bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual channel rank-based intensity weighting for quantitative co-localization of microscopy images
Authors: Singan Vasanth R , Jones Thouis R , Curran Kathleen M , Simpson Jeremy C 
Published: November 2011

Abstract

Background
Accurate quantitative co-localization is a key parameter in the context of understanding the spatial co-ordination of molecules and therefore their function in cells. Existing co-localization algorithms consider either the presence of co-occurring pixels or correlations of intensity in regions of interest. Depending on the image source, and the algorithm selected, the co-localization coefficients determined can be highly variable, and often inaccurate. Furthermore, this choice of whether co-occurrence or correlation is the best approach for quantifying co-localization remains controversial.

Results
We have developed a novel algorithm to quantify co-localization that improves on and addresses the major shortcomings of existing co-localization measures. This algorithm uses a non-parametric ranking of pixel intensities in each channel, and the difference in ranks of co-localizing pixel positions in the two channels is used to weight the coefficient. This weighting is applied to co-occurring pixels thereby efficiently combining both co-occurrence and correlation. Tests with synthetic data sets show that the algorithm is sensitive to both co-occurrence and correlation at varying levels of intensity. Analysis of biological data sets demonstrate that this new algorithm offers high sensitivity, and that it is capable of detecting subtle changes in co-localization, exemplified by studies on a well characterized cargo protein that moves through the secretory pathway of cells.

Conclusions
This algorithm provides a novel way to efficiently combine co-occurrence and correlation components in biological images, thereby generating an accurate measure of co-localization. This approach of rank weighting of intensities also eliminates the need for manual thresholding of the image, which is often a cause of error in co-localization quantification. We envisage that this tool will facilitate the quantitative analysis of a wide range of biological data sets, including high resolution confocal images, live cell time-lapse recordings, and high-throughput screening data sets.
Lost in folding space? Comparing four variants of the thermodynamic model for RNA secondary structure prediction
Authors: Janssen Stefan , Schudoma Christian , Steger Gerhard , Giegerich Robert 
Published: November 2011

Abstract

Background
Many bioinformatics tools for RNA secondary structure analysis are based on a thermodynamic model of RNA folding. They predict a single, "optimal" structure by free energy minimization, they enumerate near-optimal structures, they compute base pair probabilities and dot plots, representative structures of different abstract shapes, or Boltzmann probabilities of structures and shapes. Although all programs refer to the same physical model, they implement it with considerable variation for different tasks, and little is known about the effects of heuristic assumptions and model simplifications used by the programs on the outcome of the analysis.

Results
We extract four different models of the thermodynamic folding space which underlie the programs RNAFOLD, RNASHAPES, and RNASUBOPT. Their differences lie within the details of the energy model and the granularity of the folding space. We implement probabilistic shape analysis for all models, and introduce the shape probability shift as a robust measure of model similarity. Using four data sets derived from experimentally solved structures, we provide a quantitative evaluation of the model differences.

Conclusions
We find that search space granularity affects the computed shape probabilities less than the over- or underapproximation of free energy by a simplified energy model. Still, the approximations perform similar enough to implementations of the full model to justify their continued use in settings where computational constraints call for simpler algorithms. On the side, we observe that the rarely used level 2 shapes, which predict the complete arrangement of helices, multiloops, internal loops and bulges, include the "true" shape in a rather small number of predicted high probability shapes. This calls for an investigation of new strategies to extract high probability members from the (very large) level 2 shape space of an RNA sequence. We provide implementations of all four models, written in a declarative style that makes them easy to be modified. Based on our study, future work on thermodynamic RNA folding may make a choice of model based on our empirical data. It can take our implementations as a starting point for further program development.
Tumor-specific usage of alternative transcription start sites in colorectal cancer identified by genome-wide exon array analysis
Authors: Thorsen Kasper , Schepeler Troels , Øster Bodil , Rasmussen Mads H , Vang Søren , Wang Kai , Hansen Kristian Q , Lamy Philippe , Pedersen Jakob Skou , Eller Asger , Mansilla Francisco , Laurila Kirsti , Wiuf Carsten , Laurberg Søren , Dyrskjøt Lars , Ørntoft Torben F , Andersen Claus L 
Published: November 2011

Abstract

Background
Approximately half of all human genes use alternative transcription start sites (TSSs) to control mRNA levels and broaden the transcriptional output in healthy tissues. Aberrant expression patterns promoting carcinogenesis, however, may arise from alternative promoter usage.

Results
By profiling 108 colorectal samples using exon arrays, we identified nine genes (TCF12, OSBPL1A, TRAK1, ANK3, CHEK1, UGP2, LMO7, ACSL5, and SCIN) showing tumor-specific alternative TSS usage in both adenoma and cancer samples relative to normal mucosa. Analysis of independent exon array data sets corroborated these findings. Additionally, we confirmed the observed patterns for selected mRNAs using quantitative real-time reverse-transcription PCR. Interestingly, for some of the genes, the tumor-specific TSS usage was not restricted to colorectal cancer. A comprehensive survey of the nine genes in lung, bladder, liver, prostate, gastric, and brain cancer revealed significantly altered mRNA isoform ratios for CHEK1, OSBPL1A, and TCF12 in a subset of these cancer types.
To identify the mechanism responsible for the shift in alternative TSS usage, we antagonized the Wnt-signaling pathway in DLD1 and Ls174T colorectal cancer cell lines, which remarkably led to a shift in the preferred TSS for both OSBPL1A and TRAK1. This indicated a regulatory role of the Wnt pathway in selecting TSS, possibly also involving TP53 and SOX9, as their transcription binding sites were enriched in the promoters of the tumor preferred isoforms together with their mRNA levels being increased in tumor samples.
Finally, to evaluate the prognostic impact of the altered TSS usage, immunohistochemistry was used to show deregulation of the total protein levels of both TCF12 and OSBPL1A, corresponding to the mRNA levels observed. Furthermore, the level of nuclear TCF12 had a significant correlation to progression free survival in a cohort of 248 stage II colorectal cancer samples.

Conclusions
Alternative TSS usage in colorectal adenoma and cancer samples has been shown for nine genes, and OSBPL1A and TRAK1 were found to be regulated in vitro by Wnt signaling. TCF12 protein expression was upregulated in cancer samples and correlated with progression free survival.
Prediction of RNA Polymerase II recruitment, elongation and stalling from histone modification data
Authors: Chen Yun , Jørgensen Mette , Kolde Raivo , Zhao Xiaobei , Parker Brian , Valen Eivind , Wen Jiayu , Sandelin Albin 
Published: November 2011

Abstract

Background
Initiation and elongation of RNA polymerase II (RNAPII) transcription is regulated by both DNA sequence and chromatin signals. Recent breakthroughs make it possible to measure the chromatin state and activity of core promoters genome-wide, but dedicated computational strategies are needed to progress from descriptive annotation of data to quantitative, predictive models.

Results
Here, we describe a computational framework which with high accuracy can predict the locations of core promoters, the amount of recruited RNAPII at the promoter, the amount of elongating RNAPII in the gene body, the mRNA production originating from the promoter and finally also the stalling characteristics of RNAPII by considering both quantitative and spatial features of histone modifications around the transcription start site (TSS).
As the model framework can also pinpoint the signals that are the most influential for prediction, it can be used to infer underlying regulatory biology. For example, we show that the H3K4 di- and tri- methylation signals are strongly predictive for promoter location while the acetylation marks H3K9 and H3K27 are highly important in estimating the promoter usage. All of these four marks are found to be necessary for recruitment of RNAPII but not sufficient for the elongation. We also show that the spatial distributions of histone marks are almost as predictive as the signal strength and that a set of histone marks immediately downstream of the TSS is highly predictive of RNAPII stalling.

Conclusions
In this study we introduce a general framework to accurately predict the level of RNAPII recruitment, elongation, stalling and mRNA expression from chromatin signals. The versatility of the method also makes it ideally suited to investigate other genomic data.
Identification of novel targets for breast cancer by exploring gene switches on a genome scale
Authors: Wu Ming , Liu Li , Chan Christina 
Published: November 2011

Abstract

Background
An important feature that emerges from analyzing gene regulatory networks is the "switch-like behavior" or "bistability", a dynamic feature of a particular gene to preferentially toggle between two steady-states. The state of gene switches plays pivotal roles in cell fate decision, but identifying switches has been difficult. Therefore a challenge confronting the field is to be able to systematically identify gene switches.

Results
We propose a top-down mining approach to exploring gene switches on a genome-scale level. Theoretical analysis, proof-of-concept examples, and experimental studies demonstrate the ability of our mining approach to identify bistable genes by sampling across a variety of different conditions. Applying the approach to human breast cancer data identified genes that show bimodality within the cancer samples, such as estrogen receptor (ER) and ERBB2, as well as genes that show bimodality between cancer and non-cancer samples, where tumor-associated calcium signal transducer 2 (TACSTD2) is uncovered. We further suggest a likely transcription factor that regulates TACSTD2.

Conclusions
Our mining approach demonstrates that one can capitalize on genome-wide expression profiling to capture dynamic properties of a complex network. To the best of our knowledge, this is the first attempt in applying mining approaches to explore gene switches on a genome-scale, and the identification of TACSTD2 demonstrates that single cell-level bistability can be predicted from microarray data. Experimental confirmation of the computational results suggest TACSTD2 could be a potential biomarker and attractive candidate for drug therapy against both ER+ and ER- subtypes of breast cancer, including the triple negative subtype.
Management of asthma in pregnant women by general practitioners: A cross sectional survey
Authors: Lim Angelina S , Stewart Kay , Abramson Michael J , George Johnson 
Published: November 2011

Abstract

Background
Poorly controlled asthma can lead to maternal and fetal complications. Despite the known risks of poorly controlled asthma during pregnancy and the need for stepping up therapy when appropriate, there are concerns that management is suboptimal in primary care.
Our objective was to investigate the management of asthma during pregnancy by general practitioners providing shared maternity care.

Methods
A pre-piloted, anonymous mail survey was sent to all general practitioners (n = 842) involved in shared maternity care at six maternity hospitals in Victoria, Australia. Respondents were asked about their perceived safety of individual asthma medications during pregnancy. Approach to asthma management during pregnancy was further explored using scenarios of pregnant women with stable and deteriorating asthma and poor medication adherence.

Results
Inhaled corticosteroids (ICS) were perceived to be the safest and were the preferred preventive medication in first trimester (74.1%), whilst leukotriene receptor antagonists were the least preferred (2.9%). A quarter (25.8%) of respondents would stop or decrease patients' ICS doses during pregnancy, even when their asthma was well controlled by current therapy. In addition, 12.1% of respondents were not sure how to manage deteriorating asthma during pregnancy and opted to refer to another health professional. Almost half the respondents (48.9%) reported encountering medication nonadherence during pregnancy.

Conclusion
A lack of confidence and/or knowledge among general practitioners in managing deteriorating asthma in pregnancy was observed despite a good understanding of the safety of asthma medications during pregnancy, compliance with evidence-based guidelines in the selection of preventive medications, and self reported good asthma knowledge.
Effects of whole-body vibration on postural control in elderly: a systematic review and meta-analysis
Authors: Rogan Slavko , Hilfiker Roger , Herren Kaspar , Radlinger Lorenz , de Bruin Eling D 
Published: November 2011

Abstract

Background
This systematic review was performed to summarize the current evidence for whole body vibration (WBV) interventions on postural control in elderly.

Methods
English and German language papers in Medline, PEDro, Cinahl and the Cochrane databases were searched. Two reviewers extracted data on patients' characteristics, type of WBV intervention and outcomes. Two independent reviewers rated the methodological quality of these studies. Data were pooled using random-effects meta-analysis.

Results
Fifteen papers reporting quantitative data were included. Results from 15 papers could be pooled for a meta-analysis. The studies involved 933 participants. In 7 studies the authors investigated the effects of vibration plates generating vertical sinusoidal vibrations (VS-WBV) and 7 papers described the use of side-alternating sinusoidal vibrations (SS-WBV). One study investigated both VS-WBV and SS-WBV.
Weak to moderate evidence of an overall effect as a result of VS-WBV and SS-WBV was observed for (a) static balance for post-intervention values with a standardized mean difference (SMD) -0.06, 95% CI -0.31 to 0.18 and for change values SMD -0.26, 95% CI -1.09 to 0.57, and (b) dynamic balance for post-intervention-values SMD -0.34, 95% CI -0.60 to -0.08. For functional balance (c) an overall outcome for post-intervention values with SMD of 0.34, 95% CI -0.19 to 0.87 was found.

Conclusions
The 15 studies reviewed were of moderate methodological quality. In summary, SS-WBV seems to have a beneficial effect on dynamic balance in elderly individuals. However, the current results should be interpreted with caution because of the observed heterogeneity of training parameters and statistical methods. Future studies are warranted to evaluate the effects of WBV on postural control in an elderly population.
A de novo complete BRCA1 gene deletion identified in a Spanish woman with early bilateral breast cancer
Authors: Garcia-Casado Zaida , Romero Ignacio , Fernandez-Serra Antonio , Rubio Luis , Llopis Francisco , Garcia Ana , Llombart Pilar , Lopez-Guerrero Jose A 
Published: November 2011

Abstract

Background
Germline mutations in either of the two tumor-suppressor genes, BRCA1 and BRCA2, account for a significant proportion of hereditary breast and ovarian cancer cases. Most of these mutations consist of deletions, insertions, nonsense mutations, and splice variants, however an increasing number of large genomic rearrangements have been identified in these genes.

Methods
We analysed BRCA1 and BRCA2 genes by direct sequencing and MLPA. We confirmed the results by an alternative MLPA kit and characterized the BRCA1 deletion by Array CGH.

Results
We describe the first case of a patient with no strong family history of the disease who developed early-onset bilateral breast cancer with a de novo complete BRCA1 gene deletion in the germinal line. The detected deletion started from the region surrounding the VAT1
locus to the beginning of NBR1 gene, including the RND2, ΨBRCA1, BRCA1 and NBR2 complete genes.

Conclusion
This finding supports the large genomic rearrangement screening of BRCA genes in young breast cancer patients without family history, as well as in hereditary breast and ovarian cancer families previously tested negative for other variations.
Polymorphisms of the endothelial nitric oxide synthase (NOS3) gene in preeclampsia: a candidate-gene association study
Authors: Zdoukopoulos Nikos , Doxani Chrysa , Messinis Ioannis E , Stefanidis Ioannis , Zintzaras Elias 
Published: November 2011

Abstract

Background
The endothelial nitric oxide synthase gene (NOS3) has been proposed as a candidate gene for preeclampsia. However, studies so far have produced conflicting results. This study examines the specific role of variants and haplotypes of the NOS3 gene in a population of Caucasian origin.

Methods
We examined the association of three common variants of the NOS3 gene (4b/a, T-786C and G894T) and their haplotypes in a case-control sample of 102 patients with preeclampsia and 176 women with a history of uncomplicated pregnancies. Genotyping for the NOS3 variants was performed and odds ratios and 95% confidence intervals were obtained to evaluate the association between NOS3 polymorphisms and preeclampsia.

Results
The single locus analysis for the three variants using various genetic models and a model-free approach revealed no significant association in relation to clinical status. The analysis of haplotypes also showed lack of significant association.

Conclusions
Given the limitations of the candidate-gene approach in investigating complex traits, the evidence of our study does not support the major contributory role of these common NOS3 variants in preeclampsia. Future larger studies may help in elucidating the genetics of preeclampsia further.
A cost-effectiveness analysis of a preventive exercise program for patients with advanced head and neck cancer treated with concomitant chemo-radiotherapy
Authors: Retèl Valesca P , van der Molen Lisette , Hilgers Frans JM , Rasch Coen RN , L'Ortye Annemiek AAMHJ , Steuten Lotte MG , van Harten Wim H 
Published: November 2011

AbstractBackgroundConcomitant chemo-radiotherapy (CCRT) has become an indispensable organ, but not always function preserving treatment modality for advanced head and neck cancer. To prevent/limit the functional side effects of CCRT, special exercise programs are increasingly explored. This study presents cost-effectiveness analyses of a preventive (swallowing) exercise program (PREP) compared to usual care (UC) from a health care perspective.MethodsA Markov decision model of PREP versus UC was developed for CCRT in advanced head and neck cancer. Main outcome variables were tube dependency at one-year and number of post-CCRT hospital admission days. Primary outcome was costs per quality adjusted life years (cost/QALY), with an incremental cost-effectiveness ratio (ICER) as outcome parameter. The Expected Value of Perfect Information (EVPI) was calculated to obtain the value of further research.ResultsPREP resulted in less tube dependency (3% and 25%, respectively), and in fewer hospital admission days than UC (3.2 and 4.5 days respectively). Total costs for UC amounted to €41,986 and for PREP to €42,271. Quality adjusted life years for UC amounted to 0.68 and for PREP to 0.77. Based on costs per QALY, PREP has a higher probability of being cost-effective as long as the willingness to pay threshold for 1 additional QALY is at least €3,200/QALY. At the prevailing threshold of €20,000/QALY the probability for PREP being cost-effective compared to UC was 83%. The EVPI demonstrated potential value in undertaking additional research to reduce the existing decision uncertainty.ConclusionsBased on current evidence, PREP for CCRT in advanced head and neck cancer has the higher probability of being cost-effective when compared to UC. Moreover, the majority of sensitivity analyses produced ICERs that are well below the prevailing willingness to pay threshold for an additional QALY (range from dominance till €45,906/QALY).
Hydration studies on the archaeal protein Sso7d using NMR measurements and MD simulations
Authors: Bernini Andrea , Spiga Ottavia , Consonni Roberto , Arosio Ivana , Fusi Paola , Cirri Simone , Guagliardi Annamaria , Niccolai Neri 
Published: November 2011

Abstract

Background
How proteins approach surrounding molecules is fundamental to our understanding of the specific interactions that occur at the surface of proteins. The enhanced surface accessibility of small molecules such as organic solvents and paramagnetic probes to protein binding sites has been observed; however, the molecular basis of this finding has not been fully established. Recently, it has been suggested that hydration dynamics play a predominant role in controlling the distribution of hot spots on surface of proteins.

Results
In the present study, the hydration of the archaeal multifunctional protein Sso7d from Solfolobus solfataricus was investigated using a combination of computational and experimental data derived from molecular dynamics simulations and ePHOGSY NMR spectroscopy.

Conclusions
We obtained a convergent protein hydration landscape that indicated how the shape and stability of the Sso7d hydration shell could modulate the function of the protein. The DNA binding domain overlaps with the protein region involved in chaperon activity and this domain is hydrated only in a very small central region. This localized hydration seems to favor intermolecular approaches from a large variety of ligands. Conversely, high water density was found in surface regions of the protein where the ATP binding site is located, suggesting that surface water molecules play a role in protecting the protein from unspecific interactions.