bluuebunny/crossref_metadata_2025_split huggingface dataset:
Classification of mislabelled microarrays using robust sparse logistic regression
Authors: Bootkrajang Jakramate , Kabán Ata 
Published: February 2013

Abstract
Motivation: Previous studies reported that labelling errors are not uncommon in microarray datasets. In such cases, the training set may become misleading, and the ability of classifiers to make reliable inferences from the data is compromised. Yet, few methods are currently available in the bioinformatics literature to deal with this problem. The few existing methods focus on data cleansing alone, without reference to classification, and their performance crucially depends on some tuning parameters.
Results: In this article, we develop a new method to detect mislabelled arrays simultaneously with learning a sparse logistic regression classifier. Our method may be seen as a label-noise robust extension of the well-known and successful Bayesian logistic regression classifier. To account for possible mislabelling, we formulate a label-flipping process as part of the classifier. The regularization parameter is automatically set using Bayesian regularization, which not only saves the computation time that cross-validation would take, but also eliminates any unwanted effects of label noise when setting the regularization parameter. Extensive experiments with both synthetic data and real microarray datasets demonstrate that our approach is able to counter the bad effects of labelling errors in terms of predictive performance, it is effective at identifying marker genes and simultaneously it detects mislabelled arrays to high accuracy.
Availability: The code is available from http://cs.bham.ac.uk/∼jxb008.
Contact: J.Bootkrajang@cs.bham.ac.uk
Supplementary information: Supplementary data are available at Bioinformatics online.
eMZed: an open source framework in Python for rapid and interactive development of LC/MS data analysis workflows
Authors: Kiefer Patrick , Schmitt Uwe , Vorholt Julia A. 
Published: February 2013

Abstract
Summary: The Python-based, open-source eMZed framework was developed for mass spectrometry (MS) users to create tailored workflows for liquid chromatography (LC)/MS data analysis. The goal was to establish a unique framework with comprehensive basic functionalities that are easy to apply and allow for the extension and modification of the framework in a straightforward manner. eMZed supports the iterative development and prototyping of individual evaluation strategies by providing a computing environment and tools for inspecting and modifying underlying LC/MS data. The framework specifically addresses non-expert programmers, as it requires only basic knowledge of Python and relies largely on existing successful open-source software, e.g. OpenMS.
Availability: The framework eMZed and its documentation are freely available at http://emzed.biol.ethz.ch/. eMZed is published under the GPL 3.0 license, and an online discussion group is available at https://groups.google.com/group/emzed-users.
Contact: kiefer@micro.biol.ethz.ch
Supplementary information: Supplementary data are available at Bioinformatics online.
Operating Room Fires
Authors: Mehta Sonya P. , Bhananker Sanjay M. , Posner Karen L. , Domino Karen B. 
Published: February 2013

Abstract

Background:
To assess patterns of injury and liability associated with operating room (OR) fires, closed malpractice claims in the American Society of Anesthesiologists Closed Claims Database since 1985 were reviewed.

Methods:
All claims related to fires in the OR were compared with nonfire-related surgical anesthesia claims. An analysis of fire-related claims was performed to identify causative factors.

Results:
There were 103 OR fire claims (1.9% of 5,297 surgical claims). Electrocautery was the ignition source in 90% of fire claims. OR fire claims more frequently involved older outpatients compared with other surgical anesthesia claims (P < 0.01). Payments to patients were more often made in fire claims (P < 0.01), but payment amounts were lower (median $120,166) compared to nonfire surgical claims (median $250,000, P < 0.01). Electrocautery-induced fires (n = 93) increased over time (P < 0.01) to 4.4% claims between 2000 and 2009. Most (85%) electrocautery fires occurred during head, neck, or upper chest procedures (high-fire-risk procedures). Oxygen served as the oxidizer in 95% of electrocautery-induced OR fires (84% with open delivery system). Most electrocautery-induced fires (n = 75, 81%) occurred during monitored anesthesia care. Oxygen was administered via an open delivery system in all high-risk procedures during monitored anesthesia care. In contrast, alcohol-containing prep solutions and volatile compounds were present in only 15% of OR fires during monitored anesthesia care.

Conclusions:
Electrocautery-induced fires during monitored anesthesia care were the most common cause of OR fires claims. Recognition of the fire triad (oxidizer, fuel, and ignition source), particularly the critical role of supplemental oxygen by an open delivery system during use of the electrocautery, is crucial to prevent OR fires. Continuing education and communication among OR personnel along with fire prevention protocols in high-fire-risk procedures may reduce the occurrence of OR fires.
Propofol and Thiopental Suppress Amyloid Fibril Formation and GM1 Ganglioside Expression through the γ-Aminobutyric Acid A Receptor
Authors: Yamamoto Naoki , Arima Hajime , Sugiura Takeshi , Hirate Hiroyuki , Taniura Hideo , Suzuki Kenji , Sobue Kazuya 
Published: February 2013

Abstract

Background:
The incidence of Alzheimer disease may increase after surgical interventions. Amyloid β-protein (Aβ) fibrillogenesis, which is closely related to Alzheimer disease, is reportedly accelerated by exposure to anesthetics. However, the effects of GM1 ganglioside (GM1) on Αβ fibrillogenesis have not yet been reported. The current study was designed to examine whether the anesthetics propofol and thiopental are associated with Αβ assembly and GM1 expression on the neuronal cell surface.

Methods:
PC12N cells and cultured neuronal cells were treated with propofol or thiopental, and GM1 expression in treated and untreated cells was determined by the specific binding of horseradish peroxidase-conjugated cholera toxin subunit B (n = 5). The effects of an inhibitor of the γ-aminobutyric acid A receptor was also examined (n= 5). In addition, the effects of the anesthetics on GM1 liposome-induced Αβ assembly were investigated (n = 5). Finally, the neurotoxicity of the assembled Αβ fibrils was studied by the lactate dehydrogenase release assay (n = 6).

Results:
Propofol (31.2±4.7%) and thiopental (34.6±10.5%) decreased GM1 expression on the cell surface through the γ-aminobutyric acid A receptor. The anesthetics inhibited Αβ fibril formation from soluble Αβ in cultured neurons. Moreover, propofol and thiopental suppressed GM1-induced fibril formation in a cell-free system (propofol, 75.8±1.9%; thiopental, 83.6±1.9%) and reduced the neurotoxicity of a mixture containing Aβ and GM1 liposomes (propofol, 35.3±16.4%; thiopental, 21.3±11.6%).

Conclusions:
Propofol and thiopental have direct and indirect inhibitory effects on Αβ fibrillogenesis.
The Pseudomonas syringae Effector HopQ1 Promotes Bacterial Virulence and Interacts with Tomato 14-3-3 Proteins in a Phosphorylation-Dependent Manner
Authors: Li Wei , Yadeta Koste A. , Elmore James Mitch , Coaker Gitta 
Published: February 2013

Abstract
A key virulence strategy of bacterial pathogens is the delivery of multiple pathogen effector proteins into host cells during infection. The Hrp outer protein Q (HopQ1) effector from Pseudomonas syringae pv tomato (Pto) strain DC3000 is conserved across multiple bacterial plant pathogens. Here, we investigated the virulence function and host targets of HopQ1 in tomato (Solanum lycopersicum). Transgenic tomato lines expressing dexamethasone-inducible HopQ1 exhibited enhanced disease susceptibility to virulent Pto DC3000, the Pto ƊhrcC mutant, and decreased expression of a pathogen-associated molecular pattern-triggered marker gene after bacterial inoculation. HopQ1-interacting proteins were coimmunoprecipitated and identified by mass spectrometry. HopQ1 can associate with multiple tomato 14-3-3 proteins, including TFT1 and TFT5. HopQ1 is phosphorylated in tomato, and four phosphorylated peptides were identified by mass spectrometry. HopQ1 possesses a conserved mode I 14-3-3 binding motif whose serine-51 residue is phosphorylated in tomato and regulates its association with TFT1 and TFT5. Confocal microscopy and fractionation reveal that HopQ1 exhibits nucleocytoplasmic localization, while HopQ1 dephosphorylation mimics exhibit more pronounced nuclear localization. HopQ1 delivered from Pto DC3000 was found to promote bacterial virulence in the tomato genotype Rio Grande 76R. However, the HopQ1(S51A) mutant delivered from Pto DC3000 was unable to promote pathogen virulence. Taken together, our data demonstrate that HopQ1 enhances bacterial virulence and associates with tomato 14-3-3 proteins in a phosphorylation-dependent manner that influences HopQ1’s subcellular localization and virulence-promoting activities in planta.
Production of a High-Efficiency TILLING Population through Polyploidization
Authors: Tsai Helen , Missirian Victor , Ngo Kathie J. , Tran Robert K. , Chan Simon R. , Sundaresan Venkatesan , Comai Luca 
Published: February 2013

AbstractTargeting Induced Local Lesions in Genomes (TILLING) provides a nontransgenic method for reverse genetics that is widely applicable, even in species where other functional resources are missing or expensive to build. The efficiency of TILLING, however, is greatly facilitated by high mutation density. Species vary in the number of mutations induced by comparable mutagenic treatments, suggesting that genetic background may affect the response. Allopolyploid species have often yielded higher mutation density than diploids. To examine the effect of ploidy, we autotetraploidized the Arabidopsis (Arabidopsis thaliana) ecotype Columbia, whose diploid has been used for TILLING extensively, and mutagenized it with 50 mm ethylmethane sulfonate. While the same treatment sterilized diploid Columbia, the tetraploid M1 plants produced good seed. To determine the mutation density, we searched 528 individuals for induced mutations in 15 genes for which few or no knockout alleles were previously available. We constructed tridimensional pools from the genomic DNA of M2 plants, amplified target DNA, and subjected them to Illumina sequencing. The results were analyzed with an improved version of the mutation detection software CAMBa that accepts any pooling scheme. This small population provided a rich resource with approximately 25 mutations per queried 1.5-kb fragment, including on average four severe missense and 1.3 truncation mutations. The overall mutation density of 19.4 mutations Mb–1 is 4 times that achieved in the corresponding diploid accession, indicating that genomic redundancy engenders tolerance to high mutation density. Polyploidization of diploids will allow the production of small populations, such as less than 2,000, that provide allelic series from knockout to mild loss of function for virtually all genes.
The Regulatory Properties of Rubisco Activase Differ among Species and Affect Photosynthetic Induction during Light Transitions
Authors: Carmo-Silva A. Elizabete , Salvucci Michael E. 
Published: February 2013

Abstract
Rubisco’s catalytic chaperone, Rubisco activase (Rca), uses the energy from ATP hydrolysis to restore catalytic competence to Rubisco. In Arabidopsis (Arabidopsis thaliana), inhibition of Rca activity by ADP is fine tuned by redox regulation of the α-isoform. To elucidate the mechanism for Rca regulation in species containing only the redox-insensitive β-isoform, the response of activity to ADP was characterized for different Rca forms. When assayed in leaf extracts, Rubisco activation was significantly inhibited by physiological ratios of ADP to ATP in species containing both α-Rca and β-Rca (Arabidopsis and camelina [Camelina sativa]) or just the β-Rca (tobacco [Nicotiana tabacum]). However, Rca activity was insensitive to ADP inhibition in an Arabidopsis transformant, rwt43, which expresses only Arabidopsis β-Rca, although not in a transformant of Arabidopsis that expresses a tobacco-like β-Rca. ATP hydrolysis by recombinant Arabidopsis β-Rca was much less sensitive to inhibition by ADP than recombinant tobacco β-Rca. Mutation of 17 amino acids in the tobacco β-Rca to the corresponding Arabidopsis residues reduced ADP sensitivity. In planta, Rubisco deactivated at low irradiance except in the Arabidopsis rwt43 transformant containing an ADP-insensitive Rca. Induction of CO2 assimilation after transition from low to high irradiance was much more rapid in the rwt43 transformant compared with plants containing ADP-sensitive Rca forms. The faster rate of photosynthetic induction and a greater enhancement of growth under a fluctuating light regime by the rwt43 transformant compared with wild-type Arabidopsis suggests that manipulation of Rca regulation might provide a strategy for enhancing photosynthetic performance in certain variable light environments.
Altered Lipid Composition and Enhanced Nutritional Value of Arabidopsis Leaves following Introduction of an Algal Diacylglycerol Acyltransferase 2
Authors: Sanjaya  , Miller Rachel , Durrett Timothy P. , Kosma Dylan K. , Lydic Todd A. , Muthan Bagyalakshmi , Koo Abraham J.K. , Bukhman Yury V. , Reid Gavin E. , Howe Gregg A. , Ohlrogge John , Benning Christoph 
Published: February 2013

Abstract
Enhancement of acyl-CoA–dependent triacylglycerol (TAG) synthesis in vegetative tissues is widely discussed as a potential avenue to increase the energy density of crops. Here, we report the identification and characterization of Chlamydomonas reinhardtii diacylglycerol acyltransferase type two (DGTT) enzymes and use DGTT2 to alter acyl carbon partitioning in plant vegetative tissues. This enzyme can accept a broad range of acyl-CoA substrates, allowing us to interrogate different acyl pools in transgenic plants. Expression of DGTT2 in Arabidopsis thaliana increased leaf TAG content, with some molecular species containing very-long-chain fatty acids. The acyl compositions of sphingolipids and surface waxes were altered, and cutin was decreased. The increased carbon partitioning into TAGs in the leaves of DGTT2-expressing lines had little effect on transcripts of the sphingolipid/wax/cutin pathway, suggesting that the supply of acyl groups for the assembly of these lipids is not transcriptionally adjusted. Caterpillars of the generalist herbivore Spodoptera exigua reared on transgenic plants gained more weight. Thus, the nutritional value and/or energy density of the transgenic lines was increased by ectopic expression of DGTT2 and acyl groups were diverted from different pools into TAGs, demonstrating the interconnectivity of acyl metabolism in leaves.
Coordination of the Vernalization Response through a VIN3 and FLC Gene Family Regulatory Network in Arabidopsis
Authors: Kim Dong-Hwan , Sung Sibum 
Published: February 2013

Abstract
Vernalization is an environmentally induced epigenetic switch in which winter cold triggers epigenetic silencing of floral repressors and thus provides competence to flower in spring. Vernalization triggers the recruitment of chromatin-modifying complexes to a clade of flowering repressors that are epigenetically silenced via chromatin modifications. In Arabidopsis thaliana, VERNALIZATION INSENSITIVE3 (VIN3) and its related plant homeodomain finger proteins act together with Polycomb Repressive Complex 2 to increase repressive histone marks at floral repressor loci, including FLOWERING LOCUS C (FLC) and its related genes, by vernalization. Here, we show that VIN3 family of proteins nonredundantly functions to repress different subsets of the FLC gene family during the course of vernalization. Each VIN3 family protein binds to modified histone peptides in vitro and directly associates with specific sets of FLC gene family chromatins in vivo to mediate epigenetic silencing. In addition, members of the FLC gene family are also differentially regulated during the course of vernalization to mediate proper vernalization response. Our results show that these two gene families cooperated during the course of evolution to ensure proper vernalization response through epigenetic changes.
The learning curve for laparoscopic extended pelvic lymphadenectomy for intermediate‐ and high‐risk prostate cancer: implications for compliance with existing guidelines
Authors: Eden Christopher G. , Zacharakis Evangelos , Bott Simon 
Published: February 2013

Objective
To investigate the learning curve for performing extended pelvic lymphadenectomy (ePLND) during laparoscopic radical prostatectomy (LRP) in patients with intermediate‐ and high‐risk prostate cancer.
Patients and methods
In all, 500 patients underwent ePLND for intermediate‐ or high‐risk prostate cancer by one surgeon during a 48‐month period. A transperitoneal laparoscopic approach was used in all patients to allow adequate access to the internal iliac vessels.
The variables chosen as being the most important discriminators of the quality of ePLND were operating time, complication rate and lymph node (LN) yield.
The learning curves for ePLND were calculated using the cumulative sum and cumulative average methods and the number of procedures performed until attainment of acceptable failure rates (competence levels) was calculated. LN parameters were compared with the results from the preceding 311 cases where limited PLND was undertaken.
Results
The median (range) preoperative PSA level was 8.0(1–62.5) ng/mL and biopsy Gleason score was 7(6–10). In all, 64% of patients had intermediate‐risk and 36% had high‐risk prostate cancer. There were no intraoperative blood transfusions and no conversions to open surgery. The median (range) blood loss was 200(10–1400) mL and the postoperative transfusion rate was 1.6%.
The operating time fell at a steady rate of 2.7% after the 15th case and plateaued after 130 patients. At competence levels of 5% and 10%, the learning curve for all complications ended after 346 and 136 patients, respectively.
At a 5% competence level the learning curve for PLND‐specific complications was 40 cases and there was no learning curve at a 10% competence level.
The overall complication rate was 7.2% of which almost half (47%) were deemed to be PLND‐specific. The cumulative average of the LN counts plateaued after 150 procedures. Furthermore, the median LN count after ePLND was more than double that of the authors' historical standard PLND controls (14 vs 6, P < 0.001) and increased with experience up to the end of the series (9 to 20).
The likelihood of LN involvement (LNI) correlated with biopsy and pathological Gleason grade, clinical and pathological stage and d'Amico risk group.
Conclusions
This study suggests a learning curve of ≈130 cases for operating time, 136 cases for all complications, 40 cases for PLND‐specific complications and 150 cases for LN yield.
The risk of LNI for patients with intermediate‐ and high‐risk prostate cancer was 8.4% and 19.4%, respectively, which suggests that a significant proportion would benefit from ePLND. It also shows that ePLND can be safely incorporated into LRP, and therefore also into robot‐assisted RP, in a high‐volume setting.
Catalase gene C‐262T polymorphism: Importance in ulcerative colitis
Authors: Khodayari Siamak , Salehi Zivar , Fakhrieh Asl Saba , Aminian Keyvan , Mirzaei Gisomi Nadia , Torabi Dalivandan Saeideh 
Published: February 2013

AbstractBackground and AimReactive oxygen species (ROS) are by‐products of the cellular metabolism and have important roles in the normal physiology of the cell. However, when ROS production exceeds the antioxidant capacity, a state known as oxidative stress, damage to cellular macromolecules emerges. A crucial role in counteracting ROS is played by the enzyme catalase. A common polymorphism in the catalase (CAT) promoter region (C‐262T) alters the expression as well as blood catalase levels, and leads to a number of human diseases. Ulcerative colitis (UC) is an inflammatory condition of the large bowel that is known to be influenced by oxidative stress. In this study, we aimed to evaluate the association of CAT C‐262T polymorphism on the risk of UC.MethodsSamples were collected from 60 patients diagnosed with UC and 78 control subjects, and genotyped by allele‐specific polymerase chain reaction.ResultsWe found that CAT C‐262T genotype frequencies were significantly different between cases and controls (P = 0.002). Individuals carrying the −262C/T genotype had a greater risk for UC compared with C/C genotype (odds ratio, 4.88; 95% confidence interval, 1.73–13.75, P = 0.002).ConclusionsThis study indicates that CAT C‐262T polymorphism may be associated with UC, and that the −262C/T genotype may be a risk factor for the disease. Further studies are needed to confirm the results.
Stimulation of Naïve Monocytes and PBMCs with Coagulation Proteases Results in Thrombin‐Mediated and PAR‐1‐Dependent Cytokine Release and Cell Proliferation in PBMCs Only
Authors: Nieuwenhuizen L. , Falkenburg W. J. J. , Schutgens R. E. G. , Roosendaal G. , van Veghel K. , Biesma D. H. , Lafeber F. P. J. G. 
Published: February 2013

AbstractProtease‐activated receptors (PARs) are stimulated by proteolytic cleavage of their extracellular domain. Coagulation proteases, such as FVIIa, the binary TF‐FVIIa complex, free FXa, the ternary TF‐FVIIa‐FXa complex and thrombin, are able to stimulate PARs. Whereas the role of PARs on platelets is well known, their function in naïve monocytes and peripheral blood mononuclear cells (PBMCs) is largely unknown. This is of interest because PAR‐mediated interactions of coagulation proteases with monocytes and PBMCs in diseases with an increased activation of coagulation may promote inflammation. To evaluate PAR‐mediated inflammatory reactions in naïve monocytes and PBMCs stimulated with coagulation proteases. For this, PAR expression at protein and RNA level on naïve monocytes and PBMCs was evaluated with flow cytometry and RT‐PCR. In addition, cytokine release (IL‐1β, IL‐6, IL‐8, IL‐10, TNF‐α) in stimulated naïve and PBMC cell cultures was determined. In this study, it is demonstrated that naïve monocytes express all four PARs at the mRNA level, and PAR‐1, ‐3 and ‐4 at the protein level. Stimulation of naïve monocytes with coagulation proteases did not result in alterations in PAR expression or in the induction of inflammation involved cytokines like interleukin‐1β (IL‐1β), interleukin‐6 (IL‐6), interleukin‐8, interleukin‐10 or tumour necrosis factor‐α. In contrast, stimulation of PBMCs with coagulation proteases resulted in thrombin‐mediated induction of IL‐1β and IL‐6 cytokine production and PBMC cell proliferation in a PAR‐1‐dependent manner. These data demonstrate that naïve monocytes are not triggered by coagulation proteases, whereas thrombin is able to elicit pro‐inflammatory events in a PAR‐1‐dependent manner in PBMCs.