bluuebunny/crossref_metadata_2025_split huggingface dataset:
An approach for developing simple generic models for ecological risk assessments of fish populations
Authors: Hanson Niklas , Stark John D 
Published: July 2011

Abstract
It has been argued that current approaches for ecological risk assessment (ERA) do not provide value relevance for risk managers and that the uncertainty in the predictions is large. One important reason for this is that current approaches are based on individual-level endpoints, but the environmental protection goals are defined on the population level. Population models may be useful tools to link the individual to the population and thus increase value relevance and reduce uncertainty. However, this requires that simple models and guidance on how to use them are made available for risk assessors. In the present study, an approach for developing simple generic models for the ERA of fish populations is presented. Fish have high ecological and economic value and are frequently used in ERA. It is, therefore, highly desirable to develop better methods for ERA of fish populations. The models were based on five types of life histories, and they were set up to be useful in a number of different management scenarios based on different environmental protection goals. A decision framework was set up for three levels of models (continuous, time limited, and varying exposure) and three levels of environmental protection. Data from previously published studies were tested for two of the environmental protection levels. The models provided maximum acceptable concentrations (MAC) that fell between the MACs of traditional ERA based on acute or chronic data, respectively. Environ. Toxicol. Chem. 2011;30:2372–2383. © 2011 SETAC
Toxicokinetic-toxicodynamic modeling of quantal and graded sublethal endpoints: A brief discussion of concepts
Authors: Ashauer Roman , Agatz Annika , Albert Carlo , Ducrot Virginie , Galic Nika , Hendriks Jan , Jager Tjalling , Kretschmann Andreas , O'Connor Isabel , Rubach Mascha Nadine , Nyman Anna-Maija , Schmitt Walter , Stadnicka Julita , van den Brink Paul J , Preuss Thomas G 
Published: July 2011

Abstract
We report on the advantages and problems of using toxicokinetic-toxicodynamic (TKTD) models for the analysis, understanding, and simulation of sublethal effects. Only a few toxicodynamic approaches for sublethal effects are available. These differ in their effect mechanism and emphasis on linkages between endpoints. We discuss how the distinction between quantal and graded endpoints and the type of linkage between endpoints can guide model design and selection. Strengths and limitations of two main approaches and possible ways forward are outlined. Environ. Toxicol. Chem. 2011;30:2519–2524. © 2011 SETAC
Probucol Suppresses Enterocytic Accumulation of Amyloid‐β Induced by Saturated Fat and Cholesterol Feeding
Authors: Pallebage‐Gamarallage Menuka M. , Galloway Susan , Takechi Ryusuke , Dhaliwal Satvinder , Mamo John C. L. 
Published: July 2011

AbstractAmyloid‐β (Aβ) is secreted from lipogenic organs such as intestine and liver as an apolipoprotein of nascent triacylglycerol rich lipoproteins. Chronically elevated plasma Aβ may compromise cerebrovascular integrity and exacerbate amyloidosis—a hallmark feature of Alzheimer's disease (AD). Probucol is a hypocholesterolemic agent that reduces amyloid burden in transgenic amyloid mice, but the mechanisms for this effect are presently unclear. In this study, the effect of Probucol on intestinal lipoprotein‐Aβ homeostasis was explored. Wild‐type mice were fed a control low‐fat diet and enterocytic Aβ was stimulated by high‐fat (HF) diet enriched in 10% (w/w) saturated fat and 1% (w/w) cholesterol for the duration of 1 month. Mice treated with Probucol had the drug incorporated into the chow at 1% (w/w). Quantitative immunofluorescence was utilised to determine intestinal apolipoprotein B (apo B) and Aβ abundance. We found apo B in both the perinuclear region of the enterocytes and the lacteals in all groups. However, HF feeding and Probucol treatment increased secretion of apo B into the lacteals without any change in net villi abundance. On the other hand, HF‐induced enterocytic perinuclear Aβ was significantly attenuated by Probucol. No significant changes in Aβ were observed within the lacteals. The findings of this study support the notion that Probucol suppresses dietary fat induced stimulation of Aβ biosynthesis and attenuate availability of apo B lipoprotein‐Aβ for secretion.
The radiation burden from increasingly complex endovascular aortic aneurysm repair
Authors: Thakor Avnesh S. , Winterbottom Andrew , Mercuri Mathew , Cousins Claire , Gaunt Michael E. 
Published: July 2011

Abstract

Objectives
With increasing experience, endovascular aortic aneurysm repair (EVAR) has been extended to patients with less suitable aorto-iliac anatomy in an attempt to reduce peri-operative mortality. However, more complex EVAR procedures may take longer and can result in higher rates of complications, additional interventional procedures and more frequent radiological imaging, which may offset some of the benefit. This study determined the radiation burden for standard EVAR, as determined by the EVAR-1 trial criteria, and more complex EVAR.

Methods
A total of 123 elective patients aged >60, with aneurysms >5.5 cm who received a bifurcated stent-graft were allocated into a group based on whether or not they fulfilled strict EVAR-1 trial criteria. The mean radiation dose was calculated for each group, together with the additional radiation burden from routine pre- and post-EVAR CT examinations and pre-EVAR iliac artery embolisation.

Results
Patients not meeting the EVAR-1 trial criteria had significantly longer fluoroscopic screening times and higher radiation doses. The radiation burden in all patients was higher following exposure from routine CT examinations and following pre-EVAR iliac artery embolisation.

Conclusion
Whilst the radiation from standard EVAR is acceptable, more complicated and challenging EVARs, accompanied with additional radiological investigations and procedures, can significantly increase the radiation burden.
Dynamics and mechanism of cyclobutane pyrimidine dimer repair by DNA photolyase
Authors: Liu Zheyun , Tan Chuang , Guo Xunmin , Kao Ya-Ting , Li Jiang , Wang Lijuan , Sancar Aziz , Zhong Dongping 
Published: July 2011

Photolyase uses blue light to restore the major ultraviolet (UV)-induced DNA damage, the cyclobutane pyrimidine dimer (CPD), to two normal bases by splitting the cyclobutane ring. Our earlier studies showed that the overall repair is completed in 700 ps through a cyclic electron-transfer radical mechanism. However, the two fundamental processes, electron-tunneling pathways and cyclobutane ring splitting, were not resolved. Here, we use ultrafast UV absorption spectroscopy to show that the CPD splits in two sequential steps within 90 ps and the electron tunnels between the cofactor and substrate through a remarkable route with an intervening adenine. Site-directed mutagenesis reveals that the active-site residues are critical to achieving high repair efficiency, a unique electrostatic environment to optimize the redox potentials and local flexibility, and thus balance all catalytic reactions to maximize enzyme activity. These key findings reveal the complete spatio-temporal molecular picture of CPD repair by photolyase and elucidate the underlying molecular mechanism of the enzyme’s high repair efficiency.
Gee Fu: a sequence version and web-services database tool for genomic assembly, genome feature and NGS data
Authors: Ramirez-Gonzalez Ricardo , Caccamo Mario , MacLean Daniel 
Published: July 2011

Abstract
Summary: Scientists now use high-throughput sequencing technologies and short-read assembly methods to create draft genome assemblies in just days. Tools and pipelines like the assembler, and the workflow management environments make it easy for a non-specialist to implement complicated pipelines to produce genome assemblies and annotations very quickly. Such accessibility results in a proliferation of assemblies and associated files, often for many organisms. These assemblies get used as a working reference by lots of different workers, from a bioinformatician doing gene prediction or a bench scientist designing primers for PCR. Here we describe Gee Fu, a database tool for genomic assembly and feature data, including next-generation sequence alignments. Gee Fu is an instance of a Ruby-On-Rails web application on a feature database that provides web and console interfaces for input, visualization of feature data via AnnoJ, access to data through a web-service interface, an API for direct data access by Ruby scripts and access to feature data stored in BAM files. Gee Fu provides a platform for storing and sharing different versions of an assembly and associated features that can be accessed and updated by bench biologists and bioinformaticians in ways that are easy and useful for each.
Availability: http://tinyurl.com/geefu
Contact: dan.maclean@tsl.ac.uk
Bayesian prediction of tissue-regulated splicing using RNA sequence and cellular context
Authors: Xiong Hui Yuan , Barash Yoseph , Frey Brendan J. 
Published: July 2011

Abstract
Motivation: Alternative splicing is a major contributor to cellular diversity in mammalian tissues and relates to many human diseases. An important goal in understanding this phenomenon is to infer a ‘splicing code’ that predicts how splicing is regulated in different cell types by features derived from RNA, DNA and epigenetic modifiers.
Methods: We formulate the assembly of a splicing code as a problem of statistical inference and introduce a Bayesian method that uses an adaptively selected number of hidden variables to combine subgroups of features into a network, allows different tissues to share feature subgroups and uses a Gibbs sampler to hedge predictions and ascertain the statistical significance of identified features.
Results: Using data for 3665 cassette exons, 1014 RNA features and 4 tissue types derived from 27 mouse tissues (http://genes.toronto.edu/wasp), we benchmarked several methods. Our method outperforms all others, and achieves relative improvements of 52% in splicing code quality and up to 22% in classification error, compared with the state of the art. Novel combinations of regulatory features and novel combinations of tissues that share feature subgroups were identified using our method.
Contact: frey@psi.toronto.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
ContEst: estimating cross-contamination of human samples in next-generation sequencing data
Authors: Cibulskis Kristian , McKenna Aaron , Fennell Tim , Banks Eric , DePristo Mark , Getz Gad 
Published: July 2011

Abstract
Summary: Here, we present ContEst, a tool for estimating the level of cross-individual contamination in next-generation sequencing data. We demonstrate the accuracy of ContEst across a range of contamination levels, sources and read depths using sequencing data mixed in silico at known concentrations. We applied our tool to published cancer sequencing datasets and report their estimated contamination levels.
Availability and Implementation: ContEst is a GATK module, and distributed under a BSD style license at http://www.broadinstitute.org/cancer/cga/contest
Contact: kcibul@broadinstitute.org; gadgetz@broadinstitute.org
Supplementary information: Supplementary data is available at Bioinformatics online.
Penalized regression elucidates aberration hotspots mediating subtype-specific transcriptional responses in breast cancer
Authors: Yuan Yinyin , Rueda Oscar M. , Curtis Christina , Markowetz Florian 
Published: July 2011

AbstractMotivation: Copy number alterations (CNAs) associated with cancer are known to contribute to genomic instability and gene deregulation. Integrating CNAs with gene expression helps to elucidate the mechanisms by which CNAs act and to identify the transcriptional downstream targets of CNAs. Such analyses can help to sort functional driver events from the many accompanying passenger alterations. However, the way CNAs affect gene expression can vary in different cellular contexts, for example between different subtypes of the same cancer. Thus, it is important to develop computational approaches capable of inferring differential connectivity of regulatory networks in different cellular contexts.Results: We propose a statistical deregulation model that integrates copy number and expression data of different disease subtypes to jointly model common and differential regulatory relationships. Our model not only identifies CNAs driving gene expression changes, but at the same time also predicts differences in regulation that distinguish one cancer subtype from the other. We implement our model in a penalized regression framework and demonstrate in a simulation study the feasibility and accuracy of our approach. Subsequently, we show that this model can identify both known and novel aspects of cross-talk between the ER and NOTCH pathways in ER-negative-specific deregulations, when compared with ER-positive breast cancer. This flexible model can be applied on other modalities such as methylation or microRNA and expression to disentangle cancer signaling pathways.Availability: The Bioconductor-compliant R package DANCE is available from www.markowetzlab.org/software/Contact: yinyin.yuan@cancer.org.uk; florian.markowetz@cancer.org.uk
Exposure to sennoside–digoxin interaction and risk of digoxin toxicity: a population‐based nested case–control study†
Authors: Wang Meng‐Ting , Li I‐Hsun , Lee Wan‐Ju , Huang Tien‐Yu , Leu Hsin‐Bang , Chan Agnes L.F. 
Published: July 2011

AimsDigoxin is an important medication for heart failure (HF) patients and sennosides are widely used to treat constipation. Recently, safety concerns have been raised about a possible interaction between sennosides and digoxin, an issue that has not been studied empirically. This study therefore aimed to evaluate whether exposure to sennoside–digoxin interaction is associated with an increased risk of digoxin toxicity.Methods and resultsThis was a population‐based nested case–control study that analysed data obtained from the Taiwan National Health Insurance Research Database between 1 January 2001 and 31 December 2004. All HF patients treated with digoxin for the first time were included as the study cohort. Of these, cases were identified as subjects hospitalized for digoxin toxicity (International Classification of Diseases, Ninth Revision, Clinical Modification,ICD‐9‐CM 972.1), and matched to randomly selected controls. Use of sennosides was compared between the two groups. Odds ratios (ORs) were employed to quantify the risk associated with exposure to sennoside–digoxin interaction by conditional logistic regression. The study cohort comprised 222 527 HF patients, of whom 524 were identified as cases and 2 502 as matched controls. Use of sennosides during the 14 days preceding the index date was found to be associated with a 1.61‐fold increased risk of digoxin toxicity [95% confidence interval (CI) = 1.15, 2.25]. Additionally, a greater risk was observed for sennosides prescribed at an average daily dose ≥24 mg (adjusted OR = 1.93; 95% CI = 1.27, 2.94).ConclusionThe combined use of sennosides and digoxin was found to be associated with a modest increased risk of digoxin toxicity in HF patients.
Norepinephrine Infusion into Nucleus Basalis Elicits Microarousal in Desflurane-anesthetized Rats
Authors: Pillay Siveshigan , Vizuete Jeannette A. , McCallum J. Bruce , Hudetz Anthony G. 
Published: July 2011

Background
The nucleus basalis of Meynert of the basal forebrain has been implicated in the regulation of the state of consciousness across normal sleep-wake cycles. Its role in the modulation of general anesthesia was investigated.

Methods
Rats were chronically implanted with bilateral infusion cannulae in the nucleus basalis of Meynert and epidural electrodes to record the electroencephalogram in frontal and visual cortices. Animals were anesthetized with desflurane at a concentration required for the loss of righting reflex (4.6 ± 0.5%). Norepinephrine (17.8 nmol) or artificial cerebrospinal fluid was infused at 0.2 μl/min (1 μl total). Behavioral response to infusion was measured by scoring the orofacial, limb, and head movements, and postural changes.

Results
Behavioral responses were higher after norepinephrine (2.1 ± 1) than artificial cerebrospinal fluid (0.63 ± 0.8) infusion (P < 0.01, Student t test). Responses were brief (1-2 min), repetitive, and more frequent after norepinephrine infusion (P < 0.0001, chi-square test). Electroencephalogram delta power decreased after norepinephrine in frontal (70 ± 7%) but not in visual cortex (P < 0.05, Student t test). Simultaneously, electroencephalogram cross-approximate entropy between frontal and visual cortices increased from 3.17 ± 0.56 to 3.85 ± 0.29 after norepinephrine infusion (P < 0.01, Student t test). Behavioral activation was predictable by the decrease in frontal delta power (logistic regression, P < 0.05).

Conclusions
Norepinephrine infusion into the nucleus basalis of Meynert can modulate anesthetic depth presumably by ascending activation of the cortex. The transient nature of the responses suggests a similarity with microarousals normally observed during natural sleep, and may imply a mechanism for transient awareness under light anesthesia.
Arabidopsis MPK3 and MPK6 Play Different Roles in Basal and Oligogalacturonide- or Flagellin-Induced Resistance against Botrytis cinerea
Authors: Galletti Roberta , Ferrari Simone , De Lorenzo Giulia 
Published: July 2011

Abstract
Mitogen-activated protein kinases (MAPKs) are fundamental components of the plant innate immune system. MPK3 and MPK6 are Arabidopsis (Arabidopsis thaliana) MAPKs activated by pathogens and elicitors such as oligogalacturonides (OGs), which function as damage-associated molecular patterns, and flg22, a well-known microbe-associated molecular pattern. However, the specific contribution of MPK3 and MPK6 to the regulation of elicitor-induced defense responses is not completely defined. In this work we have investigated the roles played by these MAPKs in elicitor-induced resistance against the fungal pathogen Botrytis cinerea. Analysis of single mapk mutants revealed that lack of MPK3 increases basal susceptibility to the fungus, as previously reported, but does not significantly affect elicitor-induced resistance. Instead, lack of MPK6 has no effect on basal resistance but suppresses OG- and flg22-induced resistance to B. cinerea. Overexpression of the AP2C1 phosphatase leads to impaired OG- and flg22-induced phosphorylation of both MPK3 and MPK6, and to phenotypes that recapitulate those of the single mapk mutants. These data indicate that OG- and flg22-induced defense responses effective against B. cinerea are mainly dependent on MAPKs, with a greater contribution of MPK6.
Zinc Finger Protein5Is Required for the Control of Trichome Initiation by Acting Upstream ofZinc Finger Protein8in Arabidopsis
Authors: Zhou Zhongjing , An Lijun , Sun Lili , Zhu Shuijin , Xi Wanyan , Broun Pierre , Yu Hao , Gan Yinbo 
Published: July 2011

AbstractArabidopsis (Arabidopsis thaliana) trichome development is a model system for studying cell development, cell differentiation, and the cell cycle. Our previous studies have shown that the GLABROUS INFLORESCENCE STEMS (GIS) family genes, GIS, GIS2, and ZINC FINGER PROTEIN8 (ZFP8), control shoot maturation and epidermal cell fate by integrating gibberellins (GAs) and cytokinin signaling in Arabidopsis. Here, we show that a new C2H2 zinc finger protein, ZFP5, plays an important role in controlling trichome cell development through GA signaling. Overexpression of ZFP5 results in the formation of ectopic trichomes on carpels and other inflorescence organs. zfp5 loss-of-function mutants exhibit a reduced number of trichomes on sepals, cauline leaves, paraclades, and main inflorescence stems in comparison with wild-type plants. More importantly, it is found that ZFP5 mediates the regulation of trichome initiation by GAs. These results are consistent with ZFP5 expression patterns and the regional influence of GA on trichome initiation. The molecular analyses suggest that ZFP5 functions upstream of GIS, GIS2, ZFP8, and the key trichome initiation regulators GLABROUS1 (GL1) and GL3. Using a steroid-inducible activation of ZFP5 and chromatin immunoprecipitation experiments, we further demonstrate that ZFP8 is the direct target of ZFP5 in controlling epidermal cell differentiation.
Linkages and technology spillovers in the presence of foreign firms
Authors: Samirana Pattnayak Sanja , Thangavelu Shandre M. 
Published: July 2011

PurposeThis paper aims to examine production linkage and technology spillovers due to the presence of foreign firms in the Indian pharmaceutical industry.Design/methodology/approachThis study employs the semi‐parametric estimation method suggested by Olley and Pakes to control for unobserved firm heterogeneity that accounts for the endogeneity of input selection with respect to productivity.FindingsThe results suggest that R&D activities of foreign firms lead to positive technology spillover to local firms. However, we also found negative linkage from the activities of foreign firms. The negative linkage could be explained by the large reverse engineering activities that occur on existing drugs in the Indian pharmaceutical industry, where the enclave activities of foreign firms might be a preemptive strategy to reduce the flow of technologies to downstream local firms and to protect their firm‐specific (product) technology.Originality/valueThe results provide support for strong institutional arrangements such as giving protection for Intellectual Property Rights, which might be important for attracting and creating linkages with activities of foreign firms in the host country.
Fragmentation in the automobile manufacturing industry: evidence from Portugal
Authors: Faustino Horácio C. , Carlos Leitão Nuno 
Published: July 2011

PurposeThis paper aims to examine the determinants of vertical intra‐industry trade (VIIT) in the automobile components industry between Portugal and the European Union 27 (EU‐27) and the BRIC countries (Brazil, Russia, India and China) during the period 1995‐2006.Design/methodology/approachThe paper formulates some theoretical hypotheses that may explain the fragmentation of the production in the automobile industry. These hypotheses are tested using a dynamic panel data analysis. The estimates are more reliable because the instruments used control for the potential endogeneity of the explanatory variables.FindingsThe results indicate that VIIT is a positive function of the difference in per‐capita GDP between Portugal and its trading partners, confirming the Linder hypothesis. Moreover, there is statistical evidence that geographical distance influences negatively this type of VIIT between Portugal and the EU‐27 only. The results do not confirm the hypothesis that there is a positive correlation between differences in endowments and VIIT in the automobile components sector.Originality/valueThis paper confirms some relevant theoretical hypotheses on the causes of the fragmentation/outsourcing. The good results obtained with the Arellano and Bond GMM system estimator suggest that the building of dynamic theoretical models will be of interest to academic researchers in fragmentation theory.