NERBio: using selected word conjunctions, term normalization, and global patterns to improve biomedical named entity recognition.

PubMed

Tsai, Richard Tzong-Han; Sung, Cheng-Lung; Dai, Hong-Jie; Hung, Hsieh-Chuan; Sung, Ting-Yi; Hsu, Wen-Lian

2006-12-18

Biomedical named entity recognition (Bio-NER) is a challenging problem because, in general, biomedical named entities of the same category (e.g., proteins and genes) do not follow one standard nomenclature. They have many irregularities and sometimes appear in ambiguous contexts. In recent years, machine-learning (ML) approaches have become increasingly common and now represent the cutting edge of Bio-NER technology. This paper addresses three problems faced by ML-based Bio-NER systems. First, most ML approaches usually employ singleton features that comprise one linguistic property (e.g., the current word is capitalized) and at least one class tag (e.g., B-protein, the beginning of a protein name). However, such features may be insufficient in cases where multiple properties must be considered. Adding conjunction features that contain multiple properties can be beneficial, but it would be infeasible to include all conjunction features in an NER model since memory resources are limited and some features are ineffective. To resolve the problem, we use a sequential forward search algorithm to select an effective set of features. Second, variations in the numerical parts of biomedical terms (e.g., "2" in the biomedical term IL2) cause data sparseness and generate many redundant features. In this case, we apply numerical normalization, which solves the problem by replacing all numerals in a term with one representative numeral to help classify named entities. Third, the assignment of NE tags does not depend solely on the target word's closest neighbors, but may depend on words outside the context window (e.g., a context window of five consists of the current word plus two preceding and two subsequent words). We use global patterns generated by the Smith-Waterman local alignment algorithm to identify such structures and modify the results of our ML-based tagger. This is called pattern-based post-processing. To develop our ML-based Bio-NER system, we employ conditional random fields, which have performed effectively in several well-known tasks, as our underlying ML model. Adding selected conjunction features, applying numerical normalization, and employing pattern-based post-processing improve the F-scores by 1.67%, 1.04%, and 0.57%, respectively. The combined increase of 3.28% yields a total score of 72.98%, which is better than the baseline system that only uses singleton features. We demonstrate the benefits of using the sequential forward search algorithm to select effective conjunction feature groups. In addition, we show that numerical normalization can effectively reduce the number of redundant and unseen features. Furthermore, the Smith-Waterman local alignment algorithm can help ML-based Bio-NER deal with difficult cases that need longer context windows.

Towards an Obesity-Cancer Knowledge Base: Biomedical Entity Identification and Relation Detection

PubMed Central

Lossio-Ventura, Juan Antonio; Hogan, William; Modave, François; Hicks, Amanda; Hanna, Josh; Guo, Yi; He, Zhe; Bian, Jiang

2017-01-01

Obesity is associated with increased risks of various types of cancer, as well as a wide range of other chronic diseases. On the other hand, access to health information activates patient participation, and improve their health outcomes. However, existing online information on obesity and its relationship to cancer is heterogeneous ranging from pre-clinical models and case studies to mere hypothesis-based scientific arguments. A formal knowledge representation (i.e., a semantic knowledge base) would help better organizing and delivering quality health information related to obesity and cancer that consumers need. Nevertheless, current ontologies describing obesity, cancer and related entities are not designed to guide automatic knowledge base construction from heterogeneous information sources. Thus, in this paper, we present methods for named-entity recognition (NER) to extract biomedical entities from scholarly articles and for detecting if two biomedical entities are related, with the long term goal of building a obesity-cancer knowledge base. We leverage both linguistic and statistical approaches in the NER task, which supersedes the state-of-the-art results. Further, based on statistical features extracted from the sentences, our method for relation detection obtains an accuracy of 99.3% and a f-measure of 0.993. PMID:28503356

BANNER: an executable survey of advances in biomedical named entity recognition.

PubMed

Leaman, Robert; Gonzalez, Graciela

2008-01-01

There has been an increasing amount of research on biomedical named entity recognition, the most basic text extraction problem, resulting in significant progress by different research teams around the world. This has created a need for a freely-available, open source system implementing the advances described in the literature. In this paper we present BANNER, an open-source, executable survey of advances in biomedical named entity recognition, intended to serve as a benchmark for the field. BANNER is implemented in Java as a machine-learning system based on conditional random fields and includes a wide survey of the best techniques recently described in the literature. It is designed to maximize domain independence by not employing brittle semantic features or rule-based processing steps, and achieves significantly better performance than existing baseline systems. It is therefore useful to developers as an extensible NER implementation, to researchers as a standard for comparing innovative techniques, and to biologists requiring the ability to find novel entities in large amounts of text.

Applying Suffix Rules to Organization Name Recognition

NASA Astrophysics Data System (ADS)

Inui, Takashi; Murakami, Koji; Hashimoto, Taiichi; Utsumi, Kazuo; Ishikawa, Masamichi

This paper presents a method for boosting the performance of the organization name recognition, which is a part of named entity recognition (NER). Although gazetteers (lists of the NEs) have been known as one of the effective features for supervised machine learning approaches on the NER task, the previous methods which have applied the gazetteers to the NER were very simple. The gazetteers have been used just for searching the exact matches between input text and NEs included in them. The proposed method generates regular expression rules from gazetteers, and, with these rules, it can realize a high-coverage searches based on looser matches between input text and NEs. To generate these rules, we focus on the two well-known characteristics of NE expressions; 1) most of NE expressions can be divided into two parts, class-reference part and instance-reference part, 2) for most of NE expressions the class-reference parts are located at the suffix position of them. A pattern mining algorithm runs on the set of NEs in the gazetteers, and some frequent word sequences from which NEs are constructed are found. Then, we employ only word sequences which have the class-reference part at the suffix position as suffix rules. Experimental results showed that our proposed method improved the performance of the organization name recognition, and achieved the 84.58 F-value for evaluation data.

Open-Source Data Collection Techniques for Weapons Transfer Information

DTIC Science & Technology

2012-03-01

IR Infrared ISO International Organization for Standardization ITAR International Traffic in Arms Regulations NER Named Entity Recognition NLP ...Control Protocol UAE United Arab Emirates URI Uniform Resource Identifier URL Uniform Resource Locator USSR Union of Soviet Socialist Republics UTF...KOREA, DEMOCRATIC PEOPLE’S REPUBLIC OF North Korea KOREA, REPUBLIC OF South Korea LIBYAN ARAB JAMAHIRIYA Libya RUSSIAN FEDERATION Russia Table 3

Developing a hybrid dictionary-based bio-entity recognition technique.

PubMed

Song, Min; Yu, Hwanjo; Han, Wook-Shin

2015-01-01

Bio-entity extraction is a pivotal component for information extraction from biomedical literature. The dictionary-based bio-entity extraction is the first generation of Named Entity Recognition (NER) techniques. This paper presents a hybrid dictionary-based bio-entity extraction technique. The approach expands the bio-entity dictionary by combining different data sources and improves the recall rate through the shortest path edit distance algorithm. In addition, the proposed technique adopts text mining techniques in the merging stage of similar entities such as Part of Speech (POS) expansion, stemming, and the exploitation of the contextual cues to further improve the performance. The experimental results show that the proposed technique achieves the best or at least equivalent performance among compared techniques, GENIA, MESH, UMLS, and combinations of these three resources in F-measure. The results imply that the performance of dictionary-based extraction techniques is largely influenced by information resources used to build the dictionary. In addition, the edit distance algorithm shows steady performance with three different dictionaries in precision whereas the context-only technique achieves a high-end performance with three difference dictionaries in recall.

Developing a hybrid dictionary-based bio-entity recognition technique

PubMed Central

2015-01-01

Background Bio-entity extraction is a pivotal component for information extraction from biomedical literature. The dictionary-based bio-entity extraction is the first generation of Named Entity Recognition (NER) techniques. Methods This paper presents a hybrid dictionary-based bio-entity extraction technique. The approach expands the bio-entity dictionary by combining different data sources and improves the recall rate through the shortest path edit distance algorithm. In addition, the proposed technique adopts text mining techniques in the merging stage of similar entities such as Part of Speech (POS) expansion, stemming, and the exploitation of the contextual cues to further improve the performance. Results The experimental results show that the proposed technique achieves the best or at least equivalent performance among compared techniques, GENIA, MESH, UMLS, and combinations of these three resources in F-measure. Conclusions The results imply that the performance of dictionary-based extraction techniques is largely influenced by information resources used to build the dictionary. In addition, the edit distance algorithm shows steady performance with three different dictionaries in precision whereas the context-only technique achieves a high-end performance with three difference dictionaries in recall. PMID:26043907

PathNER: a tool for systematic identification of biological pathway mentions in the literature

PubMed Central

2013-01-01

Background Biological pathways are central to many biomedical studies and are frequently discussed in the literature. Several curated databases have been established to collate the knowledge of molecular processes constituting pathways. Yet, there has been little focus on enabling systematic detection of pathway mentions in the literature. Results We developed a tool, named PathNER (Pathway Named Entity Recognition), for the systematic identification of pathway mentions in the literature. PathNER is based on soft dictionary matching and rules, with the dictionary generated from public pathway databases. The rules utilise general pathway-specific keywords, syntactic information and gene/protein mentions. Detection results from both components are merged. On a gold-standard corpus, PathNER achieved an F1-score of 84%. To illustrate its potential, we applied PathNER on a collection of articles related to Alzheimer's disease to identify associated pathways, highlighting cases that can complement an existing manually curated knowledgebase. Conclusions In contrast to existing text-mining efforts that target the automatic reconstruction of pathway details from molecular interactions mentioned in the literature, PathNER focuses on identifying specific named pathway mentions. These mentions can be used to support large-scale curation and pathway-related systems biology applications, as demonstrated in the example of Alzheimer's disease. PathNER is implemented in Java and made freely available online at http://sourceforge.net/projects/pathner/. PMID:24555844

A study of active learning methods for named entity recognition in clinical text.

PubMed

Chen, Yukun; Lasko, Thomas A; Mei, Qiaozhu; Denny, Joshua C; Xu, Hua

2015-12-01

Named entity recognition (NER), a sequential labeling task, is one of the fundamental tasks for building clinical natural language processing (NLP) systems. Machine learning (ML) based approaches can achieve good performance, but they often require large amounts of annotated samples, which are expensive to build due to the requirement of domain experts in annotation. Active learning (AL), a sample selection approach integrated with supervised ML, aims to minimize the annotation cost while maximizing the performance of ML-based models. In this study, our goal was to develop and evaluate both existing and new AL methods for a clinical NER task to identify concepts of medical problems, treatments, and lab tests from the clinical notes. Using the annotated NER corpus from the 2010 i2b2/VA NLP challenge that contained 349 clinical documents with 20,423 unique sentences, we simulated AL experiments using a number of existing and novel algorithms in three different categories including uncertainty-based, diversity-based, and baseline sampling strategies. They were compared with the passive learning that uses random sampling. Learning curves that plot performance of the NER model against the estimated annotation cost (based on number of sentences or words in the training set) were generated to evaluate different active learning and the passive learning methods and the area under the learning curve (ALC) score was computed. Based on the learning curves of F-measure vs. number of sentences, uncertainty sampling algorithms outperformed all other methods in ALC. Most diversity-based methods also performed better than random sampling in ALC. To achieve an F-measure of 0.80, the best method based on uncertainty sampling could save 66% annotations in sentences, as compared to random sampling. For the learning curves of F-measure vs. number of words, uncertainty sampling methods again outperformed all other methods in ALC. To achieve 0.80 in F-measure, in comparison to random sampling, the best uncertainty based method saved 42% annotations in words. But the best diversity based method reduced only 7% annotation effort. In the simulated setting, AL methods, particularly uncertainty-sampling based approaches, seemed to significantly save annotation cost for the clinical NER task. The actual benefit of active learning in clinical NER should be further evaluated in a real-time setting. Copyright © 2015 Elsevier Inc. All rights reserved.

Web services-based text-mining demonstrates broad impacts for interoperability and process simplification.

PubMed

Wiegers, Thomas C; Davis, Allan Peter; Mattingly, Carolyn J

2014-01-01

The Critical Assessment of Information Extraction systems in Biology (BioCreAtIvE) challenge evaluation tasks collectively represent a community-wide effort to evaluate a variety of text-mining and information extraction systems applied to the biological domain. The BioCreative IV Workshop included five independent subject areas, including Track 3, which focused on named-entity recognition (NER) for the Comparative Toxicogenomics Database (CTD; http://ctdbase.org). Previously, CTD had organized document ranking and NER-related tasks for the BioCreative Workshop 2012; a key finding of that effort was that interoperability and integration complexity were major impediments to the direct application of the systems to CTD's text-mining pipeline. This underscored a prevailing problem with software integration efforts. Major interoperability-related issues included lack of process modularity, operating system incompatibility, tool configuration complexity and lack of standardization of high-level inter-process communications. One approach to potentially mitigate interoperability and general integration issues is the use of Web services to abstract implementation details; rather than integrating NER tools directly, HTTP-based calls from CTD's asynchronous, batch-oriented text-mining pipeline could be made to remote NER Web services for recognition of specific biological terms using BioC (an emerging family of XML formats) for inter-process communications. To test this concept, participating groups developed Representational State Transfer /BioC-compliant Web services tailored to CTD's NER requirements. Participants were provided with a comprehensive set of training materials. CTD evaluated results obtained from the remote Web service-based URLs against a test data set of 510 manually curated scientific articles. Twelve groups participated in the challenge. Recall, precision, balanced F-scores and response times were calculated. Top balanced F-scores for gene, chemical and disease NER were 61, 74 and 51%, respectively. Response times ranged from fractions-of-a-second to over a minute per article. We present a description of the challenge and summary of results, demonstrating how curation groups can effectively use interoperable NER technologies to simplify text-mining pipeline implementation. Database URL: http://ctdbase.org/ © The Author(s) 2014. Published by Oxford University Press.

Web services-based text-mining demonstrates broad impacts for interoperability and process simplification

PubMed Central

Wiegers, Thomas C.; Davis, Allan Peter; Mattingly, Carolyn J.

2014-01-01

The Critical Assessment of Information Extraction systems in Biology (BioCreAtIvE) challenge evaluation tasks collectively represent a community-wide effort to evaluate a variety of text-mining and information extraction systems applied to the biological domain. The BioCreative IV Workshop included five independent subject areas, including Track 3, which focused on named-entity recognition (NER) for the Comparative Toxicogenomics Database (CTD; http://ctdbase.org). Previously, CTD had organized document ranking and NER-related tasks for the BioCreative Workshop 2012; a key finding of that effort was that interoperability and integration complexity were major impediments to the direct application of the systems to CTD's text-mining pipeline. This underscored a prevailing problem with software integration efforts. Major interoperability-related issues included lack of process modularity, operating system incompatibility, tool configuration complexity and lack of standardization of high-level inter-process communications. One approach to potentially mitigate interoperability and general integration issues is the use of Web services to abstract implementation details; rather than integrating NER tools directly, HTTP-based calls from CTD's asynchronous, batch-oriented text-mining pipeline could be made to remote NER Web services for recognition of specific biological terms using BioC (an emerging family of XML formats) for inter-process communications. To test this concept, participating groups developed Representational State Transfer /BioC-compliant Web services tailored to CTD's NER requirements. Participants were provided with a comprehensive set of training materials. CTD evaluated results obtained from the remote Web service-based URLs against a test data set of 510 manually curated scientific articles. Twelve groups participated in the challenge. Recall, precision, balanced F-scores and response times were calculated. Top balanced F-scores for gene, chemical and disease NER were 61, 74 and 51%, respectively. Response times ranged from fractions-of-a-second to over a minute per article. We present a description of the challenge and summary of results, demonstrating how curation groups can effectively use interoperable NER technologies to simplify text-mining pipeline implementation. Database URL: http://ctdbase.org/ PMID:24919658

Named Entity Recognition in Chinese Clinical Text Using Deep Neural Network.

PubMed

Wu, Yonghui; Jiang, Min; Lei, Jianbo; Xu, Hua

2015-01-01

Rapid growth in electronic health records (EHRs) use has led to an unprecedented expansion of available clinical data in electronic formats. However, much of the important healthcare information is locked in the narrative documents. Therefore Natural Language Processing (NLP) technologies, e.g., Named Entity Recognition that identifies boundaries and types of entities, has been extensively studied to unlock important clinical information in free text. In this study, we investigated a novel deep learning method to recognize clinical entities in Chinese clinical documents using the minimal feature engineering approach. We developed a deep neural network (DNN) to generate word embeddings from a large unlabeled corpus through unsupervised learning and another DNN for the NER task. The experiment results showed that the DNN with word embeddings trained from the large unlabeled corpus outperformed the state-of-the-art CRF's model in the minimal feature engineering setting, achieving the highest F1-score of 0.9280. Further analysis showed that word embeddings derived through unsupervised learning from large unlabeled corpus remarkably improved the DNN with randomized embedding, denoting the usefulness of unsupervised feature learning.

Recognizing chemicals in patents: a comparative analysis.

PubMed

Habibi, Maryam; Wiegandt, David Luis; Schmedding, Florian; Leser, Ulf

2016-01-01

Recently, methods for Chemical Named Entity Recognition (NER) have gained substantial interest, driven by the need for automatically analyzing todays ever growing collections of biomedical text. Chemical NER for patents is particularly essential due to the high economic importance of pharmaceutical findings. However, NER on patents has essentially been neglected by the research community for long, mostly because of the lack of enough annotated corpora. A recent international competition specifically targeted this task, but evaluated tools only on gold standard patent abstracts instead of full patents; furthermore, results from such competitions are often difficult to extrapolate to real-life settings due to the relatively high homogeneity of training and test data. Here, we evaluate the two state-of-the-art chemical NER tools, tmChem and ChemSpot, on four different annotated patent corpora, two of which consist of full texts. We study the overall performance of the tools, compare their results at the instance level, report on high-recall and high-precision ensembles, and perform cross-corpus and intra-corpus evaluations. Our findings indicate that full patents are considerably harder to analyze than patent abstracts and clearly confirm the common wisdom that using the same text genre (patent vs. scientific) and text type (abstract vs. full text) for training and testing is a pre-requisite for achieving high quality text mining results.

Challenges in clinical natural language processing for automated disorder normalization.

PubMed

Leaman, Robert; Khare, Ritu; Lu, Zhiyong

2015-10-01

Identifying key variables such as disorders within the clinical narratives in electronic health records has wide-ranging applications within clinical practice and biomedical research. Previous research has demonstrated reduced performance of disorder named entity recognition (NER) and normalization (or grounding) in clinical narratives than in biomedical publications. In this work, we aim to identify the cause for this performance difference and introduce general solutions. We use closure properties to compare the richness of the vocabulary in clinical narrative text to biomedical publications. We approach both disorder NER and normalization using machine learning methodologies. Our NER methodology is based on linear-chain conditional random fields with a rich feature approach, and we introduce several improvements to enhance the lexical knowledge of the NER system. Our normalization method - never previously applied to clinical data - uses pairwise learning to rank to automatically learn term variation directly from the training data. We find that while the size of the overall vocabulary is similar between clinical narrative and biomedical publications, clinical narrative uses a richer terminology to describe disorders than publications. We apply our system, DNorm-C, to locate disorder mentions and in the clinical narratives from the recent ShARe/CLEF eHealth Task. For NER (strict span-only), our system achieves precision=0.797, recall=0.713, f-score=0.753. For the normalization task (strict span+concept) it achieves precision=0.712, recall=0.637, f-score=0.672. The improvements described in this article increase the NER f-score by 0.039 and the normalization f-score by 0.036. We also describe a high recall version of the NER, which increases the normalization recall to as high as 0.744, albeit with reduced precision. We perform an error analysis, demonstrating that NER errors outnumber normalization errors by more than 4-to-1. Abbreviations and acronyms are found to be frequent causes of error, in addition to the mentions the annotators were not able to identify within the scope of the controlled vocabulary. Disorder mentions in text from clinical narratives use a rich vocabulary that results in high term variation, which we believe to be one of the primary causes of reduced performance in clinical narrative. We show that pairwise learning to rank offers high performance in this context, and introduce several lexical enhancements - generalizable to other clinical NER tasks - that improve the ability of the NER system to handle this variation. DNorm-C is a high performing, open source system for disorders in clinical text, and a promising step toward NER and normalization methods that are trainable to a wide variety of domains and entities. (DNorm-C is open source software, and is available with a trained model at the DNorm demonstration website: http://www.ncbi.nlm.nih.gov/CBBresearch/Lu/Demo/tmTools/#DNorm.). Published by Elsevier Inc.

Using Workflows to Explore and Optimise Named Entity Recognition for Chemistry

PubMed Central

Kolluru, BalaKrishna; Hawizy, Lezan; Murray-Rust, Peter; Tsujii, Junichi; Ananiadou, Sophia

2011-01-01

Chemistry text mining tools should be interoperable and adaptable regardless of system-level implementation, installation or even programming issues. We aim to abstract the functionality of these tools from the underlying implementation via reconfigurable workflows for automatically identifying chemical names. To achieve this, we refactored an established named entity recogniser (in the chemistry domain), OSCAR and studied the impact of each component on the net performance. We developed two reconfigurable workflows from OSCAR using an interoperable text mining framework, U-Compare. These workflows can be altered using the drag-&-drop mechanism of the graphical user interface of U-Compare. These workflows also provide a platform to study the relationship between text mining components such as tokenisation and named entity recognition (using maximum entropy Markov model (MEMM) and pattern recognition based classifiers). Results indicate that, for chemistry in particular, eliminating noise generated by tokenisation techniques lead to a slightly better performance than others, in terms of named entity recognition (NER) accuracy. Poor tokenisation translates into poorer input to the classifier components which in turn leads to an increase in Type I or Type II errors, thus, lowering the overall performance. On the Sciborg corpus, the workflow based system, which uses a new tokeniser whilst retaining the same MEMM component, increases the F-score from 82.35% to 84.44%. On the PubMed corpus, it recorded an F-score of 84.84% as against 84.23% by OSCAR. PMID:21633495

Using workflows to explore and optimise named entity recognition for chemistry.

PubMed

Kolluru, Balakrishna; Hawizy, Lezan; Murray-Rust, Peter; Tsujii, Junichi; Ananiadou, Sophia

2011-01-01

Chemistry text mining tools should be interoperable and adaptable regardless of system-level implementation, installation or even programming issues. We aim to abstract the functionality of these tools from the underlying implementation via reconfigurable workflows for automatically identifying chemical names. To achieve this, we refactored an established named entity recogniser (in the chemistry domain), OSCAR and studied the impact of each component on the net performance. We developed two reconfigurable workflows from OSCAR using an interoperable text mining framework, U-Compare. These workflows can be altered using the drag-&-drop mechanism of the graphical user interface of U-Compare. These workflows also provide a platform to study the relationship between text mining components such as tokenisation and named entity recognition (using maximum entropy Markov model (MEMM) and pattern recognition based classifiers). Results indicate that, for chemistry in particular, eliminating noise generated by tokenisation techniques lead to a slightly better performance than others, in terms of named entity recognition (NER) accuracy. Poor tokenisation translates into poorer input to the classifier components which in turn leads to an increase in Type I or Type II errors, thus, lowering the overall performance. On the Sciborg corpus, the workflow based system, which uses a new tokeniser whilst retaining the same MEMM component, increases the F-score from 82.35% to 84.44%. On the PubMed corpus, it recorded an F-score of 84.84% as against 84.23% by OSCAR.

A System for Identifying Named Entities in Biomedical Text: how Results From two Evaluations Reflect on Both the System and the Evaluations

PubMed Central

Dingare, Shipra; Nissim, Malvina; Finkel, Jenny; Grover, Claire

2005-01-01

We present a maximum entropy-based system for identifying named entities (NEs) in biomedical abstracts and present its performance in the only two biomedical named entity recognition (NER) comparative evaluations that have been held to date, namely BioCreative and Coling BioNLP. Our system obtained an exact match F-score of 83.2% in the BioCreative evaluation and 70.1% in the BioNLP evaluation. We discuss our system in detail, including its rich use of local features, attention to correct boundary identification, innovative use of external knowledge resources, including parsing and web searches, and rapid adaptation to new NE sets. We also discuss in depth problems with data annotation in the evaluations which caused the final performance to be lower than optimal. PMID:18629295

The CHEMDNER corpus of chemicals and drugs and its annotation principles.

PubMed

Krallinger, Martin; Rabal, Obdulia; Leitner, Florian; Vazquez, Miguel; Salgado, David; Lu, Zhiyong; Leaman, Robert; Lu, Yanan; Ji, Donghong; Lowe, Daniel M; Sayle, Roger A; Batista-Navarro, Riza Theresa; Rak, Rafal; Huber, Torsten; Rocktäschel, Tim; Matos, Sérgio; Campos, David; Tang, Buzhou; Xu, Hua; Munkhdalai, Tsendsuren; Ryu, Keun Ho; Ramanan, S V; Nathan, Senthil; Žitnik, Slavko; Bajec, Marko; Weber, Lutz; Irmer, Matthias; Akhondi, Saber A; Kors, Jan A; Xu, Shuo; An, Xin; Sikdar, Utpal Kumar; Ekbal, Asif; Yoshioka, Masaharu; Dieb, Thaer M; Choi, Miji; Verspoor, Karin; Khabsa, Madian; Giles, C Lee; Liu, Hongfang; Ravikumar, Komandur Elayavilli; Lamurias, Andre; Couto, Francisco M; Dai, Hong-Jie; Tsai, Richard Tzong-Han; Ata, Caglar; Can, Tolga; Usié, Anabel; Alves, Rui; Segura-Bedmar, Isabel; Martínez, Paloma; Oyarzabal, Julen; Valencia, Alfonso

2015-01-01

The automatic extraction of chemical information from text requires the recognition of chemical entity mentions as one of its key steps. When developing supervised named entity recognition (NER) systems, the availability of a large, manually annotated text corpus is desirable. Furthermore, large corpora permit the robust evaluation and comparison of different approaches that detect chemicals in documents. We present the CHEMDNER corpus, a collection of 10,000 PubMed abstracts that contain a total of 84,355 chemical entity mentions labeled manually by expert chemistry literature curators, following annotation guidelines specifically defined for this task. The abstracts of the CHEMDNER corpus were selected to be representative for all major chemical disciplines. Each of the chemical entity mentions was manually labeled according to its structure-associated chemical entity mention (SACEM) class: abbreviation, family, formula, identifier, multiple, systematic and trivial. The difficulty and consistency of tagging chemicals in text was measured using an agreement study between annotators, obtaining a percentage agreement of 91. For a subset of the CHEMDNER corpus (the test set of 3,000 abstracts) we provide not only the Gold Standard manual annotations, but also mentions automatically detected by the 26 teams that participated in the BioCreative IV CHEMDNER chemical mention recognition task. In addition, we release the CHEMDNER silver standard corpus of automatically extracted mentions from 17,000 randomly selected PubMed abstracts. A version of the CHEMDNER corpus in the BioC format has been generated as well. We propose a standard for required minimum information about entity annotations for the construction of domain specific corpora on chemical and drug entities. The CHEMDNER corpus and annotation guidelines are available at: http://www.biocreative.org/resources/biocreative-iv/chemdner-corpus/.

The CHEMDNER corpus of chemicals and drugs and its annotation principles

PubMed Central

2015-01-01

The automatic extraction of chemical information from text requires the recognition of chemical entity mentions as one of its key steps. When developing supervised named entity recognition (NER) systems, the availability of a large, manually annotated text corpus is desirable. Furthermore, large corpora permit the robust evaluation and comparison of different approaches that detect chemicals in documents. We present the CHEMDNER corpus, a collection of 10,000 PubMed abstracts that contain a total of 84,355 chemical entity mentions labeled manually by expert chemistry literature curators, following annotation guidelines specifically defined for this task. The abstracts of the CHEMDNER corpus were selected to be representative for all major chemical disciplines. Each of the chemical entity mentions was manually labeled according to its structure-associated chemical entity mention (SACEM) class: abbreviation, family, formula, identifier, multiple, systematic and trivial. The difficulty and consistency of tagging chemicals in text was measured using an agreement study between annotators, obtaining a percentage agreement of 91. For a subset of the CHEMDNER corpus (the test set of 3,000 abstracts) we provide not only the Gold Standard manual annotations, but also mentions automatically detected by the 26 teams that participated in the BioCreative IV CHEMDNER chemical mention recognition task. In addition, we release the CHEMDNER silver standard corpus of automatically extracted mentions from 17,000 randomly selected PubMed abstracts. A version of the CHEMDNER corpus in the BioC format has been generated as well. We propose a standard for required minimum information about entity annotations for the construction of domain specific corpora on chemical and drug entities. The CHEMDNER corpus and annotation guidelines are available at: http://www.biocreative.org/resources/biocreative-iv/chemdner-corpus/ PMID:25810773

A method for named entity normalization in biomedical articles: application to diseases and plants.

PubMed

Cho, Hyejin; Choi, Wonjun; Lee, Hyunju

2017-10-13

In biomedical articles, a named entity recognition (NER) technique that identifies entity names from texts is an important element for extracting biological knowledge from articles. After NER is applied to articles, the next step is to normalize the identified names into standard concepts (i.e., disease names are mapped to the National Library of Medicine's Medical Subject Headings disease terms). In biomedical articles, many entity normalization methods rely on domain-specific dictionaries for resolving synonyms and abbreviations. However, the dictionaries are not comprehensive except for some entities such as genes. In recent years, biomedical articles have accumulated rapidly, and neural network-based algorithms that incorporate a large amount of unlabeled data have shown considerable success in several natural language processing problems. In this study, we propose an approach for normalizing biological entities, such as disease names and plant names, by using word embeddings to represent semantic spaces. For diseases, training data from the National Center for Biotechnology Information (NCBI) disease corpus and unlabeled data from PubMed abstracts were used to construct word representations. For plants, a training corpus that we manually constructed and unlabeled PubMed abstracts were used to represent word vectors. We showed that the proposed approach performed better than the use of only the training corpus or only the unlabeled data and showed that the normalization accuracy was improved by using our model even when the dictionaries were not comprehensive. We obtained F-scores of 0.808 and 0.690 for normalizing the NCBI disease corpus and manually constructed plant corpus, respectively. We further evaluated our approach using a data set in the disease normalization task of the BioCreative V challenge. When only the disease corpus was used as a dictionary, our approach significantly outperformed the best system of the task. The proposed approach shows robust performance for normalizing biological entities. The manually constructed plant corpus and the proposed model are available at http://gcancer.org/plant and http://gcancer.org/normalization , respectively.

Extraction of CYP chemical interactions from biomedical literature using natural language processing methods.

PubMed

Jiao, Dazhi; Wild, David J

2009-02-01

This paper proposes a system that automatically extracts CYP protein and chemical interactions from journal article abstracts, using natural language processing (NLP) and text mining methods. In our system, we employ a maximum entropy based learning method, using results from syntactic, semantic, and lexical analysis of texts. We first present our system architecture and then discuss the data set for training our machine learning based models and the methods in building components in our system, such as part of speech (POS) tagging, Named Entity Recognition (NER), dependency parsing, and relation extraction. An evaluation of the system is conducted at the end, yielding very promising results: The POS, dependency parsing, and NER components in our system have achieved a very high level of accuracy as measured by precision, ranging from 85.9% to 98.5%, and the precision and the recall of the interaction extraction component are 76.0% and 82.6%, and for the overall system are 68.4% and 72.2%, respectively.

Strand-specific Recognition of DNA Damages by XPD Provides Insights into Nucleotide Excision Repair Substrate Versatility*

PubMed Central

Buechner, Claudia N.; Heil, Korbinian; Michels, Gudrun; Carell, Thomas; Kisker, Caroline; Tessmer, Ingrid

2014-01-01

Recognition and removal of DNA damages is essential for cellular and organismal viability. Nucleotide excision repair (NER) is the sole mechanism in humans for the repair of carcinogenic UV irradiation-induced photoproducts in the DNA, such as cyclobutane pyrimidine dimers. The broad substrate versatility of NER further includes, among others, various bulky DNA adducts. It has been proposed that the 5′-3′ helicase XPD (xeroderma pigmentosum group D) protein plays a decisive role in damage verification. However, despite recent advances such as the identification of a DNA-binding channel and central pore in the protein, through which the DNA is threaded, as well as a dedicated lesion recognition pocket near the pore, the exact process of target site recognition and verification in eukaryotic NER still remained elusive. Our single molecule analysis by atomic force microscopy reveals for the first time that XPD utilizes different recognition strategies to verify structurally diverse lesions. Bulky fluorescein damage is preferentially detected on the translocated strand, whereas the opposite strand preference is observed for a cyclobutane pyrimidine dimer lesion. Both states, however, lead to similar conformational changes in the resulting specific complexes, indicating a merge to a “final” verification state, which may then trigger the recruitment of further NER proteins. PMID:24338567

Text mining in livestock animal science: introducing the potential of text mining to animal sciences.

PubMed

Sahadevan, S; Hofmann-Apitius, M; Schellander, K; Tesfaye, D; Fluck, J; Friedrich, C M

2012-10-01

In biological research, establishing the prior art by searching and collecting information already present in the domain has equal importance as the experiments done. To obtain a complete overview about the relevant knowledge, researchers mainly rely on 2 major information sources: i) various biological databases and ii) scientific publications in the field. The major difference between the 2 information sources is that information from databases is available, typically well structured and condensed. The information content in scientific literature is vastly unstructured; that is, dispersed among the many different sections of scientific text. The traditional method of information extraction from scientific literature occurs by generating a list of relevant publications in the field of interest and manually scanning these texts for relevant information, which is very time consuming. It is more than likely that in using this "classical" approach the researcher misses some relevant information mentioned in the literature or has to go through biological databases to extract further information. Text mining and named entity recognition methods have already been used in human genomics and related fields as a solution to this problem. These methods can process and extract information from large volumes of scientific text. Text mining is defined as the automatic extraction of previously unknown and potentially useful information from text. Named entity recognition (NER) is defined as the method of identifying named entities (names of real world objects; for example, gene/protein names, drugs, enzymes) in text. In animal sciences, text mining and related methods have been briefly used in murine genomics and associated fields, leaving behind other fields of animal sciences, such as livestock genomics. The aim of this work was to develop an information retrieval platform in the livestock domain focusing on livestock publications and the recognition of relevant data from cattle and pigs. For this purpose, the rather noncomprehensive resources of pig and cattle gene and protein terminologies were enriched with orthologue synonyms, integrated in the NER platform, ProMiner, which is successfully used in human genomics domain. Based on the performance tests done, the present system achieved a fair performance with precision 0.64, recall 0.74, and F(1) measure of 0.69 in a test scenario based on cattle literature.

Using nanoinformatics methods for automatically identifying relevant nanotoxicology entities from the literature.

PubMed

García-Remesal, Miguel; García-Ruiz, Alejandro; Pérez-Rey, David; de la Iglesia, Diana; Maojo, Víctor

2013-01-01

Nanoinformatics is an emerging research field that uses informatics techniques to collect, process, store, and retrieve data, information, and knowledge on nanoparticles, nanomaterials, and nanodevices and their potential applications in health care. In this paper, we have focused on the solutions that nanoinformatics can provide to facilitate nanotoxicology research. For this, we have taken a computational approach to automatically recognize and extract nanotoxicology-related entities from the scientific literature. The desired entities belong to four different categories: nanoparticles, routes of exposure, toxic effects, and targets. The entity recognizer was trained using a corpus that we specifically created for this purpose and was validated by two nanomedicine/nanotoxicology experts. We evaluated the performance of our entity recognizer using 10-fold cross-validation. The precisions range from 87.6% (targets) to 93.0% (routes of exposure), while recall values range from 82.6% (routes of exposure) to 87.4% (toxic effects). These results prove the feasibility of using computational approaches to reliably perform different named entity recognition (NER)-dependent tasks, such as for instance augmented reading or semantic searches. This research is a "proof of concept" that can be expanded to stimulate further developments that could assist researchers in managing data, information, and knowledge at the nanolevel, thus accelerating research in nanomedicine.

Gimli: open source and high-performance biomedical name recognition

PubMed Central

2013-01-01

Background Automatic recognition of biomedical names is an essential task in biomedical information extraction, presenting several complex and unsolved challenges. In recent years, various solutions have been implemented to tackle this problem. However, limitations regarding system characteristics, customization and usability still hinder their wider application outside text mining research. Results We present Gimli, an open-source, state-of-the-art tool for automatic recognition of biomedical names. Gimli includes an extended set of implemented and user-selectable features, such as orthographic, morphological, linguistic-based, conjunctions and dictionary-based. A simple and fast method to combine different trained models is also provided. Gimli achieves an F-measure of 87.17% on GENETAG and 72.23% on JNLPBA corpus, significantly outperforming existing open-source solutions. Conclusions Gimli is an off-the-shelf, ready to use tool for named-entity recognition, providing trained and optimized models for recognition of biomedical entities from scientific text. It can be used as a command line tool, offering full functionality, including training of new models and customization of the feature set and model parameters through a configuration file. Advanced users can integrate Gimli in their text mining workflows through the provided library, and extend or adapt its functionalities. Based on the underlying system characteristics and functionality, both for final users and developers, and on the reported performance results, we believe that Gimli is a state-of-the-art solution for biomedical NER, contributing to faster and better research in the field. Gimli is freely available at http://bioinformatics.ua.pt/gimli. PMID:23413997

Amplification of unscheduled DNA synthesis signal enables fluorescence-based single cell quantification of transcription-coupled nucleotide excision repair

PubMed Central

Wienholz, Franziska; Vermeulen, Wim

2017-01-01

Abstract Nucleotide excision repair (NER) comprises two damage recognition pathways: global genome NER (GG-NER) and transcription-coupled NER (TC-NER), which remove a wide variety of helix-distorting lesions including UV-induced damage. During NER, a short stretch of single-stranded DNA containing damage is excised and the resulting gap is filled by DNA synthesis in a process called unscheduled DNA synthesis (UDS). UDS is measured by quantifying the incorporation of nucleotide analogues into repair patches to provide a measure of NER activity. However, this assay is unable to quantitatively determine TC-NER activity due to the low contribution of TC-NER to the overall NER activity. Therefore, we developed a user-friendly, fluorescence-based single-cell assay to measure TC-NER activity. We combined the UDS assay with tyramide-based signal amplification to greatly increase the UDS signal, thereby allowing UDS to be quantified at low UV doses, as well as DNA-repair synthesis of other excision-based repair mechanisms such as base excision repair and mismatch repair. Importantly, we demonstrated that the amplified UDS is sufficiently sensitive to quantify TC-NER-derived repair synthesis in GG-NER-deficient cells. This assay is important as a diagnostic tool for NER-related disorders and as a research tool for obtaining new insights into the mechanism and regulation of excision repair. PMID:28088761

Transfer learning for biomedical named entity recognition with neural networks.

PubMed

Giorgi, John M; Bader, Gary D

2018-06-01

The explosive increase of biomedical literature has made information extraction an increasingly important tool for biomedical research. A fundamental task is the recognition of biomedical named entities in text (BNER) such as genes/proteins, diseases, and species. Recently, a domain-independent method based on deep learning and statistical word embeddings, called long short-term memory network-conditional random field (LSTM-CRF), has been shown to outperform state-of-the-art entity-specific BNER tools. However, this method is dependent on gold-standard corpora (GSCs) consisting of hand-labeled entities, which tend to be small but highly reliable. An alternative to GSCs are silver-standard corpora (SSCs), which are generated by harmonizing the annotations made by several automatic annotation systems. SSCs typically contain more noise than GSCs but have the advantage of containing many more training examples. Ideally, these corpora could be combined to achieve the benefits of both, which is an opportunity for transfer learning. In this work, we analyze to what extent transfer learning improves upon state-of-the-art results for BNER. We demonstrate that transferring a deep neural network (DNN) trained on a large, noisy SSC to a smaller, but more reliable GSC significantly improves upon state-of-the-art results for BNER. Compared to a state-of-the-art baseline evaluated on 23 GSCs covering four different entity classes, transfer learning results in an average reduction in error of approximately 11%. We found transfer learning to be especially beneficial for target data sets with a small number of labels (approximately 6000 or less). Source code for the LSTM-CRF is available athttps://github.com/Franck-Dernoncourt/NeuroNER/ and links to the corpora are available athttps://github.com/BaderLab/Transfer-Learning-BNER-Bioinformatics-2018/. john.giorgi@utoronto.ca. Supplementary data are available at Bioinformatics online.

Geoparsing text for characterizing urban operational environments through machine learning techniques

NASA Astrophysics Data System (ADS)

Garfinkle, Noah W.; Selig, Lucas; Perkins, Timothy K.; Calfas, George W.

2017-05-01

Increasing worldwide internet connectivity and access to sources of print and open social media has increased near realtime availability of textual information. Capabilities to structure and integrate textual data streams can contribute to more meaningful representations of operational environment factors (i.e., Political, Military, Economic, Social, Infrastructure, Information, Physical Environment, and Time [PMESII-PT]) and tactical civil considerations (i.e., Areas, Structures, Capabilities, Organizations, People and Events [ASCOPE]). However, relying upon human analysts to encode this information as it arrives quickly proves intractable. While human analysts possess an ability to comprehend context in unstructured text far beyond that of computers, automated geoparsing (the extraction of locations from unstructured text) can empower analysts to automate sifting through datasets for areas of interest. This research evaluates existing approaches to geoprocessing as well as initiating the research and development of locally-improved methods of tagging parts of text as possible locations, resolving possible locations into coordinates, and interfacing such results with human analysts. The objective of this ongoing research is to develop a more contextually-complete picture of an area of interest (AOI) including human-geographic context for events. In particular, our research is working to make improvements to geoparsing (i.e., the extraction of spatial context from documents), which requires development, integration, and validation of named-entity recognition (NER) tools, gazetteers, and entity-attribution. This paper provides an overview of NER models and methodologies as applied to geoparsing, explores several challenges encountered, presents preliminary results from the creation of a flexible geoparsing research pipeline, and introduces ongoing and future work with the intention of contributing to the efficient geocoding of information containing valuable insights into human activities in space.

ParaBTM: A Parallel Processing Framework for Biomedical Text Mining on Supercomputers.

PubMed

Xing, Yuting; Wu, Chengkun; Yang, Xi; Wang, Wei; Zhu, En; Yin, Jianping

2018-04-27

A prevailing way of extracting valuable information from biomedical literature is to apply text mining methods on unstructured texts. However, the massive amount of literature that needs to be analyzed poses a big data challenge to the processing efficiency of text mining. In this paper, we address this challenge by introducing parallel processing on a supercomputer. We developed paraBTM, a runnable framework that enables parallel text mining on the Tianhe-2 supercomputer. It employs a low-cost yet effective load balancing strategy to maximize the efficiency of parallel processing. We evaluated the performance of paraBTM on several datasets, utilizing three types of named entity recognition tasks as demonstration. Results show that, in most cases, the processing efficiency can be greatly improved with parallel processing, and the proposed load balancing strategy is simple and effective. In addition, our framework can be readily applied to other tasks of biomedical text mining besides NER.

A multistep damage recognition mechanism for global genomic nucleotide excision repair

PubMed Central

Sugasawa, Kaoru; Okamoto, Tomoko; Shimizu, Yuichiro; Masutani, Chikahide; Iwai, Shigenori; Hanaoka, Fumio

2001-01-01

A mammalian nucleotide excision repair (NER) factor, the XPC–HR23B complex, can specifically bind to certain DNA lesions and initiate the cell-free repair reaction. Here we describe a detailed analysis of its binding specificity using various DNA substrates, each containing a single defined lesion. A highly sensitive gel mobility shift assay revealed that XPC–HR23B specifically binds a small bubble structure with or without damaged bases, whereas dual incision takes place only when damage is present in the bubble. This is evidence that damage recognition for NER is accomplished through at least two steps; XPC–HR23B first binds to a site that has a DNA helix distortion, and then the presence of injured bases is verified prior to dual incision. Cyclobutane pyrimidine dimers (CPDs) were hardly recognized by XPC–HR23B, suggesting that additional factors may be required for CPD recognition. Although the presence of mismatched bases opposite a CPD potentiated XPC–HR23B binding, probably due to enhancement of the helix distortion, cell-free excision of such compound lesions was much more efficient than expected from the observed affinity for XPC–HR23B. This also suggests that additional factors and steps are required for the recognition of some types of lesions. A multistep mechanism of this sort may provide a molecular basis for ensuring the high level of damage discrimination that is required for global genomic NER. PMID:11238373

A multistep damage recognition mechanism for global genomic nucleotide excision repair.

PubMed

Sugasawa, K; Okamoto, T; Shimizu, Y; Masutani, C; Iwai, S; Hanaoka, F

2001-03-01

A mammalian nucleotide excision repair (NER) factor, the XPC-HR23B complex, can specifically bind to certain DNA lesions and initiate the cell-free repair reaction. Here we describe a detailed analysis of its binding specificity using various DNA substrates, each containing a single defined lesion. A highly sensitive gel mobility shift assay revealed that XPC-HR23B specifically binds a small bubble structure with or without damaged bases, whereas dual incision takes place only when damage is present in the bubble. This is evidence that damage recognition for NER is accomplished through at least two steps; XPC-HR23B first binds to a site that has a DNA helix distortion, and then the presence of injured bases is verified prior to dual incision. Cyclobutane pyrimidine dimers (CPDs) were hardly recognized by XPC-HR23B, suggesting that additional factors may be required for CPD recognition. Although the presence of mismatched bases opposite a CPD potentiated XPC-HR23B binding, probably due to enhancement of the helix distortion, cell-free excision of such compound lesions was much more efficient than expected from the observed affinity for XPC-HR23B. This also suggests that additional factors and steps are required for the recognition of some types of lesions. A multistep mechanism of this sort may provide a molecular basis for ensuring the high level of damage discrimination that is required for global genomic NER.

Nucleotide Excision Repair Lesion-Recognition Protein Rad4 Captures a Pre-Flipped Partner Base in a Benzo[a]pyrene-Derived DNA Lesion: How Structure Impacts the Binding Pathway.

PubMed

Mu, Hong; Geacintov, Nicholas E; Min, Jung-Hyun; Zhang, Yingkai; Broyde, Suse

2017-06-19

The xeroderma pigmentosum C protein complex (XPC) recognizes a variety of environmentally induced DNA lesions and is the key in initiating their repair by the nucleotide excision repair (NER) pathway. When bound to a lesion, XPC flips two nucleotide pairs that include the lesion out of the DNA duplex, yielding a productively bound complex that can lead to successful lesion excision. Interestingly, the efficiencies of NER vary greatly among different lesions, influencing their toxicity and mutagenicity in cells. Though differences in XPC binding may influence NER efficiency, it is not understood whether XPC utilizes different mechanisms to achieve productive binding with different lesions. Here, we investigated the well-repaired 10R-(+)-cis-anti-benzo[a]pyrene-N 2 -dG (cis-B[a]P-dG) DNA adduct in a duplex containing normal partner C opposite the lesion. This adduct is derived from the environmental pro-carcinogen benzo[a]pyrene and is likely to be encountered by NER in the cell. We have extensively investigated its binding to the yeast XPC orthologue, Rad4, using umbrella sampling with restrained molecular dynamics simulations and free energy calculations. The NMR solution structure of this lesion in duplex DNA has shown that the dC complementary to the adducted dG is flipped out of the DNA duplex in the absence of XPC. However, it is not known whether the "pre-flipped" base would play a role in its recognition by XPC. Our results show that Rad4 first captures the displaced dC, which is followed by a tightly coupled lesion-extruding pathway for productive binding. This binding path differs significantly from the one deduced for the small cis-syn cyclobutane pyrimidine dimer lesion opposite mismatched thymines [ Mu , H. , ( 2015 ) Biochemistry , 54 ( 34 ), 5263 - 7 ]. The possibility of multiple paths that lead to productive binding to XPC is consistent with the versatile lesion recognition by XPC that is required for successful NER.

Nucleotide Excision Repair Lesion-Recognition Protein Rad4 Captures a Pre-Flipped Partner Base in a Benzo[a]pyrene-Derived DNA Lesion: How Structure Impacts the Binding Pathway

PubMed Central

2017-01-01

The xeroderma pigmentosum C protein complex (XPC) recognizes a variety of environmentally induced DNA lesions and is the key in initiating their repair by the nucleotide excision repair (NER) pathway. When bound to a lesion, XPC flips two nucleotide pairs that include the lesion out of the DNA duplex, yielding a productively bound complex that can lead to successful lesion excision. Interestingly, the efficiencies of NER vary greatly among different lesions, influencing their toxicity and mutagenicity in cells. Though differences in XPC binding may influence NER efficiency, it is not understood whether XPC utilizes different mechanisms to achieve productive binding with different lesions. Here, we investigated the well-repaired 10R-(+)-cis-anti-benzo[a]pyrene-N2-dG (cis-B[a]P-dG) DNA adduct in a duplex containing normal partner C opposite the lesion. This adduct is derived from the environmental pro-carcinogen benzo[a]pyrene and is likely to be encountered by NER in the cell. We have extensively investigated its binding to the yeast XPC orthologue, Rad4, using umbrella sampling with restrained molecular dynamics simulations and free energy calculations. The NMR solution structure of this lesion in duplex DNA has shown that the dC complementary to the adducted dG is flipped out of the DNA duplex in the absence of XPC. However, it is not known whether the “pre-flipped” base would play a role in its recognition by XPC. Our results show that Rad4 first captures the displaced dC, which is followed by a tightly coupled lesion-extruding pathway for productive binding. This binding path differs significantly from the one deduced for the small cis-syn cyclobutane pyrimidine dimer lesion opposite mismatched thymines [MuH., (2015) Biochemistry, 54(34), 5263−726270861]. The possibility of multiple paths that lead to productive binding to XPC is consistent with the versatile lesion recognition by XPC that is required for successful NER. PMID:28460163

Atl1 regulates choice between global genome and transcription-coupled repair of O(6)-alkylguanines.

PubMed

Latypov, Vitaly F; Tubbs, Julie L; Watson, Amanda J; Marriott, Andrew S; McGown, Gail; Thorncroft, Mary; Wilkinson, Oliver J; Senthong, Pattama; Butt, Amna; Arvai, Andrew S; Millington, Christopher L; Povey, Andrew C; Williams, David M; Santibanez-Koref, Mauro F; Tainer, John A; Margison, Geoffrey P

2012-07-13

Nucleotide excision repair (NER) has long been known to remove DNA lesions induced by chemical carcinogens, and the molecular mechanism has been partially elucidated. Here we demonstrate that in Schizosaccharomyces pombe a DNA recognition protein, alkyltransferase-like 1 (Atl1), can play a pivotal role in selecting a specific NER pathway, depending on the nature of the DNA modification. The relative ease of dissociation of Atl1 from DNA containing small O(6)-alkylguanines allows accurate completion of global genome repair (GGR), whereas strong Atl1 binding to bulky O(6)-alkylguanines blocks GGR, stalls the transcription machinery, and diverts the damage to transcription-coupled repair. Our findings redraw the initial stages of the NER process in those organisms that express an alkyltransferase-like gene and raise the question of whether or not O(6)-alkylguanine lesions that are poor substrates for the alkyltransferase proteins in higher eukaryotes might, by analogy, signal such lesions for repair by NER. Copyright © 2012 Elsevier Inc. All rights reserved.

Collaborative biocuration--text-mining development task for document prioritization for curation.

PubMed

Wiegers, Thomas C; Davis, Allan Peter; Mattingly, Carolyn J

2012-01-01

The Critical Assessment of Information Extraction systems in Biology (BioCreAtIvE) challenge evaluation is a community-wide effort for evaluating text mining and information extraction systems for the biological domain. The 'BioCreative Workshop 2012' subcommittee identified three areas, or tracks, that comprised independent, but complementary aspects of data curation in which they sought community input: literature triage (Track I); curation workflow (Track II) and text mining/natural language processing (NLP) systems (Track III). Track I participants were invited to develop tools or systems that would effectively triage and prioritize articles for curation and present results in a prototype web interface. Training and test datasets were derived from the Comparative Toxicogenomics Database (CTD; http://ctdbase.org) and consisted of manuscripts from which chemical-gene-disease data were manually curated. A total of seven groups participated in Track I. For the triage component, the effectiveness of participant systems was measured by aggregate gene, disease and chemical 'named-entity recognition' (NER) across articles; the effectiveness of 'information retrieval' (IR) was also measured based on 'mean average precision' (MAP). Top recall scores for gene, disease and chemical NER were 49, 65 and 82%, respectively; the top MAP score was 80%. Each participating group also developed a prototype web interface; these interfaces were evaluated based on functionality and ease-of-use by CTD's biocuration project manager. In this article, we present a detailed description of the challenge and a summary of the results.

E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair.

PubMed

Singh, Randeep K; Dagnino, Lina

2016-05-03

Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis.

Sieve-based coreference resolution enhances semi-supervised learning model for chemical-induced disease relation extraction.

PubMed

Le, Hoang-Quynh; Tran, Mai-Vu; Dang, Thanh Hai; Ha, Quang-Thuy; Collier, Nigel

2016-07-01

The BioCreative V chemical-disease relation (CDR) track was proposed to accelerate the progress of text mining in facilitating integrative understanding of chemicals, diseases and their relations. In this article, we describe an extension of our system (namely UET-CAM) that participated in the BioCreative V CDR. The original UET-CAM system's performance was ranked fourth among 18 participating systems by the BioCreative CDR track committee. In the Disease Named Entity Recognition and Normalization (DNER) phase, our system employed joint inference (decoding) with a perceptron-based named entity recognizer (NER) and a back-off model with Semantic Supervised Indexing and Skip-gram for named entity normalization. In the chemical-induced disease (CID) relation extraction phase, we proposed a pipeline that includes a coreference resolution module and a Support Vector Machine relation extraction model. The former module utilized a multi-pass sieve to extend entity recall. In this article, the UET-CAM system was improved by adding a 'silver' CID corpus to train the prediction model. This silver standard corpus of more than 50 thousand sentences was automatically built based on the Comparative Toxicogenomics Database (CTD) database. We evaluated our method on the CDR test set. Results showed that our system could reach the state of the art performance with F1 of 82.44 for the DNER task and 58.90 for the CID task. Analysis demonstrated substantial benefits of both the multi-pass sieve coreference resolution method (F1 + 4.13%) and the silver CID corpus (F1 +7.3%).Database URL: SilverCID-The silver-standard corpus for CID relation extraction is freely online available at: https://zenodo.org/record/34530 (doi:10.5281/zenodo.34530). © The Author(s) 2016. Published by Oxford University Press.

Unsupervised Extraction of Diagnosis Codes from EMRs Using Knowledge-Based and Extractive Text Summarization Techniques

PubMed Central

Kavuluru, Ramakanth; Han, Sifei; Harris, Daniel

2017-01-01

Diagnosis codes are extracted from medical records for billing and reimbursement and for secondary uses such as quality control and cohort identification. In the US, these codes come from the standard terminology ICD-9-CM derived from the international classification of diseases (ICD). ICD-9 codes are generally extracted by trained human coders by reading all artifacts available in a patient’s medical record following specific coding guidelines. To assist coders in this manual process, this paper proposes an unsupervised ensemble approach to automatically extract ICD-9 diagnosis codes from textual narratives included in electronic medical records (EMRs). Earlier attempts on automatic extraction focused on individual documents such as radiology reports and discharge summaries. Here we use a more realistic dataset and extract ICD-9 codes from EMRs of 1000 inpatient visits at the University of Kentucky Medical Center. Using named entity recognition (NER), graph-based concept-mapping of medical concepts, and extractive text summarization techniques, we achieve an example based average recall of 0.42 with average precision 0.47; compared with a baseline of using only NER, we notice a 12% improvement in recall with the graph-based approach and a 7% improvement in precision using the extractive text summarization approach. Although diagnosis codes are complex concepts often expressed in text with significant long range non-local dependencies, our present work shows the potential of unsupervised methods in extracting a portion of codes. As such, our findings are especially relevant for code extraction tasks where obtaining large amounts of training data is difficult. PMID:28748227

Resolving anaphoras for the extraction of drug-drug interactions in pharmacological documents

PubMed Central

2010-01-01

Background Drug-drug interactions are frequently reported in the increasing amount of biomedical literature. Information Extraction (IE) techniques have been devised as a useful instrument to manage this knowledge. Nevertheless, IE at the sentence level has a limited effect because of the frequent references to previous entities in the discourse, a phenomenon known as 'anaphora'. DrugNerAR, a drug anaphora resolution system is presented to address the problem of co-referring expressions in pharmacological literature. This development is part of a larger and innovative study about automatic drug-drug interaction extraction. Methods The system uses a set of linguistic rules drawn by Centering Theory over the analysis provided by a biomedical syntactic parser. Semantic information provided by the Unified Medical Language System (UMLS) is also integrated in order to improve the recognition and the resolution of nominal drug anaphors. Besides, a corpus has been developed in order to analyze the phenomena and evaluate the current approach. Each possible case of anaphoric expression was looked into to determine the most effective way of resolution. Results An F-score of 0.76 in anaphora resolution was achieved, outperforming significantly the baseline by almost 73%. This ad-hoc reference line was developed to check the results as there is no previous work on anaphora resolution in pharmalogical documents. The obtained results resemble those found in related-semantic domains. Conclusions The present approach shows very promising results in the challenge of accounting for anaphoric expressions in pharmacological texts. DrugNerAr obtains similar results to other approaches dealing with anaphora resolution in the biomedical domain, but, unlike these approaches, it focuses on documents reflecting drug interactions. The Centering Theory has proved being effective at the selection of antecedents in anaphora resolution. A key component in the success of this framework is the analysis provided by the MMTx program and the DrugNer system that allows to deal with the complexity of the pharmacological language. It is expected that the positive results of the resolver increases performance of our future drug-drug interaction extraction system. PMID:20406499

E2F1 interactions with hHR23A inhibit its degradation and promote DNA repair

PubMed Central

Singh, Randeep K.; Dagnino, Lina

2016-01-01

Nucleotide excision repair (NER) is a major mechanism for removal of DNA lesions induced by exposure to UV radiation in the epidermis. Recognition of damaged DNA sites is the initial step in their repair, and requires multiprotein complexes that contain XPC and hHR23 proteins, or their orthologues. A variety of transcription factors are also involved in NER, including E2F1. In epidermal keratinocytes, UV exposure induces E2F1 phosphorylation, which allows it to recruit various NER factors to sites of DNA damage. However, the relationship between E2F1 and hHR23 proteins vis-à-vis NER has remained unexplored. We now show that E2F1 and hHR23 proteins can interact, and this interaction stabilizes E2F1, inhibiting its proteasomal degradation. Reciprocally, E2F1 regulates hHR23A subcellular localization, recruiting it to sites of DNA photodamage. As a result, E2F1 and hHR23A enhance DNA repair following exposure to UV radiation, contributing to genomic stability in the epidermis. PMID:27028861

bioNerDS: exploring bioinformatics’ database and software use through literature mining

PubMed Central

2013-01-01

Background Biology-focused databases and software define bioinformatics and their use is central to computational biology. In such a complex and dynamic field, it is of interest to understand what resources are available, which are used, how much they are used, and for what they are used. While scholarly literature surveys can provide some insights, large-scale computer-based approaches to identify mentions of bioinformatics databases and software from primary literature would automate systematic cataloguing, facilitate the monitoring of usage, and provide the foundations for the recovery of computational methods for analysing biological data, with the long-term aim of identifying best/common practice in different areas of biology. Results We have developed bioNerDS, a named entity recogniser for the recovery of bioinformatics databases and software from primary literature. We identify such entities with an F-measure ranging from 63% to 91% at the mention level and 63-78% at the document level, depending on corpus. Not attaining a higher F-measure is mostly due to high ambiguity in resource naming, which is compounded by the on-going introduction of new resources. To demonstrate the software, we applied bioNerDS to full-text articles from BMC Bioinformatics and Genome Biology. General mention patterns reflect the remit of these journals, highlighting BMC Bioinformatics’s emphasis on new tools and Genome Biology’s greater emphasis on data analysis. The data also illustrates some shifts in resource usage: for example, the past decade has seen R and the Gene Ontology join BLAST and GenBank as the main components in bioinformatics processing. Abstract Conclusions We demonstrate the feasibility of automatically identifying resource names on a large-scale from the scientific literature and show that the generated data can be used for exploration of bioinformatics database and software usage. For example, our results help to investigate the rate of change in resource usage and corroborate the suspicion that a vast majority of resources are created, but rarely (if ever) used thereafter. bioNerDS is available at http://bionerds.sourceforge.net/. PMID:23768135

DTMiner: identification of potential disease targets through biomedical literature mining

PubMed Central

Xu, Dong; Zhang, Meizhuo; Xie, Yanping; Wang, Fan; Chen, Ming; Zhu, Kenny Q.; Wei, Jia

2016-01-01

Motivation: Biomedical researchers often search through massive catalogues of literature to look for potential relationships between genes and diseases. Given the rapid growth of biomedical literature, automatic relation extraction, a crucial technology in biomedical literature mining, has shown great potential to support research of gene-related diseases. Existing work in this field has produced datasets that are limited both in scale and accuracy. Results: In this study, we propose a reliable and efficient framework that takes large biomedical literature repositories as inputs, identifies credible relationships between diseases and genes, and presents possible genes related to a given disease and possible diseases related to a given gene. The framework incorporates name entity recognition (NER), which identifies occurrences of genes and diseases in texts, association detection whereby we extract and evaluate features from gene–disease pairs, and ranking algorithms that estimate how closely the pairs are related. The F1-score of the NER phase is 0.87, which is higher than existing studies. The association detection phase takes drastically less time than previous work while maintaining a comparable F1-score of 0.86. The end-to-end result achieves a 0.259 F1-score for the top 50 genes associated with a disease, which performs better than previous work. In addition, we released a web service for public use of the dataset. Availability and Implementation: The implementation of the proposed algorithms is publicly available at http://gdr-web.rwebox.com/public_html/index.php?page=download.php. The web service is available at http://gdr-web.rwebox.com/public_html/index.php. Contact: jenny.wei@astrazeneca.com or kzhu@cs.sjtu.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online. PMID:27506226

DTMiner: identification of potential disease targets through biomedical literature mining.

PubMed

Xu, Dong; Zhang, Meizhuo; Xie, Yanping; Wang, Fan; Chen, Ming; Zhu, Kenny Q; Wei, Jia

2016-12-01

Biomedical researchers often search through massive catalogues of literature to look for potential relationships between genes and diseases. Given the rapid growth of biomedical literature, automatic relation extraction, a crucial technology in biomedical literature mining, has shown great potential to support research of gene-related diseases. Existing work in this field has produced datasets that are limited both in scale and accuracy. In this study, we propose a reliable and efficient framework that takes large biomedical literature repositories as inputs, identifies credible relationships between diseases and genes, and presents possible genes related to a given disease and possible diseases related to a given gene. The framework incorporates name entity recognition (NER), which identifies occurrences of genes and diseases in texts, association detection whereby we extract and evaluate features from gene-disease pairs, and ranking algorithms that estimate how closely the pairs are related. The F1-score of the NER phase is 0.87, which is higher than existing studies. The association detection phase takes drastically less time than previous work while maintaining a comparable F1-score of 0.86. The end-to-end result achieves a 0.259 F1-score for the top 50 genes associated with a disease, which performs better than previous work. In addition, we released a web service for public use of the dataset. The implementation of the proposed algorithms is publicly available at http://gdr-web.rwebox.com/public_html/index.php?page=download.php The web service is available at http://gdr-web.rwebox.com/public_html/index.php CONTACT: jenny.wei@astrazeneca.com or kzhu@cs.sjtu.edu.cn Supplementary information: Supplementary data are available at Bioinformatics online. © The Author 2016. Published by Oxford University Press.

Data Processing and Text Mining Technologies on Electronic Medical Records: A Review

PubMed Central

Sun, Wencheng; Li, Yangyang; Liu, Fang; Fang, Shengqun; Wang, Guoyan

2018-01-01

Currently, medical institutes generally use EMR to record patient's condition, including diagnostic information, procedures performed, and treatment results. EMR has been recognized as a valuable resource for large-scale analysis. However, EMR has the characteristics of diversity, incompleteness, redundancy, and privacy, which make it difficult to carry out data mining and analysis directly. Therefore, it is necessary to preprocess the source data in order to improve data quality and improve the data mining results. Different types of data require different processing technologies. Most structured data commonly needs classic preprocessing technologies, including data cleansing, data integration, data transformation, and data reduction. For semistructured or unstructured data, such as medical text, containing more health information, it requires more complex and challenging processing methods. The task of information extraction for medical texts mainly includes NER (named-entity recognition) and RE (relation extraction). This paper focuses on the process of EMR processing and emphatically analyzes the key techniques. In addition, we make an in-depth study on the applications developed based on text mining together with the open challenges and research issues for future work. PMID:29849998

Chemical Entity Recognition and Resolution to ChEBI

PubMed Central

Grego, Tiago; Pesquita, Catia; Bastos, Hugo P.; Couto, Francisco M.

2012-01-01

Chemical entities are ubiquitous through the biomedical literature and the development of text-mining systems that can efficiently identify those entities are required. Due to the lack of available corpora and data resources, the community has focused its efforts in the development of gene and protein named entity recognition systems, but with the release of ChEBI and the availability of an annotated corpus, this task can be addressed. We developed a machine-learning-based method for chemical entity recognition and a lexical-similarity-based method for chemical entity resolution and compared them with Whatizit, a popular-dictionary-based method. Our methods outperformed the dictionary-based method in all tasks, yielding an improvement in F-measure of 20% for the entity recognition task, 2–5% for the entity-resolution task, and 15% for combined entity recognition and resolution tasks. PMID:25937941

Sequential and ordered assembly of a large DNA repair complex on undamaged chromatin

PubMed Central

Ziani, Salim; Nagy, Zita; Alekseev, Sergey; Soutoglou, Evi; Egly, Jean-Marc

2014-01-01

In nucleotide excision repair (NER), damage recognition by XPC-hHR23b is described as a critical step in the formation of the preincision complex (PInC) further composed of TFIIH, XPA, RPA, XPG, and ERCC1-XPF. To obtain new molecular insights into the assembly of the PInC, we analyzed its formation independently of DNA damage by using the lactose operator/repressor reporter system. We observed a sequential and ordered self-assembly of the PInC operating upon immobilization of individual NER factors on undamaged chromatin and mimicking that functioning on a bona fide NER substrate. We also revealed that the recruitment of the TFIIH subunit TTDA, involved in trichothiodystrophy group A disorder (TTD-A), was key in the completion of the PInC. TTDA recruits XPA through its first 15 amino acids, depleted in some TTD-A patients. More generally, these results show that proteins forming large nuclear complexes can be recruited sequentially on chromatin in the absence of their natural DNA target and with no reciprocity in their recruitment. PMID:25154395

Nucleotide Excision Repair Proteins Rapidly Accumulate but Fail to Persist in Human XP-E (DDB2 Mutant) Cells

PubMed Central

Oh, Kyu-Seon; Imoto, Kyoko; Emmert, Steffen; Tamura, Deborah; DiGiovanna, John J.; Kraemer, Kenneth. H.

2011-01-01

The XP-E DNA damage binding protein (DDB2) is involved in early recognition of global genome DNA damage during DNA nucleotide excision repair (NER). We found that skin fibroblasts from 4 newly reported XP-E patients with numerous skin cancers and DDB2 mutations had slow repair of 6-4 photoproducts (6-4PP) and markedly reduced repair of cyclobutane pyrimidine dimers (CPD). NER proteins (XPC, XPB, XPG, XPA, and XPF) co-localized to CPD and 6-4PP positive regions immediately (< 0.1h) after localized UV irradiation in cells from the XP-E patients and normal controls. While these proteins persist in normal cells, surprisingly, within 0.5h these repair proteins were no longer detectable at the sites of DNA damage in XP-E cells. Our results indicate that DDB2 is not required for the rapid recruitment of NER proteins to sites of UV photoproducts or for partial repair of 6-4PP but is essential for normal persistence of these proteins for CPD photoproduct removal. PMID:21388382

Enhancements for a Dynamic Data Warehousing and Mining System for Large-Scale Human Social Cultural Behavioral (HSBC) Data

DTIC Science & Technology

2016-09-26

Intelligent Automation Incorporated Enhancements for a Dynamic Data Warehousing and Mining ...Enhancements for a Dynamic Data Warehousing and Mining System for N00014-16-P-3014 Large-Scale Human Social Cultural Behavioral (HSBC) Data 5b. GRANT NUMBER...Representative Media Gallery View. We perform Scraawl’s NER algorithm to the text associated with YouTube post, which classifies the named entities into

AutoMap User’s Guide

DTIC Science & Technology

2006-10-01

Hierarchy of Pre-Processing Techniques 3. NLP (Natural Language Processing) Utilities 3.1 Named-Entity Recognition 3.1.1 Example for Named-Entity... Recognition 3.2 Symbol RemovalN-Gram Identification: Bi-Grams 4. Stemming 4.1 Stemming Example 5. Delete List 5.1 Open a Delete List 5.1.1 Small...iterative and involves several key processes: • Named-Entity Recognition Named-Entity Recognition is an Automap feature that allows you to

Cdt2-mediated XPG degradation promotes gap-filling DNA synthesis in nucleotide excision repair

PubMed Central

Han, Chunhua; Wani, Gulzar; Zhao, Ran; Qian, Jiang; Sharma, Nidhi; He, Jinshan; Zhu, Qianzheng; Wang, Qi-En; Wani, Altaf A

2015-01-01

Xeroderma pigmentosum group G (XPG) protein is a structure-specific repair endonuclease, which cleaves DNA strands on the 3′ side of the DNA damage during nucleotide excision repair (NER). XPG also plays a crucial role in initiating DNA repair synthesis through recruitment of PCNA to the repair sites. However, the fate of XPG protein subsequent to the excision of DNA damage has remained unresolved. Here, we show that XPG, following its action on bulky lesions resulting from exposures to UV irradiation and cisplatin, is subjected to proteasome-mediated proteolytic degradation. Productive NER processing is required for XPG degradation as both UV and cisplatin treatment-induced XPG degradation is compromised in NER-deficient XP-A, XP-B, XP-C, and XP-F cells. In addition, the NER-related XPG degradation requires Cdt2, a component of an E3 ubiquitin ligase, CRL4Cdt2. Micropore local UV irradiation and in situ Proximity Ligation assays demonstrated that Cdt2 is recruited to the UV-damage sites and interacts with XPG in the presence of PCNA. Importantly, Cdt2-mediated XPG degradation is crucial to the subsequent recruitment of DNA polymerase δ and DNA repair synthesis. Collectively, our data support the idea of PCNA recruitment to damage sites which occurs in conjunction with XPG, recognition of the PCNA-bound XPG by CRL4Cdt2 for specific ubiquitylation and finally the protein degradation. In essence, XPG elimination from DNA damage sites clears the chromatin space needed for the subsequent recruitment of DNA polymerase δ to the damage site and completion of gap-filling DNA synthesis during the final stage of NER. PMID:25483071

nala: text mining natural language mutation mentions

PubMed Central

Cejuela, Juan Miguel; Bojchevski, Aleksandar; Uhlig, Carsten; Bekmukhametov, Rustem; Kumar Karn, Sanjeev; Mahmuti, Shpend; Baghudana, Ashish; Dubey, Ankit; Satagopam, Venkata P.; Rost, Burkhard

2017-01-01

Abstract Motivation: The extraction of sequence variants from the literature remains an important task. Existing methods primarily target standard (ST) mutation mentions (e.g. ‘E6V’), leaving relevant mentions natural language (NL) largely untapped (e.g. ‘glutamic acid was substituted by valine at residue 6’). Results: We introduced three new corpora suggesting named-entity recognition (NER) to be more challenging than anticipated: 28–77% of all articles contained mentions only available in NL. Our new method nala captured NL and ST by combining conditional random fields with word embedding features learned unsupervised from the entire PubMed. In our hands, nala substantially outperformed the state-of-the-art. For instance, we compared all unique mentions in new discoveries correctly detected by any of three methods (SETH, tmVar, or nala). Neither SETH nor tmVar discovered anything missed by nala, while nala uniquely tagged 33% mentions. For NL mentions the corresponding value shot up to 100% nala-only. Availability and Implementation: Source code, API and corpora freely available at: http://tagtog.net/-corpora/IDP4+. Contact: nala@rostlab.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:28200120

77 FR 70163 - Recognition of Entities for the Accreditation of Qualified Health Plans

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-23

... DEPARTMENT OF HEALTH AND HUMAN SERVICES [CMS-9961-N] Recognition of Entities for the Accreditation... as recognized accrediting entities for the purposes of fulfilling the accreditation requirement as... a recognized accrediting entity on a uniform timeline established by the applicable Exchange. On...

Metal binding mediated conformational change of XPA protein: a potential cytotoxic mechanism of nickel in the nucleotide excision repair

PubMed Central

Hu, Jianping; Hu, Ziheng; Zhang, Yan; Gou, Xiaojun; Mu, Ying; Wang, Lirong; Xie, Xiang-Qun

2017-01-01

Nucleotide excision repair (NER) is a pivotal life process for repairing DNA nucleotide mismatch caused by chemicals, metal ions, radiation, and other factors. As the initiation step of NER, the xeroderma pigmentosum complementation group A protein (XPA) recognizes damaged DNA molecules, and recruits the replication protein A (RPA), another important player in the NER process. The stability of the Zn2+-chelated Zn-finger domain of XPA center core portion (i.e., XPA98–210) is the foundation of its biological functionality, while the displacement of the Zn2+ by toxic metal ions (such as Ni2+, a known human carcinogen and allergen) may impair the effectiveness of NER and hence elevate the chance of carcinogenesis. In this study, we first calculated the force field parameters for the bonded model in the metal center of the XPA98–210 system, showing that the calculated results, including charges, bonds, angles etc., are congruent with previously reported results measured by spectrometry experiments and quantum chemistry computation. Then, comparative molecular dynamics simulations using these parameters revealed the changes in the conformation and motion mode of XPA98–210 Zn-finger after the substitution of Zn2+ by Ni2+. The results showed that Ni2+ dramatically disrupted the relative positions of the four Cys residues in the Zn-finger structure, forcing them to collapse from a tetrahedron into an almost planar structure. Finally, we acquired the binding mode of XPA98–210 with its ligands RPA70N and DNA based on molecular docking and structural alignment. We found that XPA98–210’s Zn-finger domain primarily binds to a V-shaped cleft in RPA70N, while the cationic band in its C-terminal subdomain participates in the recognition of damaged DNA. In addition, this article sheds light on the multi-component interaction pattern among XPA, DNA, and other NER-related proteins (i.e., RPA70N, RPA70A, RPA70B, RPA70C, RPA32, and RPA14) based on previously reported structural biology information. Thus, we derived a putative cytotoxic mechanism associated with the nickel ion, where the Ni2+ disrupts the conformation of the XPA Zn-finger, directly weakening its interaction with RPA70N, and thus lowering the effectiveness of the NER process. In sum, this work not only provides a theoretical insight into the multi-protein interactions involved in the NER process and potential cytotoxic mechanism associated with Ni2+ binding in XPA, but may also facilitate rational anti-cancer drug design based on the NER mechanism. PMID:27307058

Insight in the multilevel regulation of NER

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dijk, Madelon; Typas, Dimitris; Mullenders, Leon, E-mail: l.mullenders@lumc.nl

2014-11-15

Nucleotide excision repair (NER) is a key component of the DNA damage response (DDR) and it is essential to safeguard genome integrity against genotoxic insults. The regulation of NER is primarily mediated by protein post-translational modifications (PTMs). The NER machinery removes a wide spectrum of DNA helix distorting lesions, including those induced by solar radiation, through two sub-pathways: global genome nucleotide excision repair (GG-NER) and transcription coupled nucleotide excision repair (TC-NER). Severe clinical consequences associated with inherited NER defects, including premature ageing, neurodegeneration and extreme cancer-susceptibility, underscore the biological relevance of NER. In the last two decades most of themore » core NER machinery has been elaborately described, shifting attention to molecular mechanisms that either facilitate NER in the context of chromatin or promote the timely and accurate interplay between NER factors and various post-translational modifications. In this review, we summarize and discuss the latest findings in NER. In particular, we focus on emerging factors and novel molecular mechanisms by which NER is regulated.« less

Disease named entity recognition by combining conditional random fields and bidirectional recurrent neural networks.

PubMed

Wei, Qikang; Chen, Tao; Xu, Ruifeng; He, Yulan; Gui, Lin

2016-01-01

The recognition of disease and chemical named entities in scientific articles is a very important subtask in information extraction in the biomedical domain. Due to the diversity and complexity of disease names, the recognition of named entities of diseases is rather tougher than those of chemical names. Although there are some remarkable chemical named entity recognition systems available online such as ChemSpot and tmChem, the publicly available recognition systems of disease named entities are rare. This article presents a system for disease named entity recognition (DNER) and normalization. First, two separate DNER models are developed. One is based on conditional random fields model with a rule-based post-processing module. The other one is based on the bidirectional recurrent neural networks. Then the named entities recognized by each of the DNER model are fed into a support vector machine classifier for combining results. Finally, each recognized disease named entity is normalized to a medical subject heading disease name by using a vector space model based method. Experimental results show that using 1000 PubMed abstracts for training, our proposed system achieves an F1-measure of 0.8428 at the mention level and 0.7804 at the concept level, respectively, on the testing data of the chemical-disease relation task in BioCreative V.Database URL: http://219.223.252.210:8080/SS/cdr.html. © The Author(s) 2016. Published by Oxford University Press.

Xeroderma pigmentosum in Ghanaians: a report of three cases and review of literature.

PubMed

Adu, E J

2014-01-01

Xeroderma pigmentosum is an autosomal recessive disease with sun sensitivity, photophobia, early onset of freckling, and subsequent neoplastic changes on sun-exposed surfaces. There is cellular hypersensitivity to UV radiation and to certain chemicals in association with abnormal DNA repair. Patients with defective DNA nucleotide excision repair (NER) have defects in one of seven NER genes; xeroderma pigmentosum variants have normal NER and a defect in a polymerase gene. This is a case presentation of three patients with the features of xeroderma pigmentosum, aged 48, 15, and 14 years. The latter two patients were females. Each presented with areas of hyper-and hypo-pigmentation over sun exposed body surfaces. Each patient had a minimum of two cutaneous malignancies, distributed on the upper chest, face or scalp. The first and third patients had their lesions surgically excised and the defects were skin grafted. The second patient was treated with radiotherapy. All the lesions presented were confirmed histologically as squamous cell carcinoma. No recurrence of the malignancies has been noticed. Xeroderma pigmentosum is not rare in Ghana. Early recognition of the disease is necessary to avoid morbidity and mortality from malignant complications. The use of other treatment modalities such as sunscreens, oral retinoids, and chemical therapy with 5-fluorouracil is discussed.

Tissue specific mutagenic and carcinogenic responses in NER defective mouse models.

PubMed

Wijnhoven, Susan W P; Hoogervorst, Esther M; de Waard, Harm; van der Horst, Gijsbertus T J; van Steeg, Harry

2007-01-03

Several mouse models with defects in genes encoding components of the nucleotide excision repair (NER) pathway have been developed. In NER two different sub-pathways are known, i.e. transcription-coupled repair (TC-NER) and global-genome repair (GG-NER). A defect in one particular NER protein can lead to a (partial) defect in GG-NER, TC-NER or both. GG-NER defects in mice predispose to cancer, both spontaneous as well as UV-induced. As such these models (Xpa, Xpc and Xpe) recapitulate the human xeroderma pigmentosum (XP) syndrome. Defects in TC-NER in humans are associated with Cockayne syndrome (CS), a disease not linked to tumor development. Mice with TC-NER defects (Csa and Csb) are - except for the skin - not susceptible to develop (carcinogen-induced) tumors. Some NER factors, i.e. XPB, XPD, XPF, XPG and ERCC1 have functions outside NER, like transcription initiation and inter-strand crosslink repair. Deficiencies in these processes in mice lead to very severe phenotypes, like trichothiodystrophy (TTD) or a combination of XP and CS. In most cases these animals have a (very) short life span, display segmental progeria, but do not develop tumors. Here we will overview the available NER-related mouse models and will discuss their phenotypes in terms of (chemical-induced) tissue-specific tumor development, mutagenesis and premature aging features.

Ubiquitin-specific Protease 7 Regulates Nucleotide Excision Repair through Deubiquitinating XPC Protein and Preventing XPC Protein from Undergoing Ultraviolet Light-induced and VCP/p97 Protein-regulated Proteolysis*

PubMed Central

He, Jinshan; Zhu, Qianzheng; Wani, Gulzar; Sharma, Nidhi; Han, Chunhua; Qian, Jiang; Pentz, Kyle; Wang, Qi-en; Wani, Altaf A.

2014-01-01

Ubiquitin specific protease 7 (USP7) is a known deubiquitinating enzyme for tumor suppressor p53 and its downstream regulator, E3 ubiquitin ligase Mdm2. Here we report that USP7 regulates nucleotide excision repair (NER) via deubiquitinating xeroderma pigmentosum complementation group C (XPC) protein, a critical damage recognition factor that binds to helix-distorting DNA lesions and initiates NER. XPC is ubiquitinated during the early stage of NER of UV light-induced DNA lesions. We demonstrate that transiently compromising cellular USP7 by siRNA and chemical inhibition leads to accumulation of ubiquitinated forms of XPC, whereas complete USP7 deficiency leads to rapid ubiquitin-mediated XPC degradation upon UV irradiation. We show that USP7 physically interacts with XPC in vitro and in vivo. Overexpression of wild-type USP7, but not its catalytically inactive or interaction-defective mutants, reduces the ubiquitinated forms of XPC. Importantly, USP7 efficiently deubiquitinates XPC-ubiquitin conjugates in deubiquitination assays in vitro. We further show that valosin-containing protein (VCP)/p97 is involved in UV light-induced XPC degradation in USP7-deficient cells. VCP/p97 is readily recruited to DNA damage sites and colocalizes with XPC. Chemical inhibition of the activity of VCP/p97 ATPase causes an increase in ubiquitinated XPC on DNA-damaged chromatin. Moreover, USP7 deficiency severely impairs the repair of cyclobutane pyrimidine dimers and, to a lesser extent, affects the repair of 6-4 photoproducts. Taken together, our findings uncovered an important role of USP7 in regulating NER via deubiquitinating XPC and by preventing its VCP/p97-regulated proteolysis. PMID:25118285

A Novel Approach towards Medical Entity Recognition in Chinese Clinical Text

PubMed Central

Yu, Jian

2017-01-01

Medical entity recognition, a basic task in the language processing of clinical data, has been extensively studied in analyzing admission notes in alphabetic languages such as English. However, much less work has been done on nonstructural texts that are written in Chinese, or in the setting of differentiation of Chinese drug names between traditional Chinese medicine and Western medicine. Here, we propose a novel cascade-type Chinese medication entity recognition approach that aims at integrating the sentence category classifier from a support vector machine and the conditional random field-based medication entity recognition. We hypothesized that this approach could avoid the side effects of abundant negative samples and improve the performance of the named entity recognition from admission notes written in Chinese. Therefore, we applied this approach to a test set of 324 Chinese-written admission notes with manual annotation by medical experts. Our data demonstrated that this approach had a score of 94.2% in precision, 92.8% in recall, and 93.5% in F-measure for the recognition of traditional Chinese medicine drug names and 91.2% in precision, 92.6% in recall, and 91.7% F-measure for the recognition of Western medicine drug names. The differences in F-measure were significant compared with those in the baseline systems. PMID:29065612

Xeroderma pigmentosum complementation group G associated with Cockayne syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vermeulen, W.; Jaspers, N.G.J.; Bootsma, D.

1993-07-01

Xeroderma pigmentosum (XP) and Cockayne syndrome (CS) are two rare inherited disorders with a clinical and cellular hypersensitivity to the UV component of the sunlight spectrum. Although the two traits are generally considered as clinically and genetically distinct entities, on the biochemical level a defect in the nucleotide excision-repair (NER) pathway is involved in both. Classical CS patients are primarily deficient in the preferential repair of DNA damage in actively transcribed genes, whereas in most XP patients the genetic defect affects both [open quotes]preferential[close quotes] and [open quotes]overall[close quotes] NER modalities. Here the authors report a genetic study of twomore » unrelated, severely affected patients with the clinical characteristics of CS but with a biochemical defect typical of XP. By complementation analysis, using somatic cell fusion and nuclear microinjection of cloned repair genes, they assign these two patients to XP complementation group G, which previously was not associated with CS. This observation extends the earlier identification of two patients with a rare combined XP/CS phenotype within XP complementation groups B and D, respectively. It indicates that some mutations in at least three of the seven genes known to be involved in XP also can result in a picture of partial or even full-blown CS. It is concluded that the syndromes XP and CS are biochemically closely related and may be part of a broader clinical disease spectrum. The authors suggest, as a possible molecular mechanism underlying this relation, that the XPGC repair gene has an additional vital function, as shown for some other NER genes. 33 refs., 5 tabs.« less

Text mining of cancer-related information: review of current status and future directions.

PubMed

Spasić, Irena; Livsey, Jacqueline; Keane, John A; Nenadić, Goran

2014-09-01

This paper reviews the research literature on text mining (TM) with the aim to find out (1) which cancer domains have been the subject of TM efforts, (2) which knowledge resources can support TM of cancer-related information and (3) to what extent systems that rely on knowledge and computational methods can convert text data into useful clinical information. These questions were used to determine the current state of the art in this particular strand of TM and suggest future directions in TM development to support cancer research. A review of the research on TM of cancer-related information was carried out. A literature search was conducted on the Medline database as well as IEEE Xplore and ACM digital libraries to address the interdisciplinary nature of such research. The search results were supplemented with the literature identified through Google Scholar. A range of studies have proven the feasibility of TM for extracting structured information from clinical narratives such as those found in pathology or radiology reports. In this article, we provide a critical overview of the current state of the art for TM related to cancer. The review highlighted a strong bias towards symbolic methods, e.g. named entity recognition (NER) based on dictionary lookup and information extraction (IE) relying on pattern matching. The F-measure of NER ranges between 80% and 90%, while that of IE for simple tasks is in the high 90s. To further improve the performance, TM approaches need to deal effectively with idiosyncrasies of the clinical sublanguage such as non-standard abbreviations as well as a high degree of spelling and grammatical errors. This requires a shift from rule-based methods to machine learning following the success of similar trends in biological applications of TM. Machine learning approaches require large training datasets, but clinical narratives are not readily available for TM research due to privacy and confidentiality concerns. This issue remains the main bottleneck for progress in this area. In addition, there is a need for a comprehensive cancer ontology that would enable semantic representation of textual information found in narrative reports. Copyright © 2014 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Structural dynamics and interactions of Xeroderma pigmentosum complementation group A (XPA98-210) with damaged DNA.

PubMed

Pradhan, Sushmita; Mattaparthi, Venkata Satish Kumar

2017-10-25

Nucleotide excision repair (NER) in higher organisms repair massive DNA abrasions caused by ultraviolet rays, and various mutagens, where Xeroderma pigmentosum group A (XPA) protein is known to be involved in damage recognition step. Any mutations in XPA cause classical Xeroderma pigmentosum disease. The extent to which XPA is required in the NER is still unclear. Here, we present the comparative study on the structural and conformational changes in globular DNA binding domain of XPA 98-210 in DNA bound and DNA free state. Atomistic molecular dynamics simulation was carried out for both XPA 98-210 systems using AMBER force fields. We observed that XPA 98-210 in presence of damaged DNA exhibited more structural changes compared to XPA 98-210 in its free form. When XPA is in contact with DNA, we found marked stability of the complex due to the formation of characteristic longer antiparallel β-sheets consisting mainly lysine residues.

Photocarcinogenesis and Skin Cancer Prevention Strategies.

PubMed

Seebode, Christina; Lehmann, Janin; Emmert, Steffen

2016-03-01

In this review the basic principles of UV-induced carcinogenesis are summarized and the state of the art diagnosis and therapeutic strategies are discussed. The prevalent keratinocyte-derived neoplasms of the skin are basal cell and squamous cell carcinomas. Cutaneous melanoma is less frequent but associated with high mortality. Common risk factors for all three tumor entities include sun exposure and DNA-repair deficiencies. Photocarcinogenesis follows a multistep model of cancer development in which ultraviolet-induced DNA damage leads to mutations resulting in activation of oncogenes or silencing of tumor-suppressor genes. This ends in a cellular mutator phenotype even more prone to mutation acquisition. DNA repair, especially the nucleotide excision repair (NER) pathway, counteracts mutation formation and skin cancer development. This is vividly demonstrated by the NER-defective disorder xeroderma pigmentosum. Primary skin cancer preventative strategies, therefore, include reduction of DNA photodamage by protection from the sun. Secondary preventative strategies include skin cancer screening. This implies standard examination techniques with the naked eye, an epiluminescence microscope, or digital epiluminescence microscopy. More advanced techniques include confocal laser scan microscopy. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Human XPA and RPA DNA repair proteins participate in specific recognition of triplex-induced helical distortions

NASA Astrophysics Data System (ADS)

Vasquez, Karen M.; Christensen, Jesper; Li, Lei; Finch, Rick A.; Glazer, Peter M.

2002-04-01

Nucleotide excision repair (NER) plays a central role in maintaining genomic integrity by detecting and repairing a wide variety of DNA lesions. Xeroderma pigmentosum complementation group A protein (XPA) is an essential component of the repair machinery, and it is thought to be involved in the initial step as a DNA damage recognition and/or confirmation factor. Human replication protein A (RPA) and XPA have been reported to interact to form a DNA damage recognition complex with greater specificity for damaged DNA than XPA alone. The mechanism by which these two proteins recognize such a wide array of structures resulting from different types of DNA damage is not known. One possibility is that they recognize a common feature of the lesions, such as distortions of the helical backbone. We have tested this idea by determining whether human XPA and RPA proteins can recognize the helical distortions induced by a DNA triple helix, a noncanonical DNA structure that has been shown to induce DNA repair, mutagenesis, and recombination. We measured binding of XPA and RPA, together or separately, to substrates containing triplexes with three, two, or no strands covalently linked by psoralen conjugation and photoaddition. We found that RPA alone recognizes all covalent triplex structures, but also forms multivalent nonspecific DNA aggregates at higher concentrations. XPA by itself does not recognize the substrates, but it binds them in the presence of RPA. Addition of XPA decreases the nonspecific DNA aggregate formation. These results support the hypothesis that the NER machinery is targeted to helical distortions and demonstrate that RPA can recognize damaged DNA even without XPA.

A framework for semisupervised feature generation and its applications in biomedical literature mining.

PubMed

Li, Yanpeng; Hu, Xiaohua; Lin, Hongfei; Yang, Zhihao

2011-01-01

Feature representation is essential to machine learning and text mining. In this paper, we present a feature coupling generalization (FCG) framework for generating new features from unlabeled data. It selects two special types of features, i.e., example-distinguishing features (EDFs) and class-distinguishing features (CDFs) from original feature set, and then generalizes EDFs into higher-level features based on their coupling degrees with CDFs in unlabeled data. The advantage is: EDFs with extreme sparsity in labeled data can be enriched by their co-occurrences with CDFs in unlabeled data so that the performance of these low-frequency features can be greatly boosted and new information from unlabeled can be incorporated. We apply this approach to three tasks in biomedical literature mining: gene named entity recognition (NER), protein-protein interaction extraction (PPIE), and text classification (TC) for gene ontology (GO) annotation. New features are generated from over 20 GB unlabeled PubMed abstracts. The experimental results on BioCreative 2, AIMED corpus, and TREC 2005 Genomics Track show that 1) FCG can utilize well the sparse features ignored by supervised learning. 2) It improves the performance of supervised baselines by 7.8 percent, 5.0 percent, and 5.8 percent, respectively, in the tree tasks. 3) Our methods achieve 89.1, 64.5 F-score, and 60.1 normalized utility on the three benchmark data sets.

DrugQuest - a text mining workflow for drug association discovery.

PubMed

Papanikolaou, Nikolas; Pavlopoulos, Georgios A; Theodosiou, Theodosios; Vizirianakis, Ioannis S; Iliopoulos, Ioannis

2016-06-06

Text mining and data integration methods are gaining ground in the field of health sciences due to the exponential growth of bio-medical literature and information stored in biological databases. While such methods mostly try to extract bioentity associations from PubMed, very few of them are dedicated in mining other types of repositories such as chemical databases. Herein, we apply a text mining approach on the DrugBank database in order to explore drug associations based on the DrugBank "Description", "Indication", "Pharmacodynamics" and "Mechanism of Action" text fields. We apply Name Entity Recognition (NER) techniques on these fields to identify chemicals, proteins, genes, pathways, diseases, and we utilize the TextQuest algorithm to find additional biologically significant words. Using a plethora of similarity and partitional clustering techniques, we group the DrugBank records based on their common terms and investigate possible scenarios why these records are clustered together. Different views such as clustered chemicals based on their textual information, tag clouds consisting of Significant Terms along with the terms that were used for clustering are delivered to the user through a user-friendly web interface. DrugQuest is a text mining tool for knowledge discovery: it is designed to cluster DrugBank records based on text attributes in order to find new associations between drugs. The service is freely available at http://bioinformatics.med.uoc.gr/drugquest .

Unsupervised Medical Entity Recognition and Linking in Chinese Online Medical Text

PubMed Central

Gan, Liang; Cheng, Mian; Wu, Quanyuan

2018-01-01

Online medical text is full of references to medical entities (MEs), which are valuable in many applications, including medical knowledge-based (KB) construction, decision support systems, and the treatment of diseases. However, the diverse and ambiguous nature of the surface forms gives rise to a great difficulty for ME identification. Many existing solutions have focused on supervised approaches, which are often task-dependent. In other words, applying them to different kinds of corpora or identifying new entity categories requires major effort in data annotation and feature definition. In this paper, we propose unMERL, an unsupervised framework for recognizing and linking medical entities mentioned in Chinese online medical text. For ME recognition, unMERL first exploits a knowledge-driven approach to extract candidate entities from free text. Then, the categories of the candidate entities are determined using a distributed semantic-based approach. For ME linking, we propose a collaborative inference approach which takes full advantage of heterogenous entity knowledge and unstructured information in KB. Experimental results on real corpora demonstrate significant benefits compared to recent approaches with respect to both ME recognition and linking. PMID:29849994

Pesticide nonextractable residue formation in soil: insights from inverse modeling of degradation time series.

PubMed

Loos, Martin; Krauss, Martin; Fenner, Kathrin

2012-09-18

Formation of soil nonextractable residues (NER) is central to the fate and persistence of pesticides. To investigate pools and extent of NER formation, an established inverse modeling approach for pesticide soil degradation time series was evaluated with a Monte Carlo Markov Chain (MCMC) sampling procedure. It was found that only half of 73 pesticide degradation time series from a homogeneous soil source allowed for well-behaved identification of kinetic parameters with a four-pool model containing a parent compound, a metabolite, a volatile, and a NER pool. A subsequent simulation indeed confirmed distinct parameter combinations of low identifiability. Taking the resulting uncertainties into account, several conclusions regarding NER formation and its impact on persistence assessment could nonetheless be drawn. First, rate constants for transformation of parent compounds to metabolites were correlated to those for transformation of parent compounds to NER, leading to degradation half-lives (DegT50) typically not being larger than disappearance half-lives (DT50) by more than a factor of 2. Second, estimated rate constants were used to evaluate NER formation over time. This showed that NER formation, particularly through the metabolite pool, may be grossly underestimated when using standard incubation periods. It further showed that amounts and uncertainties in (i) total NER, (ii) NER formed from the parent pool, and (iii) NER formed from the metabolite pool vary considerably among data sets at t→∞, with no clear dominance between (ii) and (iii). However, compounds containing aromatic amine moieties were found to form significantly more total NER when extrapolating to t→∞ than the other compounds studied. Overall, our study stresses the general need for assessing uncertainties, identifiability issues, and resulting biases when using inverse modeling of degradation time series for evaluating persistence and NER formation.

Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription.

PubMed

Nadkarni, Aditi; Burns, John A; Gandolfi, Alberto; Chowdhury, Moinuddin A; Cartularo, Laura; Berens, Christian; Geacintov, Nicholas E; Scicchitano, David A

2016-01-08

DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N(6)-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti-B[c]Ph-N(6)-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N(6)-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+)-trans-anti-B[a]P-N(6)-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti-B[c]Ph-N(6)-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Nucleotide Excision Repair and Transcription-coupled DNA Repair Abrogate the Impact of DNA Damage on Transcription*

PubMed Central

Nadkarni, Aditi; Burns, John A.; Gandolfi, Alberto; Chowdhury, Moinuddin A.; Cartularo, Laura; Berens, Christian; Geacintov, Nicholas E.; Scicchitano, David A.

2016-01-01

DNA adducts derived from carcinogenic polycyclic aromatic hydrocarbons like benzo[a]pyrene (B[a]P) and benzo[c]phenanthrene (B[c]Ph) impede replication and transcription, resulting in aberrant cell division and gene expression. Global nucleotide excision repair (NER) and transcription-coupled DNA repair (TCR) are among the DNA repair pathways that evolved to maintain genome integrity by removing DNA damage. The interplay between global NER and TCR in repairing the polycyclic aromatic hydrocarbon-derived DNA adducts (+)-trans-anti-B[a]P-N6-dA, which is subject to NER and blocks transcription in vitro, and (+)-trans-anti-B[c]Ph-N6-dA, which is a poor substrate for NER but also blocks transcription in vitro, was tested. The results show that both adducts inhibit transcription in human cells that lack both NER and TCR. The (+)-trans-anti-B[a]P-N6-dA lesion exhibited no detectable effect on transcription in cells proficient in NER but lacking TCR, indicating that NER can remove the lesion in the absence of TCR, which is consistent with in vitro data. In primary human cells lacking NER, (+)-trans-anti-B[a]P-N6-dA exhibited a deleterious effect on transcription that was less severe than in cells lacking both pathways, suggesting that TCR can repair the adduct but not as effectively as global NER. In contrast, (+)-trans-anti-B[c]Ph-N6-dA dramatically reduces transcript production in cells proficient in global NER but lacking TCR, indicating that TCR is necessary for the removal of this adduct, which is consistent with in vitro data showing that it is a poor substrate for NER. Hence, both global NER and TCR enhance the recovery of gene expression following DNA damage, and TCR plays an important role in removing DNA damage that is refractory to NER. PMID:26559971

Oxidative Damage to RPA Limits the Nucleotide Excision Repair Capacity of Human Cells.

PubMed

Guven, Melisa; Brem, Reto; Macpherson, Peter; Peacock, Matthew; Karran, Peter

2015-11-01

Nucleotide excision repair (NER) protects against sunlight-induced skin cancer. Defective NER is associated with photosensitivity and a high skin cancer incidence. Some clinical treatments that cause photosensitivity can also increase skin cancer risk. Among these, the immunosuppressant azathioprine and the fluoroquinolone antibiotics ciprofloxacin and ofloxacin interact with UVA radiation to generate reactive oxygen species that diminish NER capacity by causing protein damage. The replication protein A (RPA) DNA-binding protein has a pivotal role in DNA metabolism and is an essential component of NER. The relationship between protein oxidation and NER inhibition was investigated in cultured human cells expressing different levels of RPA. We show here that RPA is limiting for NER and that oxidative damage to RPA compromises NER capability. Our findings reveal that cellular RPA is surprisingly vulnerable to oxidation, and we identify oxidized forms of RPA that are associated with impaired NER. The vulnerability of NER to inhibition by oxidation provides a connection between cutaneous photosensitivity, protein damage, and increased skin cancer risk. Our findings emphasize that damage to DNA repair proteins, as well as to DNA itself, is likely to be an important contributor to skin cancer risk.

Inoculation of soil with an Isoproturon degrading microbial community reduced the pool of "real non-extractable" Isoproturon residues.

PubMed

Zhu, Xiaomin; Schroll, Reiner; Dörfler, Ulrike; Chen, Baoliang

2018-03-01

During pesticides degradation, biogenic non-extractable residues ("apparent NER") may not share the same environmental fate and risks with the "real NER" that are bound to soil matrix. It is not clear how microbial community (MC) inoculation for pesticides degradation would influence the NER composition. To investigate degradation efficiency of pesticides Isoproturon (IPU) and NER composition following MC inoculation, clay particles harboring MC that contains the IPU degrading strain, Sphingomonas sp., were inoculated into soil receiving 14 C-labeled IPU addition. Mineralization of IPU was greatly enhanced with MC inoculation that averagely 55.9% of the applied 14 C-IPU was consumed up into 14 CO 2 during 46 days soil incubation. Isoproturon degradation was more thorough with MC than that in the control: much less amount of metabolic products (4.6% of applied IPU) and NER (35.4%) formed in MC treatment, while the percentages were respectively 30.3% for metabolites and 49.8% for NER in the control. Composition of NER shifted with MC inoculation, that relatively larger amount of IPU was incorporated into the biogenic "apparent NER" in comparison with "real NER". Besides its well-recognized role on enhancing mineralization, MC inoculation with clay particles benefits soil pesticides remediation in term of reducing "real NER" formation, which has been previously underestimated. Copyright © 2017 Elsevier Inc. All rights reserved.

Nucleotide excision repair deficient mouse models and neurological disease

PubMed Central

Niedernhofer, Laura J.

2008-01-01

Nucleotide excision repair (NER) is a highly conserved mechanism to remove helix-distorting DNA base damage. A major substrate for NER is DNA damage caused by environmental genotoxins, most notably ultraviolet radiation. Xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy are three human diseases caused by inherited defects in NER. The symptoms and severity of these diseases vary dramatically, ranging from profound developmental delay to cancer predisposition and accelerated aging. All three syndromes include neurological disease, indicating an important role for NER in protecting against spontaneous DNA damage as well. To study the pathophysiology caused by DNA damage, numerous mouse models of NER deficiency were generated by knocking-out genes required for NER or knocking-in disease-causing human mutations. This review explores the utility of these mouse models to study neurological disease caused by NER deficiency. PMID:18272436

An annotated corpus with nanomedicine and pharmacokinetic parameters

PubMed Central

Lewinski, Nastassja A; Jimenez, Ivan; McInnes, Bridget T

2017-01-01

A vast amount of data on nanomedicines is being generated and published, and natural language processing (NLP) approaches can automate the extraction of unstructured text-based data. Annotated corpora are a key resource for NLP and information extraction methods which employ machine learning. Although corpora are available for pharmaceuticals, resources for nanomedicines and nanotechnology are still limited. To foster nanotechnology text mining (NanoNLP) efforts, we have constructed a corpus of annotated drug product inserts taken from the US Food and Drug Administration’s Drugs@FDA online database. In this work, we present the development of the Engineered Nanomedicine Database corpus to support the evaluation of nanomedicine entity extraction. The data were manually annotated for 21 entity mentions consisting of nanomedicine physicochemical characterization, exposure, and biologic response information of 41 Food and Drug Administration-approved nanomedicines. We evaluate the reliability of the manual annotations and demonstrate the use of the corpus by evaluating two state-of-the-art named entity extraction systems, OpenNLP and Stanford NER. The annotated corpus is available open source and, based on these results, guidelines and suggestions for future development of additional nanomedicine corpora are provided. PMID:29066897

The endoperoxide ascaridol shows strong differential cytotoxicity in nucleotide excision repair-deficient cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abbasi, Rashda; Efferth, Thomas; Kuhmann, Christine

2012-03-15

Targeting synthetic lethality in DNA repair pathways has become a promising anti-cancer strategy. However little is known about such interactions with regard to the nucleotide excision repair (NER) pathway. Therefore, cell lines with a defect in the NER genes ERCC6 or XPC and their normal counterparts were screened with 53 chemically defined phytochemicals isolated from plants used in traditional Chinese medicine for differential cytotoxic effects. The screening revealed 12 drugs that killed NER-deficient cells more efficiently than proficient cells. Five drugs were further analyzed for IC{sub 50} values, effects on cell cycle distribution, and induction of DNA damage. Ascaridol wasmore » the most effective compound with a difference of > 1000-fold in resistance between normal and NER-deficient cells (IC{sub 50} values for cells with deficiency in ERCC6: 0.15 μM, XPC: 0.18 μM, and normal cells: > 180 μM). NER-deficiency combined with ascaridol treatment led to G2/M-phase arrest, an increased percentage of subG1 cells, and a substantially higher DNA damage induction. These results were confirmed in a second set of NER-deficient and -proficient cell lines with isogenic background. Finally, ascaridol was characterized for its ability to generate oxidative DNA damage. The drug led to a dose-dependent increase in intracellular levels of reactive oxygen species at cytotoxic concentrations, but only NER-deficient cells showed a strongly induced amount of 8-oxodG sites. In summary, ascaridol is a cytotoxic and DNA-damaging compound which generates intracellular reactive oxidative intermediates and which selectively affects NER-deficient cells. This could provide a new therapeutic option to treat cancer cells with mutations in NER genes. -- Highlights: ► Thousand-fold higher Ascaridol activity in NER-deficient versus proficient cells. ► Impaired repair of Ascaridol-induced oxidative DNA damage in NER-deficient cells. ► Selective activity of Ascaridol opens new therapy options in NER-deficient tumors.« less

Binding of calcium and target peptide to calmodulin-like protein CML19, the centrin 2 of Arabidopsis thaliana.

PubMed

La Verde, Valentina; Trande, Matteo; D'Onofrio, Mariapina; Dominici, Paola; Astegno, Alessandra

2018-03-01

Calmodulin-like protein 19 (CML19) is an Arabidopsis centrin that modulates nucleotide excision repair (NER) by binding to RAD4 protein, the Arabidopsis homolog of human Xeroderma pigmentosum complementation group C protein. Although the necessity of CML19 as a part of the RAD4 plant recognition complex for functional NER is known at a cellular level, little is known at a molecular level. Herein, we used a combination of biophysical and biochemical approaches to investigate the structural and ion and target-peptide binding properties of CML19. We found that CML19 possesses four Ca 2+ -specific binding sites, two of high affinity in the N-terminal domain and two of low affinity in the C-terminal domain. Binding of Ca 2+ to CML19 increases its alpha-helix content, stabilizes the tertiary structure, and triggers a conformational change, resulting in the exposure of a hydrophobic patch instrumental for target protein recognition. Using bioinformatics tools we identified a CML19-binding site at the C-terminus of RAD4, and through in vitro binding experiments we analyzed the interaction between a 17-mer peptide representing this site and CML19. We found that the peptide shows a high affinity for CML19 in the presence of Ca 2+ (stoichiometry 1:1) and the interaction primarily involves the C-terminal half of CML19. Copyright © 2017 Elsevier B.V. All rights reserved.

Entity recognition in the biomedical domain using a hybrid approach.

PubMed

Basaldella, Marco; Furrer, Lenz; Tasso, Carlo; Rinaldi, Fabio

2017-11-09

This article describes a high-recall, high-precision approach for the extraction of biomedical entities from scientific articles. The approach uses a two-stage pipeline, combining a dictionary-based entity recognizer with a machine-learning classifier. First, the OGER entity recognizer, which has a bias towards high recall, annotates the terms that appear in selected domain ontologies. Subsequently, the Distiller framework uses this information as a feature for a machine learning algorithm to select the relevant entities only. For this step, we compare two different supervised machine-learning algorithms: Conditional Random Fields and Neural Networks. In an in-domain evaluation using the CRAFT corpus, we test the performance of the combined systems when recognizing chemicals, cell types, cellular components, biological processes, molecular functions, organisms, proteins, and biological sequences. Our best system combines dictionary-based candidate generation with Neural-Network-based filtering. It achieves an overall precision of 86% at a recall of 60% on the named entity recognition task, and a precision of 51% at a recall of 49% on the concept recognition task. These results are to our knowledge the best reported so far in this particular task.

Chemical named entities recognition: a review on approaches and applications

PubMed Central

2014-01-01

The rapid increase in the flow rate of published digital information in all disciplines has resulted in a pressing need for techniques that can simplify the use of this information. The chemistry literature is very rich with information about chemical entities. Extracting molecules and their related properties and activities from the scientific literature to “text mine” these extracted data and determine contextual relationships helps research scientists, particularly those in drug development. One of the most important challenges in chemical text mining is the recognition of chemical entities mentioned in the texts. In this review, the authors briefly introduce the fundamental concepts of chemical literature mining, the textual contents of chemical documents, and the methods of naming chemicals in documents. We sketch out dictionary-based, rule-based and machine learning, as well as hybrid chemical named entity recognition approaches with their applied solutions. We end with an outlook on the pros and cons of these approaches and the types of chemical entities extracted. PMID:24834132

Chemical named entities recognition: a review on approaches and applications.

PubMed

Eltyeb, Safaa; Salim, Naomie

2014-01-01

The rapid increase in the flow rate of published digital information in all disciplines has resulted in a pressing need for techniques that can simplify the use of this information. The chemistry literature is very rich with information about chemical entities. Extracting molecules and their related properties and activities from the scientific literature to "text mine" these extracted data and determine contextual relationships helps research scientists, particularly those in drug development. One of the most important challenges in chemical text mining is the recognition of chemical entities mentioned in the texts. In this review, the authors briefly introduce the fundamental concepts of chemical literature mining, the textual contents of chemical documents, and the methods of naming chemicals in documents. We sketch out dictionary-based, rule-based and machine learning, as well as hybrid chemical named entity recognition approaches with their applied solutions. We end with an outlook on the pros and cons of these approaches and the types of chemical entities extracted.

Disruption of nucleotide excision repair by the human T-cell leukemia virus type 1 Tax protein.

PubMed

Kao, S Y; Marriott, S J

1999-05-01

The Tax protein of human T-cell leukemia virus type 1 (HTLV-1) is a transcriptional transactivator and viral oncogene. Since cellular transformation has been frequently linked to alterations in genome stability, we investigated the effect of Tax on nucleotide excision repair (NER), a prominent cellular DNA repair pathway. Cells expressing Tax exhibited a reduced capacity for NER as measured by unscheduled DNA synthesis and host cell reactivation assays. The cellular proliferating cell nuclear antigen (PCNA) gene product regulates DNA replication and repair pathways, including NER. Since Tax activates transcription of the PCNA promoter, we investigated whether this activity contributes to the reduction of NER. Tax increased endogenous PCNA protein expression, and analysis of Tax mutant proteins demonstrated that the reduction in NER correlated with Tax transactivation of PCNA gene expression. Direct overexpression of PCNA also reduced NER. We propose that overexpression of PCNA, and disruption of NER induced by Tax, predisposes cells to accumulate DNA damage and contributes to HTLV-1 transformation.

Effect of point substitutions within the minimal DNA-binding domain of xeroderma pigmentosum group A protein on interaction with DNA intermediates of nucleotide excision repair.

PubMed

Maltseva, E A; Krasikova, Y S; Naegeli, H; Lavrik, O I; Rechkunova, N I

2014-06-01

Xeroderma pigmentosum factor A (XPA) is one of the key proteins in the nucleotide excision repair (NER) process. The effects of point substitutions in the DNA-binding domain of XPA (positively charged lysine residues replaced by negatively charged glutamate residues: XPA K204E, K179E, K141E, and tandem mutant K141E/K179E) on the interaction of the protein with DNA structures modeling intermediates of the damage recognition and pre-incision stages in NER were analyzed. All these mutations decreased the affinity of the protein to DNA, the effect depending on the substitution and the DNA structure. The mutant as well as wild-type proteins bind with highest efficiency partly open damaged DNA duplex, and the affinity of the mutants to this DNA is reduced in the order: K204E > K179E > K141E = K141/179E. For all the mutants, decrease in DNA binding efficiency was more pronounced in the case of full duplex and single-stranded DNA than with bubble-DNA structure, the difference between protein affinities to different DNA structures increasing as DNA binding activity of the mutant decreased. No effect of the studied XPA mutations on the location of the protein on the partially open DNA duplex was observed using photoinduced crosslinking with 5-I-dUMP in different positions of the damaged DNA strand. These results combined with earlier published data suggest no direct correlation between DNA binding and activity in NER for these XPA mutants.

Functional Analysis of Nuclear Estrogen Receptors in Zebrafish Reproduction by Genome Editing Approach.

PubMed

Lu, Huijie; Cui, Yong; Jiang, Liwen; Ge, Wei

2017-07-01

Estrogens signal through both nuclear and membrane receptors with most reported effects being mediated via the nuclear estrogen receptors (nERs). Although much work has been reported on nERs in the zebrafish, there is a lack of direct genetic evidence for their functional roles and importance in reproduction. To address this issue, we undertook this study to disrupt all three nERs in the zebrafish, namely esr1 (ERα), esr2a (ERβII), and esr2b (ERβI), by the genome-editing technology clustered regularly interspaced short palindromic repeats and its associated nuclease (CRISPR/Cas9). Using this loss-of-function genetic approach, we successfully created three mutant zebrafish lines with each nER knocked out. In addition, we also generated all possible double and triple knockouts of the three nERs. The phenotypes of these mutants in reproduction were analyzed in all single, double, and triple nER knockouts in both females and males. Surprisingly, all three single nER mutant fish lines display normal reproductive development and function in both females and males, suggesting functional redundancy among these nERs. Further analysis of double and triple knockouts showed that nERs, especially Esr2a and Esr2b, were essential for female reproduction, and loss of these two nERs led to an arrest of folliculogenesis at previtellogenic stage II followed by sex reversal from female to male. In addition, the current study also revealed a unique role for Esr2a in follicle cell proliferation and transdifferentiation, follicle growth, and chorion formation. Taken together, this study provides the most comprehensive genetic analysis for differential functions of esr1, esr2a, and esr2b in fish reproduction. Copyright © 2017 Endocrine Society.

NDR1 modulates the UV-induced DNA-damage checkpoint and nucleotide excision repair

DOE Office of Scientific and Technical Information (OSTI.GOV)

Park, Jeong-Min; Choi, Ji Ye; Yi, Joo Mi

2015-06-05

Nucleotide excision repair (NER) is the sole mechanism of UV-induced DNA lesion repair in mammals. A single round of NER requires multiple components including seven core NER factors, xeroderma pigmentosum A–G (XPA–XPG), and many auxiliary effector proteins including ATR serine/threonine kinase. The XPA protein helps to verify DNA damage and thus plays a rate-limiting role in NER. Hence, the regulation of XPA is important for the entire NER kinetic. We found that NDR1, a novel XPA-interacting protein, modulates NER by modulating the UV-induced DNA-damage checkpoint. In quiescent cells, NDR1 localized mainly in the cytoplasm. After UV irradiation, NDR1 accumulated inmore » the nucleus. The siRNA knockdown of NDR1 delayed the repair of UV-induced cyclobutane pyrimidine dimers in both normal cells and cancer cells. It did not, however, alter the expression levels or the chromatin association levels of the core NER factors following UV irradiation. Instead, the NDR1-depleted cells displayed reduced activity of ATR for some set of its substrates including CHK1 and p53, suggesting that NDR1 modulates NER indirectly via the ATR pathway. - Highlights: • NDR1 is a novel XPA-interacting protein. • NDR1 accumulates in the nucleus in response to UV irradiation. • NDR1 modulates NER (nucleotide excision repair) by modulating the UV-induced DNA-damage checkpoint response.« less

Classification and modelling of non-extractable residue (NER) formation from xenobiotics in soil - a synthesis

NASA Astrophysics Data System (ADS)

Kaestner, Matthias; Nowak, Karolina; Miltner, Anja; Trapp, Stefan; Schaeffer, Andreas

2014-05-01

This presentation provides a comprehensive overview about the formation of non-extractable residues (NER) from organic pesticides and contaminants in soil and tries classifying the different types. Anthropogenic organic chemicals are deliberately (e.g. pesticides) or unintentionally (e.g. polyaromatic hydrocarbons [PAH], chlorinated solvents, pharmaceuticals) released in major amounts to nearly all compartments of the environment. Soils and sediments as complex matrices provide a wide variety of binding sites and are the major sinks for these compounds. Many of the xenobiotics entering soil undergo turnover processes and can be volatilised, leached to the groundwater, degraded by microorganisms or taken up and enriched by living organisms. Xenobiotic NER may be derived from parent compounds and primary metabolites that are sequestered (sorbed or entrapped) within the soil organic matter (type I NER) or can be covalently bound (type II NER). Especially type I NER may pose a considerably environmental risk of potential release. However, NER resulting from productive biodegradation, which means the conversion of carbon (or nitrogen) from the compounds into microbial biomass molecules during microbial degradation (type III, bioNER), do not pose any risk. Experimental and analytical approaches to clearly distinguish between the types are provided and a model to prospectively estimate their fate in soil is proposed.

Active learning for ontological event extraction incorporating named entity recognition and unknown word handling.

PubMed

Han, Xu; Kim, Jung-jae; Kwoh, Chee Keong

2016-01-01

Biomedical text mining may target various kinds of valuable information embedded in the literature, but a critical obstacle to the extension of the mining targets is the cost of manual construction of labeled data, which are required for state-of-the-art supervised learning systems. Active learning is to choose the most informative documents for the supervised learning in order to reduce the amount of required manual annotations. Previous works of active learning, however, focused on the tasks of entity recognition and protein-protein interactions, but not on event extraction tasks for multiple event types. They also did not consider the evidence of event participants, which might be a clue for the presence of events in unlabeled documents. Moreover, the confidence scores of events produced by event extraction systems are not reliable for ranking documents in terms of informativity for supervised learning. We here propose a novel committee-based active learning method that supports multi-event extraction tasks and employs a new statistical method for informativity estimation instead of using the confidence scores from event extraction systems. Our method is based on a committee of two systems as follows: We first employ an event extraction system to filter potential false negatives among unlabeled documents, from which the system does not extract any event. We then develop a statistical method to rank the potential false negatives of unlabeled documents 1) by using a language model that measures the probabilities of the expression of multiple events in documents and 2) by using a named entity recognition system that locates the named entities that can be event arguments (e.g. proteins). The proposed method further deals with unknown words in test data by using word similarity measures. We also apply our active learning method for the task of named entity recognition. We evaluate the proposed method against the BioNLP Shared Tasks datasets, and show that our method can achieve better performance than such previous methods as entropy and Gibbs error based methods and a conventional committee-based method. We also show that the incorporation of named entity recognition into the active learning for event extraction and the unknown word handling further improve the active learning method. In addition, the adaptation of the active learning method into named entity recognition tasks also improves the document selection for manual annotation of named entities.

Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text.

PubMed

Eriksson, Robert; Jensen, Peter Bjødstrup; Frankild, Sune; Jensen, Lars Juhl; Brunak, Søren

2013-01-01

Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible adverse drug events (ADEs). Based on the undesirable effects section from the summary of product characteristics (SPC) of 7446 drugs, we have built a Danish ADE dictionary. Starting from this dictionary we have developed a pipeline for identifying possible ADEs in unstructured clinical narrative text. We use a named entity recognition (NER) tagger to identify dictionary matches in the text and post-coordination rules to construct ADE compound terms. Finally, we apply post-processing rules and filters to handle, for example, negations and sentences about subjects other than the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location. The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient records. Validation was performed through manual inspection of possible ADEs, resulting in precision of 89% and recall of 75%. The presented dictionary-building method could be used to construct other ADE dictionaries. The complication of compound words in Germanic languages was addressed. Additionally, the synonym and anatomical location collapse improve the method. The developed dictionary and method can be used to identify possible ADEs in Danish clinical narratives.

Spatial variations in isostatic compensation mechanisms of the Ninetyeast Ridge and their tectonic significance

NASA Astrophysics Data System (ADS)

Sreejith, K. M.; Krishna, K. S.

2013-10-01

Ninetyeast Ridge (NER), one of the longest linear volcanic features on the Earth, offers an excellent opportunity of understanding the isostatic response to the interactions of mantle plume with the migrating mid-ocean ridge. Bathymetry, geoid, and gravity (shipborne and satellite) data along 72 closely spaced transects and 17 overlapping grids on the NER are analyzed and modeled to determine the effective elastic thickness (Te) beneath the entire ridge. The results of 2-D and 3-D flexural modeling of the NER show large spatial variations in Te values ranging from 4 to 35 km, suggesting that the ridge was compensated along its length by different isostatic mechanisms. The southern (south of 22°S latitude) and northern (north of 2°N latitude) parts of the NER have Te values of >10 and >23 km, respectively, revealing that the southern part was emplaced on a lithosphere of intermediate strength possibly on flank of the Indian plate, whereas the northern part was emplaced in an intraplate setting. In contrast, in the central part of the NER (between latitudes 22°S and 2°N), highly variable Te values (4-22 km) are estimated. The scattered Te values in the central NER suggest that this part may have evolved due to the occurrence of frequent ridge jumps caused by the interaction of Kerguelen hot spot with rapid northward migration of the Wharton spreading ridge. Residual Mantle Bouguer Anomaly (RMBA) map of the NER and adjacent basins reveals that the entire length of the NER is associated with a significant negative anomaly up to 200 mGal, indicating the presence of thickened crust or less dense mantle beneath the ridge. 3-D crustal thickness map of the NER, generated by inversion of the RMBA data, shows a thick crust ranging from 15 to 19 km. The present study clearly shows that NER possesses a highly segmented isostatic pattern with the occurrence of subcrustal underplating or subsurface loading.

True Lies: The Double Life of the Nucleotide Excision Repair Factors in Transcription and DNA Repair

PubMed Central

Le May, Nicolas; Egly, Jean-Marc; Coin, Frédéric

2010-01-01

Nucleotide excision repair (NER) is a major DNA repair pathway in eukaryotic cells. NER removes structurally diverse lesions such as pyrimidine dimers, arising upon UV irradiation or bulky chemical adducts, arising upon exposure to carcinogens and some chemotherapeutic drugs. NER defects lead to three genetic disorders that result in predisposition to cancers, accelerated aging, neurological and developmental defects. During NER, more than 30 polypeptides cooperate to recognize, incise, and excise a damaged oligonucleotide from the genomic DNA. Recent papers reveal an additional and unexpected role for the NER factors. In the absence of a genotoxic attack, the promoters of RNA polymerases I- and II-dependent genes recruit XPA, XPC, XPG, and XPF to initiate gene expression. A model that includes the growth arrest and DNA damage 45α protein (Gadd45α) and the NER factors, in order to maintain the promoter of active genes under a hypomethylated state, has been proposed but remains controversial. This paper focuses on the double life of the NER factors in DNA repair and transcription and describes the possible roles of these factors in the RNA synthesis process. PMID:20725631

Nucleotide excision repair is a potential therapeutic target in multiple myeloma

PubMed Central

Szalat, R; Samur, M K; Fulciniti, M; Lopez, M; Nanjappa, P; Cleynen, A; Wen, K; Kumar, S; Perini, T; Calkins, A S; Reznichenko, E; Chauhan, D; Tai, Y-T; Shammas, M A; Anderson, K C; Fermand, J-P; Arnulf, B; Avet-Loiseau, H; Lazaro, J-B; Munshi, N C

2018-01-01

Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents and therefore we here evaluate the role of nucleotide excision repair (NER), which is involved in the removal of bulky adducts and DNA crosslinks in MM. We first evaluated NER activity using a novel functional assay and observed a heterogeneous NER efficiency in MM cell lines and patient samples. Using next-generation sequencing data, we identified that expression of the canonical NER gene, excision repair cross-complementation group 3 (ERCC3), significantly impacted the outcome in newly diagnosed MM patients treated with alkylating agents. Next, using small RNA interference, stable knockdown and overexpression, and small-molecule inhibitors targeting xeroderma pigmentosum complementation group B (XPB), the DNA helicase encoded by ERCC3, we demonstrate that NER inhibition significantly increases sensitivity and overcomes resistance to alkylating agents in MM. Moreover, inhibiting XPB leads to the dual inhibition of NER and transcription and is particularly efficient in myeloma cells. Altogether, we show that NER impacts alkylating agents sensitivity in myeloma cells and identify ERCC3 as a potential therapeutic target in MM. PMID:28588253

LeadMine: a grammar and dictionary driven approach to entity recognition.

PubMed

Lowe, Daniel M; Sayle, Roger A

2015-01-01

Chemical entity recognition has traditionally been performed by machine learning approaches. Here we describe an approach using grammars and dictionaries. This approach has the advantage that the entities found can be directly related to a given grammar or dictionary, which allows the type of an entity to be known and, if an entity is misannotated, indicates which resource should be corrected. As recognition is driven by what is expected, if spelling errors occur, they can be corrected. Correcting such errors is highly useful when attempting to lookup an entity in a database or, in the case of chemical names, converting them to structures. Our system uses a mixture of expertly curated grammars and dictionaries, as well as dictionaries automatically derived from public resources. We show that the heuristics developed to filter our dictionary of trivial chemical names (from PubChem) yields a better performing dictionary than the previously published Jochem dictionary. Our final system performs post-processing steps to modify the boundaries of entities and to detect abbreviations. These steps are shown to significantly improve performance (2.6% and 4.0% F1-score respectively). Our complete system, with incremental post-BioCreative workshop improvements, achieves 89.9% precision and 85.4% recall (87.6% F1-score) on the CHEMDNER test set. Grammar and dictionary approaches can produce results at least as good as the current state of the art in machine learning approaches. While machine learning approaches are commonly thought of as "black box" systems, our approach directly links the output entities to the input dictionaries and grammars. Our approach also allows correction of errors in detected entities, which can assist with entity resolution.

LeadMine: a grammar and dictionary driven approach to entity recognition

PubMed Central

2015-01-01

Background Chemical entity recognition has traditionally been performed by machine learning approaches. Here we describe an approach using grammars and dictionaries. This approach has the advantage that the entities found can be directly related to a given grammar or dictionary, which allows the type of an entity to be known and, if an entity is misannotated, indicates which resource should be corrected. As recognition is driven by what is expected, if spelling errors occur, they can be corrected. Correcting such errors is highly useful when attempting to lookup an entity in a database or, in the case of chemical names, converting them to structures. Results Our system uses a mixture of expertly curated grammars and dictionaries, as well as dictionaries automatically derived from public resources. We show that the heuristics developed to filter our dictionary of trivial chemical names (from PubChem) yields a better performing dictionary than the previously published Jochem dictionary. Our final system performs post-processing steps to modify the boundaries of entities and to detect abbreviations. These steps are shown to significantly improve performance (2.6% and 4.0% F1-score respectively). Our complete system, with incremental post-BioCreative workshop improvements, achieves 89.9% precision and 85.4% recall (87.6% F1-score) on the CHEMDNER test set. Conclusions Grammar and dictionary approaches can produce results at least as good as the current state of the art in machine learning approaches. While machine learning approaches are commonly thought of as "black box" systems, our approach directly links the output entities to the input dictionaries and grammars. Our approach also allows correction of errors in detected entities, which can assist with entity resolution. PMID:25810776

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shahrukh, Hassan; Oyedun, Adetoyese Olajire; Kumar, Amit

In this study, a process model was developed to determine the net energy ratio (NER) for both regular and steam-pretreated pellet production from ligno-cellulosic biomass. NER is a ratio of the net energy output to the total net energy input from non-renewable energy source into the system. Scenarios were developed to measure the effect of temperature and level of steam pretreatment on the NER of both production processes. The NER for the base case at 6 kg h –1 is 1.29 and 5.0 for steam-pretreated and regular pellet production respectively. However, at the large scale NER would improve. The majormore » factor for NER is energy for steam and drying unit. The sensitivity analysis for the model shows that the optimum temperature for steam pretreatment is 200 °C with 50% pretreatment (Steam pretreating 50% feed stock, while the rest is undergoing regular pelletization). Uncertainty result for steam pretreated and regular pellet is 1.35 ± 0.09 and 4.52 ± 0.34 respectively.« less

Phosphorylation of XPB helicase regulates TFIIH nucleotide excision repair activity

PubMed Central

Coin, Frédéric; Auriol, Jérome; Tapias, Angel; Clivio, Pascale; Vermeulen, Wim; Egly, Jean-Marc

2004-01-01

Nucleotide excision repair (NER) removes damage from DNA in a tightly regulated multiprotein process. The xeroderma pigmentosum group B (XPB) helicase subunit of TFIIH functions in NER and transcription. The serine 751 (S751) residue of XPB was found to be phosphorylated in vivo. This phosphorylation inhibits NER and the microinjection of a phosphomimicking XPB-S751E mutant is unable to correct the NER defect of XP-B cells. Conversely, XPB-S751 dephosphorylation or its substitution with alanine (S751A) restores NER both in vivo and in vitro. Surprisingly, phospho/dephosphorylation of S751 spares TFIIH-dependent transcription. Finally, the phosphorylation of XPB-S751 does not impair the TFIIH unwinding of the DNA around the lesion, but rather prevents the 5′ incision triggered by the ERCC1-XPF endonuclease. These data support an additional role for XPB in promoting the incision of the damaged fragment and reveal a point of NER regulation on TFIIH without interference in its transcription activity. PMID:15549133

Overview of xeroderma pigmentosum proteins architecture, mutations and post-translational modifications.

PubMed

Feltes, Bruno César; Bonatto, Diego

2015-01-01

The xeroderma pigmentosum complementation group proteins (XPs), which include XPA through XPG, play a critical role in coordinating and promoting global genome and transcription-coupled nucleotide excision repair (GG-NER and TC-NER, respectively) pathways in eukaryotic cells. GG-NER and TC-NER are both required for the repair of bulky DNA lesions, such as those induced by UV radiation. Mutations in genes that encode XPs lead to the clinical condition xeroderma pigmentosum (XP). Although the roles of XPs in the GG-NER/TC-NER subpathways have been extensively studied, complete knowledge of their three-dimensional structure is only beginning to emerge. Hence, this review aims to summarize the current knowledge of mapped mutations and other structural information on XP proteins that influence their function and protein-protein interactions. We also review the possible post-translational modifications for each protein and the impact of these modifications on XP protein functions. Copyright © 2014 Elsevier B.V. All rights reserved.

A human XPC protein interactome--a resource.

PubMed

Lubin, Abigail; Zhang, Ling; Chen, Hua; White, Victoria M; Gong, Feng

2013-12-23

Global genome nucleotide excision repair (GG-NER) is responsible for identifying and removing bulky adducts from non-transcribed DNA that result from damaging agents such as UV radiation and cisplatin. Xeroderma pigmentosum complementation group C (XPC) is one of the essential damage recognition proteins of the GG-NER pathway and its dysfunction results in xeroderma pigmentosum (XP), a disorder involving photosensitivity and a predisposition to cancer. To better understand the identification of DNA damage by XPC in the context of chromatin and the role of XPC in the pathogenesis of XP, we characterized the interactome of XPC using a high throughput yeast two-hybrid screening. Our screening showed 49 novel interactors of XPC involved in DNA repair and replication, proteolysis and post-translational modifications, transcription regulation, signal transduction, and metabolism. Importantly, we validated the XPC-OTUD4 interaction by co-IP and provided evidence that OTUD4 knockdown in human cells indeed affects the levels of ubiquitinated XPC, supporting a hypothesis that the OTUD4 deubiquitinase is involved in XPC recycling by cleaving the ubiquitin moiety. This high-throughput characterization of the XPC interactome provides a resource for future exploration and suggests that XPC may have many uncharacterized cellular functions.

Poly(ADP-ribose) polymerase 1 escorts XPC to UV-induced DNA lesions during nucleotide excision repair

PubMed Central

Robu, Mihaela; Shah, Rashmi G.; Purohit, Nupur K.; Zhou, Pengbo; Naegeli, Hanspeter

2017-01-01

Xeroderma pigmentosum C (XPC) protein initiates the global genomic subpathway of nucleotide excision repair (GG-NER) for removal of UV-induced direct photolesions from genomic DNA. The XPC has an inherent capacity to identify and stabilize at the DNA lesion sites, and this function is facilitated in the genomic context by UV-damaged DNA-binding protein 2 (DDB2), which is part of a multiprotein UV–DDB ubiquitin ligase complex. The nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP1) has been shown to facilitate the lesion recognition step of GG-NER via its interaction with DDB2 at the lesion site. Here, we show that PARP1 plays an additional DDB2-independent direct role in recruitment and stabilization of XPC at the UV-induced DNA lesions to promote GG-NER. It forms a stable complex with XPC in the nucleoplasm under steady-state conditions before irradiation and rapidly escorts it to the damaged DNA after UV irradiation in a DDB2-independent manner. The catalytic activity of PARP1 is not required for the initial complex formation with XPC in the nucleoplasm but it enhances the recruitment of XPC to the DNA lesion site after irradiation. Using purified proteins, we also show that the PARP1–XPC complex facilitates the handover of XPC to the UV-lesion site in the presence of the UV–DDB ligase complex. Thus, the lesion search function of XPC in the genomic context is controlled by XPC itself, DDB2, and PARP1. Our results reveal a paradigm that the known interaction of many proteins with PARP1 under steady-state conditions could have functional significance for these proteins. PMID:28760956

Poly(ADP-ribose) polymerase 1 escorts XPC to UV-induced DNA lesions during nucleotide excision repair.

PubMed

Robu, Mihaela; Shah, Rashmi G; Purohit, Nupur K; Zhou, Pengbo; Naegeli, Hanspeter; Shah, Girish M

2017-08-15

Xeroderma pigmentosum C (XPC) protein initiates the global genomic subpathway of nucleotide excision repair (GG-NER) for removal of UV-induced direct photolesions from genomic DNA. The XPC has an inherent capacity to identify and stabilize at the DNA lesion sites, and this function is facilitated in the genomic context by UV-damaged DNA-binding protein 2 (DDB2), which is part of a multiprotein UV-DDB ubiquitin ligase complex. The nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP1) has been shown to facilitate the lesion recognition step of GG-NER via its interaction with DDB2 at the lesion site. Here, we show that PARP1 plays an additional DDB2-independent direct role in recruitment and stabilization of XPC at the UV-induced DNA lesions to promote GG-NER. It forms a stable complex with XPC in the nucleoplasm under steady-state conditions before irradiation and rapidly escorts it to the damaged DNA after UV irradiation in a DDB2-independent manner. The catalytic activity of PARP1 is not required for the initial complex formation with XPC in the nucleoplasm but it enhances the recruitment of XPC to the DNA lesion site after irradiation. Using purified proteins, we also show that the PARP1-XPC complex facilitates the handover of XPC to the UV-lesion site in the presence of the UV-DDB ligase complex. Thus, the lesion search function of XPC in the genomic context is controlled by XPC itself, DDB2, and PARP1. Our results reveal a paradigm that the known interaction of many proteins with PARP1 under steady-state conditions could have functional significance for these proteins.

Unsupervised Biomedical Named Entity Recognition: Experiments with Clinical and Biological Texts

PubMed Central

Zhang, Shaodian; Elhadad, Nóemie

2013-01-01

Named entity recognition is a crucial component of biomedical natural language processing, enabling information extraction and ultimately reasoning over and knowledge discovery from text. Much progress has been made in the design of rule-based and supervised tools, but they are often genre and task dependent. As such, adapting them to different genres of text or identifying new types of entities requires major effort in re-annotation or rule development. In this paper, we propose an unsupervised approach to extracting named entities from biomedical text. We describe a stepwise solution to tackle the challenges of entity boundary detection and entity type classification without relying on any handcrafted rules, heuristics, or annotated data. A noun phrase chunker followed by a filter based on inverse document frequency extracts candidate entities from free text. Classification of candidate entities into categories of interest is carried out by leveraging principles from distributional semantics. Experiments show that our system, especially the entity classification step, yields competitive results on two popular biomedical datasets of clinical notes and biological literature, and outperforms a baseline dictionary match approach. Detailed error analysis provides a road map for future work. PMID:23954592

Cloning of a human homolog of the yeast nucleotide excision repair gene MMS19 and interaction with transcription repair factor TFIIH via the XPB and XPD helicases.

PubMed

Seroz, T; Winkler, G S; Auriol, J; Verhage, R A; Vermeulen, W; Smit, B; Brouwer, J; Eker, A P; Weeda, G; Egly, J M; Hoeijmakers, J H

2000-11-15

Nucleotide excision repair (NER) removes UV-induced photoproducts and numerous other DNA lesions in a highly conserved 'cut-and-paste' reaction that involves approximately 25 core components. In addition, several other proteins have been identified which are dispensable for NER in vitro but have an undefined role in vivo and may act at the interface of NER and other cellular processes. An intriguing example is the Saccharomyces cerevisiae Mms19 protein that has an unknown dual function in NER and RNA polymerase II transcription. Here we report the cloning and characterization of a human homolog, designated hMMS19, that encodes a 1030 amino acid protein with 26% identity and 51% similarity to S.cerevisiae Mms19p and with a strikingly similar size. The expression profile and nuclear location are consistent with a repair function. Co-immunoprecipitation experiments revealed that hMMS19 directly interacts with the XPB and XPD subunits of NER-transcription factor TFIIH. These findings extend the conservation of the NER apparatus and the link between NER and basal transcription and suggest that hMMS19 exerts its function in repair and transcription by interacting with the XPB and XPD helicases.

Regulation and disregulation of mammalian nucleotide excision repair: A pathway to nongermline breast carcinogenesis

DOE PAGES

Latimer, Jean J.; Majekwana, Vongai J.; Pabon-Padin, Yashira R.; ...

2014-12-19

Nucleotide excision repair (NER) is important as a modulator of disease, especially in constitutive deficiencies, such as the cancer predisposition syndrome Xeroderma pigmentosum. We have found profound variation of NER capacity among normal individuals, between cell-types and during carcinogenesis. NER is a repair system for many types of DNA damage, and therefore many types of genotoxic carcinogenic exposures, including ultraviolet light, products of organic combustion, metals, oxidative stress, etc. Since NER is intimately related to cellular metabolism, requiring components of both the DNA replicative and transcription machinery, it has a narrow range of functional viability. Thus, genes in the NERmore » pathway are expressed at the low levels manifested by, for example, nuclear transcription factors. Since NER activity and gene expression vary by cell-type, it is inherently epigenetically regulated. Furthermore, this epigenetic regulation is disregulated during sporadic breast carcinogenesis. Loss of NER is one basis of genomic instability, a required element in cellular transformation, and one that potentially modulates response to therapy. In this article, we demonstrate differences in NER capacity in eight adult mouse tissues, and place this result into the context of our previous work on mouse extraembryonic tissues, normal human tissues and sporadic early stage human breast cancer.« less

Repair-Resistant DNA Lesions

PubMed Central

2017-01-01

The eukaryotic global genomic nucleotide excision repair (GG-NER) pathway is the major mechanism that removes most bulky and some nonbulky lesions from cellular DNA. There is growing evidence that certain DNA lesions are repaired slowly or are entirely resistant to repair in cells, tissues, and in cell extract model assay systems. It is well established that the eukaryotic DNA lesion-sensing proteins do not detect the damaged nucleotide, but recognize the distortions/destabilizations in the native DNA structure caused by the damaged nucleotides. In this article, the nature of the structural features of certain bulky DNA lesions that render them resistant to NER, or cause them to be repaired slowly, is compared to that of those that are good-to-excellent NER substrates. Understanding the structural features that distinguish NER-resistant DNA lesions from good NER substrates may be useful for interpreting the biological significance of biomarkers of exposure of human populations to genotoxic environmental chemicals. NER-resistant lesions can survive to replication and cause mutations that can initiate cancer and other diseases. Furthermore, NER diminishes the efficacy of certain chemotherapeutic drugs, and the design of more potent pharmaceuticals that resist repair can be advanced through a better understanding of the structural properties of DNA lesions that engender repair-resistance. PMID:28750166

Segregation of anterior temporal regions critical for retrieving names of unique and nonunique entities reflects underlying long-range connectivity

PubMed Central

Mehta, Sonya; Inoue, Kayo; Rudrauf, David; Damasio, Hanna; Tranel, Daniel; Grabowski, Thomas

2015-01-01

Lesion-deficit studies support the hypothesis that the left anterior temporal lobe (ATL) plays a critical role in retrieving names of concrete entities. They further suggest that different regions of the left ATL process different conceptual categories. Here we test the specificity of these relationships and whether the anatomical segregation is related to the underlying organization of white matter connections. We reanalyzed data from a previous lesion study of naming and recognition across five categories of concrete entities. In voxelwise logistic regressions of lesion-deficit associations, we formally incorporated measures of disconnection of long-range association fiber tracts (FTs) and covaried for recognition and non-category specific naming deficits. We also performed fiber tractwise analyses to assess whether damage to specific FTs was preferentially associated with category-selective naming deficits. Damage to the basolateral ATL was associated with naming deficits for both unique (famous faces) and non-unique entities, whereas the damage to the temporal pole was associated with naming deficits for unique entities only. This segregation pattern remained after accounting for comorbid recognition deficits or naming deficits in other categories. The tractwise analyses showed that damage to the uncinate fasciculus was associated with naming impairments for unique entities, while damage to the inferior longitudinal fasciculus was associated with naming impairments for non-unique entities. Covarying for FT transection in voxelwise analyses rendered the cortical association for unique entities more focal. These results are consistent with the partial segregation of brain system support for name retrieval of unique and non-unique entities at both the level of cortical components and underlying white matter fiber bundles. Our study reconciles theoretic accounts of the functional organization of the left ATL by revealing both category-related processing and semantic hub sectors. PMID:26707082

Net energy ratio for the production of steam pretreated biomass-based pellets

DOE PAGES

Shahrukh, Hassan; Oyedun, Adetoyese Olajire; Kumar, Amit; ...

2015-06-21

In this study, a process model was developed to determine the net energy ratio (NER) for both regular and steam-pretreated pellet production from ligno-cellulosic biomass. NER is a ratio of the net energy output to the total net energy input from non-renewable energy source into the system. Scenarios were developed to measure the effect of temperature and level of steam pretreatment on the NER of both production processes. The NER for the base case at 6 kg h –1 is 1.29 and 5.0 for steam-pretreated and regular pellet production respectively. However, at the large scale NER would improve. The majormore » factor for NER is energy for steam and drying unit. The sensitivity analysis for the model shows that the optimum temperature for steam pretreatment is 200 °C with 50% pretreatment (Steam pretreating 50% feed stock, while the rest is undergoing regular pelletization). Uncertainty result for steam pretreated and regular pellet is 1.35 ± 0.09 and 4.52 ± 0.34 respectively.« less

A transition-based joint model for disease named entity recognition and normalization.

PubMed

Lou, Yinxia; Zhang, Yue; Qian, Tao; Li, Fei; Xiong, Shufeng; Ji, Donghong

2017-08-01

Disease named entities play a central role in many areas of biomedical research, and automatic recognition and normalization of such entities have received increasing attention in biomedical research communities. Existing methods typically used pipeline models with two independent phases: (i) a disease named entity recognition (DER) system is used to find the boundaries of mentions in text and (ii) a disease named entity normalization (DEN) system is used to connect the mentions recognized to concepts in a controlled vocabulary. The main problems of such models are: (i) there is error propagation from DER to DEN and (ii) DEN is useful for DER, but pipeline models cannot utilize this. We propose a transition-based model to jointly perform disease named entity recognition and normalization, casting the output construction process into an incremental state transition process, learning sequences of transition actions globally, which correspond to joint structural outputs. Beam search and online structured learning are used, with learning being designed to guide search. Compared with the only existing method for joint DEN and DER, our method allows non-local features to be used, which significantly improves the accuracies. We evaluate our model on two corpora: the BioCreative V Chemical Disease Relation (CDR) corpus and the NCBI disease corpus. Experiments show that our joint framework achieves significantly higher performances compared to competitive pipeline baselines. Our method compares favourably to other state-of-the-art approaches. Data and code are available at https://github.com/louyinxia/jointRN. dhji@whu.edu.cn. © The Author (2017). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Fate of phenanthrene and mineralization of its non-extractable residues in an oxic soil.

PubMed

Wang, Yongfeng; Xu, Jun; Shan, Jun; Ma, Yini; Ji, Rong

2017-05-01

The fate of organic pollutants in the environment, especially the formation and stability of non-extractable (i.e., bound) residues (NERs) determines their environmental risk. Using 14 C-tracers, we studied the fate of the carcinogen phenanthrene in active or sterilized oxic loamy soil in the absence and presence of the geophagous earthworm Metaphire guillelmi and characterized the NERs derived from phenanthrene. After incubation of 14 C-phenanthrene in active soil for 28 days, 40 ± 3.1% of the initial amount was mineralized and 70.1 ± 1.9% was converted to NERs. Most of the NERs (>92%) were bound to soil humin. Silylation of the humin-bound residues released 45.3 ± 5.3% of these residues, which indicated that they were physically entrapped, whereas the remainder of the residues were chemically bound or biogenic. By contrast, in sterilized soil, only 43.4 ± 12.6% of the phenanthrene was converted to NERs and all of these residues were completely released upon silylation, which underlines the essential role of microbial activity in NER formation. The presence of M. guillelmi in active soil significantly inhibited phenanthrene mineralization (24.4 ± 2.6% mineralized), but NER formation was not significantly affected. Only a small amount of phenanthrene-derived residues (1.9-5.3% of the initial amount) accumulated in the earthworm body. When humin-bound residues were mixed with fresh soil, 33.9% (humin recovered from active soils) and 12.4% (humin recovered from sterilized soils) of the residues were mineralized after 75 days of incubation, respectively, which indicated a high bioavailability of NERs, albeit lower than the initial addition of phenanthrene. Our results indicated that many phenanthrene-derived NERs, especially those physically entrapped, are still bioavailable and may pose a toxic threat to soil organisms. Copyright © 2017 Elsevier Ltd. All rights reserved.

Automatic recognition of topic-classified relations between prostate cancer and genes using MEDLINE abstracts

PubMed Central

Chun, Hong-Woo; Tsuruoka, Yoshimasa; Kim, Jin-Dong; Shiba, Rie; Nagata, Naoki; Hishiki, Teruyoshi; Tsujii, Jun'ichi

2006-01-01

Background Automatic recognition of relations between a specific disease term and its relevant genes or protein terms is an important practice of bioinformatics. Considering the utility of the results of this approach, we identified prostate cancer and gene terms with the ID tags of public biomedical databases. Moreover, considering that genetics experts will use our results, we classified them based on six topics that can be used to analyze the type of prostate cancers, genes, and their relations. Methods We developed a maximum entropy-based named entity recognizer and a relation recognizer and applied them to a corpus-based approach. We collected prostate cancer-related abstracts from MEDLINE, and constructed an annotated corpus of gene and prostate cancer relations based on six topics by biologists. We used it to train the maximum entropy-based named entity recognizer and relation recognizer. Results Topic-classified relation recognition achieved 92.1% precision for the relation (an increase of 11.0% from that obtained in a baseline experiment). For all topics, the precision was between 67.6 and 88.1%. Conclusion A series of experimental results revealed two important findings: a carefully designed relation recognition system using named entity recognition can improve the performance of relation recognition, and topic-classified relation recognition can be effectively addressed through a corpus-based approach using manual annotation and machine learning techniques. PMID:17134477

Automatic recognition of topic-classified relations between prostate cancer and genes using MEDLINE abstracts.

PubMed

Chun, Hong-Woo; Tsuruoka, Yoshimasa; Kim, Jin-Dong; Shiba, Rie; Nagata, Naoki; Hishiki, Teruyoshi; Tsujii, Jun'ichi

2006-11-24

Automatic recognition of relations between a specific disease term and its relevant genes or protein terms is an important practice of bioinformatics. Considering the utility of the results of this approach, we identified prostate cancer and gene terms with the ID tags of public biomedical databases. Moreover, considering that genetics experts will use our results, we classified them based on six topics that can be used to analyze the type of prostate cancers, genes, and their relations. We developed a maximum entropy-based named entity recognizer and a relation recognizer and applied them to a corpus-based approach. We collected prostate cancer-related abstracts from MEDLINE, and constructed an annotated corpus of gene and prostate cancer relations based on six topics by biologists. We used it to train the maximum entropy-based named entity recognizer and relation recognizer. Topic-classified relation recognition achieved 92.1% precision for the relation (an increase of 11.0% from that obtained in a baseline experiment). For all topics, the precision was between 67.6 and 88.1%. A series of experimental results revealed two important findings: a carefully designed relation recognition system using named entity recognition can improve the performance of relation recognition, and topic-classified relation recognition can be effectively addressed through a corpus-based approach using manual annotation and machine learning techniques.

Evidence for conformational capture mechanism for damage recognition by NER protein XPC/Rad4.

NASA Astrophysics Data System (ADS)

Chakraborty, Sagnik; Steinbach, Peter J.; Paul, Debamita; Min, Jung-Hyun; Ansari, Anjum

Altered flexibility of damaged DNA sites is considered to play an important role in damage recognition by DNA repair proteins. Characterizing lesion-induced DNA dynamics has remained a challenge. We have combined ps-resolved fluorescence lifetime measurements with cytosine analog FRET pair uniquely sensitive to local unwinding/twisting to analyze DNA conformational distributions. This innovative approach maps out with unprecedented sensitivity the alternative conformations accessible to a series of DNA constructs containing 3-base-pair mismatch, suitable model lesions for the DNA repair protein xeroderma pigmentosum C (XPC) complex. XPC initiates eukaryotic nucleotide excision repair by recognizing various DNA lesions primarily through DNA deformability. Structural studies show that Rad4 (yeast ortholog of XPC) unwinds DNA at the lesion site and flips out two nucleotide pairs. Our results elucidate a broad range of conformations accessible to mismatched DNA even in the absence of the protein. Notably, the most severely distorted conformations share remarkable resemblance to the deformed conformation seen in the crystal structure of the Rad4-bound ``recognition'' complex supporting for the first time a possible ``conformational capture'' mechanism for damage recognition by XPC/Rad4. NSF Univ of Illinois-Chicago.

Contribution of microorganisms to non-extractable residue formation from biodegradable organic contaminants in soil

NASA Astrophysics Data System (ADS)

Nowak, K. M.; Girardi, C.; Miltner, A.; Schäffer, A.; Kästner, M.

2012-04-01

Biodegradation of organic contaminants in soil is actually understood as their transformation into various primary metabolites, microbial biomass, mineralisation products and non-extractable residues (NER). NER are generally considered to be composed of parent compounds or primary metabolites with hazardous potential. Up to date, however, their chemical composition remains still unclear. Studies on NER formation are limited to quantitative analyses in soils or to simple humic acids-contaminant systems. However, in the case of biodegradable organic compounds, NER may also contain microbial biomass components, e.g. fatty acids (FA) and amino acids (AA). After cell death, these biomolecules are incorporated into soil organic matter (SOM) and stabilised, ultimately forming biogenic residues which are not any more extractable. We investigated the incorporation of the 13C-label into FA and AA and their fate during biodegradation experiments in soil with isotope-labelled 2,4-dichlorophenoxyacetic acid (13C6-2,4-D) and ibuprofen (13C6-ibu) as model organic contaminants. Our study proved for the first time that nearly all NER formed from 13C6-2,4-D and 13C6-ibu in soil derived from harmless microbial biomass components stabilised in SOM. 13C-FA and 13C-AA contents in the living microbial biomass fraction decreased over time and these components were continuously incorporated into the non-living SOM pool in biotic experiments with 13C6-2,4-D and 13C6-ibu. The 13C-AA in the non-living SOM were surprisingly stable from day 32 (13C6-2,4-D) and 58 (13C6-ibu) until the end of incubation. We also studied the transformation of 13C6-2,4-D and 13C6-ibu into NER in the abiotic soil experiments. In these experiments, the total NER contents were much lower than in the corresponding biotic experiments. The absence of labelled biomolecules in the NER fraction in abiotic soils demonstrated that they consist of the potentially hazardous parent compounds and / or their metabolites. Biogenic residue formation is relevant during biodegradation of organic contaminants, whereas abiotic NER are formed from the non-biodegraded residual contaminants. Abiotic NER and biogenic residue formation are competitive processes and do not occur in a similar extent. In the biotic treatment, the rapid mineralisation of an organic compound reduces the extent of abiotic NER formation via physico-chemical interactions between a parent compound and / or its primary metabolites with SOM. Therefore, in order to properly assess the potential risks of a target contaminant in soil to humans and the environment, it is necessary to distinguish between abiotic NER and biogenic residue formation in the mass balances of contaminants.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hang, Bo; Rodriguez, Ben; Yang, Yanu

Benzene, a ubiquitous human carcinogen, forms DNA adducts through its metabolites such as p-benzoquinone (p-BQ) and hydroquinone (HQ). N(2)-(4-Hydroxyphenyl)-2'-deoxyguanosine (N(2)-4-HOPh-dG) is the principal adduct identified in vivo by (32)P-postlabeling in cells or animals treated with p-BQ or HQ. To study its effect on repair specificity and replication fidelity, we recently synthesized defined oligonucleotides containing a site-specific adduct using phosphoramidite chemistry. We here report the repair of this adduct by Escherichia coli UvrABC complex, which performs the initial damage recognition and incision steps in the nucleotide excision repair (NER) pathway. We first showed that the p-BQ-treated plasmid was efficiently cleaved bymore » the complex, indicating the formation of DNA lesions that are substrates for NER. Using a 40-mer substrate, we found that UvrABC incises the DNA strand containing N(2)-4-HOPh-dG in a dose- and time-dependent manner. The specificity of such repair was also compared with that of DNA glycosylases and damage-specific endonucleases of E. coli, both of which were found to have no detectable activity toward N(2)-4-HOPh-dG. To understand why this adduct is specifically recognized and processed by UvrABC, molecular modeling studies were performed. Analysis of molecular dynamics trajectories showed that stable G:C-like hydrogen bonding patterns of all three Watson-Crick hydrogen bonds are present within the N(2)-4-HOPh-G:C base pair, with the hydroxyphenyl ring at an almost planar position. In addition, N(2)-4-HOPh-dG has a tendency to form more stable stacking interactions than a normal G in B-type DNA. These conformational properties may be critical in differential recognition of this adduct by specific repair enzymes.« less

Automatic recognition of disorders, findings, pharmaceuticals and body structures from clinical text: an annotation and machine learning study.

PubMed

Skeppstedt, Maria; Kvist, Maria; Nilsson, Gunnar H; Dalianis, Hercules

2014-06-01

Automatic recognition of clinical entities in the narrative text of health records is useful for constructing applications for documentation of patient care, as well as for secondary usage in the form of medical knowledge extraction. There are a number of named entity recognition studies on English clinical text, but less work has been carried out on clinical text in other languages. This study was performed on Swedish health records, and focused on four entities that are highly relevant for constructing a patient overview and for medical hypothesis generation, namely the entities: Disorder, Finding, Pharmaceutical Drug and Body Structure. The study had two aims: to explore how well named entity recognition methods previously applied to English clinical text perform on similar texts written in Swedish; and to evaluate whether it is meaningful to divide the more general category Medical Problem, which has been used in a number of previous studies, into the two more granular entities, Disorder and Finding. Clinical notes from a Swedish internal medicine emergency unit were annotated for the four selected entity categories, and the inter-annotator agreement between two pairs of annotators was measured, resulting in an average F-score of 0.79 for Disorder, 0.66 for Finding, 0.90 for Pharmaceutical Drug and 0.80 for Body Structure. A subset of the developed corpus was thereafter used for finding suitable features for training a conditional random fields model. Finally, a new model was trained on this subset, using the best features and settings, and its ability to generalise to held-out data was evaluated. This final model obtained an F-score of 0.81 for Disorder, 0.69 for Finding, 0.88 for Pharmaceutical Drug, 0.85 for Body Structure and 0.78 for the combined category Disorder+Finding. The obtained results, which are in line with or slightly lower than those for similar studies on English clinical text, many of them conducted using a larger training data set, show that the approaches used for English are also suitable for Swedish clinical text. However, a small proportion of the errors made by the model are less likely to occur in English text, showing that results might be improved by further tailoring the system to clinical Swedish. The entity recognition results for the individual entities Disorder and Finding show that it is meaningful to separate the general category Medical Problem into these two more granular entity types, e.g. for knowledge mining of co-morbidity relations and disorder-finding relations. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Toward better public health reporting using existing off the shelf approaches: The value of medical dictionaries in automated cancer detection using plaintext medical data.

PubMed

Kasthurirathne, Suranga N; Dixon, Brian E; Gichoya, Judy; Xu, Huiping; Xia, Yuni; Mamlin, Burke; Grannis, Shaun J

2017-05-01

Existing approaches to derive decision models from plaintext clinical data frequently depend on medical dictionaries as the sources of potential features. Prior research suggests that decision models developed using non-dictionary based feature sourcing approaches and "off the shelf" tools could predict cancer with performance metrics between 80% and 90%. We sought to compare non-dictionary based models to models built using features derived from medical dictionaries. We evaluated the detection of cancer cases from free text pathology reports using decision models built with combinations of dictionary or non-dictionary based feature sourcing approaches, 4 feature subset sizes, and 5 classification algorithms. Each decision model was evaluated using the following performance metrics: sensitivity, specificity, accuracy, positive predictive value, and area under the receiver operating characteristics (ROC) curve. Decision models parameterized using dictionary and non-dictionary feature sourcing approaches produced performance metrics between 70 and 90%. The source of features and feature subset size had no impact on the performance of a decision model. Our study suggests there is little value in leveraging medical dictionaries for extracting features for decision model building. Decision models built using features extracted from the plaintext reports themselves achieve comparable results to those built using medical dictionaries. Overall, this suggests that existing "off the shelf" approaches can be leveraged to perform accurate cancer detection using less complex Named Entity Recognition (NER) based feature extraction, automated feature selection and modeling approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

Dictionary construction and identification of possible adverse drug events in Danish clinical narrative text

PubMed Central

Eriksson, Robert; Jensen, Peter Bjødstrup; Frankild, Sune; Jensen, Lars Juhl; Brunak, Søren

2013-01-01

Objective Drugs have tremendous potential to cure and relieve disease, but the risk of unintended effects is always present. Healthcare providers increasingly record data in electronic patient records (EPRs), in which we aim to identify possible adverse events (AEs) and, specifically, possible adverse drug events (ADEs). Materials and methods Based on the undesirable effects section from the summary of product characteristics (SPC) of 7446 drugs, we have built a Danish ADE dictionary. Starting from this dictionary we have developed a pipeline for identifying possible ADEs in unstructured clinical narrative text. We use a named entity recognition (NER) tagger to identify dictionary matches in the text and post-coordination rules to construct ADE compound terms. Finally, we apply post-processing rules and filters to handle, for example, negations and sentences about subjects other than the patient. Moreover, this method allows synonyms to be identified and anatomical location descriptions can be merged to allow appropriate grouping of effects in the same location. Results The method identified 1 970 731 (35 477 unique) possible ADEs in a large corpus of 6011 psychiatric hospital patient records. Validation was performed through manual inspection of possible ADEs, resulting in precision of 89% and recall of 75%. Discussion The presented dictionary-building method could be used to construct other ADE dictionaries. The complication of compound words in Germanic languages was addressed. Additionally, the synonym and anatomical location collapse improve the method. Conclusions The developed dictionary and method can be used to identify possible ADEs in Danish clinical narratives. PMID:23703825

Nucleotide excision repair and human syndromes.

PubMed

de Boer, J; Hoeijmakers, J H

2000-03-01

DNA damage is implicated in cancer and aging, and several DNA repair mechanisms exist that safeguard the genome from these deleterious consequences. Nucleotide excision repair (NER) removes a wide diversity of lesions, the main of which include UV-induced lesions, bulky chemical adducts and some forms of oxidative damage. The NER process involves the action of at least 30 proteins in a 'cut-and-paste'-like mechanism. The consequences of a defect in one of the NER proteins are apparent from three rare recessive syndromes: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and the photosensitive form of the brittle hair disorder trichothiodystrophy (TTD). Sun-sensitive skin is associated with skin cancer predisposition in the case of XP, but remarkably not in CS and TTD. Moreover, the spectrum of clinical symptoms differs considerably between the three syndromes. CS and TTD patients exhibit a spectrum of neurodevelopmental abnormalities and, in addition, TTD is associated with ichthyosis and brittle hair. These typical CS and TTD abnormalities are difficult to comprehend as a consequence of defective NER. This review briefly describes the biochemistry of the NER process, summarizes the clinical features of the NER disorders and speculates on the molecular basis underlying these pleitropic syndromes.

Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH).

PubMed Central

van Vuuren, A J; Vermeulen, W; Ma, L; Weeda, G; Appeldoorn, E; Jaspers, N G; van der Eb, A J; Bootsma, D; Hoeijmakers, J H; Humbert, S

1994-01-01

ERCC3 was initially identified as a gene correcting the nucleotide excision repair (NER) defect of xeroderma pigmentosum complementation group B (XP-B). The recent finding that its gene product is identical to the p89 subunit of basal transcription factor BTF2(TFIIH), opened the possibility that it is not directly involved in NER but that it regulates the transcription of one or more NER genes. Using an in vivo microinjection repair assay and an in vitro NER system based on cell-free extracts we demonstrate that ERCC3 in BTF2 is directly implicated in excision repair. Antibody depletion experiments support the idea that the p62 BTF2 subunit and perhaps the entire transcription factor function in NER. Microinjection experiments suggest that exogenous ERCC3 can exchange with ERCC3 subunits in the complex. Expression of a dominant negative K436-->R ERCC3 mutant, expected to have lost all helicase activity, completely abrogates NER and transcription and concomitantly induces a dramatic chromatin collapse. These findings establish the role of ERCC3 and probably the entire BTF2 complex in transcription in vivo which was hitherto only demonstrated in vitro. The results strongly suggest that transcription itself is a critical component for maintenance of chromatin structure. The remarkable dual role of ERCC3 in NER and transcription provides a clue in understanding the complex clinical features of some inherited repair syndromes. Images PMID:8157004

The Nucleotide Excision Repair Pathway Limits L1 Retrotransposition

PubMed Central

Servant, Geraldine; Streva, Vincent A.; Derbes, Rebecca S.; Wijetunge, Madushani I.; Neeland, Marc; White, Travis B.; Belancio, Victoria P.; Roy-Engel, Astrid M.; Deininger, Prescott L.

2017-01-01

Long interspersed elements 1 (L1) are active mobile elements that constitute almost 17% of the human genome. They amplify through a “copy-and-paste” mechanism termed retrotransposition, and de novo insertions related to these elements have been reported to cause 0.2% of genetic diseases. Our previous data demonstrated that the endonuclease complex ERCC1-XPF, which cleaves a 3′ DNA flap structure, limits L1 retrotransposition. Although the ERCC1-XPF endonuclease participates in several different DNA repair pathways, such as single-strand annealing, or in telomere maintenance, its recruitment to DNA lesions is best characterized in the nucleotide excision repair (NER) pathway. To determine if the NER pathway prevents the insertion of retroelements in the genome, we monitored the retrotransposition efficiencies of engineered L1 elements in NER-deficient cells and in their complemented versions. Core proteins of the NER pathway, XPD and XPA, and the lesion binding protein, XPC, are involved in limiting L1 retrotransposition. In addition, sequence analysis of recovered de novo L1 inserts and their genomic locations in NER-deficient cells demonstrated the presence of abnormally large duplications at the site of insertion, suggesting that NER proteins may also play a role in the normal L1 insertion process. Here, we propose new functions for the NER pathway in the maintenance of genome integrity: limitation of insertional mutations caused by retrotransposons and the prevention of potentially mutagenic large genomic duplications at the site of retrotransposon insertion events. PMID:28049704

Enhancing of chemical compound and drug name recognition using representative tag scheme and fine-grained tokenization.

PubMed

Dai, Hong-Jie; Lai, Po-Ting; Chang, Yung-Chun; Tsai, Richard Tzong-Han

2015-01-01

The functions of chemical compounds and drugs that affect biological processes and their particular effect on the onset and treatment of diseases have attracted increasing interest with the advancement of research in the life sciences. To extract knowledge from the extensive literatures on such compounds and drugs, the organizers of BioCreative IV administered the CHEMical Compound and Drug Named Entity Recognition (CHEMDNER) task to establish a standard dataset for evaluating state-of-the-art chemical entity recognition methods. This study introduces the approach of our CHEMDNER system. Instead of emphasizing the development of novel feature sets for machine learning, this study investigates the effect of various tag schemes on the recognition of the names of chemicals and drugs by using conditional random fields. Experiments were conducted using combinations of different tokenization strategies and tag schemes to investigate the effects of tag set selection and tokenization method on the CHEMDNER task. This study presents the performance of CHEMDNER of three more representative tag schemes-IOBE, IOBES, and IOB12E-when applied to a widely utilized IOB tag set and combined with the coarse-/fine-grained tokenization methods. The experimental results thus reveal that the fine-grained tokenization strategy performance best in terms of precision, recall and F-scores when the IOBES tag set was utilized. The IOBES model with fine-grained tokenization yielded the best-F-scores in the six chemical entity categories other than the "Multiple" entity category. Nonetheless, no significant improvement was observed when a more representative tag schemes was used with the coarse or fine-grained tokenization rules. The best F-scores that were achieved using the developed system on the test dataset of the CHEMDNER task were 0.833 and 0.815 for the chemical documents indexing and the chemical entity mention recognition tasks, respectively. The results herein highlight the importance of tag set selection and the use of different tokenization strategies. Fine-grained tokenization combined with the tag set IOBES most effectively recognizes chemical and drug names. To the best of the authors' knowledge, this investigation is the first comprehensive investigation use of various tag set schemes combined with different tokenization strategies for the recognition of chemical entities.

Distant neighbor base sequence context effects in human nucleotide excision repair of a benzo[a]pyrene-derived DNA lesion

PubMed Central

Cai, Yuqin; Kropachev, Konstantin; Xu, Rong; Tang, Yijin; Kolbanovskii, Marina; Kolbanovskii, Alexander; Amin, Shantu; Patel, Dinshaw J.; Broyde, Suse; Geacintov, Nicholas E.

2010-01-01

Summary The effects of non-nearest base sequences, beyond the nucleotides flanking a DNA lesion on either side, on nucleotide excision repair (NER) in extracts from human cells were investigated. We constructed two duplexes containing the same minor groove-aligned 10S (+)-trans-anti-B[a]P-N2-dG (G*) DNA adduct, derived from the environmental carcinogen benzo[a]pyrene (B[a]P): 5′-C-C-A-T-C-G*-C-T-A-C-C-3′ (CG*C-I), and 5′-C-A-C3-A4-C5-G*-C-A-C-A-C-3′ (CG*C-II). We utilized gel electrophoresis to compare the extent of DNA bending, and molecular dynamics (MD) simulations to analyze the structural characteristics of these two DNA duplexes. The NER efficiencies are 1.6 ± 0.2 times greater in the case of the CG*C-II than the CG*C-I sequence context in 135-mer duplexes. Gel electrophoresis and self-ligation circularization experiments revealed that the CG*C-II duplex is more bent than the CG*C-I duplex, while MD simulations showed that the unique -C3-A4-C5- segment in the CG*C-II duplex plays a key role. The presence of a minor groove-positioned guanine amino group, namely, the Watson-Crick partner to C3, acts as a wedge; facilitated by a highly deformable local -C3-A4- base step, this amino group allows the B[a]P ring system to produce a more enlarged minor groove in CG*C-II than in CG*C-I, as well as a local untwisting and enlarged and flexible Roll only in the CG*C-II sequence. These structural properties fit well with our prior findings that in the case of the family of minor groove 10S (+)-trans-anti-B[a]P-N2-dG lesions, flexible bends and enlarged minor groove widths (Cai et al. (2009) J. Mol. Biol., 385: 30–44) constitute NER recognition signals, and extend our understanding of sequence context effects on NER to the neighbors that are distant to the lesion. PMID:20399214

Segregation of anterior temporal regions critical for retrieving names of unique and non-unique entities reflects underlying long-range connectivity.

PubMed

Mehta, Sonya; Inoue, Kayo; Rudrauf, David; Damasio, Hanna; Tranel, Daniel; Grabowski, Thomas

2016-02-01

Lesion-deficit studies support the hypothesis that the left anterior temporal lobe (ATL) plays a critical role in retrieving names of concrete entities. They further suggest that different regions of the left ATL process different conceptual categories. Here we test the specificity of these relationships and whether the anatomical segregation is related to the underlying organization of white matter connections. We reanalyzed data from a previous lesion study of naming and recognition across five categories of concrete entities. In voxelwise logistic regressions of lesion-deficit associations, we formally incorporated measures of disconnection of long-range association fiber tracts (FTs) and covaried for recognition and non-category-specific naming deficits. We also performed fiber tractwise analyses to assess whether damage to specific FTs was preferentially associated with category-selective naming deficits. Damage to the basolateral ATL was associated with naming deficits for both unique (famous faces) and non-unique entities, whereas the damage to the temporal pole was associated with naming deficits for unique entities only. This segregation pattern remained after accounting for comorbid recognition deficits or naming deficits in other categories. The tractwise analyses showed that damage to the uncinate fasciculus (UNC) was associated with naming impairments for unique entities, while damage to the inferior longitudinal fasciculus (ILF) was associated with naming impairments for non-unique entities. Covarying for FT transection in voxelwise analyses rendered the cortical association for unique entities more focal. These results are consistent with the partial segregation of brain system support for name retrieval of unique and non-unique entities at both the level of cortical components and underlying white matter fiber bundles. Our study reconciles theoretic accounts of the functional organization of the left ATL by revealing both category-related processing and semantic hub sectors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Nucleotide excision repair-dependent DNA double-strand break formation and ATM signaling activation in mammalian quiescent cells.

PubMed

Wakasugi, Mitsuo; Sasaki, Takuma; Matsumoto, Megumi; Nagaoka, Miyuki; Inoue, Keiko; Inobe, Manabu; Horibata, Katsuyoshi; Tanaka, Kiyoji; Matsunaga, Tsukasa

2014-10-10

Histone H2A variant H2AX is phosphorylated at Ser(139) in response to DNA double-strand break (DSB) and single-stranded DNA (ssDNA) formation. UV light dominantly induces pyrimidine photodimers, which are removed from the mammalian genome by nucleotide excision repair (NER). We previously reported that in quiescent G0 phase cells, UV induces ATR-mediated H2AX phosphorylation plausibly caused by persistent ssDNA gap intermediates during NER. In this study, we have found that DSB is also generated following UV irradiation in an NER-dependent manner and contributes to an earlier fraction of UV-induced H2AX phosphorylation. The NER-dependent DSB formation activates ATM kinase and triggers the accumulation of its downstream factors, MRE11, NBS1, and MDC1, at UV-damaged sites. Importantly, ATM-deficient cells exhibited enhanced UV sensitivity under quiescent conditions compared with asynchronously growing conditions. Finally, we show that the NER-dependent H2AX phosphorylation is also observed in murine peripheral T lymphocytes, typical nonproliferating quiescent cells in vivo. These results suggest that in vivo quiescent cells may suffer from NER-mediated secondary DNA damage including ssDNA and DSB. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Cyclosporin A inhibits nucleotide excision repair via downregulation of the xeroderma pigmentosum group A and G proteins, which is mediated by calcineurin inhibition.

PubMed

Kuschal, Christiane; Thoms, Kai-Martin; Boeckmann, Lars; Laspe, Petra; Apel, Antje; Schön, Michael P; Emmert, Steffen

2011-10-01

Cyclosporin A (CsA) inhibits nucleotide excision repair (NER) in human cells, a process that contributes to the skin cancer proneness in organ transplant patients. We investigated the mechanisms of CsA-induced NER reduction by assessing all xeroderma pigmentosum (XP) genes (XPA-XPG). Western blot analyses revealed that XPA and XPG protein expression was reduced in normal human GM00637 fibroblasts exposed to 0.1 and 0.5 μm CsA. Interestingly, the CsA treatment reduced XPG, but not XPA, mRNA expression. Calcineurin knockdown in GM00637 fibroblasts using RNAi led to similar results suggesting that calcineurin-dependent signalling is involved in XPA and XPG protein regulation. CsA-induced reduction in NER could be complemented by the overexpression of either XPA or XPG protein. Likewise, XPA-deficient fibroblasts with stable overexpression of XPA (XP2OS-pCAH19WS) did not show the inhibitory effect of CsA on NER. In contrast, XPC-deficient fibroblasts overexpressing XPC showed CsA-reduced NER. Our data indicate that the CsA-induced inhibition of NER is a result of downregulation of XPA and XPG protein in a calcineurin-dependent manner. © 2011 John Wiley & Sons A/S.

XERODERMA PIGMENTOSUM, TRICHOTHIODYSTROPHY AND COCKAYNE SYNDROME: A COMPLEX GENOTYPE-PHENOTYPE RELATIONSHIP

PubMed Central

Kraemer, Kenneth H.; Patronas, Nicholas J.; Schiffmann, Raphael; Brooks, Brian P.; Tamura, Deborah; DiGiovanna, John J.

2008-01-01

Patients with the rare genetic disorders, xeroderma pigmentosum (XP), trichothiodystrophy (TTD) and Cockayne syndrome (CS) have defects in DNA nucleotide excision repair (NER). The NER pathway involves at least 28 genes. Three NER genes are also part of the basal transcription factor, TFIIH. Mutations in 11 NER genes have been associated with clinical diseases with at least 8 overlapping phenotypes. The clinical features of these patients have some similarities and but also have marked differences. NER is involved in protection against sunlight induced DNA damage. While XP patients have 1000-fold increase in susceptibility to skin cancer, TTD and CS patients have normal skin cancer risk. Several of the genes involved in NER also affect somatic growth and development. Some patients have short stature and immature sexual development. TTD patients have sulfur deficient brittle hair. Progressive sensorineural deafness is an early feature of XP and CS. Many of these clinical diseases are associated with developmental delay and progressive neurological degeneration. The main neuropathology of XP is a primary neuronal degeneration. In contrast, CS and TTD patients have reduced myelination of the brain. These complex neurological abnormalities are not related to sunlight exposure but may be caused by developmental defects as well as faulty repair of DNA damage to neuronal cells induced by oxidative metabolism or other endogenous processes. PMID:17276014

Oxidative stress-induced protein damage inhibits DNA repair and determines mutation risk and anticancer drug effectiveness

PubMed Central

McAdam, Elizabeth; Brem, Reto; Karran, Peter

2016-01-01

The relationship between sun exposure and non-melanoma skin cancer risk is well established. Solar ultraviolet radiation (UV; wavelengths 280-400 nm) is firmly implicated in skin cancer development. Nucleotide excision repair (NER) protects against cancer by removing potentially mutagenic DNA lesions induced by UVB (280-320 nm). How the 20-fold more abundant UVA (320-400 mn) component of solar UV radiation increases skin cancer risk is not understood. We demonstrate here that the contribution of UVA to the effects of UV radiation on cultured human cells is largely independent of its ability to damage DNA. Instead, the effects of UVA reflect the induction of oxidative stress that causes extensive protein oxidation. Because NER proteins are among those damaged, UVA irradiation inhibits NER and increases the cells’ susceptibility to mutation by UVB. NER inhibition is a common consequence of oxidative stress. Exposure to chemical oxidants, treatment with drugs that deplete cellular antioxidants, and interventions that interfere with glucose metabolism to disrupt the supply of cellular reducing power all inhibit NER. Tumor cells are often in a condition of oxidative stress and one effect of the NER inhibition that results from stress-induced protein oxidation is an increased sensitivity to the anticancer drug cisplatin. Statement of implication: Since NER is both a defence against cancer a significant determinant of cell survival after treatment with anticancer drugs, its attenuation by protein damage under conditions of oxidative-stress has implications for both cancer risk and for the effectiveness of anticancer therapy. PMID:27106867

Mutations in Replicative Stress Response Pathways Are Associated with S Phase-specific Defects in Nucleotide Excision Repair*

PubMed Central

Bélanger, François; Angers, Jean-Philippe; Fortier, Émile; Hammond-Martel, Ian; Costantino, Santiago; Drobetsky, Elliot; Wurtele, Hugo

2016-01-01

Nucleotide excision repair (NER) is a highly conserved pathway that removes helix-distorting DNA lesions induced by a plethora of mutagens, including UV light. Our laboratory previously demonstrated that human cells deficient in either ATM and Rad3-related (ATR) kinase or translesion DNA polymerase η (i.e. key proteins that promote the completion of DNA replication in response to UV-induced replicative stress) are characterized by profound inhibition of NER exclusively during S phase. Toward elucidating the mechanistic basis of this phenomenon, we developed a novel assay to quantify NER kinetics as a function of cell cycle in the model organism Saccharomyces cerevisiae. Using this assay, we demonstrate that in yeast, deficiency of the ATR homologue Mec1 or of any among several other proteins involved in the cellular response to replicative stress significantly abrogates NER uniquely during S phase. Moreover, initiation of DNA replication is required for manifestation of this defect, and S phase NER proficiency is correlated with the capacity of individual mutants to respond to replicative stress. Importantly, we demonstrate that partial depletion of Rfa1 recapitulates defective S phase-specific NER in wild type yeast; moreover, ectopic RPA1–3 overexpression rescues such deficiency in either ATR- or polymerase η-deficient human cells. Our results strongly suggest that reduction of NER capacity during periods of enhanced replicative stress, ostensibly caused by inordinate sequestration of RPA at stalled DNA replication forks, represents a conserved feature of the multifaceted eukaryotic DNA damage response. PMID:26578521

ToNER: A tool for identifying nucleotide enrichment signals in feature-enriched RNA-seq data.

PubMed

Promworn, Yuttachon; Kaewprommal, Pavita; Shaw, Philip J; Intarapanich, Apichart; Tongsima, Sissades; Piriyapongsa, Jittima

2017-01-01

Biochemical methods are available for enriching 5' ends of RNAs in prokaryotes, which are employed in the differential RNA-seq (dRNA-seq) and the more recent Cappable-seq protocols. Computational methods are needed to locate RNA 5' ends from these data by statistical analysis of the enrichment. Although statistical-based analysis methods have been developed for dRNA-seq, they may not be suitable for Cappable-seq data. The more efficient enrichment method employed in Cappable-seq compared with dRNA-seq could affect data distribution and thus algorithm performance. We present Transformation of Nucleotide Enrichment Ratios (ToNER), a tool for statistical modeling of enrichment from RNA-seq data obtained from enriched and unenriched libraries. The tool calculates nucleotide enrichment scores and determines the global transformation for fitting to the normal distribution using the Box-Cox procedure. From the transformed distribution, sites of significant enrichment are identified. To increase power of detection, meta-analysis across experimental replicates is offered. We tested the tool on Cappable-seq and dRNA-seq data for identifying Escherichia coli transcript 5' ends and compared the results with those from the TSSAR tool, which is designed for analyzing dRNA-seq data. When combining results across Cappable-seq replicates, ToNER detects more known transcript 5' ends than TSSAR. In general, the transcript 5' ends detected by ToNER but not TSSAR occur in regions which cannot be locally modeled by TSSAR. ToNER uses a simple yet robust statistical modeling approach, which can be used for detecting RNA 5'ends from Cappable-seq data, in particular when combining information from experimental replicates. The ToNER tool could potentially be applied for analyzing other RNA-seq datasets in which enrichment for other structural features of RNA is employed. The program is freely available for download at ToNER webpage (http://www4a.biotec.or.th/GI/tools/toner) and GitHub repository (https://github.com/PavitaKae/ToNER).

Restricting night-time eating reduces daily energy intake in healthy young men: a short-term cross-over study.

PubMed

LeCheminant, James D; Christenson, Ed; Bailey, Bruce W; Tucker, Larry A

2013-12-14

Few experimental data are available to support the notion that reducing night-time eating changes total daily energy intake (EI) or body weight in healthy adults. The present study primarily examined the short-term effect of night eating restriction (NER) on daily EI in healthy young men. It secondarily examined body weight and moods associated with NER. Using a cross-over design, twenty-nine men (20·9 (sd 2·5) years; 24·4 (sd 2·5) kg/m²) initiated a 2-week NER intervention (elimination of EI from 19.00 to 06.00 hours) and a 2-week control condition, counterbalanced and separated by a 1-week washout period. EI and macronutrient intake were assessed using computerised, multiple-pass 24 h food recalls, body weight via a digital scale and mood using the Profile of Mood States survey. Of the twenty-nine participants, twenty-seven (93 %) completed all aspects of the study. During the NER condition, the participants consumed less total energy per d than during the control condition (10 125 v. 11 146 kJ/d; F= 6·41; P= 0·018). During the NER condition, no energy was reported consumed between 19.00 and 06.00 hours; however, during the control condition, the energy intake of participants was 2920 (sd 1347) kJ/d between 19.00 and 06.00 hours. There was a significant difference in weight change between the NER (-0·4 (sd 1·1) kg) and control (+0·6 (sd 0·9) kg) conditions (F= 22·68; P< 0·001). Differences in total mood score or mood subscales between the NER and control conditions were not apparent (P>0·05). These findings provide support for NER decreasing short-term EI in healthy young men.

Recognition of chemical entities: combining dictionary-based and grammar-based approaches.

PubMed

Akhondi, Saber A; Hettne, Kristina M; van der Horst, Eelke; van Mulligen, Erik M; Kors, Jan A

2015-01-01

The past decade has seen an upsurge in the number of publications in chemistry. The ever-swelling volume of available documents makes it increasingly hard to extract relevant new information from such unstructured texts. The BioCreative CHEMDNER challenge invites the development of systems for the automatic recognition of chemicals in text (CEM task) and for ranking the recognized compounds at the document level (CDI task). We investigated an ensemble approach where dictionary-based named entity recognition is used along with grammar-based recognizers to extract compounds from text. We assessed the performance of ten different commercial and publicly available lexical resources using an open source indexing system (Peregrine), in combination with three different chemical compound recognizers and a set of regular expressions to recognize chemical database identifiers. The effect of different stop-word lists, case-sensitivity matching, and use of chunking information was also investigated. We focused on lexical resources that provide chemical structure information. To rank the different compounds found in a text, we used a term confidence score based on the normalized ratio of the term frequencies in chemical and non-chemical journals. The use of stop-word lists greatly improved the performance of the dictionary-based recognition, but there was no additional benefit from using chunking information. A combination of ChEBI and HMDB as lexical resources, the LeadMine tool for grammar-based recognition, and the regular expressions, outperformed any of the individual systems. On the test set, the F-scores were 77.8% (recall 71.2%, precision 85.8%) for the CEM task and 77.6% (recall 71.7%, precision 84.6%) for the CDI task. Missed terms were mainly due to tokenization issues, poor recognition of formulas, and term conjunctions. We developed an ensemble system that combines dictionary-based and grammar-based approaches for chemical named entity recognition, outperforming any of the individual systems that we considered. The system is able to provide structure information for most of the compounds that are found. Improved tokenization and better recognition of specific entity types is likely to further improve system performance.

Recognition of chemical entities: combining dictionary-based and grammar-based approaches

PubMed Central

2015-01-01

Background The past decade has seen an upsurge in the number of publications in chemistry. The ever-swelling volume of available documents makes it increasingly hard to extract relevant new information from such unstructured texts. The BioCreative CHEMDNER challenge invites the development of systems for the automatic recognition of chemicals in text (CEM task) and for ranking the recognized compounds at the document level (CDI task). We investigated an ensemble approach where dictionary-based named entity recognition is used along with grammar-based recognizers to extract compounds from text. We assessed the performance of ten different commercial and publicly available lexical resources using an open source indexing system (Peregrine), in combination with three different chemical compound recognizers and a set of regular expressions to recognize chemical database identifiers. The effect of different stop-word lists, case-sensitivity matching, and use of chunking information was also investigated. We focused on lexical resources that provide chemical structure information. To rank the different compounds found in a text, we used a term confidence score based on the normalized ratio of the term frequencies in chemical and non-chemical journals. Results The use of stop-word lists greatly improved the performance of the dictionary-based recognition, but there was no additional benefit from using chunking information. A combination of ChEBI and HMDB as lexical resources, the LeadMine tool for grammar-based recognition, and the regular expressions, outperformed any of the individual systems. On the test set, the F-scores were 77.8% (recall 71.2%, precision 85.8%) for the CEM task and 77.6% (recall 71.7%, precision 84.6%) for the CDI task. Missed terms were mainly due to tokenization issues, poor recognition of formulas, and term conjunctions. Conclusions We developed an ensemble system that combines dictionary-based and grammar-based approaches for chemical named entity recognition, outperforming any of the individual systems that we considered. The system is able to provide structure information for most of the compounds that are found. Improved tokenization and better recognition of specific entity types is likely to further improve system performance. PMID:25810767

Development and validation of a modified comet assay to phenotypically assess nucleotide excision repair.

PubMed

Langie, Sabine A S; Knaapen, Ad M; Brauers, Karen J J; van Berlo, Damien; van Schooten, Frederik-Jan; Godschalk, Roger W L

2006-03-01

There is an increasing need for simple and reliable approaches to phenotypically assess DNA repair capacities. Therefore, a modification of the alkaline comet assay was developed to determine the ability of human lymphocyte extracts to perform the initial steps of the nucleotide excision repair (NER) process, i.e. damage recognition and incision. Gel-embedded nucleoids from A549 cells, pre-exposed to 1 microM benzo[a]pyrene-diol-epoxide, were incubated with cell extracts from frozen or freshly isolated lymphocytes. The rate at which incisions are introduced and the subsequent increase in tail moment is indicative for the repair capacity of the extracts. Freshly prepared extracts from lymphocytes of human volunteers (n = 8) showed significant inter-individual variations in their DNA repair capacity, which correlated with the removal of bulky DNA lesions over a period of 48 h determined by (32)P-post-labelling (R(2) = 0.76, P = 0.005). Repeated measurements revealed a low inter-assay variation (11%). Storage of cell extracts for more than 3 weeks significantly reduced (up to 80%) the capacity to incise the damaged DNA as compared to freshly isolated extracts. This reduction was completely restored by addition of ATP to the extracts before use, as it is required for the incision step of NER. In contrast, extracts freshly prepared from frozen lymphocyte pellets can be used without loss of repair activity. DNA repair deficient XPA-/- and XPC-/- fibroblasts were used to further validate the assay. Although some residual capacity to incise the DNA was observed in these cells, the repair activity was restored to normal wild-type levels when a complementary mixture of both extracts (thereby restoring XPA and XPC deficiency) was used. These results demonstrate that this repair assay can be applied in molecular epidemiological studies to assess inter-individual differences in NER.

Designing Rules for Accounting Transaction Identification based on Indonesian NLP

NASA Astrophysics Data System (ADS)

Iswandi, I.; Suwardi, I. S.; Maulidevi, N. U.

2017-03-01

Recording accounting transactions carried out by the evidence of the transactions. It can be invoices, receipts, letters of intent, electricity bill, telephone bill, etc. In this paper, we proposed design of rules to identify the entities located on the sales invoice. There are some entities identified in a sales invoice, namely : invoice date, company name, invoice number, product id, product name, quantity and total price. Identification this entities using named entity recognition method. The entities generated from the rules used as a basis for automation process of data input into the accounting system.

Mutagenesis and repair induced by the DNA advanced glycation end product N2-1-(carboxyethyl)-2'-deoxyguanosine in human cells.

PubMed

Tamae, Daniel; Lim, Punnajit; Wuenschell, Gerald E; Termini, John

2011-03-29

Glycation of biopolymers by glucose-derived α-oxo-aldehydes such as methylglyoxal (MG) is believed to play a major role in the complex pathologies associated with diabetes and metabolic disease. In contrast to the extensive literature detailing the formation and physiological consequences of protein glycation, there is little information about the corresponding phenomenon for DNA. To assess the potential contribution of DNA glycation to genetic instability, we prepared shuttle vectors containing defined levels of the DNA glycation adduct N(2)-(1-carboxyethyl)-2'-deoxyguanosine (CEdG) and transfected them into isogenic human fibroblasts that differed solely in the capacity to conduct nucleotide excision repair (NER). In the NER-compromised fibroblasts, the induced mutation frequencies increased up to 18-fold relative to background over a range of ∼10-1400 CEdG adducts/10(5) dG, whereas the same substrates transfected into NER-competent cells induced a response that was 5-fold over background at the highest adduct density. The positive linear correlation (R(2) = 0.998) of mutation frequency with increasing CEdG level in NER-defective cells suggested that NER was the primary if not exclusive mechanism for repair of this adduct in human fibroblasts. Consistent with predictions from biochemical studies using CEdG-substituted oligonucleotides, guanine transversions were the predominant mutation resulting from replication of MG-modified plasmids. At high CEdG levels, significant increases in the number of AT → GC transitions were observed exclusively in NER-competent cells (P < 0.0001). This suggested the involvement of an NER-dependent mutagenic process in response to critical levels of DNA damage, possibly mediated by error-prone Y-family polymerases.

DNA damage mediated transcription arrest: Step back to go forward.

PubMed

Mullenders, Leon

2015-12-01

The disturbance of DNA helix conformation by bulky DNA damage poses hindrance to transcription elongating due to stalling of RNA polymerase at transcription blocking lesions. Stalling of RNA polymerase provokes the formation of R-loops, i.e. the formation of a DNA-RNA hybrid and a displaced single stranded DNA strand as well as displacement of spliceosomes. R-loops are processed into DNA single and double strand breaks by NER factors depending on TC-NER factors leading to genome instability. Moreover, stalling of RNA polymerase induces a strong signal for cell cycle arrest and apoptosis. These toxic and mutagenic effects are counteracted by a rapid recruitment of DNA repair proteins to perform transcription coupled nucleotide excision repair (TC-NER) to remove the blocking DNA lesions and to restore transcription. Recent studies have highlighted the role of backtracking of RNA polymerase to facilitate TC-NER and identified novel factors that play key roles in TC-NER and in restoration of transcription. On the molecular level these factors facilitate stability of the repair complex by promotion and regulation of various post-translational modifications of NER factors and chromatin substrate. In addition, the continuous flow of new factors that emerge from screening assays hints to several regulatory levels to safeguard the integrity of transcription elongation after disturbance by DNA damage that have yet to be explored. Copyright © 2015 Elsevier B.V. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shahrukh, Hassan; Oyedun, Adetoyese Olajire; Kumar, Amit

Here, a process model was developed to determine the net energy ratio (NER) for production of pellets from steam pretreated agricultural residue (AR) and energy crop (i.e. switchgrass in this case). The NER is a ratio of the net energy output to the total net energy input from non-renewable energy sources into a system. Scenarios were developed to measure the effects of temperature and level of steam pretreatment on the NER of steam pretreated AR- and switch grass-based pellets. The NER for the base case at 6 kg h -1 is 1.76 and 1.37 for steam-pretreated AR- and switchgrass-based pellets,more » respectively. The reason behind the difference is that more energy is required to dry switchgrass pellets than AR pellets. The sensitivity analysis for the model shows that the optimum temperature for steam pretreatment is 160 C with 50% pretreatment (half the feedstock is pretreated, while the rest is undergoes regular pelletization). The uncertainty results for NER for steam pretreated AR and switch grass pellets are 1.62 ± 0.10 and 1.42 ± 0.11, respectively.« less

Attenuated XPC Expression Is Not Associated with Impaired DNA Repair in Bladder Cancer

PubMed Central

Naipal, Kishan A. T.; Raams, Anja; Bruens, Serena T.; Brandsma, Inger; Verkaik, Nicole S.; Jaspers, Nicolaas G. J.; Hoeijmakers, Jan H. J.; van Leenders, Geert J. L. H.; Pothof, Joris; Kanaar, Roland; Boormans, Joost; van Gent, Dik C.

2015-01-01

Bladder cancer has a high incidence with significant morbidity and mortality. Attenuated expression of the DNA damage response protein Xeroderma Pigmentosum complementation group C (XPC) has been described in bladder cancer. XPC plays an essential role as the main initiator and damage-detector in global genome nucleotide excision repair (NER) of UV-induced lesions, bulky DNA adducts and intrastrand crosslinks, such as those made by the chemotherapeutic agent Cisplatin. Hence, XPC protein might be an informative biomarker to guide personalized therapy strategies in a subset of bladder cancer cases. Therefore, we measured the XPC protein expression level and functional NER activity of 36 bladder tumors in a standardized manner. We optimized conditions for dissociation and in vitro culture of primary bladder cancer cells and confirmed attenuated XPC expression in approximately 40% of the tumors. However, NER activity was similar to co-cultured wild type cells in all but one of 36 bladder tumors. We conclude, that (i) functional NER deficiency is a relatively rare phenomenon in bladder cancer and (ii) XPC protein levels are not useful as biomarker for NER activity in these tumors. PMID:25927440

DDB2 promotes chromatin decondensation at UV-induced DNA damage

PubMed Central

Lindh, Michael; Acs, Klara; Vrouwe, Mischa G.; Pines, Alex; van Attikum, Haico; Mullenders, Leon H.

2012-01-01

Nucleotide excision repair (NER) is the principal pathway that removes helix-distorting deoxyribonucleic acid (DNA) damage from the mammalian genome. Recognition of DNA lesions by xeroderma pigmentosum group C (XPC) protein in chromatin is stimulated by the damaged DNA-binding protein 2 (DDB2), which is part of a CUL4A–RING ubiquitin ligase (CRL4) complex. In this paper, we report a new function of DDB2 in modulating chromatin structure at DNA lesions. We show that DDB2 elicits unfolding of large-scale chromatin structure independently of the CRL4 ubiquitin ligase complex. Our data reveal a marked adenosine triphosphate (ATP)–dependent reduction in the density of core histones in chromatin containing UV-induced DNA lesions, which strictly required functional DDB2 and involved the activity of poly(adenosine diphosphate [ADP]–ribose) polymerase 1. Finally, we show that lesion recognition by XPC, but not DDB2, was strongly reduced in ATP-depleted cells and was regulated by the steady-state levels of poly(ADP-ribose) chains. PMID:22492724

Named Entity Recognition in a Hungarian NL Based QA System

NASA Astrophysics Data System (ADS)

Tikkl, Domonkos; Szidarovszky, P. Ferenc; Kardkovacs, Zsolt T.; Magyar, Gábor

In WoW project our purpose is to create a complex search interface with the following features: search in the deep web content of contracted partners' databases, processing Hungarian natural language (NL) questions and transforming them to SQL queries for database access, image search supported by a visual thesaurus that describes in a structural form the visual content of images (also in Hungarian). This paper primarily focuses on a particular problem of question processing task: the entity recognition. Before going into details we give a short overview of the project's aims.

Evaluation of linear classifiers on articles containing pharmacokinetic evidence of drug-drug interactions.

PubMed

Kolchinsky, A; Lourenço, A; Li, L; Rocha, L M

2013-01-01

Drug-drug interaction (DDI) is a major cause of morbidity and mortality. DDI research includes the study of different aspects of drug interactions, from in vitro pharmacology, which deals with drug interaction mechanisms, to pharmaco-epidemiology, which investigates the effects of DDI on drug efficacy and adverse drug reactions. Biomedical literature mining can aid both kinds of approaches by extracting relevant DDI signals from either the published literature or large clinical databases. However, though drug interaction is an ideal area for translational research, the inclusion of literature mining methodologies in DDI workflows is still very preliminary. One area that can benefit from literature mining is the automatic identification of a large number of potential DDIs, whose pharmacological mechanisms and clinical significance can then be studied via in vitro pharmacology and in populo pharmaco-epidemiology. We implemented a set of classifiers for identifying published articles relevant to experimental pharmacokinetic DDI evidence. These documents are important for identifying causal mechanisms behind putative drug-drug interactions, an important step in the extraction of large numbers of potential DDIs. We evaluate performance of several linear classifiers on PubMed abstracts, under different feature transformation and dimensionality reduction methods. In addition, we investigate the performance benefits of including various publicly-available named entity recognition features, as well as a set of internally-developed pharmacokinetic dictionaries. We found that several classifiers performed well in distinguishing relevant and irrelevant abstracts. We found that the combination of unigram and bigram textual features gave better performance than unigram features alone, and also that normalization transforms that adjusted for feature frequency and document length improved classification. For some classifiers, such as linear discriminant analysis (LDA), proper dimensionality reduction had a large impact on performance. Finally, the inclusion of NER features and dictionaries was found not to help classification.

ToNER: A tool for identifying nucleotide enrichment signals in feature-enriched RNA-seq data

PubMed Central

Promworn, Yuttachon; Kaewprommal, Pavita; Shaw, Philip J.; Intarapanich, Apichart; Tongsima, Sissades

2017-01-01

Background Biochemical methods are available for enriching 5′ ends of RNAs in prokaryotes, which are employed in the differential RNA-seq (dRNA-seq) and the more recent Cappable-seq protocols. Computational methods are needed to locate RNA 5′ ends from these data by statistical analysis of the enrichment. Although statistical-based analysis methods have been developed for dRNA-seq, they may not be suitable for Cappable-seq data. The more efficient enrichment method employed in Cappable-seq compared with dRNA-seq could affect data distribution and thus algorithm performance. Results We present Transformation of Nucleotide Enrichment Ratios (ToNER), a tool for statistical modeling of enrichment from RNA-seq data obtained from enriched and unenriched libraries. The tool calculates nucleotide enrichment scores and determines the global transformation for fitting to the normal distribution using the Box-Cox procedure. From the transformed distribution, sites of significant enrichment are identified. To increase power of detection, meta-analysis across experimental replicates is offered. We tested the tool on Cappable-seq and dRNA-seq data for identifying Escherichia coli transcript 5′ ends and compared the results with those from the TSSAR tool, which is designed for analyzing dRNA-seq data. When combining results across Cappable-seq replicates, ToNER detects more known transcript 5′ ends than TSSAR. In general, the transcript 5′ ends detected by ToNER but not TSSAR occur in regions which cannot be locally modeled by TSSAR. Conclusion ToNER uses a simple yet robust statistical modeling approach, which can be used for detecting RNA 5′ends from Cappable-seq data, in particular when combining information from experimental replicates. The ToNER tool could potentially be applied for analyzing other RNA-seq datasets in which enrichment for other structural features of RNA is employed. The program is freely available for download at ToNER webpage (http://www4a.biotec.or.th/GI/tools/toner) and GitHub repository (https://github.com/PavitaKae/ToNER). PMID:28542466

Dynamic Interaction of TTDA with TFIIH Is Stabilized by Nucleotide Excision Repair in Living Cells

PubMed Central

Theil, Arjan F; Mari, Pierre-Olivier; Hoogstraten, Deborah; Ng, Jessica M. Y; Dinant, Christoffel; Hoeijmakers, Jan H. J

2006-01-01

Transcription/repair factor IIH (TFIIH) is essential for RNA polymerase II transcription and nucleotide excision repair (NER). This multi-subunit complex consists of ten polypeptides, including the recently identified small 8-kDa trichothiodystrophy group A (TTDA)/ hTFB5 protein. Patients belonging to the rare neurodevelopmental repair syndrome TTD-A carry inactivating mutations in the TTDA/hTFB5 gene. One of these mutations completely inactivates the protein, whereas other TFIIH genes only tolerate point mutations that do not compromise the essential role in transcription. Nevertheless, the severe NER-deficiency in TTD-A suggests that the TTDA protein is critical for repair. Using a fluorescently tagged and biologically active version of TTDA, we have investigated the involvement of TTDA in repair and transcription in living cells. Under non-challenging conditions, TTDA is present in two distinct kinetic pools: one bound to TFIIH, and a free fraction that shuttles between the cytoplasm and nucleus. After induction of NER-specific DNA lesions, the equilibrium between these two pools dramatically shifts towards a more stable association of TTDA to TFIIH. Modulating transcriptional activity in cells did not induce a similar shift in this equilibrium. Surprisingly, DNA conformations that only provoke an abortive-type of NER reaction do not result into a more stable incorporation of TTDA into TFIIH. These findings identify TTDA as the first TFIIH subunit with a primarily NER-dedicated role in vivo and indicate that its interaction with TFIIH reflects productive NER. PMID:16669699

Redundancy checking algorithms based on parallel novel extension rule

NASA Astrophysics Data System (ADS)

Liu, Lei; Yang, Yang; Li, Guangli; Wang, Qi; Lü, Shuai

2017-05-01

Redundancy checking (RC) is a key knowledge reduction technology. Extension rule (ER) is a new reasoning method, first presented in 2003 and well received by experts at home and abroad. Novel extension rule (NER) is an improved ER-based reasoning method, presented in 2009. In this paper, we first analyse the characteristics of the extension rule, and then present a simple algorithm for redundancy checking based on extension rule (RCER). In addition, we introduce MIMF, a type of heuristic strategy. Using the aforementioned rule and strategy, we design and implement RCHER algorithm, which relies on MIMF. Next we design and implement an RCNER (redundancy checking based on NER) algorithm based on NER. Parallel computing greatly accelerates the NER algorithm, which has weak dependence among tasks when executed. Considering this, we present PNER (parallel NER) and apply it to redundancy checking and necessity checking. Furthermore, we design and implement the RCPNER (redundancy checking based on PNER) and NCPPNER (necessary clause partition based on PNER) algorithms as well. The experimental results show that MIMF significantly influences the acceleration of algorithm RCER in formulae on a large scale and high redundancy. Comparing PNER with NER and RCPNER with RCNER, the average speedup can reach up to the number of task decompositions when executed. Comparing NCPNER with the RCNER-based algorithm on separating redundant formulae, speedup increases steadily as the scale of the formulae is incrementing. Finally, we describe the challenges that the extension rule will be faced with and suggest possible solutions.

Character-level neural network for biomedical named entity recognition.

PubMed

Gridach, Mourad

2017-06-01

Biomedical named entity recognition (BNER), which extracts important named entities such as genes and proteins, is a challenging task in automated systems that mine knowledge in biomedical texts. The previous state-of-the-art systems required large amounts of task-specific knowledge in the form of feature engineering, lexicons and data pre-processing to achieve high performance. In this paper, we introduce a novel neural network architecture that benefits from both word- and character-level representations automatically, by using a combination of bidirectional long short-term memory (LSTM) and conditional random field (CRF) eliminating the need for most feature engineering tasks. We evaluate our system on two datasets: JNLPBA corpus and the BioCreAtIvE II Gene Mention (GM) corpus. We obtained state-of-the-art performance by outperforming the previous systems. To the best of our knowledge, we are the first to investigate the combination of deep neural networks, CRF, word embeddings and character-level representation in recognizing biomedical named entities. Copyright © 2017 Elsevier Inc. All rights reserved.

Discovering latent commercial networks from online financial news articles

NASA Astrophysics Data System (ADS)

Xia, Yunqing; Su, Weifeng; Lau, Raymond Y. K.; Liu, Yi

2013-08-01

Unlike most online social networks where explicit links among individual users are defined, the relations among commercial entities (e.g. firms) may not be explicitly declared in commercial Web sites. One main contribution of this article is the development of a novel computational model for the discovery of the latent relations among commercial entities from online financial news. More specifically, a CRF model which can exploit both structural and contextual features is applied to commercial entity recognition. In addition, a point-wise mutual information (PMI)-based unsupervised learning method is developed for commercial relation identification. To evaluate the effectiveness of the proposed computational methods, a prototype system called CoNet has been developed. Based on the financial news articles crawled from Google finance, the CoNet system achieves average F-scores of 0.681 and 0.754 in commercial entity recognition and commercial relation identification, respectively. Our experimental results confirm that the proposed shallow natural language processing methods are effective for the discovery of latent commercial networks from online financial news.

Comparative net energy ratio analysis of pellet produced from steam pretreated biomass from agricultural residues and energy crops

DOE PAGES

Shahrukh, Hassan; Oyedun, Adetoyese Olajire; Kumar, Amit; ...

2016-04-05

Here, a process model was developed to determine the net energy ratio (NER) for production of pellets from steam pretreated agricultural residue (AR) and energy crop (i.e. switchgrass in this case). The NER is a ratio of the net energy output to the total net energy input from non-renewable energy sources into a system. Scenarios were developed to measure the effects of temperature and level of steam pretreatment on the NER of steam pretreated AR- and switch grass-based pellets. The NER for the base case at 6 kg h -1 is 1.76 and 1.37 for steam-pretreated AR- and switchgrass-based pellets,more » respectively. The reason behind the difference is that more energy is required to dry switchgrass pellets than AR pellets. The sensitivity analysis for the model shows that the optimum temperature for steam pretreatment is 160 C with 50% pretreatment (half the feedstock is pretreated, while the rest is undergoes regular pelletization). The uncertainty results for NER for steam pretreated AR and switch grass pellets are 1.62 ± 0.10 and 1.42 ± 0.11, respectively.« less

Priority data on marine and estuarine resources within northeastern National Parks: Inventory and acquisition needs

USGS Publications Warehouse

Hart, Tracy E.; Neckles, Hilary A.; Kopp, Blaine S.

2013-01-01

The purpose of this project was to guide development of a strategy for the inventory and mapping of submerged natural resources associated within 10 coastal parks of the National Park Service (NPS) Northeast Region (NER; see Table 1). Priority data needs were identified by the NER Ocean Stewardship Task Force. The majority of the NER priority data needs involve the biotic, chemical, and geological characterization of the seabed. Taken collectively, this demands a consistent and unified approach to habitat classification. The Coastal and Marine Ecological Classification Standard (CMECS) is endorsed by the Federal Geographic Data Committee (FGDC-STD-018) for classifying ecological units in coastal and marine environments, and is recommended as a framework for acquiring and organizing NER data. We prepared an inventory of existing data on priority marine and estuarine natural resources within the ten NER coastal parks. This report describes the data and information sources relevant to each park and identifies gaps in available data. Overwhelmingly and uniformly across all parks, the most pressing needs are consistent, high-resolution bathymetry and seafloor characterization data. Approaches for acquiring these data using an integrated, multi-resolution sampling framework are recommended.

Anatomical entity mention recognition at literature scale

PubMed Central

Pyysalo, Sampo; Ananiadou, Sophia

2014-01-01

Motivation: Anatomical entities ranging from subcellular structures to organ systems are central to biomedical science, and mentions of these entities are essential to understanding the scientific literature. Despite extensive efforts to automatically analyze various aspects of biomedical text, there have been only few studies focusing on anatomical entities, and no dedicated methods for learning to automatically recognize anatomical entity mentions in free-form text have been introduced. Results: We present AnatomyTagger, a machine learning-based system for anatomical entity mention recognition. The system incorporates a broad array of approaches proposed to benefit tagging, including the use of Unified Medical Language System (UMLS)- and Open Biomedical Ontologies (OBO)-based lexical resources, word representations induced from unlabeled text, statistical truecasing and non-local features. We train and evaluate the system on a newly introduced corpus that substantially extends on previously available resources, and apply the resulting tagger to automatically annotate the entire open access scientific domain literature. The resulting analyses have been applied to extend services provided by the Europe PubMed Central literature database. Availability and implementation: All tools and resources introduced in this work are available from http://nactem.ac.uk/anatomytagger. Contact: sophia.ananiadou@manchester.ac.uk Supplementary Information: Supplementary data are available at Bioinformatics online. PMID:24162468

The Role of Sensory-Motor Information in Object Recognition: Evidence from Category-Specific Visual Agnosia

ERIC Educational Resources Information Center

Wolk, D.A.; Coslett, H.B.; Glosser, G.

2005-01-01

The role of sensory-motor representations in object recognition was investigated in experiments involving AD, a patient with mild visual agnosia who was impaired in the recognition of visually presented living as compared to non-living entities. AD named visually presented items for which sensory-motor information was available significantly more…

Anaplastic sarcoma of the kidney.

PubMed

Labanaris, Apostolos; Zugor, Vahudin; Smiszek, Robert; Nützel, Reinhold; Kühn, Reinhard

2009-02-15

Wilms tumor can appear with a wide spectrum of morphologic features and can sometimes cover or delay the recognition of other clinicopathologic entities of the kidney. We present a case of a new tumor entity of the kidney, namely the anaplastic sarcoma of the kidney, a tumor of high malignancy.

Enhancement of UV-induced nucleotide excision repair activity upon forskolin treatment is cell growth-dependent.

PubMed

Lee, Jeong-Min; Park, Jeong-Min; Kang, Tae-Hong

2016-10-01

Forskolin (FSK), an adenylyl cyclase activator, has recently been shown to enhance nucleotide excision repair (NER) upon UV exposure. However, our study revealed that this effect was detected in human skin epithelial ARPE19 cells only in growing cells, but not in non-cycling cells. When the cells were grown at low density (70% confluence), FSK was capable of stimulating cAMP responsive element binding (CREB) phosphorylation, a marker for FSK-stimulated PKA activation, and resulted in a significant increase of NER activity compared to control treatment. However, cells grown under 100% confluent conditions showed neither FSK-induced CREB phosphorylation nor the resulting NER enhancement. These findings indicate that cellular growth is critical for FSK-induced NER enhancement and suggest that cellular growth conditions should be considered as a variable while evaluating a reagent's pharmacotherapeutic efficacy. [BMB Reports 2016; 49(10): 566-571].

Hereditary Disorders with Defective Repair of UV-Induced DNA Damage

PubMed Central

Moriwaki, Shinichi

2013-01-01

Nucleotide excision repair (NER) is an essential system for correcting ultraviolet (UV)—induced DNA damage. Lesions remaining in DNA due to reduced capacity of NER may result in cellular death, premature aging, mutagenesis and carcinogenesis of the skin. So, NER is an important protection against these changes. There are three representative genodermatoses resulting from genetic defects in NER: xeroderma pigmentosum (XP), Cockayne syndrome (CS), and trichothiodystrophy (TTD). In Japan, CS is similarly rare but XP is more common and TTD is less common compared to Western countries. In 1998, we established the system for the diagnosis of these disorders and we have been performing DNA repair and genetic analysis for more than 400 samples since then. At present, there is no cure for any human genetic disorder. Early diagnosis and symptomatic treatment of neurological, ocular and dermatological abnormalities should contribute to prolonging life and elevating QOL in patients. PMID:23966815

A C. elegans homolog for the UV-hypersensitivity syndrome disease gene UVSSA.

PubMed

Babu, Vipin; Schumacher, Björn

2016-05-01

The transcription-coupled repair pathway (TC-NER) plays a vital role in removing transcription-blocking DNA lesions, particularly UV-induced damage. Clinical symptoms of the two TC-NER-deficiency syndromes, Cockayne syndrome (CS) and UV-hypersensitivity syndrome (UVSS) are dissimilar and the underlying molecular mechanism causing this difference in disease pathology is not yet clearly understood. UV-stimulated scaffold protein A (UVSSA) has been identified recently as a new causal gene for UVSS. Here we describe a functional homolog of the human UVSSA gene in the nematode Caenorhabditis elegans, uvs-1 (UVSSA-like-1). Mutations in uvs-1 render the animals hypersensitive to UV-B irradiation and transcription-blocking lesion-inducing illudin-M, similar to mutations in TC-NER deficient mutants. Moreover, we demonstrate that TC-NER factors including UVS-1 are required for the survival of the adult animals after UV-treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

Patient protection and Affordable Care Act; data collection to support standards related to essential health benefits; recognition of entities for the accreditation of qualified health plans. Final rule.

PubMed

2012-07-20

This final rule establishes data collection standards necessary to implement aspects of section 1302 of the Patient Protection and Affordable Care Act (Affordable Care Act), which directs the Secretary of Health and Human Services to define essential health benefits. This final rule outlines the data on applicable plans to be collected from certain issuers to support the definition of essential health benefits. This final rule also establishes a process for the recognition of accrediting entities for purposes of certification of qualified health plans.

Abstracts versus Full Texts and Patents: A Quantitative Analysis of Biomedical Entities

NASA Astrophysics Data System (ADS)

Müller, Bernd; Klinger, Roman; Gurulingappa, Harsha; Mevissen, Heinz-Theodor; Hofmann-Apitius, Martin; Fluck, Juliane; Friedrich, Christoph M.

In information retrieval, named entity recognition gives the opportunity to apply semantic search in domain specific corpora. Recently, more full text patents and journal articles became freely available. As the information distribution amongst the different sections is unknown, an analysis of the diversity is of interest.

PET Quantification of the Norepinephrine Transporter in Human Brain with (S,S)-18F-FMeNER-D2.

PubMed

Moriguchi, Sho; Kimura, Yasuyuki; Ichise, Masanori; Arakawa, Ryosuke; Takano, Harumasa; Seki, Chie; Ikoma, Yoko; Takahata, Keisuke; Nagashima, Tomohisa; Yamada, Makiko; Mimura, Masaru; Suhara, Tetsuya

2017-07-01

Norepinephrine transporter (NET) in the brain plays important roles in human cognition and the pathophysiology of psychiatric disorders. Two radioligands, ( S , S )- 11 C-MRB and ( S , S )- 18 F-FMeNER-D 2 , have been used for imaging NETs in the thalamus and midbrain (including locus coeruleus) using PET in humans. However, NET density in the equally important cerebral cortex has not been well quantified because of unfavorable kinetics with ( S , S )- 11 C-MRB and defluorination with ( S , S )- 18 F-FMeNER-D 2 , which can complicate NET quantification in the cerebral cortex adjacent to the skull containing defluorinated 18 F radioactivity. In this study, we have established analysis methods of quantification of NET density in the brain including the cerebral cortex using ( S , S )- 18 F-FMeNER-D 2 PET. Methods: We analyzed our previous ( S , S )- 18 F-FMeNER-D 2 PET data of 10 healthy volunteers dynamically acquired for 240 min with arterial blood sampling. The effects of defluorination on the NET quantification in the superficial cerebral cortex was evaluated by establishing a time stability of NET density estimations with an arterial input 2-tissue-compartment model, which guided the less-invasive reference tissue model and area under the time-activity curve methods to accurately quantify NET density in all brain regions including the cerebral cortex. Results: Defluorination of ( S , S )- 18 F-FMeNER-D 2 became prominent toward the latter half of the 240-min scan. Total distribution volumes in the superficial cerebral cortex increased with the scan duration beyond 120 min. We verified that 90-min dynamic scans provided a sufficient amount of data for quantification of NET density unaffected by defluorination. Reference tissue model binding potential values from the 90-min scan data and area under the time-activity curve ratios of 70- to 90-min data allowed for the accurate quantification of NET density in the cerebral cortex. Conclusion: We have established methods of quantification of NET densities in the brain including the cerebral cortex unaffected by defluorination using ( S , S )- 18 F-FMeNER-D 2 These results suggest that we can accurately quantify NET density with a 90-min ( S , S )- 18 F-FMeNER-D 2 scan in broad brain areas. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Outcome prediction in patients with glioblastoma by using imaging, clinical, and genomic biomarkers: focus on the nonenhancing component of the tumor.

PubMed

Jain, Rajan; Poisson, Laila M; Gutman, David; Scarpace, Lisa; Hwang, Scott N; Holder, Chad A; Wintermark, Max; Rao, Arvind; Colen, Rivka R; Kirby, Justin; Freymann, John; Jaffe, C Carl; Mikkelsen, Tom; Flanders, Adam

2014-08-01

To correlate patient survival with morphologic imaging features and hemodynamic parameters obtained from the nonenhancing region (NER) of glioblastoma (GBM), along with clinical and genomic markers. An institutional review board waiver was obtained for this HIPAA-compliant retrospective study. Forty-five patients with GBM underwent baseline imaging with contrast material-enhanced magnetic resonance (MR) imaging and dynamic susceptibility contrast-enhanced T2*-weighted perfusion MR imaging. Molecular and clinical predictors of survival were obtained. Single and multivariable models of overall survival (OS) and progression-free survival (PFS) were explored with Kaplan-Meier estimates, Cox regression, and random survival forests. Worsening OS (log-rank test, P = .0103) and PFS (log-rank test, P = .0223) were associated with increasing relative cerebral blood volume of NER (rCBVNER), which was higher with deep white matter involvement (t test, P = .0482) and poor NER margin definition (t test, P = .0147). NER crossing the midline was the only morphologic feature of NER associated with poor survival (log-rank test, P = .0125). Preoperative Karnofsky performance score (KPS) and resection extent (n = 30) were clinically significant OS predictors (log-rank test, P = .0176 and P = .0038, respectively). No genomic alterations were associated with survival, except patients with high rCBVNER and wild-type epidermal growth factor receptor (EGFR) mutation had significantly poor survival (log-rank test, P = .0306; area under the receiver operating characteristic curve = 0.62). Combining resection extent with rCBVNER marginally improved prognostic ability (permutation, P = .084). Random forest models of presurgical predictors indicated rCBVNER as the top predictor; also important were KPS, age at diagnosis, and NER crossing the midline. A multivariable model containing rCBVNER, age at diagnosis, and KPS can be used to group patients with more than 1 year of difference in observed median survival (0.49-1.79 years). Patients with high rCBVNER and NER crossing the midline and those with high rCBVNER and wild-type EGFR mutation showed poor survival. In multivariable survival models, however, rCBVNER provided unique prognostic information that went above and beyond the assessment of all NER imaging features, as well as clinical and genomic features.

Outcome Prediction in Patients with Glioblastoma by Using Imaging, Clinical, and Genomic Biomarkers: Focus on the Nonenhancing Component of the Tumor

PubMed Central

Poisson, Laila M.; Gutman, David; Scarpace, Lisa; Hwang, Scott N.; Holder, Chad A.; Wintermark, Max; Rao, Arvind; Colen, Rivka R.; Kirby, Justin; Freymann, John; Jaffe, C. Carl; Mikkelsen, Tom; Flanders, Adam

2014-01-01

Purpose To correlate patient survival with morphologic imaging features and hemodynamic parameters obtained from the nonenhancing region (NER) of glioblastoma (GBM), along with clinical and genomic markers. Materials and Methods An institutional review board waiver was obtained for this HIPAA-compliant retrospective study. Forty-five patients with GBM underwent baseline imaging with contrast material–enhanced magnetic resonance (MR) imaging and dynamic susceptibility contrast-enhanced T2*-weighted perfusion MR imaging. Molecular and clinical predictors of survival were obtained. Single and multivariable models of overall survival (OS) and progression-free survival (PFS) were explored with Kaplan-Meier estimates, Cox regression, and random survival forests. Results Worsening OS (log-rank test, P = .0103) and PFS (log-rank test, P = .0223) were associated with increasing relative cerebral blood volume of NER (rCBVNER), which was higher with deep white matter involvement (t test, P = .0482) and poor NER margin definition (t test, P = .0147). NER crossing the midline was the only morphologic feature of NER associated with poor survival (log-rank test, P = .0125). Preoperative Karnofsky performance score (KPS) and resection extent (n = 30) were clinically significant OS predictors (log-rank test, P = .0176 and P = .0038, respectively). No genomic alterations were associated with survival, except patients with high rCBVNER and wild-type epidermal growth factor receptor (EGFR) mutation had significantly poor survival (log-rank test, P = .0306; area under the receiver operating characteristic curve = 0.62). Combining resection extent with rCBVNER marginally improved prognostic ability (permutation, P = .084). Random forest models of presurgical predictors indicated rCBVNER as the top predictor; also important were KPS, age at diagnosis, and NER crossing the midline. A multivariable model containing rCBVNER, age at diagnosis, and KPS can be used to group patients with more than 1 year of difference in observed median survival (0.49–1.79 years). Conclusion Patients with high rCBVNER and NER crossing the midline and those with high rCBVNER and wild-type EGFR mutation showed poor survival. In multivariable survival models, however, rCBVNER provided unique prognostic information that went above and beyond the assessment of all NER imaging features, as well as clinical and genomic features. © RSNA, 2014 Online supplemental material is available for this article. PMID:24646147

Binding Affinity of Glycoconjugates to BACILLUS Spores and Toxins

NASA Astrophysics Data System (ADS)

Rasol, Aveen; Eassa, Souzan; Tarasenko, Olga

2010-04-01

Early recognition of Bacillus cereus group species is important since they can cause food-borne illnesses and deadly diseases in humans. Glycoconjugates (GCs) are carbohydrates covalently linked to non-sugar moieties including lipids, proteins or other entities. GCs are involved in recognition and signaling processes intrinsic to biochemical functions in cells. They also stimulate cell-cell adhesion and subsequent recognition and activation of receptors. We have demonstrated that GCs are involved in Bacillus cereus spore recognition. In the present study, we have investigated whether GCs possess the ability to bind and recognize B. cereus spores and Bacillus anthracis recombinant single toxins (sTX) and complex toxins (cTX). The affinity of GCs to spores + sTX and spores + cTX toxins was studied in the binding essay. Our results demonstrated that GC9 and GC10 were able to selectively bind to B. cereus spores and B. anthracis toxins. Different binding affinities for GCs were found toward Bacillus cereus spores + sTX and spores + cTX. Dilution of GCs does not impede the recognition and binding. Developed method provides a tool for simultaneous recognition and targeting of spores, bacteria toxins, and/or other entities.

Helicopter Maritime Environment Trainer: Software Product Specification

DTIC Science & Technology

2011-06-01

d’entraîner les pilotes d’hélicoptère à l’atterrissage sur le pont d’envol d’une frégate canadienne de patrouille dans un environnement virtuel. Le...d’entraîner les pilotes d’hélicoptère à l’atterrissage sur le pont d’envol d’une frégate canadienne de patrouille dans un environnement virtuel. Le...d’entraîner les pilotes d’hélicoptère à l’atterrissage sur le pont d’envol d’une frégate canadienne de patrouille dans un environnement virtuel. Le système

Evaluation of Biomonitoring Data from the CDC National ...

EPA Pesticide Factsheets

BACKGROUND: Biomonitoring data reported in the National Report on Human Exposure to Environmental Chemicals (NER) provide information on the presence and concentrations of more than 400 chemicals in human blood and urine. Biomonitoring Equivalents (BEs) and other risk assessment-based values now allow interpretation of these biomonitoring data in a public health risk context. OBJECTIVES: Compare the measured biomarker concentrations in the NER with BEs and similar risk assessment values to provide an across-chemical risk assessment perspective on the measured levels for approximately 130 analytes in the NER. METHODS: Available risk assessment-based biomarker screening values, including BEs and Human Biomonitoring-I (HBM-I) values from the German Human Biomonitoring Commission, were identified. Geometric mean and 95th percentile population biomarker concentrations from the NER were compared to the available screening values to generate chemical-specific hazard quotients (HQ) or cancer risk estimates. CONCLUSIONS: Several analytes in the NER approach or exceed HQ values of 1 or cancer risks greater than 1x 10-4 at the geometric mean or 95th percentile, suggesting exposure levels exceed what is considered safe in a large fraction of the population. Analytes of concern include acrylamide, dioxin-like chemicals, benzene, xylene, several metals, di-2(ethylhexyl)phthalate, and some legacy organochlorine pesticides. This analysis provides for the first time a mean

University of Glasgow at TREC 2009: Experiments with Terrier

DTIC Science & Technology

2009-11-01

identify entities in the category B subset of the corpus, we resort to an efficient dictionary -based named en- tity recognition approach.4 In particular...we build a large dictio- nary of entity names using DBPedia,5 a structured representation of Wikipedia. Dictionary entries comprise all known...aliases for each unique entity, as obtained from DBPedia (e.g., ‘Barack Obama’ is represented by the dictionary entries ‘Barack Obama’ and ‘44th President

IMMUNOLOGIC EFFECTS OF NONIONIZING ELECTROMAGNETIC RADIATION (JOURNAL VERSION)

EPA Science Inventory

Many of the studies in which animals or cells have been exposed at various frequencies and intensities of NER radiation have reported inconsistent and transient changes in the functional integrity of the immune defense system. Many of the reported immune effects of NER, however, ...

77 FR 44255 - Medicare Program; Application by the American Association of Diabetes Educators (AADE) for...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-27

...] Medicare Program; Application by the American Association of Diabetes Educators (AADE) for Continued Recognition as a National Accreditation Organization for Accrediting Entities To Furnish Outpatient Diabetes... of Diabetes Educators for continued recognition as a national accreditation program for accrediting...

Implication of SUMO E3 ligases in nucleotide excision repair.

PubMed

Tsuge, Maasa; Kaneoka, Hidenori; Masuda, Yusuke; Ito, Hiroki; Miyake, Katsuhide; Iijima, Shinji

2015-08-01

Post-translational modifications alter protein function to mediate complex hierarchical regulatory processes that are crucial to eukaryotic cellular function. The small ubiquitin-like modifier (SUMO) is an important post-translational modification that affects transcriptional regulation, nuclear localization, and the maintenance of genome stability. Nucleotide excision repair (NER) is a very versatile DNA repair system that is essential for protection against ultraviolet (UV) irradiation. The deficiencies in NER function remarkably increase the risk of skin cancer. Recent studies have shown that several NER factors are SUMOylated, which influences repair efficiency. However, how SUMOylation modulates NER has not yet been elucidated. In the present study, we performed RNAi knockdown of SUMO E3 ligases and found that, in addition to PIASy, the polycomb protein Pc2 affected the repair of cyclobutane pyrimidine dimers. PIAS1 affected both the removal of 6-4 pyrimidine pyrimidone photoproducts and cyclobutane pyrimidine dimers, whereas other SUMO E3 ligases did not affect the removal of either UV lesion.

Structure and specificity of FEN-1 from Methanopyrus kandleri

DOE PAGES

Shah, Santosh; Dunten, Pete; Stiteler, Amanda; ...

2014-11-18

DNA repair is fundamental to genome stability and is found in all three domains of life. However, many archaeal species, such as Methanopyrus kandleri, contain only a subset of the eukaryotic nucleotide excision repair (NER) homologues, and those present often contain significant differences compared to their eukaryotic homologues. To clarify the role of the NER XPG-like protein Mk0566 from M. kandleri, its biochemical activity and three dimensional structure were investigated. Ultimately, we found both to be more similar to human FEN-1 than human XPG, suggesting a biological role in replication and long-patch base excision repair rather than in NER.

Large-scale extraction of brain connectivity from the neuroscientific literature

PubMed Central

Richardet, Renaud; Chappelier, Jean-Cédric; Telefont, Martin; Hill, Sean

2015-01-01

Motivation: In neuroscience, as in many other scientific domains, the primary form of knowledge dissemination is through published articles. One challenge for modern neuroinformatics is finding methods to make the knowledge from the tremendous backlog of publications accessible for search, analysis and the integration of such data into computational models. A key example of this is metascale brain connectivity, where results are not reported in a normalized repository. Instead, these experimental results are published in natural language, scattered among individual scientific publications. This lack of normalization and centralization hinders the large-scale integration of brain connectivity results. In this article, we present text-mining models to extract and aggregate brain connectivity results from 13.2 million PubMed abstracts and 630 216 full-text publications related to neuroscience. The brain regions are identified with three different named entity recognizers (NERs) and then normalized against two atlases: the Allen Brain Atlas (ABA) and the atlas from the Brain Architecture Management System (BAMS). We then use three different extractors to assess inter-region connectivity. Results: NERs and connectivity extractors are evaluated against a manually annotated corpus. The complete in litero extraction models are also evaluated against in vivo connectivity data from ABA with an estimated precision of 78%. The resulting database contains over 4 million brain region mentions and over 100 000 (ABA) and 122 000 (BAMS) potential brain region connections. This database drastically accelerates connectivity literature review, by providing a centralized repository of connectivity data to neuroscientists. Availability and implementation: The resulting models are publicly available at github.com/BlueBrain/bluima. Contact: renaud.richardet@epfl.ch Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25609795

The Case for 8, 5’-Cyclopurine-2’-Deoxynucleosides as Endogenous DNA Lesions That Cause Neurodegeneration in Xeroderma Pigmentosum

PubMed Central

Brooks, PJ

2007-01-01

Patients with the genetic disease xeroderma pigmentosum (XP) lack the capacity to carry out a specific type of DNA repair process called nucleotide excision repair (NER). The NER pathway plays a critical role in the repair of DNA damage resulting from UV radiation. A subset of XP patients develop a profound neurodegenerative condition known as XP neurological disease. Robbins and colleagues (PNAS 75:1984–88, 1978) hypothesized that since UV light cannot reach into the human brain, XP neurological disease results from some form of endogenous DNA damage that is normally repaired by the NER pathway. In the absence of NER, the damage accumulates, causing neuronal death by blocking transcription. In this manuscript, I consider the evidence that a particular class of oxidative DNA lesions, the 8, 5’-cyclopurine-2’-deoxynucleosides, fulfills many of the criteria expected of neurodegenerative DNA lesions in XP. Specifically, these lesions are chemically stable, endogenous DNA lesions that are repaired by the NER pathway but not by any other known process, and strongly block transcription by RNA polymerase II in cells from XP patients. A similar set of criteria might be used to evaluate other candidate DNA lesions responsible for neurological diseases resulting from defects in other DNA repair mechanisms as well. PMID:17184928

Illuminate Knowledge Elements in Geoscience Literature

NASA Astrophysics Data System (ADS)

Ma, X.; Zheng, J. G.; Wang, H.; Fox, P. A.

2015-12-01

There are numerous dark data hidden in geoscience literature. Efficient retrieval and reuse of those data will greatly benefit geoscience researches of nowadays. Among the works of data rescue, a topic of interest is illuminating the knowledge framework, i.e. entities and relationships, embedded in documents. Entity recognition and linking have received extensive attention in news and social media analysis, as well as in bioinformatics. In the domain of geoscience, however, such works are limited. We will present our work on how to use knowledge bases on the Web, such as ontologies and vocabularies, to facilitate entity recognition and linking in geoscience literature. The work deploys an un-supervised collective inference approach [1] to link entity mentions in unstructured texts to a knowledge base, which leverages the meaningful information and structures in ontologies and vocabularies for similarity computation and entity ranking. Our work is still in the initial stage towards the detection of knowledge frameworks in literature, and we have been collecting geoscience ontologies and vocabularies in order to build a comprehensive geoscience knowledge base [2]. We hope the work will initiate new ideas and collaborations on dark data rescue, as well as on the synthesis of data and knowledge from geoscience literature. References: 1. Zheng, J., Howsmon, D., Zhang, B., Hahn, J., McGuinness, D.L., Hendler, J., and Ji, H. 2014. Entity linking for biomedical literature. In Proceedings of ACM 8th International Workshop on Data and Text Mining in Bioinformatics, Shanghai, China. 2. Ma, X. Zheng, J., 2015. Linking geoscience entity mentions to the Web of Data. ESIP 2015 Summer Meeting, Pacific Grove, CA.

Coupling between nucleotide excision repair and gene expression.

PubMed

Cambindo Botto, Adrián E; Muñoz, Juan C; Muñoz, Manuel J

2018-05-17

Gene expression and DNA repair are fundamental processes for life. During the last decade, accumulating experimental evidence point towards different modes of coupling between these processes. Here we discuss the molecular mechanisms by which RNAPII-dependent transcription affects repair by the Nucleotide Excision Repair system (NER) and how NER activity, through the generation of single stranded DNA intermediates and activation of the DNA damage response kinase ATR, drives gene expression in a genotoxic scenario. Since NER-dependent repair is compromised in Xeroderma Pigmentosum (XP) patients, and having in mind that these patients present a high degree of clinical heterogeneity, we speculate that some of the clinical features of XP patients can be explained by misregulation of gene expression.

Interplay of DNA repair with transcription: from structures to mechanisms.

PubMed

Deaconescu, Alexandra M; Artsimovitch, Irina; Grigorieff, Nikolaus

2012-12-01

Many DNA transactions are crucial for maintaining genomic integrity and faithful transfer of genetic information but remain poorly understood. An example is the interplay between nucleotide excision repair (NER) and transcription, also known as transcription-coupled DNA repair (TCR). Discovered decades ago, the mechanisms for TCR have remained elusive, not in small part due to the scarcity of structural studies of key players. Here we summarize recent structural information on NER/TCR factors, focusing on bacterial systems, and integrate it with existing genetic, biochemical, and biophysical data to delineate the mechanisms at play. We also review emerging, alternative modalities for recruitment of NER proteins to DNA lesions. Copyright © 2012 Elsevier Ltd. All rights reserved.

Improving the dictionary lookup approach for disease normalization using enhanced dictionary and query expansion

PubMed Central

Jonnagaddala, Jitendra; Jue, Toni Rose; Chang, Nai-Wen; Dai, Hong-Jie

2016-01-01

The rapidly increasing biomedical literature calls for the need of an automatic approach in the recognition and normalization of disease mentions in order to increase the precision and effectivity of disease based information retrieval. A variety of methods have been proposed to deal with the problem of disease named entity recognition and normalization. Among all the proposed methods, conditional random fields (CRFs) and dictionary lookup method are widely used for named entity recognition and normalization respectively. We herein developed a CRF-based model to allow automated recognition of disease mentions, and studied the effect of various techniques in improving the normalization results based on the dictionary lookup approach. The dataset from the BioCreative V CDR track was used to report the performance of the developed normalization methods and compare with other existing dictionary lookup based normalization methods. The best configuration achieved an F-measure of 0.77 for the disease normalization, which outperformed the best dictionary lookup based baseline method studied in this work by an F-measure of 0.13. Database URL: https://github.com/TCRNBioinformatics/DiseaseExtract PMID:27504009

A novel regulation mechanism of DNA repair by damage-induced and RAD23-dependent stabilization of xeroderma pigmentosum group C protein

PubMed Central

Ng, Jessica M.Y.; Vermeulen, Wim; van der Horst, Gijsbertus T.J.; Bergink, Steven; Sugasawa, Kaoru; Vrieling, Harry; Hoeijmakers, Jan H.J.

2003-01-01

Primary DNA damage sensing in mammalian global genome nucleotide excision repair (GG-NER) is performed by the xeroderma pigmentosum group C (XPC)/HR23B protein complex. HR23B and HR23A are human homologs of the yeast ubiquitin-domain repair factor RAD23, the function of which is unknown. Knockout mice revealed that mHR23A and mHR23B have a fully redundant role in NER, and a partially redundant function in embryonic development. Inactivation of both genes causes embryonic lethality, but appeared still compatible with cellular viability. Analysis of mHR23A/B double-mutant cells showed that HR23 proteins function in NER by governing XPC stability via partial protection against proteasomal degradation. Interestingly, NER-type DNA damage further stabilizes XPC and thereby enhances repair. These findings resolve the primary function of RAD23 in repair and reveal a novel DNA-damage-dependent regulation mechanism of DNA repair in eukaryotes, which may be part of a more global damage-response circuitry. PMID:12815074

Nuclear organization of nucleotide excision repair is mediated by RING1B dependent H2A-ubiquitylation

PubMed Central

Chitale, Shalaka; Richly, Holger

2017-01-01

One of the major cellular DNA repair pathways is nucleotide excision repair (NER). It is the primary pathway for repair of various DNA lesions caused by exposure to ultraviolet (UV) light, such as cyclobutane pyrimidine dimers (CPDs) and 6-4 photoproducts. Although lesion-containing DNA associates with the nuclear matrix after UV irradiation it is still not understood how nuclear organization affects NER. Analyzing unscheduled DNA synthesis (UDS) indicates that NER preferentially occurs in specific nuclear areas, viz the nucleolus. Upon inducing localized damage, we observe migration of damaged DNA towards the nucleolus. Employing a LacR-based tethering system we demonstrate that H2A-ubiquitylation via the UV-RING1B complex localizes chromatin close to the nucleolus. We further show that the H2A-ubiquitin binding protein ZRF1 resides in the nucleolus, and that it anchors ubiquitylated chromatin along with XPC. Our data thus provide insight into the sub-nuclear organization of NER and reveal a novel role for histone H2A-ubiquitylation. PMID:28416769

Synthetic Approaches to the New Drugs Approved During 2015.

PubMed

Flick, Andrew C; Ding, Hong X; Leverett, Carolyn A; Kyne, Robert E; Liu, Kevin K-C; Fink, Sarah J; O'Donnell, Christopher J

2017-08-10

New drugs introduced to the market every year represent privileged structures for particular biological targets. These new chemical entities (NCEs) provide insight into molecular recognition while serving as leads for designing future new drugs. This annual review describes the most likely process-scale synthetic approaches to 29 new chemical entities (NCEs) that were approved for the first time in 2015.

Nucleotide excision repair modulates the cytotoxic and mutagenic effects of N-n-butyl-N-nitrosourea in cultured mammalian cells as well as in mouse splenocytes in vivo.

PubMed

Bol, S A; van Steeg, H; van Oostrom, C T; Tates, A D; Vrieling, H; de Groot, A J; Mullenders, L H; van Zeeland, A A; Jansen, J G

1999-05-01

The butylating agent N-n-butyl-N-nitrosourea (BNU) was employed to study the role of nucleotide excision repair (NER) in protecting mammalian cells against the genotoxic effects of monofunctional alkylating agents. The direct acting agent BNU was found to be mutagenic in normal and XPA mouse splenocytes after a single i.p. treatment in vivo. After 25 and 35 mg/kg BNU, but not after 75 mg/ kg, 2- to 3-fold more hprt mutants were detected in splenocytes from XPA mice than from normal mice. Using O6-alkylguanine-DNA alkyltransferase (AGT)-deficient hamster cells, it was found that NER-deficient CHO UV5 cells carrying a mutation in the ERCC-2 gene were 40% more mutable towards lesions induced by BNU when compared with parental NER-proficient CHO AA8 cells. UV5 cells were 1.4-fold more sensitive to the cytotoxic effects of BNU compared with AA8 cells. To investigate whether this increased sensitivity of NER-deficient cells is modulated by AGT activity, cell survival studies were performed in human and mouse primary fibroblasts as well. BNU was 2.7-fold more toxic for mouse XPA fibroblasts compared with normal mouse fibroblasts. Comparable results were found for human fibroblasts. Taken together these data indicate that the role of NER in protecting rodent cells against the mutagenic and cytotoxic effects of the alkylating agent BNU depends on AGT.

Chemical entity recognition in patents by combining dictionary-based and statistical approaches

PubMed Central

Akhondi, Saber A.; Pons, Ewoud; Afzal, Zubair; van Haagen, Herman; Becker, Benedikt F.H.; Hettne, Kristina M.; van Mulligen, Erik M.; Kors, Jan A.

2016-01-01

We describe the development of a chemical entity recognition system and its application in the CHEMDNER-patent track of BioCreative 2015. This community challenge includes a Chemical Entity Mention in Patents (CEMP) recognition task and a Chemical Passage Detection (CPD) classification task. We addressed both tasks by an ensemble system that combines a dictionary-based approach with a statistical one. For this purpose the performance of several lexical resources was assessed using Peregrine, our open-source indexing engine. We combined our dictionary-based results on the patent corpus with the results of tmChem, a chemical recognizer using a conditional random field classifier. To improve the performance of tmChem, we utilized three additional features, viz. part-of-speech tags, lemmas and word-vector clusters. When evaluated on the training data, our final system obtained an F-score of 85.21% for the CEMP task, and an accuracy of 91.53% for the CPD task. On the test set, the best system ranked sixth among 21 teams for CEMP with an F-score of 86.82%, and second among nine teams for CPD with an accuracy of 94.23%. The differences in performance between the best ensemble system and the statistical system separately were small. Database URL: http://biosemantics.org/chemdner-patents PMID:27141091

Comparative pharmacokinetic profiles of selected irreversible tyrosine kinase inhibitors, neratinib and pelitinib, with apigenin in rat plasma by UPLC-MS/MS.

PubMed

Maher, Hadir M; Alzoman, Nourah Z; Shehata, Shereen M; Abahussain, Ashwag O

2017-04-15

Neratinib (NER) and pelitinib (PEL) are irreversible tyrosine kinase inhibitors (TKIs) that have been recently employed in cancer treatment. Apigenin (API), among other flavonoids, is known to have antioxidant, anti-proliferative, and carcinogenic effect. API can potentiate the antitumor effect of chemotherapeutic agents and/or alleviate the side effects of many anticancer agents. Since TKIs are mostly metabolized by CYP3A4 enzymes and that API could alter the enzymatic activity, potential drug interactions could be expected following their co-aministration. In the present study, a bioanalytical UPLC-MS/MS method has been developed and validated for the quantification of NER and PEL in rat plasma, using domperidone (DOM) as an internal standard. Sample preparation was carried out using solid phase extraction (SPE) with C18 cartridges with good extraction recovery of not less than 92.42% (NER) and 89.73% (PEL). Chromatographic analysis was performed on a Waters BEH C18 column with a mobile phase composed of acetonitrile and water, (70:30, v/v), each with 0.1% formic acid. Quantitation was performed using multiple reaction monitoring (MRM) of the transitions from protonated precursor ions [M+H] + , at m/z 557.30 (NER), m/z 468.21 (PEL), and at m/z 426.27 (DOM), to selected product ions at m/z 112.05 (NER), m/z 395.22 (PEL), and at m/z 175.18 (DOM). The method was fully validated as per the FDA guidelines over the concentration range of 0.5-200ng/mL with very low lower limit of quantification (LLOQ) of 0.5ng/mL for both NER and PEL. The intra- and inter-day assay precision and accuracy were evaluated for both drugs and the calculated values of percentage relative standards deviations (%RSD) and relative errors (%E r ) were within the acceptable limits (<15%) for concentrations other than LLOQ and 20% for LLOQ. The applicability of the method was extended to study the possibility of drug interactions following the oral co-administration of NER/PEL with API. Thus, this study could be readily applied in therapeutic drug monitoring (TDM) of cancerous patients receiving such drug combinations. Copyright © 2017 Elsevier B.V. All rights reserved.

Cost-effectiveness of a national exercise referral programme for primary care patients in Wales: results of a randomised controlled trial

PubMed Central

2013-01-01

Background A recent HTA review concluded that there was a need for RCTs of exercise referral schemes (ERS) for people with a medical diagnosis who might benefit from exercise. Overall, there is still uncertainty as to the cost-effectiveness of ERS. Evaluation of public health interventions places challenges on conventional health economics approaches. This economic evaluation of a national public health intervention addresses this issue of where ERS may be most cost effective through subgroup analysis, particularly important at a time of financial constraint. Method This economic analysis included 798 individuals aged 16 and over (55% of the randomised controlled trial (RCT) sample) with coronary heart disease risk factors and/or mild to moderate anxiety, depression or stress. Individuals were referred by health professionals in a primary care setting to a 16 week national exercise referral scheme (NERS) delivered by qualified exercise professionals in local leisure centres in Wales, UK. Health-related quality of life, health care services use, costs per participant in NERS, and willingness to pay for NERS were measured at 6 and 12 months. Results The base case analysis assumed a participation cost of £385 per person per year, with a mean difference in QALYs between the two groups of 0.027. The incremental cost-effectiveness ratio was £12,111 per QALY gained. Probabilistic sensitivity analysis demonstrated an 89% probability of NERS being cost-effective at a payer threshold of £30,000 per QALY. When participant payments of £1 and £2 per session were considered, the cost per QALY fell from £12,111 (base case) to £10,926 and £9,741, respectively. Participants with a mental health risk factor alone or in combination with a risk of chronic heart disease generated a lower ICER (£10,276) compared to participants at risk of chronic heart disease only (£13,060). Conclusions Results of cost-effectiveness analyses suggest that NERS is cost saving in fully adherent participants. Though full adherence to NERS (62%) was higher for the economics sample than the main sample (44%), results still suggest that NERS can be cost-effective in Wales with respect to existing payer thresholds particularly for participants with mental health and CHD risk factors. Trial registration Current Controlled Trials ISRCTN47680448 PMID:24164697

Cost-effectiveness of a national exercise referral programme for primary care patients in Wales: results of a randomised controlled trial.

PubMed

Edwards, Rhiannon Tudor; Linck, Pat; Hounsome, Natalia; Raisanen, Larry; Williams, Nefyn; Moore, Laurence; Murphy, Simon

2013-10-29

A recent HTA review concluded that there was a need for RCTs of exercise referral schemes (ERS) for people with a medical diagnosis who might benefit from exercise. Overall, there is still uncertainty as to the cost-effectiveness of ERS. Evaluation of public health interventions places challenges on conventional health economics approaches. This economic evaluation of a national public health intervention addresses this issue of where ERS may be most cost effective through subgroup analysis, particularly important at a time of financial constraint. This economic analysis included 798 individuals aged 16 and over (55% of the randomised controlled trial (RCT) sample) with coronary heart disease risk factors and/or mild to moderate anxiety, depression or stress. Individuals were referred by health professionals in a primary care setting to a 16 week national exercise referral scheme (NERS) delivered by qualified exercise professionals in local leisure centres in Wales, UK. Health-related quality of life, health care services use, costs per participant in NERS, and willingness to pay for NERS were measured at 6 and 12 months. The base case analysis assumed a participation cost of £385 per person per year, with a mean difference in QALYs between the two groups of 0.027. The incremental cost-effectiveness ratio was £12,111 per QALY gained. Probabilistic sensitivity analysis demonstrated an 89% probability of NERS being cost-effective at a payer threshold of £30,000 per QALY. When participant payments of £1 and £2 per session were considered, the cost per QALY fell from £12,111 (base case) to £10,926 and £9,741, respectively. Participants with a mental health risk factor alone or in combination with a risk of chronic heart disease generated a lower ICER (£10,276) compared to participants at risk of chronic heart disease only (£13,060). Results of cost-effectiveness analyses suggest that NERS is cost saving in fully adherent participants. Though full adherence to NERS (62%) was higher for the economics sample than the main sample (44%), results still suggest that NERS can be cost-effective in Wales with respect to existing payer thresholds particularly for participants with mental health and CHD risk factors. Current Controlled Trials ISRCTN47680448.

A study of machine-learning-based approaches to extract clinical entities and their assertions from discharge summaries.

PubMed

Jiang, Min; Chen, Yukun; Liu, Mei; Rosenbloom, S Trent; Mani, Subramani; Denny, Joshua C; Xu, Hua

2011-01-01

The authors' goal was to develop and evaluate machine-learning-based approaches to extracting clinical entities-including medical problems, tests, and treatments, as well as their asserted status-from hospital discharge summaries written using natural language. This project was part of the 2010 Center of Informatics for Integrating Biology and the Bedside/Veterans Affairs (VA) natural-language-processing challenge. The authors implemented a machine-learning-based named entity recognition system for clinical text and systematically evaluated the contributions of different types of features and ML algorithms, using a training corpus of 349 annotated notes. Based on the results from training data, the authors developed a novel hybrid clinical entity extraction system, which integrated heuristic rule-based modules with the ML-base named entity recognition module. The authors applied the hybrid system to the concept extraction and assertion classification tasks in the challenge and evaluated its performance using a test data set with 477 annotated notes. Standard measures including precision, recall, and F-measure were calculated using the evaluation script provided by the Center of Informatics for Integrating Biology and the Bedside/VA challenge organizers. The overall performance for all three types of clinical entities and all six types of assertions across 477 annotated notes were considered as the primary metric in the challenge. Systematic evaluation on the training set showed that Conditional Random Fields outperformed Support Vector Machines, and semantic information from existing natural-language-processing systems largely improved performance, although contributions from different types of features varied. The authors' hybrid entity extraction system achieved a maximum overall F-score of 0.8391 for concept extraction (ranked second) and 0.9313 for assertion classification (ranked fourth, but not statistically different than the first three systems) on the test data set in the challenge.

Urinary bladder: normal appearance and mimics of malignancy at CT urography

PubMed Central

Sadow, Cheryl A.; Anik Sahni, V.; Silverman, Stuart G.

2011-01-01

Abstract The objective of this review article is to learn how to recognize anatomic variants and benign entities that mimic bladder cancer at computed tomography (CT) urography. Building on recent data that suggest that CT urography can be used to diagnose bladder cancer, recognition of anatomic variants and benign entities will help improve radiologists’ ability to diagnose bladder cancer. PMID:21771710

FamPlex: a resource for entity recognition and relationship resolution of human protein families and complexes in biomedical text mining.

PubMed

Bachman, John A; Gyori, Benjamin M; Sorger, Peter K

2018-06-28

For automated reading of scientific publications to extract useful information about molecular mechanisms it is critical that genes, proteins and other entities be correctly associated with uniform identifiers, a process known as named entity linking or "grounding." Correct grounding is essential for resolving relationships among mined information, curated interaction databases, and biological datasets. The accuracy of this process is largely dependent on the availability of machine-readable resources associating synonyms and abbreviations commonly found in biomedical literature with uniform identifiers. In a task involving automated reading of ∼215,000 articles using the REACH event extraction software we found that grounding was disproportionately inaccurate for multi-protein families (e.g., "AKT") and complexes with multiple subunits (e.g."NF- κB"). To address this problem we constructed FamPlex, a manually curated resource defining protein families and complexes as they are commonly encountered in biomedical text. In FamPlex the gene-level constituents of families and complexes are defined in a flexible format allowing for multi-level, hierarchical membership. To create FamPlex, text strings corresponding to entities were identified empirically from literature and linked manually to uniform identifiers; these identifiers were also mapped to equivalent entries in multiple related databases. FamPlex also includes curated prefix and suffix patterns that improve named entity recognition and event extraction. Evaluation of REACH extractions on a test corpus of ∼54,000 articles showed that FamPlex significantly increased grounding accuracy for families and complexes (from 15 to 71%). The hierarchical organization of entities in FamPlex also made it possible to integrate otherwise unconnected mechanistic information across families, subfamilies, and individual proteins. Applications of FamPlex to the TRIPS/DRUM reading system and the Biocreative VI Bioentity Normalization Task dataset demonstrated the utility of FamPlex in other settings. FamPlex is an effective resource for improving named entity recognition, grounding, and relationship resolution in automated reading of biomedical text. The content in FamPlex is available in both tabular and Open Biomedical Ontology formats at https://github.com/sorgerlab/famplex under the Creative Commons CC0 license and has been integrated into the TRIPS/DRUM and REACH reading systems.

An eco-friendly direct spectrofluorimetric method for the determination of irreversible tyrosine kinase inhibitors, neratinib and pelitinib: application to stability studies.

PubMed

Maher, H M; Alzoman, N Z; Shehata, S M

2017-03-01

A new rapid and simple stability-indicating spectrofluorimetric method has been developed for the determination of two irreversible tyrosine kinase inhibitors (TKIs), neratinib (NER) and pelitinib (PEL). The method is based upon measurement of the native fluorescence intensity of both drugs at λ ex 270 nm in aqueous borate buffer solutions (pH 10.5). The fluorescence intensity recorded at 545 nm (NER) and 465 nm (PEL) were rectilinear over the concentration range of 0.1-10 μg/mL for both drugs with a high correlation coefficient (r > 0.999). The proposed method provided low limits of detection and of quantitation of 0.07, 0.11 μg/mL (NER) and 0.02, 0.05 μg/mL (PEL), respectively. The method was successfully applied for the determination of NER and PEL in bulk powder. The proposed methods were fully validated as per the International Conference on Harmonisation (ICH) guidelines. The application of the method was extended to stability studies of both NER and PEL under different forced-degradation conditions (acidic-induced, base-induced, oxidative, wet heat, and photolytic degradation). Moreover, the kinetics of the base-induced and oxidative degradation of both drugs was investigated and the pseudo-first-order rate constants and half-lives were estimated at different temperatures. Also, an Arrhenius plot was applied to predict the stability behaviour of the two drugs at room temperature. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Nucleotide Excision Repair and Vitamin D--Relevance for Skin Cancer Therapy.

PubMed

Pawlowska, Elzbieta; Wysokinski, Daniel; Blasiak, Janusz

2016-04-06

Ultraviolet (UV) radiation is involved in almost all skin cancer cases, but on the other hand, it stimulates the production of pre-vitamin D3, whose active metabolite, 1,25-dihydroxyvitamin D3 (1,25VD3), plays important physiological functions on binding with its receptor (vitamin D receptor, VDR). UV-induced DNA damages in the form of cyclobutane pyrimidine dimers or (6-4)-pyrimidine-pyrimidone photoproducts are frequently found in skin cancer and its precursors. Therefore, removing these lesions is essential for the prevention of skin cancer. As UV-induced DNA damages are repaired by nucleotide excision repair (NER), the interaction of 1,25VD3 with NER components can be important for skin cancer transformation. Several studies show that 1,25VD3 protects DNA against damage induced by UV, but the exact mechanism of this protection is not completely clear. 1,25VD3 was also shown to affect cell cycle regulation and apoptosis in several signaling pathways, so it can be considered as a potential modulator of the cellular DNA damage response, which is crucial for mutagenesis and cancer transformation. 1,25VD3 was shown to affect DNA repair and potentially NER through decreasing nitrosylation of DNA repair enzymes by NO overproduction by UV, but other mechanisms of the interaction between 1,25VD3 and NER machinery also are suggested. Therefore, the array of NER gene functioning could be analyzed and an appropriate amount of 1.25VD3 could be recommended to decrease UV-induced DNA damage important for skin cancer transformation.

Radiation Effects in 3D Integrated SOl SRAM Circuits

DTIC Science & Technology

2011-08-23

Because of the front-to- hack capacitive coupling, significant device parametric shifts can be observed unless the BOX has been engineered to...8. - l.E-12 .,..--------------, .. J5 ;::.. 5 63-MeV Protons · Tier1 • ner2 ner3 -c a • ’i 1.E-13 ----·· -----·-- ~ . = . i§ • • g • f L_

Disruption of TTDA Results in Complete Nucleotide Excision Repair Deficiency and Embryonic Lethality

PubMed Central

Theil, Arjan F.; Nonnekens, Julie; Steurer, Barbara; Mari, Pierre-Olivier; de Wit, Jan; Lemaitre, Charlène; Marteijn, Jurgen A.; Raams, Anja; Maas, Alex; Vermeij, Marcel; Essers, Jeroen; Hoeijmakers, Jan H. J.; Giglia-Mari, Giuseppina; Vermeulen, Wim

2013-01-01

The ten-subunit transcription factor IIH (TFIIH) plays a crucial role in transcription and nucleotide excision repair (NER). Inactivating mutations in the smallest 8-kDa TFB5/TTDA subunit cause the neurodevelopmental progeroid repair syndrome trichothiodystrophy A (TTD-A). Previous studies have shown that TTDA is the only TFIIH subunit that appears not to be essential for NER, transcription, or viability. We studied the consequences of TTDA inactivation by generating a Ttda knock-out (Ttda−/−) mouse-model resembling TTD-A patients. Unexpectedly, Ttda−/− mice were embryonic lethal. However, in contrast to full disruption of all other TFIIH subunits, viability of Ttda−/− cells was not affected. Surprisingly, Ttda−/− cells were completely NER deficient, contrary to the incomplete NER deficiency of TTD-A patient-derived cells. We further showed that TTD-A patient mutations only partially inactivate TTDA function, explaining the relatively mild repair phenotype of TTD-A cells. Moreover, Ttda−/− cells were also highly sensitive to oxidizing agents. These findings reveal an essential role of TTDA for life, nucleotide excision repair, and oxidative DNA damage repair and identify Ttda−/− cells as a unique class of TFIIH mutants. PMID:23637614

Mitotic regulator Nlp interacts with XPA/ERCC1 complexes and regulates nucleotide excision repair (NER) in response to UV radiation.

PubMed

Ma, Xiao-Juan; Shang, Li; Zhang, Wei-Min; Wang, Ming-Rong; Zhan, Qi-Min

2016-04-10

Cellular response to DNA damage, including ionizing radiation (IR) and UV radiation, is critical for the maintenance of genomic fidelity. Defects of DNA repair often result in genomic instability and malignant cell transformation. Centrosomal protein Nlp (ninein-like protein) has been characterized as an important cell cycle regulator that is required for proper mitotic progression. In this study, we demonstrate that Nlp is able to improve nucleotide excision repair (NER) activity and protects cells against UV radiation. Upon exposure of cells to UVC, Nlp is translocated into the nucleus. The C-terminus (1030-1382) of Nlp is necessary and sufficient for its nuclear import. Upon UVC radiation, Nlp interacts with XPA and ERCC1, and enhances their association. Interestingly, down-regulated expression of Nlp is found to be associated with human skin cancers, indicating that dysregulated Nlp might be related to the development of human skin cancers. Taken together, this study identifies mitotic protein Nlp as a new and important member of NER pathway and thus provides novel insights into understanding of regulatory machinery involved in NER. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chronic low-dose ultraviolet-induced mutagenesis in nucleotide excision repair-deficient cells.

PubMed

Haruta, Nami; Kubota, Yoshino; Hishida, Takashi

2012-09-01

UV radiation induces two major types of DNA lesions, cyclobutane pyrimidine dimers (CPDs) and 6-4 pyrimidine-pyrimidine photoproducts, which are both primarily repaired by nucleotide excision repair (NER). Here, we investigated how chronic low-dose UV (CLUV)-induced mutagenesis occurs in rad14Δ NER-deficient yeast cells, which lack the yeast orthologue of human xeroderma pigmentosum A (XPA). The results show that rad14Δ cells have a marked increase in CLUV-induced mutations, most of which are C→T transitions in the template strand for transcription. Unexpectedly, many of the CLUV-induced C→T mutations in rad14Δ cells are dependent on translesion synthesis (TLS) DNA polymerase η, encoded by RAD30, despite its previously established role in error-free TLS. Furthermore, we demonstrate that deamination of cytosine-containing CPDs contributes to CLUV-induced mutagenesis. Taken together, these results uncover a novel role for Polη in the induction of C→T transitions through deamination of cytosine-containing CPDs in CLUV-exposed NER deficient cells. More generally, our data suggest that Polη can act as both an error-free and a mutagenic DNA polymerase, depending on whether the NER pathway is available to efficiently repair damaged templates.

A de-identifier for medical discharge summaries.

PubMed

Uzuner, Ozlem; Sibanda, Tawanda C; Luo, Yuan; Szolovits, Peter

2008-01-01

Clinical records contain significant medical information that can be useful to researchers in various disciplines. However, these records also contain personal health information (PHI) whose presence limits the use of the records outside of hospitals. The goal of de-identification is to remove all PHI from clinical records. This is a challenging task because many records contain foreign and misspelled PHI; they also contain PHI that are ambiguous with non-PHI. These complications are compounded by the linguistic characteristics of clinical records. For example, medical discharge summaries, which are studied in this paper, are characterized by fragmented, incomplete utterances and domain-specific language; they cannot be fully processed by tools designed for lay language. In this paper, we show that we can de-identify medical discharge summaries using a de-identifier, Stat De-id, based on support vector machines and local context (F-measure=97% on PHI). Our representation of local context aids de-identification even when PHI include out-of-vocabulary words and even when PHI are ambiguous with non-PHI within the same corpus. Comparison of Stat De-id with a rule-based approach shows that local context contributes more to de-identification than dictionaries combined with hand-tailored heuristics (F-measure=85%). Comparison with two well-known named entity recognition (NER) systems, SNoW (F-measure=94%) and IdentiFinder (F-measure=36%), on five representative corpora show that when the language of documents is fragmented, a system with a relatively thorough representation of local context can be a more effective de-identifier than systems that combine (relatively simpler) local context with global context. Comparison with a Conditional Random Field De-identifier (CRFD), which utilizes global context in addition to the local context of Stat De-id, confirms this finding (F-measure=88%) and establishes that strengthening the representation of local context may be more beneficial for de-identification than complementing local with global context.

Empirical advances with text mining of electronic health records.

PubMed

Delespierre, T; Denormandie, P; Bar-Hen, A; Josseran, L

2017-08-22

Korian is a private group specializing in medical accommodations for elderly and dependent people. A professional data warehouse (DWH) established in 2010 hosts all of the residents' data. Inside this information system (IS), clinical narratives (CNs) were used only by medical staff as a residents' care linking tool. The objective of this study was to show that, through qualitative and quantitative textual analysis of a relatively small physiotherapy and well-defined CN sample, it was possible to build a physiotherapy corpus and, through this process, generate a new body of knowledge by adding relevant information to describe the residents' care and lives. Meaningful words were extracted through Standard Query Language (SQL) with the LIKE function and wildcards to perform pattern matching, followed by text mining and a word cloud using R® packages. Another step involved principal components and multiple correspondence analyses, plus clustering on the same residents' sample as well as on other health data using a health model measuring the residents' care level needs. By combining these techniques, physiotherapy treatments could be characterized by a list of constructed keywords, and the residents' health characteristics were built. Feeding defects or health outlier groups could be detected, physiotherapy residents' data and their health data were matched, and differences in health situations showed qualitative and quantitative differences in physiotherapy narratives. This textual experiment using a textual process in two stages showed that text mining and data mining techniques provide convenient tools to improve residents' health and quality of care by adding new, simple, useable data to the electronic health record (EHR). When used with a normalized physiotherapy problem list, text mining through information extraction (IE), named entity recognition (NER) and data mining (DM) can provide a real advantage to describe health care, adding new medical material and helping to integrate the EHR system into the health staff work environment.

A De-identifier for Medical Discharge Summaries1

PubMed Central

Uzuner, Özlem; Sibanda, Tawanda C.; Luo, Yuan; Szolovits, Peter

2008-01-01

Objective Clinical records contain significant medical information that can be useful to researchers in various disciplines. However, these records also contain personal health information (PHI) whose presence limits the use of the records outside of hospitals. The goal of de-identification is to remove all PHI from clinical records. This is a challenging task because many records contain foreign and misspelled PHI; they also contain PHI that are ambiguous with non-PHI. These complications are compounded by the linguistic characteristics of clinical records. For example, medical discharge summaries, which are studied in this paper, are characterized by fragmented, incomplete utterances and domain-specific language; they cannot be fully processed by tools designed for lay language. Methods and Results In this paper, we show that we can de-identify medical discharge summaries using a de-identifier, Stat De-id, based on support vector machines and local context (F-measure = 97% on PHI). Our representation of local context aids de-identification even when PHI include out-of-vocabulary words and even when PHI are ambiguous with non-PHI within the same corpus. Comparison of Stat De-id with a rule-based approach shows that local context contributes more to de-identification than dictionaries combined with hand-tailored heuristics (F-measure = 85%). Comparison with two well-known named entity recognition (NER) systems, SNoW (F-measure = 94%) and IdentiFinder (F-measure = 36%), on five representative corpora show that when the language of documents is fragmented, a system with a relatively thorough representation of local context can be a more effective de-identifier than systems that combine (relatively simpler) local context with global context. Comparison with a Conditional Random Field De-identifier (CRFD), which utilizes global context in addition to the local context of Stat De-id, confirms this finding (F-measure = 88%) and establishes that strengthening the representation of local context may be more beneficial for de-identification than complementing local with global context. PMID:18053696

Integrating text mining into the MGI biocuration workflow

PubMed Central

Dowell, K.G.; McAndrews-Hill, M.S.; Hill, D.P.; Drabkin, H.J.; Blake, J.A.

2009-01-01

A major challenge for functional and comparative genomics resource development is the extraction of data from the biomedical literature. Although text mining for biological data is an active research field, few applications have been integrated into production literature curation systems such as those of the model organism databases (MODs). Not only are most available biological natural language (bioNLP) and information retrieval and extraction solutions difficult to adapt to existing MOD curation workflows, but many also have high error rates or are unable to process documents available in those formats preferred by scientific journals. In September 2008, Mouse Genome Informatics (MGI) at The Jackson Laboratory initiated a search for dictionary-based text mining tools that we could integrate into our biocuration workflow. MGI has rigorous document triage and annotation procedures designed to identify appropriate articles about mouse genetics and genome biology. We currently screen ∼1000 journal articles a month for Gene Ontology terms, gene mapping, gene expression, phenotype data and other key biological information. Although we do not foresee that curation tasks will ever be fully automated, we are eager to implement named entity recognition (NER) tools for gene tagging that can help streamline our curation workflow and simplify gene indexing tasks within the MGI system. Gene indexing is an MGI-specific curation function that involves identifying which mouse genes are being studied in an article, then associating the appropriate gene symbols with the article reference number in the MGI database. Here, we discuss our search process, performance metrics and success criteria, and how we identified a short list of potential text mining tools for further evaluation. We provide an overview of our pilot projects with NCBO's Open Biomedical Annotator and Fraunhofer SCAI's ProMiner. In doing so, we prove the potential for the further incorporation of semi-automated processes into the curation of the biomedical literature. PMID:20157492

Integrating text mining into the MGI biocuration workflow.

PubMed

Dowell, K G; McAndrews-Hill, M S; Hill, D P; Drabkin, H J; Blake, J A

2009-01-01

A major challenge for functional and comparative genomics resource development is the extraction of data from the biomedical literature. Although text mining for biological data is an active research field, few applications have been integrated into production literature curation systems such as those of the model organism databases (MODs). Not only are most available biological natural language (bioNLP) and information retrieval and extraction solutions difficult to adapt to existing MOD curation workflows, but many also have high error rates or are unable to process documents available in those formats preferred by scientific journals.In September 2008, Mouse Genome Informatics (MGI) at The Jackson Laboratory initiated a search for dictionary-based text mining tools that we could integrate into our biocuration workflow. MGI has rigorous document triage and annotation procedures designed to identify appropriate articles about mouse genetics and genome biology. We currently screen approximately 1000 journal articles a month for Gene Ontology terms, gene mapping, gene expression, phenotype data and other key biological information. Although we do not foresee that curation tasks will ever be fully automated, we are eager to implement named entity recognition (NER) tools for gene tagging that can help streamline our curation workflow and simplify gene indexing tasks within the MGI system. Gene indexing is an MGI-specific curation function that involves identifying which mouse genes are being studied in an article, then associating the appropriate gene symbols with the article reference number in the MGI database.Here, we discuss our search process, performance metrics and success criteria, and how we identified a short list of potential text mining tools for further evaluation. We provide an overview of our pilot projects with NCBO's Open Biomedical Annotator and Fraunhofer SCAI's ProMiner. In doing so, we prove the potential for the further incorporation of semi-automated processes into the curation of the biomedical literature.

Improving the dictionary lookup approach for disease normalization using enhanced dictionary and query expansion.

PubMed

Jonnagaddala, Jitendra; Jue, Toni Rose; Chang, Nai-Wen; Dai, Hong-Jie

2016-01-01

The rapidly increasing biomedical literature calls for the need of an automatic approach in the recognition and normalization of disease mentions in order to increase the precision and effectivity of disease based information retrieval. A variety of methods have been proposed to deal with the problem of disease named entity recognition and normalization. Among all the proposed methods, conditional random fields (CRFs) and dictionary lookup method are widely used for named entity recognition and normalization respectively. We herein developed a CRF-based model to allow automated recognition of disease mentions, and studied the effect of various techniques in improving the normalization results based on the dictionary lookup approach. The dataset from the BioCreative V CDR track was used to report the performance of the developed normalization methods and compare with other existing dictionary lookup based normalization methods. The best configuration achieved an F-measure of 0.77 for the disease normalization, which outperformed the best dictionary lookup based baseline method studied in this work by an F-measure of 0.13.Database URL: https://github.com/TCRNBioinformatics/DiseaseExtract. © The Author(s) 2016. Published by Oxford University Press.

Building Scalable Knowledge Graphs for Earth Science

NASA Astrophysics Data System (ADS)

Ramachandran, R.; Maskey, M.; Gatlin, P. N.; Zhang, J.; Duan, X.; Bugbee, K.; Christopher, S. A.; Miller, J. J.

2017-12-01

Estimates indicate that the world's information will grow by 800% in the next five years. In any given field, a single researcher or a team of researchers cannot keep up with this rate of knowledge expansion without the help of cognitive systems. Cognitive computing, defined as the use of information technology to augment human cognition, can help tackle large systemic problems. Knowledge graphs, one of the foundational components of cognitive systems, link key entities in a specific domain with other entities via relationships. Researchers could mine these graphs to make probabilistic recommendations and to infer new knowledge. At this point, however, there is a dearth of tools to generate scalable Knowledge graphs using existing corpus of scientific literature for Earth science research. Our project is currently developing an end-to-end automated methodology for incrementally constructing Knowledge graphs for Earth Science. Semantic Entity Recognition (SER) is one of the key steps in this methodology. SER for Earth Science uses external resources (including metadata catalogs and controlled vocabulary) as references to guide entity extraction and recognition (i.e., labeling) from unstructured text, in order to build a large training set to seed the subsequent auto-learning component in our algorithm. Results from several SER experiments will be presented as well as lessons learned.

Chemical entity recognition in patents by combining dictionary-based and statistical approaches.

PubMed

Akhondi, Saber A; Pons, Ewoud; Afzal, Zubair; van Haagen, Herman; Becker, Benedikt F H; Hettne, Kristina M; van Mulligen, Erik M; Kors, Jan A

2016-01-01

We describe the development of a chemical entity recognition system and its application in the CHEMDNER-patent track of BioCreative 2015. This community challenge includes a Chemical Entity Mention in Patents (CEMP) recognition task and a Chemical Passage Detection (CPD) classification task. We addressed both tasks by an ensemble system that combines a dictionary-based approach with a statistical one. For this purpose the performance of several lexical resources was assessed using Peregrine, our open-source indexing engine. We combined our dictionary-based results on the patent corpus with the results of tmChem, a chemical recognizer using a conditional random field classifier. To improve the performance of tmChem, we utilized three additional features, viz. part-of-speech tags, lemmas and word-vector clusters. When evaluated on the training data, our final system obtained an F-score of 85.21% for the CEMP task, and an accuracy of 91.53% for the CPD task. On the test set, the best system ranked sixth among 21 teams for CEMP with an F-score of 86.82%, and second among nine teams for CPD with an accuracy of 94.23%. The differences in performance between the best ensemble system and the statistical system separately were small.Database URL: http://biosemantics.org/chemdner-patents. © The Author(s) 2016. Published by Oxford University Press.

Nuclear Magnetic Resonance Studies of an N2-Guanine Adduct Derived from the Tumorigen Dibenzo[a,l]pyrene in DNA: Impact of Adduct Stereochemistry, Size, and Local DNA Sequence on Solution Conformations

PubMed Central

2015-01-01

The dimensions and arrangements of aromatic rings (topology) in adducts derived from the reactions of polycyclic aromatic hydrocarbon (PAH) diol epoxide metabolites with DNA influence the distortions and stabilities of double-stranded DNA, and hence their recognition and processing by the human nucleotide excision repair (NER) system. Dibenzo[a,l]pyrene (DB[a,l]P) is a highly tumorigenic six-ring PAH, which contains a nonplanar and aromatic fjord region that is absent in the structurally related bay region five-ring PAH benzo[a]pyrene (B[a]P). The PAH diol epoxide–DNA adducts formed include the stereoisomeric 14S and 14Rtrans-anti-DB[a,l]P-N2-dG and the stereochemically analogous 10S- and 10R-B[a]P-N2-dG (B[a]P-dG) guanine adducts. However, nuclear magnetic resonance (NMR) solution studies of the 14S-DB[a,l]P-N2-dG adduct in DNA have not yet been presented. Here we have investigated the 14S-DB[a,l]P-N2-dG adduct in two different sequence contexts using NMR methods with distance-restrained molecular dynamics simulations. In duplexes with dC opposite the adduct deleted, a well-resolved base-displaced intercalative adduct conformation can be observed. In full duplexes, in contrast to the intercalated 14R stereoisomeric adduct, the bulky DB[a,l]P residue in the 14S adduct is positioned in a greatly widened and distorted minor groove, with significant disruptions and distortions of base pairing at the lesion site and two 5′-side adjacent base pairs. These unique structural features are significantly different from those of the stereochemically analogous but smaller B[a]P-dG adduct. The greater size and different topology of the DB[a,l]P aromatic ring system lead to greater structurally destabilizing DNA distortions that are partially compensated by stabilizing DB[a,l]P-DNA van der Waals interactions, whose combined effects impact the NER response to the adduct. These structural results broaden our understanding of the structure–function relationship in NER. PMID:24617538

Effect of the anti-neoplastic drug doxorubicin on XPD-mutated DNA repair-deficient human cells.

PubMed

Saffi, Jenifer; Agnoletto, Mateus H; Guecheva, Temenouga N; Batista, Luís F Z; Carvalho, Helotonio; Henriques, João A P; Stary, Anne; Menck, Carlos F M; Sarasin, Alain

2010-01-02

Doxorubicin (DOX), a member of the anthracycline group, is a widely used drug in cancer therapy. The mechanisms of DOX action include topoisomerase II-poisoning, free radical release, DNA adducts and interstrand cross-link (ICL) formation. Nucleotide excision repair (NER) is involved in the removal of helix-distorting lesions and chemical adducts, however, little is known about the response of NER-deficient cell lines to anti-tumoral drugs like DOX. Wild type and XPD-mutated cells, harbouring mutations in different regions of this gene and leading to XP-D, XP/CS or TTD diseases, were treated with this drug and analyzed for cell cycle arrest and DNA damage by comet assay. The formation of DSBs was also investigated by determination of gammaH2AX foci. Our results indicate that all three NER-deficient cell lines tested are more sensitive to DOX treatment, when compared to wild type cells or XP cells complemented by the wild type XPD cDNA, suggesting that NER is involved in the removal of DOX-induced lesions. The cell cycle analysis showed the characteristic G2 arrest in repair-proficient MRC5 cell line after DOX treatment, whereas the repair-deficient cell lines presented significant increase in sub-G1 fraction. The NER-deficient cell lines do not show different patterns of DNA damage formation as assayed by comet assay and phosphorylated H2AX foci formation. Knock-down of topoisomerase IIalpha with siRNA leads to increased survival in both MRC5 and XP cells, however, XP cell line still remained significantly more sensitive to the treatment by DOX. Our study suggests that the enhanced sensitivity is due to DOX-induced DNA damage that is subject to NER, as we observed decreased unscheduled DNA synthesis in XP-deficient cells upon DOX treatment. Furthermore, the complementation of the XPD-function abolished the observed sensitivity at lower DOX concentrations, suggesting that the XPD helicase activity is involved in the repair of DOX-induced lesions. Copyright (c) 2009 Elsevier B.V. All rights reserved.

Polymerization by DNA polymerase eta is blocked by cis-diamminedichloroplatinum(II) 1,3-d(GpTpG) cross-link: implications for cytotoxic effects in nucleotide excision repair-negative tumor cells.

PubMed

Chijiwa, Shotaro; Masutani, Chikahide; Hanaoka, Fumio; Iwai, Shigenori; Kuraoka, Isao

2010-03-01

cis-Diamminedichloroplatinum(II) (cisplatin) forms DNA adducts that interfere with replication and transcription. The most common adducts formed in vivo are 1,2-intrastrand d(GpG) cross-links (Pt-GG) and d(ApG) cross-links (Pt-AG), with minor amounts of 1,3-d(GpNpG) cross-links (Pt-GNG), interstrand cross-links and monoadducts. Although the relative contribution of these different adducts to toxicity is not known, literature implicates that Pt-GG and Pt-AG adducts block replication. Thus, nucleotide excision repair (NER), by which platinum adducts are excised, and translesion DNA synthesis (TLS), which permits adduct bypass, are thought to be associated with cisplatin resistance. Recent studies have reported that the clinical benefit from platinum-based chemotherapy is high if tumor cells express low levels of NER factors. To investigate the role of platinum-DNA adducts in mediating tumor cell survival by TLS, we examined whether 1,3-intrastrand d(GpTpG) platinum cross-links (Pt-GTG), which probably exist in NER-negative tumor cells but not in NER-positive tumor cells, are bypassed by the translesion DNA polymerase eta (pol eta), which is known to bypass Pt-GG. We show that pol eta can incorporate the correct deoxycytidine triphosphate opposite the first 3'-cross-linked G of Pt-GTG but cannot insert any nucleotides opposite the second intact T or the third 5'-cross-linked G of the adducts, thereby suggesting that TLS does not facilitate replication past Pt-GTG adducts. Thus, our findings implicate Pt-GNG adducts as mediating the cytotoxicity of platinum-DNA adducts in NER-negative tumors in vivo.

COMPREHENSIVE ANALYSES OF DNA REPAIR PATHWAYS, SMOKING, AND BLADDER CANCER RISK IN LOS ANGELES AND SHANGHAI

PubMed Central

Corral, Roman; Lewinger, Juan Pablo; Berg, David Van Den; Joshi, Amit D.; Yuan, Jian-Min; Gago-Dominguez, Manuela; Cortessis, Victoria K.; Pike, Malcolm C.; Conti, David V.; Thomas, Duncan C.; Edlund, Christopher K.; Gao, Yu-Tang; Xiang, Yong-Bing; Zhang, Wei; Su, Yu-Chen; Stern, Mariana C.

2014-01-01

Tobacco smoking is a bladder cancer risk factor and a source of carcinogens that induce DNA damage to urothelial cells. Using data and samples from 988 cases and 1,004 controls enrolled in the Los Angeles County Bladder Cancer Study and the Shanghai Bladder Cancer Study we investigated associations between bladder cancer risk and 632 tagSNPs that comprehensively capture genetic variation in 28 DNA repair genes from four DNA repair pathways: base excision repai, nucleotide excision repair (NER), non-homologous end-joining (NHEJ), and homologous recombination repair (HHR). Odds ratios (ORs) and 95% confidence intervals (CIs) for each tagSNP were corrected for multiple testing for all SNPs within each gene using pACT, and for genes within each pathway and across pathways with Bonferroni. Gene and pathway summary estimates were obtained using ARTP. We observed an association between bladder cancer and POLB rs7832529 (BER) (pACT = 0.003; ppathway = 0.021) among all, and SNPs in XPC (NER) and OGG1 (BER) among Chinese men and women, respectively. The NER pathway showed an overall association with risk among Chinese males (ARTP NER p = 0.034). The XRCC6 SNP rs2284082 (NHEJ), also in LD with SREBF2, showed an interaction with smoking (Smoking status interaction pgene = 0.001, ppathway = 0.008, poverall = 0.034). Our findings support a role in bladder carcinogenesis for regions that map close to or within BER (POLB, OGG1) and NER genes (XPC). A SNP that tags both the XRCC6 and SREBF2 genes strongly modifies the association between bladder cancer risk and smoking. PMID:24382701

The response of mammalian cells to UV-light reveals Rad54-dependent and independent pathways of homologous recombination.

PubMed

Eppink, Berina; Tafel, Agnieszka A; Hanada, Katsuhiro; van Drunen, Ellen; Hickson, Ian D; Essers, Jeroen; Kanaar, Roland

2011-11-10

Ultraviolet (UV) radiation-induced DNA lesions can be efficiently repaired by nucleotide excision repair (NER). However, NER is less effective during replication of UV-damaged chromosomes. In contrast, translesion DNA synthesis (TLS) and homologous recombination (HR) are capable of dealing with lesions in replicating DNA. The core HR protein in mammalian cells is the strand exchange protein RAD51, which is aided by numerous proteins, including RAD54. We used RAD54 as a cellular marker for HR to study the response of mammalian embryonic stem (ES) cells to UV irradiation. In contrast to yeast, ES cells lacking RAD54 are not UV sensitive. Here we show that the requirement for mammalian RAD54 is masked by active NER. By genetically inactivating NER and HR through disruption of the Xpa and Rad54 genes, respectively, we demonstrate the contribution of HR to chromosomal integrity upon UV irradiation. We demonstrate using chromosome fiber analysis at the individual replication fork level, that HR activity is important for the restart of DNA replication after induction of DNA damage by UV-light in NER-deficient cells. Furthermore, our data reveal RAD54-dependent and -independent contributions of HR to the cellular sensitivity to UV-light, and they uncover that RAD54 can compensate for the loss of TLS polymerase η with regard to UV-light sensitivity. In conclusion, we show that HR is important for the progression of UV-stalled replication forks in ES cells, and that protection of the fork is an interplay between HR and TLS. Copyright © 2011 Elsevier B.V. All rights reserved.

Distinct pathways for repairing mutagenic lesions induced by methylating and ethylating agents

PubMed Central

Negishi, Tomoe

2013-01-01

DNA alkylation damage can be repaired by nucleotide excision repair (NER), base excision repair (BER) or by direct removal of alkyl groups from modified bases by O 6-alkylguanine DNA alkyltransferase (AGT; E.C. 2.1.1.63). DNA mismatch repair (MMR) is also likely involved in this repair. We have investigated alkylation-induced mutagenesis in a series of NER- or AGT-deficient Escherichia coli strains, alone or in combination with defects in the MutS, MutL or MutH components of MMR. All strains used contained the Fʹprolac from strain CC102 (FʹCC102) episome capable of detecting specifically lac GC to AT reverse mutations resulting from O 6-alkylguanine. The results showed the repair of O 6-methylguanine to be performed by AGT ≫ MMR > NER in order of importance, whereas the repair of O 6-ethylguanine followed the order NER > AGT > MMR. Studies with double mutants showed that in the absence of AGT or NER repair pathways, the lack of MutS protein generally increased mutant frequencies for both methylating and ethylating agents, suggesting a repair or mutation avoidance role for this protein. However, lack of MutL or MutH protein did not increase alkylation-induced mutagenesis under these conditions and, in fact, reduced mutagenesis by the N-alkyl-N-nitrosoureas MNU and ENU. The combined results suggest that little or no alkylation damage is actually corrected by the mutHLS MMR system; instead, an as yet unspecified interaction of MutS protein with alkylated DNA may promote the involvement of a repair system other than MMR to avoid a mutagenic outcome. Furthermore, both mutagenic and antimutagenic effects of MMR were detected, revealing a dual function of the MMR system in alkylation-exposed cells. PMID:23446177

The versatile DNA nucleotide excision repair (NER) and its medical significance.

PubMed

Falik-Zaccai, Tzipora C; Keren, Zohar; Slor, Hanoch

2009-12-01

Two of DNA's worst enemies, ultraviolet light and chemical carcinogens, can cause damage to the molecule by mutating individual nucleotides or changing its physical structure. In most cases, genomic integrity is restored by specialized suites of proteins dedicated to repairing specific types of injuries. One restoration mechanism, called nucleotide excision repair (NER), recruits and coordinates the services of 20-30 proteins to recognize and remove structure-impairing lesions, including those induced by ultraviolet (UV) light. Mutations in a gene that encodes a protein from the NER machinery might cause a wide variety of rare inherited human disorders. Sun sensitivity, cancer, developmental retardation, neurodegeneration and premature aging characterize these syndromes. Identification of the causative genes and proteins in affected families in Israel allowed us to establish accurate molecular diagnosis of couples at risk, and provide them with better genetic counseling.

New FASB standard addresses revenue recognition considerations.

PubMed

McKee, Thomas E

2015-12-01

Healthcare organizations are expected to apply the following steps in revenue recognition under the new standard issued in May 2014 by the Financial Accounting Standards Board: Identify the customer contract. Identify the performance obligations in the contract. Determine the transaction price. Allocate the transaction price to the performance obligations in the contract. Recognize revenue when--or in some circumstances, as--the entity satisfies the performance obligation.

A modular framework for biomedical concept recognition

PubMed Central

2013-01-01

Background Concept recognition is an essential task in biomedical information extraction, presenting several complex and unsolved challenges. The development of such solutions is typically performed in an ad-hoc manner or using general information extraction frameworks, which are not optimized for the biomedical domain and normally require the integration of complex external libraries and/or the development of custom tools. Results This article presents Neji, an open source framework optimized for biomedical concept recognition built around four key characteristics: modularity, scalability, speed, and usability. It integrates modules for biomedical natural language processing, such as sentence splitting, tokenization, lemmatization, part-of-speech tagging, chunking and dependency parsing. Concept recognition is provided through dictionary matching and machine learning with normalization methods. Neji also integrates an innovative concept tree implementation, supporting overlapped concept names and respective disambiguation techniques. The most popular input and output formats, namely Pubmed XML, IeXML, CoNLL and A1, are also supported. On top of the built-in functionalities, developers and researchers can implement new processing modules or pipelines, or use the provided command-line interface tool to build their own solutions, applying the most appropriate techniques to identify heterogeneous biomedical concepts. Neji was evaluated against three gold standard corpora with heterogeneous biomedical concepts (CRAFT, AnEM and NCBI disease corpus), achieving high performance results on named entity recognition (F1-measure for overlap matching: species 95%, cell 92%, cellular components 83%, gene and proteins 76%, chemicals 65%, biological processes and molecular functions 63%, disorders 85%, and anatomical entities 82%) and on entity normalization (F1-measure for overlap name matching and correct identifier included in the returned list of identifiers: species 88%, cell 71%, cellular components 72%, gene and proteins 64%, chemicals 53%, and biological processes and molecular functions 40%). Neji provides fast and multi-threaded data processing, annotating up to 1200 sentences/second when using dictionary-based concept identification. Conclusions Considering the provided features and underlying characteristics, we believe that Neji is an important contribution to the biomedical community, streamlining the development of complex concept recognition solutions. Neji is freely available at http://bioinformatics.ua.pt/neji. PMID:24063607

Finding Cervical Cancer Symptoms in Swedish Clinical Text using a Machine Learning Approach and NegEx

PubMed Central

Weegar, Rebecka; Kvist, Maria; Sundström, Karin; Brunak, Søren; Dalianis, Hercules

2015-01-01

Detection of early symptoms in cervical cancer is crucial for early treatment and survival. To find symptoms of cervical cancer in clinical text, Named Entity Recognition is needed. In this paper the Clinical Entity Finder, a machine-learning tool trained on annotated clinical text from a Swedish internal medicine emergency unit, is evaluated on cervical cancer records. The Clinical Entity Finder identifies entities of the types body part, finding and disorder and is extended with negation detection using the rule-based tool NegEx, to distinguish between negated and non-negated entities. To measure the performance of the tools on this new domain, two physicians annotated a set of clinical notes from the health records of cervical cancer patients. The inter-annotator agreement for finding, disorder and body part obtained an average F-score of 0.677 and the Clinical Entity Finder extended with NegEx had an average F-score of 0.667. PMID:26958270

Finding Cervical Cancer Symptoms in Swedish Clinical Text using a Machine Learning Approach and NegEx.

PubMed

Weegar, Rebecka; Kvist, Maria; Sundström, Karin; Brunak, Søren; Dalianis, Hercules

2015-01-01

Detection of early symptoms in cervical cancer is crucial for early treatment and survival. To find symptoms of cervical cancer in clinical text, Named Entity Recognition is needed. In this paper the Clinical Entity Finder, a machine-learning tool trained on annotated clinical text from a Swedish internal medicine emergency unit, is evaluated on cervical cancer records. The Clinical Entity Finder identifies entities of the types body part, finding and disorder and is extended with negation detection using the rule-based tool NegEx, to distinguish between negated and non-negated entities. To measure the performance of the tools on this new domain, two physicians annotated a set of clinical notes from the health records of cervical cancer patients. The inter-annotator agreement for finding, disorder and body part obtained an average F-score of 0.677 and the Clinical Entity Finder extended with NegEx had an average F-score of 0.667.

Rare Disease Biospecimens and Patient Registries: Interoperability for Research Promotion, a European Example: EuroBioBank and SpainRDR-BioNER.

PubMed

Rubinstein, Yaffa R; Posada de la Paz, Manuel; Mora, Marina

2017-01-01

Well-annotated and properly preserved specimens are crucial both for diagnostic purposes and for use in basic and pre-clinical research, and are especially important for rare disease (RD) studies. Several consortia have been established in the recent years in order to facilitate research and to maximise access to rare biological samples and data stored in rare disease biobanks and registries, among them the EuroBioBank network and the Spain National Rare Disease Registry (RDR) and Biobank (BioNER).EuroBioBank, established in 2001, was the first network of RD biobanks to operate in Europe as a service distributing human DNA, cells, and tissue to the scientific community conducting research on rare diseases.The Spanish RDR and BioNER were created for facilitating rare disease research and health-related matters. The coordination of these two bodies represents an example of great scientific value as biological samples donated by patients at BioNER are linked to clinical information collected in the RDR.Rare disease biobanks and registries will need for the future to increase their effort to improve interconnection so to enable investigators to better locate samples and associated data, while protecting security of the data and privacy of the participants and adhering to international ethical and legal requirements.

Contribution of microorganisms to non-extractable residue formation during biodegradation of ibuprofen in soil.

PubMed

Nowak, Karolina M; Girardi, Cristobal; Miltner, Anja; Gehre, Matthias; Schäffer, Andreas; Kästner, Matthias

2013-02-15

Non-extractable residues (NER) formed during biodegradation of organic contaminants in soil are considered to be mainly composed of parent compounds or their primary metabolites with hazardous potential. However, in the case of biodegradable organic compounds, the soil NER may also contain microbial biomass components, for example fatty acids (FA) and amino acids (AA). After cell death, these biomolecules are subsequently incorporated into non-living soil organic matter (SOM) and are stabilised ultimately forming hardly extractable residues of biogenic origin. We investigated biodegradation of (13)C(6)-ibuprofen, in particular the metabolic incorporation of the (13)C-label into FA and AA and their fate in soil over 90 days. (13)C-FA and (13)C-AA amounts in the living microbial biomass fraction initially increased, then decreased over time and were continuously incorporated into the non-living SOM pool. The (13)C-FA in the non-living SOM remained stable from day 59 whereas the contents of (13)C-AA slightly increased until the end. After 90 days, nearly all NER were biogenic as they were made up almost completely by natural biomass compounds. The presented data demonstrated that the potential environmental risks related to the ibuprofen-derived NER are overestimated. Copyright © 2012 Elsevier B.V. All rights reserved.

Xeroderma pigmentosum complementation group C protein (XPC) serves as a general sensor of damaged DNA

PubMed Central

Shell, Steven M.; Hawkins, Edward K.; Tsai, Miaw-Sheue; Hlaing, Aye Su; Rizzo, Carmelo J.; Chazin, Walter J.

2013-01-01

The xeroderma pigmentosum complementation group C protein (XPC) serves as the primary initiating factor in the global genome nucleotide excision repair pathway (GG-NER). Recent reports suggest XPC also stimulates repair of oxidative lesions by base excision repair. However, whether XPC distinguishes among various types of DNA lesions remains unclear. Although the DNA binding properties of XPC have been studied by several groups, there is a lack of consensus over whether XPC discriminates between DNA damaged by lesions associated with NER activity versus those that are not. In this study we report a high-throughput fluorescence anisotropy assay used to measure the DNA binding affinity of XPC for a panel of DNA substrates containing a range of chemical lesions in a common sequence. Our results demonstrate that while XPC displays a preference for binding damaged DNA, the identity of the lesion has little effect on the binding affinity of XPC. Moreover, XPC was equally capable of binding to DNA substrates containing lesions not repaired by GG-NER. Our results support an indirect read-out model for sensing the presence of lesions by human XPC and suggest XPC may act as a general sensor of damaged DNA capable of recognizing DNA containing lesions not repaired by NER. PMID:24051049

Linking intended visitation to regional economic impact models of bison and elk management

USGS Publications Warehouse

Loomis, J.; Caughlan, L.

2004-01-01

This article links intended National Park visitation estimates to regional economic models to calculate the employment impacts of alternative bison and elk management strategies. The survey described alternative National Elk Refuge (NER) management actions and the effects on elk and bison populations at the NER and adjacent Grand Teton National Park (GTNP). Park visitors were then asked if they would change their number of visits with each potential management action. Results indicate there would be a 10% decrease in visitation if bison populations were reduced from 600 to 400 animals and elk populations were reduced in GTNP and the NER. The related decrease in jobs in Teton counties of Wyoming and Idaho is estimated at 5.5%. Adopting a “no active management” option of never feeding elk and bison on the NER yields about one-third the current bison population (200 bison) and about half the elk population. Visitors surveyed about this management option would take about 20% fewer trips, resulting in an 11.3% decrease in employment. Linking intended visitation surveys and regional economic models represents a useful tool for natural resource planners who must present the consequences of potential actions in Environmental Impact Statements and plans to the public and decision makers prior to any action being implemented.

Combining Open-domain and Biomedical Knowledge for Topic Recognition in Consumer Health Questions.

PubMed

Mrabet, Yassine; Kilicoglu, Halil; Roberts, Kirk; Demner-Fushman, Dina

2016-01-01

Determining the main topics in consumer health questions is a crucial step in their processing as it allows narrowing the search space to a specific semantic context. In this paper we propose a topic recognition approach based on biomedical and open-domain knowledge bases. In the first step of our method, we recognize named entities in consumer health questions using an unsupervised method that relies on a biomedical knowledge base, UMLS, and an open-domain knowledge base, DBpedia. In the next step, we cast topic recognition as a binary classification problem of deciding whether a named entity is the question topic or not. We evaluated our approach on a dataset from the National Library of Medicine (NLM), introduced in this paper, and another from the Genetic and Rare Disease Information Center (GARD). The combination of knowledge bases outperformed the results obtained by individual knowledge bases by up to 16.5% F1 and achieved state-of-the-art performance. Our results demonstrate that combining open-domain knowledge bases with biomedical knowledge bases can lead to a substantial improvement in understanding user-generated health content.

PROGRESS IN ACUTE MYELOID LEUKEMIA

PubMed Central

Kadia, Tapan M.; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M.

2014-01-01

Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

Geothermal projects funded under the NER 300 programme - current state of development and knowledge gained

NASA Astrophysics Data System (ADS)

Shortall, Ruth; Uihlein, Andreas

2017-04-01

Introduction The NER 300 programme, managed by the European Commission is one of the largest funding programmes for innovative low-carbon energy demonstration projects. NER 300 is so called because it is funded from the sale of 300 million emission allowances from the new entrants' reserve (NER) set up for the third phase of the EU emissions trading system (ETS). The programme aims to successfully demonstrate environmentally safe carbon capture and storage (CCS) and innovative renewable energy (RES) technologies on a commercial scale with a view to scaling up production of low-carbon technologies in the EU. Consequently, it supports a wide range of CCS and RES technologies (bioenergy, concentrated solar power, photovoltaics, geothermal, wind, ocean, hydropower, and smart grids). Funded projects and the role of geothermal projects for the programme In total, about EUR 2.1 billion have been awarded through the programme's 2 calls for proposals (the first awarded in December 2012, the second in July 2014). The programme has awarded around EUR 70 million funding to 3 geothermal projects in Hungary, Croatia and France. The Croatian geothermal project will enter into operation during 2017 the Hungarian in 2018, and the French in 2020. Knowledge Sharing Knowledge sharing requirements are built into the legal basis of the programme as a critical tool to lower risks in bridging the transition to large-scale production of innovative renewable energy and CCS deployment. Projects have to submit annually to the European Commission relevant knowledge gained during that year in the implementation of their project. The relevant knowledge is aggregated and disseminated by the European Commission to industry, research, government, NGO and other interest groups and associations in order to provide a better understanding of the practical challenges that arise in the important step of scaling up technologies and operating them at commercial scale. The knowledge sharing of the NER 300 programme should lead to better planning and faster introduction of low carbon technologies in the future. Content of the presentation The presentation will introduce the geothermal projects that have been awarded funding (see Annex), including their state-of-play. Insights and knowledge gained from the projects that have entered into operation will be shown and discussed. Furthermore, the presentation will provide an overview of the NER 300 programme.

The role of microalgae as biodiesel feedstock in a tropical setting: Economics, agro-energy competitiveness, and potential impacts on regional agricultural feedstock production

NASA Astrophysics Data System (ADS)

Boll, Matias G.

The objective of this study is to obtain a realistic evaluation of the potential role of microalgae as a biodiesel feedstock in a tropical setting. First, microalgae economics are estimated, including the detailed design of a 400 ha microalgae open pond production farm together with the microalgae biomass and crude oil production costs calculations. Sensitivity analysis and a stochastic evaluation of the microalgae venture chances for profit are also included. Next, microalgae potential for biodiesel production is compared to traditional oil crops such as soybeans and African palm. This comparison is performed using the Northeast Region (NER) of Brazil as background. Six potential biodiesel feedstock sources produced in the NER and microalgae are compared considering selected environmental, economic and social sustainability indicators. Finally, in the third chapter, the study proposes a cropland allocation model for the NER. The model aims to offer insights to the decision maker concerning biofuel development strategies and their impact on regional agricultural feedstock production. In the model, cropland allocation among three agriculture feedstock sectors, namely staple food, commodity export and biofuel is optimized through the use of the multiple objective technique referred to as compromise programming (CP). Our results indicate a projected microalgae total production cost of R 78,359 ha-1 (US43,533), which has a breakdown as follows: R 34,133 ha-1 (US18,963) for operating costs and R 44,226 ha-1 (US24,570) for overhead (ownership) costs. Our stochastic analysis indicates that microalgae production under the conditions assumed in the baseline scenario of this study has a 0% chance to present a positive NPV for a microalgae crude oil price of R 1.86. This price corresponds to an international oil price around US 77 bbl-1. To obtain a reasonable investment return (IRR = 12%) from the microalgae farm, an international oil price as high as US 461 bbl-1 is required. Despite the advantage of using about 14 times less cropland area (0.13 ha boe-1 ), microalgae presented significant disadvantages as compared to some of the traditional oil crops. Among these is the significant amount of N fertilizer and water demanded by microalgae production, namely 205 kg and 4,990 boe -1, about 132% and 30% higher than the second highest value among the crops compared in this study, respectively. Optimized CP scenarios expanded annual cropland allocation to 14.58 million ha in the NER, year 2017, compared to 11.04 and 12.81 million ha in current (2007) and baseline (2017) scenarios, respectively. In comparison to the baseline scenario, cropland expansions allied to the shift of the commodities export dedicated cropland to the biofuel production sector in CP scenarios significantly increased the NER fuel autonomy (95%) and reduced its R 5,126 million reais deficit baseline comprehensive feedstock trade balance by 79%. Contrary to the concerns usually referred to biofuel development, our model indicates that in the NER case, it is the commodity export, rather than the staple food agriculture feedstock production sector, that is mostly affected by the biofuel cropland allocation demand. When compared to traditional oil crops, microalgae-based biodiesel scenarios could not significantly improve regional staple food autonomy, increasing this objective by 1% only. The NER fuel autonomy, in its turn, is positively impacted in the microalgae scenarios, but the increment as compared to the traditional oil crops is rather small, namely 2% and 7% in the B5 and B10 levels, respectively. These results indicate that the potential advantages expected for the microalgae-based biodiesel introduction did not materialize for the NER. It is concluded that the adoption of microalgae-based biodiesel is not an interesting biofuel alternative for the NER of Brazil for the next ten years.

Optimality and self-organization in river deltas

NASA Astrophysics Data System (ADS)

Tejedor, A.; Longjas, A.; Edmonds, D. A.; Zaliapin, I. V.; Georgiou, T. T.; Rinaldo, A.; Foufoula-Georgiou, E.

2017-12-01

Deltas are nourished by channel networks, whose connectivity constrains, if not drives, the evolution, functionality and resilience of these systems. Understanding the coevolution of deltaic channels and their flux organization is crucial for guiding maintenance strategies of these highly stressed systems from a range of anthropogenic activities. However, in contrast to tributary channel networks, to date, no theory has been proposed to explain how deltas self-organize to distribute water and sediment to the delta top and the shoreline. Here, we hypothesize the existence of an optimality principle underlying the self-organized partition of fluxes in delta channel networks. Specifically, we hypothesize that deltas distribute water and sediment fluxes on a given delta topology such as to maximize the diversity of flux delivery to the shoreline. By introducing the concept of nonlocal Entropy Rate (nER) and analyzing ten field deltas in diverse environments, we present evidence that supports our hypothesis, suggesting that delta networks achieve dynamically accessible maxima of their nER. Furthermore, by analyzing six simulated deltas using the Delf3D model and following their topologic and flux re-organization before and after major avulsions, we further study the evolution of nER and confirm our hypothesis. We discuss how optimal flux distributions in terms of nER, when interpreted in terms of resilience, are configurations that reflect an increased ability to withstand perturbations.

Both base excision repair and nucleotide excision repair in humans are influenced by nutritional factors.

PubMed

Brevik, Asgeir; Karlsen, Anette; Azqueta, Amaya; Tirado, Anna Estaban; Blomhoff, Rune; Collins, Andrew

2011-01-01

Lack of reliable assays for DNA repair has largely prevented measurements of DNA repair from being included in human biomonitoring studies. Using newly developed modifications of the comet assay we tested whether a fruit- and antioxidant-rich plant-based intervention could affect base excision repair (BER) and nucleotide excision repair (NER) in a group of 102 male volunteers. BER and NER repair capacities were measured in lymphocytes before and after a dietary intervention lasting 8 weeks. The study had one control group, one group consuming three kiwifruits per day and one group consuming a variety of antioxidant-rich fruits and plant products in addition to their normal diet. DNA strand breaks were reduced following consumption of both kiwifruits (13%, p = 0.05) and antioxidant-rich plant products (20%, p = 0.02). Increased BER (55%, p = 0.01) and reduced NER (-39%, p < 0.01) were observed in the group consuming a wide variety of plant products. Reduced NER was also observed in the kiwifruit group (-38%, p = 0.05), but BER was not affected in this group. Here we have demonstrated that DNA repair is affected by diet and that modified versions of the comet assay can be used to assess activity of different DNA repair pathways in human biomonitoring studies. Copyright © 2010 John Wiley & Sons, Ltd.

PTEN positively regulates UVB-induced DNA damage repair

PubMed Central

Ming, Mei; Feng, Li; Shea, Christopher R.; Soltani, Keyoumars; Zhao, Baozhong; Han, Weinong; Smart, Robert C.; Trempus, Carol S.; He, Yu-Ying

2011-01-01

Non-melanoma skin cancer is the most common cancer in the U.S., where DNA-damaging UVB radiation from the sun remains the major environmental risk factor. However, the critical genetic targets of UVB radiation are undefined. Here we show that attenuating PTEN in epidermal keratinocytes is a predisposing factor for UVB-induced skin carcinogenesis in mice. In skin papilloma and squamous cell carcinoma (SCC), levels of PTEN were reduced compared to skin lacking these lesions. Likewise, there was a reduction in PTEN levels in human premalignant actinic keratosis and malignant SCC, supporting a key role for PTEN in human skin cancer formation and progression. PTEN downregulation impaired the capacity of global genomic nucleotide excision repair (GG-NER), a critical mechanism for removing UVB-induced mutagenic DNA lesions. In contrast to the response to ionizing radiation, PTEN downregulation prolonged UVB-induced growth arrest and increased the activation of the Chk1 DNA damage pathway in an AKT-independent manner, likely due to reduced DNA repair. PTEN loss also suppressed expression of the key GG-NER protein xeroderma pigmentosum C (XPC) through the AKT/p38 signaling axis. Reconstitution of XPC levels in PTEN-inhibited cells restored GG-NER capacity. Taken together, our findings define PTEN as an essential genomic gatekeeper in the skin, through its ability to positively regulate XPC-dependent GG-NER following DNA damage. PMID:21771908

Conservation of the Nucleotide Excision Repair Pathway: Characterization of Hydra Xeroderma Pigmentosum Group F Homolog

PubMed Central

Barve, Apurva; Ghaskadbi, Saroj; Ghaskadbi, Surendra

2013-01-01

Hydra, one of the earliest metazoans with tissue grade organization and nervous system, is an animal with a remarkable regeneration capacity and shows no signs of organismal aging. We have for the first time identified genes of the nucleotide excision repair (NER) pathway from hydra. Here we report cloning and characterization of hydra homolog of xeroderma pigmentosum group F (XPF) gene that encodes a structure-specific 5′ endonuclease which is a crucial component of NER. In silico analysis shows that hydra XPF amino acid sequence is very similar to its counterparts from other animals, especially vertebrates, and shows all features essential for its function. By in situ hybridization, we show that hydra XPF is expressed prominently in the multipotent stem cell niche in the central region of the body column. Ectoderm of the diploblastic hydra was shown to express higher levels of XPF as compared to the endoderm by semi-quantitative RT-PCR. Semi-quantitative RT-PCR analysis also demonstrated that interstitial cells, a multipotent and rapidly cycling stem cell lineage of hydra, express higher levels of XPF mRNA than other cell types. Our data show that XPF and by extension, the NER pathway is highly conserved during evolution. The prominent expression of an NER gene in interstitial cells may have implications for the lack of senescence in hydra. PMID:23577191

Conservation of the nucleotide excision repair pathway: characterization of hydra Xeroderma Pigmentosum group F homolog.

PubMed

Barve, Apurva; Ghaskadbi, Saroj; Ghaskadbi, Surendra

2013-01-01

Hydra, one of the earliest metazoans with tissue grade organization and nervous system, is an animal with a remarkable regeneration capacity and shows no signs of organismal aging. We have for the first time identified genes of the nucleotide excision repair (NER) pathway from hydra. Here we report cloning and characterization of hydra homolog of xeroderma pigmentosum group F (XPF) gene that encodes a structure-specific 5' endonuclease which is a crucial component of NER. In silico analysis shows that hydra XPF amino acid sequence is very similar to its counterparts from other animals, especially vertebrates, and shows all features essential for its function. By in situ hybridization, we show that hydra XPF is expressed prominently in the multipotent stem cell niche in the central region of the body column. Ectoderm of the diploblastic hydra was shown to express higher levels of XPF as compared to the endoderm by semi-quantitative RT-PCR. Semi-quantitative RT-PCR analysis also demonstrated that interstitial cells, a multipotent and rapidly cycling stem cell lineage of hydra, express higher levels of XPF mRNA than other cell types. Our data show that XPF and by extension, the NER pathway is highly conserved during evolution. The prominent expression of an NER gene in interstitial cells may have implications for the lack of senescence in hydra.

EPA New England Opens Nomination Period for Annual Environmental Merit Awards

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency office in New England is accepting nominations for New England people, organizations, government entities or businesses whose environmental achievements during the past year deserve recognition.

Unstable solar lentigo: A defined separate entity.

PubMed

Byrom, Lisa; Barksdale, Sarah; Weedon, David; Muir, Jim

2016-08-01

An unstable solar lentigo is a solar lentigo with areas of melanocytic hyperplasia not extending past the margin of the lesion. They are discrete, macular, pigmented lesions arising on sun-damaged skin and a subset of typical solar lentigos. Clinically they differ from usual solar lentigines in often being solitary or larger and darker than adjacent solar lentigines. These lesions are of clinical importance as they can arise in close proximity to lentigo maligna and in a single lesion there can be demonstrated changes of solar lentigo, unstable solar lentigo and lentigo maligna. These observations led us to conjecture that unstable solar lentigos could be a precursor lesion to lentigo maligna. In this article we examine the possibility that lentigo maligna can arise within a solar lentigo through an intermediate lesion, the unstable solar lentigo. We propose that the histopathological recognition of this entity will allow for future research into its behaviour and thus management. We review difficulties in the diagnosis of single cell predominant melanocytic proliferations and the concept of unstable lentigo in view of the literature and clinical experience supporting the proposal of its recognition as a separate entity. © 2016 The Australasian College of Dermatologists.

Sketching for Military Courses of Action Diagrams

DTIC Science & Technology

2003-01-01

the glyph bar and (optionally) spoken input2. Avoiding the need for recognition in glyphs Glyphs in nuSketch systems have two parts. The ink is the...time-stamped collection of ink strokes that comprise the base- level visual representation of the glyph. The content of the glyph is an entity in...preferred having a neat symbol drawn where they wanted it. Those who had tried ink recognition systems particularly appreciated never having to

Uncommon nucleotide excision repair phenotypes revealed by targeted high-throughput sequencing.

PubMed

Calmels, Nadège; Greff, Géraldine; Obringer, Cathy; Kempf, Nadine; Gasnier, Claire; Tarabeux, Julien; Miguet, Marguerite; Baujat, Geneviève; Bessis, Didier; Bretones, Patricia; Cavau, Anne; Digeon, Béatrice; Doco-Fenzy, Martine; Doray, Bérénice; Feillet, François; Gardeazabal, Jesus; Gener, Blanca; Julia, Sophie; Llano-Rivas, Isabel; Mazur, Artur; Michot, Caroline; Renaldo-Robin, Florence; Rossi, Massimiliano; Sabouraud, Pascal; Keren, Boris; Depienne, Christel; Muller, Jean; Mandel, Jean-Louis; Laugel, Vincent

2016-03-22

Deficient nucleotide excision repair (NER) activity causes a variety of autosomal recessive diseases including xeroderma pigmentosum (XP) a disorder which pre-disposes to skin cancer, and the severe multisystem condition known as Cockayne syndrome (CS). In view of the clinical overlap between NER-related disorders, as well as the existence of multiple phenotypes and the numerous genes involved, we developed a new diagnostic approach based on the enrichment of 16 NER-related genes by multiplex amplification coupled with next-generation sequencing (NGS). Our test cohort consisted of 11 DNA samples, all with known mutations and/or non pathogenic SNPs in two of the tested genes. We then used the same technique to analyse samples from a prospective cohort of 40 patients. Multiplex amplification and sequencing were performed using AmpliSeq protocol on the Ion Torrent PGM (Life Technologies). We identified causative mutations in 17 out of the 40 patients (43%). Four patients showed biallelic mutations in the ERCC6(CSB) gene, five in the ERCC8(CSA) gene: most of them had classical CS features but some had very mild and incomplete phenotypes. A small cohort of 4 unrelated classic XP patients from the Basque country (Northern Spain) revealed a common splicing mutation in POLH (XP-variant), demonstrating a new founder effect in this population. Interestingly, our results also found ERCC2(XPD), ERCC3(XPB) or ERCC5(XPG) mutations in two cases of UV-sensitive syndrome and in two cases with mixed XP/CS phenotypes. Our study confirms that NGS is an efficient technique for the analysis of NER-related disorders on a molecular level. It is particularly useful for phenotypes with combined features or unusually mild symptoms. Targeted NGS used in conjunction with DNA repair functional tests and precise clinical evaluation permits rapid and cost-effective diagnosis in patients with NER-defects.

Unusual ruby-sapphire transition in alluvial megacrysts, Cenozoic basaltic gem field, New England, New South Wales, Australia

NASA Astrophysics Data System (ADS)

Sutherland, Frederick L.; Graham, Ian T.; Harris, Stephen J.; Coldham, Terry; Powell, William; Belousova, Elena A.; Martin, Laure

2017-05-01

Rare ruby crystals appear among prevailing sapphire crystals mined from placers within basaltic areas in the New England gem-field, New South Wales, Australia. New England ruby (NER) has distinctive trace element features compared to those from ruby elsewhere in Australia and indeed most ruby from across the world. The NER suite includes ruby (up to 3370 ppm Cr), pink sapphire (up to 1520 ppm Cr), white sapphire (up to 910 ppm) and violet, mauve, purple, or bluish sapphire (up to 1410 ppm Cr). Some crystals show outward growth banding in this respective colour sequence. All four colour zones are notably high in Ga (up to 310 ppm) and Si (up to 1820 ppm). High Ga and Ga/Mg values are unusual in ruby and its trace element plots (laser ablation-inductively coupled plasma-mass spectrometry) and suggests that magmatic-metasomatic inputs were involved in the NER suite genesis. In situ oxygen isotope analyses (secondary ion mass spectrometry) across the NER suite colour range showed little variation (n = 22; δ18O = 4.4 ± 0.4, 2σ error), and are values typical for corundum associated with ultramafic/mafic rocks. The isolated NER xenocryst suite, corroded by basalt transport and with few internal inclusions, presents a challenge in deciphering its exact origin. Detailed consideration of its high Ga chemistry in relation to the known geology of the surrounding region was used to narrow down potential sources. These include Late Palaeozoic-Triassic fractionated I-type granitoid magmas or Mesozoic-Cenozoic felsic fractionates from basaltic magmas that interacted with early Palaeozoic Cr-bearing ophiolite bodies in the New England Orogen. Other potential sources may lie deeper within lower crust-mantle metamorphic assemblages, but need to match the anomalous high-Ga geochemistry of the New England ruby suite.

Silymarin Protects Epidermal Keratinocytes from Ultraviolet Radiation-Induced Apoptosis and DNA Damage by Nucleotide Excision Repair Mechanism

PubMed Central

Katiyar, Santosh K.; Mantena, Sudheer K.; Meeran, Syed M.

2011-01-01

Solar ultraviolet (UV) radiation is a well recognized epidemiologic risk factor for melanoma and non-melanoma skin cancers. This observation has been linked to the accumulation of UVB radiation-induced DNA lesions in cells, and that finally lead to the development of skin cancers. Earlier, we have shown that topical treatment of skin with silymarin, a plant flavanoid from milk thistle (Silybum marianum), inhibits photocarcinogenesis in mice; however it is less understood whether chemopreventive effect of silymarin is mediated through the repair of DNA lesions in skin cells and that protect the cells from apoptosis. Here, we show that treatment of normal human epidermal keratinocytes (NHEK) with silymarin blocks UVB-induced apoptosis of NHEK in vitro. Silymarin reduces the amount of UVB radiation-induced DNA damage as demonstrated by reduced amounts of cyclobutane pyrimidine dimers (CPDs) and as measured by comet assay, and that ultimately may lead to reduced apoptosis of NHEK. The reduction of UV radiation-induced DNA damage by silymarin appears to be related with induction of nucleotide excision repair (NER) genes, because UV radiation-induced apoptosis was not blocked by silymarin in NER-deficient human fibroblasts. Cytostaining and dot-blot analysis revealed that silymarin repaired UV-induced CPDs in NER-proficient fibroblasts from a healthy individual but did not repair UV-induced CPD-positive cells in NER-deficient fibroblasts from patients suffering from xeroderma pigmentosum complementation-A disease. Similarly, immunohistochemical analysis revealed that silymarin did not reduce the number of UVB-induced sunburn/apoptotic cells in the skin of NER-deficient mice, but reduced the number of sunburn cells in their wild-type counterparts. Together, these results suggest that silymarin exert the capacity to reduce UV radiation-induced DNA damage and, thus, prevent the harmful effects of UV radiation on the genomic stability of epidermal cells. PMID:21731736

ATR- and ATM-Mediated DNA Damage Response Is Dependent on Excision Repair Assembly during G1 but Not in S Phase of Cell Cycle.

PubMed

Ray, Alo; Blevins, Chessica; Wani, Gulzar; Wani, Altaf A

2016-01-01

Cell cycle checkpoint is mediated by ATR and ATM kinases, as a prompt early response to a variety of DNA insults, and culminates in a highly orchestrated signal transduction cascade. Previously, we defined the regulatory role of nucleotide excision repair (NER) factors, DDB2 and XPC, in checkpoint and ATR/ATM-dependent repair pathway via ATR and ATM phosphorylation and recruitment to ultraviolet radiation (UVR)-induced damage sites. Here, we have dissected the molecular mechanisms of DDB2- and XPC- mediated regulation of ATR and ATM recruitment and activation upon UVR exposures. We show that the ATR and ATM activation and accumulation to UVR-induced damage not only depends on DDB2 and XPC, but also on the NER protein XPA, suggesting that the assembly of an active NER complex is essential for ATR and ATM recruitment. ATR and ATM localization and H2AX phosphorylation at the lesion sites occur as early as ten minutes in asynchronous as well as G1 arrested cells, showing that repair and checkpoint-mediated by ATR and ATM starts early upon UV irradiation. Moreover, our results demonstrated that ATR and ATM recruitment and H2AX phosphorylation are dependent on NER proteins in G1 phase, but not in S phase. We reasoned that in G1 the UVR-induced ssDNA gaps or processed ssDNA, and the bound NER complex promote ATR and ATM recruitment. In S phase, when the UV lesions result in stalled replication forks with long single-stranded DNA, ATR and ATM recruitment to these sites is regulated by different sets of proteins. Taken together, these results provide evidence that UVR-induced ATR and ATM recruitment and activation differ in G1 and S phases due to the existence of distinct types of DNA lesions, which promote assembly of different proteins involved in the process of DNA repair and checkpoint activation.

49 CFR 26.73 - What are other rules affecting certification?

Code of Federal Regulations, 2011 CFR

2011-10-01

... decisions, whether a firm has exhibited a pattern of conduct indicating its involvement in attempts to evade... cannot be certified. (f) Recognition of a business as a separate entity for tax or corporate purposes is...

49 CFR 26.73 - What are other rules affecting certification?

Code of Federal Regulations, 2010 CFR

2010-10-01

... decisions, whether a firm has exhibited a pattern of conduct indicating its involvement in attempts to evade... cannot be certified. (f) Recognition of a business as a separate entity for tax or corporate purposes is...

Tactile agnosia. Casuistic evidence and theoretical remarks on modality-specific meaning representations and sensorimotor integration.

PubMed

Platz, T

1996-10-01

Somaesthetic, motor and cognitive functions were studied in a man with impaired tactile object-recognition (TOR) in his left hand due to a right parietal convexity meningeoma which had been surgically removed. Primary motor and somatosensory functions were not impaired, and discriminative abilities for various tactile aspects and cognitive skills were preserved. Nevertheless, the patient could often not appreciate the object's nature or significance when it was placed in his left hand and was unable to name or to describe or demonstrate the use of these objects. Therefore, he can be regarded as an example of associative tactile agnosia. The view is taken and elaborated that defective modality-specific meaning representations account for associative tactile agnosia. These meaning representations are conceptualized as learned unimodal feature-entity relationships which are thought to be defective in tactile agnosia. In line with this hypothesis, tactile feature analysis and cross-modal matching of features were largely preserved in the investigated patient, while combining features to form entities was defective in the tactile domain. The alternative hypothesis of agnosia as deficit of cross-modal association of features was not supported. The presumed distributed functional network responsible for TOR is thought to involve perception of features, object recognition and related tactile motor behaviour interactively. A deficit leading primarily to impaired combining features to form entities can therefore be expected to result in additional minor impairment of related perceptual-motor processes. Unilaterality of the gnostic deficit can be explained by a lateralized organization of the functional network responsible for tactile recognition of objects.

A unified model for the molecular basis of Xeroderma pigmentosum-Cockayne Syndrome

PubMed Central

Moriel-Carretero, María; Herrera-Moyano, Emilia; Aguilera, Andrés

2015-01-01

Nucleotide Excision Repair (NER) is a pathway that removes lesions distorting the DNA helix. The molecular basis of the rare diseases Xeroderma pigmentosum (XP) and Cockayne Syndrome (CS) are explained based on the defects happening in 2 NER branches: Global-Genome Repair and Transcription-Coupled Repair, respectively. Nevertheless, both afflictions sporadically occur together, giving rise to XP/CS; however, the molecular basis of XP/CS is not understood very well. Many efforts have been made to clarify why mutations in only 4 NER genes, namely XPB, XPD, XPF and XPG, are the basis of this disease. Effort has also been made to unravel why mutations within these genes lead to XP, XP/CS, or other pathologies. We have recently contributed to the disclosure of this puzzle by characterizing Rad3/XPD mutations in Saccharomyces cerevisiae and human cells. Based on our, and others', observations, we propose a model compatible with all XP/CS cases and the current bibliography. PMID:26460500

Structure and mechanism of the UvrA-UvrB DNA damage sensor

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pakotiprapha, Danaya; Samuels, Martin; Shen, Koning

2012-04-17

Nucleotide excision repair (NER) is used by all organisms to eliminate DNA lesions. We determined the structure of the Geobacillus stearothermophilus UvrA-UvrB complex, the damage-sensor in bacterial NER and a new structure of UvrA. We observe that the DNA binding surface of UvrA, previously found in an open shape that binds damaged DNA, also exists in a closed groove shape compatible with native DNA only. The sensor contains two UvrB molecules that flank the UvrA dimer along the predicted path for DNA, ~80 Å from the lesion. We show that the conserved signature domain II of UvrA mediates a nexusmore » of contacts among UvrA, UvrB and DNA. Further, in our new structure of UvrA, this domain adopts an altered conformation while an adjacent nucleotide binding site is vacant. Our findings raise unanticipated questions about NER and also suggest a revised picture of its early stages.« less

Neurodegeneration as the presenting symptom in 2 adults with xeroderma pigmentosum complementation group F

PubMed Central

Shanbhag, Niraj M.; Geschwind, Michael D.; DiGiovanna, John J.; Groden, Catherine; Godfrey, Rena; Yousefzadeh, Matthew J.; Wade, Erin A.; Niedernhofer, Laura J.; Malicdan, May Christine V.; Kraemer, Kenneth H.; Gahl, William A.

2018-01-01

Objective To describe the features of 2 unrelated adults with xeroderma pigmentosum complementation group F (XP-F) ascertained in a neurology care setting. Methods We report the clinical, imaging, molecular, and nucleotide excision repair (NER) capacity of 2 middle-aged women with progressive neurodegeneration ultimately diagnosed with XP-F. Results Both patients presented with adult-onset progressive neurologic deterioration involving chorea, ataxia, hearing loss, cognitive deficits, profound brain atrophy, and a history of skin photosensitivity, skin freckling, and/or skin neoplasms. We identified compound heterozygous pathogenic mutations in ERCC4 and confirmed deficient NER capacity in skin fibroblasts from both patients. Conclusions These cases illustrate the role of NER dysfunction in neurodegeneration and how adult-onset neurodegeneration could be the major symptom bringing XP-F patients to clinical attention. XP-F should be considered by neurologists in the differential diagnosis of patients with adult-onset progressive neurodegeneration accompanied by global brain atrophy and a history of heightened sun sensitivity, excessive freckling, and skin malignancies. PMID:29892709

Social Media: More Than Just a Communications Medium

DTIC Science & Technology

2012-03-14

video-hosting web services with the recognition that “Internet-based capabilities are integral to operations across the Department of Defense.”10...as DoD and the government as a whole, the U.S. Army’s recognition of social media’s unique relationship to time and speed is a step forward toward...populated size of social media entities, Alexa , the leader in free global web analytics, provides an updated list of the top 500 websites on the Internet

Nomination Period Extended for EPA’s New England Annual Environmental Merit Awards

EPA Pesticide Factsheets

The U.S. Environmental Protection Agency’s New England office has extended the deadline to submit nominations for New England people, organizations, government entities or businesses whose environmental achievements during the past year deserve recognition

Wide-threat detection: recognition of adversarial missions and activity patterns in Empire Challenge 2009

NASA Astrophysics Data System (ADS)

Levchuk, Georgiy; Shabarekh, Charlotte; Furjanic, Caitlin

2011-06-01

In this paper, we present results of adversarial activity recognition using data collected in the Empire Challenge (EC 09) exercise. The EC09 experiment provided an opportunity to evaluate our probabilistic spatiotemporal mission recognition algorithms using the data from live air-born and ground sensors. Using ambiguous and noisy data about locations of entities and motion events on the ground, the algorithms inferred the types and locations of OPFOR activities, including reconnaissance, cache runs, IED emplacements, logistics, and planning meetings. In this paper, we present detailed summary of the validation study and recognition accuracy results. Our algorithms were able to detect locations and types of over 75% of hostile activities in EC09 while producing 25% false alarms.

Causes of childhood blindness in the northeastern states of India.

PubMed

Bhattacharjee, Harsha; Das, Kalyan; Borah, Rishi Raj; Guha, Kamalesh; Gogate, Parikshit; Purukayastha, S; Gilbert, Clare

2008-01-01

The northeastern region (NER) of India is geographically isolated and ethno-culturally different from the rest of the country. There is lacuna regarding the data on causes of blindness and severe visual impairment in children from this region. To determine the causes of severe visual impairment and blindness amongst children from schools for the blind in the four states of NER of India. Survey of children attending special education schools for the blind in the NER. Blind and severely visually impaired children (best corrected visual acuity < 20/200 in the better eye, aged up to 16 years) underwent visual acuity estimation, external ocular examination, retinoscopy and fundoscopy. Refraction and low vision workup was done where indicated. World Health Organization's reporting form was used to code anatomical and etiological causes of visual loss. Microsoft Excel Windows software with SPSS. A total of 376 students were examined of whom 258 fulfilled the eligibility criteria. The major anatomical causes of visual loss amongst the 258 were congenital anomalies (anophthalmos, microphthalmos) 93 (36.1%); corneal conditions (scarring, vitamin A deficiency) 94 (36.7%); cataract or aphakia 28 (10.9%), retinal disorders 15 (5.8%) and optic atrophy 14 (5.3%). Nearly half of the children were blind from conditions which were either preventable or treatable (48.5%). Nearly half the childhood blindness in the NER states of India is avoidable and Vitamin A deficiency forms an important component unlike other Indian states. More research and multisectorial effort is needed to tackle congenital anomalies.

Poly(ADP-ribose) Contributes to an Association between Poly(ADP-ribose) Polymerase-1 and Xeroderma Pigmentosum Complementation Group A in Nucleotide Excision Repair*

PubMed Central

King, Brenee S.; Cooper, Karen L.; Liu, Ke Jian; Hudson, Laurie G.

2012-01-01

Exposure to ultraviolet radiation (UVR) promotes the formation of UVR-induced, DNA helix distorting photolesions such as (6-4) pyrimidine-pyrimidone photoproducts and cyclobutane pyrimidine dimers. Effective repair of such lesions by the nucleotide excision repair (NER) pathway is required to prevent DNA mutations and chromosome aberrations. Poly(ADP-ribose) polymerase-1 (PARP-1) is a zinc finger protein with well documented involvement in base excision repair. PARP-1 is activated in response to DNA damage and catalyzes the formation of poly(ADP-ribose) subunits that assist in the assembly of DNA repair proteins at sites of damage. In this study, we present evidence for PARP-1 contributions to NER, extending the knowledge of PARP-1 function in DNA repair beyond the established role in base excision repair. Silencing the PARP-1 protein or inhibiting PARP activity leads to retention of UVR-induced photolesions. PARP activation following UVR exposure promotes association between PARP-1 and XPA, a central protein in NER. Administration of PARP inhibitors confirms that poly(ADP-ribose) facilitates PARP-1 association with XPA in whole cell extracts, in isolated chromatin complexes, and in vitro. Furthermore, inhibition of PARP activity decreases UVR-stimulated XPA chromatin association, illustrating that these relationships occur in a meaningful context for NER. These results provide a mechanistic link for PARP activity in the repair of UVR-induced photoproducts. PMID:23038248

Expression of domains for protein-protein interaction of nucleotide excision repair proteins modifies cancer cell sensitivity to platinum derivatives and genomic stability.

PubMed

Jordheim, Lars Petter; Cros-Perrial, Emeline; Matera, Eva-Laure; Bouledrak, Karima; Dumontet, Charles

2014-10-01

Nucleotide excision repair (NER) is involved in the repair of DNA damage caused by platinum derivatives and has been shown to decrease the cytotoxic activity of these drugs. Because protein-protein interactions are essential for NER activity, we transfected human cancer cell lines (A549 and HCT116) with plasmids coding the amino acid sequences corresponding to the interacting domains between excision repair cross-complementation group 1 (ERCC1) and xeroderma pigmentosum, complementation group A (XPA), as well as ERCC1 and xeroderma pigmentosum, complementation group F (XPF), all NER proteins. Using the 3-(4,5-dimethyl-2 thiazoyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and annexin V staining, we showed that transfected A549 cells were sensitized 1.2-2.2-fold to carboplatin and that transfected HCT116 cells were sensitized 1.4-5.4-fold to oxaliplatin in vitro. In addition, transfected cells exhibited modified in vivo sensitivity to the same drugs. Finally, in particular cell models of the interaction between ERCC1 and XPF, DNA repair was decreased, as evidenced by increased phosphorylation of the histone 2AX after exposure to mitomycin C, and genomic instability was increased, as determined by comparative genomic hybridization studies. The results indicate that the interacting peptides act as dominant negatives and decrease NER activity through inhibition of protein-protein interactions. © 2014 Wiley Publishing Asia Pty Ltd.

Identifying interactions between chemical entities in biomedical text.

PubMed

Lamurias, Andre; Ferreira, João D; Couto, Francisco M

2014-10-23

Interactions between chemical compounds described in biomedical text can be of great importance to drug discovery and design, as well as pharmacovigilance. We developed a novel system, \\"Identifying Interactions between Chemical Entities\\" (IICE), to identify chemical interactions described in text. Kernel-based Support Vector Machines first identify the interactions and then an ensemble classifier validates and classifies the type of each interaction. This relation extraction module was evaluated with the corpus released for the DDI Extraction task of SemEval 2013, obtaining results comparable to state-of-the-art methods for this type of task. We integrated this module with our chemical named entity recognition module and made the whole system available as a web tool at www.lasige.di.fc.ul.pt/webtools/iice.

Identifying interactions between chemical entities in biomedical text.

PubMed

Lamurias, Andre; Ferreira, João D; Couto, Francisco M

2014-12-01

Interactions between chemical compounds described in biomedical text can be of great importance to drug discovery and design, as well as pharmacovigilance. We developed a novel system, "Identifying Interactions between Chemical Entities" (IICE), to identify chemical interactions described in text. Kernel-based Support Vector Machines first identify the interactions and then an ensemble classifier validates and classifies the type of each interaction. This relation extraction module was evaluated with the corpus released for the DDI Extraction task of SemEval 2013, obtaining results comparable to stateof- the-art methods for this type of task. We integrated this module with our chemical named entity recognition module and made the whole system available as a web tool at www.lasige.di.fc.ul.pt/webtools/iice.

Structured prediction models for RNN based sequence labeling in clinical text.

PubMed

Jagannatha, Abhyuday N; Yu, Hong

2016-11-01

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies for structured prediction in order to improve the exact phrase detection of various medical entities.

Structured prediction models for RNN based sequence labeling in clinical text

PubMed Central

Jagannatha, Abhyuday N; Yu, Hong

2016-01-01

Sequence labeling is a widely used method for named entity recognition and information extraction from unstructured natural language data. In clinical domain one major application of sequence labeling involves extraction of medical entities such as medication, indication, and side-effects from Electronic Health Record narratives. Sequence labeling in this domain, presents its own set of challenges and objectives. In this work we experimented with various CRF based structured learning models with Recurrent Neural Networks. We extend the previously studied LSTM-CRF models with explicit modeling of pairwise potentials. We also propose an approximate version of skip-chain CRF inference with RNN potentials. We use these methodologies1 for structured prediction in order to improve the exact phrase detection of various medical entities. PMID:28004040

Detailed structure and tectonics of the Ninetyeast Ridge near Site ODP 758 (on new geophysical data from KNOX06RR cruise of R/V Roger Revelle)

NASA Astrophysics Data System (ADS)

Levchenko, O.; Eisin, A. E.; Ivanenko, A. N.; Marinova, J. G.; Paul, C. F.; Sborshchikov, I. M.; Sager, W. W.

2008-12-01

Detailed geophysical survey was carried out during the NSF-funded KNOX06RR cruise of R/V Roger Revelle in July 2007 over the ~70×70 km area near ODP Site 758, the northern Ninetyeast Ridge (NER). In addition to multibeam echo-sounder bathymetry, 3.5 kHz echo-sounder profiles, magnetic, and gravity data, high-resolution multichannel seismic reflection data were collected on eight orthogonal profiles of total length ~270 km. Large NE-trending depressions with complicated horst and graben morphology dominate the whole detailed survey area. The numerous basement faults extend upward into overlying sediments filling out these depressions. Thickness of the sedimentary fill is highly variable due to very rough basement topography, and is up to 800 m maximum. This fill is divided in two clear sedimentary layers: transparent pelagic sediments above and stratified shallow-water ones below. Two high ~400-450 m isometric seamounts extend from the surrounding NER seafloor. High-resolution seismic records show that these igneous basement highs are covered by thin transparent pelagic sediments which hamper the dredging of volcanic rocks. Seismic stratigraphy analyses for sedimentary cover over the seamounts buried slopes suggest that they seem to be recent volcanoes superimposed on the main NER edifice. Both volcanoes are clearly delineated in the constructed map of total anomaly magnetic field. Since water depths are ~2.5 km above these seamounts, the lower edge of the magnetic body in these volcanoes is situated deep at ~7 km under sea level. That appears to represent deep roots of the volcanoes. Preliminary magnetic modeling shows that they were generated during negative chron of the geomagnetic scale rather not long ago and not far from their present location, seeming to confirm the inference that these volcanoes are recent in origin. In general, one may assume a secondary phase of magmatic activity on the NER. It is important to reveal, any recent phase of tectonic and magnetic activity occurred over the northern NER during the same time of well-known intense intraplate deformation in the Central Indian Basin which was initiated ~8 Ma in response to growing regional compression due to continental collision Hindustan and Eurasia. It appears to be nonrandom that this NER segment is located in an anomalous zone of high oceanic intraplate seismicity. Seismic stratigraphy analyses of high-resolution seismic records over the fault features simultaneously with careful study of reflectors on the buried slopes of the recent volcanoes will allow us to examine this problem.

Involvement of noradrenergic and corticoid receptors in the consolidation of the lasting anxiogenic effects of predator stress.

PubMed

Adamec, R; Muir, C; Grimes, M; Pearcey, K

2007-05-16

The roles of beta-NER (beta-noradrenergic receptor), GR (glucocorticoid) and mineral corticoid receptors (MR) in the consolidation of anxiogenic effects of predator stress were studied. One minute after predator stress, different groups of rats were injected (ip) with vehicle, propranolol (beta-NER blocker, 5 and 10 mg/kg), mifepristone (RU486, GR blocker, 20 mg/kg), spironolactone (MR blocker, 50 mg/kg), propranolol (5 mg/kg) plus RU486 (20 mg/kg) or the anxiolytic, chloradiazepoxide (CPZ, 10 mg/kg). One week later, rodent anxiety was assessed in elevated plus maze, hole board, light/dark box, social interaction and acoustic startle. Considering all tests except startle, propranolol dose dependently blocked consolidation of lasting anxiogenic effects of predator stress in all tests. GR receptor block alone was ineffective. However, GR block in combination with an ineffective dose of propranolol did blocked consolidation of predator stress effects in all tests, suggesting a synergism between beta-NER and GR. Surprisingly, MR block prevented consolidation of anxiogenic effects in all tests except the light/dark box. CPZ post stress was ineffective against the anxiogenic impact of predator stress. Study of startle was complicated by the fact that anxiogenic effects of stress on startle amplitude manifested as both an increase and a decrease in startle amplitude. Suppression of startle occurred in stressed plus vehicle injected groups handled three times prior to predator stress. In contrast, stressed plus vehicle rats handled five times prior to predator stress showed increases in startle, as did all predator stressed only groups. Mechanisms of consolidation of the different startle responses appear to differ. CPZ post stress blocked startle suppression but not enhancement of startle. Propranolol post stress had no effect on either suppression or enhancement of startle. GR block alone post stress prevented suppression of startle, but not enhancement. In contrast blocking GR and beta-NER together prevented startle enhancement. MR block also prevented startle enhancement. Effects of MR block on startle suppression were not tested. Delay of habituation to startle was found in all stressed rats. Consolidation of delay of habituation was blocked or attenuated by post stress MR block, GR plus beta-NER block and CPZ but not by post stress GR or beta-NER block alone. Taken together, present findings suggest consolidation of lasting anxiogenic effects of predator stress may share some of the same neurochemical mechanisms implicated in some forms of fear memory consolidation. Implications of these findings for the study of stress-induced changes in affect including posttraumatic stress disorder (PTSD) are discussed.

Geothermal projects funded under the NER 300 programme - current state of development and knowledge gained

NASA Astrophysics Data System (ADS)

Uihlein, Andreas; Salto Saura, Lourdes; Sigfusson, Bergur; Lichtenvort, Kerstin; Gagliardi, Filippo

2015-04-01

Introduction The NER 300 programme, managed by the European Commission is one of the largest funding programmes for innovative low-carbon energy demonstration projects. NER 300 is so called because it is funded from the sale of 300 million emission allowances from the new entrants' reserve (NER) set up for the third phase of the EU emissions trading system (ETS). The programme aims to successfully demonstrate environmentally safe carbon capture and storage (CCS) and innovative renewable energy (RES) technologies on a commercial scale with a view to scaling up production of low-carbon technologies in the EU. Consequently, it supports a wide range of CCS and RES technologies (bioenergy, concentrated solar power, photovoltaics, geothermal, wind, ocean, hydropower, and smart grids). Funded projects and the role of geothermal projects for the programme In total, about EUR 2.1 billion have been awarded to 39 projects through the programme's 2 calls for proposals (the first awarded in December 2012, the second in July 2014). The programme has awarded around 70 mEUR funding to 3 geothermal projects in Hungary, Croatia and France (see Annex). The Hungarian geothermal project awarded funding under the first call will enter into operation at the end of 2015 and the rest are expected to start in 2016 (HR) and in 2018 (FR), respectively. Knowledge Sharing Knowledge sharing requirements are built into the legal basis of the programme as a critical tool to lower risks in bridging the transition to large-scale production of innovative renewable energy and CCS deployment. Projects have to submit annually to the European Commission relevant knowledge gained during that year in the implementation of their project. The relevant knowledge is aggregated and disseminated by the European Commission to industry, research, government, NGO and other interest groups and associations in order to provide a better understanding of the practical challenges that arise in the important step of scaling up technologies and operating them at commercial scale. The knowledge sharing of the NER 300 programme should lead to better planning and faster introduction of low carbon technologies in the future. Content of the presentation The presentation will introduce the geothermal projects that have been awarded funding, including their state-of-play. Insights and knowledge gained from the projects that have entered into operation will be shown and discussed. Furthermore, the presentation will provide an overview of the NER 300 programme.

GASB Achieves Standardization, Recognition.

ERIC Educational Resources Information Center

Bissell, George E.

1986-01-01

In 1984 the Governmental Accounting Standards Board, created to solidify accounting principles for government entities, enumerated Generally Accepted Accounting Principles endorsed by the American Institute of Certified Public Accountants and the National Council on Governmental Accounting. These principles have recently been approved for school…

A neural joint model for entity and relation extraction from biomedical text.

PubMed

Li, Fei; Zhang, Meishan; Fu, Guohong; Ji, Donghong

2017-03-31

Extracting biomedical entities and their relations from text has important applications on biomedical research. Previous work primarily utilized feature-based pipeline models to process this task. Many efforts need to be made on feature engineering when feature-based models are employed. Moreover, pipeline models may suffer error propagation and are not able to utilize the interactions between subtasks. Therefore, we propose a neural joint model to extract biomedical entities as well as their relations simultaneously, and it can alleviate the problems above. Our model was evaluated on two tasks, i.e., the task of extracting adverse drug events between drug and disease entities, and the task of extracting resident relations between bacteria and location entities. Compared with the state-of-the-art systems in these tasks, our model improved the F1 scores of the first task by 5.1% in entity recognition and 8.0% in relation extraction, and that of the second task by 9.2% in relation extraction. The proposed model achieves competitive performances with less work on feature engineering. We demonstrate that the model based on neural networks is effective for biomedical entity and relation extraction. In addition, parameter sharing is an alternative method for neural models to jointly process this task. Our work can facilitate the research on biomedical text mining.

PKDE4J: Entity and relation extraction for public knowledge discovery.

PubMed

Song, Min; Kim, Won Chul; Lee, Dahee; Heo, Go Eun; Kang, Keun Young

2015-10-01

Due to an enormous number of scientific publications that cannot be handled manually, there is a rising interest in text-mining techniques for automated information extraction, especially in the biomedical field. Such techniques provide effective means of information search, knowledge discovery, and hypothesis generation. Most previous studies have primarily focused on the design and performance improvement of either named entity recognition or relation extraction. In this paper, we present PKDE4J, a comprehensive text-mining system that integrates dictionary-based entity extraction and rule-based relation extraction in a highly flexible and extensible framework. Starting with the Stanford CoreNLP, we developed the system to cope with multiple types of entities and relations. The system also has fairly good performance in terms of accuracy as well as the ability to configure text-processing components. We demonstrate its competitive performance by evaluating it on many corpora and found that it surpasses existing systems with average F-measures of 85% for entity extraction and 81% for relation extraction. Copyright © 2015 Elsevier Inc. All rights reserved.

Incision of trivalent chromium [Cr(III)]-induced DNA damage by Bacillus caldotenax UvrABC endonuclease.

PubMed

O'Brien, Travis J; Jiang, Guohui; Chun, Gina; Mandel, H George; Westphal, Craig S; Kahen, Kaveh; Montaser, Akbar; States, J Christopher; Patierno, Steven R

2006-11-07

Some hexavalent chromium [Cr(VI)]-containing compounds are lung carcinogens. Once within cells, Cr(VI) is reduced to trivalent chromium [Cr(III)] which displays an affinity for both DNA bases and the phosphate backbone. A diverse array of genetic lesions is produced by Cr including Cr-DNA monoadducts, DNA interstrand crosslinks (ICLs), DNA-Cr-protein crosslinks (DPCs), abasic sites, DNA strand breaks and oxidized bases. Despite the large amount of information available on the genotoxicity of Cr, little is known regarding the molecular mechanisms involved in the removal of these lesions from damaged DNA. Recent work indicates that nucleotide excision repair (NER) is involved in the processing of Cr-DNA adducts in human and rodent cells. In order to better understand this process at the molecular level and begin to identify the Cr-DNA adducts processed by NER, the incision of CrCl(3) [Cr(III)]-damaged plasmid DNA was studied using a thermal-resistant UvrABC NER endonuclease from Bacillus caldotenax (Bca). Treatment of plasmid DNA with Cr(III) (as CrCl(3)) increased DNA binding as a function of dose. For example, at a Cr(III) concentration of 1 microM we observed approximately 2 Cr(III)-DNA adducts per plasmid. At this same concentration of Cr(III) we found that approximately 17% of the plasmid DNA contained ICLs ( approximately 0.2 ICLs/plasmid). When plasmid DNA treated with Cr(III) (1 microM) was incubated with Bca UvrABC we observed approximately 0.8 incisions/plasmid. The formation of endonuclease IV-sensitive abasic lesions or Fpg-sensitive oxidized DNA bases was not detected suggesting that the incision of Cr(III)-damaged plasmid DNA by UvrABC was not related to the generation of oxidized DNA damage. Taken together, our data suggest that a sub-fraction of Cr(III)-DNA adducts is recognized and processed by the prokaryotic NER machinery and that ICLs are not necessarily the sole lesions generated by Cr(III) that are substrates for NER.

Nutritional Quality of Preparations Based on Döner Kebab Sold in Two Towns of Veneto Region, Italy: Preliminary Results

PubMed Central

Panozzo, Monica; Magro, Luciano; Erle, Ilario; Ferrarini, Stefano; Murari, Riccardo; Masaro, Simone

2015-01-01

The sampling activity for this study was performed between September and October 2012. It involved seven shops in Verona, eleven in Vicenza and two in its province (Bassano del Grappa), northern Italy. The scope was to measure the values of energy and nutritional components and to identify the profile of fatty acids in a serving of ready to eat Döner Kebab. The samples were collected according to the usual proportions of this preparation, keeping all the components (bread, meat, vegetables and sauces) separated in different bags. In the laboratory, each component was weighed and, after pooling, processed for the analytical determination of humidity, crude protein, lipid content and fatty acid profile, ashes, sodium (salt), carbohydrate, collagen (measured only in meat) and fibre. The results showed a highly standardized recipe, while the comparison between the two towns showed a significant difference in carbohydrate concentration (mainly due to the quantity of bread used). By observing data on the serving sizes sampled (274 to 618 g) and the nutritional values obtained, Döner Kebab can be seen as a ready to eat dish providing much energy: on average a serving size covers 45 and 36% of the recommended daily intake of energy, 95.7 and 82.1% of protein, 42.5 and 33.4% of saturated fatty acids for females and males, respectively, and 85.5% of salt regardless of gender. Döner Kebab can be considered as an occasional substitute to one of the two main meals of the day. PMID:27800390

Causes of childhood blindness in the northeastern states of India

PubMed Central

Bhattacharjee, Harsha; Das, Kalyan; Borah, Rishi Raj; Guha, Kamalesh; Purukayastha, S; Gilbert, Clare

2008-01-01

Background: The northeastern region (NER) of India is geographically isolated and ethno-culturally different from the rest of the country. There is lacuna regarding the data on causes of blindness and severe visual impairment in children from this region. Aim: To determine the causes of severe visual impairment and blindness amongst children from schools for the blind in the four states of NER of India. Design and Setting: Survey of children attending special education schools for the blind in the NER. Materials and Methods: Blind and severely visually impaired children (best corrected visual acuity <20/200 in the better eye, aged up to 16 years) underwent visual acuity estimation, external ocular examination, retinoscopy and fundoscopy. Refraction and low vision workup was done where indicated. World Health Organization′s reporting form was used to code anatomical and etiological causes of visual loss. Statistical Analysis: Microsoft Excel Windows software with SPSS. Results: A total of 376 students were examined of whom 258 fulfilled the eligibility criteria. The major anatomical causes of visual loss amongst the 258 were congenital anomalies (anophthalmos, microphthalmos) 93 (36.1%); corneal conditions (scarring, vitamin A deficiency) 94 (36.7%); cataract or aphakia 28 (10.9%), retinal disorders 15 (5.8%) and optic atrophy 14 (5.3%). Nearly half of the children were blind from conditions which were either preventable or treatable (48.5%). Conclusion: Nearly half the childhood blindness in the NER states of India is avoidable and Vitamin A deficiency forms an important component unlike other Indian states. More research and multisectorial effort is needed to tackle congenital anomalies. PMID:18974521

Occupancy of Norepinephrine Transporter by Duloxetine in Human Brains Measured by Positron Emission Tomography with (S,S)-[18F]FMeNER-D2.

PubMed

Moriguchi, Sho; Takano, Harumasa; Kimura, Yasuyuki; Nagashima, Tomohisa; Takahata, Keisuke; Kubota, Manabu; Kitamura, Soichiro; Ishii, Tatsuya; Ichise, Masanori; Zhang, Ming-Rong; Shimada, Hitoshi; Mimura, Masaru; Meyer, Jeffrey H; Higuchi, Makoto; Suhara, Tetsuya

2017-12-01

The norepinephrine transporter in the brain has been targeted in the treatment of psychiatric disorders. Duloxetine is a serotonin and norepinephrine reuptake inhibitor that has been widely used for the treatment of depression. However, the relationship between dose and plasma concentration of duloxetine and norepinephrine transporter occupancy in the human brain has not been determined. In this study, we examined norepinephrine transporter occupancy by different doses of duloxetine. We calculated norepinephrine transporter occupancies from 2 positron emission tomography scans using (S,S)-[18F]FMeNER-D2 before and after a single oral dose of duloxetine (20 mg, n = 3; 40 mg, n = 3; 60 mg, n =2). Positron emission tomography scans were performed from 120 to 180 minutes after an i.v. bolus injection of (S,S)-[18F]FMeNER-D2. Venous blood samples were taken to measure the plasma concentration of duloxetine just before and after the second positron emission tomography scan. Norepinephrine transporter occupancy by duloxetine was 29.7% at 20 mg, 30.5% at 40 mg, and 40.0% at 60 mg. The estimated dose of duloxetine inducing 50% norepinephrine transporter occupancy was 76.8 mg, and the estimated plasma drug concentration inducing 50% norepinephrine transporter occupancy was 58.0 ng/mL. Norepinephrine transporter occupancy by clinical doses of duloxetine was approximately 30% to 40% in human brain as estimated using positron emission tomography with (S,S)-[18F]FMeNER-D2. © The Author 2017. Published by Oxford University Press on behalf of CINP.

DNA repair factor XPC is modified by SUMO-1 and ubiquitin following UV irradiation

PubMed Central

Wang, Qi-En; Zhu, Qianzheng; Wani, Gulzar; El-Mahdy, Mohamed A.; Li, Jinyou; Wani, Altaf A.

2005-01-01

Nucleotide excision repair (NER) is the major DNA repair process that removes diverse DNA lesions including UV-induced photoproducts. There are more than 20 proteins involved in NER. Among them, XPC is thought to be one of the first proteins to recognize DNA damage during global genomic repair (GGR), a sub-pathway of NER. In order to study the mechanism through which XPC participates in GGR, we investigated the possible modifications of XPC protein upon UV irradiation in mammalian cells. Western blot analysis of cell lysates from UV-irradiated normal human fibroblast, prepared by direct boiling in an SDS lysis buffer, showed several anti-XPC antibody-reactive bands with molecular weight higher than the original XPC protein. The reciprocal immunoprecipitation and siRNA transfection analysis demonstrated that XPC protein is modified by SUMO-1 and ubiquitin. By using several NER-deficient cell lines, we found that DDB2 and XPA are required for UV-induced XPC modifications. Interestingly, both the inactivation of ubiquitylation and the treatment of proteasome inhibitors quantitatively inhibited the UV-induced XPC modifications. Furthermore, XPC protein is degraded significantly following UV irradiation in XP-A cells in which sumoylation of XPC does not occur. Taken together, we conclude that XPC protein is modified by SUMO-1 and ubiquitin following UV irradiation and these modifications require the functions of DDB2 and XPA, as well as the ubiquitin–proteasome system. Our results also suggest that at least one function of UV-induced XPC sumoylation is related to the stabilization of XPC protein. PMID:16030353

Moderating effects of childhood maltreatment on associations between social information processing and adult aggression

PubMed Central

Chen, P.; Coccaro, E. F.; Lee, R.; Jacobson, K. C.

2014-01-01

Background Associations between early life maltreatment, social information processing (SIP) and aggression in childhood and adolescence have been widely documented. Few studies have examined the importance of childhood maltreatment independent of SIP in the etiology of adult aggression. Furthermore, moderating effects of childhood maltreatment on the SIP–aggression links have not been explored. Method Hierarchical, multi-level models were fitted to data from n=2752 twins aged 20–55 years from the PennTwins Cohort. Adult aggression was assessed with the Life History of Aggression questionnaire. Childhood maltreatment was measured using the Childhood Trauma Questionnaire. Two aspects of SIP were examined : hostile attribution biases (HAB) ; negative emotional responses (NER). Results Childhood maltreatment was positively correlated with adult aggression, independently of HAB and NER. In addition, childhood maltreatment moderated the relationships between both aspects of SIP and adult aggression. Specifically, the relationship between NER and aggression was stronger among individuals with higher levels of childhood maltreatment and NER was not associated with aggression for adults who experienced low levels of childhood maltreatment. Moderating effects of childhood maltreatment on the NER–aggression link were supported for total childhood maltreatment, emotional neglect and emotional abuse. In contrast, HAB was more strongly associated with adult aggression at lower levels of emotional abuse and physical neglect. Conclusions The current study provides insight into the mechanisms by which early life experiences influence adult aggression. Our findings suggest that childhood maltreatment may not only lead to increased levels of aggression in adulthood but may also modify the associations between SIP and adult aggression. PMID:22008562

Identification of a Plastid-Localized Bifunctional Nerolidol/Linalool Synthase in Relation to Linalool Biosynthesis in Young Grape Berries

PubMed Central

Zhu, Bao-Qing; Cai, Jian; Wang, Zhi-Qun; Xu, Xiao-Qing; Duan, Chang-Qing; Pan, Qiu-Hong

2014-01-01

Monoterpenoids are a diverse class of natural products and contribute to the important varietal aroma of certain Vitis vinifera grape cultivars. Among the typical monoterpenoids, linalool exists in almost all grape varieties. A gene coding for a nerolidol/linalool (NES/LINS) synthase was evaluated in the role of linalool biosynthesis in grape berries. Enzyme activity assay of this recombinant protein revealed that it could convert geranyl diphosphate and farnesyl diphosphate into linalool and nerolidol in vitro, respectively, and thus it was named VvRILinNer. However, localization experiment showed that this enzyme was only localized to chloroplasts, which indicates that VvRILinNer functions in the linalool production in vivo. The patterns of gene expression and linalool accumulation were analyzed in the berries of three grape cultivars (“Riesling”, “Cabernet Sauvignon”, “Gewurztraminer”) with significantly different levels of monoterpenoids. The VvRILinNer was considered to be mainly responsible for the synthesis of linalool at the early developmental stage. This finding has provided us with new knowledge to uncover the complex monoterpene biosynthesis in grapes. PMID:25470020

Ordered Conformational Changes in Damaged DNA Induced by Nucleotide Excision Repair Factors*

PubMed Central

Tapias, Angels; Auriol, Jerome; Forget, Diane; Enzlin, Jacqueline H.; Schärer, Orlando D; Coin, Frederic; Coulombe, Benoit; Egly, Jean-Marc

2015-01-01

In response to genotoxic attacks, cells activate sophisticated DNA repair pathways such as nucleotide excision repair (NER), which consists of damage removal via dual incision and DNA resynthesis. Using permanganate footprinting as well as highly purified factors, we show that NER is a dynamic process that takes place in a number of successive steps during which the DNA is remodeled around the lesion in response to the various NER factors. XPC/HR23B first recognizes the damaged structure and initiates the opening of the helix from position −3 to +6. TFIIH is then recruited and, in the presence of ATP, extends the opening from position −6 to +6; it also displaces XPC downstream from the lesion, thereby providing the topological structure for recruiting XPA and RPA, which will enlarge the opening. Once targeted by XPG, the damaged DNA is further melted from position −19 to +8. XPG and XPF/ERCC1 endo-nucleases then cut the damaged DNA at the limit of the opened structure that was previously “labeled” by the positioning of XPC/HR23B and TFIIH. PMID:14981083

Stimulation of ribosomal RNA gene promoter by transcription factor Sp1 involves active DNA demethylation by Gadd45-NER pathway.

PubMed

Rajput, Pallavi; Pandey, Vijaya; Kumar, Vijay

2016-08-01

The well-studied Pol II transcription factor Sp1 has not been investigated for its regulatory role in rDNA transcription. Here, we show that Sp1 bound to specific sites on rDNA and localized into the nucleoli during the G1 phase of cell cycle to activate rDNA transcription. It facilitated the recruitment of Pol I pre-initiation complex and impeded the binding of nucleolar remodeling complex (NoRC) to rDNA resulting in the formation of euchromatin active state. More importantly, Sp1 also orchestrated the site-specific binding of Gadd45a-nucleotide excision repair (NER) complex resulting in active demethylation and transcriptional activation of rDNA. Interestingly, knockdown of Sp1 impaired rDNA transcription due to reduced engagement of the Gadd45a-NER complex and hypermethylation of rDNA. Thus, the present study unveils a novel role of Sp1 in rDNA transcription involving promoter demethylation. Copyright © 2016 Elsevier B.V. All rights reserved.

A rapid non-radioactive technique for measurement of repair synthesis in primary human fibroblasts by incorporation of ethynyl deoxyuridine (EdU).

PubMed

Limsirichaikul, Siripan; Niimi, Atsuko; Fawcett, Heather; Lehmann, Alan; Yamashita, Shunichi; Ogi, Tomoo

2009-03-01

Xeroderma pigmentosum (XP) is an autosomal recessive genetic disorder. Afflicted patients show extreme sun-sensitivity and skin cancer predisposition. XP is in most cases associated with deficient nucleotide excision repair (NER), which is the process responsible for removing photolesions from DNA. Measuring NER activity by nucleotide incorporation into repair patches, termed 'unscheduled DNA synthesis (UDS)', is one of the most commonly used assays for XP-diagnosis and NER research. We have established a rapid and accurate procedure for measuring UDS by replacement of thymidine with 5-ethynyl-2'-deoxyuridine (EdU). EdU incorporated into repair patches can be directly conjugated to fluorescent azide derivatives, thereby obviating the need for either radiolabeled thymidine or denaturation and antibody detection of incorporated bromodeoxyuridine (BrdU). We demonstrate that the EdU incorporation assay is compatible with conventional techniques such as immunofluorescent staining and labeling of cells with micro-latex beads. Importantly, we can complete the entire UDS assay within half a day from preparation of the assay coverslips; this technique may prove useful as a method for XP diagnosis.

DNA damage leads to progressive replicative decline but extends the life span of long-lived mutant animals.

PubMed

Lans, H; Lindvall, J M; Thijssen, K; Karambelas, A E; Cupac, D; Fensgård, O; Jansen, G; Hoeijmakers, J H J; Nilsen, H; Vermeulen, W

2013-12-01

Human-nucleotide-excision repair (NER) deficiency leads to different developmental and segmental progeroid symptoms of which the pathogenesis is only partially understood. To understand the biological impact of accumulating spontaneous DNA damage, we studied the phenotypic consequences of DNA-repair deficiency in Caenorhabditis elegans. We find that DNA damage accumulation does not decrease the adult life span of post-mitotic tissue. Surprisingly, loss of functional ERCC-1/XPF even further extends the life span of long-lived daf-2 mutants, likely through an adaptive activation of stress signaling. Contrariwise, NER deficiency leads to a striking transgenerational decline in replicative capacity and viability of proliferating cells. DNA damage accumulation induces severe, stochastic impairment of development and growth, which is most pronounced in NER mutants that are also impaired in their response to ionizing radiation and inter-strand crosslinks. These results suggest that multiple DNA-repair pathways can protect against replicative decline and indicate that there might be a direct link between the severity of symptoms and the level of DNA-repair deficiency in patients.

Artificial Neural Networks for Processing Graphs with Application to Image Understanding: A Survey

NASA Astrophysics Data System (ADS)

Bianchini, Monica; Scarselli, Franco

In graphical pattern recognition, each data is represented as an arrangement of elements, that encodes both the properties of each element and the relations among them. Hence, patterns are modelled as labelled graphs where, in general, labels can be attached to both nodes and edges. Artificial neural networks able to process graphs are a powerful tool for addressing a great variety of real-world problems, where the information is naturally organized in entities and relationships among entities and, in fact, they have been widely used in computer vision, f.i. in logo recognition, in similarity retrieval, and for object detection. In this chapter, we propose a survey of neural network models able to process structured information, with a particular focus on those architectures tailored to address image understanding applications. Starting from the original recursive model (RNNs), we subsequently present different ways to represent images - by trees, forests of trees, multiresolution trees, directed acyclic graphs with labelled edges, general graphs - and, correspondingly, neural network architectures appropriate to process such structures.

Controls on ferromanganese crust composition and reconnaissance resource potential, Ninetyeast Ridge, Indian Ocean

USGS Publications Warehouse

Hein, James; Conrad, Tracey A.; Mizell, Kira; Banakar, Virupaxa K.; Frey, Frederick A.; Sager, William W.

2016-01-01

The southern third of NER has Fe-Mn crusts with the highest Co (0.91%), Ni (0.43%), ΣREY (0.33%), Cu (0.22%), Te (146 ppm), Pt (1.5 ppm), Ru (52 ppb), and Rh (99 ppb) contents. These are among the highest Pt, Ru, and Rh concentrations measured in marine Fe-Mn deposits. Because of these high metal concentrations, exploration is warranted for the southern sector of the NER, especially at shallower-water sites where the platinum group elements (PGE) and Co are likely to be even more enriched.

Development of the use of conversational cues to assess reality status

PubMed Central

Woolley, Jacqueline D.; Ma, Lili; Lopez-Mobilia, Gabriel

2011-01-01

In this study we assessed children’s ability to use information overheard in other people’s conversations to judge the reality status of a novel entity. Three- to 9-year-old children (N = 101) watched video clips in which two adults conversed casually about a novel being. Videos contained statements that either explicitly denied, explicitly affirmed, or implicitly acknowledged the entity’s existence. Results indicated that children of all ages used statements of denial to discount the reality status of the novel entity, but that this ability improved with age. By age 5, children used implicit existence cues to judge a novel entity as being real. Not until age 9, however, did children begin to doubt the existence of entities whose reality status was explicitly affirmed in conversation. Overall, results indicate that the ability to use conversational cues to determine reality status is present in some children as early as age 3, but recognition of the nuanced language of belief continues to develop during the elementary-school years. PMID:22241965

Idiopathic Noncirrhotic Portal Hypertension: An Appraisal

PubMed Central

Lee, Hwajeong; Rehman, Aseeb Ur; Fiel, M. Isabel

2016-01-01

Idiopathic noncirrhotic portal hypertension is a poorly defined clinical condition of unknown etiology. Patients present with signs and symptoms of portal hypertension without evidence of cirrhosis. The disease course appears to be indolent and benign with an overall better outcome than cirrhosis, as long as the complications of portal hypertension are properly managed. This condition has been recognized in different parts of the world in diverse ethnic groups with variable risk factors, resulting in numerous terminologies and lack of standardized diagnostic criteria. Therefore, although the diagnosis of idiopathic noncirrhotic portal hypertension requires clinical exclusion of other conditions that can cause portal hypertension and histopathologic confirmation, this entity is under-recognized clinically as well as pathologically. Recent studies have demonstrated that variable histopathologic entities with different terms likely represent a histologic spectrum of a single entity of which obliterative portal venopathy might be an underlying pathogenesis. This perception calls for standardization of the nomenclature and formulation of widely accepted diagnostic criteria, which will facilitate easier recognition of this disorder and will highlight awareness of this entity. PMID:26563701

The Halogen Bond

PubMed Central

2016-01-01

The halogen bond occurs when there is evidence of a net attractive interaction between an electrophilic region associated with a halogen atom in a molecular entity and a nucleophilic region in another, or the same, molecular entity. In this fairly extensive review, after a brief history of the interaction, we will provide the reader with a snapshot of where the research on the halogen bond is now, and, perhaps, where it is going. The specific advantages brought up by a design based on the use of the halogen bond will be demonstrated in quite different fields spanning from material sciences to biomolecular recognition and drug design. PMID:26812185

Assessment of disease named entity recognition on a corpus of annotated sentences.

PubMed

Jimeno, Antonio; Jimenez-Ruiz, Ernesto; Lee, Vivian; Gaudan, Sylvain; Berlanga, Rafael; Rebholz-Schuhmann, Dietrich

2008-04-11

In recent years, the recognition of semantic types from the biomedical scientific literature has been focused on named entities like protein and gene names (PGNs) and gene ontology terms (GO terms). Other semantic types like diseases have not received the same level of attention. Different solutions have been proposed to identify disease named entities in the scientific literature. While matching the terminology with language patterns suffers from low recall (e.g., Whatizit) other solutions make use of morpho-syntactic features to better cover the full scope of terminological variability (e.g., MetaMap). Currently, MetaMap that is provided from the National Library of Medicine (NLM) is the state of the art solution for the annotation of concepts from UMLS (Unified Medical Language System) in the literature. Nonetheless, its performance has not yet been assessed on an annotated corpus. In addition, little effort has been invested so far to generate an annotated dataset that links disease entities in text to disease entries in a database, thesaurus or ontology and that could serve as a gold standard to benchmark text mining solutions. As part of our research work, we have taken a corpus that has been delivered in the past for the identification of associations of genes to diseases based on the UMLS Metathesaurus and we have reprocessed and re-annotated the corpus. We have gathered annotations for disease entities from two curators, analyzed their disagreement (0.51 in the kappa-statistic) and composed a single annotated corpus for public use. Thereafter, three solutions for disease named entity recognition including MetaMap have been applied to the corpus to automatically annotate it with UMLS Metathesaurus concepts. The resulting annotations have been benchmarked to compare their performance. The annotated corpus is publicly available at ftp://ftp.ebi.ac.uk/pub/software/textmining/corpora/diseases and can serve as a benchmark to other systems. In addition, we found that dictionary look-up already provides competitive results indicating that the use of disease terminology is highly standardized throughout the terminologies and the literature. MetaMap generates precise results at the expense of insufficient recall while our statistical method obtains better recall at a lower precision rate. Even better results in terms of precision are achieved by combining at least two of the three methods leading, but this approach again lowers recall. Altogether, our analysis gives a better understanding of the complexity of disease annotations in the literature. MetaMap and the dictionary based approach are available through the Whatizit web service infrastructure (Rebholz-Schuhmann D, Arregui M, Gaudan S, Kirsch H, Jimeno A: Text processing through Web services: Calling Whatizit. Bioinformatics 2008, 24:296-298).

Histone deacetylases (HDACs) in XPC gene silencing and bladder cancer

PubMed Central

2011-01-01

Bladder cancer is one of the most common malignancies and causes hundreds of thousands of deaths worldwide each year. Bladder cancer is strongly associated with exposure to environmental carcinogens. It is believed that DNA damage generated by environmental carcinogens and their metabolites causes development of bladder cancer. Nucleotide excision repair (NER) is the major DNA repair pathway for repairing bulk DNA damage generated by most environmental carcinogens, and XPC is a DNA damage recognition protein required for initiation of the NER process. Recent studies demonstrate reduced levels of XPC protein in tumors for a majority of bladder cancer patients. In this work we investigated the role of histone deacetylases (HDACs) in XPC gene silencing and bladder cancer development. The results of our HDAC inhibition study revealed that the treatment of HTB4 and HTB9 bladder cancer cells with the HDAC inhibitor valproic acid (VPA) caused an increase in transcription of the XPC gene in these cells. The results of our chromatin immunoprecipitation (ChIP) studies indicated that the VPA treatment caused increased binding of both CREB1 and Sp1 transcription factors at the promoter region of the XPC gene for both HTB4 and HTB9 cells. The results of our immunohistochemistry (IHC) staining studies further revealed a strong correlation between the over-expression of HDAC4 and increased bladder cancer occurrence (p < 0.001) as well as a marginal significance of increasing incidence of HDAC4 positivity seen with an increase in severity of bladder cancer (p = 0.08). In addition, the results of our caspase 3 activation studies demonstrated that prior treatment with VPA increased the anticancer drug cisplatin-induced activation of caspase 3 in both HTB4 and HTB9 cells. All of these results suggest that the HDACs negatively regulate transcription of the XPC gene in bladder cancer cells and contribute to the severity of bladder tumors. PMID:21507255

Amplifying Electrochemical Indicators

NASA Technical Reports Server (NTRS)

Fan, Wenhong; Li, Jun; Han, Jie

2004-01-01

Dendrimeric reporter compounds have been invented for use in sensing and amplifying electrochemical signals from molecular recognition events that involve many chemical and biological entities. These reporter compounds can be formulated to target specific molecules or molecular recognition events. They can also be formulated to be, variously, hydrophilic or amphiphilic so that they are suitable for use at interfaces between (1) aqueous solutions and (2) electrodes connected to external signal-processing electronic circuits. The invention of these reporter compounds is expected to enable the development of highly miniaturized, low-power-consumption, relatively inexpensive, mass-producible sensor units for diverse applications.

Adam, Eve and the reflux enigma: age and sex differences across the gastro-oesophageal reflux spectrum.

PubMed

Royston, Christine; Bardhan, Karna D

2017-06-01

We present demographic differences across the gastro-oesophageal reflux disease (GORD) spectrum in a UK District General Hospital. Data were prospectively collected over 37 years. At endoscopy patients were categorized as: erosive oesophagitis (EO), Barrett's oesophagus (BO) or nonerosive reflux disease (NER). Analysis 1: comparison of EO, BO and NER 1977-2001 when the database for GORD without BO closed. Analysis 2: demographic differences in oesophageal adenocarcinoma (OAC) in total BO population diagnosed 1977-2011. GORD 1977-2001 (n=11 944): sex, male predominance in EO and BO but not NER; male : female ratios, 1.81, 1.65, 0.87, respectively (P<0.0001); mean age at presentation, EO 54 years, BO 62 years, NER 50 years; women were older than men by 10, 7 and 6 years, respectively.BO 1977-2011: prevalent OAC, 87/1468 (6%); male : female ratio, 4.1 (P<0.0001); incident OAC, 54/1381 (3.9%); male : female ratio, 3.5 (P<0.0001). Among all BO, more men developed OAC (3 vs. 0.9%). Within each sex, proportion of OAC higher among men (4.9 vs. 2.3%); at OAC diagnosis women were slightly but not significantly older (69.9 vs. 72.3 years, P=0.322). Two views may explain our findings. First, women have either milder reflux, or reduced mucosal sensitivity hence reflux remains silent for longer. Alternatively, women genuinely develop reflux later, that is, are more protected and for longer from developing GORD and its complications. Early evidence is emerging that female sex hormones may indeed have a protective role in GORD during the reproductive period. We suggest reflux and its consequences may be an example of 'protection' conferred on Eve.

Nuclear and membrane estrogen receptor antagonists induce similar mTORC2 activation-reversible changes in synaptic protein expression and actin polymerization in the mouse hippocampus.

PubMed

Xing, Fang-Zhou; Zhao, Yan-Gang; Zhang, Yuan-Yuan; He, Li; Zhao, Ji-Kai; Liu, Meng-Ying; Liu, Yan; Zhang, Ji-Qiang

2018-06-01

Estrogens play pivotal roles in hippocampal synaptic plasticity through nuclear receptors (nERs; including ERα and ERβ) and the membrane receptor (mER; also called GPR30), but the underlying mechanism and the contributions of nERs and mER remain unclear. Mammalian target of rapamycin complex 2 (mTORC2) is involved in actin cytoskeleton polymerization and long-term memory, but whether mTORC2 is involved in the regulation of hippocampal synaptic plasticity by ERs is unclear. We treated animals with nER antagonists (MPP/PHTPP) or the mER antagonist (G15) alone or in combination with A-443654, an activator of mTORC2. Then, we examined the changes in hippocampal SRC-1 expression, mTORC2 signaling (rictor and phospho-AKTSer473), actin polymerization (phospho-cofilin and profilin-1), synaptic protein expression (GluR1, PSD95, spinophilin, and synaptophysin), CA1 spine density, and synapse density. All of the examined parameters except synaptophysin expression were significantly decreased by MPP/PHTPP and G15 treatment. MPP/PHTPP and G15 induced a similar decrease in most parameters except p-cofilin, GluR1, and spinophilin expression. The ER antagonist-induced decreases in these parameters were significantly reversed by mTORC2 activation, except for the change in SRC-1, rictor, and synaptophysin expression. nERs and mER contribute similarly to the changes in proteins and structures associated with synaptic plasticity, and mTORC2 may be a novel target of hippocampal-dependent dementia such as Alzheimer's disease as proposed by previous studies. © 2018 John Wiley & Sons Ltd.

Silibinin enhances the repair of ultraviolet B-induced DNA damage by activating p53-dependent nucleotide excision repair mechanism in human dermal fibroblasts

PubMed Central

Guillermo-Lagae, Ruth; Deep, Gagan; Ting, Harold; Agarwal, Chapla; Agarwal, Rajesh

2015-01-01

Ultraviolet radiation B (UVB) is the main cause of DNA damage in epidermal cells; and if not repaired, this DNA damage leads to skin cancer. In earlier studies, we have reported that natural flavonolignan silibinin exerts strong chemopreventive efficacy against UVB-induced skin damage and carcinogenesis; however mechanistic studies are still being actively pursued. Here, we investigated the role of nucleotide excision repair (NER) pathway in silibinin's efficacy to repair UVB-induced DNA damage. Normal human dermal fibroblasts (NHDFs) were exposed to UVB (1 mJ/cm2) with pre- or post- silibinin (100 μM) treatment, and cyclobutane pyrimidine dimers (CPDs) formation/repair was measured. Results showed that post-UVB silibinin treatment accelerates DNA repair via activating the NER pathway including the expression of XPA (xeroderma pigmentosum complementation group A), XPB, XPC, and XPG. In UVB exposed fibroblasts, silibinin treatment also increased p53 and GADD45α expression; the key regulators of the NER pathway and DNA repair. Consistently, post-UVB silibinin treatment increased the mRNA transcripts of XPA and GADD45α. Importantly, silibinin showed no effect on UVB-induced DNA damage repair in XPA- and XPB-deficient human dermal fibroblasts suggesting their key role in silibinin-mediated DNA damage repair. Moreover, in the presence of pifithrin-α, an inhibitor of p53, the DNA repair efficacy of silibinin was compromised associated with a reduction in XPA and GADD45α transcripts. Together, these findings suggest that silibinin's efficacy against UVB-induced photodamage is primarily by inhibiting NER and p53; and these findings further support silibinin's usage as a potential inexpensive, effective, and non-toxic agent for skin cancer chemoprevention. PMID:26447614

Silibinin enhances the repair of ultraviolet B-induced DNA damage by activating p53-dependent nucleotide excision repair mechanism in human dermal fibroblasts.

PubMed

Guillermo-Lagae, Ruth; Deep, Gagan; Ting, Harold; Agarwal, Chapla; Agarwal, Rajesh

2015-11-24

Ultraviolet radiation B (UVB) is the main cause of DNA damage in epidermal cells; and if not repaired, this DNA damage leads to skin cancer. In earlier studies, we have reported that natural flavonolignan silibinin exerts strong chemopreventive efficacy against UVB-induced skin damage and carcinogenesis; however mechanistic studies are still being actively pursued. Here, we investigated the role of nucleotide excision repair (NER) pathway in silibinin's efficacy to repair UVB-induced DNA damage. Normal human dermal fibroblasts (NHDFs) were exposed to UVB (1 mJ/cm2) with pre- or post- silibinin (100 μM) treatment, and cyclobutane pyrimidine dimers (CPDs) formation/repair was measured. Results showed that post-UVB silibinin treatment accelerates DNA repair via activating the NER pathway including the expression of XPA (xeroderma pigmentosum complementation group A), XPB, XPC, and XPG. In UVB exposed fibroblasts, silibinin treatment also increased p53 and GADD45α expression; the key regulators of the NER pathway and DNA repair. Consistently, post-UVB silibinin treatment increased the mRNA transcripts of XPA and GADD45α. Importantly, silibinin showed no effect on UVB-induced DNA damage repair in XPA- and XPB-deficient human dermal fibroblasts suggesting their key role in silibinin-mediated DNA damage repair. Moreover, in the presence of pifithrin-α, an inhibitor of p53, the DNA repair efficacy of silibinin was compromised associated with a reduction in XPA and GADD45α transcripts. Together, these findings suggest that silibinin's efficacy against UVB-induced photodamage is primarily by inhibiting NER and p53; and these findings further support silibinin's usage as a potential inexpensive, effective, and non-toxic agent for skin cancer chemoprevention.

Elevated Urinary Levels of 8-Hydroxy-2'-deoxyguanosine in a Japanese Child of Xeroderma Pigmentosum/Cockayne Syndrome Complex with Infantile Onset of Nephrotic Syndrome.

PubMed

Kondo, Daiki; Noguchi, Atsuko; Tamura, Hiroaki; Tsuchida, Satoko; Takahashi, Ikuko; Kubota, Hiroki; Yano, Tamami; Oyama, Chikako; Sawaishi, Yukio; Moriwaki, Shinichi; Takahashi, Tsutomu

2016-07-01

Nucleotide excision repair (NER) is an essential biological pathway protecting against ultraviolet light-induced DNA damage. Deficient NER causes a group of rare genetic disorders including two autosomal recessive diseases, xeroderma pigmentosum (XP) and Cockayne syndrome (CS). In addition to the cutaneous photosensitivity shared in XP and CS, CS is featured by growth failure, neurological deterioration, microcephaly, and deep sunken eyes. XP/CS complex is an extremely rare type of NER disorder with a distinct phenotype that is characterized by the skin and eye pathology of XP and the somatic and neurological abnormalities of CS. Some of CS cases have been reported to be complicated with renal failure, but the genetic background or the etiology of the renal failure has not been reported. We herein report a 1-year-old Japanese boy with XP/CS complex, complicated by nephrotic syndrome. Diagnosis was confirmed by the presence of compound heterozygous mutations, G47R (c.139G>A) and R616G (c.1846C>G), in the excision repair cross-complementation group 2 (ERCC2) gene. The kidney biopsies, performed at the age of 1 year and 2 months, revealed diffuse expansion of the mesangial matrix and segmental glomerulosclerosis under light microscopy, and diffused thin capillary walls with partially lamellated regions under electron microscopy. Notably, high levels of urinary 8-hydroxy-2'-deoxyguanosin, known as an oxidative stress marker, were observed during the clinical course. The patient died at the age of 1 year and 11 months because of renal failure. We suggest the involvement of oxidative stress in the pathogenesis of nephrotic syndrome in NER disorders.

Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vermeulen, W.; Kleijer, W.J.; Bootsma, D.

1994-02-01

The human DNA excision repair gene ERCC3 specifically corrects the nucleotide excision repair (NER) defect of xeroderma pigmentosum (XP) complementation group B. In addition to its function in NER, the ERCC3 DNA helicase was recently identified as one of the components of the human BTF2/TFIIH transcription factor complex, which is required for initiation of transcription of class II genes. To date, a single patient (XP11BE) has been assigned to this XP group B (XP-B), with the remarkable conjunction of two autosomal recessive DNA repair deficiency disorders: XP and Cockayne syndrome (CS). The intriguing involvement of the ERCC3 protein in themore » vital process of transcription may provide an explanation for the rarity, severity, and wide spectrum of clinical features in this complementation group. Here the authors report the identification of two new XP-B patients: XPCS1BA and XPCS2BA (siblings), by microneedle injection of the cloned ERCC3 repair gene as well as by cell hybridization. Molecular analysis of the ERCC3 gene in both patients revealed a single base substitution causing a missense mutation in a region that is completely conserved in yeast, Drosophila, mouse, and human ERCC3. As in patient XP11BE, the expression of only one allele (paternal) is detected. The mutation causes a virtually complete inactivation of the NER function of the protein. Despite this severe NER defect, both patients display a late onset of neurologic impairment, mild cutaneous symptoms, and a striking absence of skin tumors even at an age of >40 years. Analysis of the frequency of hprt[sup [minus

Persistence of Repair Proteins at Unrepaired DNA Damage Distinguishes Diseases with ERCC2 (XPD) Mutations: Cancer-Prone Xeroderma Pigmentosum vs. Non-Cancer-Prone Trichothiodystrophy

PubMed Central

Boyle, Jennifer; Ueda, Takahiro; Oh, Kyu-Seon; Imoto, Kyoko; Tamura, Deborah; Jagdeo, Jared; Khan, Sikandar G.; Nadem, Carine; DiGiovanna, John J.; Kraemer, Kenneth H.

2012-01-01

Patients with xeroderma pigmentosum (XP) have a 1,000-fold increase in ultraviolet (UV)-induced skin cancers while trichothiodystrophy (TTD) patients, despite mutations in the same genes, ERCC2 (XPD) or ERCC3 (XPB), are cancer-free. Unlike XP cells, TTD cells have a nearly normal rate of removal of UV-induced 6-4 photoproducts (6-4PP) in their DNA and low levels of the basal transcription factor, TFIIH. We examined seven XP, TTD, and XP/TTD complex patients and identified mutations in the XPD gene. We discovered large differences in nucleotide excision repair (NER) protein recruitment to sites of localized UV damage in TTD cells compared to XP or normal cells. XPC protein was rapidly localized in all cells. XPC was redistributed in TTD, and normal cells by 3 hr postirradiation, but remained localized in XP cells at 24-hr postirradiation. In XP cells recruitment of other NER proteins (XPB, XPD, XPG, XPA, and XPF) was also delayed and persisted at 24 hr (p < 0.001). In TTD cells with defects in the XPD, XPB, or GTF2H5 (TTDA) genes, in contrast, recruitment of these NER proteins was reduced compared to normals at early time points (p < 0.001) and remained low at 24 hr postirradiation. These data indicate that in XP persistence of NER proteins at sites of unrepaired DNA damage is associated with greatly increased skin cancer risk possibly by blockage of translesion DNA synthesis. In contrast, in TTD, low levels of unstable TFIIH proteins do not accumulate at sites of unrepaired photoproducts and may permit normal translesion DNA synthesis without increased skin cancer. PMID:18470933

Mining heart disease risk factors in clinical text with named entity recognition and distributional semantic models.

PubMed

Urbain, Jay

2015-12-01

We present the design, and analyze the performance of a multi-stage natural language processing system employing named entity recognition, Bayesian statistics, and rule logic to identify and characterize heart disease risk factor events in diabetic patients over time. The system was originally developed for the 2014 i2b2 Challenges in Natural Language in Clinical Data. The system's strengths included a high level of accuracy for identifying named entities associated with heart disease risk factor events. The system's primary weakness was due to inaccuracies when characterizing the attributes of some events. For example, determining the relative time of an event with respect to the record date, whether an event is attributable to the patient's history or the patient's family history, and differentiating between current and prior smoking status. We believe these inaccuracies were due in large part to the lack of an effective approach for integrating context into our event detection model. To address these inaccuracies, we explore the addition of a distributional semantic model for characterizing contextual evidence of heart disease risk factor events. Using this semantic model, we raise our initial 2014 i2b2 Challenges in Natural Language of Clinical data F1 score of 0.838 to 0.890 and increased precision by 10.3% without use of any lexicons that might bias our results. Copyright © 2015 Elsevier Inc. All rights reserved.

The Cerebro-oculo-facio-skeletal Syndrome Point Mutation F231L in the ERCC1 DNA Repair Protein Causes Dissociation of the ERCC1-XPF Complex*

PubMed Central

Faridounnia, Maryam; Wienk, Hans; Kovačič, Lidija; Folkers, Gert E.; Jaspers, Nicolaas G. J.; Kaptein, Robert; Hoeijmakers, Jan H. J.; Boelens, Rolf

2015-01-01

The ERCC1-XPF heterodimer, a structure-specific DNA endonuclease, is best known for its function in the nucleotide excision repair (NER) pathway. The ERCC1 point mutation F231L, located at the hydrophobic interaction interface of ERCC1 (excision repair cross-complementation group 1) and XPF (xeroderma pigmentosum complementation group F), leads to severe NER pathway deficiencies. Here, we analyze biophysical properties and report the NMR structure of the complex of the C-terminal tandem helix-hairpin-helix domains of ERCC1-XPF that contains this mutation. The structures of wild type and the F231L mutant are very similar. The F231L mutation results in only a small disturbance of the ERCC1-XPF interface, where, in contrast to Phe231, Leu231 lacks interactions stabilizing the ERCC1-XPF complex. One of the two anchor points is severely distorted, and this results in a more dynamic complex, causing reduced stability and an increased dissociation rate of the mutant complex as compared with wild type. These data provide a biophysical explanation for the severe NER deficiencies caused by this mutation. PMID:26085086

Cockayne syndrome pathogenesis: lessons from mouse models.

PubMed

Jaarsma, Dick; van der Pluijm, Ingrid; van der Horst, Gijsbertus T J; Hoeijmakers, Jan H J

2013-01-01

Cockayne syndrome (CS) is a rare multisystem disorder characterized by cachectic dwarfism, nervous system abnormalities and features of premature aging. CS symptoms are associated with mutations in 5 genes, CSA, CSB, XPB, XPD and XPG encoding for proteins involved in the transcription-coupled subpathway of nucleotide excision DNA repair (NER). Mutant mice have been generated for all CS-associated genes and provide tools to examine how the cellular defects translate into CS symptoms. Mice deficient for Csa or Csb genetically mimic CS in man, and develop mild CS symptoms including reduced fat tissue, photoreceptor cell loss, and mild, but characteristic, nervous system pathology. These mild CS models are converted into severe CS models with short life span, progressive nervous system degeneration and cachectic dwarfism after simultaneous complete inactivation of global genome NER. A spectrum of mild-to-severe CS-like symptoms occurs in Xpb, Xpd, and Xpg mice that genetically mimic patients with a disorder that combines CS symptoms with another NER syndrome, xeroderma pigmentosum. In conclusion, CS mouse models mice develop a range of CS phenotypes and open promising perspectives for testing interventional approaches. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Generation of DNA single-strand displacement by compromised nucleotide excision repair

PubMed Central

Godon, Camille; Mourgues, Sophie; Nonnekens, Julie; Mourcet, Amandine; Coin, Fréderic; Vermeulen, Wim; Mari, Pierre-Olivier; Giglia-Mari, Giuseppina

2012-01-01

Nucleotide excision repair (NER) is a precisely coordinated process essential to avoid DNA damage-induced cellular malfunction and mutagenesis. Here, we investigate the mechanistic details and effects of the NER machinery when it is compromised by a pathologically significant mutation in a subunit of the repair/transcription factor TFIIH, namely XPD. In contrast to previous studies, we find that no single- or double-strand DNA breaks are produced at early time points after UV irradiation of cells bearing a specific XPD mutation, despite the presence of a clear histone H2AX phosphorylation (γH2AX) signal in the UV-exposed areas. We show that the observed γH2AX signal can be explained by the presence of longer single-strand gaps possibly generated by strand displacement. Our in vivo measurements also indicate a strongly reduced TFIIH-XPG binding that could promote single-strand displacement at the site of UV lesions. This finding not only highlights the crucial role of XPG's interactions with TFIIH for proper NER, but also sheds new light on how a faulty DNA repair process can induce extreme genomic instability in human patients. PMID:22863773

RPA and XPA interaction with DNA structures mimicking intermediates of the late stages in nucleotide excision repair

PubMed Central

Maltseva, Ekaterina A.

2018-01-01

Replication protein A (RPA) and the xeroderma pigmentosum group A (XPA) protein are indispensable for both pathways of nucleotide excision repair (NER). Here we analyze the interaction of RPA and XPA with DNA containing a flap and different size gaps that imitate intermediates of the late NER stages. Using gel mobility shift assays, we found that RPA affinity for DNA decreased when DNA contained both extended gap and similar sized flap in comparison with gapped-DNA structure. Moreover, crosslinking experiments with the flap-gap DNA revealed that RPA interacts mainly with the ssDNA platform within the long gap and contacts flap in DNA with a short gap. XPA exhibits higher affinity for bubble-DNA structures than to flap-gap-containing DNA. Protein titration analysis showed that formation of the RPA-XPA-DNA ternary complex depends on the protein concentration ratio and these proteins can function as independent players or in tandem. Using fluorescently-labelled RPA, direct interaction of this protein with XPA was detected and characterized quantitatively. The data obtained allow us to suggest that XPA can be involved in the post-incision NER stages via its interaction with RPA. PMID:29320546

Preclinical Corrective Gene Transfer in Xeroderma Pigmentosum Human Skin Stem Cells

PubMed Central

Warrick, Emilie; Garcia, Marta; Chagnoleau, Corinne; Chevallier, Odile; Bergoglio, Valérie; Sartori, Daniela; Mavilio, Fulvio; Angulo, Jaime F; Avril, Marie-Françoise; Sarasin, Alain; Larcher, Fernando; Del Rio, Marcela; Bernerd, Françoise; Magnaldo, Thierry

2012-01-01

Xeroderma pigmentosum (XP) is a devastating disease associated with dramatic skin cancer proneness. XP cells are deficient in nucleotide excision repair (NER) of bulky DNA adducts including ultraviolet (UV)-induced mutagenic lesions. Approaches of corrective gene transfer in NER-deficient keratinocyte stem cells hold great hope for the long-term treatment of XP patients. To face this challenge, we developed a retrovirus-based strategy to safely transduce the wild-type XPC gene into clonogenic human primary XP-C keratinocytes. De novo expression of XPC was maintained in both mass population and derived independent candidate stem cells (holoclones) after more than 130 population doublings (PD) in culture upon serial propagation (>1040 cells). Analyses of retrovirus integration sequences in isolated keratinocyte stem cells suggested the absence of adverse effects such as oncogenic activation or clonal expansion. Furthermore, corrected XP-C keratinocytes exhibited full NER capacity as well as normal features of epidermal differentiation in both organotypic skin cultures and in a preclinical murine model of human skin regeneration in vivo. The achievement of a long-term genetic correction of XP-C epidermal stem cells constitutes the first preclinical model of ex vivo gene therapy for XP-C patients. PMID:22068429

Transcription-coupled repair of UV damage in the halophilic archaea.

PubMed

Stantial, Nicole; Dumpe, Jarrod; Pietrosimone, Kathryn; Baltazar, Felicia; Crowley, David J

2016-05-01

Transcription-coupled repair (TCR) is a subpathway of nucleotide excision repair (NER) in which excision repair proteins are targeted to RNA polymerase-arresting lesions located in the transcribed strand of active genes. TCR has been documented in a variety of bacterial and eukaryotic organisms but has yet to be observed in the Archaea. We used Halobacterium sp. NRC-1 and Haloferax volcanii to determine if TCR occurs in the halophilic archaea. Following UV irradiation of exponentially growing cultures, we quantified the rate of repair of cyclobutane pyrimidine dimers in the two strands of the rpoB2B1A1A2 and the trpDFEG operons of Halobacterium sp. NRC-1 and the pts operon of H. volcanii through the use of a Southern blot assay and strand-specific probes. TCR was observed in all three operons and was dependent on the NER gene uvrA in Halobacterium sp. NRC-1, but not in H. volcanii. The halophilic archaea likely employ a novel mechanism for TCR in which an as yet unknown coupling factor recognizes the arrested archaeal RNA polymerase complex and recruits certain NER proteins to complete the process. Copyright © 2016 Elsevier B.V. All rights reserved.

RPA and XPA interaction with DNA structures mimicking intermediates of the late stages in nucleotide excision repair.

PubMed

Krasikova, Yuliya S; Rechkunova, Nadejda I; Maltseva, Ekaterina A; Lavrik, Olga I

2018-01-01

Replication protein A (RPA) and the xeroderma pigmentosum group A (XPA) protein are indispensable for both pathways of nucleotide excision repair (NER). Here we analyze the interaction of RPA and XPA with DNA containing a flap and different size gaps that imitate intermediates of the late NER stages. Using gel mobility shift assays, we found that RPA affinity for DNA decreased when DNA contained both extended gap and similar sized flap in comparison with gapped-DNA structure. Moreover, crosslinking experiments with the flap-gap DNA revealed that RPA interacts mainly with the ssDNA platform within the long gap and contacts flap in DNA with a short gap. XPA exhibits higher affinity for bubble-DNA structures than to flap-gap-containing DNA. Protein titration analysis showed that formation of the RPA-XPA-DNA ternary complex depends on the protein concentration ratio and these proteins can function as independent players or in tandem. Using fluorescently-labelled RPA, direct interaction of this protein with XPA was detected and characterized quantitatively. The data obtained allow us to suggest that XPA can be involved in the post-incision NER stages via its interaction with RPA.

Effects of the updated national emission regulation in China on circulating fluidized bed boilers and the solutions to meet them.

PubMed

Li, Jingji; Yang, Hairui; Wu, Yuxin; Lv, Junfu; Yue, Guangxi

2013-06-18

The advantage of circulating fluidized bed (CFB) boilers in China is their ability to utilize low rank coal with low cost emission control. However, the new National Emission Regulation (NER) issued in early 2012 brings much more stringent challenges on the CFB industries, which also causes much attention from other countries. Based on the principle of a CFB boiler and previous operating experience, it is possible for the CFB boilers to meet the new NER and maintain the advantage of low cost emission control, while, more influences should be considered in their design and operation. To meet the requirement of the new NER, the fly ash collector should adopt a bag house or combination of electrostatic precipitator and bag filter to ensure dust emissions of less than 30 mg · Nm(-3). For SO2 emission control, the bed temperature should be strictly lower than 900 °C to maintain high reactivity and pores. The limestone particle size distribution should be ranged within a special scope to optimize the residence time and gas-solid reaction. At the same time, the injecting point should be optimized to ensure fast contact of lime with oxygen. In such conditions, the desulfurization efficiency could be increased more than 90%. For lower sulfur content fuels (<1.5%, referred value based on the heating value of standard coal of China), increasing Ca/S enough could decrease SO2 emissions lower than that of the new NER, 100 mg · Nm(-3). For fuels with sulfur content higher than 1.5%, some simplified systems for flue gas desulfurization, such as flash dryer absorber (FDA), are needed. And the NOx emissions of a CFB can be controlled to less than 100 mg · Nm(-3) without any equipment at a bed temperature lower than 900 °C for fuels with low volatiles content (<12%), while for fuels with high volatiles, selective non-catalytic reduction (SNCR) should be considered. Due to the unique temperature in CFB as well as the circulating ash, the efficiency of SNCR could reach as high as 70%. The Hg emission of CFB is very low for the new NER due to its innate property.

48 CFR 919.7005 - Eligibility to be a Mentor.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Eligibility to be a Mentor... PROGRAMS SMALL BUSINESS PROGRAMS The Department of Energy Mentor-Protege Program 919.7005 Eligibility to be a Mentor. To be eligible for recognition by DOE as a Mentor, an entity must be performing at least...

Pathologic childhood aerophagia: a recognizable clinical entity.

PubMed

Gauderer, M W; Halpin, T C; Izant, R J

1981-06-01

Pathologic childhood aerophagia is a rarely recognized, often poorly treated entity that has remained almost undescribed in either the surgical or pediatric literature. In only 1 of 9 children the condition was recognized at presentation. The initial diagnosis of the others was Hirschsprung's disease (2), malabsorption syndrome (3), gastric outlet syndrome (1), constipation (1), and esophagitis (1). Five were hospitalized and two underwent surgical procedures. History disclosed a remarkably constant triad: previous normal stooling pattern, visible and often audible air swallowing and excessive flatus. Physical examination often demonstrated a markedly or intermittently distended and tympanitic abdomen. Abdominal musculature was thinned in children with chronic aerophagia. Roentgenographic evaluation showed massively distended loops of intestine throughout without associated air-fluid levels. There was marked compression of the diaphragm with limited excursion in some. Laboratory and malabsorption testing was normal. Treatment is limited to recognition of the problem, nasogastric decompression in severe cases and psychologic counseling when symptoms persist in the older child. The recognition of this condition may lead to a better understanding of its pathophysiology and will reduce the number of unnecessary admissions or surgical procedures.

Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Tumors of the Salivary Gland.

PubMed

Seethala, Raja R; Stenman, Göran

2017-03-01

The salivary gland section in the 4th edition of the World Health Organization classification of head and neck tumors features the description and inclusion of several entities, the most significant of which is represented by (mammary analogue) secretory carcinoma. This entity was extracted mainly from acinic cell carcinoma based on recapitulation of breast secretory carcinoma and a shared ETV6-NTRK3 gene fusion. Also new is the subsection of "Other epithelial lesions," for which key entities include sclerosing polycystic adenosis and intercalated duct hyperplasia. Many entities have been compressed into their broader categories given clinical and morphologic similarities, or transitioned to a different grouping as was the case with low-grade cribriform cystadenocarcinoma reclassified as intraductal carcinoma (with the applied qualifier of low-grade). Specific grade has been removed from the names of the salivary gland entities such as polymorphous adenocarcinoma, providing pathologists flexibility in assigning grade and allowing for recognition of a broader spectrum within an entity. Cribriform adenocarcinoma of (minor) salivary gland origin continues to be divisive in terms of whether it should be recognized as a distinct category. This chapter also features new key concepts such as high-grade transformation. The new paradigm of translocations and gene fusions being common in salivary gland tumors is featured heavily in this chapter.

[From Algebra as art to School Algebra : The textbooks written by Pierre de La Ramée, Bernard Salignac and Lazare Schöner].

PubMed

Loget, François

2011-01-01

Bernard Salignac and Lazare Schöner both published a treatise based on La Ramée's Algebra. Why did they endeavour to republish a book that their master had abandoned ? What changes did they make in the original ? They turned algebra into apedagogical discipline at a time when Ramism was making its presence felt in some Northern European educational establishments. Salignac took La Ramée's thoughts concerning the language of mathematics further and offered an original and precocious contribution to what I call the "scriptural turn" of mathematics at the end of the 16(th) century.

Investigating the Improvement of Decoding Abilities and Working Memory in Children with Incremental or Entity Personal Conceptions of Intelligence: Two Case Reports

PubMed Central

Alesi, Marianna; Rappo, Gaetano; Pepi, Annamaria

2016-01-01

One of the most significant current discussions has led to the hypothesis that domain-specific training programs alone are not enough to improve reading achievement or working memory abilities. Incremental or Entity personal conceptions of intelligence may be assumed to be an important prognostic factor to overcome domain-specific deficits. Specifically, incremental students tend to be more oriented toward change and autonomy and are able to adopt more efficacious strategies. This study aims at examining the effect of personal conceptions of intelligence to strengthen the efficacy of a multidimensional intervention program in order to improve decoding abilities and working memory. Participants included two children (M age = 10 years) with developmental dyslexia and different conceptions of intelligence. The children were tested on a whole battery of reading and spelling tests commonly used in the assessment of reading disabilities in Italy. Afterwards, they were given a multimedia test to measure motivational factors such as conceptions of intelligence and achievement goals. The children took part in the T.I.R.D. Multimedia Training for the Rehabilitation of Dyslexia (Rappo and Pepi, 2010) reinforced by specific units to improve verbal working memory for 3 months. This training consisted of specific tasks to rehabilitate both visual and phonological strategies (sound blending, word segmentation, alliteration test and rhyme test, letter recognition, digraph recognition, trigraph recognition, and word recognition as samples of visual tasks) and verbal working memory (rapid words and non-words recognition). Posttest evaluations showed that the child holding the incremental theory of intelligence improved more than the child holding a static representation. On the whole this study highlights the importance of treatment programs in which both specificity of deficits and motivational factors are both taken into account. There is a need to plan multifaceted intervention programs based on a transverse approach, considering both cognitive and motivational factors. PMID:26779069

p21 differentially regulates DNA replication and DNA-repair-associated processes after UV irradiation.

PubMed

Soria, Gaston; Speroni, Juliana; Podhajcer, Osvaldo L; Prives, Carol; Gottifredi, Vanesa

2008-10-01

Although p21 upregulation is required to block cell-cycle progression following many types of genotoxic insult, UV irradiation triggers p21 proteolysis. The significance of the increased p21 turnover is unclear and might be associated with DNA repair. While the role of p21 in nucleotide excision repair (NER) remains controversial, recent reports have explored its effect on translesion DNA synthesis (TLS), a process that avoids replication blockage during S phase. Herein, we analyze the effect of p21 on different PCNA-driven processes including DNA replication, NER and TLS. Whereas only the CDK-binding domain of p21 is required for cell-cycle arrest in unstressed cells, neither the CDK-binding nor the PCNA-binding domain of p21 is able to block early and late steps of NER. Intriguingly, through its PCNA-binding domain, p21 inhibits the interaction of the TLS polymerase, pol eta (pol eta), with PCNA and impairs the assembly of pol eta foci after UV. Moreover, this obstruction correlates with accumulation of phosphorylated H2AX and increased apoptosis. By showing that p21 is a negative regulator of PCNA-pol eta interaction, our data unveil a link between efficient TLS and UV-induced degradation of p21.

Delineating the requirements for spontaneous DNA damage resistance pathways in genome maintenance and viability in Saccharomyces cerevisiae.

PubMed

Morey, Natalie J; Doetsch, Paul W; Jinks-Robertson, Sue

2003-06-01

Cellular metabolic processes constantly generate reactive species that damage DNA. To counteract this relentless assault, cells have developed multiple pathways to resist damage. The base excision repair (BER) and nucleotide excision repair (NER) pathways remove damage whereas the recombination (REC) and postreplication repair (PRR) pathways bypass the damage, allowing deferred removal. Genetic studies in yeast indicate that these pathways can process a common spontaneous lesion(s), with mutational inactivation of any pathway increasing the burden on the remaining pathways. In this study, we examine the consequences of simultaneously compromising three or more of these pathways. Although the presence of a functional BER pathway alone is able to support haploid growth, retention of the NER, REC, or PRR pathway alone is not, indicating that BER is the key damage resistance pathway in yeast and may be responsible for the removal of the majority of either spontaneous DNA damage or specifically those lesions that are potentially lethal. In the diploid state, functional BER, NER, or REC alone can support growth, while PRR alone is insufficient for growth. In diploids, the presence of PRR alone may confer a lethal mutation load or, alternatively, PRR alone may be insufficient to deal with potentially lethal, replication-blocking lesions.

Processing closely spaced lesions during Nucleotide Excision Repair triggers mutagenesis in E. coli

PubMed Central

Isogawa, Asako; Fujii, Shingo

2017-01-01

It is generally assumed that most point mutations are fixed when damage containing template DNA undergoes replication, either right at the fork or behind the fork during gap filling. Here we provide genetic evidence for a pathway, dependent on Nucleotide Excision Repair, that induces mutations when processing closely spaced lesions. This pathway, referred to as Nucleotide Excision Repair-induced Mutagenesis (NERiM), exhibits several characteristics distinct from mutations that occur within the course of replication: i) following UV irradiation, NER-induced mutations are fixed much more rapidly (t ½ ≈ 30 min) than replication dependent mutations (t ½ ≈ 80–100 min) ii) NERiM specifically requires DNA Pol IV in addition to Pol V iii) NERiM exhibits a two-hit dose-response curve that suggests processing of closely spaced lesions. A mathematical model let us define the geometry (infer the structure) of the toxic intermediate as being formed when NER incises a lesion that resides in close proximity of another lesion in the complementary strand. This critical NER intermediate requires Pol IV / Pol II for repair, it is either lethal if left unrepaired or mutation-prone when repaired. Finally, NERiM is found to operate in stationary phase cells providing an intriguing possibility for ongoing evolution in the absence of replication. PMID:28686598

TFIIH Subunit Alterations Causing Xeroderma Pigmentosum and Trichothiodystrophy Specifically Disturb Several Steps during Transcription

PubMed Central

Singh, Amita; Compe, Emanuel; Le May, Nicolas; Egly, Jean-Marc

2015-01-01

Mutations in genes encoding the ERCC3 (XPB), ERCC2 (XPD), and GTF2H5 (p8 or TTD-A) subunits of the transcription and DNA-repair factor TFIIH lead to three autosomal-recessive disorders: xeroderma pigmentosum (XP), XP associated with Cockayne syndrome (XP/CS), and trichothiodystrophy (TTD). Although these diseases were originally associated with defects in DNA repair, transcription deficiencies might be also implicated. By using retinoic acid receptor beta isoform 2 (RARB2) as a model in several cells bearing mutations in genes encoding TFIIH subunits, we observed that (1) the recruitment of the TFIIH complex was altered at the activated RARB2 promoter, (2) TFIIH participated in the recruitment of nucleotide excision repair (NER) factors during transcription in a manner different from that observed during NER, and (3) the different TFIIH variants disturbed transcription by having distinct consequences on post-translational modifications of histones, DNA-break induction, DNA demethylation, and gene-loop formation. The transition from heterochromatin to euchromatin was disrupted depending on the variant, illustrating the fact that TFIIH, by contributing to NER factor recruitment, orchestrates chromatin remodeling. The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals. PMID:25620205

The rem mutations in the ATP-binding groove of the Rad3/XPD helicase lead to Xeroderma pigmentosum-Cockayne syndrome-like phenotypes.

PubMed

Herrera-Moyano, Emilia; Moriel-Carretero, María; Montelone, Beth A; Aguilera, Andrés

2014-12-01

The eukaryotic TFIIH complex is involved in Nucleotide Excision Repair and transcription initiation. We analyzed three yeast mutations of the Rad3/XPD helicase of TFIIH known as rem (recombination and mutation phenotypes). We found that, in these mutants, incomplete NER reactions lead to replication fork breaking and the subsequent engagement of the homologous recombination machinery to restore them. Nevertheless, the penetrance varies among mutants, giving rise to a phenotype gradient. Interestingly, the mutations analyzed reside at the ATP-binding groove of Rad3 and in vivo experiments reveal a gain of DNA affinity upon damage of the mutant Rad3 proteins. Since mutations at the ATP-binding groove of XPD in humans are present in the Xeroderma pigmentosum-Cockayne Syndrome (XP-CS), we recreated rem mutations in human cells, and found that these are XP-CS-like. We propose that the balance between the loss of helicase activity and the gain of DNA affinity controls the capacity of TFIIH to open DNA during NER, and its persistence at both DNA lesions and promoters. This conditions NER efficiency and transcription resumption after damage, which in human cells would explain the XP-CS phenotype, opening new perspectives to understand the molecular basis of the role of XPD in human disease.

Chromosomal localization of three repair genes: The xeroderma pigmentosum group C gene and two human homologs of yeast RAD23

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spek, P.J. van der; Smit, E.M.E.; Beverloo, H.B.

1994-10-01

The nucleotide excision repair (NER) disorder xeroderma pigmentosum (XP) is characterized by sun (UV) sensitivity, predisposition to skin cancer, and extensive genetic heterogeneity. Recently, we reported the cloning and analysis of three human NER genes, XPC, HHR23A, and HHR23B. The previously cloned XPC gene is involved in the common XP complementation group C, which is defective in excision repair of nontranscribed sequences in the genome. The XPC protein was found to be complexed with the product of HHR23B, one of the two human homologs of the Saccharomyes cerevisiae NER gene RAD23. Here we present the chromosomal localization by in situmore » hybridization using haptenized probes of all three genes. The HHR23A gene was assigned to chromosome 19p13.2. Interestingly, the HHR23B and XPC genes, the product of which forms a tight complex, were found to colocalize on band 3p25.1. Pulsed-field gel electrophoresis revealed that the HHR23B and XPC genes possibly share a MluI restriction fragment of about 625 kb. Potential involvement of the HHR23 genes in human genetic disorders is discussed. 53 refs., 4 figs., 2 tabs.« less

The Cerebro-oculo-facio-skeletal Syndrome Point Mutation F231L in the ERCC1 DNA Repair Protein Causes Dissociation of the ERCC1-XPF Complex.

PubMed

Faridounnia, Maryam; Wienk, Hans; Kovačič, Lidija; Folkers, Gert E; Jaspers, Nicolaas G J; Kaptein, Robert; Hoeijmakers, Jan H J; Boelens, Rolf

2015-08-14

The ERCC1-XPF heterodimer, a structure-specific DNA endonuclease, is best known for its function in the nucleotide excision repair (NER) pathway. The ERCC1 point mutation F231L, located at the hydrophobic interaction interface of ERCC1 (excision repair cross-complementation group 1) and XPF (xeroderma pigmentosum complementation group F), leads to severe NER pathway deficiencies. Here, we analyze biophysical properties and report the NMR structure of the complex of the C-terminal tandem helix-hairpin-helix domains of ERCC1-XPF that contains this mutation. The structures of wild type and the F231L mutant are very similar. The F231L mutation results in only a small disturbance of the ERCC1-XPF interface, where, in contrast to Phe(231), Leu(231) lacks interactions stabilizing the ERCC1-XPF complex. One of the two anchor points is severely distorted, and this results in a more dynamic complex, causing reduced stability and an increased dissociation rate of the mutant complex as compared with wild type. These data provide a biophysical explanation for the severe NER deficiencies caused by this mutation. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Synthetic approaches to the 2009 new drugs.

PubMed

Liu, Kevin K-C; Sakya, Subas M; O'Donnell, Christopher J; Flick, Andrew C; Li, Jin

2011-02-01

New drugs are introduced to the market every year and each individual drug represents a privileged structure for its biological target. These new chemical entities (NCEs) provide insights into molecular recognition and also serve as leads for designing future new drugs. This review covers the syntheses of 21 NCEs marketed in 2009. Copyright © 2011 Elsevier Ltd. All rights reserved.

Algae biodiesel life cycle assessment using current commercial data.

PubMed

Passell, Howard; Dhaliwal, Harnoor; Reno, Marissa; Wu, Ben; Ben Amotz, Ami; Ivry, Etai; Gay, Marcus; Czartoski, Tom; Laurin, Lise; Ayer, Nathan

2013-11-15

Autotrophic microalgae represent a potential feedstock for transportation fuels, but life cycle assessment (LCA) studies based on laboratory-scale or theoretical data have shown mixed results. We attempt to bridge the gap between laboratory-scale and larger scale biodiesel production by using cultivation and harvesting data from a commercial algae producer with ∼1000 m(2) production area (the base case), and compare that with a hypothetical scaled up facility of 101,000 m(2) (the future case). Extraction and separation data are from Solution Recovery Services, Inc. Conversion and combustion data are from the Greenhouse Gases, Regulated Emissions, and Energy Use in Transportation Model (GREET). The LCA boundaries are defined as "pond-to-wheels". Environmental impacts are quantified as NER (energy in/energy out), global warming potential, photochemical oxidation potential, water depletion, particulate matter, and total NOx and SOx. The functional unit is 1 MJ of energy produced in a passenger car. Results for the base case and the future case show an NER of 33.4 and 1.37, respectively and GWP of 2.9 and 0.18 kg CO2-equivalent, respectively. In comparison, petroleum diesel and soy diesel show an NER of 0.18 and 0.80, respectively and GWP of 0.12 and 0.025, respectively. A critical feature in this work is the low algal productivity (3 g/m(2)/day) reported by the commercial producer, relative to the much higher productivities (20-30 g/m(2)/day) reported by other sources. Notable results include a sensitivity analysis showing that algae with an oil yield of 0.75 kg oil/kg dry biomass in the future case can bring the NER down to 0.64, more comparable with petroleum diesel and soy biodiesel. An important assumption in this work is that all processes are fully co-located and that no transport of intermediate or final products from processing stage to stage is required. Copyright © 2013 Elsevier Ltd. All rights reserved.

Newly identified CHO ERCC3/XPB mutations and phenotype characterization

PubMed Central

Rybanská, Ivana; Gurský, Ján; Fašková, Miriam; Salazar, Edmund P.; Kimlíčková-Polakovičová, Erika; Kleibl, Karol; Thompson, Larry H.; Piršel, Miroslav

2010-01-01

Nucleotide excision repair (NER) is a complex multistage process involving many interacting gene products to repair a wide range of DNA lesions. Genetic defects in NER cause human hereditary diseases including xeroderma pigmentosum (XP), Cockayne syndrome (CS), trichothiodystrophy and a combined XP/CS overlapping symptom. One key gene product associated with all these disorders is the excision repair cross-complementing 3/xeroderma pigmentosum B (ERCC3/XPB) DNA helicase, a subunit of the transcription factor IIH complex. ERCC3 is involved in initiation of basal transcription and global genome repair as well as in transcription-coupled repair (TCR). The hamster ERCC3 gene shows high degree of homology with the human ERCC3/XPB gene. We identified new mutations in the Chinese hamster ovary cell ERCC3 gene and characterized the role of hamster ERCC3 protein in DNA repair of ultraviolet (UV)-induced and oxidative DNA damage. All but one newly described mutations are located in the protein C-terminal region around the last intron–exon boundary. Due to protein truncations or frameshifts, they lack amino acid Ser751, phosphorylation of which prevents the 5′ incision of the UV-induced lesion during NER. Thus, despite the various locations of the mutations, their phenotypes are similar. All ercc3 mutants are extremely sensitive to UV-C light and lack recovery of RNA synthesis (RRS), confirming a defect in TCR of UV-induced damage. Their limited global genome NER capacity averages ∼8%. We detected modest sensitivity of ercc3 mutants to the photosensitizer Ro19-8022, which primarily introduces 8-oxoguanine lesions into DNA. Ro19-8022-induced damage interfered with RRS, and some of the ercc3 mutants had delayed kinetics. All ercc3 mutants showed efficient base excision repair (BER). Thus, the positions of the mutations have no effect on the sensitivity to, and repair of, Ro19-8022-induced DNA damage, suggesting that the ERCC3 protein is not involved in BER. PMID:19942596

Nucleotide Excision Repair Gene Polymorphisms, Meat Intake and Colon Cancer Risk

PubMed Central

Steck, Susan E.; Butler, Lesley M.; Keku, Temitope; Antwi, Samuel; Galanko, Joseph; Sandler, Robert S.; Hu, Jennifer J.

2014-01-01

Purpose Much of the DNA damage from colon cancer-related carcinogens, including heterocyclic amines (HCA) and polycyclic aromatic hydrocarbons (PAH) from red meat cooked at high temperature, are repaired by the nucleotide excision repair (NER) pathway. Thus, we examined whether NER non-synonymous single nucleotide polymorphisms (nsSNPs) modified the association between red meat intake and colon cancer risk. Methods The study consists of 244 African-American and 311 white colon cancer cases and population-based controls (331 African Americans and 544 whites) recruited from 33 counties in North Carolina from 1996 to 2000. Information collected by food frequency questionnaire on meat intake and preparation methods were used to estimate HCA and benzo(a)pyrene (BaP, a PAH) intake. We tested 7 nsSNPs in 5 NER genes: XPC A499V and K939Q, XPD D312N and K751Q, XPF R415Q, XPG D1104H, and RAD23B A249V. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated using unconditional logistic regression. Results Among African Americans, we observed a statistically significant positive association between colon cancer risk and XPC 499 AV+VV genotype (OR=1.7, 95% CI: 1.1, 2.7, AA as referent), and an inverse association with XPC 939 QQ (OR=0.3, 95%CI: 0.2, 0.8, KK as referent). These associations were not observed among whites. For both races combined, there was interaction between the XPC 939 genotype, well-done red meat intake and colon cancer risk (OR=1.5, 95% CI=1.0, 2.2 for high well-done red meat and KK genotype as compared to low well-done red meat and KK genotype, pinteraction =0.05). Conclusions Our data suggest that NER nsSNPs are associated with colon cancer risk and may modify the association between well-done red meat intake and colon cancer risk. PMID:24607854

Xeroderma Pigmentosum Group A Suppresses Mutagenesis Caused by Clustered Oxidative DNA Adducts in the Human Genome.

PubMed

Sassa, Akira; Kamoshita, Nagisa; Kanemaru, Yuki; Honma, Masamitsu; Yasui, Manabu

2015-01-01

Clustered DNA damage is defined as multiple sites of DNA damage within one or two helical turns of the duplex DNA. This complex damage is often formed by exposure of the genome to ionizing radiation and is difficult to repair. The mutagenic potential and repair mechanisms of clustered DNA damage in human cells remain to be elucidated. In this study, we investigated the involvement of nucleotide excision repair (NER) in clustered oxidative DNA adducts. To identify the in vivo protective roles of NER, we established a human cell line lacking the NER gene xeroderma pigmentosum group A (XPA). XPA knockout (KO) cells were generated from TSCER122 cells derived from the human lymphoblastoid TK6 cell line. To analyze the mutagenic events in DNA adducts in vivo, we previously employed a system of tracing DNA adducts in the targeted mutagenesis (TATAM), in which DNA adducts were site-specifically introduced into intron 4 of thymidine kinase genes. Using the TATAM system, one or two tandem 7,8-dihydro-8-oxoguanine (8-oxoG) adducts were introduced into the genomes of TSCER122 or XPA KO cells. In XPA KO cells, the proportion of mutants induced by a single 8-oxoG (7.6%) was comparable with that in TSCER122 cells (8.1%). In contrast, the lack of XPA significantly enhanced the mutant proportion of tandem 8-oxoG in the transcribed strand (12%) compared with that in TSCER122 cells (7.4%) but not in the non-transcribed strand (12% and 11% in XPA KO and TSCER122 cells, respectively). By sequencing the tandem 8-oxoG-integrated loci in the transcribed strand, we found that the proportion of tandem mutations was markedly increased in XPA KO cells. These results indicate that NER is involved in repairing clustered DNA adducts in the transcribed strand in vivo.

Xeroderma Pigmentosum Group A Suppresses Mutagenesis Caused by Clustered Oxidative DNA Adducts in the Human Genome

PubMed Central

Sassa, Akira; Kamoshita, Nagisa; Kanemaru, Yuki; Honma, Masamitsu; Yasui, Manabu

2015-01-01

Clustered DNA damage is defined as multiple sites of DNA damage within one or two helical turns of the duplex DNA. This complex damage is often formed by exposure of the genome to ionizing radiation and is difficult to repair. The mutagenic potential and repair mechanisms of clustered DNA damage in human cells remain to be elucidated. In this study, we investigated the involvement of nucleotide excision repair (NER) in clustered oxidative DNA adducts. To identify the in vivo protective roles of NER, we established a human cell line lacking the NER gene xeroderma pigmentosum group A (XPA). XPA knockout (KO) cells were generated from TSCER122 cells derived from the human lymphoblastoid TK6 cell line. To analyze the mutagenic events in DNA adducts in vivo, we previously employed a system of tracing DNA adducts in the targeted mutagenesis (TATAM), in which DNA adducts were site-specifically introduced into intron 4 of thymidine kinase genes. Using the TATAM system, one or two tandem 7,8-dihydro-8-oxoguanine (8-oxoG) adducts were introduced into the genomes of TSCER122 or XPA KO cells. In XPA KO cells, the proportion of mutants induced by a single 8-oxoG (7.6%) was comparable with that in TSCER122 cells (8.1%). In contrast, the lack of XPA significantly enhanced the mutant proportion of tandem 8-oxoG in the transcribed strand (12%) compared with that in TSCER122 cells (7.4%) but not in the non-transcribed strand (12% and 11% in XPA KO and TSCER122 cells, respectively). By sequencing the tandem 8-oxoG-integrated loci in the transcribed strand, we found that the proportion of tandem mutations was markedly increased in XPA KO cells. These results indicate that NER is involved in repairing clustered DNA adducts in the transcribed strand in vivo. PMID:26559182

BioTextQuest: a web-based biomedical text mining suite for concept discovery.

PubMed

Papanikolaou, Nikolas; Pafilis, Evangelos; Nikolaou, Stavros; Ouzounis, Christos A; Iliopoulos, Ioannis; Promponas, Vasilis J

2011-12-01

BioTextQuest combines automated discovery of significant terms in article clusters with structured knowledge annotation, via Named Entity Recognition services, offering interactive user-friendly visualization. A tag-cloud-based illustration of terms labeling each document cluster are semantically annotated according to the biological entity, and a list of document titles enable users to simultaneously compare terms and documents of each cluster, facilitating concept association and hypothesis generation. BioTextQuest allows customization of analysis parameters, e.g. clustering/stemming algorithms, exclusion of documents/significant terms, to better match the biological question addressed. http://biotextquest.biol.ucy.ac.cy vprobon@ucy.ac.cy; iliopj@med.uoc.gr Supplementary data are available at Bioinformatics online.

Recognition of a person named entity from the text written in a natural language

NASA Astrophysics Data System (ADS)

Dolbin, A. V.; Rozaliev, V. L.; Orlova, Y. A.

2017-01-01

This work is devoted to the semantic analysis of texts, which were written in a natural language. The main goal of the research was to compare latent Dirichlet allocation and latent semantic analysis to identify elements of the human appearance in the text. The completeness of information retrieval was chosen as the efficiency criteria for methods comparison. However, it was insufficient to choose only one method for achieving high recognition rates. Thus, additional methods were used for finding references to the personality in the text. All these methods are based on the created information model, which represents person’s appearance.

Severe anion gap metabolic acidosis from acetaminophen use secondary to 5-oxoproline (pyroglutamic acid) accumulation.

PubMed

Zand, Ladan; Muriithi, Angela; Nelsen, Eric; Franco, Pablo M; Greene, Eddie L; Qian, Qi; El-Zoghby, Ziad M

2012-12-01

Anion gap metabolic acidosis (AGMA) is commonly encountered in medical practice. Acetaminophen-induced AGMA is, however, not widely recognized. We report 2 cases of high anion gap metabolic acidosis secondary to 5-oxoproline accumulation resulting from acetaminophen consumption: the first case caused by acute one-time ingestion of large quantities of acetaminophen and the second case caused by chronic repeated ingestion in a patient with chronic liver disease. Recognition of this entity facilitated timely diagnosis and effective treatment. Given acetaminophen is commonly used over the counter medication, increased recognition of this adverse effect is of important clinical significance.

Near Real Time Analytics of Human Sensor Networks in the Realm of Big Data

NASA Astrophysics Data System (ADS)

Aulov, O.; Halem, M.

2012-12-01

With the prolific development of social media, emergency responders have an increasing interest in harvesting social media from outlets such as Flickr, Twitter, and Facebook, in order to assess the scale and specifics of extreme events including wild fires, earthquakes, terrorist attacks, oil spills, etc. A number of experimental platforms have successfully been implemented to demonstrate the utilization of social media data in extreme events, including Twitter Earthquake Detector, which relied on tweets for earthquake monitoring; AirTwitter, which used tweets for air quality reporting; and our previous work, using Flickr data as boundary value forcings to improve the forecast of oil beaching in the aftermath of the Deepwater Horizon oil spill. The majority of these platforms addressed a narrow, specific type of emergency and harvested data from a particular outlet. We demonstrate an interactive framework for monitoring, mining and analyzing a plethora of heterogeneous social media sources for a diverse range of extreme events. Our framework consists of three major parts: a real time social media aggregator, a data processing and analysis engine, and a web-based visualization and reporting tool. The aggregator gathers tweets, Facebook comments from fan pages, Google+ posts, forum discussions, blog posts (such as LiveJournal and Blogger.com), images from photo-sharing platforms (such as Flickr, Picasa), videos from video-sharing platforms (youtube, Vimeo), and so forth. The data processing and analysis engine pre-processes the aggregated information and annotates it with geolocation and sentiment information. In many cases, the metadata of the social media posts does not contain geolocation information—-however, a human reader can easily guess from the body of the text what location is discussed. We are automating this task by use of Named Entity Recognition (NER) algorithms and a gazetteer service. The visualization and reporting tool provides a web-based, user-friendly interface that provides time-series analysis and plotting tools, geo-spacial visualization tools with interactive maps, and cause-effect inference tools. We demonstrate how we address big data challenges of monitoring, aggregating and analyzing vast amounts of social media data at a near realtime. As a result, our framework not only allows emergency responders to augment their situational awareness with social media information, but can also allow them to extract geophysical data and incorporate it into their analysis models.

THE ROLE OF THE RETINOBLASTOMA/E2F1 TUMOR SUPPRESSOR PATHWAY IN THE LESION RECOGNITION STEP OF NUCLEOTIDE EXCISION REPAIR

PubMed Central

Lin, Patrick S.; McPherson, Lisa A.; Chen, Aubrey Y.; Sage, Julien; Ford, James M.

2009-01-01

The retinoblastoma Rb/E2F tumor suppressor pathway plays a major role in the regulation of mammalian cell cycle progression. The pRb protein, along with closely related proteins p107 and p130, exerts its anti-proliferative effects by binding to the E2F family of transcription factors known to regulate essential genes throughout the cell cycle. We sought to investigate the role of the Rb/E2F1 pathway in the lesion recognition step of nucleotide excision repair (NER) in mouse embryonic fibroblasts (MEFs). Rb−/−;p107−/−;p130−/− MEFs repaired both cyclobutane pyrimidine dimers (CPD) and 6-4 photoproducts (6-4PPs) at higher efficiency than did wildtype cells following UV-C irradiation. The expression of damaged DNA binding gene DDB2 involved in the DNA lesion recognition step was elevated in the Rb family-deficient MEFs. To determine if the enhanced DNA repair in the absence of the Rb gene family is due to the derepression of E2F1, we assayed the ability of E2F1-deficient cells to repair damaged DNA and demonstrated that E2F1−/− MEFs are impaired for the removal of both CPDs and 6-4PPs. Furthermore, wildtype cells induced a higher expression of DDB2 and xeroderma pigmentosum gene XPC transcript levels than did E2F1−/− cells following UV-C irradiation. Using an E2F SiteScan algorithm, we uncovered a putative E2F-responsive element in the XPC promoter upstream of the transcription start site. We showed with chromatin immunoprecipitation assays the binding of E2F1 to the XPC promoter in a UV-dependent manner, suggesting that E2F1 is a transcriptional regulator of XPC. Our study identifies a novel E2F1 gene target and further supports the growing body of evidence that the Rb/E2F1 tumor suppressor pathway is involved in the regulation of the DNA lesion recognition step of nucleotide excision repair. PMID:19376752

Transformed Telepresence and Its Association with Learning in Computer-Supported Collaborative Learning: A Case Study in English Learning and Its Evaluation

ERIC Educational Resources Information Center

Ting, Yu-Liang; Tai, Yaming; Chen, Jun-Horng

2017-01-01

Telepresence has been playing an important role in a mediated learning environment. However, the current design of telepresence seems to be dominated by the emulation of physical human presence. With reference to social constructivism learning and the recognition of individuals as intelligent entities, this study explored the transformation of…

Hereditary neuropathy with liability to pressure palsies occurring during military training.

PubMed

Delacour, H; Bompaire, F; Biale, L; Sallansonnet-Froment, M; Ceppa, F; Burnat, P

2012-03-01

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal-dominant peripheral neuropathy characterized by recurrent isolated nerve palsies, which are precipitated by trivial compression and trauma. Although HNPP has been well-described in literature, it often goes unrecognized. We report a case of HNPP occurring during military training to promote recognition and proper management of this entity.

Recognition of human activity characteristics based on state transitions modeling technique

NASA Astrophysics Data System (ADS)

Elangovan, Vinayak; Shirkhodaie, Amir

2012-06-01

Human Activity Discovery & Recognition (HADR) is a complex, diverse and challenging task but yet an active area of ongoing research in the Department of Defense. By detecting, tracking, and characterizing cohesive Human interactional activity patterns, potential threats can be identified which can significantly improve situation awareness, particularly, in Persistent Surveillance Systems (PSS). Understanding the nature of such dynamic activities, inevitably involves interpretation of a collection of spatiotemporally correlated activities with respect to a known context. In this paper, we present a State Transition model for recognizing the characteristics of human activities with a link to a prior contextbased ontology. Modeling the state transitions between successive evidential events determines the activities' temperament. The proposed state transition model poses six categories of state transitions including: Human state transitions of Object handling, Visibility, Entity-entity relation, Human Postures, Human Kinematics and Distance to Target. The proposed state transition model generates semantic annotations describing the human interactional activities via a technique called Casual Event State Inference (CESI). The proposed approach uses a low cost kinect depth camera for indoor and normal optical camera for outdoor monitoring activities. Experimental results are presented here to demonstrate the effectiveness and efficiency of the proposed technique.

A system for de-identifying medical message board text.

PubMed

Benton, Adrian; Hill, Shawndra; Ungar, Lyle; Chung, Annie; Leonard, Charles; Freeman, Cristin; Holmes, John H

2011-06-09

There are millions of public posts to medical message boards by users seeking support and information on a wide range of medical conditions. It has been shown that these posts can be used to gain a greater understanding of patients' experiences and concerns. As investigators continue to explore large corpora of medical discussion board data for research purposes, protecting the privacy of the members of these online communities becomes an important challenge that needs to be met. Extant entity recognition methods used for more structured text are not sufficient because message posts present additional challenges: the posts contain many typographical errors, larger variety of possible names, terms and abbreviations specific to Internet posts or a particular message board, and mentions of the authors' personal lives. The main contribution of this paper is a system to de-identify the authors of message board posts automatically, taking into account the aforementioned challenges. We demonstrate our system on two different message board corpora, one on breast cancer and another on arthritis. We show that our approach significantly outperforms other publicly available named entity recognition and de-identification systems, which have been tuned for more structured text like operative reports, pathology reports, discharge summaries, or newswire.

Development of an acoustic wave based biosensor for vapor phase detection of small molecules

NASA Astrophysics Data System (ADS)

Stubbs, Desmond

For centuries scientific ingenuity and innovation have been influenced by Mother Nature's perfect design. One of her more elusive designs is that of the sensory olfactory system, an array of highly sensitive receptors responsible for chemical vapor recognition. In the animal kingdom this ability is magnified among canines where ppt (parts per trillion) sensitivity values have been reported. Today, detection dogs are considered an essential part of the US drug and explosives detection schemes. However, growing concerns about their susceptibility to extraneous odors have inspired the development of highly sensitive analytical detection tools or biosensors known as "electronic noses". In general, biosensors are distinguished from chemical sensors in that they use an entity of biological origin (e.g. antibody, cell, enzyme) immobilized onto a surface as the chemically-sensitive film on the device. The colloquial view is that the term "biosensors" refers to devices which detect the presence of entities of biological origin, such as proteins or single-stranded DNA and that this detection must take place in a liquid. Our biosensor utilizes biomolecules, specifically IgG monoclonal antibodies, to achieve molecular recognition of relatively small molecules in the vapor phase.

NMR structure of the DNA decamer duplex containing double T*G mismatches of cis-syn cyclobutane pyrimidine dimer: implications for DNA damage recognition by the XPC-hHR23B complex.

PubMed

Lee, Joon-Hwa; Park, Chin-Ju; Shin, Jae-Sun; Ikegami, Takahisa; Akutsu, Hideo; Choi, Byong-Seok

2004-01-01

The cis-syn cyclobutane pyrimidine dimer (CPD) is a cytotoxic, mutagenic and carcinogenic DNA photoproduct and is repaired by the nucleotide excision repair (NER) pathway in mammalian cells. The XPC-hHR23B complex as the initiator of global genomic NER binds to sites of certain kinds of DNA damage. Although CPDs are rarely recognized by the XPC-hHR23B complex, the presence of mismatched bases opposite a CPD significantly increased the binding affinity of the XPC-hHR23B complex to the CPD. In order to decipher the properties of the DNA structures that determine the binding affinity for XPC-hHR23B to DNA, we carried out structural analyses of the various types of CPDs by NMR spectroscopy. The DNA duplex which contains a single 3' T*G wobble pair in a CPD (CPD/GA duplex) induces little conformational distortion. However, severe distortion of the helical conformation occurs when a CPD contains double T*G wobble pairs (CPD/GG duplex) even though the T residues of the CPD form stable hydrogen bonds with the opposite G residues. The helical bending angle of the CPD/GG duplex was larger than those of the CPD/GA duplex and properly matched CPD/AA duplex. The fluctuation of the backbone conformation and significant changes in the widths of the major and minor grooves at the double T*G wobble paired site were also observed in the CPD/GG duplex. These structural features were also found in a duplex that contains the (6-4) adduct, which is efficiently recognized by the XPC-hHR23B complex. Thus, we suggest that the unique structural features of the DNA double helix (that is, helical bending, flexible backbone conformation, and significant changes of the major and/or minor grooves) might be important factors in determining the binding affinity of the XPC-hHR23B complex to DNA.

Spermatogenesis is not impaired in a nucleotide excision repair-deficient min mouse model with or without neonatal mutagen treatment.

PubMed

Andreassen, Ashild; Steffensen, Inger-Lise; Olsen, Ann-Karin; Tanaka, Kiyoji; Wiger, Richard

2011-01-01

Mice deficient in the xeroderma pigmentosum group A gene (Xpa) exhibit impaired nucleotide excision repair (NER) and are expected to accumulate bulky DNA adducts when subjected to certain compounds (eg, heterocyclic amines). Multiple intestinal neoplasia (Min) mice (B6(Min)(/+)) are particularly sensitive to low concentrations of mutagenic compounds in food. They develop intestinal tumors spontaneously, and the number and size of the tumors increase following exposure to 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), which humans are exposed to via fried food. We previously reported that NER is inefficient in adult testicular cells. Reduced NER (genetic deficiency; Xpa(-/-)) is expected to represent risk factors for PhIP-induced genotoxicity and could possibly disturb spermatogenesis, particularly in B6(Min)(/+) mice. We therefore studied spermatogenesis in mice with combinations of Xpa and Min or wild-type genotypes 11 weeks after exposure to PhIP on days 3 to 6. Fewer offspring were obtained from B6(Min)(/+)Xpa(-/-) than from B6(Min)(/+)Xpa(+/+) or B6(Min)(/+)Xpa(+/-). Distributions of the different testicular cell types, indicative of normal spermatogenesis and relative testes weights, did not differ significantly in PhIP-exposed or unexposed mice regardless of their genotypes. We conclude that the removal of bulky DNA adducts does not seem to be essential for normal spermatogenesis.

Active transcriptomic and proteomic reprogramming in the C. elegans nucleotide excision repair mutant xpa-1.

PubMed

Arczewska, Katarzyna D; Tomazella, Gisele G; Lindvall, Jessica M; Kassahun, Henok; Maglioni, Silvia; Torgovnick, Alessandro; Henriksson, Johan; Matilainen, Olli; Marquis, Bryce J; Nelson, Bryant C; Jaruga, Pawel; Babaie, Eshrat; Holmberg, Carina I; Bürglin, Thomas R; Ventura, Natascia; Thiede, Bernd; Nilsen, Hilde

2013-05-01

Transcription-blocking oxidative DNA damage is believed to contribute to aging and to underlie activation of oxidative stress responses and down-regulation of insulin-like signaling (ILS) in Nucleotide Excision Repair (NER) deficient mice. Here, we present the first quantitative proteomic description of the Caenorhabditis elegans NER-defective xpa-1 mutant and compare the proteome and transcriptome signatures. Both methods indicated activation of oxidative stress responses, which was substantiated biochemically by a bioenergetic shift involving increased steady-state reactive oxygen species (ROS) and Adenosine triphosphate (ATP) levels. We identify the lesion-detection enzymes of Base Excision Repair (NTH-1) and global genome NER (XPC-1 and DDB-1) as upstream requirements for transcriptomic reprogramming as RNA-interference mediated depletion of these enzymes prevented up-regulation of genes over-expressed in the xpa-1 mutant. The transcription factors SKN-1 and SLR-2, but not DAF-16, were identified as effectors of reprogramming. As shown in human XPA cells, the levels of transcription-blocking 8,5'-cyclo-2'-deoxyadenosine lesions were reduced in the xpa-1 mutant compared to the wild type. Hence, accumulation of cyclopurines is unlikely to be sufficient for reprogramming. Instead, our data support a model where the lesion-detection enzymes NTH-1, XPC-1 and DDB-1 play active roles to generate a genomic stress signal sufficiently strong to result in transcriptomic reprogramming in the xpa-1 mutant.

The rem Mutations in the ATP-Binding Groove of the Rad3/XPD Helicase Lead to Xeroderma pigmentosum-Cockayne Syndrome-Like Phenotypes

PubMed Central

Montelone, Beth A.; Aguilera, Andrés

2014-01-01

The eukaryotic TFIIH complex is involved in Nucleotide Excision Repair and transcription initiation. We analyzed three yeast mutations of the Rad3/XPD helicase of TFIIH known as rem (recombination and mutation phenotypes). We found that, in these mutants, incomplete NER reactions lead to replication fork breaking and the subsequent engagement of the homologous recombination machinery to restore them. Nevertheless, the penetrance varies among mutants, giving rise to a phenotype gradient. Interestingly, the mutations analyzed reside at the ATP-binding groove of Rad3 and in vivo experiments reveal a gain of DNA affinity upon damage of the mutant Rad3 proteins. Since mutations at the ATP-binding groove of XPD in humans are present in the Xeroderma pigmentosum-Cockayne Syndrome (XP-CS), we recreated rem mutations in human cells, and found that these are XP-CS-like. We propose that the balance between the loss of helicase activity and the gain of DNA affinity controls the capacity of TFIIH to open DNA during NER, and its persistence at both DNA lesions and promoters. This conditions NER efficiency and transcription resumption after damage, which in human cells would explain the XP-CS phenotype, opening new perspectives to understand the molecular basis of the role of XPD in human disease. PMID:25500814

Binding of RDX to Cell Wall Components of Pinus sylvestris and Picea glauca and Three-Year Mineralisation Study of Tissue-Associated RDX Residues.

PubMed

Schoenmuth, Bernd; Schenke, Detlef; Scharnhorst, Tanja; Combrinck, Sandra; McCrindle, Robert I; Mueller, Jakob O; Büttner, Carmen; Pestemer, Wilfried

2015-01-01

Contamination of soils with the explosive hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX, Research Department Explosive) as a result of military applications is a large-area problem globally. Since coniferous trees dominate the vegetation of large areas of military land in Central Europe, particularly in Germany, the long-term fate of (14)C-RDX in the conifers Scots pine and Dwarf Alberta spruce was studied. Acetic acid was the most effective solvent for the removal of extractable RDX residues from homogenates of RDX-laden tree material (85%, 80-90% and 64-80% for roots, wood and needles, respectively). On average, only a fifth of RDX-derived (14)C was bound in non-extractable residues (NER). Within the main cell wall compartments, lignin was the dominant binding site for NER (needles: 32-62%; roots: 38-42%). Hemicellulose (needles: 11-18%; roots: 6-11%) and cellulose (needles: 12-24%; roots: 1-2%) were less involved in binding and a considerable proportion of NER (needles: 15-24%; roots: 59-51%) was indigestible. After three-year incubation in rot chambers, mineralisation of tree-associated (14)C-RDX to (14)CO2 clearly dominated the mass balance in both tree species with 48-83%. 13-33% of (14)C-RDX-derived radioactivity remained in an unleachable form and the remobilisation by water leaching was negligible (< 2%).

Mobile phone specific electromagnetic fields induce transient DNA damage and nucleotide excision repair in serum-deprived human glioblastoma cells.

PubMed

Al-Serori, Halh; Ferk, Franziska; Kundi, Michael; Bileck, Andrea; Gerner, Christopher; Mišík, Miroslav; Nersesyan, Armen; Waldherr, Monika; Murbach, Manuel; Lah, Tamara T; Herold-Mende, Christel; Collins, Andrew R; Knasmüller, Siegfried

2018-01-01

Some epidemiological studies indicate that the use of mobile phones causes cancer in humans (in particular glioblastomas). It is known that DNA damage plays a key role in malignant transformation; therefore, we investigated the impact of the UMTS signal which is widely used in mobile telecommunications, on DNA stability in ten different human cell lines (six brain derived cell lines, lymphocytes, fibroblasts, liver and buccal tissue derived cells) under conditions relevant for users (SAR 0.25 to 1.00 W/kg). We found no evidence for induction of damage in single cell gel electrophoresis assays when the cells were cultivated with serum. However, clear positive effects were seen in a p53 proficient glioblastoma line (U87) when the cells were grown under serum free conditions, while no effects were found in p53 deficient glioblastoma cells (U251). Further experiments showed that the damage disappears rapidly in U87 and that exposure induced nucleotide excision repair (NER) and does not cause double strand breaks (DSBs). The observation of NER induction is supported by results of a proteome analysis indicating that several proteins involved in NER are up-regulated after exposure to UMTS; additionally, we found limited evidence for the activation of the γ-interferon pathway. The present findings show that the signal causes transient genetic instability in glioma derived cells and activates cellular defense systems.

TFIIH subunit alterations causing xeroderma pigmentosum and trichothiodystrophy specifically disturb several steps during transcription.

PubMed

Singh, Amita; Compe, Emanuel; Le May, Nicolas; Egly, Jean-Marc

2015-02-05

Mutations in genes encoding the ERCC3 (XPB), ERCC2 (XPD), and GTF2H5 (p8 or TTD-A) subunits of the transcription and DNA-repair factor TFIIH lead to three autosomal-recessive disorders: xeroderma pigmentosum (XP), XP associated with Cockayne syndrome (XP/CS), and trichothiodystrophy (TTD). Although these diseases were originally associated with defects in DNA repair, transcription deficiencies might be also implicated. By using retinoic acid receptor beta isoform 2 (RARB2) as a model in several cells bearing mutations in genes encoding TFIIH subunits, we observed that (1) the recruitment of the TFIIH complex was altered at the activated RARB2 promoter, (2) TFIIH participated in the recruitment of nucleotide excision repair (NER) factors during transcription in a manner different from that observed during NER, and (3) the different TFIIH variants disturbed transcription by having distinct consequences on post-translational modifications of histones, DNA-break induction, DNA demethylation, and gene-loop formation. The transition from heterochromatin to euchromatin was disrupted depending on the variant, illustrating the fact that TFIIH, by contributing to NER factor recruitment, orchestrates chromatin remodeling. The subtle transcriptional differences found between various TFIIH variants thus participate in the phenotypic variability observed among XP, XP/CS, and TTD individuals. Copyright © 2015 The American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.

FANCJ localization by mismatch repair is vital to maintain genomic integrity after UV irradiation.

PubMed

Guillemette, Shawna; Branagan, Amy; Peng, Min; Dhruva, Aashana; Schärer, Orlando D; Cantor, Sharon B

2014-02-01

Nucleotide excision repair (NER) is critical for the repair of DNA lesions induced by UV radiation, but its contribution in replicating cells is less clear. Here, we show that dual incision by NER endonucleases, including XPF and XPG, promotes the S-phase accumulation of the BRCA1 and Fanconi anemia-associated DNA helicase FANCJ to sites of UV-induced damage. FANCJ promotes replication protein A phosphorylation and the arrest of DNA synthesis following UV irradiation. Interaction defective mutants of FANCJ reveal that BRCA1 binding is not required for FANCJ localization, whereas interaction with the mismatch repair (MMR) protein MLH1 is essential. Correspondingly, we find that FANCJ, its direct interaction with MLH1, and the MMR protein MSH2 function in a common pathway in response to UV irradiation. FANCJ-deficient cells are not sensitive to killing by UV irradiation, yet we find that DNA mutations are significantly enhanced. Thus, we considered that FANCJ deficiency could be associated with skin cancer. Along these lines, in melanoma we found several somatic mutations in FANCJ, some of which were previously identified in hereditary breast cancer and Fanconi anemia. Given that, mutations in XPF can also lead to Fanconi anemia, we propose collaborations between Fanconi anemia, NER, and MMR are necessary to initiate checkpoint activation in replicating human cells to limit genomic instability.

Square bananas, blue horses: the relative weight of shape and color in concept recognition and representation

PubMed Central

Scorolli, Claudia; Borghi, Anna M.

2015-01-01

The present study investigates the role that shape and color play in the representation of animate (i.e., animals) and inanimate manipulable entities (i.e., fruits), and how the importance of these features is modulated by different tasks. Across three experiments participants were shown either images of entities (e.g., a sheep or a pineapple) or images of the same entities modified in color (e.g., a blue pineapple) or in shape (e.g., an elongated pineapple). In Experiment 1 we asked participants to categorize the entities as fruit or animal. Results showed that with animals color does not matter, while shape modifications determined a deterioration of the performance – stronger for fruit than for animals. To better understand our findings, in Experiments 2 we asked participants to judge if entities were graspable (manipulation evaluation task). Participants were faster with manipulable entities (fruit) than with animals; moreover alterations in shape affected the response latencies more for animals than for fruit. In Experiment 3 (motion evaluation task), we replicated the disadvantage for shape-altered animals, while with fruits shape and color modifications produced no effect. By contrasting shape- and color- alterations the present findings provide information on shape/color relative weight, suggesting that the action based property of shape is more crucial than color for fruit categorization, while with animals it is critical for both manipulation and motion tasks. This contextual dependency is further revealed by explicit judgments on similarity – between the altered entities and the prototypical ones – provided after the different tasks. These results extend current literature on affordances and biofunctionally embodied understanding, revealing the relative robustness of biofunctional activity compared to intellectual one. PMID:26500593

Single-Molecule View of Small RNA-Guided Target Search and Recognition.

PubMed

Globyte, Viktorija; Kim, Sung Hyun; Joo, Chirlmin

2018-05-20

Most everyday processes in life involve a necessity for an entity to locate its target. On a cellular level, many proteins have to find their target to perform their function. From gene-expression regulation to DNA repair to host defense, numerous nucleic acid-interacting proteins use distinct target search mechanisms. Several proteins achieve that with the help of short RNA strands known as guides. This review focuses on single-molecule advances studying the target search and recognition mechanism of Argonaute and CRISPR (clustered regularly interspaced short palindromic repeats) systems. We discuss different steps involved in search and recognition, from the initial complex prearrangement into the target-search competent state to the final proofreading steps. We focus on target search mechanisms that range from weak interactions, to one- and three-dimensional diffusion, to conformational proofreading. We compare the mechanisms of Argonaute and CRISPR with a well-studied target search system, RecA.

Door recognition in cluttered building interiors using imagery and lidar data

NASA Astrophysics Data System (ADS)

Díaz-Vilariño, L.; Martínez-Sánchez, J.; Lagüela, S.; Armesto, J.; Khoshelham, K.

2014-06-01

Building indoors reconstruction is an active research topic due to the importance of the wide range of applications to which they can be subjected, from architecture and furniture design, to movies and video games editing, or even crime scene investigation. Among the constructive elements defining the inside of a building, doors are important entities in applications like routing and navigation, and their automated recognition is advantageous e.g. in case of large multi-storey buildings with many office rooms. The inherent complexity of the automation of the recognition process is increased by the presence of clutter and occlusions, difficult to avoid in indoor scenes. In this work, we present a pipeline of techniques used for the reconstruction and interpretation of building interiors using information acquired in the form of point clouds and images. The methodology goes in depth with door detection and labelling as either opened, closed or furniture (false positive)

The psychology of corporate rights: Perception of corporate versus individual rights to religious liberty, privacy, and free speech.

PubMed

Mentovich, Avital; Huq, Aziz; Cerf, Moran

2016-04-01

The U.S. Supreme Court has increasingly expanded the scope of constitutional rights granted to corporations and other collective entities. Although this tendency receives widespread public and media attention, little empirical research examines how people ascribe rights, commonly thought to belong to natural persons, to corporations. This article explores this issue in 3 studies focusing on different rights (religious liberty, privacy, and free speech). We examined participants' willingness to grant a given right while manipulating the type of entity at stake (from small businesses, to larger corporations, to for-profit and nonprofit companies), and the identity of the right holder (from employees, to owners, to the company itself as a separate entity). We further examined the role of political ideology in perceptions of rights. Results indicated a significant decline in the degree of recognition of entities' rights (the company itself) in comparison to natural persons' rights (owners and employees). Results also demonstrated an effect of the type of entity at stake: Larger, for-profit businesses were less likely to be viewed as rights holders compared with nonprofit entities. Although both tendencies persisted across the ideological spectrum, ideological differences emerged in the relations between corporate and individual rights: these were positively related among conservatives but negatively related among liberals. Finally, we found that the desire to protect citizens (compared with businesses) underlies individuals' willingness to grant rights to companies. These findings show that people (rather than corporations) are more appropriate recipients of rights, and can explain public backlash to judicial expansions of corporate rights. (c) 2016 APA, all rights reserved).

Atypical presentations of methemoglobinemia from benzocaine spray.

PubMed

Tantisattamo, Ekamol; Suwantarat, Nuntra; Vierra, Joseph R; Evans, Samuel J

2011-06-01

Widely used for local anesthesia, especially prior to endoscopic procedures, benzocaine spray is one of the most common causes of iatrogenic methemoglobinemia. The authors report an atypical case of methemoglobinemia in a woman presenting with pale skin and severe hypoxemia, after a delayed repeat exposure to benzocaine spray. Early recognition and prompt management of methemoglobinemia is needed in order to lessen morbidity and mortality from this entity.

Cell type-specific hypersensitivity to oxidative damage in CSB and XPA mice.

PubMed

de Waard, Harm; de Wit, Jan; Gorgels, Theo G M F; van den Aardweg, Gerard; Andressoo, Jaan Olle; Vermeij, Marcel; van Steeg, Harry; Hoeijmakers, Jan H J; van der Horst, Gijsbertus T J

2003-01-02

Mutations in the CSB gene cause Cockayne syndrome (CS), a rare inherited disorder, characterized by UV-sensitivity, severe neurodevelopmental and progeroid symptoms. CSB functions in the transcription-coupled repair (TCR) sub-pathway of nucleotide excision repair (NER), responsible for the removal of UV-induced and other helix-distorting lesions from the transcribed strand of active genes. Several lines of evidence support the notion that the CSB TCR defect extends to other non-NER type transcription-blocking lesions, notably various kinds of oxidative damage, which may provide an explanation for part of the severe CS phenotype. We used genetically defined mouse models to examine the relationship between the CSB defect and sensitivity to oxidative damage in different cell types and at the level of the intact organism. The main conclusions are: (1) CSB(-/-) mouse embryo fibroblasts (MEFs) exhibit a clear hypersensitivity to ionizing radiation, extending the findings in genetically heterogeneous human CSB fibroblasts to another species. (2) CSB(-/-) MEFs are highly sensitive to paraquat, strongly indicating that the increased cytotoxicity is due to oxidative damage. (3) The hypersenstivity is independent of genetic background and directly related to the CSB defect and is not observed in totally NER-deficient XPA MEFs. (4) Wild type embryonic stem (ES) cells display an increased sensitivity to ionizing radiation compared to fibroblasts. Surprisingly, the CSB deficiency has only a very minor additional effect on ES cell sensitivity to oxidative damage and is comparable to that of an XPA defect, indicating cell type-specific differences in the contribution of TCR and NER to cellular survival. (5) Similar to ES cells, CSB and XPA mice both display a minor sensitivity to whole-body X-ray exposure. This suggests that the response of an intact organism to radiation is largely determined by the sensitivity of stem cells, rather than differentiated cells. These findings establish the role of transcription-coupled repair in resistance to oxidative damage and reveal a cell- and organ-specific impact of this repair pathway to the clinical phenotype of CS and XP.

Quantifying uncertainty in future floods and drought conditions in the Northeastern United States using regionally downscaled climate projections

NASA Astrophysics Data System (ADS)

Siddique, R.; Wu, C.; Karmalkar, A.; Bradley, R. S.; Palmer, R. N.

2017-12-01

Northeastern region (NER) of the United States (US) has been projected to be a place where climate change can have the most severe impacts. These impacts include, but are not limited to, increases in the following: extreme precipitation events, temperature, flood magnitudes, flood frequencies, droughts, and sea level rise. In this study, we estimate the frequency of hydrological extremes under different climate change scenarios using regionally downscaled climate projections from a limited number of selected models from the fifth phase of Coupled Model Intercomparison Project (CMIP5). The models are chosen to minimize the loss of key climate information relevant to the NER. Precipitation and temperature from the selected models are forced into a distributed hydrological model called Hydrology Laboratory - Research Distributed Hydrological Model (HL-RDHM) to obtain streamflows for two different time regimes, near-term (20-50 years out) and long-term (50-80 years out). For this, two climate emission scenarios will be considered: RCP 4.5 and RCP 8.5. The impacts of the climate projections on the streamflows are then evaluated across different watershed scales in the NER. Among different metrics, we employ: 1) Flood Events - return period of 1 year, 10 year, 20 year, 50 year, and 100 year flood events and 2) Drought Events -low flow events associated with the 7-day 10 year low flow, number of days per month that will be below the historic monthly average, number of days per month that will be below the 25 percentile monthly historic average, changes in the 30-day and 60-day cumulative summer flows, and the timing and magnitude of spring run-off. For estimates of the climate impacts on low and high flows, only the unregulated watersheds are taken into consideration. Ensembles of streamflows obtained by forcing different climate projections are used to quantify and account for the associated uncertainties. Thus, the outcomes of this study are expected to guide regional decision makers on potential impacts of climate change on hydrological extreme events and water resources across different spatial scales within NER of the US.

Assessment of regional downscaling simulations for long term mean, excess and deficit Indian Summer Monsoons

NASA Astrophysics Data System (ADS)

Varikoden, Hamza; Mujumdar, M.; Revadekar, J. V.; Sooraj, K. P.; Ramarao, M. V. S.; Sanjay, J.; Krishnan, R.

2018-03-01

This study undertakes a comprehensive assessment of dynamical downscaling of summer monsoon (June-September; JJAS) rainfall over heterogeneous regions namely the Western Ghats (WG), Central India (CI) and North-Eastern Region (NER) for long term mean, excess and deficit episodes for the historical period from 1951 to 2005. This downscaling assessment is based on six Coordinated Regional Climate Downscaling Experiments (CORDEX) for South Asia (SAS) region, their five driving Global Climate Models (GCM) simulations along with observations from India Meteorological Department (IMD) and Asian Precipitation Highly Resolved Observational Integrated Towards Evaluation for Water Resources (APHRODITE). The analysis reveals an overall reduction of dry bias in rainfall across the regions of Indian sub-continent in most of the downscaled CORDEX-SAS models and in their ensemble mean as compared to that of driving GCMs. The interannual variabilities during historical period are reasonably captured by the ensemble means of CORDEX-SAS simulations with an underestimation of 0.43%, 38% and 52% for the WG, CI and NER, respectively. Upon careful examination of the CORDEX-SAS models and their driving GCMs revealed considerable improvement in the regionally downscaled rainfall. The value addition of dynamical downscaling is apparent over the WG in Regional Climate Model (RCM) simulations with an improvement of more than 30% for the long term mean, excess and deficit episodes from their driving GCMs. In the case of NER, the improvement in the downscaled rainfall product is more than 10% for all the episodes. However, the value addition in the CORDEX-SAS simulations for CI region, dominantly influenced by synoptic scale processes, is not clear. Nevertheless, the reduction of dry bias in the complex topographical regions is remarkable. The relative performance of dynamical downscaling of rainfall over complex topography in response to local forcing and orographic lifting depict the value addition (30% over WG and 10% over NER, with a statistical significance of more than 5% level), when compared with the synoptic scale system induced rainfall over the plains of central-India.

Network analysis of named entity co-occurrences in written texts

NASA Astrophysics Data System (ADS)

Amancio, Diego Raphael

2016-06-01

The use of methods borrowed from statistics and physics to analyze written texts has allowed the discovery of unprecedent patterns of human behavior and cognition by establishing links between models features and language structure. While current models have been useful to unveil patterns via analysis of syntactical and semantical networks, only a few works have probed the relevance of investigating the structure arising from the relationship between relevant entities such as characters, locations and organizations. In this study, we represent entities appearing in the same context as a co-occurrence network, where links are established according to a null model based on random, shuffled texts. Computational simulations performed in novels revealed that the proposed model displays interesting topological features, such as the small world feature, characterized by high values of clustering coefficient. The effectiveness of our model was verified in a practical pattern recognition task in real networks. When compared with traditional word adjacency networks, our model displayed optimized results in identifying unknown references in texts. Because the proposed representation plays a complementary role in characterizing unstructured documents via topological analysis of named entities, we believe that it could be useful to improve the characterization of written texts (and related systems), specially if combined with traditional approaches based on statistical and deeper paradigms.

Supramolecular chemistry-general principles and selected examples from anion recognition and metallosupramolecular chemistry.

PubMed

Albrecht, Markus

2007-12-01

This review gives an introduction into supramolecular chemistry describing in the first part general principles, focusing on terms like noncovalent interaction, molecular recognition, self-assembly, and supramolecular function. In the second part those will be illustrated by simple examples from our laboratories. Supramolecular chemistry is the science that bridges the gap between the world of molecules and nanotechnology. In supramolecular chemistry noncovalent interactions occur between molecular building blocks, which by molecular recognition and self-assembly form (functional) supramolecular entities. It is also termed the "chemistry of the noncovalent bond." Molecular recognition is based on geometrical complementarity based on the "key-and-lock" principle with nonshape-dependent effects, e.g., solvatization, being also highly influential. Self-assembly leads to the formation of well-defined aggregates. Hereby the overall structure of the target ensemble is controlled by the symmetry features of the certain building blocks. Finally, the aggregates can possess special properties or supramolecular functions, which are only found in the ensemble but not in the participating molecules. This review gives an introduction on supramolecular chemistry and illustrates the fundamental principles by recent examples from our group.

Analysis of repair and PCNA complex formation induced by ionizing radiation in human fibroblast cell lines.

PubMed

Karmakar, P; Balajee, A S; Natarajan, A T

2001-05-01

Proliferating cell nuclear antigen (PCNA), an auxiliary factor for DNA polymerase delta and epsilon, is involved in both DNA replication and repair. Previous studies in vitro have demonstrated the requirement of PCNA in the resynthesis step of nucleotide excision repair (NER) and base excision repair (BER). Using a native chromatin template isolated under near physiological conditions, we have analysed the involvement of PCNA in the BER pathway in different NER defective human cell lines. The repair sites and PCNA were visualized by indirect immunolabelling followed by fluorescence microscopy. The results indicate that exposure to X-rays triggers the induction of PCNA in all the three human fibroblast cell lines studied, namely normal, xeroderma pigmentosum group A (XP-A) and Cockayne syndrome group B (CS-B). In all the cell lines, induction of PCNA and repair patches occurred in a dose- and time-dependent fashion. Induction of repair patches in NER-deficient XP-A cells suggests that the X-ray-induced lesions are largely repaired via the BER pathway involving PCNA as one of the key components of this pathway. X-ray-induced repair synthesis was greatly inhibited by treatment of cells with DNA polymerase inhibitors aphidicolin and cytosine arabinoside. Interestingly, inhibition of repair resynthesis did not affect the intensity of PCNA staining in X-irradiated cells indicating that the PCNA may be required for the BER pathway at a step preceding the resynthesis step.

GTF2E2 Mutations Destabilize the General Transcription Factor Complex TFIIE in Individuals with DNA Repair-Proficient Trichothiodystrophy

PubMed Central

Kuschal, Christiane; Botta, Elena; Orioli, Donata; Digiovanna, John J.; Seneca, Sara; Keymolen, Kathelijn; Tamura, Deborah; Heller, Elizabeth; Khan, Sikandar G.; Caligiuri, Giuseppina; Lanzafame, Manuela; Nardo, Tiziana; Ricotti, Roberta; Peverali, Fiorenzo A.; Stephens, Robert; Zhao, Yongmei; Lehmann, Alan R.; Baranello, Laura; Levens, David; Kraemer, Kenneth H.; Stefanini, Miria

2016-01-01

The general transcription factor IIE (TFIIE) is essential for transcription initiation by RNA polymerase II (RNA pol II) via direct interaction with the basal transcription/DNA repair factor IIH (TFIIH). TFIIH harbors mutations in two rare genetic disorders, the cancer-prone xeroderma pigmentosum (XP) and the cancer-free, multisystem developmental disorder trichothiodystrophy (TTD). The phenotypic complexity resulting from mutations affecting TFIIH has been attributed to the nucleotide excision repair (NER) defect as well as to impaired transcription. Here, we report two unrelated children showing clinical features typical of TTD who harbor different homozygous missense mutations in GTF2E2 (c.448G>C [p.Ala150Pro] and c.559G>T [p.Asp187Tyr]) encoding the beta subunit of transcription factor IIE (TFIIEβ). Repair of ultraviolet-induced DNA damage was normal in the GTF2E2 mutated cells, indicating that TFIIE was not involved in NER. We found decreased protein levels of the two TFIIE subunits (TFIIEα and TFIIEβ) as well as decreased phosphorylation of TFIIEα in cells from both children. Interestingly, decreased phosphorylation of TFIIEα was also seen in TTD cells with mutations in ERCC2, which encodes the XPD subunit of TFIIH, but not in XP cells with ERCC2 mutations. Our findings support the theory that TTD is caused by transcriptional impairments that are distinct from the NER disorder XP. PMID:26996949

Binding Pattern Elucidation of NNK and NNAL Cigarette Smoke Carcinogens with NER Pathway Enzymes: an Onco- Informatics Study.

PubMed

Jamal, Qazi Mohammad Sajid; Dhasmana, Anupam; Lohani, Mohtashim; Firdaus, Sumbul; Ansari, Md Yousuf; Sahoo, Ganesh Chandra; Haque, Shafiul

2015-01-01

Cigarette smoke derivatives like NNK (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone) and NNAL (4-(methylnitrosamino)-1-(3-pyridyl)-1-butan-1-ol) are well-known carcinogens. We analyzed the interaction of enzymes involved in the NER (nucleotide excision repair) pathway with ligands (NNK and NNAL). Binding was characterized for the enzymes sharing equivalent or better interaction as compared to +Ve control. The highest obtained docking energy between NNK and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.13 kcal/mol, -7.27 kcal/mol, -8.05 kcal/mol and -7.58 kcal/mol respectively. Similarly the highest obtained docking energy between NNAL and enzymes RAD23A, CCNH, CDK7, and CETN2 were -7.46 kcal/mol, -7.94 kcal/mol, -7.83 kcal/mol and -7.67 kcal/mol respectively. In order to find out the effect of NNK and NNAL on enzymes involved in the NER pathway applying protein-protein interaction and protein-complex (i.e. enzymes docked with NNK/NNAL) interaction analysis. It was found that carcinogens are well capable to reduce the normal functioning of genes like RAD23A (HR23A), CCNH, CDK7 and CETN2. In silico analysis indicated loss of functions of these genes and their corresponding enzymes, which possibly might be a cause for alteration of DNA repair pathways leading to damage buildup and finally contributing to cancer formation.

Xeroderma Pigmentosum-Trichothiodystrophy overlap patient with novel XPD/ERCC2 mutation

PubMed Central

Kralund, Henrik H.; Ousager, Lilian; Jaspers, Nicolaas G.; Raams, Anja; Pedersen, Erling B.; Gade, Else; Bygum, Anette

2013-01-01

Xeroderma Pigmentosum (XP), Trichothiodystrophy (TTD) and Cockayne Syndrome (CS) are rare, recessive disorders caused by mutational defects in the Nucleotide Excision Repair (NER) pathway and/or disruption of basic cellular DNA transcription. To date, a multitude of mutations in the XPD/ERCC2 gene have been described, many of which give rise to NER- and DNA transcription related diseases, which share certain diagnostic features and few overlap patients have been described. Despite increasing understanding of the roles of XPD/ERCC2 in mammalian cells, there is still weak predictability of somatic outcome from many of these mutations. We demonstrate a patient, believed to represent an overlap between XP and TTD/CS. In addition to other organ dysfunctions, the young man presented with Photosensitivity, Ichthyosis, Brittle hair, Impaired physical and mental development, Decreased fertility and Short stature (PIBIDS) suggestive of TTD, but lacking the almost patognomonic “tiger tail” banding of the hair under polarized light. Additionally, he developed basal cell carcinoma aged 28, as well as adult onset kidney failure, features normally not associated with TTD but rather XP/CS. His freckled appearance also suggested XP, but fibroblast cultures only demonstrated x2 UV-sensitivity with expected NER and TFIIH-activity decrease. Genetic sequencing of the XPD/ERCC2 gene established the patient as heterozygote compound with a novel, N-terminal Y18H mutation and a known C-terminal (TTD) mutation, A725P. The possible interplay between gene products and the patient phenotype is discussed. PMID:25002996

Predicting isoproturon long-term mineralization from short-term experiment: Can this be a suitable approach?

PubMed

Wang, Fang; Dörfler, Ulrike; Jiang, Xin; Schroll, Reiner

2016-02-01

A worldwide used pesticide - isoproturon (IPU) - was selected to test whether short-term experiments can be used to predict long-term mineralization of IPU in soil. IPU-mineralization was measured for 39 and 265 days in four different agricultural soils with a low mineralization dynamic. Additionally, in one soil IPU dissipation, formation and dissipation of metabolites, formation of non-extractable residues (NER) and (14)C-microbial biomass from (14)C-IPU were monitored for 39 and 265 days. The data from short-term and long-term experiments were used for model fitting. The long-term dynamics of IPU mineralization were considerably overestimated by the short-term experiments in two soils with neutral pH, while in two other soils with low pH and lower mineralization, the long-term mineralization of IPU could be sufficiently predicted. Additional investigations in one of the soils with neutral pH showed that dissipation of IPU and metabolites could be correctly predicted by the short-term experiment. However, the formation of NER and (14)C-microbial biomass were remarkably overestimated by the short-term experiment. Further, it could be shown that the released NER and (14)C-microbial biomass were the main contributors of (14)CO2 formation at later incubation stages. Taken together, our results indicate that in soils with neutral pH short-term experiments were inadequate to predict the long-term mineralization of IPU. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multiple repair pathways mediate tolerance to chemotherapeutic cross-linking agents in vertebrate cells.

PubMed

Nojima, Kuniharu; Hochegger, Helfrid; Saberi, Alihossein; Fukushima, Toru; Kikuchi, Koji; Yoshimura, Michio; Orelli, Brian J; Bishop, Douglas K; Hirano, Seiki; Ohzeki, Mioko; Ishiai, Masamichi; Yamamoto, Kazuhiko; Takata, Minoru; Arakawa, Hiroshi; Buerstedde, Jean-Marie; Yamazoe, Mitsuyoshi; Kawamoto, Takuo; Araki, Kasumi; Takahashi, Jun A; Hashimoto, Nobuo; Takeda, Shunichi; Sonoda, Eiichiro

2005-12-15

Cross-linking agents that induce DNA interstrand cross-links (ICL) are widely used in anticancer chemotherapy. Yeast genetic studies show that nucleotide excision repair (NER), Rad6/Rad18-dependent postreplication repair, homologous recombination, and cell cycle checkpoint pathway are involved in ICL repair. To study the contribution of DNA damage response pathways in tolerance to cross-linking agents in vertebrates, we made a panel of gene-disrupted clones from chicken DT40 cells, each defective in a particular DNA repair or checkpoint pathway, and measured the sensitivities to cross-linking agents, including cis-diamminedichloroplatinum (II) (cisplatin), mitomycin C, and melphalan. We found that cells harboring defects in translesion DNA synthesis (TLS), Fanconi anemia complementation groups (FANC), or homologous recombination displayed marked hypersensitivity to all the cross-linking agents, whereas NER seemed to play only a minor role. This effect of replication-dependent repair pathways is distinctively different from the situation in yeast, where NER seems to play a major role in dealing with ICL. Cells deficient in Rev3, the catalytic subunit of TLS polymerase Polzeta, showed the highest sensitivity to cisplatin followed by fanc-c. Furthermore, epistasis analysis revealed that these two mutants work in the same pathway. Our genetic comprehensive study reveals a critical role for DNA repair pathways that release DNA replication block at ICLs in cellular tolerance to cross-linking agents and could be directly exploited in designing an effective chemotherapy.

Discovering biomedical semantic relations in PubMed queries for information retrieval and database curation

PubMed Central

Huang, Chung-Chi; Lu, Zhiyong

2016-01-01

Identifying relevant papers from the literature is a common task in biocuration. Most current biomedical literature search systems primarily rely on matching user keywords. Semantic search, on the other hand, seeks to improve search accuracy by understanding the entities and contextual relations in user keywords. However, past research has mostly focused on semantically identifying biological entities (e.g. chemicals, diseases and genes) with little effort on discovering semantic relations. In this work, we aim to discover biomedical semantic relations in PubMed queries in an automated and unsupervised fashion. Specifically, we focus on extracting and understanding the contextual information (or context patterns) that is used by PubMed users to represent semantic relations between entities such as ‘CHEMICAL-1 compared to CHEMICAL-2.’ With the advances in automatic named entity recognition, we first tag entities in PubMed queries and then use tagged entities as knowledge to recognize pattern semantics. More specifically, we transform PubMed queries into context patterns involving participating entities, which are subsequently projected to latent topics via latent semantic analysis (LSA) to avoid the data sparseness and specificity issues. Finally, we mine semantically similar contextual patterns or semantic relations based on LSA topic distributions. Our two separate evaluation experiments of chemical-chemical (CC) and chemical–disease (CD) relations show that the proposed approach significantly outperforms a baseline method, which simply measures pattern semantics by similarity in participating entities. The highest performance achieved by our approach is nearly 0.9 and 0.85 respectively for the CC and CD task when compared against the ground truth in terms of normalized discounted cumulative gain (nDCG), a standard measure of ranking quality. These results suggest that our approach can effectively identify and return related semantic patterns in a ranked order covering diverse bio-entity relations. To assess the potential utility of our automated top-ranked patterns of a given relation in semantic search, we performed a pilot study on frequently sought semantic relations in PubMed and observed improved literature retrieval effectiveness based on post-hoc human relevance evaluation. Further investigation in larger tests and in real-world scenarios is warranted. PMID:27016698

Atypical Presentations of Methemoglobinemia from Benzocaine Spray

PubMed Central

Suwantarat, Nuntra; Vierra, Joseph R; Evans, Samuel J

2011-01-01

Widely used for local anesthesia, especially prior to endoscopic procedures, benzocaine spray is one of the most common causes of iatrogenic methemoglobinemia. The authors report an atypical case of methemoglobinemia in a woman presenting with pale skin and severe hypoxemia, after a delayed repeat exposure to benzocaine spray. Early recognition and prompt management of methemoglobinemia is needed in order to lessen morbidity and mortality from this entity. PMID:22162610

Diagnosis of B-Cell Non-Hodgkin Lymphomas with Small-/Intermediate-Sized Cells in Cytopathology

PubMed Central

Schwock, Joerg; Geddie, William R.

2012-01-01

Fine needle sampling is a fast, safe, and potentially cost-effective method of obtaining tissue for cytomorphologic assessment aimed at both initial triage and, in some cases, complete diagnosis of patients that present clinically with lymphadenopathy. The cytologic diagnosis of B-cell non-Hodgkin lymphomas composed of small-/intermediate-sized cells, however, has been seen as an area of great difficulty even for experienced observers due to the morphologic overlap between lymphoma and reactive lymphadenopathies as well as between the lymphoma entities themselves. Although ancillary testing has improved diagnostic accuracy, the results from these tests must be interpreted within the morphological and clinical context to avoid misinterpretation. Importantly, the recognition of specific cytologic features is crucial in guiding the appropriate selection of ancillary tests which will either confirm or refute a tentative diagnosis. For these reasons, we here review the cytologic characteristics particular to five common B-cell non-Hodgkin lymphomas which typically cause the most diagnostic confusion based on cytological assessment alone: marginal zone lymphoma, follicular lymphoma, mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, and lymphoplasmacytic lymphoma. We summarize the most pertinent cytomorphologic features for each entity as well as for reactive lymphoid hyperplasia, contrast them with each other to facilitate their recognition, and highlight common diagnostic pitfalls. PMID:22693682

Printable, scannable biometric templates for secure documents and materials

NASA Astrophysics Data System (ADS)

Cambier, James L.; Musgrave, Clyde

2000-04-01

Biometric technology has been widely acknowledged as an effective means for enhancing private and public security through applications in physical access control, computer and computer network access control, medical records protection, banking security, public identification programs, and others. Nearly all of these applications involve use of a biometric token to control access to a physical entity or private information. There are also unique benefits to be derived from attaching a biometric template to a physical entity such as a document, package, laboratory sample, etc. Such an association allows fast, reliable, and highly accurate association of an individual person's identity to the physical entity, and can be used to enhance security, convenience, and privacy in many types of transactions. Examples include authentication of documents, tracking of laboratory samples in a testing environment, monitoring the movement of physical evidence within the criminal justice system, and authenticating the identity of both sending and receiving parties in shipment of high value parcels. A system is described which combines a biometric technology based on iris recognition with a printing and scanning technology for high-density bar codes.

40 CFR 1051.137 - What are the consumer labeling requirements?

Code of Federal Regulations, 2011 CFR

2011-07-01

... final deteriorated emission level. Round the resulting normalized emission rate for your vehicle to one... name, vehicle model name, engine description (500 cc two-stroke with DFI), the NER, and a brief...

40 CFR 1051.137 - What are the consumer labeling requirements?

Code of Federal Regulations, 2012 CFR

2012-07-01

... final deteriorated emission level. Round the resulting normalized emission rate for your vehicle to one... name, vehicle model name, engine description (500 cc two-stroke with DFI), the NER, and a brief...

40 CFR 1051.137 - What are the consumer labeling requirements?

Code of Federal Regulations, 2014 CFR

2014-07-01

... final deteriorated emission level. Round the resulting normalized emission rate for your vehicle to one... name, vehicle model name, engine description (500 cc two-stroke with DFI), the NER, and a brief...

40 CFR 1051.137 - What are the consumer labeling requirements?

Code of Federal Regulations, 2013 CFR

2013-07-01

... final deteriorated emission level. Round the resulting normalized emission rate for your vehicle to one... name, vehicle model name, engine description (500 cc two-stroke with DFI), the NER, and a brief...

Mining Adverse Drug Reactions in Social Media with Named Entity Recognition and Semantic Methods.

PubMed

Chen, Xiaoyi; Deldossi, Myrtille; Aboukhamis, Rim; Faviez, Carole; Dahamna, Badisse; Karapetiantz, Pierre; Guenegou-Arnoux, Armelle; Girardeau, Yannick; Guillemin-Lanne, Sylvie; Lillo-Le-Louët, Agnès; Texier, Nathalie; Burgun, Anita; Katsahian, Sandrine

2017-01-01

Suspected adverse drug reactions (ADR) reported by patients through social media can be a complementary source to current pharmacovigilance systems. However, the performance of text mining tools applied to social media text data to discover ADRs needs to be evaluated. In this paper, we introduce the approach developed to mine ADR from French social media. A protocol of evaluation is highlighted, which includes a detailed sample size determination and evaluation corpus constitution. Our text mining approach provided very encouraging preliminary results with F-measures of 0.94 and 0.81 for recognition of drugs and symptoms respectively, and with F-measure of 0.70 for ADR detection. Therefore, this approach is promising for downstream pharmacovigilance analysis.

Polyvalent Recognition of Biopolymers:The Design of Potent Inhibitors of Anthrax Toxin

NASA Astrophysics Data System (ADS)

Kane, Ravi

2007-03-01

Polyvalency -- the simultaneous binding of multiple ligands on one entity to multiple receptors on another -- is a phenomenon that is ubiquitous in nature. We are using a biomimetic approach, inspired by polyvalency, to design potent inhibitors of anthrax toxin. Since the major symptoms and death from anthrax are due primarily to the action of anthrax toxin, the toxin is a prime target for therapeutic intervention. We describe the design of potent polyvalent anthrax toxin inhibitors, and will discuss the role of pattern matching in polyvalent recognition. Pattern-matched polyvalent inhibitors can neutralize anthrax toxin in vivo, and may enable the successful treatment of anthrax during the later stages of the disease, when antibiotic treatment is ineffective.

On the Design of Smart Homes: A Framework for Activity Recognition in Home Environment.

PubMed

Cicirelli, Franco; Fortino, Giancarlo; Giordano, Andrea; Guerrieri, Antonio; Spezzano, Giandomenico; Vinci, Andrea

2016-09-01

A smart home is a home environment enriched with sensing, actuation, communication and computation capabilities which permits to adapt it to inhabitants preferences and requirements. Establishing a proper strategy of actuation on the home environment can require complex computational tasks on the sensed data. This is the case of activity recognition, which consists in retrieving high-level knowledge about what occurs in the home environment and about the behaviour of the inhabitants. The inherent complexity of this application domain asks for tools able to properly support the design and implementation phases. This paper proposes a framework for the design and implementation of smart home applications focused on activity recognition in home environments. The framework mainly relies on the Cloud-assisted Agent-based Smart home Environment (CASE) architecture offering basic abstraction entities which easily allow to design and implement Smart Home applications. CASE is a three layered architecture which exploits the distributed multi-agent paradigm and the cloud technology for offering analytics services. Details about how to implement activity recognition onto the CASE architecture are supplied focusing on the low-level technological issues as well as the algorithms and the methodologies useful for the activity recognition. The effectiveness of the framework is shown through a case study consisting of a daily activity recognition of a person in a home environment.

Molecular recognition at methyl methacrylate/n-butyl acrylate (MMA/nBA) monomer unit boundaries of phospholipids at p-MMA/nBA copolymer surfaces.

PubMed

Yu, Min; Urban, Marek W; Sheng, Yinghong; Leszczynski, Jerzy

2008-09-16

Lipid structural features and their interactions with proteins provide a useful vehicle for further advances in membrane proteins research. To mimic one of potential lipid-protein interactions we synthesized poly(methyl methacrylate/ n-butyl acrylate) (p-MMA/nBA) colloidal particles that were stabilized by phospholipid (PLs). Upon the particle coalescence, PL stratification resulted in the formation of surface localized ionic clusters (SLICs). These entities are capable of recognizing MMA/nBA monomer interfaces along the p-MMA/nBA copolymer backbone and form crystalline SLICs at the monomer interface. By utilizing attenuated total reflectance Fourier transform infrared (ATR FT-IR) spectroscopy and selected area electron diffraction (SAD) combined with ab initio calculations, studies were conducted that identified the origin of SLICs as well as their structural features formed on the surface of p-MMA/nBA copolymer films stabilized by 1,2-dilauroyl-sn-glycero-3-phosphocholine (DLPC) PL. Specific entities responsible for SLIC formation are selective noncovalent bonds of anionic phosphate and cationic quaternary ammonium segments of DLPC that interact with two neighboring carbonyl groups of nBA and MMA monomers of the p-MMA/nBA polymer backbone. To the best of our knowledge this is the first example of molecular recognition facilitated by coalescence of copolymer colloidal particles and the ability of PLs to form SLICs at the boundaries of the neighboring MMA and nBA monomer units of the p-MMA/nBA chain. The dominating noncovalent bonds responsible for the molecular recognition is a combination of H-bonding and electrostatic interactions.

Xeroderma Pigmentosum - Facts and Perspectives.

PubMed

Lehmann, Janin; Seebode, Christina; Martens, Marie Christine; Emmert, Steffen

2018-02-01

Ultraviolet (UV)-induced DNA lesions are almost exclusively removed by the nucleotide excision repair (NER) pathway, which is essential for prevention of skin cancer development. Patients with xeroderma pigmentosum (XP) are extremely sun sensitive due to a genetic defect in components of the NER cascade. They present with first signs of premature skin aging at an early age, with a considerably increased risk of developing UV-induced skin cancer. XP belongs to the group of DNA repair defective disorders that are mainly diagnosed in the clinic and in hindsight confirmed at the molecular level. Unfortunately, there are no causative treatment options for this rare, autosomal-recessive disorder, emphasizing the importance of an early diagnosis. Subsequently, UV-protective measures such as the reduction of exposure to environmental UV and regular skin cancer screenings should be undertaken to substantially improve prognosis as well as the disease course. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Rapid Diagnosis of Arbovirus and Arenavirus Infections by Immunofluorescence.

DTIC Science & Technology

1984-12-31

rivers have been tested against Ebola, Lassa and Marburg viruses . Only positives with Ebola virus were found with the monovalent slides. One serum gave...recognition as a disease entity. DIVELOPMK OF THE ELISA TEST FOR CCHF VIRUSES . We have used detected CCHF virus infected cells by ELISA. This system offers...CCHF) virus was developed using infected, formalin-fixed CER cells as antigen. A retrospective serologic survey of equatorial Africa for antibodies

Successful medical management of a case of Austrian syndrome-an uncommon entity in the modern antibiotic era: a case report.

PubMed

Rahim, Muhammad Abdur; Zaman, Shahana; Haque, Hasna Fahmima; Afroze, Samira Rahat; Uddin, Khwaja Nazim

2017-09-06

Austrian syndrome-the combination of meningitis, pneumonia and infective endocarditis due to Streptococcus pneumoniae infection, is a rare entity. In literature only a few hundreds of cases are reported but surprisingly we did not find any report on Austrian syndrome in or from Bangladesh. We report the case history of a middle aged Bangladeshi diabetic man, who had fever, cough, shortness of breath and altered mentation. He had tachycardia, bi-basal lung crepitations, new cardiac murmurs and meningism. Diagnostic work-up revealed Austrian syndrome. Because of the rarity of the condition, this case is reported. A case of pneumococcal pneumonia or meningitis should raise suspicion of concomitant endocarditis and Austrian syndrome, specially if there is heart failure, as early recognition and treatment may appear life-saving.

The Mechanism of Nucleotide Excision Repair-Mediated UV-Induced Mutagenesis in Nonproliferating Cells

PubMed Central

Kozmin, Stanislav G.; Jinks-Robertson, Sue

2013-01-01

Following the irradiation of nondividing yeast cells with ultraviolet (UV) light, most induced mutations are inherited by both daughter cells, indicating that complementary changes are introduced into both strands of duplex DNA prior to replication. Early analyses demonstrated that such two-strand mutations depend on functional nucleotide excision repair (NER), but the molecular mechanism of this unique type of mutagenesis has not been further explored. In the experiments reported here, an ade2 adeX colony-color system was used to examine the genetic control of UV-induced mutagenesis in nondividing cultures of Saccharomyces cerevisiae. We confirmed a strong suppression of two-strand mutagenesis in NER-deficient backgrounds and demonstrated that neither mismatch repair nor interstrand crosslink repair affects the production of these mutations. By contrast, proteins involved in the error-prone bypass of DNA damage (Rev3, Rev1, PCNA, Rad18, Pol32, and Rad5) and in the early steps of the DNA-damage checkpoint response (Rad17, Mec3, Ddc1, Mec1, and Rad9) were required for the production of two-strand mutations. There was no involvement, however, for the Pol η translesion synthesis DNA polymerase, the Mms2-Ubc13 postreplication repair complex, downstream DNA-damage checkpoint factors (Rad53, Chk1, and Dun1), or the Exo1 exonuclease. Our data support models in which UV-induced mutagenesis in nondividing cells occurs during the Pol ζ-dependent filling of lesion-containing, NER-generated gaps. The requirement for specific DNA-damage checkpoint proteins suggests roles in recruiting and/or activating factors required to fill such gaps. PMID:23307894

XPC and human homologs of RAD23: intracellular localization and relationship to other nucleotide excision repair complexes.

PubMed Central

van der Spek, P J; Eker, A; Rademakers, S; Visser, C; Sugasawa, K; Masutani, C; Hanaoka, F; Bootsma, D; Hoeijmakers, J H

1996-01-01

The xeroderma pigmentosum syndrome complementation group C (XP-C) is due to a defect in the global genome repair subpathway of nucleotide excision repair (NER). The XPC protein is complexed with HHR23B, one of the two human homologs of the yeast NER protein, RAD23 (Masutani at al. (1994) EMBO J. 8, 1831-1843). Using heparin chromatography, gel filtration and native gel electrophoresis we demonstrate that the majority of HHR23B is in a free, non-complexed form, and that a minor fraction is tightly associated with XPC. In contrast, we cannot detect any bound HHR23A. Thus the HHR23 proteins may have an additional function independent of XPC. The fractionation behaviour suggests that the non-bound forms of the HHR23 proteins are not necessary for the core of the NER reaction. Although both HHR23 proteins share a high level of overall homology, they migrate very differently on native gels, pointing to a difference in conformation. Gel filtration suggests the XPC-HHR23B heterodimer resides in a high MW complex. However, immunodepletion studies starting from repair-competent Manley extracts fall to reveal a stable association of a significant fraction of the HHR23 proteins or the XPC-HHR23B complex with the basal transcription/repair factor TFIIH, or with the ERCC1 repair complex. Consistent with a function in repair or DNA/chromatin metabolism, immunofluorescence studies show all XPC, HHR23B and (the free) HHR23A to reside in the nucleus. PMID:8692695

Polychlorinated biphenyl quinone induces oxidative DNA damage and repair responses: The activations of NHEJ, BER and NER via ATM-p53 signaling axis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Hui; Shi, Qiong; Song, Xiufang

2015-07-01

Our previous studies demonstrated that polychlorinated biphenyl (PCB) quinone induced oxidative DNA damage in HepG2 cells. To promote genomic integrity, DNA damage response (DDR) coordinates cell-cycle transitions, DNA repair and apoptosis. PCB quinone-induced cell cycle arrest and apoptosis have been documented, however, whether PCB quinone insult induce DNA repair signaling is still unknown. In this study, we identified the activation of DDR and corresponding signaling events in HepG2 cells upon the exposure to a synthetic PCB quinone, PCB29-pQ. Our data illustrated that PCB29-pQ induces the phosphorylation of p53, which was mediated by ataxia telangiectasia mutated (ATM) protein kinase. The observedmore » phosphorylated histone H2AX (γ-H2AX) foci and the elevation of 8-hydroxy-2′-deoxyguanosine (8-OHdG) indicated that DDR was stimulated by PCB29-pQ treatment. Additionally, we found PCB29-pQ activates non-homologous end joining (NHEJ), base excision repair (BER) and nucleotide excision repair (NER) signalings. However, these repair pathways are not error-free processes and aberrant repair of DNA damage may cause the potential risk of carcinogenesis and mutagenesis. - Highlights: • Polychlorinated biphenyl quinone induces oxidative DNA damage in HepG2 cells. • The elevation of γ-H2AX and 8-OHdG indicates the activation of DNA damage response. • ATM-p53 signaling acts as the DNA damage sensor and effector. • Polychlorinated biphenyl quinone activates NHEJ, BER and NER signalings.« less

Associations between expression levels of nucleotide excision repair proteins in lymphoblastoid cells and risk of squamous cell carcinoma of the head and neck.

PubMed

Han, Peng; Liu, Hongliang; Shi, Qiong; Liu, Zhensheng; Troy, Jesse D; Lee, Walter T; Zevallos, Jose P; Li, Guojun; Sturgis, Erich M; Wei, Qingyi

2018-06-01

Squamous cell carcinoma of head and neck (SCCHN) is one of the most common malignancies worldwide, and nucleotide excision repair (NER) is involved in SCCHN susceptibility. In this analysis of 349 newly diagnosed SCCHN patients and 295 cancer-free controls, we investigated whether expression levels of eight core NER proteins were associated with risk of SCCHN. We quantified NER protein expression levels in cultured peripheral lymphocytes using a reverse-phase protein microarray. Compared with the controls, SCCHN patients had statistically significantly lower expression levels of ERCC3 and XPA (P = 0.001 and 0.001, respectively). After dividing the subjects by controls' median values of expression levels, we found a dose-dependent association between an increased risk of SCCHN and low expression levels of ERCC3 (adjusted OR, 1.75, and 95% CI: 1.26-2.42; P trend  = 0.008) and XPA (adjusted OR, 1.88; 95% CI, 1.35-2.60; P trend  = 0.001). We also identified a significant multiplicative interaction between smoking status and ERCC3 expression levels (P = 0.014). Finally, after integrating demographic and clinical variables, we found that the addition of ERCC3 and XPA expression levels to the model significantly improved the sensitivity of the expanded model on SCCHN risk. In conclusion, reduced protein expression levels of ERCC3 and XPA were associated with an increased risk of SCCHN. However, these results need to be confirmed in additional large studies. © 2018 Wiley Periodicals, Inc.

Genome-wide map of Apn1 binding sites under oxidative stress in Saccharomyces cerevisiae.

PubMed

Morris, Lydia P; Conley, Andrew B; Degtyareva, Natalya; Jordan, I King; Doetsch, Paul W

2017-11-01

The DNA is cells is continuously exposed to reactive oxygen species resulting in toxic and mutagenic DNA damage. Although the repair of oxidative DNA damage occurs primarily through the base excision repair (BER) pathway, the nucleotide excision repair (NER) pathway processes some of the same lesions. In addition, damage tolerance mechanisms, such as recombination and translesion synthesis, enable cells to tolerate oxidative DNA damage, especially when BER and NER capacities are exceeded. Thus, disruption of BER alone or disruption of BER and NER in Saccharomyces cerevisiae leads to increased mutations as well as large-scale genomic rearrangements. Previous studies demonstrated that a particular region of chromosome II is susceptible to chronic oxidative stress-induced chromosomal rearrangements, suggesting the existence of DNA damage and/or DNA repair hotspots. Here we investigated the relationship between oxidative damage and genomic instability utilizing chromatin immunoprecipitation combined with DNA microarray technology to profile DNA repair sites along yeast chromosomes under different oxidative stress conditions. We targeted the major yeast AP endonuclease Apn1 as a representative BER protein. Our results indicate that Apn1 target sequences are enriched for cytosine and guanine nucleotides. We predict that BER protects these sites in the genome because guanines and cytosines are thought to be especially susceptible to oxidative attack, thereby preventing large-scale genome destabilization from chronic accumulation of DNA damage. Information from our studies should provide insight into how regional deployment of oxidative DNA damage management systems along chromosomes protects against large-scale rearrangements. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Evolution of NASA's Near-Earth Tracking and Data Relay Satellite System (TDRSS)

NASA Technical Reports Server (NTRS)

Flaherty, Roger; Stocklin, Frank; Weinberg, Aaron

2006-01-01

NASA's Tracking and Data Relay Satellite System (TDRSS) is now in its 23rd year of operations and its spacecraft fleet includes three second-generation spacecraft launched since the year 2000; a figure illustrates the first generation TDRSS spacecraft. During this time frame the TDRSS has provided communications relay support to a broad range of missions, with emphasis on low-earth-orbiting (LEO) spacecraft that include unmanned science spacecraft (e.g., Hubble Space Telescope), and human spaceflight (Space Shuttle and Space Station). Furthermore, the TDRSS has consistently demonstrated its uniqueness and adaptability in several ways. First, its S- and K-band services, combined with its multi-band/steerable single-access (SA) antennas and ground-based configuration flexibility, have permitted the mission set to expand to unique users such as scientific balloons and launch vehicles. Second, the bent-pipe nature of the system has enabled the introduction of new/improved services via technology insertion and upgrades at each of the ground terminals; a specific example here is the Demand Access Service (DAS), which, for example, is currently providing science-alert support to NASA science missions Third, the bent-pipe nature of the system, combined with the flexible ground-terminal signal processing architecture has permitted the demonstration/vaIidation of new techniques/services/technologies via a real satellite channel; over the past 10+ years these have, for example, included demonstrations/evaluations of emerging modulation/coding techniques. Given NASA's emerging Exploration plans, with missions beginning later this decade and expanding for decades to come, NASA is currently planning the development of a seamless, NASA-wide architecture that must accommodate missions from near-earth to deep space. Near-earth elements include Ground-Network (GN) and Near-Earth Relay (NER) components and both must efficiently and seamlessly support missions that encompass: earth orbit, including dedicated science missions and lunar support/cargo vehicles; earth/moon transit; lunar in-situ operations; and other missions within approximately 2 million km of earth (e.g., at the sun/earth libration points). Given that the NER is an evolution of TDRSS, one element of this NASA-wide architecture development activity is a trade study of future NER architecture candidates. The present paper focuses on trade study aspects associated with the NER, highlights study elements, and provides representative interim results.

Impact of Aerosols on Shortwave and Photosynthetically Active Radiation Balance over Sub-tropical Region in South Asia: Observational and Modeling Approach

NASA Astrophysics Data System (ADS)

Subba, T.; Pathak, B.

2016-12-01

The North-East Indian Region (NER) (22-30ºN, 89-98ºE) in south Asia sandwiched between two global biodiversity hotspots namely, Himalaya and Indo-Burma, assumes significance owing to its unique topography with mountains in the north, east and south and densely populated Indo Gangetic plains (IGP) towards the west resulting in complex aerosol system. Multi-year (2010-2014) concurrent measurements of aerosol properties and the shortwave radiation budget are examined over four geographically distinct stations of NER operational under Indian Space Research organization's ARFINET (Aerosol Radiative Forcing over India NETwork). An attempt has been made to lessen the ambiguity of forcing estimation by validating the radiative transfer modelled ARF with the CNR4 net radiometer measured values (r2 0.98). The Normalized Difference Vegetation Index and its dependence on the extinction of the photosynthetically active radiation (PAR) due to aerosol are assessed. The spring time enhancement of aerosols in the column has shown significant surface cooling (ARF = -48 ± 5 Wm-2) over the region, while the very high Black Carbon (BC) mass concentrations near the surface (SSA > 0.8) leads to significant atmospheric warming (ARF = +41 ± 7 Wm-2) in the shortwave range. Radiative forcing estimates reveal that the atmospheric forcing by BC could be as high as +30Wm-2 over the western part, which are significantly higher than the eastern part with a consequent heating rate of 1.5 K day-1 revealing an east-west asymmetry over NER. The impact of BC aerosols on the photosynthetic rate varies among different locations ranging from -5±2 Wm-2 to -25±3 Wm-2. Almost 70% of the total atmospheric shortwave radiative absorption is attributed to just 10% contribution of Black Carbon (BC) to total mass concentration and causes a reduction of more than 30% of PAR reaching the surface over Brahmaputra valley due to direct radiative effect. Comparison of previous and the present study shows highest surface dimming is observed in west-Asia followed by IGP and west-India. Surface radiative reduction over NER is comparable to south-India standing on the third place which is still higher than that of the Himalayan and Oceanic regions.

Operational Remote Sensing Services in North Eastern Region of India for Natural Resources Management, Early Warning for Disaster Risk Reduction and Dissemination of Information and Services

NASA Astrophysics Data System (ADS)

Raju, P. L. N.; Sarma, K. K.; Barman, D.; Handique, B. K.; Chutia, D.; Kundu, S. S.; Das, R. Kr.; Chakraborty, K.; Das, R.; Goswami, J.; Das, P.; Devi, H. S.; Nongkynrih, J. M.; Bhusan, K.; Singh, M. S.; Singh, P. S.; Saikhom, V.; Goswami, C.; Pebam, R.; Borgohain, A.; Gogoi, R. B.; Singh, N. R.; Bharali, A.; Sarma, D.; Lyngdoh, R. B.; Mandal, P. P.; Chabukdhara, M.

2016-06-01

North Eastern Region (NER) of India comprising of eight states considered to be most unique and one of the most challenging regions to govern due to its unique physiographic condition, rich biodiversity, disaster prone and diverse socio-economic characteristics. Operational Remote Sensing services increased manifolds in the region with the establishment of North Eastern Space Applications Centre (NESAC) in the year 2000. Since inception, NESAC has been providing remote sensing services in generating inventory, planning and developmental activities, and management of natural resources, disasters and dissemination of information and services through geo-web services for NER. The operational remote sensing services provided by NESAC can be broadly divided into three categories viz. natural resource planning and developmental services, disaster risk reduction and early warning services and information dissemination through geo-portal services. As a apart of natural resources planning and developmental services NESAC supports the state forest departments in preparing the forest working plans by providing geospatial inputs covering entire NER, identifying the suitable culturable wastelands for cultivation of silkworm food plants, mapping of natural resources such as land use/land cover, wastelands, land degradation etc. on temporal basis. In the area of disaster risk reduction, NESAC has initiated operational services for early warning and post disaster assessment inputs for flood early warning system (FLEWS) using satellite remote sensing, numerical weather prediction, hydrological modeling etc.; forest fire alert system with actionable attribute information; Japanese Encephalitis Early Warning System (JEWS) based on mosquito vector abundance, pig population and historical disease intensity and agriculture drought monitoring for the region. The large volumes of geo-spatial databases generated as part of operational services are made available to the administrators and local government bodies for better management, preparing prospective planning, and sustainable use of available resources. The knowledge dissemination is being done through online web portals wherever the internet access is available and as well as offline space based information kiosks, where the internet access is not available or having limited bandwidth availability. This paper presents a systematic and comprehensive study on the remote sensing services operational in NER of India for natural resources management, disaster risk reduction and dissemination of information and services, in addition to outlining future areas and direction of space applications for the region.

Data Type Registry - Cross Road Between Catalogs, Data And Semantics

NASA Astrophysics Data System (ADS)

Richard, S. M.; Zaslavsky, I.; Bristol, S.

2017-12-01

As more data become accessible online, the opportunity is increasing to improve search for information within datasets and for automating some levels of data integration. A prerequisite for these advances is indexing the kinds of information that are present in datasets and providing machine actionable descriptions of data structures. We are exploring approaches to enabling these capabilities in the EarthCube DigitalCrust and Data Discovery Hub Building Block projects, building on the Data type registry (DTR) workgroup activity in the Research Data Alliance. We are prototyping a registry implementation using the CNRI Cordra platform and API to enable 'deep registration' of datasets for building hydrogeologic models of the Earth's Crust, and executing complex science scenarios for river chemistry and coral bleaching data. These use cases require the ability to respond to queries such as: What are properties of Entity X; What entities include property Y (or L, M, N…), and What DataTypes are about Entity X and include property Y. Development of the registry to enable these capabilities requires more in-depth metadata than is commonly available, so we are also exploring approaches to analyzing simple tabular data to automate recognition of entities and properties, and assist users with establishing semantic mappings to data integration vocabularies. This poster will review the current capabilities and implementation of a data type registry.

Considering context: reliable entity networks through contextual relationship extraction

NASA Astrophysics Data System (ADS)

David, Peter; Hawes, Timothy; Hansen, Nichole; Nolan, James J.

2016-05-01

Existing information extraction techniques can only partially address the problem of exploiting unreadable-large amounts text. When discussion of events and relationships is limited to simple, past-tense, factual descriptions of events, current NLP-based systems can identify events and relationships and extract a limited amount of additional information. But the simple subset of available information that existing tools can extract from text is only useful to a small set of users and problems. Automated systems need to find and separate information based on what is threatened or planned to occur, has occurred in the past, or could potentially occur. We address the problem of advanced event and relationship extraction with our event and relationship attribute recognition system, which labels generic, planned, recurring, and potential events. The approach is based on a combination of new machine learning methods, novel linguistic features, and crowd-sourced labeling. The attribute labeler closes the gap between structured event and relationship models and the complicated and nuanced language that people use to describe them. Our operational-quality event and relationship attribute labeler enables Warfighters and analysts to more thoroughly exploit information in unstructured text. This is made possible through 1) More precise event and relationship interpretation, 2) More detailed information about extracted events and relationships, and 3) More reliable and informative entity networks that acknowledge the different attributes of entity-entity relationships.

Congenital brain infections.

PubMed

Arbelaez, Andres; Restrepo, Feliza; Davila, Jorge; Castillo, Mauricio

2014-06-01

Pediatric congenital intracranial infections are a group of different and important entities that constitute a small percentage of all pediatric infections. The causal factors and clinical presentations are different in children compared with adults. They require early recognition because delay diagnosis and initiation of treatment may have catastrophic consequences. Despite improvements in prenatal screening, vaccine safety, and antibiotics, infections of the central nervous system remain an important cause of neurological disabilities worldwide. This article reviews the most common congenital infections and their imaging findings.

Follicular variant of seborrheic dermatitis: is it identical to Malassezia folliculitis?

PubMed

Valentine, Mark C

2011-01-01

Follicular accentuation in some patients with seborrheic dermatitis of the back and chest has been recognized for more than a century. The recognition of Malassezia folliculitis in recent decades has led to some confusion regarding categorization of these cases. The author proposes that there is sufficient clinical variation between the typical case of Malassezia folliculitis and patients with follicular seborrheic dermatitis to justify continued separation of these entities until further study provides more clarification.

Discovering biomedical semantic relations in PubMed queries for information retrieval and database curation.

PubMed

Huang, Chung-Chi; Lu, Zhiyong

2016-01-01

Identifying relevant papers from the literature is a common task in biocuration. Most current biomedical literature search systems primarily rely on matching user keywords. Semantic search, on the other hand, seeks to improve search accuracy by understanding the entities and contextual relations in user keywords. However, past research has mostly focused on semantically identifying biological entities (e.g. chemicals, diseases and genes) with little effort on discovering semantic relations. In this work, we aim to discover biomedical semantic relations in PubMed queries in an automated and unsupervised fashion. Specifically, we focus on extracting and understanding the contextual information (or context patterns) that is used by PubMed users to represent semantic relations between entities such as 'CHEMICAL-1 compared to CHEMICAL-2' With the advances in automatic named entity recognition, we first tag entities in PubMed queries and then use tagged entities as knowledge to recognize pattern semantics. More specifically, we transform PubMed queries into context patterns involving participating entities, which are subsequently projected to latent topics via latent semantic analysis (LSA) to avoid the data sparseness and specificity issues. Finally, we mine semantically similar contextual patterns or semantic relations based on LSA topic distributions. Our two separate evaluation experiments of chemical-chemical (CC) and chemical-disease (CD) relations show that the proposed approach significantly outperforms a baseline method, which simply measures pattern semantics by similarity in participating entities. The highest performance achieved by our approach is nearly 0.9 and 0.85 respectively for the CC and CD task when compared against the ground truth in terms of normalized discounted cumulative gain (nDCG), a standard measure of ranking quality. These results suggest that our approach can effectively identify and return related semantic patterns in a ranked order covering diverse bio-entity relations. To assess the potential utility of our automated top-ranked patterns of a given relation in semantic search, we performed a pilot study on frequently sought semantic relations in PubMed and observed improved literature retrieval effectiveness based on post-hoc human relevance evaluation. Further investigation in larger tests and in real-world scenarios is warranted. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the US.

Intraosseous calcium migration in calcifying tendinitis: a rare cause of single sclerotic injury in the humeral head (2010: 2b).

PubMed

Martin, S; Rapariz, J M

2010-05-01

Intratendinous deposits of hydroxyapatite crystals are very common, particularly in the rotator cuff. In rare cases, the calcium located in the thickness of the supraspinatus tendon can suffer intraosseous migration into the greater tuberosity. We present a case of this rare entity: a 28-year-old patient who attended with pain and functional weakness in the left shoulder. The plain radiograph showed a sclerotic lesion in the greater tuberosity of the humeral head with a radiolucent halo. The MRI showed a lytic lesion containing the calcium inside and associated with an extensive pattern of oedema of the accompanying bone marrow. A plain radiograph taken 6 months before showed a calcifying tendinitis in the thickness of the supraspinatus tendon. A large number of entities can present as single sclerotic lesions of the humeral head. The diagnostic key lies in the existence of the calcifying tendinitis in the earlier study. The treatment of this disease consists of surgical removal of the calcium. The recognition of this entity is important to avoid unnecessary complementary tests and aggressive surgery, given that the surgical treatment is curative and leads to disappearance of the symptoms.

σ-Hole Bond vs π-Hole Bond: A Comparison Based on Halogen Bond.

PubMed

Wang, Hui; Wang, Weizhou; Jin, Wei Jun

2016-05-11

The σ-hole and π-hole are the regions with positive surface electrostatic potential on the molecule entity; the former specifically refers to the positive region of a molecular entity along extension of the Y-Ge/P/Se/X covalent σ-bond (Y = electron-rich group; Ge/P/Se/X = Groups IV-VII), while the latter refers to the positive region in the direction perpendicular to the σ-framework of the molecular entity. The directional noncovalent interactions between the σ-hole or π-hole and the negative or electron-rich sites are named σ-hole bond or π-hole bond, respectively. The contributions from electrostatic, charge transfer, and other terms or Coulombic interaction to the σ-hole bond and π-hole bond were reviewed first followed by a brief discussion on the interplay between the σ-hole bond and the π-hole bond as well as application of the two types of noncovalent interactions in the field of anion recognition. It is expected that this review could stimulate further development of the σ-hole bond and π-hole bond in theoretical exploration and practical application in the future.

Case Report: Diagnosis of a Rare Plaque-Like Dermal Fibroma Successfully Treated With Mohs Surgery.

PubMed

Gill, Pavandeep; Arlette, John; Shiau, Carolyn J; Abi Daoud, Marie S

CD34-positive plaque-like dermal fibroma (PDF) is a poorly characterised benign dermal neoplasm that has a wide differential diagnosis. It can be mistaken for other entities on superficial biopsy and be overtreated, leading to unnecessary worry and extensive surgery. To report on an uncommon presentation of this entity, the histopathologic differential diagnosis of PDF, and a novel treatment method. Clinical and histopathological information was obtained for a PDF lesion on a 75-year-old man. On superficial biopsy, the PDF lesion was misinterpreted as a possible neurothekeoma. Successful Mohs surgery and genetic testing confirmed the diagnosis of PDF, and the patient received appropriate tissue-sparing surgical management. This case adds to our current knowledge about PDF and highlights the importance of early recognition of these lesions to direct appropriate diagnostic testing (full-thickness biopsy) and management. This case confirms successful management with Mohs surgery.

Building Structured Personal Health Records from Photographs of Printed Medical Records.

PubMed

Li, Xiang; Hu, Gang; Teng, Xiaofei; Xie, Guotong

2015-01-01

Personal health records (PHRs) provide patient-centric healthcare by making health records accessible to patients. In China, it is very difficult for individuals to access electronic health records. Instead, individuals can easily obtain the printed copies of their own medical records, such as prescriptions and lab test reports, from hospitals. In this paper, we propose a practical approach to extract structured data from printed medical records photographed by mobile phones. An optical character recognition (OCR) pipeline is performed to recognize text in a document photo, which addresses the problems of low image quality and content complexity by image pre-processing and multiple OCR engine synthesis. A series of annotation algorithms that support flexible layouts are then used to identify the document type, entities of interest, and entity correlations, from which a structured PHR document is built. The proposed approach was applied to real world medical records to demonstrate the effectiveness and applicability.

Building Structured Personal Health Records from Photographs of Printed Medical Records

PubMed Central

Li, Xiang; Hu, Gang; Teng, Xiaofei; Xie, Guotong

2015-01-01

Personal health records (PHRs) provide patient-centric healthcare by making health records accessible to patients. In China, it is very difficult for individuals to access electronic health records. Instead, individuals can easily obtain the printed copies of their own medical records, such as prescriptions and lab test reports, from hospitals. In this paper, we propose a practical approach to extract structured data from printed medical records photographed by mobile phones. An optical character recognition (OCR) pipeline is performed to recognize text in a document photo, which addresses the problems of low image quality and content complexity by image pre-processing and multiple OCR engine synthesis. A series of annotation algorithms that support flexible layouts are then used to identify the document type, entities of interest, and entity correlations, from which a structured PHR document is built. The proposed approach was applied to real world medical records to demonstrate the effectiveness and applicability. PMID:26958219

Gene/protein name recognition based on support vector machine using dictionary as features.

PubMed

Mitsumori, Tomohiro; Fation, Sevrani; Murata, Masaki; Doi, Kouichi; Doi, Hirohumi

2005-01-01

Automated information extraction from biomedical literature is important because a vast amount of biomedical literature has been published. Recognition of the biomedical named entities is the first step in information extraction. We developed an automated recognition system based on the SVM algorithm and evaluated it in Task 1.A of BioCreAtIvE, a competition for automated gene/protein name recognition. In the work presented here, our recognition system uses the feature set of the word, the part-of-speech (POS), the orthography, the prefix, the suffix, and the preceding class. We call these features "internal resource features", i.e., features that can be found in the training data. Additionally, we consider the features of matching against dictionaries to be external resource features. We investigated and evaluated the effect of these features as well as the effect of tuning the parameters of the SVM algorithm. We found that the dictionary matching features contributed slightly to the improvement in the performance of the f-score. We attribute this to the possibility that the dictionary matching features might overlap with other features in the current multiple feature setting. During SVM learning, each feature alone had a marginally positive effect on system performance. This supports the fact that the SVM algorithm is robust on the high dimensionality of the feature vector space and means that feature selection is not required.

Naming and recognizing famous faces in temporal lobe epilepsy.

PubMed

Glosser, G; Salvucci, A E; Chiaravalloti, N D

2003-07-08

To assess naming and recognition of faces of familiar famous people in patients with epilepsy before and after anterior temporal lobectomy (ATL). Color photographs of famous people were presented for naming and description to 63 patients with temporal lobe epilepsy (TLE) either before or after ATL and to 10 healthy age- and education-matched controls. Spontaneous naming of photographed famous people was impaired in all patient groups, but was most abnormal in patients who had undergone left ATL. When allowed to demonstrate knowledge of the famous faces through verbal descriptions, rather than naming, patients with left TLE, left ATL, and right TLE improved to normal levels, but patients with right ATL were still impaired, suggesting a new deficit in identifying famous faces. Naming of famous people was related to naming of other common objects, verbal memory, and perceptual discrimination of faces. Recognition of the identity of pictured famous people was more related to visuospatial perception and memory. Lesions in anterior regions of the right temporal lobe impair recognition of the identities of familiar faces, as well as the learning of new faces. Lesions in the left temporal lobe, especially in anterior regions, disrupt access to the names of known people, but do not affect recognition of the identities of famous faces. Results are consistent with the hypothesized role of lateralized anterior temporal lobe structures in facial recognition and naming of unique entities.

Estimating decades-long trends in petroleum field energy return on investment (EROI) with an engineering-based model.

PubMed

Tripathi, Vinay S; Brandt, Adam R

2017-01-01

This paper estimates changes in the energy return on investment (EROI) for five large petroleum fields over time using the Oil Production Greenhouse Gas Emissions Estimator (OPGEE). The modeled fields include Cantarell (Mexico), Forties (U.K.), Midway-Sunset (U.S.), Prudhoe Bay (U.S.), and Wilmington (U.S.). Data on field properties and production/processing parameters were obtained from a combination of government and technical literature sources. Key areas of uncertainty include details of the oil and gas surface processing schemes. We aim to explore how long-term trends in depletion at major petroleum fields change the effective energetic productivity of petroleum extraction. Four EROI ratios are estimated for each field as follows: The net energy ratio (NER) and external energy ratio (EER) are calculated, each using two measures of energy outputs, (1) oil-only and (2) all energy outputs. In all cases, engineering estimates of inputs are used rather than expenditure-based estimates (including off-site indirect energy use and embodied energy). All fields display significant declines in NER over the modeling period driven by a combination of (1) reduced petroleum production and (2) increased energy expenditures on recovery methods such as the injection of water, steam, or gas. The fields studied had NER reductions ranging from 46% to 88% over the modeling periods (accounting for all energy outputs). The reasons for declines in EROI differ by field. Midway-Sunset experienced a 5-fold increase in steam injected per barrel of oil produced. In contrast, Prudhoe Bay has experienced nearly a 30-fold increase in amount of gas processed and reinjected per unit of oil produced. In contrast, EER estimates are subject to greater variability and uncertainty due to the relatively small magnitude of external energy investments in most cases.

Lifecycle assessment of microalgae to biofuel: Comparison of thermochemical processing pathways

DOE PAGES

Bennion, Edward P.; Ginosar, Daniel M.; Moses, John; ...

2015-01-16

Microalgae are currently being investigated as a renewable transportation fuel feedstock based on various advantages that include high annual yields, utilization of poor quality land, does not compete with food, and can be integrated with various waste streams. This study focuses on directly assessing the impact of two different thermochemical conversion technologies on the microalgae to biofuel process through life cycle assessment. A system boundary of a “well to pump” (WTP) is defined and includes sub-process models of the growth, dewatering, thermochemical bio-oil recovery, bio-oil stabilization, conversion to renewable diesel, and transport to the pump. Models were validated with experimentalmore » and literature data and are representative of an industrial-scale microalgae to biofuel process. Two different thermochemical bio-oil conversion systems are modeled and compared on a systems level, hydrothermal liquefaction (HTL) and pyrolysis. The environmental impact of the two pathways were quantified on the metrics of net energy ratio (NER), defined here as energy consumed over energy produced, and greenhouse gas (GHG) emissions. Results for WTP biofuel production through the HTL pathway were determined to be 1.23 for the NER and GHG emissions of -11.4 g CO 2-eq (MJ renewable diesel) -1. WTP biofuel production through the pyrolysis pathway results in a NER of 2.27 and GHG emissions of 210 g CO2 eq (MJ renewable diesel)-1. The large environmental impact associated with the pyrolysis pathway is attributed to feedstock drying requirements and combustion of co-products to improve system energetics. Discussion focuses on a detailed breakdown of the overall process energetics and GHGs, impact of modeling at laboratory- scale compared to industrial-scale, environmental impact sensitivity to engineering systems input parameters for future focused research and development and a comparison of results to literature.« less

Evidence for a repair enzyme complex involving ERCC1 and complementing activities of ERCC4, ERCC11 and xeroderma pigmentosum group F.

PubMed Central

van Vuuren, A J; Appeldoorn, E; Odijk, H; Yasui, A; Jaspers, N G; Bootsma, D; Hoeijmakers, J H

1993-01-01

Nucleotide excision repair (NER), one of the major cellular DNA repair systems, removes a wide range of lesions in a multi-enzyme reaction. In man, a NER defect due to a mutation in one of at least 11 distinct genes, can give rise to the inherited repair disorders xeroderma pigmentosum (XP), Cockayne's syndrome or PIBIDS, a photosensitive form of the brittle hair disease trichothiodystrophy. Laboratory-induced NER-deficient mutants of cultured rodent cells have been classified into 11 complementation groups (CGs). Some of these have been shown to correspond with human disorders. In cell-free extracts prepared from rodent CGs 1-5 and 11, but not in a mutant from CG6, we find an impaired repair of damage induced in plasmids by UV light and N-acetoxy-acetylaminofluorene. Complementation analysis in vitro of rodent CGs is accomplished by pairwise mixing of mutant extracts. The results show that mutants from groups 2, 3, 5 and XP-A can complement all other CGs tested. However, selective non-complementation in vitro was observed in mutual mixtures of groups 1, 4, 11 and XP-F, suggesting that the complementing activities involved somehow affect each other. Depletion of wild-type human extracts from ERCC1 protein using specific anti-ERCC1 antibodies concomitantly removed the correcting activities for groups 4, 11 and XP-F, but not those for the other CGs. Furthermore, we find that 33 kDa ERCC1 protein sediments as a high mol. wt species of approximately 120 kDa in a native glycerol gradient.(ABSTRACT TRUNCATED AT 250 WORDS) Images PMID:8253091

Transcriptional consequences of XPA disruption in human cell lines

PubMed Central

Manandhar, Mandira; Lowery, Megan G.; Boulware, Karen S.; Lin, Kevin H.; Lu, Yue; Wood, Richard D.

2017-01-01

Nucleotide excision repair (NER) in mammalian cells requires the xeroderma pigmentosum group A protein (XPA) as a core factor. Remarkably, XPA and other NER proteins have been detected by chromatin immunoprecipitation at some active promoters, and NER deficiency is reported to influence the activated transcription of selected genes. However, the global influence of XPA on transcription in human cells has not been determined. We analyzed the human transcriptome by RNA sequencing (RNA-Seq). We first confirmed that XPA is confined to the cell nucleus even in the absence of external DNA damage, in contrast to previous reports that XPA is normally resident in the cytoplasm and is imported following DNA damage. We then analyzed four genetically matched human cell line pairs deficient or proficient in XPA. Of the ∼14,000 genes transcribed in each cell line, 325 genes (2%) had a significant XPA-dependent directional change in gene expression that was common to all four pairs (with a false discovery rate of 0.05). These genes were enriched in pathways for the maintenance of mitochondria. Only 27 common genes were different by more than 1.5-fold. The most significant hits were AKR1C1 and AKR1C2, involved in steroid hormone metabolism. AKR1C2 protein was lower in all of the immortalized XPA-deficient cells. Retinoic acid treatment led to modest XPA-dependent activation of some genes with transcription-related functions. We conclude that XPA status does not globally influence human gene transcription. However, XPA significantly influences expression of a small subset of genes important for mitochondrial functions and steroid hormone metabolism. The results may help explain defects in neurological function and sterility in individuals with xeroderma pigmentosum. PMID:28704716

Phosphorylation of Nucleotide Excision Repair Factor Xeroderma Pigmentosum Group A by Ataxia Telangiectasia Mutated and Rad3-Related-Dependent Checkpoint Pathway Promotes Cell Survival in Response to UV Irradiation

PubMed Central

Wu, Xiaoming; Shell, Steven M.; Yang, Zhengguan; Zou, Yue

2006-01-01

DNA damage triggers complex cellular responses in eukaryotic cells, including initiation of DNA repair and activation of cell cycle checkpoints. In addition to inducing cell cycle arrest, checkpoint also has been suggested to modulate a variety of other cellular processes in response to DNA damage. In this study, we present evidence showing that the cellular function of xeroderma pigmentosum group A (XPA), a major nucleotide excision repair (NER) factor, could be modulated by checkpoint kinase ataxia-telangiectasia mutated and Rad3-related (ATR) in response to UV irradiation. We observed the apparent interaction and colocalization of XPA with ATR in response to UV irradiation. We showed that XPA was a substrate for in vitro phosphorylation by phosphatidylinositol-3-kinase-related kinase family kinases whereas in cells XPA was phosphorylated in an ATR-dependent manner and stimulated by UV irradiation. The Ser196 of XPA was identified as a biologically significant residue to be phosphorylated in vivo. The XPA-deficient cells complemented with XPA-S196A mutant, in which Ser196 was substituted with an alanine, displayed significantly higher UV sensitivity compared with the XPA cells complemented with wild-type XPA. Moreover, substitution of Ser196 with aspartic acid for mimicking the phosphorylation of XPA increased the cell survival to UV irradiation. Taken together, our results revealed a potential physical and functional link between NER and the ATR-dependent checkpoint pathway in human cells and suggested that the ATR checkpoint pathway could modulate the cellular activity of NER through phosphorylation of XPA at Ser196 on UV irradiation. PMID:16540648

Estimating decades-long trends in petroleum field energy return on investment (EROI) with an engineering-based model

PubMed Central

Tripathi, Vinay S.

2017-01-01

This paper estimates changes in the energy return on investment (EROI) for five large petroleum fields over time using the Oil Production Greenhouse Gas Emissions Estimator (OPGEE). The modeled fields include Cantarell (Mexico), Forties (U.K.), Midway-Sunset (U.S.), Prudhoe Bay (U.S.), and Wilmington (U.S.). Data on field properties and production/processing parameters were obtained from a combination of government and technical literature sources. Key areas of uncertainty include details of the oil and gas surface processing schemes. We aim to explore how long-term trends in depletion at major petroleum fields change the effective energetic productivity of petroleum extraction. Four EROI ratios are estimated for each field as follows: The net energy ratio (NER) and external energy ratio (EER) are calculated, each using two measures of energy outputs, (1) oil-only and (2) all energy outputs. In all cases, engineering estimates of inputs are used rather than expenditure-based estimates (including off-site indirect energy use and embodied energy). All fields display significant declines in NER over the modeling period driven by a combination of (1) reduced petroleum production and (2) increased energy expenditures on recovery methods such as the injection of water, steam, or gas. The fields studied had NER reductions ranging from 46% to 88% over the modeling periods (accounting for all energy outputs). The reasons for declines in EROI differ by field. Midway-Sunset experienced a 5-fold increase in steam injected per barrel of oil produced. In contrast, Prudhoe Bay has experienced nearly a 30-fold increase in amount of gas processed and reinjected per unit of oil produced. In contrast, EER estimates are subject to greater variability and uncertainty due to the relatively small magnitude of external energy investments in most cases. PMID:28178318

A novel XPD mutation in a compound heterozygote; the mutation in the second allele is present in three homozygous patients with mild sun sensitivity.

PubMed

Falik-Zaccai, Tzipora C; Erel-Segal, Reut; Horev, Liran; Bitterman-Deutsch, Ora; Koka, Sivan; Chaim, Sara; Keren, Zohar; Kalfon, Limor; Gross, Bella; Segal, Zvi; Orgal, Shlomi; Shoval, Yishay; Slor, Hanoch; Spivak, Graciela; Hanawalt, Philip C

2012-08-01

The XPD protein plays a pivotal role in basal transcription and in nucleotide excision repair (NER) as one of the ten known components of the transcription factor TFIIH. Mutations in XPD can result in the DNA repair-deficient diseases xeroderma pigmentosum (XP), trichothiodystrophy (TTD), cerebro-oculo-facial-skeletal syndrome, and in combined phenotypes such as XP/Cockayne syndrome and XP/TTD. We describe here an 18-year-old individual with mild sun sensitivity, no neurological abnormalities and no tumors, who carries a p.R683Q mutation in one allele, and the novel p.R616Q mutation in the other allele of the XPD gene. We also describe four patients from one family, homozygous for the identical p.R683Q mutation in XPD, who exhibit mild skin pigmentation and loss of tendon reflexes. Three homozygous patients presented with late-onset skin tumors, and two with features of premature aging and moderate cognitive decline. Cells from the compound heterozygous individual and from one of the patients homozygous for p.R683Q exhibited similar responses to UV irradiation: reduced viability and defective overall removal of UV-induced cyclobutane pyrimidine dimers, implying deficient global genomic NER. Cells from the compound heterozygous subject also failed to recover RNA synthesis after UV, indicating defective transcription-coupled NER. Mutations affecting codon 616 in XPD generally result in functionally null proteins; we hypothesize that the phenotype of the heterozygous patient results solely from expression of the p.R683Q allele. This study illustrates the importance of detailed follow up with sun sensitive individuals, to ensure appropriate prophylaxis and to understand the mechanistic basis of the implicated hereditary disease. Copyright © 2012 Wiley Periodicals, Inc.

Life cycle assessment of microalgae to biofuel: Thermochemical processing through hydrothermal liquefaction or pyrolysis

NASA Astrophysics Data System (ADS)

Bennion, Edward P.

Microalgae are currently being investigated as a renewable transportation fuel feedstock based on various advantages that include high annual yields, utilization of poor quality land, does not compete with food, and can be integrated with various waste streams. This study focuses on directly assessing the impact of two different thermochemical conversion technologies on the microalgae-to-biofuel process through life cycle assessment. A system boundary of a "well to pump" (WTP) is defined and includes sub-process models of the growth, dewatering, thermochemical bio-oil recovery, bio-oil stabilization, conversion to renewable diesel, and transport to the pump. Models were validated with experimental and literature data and are representative of an industrial-scale microalgae-to-biofuel process. Two different thermochemical bio-oil conversion systems are modeled and compared on a systems level, hydrothermal liquefaction (HTL) and pyrolysis. The environmental impact of the two pathways were quantified on the metrics of net energy ratio (NER), defined here as energy consumed over energy produced, and greenhouse gas (GHG) emissions. Results for WTP biofuel production through the HTL pathway were determined to be 1.23 for the NER and GHG emissions of -11.4 g CO2 eq (MJ renewable diesel)-1. WTP biofuel production through the pyrolysis pathway results in a NER of 2.27 and GHG emissions of 210 g CO2 eq (MJ renewable diesel)-1. The large environmental impact associated with the pyrolysis pathway is attributed to feedstock drying requirements and combustion of co-products to improve system energetics. Discussion focuses on a detailed breakdown of the overall process energetics and GHGs, impact of modeling at laboratory-scale compared to industrial-scale, environmental impact sensitivity to engineering systems input parameters for future focused research and development, and a comparison of results to literature.

Effect of Crumb Rubber and Warm Mix Additives on Asphalt Aging, Rheological, and Failure Properties

NASA Astrophysics Data System (ADS)

Agrawal, Prashant

Asphalt-rubber mixtures have been shown to have useful properties with respect to distresses observed in asphalt concrete pavements. The most notable change in properties is a large increase in viscosity and improved low-temperature cracking resistance. Warm mix additives can lower production and compaction temperatures. Lower temperatures reduce harmful emissions and lower energy consumption, and thus provide environmental benefits and cut costs. In this study, the effects of crumb rubber modification on various asphalts such as California Valley, Boscan, Alaska North Slope, Laguna and Cold Lake were also studied. The materials used for warm mix modification were obtained from various commercial sources. The RAF binder was produced by Imperial Oil in their Nanticoke, Ontario, refinery on Lake Erie. A second commercial PG 52-34 (hereafter denoted as NER) was obtained/sampled during the construction of a northern Ontario MTO contract. Some regular tests such as Dynamic Shear Rheometer (DSR) and Bending Beam Rheometer (BBR), Multiple Stress Creep Recovery (MSCR) and some modified new protocols such as the extended BBR test (LS-308) and the Double-Edge Notched Tension (DENT) test (LS-299) are used to study, the effect of warm mix and a host of other additives on rheological, aging and failure properties. A comparison in the properties of RAF and NER asphalts has also been made as RAF is good quality asphalt and NER is bad quality asphalt. From the studies the effect of additives on chemical and physical hardening tendencies was found to be significant. The asphalt samples tested in this study showed a range of tendencies for chemical and physical hardening.

Xeroderma pigmentosum genes and melanoma risk.

PubMed

Paszkowska-Szczur, K; Scott, R J; Serrano-Fernandez, P; Mirecka, A; Gapska, P; Górski, B; Cybulski, C; Maleszka, R; Sulikowski, M; Nagay, L; Lubinski, J; Dębniak, T

2013-09-01

Xeroderma pigmentosum is a rare autosomal recessive disease that is associated with a severe deficiency in nucleotide excision repair. The presence of a distinct the nucleotide excision repair (NER) mutation signature in melanoma suggests that perturbations in this critical repair process are likely to be involved with disease risk. We hypothesized that persons with polymorphic NER gene(s) are likely to have reduced NER activity and are consequently at an increased risk of melanoma development. We assessed the association between 94 SNPs within seven XP genes (XPA-XPG) and the melanoma risk in the Polish population. We genotyped 714 unselected melanoma patients and 1,841 healthy adults to determine if there were any polymorphisms differentially represented in the disease group. We found that a significantly decreased risk of melanoma was associated with the Xeroderma pigmentosum complementation (XPC) rs2228000_CT genotype (odds ratio [OR] = 0.15; p < 0.001) and the rs2228000_TT genotype (OR = 0.11; p < 0.001) compared to the reference genotype. Haplotype analysis within XPC revealed the rs2228001_A + G1475A_G + G2061A_A + rs2228000_T + rs3731062_C haplotype (OR = 0.26; p < 0.05) was associated with a significantly decreased disease risk. The haplotype analysis within the Xeroderma pigmentosum group D (XPD) showed a modest association between two haplotypes and a decrease in melanoma risk. There were no major differences between the prevalence of the XP polymorphisms among young or older patients with melanoma. Linkage disequilibrium of XPC: rs2228001, G1475A, G2061A, rs2228000 and rs3731062 was found. The data from our study support the notion that only XPC and XPD genes are associated with melanoma susceptibility. Copyright © 2013 UICC.

Effect of pyrochar and hydrochar amendments on the mineralization of the herbicide isoproturon in an agricultural soil.

PubMed

Eibisch, Nina; Schroll, Reiner; Fuß, Roland

2015-09-01

Carbon (C)-rich, solid products from pyrolysis (pyrochars) and hydrothermal carbonization (HTC, hydrochars) are expected to reduce the bioavailability and bioaccessibility of pesticides as side effect of soil addition. To compare effects of different feedstocks (digestate, miscanthus, woodchips) and production processes (pyrolysis at 750°C, HTC at 200°C and 250°C), (14)C-labeled isoproturon (IPU) was applied at 0.75 kg ha(-)(1) to loamy sand amended either with 0.5% or 5% pyrochars or hydrochars, which was then incubated for 50d. Mineralization of IPU was measured as (14)C-CO2 released from soil-char composites. Pore-water and methanol extractable (14)C-IPU was quantified as well as non-extractable (14)C-residues (NER). Furthermore, C mineralization of pyrochars, hydrochars and feedstocks was studied to assess the relationship between IPU bioaccessibility and char decomposability. In pure soil, 8.1% of applied IPU was mineralized after 50d. This was reduced more strongly in pyrochar treatments (81 ± 6% reduction) than in hydrochar treatments (56 ± 25% reduction). Different feedstocks had no significantly different effect when 5% char was added, but their effect was significant and dependent on the production process in 0.5% amendments. Pesticide binding can occur by surface sorption as well as by diffusion and subsequent occlusion in micropores. The latter can be expected to result in high amounts of NER, as it was observed in the pyrochar treatments. Hydrochars were less stable than pyrochars and contained lower amounts of NER. Thus, in hydrochar amended soils, better accessibility of IPU to microbial degradation may be a result of full char decomposition within decades ensuring controlled pesticide degradation. Copyright © 2014 Elsevier Ltd. All rights reserved.

A CRF-based system for recognizing chemical entity mentions (CEMs) in biomedical literature

PubMed Central

2015-01-01

Background In order to improve information access on chemical compounds and drugs (chemical entities) described in text repositories, it is very crucial to be able to identify chemical entity mentions (CEMs) automatically within text. The CHEMDNER challenge in BioCreative IV was specially designed to promote the implementation of corresponding systems that are able to detect mentions of chemical compounds and drugs, which has two subtasks: CDI (Chemical Document Indexing) and CEM. Results Our system processing pipeline consists of three major components: pre-processing (sentence detection, tokenization), recognition (CRF-based approach), and post-processing (rule-based approach and format conversion). In our post-challenge system, the cost parameter in CRF model was optimized by 10-fold cross validation with grid search, and word representations feature induced by Brown clustering method was introduced. For the CEM subtask, our official runs were ranked in top position by obtaining maximum 88.79% precision, 69.08% recall and 77.70% balanced F-measure, which were improved further to 88.43% precision, 76.48% recall and 82.02% balanced F-measure in our post-challenge system. Conclusions In our system, instead of extracting a CEM as a whole, we regarded it as a sequence labeling problem. Though our current system has much room for improvement, our system is valuable in showing that the performance in term of balanced F-measure can be improved largely by utilizing large amounts of relatively inexpensive un-annotated PubMed abstracts and optimizing the cost parameter in CRF model. From our practice and lessons, if one directly utilizes some open-source natural language processing (NLP) toolkits, such as OpenNLP, Standford CoreNLP, false positive (FP) rate may be very high. It is better to develop some additional rules to minimize the FP rate if one does not want to re-train the related models. Our CEM recognition system is available at: http://www.SciTeMiner.org/XuShuo/Demo/CEM. PMID:25810768

Synthetic approaches to the 2014 new drugs.

PubMed

Flick, Andrew C; Ding, Hong X; Leverett, Carolyn A; Kyne, Robert E; Liu, Kevin K-C; Fink, Sarah J; O'Donnell, Christopher J

2016-05-01

New drugs introduced to the market every year represent privileged structures for particular biological targets. These new chemical entities (NCEs) provide insight into molecular recognition and also serve as leads for designing future new drugs. This annual review covers the synthesis of thirty-seven NCEs that were approved for the first time in 2014 and one drug which was approved in 2013 and was not covered in a previous edition of this review. Copyright © 2016 Elsevier Ltd. All rights reserved.

Majestic C Team, LLC - Clean Water Act Public Notice

EPA Pesticide Factsheets

The EPA is providing notice of a proposed Administrative Penalty Assessment against Majestic C Team, LLC., which owns a residential construction site located at 168th St and State St in Omaha, NE for alleged violations of its NPDES permit (permit No. NER11

Melanocortin 1 Receptor: Structure, Function, and Regulation

PubMed Central

Wolf Horrell, Erin M.; Boulanger, Mary C.; D’Orazio, John A.

2016-01-01

The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair (NER), the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts NER. PMID:27303435

Lossless compression of AVIRIS data: Comparison of methods and instrument constraints

NASA Technical Reports Server (NTRS)

Roger, R. E.; Arnold, J. F.; Cavenor, M. C.; Richards, J. A.

1992-01-01

A family of lossless compression methods, allowing exact image reconstruction, are evaluated for compressing Airborne Visible/Infrared Imaging Spectrometers (AVIRIS) image data. The methods are used on Differential Pulse Code Modulation (DPCM). The compressed data have an entropy of order 6 bits/pixel. A theoretical model indicates that significantly better lossless compression is unlikely to be achieved because of limits caused by the noise in the AVIRIS channels. AVIRIS data differ from data produced by other visible/near-infrared sensors, such as LANDSAT-TM or SPOT, in several ways. Firstly, the data are recorded at a greater resolution (12 bits, though packed into 16-bit words). Secondly, the spectral channels are relatively narrow and provide continuous coverage of the spectrum so that the data in adjacent channels are generally highly correlated. Thirdly, the noise characteristics of the AVIRIS are defined by the channels' Noise Equivalent Radiances (NER's), and these NER's show that, at some wavelengths, the least significant 5 or 6 bits of data are essentially noise.

Xeroderma pigmentosum and other diseases of human premature aging and DNA repair: Molecules to patients

PubMed Central

Niedernhofer, Laura J.; Bohr, Vilhelm A.; Sander, Miriam; Kraemer, Kenneth H.

2012-01-01

A workshop1 to share, consider and discuss the latest developments in understanding xeroderma pigmentosum and other human diseases caused by defects in nucleotide excision repair (NER) of DNA damage was held on September 21–24, 2010 in Virginia. It was attended by approximately 100 researchers and clinicians, as well as several patients and representatives of patient support groups. This was the third in a series of workshops with similar design and goals: to emphasize discussion and interaction among participants as well as open exchange of information and ideas. The participation of patients, their parents and physicians was an important feature of this and the preceding two workshops. Topics discussed included the natural history and clinical features of the diseases, clinical and laboratory diagnosis of these rare diseases, therapeutic strategies, mouse models of neurodegeneration, molecular analysis of accelerated aging, impact of transcriptional defects and mitochondrial dysfunction on neurodegeneration, and biochemical insights into mechanisms of NER and base excision repair. PMID:21708183

Mediator MED23 Links Pigmentation and DNA Repair through the Transcription Factor MITF.

PubMed

Xia, Min; Chen, Kun; Yao, Xiao; Xu, Yichi; Yao, Jiaying; Yan, Jun; Shao, Zhen; Wang, Gang

2017-08-22

DNA repair is related to many physiological and pathological processes, including pigmentation. Little is known about the role of the transcriptional cofactor Mediator complex in DNA repair and pigmentation. Here, we demonstrate that Mediator MED23 plays an important role in coupling UV-induced DNA repair to pigmentation. The loss of Med23 specifically impairs the pigmentation process in melanocyte-lineage cells and in zebrafish. Med23 deficiency leads to enhanced nucleotide excision repair (NER) and less DNA damage following UV radiation because of the enhanced expression and recruitment of NER factors to chromatin for genomic stability. Integrative analyses of melanoma cells reveal that MED23 controls the expression of a melanocyte master regulator, Mitf, by modulating its distal enhancer activity, leading to opposing effects on pigmentation and DNA repair. Collectively, the Mediator MED23/MITF axis connects DNA repair to pigmentation, thus providing molecular insights into the DNA damage response and skin-related diseases. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Inefficient DNA Repair Is an Aging-Related Modifier of Parkinson's Disease.

PubMed

Sepe, Sara; Milanese, Chiara; Gabriels, Sylvia; Derks, Kasper W J; Payan-Gomez, Cesar; van IJcken, Wilfred F J; Rijksen, Yvonne M A; Nigg, Alex L; Moreno, Sandra; Cerri, Silvia; Blandini, Fabio; Hoeijmakers, Jan H J; Mastroberardino, Pier G

2016-05-31

The underlying relation between Parkinson's disease (PD) etiopathology and its major risk factor, aging, is largely unknown. In light of the causative link between genome stability and aging, we investigate a possible nexus between DNA damage accumulation, aging, and PD by assessing aging-related DNA repair pathways in laboratory animal models and humans. We demonstrate that dermal fibroblasts from PD patients display flawed nucleotide excision repair (NER) capacity and that Ercc1 mutant mice with mildly compromised NER exhibit typical PD-like pathological alterations, including decreased striatal dopaminergic innervation, increased phospho-synuclein levels, and defects in mitochondrial respiration. Ercc1 mouse mutants are also more sensitive to the prototypical PD toxin MPTP, and their transcriptomic landscape shares important similarities with that of PD patients. Our results demonstrate that specific defects in DNA repair impact the dopaminergic system and are associated with human PD pathology and might therefore constitute an age-related risk factor for PD. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

DNA Damage Induced by Alkylating Agents and Repair Pathways

PubMed Central

Kondo, Natsuko; Takahashi, Akihisa; Ono, Koji; Ohnishi, Takeo

2010-01-01

The cytotoxic effects of alkylating agents are strongly attenuated by cellular DNA repair processes, necessitating a clear understanding of the repair mechanisms. Simple methylating agents form adducts at N- and O-atoms. N-methylations are removed by base excision repair, AlkB homologues, or nucleotide excision repair (NER). O6-methylguanine (MeG), which can eventually become cytotoxic and mutagenic, is repaired by O6-methylguanine-DNA methyltransferase, and O6MeG:T mispairs are recognized by the mismatch repair system (MMR). MMR cannot repair the O6MeG/T mispairs, which eventually lead to double-strand breaks. Bifunctional alkylating agents form interstrand cross-links (ICLs) which are more complex and highly cytotoxic. ICLs are repaired by complex of NER factors (e.g., endnuclease xeroderma pigmentosum complementation group F-excision repair cross-complementing rodent repair deficiency complementation group 1), Fanconi anemia repair, and homologous recombination. A detailed understanding of how cells cope with DNA damage caused by alkylating agents is therefore potentially useful in clinical medicine. PMID:21113301

On certain development aspects of an ipsas-based system-target approach to evaluation of net asset sustainability level projects in high-rise construction

NASA Astrophysics Data System (ADS)

Kazaryan, Ruben

2018-03-01

Problems of accounting and reporting of net assets and the procedure of their formation taking into account the specifics of the economic and legal status of property of a non-commercial autonomous institution are some of the most controversial in the accounting for entities of the public sector. The study focuses on justification of accounting rules for net assets of public sector entities. The methods used in the study are as follows: comparison, synthesis, analysis, logical approach, and system approach. The article examines legal aspects and specifics of recognition of assets of public sector entities in accordance with IPSAS standards (International Public Sector Accounting Standards are a set of accounting standards issued by IPSASB (Council for International Financial Reporting Standards for Public Sector Organizations) used by state-owned enterprises worldwide in preparation of financial statements as of the 31st of August, 2015. The most crucial factor in the modeling of key performance indicators of the system-target approach to estimation of the sustainability level of net assets on the basis of IPSAS is a multicriterial evaluation of the basic management strategy for quality system elements used in operational and strategic planning projects operations in high-rise construction. We offer an alternative evaluation of assets due to be returned to the right holder (the state controller) in the event of liquidation of a public sector entity.

The Use of NMR to Study Transient Carbohydrate-Protein Interactions.

PubMed

Nieto, Pedro M

2018-01-01

Carbohydrates are biologically ubiquitous and are essential to the existence of all known living organisms. Although they are better known for their role as energy sources (glucose/glycogen or starch) or structural elements (chitin or cellulose), carbohydrates also participate in the recognition events of molecular recognition processes. Such interactions with other biomolecules (nucleic acids, proteins, and lipids) are fundamental to life and disease. This review focuses on the application of NMR methods to understand at the atomic level the mechanisms by which sugar molecules can be recognized by proteins to form complexes, creating new entities with different properties to those of the individual component molecules. These processes have recently gained attention as new techniques have been developed, while at the same time old techniques have been reinvented and adapted to address newer emerging problems.

Handwritten-word spotting using biologically inspired features.

PubMed

van der Zant, Tijn; Schomaker, Lambert; Haak, Koen

2008-11-01

For quick access to new handwritten collections, current handwriting recognition methods are too cumbersome. They cannot deal with the lack of labeled data and would require extensive laboratory training for each individual script, style, language and collection. We propose a biologically inspired whole-word recognition method which is used to incrementally elicit word labels in a live, web-based annotation system, named Monk. Since human labor should be minimized given the massive amount of image data, it becomes important to rely on robust perceptual mechanisms in the machine. Recent computational models of the neuro-physiology of vision are applied to isolated word classification. A primate cortex-like mechanism allows to classify text-images that have a low frequency of occurrence. Typically these images are the most difficult to retrieve and often contain named entities and are regarded as the most important to people. Usually standard pattern-recognition technology cannot deal with these text-images if there are not enough labeled instances. The results of this retrieval system are compared to normalized word-image matching and appear to be very promising.

Associated impairment of the categories of conspecifics and biological entities: cognitive and neuroanatomical aspects of a new case.

PubMed

Capitani, Erminio; Chieppa, Francesca; Laiacona, Marcella

2010-05-01

Case A.C.A. presented an associated impairment of visual recognition and semantic knowledge for celebrities and biological objects. This case was relevant for (a) the neuroanatomical correlations, and (b) the relationship between visual recognition and semantics within the biological domain and the conspecifics domain. A.C.A. was not affected by anterior temporal damage. Her bilateral vascular lesions were localized on the medial and inferior temporal gyrus on the right and on the intermediate fusiform gyrus on the left, without concomitant lesions of the parahippocampal gyrus or posterior fusiform. Data analysis was based on a novel methodology developed to estimate the rate of stored items in the visual structural description system (SDS) or in the face recognition unit. For each biological object, no particular correlation was found between the visual information accessed through the semantic system and that tapped by the picture reality judgement. Findings are discussed with reference to whether a putative resource commonality is likely between biological objects and conspecifics, and whether or not either category may depend on an exclusive neural substrate.

Molecularly Imprinted Polymers: Present and Future Prospective

PubMed Central

Vasapollo, Giuseppe; Sole, Roberta Del; Mergola, Lucia; Lazzoi, Maria Rosaria; Scardino, Anna; Scorrano, Sonia; Mele, Giuseppe

2011-01-01

Molecular Imprinting Technology (MIT) is a technique to design artificial receptors with a predetermined selectivity and specificity for a given analyte, which can be used as ideal materials in various application fields. Molecularly Imprinted Polymers (MIPs), the polymeric matrices obtained using the imprinting technology, are robust molecular recognition elements able to mimic natural recognition entities, such as antibodies and biological receptors, useful to separate and analyze complicated samples such as biological fluids and environmental samples. The scope of this review is to provide a general overview on MIPs field discussing first general aspects in MIP preparation and then dealing with various application aspects. This review aims to outline the molecularly imprinted process and present a summary of principal application fields of molecularly imprinted polymers, focusing on chemical sensing, separation science, drug delivery and catalysis. Some significant aspects about preparation and application of the molecular imprinting polymers with examples taken from the recent literature will be discussed. Theoretical and experimental parameters for MIPs design in terms of the interaction between template and polymer functionalities will be considered and synthesis methods for the improvement of MIP recognition properties will also be presented. PMID:22016636

HINDBRAIN AND CRANIAL NERVE DYSMORPHOGENESIS RESULT FROM ACUTE MATERNAL ETHANOL ADMINISTRATION

EPA Science Inventory

Acute exposure of mouse embryos to ethanol during stages of hindbrain segmentation results in excessive cell death in specific cell populations. This study details the ethanol-induced cell loss and defines the subsequent effects of this early insult on rhombomere and cranial ner...

The Role of Measurement Error in Familiar Statistics

DTIC Science & Technology

2006-06-01

Manual of Mental Disorders (3rd ed., revised; American Psychiatric Association, 1987) for the clinical conditions of anorexia nervosa and borderline...borderline personality disorder, anorexia ner’vosa, and a control group. Family Process, 39, 345-358. Hunter, J. E., & Schmidt, F. L. (1976). A critical

Up-regulation of nucleotide excision repair in mouse lung and liver following chronic exposure to aflatoxin B{sub 1} and its dependence on p53 genotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mulder, Jeanne E.; Bondy, Genevieve S.; Mehta, Rekha

Aflatoxin B{sub 1} (AFB{sub 1}) is biotransformed in vivo into an epoxide metabolite that forms DNA adducts that may induce cancer if not repaired. p53 is a tumor suppressor gene implicated in the regulation of global nucleotide excision repair (NER). Male heterozygous p53 knockout (B6.129-Trp53{sup tm1Brd}N5, Taconic) and wild-type mice were exposed to 0, 0.2 or 1.0 ppm AFB{sub 1} for 26 weeks. NER activity was assessed with an in vitro assay, using AFB{sub 1}-epoxide adducted plasmid DNA as a substrate. For wild-type mice, repair of AFB{sub 1}–N7-Gua adducts was 124% and 96% greater in lung extracts from mice exposedmore » to 0.2 ppm and 1.0 ppm AFB{sub 1} respectively, and 224% greater in liver extracts from mice exposed to 0.2 ppm AFB{sub 1} (p < 0.05). In heterozygous p53 knockout mice, repair of AFB{sub 1}–N7-Gua was only 45% greater in lung extracts from mice exposed to 0.2 ppm AFB{sub 1} (p < 0.05), and no effect was observed in lung extracts from mice treated with 1.0 ppm AFB{sub 1} or in liver extracts from mice treated with either AFB{sub 1} concentration. p53 genotype did not affect basal levels of repair. AFB{sub 1} exposure did not alter repair of AFB{sub 1}-derived formamidopyrimidine adducts in lung or liver extracts of either mouse genotype nor did it affect XPA or XPB protein levels. In summary, chronic exposure to AFB{sub 1} increased NER activity in wild-type mice, and this response was diminished in heterozygous p53 knockout mice, indicating that loss of one allele of p53 limits the ability of NER to be up-regulated in response to DNA damage. - Highlights: • Mice are chronically exposed to low doses of the mycotoxin aflatoxin B{sub 1} (AFB{sub 1}). • The effects of AFB{sub 1} and p53 status on nucleotide excision repair are investigated. • AFB{sub 1} increases nucleotide excision repair in wild type mouse lung and liver. • This increase is attenuated in p53 heterozygous mouse lung and liver. • Results portray the role of p53 in nucleotide excision repair after AFB{sub 1} exposure.« less

Aerosol characteristics in north-east India using ARFINET spectral optical depth measurements

NASA Astrophysics Data System (ADS)

Pathak, B.; Subba, T.; Dahutia, P.; Bhuyan, P. K.; Moorthy, K. Krishna; Gogoi, M. M.; Babu, S. Suresh; Chutia, L.; Ajay, P.; Biswas, J.; Bharali, C.; Borgohain, A.; Dhar, P.; Guha, A.; De, B. K.; Banik, T.; Chakraborty, M.; Kundu, S. S.; Sudhakar, S.; Singh, S. B.

2016-01-01

Four years (2010-2014) of spectral aerosol optical depth (AOD) data from 4 Indian Space Research Organisation's ARFINET (Aerosol Radiative Forcing over India) stations (Shillong, Agartala, Imphal and Dibrugarh) in the North-Eastern Region (NER) of India (lying between 22-30°N and 89-98°E) are synthesized to evolve a regional aerosol representation, for the first time. Results show that the columnar AOD (an indicator of the column abundance of aerosols) is highest at Agartala (0.80 ± 0.24) in the west and lowest at Imphal (0.59 ± 0.23) in the east in the pre-monsoon season due to intense anthropogenic bio-mass burning in this region aided by long-range transport from the high aerosol laden regions of the Indo-Gangetic Plains (IGP), polluted Bangladesh and Bay of Bengal. In addition to local biogenic aerosols and pollutants emitted from brick kilns, oil/gas fields, household bio-fuel/fossil-fuel, vehicles, industries. Aerosol distribution and climatic impacts show a west to east gradient within the NER. For example, the climatological mean AODs are 0.67 ± 0.26, 0.52 ± 0.14, 0.40 ± 0.17 and 0.41 ± 0.23 respectively in Agartala, Shillong, Imphal and Dibrugarh which are geographically located from west to east within the NER. The average aerosol burden in NER ranks second highest with climatological mean AOD 0.49 ± 0.2 next to the Indo-Gangetic Plains where the climatological mean AOD is 0.64 ± 0.2 followed by the South and South-East Asia region. Elevated aerosol layers are observed over the eastern most stations Dibrugarh and Imphal, while at the western stations the concentrations are high near the surface. The climate implications of aerosols are evaluated in terms of aerosol radiative forcing (ARF) and consequent heating of the atmosphere in the region which follows AOD and exhibit high values in pre-monsoon season at all the locations except in Agartala. The highest ARF in the atmosphere occurs in the pre-monsoon season ranging from 48.6 Wm-2 in Agartala to 25.1 Wm-2 in Imphal. Winter radiative forcing follows that in pre-monsoon season at these locations. The heating rate is high at 1.2 K day-1 and 1.0 K day-1 over Shillong and Dibrugarh respectively in this season. However, Agartala experiences higher surface forcing (-56.5 Wm-2) and consequent larger heating of the atmosphere of 1.6 K day-1 in winter.

CD-REST: a system for extracting chemical-induced disease relation in literature.

PubMed

Xu, Jun; Wu, Yonghui; Zhang, Yaoyun; Wang, Jingqi; Lee, Hee-Jin; Xu, Hua

2016-01-01

Mining chemical-induced disease relations embedded in the vast biomedical literature could facilitate a wide range of computational biomedical applications, such as pharmacovigilance. The BioCreative V organized a Chemical Disease Relation (CDR) Track regarding chemical-induced disease relation extraction from biomedical literature in 2015. We participated in all subtasks of this challenge. In this article, we present our participation system Chemical Disease Relation Extraction SysTem (CD-REST), an end-to-end system for extracting chemical-induced disease relations in biomedical literature. CD-REST consists of two main components: (1) a chemical and disease named entity recognition and normalization module, which employs the Conditional Random Fields algorithm for entity recognition and a Vector Space Model-based approach for normalization; and (2) a relation extraction module that classifies both sentence-level and document-level candidate drug-disease pairs by support vector machines. Our system achieved the best performance on the chemical-induced disease relation extraction subtask in the BioCreative V CDR Track, demonstrating the effectiveness of our proposed machine learning-based approaches for automatic extraction of chemical-induced disease relations in biomedical literature. The CD-REST system provides web services using HTTP POST request. The web services can be accessed fromhttp://clinicalnlptool.com/cdr The online CD-REST demonstration system is available athttp://clinicalnlptool.com/cdr/cdr.html. Database URL:http://clinicalnlptool.com/cdr;http://clinicalnlptool.com/cdr/cdr.html. © The Author(s) 2016. Published by Oxford University Press.

Recognition of medication information from discharge summaries using ensembles of classifiers.

PubMed

Doan, Son; Collier, Nigel; Xu, Hua; Pham, Hoang Duy; Tu, Minh Phuong

2012-05-07

Extraction of clinical information such as medications or problems from clinical text is an important task of clinical natural language processing (NLP). Rule-based methods are often used in clinical NLP systems because they are easy to adapt and customize. Recently, supervised machine learning methods have proven to be effective in clinical NLP as well. However, combining different classifiers to further improve the performance of clinical entity recognition systems has not been investigated extensively. Combining classifiers into an ensemble classifier presents both challenges and opportunities to improve performance in such NLP tasks. We investigated ensemble classifiers that used different voting strategies to combine outputs from three individual classifiers: a rule-based system, a support vector machine (SVM) based system, and a conditional random field (CRF) based system. Three voting methods were proposed and evaluated using the annotated data sets from the 2009 i2b2 NLP challenge: simple majority, local SVM-based voting, and local CRF-based voting. Evaluation on 268 manually annotated discharge summaries from the i2b2 challenge showed that the local CRF-based voting method achieved the best F-score of 90.84% (94.11% Precision, 87.81% Recall) for 10-fold cross-validation. We then compared our systems with the first-ranked system in the challenge by using the same training and test sets. Our system based on majority voting achieved a better F-score of 89.65% (93.91% Precision, 85.76% Recall) than the previously reported F-score of 89.19% (93.78% Precision, 85.03% Recall) by the first-ranked system in the challenge. Our experimental results using the 2009 i2b2 challenge datasets showed that ensemble classifiers that combine individual classifiers into a voting system could achieve better performance than a single classifier in recognizing medication information from clinical text. It suggests that simple strategies that can be easily implemented such as majority voting could have the potential to significantly improve clinical entity recognition.

Loss of Nucleotide Excision Repair as a Source of Genomic Instability in Breast Cancer

DTIC Science & Technology

2006-06-01

requiring millions of cells and DNA extraction techniques. Therefore, this approach may prove useful for determining NER activity from clinical... grapefruit juice per day, as this has been shown to cause liver problems when people are also taking lovastatin. Drinking less than this amount (for

77 FR 49021 - Minor Boundary Revision at Theodore Roosevelt Inaugural National Historic Site

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

... DEPARTMENT OF THE INTERIOR National Park Service [NPS-NER-THRI-10649; 1960-726] Minor Boundary Revision at Theodore Roosevelt Inaugural National Historic Site AGENCY: National Park Service, Interior. ACTION: Notification of Boundary Revision. SUMMARY: Notice is hereby given that, pursuant to 16 U.S.C...

Evaluation of Biomonitoring Data from the CDC National Exposure Report in a Risk Assessment Context: Perspectives across Chemicals

EPA Science Inventory

BACKGROUND: Biomonitoring data reported in the National Report on Human Exposure to Environmental Chemicals (NER) provide information on the presence and concentrations of more than 400 chemicals in human blood and urine. Biomonitoring Equivalents (BEs) and other risk assessment...

"The Plan(ner) Is Always Changing": Self-Directed Funding for Children with Hearing Loss

ERIC Educational Resources Information Center

Simpson, Andrea; Stewart, Lauryn; Douglas, Jacinta

2016-01-01

This study investigated the experience of families with young children with hearing loss participating in a self-directed funding scheme in Australia. Eleven hearing caregivers, one male, participated in qualitative semi-structured interviews. Analysis was undertaken using a phenomenological inspired thematic analysis approach. Major themes…

Building a protein name dictionary from full text: a machine learning term extraction approach.

PubMed

Shi, Lei; Campagne, Fabien

2005-04-07

The majority of information in the biological literature resides in full text articles, instead of abstracts. Yet, abstracts remain the focus of many publicly available literature data mining tools. Most literature mining tools rely on pre-existing lexicons of biological names, often extracted from curated gene or protein databases. This is a limitation, because such databases have low coverage of the many name variants which are used to refer to biological entities in the literature. We present an approach to recognize named entities in full text. The approach collects high frequency terms in an article, and uses support vector machines (SVM) to identify biological entity names. It is also computationally efficient and robust to noise commonly found in full text material. We use the method to create a protein name dictionary from a set of 80,528 full text articles. Only 8.3% of the names in this dictionary match SwissProt description lines. We assess the quality of the dictionary by studying its protein name recognition performance in full text. This dictionary term lookup method compares favourably to other published methods, supporting the significance of our direct extraction approach. The method is strong in recognizing name variants not found in SwissProt.

Wolf in Sheep's Clothing: Primary Lung Cancer Mimicking Benign Entities.

PubMed

Snoeckx, Annemie; Dendooven, Amélie; Carp, Laurens; Desbuquoit, Damien; Spinhoven, Maarten J; Lauwers, Patrick; Van Schil, Paul E; van Meerbeeck, Jan P; Parizel, Paul M

2017-10-01

Lung cancer is the most common cancer worldwide. On imaging, it typically presents as mass or nodule. Recognition of these typical cases is often straightforward, whereas diagnosis of uncommon manifestations of primary lung cancer is far more challenging. Lung cancer can mimic a variety of benign entities, including pneumonia, lung abscess, postinfectious scarring, atelectasis, a mediastinal mass, emphysema and granulomatous diseases. Correlation with previous history, clinical and biochemical parameters is necessary in the assessment of these cases, but often aspecific and inconclusive. Whereas 18 F-fluorodeoxyglucose ( 18 F-FDG) Positron Emission Tomography is the cornerstone in staging of lung cancer, its role in diagnosis of these uncommon manifestations is less straightforward since benign entities can present with increased 18 F-FDG-uptake and, on the other hand, a number of these uncommon lung cancer manifestations do not exhibit increased uptake. Chest Computed Tomography (CT) is the imaging modality of choice for both lesion detection and characterization. In this pictorial review we present the wide imaging spectrum of CT-findings as well as radiologic-pathologic correlation of these uncommon lung cancer manifestations. Knowledge of the many faces of lung cancer is crucial for early diagnosis and subsequent treatment. A multidisciplinary approach in these cases is mandatory. Copyright © 2017 Elsevier B.V. All rights reserved.

Building a protein name dictionary from full text: a machine learning term extraction approach

PubMed Central

Shi, Lei; Campagne, Fabien

2005-01-01

Background The majority of information in the biological literature resides in full text articles, instead of abstracts. Yet, abstracts remain the focus of many publicly available literature data mining tools. Most literature mining tools rely on pre-existing lexicons of biological names, often extracted from curated gene or protein databases. This is a limitation, because such databases have low coverage of the many name variants which are used to refer to biological entities in the literature. Results We present an approach to recognize named entities in full text. The approach collects high frequency terms in an article, and uses support vector machines (SVM) to identify biological entity names. It is also computationally efficient and robust to noise commonly found in full text material. We use the method to create a protein name dictionary from a set of 80,528 full text articles. Only 8.3% of the names in this dictionary match SwissProt description lines. We assess the quality of the dictionary by studying its protein name recognition performance in full text. Conclusion This dictionary term lookup method compares favourably to other published methods, supporting the significance of our direct extraction approach. The method is strong in recognizing name variants not found in SwissProt. PMID:15817129

Orientation estimation of anatomical structures in medical images for object recognition

NASA Astrophysics Data System (ADS)

Bağci, Ulaş; Udupa, Jayaram K.; Chen, Xinjian

2011-03-01

Recognition of anatomical structures is an important step in model based medical image segmentation. It provides pose estimation of objects and information about "where" roughly the objects are in the image and distinguishing them from other object-like entities. In,1 we presented a general method of model-based multi-object recognition to assist in segmentation (delineation) tasks. It exploits the pose relationship that can be encoded, via the concept of ball scale (b-scale), between the binary training objects and their associated grey images. The goal was to place the model, in a single shot, close to the right pose (position, orientation, and scale) in a given image so that the model boundaries fall in the close vicinity of object boundaries in the image. Unlike position and scale parameters, we observe that orientation parameters require more attention when estimating the pose of the model as even small differences in orientation parameters can lead to inappropriate recognition. Motivated from the non-Euclidean nature of the pose information, we propose in this paper the use of non-Euclidean metrics to estimate orientation of the anatomical structures for more accurate recognition and segmentation. We statistically analyze and evaluate the following metrics for orientation estimation: Euclidean, Log-Euclidean, Root-Euclidean, Procrustes Size-and-Shape, and mean Hermitian metrics. The results show that mean Hermitian and Cholesky decomposition metrics provide more accurate orientation estimates than other Euclidean and non-Euclidean metrics.

Charles Bonnet syndrome: three cases in the emergency department.

PubMed

Frost, Elizabeth J; Mottley, J Lawrence; Edlow, Jonathan A

2012-05-01

Charles Bonnet Syndrome (CBS) is a cause of visual hallucinations in elderly patients that is often unrecognized by emergency physicians and has a relatively benign course. As the population ages, it is likely that the number of cases of CBS will increase (and thus, the numbers of those who present to an Emergency Department [ED] will be increasing). The case reports presented in this article will facilitate the recognition of CBS by the emergency physician. We describe 3 patients who presented to one ED for visual disturbances and were diagnosed with CBS in a 4-month time period. Recognition of this unusual but stereotypical cause of visual disturbances facilitates an accurate diagnosis, and spares patients the time and expense of blood testing, imaging, and consultations. If emergency physicians begin to recognize this benign entity, we can provide improved (and safer) patient care with appropriate ED interventions. Copyright © 2012 Elsevier Inc. All rights reserved.

Regulatory Forum Opinion Piece*: Dispelling Confusing Pathology Terminology: Recognition and Interpretation of Selected Rodent Renal Tubule Lesions.

PubMed

Seely, John Curtis; Frazier, Kendall S

2015-06-01

Renal tubule lesions often prove troublesome for toxicologic pathologists because of the diverse nature and interrelated cell types within the kidney and the presence of spontaneous lesions with overlapping morphologies similar to those induced by renal toxicants. Although there are a number of guidance documents available citing straightforward diagnostic criteria of tubule lesions for the pathologist to refer to, most are presented without further advice on the when to or to the why and the why not of diagnosing one lesion over another. Documents presenting diagnostic perspectives and recommendations derived from an author's experience are limited since guidance documents are generally based on descriptive observations. In this Regulatory Forum opinion piece, the authors attempt to dispel confusing renal tubule lesion terminology in laboratory animal species by suggesting histological advice on the recognition and interpretation of these complex entities. © 2015 by The Author(s).

Collaboration between human and nonhuman players in Night Vision Tactical Trainer-Shadow

NASA Astrophysics Data System (ADS)

Berglie, Stephen T.; Gallogly, James J.

2016-05-01

The Night Vision Tactical Trainer - Shadow (NVTT-S) is a U.S. Army-developed training tool designed to improve critical Manned-Unmanned Teaming (MUMT) communication skills for payload operators in Unmanned Aerial Sensor (UAS) crews. The trainer is composed of several Government Off-The-Shelf (GOTS) simulation components and takes the trainee through a series of escalating engagements using tactically relevant, realistically complex, scenarios involving a variety of manned, unmanned, aerial, and ground-based assets. The trainee is the only human player in the game and he must collaborate, from his web-based mock operating station, with various non-human players via spoken natural language over simulated radio in order to execute the training missions successfully. Non-human players are modeled in two complementary layers - OneSAF provides basic background behaviors for entities while NVTT provides higher level models that control entity actions based on intent extracted from the trainee's spoken natural dialog with game entities. Dialog structure is modeled based on Army standards for communication and verbal protocols. This paper presents an architecture that integrates the U.S. Army's Night Vision Image Generator (NVIG), One Semi- Automated Forces (OneSAF), a flight dynamics model, as well as Commercial Off The Shelf (COTS) speech recognition and text to speech products to effect an environment with sufficient entity counts and fidelity to enable meaningful teaching and reinforcement of critical communication skills. It further demonstrates the model dynamics and synchronization mechanisms employed to execute purpose-built training scenarios, and to achieve ad-hoc collaboration on-the-fly between human and non-human players in the simulated environment.

Constitutional dynamic chemistry: bridge from supramolecular chemistry to adaptive chemistry.

PubMed

Lehn, Jean-Marie

2012-01-01

Supramolecular chemistry aims at implementing highly complex chemical systems from molecular components held together by non-covalent intermolecular forces and effecting molecular recognition, catalysis and transport processes. A further step consists in the investigation of chemical systems undergoing self-organization, i.e. systems capable of spontaneously generating well-defined functional supramolecular architectures by self-assembly from their components, thus behaving as programmed chemical systems. Supramolecular chemistry is intrinsically a dynamic chemistry in view of the lability of the interactions connecting the molecular components of a supramolecular entity and the resulting ability of supramolecular species to exchange their constituents. The same holds for molecular chemistry when the molecular entity contains covalent bonds that may form and break reversibility, so as to allow a continuous change in constitution by reorganization and exchange of building blocks. These features define a Constitutional Dynamic Chemistry (CDC) on both the molecular and supramolecular levels.CDC introduces a paradigm shift with respect to constitutionally static chemistry. The latter relies on design for the generation of a target entity, whereas CDC takes advantage of dynamic diversity to allow variation and selection. The implementation of selection in chemistry introduces a fundamental change in outlook. Whereas self-organization by design strives to achieve full control over the output molecular or supramolecular entity by explicit programming, self-organization with selection operates on dynamic constitutional diversity in response to either internal or external factors to achieve adaptation.The merging of the features: -information and programmability, -dynamics and reversibility, -constitution and structural diversity, points to the emergence of adaptive and evolutive chemistry, towards a chemistry of complex matter.

Entity Recognition Via Multimodal Sensor Fusion With Smart Phones

DTIC Science & Technology

2015-03-26

Xs ,t|Et = 1] P[ Xs ,t|Et = 0] ≥ τ However, an event such as an earthquake, due to its’ rarity, does not have suffi- cient data to obtain good...Faulkner et al. develop a methodology to estimate the distribution of normal observations over time L̂0( Xs ,t) = P̂[ Xs ,t|Et = 0] for non-events. This is done...by using a parametric 37 approach: P[ Xs ,t|Et0] = φ( Xs ,t, θ) This model improves when the time span of sensing increases and thus the availability of

A systematic approach to emergencies in uveitis.

PubMed

Al-Dhibi, Hassan A; Al-Mahmood, Ammar M; Arevalo, J Fernando

2014-01-01

Uveitis is a common cause of preventable blindness although it is consider a sight-threatening condition particularly in cases with posterior segment inflammation. To deal with emergency conditions in uveitis, we must aware of the essential signs and symptoms that reflect a true uveitic emergency. Failure to recognize these essential signs and symptoms of a true uveitic emergency may result in a devastating visual outcome. This review provides general ophthalmologists and residents, clinical guidelines for the main uveitic entities that require immediate recognition and urgent intervention in the emergency room to prevent severe permanent visual loss.

Virtual imaging in sports broadcasting: an overview

NASA Astrophysics Data System (ADS)

Tan, Yi

2003-04-01

Virtual imaging technology is being used to augment television broadcasts -- virtual objects are seamlessly inserted into the video stream to appear as real entities to TV audiences. Virtual advertisements, the main application of this technology, are providing opportunities to improve the commercial value of television programming while enhancing the contents and the entertainment aspect of these programs. State-of-the-art technologies, such as image recognition, motion tracking and chroma keying, are central to a virtual imaging system. This paper reviews the general framework, the key techniques, and the sports broadcasting applications of virtual imaging technology.

OSCAR4: a flexible architecture for chemical text-mining.

PubMed

Jessop, David M; Adams, Sam E; Willighagen, Egon L; Hawizy, Lezan; Murray-Rust, Peter

2011-10-14

The Open-Source Chemistry Analysis Routines (OSCAR) software, a toolkit for the recognition of named entities and data in chemistry publications, has been developed since 2002. Recent work has resulted in the separation of the core OSCAR functionality and its release as the OSCAR4 library. This library features a modular API (based on reduction of surface coupling) that permits client programmers to easily incorporate it into external applications. OSCAR4 offers a domain-independent architecture upon which chemistry specific text-mining tools can be built, and its development and usage are discussed.

Animates are better remembered than inanimates: further evidence from word and picture stimuli.

PubMed

Bonin, Patrick; Gelin, Margaux; Bugaiska, Aurélia

2014-04-01

In three experiments, we showed that animate entities are remembered better than inanimate entities. Experiment 1 revealed better recall for words denoting animate than inanimate items. Experiment 2 replicated this finding with the use of pictures. In Experiment 3, we found better recognition for animate than for inanimate words. Importantly, we also found a higher recall rate of “remember” than of “know” responses for animates, whereas the recall rates were similar for the two types of responses for inanimate items. This finding suggests that animacy enhances not only the quantity but also the quality of memory traces, through the recall of contextual details of previous experiences (i.e., episodic memory). Finally, in Experiment 4, we tested whether the animacy effect was due to animate items being richer in terms of sensory features than inanimate items. The findings provide further evidence for the functionalist view of memory championed by Nairne and coworkers (Nairne, 2010; Nairne & Pandeirada, Cognitive Psychology, 61 :1–22, 2010a, 2010b).

Assessing the Representation of Occupation Information in Free-Text Clinical Documents Across Multiple Sources

PubMed Central

Lindemann, Elizabeth A.; Chen, Elizabeth S.; Rajamani, Sripriya; Manohar, Nivedha; Wang, Yan; Melton, Genevieve B.

2017-01-01

There has been increasing recognition of the key role of social determinants like occupation on health. Given the relatively poor understanding of occupation information in electronic health records (EHRs), we sought to characterize occupation information within free-text clinical document sources. From six distinct clinical sources, 868 total occupation-related sentences were identified for the study corpus. Building off approaches from previous studies, refined annotation guidelines were created using the National Institute for Occupational Safety and Health Occupational Data for Health data model with elements added to increase granularity. Our corpus generated 2,005 total annotations representing 39 of 41 entity types from the enhanced data model. Highest frequency entities were: Occupation Description (17.7%); Employment Status – Not Specified (12.5%); Employer Name (11.0%); Subject (9.8%); Industry Description (6.2%). Our findings support the value for standardizing entry of EHR occupation information to improve data quality for improved patient care and secondary uses of this information. PMID:29295142

Synthetically programmable nanoparticle superlattices using a hollow three-dimensional spacer approach.

PubMed

Auyeung, Evelyn; Cutler, Joshua I; Macfarlane, Robert J; Jones, Matthew R; Wu, Jinsong; Liu, George; Zhang, Ke; Osberg, Kyle D; Mirkin, Chad A

2011-12-11

Crystalline nanoparticle arrays and superlattices with well-defined geometries can be synthesized by using appropriate electrostatic, hydrogen-bonding or biological recognition interactions. Although superlattices with many distinct geometries can be produced using these approaches, the library of achievable lattices could be increased by developing a strategy that allows some of the nanoparticles within a binary lattice to be replaced with 'spacer' entities that are constructed to mimic the behaviour of the nanoparticles they replace, even though they do not contain an inorganic core. The inclusion of these spacer entities within a known binary superlattice would effectively delete one set of nanoparticles without affecting the positions of the other set. Here, we show how hollow DNA nanostructures can be used as 'three-dimensional spacers' within nanoparticle superlattices assembled through programmable DNA interactions. We show that this strategy can be used to form superlattices with five distinct symmetries, including one that has never before been observed in any crystalline material.

High-recall protein entity recognition using a dictionary

PubMed Central

Kou, Zhenzhen; Cohen, William W.; Murphy, Robert F.

2010-01-01

Protein name extraction is an important step in mining biological literature. We describe two new methods for this task: semiCRFs and dictionary HMMs. SemiCRFs are a recently-proposed extension to conditional random fields that enables more effective use of dictionary information as features. Dictionary HMMs are a technique in which a dictionary is converted to a large HMM that recognizes phrases from the dictionary, as well as variations of these phrases. Standard training methods for HMMs can be used to learn which variants should be recognized. We compared the performance of our new approaches to that of Maximum Entropy (Max-Ent) and normal CRFs on three datasets, and improvement was obtained for all four methods over the best published results for two of the datasets. CRFs and semiCRFs achieved the highest overall performance according to the widely-used F-measure, while the dictionary HMMs performed the best at finding entities that actually appear in the dictionary—the measure of most interest in our intended application. PMID:15961466

Tuberculosis-associated Fibrosing Mediastinitis: Case Report and Literature Review.

PubMed

Tan, Ronald; Martires, Joanne; Kamangar, Nader

2016-01-01

Fibrosing mediastinitis is a rare condition defined by the presence of fibrotic mediastinal infiltrates that obliterate normal fat planes. It is a late complication of a previous granulomatous infection, such as histoplasmosis or tuberculosis (TB). Due to its rarity, fibrosing mediastinitis is often under-recognized, and the clinical presentation is variable and dependent on the extent of infiltration or encasement of structures within the mediastinum. We present a case of fibrosing mediastinitis in a man with a prior history of TB, who presented with progressive dyspnea and was found to have chronic mediastinal soft tissue opacities and pulmonary hypertension. His diagnosis was delayed due to the lack of recognition of this clinical/radiographic entity. Fibrosing mediastinitis is a rare entity usually caused by granulomatous disease. Most cases develop as a late complication of histoplasmosis or TB. The presence of calcified mediastinal soft tissue infiltrates on advanced chest imaging can be diagnostic of fibrosing mediastinitis in patients with a prior history of a granulomatous infection once active processes such as malignancy are excluded.

WHERE MULTIFUNCTIONAL DNA REPAIR PROTEINS MEET: MAPPING THE INTERACTION DOMAINS BETWEEN XPG AND WRN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rangaraj, K.; Cooper, P.K.; Trego, K.S.

The rapid recognition and repair of DNA damage is essential for the maintenance of genomic integrity and cellular survival. Multiple complex and interconnected DNA damage responses exist within cells to preserve the human genome, and these repair pathways are carried out by a specifi c interplay of protein-protein interactions. Thus a failure in the coordination of these processes, perhaps brought about by a breakdown in any one multifunctional repair protein, can lead to genomic instability, developmental and immunological abnormalities, cancer and premature aging. This study demonstrates a novel interaction between two such repair proteins, Xeroderma pigmentosum group G protein (XPG)more » and Werner syndrome helicase (WRN), that are both highly pleiotropic and associated with inherited genetic disorders when mutated. XPG is a structure-specifi c endonuclease required for the repair of UV-damaged DNA by nucleotide excision repair (NER), and mutations in XPG result in the diseases Xeroderma pigmentosum (XP) and Cockayne syndrome (CS). A loss of XPG incision activity results in XP, whereas a loss of non-enzymatic function(s) of XPG causes CS. WRN is a multifunctional protein involved in double-strand break repair (DSBR), and consists of 3’–5’ DNA-dependent helicase, 3’–5’ exonuclease, and single-strand DNA annealing activities. Nonfunctional WRN protein leads to Werner syndrome, a premature aging disorder with increased cancer incidence. Far Western analysis was used to map the interacting domains between XPG and WRN by denaturing gel electrophoresis, which separated purifi ed full length and recombinant XPG and WRN deletion constructs, based primarily upon the length of each polypeptide. Specifi c interacting domains were visualized when probed with the secondary protein of interest which was then detected by traditional Western analysis using the antibody of the secondary protein. The interaction between XPG and WRN was mapped to the C-terminal region of XPG as well as the C-terminal region of WRN. The physical interaction between XPG and WRN links NER, (made evident by the disease XP) with DSBR, which imparts additional knowledge of the overlapping nature of these two proteins and the previously distinct DNA repair pathways they are associated with. Since genomic integrity is constantly threatened by both endogenous and exogenous (internal and external) damage, understanding the roles of these proteins in coordinating DNA repair processes with replication will signifi cantly further understanding how defects instigate physiological consequences in response to various DNA damaging sources. This ultimately contributes to our understanding of cancer and premature aging.« less

77 FR 71612 - Minor Boundary Revision of Saratoga National Historical Park

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-03

..., owned respectively by Open Space Conservancy, Inc., and the State of New York, will be donated to the... DEPARTMENT OF THE INTERIOR National Park Service [NPS-NER-SARA-11235; 4901-726] Minor Boundary... make minor boundary revisions to areas of the National Park System. The Committees have been so...

78 FR 28619 - Boston Harbor Islands Advisory Council Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-15

... DEPARTMENT OF THE INTERIOR [NPS-NER-BOHA-12921: PPMPSPD1Z.YM0000: PPNEBOHAS1] Boston Harbor.... SUMMARY: This notice announces a meeting of the Boston Harbor Islands Advisory Council. The agenda... park update. DATES: Date/Time: June 5, 2013, 4:00 p.m. to 6:00 p.m. (EASTERN). Location: Boston Society...

Consequence Management Symposium

DTIC Science & Technology

2001-09-01

AND SUBTITLE Consequence Management Symposium 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e...log i cal agents and their effects was deemed essen tial for “first respond ers,” includ ing emer gency medi cal and hospi tal prac ti tio ners

A dynamic neural field model of temporal order judgments.

PubMed

Hecht, Lauren N; Spencer, John P; Vecera, Shaun P

2015-12-01

Temporal ordering of events is biased, or influenced, by perceptual organization-figure-ground organization-and by spatial attention. For example, within a region assigned figural status or at an attended location, onset events are processed earlier (Lester, Hecht, & Vecera, 2009; Shore, Spence, & Klein, 2001), and offset events are processed for longer durations (Hecht & Vecera, 2011; Rolke, Ulrich, & Bausenhart, 2006). Here, we present an extension of a dynamic field model of change detection (Johnson, Spencer, Luck, & Schöner, 2009; Johnson, Spencer, & Schöner, 2009) that accounts for both the onset and offset performance for figural and attended regions. The model posits that neural populations processing the figure are more active, resulting in a peak of activation that quickly builds toward a detection threshold when the onset of a target is presented. This same enhanced activation for some neural populations is maintained when a present target is removed, creating delays in the perception of the target's offset. We discuss the broader implications of this model, including insights regarding how neural activation can be generated in response to the disappearance of information. (c) 2015 APA, all rights reserved).

XPD Helicase Structures And Activities: Insights Into the Cancer And Aging Phenotypes From XPD Mutations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, L.; Fuss, J.O.; Cheng, Q.J.

2009-05-18

Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicasemore » activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.« less

XPD Helicase Structures and Activities: Insights into the Cancer and Aging Phenotypes from XPD Mutations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tainer, John; Fan, Li; Fuss, Jill O.

2008-06-02

Mutations in XPD helicase, required for nucleotide excision repair (NER) as part of the transcription/repair complex TFIIH, cause three distinct phenotypes: cancer-prone xeroderma pigmentosum (XP), or aging disorders Cockayne syndrome (CS), and trichothiodystrophy (TTD). To clarify molecular differences underlying these diseases, we determined crystal structures of the XPD catalytic core from Sulfolobus acidocaldarius and measured mutant enzyme activities. Substrate-binding grooves separate adjacent Rad51/RecA-like helicase domains (HD1, HD2) and an arch formed by 4FeS and Arch domains. XP mutations map along the HD1 ATP-binding edge and HD2 DNA-binding channel and impair helicase activity essential for NER. XP/CS mutations both impair helicasemore » activity and likely affect HD2 functional movement. TTD mutants lose or retain helicase activity but map to sites in all four domains expected to cause framework defects impacting TFIIH integrity. These results provide a foundation for understanding disease consequences of mutations in XPD and related 4Fe-4S helicases including FancJ.« less

Replication-mediated disassociation of replication protein A-XPA complex upon DNA damage: implications for RPA handing off.

PubMed

Jiang, Gaofeng; Zou, Yue; Wu, Xiaoming

2012-08-01

RPA (replication protein A), the eukaryotic ssDNA (single-stranded DNA)-binding protein, participates in most cellular processes in response to genotoxic insults, such as NER (nucleotide excision repair), DNA, DSB (double-strand break) repair and activation of cell cycle checkpoint signalling. RPA interacts with XPA (xeroderma pigmentosum A) and functions in early stage of NER. We have shown that in cells the RPA-XPA complex disassociated upon exposure of cells to high dose of UV irradiation. The dissociation required replication stress and was partially attributed to tRPA hyperphosphorylation. Treatment of cells with CPT (camptothecin) and HU (hydroxyurea), which cause DSB DNA damage and replication fork collapse respectively and also leads to the disruption of RPA-XPA complex. Purified RPA and XPA were unable to form complex in vitro in the presence of ssDNA. We propose that the competition-based RPA switch among different DNA metabolic pathways regulates the dissociation of RPA with XPA in cells after DNA damage. The biological significances of RPA-XPA complex disruption in relation with checkpoint activation, DSB repair and RPA hyperphosphorylation are discussed.

Thomson scattering density calibration by Rayleigh and rotational Raman scattering on NSTX.

PubMed

LeBlanc, B P

2008-10-01

The multipoint Thomson scattering diagnostic measures the profiles of the electron temperature T(e)(R) and density n(e)(R) on the horizontal midplane of NSTX. Normal operation makes use of Rayleigh scattering in nitrogen or argon to derive the density profile. While the Rayleigh scattering n(e)(R) calibration has been validated by comparison to other density measurements and through its correlation with plasma phenomena, it does require dedicated detectors at the laser wavelength in this filter polychromator based diagnostic. The presence of dust and/or stray laser light precludes routine use of these dedicated spectral channels for Thomson scattering measurement. Hence it is of interest to investigate the use of Raman scattering in nitrogen for the purpose of density calibration since it could free up detection equipment, which could then be used for the instrumentation of additional radial channels. In this paper the viewing optics "geometrical factor" profiles obtained from Rayleigh and Raman scattering are compared. While both techniques agree nominally, residual effects on the order of 10% remain and will be discussed.

Overexpression of xeroderma pigmentosum group C decreases the chemotherapeutic sensitivity of colorectal carcinoma cells to cisplatin.

PubMed

Zhang, Yi; Cao, Jia; Meng, Yanni; Qu, Chunying; Shen, Feng; Xu, Leiming

2018-05-01

Xeroderma pigmentosum group C (XPC) is a DNA-damage-recognition gene active at the early stage of DNA repair. XPC also participates in regulation of cell-cycle checkpoint and DNA-damage-induced apoptosis. In the present study, the expression levels of genes involved in nucleotide excision repair (NER) were assessed in human colorectal cancer (CRC) tissue. This analysis revealed that expression of XPC mRNA significantly increased in colorectal carcinoma tissues compared with matched normal controls. Expression of XPC gradually increased along with the degree of progression of CRC. In vitro , an XTT assay demonstrated that small interfering RNA (siRNA) targeting XPC significantly increased the sensitivity of CRC SW480 cells to cisplatin, whereas cells transfected with a XPC-overexpression plasmid became more resistant to cisplatin. Furthermore, flow cytometry revealed that the proportion of apoptotic cells significantly increased in XPC-knockdown cells upon cisplatin treatment. However, the overexpression XPC significantly increased the resistance of cells to cisplatin. In vivo , tumor growth was significantly reduced in tumor-bearing mice when the XPC gene was knocked down. Upregulation of the expression of pro-apoptotic Bcl-associated X and downregulation of the anti-apoptotic B-cell lymphoma 2 proteins was observed in the implanted tumor tissue. In conclusion, XPC serves a key role in chemotherapeutic sensitivity of CRC to cisplatin, meaning that it may be a potential target for chemotherapy of CRC.

Landslide susceptibility assessment and validation in the framework of municipal planning in Portugal: the case of Loures Municipality.

PubMed

Guillard, Clemence; Zezere, Jose

2012-10-01

The legislation that demands the evaluation of landslide susceptibility in Portugal at the municipal level is the National Ecological Reserve (NER). A methodology for the evaluation of landslide susceptibility to be used in municipal planning is applied in Loures Municipality (169.3 km²) located north of Lisbon (Portugal). A landslide inventory was made for the whole area interpreting orthophoto maps and aerial photographs and using standard geomorphologic techniques in field work. It consists of 686 polygons, each polygon representing a rotational, a deep translational or a shallow translational slide, and is integrated into a GIS database. Landslide susceptibility is evaluated using algorithms based on statistical/probabilistic analysis (Information Value Method) over unique-condition terrain units in a raster basis. Three susceptibility models are elaborated independently according to the type of slide (rotational, deep translational, shallow translational). The landslide susceptibility maps are prepared by sorting all pixels according to the pixel susceptibility value in descending order. The robustness and accuracy of the landslide susceptibility models are evaluated by prediction-rate curves, which are used for the quantitative interpretation of the landslide susceptibility maps. Unstable slopes that have to be included into the National Ecological Reserve are extracted from the three susceptibility maps following the general rules to draw the NER that state that the area to be included in the NER should guarantee the inclusion of at least 70 % of the landslides identified in the landslide inventory. The obtained results allow us to conclude that 70 % of the future landslides should occur in these areas, classified as most susceptible to landslides corresponding to 20.3 % of the total area of Municipality. Thus, the consideration of these 20.3 % as regards prevention and protection of landslide risk could potentially reduce damage resulting from 70 % of future landslides in the Loures Municipality.

Angular dependence of etch rates in the etching of poly-Si and fluorocarbon polymer using SF6, C4F8, and O2 plasmas

NASA Astrophysics Data System (ADS)

Min, Jae-Ho; Lee, Gyeo-Re; Lee, Jin-Kwan; Moon, Sang Heup; Kim, Chang-Koo

2004-05-01

The dependences of etch rates on the angle of ions incident on the substrate surface in four plasma/substrate systems that constitute the advanced Bosch process were investigated using a Faraday cage designed for the accurate control of the ion-incident angle. The four systems, established by combining discharge gases and substrates, were a SF6/poly-Si, a SF6/fluorocarbon polymer, an O2/fluorocarbon polymer, and a C4F8/Si. In the case of SF6/poly-Si, the normalized etch rates (NERs), defined as the etch rates normalized by the rate on the horizontal surface, were higher at all angles than values predicted from the cosine of the ion-incident angle. This characteristic curve shape was independent of changes in process variables including the source power and bias voltage. Contrary to the earlier case, the NERs for the O2/polymer decreased and eventually reached much lower values than the cosine values at angles between 30° and 70° when the source power was increased and the bias voltage was decreased. On the other hand, the NERs for the SF6/polymer showed a weak dependence on the process variables. In the case of C4F8/Si, which is used in the Bosch process for depositing a fluorocarbon layer on the substrate surface, the deposition rate varied with the ion incident angle, showing an S-shaped curve. These characteristic deposition rate curves, which were highly dependent on the process conditions, could be divided into four distinct regions: a Si sputtering region, an ion-suppressed polymer deposition region, an ion-enhanced polymer deposition region, and an ion-free polymer deposition region. Based on the earlier characteristic angular dependences of the etch (or deposition) rates in the individual systems, ideal process conditions for obtaining an anisotropic etch profile in the advanced Bosch process are proposed. .

Coordination of Rad1-Rad10 interactions with Msh2-Msh3, Saw1 and RPA is essential for functional 3' non-homologous tail removal.

PubMed

Eichmiller, Robin; Medina-Rivera, Melisa; DeSanto, Rachel; Minca, Eugen; Kim, Christopher; Holland, Cory; Seol, Ja-Hwan; Schmit, Megan; Oramus, Diane; Smith, Jessica; Gallardo, Ignacio F; Finkelstein, Ilya J; Lee, Sang Eun; Surtees, Jennifer A

2018-06-01

Double strand DNA break repair (DSBR) comprises multiple pathways. A subset of DSBR pathways, including single strand annealing, involve intermediates with 3' non-homologous tails that must be removed to complete repair. In Saccharomyces cerevisiae, Rad1-Rad10 is the structure-specific endonuclease that cleaves the tails in 3' non-homologous tail removal (3' NHTR). Rad1-Rad10 is also an essential component of the nucleotide excision repair (NER) pathway. In both cases, Rad1-Rad10 requires protein partners for recruitment to the relevant DNA intermediate. Msh2-Msh3 and Saw1 recruit Rad1-Rad10 in 3' NHTR; Rad14 recruits Rad1-Rad10 in NER. We created two rad1 separation-of-function alleles, rad1R203A,K205A and rad1R218A; both are defective in 3' NHTR but functional in NER. In vitro, rad1R203A,K205A was impaired at multiple steps in 3' NHTR. The rad1R218A in vivo phenotype resembles that of msh2- or msh3-deleted cells; recruitment of rad1R218A-Rad10 to recombination intermediates is defective. Interactions among rad1R218A-Rad10 and Msh2-Msh3 and Saw1 are altered and rad1R218A-Rad10 interactions with RPA are compromised. We propose a model in which Rad1-Rad10 is recruited and positioned at the recombination intermediate through interactions, between Saw1 and DNA, Rad1-Rad10 and Msh2-Msh3, Saw1 and Msh2-Msh3 and Rad1-Rad10 and RPA. When any of these interactions is altered, 3' NHTR is impaired.

Analysis of DNA binding by human factor xeroderma pigmentosum complementation group A (XPA) provides insight into its interactions with nucleotide excision repair substrates.

PubMed

Sugitani, Norie; Voehler, Markus W; Roh, Michelle S; Topolska-Woś, Agnieszka M; Chazin, Walter J

2017-10-13

Xeroderma pigmentosum (XP) complementation group A (XPA) is an essential scaffolding protein in the multiprotein nucleotide excision repair (NER) machinery. The interaction of XPA with DNA is a core function of this protein; a number of mutations in the DNA-binding domain (DBD) are associated with XP disease. Although structures of the central globular domain of human XPA and data on binding of DNA substrates have been reported, the structural basis for XPA's DNA-binding activity remains unknown. X-ray crystal structures of the central globular domain of yeast XPA (Rad14) with lesion-containing DNA duplexes have provided valuable insights, but the DNA substrates used for this study do not correspond to the substrates of XPA as it functions within the NER machinery. To better understand the DNA-binding activity of human XPA in NER, we used NMR to investigate the interaction of its DBD with a range of DNA substrates. We found that XPA binds different single-stranded/double-stranded junction DNA substrates with a common surface. Comparisons of our NMR-based mapping of binding residues with the previously reported Rad14-DNA crystal structures revealed similarities and differences in substrate binding between XPA and Rad14. This includes direct evidence for DNA contacts to the residues extending C-terminally from the globular core, which are lacking in the Rad14 construct. Moreover, mutation of the XPA residue corresponding to Phe-262 in Rad14, previously reported as being critical for DNA binding, had only a moderate effect on the DNA-binding activity of XPA. The DNA-binding properties of several disease-associated mutations in the DBD were investigated. These results suggest that for XPA mutants exhibiting altered DNA-binding properties, a correlation exists between the extent of reduction in DNA-binding affinity and the severity of symptoms in XP patients. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Genetic polymorphisms in 19q13.3 genes associated with alteration of repair capacity to BPDE-DNA adducts in primary cultured lymphocytes.

PubMed

Xiao, Mingyang; Xiao, Sha; Straaten, Tahar van der; Xue, Ping; Zhang, Guopei; Zheng, Xiao; Zhang, Qianye; Cai, Yuan; Jin, Cuihong; Yang, Jinghua; Wu, Shengwen; Zhu, Guolian; Lu, Xiaobo

2016-12-01

Benzo[a]pyrene(B[a]P), and its ultimate metabolite Benzo[a]pyrene 7,8-diol 9,10-epoxide (BPDE), are classic DNA damaging carcinogens. DNA damage in cells caused by BPDE is normally repaired by Nucleotide Excision Repair (NER) and Base Excision Repair (BER). Genetic variations in NER and BER can change individual DNA repair capacity to DNA damage induced by BPDE. In the present study we determined the number of in vitro induced BPDE-DNA adducts in lymphocytes, to reflect individual susceptibility to Polycyclic aromatic hydrocarbons (PAHs)-induced carcinogenesis. The BPDE-DNA adduct level in lymphocytes were assessed by high performance liquid chromatography (HPLC) in 281 randomly selected participants. We genotyped for 9 single nucleotide polymorphisms (SNPs) in genes involved in NER (XPB rs4150441, XPC rs2228001, rs2279017 and XPF rs4781560), BER (XRCC1 rs25487, rs25489 and rs1799782) and genes located on chromosome 19q13.2-3 (PPP1R13L rs1005165 and CAST rs967591). We found that 3 polymorphisms in chromosome 19q13.2-3 were associated with lower levels of BPDE-DNA adducts (MinorT allele in XRCC1 rs1799782, minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571). In addition, a modified comet assay was performed to further confirm the above conclusions. We found both minor T allele in PPP1R13L rs1005165 and minor A allele in CAST rs967571 were associated with the lower levels of BPDE-adducts. Our data suggested that the variant genotypes of genes in chromosome 19q13.2-3 are associated with the alteration of repair efficiency to DNA damage caused by Benzo[a]pyrene, and may contribute to enhance predictive value for individual's DNA repair capacity in response to environmental carcinogens. Copyright © 2016 Elsevier B.V. All rights reserved.

Using Ontologies for the Online Recognition of Activities of Daily Living†

PubMed Central

2018-01-01

The recognition of activities of daily living is an important research area of interest in recent years. The process of activity recognition aims to recognize the actions of one or more people in a smart environment, in which a set of sensors has been deployed. Usually, all the events produced during each activity are taken into account to develop the classification models. However, the instant in which an activity started is unknown in a real environment. Therefore, only the most recent events are usually used. In this paper, we use statistics to determine the most appropriate length of that interval for each type of activity. In addition, we use ontologies to automatically generate features that serve as the input for the supervised learning algorithms that produce the classification model. The features are formed by combining the entities in the ontology, such as concepts and properties. The results obtained show a significant increase in the accuracy of the classification models generated with respect to the classical approach, in which only the state of the sensors is taken into account. Moreover, the results obtained in a simulation of a real environment under an event-based segmentation also show an improvement in most activities. PMID:29662011

Space Technology: A study of the significance of recognition for innovators of spinoff technologies. A case study on the impact of the space technology hall of fame award

NASA Technical Reports Server (NTRS)

1993-01-01

This report represents the preliminary effort in studying the significance of recognition for innovators of spinoff technologies. The purpose of this initial year's effort in this area was to gather preliminary data and define the direction for the remainder of the research. This report focuses on the most recent recipients of the Hall of Fame Award, the developers of liquid-cooled garments. Liquid-cooled garments technology and its spinoffs were used as a case study to define and explore the factors involved in technology transfer and to consider the possible incentives in developing commercial applications including the Hall of Fame Award. Through interviews, views of award recipients were obtained on factors encouraging spinoffs as well as impediments to spinoffs. The researchers observed complex inter-relationships among the significant entities (government, individuals, large and small business), the importance of people, the importance of resource availability, and the significance of intrinsic motivation; drew preliminary conclusions pertaining to the direct and indirect influence of recognition like the Hall of Fame Award; and planned the direction for next year's follow-on research.

Precision autophagy directed by receptor regulators - emerging examples within the TRIM family.

PubMed

Kimura, Tomonori; Mandell, Michael; Deretic, Vojo

2016-03-01

Selective autophagy entails cooperation between target recognition and assembly of the autophagic apparatus. Target recognition is conducted by receptors that often recognize tags, such as ubiquitin and galectins, although examples of selective autophagy independent of these tags are emerging. It is less known how receptors cooperate with the upstream autophagic regulators, beyond the well-characterized association of receptors with Atg8 or its homologs, such as LC3B (encoded by MAP1LC3B), on autophagic membranes. The molecular details of the emerging role in autophagy of the family of proteins called TRIMs shed light on the coordination between cargo recognition and the assembly and activation of the principal autophagy regulators. In their autophagy roles, TRIMs act both as receptors and as platforms ('receptor regulators') for the assembly of the core autophagy regulators, such as ULK1 and Beclin 1 in their activated state. As autophagic receptors, TRIMs can directly recognize endogenous or exogenous targets, obviating a need for intermediary autophagic tags, such as ubiquitin and galectins. The receptor and regulatory features embodied within the same entity allow TRIMs to govern cargo degradation in a highly exact process termed 'precision autophagy'. © 2016. Published by The Company of Biologists Ltd.

Enhancing the performance of cooperative face detector by NFGS

NASA Astrophysics Data System (ADS)

Yesugade, Snehal; Dave, Palak; Srivastava, Srinkhala; Das, Apurba

2015-07-01

Computerized human face detection is an important task of deformable pattern recognition in today's world. Especially in cooperative authentication scenarios like ATM fraud detection, attendance recording, video tracking and video surveillance, the accuracy of the face detection engine in terms of accuracy, memory utilization and speed have been active areas of research for the last decade. The Haar based face detection or SIFT and EBGM based face recognition systems are fairly reliable in this regard. But, there the features are extracted in terms of gray textures. When the input is a high resolution online video with a fairly large viewing area, Haar needs to search for face everywhere (say 352×250 pixels) and every time (e.g., 30 FPS capture all the time). In the current paper we have proposed to address both the aforementioned scenarios by a neuro-visually inspired method of figure-ground segregation (NFGS) [5] to result in a two-dimensional binary array from gray face image. The NFGS would identify the reference video frame in a low sampling rate and updates the same with significant change of environment like illumination. The proposed algorithm would trigger the face detector only when appearance of a new entity is encountered into the viewing area. To address the detection accuracy, classical face detector would be enabled only in a narrowed down region of interest (RoI) as fed by the NFGS. The act of updating the RoI would be done in each frame online with respect to the moving entity which in turn would improve both FR (False Rejection) and FA (False Acceptance) of the face detection system.

Acute Splenic Sequestration Crisis in Adult Sickle Cell Disease: A Report of 16 Cases.

PubMed

Naymagon, Leonard; Pendurti, Gopichand; Billett, Henny H

2015-01-01

Acute splenic sequestration crisis (ASSC), characterized by rapidly progressive anemia and circulatory compromise in the setting of sudden splenic enlargement, is an uncommon entity among adult sickle cell patients. We reviewed cases of adult ASSC encountered at our institution to generate insight into the recognition, diagnosis, and treatment of the condition. Cases of adult ASSC during a 10-year period were identified retrospectively. Patient charts were reviewed for laboratory and imaging results; demographic data and clinical course were collected and reviewed. Sixteen cases of adult ASSC were identified. Most patients presented with pain crisis; only four of 16 patients presented with abdominal pain. The maximum decreases in hemoglobin (Hb) (42.0%) and platelets (62.1%) occurred at day 2.9, delaying identification and treatment. Hemodynamic instability played a large role in dictating risk stratification. Therapy consisted of transfusion (14/16) and splenectomy (5/16). No recurrences were noted in a mean follow-up time of 5.3 years but review of patients' charts demonstrated that at least one of the patients had two prior episodes. Adult ASSC may present with non specific findings and patients may not deteriorate until several days into a previously uneventful hospital course. Changes in platelet counts may be more reliable markers than changes in Hb level since red cell transfusions may interfere with assessments of the sequestration process. This case series of adult ASSC, the largest reported in the literature to date, highlights common clinical, laboratory, radiological, and pathological features of this uncommon entity and helps to guide recognition, diagnosis, and treatment.

Consumers' Use of UMLS Concepts on Social Media: Diabetes-Related Textual Data Analysis in Blog and Social Q&A Sites.

PubMed

Park, Min Sook; He, Zhe; Chen, Zhiwei; Oh, Sanghee; Bian, Jiang

2016-11-24

The widely known terminology gap between health professionals and health consumers hinders effective information seeking for consumers. The aim of this study was to better understand consumers' usage of medical concepts by evaluating the coverage of concepts and semantic types of the Unified Medical Language System (UMLS) on diabetes-related postings in 2 types of social media: blogs and social question and answer (Q&A). We collected 2 types of social media data: (1) a total of 3711 blogs tagged with "diabetes" on Tumblr posted between February and October 2015; and (2) a total of 58,422 questions and associated answers posted between 2009 and 2014 in the diabetes category of Yahoo! Answers. We analyzed the datasets using a widely adopted biomedical text processing framework Apache cTAKES and its extension YTEX. First, we applied the named entity recognition (NER) method implemented in YTEX to identify UMLS concepts in the datasets. We then analyzed the coverage and the popularity of concepts in the UMLS source vocabularies across the 2 datasets (ie, blogs and social Q&A). Further, we conducted a concept-level comparative coverage analysis between SNOMED Clinical Terms (SNOMED CT) and Open-Access Collaborative Consumer Health Vocabulary (OAC CHV)-the top 2 UMLS source vocabularies that have the most coverage on our datasets. We also analyzed the UMLS semantic types that were frequently observed in our datasets. We identified 2415 UMLS concepts from blog postings, 6452 UMLS concepts from social Q&A questions, and 10,378 UMLS concepts from the answers. The medical concepts identified in the blogs can be covered by 56 source vocabularies in the UMLS, while those in questions and answers can be covered by 58 source vocabularies. SNOMED CT was the dominant vocabulary in terms of coverage across all the datasets, ranging from 84.9% to 95.9%. It was followed by OAC CHV (between 73.5% and 80.0%) and Metathesaurus Names (MTH) (between 55.7% and 73.5%). All of the social media datasets shared frequent semantic types such as "Amino Acid, Peptide, or Protein," "Body Part, Organ, or Organ Component," and "Disease or Syndrome." Although the 3 social media datasets vary greatly in size, they exhibited similar conceptual coverage among UMLS source vocabularies and the identified concepts showed similar semantic type distributions. As such, concepts that are both frequently used by consumers and also found in professional vocabularies such as SNOMED CT can be suggested to OAC CHV to improve its coverage. ©Min Sook Park, Zhe He, Zhiwei Chen, Sanghee Oh, Jiang Bian. Originally published in JMIR Medical Informatics (http://medinform.jmir.org), 24.11.2016.

Consumers’ Use of UMLS Concepts on Social Media: Diabetes-Related Textual Data Analysis in Blog and Social Q&A Sites

PubMed Central

Chen, Zhiwei; Oh, Sanghee; Bian, Jiang

2016-01-01

Background The widely known terminology gap between health professionals and health consumers hinders effective information seeking for consumers. Objective The aim of this study was to better understand consumers’ usage of medical concepts by evaluating the coverage of concepts and semantic types of the Unified Medical Language System (UMLS) on diabetes-related postings in 2 types of social media: blogs and social question and answer (Q&A). Methods We collected 2 types of social media data: (1) a total of 3711 blogs tagged with “diabetes” on Tumblr posted between February and October 2015; and (2) a total of 58,422 questions and associated answers posted between 2009 and 2014 in the diabetes category of Yahoo! Answers. We analyzed the datasets using a widely adopted biomedical text processing framework Apache cTAKES and its extension YTEX. First, we applied the named entity recognition (NER) method implemented in YTEX to identify UMLS concepts in the datasets. We then analyzed the coverage and the popularity of concepts in the UMLS source vocabularies across the 2 datasets (ie, blogs and social Q&A). Further, we conducted a concept-level comparative coverage analysis between SNOMED Clinical Terms (SNOMED CT) and Open-Access Collaborative Consumer Health Vocabulary (OAC CHV)—the top 2 UMLS source vocabularies that have the most coverage on our datasets. We also analyzed the UMLS semantic types that were frequently observed in our datasets. Results We identified 2415 UMLS concepts from blog postings, 6452 UMLS concepts from social Q&A questions, and 10,378 UMLS concepts from the answers. The medical concepts identified in the blogs can be covered by 56 source vocabularies in the UMLS, while those in questions and answers can be covered by 58 source vocabularies. SNOMED CT was the dominant vocabulary in terms of coverage across all the datasets, ranging from 84.9% to 95.9%. It was followed by OAC CHV (between 73.5% and 80.0%) and Metathesaurus Names (MTH) (between 55.7% and 73.5%). All of the social media datasets shared frequent semantic types such as “Amino Acid, Peptide, or Protein,” “Body Part, Organ, or Organ Component,” and “Disease or Syndrome.” Conclusions Although the 3 social media datasets vary greatly in size, they exhibited similar conceptual coverage among UMLS source vocabularies and the identified concepts showed similar semantic type distributions. As such, concepts that are both frequently used by consumers and also found in professional vocabularies such as SNOMED CT can be suggested to OAC CHV to improve its coverage. PMID:27884812

Microplane Model for Fracture Analysis of Concrete Structures

DTIC Science & Technology

1983-05-01

Curves for Cot,- Proceadings, Intern. Sympositim cai Numevical crete io Tension," Mater ils ,tndI : Str ~tuiztres d.- Un R. /na~gr No I., an. o196.9...and 226. ivinsterwalder, K, , "Festigkeit und Verfor- mung van Bet an lniter- 7.oRsIannitgenl, Duo tsatho 8. Kr~ner, h. , Zur 2’lastischen Verformung

Chesapeake Bay Riparian Handbook: A Guide for Establishing and Maintaining Riparian Forest Buffers

Treesearch

Roxane Palone; Albert Todd

1998-01-01

The Purpose of This Handbook Riparian forest buffers have been identified as avaluable nutrient reduction tool when used inconjunction with other conservation practices. For this reason, the Chesapeake Bay Programhas targeted riparian forests as a key habitat for restoration. The purpose of this handbook is toprovide professional land managers and plan-ners with the...

Prediction of Supersonic Store Separation Characteristics Including Fuselage and Stores of Noncircular Cross Section. Volume II. Users Manual for the Computer Program.

DTIC Science & Technology

1980-11-01

CMACH $ FMACH) 132 TRJTRY STOP normal termination (test: TIME > TIMEF-0.00001 or NDIFEQ = 1) BDCOEF message warning - NAFLD exceeds blank common...BDCOEF**, NTAP7- , IUB= , NAFLD = . (Test: NAFLD > NADIM) CRFWBD STOP 001 (Test: NER > 1; equation solution singular) INVER2 STOP **Matrix is singular

A Compass in Need of Alignment: Does United States Air Force Fighter Doctrine Adequately Cover Contingency Operations?

DTIC Science & Technology

1989-12-13

New York: Harcourt Brace Jovancv’.ch, 1983. Ben-Porat, Yeshayahu, Haber , Eitan and Schiff, Zeev. Entebbe Rescue. Trans. Louis Williams. New York...Times 25 Sept.e:ner 1989: pp. 16-17, 22-24, 84. Barth, Fritz J., Captain, USMC. "Stemming Nuclear Terrorism.- U.S. Naval Institute Proceedings, December

Detection of PrP(Sc) in peripheral tissues of clinically affected cattle after oral challenge with bovine spongiform encephalopathy

USDA-ARS?s Scientific Manuscript database

Bovine spongiform encephalopathy (BSE) is a fatal neurodegenerative prion disease that affects cattle and can be transmitted to human beings as new variant Creutzfeldt-Jakob disease (vCJD). A protease-resistant, disease-associated isoform of the prion protein (PrP**Sc) accumulates in the central ner...

POLYMORPHISMS IN THE DNA BASE EXCISION REPAIR GENES APEX1 AND XRCC1 AND LUNG CANCER RISK IN XUAN WEI, CHINA

EPA Science Inventory

The lung cancer mortality rate in Xuan Wei County is among the highest in China and has been attributed to exposure to indoor smoky coal emissions that contain very high levels of polycyclic aromatic hydrocarbons (PAHs). Nucleotide excision repair (NER) plays a key role in revers...

Persistently Elevated Somatic Mutation as a Biomarker for Clinically Relevant Exposures in GWI

DTIC Science & Technology

2017-10-01

radiation and/or chemicals. However, since some, but not...microarray data in breast cancer and acute myelogenous leukemia, for this analysis. Figure 1. Expression of NER genes in 10 GWI patients (red...undergoing genotoxic radio- and/or chemotherapy and victims of radiation accidents and A-bomb survivors. Perhaps because the published

Molecular Determinants of Radio Resistance in Prostate Cancer

DTIC Science & Technology

2005-08-01

Pathway Gene Accession # Ratio H/N Ratio Hypoxia/Normoxla (Log,) NER ERCCt NM001983 1.3 BER APE,2 NM_014481 1.0 MMR PMS2 NM_000535 1.3 HR RAD51...cross-complementing group 1; APEX2, apurinic!apyrimidinic endonuclease/redox factor 2; PMS2 , postmeiotic segregation increased 2; RAD51, RAD51 homolog

Basic perceptual changes that alter meaning and neural correlates of recognition memory

PubMed Central

Gao, Chuanji; Hermiller, Molly S.; Voss, Joel L.; Guo, Chunyan

2015-01-01

It is difficult to pinpoint the border between perceptual and conceptual processing, despite their treatment as distinct entities in many studies of recognition memory. For instance, alteration of simple perceptual characteristics of a stimulus can radically change meaning, such as the color of bread changing from white to green. We sought to better understand the role of perceptual and conceptual processing in memory by identifying the effects of changing a basic perceptual feature (color) on behavioral and neural correlates of memory in circumstances when this change would be expected to either change the meaning of a stimulus or to have no effect on meaning (i.e., to influence conceptual processing or not). Abstract visual shapes (“squiggles”) were colorized during study and presented during test in either the same color or a different color. Those squiggles that subjects found to resemble meaningful objects supported behavioral measures of conceptual priming, whereas meaningless squiggles did not. Further, changing color from study to test had a selective effect on behavioral correlates of priming for meaningful squiggles, indicating that color change altered conceptual processing. During a recognition memory test, color change altered event-related brain potential (ERP) correlates of memory for meaningful squiggles but not for meaningless squiggles. Specifically, color change reduced the amplitude of frontally distributed N400 potentials (FN400), implying that these potentials indicated conceptual processing during recognition memory that was sensitive to color change. In contrast, color change had no effect on FN400 correlates of recognition for meaningless squiggles, which were overall smaller in amplitude than for meaningful squiggles (further indicating that these potentials signal conceptual processing during recognition). Thus, merely changing the color of abstract visual shapes can alter their meaning, changing behavioral and neural correlates of memory. These findings are relevant to understanding similarities and distinctions between perceptual and conceptual processing as well as the functional interpretation of neural correlates of recognition memory. PMID:25717298

Conservation genetics of North American freshwater mussels Amblema and Megalonaias

USGS Publications Warehouse

Mulvey, M.; Lydeard, C.; Pyer, D.L.; Hicks, K.M.; Brim-Box, J.; Williams, J.D.; Butler, R.S.

1997-01-01

Freshwater bivalves are among the most endangered groups of organisms in North America. Efforts to protect the declining mussel fauna are confounded by ambiguities associated with recognition of distinct evolutionary entities or species. This, in part, is due to the paucity of reliable morphological characters for differentiating taxa. We have employed allozymes and DNA sequence data to search for diagnosably distinct evolutionary entities within two problematic genera of unionid mussels, Amblema and Megalonaias. Within the genus Amblema three species are recognized based on our DNA sequence data for the mitochondrial 16S rRNA and allozyme data (Amblema neislerii, A. plicata, and A. elliotti). Only one taxonomically distinct entity is recognized within the genus Megalonaias—M. nervosa. Megalonaias boykiniana of the Apalachicolan Region is not diagnosable and does not warrant specific taxonomic status. Interestingly, Megalonaias from west of the Mississippi River, including the Mississippi, exhibited an allozyme and mtDNA haplotype frequency shift suggestive of an east-west dichotomy. The results of this study eliminate one subspecies of Amblema and increase the range of A. plicata. This should not affect the conservation status of “currently stable” assigned to A. plicata by Williams et al. (1993). The conservation status of A. elliotti needs to be reexamined because its distribution appears to be limited to the Coosa River System in Alabama and Georgia.

TwiMed: Twitter and PubMed Comparable Corpus of Drugs, Diseases, Symptoms, and Their Relations

PubMed Central

Miyao, Yusuke; Collier, Nigel

2017-01-01

Background Work on pharmacovigilance systems using texts from PubMed and Twitter typically target at different elements and use different annotation guidelines resulting in a scenario where there is no comparable set of documents from both Twitter and PubMed annotated in the same manner. Objective This study aimed to provide a comparable corpus of texts from PubMed and Twitter that can be used to study drug reports from these two sources of information, allowing researchers in the area of pharmacovigilance using natural language processing (NLP) to perform experiments to better understand the similarities and differences between drug reports in Twitter and PubMed. Methods We produced a corpus comprising 1000 tweets and 1000 PubMed sentences selected using the same strategy and annotated at entity level by the same experts (pharmacists) using the same set of guidelines. Results The resulting corpus, annotated by two pharmacists, comprises semantically correct annotations for a set of drugs, diseases, and symptoms. This corpus contains the annotations for 3144 entities, 2749 relations, and 5003 attributes. Conclusions We present a corpus that is unique in its characteristics as this is the first corpus for pharmacovigilance curated from Twitter messages and PubMed sentences using the same data selection and annotation strategies. We believe this corpus will be of particular interest for researchers willing to compare results from pharmacovigilance systems (eg, classifiers and named entity recognition systems) when using data from Twitter and from PubMed. We hope that given the comprehensive set of drug names and the annotated entities and relations, this corpus becomes a standard resource to compare results from different pharmacovigilance studies in the area of NLP. PMID:28468748

BioCreative V CDR task corpus: a resource for chemical disease relation extraction.

PubMed

Li, Jiao; Sun, Yueping; Johnson, Robin J; Sciaky, Daniela; Wei, Chih-Hsuan; Leaman, Robert; Davis, Allan Peter; Mattingly, Carolyn J; Wiegers, Thomas C; Lu, Zhiyong

2016-01-01

Community-run, formal evaluations and manually annotated text corpora are critically important for advancing biomedical text-mining research. Recently in BioCreative V, a new challenge was organized for the tasks of disease named entity recognition (DNER) and chemical-induced disease (CID) relation extraction. Given the nature of both tasks, a test collection is required to contain both disease/chemical annotations and relation annotations in the same set of articles. Despite previous efforts in biomedical corpus construction, none was found to be sufficient for the task. Thus, we developed our own corpus called BC5CDR during the challenge by inviting a team of Medical Subject Headings (MeSH) indexers for disease/chemical entity annotation and Comparative Toxicogenomics Database (CTD) curators for CID relation annotation. To ensure high annotation quality and productivity, detailed annotation guidelines and automatic annotation tools were provided. The resulting BC5CDR corpus consists of 1500 PubMed articles with 4409 annotated chemicals, 5818 diseases and 3116 chemical-disease interactions. Each entity annotation includes both the mention text spans and normalized concept identifiers, using MeSH as the controlled vocabulary. To ensure accuracy, the entities were first captured independently by two annotators followed by a consensus annotation: The average inter-annotator agreement (IAA) scores were 87.49% and 96.05% for the disease and chemicals, respectively, in the test set according to the Jaccard similarity coefficient. Our corpus was successfully used for the BioCreative V challenge tasks and should serve as a valuable resource for the text-mining research community.Database URL: http://www.biocreative.org/tasks/biocreative-v/track-3-cdr/. Published by Oxford University Press 2016. This work is written by US Government employees and is in the public domain in the United States.

TwiMed: Twitter and PubMed Comparable Corpus of Drugs, Diseases, Symptoms, and Their Relations.

PubMed

Alvaro, Nestor; Miyao, Yusuke; Collier, Nigel

2017-05-03

Work on pharmacovigilance systems using texts from PubMed and Twitter typically target at different elements and use different annotation guidelines resulting in a scenario where there is no comparable set of documents from both Twitter and PubMed annotated in the same manner. This study aimed to provide a comparable corpus of texts from PubMed and Twitter that can be used to study drug reports from these two sources of information, allowing researchers in the area of pharmacovigilance using natural language processing (NLP) to perform experiments to better understand the similarities and differences between drug reports in Twitter and PubMed. We produced a corpus comprising 1000 tweets and 1000 PubMed sentences selected using the same strategy and annotated at entity level by the same experts (pharmacists) using the same set of guidelines. The resulting corpus, annotated by two pharmacists, comprises semantically correct annotations for a set of drugs, diseases, and symptoms. This corpus contains the annotations for 3144 entities, 2749 relations, and 5003 attributes. We present a corpus that is unique in its characteristics as this is the first corpus for pharmacovigilance curated from Twitter messages and PubMed sentences using the same data selection and annotation strategies. We believe this corpus will be of particular interest for researchers willing to compare results from pharmacovigilance systems (eg, classifiers and named entity recognition systems) when using data from Twitter and from PubMed. We hope that given the comprehensive set of drug names and the annotated entities and relations, this corpus becomes a standard resource to compare results from different pharmacovigilance studies in the area of NLP. ©Nestor Alvaro, Yusuke Miyao, Nigel Collier. Originally published in JMIR Public Health and Surveillance (http://publichealth.jmir.org), 03.05.2017.

Cholesterol granuloma of the petrous apex: CT diagnosis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lo, W.W.M.; Solti-Bohman, L.G.; Brackmann, D.E.

Cholesterol granuloma of the petrous apex is a readily recognizable and treatable entity that is more common than previously realized. Cholesterol granuloma grows slowly in the petrous apex as a mass lesion until it produces hearing loss, tinnitus, vertigo, and facial twitching. Twelve cases of cholesterol granuloma of the petrous apex are illustrated; ten of these analyzed in detail, especially with respect to CT findings. A sharply and smoothly marginated expansile lesion in the petrous apex, isodense with plain and nonenhancing on CT, is in all probability a cholesterol granuloma. Preoperative recognition by CT is important for planning proper treatment.

Controversies in cardiovascular care: silent myocardial ischemia

NASA Technical Reports Server (NTRS)

Hollenberg, N. K.

1987-01-01

The objective evidence of silent myocardial ischemia--ischemia in the absence of classical chest pain--includes ST-segment shifts (usually depression), momentary left ventricular failure, and perfusion defects on scintigraphic studies. Assessment of angina patients with 24-hour ambulatory monitoring may uncover episodes of silent ischemia, the existence of which may give important information regarding prognosis and may help structure a more effective therapeutic regimen. The emerging recognition of silent ischemia as a significant clinical entity may eventually result in an expansion of current therapy--not only to ameliorate chest pain, but to minimize or eliminate ischemia in the absence of chest pain.

Occurrence of Double Monoclonal Bands on Protein Electrophoresis: An Unusual Finding.

PubMed

Srinivasan, Vishrut K; Bhagat, Priyanka; Bansal, Frainey; Chhabra, Seema

2016-06-01

Various techniques of protein electrophoresis are used for detection of monoclonal proteins/paraproteins in serum and/or urine of patients with monoclonal gammopathies. These are detected as the so-called 'M' bands (monoclonal bands) on serum protein electrophoresis and/or immunofixation electrophoresis. In most cases, a single M-band is detected. However, more than one M-band can be detected in the samples of a minor proportion of patients. This condition is termed as 'double gammopathy' or 'biclonal gammopathy'. A knowledge of such an unusual occurrence is essential for recognition and appropriate interpretation of this entity.

A Systematic Approach to Emergencies in Uveitis

PubMed Central

Al-Dhibi, Hassan A.; Al-Mahmood, Ammar M.; Arevalo, J. Fernando

2014-01-01

Uveitis is a common cause of preventable blindness although it is consider a sight-threatening condition particularly in cases with posterior segment inflammation. To deal with emergency conditions in uveitis, we must aware of the essential signs and symptoms that reflect a true uveitic emergency. Failure to recognize these essential signs and symptoms of a true uveitic emergency may result in a devastating visual outcome. This review provides general ophthalmologists and residents, clinical guidelines for the main uveitic entities that require immediate recognition and urgent intervention in the emergency room to prevent severe permanent visual loss. PMID:25100911

OSCAR4: a flexible architecture for chemical text-mining

PubMed Central

2011-01-01

The Open-Source Chemistry Analysis Routines (OSCAR) software, a toolkit for the recognition of named entities and data in chemistry publications, has been developed since 2002. Recent work has resulted in the separation of the core OSCAR functionality and its release as the OSCAR4 library. This library features a modular API (based on reduction of surface coupling) that permits client programmers to easily incorporate it into external applications. OSCAR4 offers a domain-independent architecture upon which chemistry specific text-mining tools can be built, and its development and usage are discussed. PMID:21999457

A Systematic Approach for Discovering Novel, Clinically Relevant Bacteria

PubMed Central

Simmon, Keith E.; Fisher, Mark A.

2012-01-01

Sequencing of the 16S rRNA gene (16S) is a reference method for bacterial identification. Its expanded use has led to increased recognition of novel bacterial species. In most clinical laboratories, novel species are infrequently encountered, and their pathogenic potential is often difficult to assess. We reviewed partial 16S sequences from >26,000 clinical isolates, analyzed during February 2006–June 2010, and identified 673 that have <99% sequence identity with valid reference sequences and are thus possibly novel species. Of these 673 isolates, 111 may represent novel genera (<95% identity). Isolates from 95 novel taxa were recovered from multiple patients, indicating possible clinical relevance. Most repeatedly encountered novel taxa belonged to the genera Nocardia (14 novel taxa, 42 isolates) and Actinomyces (12 novel taxa, 52 isolates). This systematic approach for recognition of novel species with potential diagnostic or therapeutic relevance provides a basis for epidemiologic surveys and improvement of sequence databases and may lead to identification of new clinical entities. PMID:22377371

Temporally extended self-awareness and affective engagement in three-year-olds.

PubMed

Zocchi, Silvia; Borasio, Francesca; Rivolta, Davide; Rositano, Luana; Scotti, Ilaria; Liccione, Davide

2018-01-01

The aim of the current study was to analyze the role of affective engagement during social interaction on the emergence of a temporally extended self (TES). A Delayed Self Recognition task was administered in two different social contexts: in presence of the mother ("Mother condition") or in presence of an unfamiliar person ("Experimenter condition"). The same sample of 71 tree-year-olds was tested twice in these two treatment conditions. Results showed higher self-recognition scores in the "Mother condition". These findings are consistent with developing-self theories that emphasize the impact of reciprocal social interaction on the emergence of self-awareness, and support a conception of the Self as a dialogic entity. We interpreted this link as a evidence that, when completing the procedure with their mother, children are aware of her attention, which corresponds to a familiar mode of self-perception, as well as to a peculiar affective consciousness of Self. Copyright © 2017 Elsevier Inc. All rights reserved.

An update on the recognition and treatment of non-convulsive status epilepticus in the intensive care unit.

PubMed

Kinney, Michael O; Kaplan, Peter W

2017-10-01

Non-convulsive status epilepticus (NCSE) is a complex and diverse condition which is often an under-recognised entity in the intensive care unit. When NCSE is identified the optimal treatment strategy is not always clear. Areas covered: This review is based on a literature review of the key literature in the field over the last 5-10 years. The articles were selected based on their importance to the field by the authors. Expert commentary: This review discusses the complex situations when a neurological consultation may occur in a critical care setting and provides an update on the latest evidence regarding the recognition of NCSE and the decision making around determining the aggressiveness of treatment. It also considers the ictal-interictal continuum of conditions which may be met with, particularly in the era of continuous EEG, and provides an approach for dealing with these. Suggestions for how the field will develop are discussed.

Improving recognition of hepatic perivascular epithelioid cell tumor: Case report and literature review.

PubMed

Maebayashi, Toshiya; Abe, Katsumi; Aizawa, Takuya; Sakaguchi, Masakuni; Ishibashi, Naoya; Abe, Osamu; Takayama, Tadatoshi; Nakayama, Hisashi; Matsuoka, Shunichi; Nirei, Kazushige; Nakamura, Hitomi; Ogawa, Masahiro; Sugitani, Masahiko

2015-05-07

A 58-year-old man presented with the chief complaint of abdominal bloating and was incidentally found to have a liver tumor. As diagnostic imaging studies could not rule out malignancy, the patient underwent partial resection of segment 3 of the liver. The lesion pathologically showed eosinophilic proliferation, in addition to immunohistochemical positivity for human melanoma black 45 and Melan-A, thereby leading to the diagnosis of a hepatic perivascular epithelioid cell tumor (PEComa). A PEComa arising from the liver is relatively rare. Moreover, the name 'PEComa' has not yet been widely recognized, and the same disease entity has been called epithelioid angiomyolipoma (EAML), further diminishing the recognition of PEComa. In addition, PEComa imaging findings mimic those of malignant liver tumors, and clinically, this tumor tends to enlarge. Therefore, a PEComa is difficult to diagnose. We conducted a systematic review of PEComa and EAML cases and discuss the results, including findings useful for differentiating perivascular epithelioid cell tumors from malignant liver tumors.

Improving recognition of hepatic perivascular epithelioid cell tumor: Case report and literature review

PubMed Central

Maebayashi, Toshiya; Abe, Katsumi; Aizawa, Takuya; Sakaguchi, Masakuni; Ishibashi, Naoya; Abe, Osamu; Takayama, Tadatoshi; Nakayama, Hisashi; Matsuoka, Shunichi; Nirei, Kazushige; Nakamura, Hitomi; Ogawa, Masahiro; Sugitani, Masahiko

2015-01-01

A 58-year-old man presented with the chief complaint of abdominal bloating and was incidentally found to have a liver tumor. As diagnostic imaging studies could not rule out malignancy, the patient underwent partial resection of segment 3 of the liver. The lesion pathologically showed eosinophilic proliferation, in addition to immunohistochemical positivity for human melanoma black 45 and Melan-A, thereby leading to the diagnosis of a hepatic perivascular epithelioid cell tumor (PEComa). A PEComa arising from the liver is relatively rare. Moreover, the name ‘PEComa’ has not yet been widely recognized, and the same disease entity has been called epithelioid angiomyolipoma (EAML), further diminishing the recognition of PEComa. In addition, PEComa imaging findings mimic those of malignant liver tumors, and clinically, this tumor tends to enlarge. Therefore, a PEComa is difficult to diagnose. We conducted a systematic review of PEComa and EAML cases and discuss the results, including findings useful for differentiating perivascular epithelioid cell tumors from malignant liver tumors. PMID:25954119

Identification of related gene/protein names based on an HMM of name variations.

PubMed

Yeganova, L; Smith, L; Wilbur, W J

2004-04-01

Gene and protein names follow few, if any, true naming conventions and are subject to great variation in different occurrences of the same name. This gives rise to two important problems in natural language processing. First, can one locate the names of genes or proteins in free text, and second, can one determine when two names denote the same gene or protein? The first of these problems is a special case of the problem of named entity recognition, while the second is a special case of the problem of automatic term recognition (ATR). We study the second problem, that of gene or protein name variation. Here we describe a system which, given a query gene or protein name, identifies related gene or protein names in a large list. The system is based on a dynamic programming algorithm for sequence alignment in which the mutation matrix is allowed to vary under the control of a fully trainable hidden Markov model.

A systematic approach for discovering novel, clinically relevant bacteria.

PubMed

Schlaberg, Robert; Simmon, Keith E; Fisher, Mark A

2012-03-01

Sequencing of the 16S rRNA gene (16S) is a reference method for bacterial identification. Its expanded use has led to increased recognition of novel bacterial species. In most clinical laboratories, novel species are infrequently encountered, and their pathogenic potential is often difficult to assess. We reviewed partial 16S sequences from >26,000 clinical isolates, analyzed during February 2006-June 2010, and identified 673 that have <99% sequence identity with valid reference sequences and are thus possibly novel species. Of these 673 isolates, 111 may represent novel genera (<95% identity). Isolates from 95 novel taxa were recovered from multiple patients, indicating possible clinical relevance. Most repeatedly encountered novel taxa belonged to the genera Nocardia (14 novel taxa, 42 isolates) and Actinomyces (12 novel taxa, 52 isolates). This systematic approach for recognition of novel species with potential diagnostic or therapeutic relevance provides a basis for epidemiologic surveys and improvement of sequence databases and may lead to identification of new clinical entities.

A new method for recognizing quadric surfaces from range data and its application to telerobotics and automation, final phase

NASA Technical Reports Server (NTRS)

Mielke, Roland; Dcunha, Ivan; Alvertos, Nicolas

1994-01-01

In the final phase of the proposed research a complete top to down three dimensional object recognition scheme has been proposed. The various three dimensional objects included spheres, cones, cylinders, ellipsoids, paraboloids, and hyperboloids. Utilizing a newly developed blob determination technique, a given range scene with several non-cluttered quadric surfaces is segmented. Next, using the earlier (phase 1) developed alignment scheme, each of the segmented objects are then aligned in a desired coordinate system. For each of the quadric surfaces based upon their intersections with certain pre-determined planes, a set of distinct features (curves) are obtained. A database with entities such as the equations of the planes and angular bounds of these planes has been created for each of the quadric surfaces. Real range data of spheres, cones, cylinders, and parallelpipeds have been utilized for the recognition process. The developed algorithm gave excellent results for the real data as well as for several sets of simulated range data.

40 CFR 1051.145 - What provisions apply only for a limited time?

Code of Federal Regulations, 2012 CFR

2012-07-01

... nitrogen in g/kW-hr. (ii) For engines below 225 cc, use the following equation: NER = 9.898 × log [(HC+NOX... oxides of nitrogen in g/kW-hr. (c) [Reserved] (d) Phase-in flexibility. For model years before 2014, if... model years, you may have a negative balance of emission credits relative to the permeation emission...

40 CFR 1051.145 - What provisions apply only for a limited time?

Code of Federal Regulations, 2013 CFR

2013-07-01

... nitrogen in g/kW-hr. (ii) For engines below 225 cc, use the following equation: NER = 9.898 × log [(HC+NOX... oxides of nitrogen in g/kW-hr. (c) [Reserved] (d) Phase-in flexibility. For model years before 2014, if... model years, you may have a negative balance of emission credits relative to the permeation emission...

40 CFR 1051.145 - What provisions apply only for a limited time?

Code of Federal Regulations, 2014 CFR

2014-07-01

... nitrogen in g/kW-hr. (ii) For engines below 225 cc, use the following equation: NER = 9.898 × log [(HC+NOX... oxides of nitrogen in g/kW-hr. (c) [Reserved] (d) Phase-in flexibility. For model years before 2014, if... model years, you may have a negative balance of emission credits relative to the permeation emission...

40 CFR 1051.145 - What provisions apply only for a limited time?

Code of Federal Regulations, 2011 CFR

2011-07-01

... nitrogen in g/kW-hr. (ii) For engines below 225 cc, use the following equation: NER = 9.898 × log [(HC+NOX... oxides of nitrogen in g/kW-hr. (c) [Reserved] (d) Phase-in flexibility. For model years before 2014, if... model years, you may have a negative balance of emission credits relative to the permeation emission...

40 CFR 1051.145 - What provisions apply only for a limited time?

Code of Federal Regulations, 2010 CFR

2010-07-01

... nitrogen in g/kW-hr. (ii) For engines below 225 cc, use the following equation: NER = 9.898 × log [(HC+NOX... oxides of nitrogen in g/kW-hr. (c) [Reserved] (d) Phase-in flexibility. For model years before 2014, if... model years, you may have a negative balance of emission credits relative to the permeation emission...

The United States Merchant Marine Academy Historic District: Nomination to the National Register of Historic Places

DTIC Science & Technology

2014-10-01

the determination of effect of federal... The USMMA is the nation’s only federally- owned educational facility for the advanced training of merchant mari- ners. This work determined the ...met through the design of the buildings that survive on the district’s grounds. The district was listed by the NRHP in August 2014 as

Entropy and optimality in river deltas

NASA Astrophysics Data System (ADS)

Tejedor, Alejandro; Longjas, Anthony; Edmonds, Douglas A.; Zaliapin, Ilya; Georgiou, Tryphon T.; Rinaldo, Andrea; Foufoula-Georgiou, Efi

2017-10-01

The form and function of river deltas is intricately linked to the evolving structure of their channel networks, which controls how effectively deltas are nourished with sediments and nutrients. Understanding the coevolution of deltaic channels and their flux organization is crucial for guiding maintenance strategies of these highly stressed systems from a range of anthropogenic activities. To date, however, a unified theory explaining how deltas self-organize to distribute water and sediment up to the shoreline remains elusive. Here, we provide evidence for an optimality principle underlying the self-organized partition of fluxes in delta channel networks. By introducing a suitable nonlocal entropy rate (nER) and by analyzing field and simulated deltas, we suggest that delta networks achieve configurations that maximize the diversity of water and sediment flux delivery to the shoreline. We thus suggest that prograding deltas attain dynamically accessible optima of flux distributions on their channel network topologies, thus effectively decoupling evolutionary time scales of geomorphology and hydrology. When interpreted in terms of delta resilience, high nER configurations reflect an increased ability to withstand perturbations. However, the distributive mechanism responsible for both diversifying flux delivery to the shoreline and dampening possible perturbations might lead to catastrophic events when those perturbations exceed certain intensity thresholds.

Physical chemistry of Nanogap-Enhanced Raman Scattering (NERS)

NASA Astrophysics Data System (ADS)

Suh, Yung Doug; Kim, Hyun Woo

2017-08-01

Plasmonically coupled electromagnetic field localization has generated a variety of new concepts and applications, and this has been one of the hottest topics in nanoscience, materials science, chemistry, physics and engineering and increasingly more important over the last decade. In particular, plasmonically coupled nanostructures with ultra-small gap ( 1-nm or smaller) gap have been of special interest due to their ultra-strong optical properties that can be useful for a variety of signal enhancements such surface-enhanced Raman scattering (SERS) and nanoantenna. These promising nanostructures with extraordinarily strong optical signal, however, have rendered a limited success in widespread use and commercialization largely due to the lack of designing principles, high-yield synthetic strategies with nm-level structural controllability and reproducibility and lack of systematic single-molecule and single-particle level studies. All these are extremely important challenges because even small changes ( 1 nm) of the coupled nanogap structures can significant affect plasmon mode and signal intensity and therefore structural and signal reproducibility and controllability can be in question. The plasmonic nanogap-enhanced Raman scattering (NERS) is defined as the plasmonic nanogap-based Raman signal enhancement within plasmonic nanogap particles with 1 nm gap and a Raman dye positioned inside the gap.

Survey of patient dosimetry for head and neck cancer patients undergoing external radiotherapy treatment: a study from northeastern hospitals of India.

PubMed

Sharma, Arunkumar B; Singh, Tomcha Th; Singh, Khelendra N; Gartia, R K

2009-01-01

To study dosimetry of patients during the external radiotherapy of head and neck cancers from different hospitals of the northeastern region (NER) of India. 35 confirmed cases of head and neck cancers reporting to three different hospitals in the NER of India who underwent radiation treatment were the materials for the study. Dosimetry was carried out at 8(eight) anatomical points to these patients, namely, target (entrance and exit points), forehead, chest, abdomen, gonad, arm, and leg respectively by thermoluminescence (TL) as well as optically stimulated luminescence (OSL) dosimeters. Unlike conventional appliances, we used common iodized salt as TL/OSL phosphor. Patient dosimetry was found to vary with an average of 1.17 +/- 0.39 Sv at forehead, 1.24 +/- 0.39 Sv at chest, 0.52 +/- 0.13 Sv at gonad to a minimum of 0.26 +/- 0.07 Sv at leg areas when exposed to a cumulative dose of 65 Sv at the target. Maximum dose received from a stray radiation is about 1.5 Sv at forehead/chest and dosimetry of patient among the three centers is not significantly different at the 5% level of probability.

Combined loss of three DNA damage response pathways renders C. elegans intolerant to light.

PubMed

van Bostelen, Ivo; Tijsterman, Marcel

2017-06-01

Infliction of DNA damage initiates a complex cellular reaction - the DNA damage response - that involves both signaling and DNA repair networks with many redundancies and parallel pathways. Here, we reveal the three strategies that the simple multicellular eukaryote, C. elegans, uses to deal with DNA damage induced by light. Separately inactivating repair or replicative bypass of photo-lesions results in cellular hypersensitivity towards UV-light, but impeding repair of replication associated DNA breaks does not. Yet, we observe an unprecedented synergistic relationship when these pathways are inactivated in combination. C. elegans mutants that lack nucleotide excision repair (NER), translesion synthesis (TLS) and alternative end joining (altEJ) grow undisturbed in the dark, but become sterile when grown in light. Even exposure to very low levels of normal daylight impedes animal growth. We show that NER and TLS operate to suppress the formation of lethal DNA breaks that require polymerase theta-mediated end joining (TMEJ) for their repair. Our data testifies to the enormous genotoxicity of light and to the demand of multiple layers of protection against an environmental threat that is so common. Copyright © 2017 Elsevier B.V. All rights reserved.

Techno-economic and life-cycle assessment of an attached growth algal biorefinery.

PubMed

Barlow, Jay; Sims, Ronald C; Quinn, Jason C

2016-11-01

This study examined the sustainability of generating renewable diesel via hydrothermal liquefaction (HTL) of biomass from a rotating algal biofilm reactor. Pilot-scale growth studies and laboratory-scale HTL experiments were used to validate an engineering system model. The engineering system model served as the foundation to evaluate the economic feasibility and environmental impact of the system at full scale. Techno-economic results indicate that biomass feedstock costs dominated the minimum fuel selling price (MFSP), with a base case of $104.31per gallon. Life-cycle assessment results show a base-case global warming potential (GWP) of 80gCO2-eMJ(-1) and net energy ratio (NER) of 1.65 based on a well-to-product system boundary. Optimization of the system reduces MFSP, GWP and NER to $11.90Gal(-1), -44gCO2-eMJ(-1), and 0.33, respectively. The systems-level impacts of integrating algae cultivation with wastewater treatment were found to significantly reduce environmental impact. Sensitivity analysis showed that algal productivity most significantly affected fuel selling price, emphasizing the importance of optimizing biomass productivity. Copyright © 2016 Elsevier Ltd. All rights reserved.