. From the results obtained in this work, it is possible to design a product with specific physicochemical, functional and nutritional properties using the appropriate moisture and temperature during extrusion.
Purification and characterisation of two acidic peroxidase isoforms from the sheaths of bamboo shoots
Authors: Hsu Shou‐Kuo , Chung Yun‐Chin , Chang Chen‐Tien , Sung Hsien‐Yi 
Published: June 2012

SummaryThree isoforms of peroxidase (POD) were isolated from the sheaths of bamboo shoots by chromatofocusing on Polybuffer exchanger PBE 94. POD‐A was partially purified, and POD‐B and POD‐C were purified and characterised. POD‐A was a basic peroxidase, whereas POD‐B and POD‐C were acidic peroxidases with different isoelectric points. Using o‐phenylenediamine (OPD) as a hydrogen‐donor, the optimum temperatures for function of POD‐B and POD‐C were 55 and 45–55 °C, respectively, while both had the same optimum pH of 4.5. Both isoforms were stable between 30 and 60 °C and between pH 4.5 and 10. The activities of the POD isoforms towards hydrogen‐donors were both pH and concentration dependent. Under optimal conditions, POD‐B and POD‐C catalysed the oxidation of catechol, pyrogallol, and OPD at higher rates than guaiacol, o‐dianisidine and 2, 2’‐azino‐bis‐ (3‐ethylbenzothiazoline‐6‐sulphonic acid). Both isoforms were almost completely inhibited by chemical modification reagent diethyl pyrocarbonate (4.5 mM).