Using i2b2 to Bootstrap Rural Health Analytics and Learning Networks

PubMed Central

Harris, Daniel R.; Baus, Adam D.; Harper, Tamela J.; Jarrett, Traci D.; Pollard, Cecil R.; Talbert, Jeffery C.

2017-01-01

We demonstrate that the open-source i2b2 (Informatics for Integrating Biology and the Bedside) data model can be used to bootstrap rural health analytics and learning networks. These networks promote communication and research initiatives by providing the infrastructure necessary for sharing data and insights across a group of healthcare and research partners. Data integration remains a crucial challenge in connecting rural healthcare sites with a common data sharing and learning network due to the lack of interoperability and standards within electronic health records. The i2b2 data model acts as a point of convergence for disparate data from multiple healthcare sites. A consistent and natural data model for healthcare data is essential for overcoming integration issues, but challenges such as those caused by weak data standardization must still be addressed. We describe our experience in the context of building the West Virginia/Kentucky Health Analytics and Learning Network, a collaborative, multi-state effort connecting rural healthcare sites. PMID:28261006

Using i2b2 to Bootstrap Rural Health Analytics and Learning Networks.

PubMed

Harris, Daniel R; Baus, Adam D; Harper, Tamela J; Jarrett, Traci D; Pollard, Cecil R; Talbert, Jeffery C

2016-08-01

We demonstrate that the open-source i2b2 (Informatics for Integrating Biology and the Bedside) data model can be used to bootstrap rural health analytics and learning networks. These networks promote communication and research initiatives by providing the infrastructure necessary for sharing data and insights across a group of healthcare and research partners. Data integration remains a crucial challenge in connecting rural healthcare sites with a common data sharing and learning network due to the lack of interoperability and standards within electronic health records. The i2b2 data model acts as a point of convergence for disparate data from multiple healthcare sites. A consistent and natural data model for healthcare data is essential for overcoming integration issues, but challenges such as those caused by weak data standardization must still be addressed. We describe our experience in the context of building the West Virginia/Kentucky Health Analytics and Learning Network, a collaborative, multi-state effort connecting rural healthcare sites.

Integrating Multimodal Radiation Therapy Data into i2b2.

PubMed

Zapletal, Eric; Bibault, Jean-Emmanuel; Giraud, Philippe; Burgun, Anita

2018-04-01

 Clinical data warehouses are now widely used to foster clinical and translational research and the Informatics for Integrating Biology and the Bedside (i2b2) platform has become a de facto standard for storing clinical data in many projects. However, to design predictive models and assist in personalized treatment planning in cancer or radiation oncology, all available patient data need to be integrated into i2b2, including radiation therapy data that are currently not addressed in many existing i2b2 sites.  To use radiation therapy data in projects related to rectal cancer patients, we assessed the feasibility of integrating radiation oncology data into the i2b2 platform.  The Georges Pompidou European Hospital, a hospital from the Assistance Publique - Hôpitaux de Paris group, has developed an i2b2-based clinical data warehouse of various structured and unstructured clinical data for research since 2008. To store and reuse various radiation therapy data-dose details, activities scheduling, and dose-volume histogram (DVH) curves-in this repository, we first extracted raw data by using some reverse engineering techniques and a vendor's application programming interface. Then, we implemented a hybrid storage approach by combining the standard i2b2 "Entity-Attribute-Value" storage mechanism with a "JavaScript Object Notation (JSON) document-based" storage mechanism without modifying the i2b2 core tables. Validation was performed using (1) the Business Objects framework for replicating vendor's application screens showing dose details and activities scheduling data and (2) the R software for displaying the DVH curves.  We developed a pipeline to integrate the radiation therapy data into the Georges Pompidou European Hospital i2b2 instance and evaluated it on a cohort of 262 patients. We were able to use the radiation therapy data on a preliminary use case by fetching the DVH curve data from the clinical data warehouse and displaying them in a R chart. �

Interacting TCP and NLP transcription factors control plant responses to nitrate availability.

PubMed

Guan, Peizhu; Ripoll, Juan-José; Wang, Renhou; Vuong, Lam; Bailey-Steinitz, Lindsay J; Ye, Dening; Crawford, Nigel M

2017-02-28

Plants have evolved adaptive strategies that involve transcriptional networks to cope with and survive environmental challenges. Key transcriptional regulators that mediate responses to environmental fluctuations in nitrate have been identified; however, little is known about how these regulators interact to orchestrate nitrogen (N) responses and cell-cycle regulation. Here we report that teosinte branched1/cycloidea/proliferating cell factor1-20 (TCP20) and NIN-like protein (NLP) transcription factors NLP6 and NLP7, which act as activators of nitrate assimilatory genes, bind to adjacent sites in the upstream promoter region of the nitrate reductase gene, NIA1 , and physically interact under continuous nitrate and N-starvation conditions. Regions of these proteins necessary for these interactions were found to include the type I/II Phox and Bem1p (PB1) domains of NLP6&7, a protein-interaction module conserved in animals for nutrient signaling, and the histidine- and glutamine-rich domain of TCP20, which is conserved across plant species. Under N starvation, TCP20-NLP6&7 heterodimers accumulate in the nucleus, and this coincides with TCP20 and NLP6&7-dependent up-regulation of nitrate assimilation and signaling genes and down-regulation of the G 2 /M cell-cycle marker gene, CYCB1;1 TCP20 and NLP6&7 also support root meristem growth under N starvation. These findings provide insights into how plants coordinate responses to nitrate availability, linking nitrate assimilation and signaling with cell-cycle progression.

The role of centrosomal Nlp in the control of mitotic progression and tumourigenesis.

PubMed

Li, J; Zhan, Q

2011-05-10

The human centrosomal ninein-like protein (Nlp) is a new member of the γ-tubulin complexes binding proteins (GTBPs) that is essential for proper execution of various mitotic events. The primary function of Nlp is to promote microtubule nucleation that contributes to centrosome maturation, spindle formation and chromosome segregation. Its subcellular localisation and protein stability are regulated by several crucial mitotic kinases, such as Plk1, Nek2, Cdc2 and Aurora B. Several lines of evidence have linked Nlp to human cancer. Deregulation of Nlp in cell models results in aberrant spindle, chromosomal missegregation and multinulei, and induces chromosomal instability and renders cells tumourigenic. Overexpression of Nlp induces anchorage-independent growth and immortalised primary cell transformation. In addition, we first demonstrate that the expression of Nlp is elevated primarily due to NLP gene amplification in human breast cancer and lung carcinoma. Consistently, transgenic mice overexpressing Nlp display spontaneous tumours in breast, ovary and testicle, and show rapid onset of radiation-induced lymphoma, indicating that Nlp is involved in tumourigenesis. This review summarises our current knowledge of physiological roles of Nlp, with an emphasis on its potentials in tumourigenesis.

The role of centrosomal Nlp in the control of mitotic progression and tumourigenesis

PubMed Central

Li, J; Zhan, Q

2011-01-01

The human centrosomal ninein-like protein (Nlp) is a new member of the γ-tubulin complexes binding proteins (GTBPs) that is essential for proper execution of various mitotic events. The primary function of Nlp is to promote microtubule nucleation that contributes to centrosome maturation, spindle formation and chromosome segregation. Its subcellular localisation and protein stability are regulated by several crucial mitotic kinases, such as Plk1, Nek2, Cdc2 and Aurora B. Several lines of evidence have linked Nlp to human cancer. Deregulation of Nlp in cell models results in aberrant spindle, chromosomal missegregation and multinulei, and induces chromosomal instability and renders cells tumourigenic. Overexpression of Nlp induces anchorage-independent growth and immortalised primary cell transformation. In addition, we first demonstrate that the expression of Nlp is elevated primarily due to NLP gene amplification in human breast cancer and lung carcinoma. Consistently, transgenic mice overexpressing Nlp display spontaneous tumours in breast, ovary and testicle, and show rapid onset of radiation-induced lymphoma, indicating that Nlp is involved in tumourigenesis. This review summarises our current knowledge of physiological roles of Nlp, with an emphasis on its potentials in tumourigenesis. PMID:21505454

Blood-Injection-Injury (B-I-I) Specific Phobia Affects the Outcome of Hypoxic Challenge Testing.

PubMed

Spurling, Kristofer J; McGoldrick, Veronica P

2017-05-01

Blood-injection-injury (B-I-I) phobia is capable of producing inaccurate hypoxic challenge testing results due to anxiety-induced hyperventilation. A 69-yr-old woman with a history of hypersensitivity pneumonitis, restrictive spirometry, exercise desaturation requiring supplementary oxygen on mobilizing, reduced DLco, and B-I-I phobia was referred for hypoxic challenge testing (HCT) to assess in-flight oxygen requirements. HCT was performed by breathing a 15% FIo2 gas mixture, simulating the available oxygen in ambient air onboard aircraft pressurized to an equivalent altitude of 8000 ft. Spo2 fell to a nadir value of 81% during HCT, although it rapidly increased to 89% during the first of two attempts at blood gas sampling. A resultant blood gas sample showed an acceptable Po2 outside the criteria for recommending in-flight oxygen and a reduced Pco2. Entering the nadir Spo2 value into the Severinghaus equation gives an estimated arterial Po2 of 6 kPa (45 mmHg), which was felt to be more representative of resting values during HCT, and in-flight oxygen was recommended. While hyperventilation is an expected response to hypoxia, transient rises in Spo2 coinciding with threat of injury are likely to be attributable to emotional stress-induced hyperventilation, characteristic of B-I-I specific phobia and expected during the anticipation of exteroceptive threat, even in normal subjects. In summary, should excessive hyperventilation be detected during HCT and coincide with transient increases in Spo2, HCT should be repeated using Spo2 only as a guide to the level of hypoxemia, and Spo2 maintained using supplementary oxygen in accordance with alternative methods described in guidelines.Spurling KJ, McGoldrick VP. Blood-injection-injury (B-I-I) specific phobia affects the outcome of hypoxic challenge testing. Aerosp Med Hum Perform. 2017; 88(5):503-506.

Combining clinical and genomics queries using i2b2 – Three methods

PubMed Central

Murphy, Shawn N.; Avillach, Paul; Bellazzi, Riccardo; Phillips, Lori; Gabetta, Matteo; Eran, Alal; McDuffie, Michael T.; Kohane, Isaac S.

2017-01-01

We are fortunate to be living in an era of twin biomedical data surges: a burgeoning representation of human phenotypes in the medical records of our healthcare systems, and high-throughput sequencing making rapid technological advances. The difficulty representing genomic data and its annotations has almost by itself led to the recognition of a biomedical “Big Data” challenge, and the complexity of healthcare data only compounds the problem to the point that coherent representation of both systems on the same platform seems insuperably difficult. We investigated the capability for complex, integrative genomic and clinical queries to be supported in the Informatics for Integrating Biology and the Bedside (i2b2) translational software package. Three different data integration approaches were developed: The first is based on Sequence Ontology, the second is based on the tranSMART engine, and the third on CouchDB. These novel methods for representing and querying complex genomic and clinical data on the i2b2 platform are available today for advancing precision medicine. PMID:28388645

Vaccination with canine parvovirus type 2 (CPV-2) protects against challenge with virulent CPV-2b and CPV-2c.

PubMed

Siedek, Elisabeth M; Schmidt, Holger; Sture, Gordon H; Raue, Rüdiger

2011-01-01

Mutations in canine parvovirus (CPV) field isolates have created concerns regarding the ability of vaccines containing CPV-2 to protect against infection with the newly identified antigenic types CPV-2b and CPV-2c. To address this concern, the efficacy of CPV-2 strain NL-35-D currently in use as a commercial vaccine was demonstrated against an oral challenge with CPV-2b and CPV-2c, respectively. Clinically healthy specific pathogen free Beagle dogs were either vaccinated or treated with water for injection first at 8-9 weeks of age and again at 11-12 weeks of age. All dogs were challenged either with CPV-2b or CPV-2c three weeks after the second vaccination. During the two week period following challenge, clinical signs, white blood cell counts, serology by haemagglutination inhibition (HI) and serum neutralisation tests, and virus shedding by haemagglutination test were assessed. All control dogs developed clinical signs of parvovirosis (including pyrexia and leucopenia) and shed virus. Vaccinated dogs seroconverted (HI titres > or =80), remained healthy throughout the study and shed more than 100 times less virus than controls. In conclusion, vaccination with the low passage, high titre CPV-2 strain NL-35-D cross-protects dogs against virulent challenges with CPV-2b or CPV-2c by preventing disease and substantially reducing viral shedding.

A pharmacological study of NLP-12 neuropeptide signaling in free-living and parasitic nematodes.

PubMed

Peeters, Lise; Janssen, Tom; De Haes, Wouter; Beets, Isabel; Meelkop, Ellen; Grant, Warwick; Schoofs, Liliane

2012-03-01

NLP-12a and b have been identified as cholecystokinin/sulfakinin-like neuropeptides in the free-living nematode Caenorhabditis elegans. They are suggested to play an important role in the regulation of digestive enzyme secretion and fat storage. This study reports on the identification and characterization of an NLP-12-like peptide precursor gene in the rat parasitic nematode Strongyloides ratti. The S. ratti NLP-12 peptides are able to activate both C. elegans CKR-2 receptor isoforms in a dose-dependent way with affinities in the same nanomolar range as the native C. elegans NLP-12 peptides. The C-terminal RPLQFamide sequence motif of the NLP-12 peptides is perfectly conserved between free-living and parasitic nematodes. Based on systemic amino acid replacements the Arg-, Leu- and Phe- residues appear to be critical for high-affinity receptor binding. Finally, a SAR analysis revealed the essential pharmacophore in C. elegans NLP-12b to be the pentapeptide RPLQFamide. Copyright © 2011 Elsevier Inc. All rights reserved.

Characterization of necrosis-inducing NLP proteins in Phytophthora capsici

PubMed Central

2014-01-01

Background Effector proteins function not only as toxins to induce plant cell death, but also enable pathogens to suppress or evade plant defense responses. NLP-like proteins are considered to be effector proteins, and they have been isolated from bacteria, fungi, and oomycete plant pathogens. There is increasing evidence that NLPs have the ability to induce cell death and ethylene accumulation in plants. Results We evaluated the expression patterns of 11 targeted PcNLP genes by qRT-PCR at different time points after infection by P. capsici. Several PcNLP genes were strongly expressed at the early stages in the infection process, but the expression of other PcNLP genes gradually increased to a maximum at late stages of infection. The genes PcNLP2, PcNLP6 and PcNLP14 showed the highest expression levels during infection by P. capsici. The necrosis-inducing activity of all targeted PcNLP genes was evaluated using heterologous expression by PVX agroinfection of Capsicum annuum and Nicotiana benthamiana and by Western blot analysis. The members of the PcNLP family can induce chlorosis or necrosis during infection of pepper and tobacco leaves, but the chlorotic or necrotic response caused by PcNLP genes was stronger in pepper leaves than in tobacco leaves. Moreover, PcNLP2, PcNLP6, and PcNLP14 caused the largest chlorotic or necrotic areas in both host plants, indicating that these three genes contribute to strong virulence during infection by P. capsici. This was confirmed through functional evaluation of their silenced transformants. In addition, we further verified that four conserved residues are putatively active sites in PcNLP1 by site-directed mutagenesis. Conclusions Each targeted PcNLP gene affects cells or tissues differently depending upon the stage of infection. Most PcNLP genes could trigger necrotic or chlorotic responses when expressed in the host C. annuum and the non-host N. benthamiana. Individual PcNLP genes have different phytotoxic effects, and PcNLP

Characterization of necrosis-inducing NLP proteins in Phytophthora capsici.

PubMed

Feng, Bao-Zhen; Zhu, Xiao-Ping; Fu, Li; Lv, Rong-Fei; Storey, Dylan; Tooley, Paul; Zhang, Xiu-Guo

2014-05-08

Effector proteins function not only as toxins to induce plant cell death, but also enable pathogens to suppress or evade plant defense responses. NLP-like proteins are considered to be effector proteins, and they have been isolated from bacteria, fungi, and oomycete plant pathogens. There is increasing evidence that NLPs have the ability to induce cell death and ethylene accumulation in plants. We evaluated the expression patterns of 11 targeted PcNLP genes by qRT-PCR at different time points after infection by P. capsici. Several PcNLP genes were strongly expressed at the early stages in the infection process, but the expression of other PcNLP genes gradually increased to a maximum at late stages of infection. The genes PcNLP2, PcNLP6 and PcNLP14 showed the highest expression levels during infection by P. capsici. The necrosis-inducing activity of all targeted PcNLP genes was evaluated using heterologous expression by PVX agroinfection of Capsicum annuum and Nicotiana benthamiana and by Western blot analysis. The members of the PcNLP family can induce chlorosis or necrosis during infection of pepper and tobacco leaves, but the chlorotic or necrotic response caused by PcNLP genes was stronger in pepper leaves than in tobacco leaves. Moreover, PcNLP2, PcNLP6, and PcNLP14 caused the largest chlorotic or necrotic areas in both host plants, indicating that these three genes contribute to strong virulence during infection by P. capsici. This was confirmed through functional evaluation of their silenced transformants. In addition, we further verified that four conserved residues are putatively active sites in PcNLP1 by site-directed mutagenesis. Each targeted PcNLP gene affects cells or tissues differently depending upon the stage of infection. Most PcNLP genes could trigger necrotic or chlorotic responses when expressed in the host C. annuum and the non-host N. benthamiana. Individual PcNLP genes have different phytotoxic effects, and PcNLP2, PcNLP6, and PcNLP14 may

i3b3: Infobuttons for i2b2 as a Mechanism for Investigating the Information Needs of Clinical Researchers.

PubMed

Kennell, Timothy; Dempsey, Donald M; Cimino, James J

2016-01-01

The information needs of clinicians, as they interact with the EHR, are well-studied. Clinical researchers also interact with the EHR and, while they might be expected to have some similar needs, the unique needs that arise due to nature of their work remain largely unstudied. For clinicians, infobuttons (context-aware hyperlinks) provide a mechanism of studying these information needs. Here we describe the integration of infobuttons into i2b2, a popular data warehouse commonly used by clinical researchers, using a plugin. A preliminary survey of i2b2 developers suggests a general interest in infobuttons for i2b2 and indicates good likelihood for their deployment, where they may be used as a tool for further studying these needs in greater detail.

Differential Conductance Measurements of MgB2/I/Pb Heterojunctions and all-MgB2 Junctions

NASA Astrophysics Data System (ADS)

Cusick, David; Eckhardt, Matthew; Dai, Wenqing; Li, Qi; Chen, Ke; Cunnane, Daniel; Zhuang, C. G.; Xi, X. X.; Naito, Michio; Ramos, Roberto

2015-03-01

We present our work characterizing several types of Magnesium Diboride Josephson junctions, including MgB2/I/Pb heterojunctions and all-MgB2 junctions. We will report on the I-V and dI/dV-V data collected at various temperatures using both a cryocooler-based experimental platform between 2 and 20 Kelvin and using a 3He probe platform between 0.3 and 1.0 Kelvin. These were both developed by undergraduates in a liberal arts university. Using high-sampling rates with a 24-bit data acquisition card and access to a broad of range of temperatures, we track and report energy gap distributions and temperature-dependent features of dI/dV peaks of MgB2, comparing these with theoretical predictions. R.C.R. acknowledges support from National Science Foundation Grant # DMR-1206561.

Assessing Question Quality Using NLP

ERIC Educational Resources Information Center

Kopp, Kristopher J.; Johnson, Amy M.; Crossley, Scott A.; McNamara, Danielle S.

2017-01-01

An NLP algorithm was developed to assess question quality to inform feedback on questions generated by students within iSTART (an intelligent tutoring system that teaches reading strategies). A corpus of 4575 questions was coded using a four-level taxonomy. NLP indices were calculated for each question and machine learning was used to predict…

An i2b2-based, generalizable, open source, self-scaling chronic disease registry

PubMed Central

Quan, Justin; Ortiz, David M; Bousvaros, Athos; Ilowite, Norman T; Inman, Christi J; Marsolo, Keith; McMurry, Andrew J; Sandborg, Christy I; Schanberg, Laura E; Wallace, Carol A; Warren, Robert W; Weber, Griffin M; Mandl, Kenneth D

2013-01-01

Objective Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. Materials and methods Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. Results The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. Discussion We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. Conclusions The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases. PMID:22733975

An i2b2-based, generalizable, open source, self-scaling chronic disease registry.

PubMed

Natter, Marc D; Quan, Justin; Ortiz, David M; Bousvaros, Athos; Ilowite, Norman T; Inman, Christi J; Marsolo, Keith; McMurry, Andrew J; Sandborg, Christy I; Schanberg, Laura E; Wallace, Carol A; Warren, Robert W; Weber, Griffin M; Mandl, Kenneth D

2013-01-01

Registries are a well-established mechanism for obtaining high quality, disease-specific data, but are often highly project-specific in their design, implementation, and policies for data use. In contrast to the conventional model of centralized data contribution, warehousing, and control, we design a self-scaling registry technology for collaborative data sharing, based upon the widely adopted Integrating Biology & the Bedside (i2b2) data warehousing framework and the Shared Health Research Information Network (SHRINE) peer-to-peer networking software. Focusing our design around creation of a scalable solution for collaboration within multi-site disease registries, we leverage the i2b2 and SHRINE open source software to create a modular, ontology-based, federated infrastructure that provides research investigators full ownership and access to their contributed data while supporting permissioned yet robust data sharing. We accomplish these objectives via web services supporting peer-group overlays, group-aware data aggregation, and administrative functions. The 56-site Childhood Arthritis & Rheumatology Research Alliance (CARRA) Registry and 3-site Harvard Inflammatory Bowel Diseases Longitudinal Data Repository now utilize i2b2 self-scaling registry technology (i2b2-SSR). This platform, extensible to federation of multiple projects within and between research networks, encompasses >6000 subjects at sites throughout the USA. We utilize the i2b2-SSR platform to minimize technical barriers to collaboration while enabling fine-grained control over data sharing. The implementation of i2b2-SSR for the multi-site, multi-stakeholder CARRA Registry has established a digital infrastructure for community-driven research data sharing in pediatric rheumatology in the USA. We envision i2b2-SSR as a scalable, reusable solution facilitating interdisciplinary research across diseases.

Hierarchical semantic structures for medical NLP.

PubMed

Taira, Ricky K; Arnold, Corey W

2013-01-01

We present a framework for building a medical natural language processing (NLP) system capable of deep understanding of clinical text reports. The framework helps developers understand how various NLP-related efforts and knowledge sources can be integrated. The aspects considered include: 1) computational issues dealing with defining layers of intermediate semantic structures to reduce the dimensionality of the NLP problem; 2) algorithmic issues in which we survey the NLP literature and discuss state-of-the-art procedures used to map between various levels of the hierarchy; and 3) implementation issues to software developers with available resources. The objective of this poster is to educate readers to the various levels of semantic representation (e.g., word level concepts, ontological concepts, logical relations, logical frames, discourse structures, etc.). The poster presents an architecture for which diverse efforts and resources in medical NLP can be integrated in a principled way.

Development and evaluation of task-specific NLP framework in China.

PubMed

Ge, Caixia; Zhang, Yinsheng; Huang, Zhenzhen; Jia, Zheng; Ju, Meizhi; Duan, Huilong; Li, Haomin

2015-01-01

Natural language processing (NLP) has been designed to convert narrative text into structured data. Although some general NLP architectures have been developed, a task-specific NLP framework to facilitate the effective use of data is still a challenge in lexical resource limited regions, such as China. The purpose of this study is to design and develop a task-specific NLP framework to extract targeted information from particular documents by adopting dedicated algorithms on current limited lexical resources. In this framework, a shared and evolving ontology mechanism was designed. The result has shown that such a free text driven platform will accelerate the NLP technology acceptance in China.

Automated Report Generation for Research Data Repositories: From i2b2 to PDF.

PubMed

Thiemann, Volker S; Xu, Tingyan; Röhrig, Rainer; Majeed, Raphael W

2017-01-01

We developed an automated toolchain to generate reports of i2b2 data. It is based on free open source software and runs on a Java Application Server. It is sucessfully used in an ED registry project. The solution is highly configurable and portable to other projects based on i2b2 or compatible factual data sources.

NLP-1: a DNA intercalating hypoxic cell radiosensitizer and cytotoxin

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

Panicucci, R.; Heal, R.; Laderoute, K.

The 2-nitroimidazole linked phenanthridine, NLP-1 (5-(3-(2-nitro-1-imidazoyl)-propyl)-phenanthridinium bromide), was synthesized with the rationale of targeting the nitroimidazole to DNA via the phenanthridine ring. The drug is soluble in aqueous solution (greater than 25 mM) and stable at room temperature. It binds to DNA with a binding constant 1/30 that of ethidium bromide. At a concentration of 0.5 mM, NLP-1 is 8 times more toxic to hypoxic than aerobic cells at 37 degrees C. This concentration is 40 times less than the concentration of misonidazole, a non-intercalating 2-nitroimidazole, required for the same degree of hypoxic cell toxicity. The toxicity of NLP-1 ismore » reduced at least 10-fold at 0 degrees C. Its ability to radiosensitize hypoxic cells is similar to misonidazole at 0 degrees C. Thus the putative targeting of the 2-nitroimidazole, NLP-1, to DNA, via its phenanthridine group, enhances its hypoxic toxicity, but not its radiosensitizing ability under the present test conditions. NLP-1 represents a lead compound for intercalating 2-nitroimidazoles with selective toxicity for hypoxic cells.« less

Overexpression of centrosomal protein Nlp confers breast carcinoma resistance to paclitaxel.

PubMed

Zhao, Weihong; Song, Yongmei; Xu, Binghe; Zhan, Qimin

2012-02-01

Nlp (ninein-like protein), an important molecule involved in centrosome maturation and spindle formation, plays an important role in tumorigenesis and its abnormal expression was recently observed in human breast and lung cancers. In this study, the correlation between overexpression of Nlp and paclitaxel chemosensitivity was investigated to explore the mechanisms of resistance to paclitaxel and to understand the effect of Nlp upon apoptosis induced by chemotherapeutic agents. Nlp expression vector was stably transfected into breast cancer MCF-7 cells. With Nlp overexpression, the survival rates, cell cycle distributions and apoptosis were analyzed in transfected MCF-7 cells by MTT test and FCM approach. The immunofluorescent assay was employed to detect the changes of microtubule after paclitaxel treatment. Immunoblotting analysis was used to examine expression of centrosomal proteins and apoptosis associated proteins. Subsequently, Nlp expression was retrospectively examined with 55 breast cancer samples derived from paclitaxel treated patients. Interestingly, the survival rates of MCF-7 cells with Nlp overexpressing were higher than that of control after paclitaxel treatment. Nlp overexpression promoted G2-M arrest and attenuated apoptosis induced by paclitaxel, which was coupled with elevated Bcl-2 protein. Nlp expression significantly lessened the microtubule polymerization and bundling elicited by paclitaxel attributing to alteration on the structure or dynamics of β-tubulin but not on its expression. The breast cancer patients with high expression of Nlp were likely resistant to the treatment of paclitaxel, as the response rate in Nlp negative patients was 62.5%, whereas was 58.3 and 15.8% in Nlp (+) and Nlp (++) patients respectively (p = 0.015). Nlp expression was positive correlated with those of Plk1 and PCNA. These findings provide insights into more rational chemotherapeutic regimens in clinical practice, and more effective approaches might be

Electronic and structural properties of B i2S e3:Cu

NASA Astrophysics Data System (ADS)

Sobczak, Kamil; Strak, Pawel; Kempisty, Pawel; Wolos, Agnieszka; Hruban, Andrzej; Materna, Andrzej; Borysiuk, Jolanta

2018-04-01

Electronic and structural properties of B i2S e3 and its extension to copper doped B i2S e3:Cu were studied using combined ab initio simulations and transmission electron microscopy based techniques, including electron energy loss spectroscopy, energy filtered transmission electron microscopy, and energy dispersive x-ray spectroscopy. The stability of the mixed phases was investigated for substitutional and intercalation changes of basic B i2S e3 structure. Four systems were compared: B i2S e3 , structures obtaining by Cu intercalation of the van der Waals gap, by substitution of Bi by Cu in quintuple layers, and C u2Se . The structures were identified and their electronic properties were obtained. Transmission electron microscopy measurements of B i2S e3 and the B i2S e3:Cu system identified the first structure as uniform and the second as composite, consisting of a nonuniform lower-Cu-content matrix and randomly distributed high-Cu-concentration precipitates. Critical comparison of the ab initio and experimental data identified the matrix as having a B i2S e3 dominant part with randomly distributed Cu-intercalated regions having 1Cu-B i2S e3 structure. The precipitates were determined to have 3Cu-B i2S e3 structure.

Gene expression and pharmacology of nematode NLP-12 neuropeptides.

PubMed

McVeigh, Paul; Leech, Suzie; Marks, Nikki J; Geary, Timothy G; Maule, Aaron G

2006-05-31

This study examines the biology of NLP-12 neuropeptides in Caenorhabditis elegans, and in the parasitic nematodes Ascaris suum and Trichostrongylus colubriformis. DYRPLQFamide (1 nM-10 microM; n > or =6) produced contraction of innervated dorsal and ventral Ascaris body wall muscle preparations (10 microM, 6.8+/-1.9 g; 1 microM, 4.6+/-1.8 g; 0.1 microM, 4.1+/-2.0 g; 10 nM, 3.8+/-2.0 g; n > or =6), and also caused a qualitatively similar, but quantitatively lower contractile response (10 microM, 4.0+/-1.5 g, n=6) on denervated muscle strips. Ovijector muscle displayed no measurable response (10 microM, n=5). nlp-12 cDNAs were characterised from A. suum (As-nlp-12) and T. colubriformis (Tc-nlp-12), both of which show sequence similarity to C. elegans nlp-12, in that they encode multiple copies of -LQFamide peptides. In C. elegans, reverse transcriptase (RT)-PCR analysis showed that nlp-12 was transcribed throughout the life cycle, suggesting that DYRPLQFamide plays a constitutive role in the nervous system of this nematode. Transcription was also identified in both L3 and adult stages of T. colubriformis, in which Tc-nlp-12 is expressed in a single tail neurone. Conversely, As-nlp-12 is expressed in both head and tail tissue of adult female A. suum, suggesting species-specific differences in the transcription pattern of this gene.

A Fast Healthcare Interoperability Resources (FHIR) layer implemented over i2b2.

PubMed

Boussadi, Abdelali; Zapletal, Eric

2017-08-14

Standards and technical specifications have been developed to define how the information contained in Electronic Health Records (EHRs) should be structured, semantically described, and communicated. Current trends rely on differentiating the representation of data instances from the definition of clinical information models. The dual model approach, which combines a reference model (RM) and a clinical information model (CIM), sets in practice this software design pattern. The most recent initiative, proposed by HL7, is called Fast Health Interoperability Resources (FHIR). The aim of our study was to investigate the feasibility of applying the FHIR standard to modeling and exposing EHR data of the Georges Pompidou European Hospital (HEGP) integrating biology and the bedside (i2b2) clinical data warehouse (CDW). We implemented a FHIR server over i2b2 to expose EHR data in relation with five FHIR resources: DiagnosisReport, MedicationOrder, Patient, Encounter, and Medication. The architecture of the server combines a Data Access Object design pattern and FHIR resource providers, implemented using the Java HAPI FHIR API. Two types of queries were tested: query type #1 requests the server to display DiagnosticReport resources, for which the diagnosis code is equal to a given ICD-10 code. A total of 80 DiagnosticReport resources, corresponding to 36 patients, were displayed. Query type #2, requests the server to display MedicationOrder, for which the FHIR Medication identification code is equal to a given code expressed in a French coding system. A total of 503 MedicationOrder resources, corresponding to 290 patients, were displayed. Results were validated by manually comparing the results of each request to the results displayed by an ad-hoc SQL query. We showed the feasibility of implementing a Java layer over the i2b2 database model to expose data of the CDW as a set of FHIR resources. An important part of this work was the structural and semantic mapping between the

BigQ: a NoSQL based framework to handle genomic variants in i2b2.

PubMed

Gabetta, Matteo; Limongelli, Ivan; Rizzo, Ettore; Riva, Alberto; Segagni, Daniele; Bellazzi, Riccardo

2015-12-29

Precision medicine requires the tight integration of clinical and molecular data. To this end, it is mandatory to define proper technological solutions able to manage the overwhelming amount of high throughput genomic data needed to test associations between genomic signatures and human phenotypes. The i2b2 Center (Informatics for Integrating Biology and the Bedside) has developed a widely internationally adopted framework to use existing clinical data for discovery research that can help the definition of precision medicine interventions when coupled with genetic data. i2b2 can be significantly advanced by designing efficient management solutions of Next Generation Sequencing data. We developed BigQ, an extension of the i2b2 framework, which integrates patient clinical phenotypes with genomic variant profiles generated by Next Generation Sequencing. A visual programming i2b2 plugin allows retrieving variants belonging to the patients in a cohort by applying filters on genomic variant annotations. We report an evaluation of the query performance of our system on more than 11 million variants, showing that the implemented solution scales linearly in terms of query time and disk space with the number of variants. In this paper we describe a new i2b2 web service composed of an efficient and scalable document-based database that manages annotations of genomic variants and of a visual programming plug-in designed to dynamically perform queries on clinical and genetic data. The system therefore allows managing the fast growing volume of genomic variants and can be used to integrate heterogeneous genomic annotations.

Excitation of O 2(a 1Δ g, b 1Σ g+) and I( 2P 1/2) by energy transfer from I 2(A, A' 3Π 1,2u) in solid rare gases

NASA Astrophysics Data System (ADS)

Böhling, R.; Becker, A. C.; Minaev, B. F.; Seranski, K.; Schurath, U.

1990-04-01

O 2a 1Δ g, b 1Σ g+ → X 3Σ g- and I 2P 1/2→ 2P 3/4 fluorescence occurs in I 2/O 2-doped rare gas matrices when I 2 is excited with visible laser light. O 2(a 1Δ g) and I( 2P 1/2) are populated independently by near-resonant energy transfer from the metastable triplet states of I 2. The doublet splitting of the O 2a→X band, which peaks at 7879 and 7863 cm -1 in argon, is interpreted as sensitized emission from O 2 trapped in distinct nearest neighbour positions of the donor 3I 2. Annealing reverses the intensity of the doublet, showing that the sites can be interconverted. It is suggested that the a→X emission rate is enhanced by the sensitizer, causing a lifetime reduction of the a 1Δ g state from 79 s in pure argon to 21 and 3±1 s next to I 2. The long-lived O 2(a 1Δ g) state is the precursor of I 2-sensitized emission from O 2(b 1Σ g+). The lifetime of O 2(b 1Σ g+) is reduced from 24.5 ms in pure argon to 17±1 ms in the presence of I 2.

Expression of Caenorhabditis elegans antimicrobial peptide NLP-31 in Escherichia coli

NASA Astrophysics Data System (ADS)

Lim, Mei-Perng; Nathan, Sheila

2014-09-01

Burkholderia pseudomallei is the causative agent of melioidosis, a fulminant disease endemic in Southeast Asia and Northern Australia. The standardized form of therapy is antibiotics treatment; however, the bacterium has become increasingly resistant to these antibiotics. This has spurred the need to search for alternative therapeutic agents. Antimicrobial peptides (AMPs) are small proteins that possess broad-spectrum antimicrobial activity. In a previous study, the nematode Caenorhabditis elegans was infected by B. pseudomallei and a whole animal transcriptome analysis identified a number of AMP-encoded genes which were induced significantly in the infected worms. One of the AMPs identified is NLP-31 and to date, there are no reports of anti-B. pseudomallei activity demonstrated by NLP-31. To produce NLP-31 protein for future studies, the gene encoding for NLP-31 was cloned into the pET32b expression vector and transformed into Escherichia coli BL21(DE3). Protein expression was induced with 1 mM IPTG for 20 hours at 20°C and recombinant NLP-31 was detected in the soluble fraction. Taken together, a simple optimized heterologous production of AMPs in an E. coli expression system has been successfully developed.

30 CFR 57.22238 - Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). 57.22238 Section 57.22238 Mineral Resources MINE SAFETY AND HEALTH ADMINISTRATION... Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 2.0 percent in the mine...

30 CFR 57.22238 - Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Actions at 2.0 percent methane (I-B, II-B, V-B... AND NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22238 Actions at 2.0 percent methane (I-B, II-B, V-B, and VI mines). If methane reaches 2.0 percent in the mine...

Secondary Use of Claims Data from the Austrian Health Insurance System with i2b2: A Pilot Study.

PubMed

Endel, Florian; Duftschmid, Georg

2016-01-01

In conformity with increasing international efforts to reuse routine health data for scientific purposes, the Main Association of Austrian Social Security Organisations provides pseudonymized claims data of the Austrian health care system for clinical research. We aimed to examine, whether an integration of the corresponding database into i2b2 would be possible and provide benefits. We applied docker-based software containers and data transformations to set up the system. To assess the benefits of i2b2 we plan to reenact the task of cohort formation of an earlier research project. The claims database was successfully integrated into i2b2. The docker-based installation approach will be published as git repository. The assessment of i2b2's benefits is currently work in progress and will be presented at the conference. Docker enables a flexible, reproducible, and resource-efficient installation of i2b2 within the restricted environment implied by our highly secured target system. First preliminary tests indicated several potential benefits of i2b2 compared to the methods applied during the earlier research project.

Serving the enterprise and beyond with informatics for integrating biology and the bedside (i2b2)

PubMed Central

Weber, Griffin; Mendis, Michael; Gainer, Vivian; Chueh, Henry C; Churchill, Susanne; Kohane, Isaac

2010-01-01

Informatics for Integrating Biology and the Bedside (i2b2) is one of seven projects sponsored by the NIH Roadmap National Centers for Biomedical Computing (http://www.ncbcs.org). Its mission is to provide clinical investigators with the tools necessary to integrate medical record and clinical research data in the genomics age, a software suite to construct and integrate the modern clinical research chart. i2b2 software may be used by an enterprise's research community to find sets of interesting patients from electronic patient medical record data, while preserving patient privacy through a query tool interface. Project-specific mini-databases (“data marts”) can be created from these sets to make highly detailed data available on these specific patients to the investigators on the i2b2 platform, as reviewed and restricted by the Institutional Review Board. The current version of this software has been released into the public domain and is available at the URL: http://www.i2b2.org/software. PMID:20190053

Ensembles of NLP Tools for Data Element Extraction from Clinical Notes.

PubMed

Kuo, Tsung-Ting; Rao, Pallavi; Maehara, Cleo; Doan, Son; Chaparro, Juan D; Day, Michele E; Farcas, Claudiu; Ohno-Machado, Lucila; Hsu, Chun-Nan

2016-01-01

Natural Language Processing (NLP) is essential for concept extraction from narrative text in electronic health records (EHR). To extract numerous and diverse concepts, such as data elements (i.e., important concepts related to a certain medical condition), a plausible solution is to combine various NLP tools into an ensemble to improve extraction performance. However, it is unclear to what extent ensembles of popular NLP tools improve the extraction of numerous and diverse concepts. Therefore, we built an NLP ensemble pipeline to synergize the strength of popular NLP tools using seven ensemble methods, and to quantify the improvement in performance achieved by ensembles in the extraction of data elements for three very different cohorts. Evaluation results show that the pipeline can improve the performance of NLP tools, but there is high variability depending on the cohort.

Metadata-driven Clinical Data Loading into i2b2 for Clinical and Translational Science Institutes.

PubMed

Post, Andrew R; Pai, Akshatha K; Willard, Richard; May, Bradley J; West, Andrew C; Agravat, Sanjay; Granite, Stephen J; Winslow, Raimond L; Stephens, David S

2016-01-01

Clinical and Translational Science Award (CTSA) recipients have a need to create research data marts from their clinical data warehouses, through research data networks and the use of i2b2 and SHRINE technologies. These data marts may have different data requirements and representations, thus necessitating separate extract, transform and load (ETL) processes for populating each mart. Maintaining duplicative procedural logic for each ETL process is onerous. We have created an entirely metadata-driven ETL process that can be customized for different data marts through separate configurations, each stored in an extension of i2b2 's ontology database schema. We extended our previously reported and open source Eureka! Clinical Analytics software with this capability. The same software has created i2b2 data marts for several projects, the largest being the nascent Accrual for Clinical Trials (ACT) network, for which it has loaded over 147 million facts about 1.2 million patients.

Metadata-driven Clinical Data Loading into i2b2 for Clinical and Translational Science Institutes

PubMed Central

Post, Andrew R.; Pai, Akshatha K.; Willard, Richard; May, Bradley J.; West, Andrew C.; Agravat, Sanjay; Granite, Stephen J.; Winslow, Raimond L.; Stephens, David S.

2016-01-01

Clinical and Translational Science Award (CTSA) recipients have a need to create research data marts from their clinical data warehouses, through research data networks and the use of i2b2 and SHRINE technologies. These data marts may have different data requirements and representations, thus necessitating separate extract, transform and load (ETL) processes for populating each mart. Maintaining duplicative procedural logic for each ETL process is onerous. We have created an entirely metadata-driven ETL process that can be customized for different data marts through separate configurations, each stored in an extension of i2b2 ‘s ontology database schema. We extended our previously reported and open source Eureka! Clinical Analytics software with this capability. The same software has created i2b2 data marts for several projects, the largest being the nascent Accrual for Clinical Trials (ACT) network, for which it has loaded over 147 million facts about 1.2 million patients. PMID:27570667

Phylogenetic, expression and functional characterizations of the maize NLP transcription factor family reveal a role in nitrate assimilation and signaling.

PubMed

Wang, Zhangkui; Zhang, Lei; Sun, Ci; Gu, Riliang; Mi, Guohua; Yuan, Lixing

2018-01-24

Although nitrate represents an important nitrogen (N) source for maize, a major crop of dryland areas, the molecular mechanisms of nitrate uptake and assimilation remain poorly understood. Here, we identified nine maize NIN-like protein (ZmNLP) genes and analyzed the function of one member, ZmNLP3.1, in nitrate nutrition and signaling. The NLP family genes were clustered into three clades in a phylogenic tree. Comparative genomic analysis showed that most ZmNLP genes had collinear relationships to the corresponding NLPs in rice, and that the expansion of the ZmNLP family resulted from segmental duplications in the maize genome. Quantitative PCR analysis revealed the expression of ZmNLP2.1, ZmNLP2.2, ZmNLP3.1, ZmNLP3.2, ZmNLP3.3, and ZmNLP3.4 was induced by nitrate in maize roots. The function of ZmNLP3.1 was investigated by overexpressing it in the Arabidopsis nlp7-1 mutant, which is defective in the AtNLP7 gene for nitrate signaling and assimilation. Ectopic expression of ZmNLP3.1 restored the N-deficient phenotypes of nlp7-1 under nitrate-replete conditions in terms of shoot biomass, root morphology and nitrate assimilation. Furthermore, the nitrate induction of NRT2.1, NIA1, and NiR1 gene expression was recovered in the 35S::ZmNLP3.1/nlp7-1 transgenic lines, indicating that ZmNLP3.1 plays essential roles in nitrate signaling. Taken together, these results suggest that ZmNLP3.1 plays an essential role in regulating nitrate signaling and assimilation processes, and represents a valuable candidate for developing transgenic maize cultivars with high N-use efficiency. This article is protected by copyright. All rights reserved.

A PCV2 vaccine based on genotype 2b is more effective than a 2a-based vaccine to protect against PCV2b or combined PCV2a/2b viremia in pigs with concurrent PCV2, PRRSV and PPV infection.

PubMed

Opriessnig, Tanja; O'Neill, Kevin; Gerber, Priscilla F; de Castro, Alessandra M M G; Gimenéz-Lirola, Luis G; Beach, Nathan M; Zhou, Lei; Meng, Xiang-Jin; Wang, Chong; Halbur, Patrick G

2013-01-07

The predominant genotype of porcine circovirus (PCV) in the pig population today is PCV2b yet PCV2a-based commercial vaccines are considered effective in protecting against porcine circovirus associated disease. The objective of this study was to compare the ability of PCV2a- and PCV2b-based vaccines to control PCV2b viremia in a challenge model that mimics the U.S. field situation. Sixty-three pigs were randomly assigned to one of eight groups. Sixteen pigs were vaccinated with an experimental live-attenuated chimeric PCV1-2a vaccine based on genotype 2a and another 16 pigs with a chimeric PCV1-2b vaccine based on genotype 2b. Challenge was done 28 days post vaccination (dpv) using PCV2b (or a combination of PCV2a and PCV2b), porcine reproductive and respiratory syndrome virus (PRRSV), and porcine parvovirus (PPV) to mimic what commonly occurs in the field. The experiment was terminated 21 days post challenge (dpc) or 49dpv. Pigs vaccinated with the chimeric PCV1-2b vaccine had significantly higher levels of PCV1-2b viremia and shedding of the PCV1-2b vaccine virus in feces and nasal secretions but also a more robust humoral immune response as evidenced by significantly higher ELISA S/P ratios compared to the PCV1-2a vaccination. Regardless of challenge, the PCV1-2b vaccination significantly reduced the prevalence and amount of PCV2 viremia compared to the PCV1-2a vaccination. Interestingly, in the non-vaccinated pigs concurrent PCV2a infection resulted in clinical disease and increased macroscopic lung lesions compared to pigs challenged with PCV2b alone, further supporting the idea that concurrent PCV2a/PCV2b infection is necessary for optimal PCV2 replication. Copyright © 2012 Elsevier Ltd. All rights reserved.

Ensembles of NLP Tools for Data Element Extraction from Clinical Notes

PubMed Central

Kuo, Tsung-Ting; Rao, Pallavi; Maehara, Cleo; Doan, Son; Chaparro, Juan D.; Day, Michele E.; Farcas, Claudiu; Ohno-Machado, Lucila; Hsu, Chun-Nan

2016-01-01

Natural Language Processing (NLP) is essential for concept extraction from narrative text in electronic health records (EHR). To extract numerous and diverse concepts, such as data elements (i.e., important concepts related to a certain medical condition), a plausible solution is to combine various NLP tools into an ensemble to improve extraction performance. However, it is unclear to what extent ensembles of popular NLP tools improve the extraction of numerous and diverse concepts. Therefore, we built an NLP ensemble pipeline to synergize the strength of popular NLP tools using seven ensemble methods, and to quantify the improvement in performance achieved by ensembles in the extraction of data elements for three very different cohorts. Evaluation results show that the pipeline can improve the performance of NLP tools, but there is high variability depending on the cohort. PMID:28269947

Annotating longitudinal clinical narratives for de-identification: The 2014 i2b2/UTHealth corpus.

PubMed

Stubbs, Amber; Uzuner, Özlem

2015-12-01

The 2014 i2b2/UTHealth natural language processing shared task featured a track focused on the de-identification of longitudinal medical records. For this track, we de-identified a set of 1304 longitudinal medical records describing 296 patients. This corpus was de-identified under a broad interpretation of the HIPAA guidelines using double-annotation followed by arbitration, rounds of sanity checking, and proof reading. The average token-based F1 measure for the annotators compared to the gold standard was 0.927. The resulting annotations were used both to de-identify the data and to set the gold standard for the de-identification track of the 2014 i2b2/UTHealth shared task. All annotated private health information were replaced with realistic surrogates automatically and then read over and corrected manually. The resulting corpus is the first of its kind made available for de-identification research. This corpus was first used for the 2014 i2b2/UTHealth shared task, during which the systems achieved a mean F-measure of 0.872 and a maximum F-measure of 0.964 using entity-based micro-averaged evaluations. Copyright © 2015 Elsevier Inc. All rights reserved.

Commercial PCV2a-based vaccines are effective in protecting naturally PCV2b-infected finisher pigs against experimental challenge with a 2012 mutant PCV2.

PubMed

Opriessnig, Tanja; Gerber, Priscilla F; Xiao, Chao-Ting; Halbur, Patrick G; Matzinger, Shannon R; Meng, Xiang-Jin

2014-07-23

Current commercial PCV2 vaccines are all based on PCV2a and have been shown to be effective in reducing PCV2a and PCV2b viremia and PCV2-associated lesions and disease. The recent emergence of novel mutant PCV2 (mPCV2) strains and linkage of mPCV2 with cases of porcine circovirus associated disease (PCVAD) in vaccinated herds have raised concerns over emergence of vaccine-escape mutants and reduced efficacy of PCV2a-based vaccines. The aim of this study was to determine the ability of three commercial PCV2a-based vaccines administered in the presence of an ongoing PCV2b infection and passively-acquired anti-PCV2 antibodies to protect conventional pigs against experimental challenge with mPCV2 at 11 weeks of age. Fifty naturally PCV2b-infected 2-week-old pigs were divided into five treatment groups with 10 pigs each. Pigs were unvaccinated (positive and negative controls) or vaccinated at 3 (VAC-A, VAC-B, VAC-C) and at 5 weeks of age (VAC-C). At 11 weeks of age, all pigs except the negative controls were challenged with a 2012 U.S. strain of mPCV2. The experiment was terminated 21 days after challenge. Under the conditions of this study, vaccinated pigs were protected against PCV2 viremia and lesions whereas non-vaccinated pigs were not. Moreover, concurrent PCV2b and mPCV2 infection was demonstrated in all positive controls and 3/10 had microscopic lesions consistent with PCVAD while negative controls infected with PCV2b alone did not develop PCVAD. The results indicate that concurrent PCV2b/mPCV2 infection can trigger PCVAD development and that commercial vaccines are effective in protecting conventional pigs against emerging mPCV2 strains. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

Insights into substrate specificity of NlpC/P60 cell wall hydrolases containing bacterial SH3 domains

DOE PAGES

Xu, Qingping; Mengin-Lecreulx, Dominique; Liu, Xueqian W.; ...

2015-09-15

Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. In addition, these enzymes all have γ-d-Glu-A 2pm (A 2pm is diaminopimelic acid) cysteine amidase (ordl-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminall-Ala. Their crystal structures revealed a highly conserved structuremore » consisting of two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation.Peptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural analysis of three modular NlpC/P60 hydrolases, one lysin, and two recycling enzymes

Insights into substrate specificity of NlpC/P60 cell wall hydrolases containing bacterial SH3 domains

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

Xu, Qingping; Mengin-Lecreulx, Dominique; Liu, Xueqian W.

Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. In addition, these enzymes all have γ-d-Glu-A 2pm (A 2pm is diaminopimelic acid) cysteine amidase (ordl-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminall-Ala. Their crystal structures revealed a highly conserved structuremore » consisting of two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation.Peptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural analysis of three modular NlpC/P60 hydrolases, one lysin, and two recycling enzymes

Insights into Substrate Specificity of NlpC/P60 Cell Wall Hydrolases Containing Bacterial SH3 Domains

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

Xu, Qingping; Mengin-Lecreulx, Dominique; Liu, Xueqian W.

ABSTRACT Bacterial SH3 (SH3b) domains are commonly fused with papain-like Nlp/P60 cell wall hydrolase domains. To understand how the modular architecture of SH3b and NlpC/P60 affects the activity of the catalytic domain, three putative NlpC/P60 cell wall hydrolases were biochemically and structurally characterized. These enzymes all have γ-d-Glu-A 2pm (A 2pm is diaminopimelic acid) cysteine amidase (ordl-endopeptidase) activities but with different substrate specificities. One enzyme is a cell wall lysin that cleaves peptidoglycan (PG), while the other two are cell wall recycling enzymes that only cleave stem peptides with an N-terminall-Ala. Their crystal structures revealed a highly conserved structure consistingmore » of two SH3b domains and a C-terminal NlpC/P60 catalytic domain, despite very low sequence identity. Interestingly, loops from the first SH3b domain dock into the ends of the active site groove of the catalytic domain, remodel the substrate binding site, and modulate substrate specificity. Two amino acid differences at the domain interface alter the substrate binding specificity in favor of stem peptides in recycling enzymes, whereas the SH3b domain may extend the peptidoglycan binding surface in the cell wall lysins. Remarkably, the cell wall lysin can be converted into a recycling enzyme with a single mutation. IMPORTANCEPeptidoglycan is a meshlike polymer that envelops the bacterial plasma membrane and bestows structural integrity. Cell wall lysins and recycling enzymes are part of a set of lytic enzymes that target covalent bonds connecting the amino acid and amino sugar building blocks of the PG network. These hydrolases are involved in processes such as cell growth and division, autolysis, invasion, and PG turnover and recycling. To avoid cleavage of unintended substrates, these enzymes have very selective substrate specificities. Our biochemical and structural analysis of three modular NlpC/P60 hydrolases, one lysin, and two recycling

Evaluation of Natural Language Processing (NLP) Systems to Annotate Drug Product Labeling with MedDRA Terminology.

PubMed

Ly, Thomas; Pamer, Carol; Dang, Oanh; Brajovic, Sonja; Haider, Shahrukh; Botsis, Taxiarchis; Milward, David; Winter, Andrew; Lu, Susan; Ball, Robert

2018-05-31

The FDA Adverse Event Reporting System (FAERS) is a primary data source for identifying unlabeled adverse events (AEs) in a drug or biologic drug product's postmarketing phase. Many AE reports must be reviewed by drug safety experts to identify unlabeled AEs, even if the reported AEs are previously identified, labeled AEs. Integrating the labeling status of drug product AEs into FAERS could increase report triage and review efficiency. Medical Dictionary for Regulatory Activities (MedDRA) is the standard for coding AE terms in FAERS cases. However, drug manufacturers are not required to use MedDRA to describe AEs in product labels. We hypothesized that natural language processing (NLP) tools could assist in automating the extraction and MedDRA mapping of AE terms in drug product labels. We evaluated the performance of three NLP systems, (ETHER, I2E, MetaMap) for their ability to extract AE terms from drug labels and translate the terms to MedDRA Preferred Terms (PTs). Pharmacovigilance-based annotation guidelines for extracting AE terms from drug labels were developed for this study. We compared each system's output to MedDRA PT AE lists, manually mapped by FDA pharmacovigilance experts using the guidelines, for ten drug product labels known as the "gold standard AE list" (GSL) dataset. Strict time and configuration conditions were imposed in order to test each system's capabilities under conditions of no human intervention and minimal system configuration. Each NLP system's output was evaluated for precision, recall and F measure in comparison to the GSL. A qualitative error analysis (QEA) was conducted to categorize a random sample of each NLP system's false positive and false negative errors. A total of 417, 278, and 250 false positive errors occurred in the ETHER, I2E, and MetaMap outputs, respectively. A total of 100, 80, and 187 false negative errors occurred in ETHER, I2E, and MetaMap outputs, respectively. Precision ranged from 64% to 77%, recall from 64

RNAi-mediated disruption of neuropeptide genes, nlp-3 and nlp-12, cause multiple behavioral defects in Meloidogyne incognita.

PubMed

Dash, Manoranjan; Dutta, Tushar K; Phani, Victor; Papolu, Pradeep K; Shivakumara, Tagginahalli N; Rao, Uma

2017-08-26

Owing to the current deficiencies in chemical control options and unavailability of novel management strategies, root-knot nematode (M. incognita) infections remain widespread with significant socio-economic impacts. Helminth nervous systems are peptide-rich and appear to be putative drug targets that could be exploited by antihelmintic chemotherapy. Herein, to characterize the novel peptidergic neurotransmitters, in silico mining of M. incognita genomic and transciptomic datasets revealed the presence of 16 neuropeptide-like protein (nlp) genes with structural hallmarks of neuropeptide preproproteins; among which 13 nlps were PCR-amplified and sequenced. Two key nlp genes (Mi-nlp-3 and Mi-nlp-12) were localized to the basal bulb and tail region of nematode body via in situ hybridization assay. Mi-nlp-3 and Mi-nlp-12 were greatly expressed (in qRT-PCR assay) in the pre-parasitic juveniles and adult females, suggesting the association of these genes in host recognition, development and reproduction of M. incognita. In vitro knockdown of Mi-nlp-3 and Mi-nlp-12 via RNAi demonstrated the significant reduction in attraction and penetration of M. incognita in tomato root in Pluronic gel medium. A pronounced perturbation in development and reproduction of NLP-silenced worms was also documented in adzuki beans in CYG growth pouches. The deleterious phenotypes obtained due to NLP knockdown suggests that transgenic plants engineered to express RNA constructs targeting nlp genes may emerge as an environmentally viable option to manage nematode problems in crop plants. Copyright © 2017 Elsevier Inc. All rights reserved.

Common data model for natural language processing based on two existing standard information models: CDA+GrAF.

PubMed

Meystre, Stéphane M; Lee, Sanghoon; Jung, Chai Young; Chevrier, Raphaël D

2012-08-01

An increasing need for collaboration and resources sharing in the Natural Language Processing (NLP) research and development community motivates efforts to create and share a common data model and a common terminology for all information annotated and extracted from clinical text. We have combined two existing standards: the HL7 Clinical Document Architecture (CDA), and the ISO Graph Annotation Format (GrAF; in development), to develop such a data model entitled "CDA+GrAF". We experimented with several methods to combine these existing standards, and eventually selected a method wrapping separate CDA and GrAF parts in a common standoff annotation (i.e., separate from the annotated text) XML document. Two use cases, clinical document sections, and the 2010 i2b2/VA NLP Challenge (i.e., problems, tests, and treatments, with their assertions and relations), were used to create examples of such standoff annotation documents, and were successfully validated with the XML schemata provided with both standards. We developed a tool to automatically translate annotation documents from the 2010 i2b2/VA NLP Challenge format to GrAF, and automatically generated 50 annotation documents using this tool, all successfully validated. Finally, we adapted the XSL stylesheet provided with HL7 CDA to allow viewing annotation XML documents in a web browser, and plan to adapt existing tools for translating annotation documents between CDA+GrAF and the UIMA and GATE frameworks. This common data model may ease directly comparing NLP tools and applications, combining their output, transforming and "translating" annotations between different NLP applications, and eventually "plug-and-play" of different modules in NLP applications. Copyright © 2011 Elsevier Inc. All rights reserved.

Clinical Natural Language Processing in languages other than English: opportunities and challenges.

PubMed

Névéol, Aurélie; Dalianis, Hercules; Velupillai, Sumithra; Savova, Guergana; Zweigenbaum, Pierre

2018-03-30

Natural language processing applied to clinical text or aimed at a clinical outcome has been thriving in recent years. This paper offers the first broad overview of clinical Natural Language Processing (NLP) for languages other than English. Recent studies are summarized to offer insights and outline opportunities in this area. We envision three groups of intended readers: (1) NLP researchers leveraging experience gained in other languages, (2) NLP researchers faced with establishing clinical text processing in a language other than English, and (3) clinical informatics researchers and practitioners looking for resources in their languages in order to apply NLP techniques and tools to clinical practice and/or investigation. We review work in clinical NLP in languages other than English. We classify these studies into three groups: (i) studies describing the development of new NLP systems or components de novo, (ii) studies describing the adaptation of NLP architectures developed for English to another language, and (iii) studies focusing on a particular clinical application. We show the advantages and drawbacks of each method, and highlight the appropriate application context. Finally, we identify major challenges and opportunities that will affect the impact of NLP on clinical practice and public health studies in a context that encompasses English as well as other languages.

Ultrafast dynamics of an unoccupied surface resonance state in B i2T e2Se

NASA Astrophysics Data System (ADS)

Munisa, Nurmamat; Krasovskii, E. E.; Ishida, Y.; Sumida, K.; Chen, Jiahua; Yoshikawa, T.; Chulkov, E. V.; Kokh, K. A.; Tereshchenko, O. E.; Shin, S.; Kimura, Akio

2018-03-01

Electronic structure and electron dynamics in the ternary topological insulator B i2T e2Se are studied with time- and angle-resolved photoemission spectroscopy using optical pumping. An unoccupied surface resonance split off from the bulk conduction band previously indirectly observed in scanning tunneling measurements is spectroscopically identified. Furthermore, an unoccupied topological surface state (TSS) is found, which is serendipitously located at about 1.5 eV above the occupied TSS, thereby facilitating direct optical transitions between the two surface states at ℏ ω =1.5 eV in an n -type topological insulator. An appreciable nonequilibrium population of the bottom of the bulk conduction band is observed for longer than 15 ps after the pump pulse. This leads to a long recovery time of the lower TSS, which is constantly populated by the electrons coming from the bulk conduction band. Our results demonstrate B i2T e2Se to be an ideal platform for designing future optoelectronic devices based on topological insulators.

Relationship of angiotensin I-converting enzyme (ACE) and bradykinin B2 receptor (BDKRB2) polymorphism with diabetic nephropathy.

PubMed

Zou, Honghong; Wu, Guoqing; Lv, Jinlei; Xu, Gaosi

2017-06-01

To determine whether ACE 2 I/D and BDKRB2 3 +9/-9 polymorphism causatively affect diabetic nephropathy progression RESULTS: STZ-induced metabolic disorder, as well as inflammatory responses, was significantly aggravated in ACE II-B2R 4 +9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp diabetic mice but not ACE II-B2R-9bp, indicating the genetic susceptibility of ACE DD or B2R+9bp to diabetic nephropathy. Furthermore, ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp rather than ACE II-B2R-9bp, worsened renal performance and enhanced pathological alterations induced by STZ. Markedly elevated monocyte chemoattractant protein-1(MCP-1), podocin, osteopontin (OPN), transforming growth factor-β1 (TGF-β1), and reduced nephrin, podocin were also detected both in diabetic mice and podocytes under hyperglycemic conditions in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp, versus ACE II-B2R-9bp. In addition, high glucose-induced mitochondrial oxidative stress and cell apoptosis were observably increased in response to ACE II-B2R+9bp, ACE DD-B2R+9bp, or ACE DD-B2R-9bp but not ACE II-B2R-9bp. We provide first evidence indicating the causation between ACE DD or B2R+9bp genotype and the increased risk for diabetic nephropathy, broadening our horizon about the role of genetic modulators in this disease. Copyright © 2017 Elsevier B.V. All rights reserved.

A family with autosomal dominant mutilating neuropathy not linked to either Charcot-Marie-Tooth disease type 2B (CMT2B) or hereditary sensory neuropathy type I (HSN I) loci.

PubMed

Bellone, Emilia; Rodolico, Carmelo; Toscano, Antonio; Di Maria, Emilio; Cassandrini, Denise; Pizzuti, Antonio; Pigullo, Simona; Mazzeo, Anna; Macaione, Vincenzo; Girlanda, Paolo; Vita, Giuseppe; Ajmar, Franco; Mandich, Paola

2002-03-01

Sensory loss and ulcero-mutilating features have been observed in hereditary sensory neuropathy type I and in hereditary motor and sensory neuropathy type IIB, also referred as Charcot-Marie-Tooth disease type 2B. To date two loci associated with ulcero-mutilating neuropathy have been described: CMT2B at 3q13-q22 and HSN I at 9q22.1-q22.3. We performed linkage analysis with chromosomal markers representing the hereditary sensory neuropathy type I and Charcot-Marie-Tooth disease type 2B loci on an Italian family with a severe distal sensory loss leading to an ulcero-mutilating peripheral neuropathy. Negative likelihood-of-odds scores excluded any evidence of linkage to both chromosome 3q13 and chromosome 9q22 markers, confirming the genetic heterogeneity of this clinical entity and the presence of a third locus responsible for ulcero-mutilating neuropathies.

Life-span extension by dietary restriction is mediated by NLP-7 signaling and coelomocyte endocytosis in C. elegans.

PubMed

Park, Sang-Kyu; Link, Christopher D; Johnson, Thomas E

2010-02-01

Recent studies have shown that the rate of aging can be modulated by diverse interventions. Dietary restriction is the most widely used intervention to promote longevity; however, the mechanisms underlying the effect of dietary restriction remain elusive. In a previous study, we identified two novel genes, nlp-7 and cup-4, required for normal longevity in Caenorhabditis elegans. nlp-7 is one of a set of neuropeptide-like protein genes; cup-4 encodes an ion-channel involved in endocytosis by coelomocytes. Here, we assess whether nlp-7 and cup-4 mediate longevity increases by dietary restriction. RNAi of nlp-7 or cup-4 significantly reduces the life span of the eat-2 mutant, a genetic model of dietary restriction, but has no effect on the life span of long-lived mutants resulting from reduced insulin/IGF-1 signaling or dysfunction of the mitochondrial electron transport chain. The life-span extension observed in wild-type N2 worms by dietary restriction using bacterial dilution is prevented significantly in nlp-7 and cup-4 mutants. RNAi knockdown of genes encoding candidate receptors of NLP-7 and genes involved in endocytosis by coelomocytes also specifically shorten the life span of the eat-2 mutant. We conclude that two novel pathways, NLP-7 signaling and endocytosis by coelomocytes, are required for life extension under dietary restriction in C. elegans.

A moderate elevation of circulating levels of IGF-I does not alter ErbB2 induced mammary tumorigenesis

PubMed Central

2011-01-01

Background Epidemiological evidence suggests that moderately elevated levels of circulating insulin-like growth factor-I (IGF-I) are associated with increased risk of breast cancer in women. How circulating IGF-I may promote breast cancer incidence is unknown, however, increased IGF-I signaling is linked to trastuzumab resistance in ErbB2 positive breast cancer. Few models have directly examined the effect of moderately high levels of circulating IGF-I on breast cancer initiation and progression. The purpose of this study was to assess the ability of circulating IGF-I to independently initiate mammary tumorigenesis and/or accelerate the progression of ErbB2 mediated mammary tumor growth. Methods We crossed heterozygous TTR-IGF-I mice with heterozygous MMTV-ErbB2 mice to generate 4 different genotypes: TTR-IGF-I/MMTV-ErbB2 (bigenic), TTR-IGF-I only, MMTV-ErbB2 only, and wild type (wt). Virgin females were palpated twice a week and harvested when tumors reached 1000 mm3. For study of normal development, blood and tissue were harvested at 4, 6 and 9 weeks of age in TTR-IGF-I and wt mice. Results TTR-IGF-I and TTR-IGF-I/ErbB2 bigenic mice showed a moderate 35% increase in circulating total IGF-I compared to ErbB2 and wt control mice. Elevation of circulating IGF-I had no effect upon pubertal mammary gland development. The transgenic increase in IGF-I alone wasn't sufficient to initiate mammary tumorigenesis. Elevated circulating IGF-I had no effect upon ErbB2-induced mammary tumorigenesis or metastasis, with median time to tumor formation being 30 wks and 33 wks in TTR-IGF-I/ErbB2 bigenic and ErbB2 mice respectively (p = 0.65). Levels of IGF-I in lysates from ErbB2/TTR-IGF-I tumors compared to ErbB2 was elevated in a similar manner to the circulating IGF-I, however, there was no effect on the rate of tumor growth (p = 0.23). There were no morphological differences in tumor type (solid adenocarcinomas) between bigenic and ErbB2 mammary glands. Conclusion Using the first

Use of the i2b2 research query tool to conduct a matched case-control clinical research study: advantages, disadvantages and methodological considerations.

PubMed

Johnson, Emilie K; Broder-Fingert, Sarabeth; Tanpowpong, Pornthep; Bickel, Jonathan; Lightdale, Jenifer R; Nelson, Caleb P

2014-01-30

A major aim of the i2b2 (informatics for integrating biology and the bedside) clinical data informatics framework aims to create an efficient structure within which patients can be identified for clinical and translational research projects.Our objective was to describe the respective roles of the i2b2 research query tool and the electronic medical record (EMR) in conducting a case-controlled clinical study at our institution. We analyzed the process of using i2b2 and the EMR together to generate a complete research database for a case-control study that sought to examine risk factors for kidney stones among gastrostomy tube (G-tube) fed children. Our final case cohort consisted of 41/177 (23%) of potential cases initially identified by i2b2, who were matched with 80/486 (17%) of potential controls. Cases were 10 times more likely to be excluded for inaccurate coding regarding stones vs. inaccurate coding regarding G-tubes. A majority (67%) of cases were excluded due to not meeting clinical inclusion criteria, whereas a majority of control exclusions (72%) occurred due to inadequate clinical data necessary for study completion. Full dataset assembly required complementary information from i2b2 and the EMR. i2b2 was critical as a query analysis tool for patient identification in our case-control study. Patient identification via procedural coding appeared more accurate compared with diagnosis coding. Completion of our investigation required iterative interplay of i2b2 and the EMR to assemble the study cohort.

A Clinical Data Warehouse Based on OMOP and i2b2 for Austrian Health Claims Data.

PubMed

Rinner, Christoph; Gezgin, Deniz; Wendl, Christopher; Gall, Walter

2018-01-01

To develop simulation models for healthcare related questions clinical data can be reused. Develop a clinical data warehouse to harmonize different data sources in a standardized manner and get a reproducible interface for clinical data reuse. The Kimball life cycle for the development of data warehouse was used. The development is split into the technical, the data and the business intelligence pathway. Sample data was persisted in the Observational Medical Outcomes Partnership (OMOP) Common Data Model (CDM). The i2b2 clinical data warehouse tools were used to query the OMOP CDM by applying the new i2b2 multi-fact table feature. A clinical data warehouse was set up and sample data, data dimensions and ontologies for Austrian health claims data were created. The ability of the standardized data access layer to create and apply simulation models will be evaluated next.

The structure, stability, and infrared spectrum of B 2N, B 2N +, B 2N -, BO, B 2O and B 2N 2.

NASA Astrophysics Data System (ADS)

Martin, J. M. L.; François, J. P.; Gijbels, R.

1992-05-01

The structure, infrared spectrum, and heat of formation of B 2N, B 2N -, BO, and B 2O have been studied ab initio. B 2N is very stable; B 2O even more so. B 2N, B 2N -, B 2O, and probably B 2N + have symmetric linear ground-state structures; for B 2O, an asymmetric linear structure lies about 12 kcal/mol above the ground state. B 2N +, B 2N - and B 2O have intense asymmetric stretching frequencies, predicted near 870, 1590 and 1400 cm -1, respectively. Our predicted harmonic frequencies and isotopic shifts for B 2O confirm the recent experimental identification by Andrews and Burkholder. Absorptions at 1889.5 and 1998.5 cm -1 in noble-gas trapped boron nitride vapor belong the BNB and BNBN ( 3Π), respectively; a tentative assignment of 882.5 cm -1 to BNB + is proposed. Total atomization energies Σ De (Σ D0) are computed (accuracy ±2 kcal/mol) as: BO 193.1 (190.4), B 2O 292.5 (288.7), B 2N 225.0 (250.3) kcal/mol. The ionization potential and electron affinity of B 2N are predicted to be 8.62±0.1 and 3.34±0.1 eV. The MP4-level additivity approximations involved in G1 theory results in errors on the order of 1 kcal/mol in the Σ De values.

The nido-osmaboranes [2,2,2-(CO)(PPh(3))(2)-nido-2-OsB(5)H(9)] and [6,6,6-(CO)(PPh(3))(2)-nido-6-OsB(9)H(13)].

PubMed

Bould, J; Kennedy, J D; Thomas, R L; Rath, N P; Barton, L

2001-11-01

The structural characterization of the osmahexaborane 2-carbonyl-2,2-bis(triphenylphosphine)-nido-2-osmahexaborane(9), [Os(B(5)H(9))(C(18)H(15)P)(2)(CO)], (I), a metallaborane analogue of B(6)H(10), confirms the structure proposed from NMR spectroscopy. The structure of the osmadecaborane 6-carbonyl-6,6-bis(triphenylphosphine)-nido-6-osmadecaborane(13), [Os(B(9)H(13))(C(18)H(15)P)(2)(CO)], (IV), is similarly confirmed. The short basal B-B distance of 1.652 (8) A in (I), not bridged by an H atom, mirrors that in the parent hexaborane(10) [1.626 (4) A].

Studies on B-cell memory. III. T-dependent aspect of B memory generation in mice immunized with T-independent type-2(TI-2) antigen.

PubMed

Hosokawa, T; Tanaka, Y; Aoike, A; Kawai, K; Muramatsu, S

1984-09-01

The time course of B-cell memory development to a dinitrophenyl (DNP) T-independent type-2 (TI-2) antigen was investigated by adoptive cell transfer. Strong IgM and IgG memory developed in BALB/c mice after immunization with DNP-dextran, to be recalled by challenge with either T-dependent (TD) antigen or TI-2 antigen. However, only weak IgM memory and very feeble IgG memory were detected in athymic nude mice receiving the same immunization as euthymic mice. Once memory was established under probable T cell influence, its recall by TI-2 antigen challenge seemed independent of T cell help and did not require sharing of carriers between priming and challenge antigens. The following may be concluded. (i) Long-term IgM and IgG memory is induced by TI-2 antigen priming in the presence of functional T cells. (ii) The class switch from IgM to IgG in the memory B cell pool is driven effectively by TI-2 antigen and is probably T cell-dependent.

Vaccination of dogs with canine parvovirus type 2b (CPV-2b) induces neutralising antibody responses to CPV-2a and CPV-2c.

PubMed

Wilson, Stephen; Illambas, Joanna; Siedek, Elisabeth; Stirling, Catrina; Thomas, Anne; Plevová, Edita; Sture, Gordon; Salt, Jeremy

2014-09-22

Since the identification of canine parvovirus type 2, three variants have subsequently been observed differing from the historical CPV-2 and each other by 1-2 amino acids only. As a result there has been considerable research into differential diagnostics, with some researchers indicating there is a need for new vaccines containing different strains of CPV-2. In this study we investigated whether vaccination with a CPV-2b containing vaccine would induce cross-reactive antibody responses to the other CPV-2 variants. Two studies where dogs were vaccinated with a multivalent vaccine, subsequently challenged with CPV-2b and sera samples analysed are presented. Six week old pups with defined serological status were vaccinated twice, three weeks apart and challenged either 5 weeks (MDA override study) or one year after vaccination (duration of immunity study). Sera samples were collected before each vaccination and at periods throughout each study. In each study the antibody profiles were very similar; serological responses against CPV-2a, CPV-2b and CPV-2c were higher than those for CPV-2. Nevertheless, responses against CPV-2 were well above levels considered clinically protective. In each study dogs also showed a rapid increase in antibody titres following vaccination, reached a plateau following second vaccination with a slight decline to challenge after which rapid anamnestic responses were seen. Evaluation of the serological responses suggests vaccination with CPV-2b would cross-protect against CPV-2a and CPV-2c, as well as against CPV-2 which is now extinct in the field. In conclusion we have demonstrated that vaccination of minimum aged dogs with a multivalent vaccine containing the CPV-2b variant strain will induce serological responses which are cross-reactive against all currently circulating field strains, CPV-2a and CPV-2c, and the now extinct field strain CPV-2. Copyright © 2014 Elsevier Ltd. All rights reserved.

NLP is a novel transcription regulator involved in VSG expression site control in Trypanosoma brucei.

PubMed

Narayanan, Mani Shankar; Kushwaha, Manish; Ersfeld, Klaus; Fullbrook, Alexander; Stanne, Tara M; Rudenko, Gloria

2011-03-01

Trypanosoma brucei mono-allelically expresses one of approximately 1500 variant surface glycoprotein (VSG) genes while multiplying in the mammalian bloodstream. The active VSG is transcribed by RNA polymerase I in one of approximately 15 telomeric VSG expression sites (ESs). T. brucei is unusual in controlling gene expression predominantly post-transcriptionally, and how ESs are mono-allelically controlled remains a mystery. Here we identify a novel transcription regulator, which resembles a nucleoplasmin-like protein (NLP) with an AT-hook motif. NLP is key for ES control in bloodstream form T. brucei, as NLP knockdown results in 45- to 65-fold derepression of the silent VSG221 ES. NLP is also involved in repression of transcription in the inactive VSG Basic Copy arrays, minichromosomes and procyclin loci. NLP is shown to be enriched on the 177- and 50-bp simple sequence repeats, the non-transcribed regions around rDNA and procyclin, and both active and silent ESs. Blocking NLP synthesis leads to downregulation of the active ES, indicating that NLP plays a role in regulating appropriate levels of transcription of ESs in both their active and silent state. Discovery of the unusual transcription regulator NLP provides new insight into the factors that are critical for ES control.

Towards liquid-helium-free, persistent-mode MgB2 MRI magnets: FBML experience

NASA Astrophysics Data System (ADS)

Iwasa, Yukikazu

2017-05-01

In this article I present our experience at the Magnet Technology Division of the MIT Francis Bitter Magnet Laboratory on liquid-helium (LHe)-free, persistent-mode MgB2 MRI magnets. Before reporting on our MgB2 magnets, I first summarize the basic work that we began in the late 1990s to develop LHe-free, high-temperature superconductor (HTS) magnets cooled in solid cryogen—I begin by discussing the enabling feature, particularly of solid nitrogen (SN2), for adiabatic HTS magnets. The next topic is our first LHe-free, SN2-HTS magnet, for which we chose Bi2223 because in the late 1990s Bi2223 was the only HTS available to build an HTS magnet. I then move on to two MgB2 magnets, I and II, developed after discovery of MgB2 in 2000. The SN2-MgB2 Magnet II—0.5 T/240 mm, SN2-cooled, and operated in persistent mode—was completed in January 2016. The final major topic in this article is a tabletop LHe-free, persistent-mode 1.5 T/70 mm SN2-MgB2 ‘finger’ MRI magnet for osteoporosis screening—we expect to begin this project in 2017. Before concluding this article, I present my current view on challenges and prospects for MgB2 MRI magnets.

Towards Liquid-Helium-Free, Persistent-Mode MgB2 MRI Magnets: FBML Experience.

PubMed

Iwasa, Yukikazu

2017-01-01

In this article I present our experience at the Magnet Technology Division of the MIT Francis Bitter Magnet Laboratory on liquid-helium (LHe)-free, persistent-mode MgB 2 MRI magnets. Before reporting on our MgB 2 magnets, I first summarize the basic work that we began in the late 1990s to develop LHe-free, high-temperature superconductor (HTS) magnets cooled in solid cryogen-I begin by discussing the enabling feature, particularly of solid nitrogen (SN2), for adiabatic HTS magnets. The next topic is our first LHe-free, SN2-HTS magnet, for which we chose Bi2223 because in the late 1990s Bi2223 was the only HTS available to build an HTS magnet. I then move on to two MgB 2 magnets, I and II, developed after discovery of MgB 2 in 2000. The SN2-MgB 2 Magnet II-0.5-T/240-mm, SN2-cooled, and operated in persistent mode-was completed in January 2016. The final major topic in this article is a tabletop LHe-free, persistent-mode 1.5-T/70-mm SN2-MgB 2 "finger" MRI magnet for osteoporosis screening-we expect to begin this project in 2017. Before concluding this article, I present my current view on challenges and prospects for MgB 2 MRI magnets.

Towards Liquid-Helium-Free, Persistent-Mode MgB2 MRI Magnets: FBML Experience

PubMed Central

Iwasa, Yukikazu

2017-01-01

In this article I present our experience at the Magnet Technology Division of the MIT Francis Bitter Magnet Laboratory on liquid-helium (LHe)-free, persistent-mode MgB2 MRI magnets. Before reporting on our MgB2 magnets, I first summarize the basic work that we began in the late 1990s to develop LHe-free, high-temperature superconductor (HTS) magnets cooled in solid cryogen—I begin by discussing the enabling feature, particularly of solid nitrogen (SN2), for adiabatic HTS magnets. The next topic is our first LHe-free, SN2-HTS magnet, for which we chose Bi2223 because in the late 1990s Bi2223 was the only HTS available to build an HTS magnet. I then move on to two MgB2 magnets, I and II, developed after discovery of MgB2 in 2000. The SN2-MgB2 Magnet II—0.5-T/240-mm, SN2-cooled, and operated in persistent mode—was completed in January 2016. The final major topic in this article is a tabletop LHe-free, persistent-mode 1.5-T/70-mm SN2-MgB2 “finger” MRI magnet for osteoporosis screening—we expect to begin this project in 2017. Before concluding this article, I present my current view on challenges and prospects for MgB2 MRI magnets. PMID:29568161

Role of the He I and He II metastables in the resonance 2p 2P°1/2, 3/2 B III level population

NASA Astrophysics Data System (ADS)

Djeniže, S.; Srećković, A.; Bukvić, S.

2007-01-01

Aims:The aim of this work is to present atomic processes which lead to an extra population of the 2p ~^2P°1/2, 3/2 B III resonance levels in helium plasma generating intense radiation in the B III 206.578 nm and 206.723 nm lines. Methods: The line profiles were recorded using a step-by-step (7.3 pm) technique which provides monitoring of the line shapes continually during the plasma decay and gives the possibility to compare line shapes at various times in the same plasma. Results: On the basis of the line intensity decays of the doubly ionized boron resonance spectral lines in laboratory nitrogen and helium plasmas, we have found the existence of a permanent energy transfer from He I and He II metastables to the 2p ^2P°1/2, 3/2 B III resonance levels. The shapes of the mentioned lines are also observed. At electron temperatures of about 18 000 K and electron densities about 1.1× 1023 m-3, the Stark broadening was found as a main B III line broadening mechanism. The measured Stark widths (W) are compared with the Doppler width (W_D) and with the splitting in the hyperfine structure (Δ_hfs). Our measured W data are found to be much higher than results obtained by means of various theoretical approaches. Conclusions: . The He I and He II metastables over populate the B III resonance levels leading to populations higher than predicted by LTE model. Consequently, the emitted B III resonance lines are more intense than expected from LTE model. This fact can be of importance if B III resonance line intensities are used for abundance determination purposes in astrophysics. Similar behavior can be expected for some lines emitted by astrophysical interesting emitters: Al III, Si III, Sc III, Cr III, V III, Ti III, Fe III, Co III, Ni III, Ga III, Zr III, Y III, Nb III, In III, Sn III, Sb III, Au III, Pb III and Bi III in hot and dense helium plasmas.

Open Source Clinical NLP - More than Any Single System.

PubMed

Masanz, James; Pakhomov, Serguei V; Xu, Hua; Wu, Stephen T; Chute, Christopher G; Liu, Hongfang

2014-01-01

The number of Natural Language Processing (NLP) tools and systems for processing clinical free-text has grown as interest and processing capability have surged. Unfortunately any two systems typically cannot simply interoperate, even when both are built upon a framework designed to facilitate the creation of pluggable components. We present two ongoing activities promoting open source clinical NLP. The Open Health Natural Language Processing (OHNLP) Consortium was originally founded to foster a collaborative community around clinical NLP, releasing UIMA-based open source software. OHNLP's mission currently includes maintaining a catalog of clinical NLP software and providing interfaces to simplify the interaction of NLP systems. Meanwhile, Apache cTAKES aims to integrate best-of-breed annotators, providing a world-class NLP system for accessing clinical information within free-text. These two activities are complementary. OHNLP promotes open source clinical NLP activities in the research community and Apache cTAKES bridges research to the health information technology (HIT) practice.

Effect of porcine circovirus type 2 (PCV2) vaccination on PCV2-viremic piglets after experimental PCV2 challenge.

PubMed

Seo, Hwi Won; Park, Changhoon; Han, Kiwon; Chae, Chanhee

2014-02-02

The objective of this study was to evaluate the effect of porcine circovirus type 2 (PCV2) vaccines on PCV2-viremic and -seropositive piglets born from naturally PCV2-infected sows against postnatal PCV2 challenge. The experimental design was aimed at mimicking commercial swine rearing conditions to evaluate the response of the PCV2 vaccine on PCV2-viremic and -seropositive piglets after experimental PCV2 challenge. PCV2a (or 2b)-viremic piglets received a PCV2 vaccine at 21 days of age followed by a PCV2b (or 2a) challenge at 49 days of age (28 days post vaccination). The PCV2 vaccines elicited a high level of humoral (as measured by immunoperoxidase monolayer assay and neutralizing antibody titers) and cellular (as measured by the frequency of PCV2-specific interferon-γ-secreting cells) immune response in the PCV2-viremic piglets after vaccination even in the presence of maternally derived antibodies (MDA). The initial infection of PCV2 in the pigs was not affected by PCV2 vaccination, however the challenging PCV2 was reduced by PCV2 vaccination on PCV2-viremic pigs. The results from this study demonstrate that the PCV2 vaccine used in this study is effective at reducing PCV2 viremia and lymphoid PCV2 DNA, even for PCV2-viremic pigs with passively acquired MDA at the time of vaccination.

Effect of porcine circovirus type 2 (PCV2) vaccination on PCV2-viremic piglets after experimental PCV2 challenge

PubMed Central

2014-01-01

The objective of this study was to evaluate the effect of porcine circovirus type 2 (PCV2) vaccines on PCV2-viremic and -seropositive piglets born from naturally PCV2-infected sows against postnatal PCV2 challenge. The experimental design was aimed at mimicking commercial swine rearing conditions to evaluate the response of the PCV2 vaccine on PCV2-viremic and -seropositive piglets after experimental PCV2 challenge. PCV2a (or 2b)-viremic piglets received a PCV2 vaccine at 21 days of age followed by a PCV2b (or 2a) challenge at 49 days of age (28 days post vaccination). The PCV2 vaccines elicited a high level of humoral (as measured by immunoperoxidase monolayer assay and neutralizing antibody titers) and cellular (as measured by the frequency of PCV2-specific interferon-γ-secreting cells) immune response in the PCV2-viremic piglets after vaccination even in the presence of maternally derived antibodies (MDA). The initial infection of PCV2 in the pigs was not affected by PCV2 vaccination, however the challenging PCV2 was reduced by PCV2 vaccination on PCV2-viremic pigs. The results from this study demonstrate that the PCV2 vaccine used in this study is effective at reducing PCV2 viremia and lymphoid PCV2 DNA, even for PCV2-viremic pigs with passively acquired MDA at the time of vaccination. PMID:24484292

A comprehensive clinical research database based on CDISC ODM and i2b2.

PubMed

Meineke, Frank A; Stäubert, Sebastian; Löbe, Matthias; Winter, Alfred

2014-01-01

We present a working approach for a clinical research database as part of an archival information system. The CDISC ODM standard is target for clinical study and research relevant routine data, thus decoupling the data ingest process from the access layer. The presented research database is comprehensive as it covers annotating, mapping and curation of poorly annotated source data. Besides a conventional relational database the medical data warehouse i2b2 serves as main frontend for end-users. The system we developed is suitable to support patient recruitment, cohort identification and quality assurance in daily routine.

Knowledge representation and management: benefits and challenges of the semantic web for the fields of KRM and NLP.

PubMed

Rassinoux, A-M

2011-01-01

To summarize excellent current research in the field of knowledge representation and management (KRM). A synopsis of the articles selected for the IMIA Yearbook 2011 is provided and an attempt to highlight the current trends in the field is sketched. This last decade, with the extension of the text-based web towards a semantic-structured web, NLP techniques have experienced a renewed interest in knowledge extraction. This trend is corroborated through the five papers selected for the KRM section of the Yearbook 2011. They all depict outstanding studies that exploit NLP technologies whenever possible in order to accurately extract meaningful information from various biomedical textual sources. Bringing semantic structure to the meaningful content of textual web pages affords the user with cooperative sharing and intelligent finding of electronic data. As exemplified by the best paper selection, more and more advanced biomedical applications aim at exploiting the meaningful richness of free-text documents in order to generate semantic metadata and recently to learn and populate domain ontologies. These later are becoming a key piece as they allow portraying the semantics of the Semantic Web content. Maintaining their consistency with documents and semantic annotations that refer to them is a crucial challenge of the Semantic Web for the coming years.

Automated population of an i2b2 clinical data warehouse from an openEHR-based data repository.

PubMed

Haarbrandt, Birger; Tute, Erik; Marschollek, Michael

2016-10-01

Detailed Clinical Model (DCM) approaches have recently seen wider adoption. More specifically, openEHR-based application systems are now used in production in several countries, serving diverse fields of application such as health information exchange, clinical registries and electronic medical record systems. However, approaches to efficiently provide openEHR data to researchers for secondary use have not yet been investigated or established. We developed an approach to automatically load openEHR data instances into the open source clinical data warehouse i2b2. We evaluated query capabilities and the performance of this approach in the context of the Hanover Medical School Translational Research Framework (HaMSTR), an openEHR-based data repository. Automated creation of i2b2 ontologies from archetypes and templates and the integration of openEHR data instances from 903 patients of a paediatric intensive care unit has been achieved. In total, it took an average of ∼2527s to create 2.311.624 facts from 141.917 XML documents. Using the imported data, we conducted sample queries to compare the performance with two openEHR systems and to investigate if this representation of data is feasible to support cohort identification and record level data extraction. We found the automated population of an i2b2 clinical data warehouse to be a feasible approach to make openEHR data instances available for secondary use. Such an approach can facilitate timely provision of clinical data to researchers. It complements analytics based on the Archetype Query Language by allowing querying on both, legacy clinical data sources and openEHR data instances at the same time and by providing an easy-to-use query interface. However, due to different levels of expressiveness in the data models, not all semantics could be preserved during the ETL process. Copyright © 2016 Elsevier Inc. All rights reserved.

Open Source Clinical NLP – More than Any Single System

PubMed Central

Masanz, James; Pakhomov, Serguei V.; Xu, Hua; Wu, Stephen T.; Chute, Christopher G.; Liu, Hongfang

2014-01-01

The number of Natural Language Processing (NLP) tools and systems for processing clinical free-text has grown as interest and processing capability have surged. Unfortunately any two systems typically cannot simply interoperate, even when both are built upon a framework designed to facilitate the creation of pluggable components. We present two ongoing activities promoting open source clinical NLP. The Open Health Natural Language Processing (OHNLP) Consortium was originally founded to foster a collaborative community around clinical NLP, releasing UIMA-based open source software. OHNLP’s mission currently includes maintaining a catalog of clinical NLP software and providing interfaces to simplify the interaction of NLP systems. Meanwhile, Apache cTAKES aims to integrate best-of-breed annotators, providing a world-class NLP system for accessing clinical information within free-text. These two activities are complementary. OHNLP promotes open source clinical NLP activities in the research community and Apache cTAKES bridges research to the health information technology (HIT) practice. PMID:25954581

Scaling-up NLP Pipelines to Process Large Corpora of Clinical Notes.

PubMed

Divita, G; Carter, M; Redd, A; Zeng, Q; Gupta, K; Trautner, B; Samore, M; Gundlapalli, A

2015-01-01

This article is part of the Focus Theme of Methods of Information in Medicine on "Big Data and Analytics in Healthcare". This paper describes the scale-up efforts at the VA Salt Lake City Health Care System to address processing large corpora of clinical notes through a natural language processing (NLP) pipeline. The use case described is a current project focused on detecting the presence of an indwelling urinary catheter in hospitalized patients and subsequent catheter-associated urinary tract infections. An NLP algorithm using v3NLP was developed to detect the presence of an indwelling urinary catheter in hospitalized patients. The algorithm was tested on a small corpus of notes on patients for whom the presence or absence of a catheter was already known (reference standard). In planning for a scale-up, we estimated that the original algorithm would have taken 2.4 days to run on a larger corpus of notes for this project (550,000 notes), and 27 days for a corpus of 6 million records representative of a national sample of notes. We approached scaling-up NLP pipelines through three techniques: pipeline replication via multi-threading, intra-annotator threading for tasks that can be further decomposed, and remote annotator services which enable annotator scale-out. The scale-up resulted in reducing the average time to process a record from 206 milliseconds to 17 milliseconds or a 12- fold increase in performance when applied to a corpus of 550,000 notes. Purposely simplistic in nature, these scale-up efforts are the straight forward evolution from small scale NLP processing to larger scale extraction without incurring associated complexities that are inherited by the use of the underlying UIMA framework. These efforts represent generalizable and widely applicable techniques that will aid other computationally complex NLP pipelines that are of need to be scaled out for processing and analyzing big data.

Activity patterns of the B31/B32 pattern initiators innervating the I2 muscle of the buccal mass during normal feeding movements in Aplysia californica.

PubMed

Hurwitz, I; Neustadter, D; Morton, D W; Chiel, H J; Susswein, A J

1996-04-01

1. B31 and B32 are pattern-initiator neurons in the buccal ganglia of Aplysia. Along with the B61/B62 neurons, B31/B32 are also motor neurons that innervate the 12 buccal muscle via the I2 nerve. This research was aimed at determining the physiological functions of the B31/B32 and B61/B62 neurons, and of the I2 muscle. 2. Stimulating the I2 muscle in the radula rest position produces radula protraction. In addition, in behaving animals lesioning either the muscle or the I2 nerve greatly reduces radula protraction. 3. During buccal motor programs in reduced preparations, B31/B32 and B61/62 fire preceding activity in neuron B4, whose firing indicates the onset of radula retraction. In addition, during both ingestion-like and rejection-like patterns the activity in the I2 nerve is correlated with protraction. 4. B31/B32 fire at frequencies of 15-25 Hz. Neither B31/B32 nor B61/B62 elicit facilitating end-junction potentials (EJPs) and electromyograms (EMGs) in the I2 muscle. EMGs from B31/B32 are smaller than those from B61/B62. B31/B32 and B61/B62 innervate all areas of the muscle approximately uniformly. 5. In behaving animals, EMGs consistent with B31/B32 activity are seen in the I2 muscle during the protraction phase of biting, swallowing, and rejection movements. In addition, the I2 muscle receives inputs that cannot be attributed to either the B31/B32 or B61/B62 neurons, either because the potentials are too large, firing frequencies are too low, or a prominent facilitation is seen. Such potentials are associated with lip movements, and also with radula retraction. 6. EMGs were recorded from the I2 muscle during feeding behavior after a lesion of the I2 nerve. Animals that had severe deficits in protraction showed no activity consistent with B31/B32 or B61/B62, but did show activity during retraction. 7. Our data indicate that the I2 muscle and the B31/B32 motor neurons are essential constituents contributing to protraction movements. Activity in these neurons is

HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR expression in infertile women with endometriosis.

PubMed

Osiński, Maciej; Wirstlein, Przemysław; Wender-Ożegowska, Ewa; Mikołajczyk, Mateusz; Jagodziński, Paweł Piotr; Szczepańska, Małgorzata

2018-01-01

The development of endometriosis is associated with changes in the expression of genes encoding the 3β-hydroxysteroid dehydrogenase type II (HSD3B2) and 17β-hydroxysteroid dehydrogenase type II (HSD17B2), estrogen receptors 1 (ESR1) and 2 (ESR2) and the androgen receptor (AR). However, little is known about the expression of HSD3B2, HSD17B1, HSD17B2, ESR1 ESR2 and AR during the endometrial phases in eutopic endometrium from infertile women with endometriosis. Using RT-qPCR analysis, we assessed the expression of the studied genes in the follicular and luteal phases in eutopic endometrium from fertile women (n = 17) and infertile women (n = 35) with endometriosis. In the mid-follicular eutopic endometrium, we observed a significant increase in HSD3B2 transcript levels in all infertile women with endometriosis (p = 0.003), in infertile women with stage I/II endometriosis (p = 0.008) and in infertile women with stage III/IV endometriosis (p = 0.009) compared to all fertile women. There was a significant increase in ESR1 tran-scripts in all infertile women with endometriosis (p = 0.008) and in infertile women with stage I/II endometriosis (p = 0.019) and in infertile women with stage III/IV endometriosis (p = 0.023) compared to all fertile women. In the mid-luteal eutopic endometrium, we did not observe significant differences in HSD3B2, HSD17B1, HSD17B2, ESR1, ESR2 and AR transcripts between infertile women with endometriosis and fertile women. Observed significant increase in HSD3B2 and ESR1 transcripts in follicular eutopic endometrium from infer-tile women with endometriosis may be related to abnormal biological effect of E2 in endometrium, further affecting the development of human embryos.

Clinical documentation variations and NLP system portability: a case study in asthma birth cohorts across institutions.

PubMed

Sohn, Sunghwan; Wang, Yanshan; Wi, Chung-Il; Krusemark, Elizabeth A; Ryu, Euijung; Ali, Mir H; Juhn, Young J; Liu, Hongfang

2017-11-30

To assess clinical documentation variations across health care institutions using different electronic medical record systems and investigate how they affect natural language processing (NLP) system portability. Birth cohorts from Mayo Clinic and Sanford Children's Hospital (SCH) were used in this study (n = 298 for each). Documentation variations regarding asthma between the 2 cohorts were examined in various aspects: (1) overall corpus at the word level (ie, lexical variation), (2) topics and asthma-related concepts (ie, semantic variation), and (3) clinical note types (ie, process variation). We compared those statistics and explored NLP system portability for asthma ascertainment in 2 stages: prototype and refinement. There exist notable lexical variations (word-level similarity = 0.669) and process variations (differences in major note types containing asthma-related concepts). However, semantic-level corpora were relatively homogeneous (topic similarity = 0.944, asthma-related concept similarity = 0.971). The NLP system for asthma ascertainment had an F-score of 0.937 at Mayo, and produced 0.813 (prototype) and 0.908 (refinement) when applied at SCH. The criteria for asthma ascertainment are largely dependent on asthma-related concepts. Therefore, we believe that semantic similarity is important to estimate NLP system portability. As the Mayo Clinic and SCH corpora were relatively homogeneous at a semantic level, the NLP system, developed at Mayo Clinic, was imported to SCH successfully with proper adjustments to deal with the intrinsic corpus heterogeneity. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Anisotropic type-I superconductivity and anomalous superfluid density in OsB2

NASA Astrophysics Data System (ADS)

Bekaert, J.; Vercauteren, S.; Aperis, A.; Komendová, L.; Prozorov, R.; Partoens, B.; Milošević, M. V.

2016-10-01

We present a microscopic study of superconductivity in OsB2, and discuss the origin and characteristic length scales of the superconducting state. From first-principles we show that OsB2 is characterized by three different Fermi sheets, and we prove that this fermiology complies with recent quantum-oscillation experiments. Using the found microscopic properties, and experimental data from the literature, we employ Ginzburg-Landau relations to reveal that OsB2 is a distinctly type-I superconductor with a very low Ginzburg-Landau parameter κ —a rare property among compound materials. We show that the found coherence length and penetration depth corroborate the measured thermodynamic critical field. Moreover, our calculation of the superconducting gap structure using anisotropic Eliashberg theory and ab initio calculated electron-phonon interaction as input reveals a single but anisotropic gap. The calculated gap spectrum is shown to give an excellent account for the unconventional behavior of the superfluid density of OsB2 measured in experiments as a function of temperature. This reveals that gap anisotropy can explain such behavior, observed in several compounds, which was previously attributed solely to a two-gap nature of superconductivity.

Anisotropic type-I superconductivity and anomalous superfluid density in OsB 2

DOE PAGES

Bekaert, Jonas; Vercauteren, S.; Aperis, A.; ...

2016-10-12

Here, we present a microscopic study of superconductivity in OsB 2, and discuss the origin and characteristic length scales of the superconducting state. From first-principles we show that OsB 2 is characterized by three different Fermi sheets, and we prove that this fermiology complies with recent quantum-oscillation experiments. Using the found microscopic properties, and experimental data from the literature, we employ Ginzburg-Landau relations to reveal that OsB 2 is a distinctly type-I superconductor with a very low Ginzburg-Landau parameter κ—a rare property among compound materials. We show that the found coherence length and penetration depth corroborate the measured thermodynamic criticalmore » field. Moreover, our calculation of the superconducting gap structure using anisotropic Eliashberg theory and ab initio calculated electron-phonon interaction as input reveals a single but anisotropic gap. The calculated gap spectrum is shown to give an excellent account for the unconventional behavior of the superfluid density of OsB 2 measured in experiments as a function of temperature. This reveals that gap anisotropy can explain such behavior, observed in several compounds, which was previously attributed solely to a two-gap nature of superconductivity.« less

Porcine circovirus type 2 induces the activation of nuclear factor kappa B by I{kappa}B{alpha} degradation

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

Wei Li; Kwang, Jimmy; Wang Jin

The transcription factor NF-{kappa}B is commonly activated upon virus infection and a key player in the induction and regulation of the host immune response. The present study demonstrated for the first time that porcine circovirus type 2 (PCV2), which is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome, can activate NF-{kappa}B in PCV2-infected PK15 cells. In PCV2-infected cells, NF-{kappa}B was activated concomitantly with viral replication, which was characterized by increased DNA binding activity, translocation of NF-{kappa}B p65 from the cytoplasm to the nucleus, as well as degradation and phosphorylation of I{kappa}B{alpha} protein. We further demonstratedmore » PCV2-induced activation of NF-{kappa}B and colocalization of p65 nuclear translocation with virus replication in cultured cells. Treatment of cells with CAPE, a selective inhibitor of NF-{kappa}B activation, reduced virus protein expression and progeny production followed by decreasing PCV2-induced apoptotic caspase activity, indicating the involvement of this transcription factor in induction of cell death. Taken together, these data suggest that NF-{kappa}B activation is important for PCV2 replication and contributes to virus-mediated changes in host cells. The results presented here provide a basis for understanding molecular mechanism of PCV2 infection.« less

β -B i2O3 under compression: Optical and elastic properties and electron density topology analysis

NASA Astrophysics Data System (ADS)

Pereira, A. L. J.; Gomis, O.; Sans, J. A.; Contreras-García, J.; Manjón, F. J.; Rodríguez-Hernández, P.; Muñoz, A.; Beltrán, A.

2016-06-01

We report a joint experimental and theoretical study of the optical properties of tetragonal bismuth oxide (β -B i2O3 ) at high pressure by means of optical absorption measurements combined with ab initio electronic band structure calculations. Our results are consistent with previous results that show the presence of a second-order isostructural phase transition in B i2O3 (from β to β') around 2 GPa and a phase transition above 15 GPa combined with a pressure-induced amorphization above 17-20 GPa. In order to further understand the pressure-induced phase transitions and amorphization occurring in β -B i2O3 , we theoretically studied the mechanical and dynamical stability of the tetragonal structures of β - and β'-B i2O3 at high pressure through calculations of their elastic constants, elastic stiffness coefficients, and phonon dispersion curves. The pressure dependence of the elastic stiffness coefficients and phonon dispersion curves confirms that the isostructural phase transition near 2 GPa is of ferroelastic nature. Furthermore, a topological study of the electron density shows that the ferroelastic transition is not caused by a change in number of critical points (cusp catastrophe), but by the equalization of the electron densities of both independent O atoms in the unit cell due to a local rise in symmetry. Finally, from theoretical simulations, β'-B i2O3 is found to be mechanically and dynamically stable at least up to 26.7 GPa under hydrostatic conditions; thus, the pressure-induced amorphization reported above 17-20 GPa in powder β'-B i2O3 using methanol-ethanol-water as pressure-transmitting medium could be related to the frustration of a reconstructive phase transition at room temperature and the presence of mechanical or dynamical instabilities under nonhydrostatic conditions.

Major histocompatibility complex class I-deficient NOD-B2mnull mice are diabetes and insulitis resistant.

PubMed

Serreze, D V; Leiter, E H; Christianson, G J; Greiner, D; Roopenian, D C

1994-03-01

Specific allelic combinations within the class II region of the major histocompatibility complex (MHC) represent a major genetic component for susceptibility to autoimmune insulin-dependent diabetes mellitus (IDDM) in humans. We produced and used a stock of NOD/Lt mice congenic for a functionally inactivated beta 2-microglobulin (B2mnull) locus to assess whether there was an absolute requirement for MHC class I expression and/or CD8+ T-cells in diabetogenesis. These NOD-B2mnull mice do not express cell surface MHC class I molecules or produce detectable levels of CD8+ T-cells and are diabetes and insulitis resistant. Previous results from transgenic mouse models indicated that intracellular accumulation of MHC class I molecules negatively affects pancreatic beta-cell function and can result in the development of nonautoimmune insulin-dependent diabetes mellitus (IDDM). MHC class I molecules have been shown to accumulate intracellularly in the presence of a disrupted B2m locus, but this mutation does not negatively affect plasma insulin levels in either NOD/Lt mice or in those of a mixed 129 and C57BL/6 genetic background. Interestingly, 14% of the male mice in this mixed background did develop hyperinsulinemia (> 1,500 pM) independent of the disrupted B2m locus, suggesting that these mice could conceivably develop insulin-resistant diabetes. However, none of these mice became diabetic at up to 22 months of age. Thus, elimination of cell surface MHC class I expression with a disrupted B2m gene blocks autoimmune diabetes in NOD/Lt mice, without engendering a separate, distinct form of glucose intolerance.

Pressure effect on the superconducting and the normal state of β -B i2Pd

NASA Astrophysics Data System (ADS)

Pristáš, G.; Orendáč, Mat.; Gabáni, S.; Kačmarčík, J.; Gažo, E.; Pribulová, Z.; Correa-Orellana, A.; Herrera, E.; Suderow, H.; Samuely, P.

2018-04-01

The pressure effect up to 24.0 kbar on superconducting and normal-state properties of β -B i2Pd single crystal (Tc≈4.98 K at ambient pressure) has been investigated by measurements of the electrical resistivity. In addition, we have performed the heat capacity measurements in the temperature range 0.7-300 K at ambient pressure. The recent calculations of electronic density of states, electron-phonon interaction spectral function, and phonon density of states of β -B i2Pd [Zheng and Margine, Phys. Rev. B 95, 014512 (2017), 10.1103/PhysRevB.95.014512], are used to fit the resistivity and the heat capacity data. In the superconducting state we have focused on the influence of pressure on the superconducting transition temperature Tc and upper critical field Hc 2 and a negative effect with d Tc/d p =-0.025 K /kbar and d Hc 2/d p =-8 mT /kbar is found. A simplified Bloch-Grüneisen model was used to analyze the pressure effect on the temperature dependence of the normal-state resistivity. The obtained results point to a decrease of the electron-phonon coupling parameter λ and to a shift of phonon frequencies to higher values with pressure. Moreover, the temperature dependence of the normal-state resistivity follows a T2 dependence above Tc up to about 25 K. Together with the enhanced value of Sommerfeld coefficient γ =13.23 mJ mo l-1K-2 these results point to a certain role of the electron-electron interaction in the superconducting pairing mechanism in β -B i2Pd .

Topical herpes simplex virus 2 (HSV-2) vaccination with human papillomavirus vectors expressing gB/gD ectodomains induces genital-tissue-resident memory CD8+ T cells and reduces genital disease and viral shedding after HSV-2 challenge.

PubMed

Çuburu, Nicolas; Wang, Kening; Goodman, Kyle N; Pang, Yuk Ying; Thompson, Cynthia D; Lowy, Douglas R; Cohen, Jeffrey I; Schiller, John T

2015-01-01

No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8(+) T cells that were able to secrete gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8(+) T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection. Genital herpes is a highly prevalent chronic disease caused by

Topical Herpes Simplex Virus 2 (HSV-2) Vaccination with Human Papillomavirus Vectors Expressing gB/gD Ectodomains Induces Genital-Tissue-Resident Memory CD8+ T Cells and Reduces Genital Disease and Viral Shedding after HSV-2 Challenge

PubMed Central

Çuburu, Nicolas; Wang, Kening; Goodman, Kyle N.; Pang, Yuk Ying; Thompson, Cynthia D.; Lowy, Douglas R.; Cohen, Jeffrey I.

2014-01-01

ABSTRACT No herpes simplex virus 2 (HSV-2) vaccine has been licensed for use in humans. HSV-2 glycoproteins B (gB) and D (gD) are targets of neutralizing antibodies and T cells, but clinical trials involving intramuscular (i.m.) injection of HSV-2 gB and gD in adjuvants have not been effective. Here we evaluated intravaginal (ivag) genetic immunization of C57BL/6 mice with a replication-defective human papillomavirus pseudovirus (HPV PsV) expressing HSV-2 gB (HPV-gB) or gD (HPV-gD) constructs to target different subcellular compartments. HPV PsV expressing a secreted ectodomain of gB (gBsec) or gD (gDsec), but not PsV expressing a cytoplasmic or membrane-bound form, induced circulating and intravaginal-tissue-resident memory CD8+ T cells that were able to secrete gamma interferon (IFN-γ) and tumor necrosis factor alpha (TNF-α) as well as moderate levels of serum HSV neutralizing antibodies. Combined immunization with HPV-gBsec and HPV-gDsec (HPV-gBsec/gDsec) vaccines conferred longer survival after vaginal challenge with HSV-2 than immunization with HPV-gBsec or HPV-gDsec alone. HPV-gBsec/gDsec ivag vaccination was associated with a reduced severity of genital lesions and lower levels of viral shedding in the genital tract after HSV-2 challenge. In contrast, intramuscular vaccination with a soluble truncated gD protein (gD2t) in alum and monophosphoryl lipid A (MPL) elicited high neutralizing antibody titers and improved survival but did not reduce genital lesions and viral shedding. Vaccination combining ivag HPV-gBsec/gDsec and i.m. gD2t-alum-MPL improved survival and reduced genital lesions and viral shedding. Finally, high levels of circulating HSV-2-specific CD8+ T cells, but not serum antibodies, correlated with reduced viral shedding. Taken together, our data underscore the potential of HPV PsV as a platform for a topical mucosal vaccine to control local manifestations of primary HSV-2 infection. IMPORTANCE Genital herpes is a highly prevalent chronic

Launch flexibility using NLP guidance and remote wind sensing

NASA Technical Reports Server (NTRS)

Cramer, Evin J.; Bradt, Jerre E.; Hardtla, John W.

1990-01-01

This paper examines the use of lidar wind measurements in the implementation of a guidance strategy for a nonlinear programming (NLP) launch guidance algorithm. The NLP algorithm uses B-spline command function representation for flexibility in the design of the guidance steering commands. Using this algorithm, the guidance system solves a two-point boundary value problem at each guidance update. The specification of different boundary value problems at each guidance update provides flexibility that can be used in the design of the guidance strategy. The algorithm can use lidar wind measurements for on pad guidance retargeting and for load limiting guidance steering commands. Examples presented in the paper use simulated wind updates to correct wind induced final orbit errors and to adjust the guidance steering commands to limit the product of the dynamic pressure and angle-of-attack for launch vehicle load alleviation.

Validation of Eye Movements Model of NLP through Stressed Recalls.

ERIC Educational Resources Information Center

Sandhu, Daya S.

Neurolinguistic Progamming (NLP) has emerged as a new approach to counseling and psychotherapy. Though not to be confused with computer programming, NLP does claim to program, deprogram, and reprogram clients' behaviors with the precision and expedition akin to computer processes. It is as a tool for therapeutic communication that NLP has rapidly…

Automated realtime data import for the i2b2 clinical data warehouse: introducing the HL7 ETL cell.

PubMed

Majeed, Raphael W; Röhrig, Rainer

2012-01-01

Clinical data warehouses are used to consolidate all available clinical data from one or multiple organizations. They represent an important source for clinical research, quality management and controlling. Since its introduction, the data warehouse i2b2 gathered a large user base in the research community. Yet, little work has been done on the process of importing clinical data into data warehouses using existing standards. In this article, we present a novel approach of utilizing the clinical integration server as data source, commonly available in most hospitals. As information is transmitted through the integration server, the standardized HL7 message is immediately parsed and inserted into the data warehouse. Evaluation of import speeds suggest feasibility of the provided solution for real-time processing of HL7 messages. By using the presented approach of standardized data import, i2b2 can be used as a plug and play data warehouse, without the hurdle of customized import for every clinical information system or electronic medical record. The provided solution is available for download at http://sourceforge.net/projects/histream/.

Combating Weapons of Mass Destruction: Models, Complexity, and Algorithms in Complex Dynamic and Evolving Networks

DTIC Science & Technology

2015-11-01

NLP Blondel Oslom Infomap 0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1 N M I (N = 5 0 0 0 ) µ SCD SCD- NLP Blondel Oslom Infomap A...Networks with minC ,maxC unconstrained. 0 0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1 N M I (N = 1 0 0 0 ) µ SCD SCD- NLP Blondel Oslom Infomap 0...0.2 0.4 0.6 0.8 1 0 0.2 0.4 0.6 0.8 1 N M I (N = 5 0 0 0 ) µ SCD SCD- NLP Blondel Oslom Infomap B

Preferential Eu Site Occupation and Its Consequences in the Ternary Luminescent Halides AB 2 I 5 : Eu 2 + ( A = Li – Cs ; B = Sr , Ba)

DOE PAGES

Fang, C.  M.; Biswas, Koushik

2015-07-22

Several rare-earth-doped, heavy-metal halides have recently been identified as potential next-generation luminescent materials with high efficiency at low cost. AB 2I 5:Eu 2+ (A=Li–Cs; B=Sr, Ba) is one such family of halides. Its members, such as CsBa 2I 5:Eu 2+ and KSr 2I 5:Eu 2+, are currently being investigated as high-performance scintillators with improved sensitivity, light yield, and energy resolution less than 3% at 662 keV. Within the AB 2I 5 family, our first-principles-based calculations reveal two remarkably different trends in Eu site occupation. The substitutional Eu ions occupy both eightfold-coordinated B1(VIII) and the sevenfold-coordinated B2(VII) sites in the Sr-containingmore » compounds. However, in the Ba-containing crystals, Eu ions strongly prefer the B2(VII)sites. This random versus preferential distribution of Eu affects their electronic properties. The calculations also suggest that in the Ba-containing compounds one can expect the formation of Eu-rich domains. These results provide atomistic insight into recent experimental observations about the concentration and temperature effects in Eu-doped CsBa 2I 5. We discuss the implications of our results with respect to luminescent properties and applications. We also hypothesize Sr, Ba-mixed quaternary iodides ABa VIIISr VIII 5:Eu as scintillators having enhanced homogeneity and electronic properties.« less

78 FR 64430 - Mixed Straddles; Straddle-by-Straddle Identification Under Section 1092(b)(2)(A)(i)(I); Correction

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-29

... Mixed Straddles; Straddle-by-Straddle Identification Under Section 1092(b)(2)(A)(i)(I); Correction... amendments to proposed regulations relating to guidance for taxpayers electing to establish a mixed straddle... to establish a mixed straddle using straddle-by-straddle identification. DATES: Comments must be...

Performance of a Natural Language Processing (NLP) Tool to Extract Pulmonary Function Test (PFT) Reports from Structured and Semistructured Veteran Affairs (VA) Data.

PubMed

Sauer, Brian C; Jones, Barbara E; Globe, Gary; Leng, Jianwei; Lu, Chao-Chin; He, Tao; Teng, Chia-Chen; Sullivan, Patrick; Zeng, Qing

2016-01-01

Pulmonary function tests (PFTs) are objective estimates of lung function, but are not reliably stored within the Veteran Health Affairs data systems as structured data. The aim of this study was to validate the natural language processing (NLP) tool we developed-which extracts spirometric values and responses to bronchodilator administration-against expert review, and to estimate the number of additional spirometric tests identified beyond the structured data. All patients at seven Veteran Affairs Medical Centers with a diagnostic code for asthma Jan 1, 2006-Dec 31, 2012 were included. Evidence of spirometry with a bronchodilator challenge (BDC) was extracted from structured data as well as clinical documents. NLP's performance was compared against a human reference standard using a random sample of 1,001 documents. In the validation set NLP demonstrated a precision of 98.9 percent (95 percent confidence intervals (CI): 93.9 percent, 99.7 percent), recall of 97.8 percent (95 percent CI: 92.2 percent, 99.7 percent), and an F-measure of 98.3 percent for the forced vital capacity pre- and post pairs and precision of 100 percent (95 percent CI: 96.6 percent, 100 percent), recall of 100 percent (95 percent CI: 96.6 percent, 100 percent), and an F-measure of 100 percent for the forced expiratory volume in one second pre- and post pairs for bronchodilator administration. Application of the NLP increased the proportion identified with complete bronchodilator challenge by 25 percent. This technology can improve identification of PFTs for epidemiologic research. Caution must be taken in assuming that a single domain of clinical data can completely capture the scope of a disease, treatment, or clinical test.

The Vaporization of B2O3(l) to B2O3(g) and B2O2(g)

NASA Technical Reports Server (NTRS)

Jacobson, Nathan S.; Myers, Dwight L.

2011-01-01

The vaporization of B2O3 in a reducing environment leads to formation of both B2O3(g) and B2O2(g). While formation of B2O3(g) is well understood, many questions about the formation of B2O2(g) remain. Previous studies using B(s) + B2O3(l) have led to inconsistent thermodynamic data. In this study, it was found that after heating, B(s) and B2O3(l) appear to separate and variations in contact area likely led to the inconsistent vapor pressures of B2O2(g). To circumvent this problem, an activity of boron is fixed with a two-phase mixture of FeB and Fe2B. Both second and third law enthalpies of formation were measured for B2O2(g) and B2O3(g). From these the enthalpies of formation at 298.15 K are calculated to be -479.9 +/- 41.5 kJ/mol for B2O2(g) and -833.4 +/- 13.1 kJ/mol for B2O3(g). Ab initio calculations to determine the enthalpies of formation of B2O2(g) and B2O3(g) were conducted using the W1BD composite method and show good agreement with the experimental values.

Identification of pyrolysis products of the new psychoactive substance 2-amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) and its iodo analogue bk-2C-I.

PubMed

Texter, Kelly B; Waymach, Rachel; Kavanagh, Pierce V; O'Brien, John E; Talbot, Brian; Brandt, Simon D; Gardner, Elizabeth A

2018-01-01

2-Amino-1-(4-bromo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-B) has recently emerged as a new psychoactive substance (NPS). It is most commonly consumed orally, although there are indications that it might also be ingested by inhalation or 'smoking'. Information about the stability of bk-2C-B when exposed to heat is unavailable and the potential for pyrolytic degradation and formation of unknown substances available for inhalation prompted an investigation using a simulated 'meth pipe' scenario. Twelve products following pyrolysis of bk-2C-B were detected and verified by organic synthesis of the corresponding standards. In addition, 2-amino-1-(4-iodo-2,5-dimethoxyphenyl)ethanone hydrochloride (bk-2C-I) was characterized for the first time and subjected to pyrolysis as well. Similar products were formed, which indicated that the replacement of the bromo with the iodo substituent did not affect the pyrolysis pattern under the conditions used. Two additional products were detected in the bk-2C-I pyrolates, namely 1-(2,5-dimethoxyphenyl)-ethanone and 1-iodo-4-ethenyl-5-methoxyphenol. The potential ingestion of pyrolysis products with unknown toxicity adds an element of concern. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Effect of Royal Jelly Intake on Serum Glucose, Apolipoprotein A-I (ApoA-I), Apolipoprotein B (ApoB) and ApoB/ApoA-I Ratios in Patients with Type 2 Diabetes: A Randomized, Double-Blind Clinical Trial Study.

PubMed

Khoshpey, Basemeh; Djazayeri, Shima; Amiri, Fatemehsadat; Malek, Mojtaba; Hosseini, Agha Fateme; Hosseini, Sharieh; Shidfar, Shahrzad; Shidfar, Farzad

2016-08-01

Type 2 diabetes is the most common metabolic disorder worldwide. Evidence supports a role for royal jelly (RJ) in reduction of serum glucose and lipids in animals and healthy subjects. The purpose of this study was to determine the effect of RJ intake on serum glucose, apolipoprotein A-I (ApoA-I), apolipoprotein B (ApoB) and ApoB/ApoA-I ratios in patients with type 2 diabetes. Fifty patients with type 2 diabetes participated in a double-blind, placebo-controlled study. The participants were randomly divided into RJ and placebo groups and were given doses of 1000 mg royal jelly or placebo 3 times a day for 8 weeks, respectively. Weight, height, fasting blood glucose, ApoA-I and ApoB were measured at baseline and endpoint. There were no significant differences in baseline characteristics and dietary intakes between groups. The mean difference in glucose concentrations decreased in the RJ group (-9.4 mg/dL vs. 4 mg/dL; p=0.011). The mean difference in ApoA-I concentrations increased in the RJ group (34.4 mg/dL vs. -1.08 mg/dL; p=0.013). There was a significant decrease in mean difference of ApoB/ApoA-I in the RJ group compared with the placebo group (0.008 vs. 0.13; p<0.044), respectively. These data suggest that RJ intake may have desirable effects on serum glucose, Apo-A-I concentrations and ApoB/ApoA-I ratios in people with type 2 diabetes. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

Identification and functional analysis of the NLP-encoding genes from the phytopathogenic oomycete Phytophthora capsici.

PubMed

Chen, Xiao-Ren; Huang, Shen-Xin; Zhang, Ye; Sheng, Gui-Lin; Li, Yan-Peng; Zhu, Feng

2018-03-23

Phytophthora capsici is a hemibiotrophic, phytopathogenic oomycete that infects a wide range of crops, resulting in significant economic losses worldwide. By means of a diverse arsenal of secreted effector proteins, hemibiotrophic pathogens may manipulate plant cell death to establish a successful infection and colonization. In this study, we described the analysis of the gene family encoding necrosis- and ethylene-inducing peptide 1 (Nep1)-like proteins (NLPs) in P. capsici, and identified 39 real NLP genes and 26 NLP pseudogenes. Out of the 65 predicted NLP genes, 48 occur in groups with two or more genes, whereas the remainder appears to be singletons distributed randomly among the genome. Phylogenetic analysis of the 39 real NLPs delineated three groups. Key residues/motif important for the effector activities are degenerated in most NLPs, including the nlp24 peptide consisting of the conserved region I (11-aa immunogenic part) and conserved region II (the heptapeptide GHRHDWE motif) that is important for phytotoxic activity. Transcriptional profiling of eight selected NLP genes indicated that they were differentially expressed during the developmental and plant infection phases of P. capsici. Functional analysis of ten cloned NLPs demonstrated that Pc11951, Pc107869, Pc109174 and Pc118548 were capable of inducing cell death in the Solanaceae, including Nicotiana benthamiana and hot pepper. This study provides an overview of the P. capsici NLP gene family, laying a foundation for further elucidating the pathogenicity mechanism of this devastating pathogen.

Discovery of nitrate-CPK-NLP signalling in central nutrient-growth networks

PubMed Central

Liu, Kun-hsiang; Niu, Yajie; Konishi, Mineko; Wu, Yue; Du, Hao; Sun Chung, Hoo; Li, Lei; Boudsocq, Marie; McCormack, Matthew; Maekawa, Shugo; Ishida, Tetsuya; Zhang, Chao; Shokat, Kevan; Yanagisawa, Shuichi; Sheen, Jen

2018-01-01

Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report novel Ca2+ signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots. A nitrate-sensitized and targeted functional genomic screen identifies subgroup III Ca2+-sensor protein kinases (CPKs) as master regulators orchestrating primary nitrate responses. A chemical switch with the engineered CPK10(M141G) kinase enables conditional analyses of cpk10,30,32 to define comprehensive nitrate-associated regulatory and developmental programs, circumventing embryo lethality. Nitrate-CPK signalling phosphorylates conserved NIN-LIKE PROTEIN (NLP) transcription factors (TFs) to specify reprogramming of gene sets for downstream TFs, transporters, N-assimilation, C/N-metabolism, redox, signalling, hormones, and proliferation. Conditional cpk10,30,32 and nlp7 similarly impair nitrate-stimulated system-wide shoot growth and root establishment. The nutrient-coupled Ca2+ signalling network integrates transcriptome and cellular metabolism with shoot-root coordination and developmental plasticity in shaping organ biomass and architecture. PMID:28489820

Eudicot plant-specific sphingolipids determine host selectivity of microbial NLP cytolysins.

PubMed

Lenarčič, Tea; Albert, Isabell; Böhm, Hannah; Hodnik, Vesna; Pirc, Katja; Zavec, Apolonija B; Podobnik, Marjetka; Pahovnik, David; Žagar, Ema; Pruitt, Rory; Greimel, Peter; Yamaji-Hasegawa, Akiko; Kobayashi, Toshihide; Zienkiewicz, Agnieszka; Gömann, Jasmin; Mortimer, Jenny C; Fang, Lin; Mamode-Cassim, Adiilah; Deleu, Magali; Lins, Laurence; Oecking, Claudia; Feussner, Ivo; Mongrand, Sébastien; Anderluh, Gregor; Nürnberger, Thorsten

2017-12-15

Necrosis and ethylene-inducing peptide 1-like (NLP) proteins constitute a superfamily of proteins produced by plant pathogenic bacteria, fungi, and oomycetes. Many NLPs are cytotoxins that facilitate microbial infection of eudicot, but not of monocot plants. Here, we report glycosylinositol phosphorylceramide (GIPC) sphingolipids as NLP toxin receptors. Plant mutants with altered GIPC composition were more resistant to NLP toxins. Binding studies and x-ray crystallography showed that NLPs form complexes with terminal monomeric hexose moieties of GIPCs that result in conformational changes within the toxin. Insensitivity to NLP cytolysins of monocot plants may be explained by the length of the GIPC head group and the architecture of the NLP sugar-binding site. We unveil early steps in NLP cytolysin action that determine plant clade-specific toxin selectivity. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Usability Evaluation of NLP-PIER: A Clinical Document Search Engine for Researchers.

PubMed

Hultman, Gretchen; McEwan, Reed; Pakhomov, Serguei; Lindemann, Elizabeth; Skube, Steven; Melton, Genevieve B

2017-01-01

NLP-PIER (Natural Language Processing - Patient Information Extraction for Research) is a self-service platform with a search engine for clinical researchers to perform natural language processing (NLP) queries using clinical notes. We conducted user-centered testing of NLP-PIER's usability to inform future design decisions. Quantitative and qualitative data were analyzed. Our findings will be used to improve the usability of NLP-PIER.

Ground Truth Creation for Complex Clinical NLP Tasks - an Iterative Vetting Approach and Lessons Learned.

PubMed

Liang, Jennifer J; Tsou, Ching-Huei; Devarakonda, Murthy V

2017-01-01

Natural language processing (NLP) holds the promise of effectively analyzing patient record data to reduce cognitive load on physicians and clinicians in patient care, clinical research, and hospital operations management. A critical need in developing such methods is the "ground truth" dataset needed for training and testing the algorithms. Beyond localizable, relatively simple tasks, ground truth creation is a significant challenge because medical experts, just as physicians in patient care, have to assimilate vast amounts of data in EHR systems. To mitigate potential inaccuracies of the cognitive challenges, we present an iterative vetting approach for creating the ground truth for complex NLP tasks. In this paper, we present the methodology, and report on its use for an automated problem list generation task, its effect on the ground truth quality and system accuracy, and lessons learned from the effort.

BRCA1 interaction of centrosomal protein Nlp is required for successful mitotic progression.

PubMed

Jin, Shunqian; Gao, Hua; Mazzacurati, Lucia; Wang, Yang; Fan, Wenhong; Chen, Qiang; Yu, Wei; Wang, Mingrong; Zhu, Xueliang; Zhang, Chuanmao; Zhan, Qimin

2009-08-21

Breast cancer susceptibility gene BRCA1 is implicated in the control of mitotic progression, although the underlying mechanism(s) remains to be further defined. Deficiency of BRCA1 function leads to disrupted mitotic machinery and genomic instability. Here, we show that BRCA1 physically interacts and colocalizes with Nlp, an important molecule involved in centrosome maturation and spindle formation. Interestingly, Nlp centrosomal localization and its protein stability are regulated by normal cellular BRCA1 function because cells containing BRCA1 mutations or silenced for endogenous BRCA1 exhibit disrupted Nlp colocalization to centrosomes and enhanced Nlp degradation. Its is likely that the BRCA1 regulation of Nlp stability involves Plk1 suppression. Inhibition of endogenous Nlp via the small interfering RNA approach results in aberrant spindle formation, aborted chromosomal segregation, and aneuploidy, which mimic the phenotypes of disrupted BRCA1. Thus, BRCA1 interaction of Nlp might be required for the successful mitotic progression, and abnormalities of Nlp lead to genomic instability.

Expression of an oxalate decarboxylase impairs the necrotic effect induced by Nep1-like protein (NLP) of Moniliophthora perniciosa in transgenic tobacco.

PubMed

da Silva, Leonardo F; Dias, Cristiano V; Cidade, Luciana C; Mendes, Juliano S; Pirovani, Carlos P; Alvim, Fátima C; Pereira, Gonçalo A G; Aragão, Francisco J L; Cascardo, Júlio C M; Costa, Marcio G C

2011-07-01

Oxalic acid (OA) and Nep1-like proteins (NLP) are recognized as elicitors of programmed cell death (PCD) in plants, which is crucial for the pathogenic success of necrotrophic plant pathogens and involves reactive oxygen species (ROS). To determine the importance of oxalate as a source of ROS for OA- and NLP-induced cell death, a full-length cDNA coding for an oxalate decarboxylase (FvOXDC) from the basidiomycete Flammulina velutipes, which converts OA into CO(2) and formate, was overexpressed in tobacco plants. The transgenic plants contained less OA and more formic acid compared with the control plants and showed enhanced resistance to cell death induced by exogenous OA and MpNEP2, an NLP of the hemibiotrophic fungus Moniliophthora perniciosa. This resistance was correlated with the inhibition of ROS formation in the transgenic plants inoculated with OA, MpNEP2, or a combination of both PCD elicitors. Taken together, these results have established a pivotal function for oxalate as a source of ROS required for the PCD-inducing activity of OA and NLP. The results also indicate that FvOXDC represents a potentially novel source of resistance against OA- and NLP-producing pathogens such as M. perniciosa, the causal agent of witches' broom disease of cacao (Theobroma cacao L.).

The physical and chemical structure of Sagittarius B2. II. Continuum millimeter emission of Sgr B2(M) and Sgr B2(N) with ALMA

NASA Astrophysics Data System (ADS)

Sánchez-Monge, Á.; Schilke, P.; Schmiedeke, A.; Ginsburg, A.; Cesaroni, R.; Lis, D. C.; Qin, S.-L.; Müller, H. S. P.; Bergin, E.; Comito, C.; Möller, Th.

2017-07-01

Context. The two hot molecular cores Sgr B2(M) and Sgr B2(N), which are located at the center of the giant molecular cloud complex Sagittarius B2, have been the targets of numerous spectral line surveys, revealing a rich and complex chemistry. Aims: We seek to characterize the physical and chemical structure of the two high-mass star-forming sites Sgr B2(M) and Sgr B2(N) using high-angular resolution observations at millimeter wavelengths, reaching spatial scales of about 4000 au. Methods: We used the Atacama Large Millimeter/submillimeter Array (ALMA) to perform an unbiased spectral line survey of both regions in the ALMA band 6 with a frequency coverage from 211 GHz to 275 GHz. The achieved angular resolution is 0.̋4, which probes spatial scales of about 4000 au, I.e., able to resolve different cores and fragments. In order to determine the continuum emission in these line-rich sources, we used a new statistical method, STATCONT, which has been applied successfully to this and other ALMA datasets and to synthetic observations. Results: We detect 27 continuum sources in Sgr B2(M) and 20 sources in Sgr B2(N). We study the continuum emission variation across the ALMA band 6 (I.e., spectral index) and compare the ALMA 1.3 mm continuum emission with previous SMA 345 GHz and VLA 40 GHz observations to study the nature of the sources detected. The brightest sources are dominated by (partially optically thick) dust emission, while there is an important degree of contamination from ionized gas free-free emission in weaker sources. While the total mass in Sgr B2(M) is distributed in many fragments, most of the mass in Sgr B2(N) arises from a single object, with filamentary-like structures converging toward the center. There seems to be a lack of low-mass dense cores in both regions. We determine H2 volume densities for the cores of about 107-109 cm-3 (or 105-107 M⊙ pc-3), I.e., one to two orders of magnitude higher than the stellar densities of super star clusters. We

The Role of NLP in Teachers' Classroom Discourse

ERIC Educational Resources Information Center

Millrood, Radislav

2004-01-01

Neuro-linguistic programming (NLP) is an approach to language teaching which is claimed to help achieve excellence in learner performance. Yet there is little evidence of the impact that NLP techniques in teachers' discourse can have on learners. The article draws on workshops with teachers where classroom simulations were used to raise teachers'…

Mining protein phosphorylation information from biomedical literature using NLP parsing and Support Vector Machines.

PubMed

Raja, Kalpana; Natarajan, Jeyakumar

2018-07-01

Extraction of protein phosphorylation information from biomedical literature has gained much attention because of the importance in numerous biological processes. In this study, we propose a text mining methodology which consists of two phases, NLP parsing and SVM classification to extract phosphorylation information from literature. First, using NLP parsing we divide the data into three base-forms depending on the biomedical entities related to phosphorylation and further classify into ten sub-forms based on their distribution with phosphorylation keyword. Next, we extract the phosphorylation entity singles/pairs/triplets and apply SVM to classify the extracted singles/pairs/triplets using a set of features applicable to each sub-form. The performance of our methodology was evaluated on three corpora namely PLC, iProLink and hPP corpus. We obtained promising results of >85% F-score on ten sub-forms of training datasets on cross validation test. Our system achieved overall F-score of 93.0% on iProLink and 96.3% on hPP corpus test datasets. Furthermore, our proposed system achieved best performance on cross corpus evaluation and outperformed the existing system with recall of 90.1%. The performance analysis of our unique system on three corpora reveals that it extracts protein phosphorylation information efficiently in both non-organism specific general datasets such as PLC and iProLink, and human specific dataset such as hPP corpus. Copyright © 2018 Elsevier B.V. All rights reserved.

On the oxidation of the three-dimensional aromatics [B(12)X(12)](2-) (X=F, Cl, Br, I).

PubMed

Boeré, René T; Derendorf, Janis; Jenne, Carsten; Kacprzak, Sylwia; Kessler, Mathias; Riebau, Rainer; Riedel, Sebastian; Roemmele, Tracey L; Rühle, Monika; Scherer, Harald; Vent-Schmidt, Thomas; Warneke, Jonas; Weber, Stefan

2014-04-07

The perhalogenated closo-dodecaborate dianions [B12 X12 ](2-) (X=H, F, Cl, Br, I) are three-dimensional counterparts to the two-dimensional aromatics C6 X6 (X=H, F, Cl, Br, I). Whereas oxidation of the parent compounds [B12 H12 ](2-) and benzene does not lead to isolable radicals, the perhalogenated analogues can be oxidized by chemical or electrochemical methods to give stable radicals. The chemical oxidation of the closo-dodecaborate dianions [B12 X12 ](2-) with the strong oxidizer AsF5 in liquid sulfur dioxide (lSO2 ) yielded the corresponding radical anions [B12 X12 ](⋅-) (X=F, Cl, Br). The presence of radical ions was proven by EPR and UV/Vis spectroscopy and supported by quantum chemical calculations. Use of an excess amount of the oxidizing agent allowed the synthesis of the neutral perhalogenated hypercloso-boranes B12 X12 (X=Cl, Br). These compounds were characterized by single-crystal X-ray diffraction of dark blue B12 Cl12 and [Na(SO2 )6 ][B12 Br12 ]⋅B12 Br12 . Sublimation of the crude reaction products that contained B12 X12 (X=Cl, Br) resulted in pure dark blue B12 Cl12 or decomposition to red B9 Br9 , respectively. The energetics of the oxidation processes in the gas phase were calculated by DFT methods at the PBE0/def2-TZVPP level of theory. They revealed the trend of increasing ionization potentials of the [B12 X12 ](2-) dianions by going from fluorine to bromine as halogen substituent. The oxidation of all [B12 X12 ](2-) dianions was also studied in the gas phase by mass spectrometry in an ion trap. The electrochemical oxidation of the closo-dodecaborate dianions [B12 X12 ](2-) (X=F, Cl, Br, I) by cyclic and Osteryoung square-wave voltammetry in liquid sulfur dioxide or acetonitrile showed very good agreement with quantum chemical calculations in the gas phase. For [B12 X12 ](2-) (X=F, Cl, Br) the first and second oxidation processes are detected. Whereas the first process is quasi-reversible (with oxidation potentials in the range between +1

Pressure-induced multiband superconductivity in pyrite PtB i2 with perfect electron-hole compensation

NASA Astrophysics Data System (ADS)

Chen, Xuliang; Shao, Dexi; Gu, Chuanchuan; Zhou, Yonghui; An, Chao; Zhou, Ying; Zhu, Xiangde; Chen, Tong; Tian, Mingliang; Sun, Jian; Yang, Zhaorong

2018-05-01

We report on the discovery of pressure-induced superconductivity in the compensated semimetal pyrite PtB i2 , which exhibits extreme magnetoresistance (XMR) and nontrivial band structure at ambient pressure. The appearance of superconductivity, first observed at PC˜13 GPa with an onset critical temperature TC of ˜2.2 K , is accompanied by a pronounced enhancement of the density of electrons and holes based on Hall-effect measurements. Upon further compression, TC remains almost unchanged up to 50.0 GPa; remarkably, the perfect electron-hole compensation still holds, while the carrier mobility greatly reduces. No evident trace of structural phase transitions is detected through synchrotron x-ray diffraction over the measured pressure range of 1.5-51.2 GPa. These results highlight a multiband characteristic of the observed superconductivity, making pyrite PtB i2 unique among the compensated XMR materials where the pressure-induced superconductivity usually links to structural transitions and carrier imbalance.

An early illness recognition framework using a temporal Smith Waterman algorithm and NLP.

PubMed

Hajihashemi, Zahra; Popescu, Mihail

2013-01-01

In this paper we propose a framework for detecting health patterns based on non-wearable sensor sequence similarity and natural language processing (NLP). In TigerPlace, an aging in place facility from Columbia, MO, we deployed 47 sensor networks together with a nursing electronic health record (EHR) system to provide early illness recognition. The proposed framework utilizes sensor sequence similarity and NLP on EHR nursing comments to automatically notify the physician when health problems are detected. The reported methodology is inspired by genomic sequence annotation using similarity algorithms such as Smith Waterman (SW). Similarly, for each sensor sequence, we associate health concepts extracted from the nursing notes using Metamap, a NLP tool provided by Unified Medical Language System (UMLS). Since sensor sequences, unlike genomics ones, have an associated time dimension we propose a temporal variant of SW (TSW) to account for time. The main challenges presented by our framework are finding the most suitable time sequence similarity and aggregation of the retrieved UMLS concepts. On a pilot dataset from three Tiger Place residents, with a total of 1685 sensor days and 626 nursing records, we obtained an average precision of 0.64 and a recall of 0.37.

Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

PubMed

Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

2017-01-29

Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased expression of Nlp, a potential oncogene in ovarian cancer, and its implication in carcinogenesis.

PubMed

Qu, Danni; Qu, Hongyan; Fu, Ming; Zhao, Xuelian; Liu, Rong; Sui, Lihua; Zhan, Qimin

2008-08-01

Nlp (Ninein-like protein), a novel centrosome protein involved in microtubule nucleation, has been studied extensively in our laboratory, and its overexpression has been found in some human tumors. To understand the role of Nlp in human ovarian cancer development, we studied the correlation of Nlp expression with clinicopathological parameters and survival in epithelial ovarian cancer, and the impact of Nlp overexpression on ovarian cancer cells. Nlp expression in normal, borderline, benign and malignant epithelial ovarian tissues was examined by immunohistochemistry. The correlation between Nlp expression and tumor grade, FIGO stage and histological type was also evaluated. Survival was calculated using Kaplan-Meier estimates. Cell proliferation and apoptosis were assayed after stable transfection of pEGFP-C3-Nlp or empty vector in human ovarian cancer cell line SKOV3. Nlp was positive in 1 of 10 (10%) normal ovarian tissues, 5 of 34 (14.7%) benign tumors, 9 of 26 (34.6%) borderline tumors and 73 of 131 (56.0%) ovarian tumors. Nlp immunoreactivity intensity significantly correlated with tumor grade, but not with FIGO stage or histological type. Kaplan-Meier curves showed that Nlp overexpression was marginally associated with decreased overall survival. Overexpression of Nlp enhanced proliferation and inhibited apoptosis induced by paclitaxel in the SKOV3 cell line. Overexpression of Nlp in ovarian tumors raises the possibility that Nlp may play a role in ovarian carcinogenesis.

NLP-12 engages different UNC-13 proteins to potentiate tonic and evoked release.

PubMed

Hu, Zhitao; Vashlishan-Murray, Amy B; Kaplan, Joshua M

2015-01-21

A neuropeptide (NLP-12) and its receptor (CKR-2) potentiate tonic and evoked ACh release at Caenorhabditis elegans neuromuscular junctions. Increased evoked release is mediated by a presynaptic pathway (egl-30 Gαq and egl-8 PLCβ) that produces DAG, and by DAG binding to short and long UNC-13 proteins. Potentiation of tonic ACh release persists in mutants deficient for egl-30 Gαq and egl-8 PLCβ and requires DAG binding to UNC-13L (but not UNC-13S). Thus, NLP-12 adjusts tonic and evoked release by distinct mechanisms. Copyright © 2015 the authors 0270-6474/15/351038-05$15.00/0.

Cyclopentadienylniobium and -molybdenum phosphorodithioate complexes. X-ray crystal structures of CpNbCl sub 3 (S sub 2 P(OPr sup i ) sub 2 ), CpNbCl(. mu. -Cl) sub 2 Nb(S sub 2 P(OPr sup i ) sub 2 )Cp, and cis-Cp prime Mo(CO) sub 2 (S sub 2 P(OPr sup i ) sub 2 )

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

Woodward, S.; Riaz, U.; Curtis, M.D.

1990-10-01

Reaction of CpNbCl{sub 4} (Cp = {eta}-C{sub 5}H{sub 5}) with (Pr{sup i}O){sub 2}P(S)(SH) in the presence of NEt{sub 3} yields CpNbCl{sub 3}(S{sub 2}P(S{sub 2}Pr{sup i}){sub 2}) (1). Reduction of 1 with Na/Hg affords the Nb-Nb-bonded complex CpNbCl({mu}-Cl){sub 2}Nb(S{sub 2}P(OR){sub 2})Cp (2). In refluxing toluene, (Pr{sup i}O){sub 2}P(S)(SH) with (Cp{prime}Mo(CO){sub 3}){sub 2} (Cp{prime} = {eta}-C{sub 5}H{sub 4}Me) gives cis-Cp{prime}Mo(CO){sub 2}(S{sub 2}P(OPr{sup i}){sub 2}) (3). Oxidation of 3 with I{sub 2} affords Cp{prime}MoI{sub 2}(CO)(S{sub 2}P(OPr{sup i}){sub 2}) (4). The crystal structures of 1-3 are compared. For 1, triclinic, P{bar 1}, a = 7.122 (3) {angstrom}, b = 11.365 (4) {angstrom}, c =more » 12.532 (4) {angstrom}, {alpha} = 77.38 (3){degree}, {beta} = 89.08 (3){degree}, {gamma} = 72.87 (3){degree}, V = 944.5 (8) {angstrom}{sup 3}. For 2, triclinic, P{bar 1}, a = 7.251 (3) {angstrom}, b = 12.386 (5) {angstrom}, c = 13.988 (5) {angstrom}, {alpha} = 102.66 (3){degree}, {beta} = 103.56 (3){degree}, {gamma} = 94.66 (3){degree}, V = 1180.0 (8) {angstrom}{sup 3}, Z = 2. For 3, orthorhombic, Pbca, a = 12.703 (3) {angstrom}, b = 16.707 (4) {angstrom}, c = 18.398 (4) {angstrom}, V = 3904.4 (17) {angstrom}{sup 3}, Z = 8.« less

Discovery of nitrate-CPK-NLP signalling in central nutrient-growth networks.

PubMed

Liu, Kun-Hsiang; Niu, Yajie; Konishi, Mineko; Wu, Yue; Du, Hao; Sun Chung, Hoo; Li, Lei; Boudsocq, Marie; McCormack, Matthew; Maekawa, Shugo; Ishida, Tetsuya; Zhang, Chao; Shokat, Kevan; Yanagisawa, Shuichi; Sheen, Jen

2017-05-18

Nutrient signalling integrates and coordinates gene expression, metabolism and growth. However, its primary molecular mechanisms remain incompletely understood in plants and animals. Here we report unique Ca 2+ signalling triggered by nitrate with live imaging of an ultrasensitive biosensor in Arabidopsis leaves and roots. A nitrate-sensitized and targeted functional genomic screen identifies subgroup III Ca 2+ -sensor protein kinases (CPKs) as master regulators that orchestrate primary nitrate responses. A chemical switch with the engineered mutant CPK10(M141G) circumvents embryo lethality and enables conditional analyses of cpk10 cpk30 cpk32 triple mutants to define comprehensive nitrate-associated regulatory and developmental programs. Nitrate-coupled CPK signalling phosphorylates conserved NIN-LIKE PROTEIN (NLP) transcription factors to specify the reprogramming of gene sets for downstream transcription factors, transporters, nitrogen assimilation, carbon/nitrogen metabolism, redox, signalling, hormones and proliferation. Conditional cpk10 cpk30 cpk32 and nlp7 mutants similarly impair nitrate-stimulated system-wide shoot growth and root establishment. The nutrient-coupled Ca 2+ signalling network integrates transcriptome and cellular metabolism with shoot-root coordination and developmental plasticity in shaping organ biomass and architecture.

BRCA1 Interaction of Centrosomal Protein Nlp Is Required for Successful Mitotic Progression*♦

PubMed Central

Jin, Shunqian; Gao, Hua; Mazzacurati, Lucia; Wang, Yang; Fan, Wenhong; Chen, Qiang; Yu, Wei; Wang, Mingrong; Zhu, Xueliang; Zhang, Chuanmao; Zhan, Qimin

2009-01-01

Breast cancer susceptibility gene BRCA1 is implicated in the control of mitotic progression, although the underlying mechanism(s) remains to be further defined. Deficiency of BRCA1 function leads to disrupted mitotic machinery and genomic instability. Here, we show that BRCA1 physically interacts and colocalizes with Nlp, an important molecule involved in centrosome maturation and spindle formation. Interestingly, Nlp centrosomal localization and its protein stability are regulated by normal cellular BRCA1 function because cells containing BRCA1 mutations or silenced for endogenous BRCA1 exhibit disrupted Nlp colocalization to centrosomes and enhanced Nlp degradation. Its is likely that the BRCA1 regulation of Nlp stability involves Plk1 suppression. Inhibition of endogenous Nlp via the small interfering RNA approach results in aberrant spindle formation, aborted chromosomal segregation, and aneuploidy, which mimic the phenotypes of disrupted BRCA1. Thus, BRCA1 interaction of Nlp might be required for the successful mitotic progression, and abnormalities of Nlp lead to genomic instability. PMID:19509300

Robo-Sensei's NLP-Based Error Detection and Feedback Generation

ERIC Educational Resources Information Center

Nagata, Noriko

2009-01-01

This paper presents a new version of Robo-Sensei's NLP (Natural Language Processing) system which updates the version currently available as the software package "ROBO-SENSEI: Personal Japanese Tutor" (Nagata, 2004). Robo-Sensei's NLP system includes a lexicon, a morphological generator, a word segmentor, a morphological parser, a syntactic…

Community challenges in biomedical text mining over 10 years: success, failure and the future

PubMed Central

Huang, Chung-Chi

2016-01-01

One effective way to improve the state of the art is through competitions. Following the success of the Critical Assessment of protein Structure Prediction (CASP) in bioinformatics research, a number of challenge evaluations have been organized by the text-mining research community to assess and advance natural language processing (NLP) research for biomedicine. In this article, we review the different community challenge evaluations held from 2002 to 2014 and their respective tasks. Furthermore, we examine these challenge tasks through their targeted problems in NLP research and biomedical applications, respectively. Next, we describe the general workflow of organizing a Biomedical NLP (BioNLP) challenge and involved stakeholders (task organizers, task data producers, task participants and end users). Finally, we summarize the impact and contributions by taking into account different BioNLP challenges as a whole, followed by a discussion of their limitations and difficulties. We conclude with future trends in BioNLP challenge evaluations. PMID:25935162

The pleiotropic transcriptional regulator NlpR contributes to the modulation of nitrogen metabolism, lipogenesis and triacylglycerol accumulation in oleaginous rhodococci.

PubMed

Hernández, Martín A; Lara, Julia; Gago, Gabriela; Gramajo, Hugo; Alvarez, Héctor M

2017-01-01

The regulatory mechanisms involved in lipogenesis and triacylglycerol (TAG) accumulation are largely unknown in oleaginous rhodococci. In this study a regulatory protein (here called NlpR: Nitrogen lipid Regulator), which contributes to the modulation of nitrogen metabolism, lipogenesis and triacylglycerol accumulation in oleaginous rhodococci was identified. Under nitrogen deprivation conditions, in which TAG accumulation is stimulated, the nlpR gene was significantly upregulated, whereas a significant decrease of its expression and TAG accumulation occurred when cerulenin was added. The nlpR disruption negatively affected the nitrate/nitrite reduction as well as lipid biosynthesis under nitrogen-limiting conditions. In contrast, its overexpression increased TAG production during cultivation of cells in nitrogen-rich media. A putative 'NlpR-binding motif' upstream of several genes related to nitrogen and lipid metabolisms was found. The nlpR disruption in RHA1 strain led to a reduced transcription of genes involved in nitrate/nitrite assimilation, as well as in fatty acid and TAG biosynthesis. Purified NlpR was able to bind to narK, nirD, fasI, plsC and atf3 promoter regions. It was suggested that NlpR acts as a pleiotropic transcriptional regulator by activating of nitrate/nitrite assimilation genes and others genes involved in fatty acid and TAG biosynthesis, in response to nitrogen deprivation. © 2016 John Wiley & Sons Ltd.

Secretion of apolipoproteins A-I and B by HepG2 cells: regulation by substrates and metabolic inhibitors.

PubMed

Kempen, H J; Imbach, A P; Giller, T; Neumann, W J; Hennes, U; Nakada, N

1995-08-01

It was the aim of this study to i) compare the effects of glucose and other hexoses with that of oleate on secretion of apolipoproteins (apos) A-I and B by HepG2 cells, and ii) document the effect of various metabolic inhibitors on the secretion of these apos in the absence or presence of extra glucose/oleate. i) The addition of 10 mM glucose increased secretion of apoA-I and apoB, as measured by enzyme immunoassay, by about 60% when cells were incubated for 48 h in DMEM + 10% fetal calf serum. The addition of extra glucose also increased the mRNA levels for these apos. Increased radioactivity was also found in these apolipoproteins by immunoprecipitation after metabolic labeling with [35S]methionine for 48 h. However, in a pulse-chase experiment (15 min labeling, 2 h chase), glucose was found to increase apoA-I synthesis but not apoB synthesis. More labeled apoB appeared in the medium during the chase because glucose inhibited its intracellular degradation. The effect of glucose on secretion of these apos could be mimicked by fructose and mannose but not by 6-deoxyglucose, showing that the hexoses must enter the cells and be phosphorylated. In contrast, the addition of 0.5 mM oleate had a weak inhibitory effect on secretion of apoA-I whereas it increased the secretion of apoB by more than twofold. The combination of 10 mM glucose and 0.5 mM oleate had no greater effect than glucose alone on apoA-I secretion but increased apoB secretion by fourfold. ii) Inhibiting glycolysis (by glucosamine) lowered secretion of both apoA-I and apoB, while inhibiting lipogenesis (using 8-Br-cyclic AMP or 5-(tetradecyloxy)-2-furancarboxylic acid (TOFA)) did not affect apoA-I secretion but clearly decreased that of apoB. However, the inhibitory effect of TOFA on apoB secretion was much smaller in the presence of 0.5 mM oleate instead of extra glucose. Actinomycin-D and cycloheximide strongly suppressed the stimulatory effect of glucose on secretion of both apolipoproteins

High-pressure behavior of A 2 B 2 O 7 pyrochlore (A=Eu, Dy; B=Ti, Zr)

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

Rittman, Dylan R.; Turner, Katlyn M.; Park, Sulgiye

2017-01-28

In situ high-pressure X-ray diffraction and Raman spectroscopy were used to determine the influence of composition on the high-pressure behavior of A 2B 2O 7 pyrochlore (A=Eu, Dy; B=Ti, Zr) up to ~50GPa. Based on X-ray diffraction results, all compositions transformed to the high-pressure cotunnite structure. The B-site cation species had a larger effect on the transition pressure than the A-site cation species, with the onset of the phase transformation occurring at ~41 GPa for B=Ti and ~16 GPa B=Zr. However, the A-site cation affected the kinetics of the phase transformation, with the transformation for compositions with the smaller ionicmore » radii, i.e., A=Dy, proceeding faster than those with a larger ionic radii, i.e., A=Eu. These results were consistent with previous work in which the radius-ratio of the A- and B-site cations determined the energetics of disordering, and compositions with more similarly sized A- and B-site cations had a lower defect formation energy. Raman spectra revealed differences in the degree of short-range order of the different compositions. Due to the large phase fraction of cotunnite at high pressure for B=Zr compositions, Raman modes for cotunnite could be observed, with more modes recorded for A=Eu than A=Dy. These additional modes are attributed to increased short-to-medium range ordering in the initially pyrochlore structured Eu 2Zr 2O 7 as compared with the initially defect-fluorite structured Dy 2Zr 2O 7.« less

Telecom 2-B and 2-C (TC2B and TC2C)

NASA Technical Reports Server (NTRS)

Dulac, J.; Alvarez, H.

1991-01-01

The DSN (Deep Space Network) mission support requirements for Telecom 2-B and 2-C (TC2B and TC2C) are summarized. These Telecom missions will provide high-speed data link applications, telephone, and television service between France and overseas territories as a follow-on to TC2A. Mission objectives are outlined and the DSN support requirements are defined through the presentation of tables and narratives describing the spacecraft flight profile; DSN support coverage; frequency assignments; support parameters for telemetry, command and support systems; and tracking support responsibility.

Community challenges in biomedical text mining over 10 years: success, failure and the future.

PubMed

Huang, Chung-Chi; Lu, Zhiyong

2016-01-01

One effective way to improve the state of the art is through competitions. Following the success of the Critical Assessment of protein Structure Prediction (CASP) in bioinformatics research, a number of challenge evaluations have been organized by the text-mining research community to assess and advance natural language processing (NLP) research for biomedicine. In this article, we review the different community challenge evaluations held from 2002 to 2014 and their respective tasks. Furthermore, we examine these challenge tasks through their targeted problems in NLP research and biomedical applications, respectively. Next, we describe the general workflow of organizing a Biomedical NLP (BioNLP) challenge and involved stakeholders (task organizers, task data producers, task participants and end users). Finally, we summarize the impact and contributions by taking into account different BioNLP challenges as a whole, followed by a discussion of their limitations and difficulties. We conclude with future trends in BioNLP challenge evaluations. Published by Oxford University Press 2015. This work is written by US Government employees and is in the public domain in the US.

Polo-like kinase 1 regulates Nlp, a centrosome protein involved in microtubule nucleation.

PubMed

Casenghi, Martina; Meraldi, Patrick; Weinhart, Ulrike; Duncan, Peter I; Körner, Roman; Nigg, Erich A

2003-07-01

In animal cells, most microtubules are nucleated at centrosomes. At the onset of mitosis, centrosomes undergo a structural reorganization, termed maturation, which leads to increased microtubule nucleation activity. Centrosome maturation is regulated by several kinases, including Polo-like kinase 1 (Plk1). Here, we identify a centrosomal Plk1 substrate, termed Nlp (ninein-like protein), whose properties suggest an important role in microtubule organization. Nlp interacts with two components of the gamma-tubulin ring complex and stimulates microtubule nucleation. Plk1 phosphorylates Nlp and disrupts both its centrosome association and its gamma-tubulin interaction. Overexpression of an Nlp mutant lacking Plk1 phosphorylation sites severely disturbs mitotic spindle formation. We propose that Nlp plays an important role in microtubule organization during interphase, and that the activation of Plk1 at the onset of mitosis triggers the displacement of Nlp from the centrosome, allowing the establishment of a mitotic scaffold with enhanced microtubule nucleation activity.

DE and NLP Based QPLS Algorithm

NASA Astrophysics Data System (ADS)

Yu, Xiaodong; Huang, Dexian; Wang, Xiong; Liu, Bo

As a novel evolutionary computing technique, Differential Evolution (DE) has been considered to be an effective optimization method for complex optimization problems, and achieved many successful applications in engineering. In this paper, a new algorithm of Quadratic Partial Least Squares (QPLS) based on Nonlinear Programming (NLP) is presented. And DE is used to solve the NLP so as to calculate the optimal input weights and the parameters of inner relationship. The simulation results based on the soft measurement of diesel oil solidifying point on a real crude distillation unit demonstrate that the superiority of the proposed algorithm to linear PLS and QPLS which is based on Sequential Quadratic Programming (SQP) in terms of fitting accuracy and computational costs.

Management of ErbB2-positive Breast Cancer: Insights from Preclinical and Clinical Studies with Lapatinib

PubMed Central

Vogel, Charles; Chan, Arlene; Gril, Brunilde; Kim, Sung-Bae; Kurebayashi, Junichi; Liu, Li; Lu, Yen-Shen; Moon, Hanlim

2010-01-01

The management of human epidermal growth factor receptor 2-positive (ErbB2+) breast cancer is challenging; patients with ErbB2+ breast tumors have more aggressive disease and a poor prognosis. The increasing incidence of breast cancer in Asia and the limitations of existing treatments pose additional challenges. In this review, we summarize the preclinical and clinical evidence that indicates how lapatinib, a novel inhibitor that targets the human epidermal growth factor receptor (ErbB1) and ErbB2 may help clinicians address four particularly challenging issues in the management of ErbB2+ breast cancer. These issues are: (i) trastuzumab therapy failure, (ii) development of central nervous system metastases, (iii) minimizing toxicity and (iv) selecting the most appropriate partners (chemotherapy and non-chemotherapy) for combination therapy with lapatinib. Lapatinib, in combination with chemotherapeutic agents, such as capecitabine, provides clinical benefits to patients with ErbB2+ breast cancer, including patients who develop progressive disease on trastuzumab. Lapatinib, in combination with non-chemotherapeutic agents, such as letrozole, may also provide a chemotherapy-free treatment option for postmenopausal patients with estrogen receptor-positive/ErbB2+ metastatic breast cancer. Encouraging results have also emerged regarding the synergistic effects of lapatinib in combination with other agents for the treatment of ErbB2+ breast cancer. Promising findings have also been reported for the use of lapatinib to prevent and treat central nervous system metastases. Collectively, these results indicate that the judicious use of lapatinib, an effective oral therapy with a manageable toxicity profile, can enhance the management of patients with ErbB2+ breast cancer. PMID:20542996

Management of ErbB2-positive breast cancer: insights from preclinical and clinical studies with lapatinib.

PubMed

Vogel, Charles; Chan, Arlene; Gril, Brunilde; Kim, Sung-Bae; Kurebayashi, Junichi; Liu, Li; Lu, Yen-Shen; Moon, Hanlim

2010-11-01

The management of human epidermal growth factor receptor 2-positive (ErbB2+) breast cancer is challenging; patients with ErbB2+ breast tumors have more aggressive disease and a poor prognosis. The increasing incidence of breast cancer in Asia and the limitations of existing treatments pose additional challenges. In this review, we summarize the preclinical and clinical evidence that indicates how lapatinib, a novel inhibitor that targets the human epidermal growth factor receptor (ErbB1) and ErbB2 may help clinicians address four particularly challenging issues in the management of ErbB2+ breast cancer. These issues are: (i) trastuzumab therapy failure, (ii) development of central nervous system metastases, (iii) minimizing toxicity and (iv) selecting the most appropriate partners (chemotherapy and non-chemotherapy) for combination therapy with lapatinib. Lapatinib, in combination with chemotherapeutic agents, such as capecitabine, provides clinical benefits to patients with ErbB2+ breast cancer, including patients who develop progressive disease on trastuzumab. Lapatinib, in combination with non-chemotherapeutic agents, such as letrozole, may also provide a chemotherapy-free treatment option for postmenopausal patients with estrogen receptor-positive/ErbB2+ metastatic breast cancer. Encouraging results have also emerged regarding the synergistic effects of lapatinib in combination with other agents for the treatment of ErbB2+ breast cancer. Promising findings have also been reported for the use of lapatinib to prevent and treat central nervous system metastases. Collectively, these results indicate that the judicious use of lapatinib, an effective oral therapy with a manageable toxicity profile, can enhance the management of patients with ErbB2+ breast cancer.

Feasibility of Homomorphic Encryption for Sharing I2B2 Aggregate-Level Data in the Cloud

PubMed Central

Raisaro, Jean Louis; Klann, Jeffrey G; Wagholikar, Kavishwar B; Estiri, Hossein; Hubaux, Jean-Pierre; Murphy, Shawn N

2018-01-01

The biomedical community is lagging in the adoption of cloud computing for the management of medical data. The primary obstacles are concerns about privacy and security. In this paper, we explore the feasibility of using advanced privacy-enhancing technologies in order to enable the sharing of sensitive clinical data in a public cloud. Our goal is to facilitate sharing of clinical data in the cloud by minimizing the risk of unintended leakage of sensitive clinical information. In particular, we focus on homomorphic encryption, a specific type of encryption that offers the ability to run computation on the data while the data remains encrypted. This paper demonstrates that homomorphic encryption can be used efficiently to compute aggregating queries on the ciphertexts, along with providing end-to-end confidentiality of aggregate-level data from the i2b2 data model. PMID:29888067

Feasibility of Homomorphic Encryption for Sharing I2B2 Aggregate-Level Data in the Cloud.

PubMed

Raisaro, Jean Louis; Klann, Jeffrey G; Wagholikar, Kavishwar B; Estiri, Hossein; Hubaux, Jean-Pierre; Murphy, Shawn N

2018-01-01

The biomedical community is lagging in the adoption of cloud computing for the management of medical data. The primary obstacles are concerns about privacy and security. In this paper, we explore the feasibility of using advanced privacy-enhancing technologies in order to enable the sharing of sensitive clinical data in a public cloud. Our goal is to facilitate sharing of clinical data in the cloud by minimizing the risk of unintended leakage of sensitive clinical information. In particular, we focus on homomorphic encryption, a specific type of encryption that offers the ability to run computation on the data while the data remains encrypted. This paper demonstrates that homomorphic encryption can be used efficiently to compute aggregating queries on the ciphertexts, along with providing end-to-end confidentiality of aggregate-level data from the i2b2 data model.

High-pressure behavior of A 2 B 2 O 7 pyrochlore (A=Eu, Dy; B=Ti, Zr)

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

Rittman, Dylan R.; Turner, Katlyn M.; Park, Sulgiye

2017-01-24

In situ high-pressure X-ray diffraction and Raman spectroscopy were used to determine the influence of composition on the high-pressure behavior of A 2B 2O 7 pyrochlore (A = Eu, Dy; B = Ti, Zr) up to ~50 GPa. Based on X-ray diffraction results, all compositions transformed to the high-pressure cotunnite structure. The B-site cation species had a larger effect on the transition pressure than the A-site cation species, with the onset of the phase transformation occurring at ~41 GPa for B = Ti and ~16 GPa B = Zr. But, the A-site cation affected the kinetics of the phase transformation,more » with the transformation for compositions with the smaller ionic radii, i.e., A = Dy, proceeding faster than those with a larger ionic radii, i.e., A = Eu. Our results were consistent with previous work in which the radius-ratio of the A- and B-site cations determined the energetics of disordering, and compositions with more similarly sized A- and B-site cations had a lower defect formation energy. Raman spectra revealed differences in the degree of short-range order of the different compositions. Due to the large phase fraction of cotunnite at high pressure for B = Zr compositions, Raman modes for cotunnite could be observed, with more modes recorded for A = Eu than A = Dy. These additional modes are attributed to increased short-to-medium range ordering in the initially pyrochlore structured Eu 2Zr 2O 7 as compared with the initially defect-fluorite structured Dy 2Zr 2O 7.« less

Structure investigation of maltacine B1a, B1b, B2a and B2b: cyclic peptide lactones of the maltacine complex from Bacillus subtilis.

PubMed

Hagelin, Gunnar

2005-04-01

A new complex of cyclic peptide lactone antibiotics from Bacillus subtilis, which we named maltacines, has recently been described. The structure elucidation of four of them is reported in this paper. The amino acid sequences and structures of the peptides were found by MSn of the ring-opened linear peptides that gave uninterrupted sequences of Bn and Y''n ions. The identities of three unknown residues in the sequences were solved by a combination of derivatization with phenyl isothiocyanate (PITC), high-resolution mass spectrometry and H/D exchange. The nature and position of the cyclic structure were revealed by a chemoselective ring opening with Na18OH and was found to be a lactone formed between a hydroxyl of residue number 4 and the C-terminal amino acid number 12. For verification of the structure of the B2+ ion, peptides with different combinations of P/Q and P/K at the N-terminus were synthesized. The structures of the four peptides were found to be as follows: B1a/B2a, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-Orn-103-Y-I-OH); and B1b/B2b, cyclo-4,12(P-Q-Y-HNLeu-A-E-T-Y-K-103-Y-I-OH). Copyright 2005 John Wiley & Sons, Ltd.

Absence of quantum anomalous Hall state in 4 d transition-metal-doped B i2S e3 : An ab initio study

NASA Astrophysics Data System (ADS)

Deng, Bei; Liu, Feng; Zhu, Junyi

2017-11-01

The realization of insulating ferromagnetic states in topological insulator (TI) systems, with sufficiently high Curie temperatures (TC) and large magnetically induced gaps, has been the key bottleneck towards the realization of the quantum anomalous Hall effect (QAHE). Despite the limited reports on 3 d or 4 f transition-metal (TM)-doped B i2S e3 , there remains a lack of systematic studies on 4 d TMs, which may be potential candidates since the atomic sizes of 4 d TMs and that of Bi are similar. Here, we report a theoretical work that probes the magnetic behaviors of the 4 d TM-doped B i2S e3 system. We discovered that among the 4 d TMs, Nb and Mo can create magnetic moments of 1.76 and 2.96 μ B in B i2S e3 , respectively. While Mo yields a stable gapless antiferromagnetic ground state, Nb favors a strong ferromagnetic order, with the magnetic coupling strength (TC) ˜6 times of that induced by the traditional Cr impurity. Yet, we found that Nb is still unfavorable to support the QAH state in B i2S e3 because of the reduced correlation in the t2 g band that gives a gapless character. This rationale is not only successful in interpreting why Nb, the strongest candidate among 4 d TMs for achieving ferromagnetism in B i2S e3 , actually cannot lead to QAHE in the B i2S e3 system even with the assistance of codoping but also is particularly important to fully understand the mechanism of acquisition of insulating ferromagnetic states inside TI. On the other hand, we discovered that Mo-doped B i2S e3 favors strong antiferromagnetic states and may lead to superconducting states.

The neuropeptide NLP-22 regulates a sleep-like state in Caenorhabditis elegans

PubMed Central

Nelson, MD; Trojanowski, NF; George-Raizen, JB; Smith, CJ; Yu, C-C; Fang-Yen, C; Raizen, DM

2013-01-01

Neuropeptides play central roles in the regulation of homeostatic behaviors such as sleep and feeding. Caenorhabditis elegans displays sleep-like quiescence of locomotion and feeding during a larval transition stage called lethargus and feeds during active larval and adult stages. Here we show that the neuropeptide NLP-22 is a regulator of Caenorhabditis elegans sleep-like quiescence observed during lethargus. nlp-22 shows cyclical mRNA expression in synchrony with lethargus; it is regulated by LIN-42, an orthologue of the core circadian protein PERIOD; and it is expressed solely in the two RIA interneurons. nlp-22 and the RIA interneurons are required for normal lethargus quiescence, and forced expression of nlp-22 during active stages causes anachronistic locomotion and feeding quiescence. Optogenetic stimulation of RIA interneurons has a movement-promoting effect, demonstrating functional complexity in a single neuron type. Our work defines a quiescence-regulating role for NLP-22 and expands our knowledge of the neural circuitry controlling Caenorhabditis elegans behavioral quiescence. PMID:24301180

The neuropeptide NLP-22 regulates a sleep-like state in Caenorhabditis elegans.

PubMed

Nelson, M D; Trojanowski, N F; George-Raizen, J B; Smith, C J; Yu, C-C; Fang-Yen, C; Raizen, D M

2013-01-01

Neuropeptides have central roles in the regulation of homoeostatic behaviours such as sleep and feeding. Caenorhabditis elegans displays sleep-like quiescence of locomotion and feeding during a larval transition stage called lethargus and feeds during active larval and adult stages. Here we show that the neuropeptide NLP-22 is a regulator of Caenorhabditis elegans sleep-like quiescence observed during lethargus. nlp-22 shows cyclical mRNA expression in synchrony with lethargus; it is regulated by LIN-42, an orthologue of the core circadian protein PERIOD; and it is expressed solely in the two RIA interneurons. nlp-22 and the RIA interneurons are required for normal lethargus quiescence, and forced expression of nlp-22 during active stages causes anachronistic locomotion and feeding quiescence. Optogenetic stimulation of the RIA interneurons has a movement-promoting effect, demonstrating functional complexity in a single-neuron type. Our work defines a quiescence-regulating role for NLP-22 and expands our knowledge of the neural circuitry controlling Caenorhabditis elegans behavioural quiescence.

Do two current canine parvovirus type 2 and 2b vaccines provide protection against the new type 2c variant?

PubMed

Larson, Laurie J; Schultz, R D

2008-01-01

Three groups (n=9 or 10) of 12-week-old canine parvovirus type 2 (CPV-2) antibody-negative puppies were vaccinated: one group with a product containing modified-live CPV-2b (Galaxy DA2PPv; Schering-Plough Animal Health), one group with a product containing modified-live CPV-2 (Continuum DAP, Intervet), and one group (controls) with sterile saline. All puppies receiving CPV-2 and CPV-2b vaccines developed antibody as determined by the hemagglutination inhibition assay. All groups of puppies were challenged with a combination of virulent CPV-2b and CPV-2c 5 weeks after vaccination. All puppies in the CPV-2 and CPV-2b vaccinated groups were protected from disease, whereas all control group puppies developed disease and 50% died or were euthanized. This study demonstrated that the CPV-2 and CPV-2b vaccine components of the Continuum DAP and Galaxy DA2PPv products, respectively, provided protection against the CPV-2b virus and also provided complete protection against the new CPV-2c variant.

The NLP toxin family in Phytophthora sojae includes rapidly evolving groups that lack necrosis-inducing activity.

PubMed

Dong, Suomeng; Kong, Guanghui; Qutob, Dinah; Yu, Xiaoli; Tang, Junli; Kang, Jixiong; Dai, Tingting; Wang, Hai; Gijzen, Mark; Wang, Yuanchao

2012-07-01

Necrosis- and ethylene-inducing-like proteins (NLP) are widely distributed in eukaryotic and prokaryotic plant pathogens and are considered to be important virulence factors. We identified, in total, 70 potential Phytophthora sojae NLP genes but 37 were designated as pseudogenes. Sequence alignment of the remaining 33 NLP delineated six groups. Three of these groups include proteins with an intact heptapeptide (Gly-His-Arg-His-Asp-Trp-Glu) motif, which is important for necrosis-inducing activity, whereas the motif is not conserved in the other groups. In total, 19 representative NLP genes were assessed for necrosis-inducing activity by heterologous expression in Nicotiana benthamiana. Surprisingly, only eight genes triggered cell death. The expression of the NLP genes in P. sojae was examined, distinguishing 20 expressed and 13 nonexpressed NLP genes. Real-time reverse-transcriptase polymerase chain reaction results indicate that most NLP are highly expressed during cyst germination and infection stages. Amino acid substitution ratios (Ka/Ks) of 33 NLP sequences from four different P. sojae strains resulted in identification of positive selection sites in a distinct NLP group. Overall, our study indicates that expansion and pseudogenization of the P. sojae NLP family results from an ongoing birth-and-death process, and that varying patterns of expression, necrosis-inducing activity, and positive selection suggest that NLP have diversified in function.

Spectroscopic constants and potential energy curve of the iodine weakly bound 1u state correlating with the I(2P1/2) + I(2P1/2) dissociation limit

NASA Astrophysics Data System (ADS)

Akopyan, M. E.; Baturo, V. V.; Lukashov, S. S.; Poretsky, S. A.; Pravilov, A. M.

2015-01-01

The stepwise three-step three-color laser population of the I2(β1g, νβ, Jβ) rovibronic states via the B0u+, νB, JB rovibronic states and rovibronic levels of the 1u(bb) and 0g+(bb) states mixed by hyperfine interaction is used for determination of rovibronic level energies of the weakly bound I2(1u(bb)) state. Dunham coefficients of the state, Yi0 (i = 0-3), Yi1 (i = 0-2), Y02 and Y12 for the {{v}{{1u}}} = 1-5, 8, 10, 15 and {{J}{{1u}}} ≈ 9-87 ranges, the dissociation energy of the state, De, and equilibrium I-I distance, Re, as well as the potential energy curve are determined. There are aperiodicities in the excitation spectrum corresponding to the β, νβ = 23, Jβ ← 1u(bb), ν1u = 4, 5, J1u progressions in the I2 + Rg = He, Ar mixture, namely, a great number of lines which do not coincide with the R or P line progressions. Their positions conflict with the ΔJ-even selection rule. Furthermore, they do not correspond to the ΔJ-odd progression.

Kinetic analysis of MgB2 layer formation in advanced internal magnesium infiltration (AIMI) processed MgB2 wires

PubMed Central

Li, G. Z.; Sumption, M. D.; Collings, E. W.

2015-01-01

Significantly enhanced critical current density (Jc) for MgB2 superconducting wires can be obtained following the advanced internal Mg infiltration (AIMI) route. But unless suitable precautions are taken, the AIMI-processed MgB2 wires will exhibit incomplete MgB2 layer formation, i.e. reduced superconductor core size and hence suppressed current-carrying capability. Microstructural characterization of AIMI MgB2 wires before and after the heat treatment reveals that the reaction mechanism changes from a “Mg infiltration-reaction” at the beginning of the heat treatment to a “Mg diffusion-reaction” once a dense MgB2 layer is formed. A drastic drop in the Mg transport rate from infiltration to diffusion causes the termination of the MgB2 core growth. To quantify this process, a two-stage kinetic model is built to describe the MgB2 layer formation and growth. The derived kinetic model and the associated experimental observations indicate that fully reacted AIMI-processed MgB2 wires can be achieved following the optimization of B particle size, B powder packing density, MgB2 reaction activation energy and its response to the additions of dopants. PMID:26973431

Spectroscopic properties of Er(3+)/Yb(3+) co-doped Bi(2)O(3)-B(2)O(3)-GeO(2) glasses.

PubMed

Zhang, Xudong; Xu, Tiefeng; Nie, Qiuhua; Dai, Shixun; Shen, Xiang; Zhang, Xianghua

2007-05-01

Er(3+)/Yb(3+) co-doped 60Bi(2)O(3)-(40 - x)B(2)O(3)-xGeO(2) (BBG; x=0, 5, 10, 15 mol%) glasses that are suitable for fiber lasers, amplifiers have been fabricated and characterized. The absorption spectra, emission spectra, and lifetime of the (4)I(13/2) level and quantum efficiency of Er(3+):(4)I(13/2) --> (4)I(15/2) transition were measured and calculated. With the substitution of GeO(2) for B(2)O(3), both Delta lambda(eff) and sigma(e) decrease from 75 to 71 nm and 9.88 to 8.12 x 10(-21) cm(2), respectively. The measured lifetime of the (4)I(13/2) level and quantum efficiency of Er(3+):(4)I(13/2) --> (4)I(15/2) transition increase from 1.18 to 1.5 ms and 36.2% to 43.2%, respectively. The emission spectra of Er(3+):(4)I(13/2) --> (4)I(15/2) transition was also analyzed using a peak-fit routine, and an equivalent four-level system was proposed to estimate the stark splitting for the (4)I(15/2) and (4)I(13/2) levels of Er(3+) in the BBG glasses. The results indicate that the (4)I(13/2) --> (4)I(15/2) emission of Er(3+) can be exhibit a considerable broadening due to a significant enhance the peak A, and D emission.

HTP-NLP: A New NLP System for High Throughput Phenotyping.

PubMed

Schlegel, Daniel R; Crowner, Chris; Lehoullier, Frank; Elkin, Peter L

2017-01-01

Secondary use of clinical data for research requires a method to quickly process the data so that researchers can quickly extract cohorts. We present two advances in the High Throughput Phenotyping NLP system which support the aim of truly high throughput processing of clinical data, inspired by a characterization of the linguistic properties of such data. Semantic indexing to store and generalize partially-processed results and the use of compositional expressions for ungrammatical text are discussed, along with a set of initial timing results for the system.

Mapping Partners Master Drug Dictionary to RxNorm using an NLP-based approach.

PubMed

Zhou, Li; Plasek, Joseph M; Mahoney, Lisa M; Chang, Frank Y; DiMaggio, Dana; Rocha, Roberto A

2012-08-01

To develop an automated method based on natural language processing (NLP) to facilitate the creation and maintenance of a mapping between RxNorm and a local medication terminology for interoperability and meaningful use purposes. We mapped 5961 terms from Partners Master Drug Dictionary (MDD) and 99 of the top prescribed medications to RxNorm. The mapping was conducted at both term and concept levels using an NLP tool, called MTERMS, followed by a manual review conducted by domain experts who created a gold standard mapping. The gold standard was used to assess the overall mapping between MDD and RxNorm and evaluate the performance of MTERMS. Overall, 74.7% of MDD terms and 82.8% of the top 99 terms had an exact semantic match to RxNorm. Compared to the gold standard, MTERMS achieved a precision of 99.8% and a recall of 73.9% when mapping all MDD terms, and a precision of 100% and a recall of 72.6% when mapping the top prescribed medications. The challenges and gaps in mapping MDD to RxNorm are mainly due to unique user or application requirements for representing drug concepts and the different modeling approaches inherent in the two terminologies. An automated approach based on NLP followed by human expert review is an efficient and feasible way for conducting dynamic mapping. Copyright © 2011 Elsevier Inc. All rights reserved.

Gold(I) Complexes of the Geminal Phosphinoborane tBu2PCH2BPh2

PubMed Central

2018-01-01

In this work, we explored the coordination properties of the geminal phosphinoborane tBu2PCH2BPh2 (2) toward different gold(I) precursors. The reaction of 2 with an equimolar amount of the sulfur-based complex (Me2S)AuCl resulted in displacement of the SMe2 ligand and formation of linear phosphine gold(I) chloride 3. Using an excess of ligand 2, bisligated complex 4 was formed and showed dynamic behavior at room temperature. Changing the gold(I) metal precursor to the phosphorus-based complex, (Ph3P)AuCl impacted the coordination behavior of ligand 2. Namely, the reaction of ligand 2 with (Ph3P)AuCl led to the heterolytic cleavage of the gold–chloride bond, which is favored over PPh3 ligand displacement. To the best of our knowledge, 2 is the first example of a P/B-ambiphilic ligand capable of cleaving the gold–chloride bond. The coordination chemistry of 2 was further analyzed by density functional theory calculations. PMID:29732451

Gold(I) Complexes of the Geminal Phosphinoborane tBu2PCH2BPh2.

PubMed

Boom, Devin H A; Ehlers, Andreas W; Nieger, Martin; Devillard, Marc; Bouhadir, Ghenwa; Bourissou, Didier; Slootweg, J Chris

2018-04-30

In this work, we explored the coordination properties of the geminal phosphinoborane t Bu 2 PCH 2 BPh 2 ( 2 ) toward different gold(I) precursors. The reaction of 2 with an equimolar amount of the sulfur-based complex (Me 2 S)AuCl resulted in displacement of the SMe 2 ligand and formation of linear phosphine gold(I) chloride 3 . Using an excess of ligand 2 , bisligated complex 4 was formed and showed dynamic behavior at room temperature. Changing the gold(I) metal precursor to the phosphorus-based complex, (Ph 3 P)AuCl impacted the coordination behavior of ligand 2 . Namely, the reaction of ligand 2 with (Ph 3 P)AuCl led to the heterolytic cleavage of the gold-chloride bond, which is favored over PPh 3 ligand displacement. To the best of our knowledge, 2 is the first example of a P/B-ambiphilic ligand capable of cleaving the gold-chloride bond. The coordination chemistry of 2 was further analyzed by density functional theory calculations.

MICROWAVE SPECTRA AND GEOMETRIES OF C2H_{2\\cdots AgI} and C2H_{4\\cdots AgI}

NASA Astrophysics Data System (ADS)

Stephens, Susanna L.; Tew, David Peter; Walker, Nick; Legon, Anthony

2015-06-01

A chirped-pulse Fourier transform microwave spectrometer has been used to measure the microwave spectra of both C2H_{2\\cdots AgI} and C2H_{4\\cdots AgI}. These complexes are generated via laser ablation at 532 nm of a silver surface in the presence of CF3I and either C2H_{2} or C2H_{4} and argon and are stabilized by a supersonic expansion. Rotational (A0, B0, C0) and centrifugal distortion constants (ΔJ and ΔJK) of each molecule have been determined as well the nuclear electric quadrupole coupling constants the iodine atom (χaa(I) and χbb-χcc(I)). The spectrum of each molecule is consistent with a C2v structure in which the metal atom interacts with the π-orbital of the ethene or ethyne molecule. Isotopic substitutions of atoms within the C2H_{2} or C2H_{4} subunits are in progress and in conjunction with high level ab initio calculations will allow for accurate determination of the geometry of each molecule. These to complexes are put in the context of the recently studied H2S\\cdots AgI, OC\\cdotsAgI, H3N\\cdots AgI and (CH3)_{3N\\cdots AgI}. S.Z. Riaz, S.L. Stephens, W. Mizukami, D.P. Tew, N.R. Walker, A.C. Legon, Chem. Phys. Let., 531, 1-12 (2012) S.L. Stephens, W. Mizukami, D.P. Tew, N.R. Walker, A.C. Legon, J. Chem. Phys., 136(6), 064306 (2012) D.M. Bittner, D.P. Zaleski, S.L. Stephens, N.R. Walker, A.C. Legon, Study in progress.

A hybrid model for automatic identification of risk factors for heart disease.

PubMed

Yang, Hui; Garibaldi, Jonathan M

2015-12-01

Coronary artery disease (CAD) is the leading cause of death in both the UK and worldwide. The detection of related risk factors and tracking their progress over time is of great importance for early prevention and treatment of CAD. This paper describes an information extraction system that was developed to automatically identify risk factors for heart disease in medical records while the authors participated in the 2014 i2b2/UTHealth NLP Challenge. Our approaches rely on several nature language processing (NLP) techniques such as machine learning, rule-based methods, and dictionary-based keyword spotting to cope with complicated clinical contexts inherent in a wide variety of risk factors. Our system achieved encouraging performance on the challenge test data with an overall micro-averaged F-measure of 0.915, which was competitive to the best system (F-measure of 0.927) of this challenge task. Copyright © 2015 Elsevier Inc. All rights reserved.

H2-K(b) and H2-D(b) regulate cerebellar long-term depression and limit motor learning.

PubMed

McConnell, Michael J; Huang, Yanhua H; Datwani, Akash; Shatz, Carla J

2009-04-21

There are more than 50 class I MHC (MHCI) molecules in the mouse genome, some of which are now known to be expressed in neurons; however, the role of classical MHCI molecules in synaptic plasticity is unknown. We report that the classical MHCI molecules, H2-K(b) and H2-D(b), are co-expressed by Purkinje cells (PCs). In the cerebellum of mice deficient for both H2-K(b) and H2-D(b) (K(b)D(b-/-)), there is a lower threshold for induction of long-term depression (LTD) at parallel fiber to PC synapses. This change may be a result of additional glutamate release observed at K(b)D(b-/-) CF to PC synapses, which are thought to "train" the cerebellar circuit. A behavioral correlate of cerebellar LTD is motor learning; acquisition and retention of a Rotarod behavioral task is significantly better in K(b)D(b-/-) mice than in WT cohorts. These physiological and behavioral phenotypes in K(b)D(b-/-) mice reveal a surprising role for classical MHCI molecules in synaptic plasticity and motor learning.

Ethyl caffeate suppresses NF-kappaB activation and its downstream inflammatory mediators, iNOS, COX-2, and PGE2 in vitro or in mouse skin.

PubMed

Chiang, Yi-Ming; Lo, Chiu-Ping; Chen, Yi-Ping; Wang, Sheng-Yang; Yang, Ning-Sun; Kuo, Yueh-Hsiung; Shyur, Lie-Fen

2005-10-01

Ethyl caffeate, a natural phenolic compound, was isolated from Bidens pilosa, a medicinal plant popularly used for treating certain inflammatory syndromes. The purpose of this study was to investigate the structural activity, and the anti-inflammatory functions and mechanism(s) of ethyl caffeate. Ethyl caffeate was found to markedly suppress the lipopolysaccharide (LPS)-induced nitric oxide (NO) production (IC(50) = 5.5 microg ml(-1)), mRNA and protein expressions of inducible nitric oxide synthase (iNOS), and prostaglandin E(2) (PGE(2)) production in RAW 264.7 macrophages. Transient gene expression assays using human cox-2 promoter construct revealed that ethyl caffeate exerted an inhibitory effect on cox-2 transcriptional activity in 12-O-tetradecanoylphorbol-13-acetate (TPA)-treated MCF-7 cells. Immunohistochemical studies of mouse skin demonstrated that TPA-induced COX-2 expression was significantly inhibited by ethyl caffeate with a superior effect to that of celecoxib, a nonsteroidal anti-inflammatory drug. The phosphorylation and degradation of inhibitor kappaB (IkappaB) and the translocation of nuclear transcription factor-kappaB (NF-kappaB) into the nucleus, as well as the activation of mitogen-activated protein kinases (MAPKs) induced by LPS in macrophages, were not affected by ethyl caffeate. Ethyl caffeate, however, could inhibit NF-kappaB activation by impairing the binding of NF-kappaB to its cis-acting element. These results suggest that ethyl caffeate suppresses iNOS and COX-2 expressions partly through the inhibition of the NF-kappaB.DNA complex formation. Structure-activity relationship analyses suggested that the catechol moiety and alpha,beta-unsaturated ester group in ethyl caffeate are important and essential structural features for preventing NF-kappaB.DNA complex formation. This study provides an insight into the probable mechanism(s) underlying the anti-inflammatory and therapeutic properties of ethyl caffeate.

Dissociation of iodine molecules and singlet oxygen generation in O2 - I2 mixture induced by 1315-nm laser radiation

NASA Astrophysics Data System (ADS)

Zagidullin, M. V.; Khvatov, N. A.; Malyshev, M. S.; Azyazov, V. N.

2017-11-01

It is observed that laser light at a wavelength of 1315 nm induces continuous stable fluorescence at the O2(b1Σ → X3Σ) and I2(B3Πu → X1Σ) bands in a O2 - I2 mixture preliminarily irradiated at a wavelength of 532 nm to achieve partial photolysis of iodine molecules. This testifies to generation of iodine atoms and excited O2(a1Δ), O2(b1Σ), and I2(B3Πu) molecules in the O2 - I2 mixture under irradiation at 1315 nm.

Oral application of freeze-dried yeast particles expressing the PCV2b Cap protein on their surface induce protection to subsequent PCV2b challenge in vivo.

PubMed

Patterson, Robert; Eley, Thomas; Browne, Christopher; Martineau, Henny M; Werling, Dirk

2015-11-17

Porcine circovirus type 2 (PCV2) is now endemic in every major pig producing country, causing PCV-associated disease (PCVAD), linked with large scale economic losses. Current vaccination strategies are based on the capsid protein of the virus and are reasonably successful in preventing PCVAD but fail to induce sterile immunity. Additionally, vaccinating whole herds is expensive and time consuming. In the present study a "proof of concept" vaccine trial was employed to test the effectiveness of powdered freeze-dried recombinant Saccharomyces cerevisiae yeast stably expressing the capsid protein of PCV2b on its surface as an orally applied vaccine. PCV2-free pigs were given 3 doses of vaccine or left un-vaccinated before challenge with a defined PCV2b strain. Rectal temperatures were measured and serum and faeces samples were collected weekly. At the end of the study, pigs were euthanized, tissue samples taken and tested for PCV2b load by qPCR and immunohistochemistry. The peak of viraemia in sera and faeces of unvaccinated pigs was higher than that of vaccinated pigs. Additionally more sIgA was found in faeces of vaccinated pigs than unvaccinated. Vaccination was associated with lower serum concentrations of TNFα and IL-1β but higher concentrations of IFNα and IFNγ in comparison to the unvaccinated animals. At the end of the trial, a higher viral load was found in several lymphatic tissues and the ileum of unvaccinated pigs in comparison to vaccinated pigs. The difference between groups was especially apparent in the ileum. The results presented here demonstrate a possible use for recombinant S. cerevisiae expressing viral proteins as an oral vaccine against PCV2. A powdered freeze-dried recombinant S. cerevisiae used as an oral vaccine could be mixed with feed and may offer a cheap and less labour intensive alternative to inoculation with the additional advantage that no cooling chain would be required for vaccine transport and storage. Copyright © 2015 The

Function of brain α2B-adrenergic receptor characterized with subtype-selective α2B antagonist and KO mice.

PubMed

Luhrs, Lauren; Manlapaz, Cynthia; Kedzie, Karen; Rao, Sandhya; Cabrera-Ghayouri, Sara; Donello, John; Gil, Daniel

2016-12-17

Noradrenergic signaling, through the α 2A and α 2C adrenergic receptors modulates the cognitive and behavioral symptoms of disorders such as schizophrenia, attention deficit hyperactivity disorder (ADHD), and addiction. However, it is unknown whether the α 2B receptor has any significant role in CNS function. The present study elucidates the potential role of the α 2B receptor in CNS function via the discovery and use of the first subtype-selective α 2B antagonist (AGN-209419), and behavioral analyses of α-receptor knockout (KO) mice. Using AGN-209419 as radioligand, α 2B receptor binding sites were identified within the olfactory bulb, cortex, thalamus, cerebellum, and striatum. Based on the observed expression patterns of α 2 subtypes in the brain, we compared α 2B KO, α 2A KO and α 2C KO mice behavioral phenotypes with their respective wild-type lines in anxiety (plus maze), compulsive (marble burying), and sensorimotor (prepulse inhibition) tasks. α 2B KO mice exhibited increased marble burying and α 2C KO mice exhibited an increased startle response to a pulse stimulus, but otherwise intact prepulse inhibition. To further explore compulsive behavior, we evaluated novelty-induced locomotor hyperactivity and found that α 2B KO and α 2C KO mice exhibited increased locomotion in the open field. Interestingly, when challenged with amphetamine, α 2C KO mice increased activity at lower doses relative to either α 2A KO or WT mice. However, α 2B KO mice exhibited stereotypy at doses of amphetamine that were only locomotor stimulatory to all other genotypes. Following co-administration of AGN-209419 with low-dose amphetamine in WT mice, stereotypy was observed, mimicking the α 2B KO phenotype. These findings suggest that the α 2B receptor is involved in CNS behaviors associated with sensorimotor gating and compulsivity, and may be therapeutically relevant for disorders such as schizophrenia, ADHD, post-traumatic stress disorder, addiction, and

A new superhard material: Osmium diboride OsB 2

NASA Astrophysics Data System (ADS)

Hebbache, M.; Stuparević, L.; Živković, D.

2006-08-01

Superhard materials have many industrial applications, wherever resistance to abrasion and wear are important. The synthesis of new superhard materials is one of the great challenges to scientists. We re-examined the phase diagram of the binary osmium-boron system and confirmed the existence of two hexagonal phases, OsB 1.1, Os 2B 3, and an orthorhombic phase, OsB 2. Almost nothing is known about the physical properties of osmium borides. Microhardness measurements show that OsB 2 is extremely hard. Ab initio calculations show that this is due to formation of covalent bonds between boron atoms. OsB 2 is also a low compressibility material. It can be used as hard coating.

Humoral immunity targeting site I of antigenic domain 2 of glycoprotein B upon immunization with different cytomegalovirus candidate vaccines.

PubMed

Axelsson, Fredrika; Adler, Stuart P; Lamarre, Alain; Ohlin, Mats

2007-12-21

Glycoprotein B (gB) is a major component in several vaccines that are under development for prevention of disease by cytomegalovirus. It contains multiple determinants that are targets for neutralizing antibodies. One of them is site I of antigenic domain 2 (AD-2). The epitope, defined by short peptides, is quite conserved between different isolates. However, it is poorly immunogenic in natural infection. In this study we investigated the extent to which different vaccines, attenuated live Towne vaccine with or without priming with a canarypox virus coding for gB, or a recombinant gB vaccine adjuvanted with MF59, induced antibodies to this epitope. As in natural infection only a fraction of all subjects developed antibody responses against site I of AD-2 following vaccination. We suggest that strategies that enhance immunogenicity of this epitope will improve vaccine efficacy.

Enhancing the photoelectrochemical response of TiO2 nanotubes through their nanodecoration by pulsed-laser-deposited Ag nanoparticles

NASA Astrophysics Data System (ADS)

Trabelsi, K.; Hajjaji, A.; Gaidi, M.; Bessais, B.; El Khakani, M. A.

2017-08-01

We report on the pulsed laser deposition (PLD) based nanodecoration of titanium dioxide (TiO2) nanotube arrays (NTAs) by Ag nanoparticles (NPs). We focus here on the investigation of the effect of the number of laser ablation pulses (NLP) of the silver target on both the average size of the Ag-NPs and the photoelectrochemical conversion efficiency of the Ag-NP decorated TiO2-NT based photoanodes. By varying the NLP, we were able to not only control the size of the PLD-deposited Ag nanoparticles from 20 to ˜50 nm, but also to increase concomitantly the surface coverage of the TiO2 NTAs by Ag-NPs. The red-shifting of the surface plasmon resonance peak of the PLD-deposited Ag-NPs deposited onto quartz substrates confirmed the increase of their size as the NLP is increased from 500 to 10 000. By investigating the photo-electrochemical properties of Ag-NP decorated TiO2-NTAs, by means of linear sweep cyclic voltammetry under UV-Vis illumination, we found that the generated photocurrent is sensitive to the size of the Ag-NPs and reaches a maximum value at NLP =500 (i.e.,; Ag-NP size of ˜20 nm). For NLP = 500, the photoconversion efficiency of the Ag-NP decorated TiO2-NTAs is shown to reach a maximum of 4.5% (at 0.5 V vs Ag/AgCl). The photocurrent enhancement of Ag-NP decorated TiO2-NTAs is believed to result from the additional light harvesting enabled by the ability of Ag-NPs to absorb visible irradiation caused by various localized surface plasmon resonances, which in turn depend on the size and interdistance of the Ag nanoparticles.

Semantic characteristics of NLP-extracted concepts in clinical notes vs. biomedical literature.

PubMed

Wu, Stephen; Liu, Hongfang

2011-01-01

Natural language processing (NLP) has become crucial in unlocking information stored in free text, from both clinical notes and biomedical literature. Clinical notes convey clinical information related to individual patient health care, while biomedical literature communicates scientific findings. This work focuses on semantic characterization of texts at an enterprise scale, comparing and contrasting the two domains and their NLP approaches. We analyzed the empirical distributional characteristics of NLP-discovered named entities in Mayo Clinic clinical notes from 2001-2010, and in the 2011 MetaMapped Medline Baseline. We give qualitative and quantitative measures of domain similarity and point to the feasibility of transferring resources and techniques. An important by-product for this study is the development of a weighted ontology for each domain, which gives distributional semantic information that may be used to improve NLP applications.

iTOUGH2 v7.1

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

FINSTERLE, STEFAN; JUNG, YOOJIN; KOWALSKY, MICHAEL

2016-09-15

iTOUGH2 (inverse TOUGH2) provides inverse modeling capabilities for TOUGH2, a simulator for multi-dimensional, multi-phase, multi-component, non-isothermal flow and transport in fractured porous media. iTOUGH2 performs sensitivity analyses, data-worth analyses, parameter estimation, and uncertainty propagation analyses in geosciences and reservoir engineering and other application areas. iTOUGH2 supports a number of different combinations of fluids and components (equation-of-state (EOS) modules). In addition, the optimization routines implemented in iTOUGH2 can also be used for sensitivity analysis, automatic model calibration, and uncertainty quantification of any external code that uses text-based input and output files using the PEST protocol. iTOUGH2 solves the inverse problem bymore » minimizing a non-linear objective function of the weighted differences between model output and the corresponding observations. Multiple minimization algorithms (derivative-free, gradient-based, and second-order; local and global) are available. iTOUGH2 also performs Latin Hypercube Monte Carlo simulations for uncertainty propagation analyses. A detailed residual and error analysis is provided. This upgrade includes (a) global sensitivity analysis methods, (b) dynamic memory allocation (c) additional input features and output analyses, (d) increased forward simulation capabilities, (e) parallel execution on multicore PCs and Linux clusters, and (f) bug fixes. More details can be found at http://esd.lbl.gov/iTOUGH2.« less

Experimenting with semantic web services to understand the role of NLP technologies in healthcare.

PubMed

Jagannathan, V

2006-01-01

NLP technologies can play a significant role in healthcare where a predominant segment of the clinical documentation is in text form. In a graduate course focused on understanding semantic web services at West Virginia University, a class project was designed with the purpose of exploring potential use for NLP-based abstraction of clinical documentation. The role of NLP-technology was simulated using human abstractors and various workflows were investigated using public domain workflow and semantic web service technologies. This poster explores the potential use of NLP and the role of workflow and semantic web technologies in developing healthcare IT environments.

Prediction and identification of potential immunodominant epitopes in glycoproteins B, C, E, G, and I of herpes simplex virus type 2.

PubMed

Pan, Mingjie; Wang, Xingsheng; Liao, Jianmin; Yin, Dengke; Li, Suqin; Pan, Ying; Wang, Yao; Xie, Guangyan; Zhang, Shumin; Li, Yuexi

2012-01-01

Twenty B candidate epitopes of glycoproteins B (gB2), C (gC2), E (gE2), G (gG2), and I (gI2) of herpes simplex virus type 2 (HSV-2) were predicted using DNAstar, Biosun, and Antheprot methods combined with the polynomial method. Subsequently, the biological functions of the peptides were tested via experiments in vitro. Among the 20 epitope peptides, 17 could react with the antisera to the corresponding parent proteins in the EIA tests. In particular, five peptides, namely, gB2(466-473) (EQDRKPRN), gC2(216-223) (GRTDRPSA), gE2(483-491) (DPPERPDSP), gG2(572-579) (EPPDDDDS), and gI2(286-295) (CRRRYRRPRG) had strong reaction with the antisera. All conjugates of the five peptides with the carrier protein BSA could stimulate mice into producing antibodies. The antisera to these peptides reacted strongly with the corresponding parent glycoproteins during the Western Blot tests, and the peptides reacted strongly with the antibodies against the parent glycoproteins during the EIA tests. The antisera against the five peptides could neutralize HSV-2 infection in vitro, which has not been reported until now. These results suggest that the immunodominant epitopes screened using software algorithms may be used for virus diagnosis and vaccine design against HSV-2.

Challenges in adapting existing clinical natural language processing systems to multiple, diverse health care settings.

PubMed

Carrell, David S; Schoen, Robert E; Leffler, Daniel A; Morris, Michele; Rose, Sherri; Baer, Andrew; Crockett, Seth D; Gourevitch, Rebecca A; Dean, Katie M; Mehrotra, Ateev

2017-09-01

Widespread application of clinical natural language processing (NLP) systems requires taking existing NLP systems and adapting them to diverse and heterogeneous settings. We describe the challenges faced and lessons learned in adapting an existing NLP system for measuring colonoscopy quality. Colonoscopy and pathology reports from 4 settings during 2013-2015, varying by geographic location, practice type, compensation structure, and electronic health record. Though successful, adaptation required considerably more time and effort than anticipated. Typical NLP challenges in assembling corpora, diverse report structures, and idiosyncratic linguistic content were greatly magnified. Strategies for addressing adaptation challenges include assessing site-specific diversity, setting realistic timelines, leveraging local electronic health record expertise, and undertaking extensive iterative development. More research is needed on how to make it easier to adapt NLP systems to new clinical settings. A key challenge in widespread application of NLP is adapting existing systems to new clinical settings. © The Author 2017. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Ascorbic acid deficiency decreases hepatic cytochrome P-450, especially CYP2B1/2B2, and simultaneously induces heme oxygenase-1 gene expression in scurvy-prone ODS rats.

PubMed

Kobayashi, Misato; Hoshinaga, Yukiko; Miura, Natsuko; Tokuda, Yuki; Shigeoka, Shigeru; Murai, Atsushi; Horio, Fumihiko

2014-01-01

The mechanisms underlying the decrease in hepatic cytochrome P-450 (CYP) content in ascorbic acid deficiency was investigated in scurvy-prone ODS rats. First, male ODS rats were fed a diet containing sufficient ascorbic acid (control) or a diet without ascorbic acid (deficient) for 18 days, with or without the intraperitoneal injection of phenobarbital. Ascorbic acid deficiency decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial cytochrome oxidase (COX) complex IV subunit I protein, and simultaneously increased heme oxygenase-1 protein in microsomes and mitochondria. Next, heme oxygenase-1 inducers, that is lipopolysaccharide and hemin, were administered to phenobaribital-treated ODS rats fed sufficient ascorbic acid. The administration of these inducers decreased hepatic microsomal total CYP content, CYP2B1/2B2 protein, and mitochondrial COX complex IV subunit I protein. These results suggested that the stimulation of hepatic heme oxygenase-1 expression by ascorbic acid deficiency caused the decrease in CYP content in liver.

Compendium of Shock Wave Data. Volume 2, Revision 1. Section A2. Inorganic Compounds Section B. Hydrocarbons

DTIC Science & Technology

1977-06-01

5K9AR uret 14’T17 TABLE I TUNGSTEN CARBIDE 53-23--- 1 B i 5 4fL 3 2 0 int IU aF n PAGE 4011.1 ś-1---I RUtILFr. CRYSTAL AND NATURAL (TIIANIUM OXIDCl...COtMIENTS : I I SOURCE: KOIR1ER. 5. B .. SINITSYN. M, V., ruNIIKOV. A, I., UR1. IN. V, a. AND BLINOV . A. V. SOVIET PHYS-.JIEP. VOL. 20. P. 911 119651...AO Uii Coaapendiux of* ýIoek Wave Daa.3otion A2. Inorganuic Compounds. Oection B , "r~iooarbona. ______________ I. Ca"TRACT 09GOAMY wmuimea Lawrt

Mutational Studies Uncover Non-Native Structure in the Dimeric Kinetic Intermediate of the H2A-H2B Heterodimer

PubMed Central

Stump, Matthew R.; Gloss, Lisa M.

2010-01-01

The folding pathway of the histone H2A-H2B heterodimer minimally includes an on-pathway, dimeric, burst-phase intermediate, I2. The partially folded H2A and H2B monomers populated at equilibrium were characterized as potential monomeric kinetic intermediates. Folding kinetics were compared for initiation from isolated, folded monomers and the heterodimer unfolded in 4 M urea. The observed rates were virtually identical above 0.4 M urea, exhibiting a log-linear relationship on the final denaturant concentration. Below ~0.4 M urea (concentrations inaccessible from the 4 M urea unfolded state), a roll-over in the rates was observed; this suggests that a component of the I2 ensemble contains non-native structure that rearranges/isomerizes to a more native-like species. The contribution of helix propensity to the stability of the I2 ensemble was assessed with a set of H2A-H2B mutants containing Ala and Gly replacements at nine sites, focusing mainly on the long, central α2 helix. Equilibrium and kinetic folding/unfolding data were collected to determine the effects of the mutations on the stability of I2 and the transition state between I2 and N2. This limited mutational study indicated that residues in the α2 helices of H2A and H2B, as well as α1 of H2B and both the C-terminus of α3 and the short αC helix of H2A contribute to the stability of the I2 burst phase species. Interestingly, at least eight of the nine targeted residues stabilize I2 by interactions that are non-native to some extent. Given that destabilizing I2 and these non-native interactions does not accelerate folding, it is concluded that the native and non-native structure present in the I2 ensemble enables efficient folding of H2A-H2B. PMID:20600120

Performance of a Natural Language Processing (NLP) Tool to Extract Pulmonary Function Test (PFT) Reports from Structured and Semistructured Veteran Affairs (VA) Data

PubMed Central

Sauer, Brian C.; Jones, Barbara E.; Globe, Gary; Leng, Jianwei; Lu, Chao-Chin; He, Tao; Teng, Chia-Chen; Sullivan, Patrick; Zeng, Qing

2016-01-01

Introduction/Objective: Pulmonary function tests (PFTs) are objective estimates of lung function, but are not reliably stored within the Veteran Health Affairs data systems as structured data. The aim of this study was to validate the natural language processing (NLP) tool we developed—which extracts spirometric values and responses to bronchodilator administration—against expert review, and to estimate the number of additional spirometric tests identified beyond the structured data. Methods: All patients at seven Veteran Affairs Medical Centers with a diagnostic code for asthma Jan 1, 2006–Dec 31, 2012 were included. Evidence of spirometry with a bronchodilator challenge (BDC) was extracted from structured data as well as clinical documents. NLP’s performance was compared against a human reference standard using a random sample of 1,001 documents. Results: In the validation set NLP demonstrated a precision of 98.9 percent (95 percent confidence intervals (CI): 93.9 percent, 99.7 percent), recall of 97.8 percent (95 percent CI: 92.2 percent, 99.7 percent), and an F-measure of 98.3 percent for the forced vital capacity pre- and post pairs and precision of 100 percent (95 percent CI: 96.6 percent, 100 percent), recall of 100 percent (95 percent CI: 96.6 percent, 100 percent), and an F-measure of 100 percent for the forced expiratory volume in one second pre- and post pairs for bronchodilator administration. Application of the NLP increased the proportion identified with complete bronchodilator challenge by 25 percent. Discussion/Conclusion: This technology can improve identification of PFTs for epidemiologic research. Caution must be taken in assuming that a single domain of clinical data can completely capture the scope of a disease, treatment, or clinical test. PMID:27376095

B11 NMR in the layered diborides OsB2 and RuB2

NASA Astrophysics Data System (ADS)

Suh, B. J.; Zong, X.; Singh, Y.; Niazi, A.; Johnston, D. C.

2007-10-01

B11 nuclear magnetic resonance (NMR) measurements have been performed on B11 enriched OsB2 and RuB2 polycrystalline powder samples in an external field of 4.7T and in the temperature range, 4.2KB2 and RuB2 , respectively. The experimental results indicate that a p character dominates the conduction electron wave function at the B site with a negligibly small s character in both compounds.

A comparison of 2-phenyl-2-(1-piperidinyl)propane (ppp), 1,1',1''-phosphinothioylidynetrisaziridine (thioTEPA), clopidogrel, and ticlopidine as selective inactivators of human cytochrome P450 2B6.

PubMed

Walsky, Robert L; Obach, R Scott

2007-11-01

The use of selective chemical inhibitors of human cytochrome P450 (P450) enzymes represents a powerful method by which the relative contributions of various human P450 enzymes to the metabolism of drugs can be determined. However, the identification of CYP2B6 in the metabolism of drugs has been more challenging because of the lack of a well established inhibitor of this enzyme. In this report, we describe the selectivity of 2-phenyl-2-(1-piperidinyl)propane (PPP) as an inactivator of CYP2B6 and compare this selectivity versus other CYP2B6 inactivators: 1,1',1''-phosphinothioylidynetrisaziridine (thioTEPA), clopidogrel, and ticlopidine. Values of K(I) and k(inact) for PPP were 5.6 microM and 0.13/min for bupropion hydroxylase catalyzed by pooled human liver microsomes, and values for thioTEPA were similar (4.8 microM and 0.20/min, respectively). Intrinsic inactivation capability was considerably greater for clopidogrel because of a greater k(inact) value (1.9/min). Ticlopidine was potent with K(I) and k(inact) values of 0.32 microM and 0.43/min, respectively. The selectivity of these four agents for CYP2B6 was determined by testing their effects on other human P450 enzyme activities using conditions that yield approximately 90% inactivation of CYP2B6 activity. The results showed that preincubation of human liver microsomes with PPP at 30 microM for 30 min provided more selective inhibition for CYP2B6 than thioTEPA, clopidogrel, and ticlopidine. Furthermore, the use of clopidogrel is complicated by the observation that this agent is not stable in the presence of human liver microsomes, even without addition of NADPH. Therefore, PPP can serve as a selective chemical inactivator of CYP2B6 and be used to define the role of CYP2B6 in the metabolism of drugs.

Photodissociation of CF2ICF2I in solid para-hydrogen: infrared spectra of anti- and gauche-˙C2F4I radicals.

PubMed

Haupa, Karolina Anna; Lim, Manho; Lee, Yuan-Pern

2018-05-09

The photolysis of 1,2-diiodotetrafluoroethane (CF2ICF2I) has served as a prototypical system in ultrafast reaction dynamics. Even though the intermediates, anti- and gauche-iodotetrafluoroethyl (˙C2F4I) radicals, have been characterized with electron diffraction and X-ray diffraction, their infrared spectra are unreported. We report the formation and infrared identification of these radical intermediates upon ultraviolet photodissociation of CF2ICF2I in solid para-hydrogen (p-H2) at 3.3 K. Lines at 1364.9/1358.5, 1283.2, 1177.1, 1162.2, 1126.8, 837.3, 658.0, 574.2, and 555.2 cm-1 are assigned to anti-˙C2F4I, and lines at 1325.9, 1259.7, 1143.4, 1063.4, 921.0, and 765.3 cm-1 to gauche-˙C2F4I. A secondary photodissociation leading to C2F4 was also observed. The assignments were derived according to behavior on secondary photolysis, comparison of the vibrational wavenumbers and the IR intensities of the observed lines with values predicted with the B3PW91/aug-cc-pVTZ-pp method. This spectral identification provides valuable information for future direct spectral probes of these important intermediates.

Curcumin by down-regulating NF-kB and elevating Nrf2, reduces brain edema and neurological dysfunction after cerebral I/R.

PubMed

Li, Wei; Suwanwela, Nijasri C; Patumraj, Suthiluk

2016-07-01

Oxidation, inflammation, and apoptosis are three critical factors for the pathogenic mechanism of cerebral ischemia/reperfusion (I/R) injury. Curcumin exhibits substantial biological properties via anti-oxidation, anti-inflammation and anti-apoptotic effects; however, the molecular mechanism underlying the effects of curcumin against cerebral I/R injury remains unclear. To investigate the effects of curcumin on cerebral I/R injury associated with water content, infarction volume, and the expression of nuclear factor-kappa-B (NF-κB) and nuclear factor-erythroid-related factor-2 (Nrf2). Middle cerebral artery occlusion (MCAO, 1-hour occlusion and 24-hour reperfusion) was performed in male Wistar rats (n=64) as a cerebral I/R injury model. In the MCAO+CUR group, the rats were administered curcumin (300mg/kg BW, i.p.) at 30min after occlusion. The same surgical procedures were performed in SHAM rats without MCAO occlusion. At 24h post-operation, the parameters, including neurological deficit scores, blood brain barrier (BBB) disruption, water content, and infarction volume, were determined. Brain tissue NF-κB and Nrf2 expression levels were assayed through immunohistochemistry. Compared with the SHAM group, BBB disruption, neurological deficit, and increased brain water content and infarction volume were markedly demonstrated in the MCAO group. NF-κB expression was enhanced in the MCAO group. However, in the MCAO+CUR group, the upregulation of Nrf2, an anti-oxidation related protein, was consistent with a significant decline in the water content, infarction volume, and NF-κB expression. The protective effects of curcumin against cerebral I/R injury reflect anti-oxidation, anti-inflammation and anti-apoptotic activities, resulting in the elevation of Nrf2 and down-regulation of NF-κB. Copyright © 2015 Elsevier Inc. All rights reserved.

Scintillation properties of Eu 2+-doped KBa 2I 5 and K 2BaI 4

DOE PAGES

Stand, L.; Zhuravleva, M.; Chakoumakos, Bryan C.; ...

2015-09-25

We report two new ternary metal halide scintillators, KBa 2I 5 and K 2BaI 4, activated with divalent europium. Single crystal X-ray diffraction measurements confirmed that KBa 2I 5 has a monoclinic structure (P2 1/c) and that K 2BaI 4 has a rhombohedral structure (R3c). Differential scanning calorimetry showed singular melting and crystallization points, making these compounds viable candidates for melt growth. We grew 13 mm diameter single crystals of KBa 2I 5:Eu 2+ and K 2BaI 4:Eu2+ in evacuated quartz ampoules via the vertical Bridgman technique. The optimal Eu 2+ concentration was 4% for KBa 2I 5 and 7%more » for K 2BaI 4. The X-ray excited emissions at 444 nm for KBa 2I 5:Eu 4% and 448 nm for K 2BaI 4:Eu 7% arise from the 5d-4f radiative transition in Eu 2+. KBa 2I 5:Eu 4% has a light yield of 90,000 photons/MeV, with an energy resolution of 2.4% and K 2BaI 4:Eu 7% has a light yield of 63,000 ph/MeV, with an energy resolution of 2.9% at 662 keV. Both crystals have an excellent proportional response to a wide range of gamma-ray energies.« less

Oleamide suppresses lipopolysaccharide-induced expression of iNOS and COX-2 through inhibition of NF-kappaB activation in BV2 murine microglial cells.

PubMed

Oh, Young Taek; Lee, Jung Yeon; Lee, Jinhwa; Lee, Ju Hie; Kim, Ja-Eun; Ha, Joohun; Kang, Insug

2010-05-03

Oleamide (cis-9-octadecenamide) is an endogenous sleep-inducing fatty acid amide that accumulates in the cerebrospinal fluid of the sleep-deprived animals. Microglia are the major immune cells involved in neuroinflammation causing brain damage during infection, ischemia, and neurodegenerative disease. In this study, we examined the effects of oleamide on LPS-induced production of proinflammatory mediators and the mechanisms involved in BV2 microglia. Oleamide inhibited LPS-induced production of NO and prostaglandin E2 as well as expression of iNOS and COX-2. We showed that oleamide blocked LPS-induced NF-kappaB activation and phosphorylation of inhibitor kappaB kinase (IKK). We also showed that oleamide inhibited LPS-induced phosphorylation of Akt, p38 MAPK, and ERK, activation of PI 3-kinase, and accumulation of reactive oxygen species (ROS). Finally, we showed that a specific antagonist of the CB2 receptor, AM630, blocked the inhibitory effects of oleamide on LPS-induced production of proinflammatory mediators and activation of NF-kappaB. Taken together, our results suggest that oleamide shows an anti-inflammatory effect through inhibition of NF-kappaB activation in LPS-stimulated BV2 microglia. 2010 Elsevier Ireland Ltd. All rights reserved.

v3NLP Framework: Tools to Build Applications for Extracting Concepts from Clinical Text

PubMed Central

Divita, Guy; Carter, Marjorie E.; Tran, Le-Thuy; Redd, Doug; Zeng, Qing T; Duvall, Scott; Samore, Matthew H.; Gundlapalli, Adi V.

2016-01-01

Introduction: Substantial amounts of clinically significant information are contained only within the narrative of the clinical notes in electronic medical records. The v3NLP Framework is a set of “best-of-breed” functionalities developed to transform this information into structured data for use in quality improvement, research, population health surveillance, and decision support. Background: MetaMap, cTAKES and similar well-known natural language processing (NLP) tools do not have sufficient scalability out of the box. The v3NLP Framework evolved out of the necessity to scale-up these tools up and provide a framework to customize and tune techniques that fit a variety of tasks, including document classification, tuned concept extraction for specific conditions, patient classification, and information retrieval. Innovation: Beyond scalability, several v3NLP Framework-developed projects have been efficacy tested and benchmarked. While v3NLP Framework includes annotators, pipelines and applications, its functionalities enable developers to create novel annotators and to place annotators into pipelines and scaled applications. Discussion: The v3NLP Framework has been successfully utilized in many projects including general concept extraction, risk factors for homelessness among veterans, and identification of mentions of the presence of an indwelling urinary catheter. Projects as diverse as predicting colonization with methicillin-resistant Staphylococcus aureus and extracting references to military sexual trauma are being built using v3NLP Framework components. Conclusion: The v3NLP Framework is a set of functionalities and components that provide Java developers with the ability to create novel annotators and to place those annotators into pipelines and applications to extract concepts from clinical text. There are scale-up and scale-out functionalities to process large numbers of records. PMID:27683667

Anti-ErbB-2 mAb therapy requires type I and II interferons and synergizes with anti-PD-1 or anti-CD137 mAb therapy.

PubMed

Stagg, John; Loi, Sherene; Divisekera, Upulie; Ngiow, Shin Foong; Duret, Helene; Yagita, Hideo; Teng, Michele W; Smyth, Mark J

2011-04-26

Trastuzumab, a monoclonal antibody targeting human epidermal growth factor receptor-2 (HER2/ErbB-2), has become the mainstay of treatment for HER2-positive breast cancer. Nevertheless, its exact mechanism of action has not been fully elucidated. Although several studies suggest that Fc receptor-expressing immune cells are involved in trastuzumab therapy, the relative contribution of lymphocyte-mediated cellular cytotoxicity and antitumor cytokines remains unknown. We report here that anti-ErbB-2 mAb therapy is dependent on the release of type I and type II IFNs but is independent of perforin or FasL. Our study thus challenges the notion that classical antibody-dependent, lymphocyte-mediated cellular cytotoxicity is important for trastuzumab. We demonstrate that anti-ErbB-2 mAb therapy of experimental tumors derived from MMTV-ErbB-2 transgenic mice triggers MyD88-dependent signaling and primes IFN-γ-producing CD8+ T cells. Adoptive cell transfer of purified T cell subsets confirmed the essential role of IFN-γ-producing CD8+ T cells. Notably, anti-ErbB-2 mAb therapy was independent of IL-1R or IL-17Ra signaling. Finally, we investigated whether immunostimulatory approaches with antibodies against programmed death-1 (PD-1) or 41BB (CD137) could be used to capitalize on the immune-mediated effects of trastuzumab. We demonstrate that anti-PD-1 or anti-CD137 mAb can significantly improve the therapeutic activity of anti-ErbB-2 mAb in immunocompetent mice.

Synthesis, structure and reactivity of rare-earth metallacarborane alkyls [η(1):η(5)-O(CH2)2C2B9H9]Ln(σ:η(1)-CH2C6H4-o-NMe2)(THF)2.

PubMed

Yang, Jingying; Xie, Zuowei

2015-04-14

Rare-earth metallacarborane alkyls can be stabilized by the incorporation of a functional sidearm into both π and σ ligands. Reaction of [Me3NH][7,8-O(CH2)2-7,8-C2B9H10] with one equiv. of Ln(CH2C6H4-o-NMe2)3 gave metallacarborane alkyls [η(1):η(5)-O(CH2)2C2B9H9]Ln(σ:η(1)-CH2C6H4-o-NMe2)(THF)2 (Ln = Y (), Gd (), Er ()) via alkane elimination. They represent the first examples of rare-earth metallacarborane alkyls. Treatment of with RN[double bond, length as m-dash]C[double bond, length as m-dash]NR (R = Cy, (i)Pr) or 2-benzoylpyridine afforded the corresponding mono-insertion products [η(1):η(5)-O(CH2)2C2B9H9]Y[η(2)-(RN)2C(CH2C6H4-o-NMe2)](DME) (R = Cy (), (i)Pr ()) or [η(1):η(5)-O(CH2)2C2B9H9]Y[C5H4NC(Ph)(CH2C6H4-o-NMe2)O](THF)2 (), respectively. Complex also reacted with ArNCO or ArNC (Ar = 2,6-diisopropylphenyl, 2,6-dimethylphenyl) to give di-insertion products [η(1):η(5)-O(CH2)2C2B9H9]Y[OC([double bond, length as m-dash]NC6H3Me2)N(C6H3Me2)C(CH2C6H4-o-NMe2)O](THF)2 () or [η(1):η(5)-O(CH2)2C2B9H9]Y[C([double bond, length as m-dash]NC6H3(i)Pr2)C([double bond, length as m-dash]NC6H3(i)Pr2)(CH2C6H4-o-NMe2)](DME) (). These results showed that the reactivity pattern of the Ln-C σ bond in rare-earth metallacarborane alkyls was dependent on the nature of the unsaturated organic molecules. New complexes were characterized by various spectroscopic techniques and elemental analysis. Some were further confirmed by single-crystal X-ray analysis.

A Model-based B2B (Batch to Batch) Control for An Industrial Batch Polymerization Process

NASA Astrophysics Data System (ADS)

Ogawa, Morimasa

This paper describes overview of a model-based B2B (batch to batch) control for an industrial batch polymerization process. In order to control the reaction temperature precisely, several methods based on the rigorous process dynamics model are employed at all design stage of the B2B control, such as modeling and parameter estimation of the reaction kinetics which is one of the important part of the process dynamics model. The designed B2B control consists of the gain scheduled I-PD/II2-PD control (I-PD with double integral control), the feed-forward compensation at the batch start time, and the model adaptation utilizing the results of the last batch operation. Throughout the actual batch operations, the B2B control provides superior control performance compared with that of conventional control methods.

High-Resolution Synchrotron Infrared Spectroscopy of Thiophosgene: the νb{1}, νb{5}, 2νb{4}, and νb{2} + 2νb{6} bands

NASA Astrophysics Data System (ADS)

McKellar, Bob; Billinghurst, Brant E.

2015-06-01

Thiophosgene (Cl_2CS) is a favorite model system for studies of photophysics, vibrational dynamics, and intersystem interactions. But at high resolution its infrared spectrum is very congested due to hot bands and multiple isotopic species. Previously, we reported the first high resolution IR study of this molecule, analyzing the νb{2} (504 wn) and νb{4} (471 wn) fundamental bands. Here we continue, with analysis of the νb{1} (1139 wn) and νb{5} (820 wn) fundamentals for the two most abundant isotopologues, 35Cl2CS and 35Cl37ClCS, based on spectra with a resolution of about 0.001 wn obtained at the Canadian Light Source far-infrared beamline using synchrotron radiation and a Bruker IFS125 Fourier transform spectrometer. The νb{2} + νb{4} (942 wn) and νb{2} + 2νb{6} (1104 wn) bands are also studied here. But so far the νb{2} + νb{6} combination band (795 wn) resists analysis, as do the weak νb{3} (292.9 wn) and νb{6} (≈300? wn) fundamentals. A.R.W. McKellar, B.E.Billinghurst, J. Mol. Spectrosc. 260, 66 (2010).

Transplantation of A2 and A2B kidneys from deceased donors into B waiting list candidates increases their transplantation rate.

PubMed

Bryan, Christopher F; Nelson, Paul W; Shield, Charles F; Ross, Gilbert; Warady, Bradley; Murillo, Daniel; Winklhofer, Franz T

2004-01-01

Transplant centers in the Midwest Transplant Network began transplanting kidneys from A2 or A2B donors into blood group B and O patients in 1986. Since 1991, an OPTN/UNOS variance has permitted us to allocate these kidneys preferentially into B and O waiting list patients. With more than 10 years of experience we have noted the following: 1. Thirty-one percent more blood group B patients were transplanted by allocating them A2 or A2B kidneys from our deceased donors. 2. Ten-year graft survival for B recipients of an A2 or A2B kidney (72%) was equivalent to that for B recipients of a B kidney (69%). 3. Type B recipients of simultaneous pancreas-kidney transplants (n=4) also did well with A2 or A2B organs. 4. Non-A recipients were transplanted only when their anti-A IgG titer history was consistently low (< or =4). 5. Most (90%) blood group B patients had a low anti-A IgG titer history; whereas, only one-third of blood group O patients had a low titer history. 6. Neither ethnicity nor HLA class I sensitization level influenced the anti-A IgG titer history. 7. In an OPO with mostly (87%) white donors, nearly 20% of blood group A donors were A2. 8. Waiting time until transplantation was lower for B patients who received an A2 or A2B kidney than for those who received a B or O kidney. 9. Our OPO blood group B waiting list was reduced from 25 low PRA (<40%) B candidates in 1994 to 4 in July, 2004. 10. Blood group A candidates received 6.4% fewer transplants with our A2/A2B--> B allocation algorithm. 11. Minority patients were transplanted at the same rate when using the A2/A2B--> B allocation algorithm as when using the standard UNOS algorithm for allocating B and O kidneys--> B patients.

A Customizable Importer for the Clinical Data Warehouses PaDaWaN and I2B2.

PubMed

Fette, Georg; Kaspar, Mathias; Dietrich, Georg; Ertl, Maximilian; Krebs, Jonathan; Stoerk, Stefan; Puppe, Frank

2017-01-01

In recent years, clinical data warehouses (CDW) storing routine patient data have become more and more popular to support scientific work in the medical domain. Although CDW systems provide interfaces to import new data, these interfaces have to be used by processing tools that are often not included in the systems themselves. In order to establish an extraction-transformation-load (ETL) workflow, already existing components have to be taken or new components have to be developed to perform the load part of the ETL. We present a customizable importer for the two CDW systems PaDaWaN and I2B2, which is able to import the most common import formats (plain text, CSV and XML files). In order to be run, the importer only needs a configuration file with the user credentials for the target CDW and a list of XML import configuration files, which determine how already exported data is indented to be imported. The importer is provided as a Java program, which has no further software requirements.

Pressure-induced topological insulator-to-metal transition and superconductivity in Sn-doped B i1.1S b0.9T e2S

NASA Astrophysics Data System (ADS)

An, Chao; Chen, Xuliang; Wu, Bin; Zhou, Yonghui; Zhou, Ying; Zhang, Ranran; Park, Changyong; Song, Fengqi; Yang, Zhaorong

2018-05-01

Tetradymite-type topological insulator Sn-doped B i1.1S b0.9T e2S (Sn-BSTS), with a surface state Dirac point energy well isolated from the bulk valence and conduction bands, is an ideal platform for studying the topological transport phenomena. Here, we present high-pressure transport studies on single-crystal Sn-BSTS, combined with Raman scattering and synchrotron x-ray diffraction measurements. Over the studied pressure range of 0.7-37.2 GPa, three critical pressure points can be observed: (i) At ˜9 GPa, a pressure-induced topological insulator-to-metal transition is revealed due to closure of the bulk band gap, which is accompanied by changes in slope of the Raman frequencies and a minimum in c /a within the pristine rhombohedral structure (R -3 m ); (ii) at ˜13 GPa, superconductivity is observed to emerge, along with the R -3 m to a C 2 /c (monoclinic) structural transition; (iii) at ˜24 GPa, the superconducting transition onset temperature TC reaches a maximum of ˜12 K , accompanied by a second structural transition from the C 2 /c to a body-centered cubic I m -3 m phase.

Effect of B2O3 on luminescence of erbium doped tellurite glasses.

PubMed

Shen, Xiang; Nie, Qiuhua; Xu, Tiefeng; Dai, Shixun; Wang, Xunsi

2007-02-01

The B2O3 was introduced into the Er3+ doped TeO2-ZnO-Na2O glass to increase the phonon energy of the host. The effect of B2O3 on the non-radiative rate of the 4I11/2-->4I13/2 transition of Er3+, the lifetime of the 4I11/2 and 4I13/2 levels, the green and red upconversion emissions intensity, and the 4I13/2-->4I15/2 emission intensity was discussed. The results show that the phonon energy of boro-tellurite glass is close to that of germanate glass and is quite smaller than that of borate glass. The lifetime of 4I11/2 level and the upconversion emissions decrease with increasing B2O3 concentration. The higher OH group concentration presented in the boro-tellurite glass may shorten the lifetime of 4I13/2 level and also reduce the quantum efficiency of 4I13/2-->4I15/2 emission. The future dehydrating procedures are suggested to enhance the efficiency of amplification at 1.5 microm band.

Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice.

PubMed

Shao, Shujuan; Liu, Rong; Wang, Yang; Song, Yongmei; Zuo, Lihui; Xue, Liyan; Lu, Ning; Hou, Ning; Wang, Mingrong; Yang, Xiao; Zhan, Qimin

2010-02-01

Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target.

Identification of UGT2B9*2 and UGT2B33 isolated from female rhesus monkey liver.

PubMed

Dean, Brian; Arison, Byron; Chang, Steve; Thomas, Paul E; King, Christopher

2004-06-01

Two UDP-glucuronosyltransferases (UGT2B9(*)2 and UGT2B33) have been isolated from female rhesus monkey liver. Microsomal preparations of the cell lines expressing the UGTs catalyzed the glucuronidation of the general substrate 7-hydroxy-4-(trifluoromethyl)coumarin in addition to selected estrogens (beta-estradiol and estriol) and opioids (morphine, naloxone, and naltrexone). UGT2B9(*)2 displayed highest efficiency for beta-estradiol-17-glucuronide production and did not catalyze the glucuronidation of naltrexone. UGT2B33 displayed highest efficiency for estriol and did not catalyze the glucuronidation of beta-estradiol. UGT2B9(*)2 was found also to catalyze the glucuronidation of 4-hydroxyestrone, 16-epiestriol, and hyodeoxycholic acid, while UGT2B33 was capable of conjugating 4-hydroxyestrone, androsterone, diclofenac, and hyodeoxycholic acid. Three glucocorticoids (cortisone, cortisol, and corticosterone) were not substrates for glucuronidation by liver or kidney microsomes or any expressed UGTs. Our current data suggest the use of beta-estradiol-3-glucuronidation, beta-estradiol-17-glucuronidation, and estriol-17-glucuronidation to assay UGT1A01, UGT2B9(*)2, and UGT2B33 activity in rhesus liver microsomes, respectively.

Smad7 mediates inhibition of Saos2 osteosarcoma cell differentiation by NF{kappa}B

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

Eliseev, Roman A.; Schwarz, Edward M.; Zuscik, Michael J.

2006-01-01

The transcription factor NF{kappa}B is constitutively activated in various tumor cells where it promotes proliferation and represses apoptosis. The bone morphogenetic proteins (BMPs) delay cell proliferation and promote differentiation and apoptosis of bone cells through activation of Smad downstream effectors and via Smad-independent mechanisms. Thus, NF{kappa}B and BMP pathways play opposing roles in regulating osteoblastic cell fate. Here, we show that in osteosarcoma Saos2 osteoblasts, NF{kappa}B regulates the activity of the BMP/Smad signaling. Inhibition of NF{kappa}B by overexpression of mI{kappa}B leads to the induction of osteoblast differentiation. Saos2 cells overexpressing mI{kappa}B (Saos2-mI{kappa}B) exhibit higher expression of osteoblast phenotypic genes suchmore » as alkaline phosphatase, Runx2 and osteocalcin and are more responsive to BMP2 in comparison to wild-type cells (Saos2-wt) or empty vector infected controls (Saos2-EV). Furthermore, BMP-2 signaling and Smad phosphorylation are significantly increased in Saos2-mI{kappa}B cells in comparison to Saos2-EV cells. Inhibition of NF{kappa}B signaling in Saos2-mI{kappa}B cells is associated with decreased expression of the BMP signaling inhibitor Smad7. While gain of Smad7 function in Saos2-mI{kappa}B cells results in inhibition of BMP signaling, anti-sense knockdown of Smad7 in Saos2-EV cells leads to upregulation of BMP signaling. We therefore conclude that in osteosarcoma Saos2 cells, NF{kappa}B represses BMP/Smad signaling and BMP2-induced differentiation through Smad7.« less

Combustion synthesis of AlB2-Al2O3 composite powders with AlB2 nanowire structures

NASA Astrophysics Data System (ADS)

Yang, Pan; Xiao, Guoqing; Ding, Donghai; Ren, Yun; Yang, Shoulei; Lv, Lihua; Hou, Xing

2018-05-01

Using of Al and B2O3 powders as starting materials, and Mg-Al alloy as additives, AlB2-Al2O3 composite powders with AlB2 nanowire structures were successfully fabricated via combustion synthesis method in Ar atmosphere at a pressure of 1.5 MPa. The effect of different amount of Mg-Al alloy on the phase compositions and morphology of the combustion products was investigated. The results revealed that AlB2 and Al2O3 increased, whereas Al decreased with the content of Mg-Al alloy increasing. The impurities MgAl2O4 and AlB12 would exist in the sample with adding of 18 wt% Mg-Al alloy. Interestingly, FESEM/TEM/EDS results showed that AlB2 nanowires were observed in the products when the content of Mg-Al alloy is 6 wt% and 12 wt%. The more AlB2 nanowires can be found as the content of Mg-Al alloy increased. And the yield of AlB2 nanowires with the diameter of about 200 nanometers (nm) and the length up to several tens of micrometers (μm) in the combustion product is highest when the content of Mg-Al alloy is 12 wt%. The vapor, such as Mg-Al (g), B2O2 (g), AlO (g) and Al2O (g), produced during the process of combustion synthesis, reacted with each other to yield AlB2 nanowires by vapor-solid (VS) mechanism and the corresponding model was also proposed.

Electrodynamic properties of the semimetallic Dirac material SrMnB i2 : Two-carrier-model analysis

NASA Astrophysics Data System (ADS)

Park, H. J.; Park, Byung Cheol; Lee, Min-Cheol; Jeong, D. W.; Park, Joonbum; Kim, Jun Sung; Ji, Hyo Seok; Shim, J. H.; Kim, K. W.; Moon, S. J.; Kim, Hyeong-Do; Cho, Deok-Yong; Noh, T. W.

2017-10-01

The electrodynamics of free carriers in the semimetallic Dirac material SrMnB i2 was investigated using optical spectroscopy and first-principles calculations. Using a two-carrier-model analysis, the total free-carrier response was successfully decomposed into individual contributions from Dirac fermions and non-Dirac free carriers. Possible roles of chiral pseudospin, spin-orbit interaction (SOI), antiferromagnetism, and electron-phonon (e -p h ) coupling in the Dirac fermion transport were also addressed. The Dirac fermions possess a low scattering rate of ˜10 meV at low temperature and thereby experience coherent transport. However, at high temperatures, we observed that the Dirac fermion transport becomes significantly incoherent, possibly due to strong e -p h interactions. The SOI-induced gap and antiferromagnetism play minor roles in the electrodynamics of the free carriers in SrMnB i2 . We also observed a seemingly optical-gap-like feature near 120 meV, which emerges at low temperatures but becomes filled in with increasing temperature. This gap-filling phenomenon is ascribed to phonon-assisted indirect transitions promoted at high temperatures.

The selectivity of conantokin-G for ion channel inhibition of NR2B subunit-containing NMDA receptors is regulated by amino acid residues in the S2 region of NR2B

PubMed Central

Sheng, Zhenyu; Liang, Zhong; Geiger, James H.; Prorok, Mary; Castellino, Francis J.

2009-01-01

The conantokins are short, naturally-occurring peptides that inhibit ion flow through N-methyl-D-aspartate receptor (NMDAR) channels. One member of this peptide family, conantokin-G (con-G), specifically antagonizes NR2B-containing NMDAR channels, whereas other known conantokins are less selective inhibitors with regard to the nature of the NR2 subunit of the NMDAR complex. In order to define the molecular determinants of NR2B that govern con-G selectivity, we evaluated the ability of con-G to inhibit NMDAR ion channels expressed in human embryonic kidney (HEK)293 cells transfected with NR1, in combination with various NR2A/2B chimeras and point mutants, by electrophysiology using cells voltage-clamped in the whole cell configuration. We found that a variant of the con-G-insensitive subunit, NR2A, in which the 158 residues comprising the S2 peptide segment (E657-I814) were replaced by the corresponding S2 region of NR2B (E658-I815), results in receptors that are highly sensitive to inhibition by con-G. Of the 22 amino acids that are different between the NR2A-S2 and the NR2B-S2 regions, exchange of one of these, M739 of NR2B for the equivalent K738 of NR2A, was sufficient to completely import the inhibitory activity of con-G into NR1b/NR2A-containing NMDARs. Some reinforcement of this effect was found by substitution of a second amino acid, K755 of NR2B for Y754 of NR2A. The discovery of the molecular determinants of NR2B selectivity with con-G has implications for the design of subunit-selective neurobiological probes and drug therapies, in addition to advancing our understanding of NR2B- versus NR2A-mediated neurological processes. PMID:19427876

Word Frequency Analysis. MOS: 12B. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

2 BURNING 16 RURNS 1 9 BJRRS- I BUP $I-ON-TARGET 9 5UJR STE R 2 RP ES I PIG PU 1 UR S11 N-TVPE...TV f 37 SHJFT ?7 STAKES 37 SUPPORT 37 SITMM 36 ADJUSTMrNT ?b.. 36 ATTACII 36- BEING .... 36 P . .. It# OIKP TIfOt 36 EXPOSED 36 IAW 16 I NSTRUICT IONS...APPENDIX lb ARTIFICIAL 16 ASSEPRLED . 6 ASLFC 16 BREAK 16 BREECH 16 BURNS 16 CA D 16 CLEARED --- to ELcCERISr- - --- -CVRT ( lb -UUI(OT ONNECTCR 1b

Cyclometalated products of [(COE)(2)RhCl](2) and 1,3-(RSCH(2))(2)C(6)H(4) (R = (t)Bu, (i)Pr) Are Dimeric. Synthesis, molecular structures, and solution dynamics of [mu-ClRh(H)(RSCH(2))(2)C(6)H(3)-2,6](2).

PubMed

Evans, Daniel R; Huang, Mingsheng; Seganish, W Michael; Chege, Esther W; Lam, Yiu-Fai; Fettinger, James C; Williams, Tracie L

2002-05-20

Two tridentate thioether pincer ligands, 1,3-(RSCH(2))(2)C(6)H(4) (R = (t)()Bu, 1a; R = (i)()Pr, 1b) underwent cyclometalation using [(COE)(2)RhCl](2) in air/moisture-free benzene at room temperature. The resultant complexes, [mu-ClRh(H)(RSCH(2))(2)C(6)H(3)-2,6](2) (R = (t)Bu, 2a; R = (i)Pr, 2b) are dimeric both in the solid state and in solution. A battery of variable-temperature one- and two-dimensional (1)H NMR experiments showed conclusively that both complexes undergo dynamic exchange in solution. Exchange between two dimeric diastereomers of 2a in solution occurred via rotation about the Rh-C(ipso) bond. The dynamic exchange of 2b was significantly more complex as an additional exchange mechanism, sulfur inversion, occurred, which resulted in the exchange between several diastereomers in solution.

Comparison of Caenorhabditis elegans NLP peptides with arthropod neuropeptides.

PubMed

Husson, Steven J; Lindemans, Marleen; Janssen, Tom; Schoofs, Liliane

2009-04-01

Neuropeptides are small messenger molecules that can be found in all metazoans, where they govern a diverse array of physiological processes. Because neuropeptides seem to be conserved among pest species, selected peptides can be considered as attractive targets for drug discovery. Much can be learned from the model system Caenorhabditis elegans because of the availability of a sequenced genome and state-of-the-art postgenomic technologies that enable characterization of endogenous peptides derived from neuropeptide-like protein (NLP) precursors. Here, we provide an overview of the NLP peptide family in C. elegans and discuss their resemblance with arthropod neuropeptides and their relevance for anthelmintic discovery.

Centrosomal Nlp is an oncogenic protein that is gene-amplified in human tumors and causes spontaneous tumorigenesis in transgenic mice

PubMed Central

Shao, Shujuan; Liu, Rong; Wang, Yang; Song, Yongmei; Zuo, Lihui; Xue, Liyan; Lu, Ning; Hou, Ning; Wang, Mingrong; Yang, Xiao; Zhan, Qimin

2010-01-01

Disruption of mitotic events contributes greatly to genomic instability and results in mutator phenotypes. Indeed, abnormalities of mitotic components are closely associated with malignant transformation and tumorigenesis. Here we show that ninein-like protein (Nlp), a recently identified BRCA1-associated centrosomal protein involved in microtubule nucleation and spindle formation, is an oncogenic protein. Nlp was found to be overexpressed in approximately 80% of human breast and lung carcinomas analyzed. In human lung cancers, this deregulated expression was associated with NLP gene amplification. Further analysis revealed that Nlp exhibited strong oncogenic properties; for example, it conferred to NIH3T3 rodent fibroblasts the capacity for anchorage-independent growth in vitro and tumor formation in nude mice. Consistent with these data, transgenic mice overexpressing Nlp displayed spontaneous tumorigenesis in the breast, ovary, and testicle within 60 weeks. In addition, Nlp overexpression induced more rapid onset of radiation-induced lymphoma. Furthermore, mouse embryonic fibroblasts (MEFs) derived from Nlp transgenic mice showed centrosome amplification, suggesting that Nlp overexpression mimics BRCA1 loss. These findings demonstrate that Nlp abnormalities may contribute to genomic instability and tumorigenesis and suggest that Nlp might serve as a potential biomarker for clinical diagnosis and therapeutic target. PMID:20093778

Predicate Matching in NLP: A Review of Research on the Preferred Representational System.

ERIC Educational Resources Information Center

Sharpley, Christopher F.

1984-01-01

Reviews 15 studies that have investigated the use of the Preferred Representational System (PRS) in Neurolinguistic Programming (NLP). Aspects of design, methodology, population and dependent measures are evaluated, with comments on the outcomes obtained. Results suggested that there is little supportive evidence for the use of PRS in the NLP.…

NLP as a communication strategy tool in libraries

NASA Astrophysics Data System (ADS)

Koulouris, Alexandros; Sakas, Damianos P.; Giannakopoulos, Georgios

2015-02-01

The role of communication is a catalyst for the proper function of an organization. This paper focuses on libraries, where the communication is crucial for their success. In our opinion, libraries in Greece are suffering from the lack of communication and marketing strategy. Communication has many forms and manifestations. A key aspect of communication is body language, which has a dominant communication tool the neuro-linguistic programming (NLP). The body language is a system that expresses and transfers messages, thoughts and emotions. More and more organizations in the public sector and companies in the private sector base their success on the communication skills of their personnel. The NLP suggests several methods to obtain excellent relations in the workplace and to develop ideal communication. The NLP theory is mainly based on the development of standards (communication model) that guarantees the expected results. This research was conducted and analyzed in two parts, the qualitative and the quantitative. The findings mainly confirm the need for proper communication within libraries. In the qualitative research, the interviewees were aware of communication issues, although some gaps in that knowledge were observed. Even this slightly lack of knowledge, highlights the need for constant information through educational programs. This is particularly necessary for senior executives of libraries, who should attend relevant seminars and refresh their knowledge on communication related issues.

Chain Reaction Mechanism for I2 Dissociation in the O2 (1 delta)-I Atom Laser.

DTIC Science & Technology

1983-09-20

The principal injected gases in this study were 12 (+Ar) and H2 0(+.Ar). We continue to use the method of flow replacement, whereby a pure Ar stream...conditions exist for small H20 densities. The identification of intermediate states in a kinetic mechanist b. indirect methods is always unsatisfactory...and e.’Irr-’tr1,ic o ""n"a i : n es a ppl ele-Ic- trcon i cs, senienndoztor cry" stal1 and itevice :1-i. , radi -metci, ima ’In4; -’ i’ -t er- wace

Co-Targeting HER2 and EphB4 Pathways

DTIC Science & Technology

2013-09-01

soluble EphB4 decoy receptor that efficiently blocks EphB4/EphB2 signaling. A phase I study for solid tumors using this agent given intravenously...June 2013 3 . DATES COVERED 4. TITLE AND SUBTITLE Co-Targeting HER2 and EphB4 Pathways 5a. CONTRACT NUMBER W81XWH-11-1-0471 5b. GRANT...13. SUPPLEMENTARY NOTES 14. ABSTRACT Multiple receptor pathways allow for redundancy in growth pathways that are dysregulated in cancer and lead to

Lycorine inhibits lipopolysaccharide-induced iNOS and COX-2 up-regulation in RAW264.7 cells through suppressing P38 and STATs activation and increases the survival rate of mice after LPS challenge.

PubMed

Kang, Jingjing; Zhang, Yushun; Cao, Xiang; Fan, Jie; Li, Guilan; Wang, Qi; Diao, Ying; Zhao, Zhihui; Luo, Lan; Yin, Zhimin

2012-01-01

As a natural alkaloid extracted from Amaryllidaceae, lycorine shows various biological effects on tumor cells. Here we show that lycorine dose-dependently inhibited the LPS-induced up-regulation of nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein level in RAW264.7 cells. Besides, it also inhibited NO, PGE(2), TNF-α and IL-6 release from LPS-treated RAW264.7 cells. RT-PCR experiments showed that lycorine suppressed LPS-induced iNOS but not COX-2 gene expression. Moreover, lycorine decreased LPS-induced mortality in mice. Mechanistically, LPS-induced activation of P38 and STATs pathways was suppressed significantly by lycorine. In addition, lycorine did not interfere with the phosphorylation of ERK1/2, JNK1/2 and NF-κB pathways. In conclusion, lycorine inhibits LPS-induced production of pro-inflammatory mediators and increases the survival rate of mice after LPS challenge, suggesting that lycorine could play an anti-inflammatory role in response to LPS. Copyright © 2011 Elsevier B.V. All rights reserved.

Improved potentials and Born-Oppenheimer corrections by new measurements of transitions of 129I2 and 127I 129I in the B3 Pi_O^+_u - X1 Σ^+_g band system

NASA Astrophysics Data System (ADS)

Salumbides, E. J.; Eikema, K. S. E.; Ubachs, W.; Hollenstein, U.; Knöckel, H.; Tiemann, E.

2008-04-01

The light from one single frequency cw laser was employed in a double saturation spectroscopy experiment to record high resolution spectra of 129I2 and 127I129I together with spectra of 127I2 which is used as a simultaneous frequency reference. Two separate saturation spectroscopy set ups were used. The frequencies of lines of 129I2 and 127I129I were determined with respect to lines of 127I2. More than 380 frequency differences between lines of 127I2 and of the other isotopomers have been included in the data set. By a direct potential fit a precise description of the potential energy curves of the B and the X state and of effective Born-Oppenheimer correction functions valid for all three isotopomers of I2 are given.

C3-PRO: Connecting ResearchKit to the Health System Using i2b2 and FHIR.

PubMed

Pfiffner, Pascal B; Pinyol, Isaac; Natter, Marc D; Mandl, Kenneth D

2016-01-01

A renewed interest by consumer information technology giants in the healthcare domain is focused on transforming smartphones into personal health data storage devices. With the introduction of the open source ResearchKit, Apple provides a framework for researchers to inform and consent research subjects, and to readily collect personal health data and patient reported outcomes (PRO) from distributed populations. However, being research backend agnostic, ResearchKit does not provide data transmission facilities, leaving research apps disconnected from the health system. Personal health data and PROs are of the most value when presented in context along with health system data. Our aim was to build a toolchain that allows easy and secure integration of personal health and PRO data into an open source platform widely adopted across 140 academic medical centers. We present C3-PRO: the Consent, Contact, and Community framework for Patient Reported Outcomes. This open source toolchain connects, in a standards-compliant fashion, any ResearchKit app to the widely-used clinical research infrastructure Informatics for Integrating Biology and the Bedside (i2b2). C3-PRO leverages the emerging health data standard Fast Healthcare Interoperability Resources (FHIR).

C3-PRO: Connecting ResearchKit to the Health System Using i2b2 and FHIR

PubMed Central

Pfiffner, Pascal B.; Pinyol, Isaac; Natter, Marc D.; Mandl, Kenneth D.

2016-01-01

A renewed interest by consumer information technology giants in the healthcare domain is focused on transforming smartphones into personal health data storage devices. With the introduction of the open source ResearchKit, Apple provides a framework for researchers to inform and consent research subjects, and to readily collect personal health data and patient reported outcomes (PRO) from distributed populations. However, being research backend agnostic, ResearchKit does not provide data transmission facilities, leaving research apps disconnected from the health system. Personal health data and PROs are of the most value when presented in context along with health system data. Our aim was to build a toolchain that allows easy and secure integration of personal health and PRO data into an open source platform widely adopted across 140 academic medical centers. We present C3-PRO: the Consent, Contact, and Community framework for Patient Reported Outcomes. This open source toolchain connects, in a standards-compliant fashion, any ResearchKit app to the widely-used clinical research infrastructure Informatics for Integrating Biology and the Bedside (i2b2). C3-PRO leverages the emerging health data standard Fast Healthcare Interoperability Resources (FHIR). PMID:27031856

Flow Simulation of N2B Hybrid Wing Body Configuration

NASA Technical Reports Server (NTRS)

Kim, Hyoungjin; Liou, Meng-Sing

2012-01-01

The N2B hybrid wing body aircraft was conceptually designed to meet environmental and performance goals for the N+2 generation transport set by the subsonic fixed wing project. In this study, flow fields around the N2B configuration is simulated using a Reynolds-averaged Navier-Stokes flow solver using unstructured meshes. Boundary conditions at engine fan face and nozzle exhaust planes are provided by response surfaces of the NPSS thermodynamic engine cycle model. The present flow simulations reveal challenging design issues arising from boundary layer ingestion offset inlet and nacelle-airframe interference. The N2B configuration can be a good test bed for application of multidisciplinary design optimization technology.

Textured Nd2Fe14B flakes with enhanced coercivity

NASA Astrophysics Data System (ADS)

Cui, B. Z.; Zheng, L. Y.; Marinescu, M.; Liu, J. F.; Hadjipanayis, G. C.

2012-04-01

Morphology, structure, and magnetic properties of the [001] textured Nd2Fe14B nanocrystalline flakes prepared by surfactant-assisted high energy ball milling (HEBM) and subsequent annealing were studied. These flakes have a thickness of 80-200 nm, a length of 0.5-10 μm, and an average grain size of 10-14 nm. The addition of some amount of Dy, Nd70Cu30 alloy, and an appropriate post annealing increased the coercivity iHc of the Nd2Fe14B flakes. iHc was 3.7, 4.3, and 5.7 kOe for the Nd15.5Fe78.5B6, Nd14Dy1.5Fe78.5B6 and 83.3 wt.% Nd14Dy1.5Fe78.5B6 + 16.7 wt.% Nd70Cu30 flakes prepared by HEBM for 5 h in heptane with 20 wt.% oleylamine, respectively. After annealing at 450 °C for 0.5 h, their iHc increased to 5.1, 6.2, and 7.0 kOe, respectively. Anisotropic magnetic behavior was found in all of the as-milled and annealed flakes. Both, the thickening of Nd-rich phase at grain boundaries via diffusion of Nd70Cu30 and the surface modification of the Nd2Fe14B flake could be the main reasons for the coercivity enhancement in the as-milled and annealed Nd70Cu30-added Nd2Fe14B flakes.

Using the Internet for B2B Activities: A Review and Future Directions for Research.

ERIC Educational Resources Information Center

Gattiker, Urs E.; Perlusz, Stefano; Bohmann, Kristoffer

2000-01-01

Illustrates some of the challenges that electronic commerce practitioners and researchers face, focusing on business to business (B2B) transactions. Highlights include a conceptual framework of Web user behavior; purchasing context; socio-demographic characteristics; cultural factors; economic factors; attitudes toward information technology;…

Grb2 regulates B-cell maturation, B-cell memory responses and inhibits B-cell Ca2+ signalling.

PubMed

Ackermann, Jochen A; Radtke, Daniel; Maurberger, Anna; Winkler, Thomas H; Nitschke, Lars

2011-04-20

Grb2 is a ubiquitously expressed adaptor protein, which activates Ras and MAP kinases in growth factor receptor signalling, while in B-cell receptor (BCR) signalling this role is controversial. In B cell lines it was shown that Grb2 can inhibit BCR-induced Ca(2+) signalling. Nonetheless, the physiological role of Grb2 in primary B cells is still unknown. We generated a B-cell-specific Grb2-deficient mouse line, which had a severe reduction of mature follicular B cells in the periphery due to a differentiation block and decreased B-cell survival. Moreover, we found several changes in important signalling pathways: enhanced BCR-induced Ca(2+) signalling, alterations in mitogen-activated protein kinase activation patterns and strongly impaired Akt activation, the latter pointing towards a defect in PI3K signalling. Interestingly, B-cell-specific Grb2-deficient mice showed impaired IgG and B-cell memory responses, and impaired germinal centre formation. Thus, Grb2-dependent signalling pathways are crucial for lymphocyte differentiation processes, as well as for control of secondary humoral immune responses.

30 CFR 203.2 - How can I obtain royalty relief?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 2 2011-07-01 2011-07-01 false How can I obtain royalty relief? 203.2 Section....2 How can I obtain royalty relief? We may reduce or suspend royalties for Outer Continental Shelf... production. (See §§ 203.50 through 203.56.) (b) Located in a designated GOM deep water area (i.e., 200 meters...

Rare ADAR and RNASEH2B variants and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis.

PubMed

Beyer, Ulrike; Brand, Frank; Martens, Helge; Weder, Julia; Christians, Arne; Elyan, Natalie; Hentschel, Bettina; Westphal, Manfred; Schackert, Gabriele; Pietsch, Torsten; Hong, Bujung; Krauss, Joachim K; Samii, Amir; Raab, Peter; Das, Anibh; Dumitru, Claudia A; Sandalcioglu, I Erol; Hakenberg, Oliver W; Erbersdobler, Andreas; Lehmann, Ulrich; Reifenberger, Guido; Weller, Michael; Reijns, Martin A M; Preller, Matthias; Wiese, Bettina; Hartmann, Christian; Weber, Ruthild G

2017-12-01

In search of novel germline alterations predisposing to tumors, in particular to gliomas, we studied a family with two brothers affected by anaplastic gliomas, and their father and paternal great-uncle diagnosed with prostate carcinoma. In this family, whole-exome sequencing yielded rare, simultaneously heterozygous variants in the Aicardi-Goutières syndrome (AGS) genes ADAR and RNASEH2B co-segregating with the tumor phenotype. AGS is a genetically induced inflammatory disease particularly of the brain, which has not been associated with a consistently increased cancer risk to date. By targeted sequencing, we identified novel ADAR and RNASEH2B variants, and a 3- to 17-fold frequency increase of the AGS mutations ADAR,c.577C>G;p.(P193A) and RNASEH2B,c.529G>A;p.(A177T) in the germline of familial glioma patients as well as in test and validation cohorts of glioblastomas and prostate carcinomas versus ethnicity-matched controls, whereby rare RNASEH2B variants were significantly more frequent in familial glioma patients. Tumors with ADAR or RNASEH2B variants recapitulated features of AGS, such as calcification and increased type I interferon expression. Patients carrying ADAR or RNASEH2B variants showed upregulation of interferon-stimulated gene (ISG) transcripts in peripheral blood as seen in AGS. An increased ISG expression was also induced by ADAR and RNASEH2B variants in tumor cells and was blocked by the JAK inhibitor Ruxolitinib. Our data implicate rare variants in the AGS genes ADAR and RNASEH2B and a type I interferon signature in glioma and prostate carcinoma risk and tumorigenesis, consistent with a genetic basis underlying inflammation-driven malignant transformation in glioma and prostate carcinoma development.

Phase and Physicochemical Properties Diagrams of Quaternary System Li2B4O7 + Na2B4O7 + Mg2B6O11 + H2O

NASA Astrophysics Data System (ADS)

Wang, Shi-qiang; Du, Xue-min; Jing, Yan; Guo, Ya-fei; Deng, Tian-long

2017-12-01

The phase and physicochemical properties diagrams of the quaternary system (Li2B4O7 + Na2B4O7 + Mg2B6O11) at 288.15 K and 0.1 MPa were constructed using the solubilities, densities, and refractive indices measured. In the phase diagrams of the system there are one invariant point, three univariant isothermic dissolution curves, and three crystallization regions corresponding to Li2B4O7 · 3H2O, Na2B4O7 · 10H2O, and Mg2B6O11 · 15H2O, respectively. The solution density, refractive index of the quaternary system changes regularly with the increasing of Li2B4O7 concentration. The calculated values of density and refractive index using empirical equations of the quaternary system are in good agreement with the experimental values.

Department of Defense Materiel Distribution System Study. Volume 3, Book 2. Appendices A, B and C

DTIC Science & Technology

1978-07-01

i . Oil .362 .00 382 13 971 13 .879,230 .00 1 .29b , 168 .00 38M 106 78b 61 . 719,799 .00 1,281 .136 .00 386 18...7 2 1302 Oil oJ7 b3V 1 73 bb2 b16 b 1 I bVU 803 127 bOO 612 326 16U V36 bbD 3b3 212 VI 1 2ib 0rt3 b6b 7V0 ObV 1 30 b7 1 82... luv 1 10 I I I 1 1 i 1 I J I I N 1 lb 1 1 6 1 I / 1 1 I ) 1 I "

Inappropriate Expression of an NLP Effector in Colletotrichum orbiculare Impairs Infection on Cucurbitaceae Cultivars via Plant Recognition of the C-Terminal Region.

PubMed

Azmi, Nur Sabrina Ahmad; Singkaravanit-Ogawa, Suthitar; Ikeda, Kyoko; Kitakura, Saeko; Inoue, Yoshihiro; Narusaka, Yoshihiro; Shirasu, Ken; Kaido, Masanori; Mise, Kazuyuki; Takano, Yoshitaka

2018-01-01

The hemibiotrophic pathogen Colletotrichum orbiculare preferentially expresses a necrosis and ethylene-inducing peptide 1 (Nep1)-like protein named NLP1 during the switch to necrotrophy. Here, we report that the constitutive expression of NLP1 in C. orbiculare blocks pathogen infection in multiple Cucurbitaceae cultivars via their enhanced defense responses. NLP1 has a cytotoxic activity that induces cell death in Nicotiana benthamiana. However, C. orbiculare transgenic lines constitutively expressing a mutant NLP1 lacking the cytotoxic activity still failed to infect cucumber, indicating no clear relationship between cytotoxic activity and the NLP1-dependent enhanced defense. NLP1 also possesses the microbe-associated molecular pattern (MAMP) sequence called nlp24, recognized by Arabidopsis thaliana at its central region, similar to NLPs of other pathogens. Surprisingly, inappropriate expression of a mutant NLP1 lacking the MAMP signature is also effective for blocking pathogen infection, uncoupling the infection block from the corresponding MAMP. Notably, the deletion analyses of NLP1 suggested that the C-terminal region of NLP1 is critical to enhance defense in cucumber. The expression of mCherry fused with the C-terminal 32 amino acids of NLP1 was enough to trigger the defense of cucurbits, revealing that the C-terminal region of the NLP1 protein is recognized by cucurbits and, then, terminates C. orbiculare infection.

Identification of a second binding site on the TRIM25 B30.2 domain.

PubMed

D'Cruz, Akshay A; Kershaw, Nadia J; Hayman, Thomas J; Linossi, Edmond M; Chiang, Jessica J; Wang, May K; Dagley, Laura F; Kolesnik, Tatiana B; Zhang, Jian-Guo; Masters, Seth L; Griffin, Michael D W; Gack, Michaela U; Murphy, James M; Nicola, Nicos A; Babon, Jeffrey J; Nicholson, Sandra E

2018-01-23

The r etinoic acid- i nducible g ene- I (RIG-I) receptor recognizes short 5'-di- and triphosphate base-paired viral RNA and is a critical mediator of the innate immune response against viruses such as influenza A, Ebola, HIV and hepatitis C. This response is reported to require an orchestrated interaction with the tri partite m otif 25 (TRIM25) B30.2 protein-interaction domain. Here, we present a novel second RIG-I-binding interface on the TRIM25 B30.2 domain that interacts with CARD1 and CARD2 ( c aspase a ctivation and r ecruitment d omains) of RIG-I and is revealed by the removal of an N-terminal α-helix that mimics dimerization of the full-length protein. Further characterization of the TRIM25 coiled-coil and B30.2 regions indicated that the B30.2 domains move freely on a flexible tether, facilitating RIG-I CARD recruitment. The identification of a dual binding mode for the TRIM25 B30.2 domain is a first for the SPRY/B30.2 domain family and may be a feature of other SPRY/B30.2 family members. © 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

A Live-Attenuated Chimeric Porcine Circovirus Type 2 (PCV2) Vaccine Is Transmitted to Contact Pigs but Is Not Upregulated by Concurrent Infection with Porcine Parvovirus (PPV) and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) and Is Efficacious in a PCV2b-PRRSV-PPV Challenge Model▿

PubMed Central

Opriessnig, T.; Shen, H. G.; Pal, N.; Ramamoorthy, S.; Huang, Y. W.; Lager, K. M.; Beach, N. M.; Halbur, P. G.; Meng, X. J.

2011-01-01

The live chimeric porcine circovirus type 2 (PCV2) vaccine with the capsid gene of the emerging subtype 2b cloned in the genomic backbone of the nonpathogenic PCV1 is attenuated in vivo and induces protective immunity against PCV2. To further determine the safety and efficacy of this experimental vaccine, we tested for evidence of pig-to-pig transmission by commingling nonvaccinated and vaccinated pigs, determined potential upregulation by simultaneous vaccination and infection with porcine parvovirus (PPV) and porcine reproductive and respiratory syndrome virus (PRRSV), and determined vaccine efficacy by challenging pigs 4 weeks after vaccination with PCV2b, PRRSV, and PPV. Forty-six 21-day-old, PCV2-naïve pigs were randomly assigned to one of six groups. Twenty-nine of 46 pigs were challenged with PCV2b, PRRSV, and PPV at day 28, 8/46 remained nonvaccinated and nonchallenged and served as negative controls, and 9/46 remained nonchallenged and served as vaccination controls. All animals were necropsied at day 49. PCV1-PCV2 viremia was detected in nonvaccinated contact pigs commingled with vaccinated pigs, indicating pig-to-pig transmission; however, PCV1-PCV2 DNA levels remained low in all vaccinated and contact pigs regardless of concurrent infection. Finally, vaccination 28 days before challenge resulted in significantly (P < 0.05) decreased amounts of PCV2 in tissues and sera and significantly (P < 0.05) reduced macroscopic and microscopic lesions. The results of this study indicate that the experimental live-attenuated chimeric PCV2 vaccine, although transmissible to contact pigs, remains attenuated in pigs concurrently infected with PRRSV and PPV and induces protective immunity against PCV2b when it is administered 28 days before PCV2 exposure. PMID:21653745

A live-attenuated chimeric porcine circovirus type 2 (PCV2) vaccine is transmitted to contact pigs but is not upregulated by concurrent infection with porcine parvovirus (PPV) and porcine reproductive and respiratory syndrome virus (PRRSV) and is efficacious in a PCV2b-PRRSV-PPV challenge model.

PubMed

Opriessnig, T; Shen, H G; Pal, N; Ramamoorthy, S; Huang, Y W; Lager, K M; Beach, N M; Halbur, P G; Meng, X J

2011-08-01

The live chimeric porcine circovirus type 2 (PCV2) vaccine with the capsid gene of the emerging subtype 2b cloned in the genomic backbone of the nonpathogenic PCV1 is attenuated in vivo and induces protective immunity against PCV2. To further determine the safety and efficacy of this experimental vaccine, we tested for evidence of pig-to-pig transmission by commingling nonvaccinated and vaccinated pigs, determined potential upregulation by simultaneous vaccination and infection with porcine parvovirus (PPV) and porcine reproductive and respiratory syndrome virus (PRRSV), and determined vaccine efficacy by challenging pigs 4 weeks after vaccination with PCV2b, PRRSV, and PPV. Forty-six 21-day-old, PCV2-naïve pigs were randomly assigned to one of six groups. Twenty-nine of 46 pigs were challenged with PCV2b, PRRSV, and PPV at day 28, 8/46 remained nonvaccinated and nonchallenged and served as negative controls, and 9/46 remained nonchallenged and served as vaccination controls. All animals were necropsied at day 49. PCV1-PCV2 viremia was detected in nonvaccinated contact pigs commingled with vaccinated pigs, indicating pig-to-pig transmission; however, PCV1-PCV2 DNA levels remained low in all vaccinated and contact pigs regardless of concurrent infection. Finally, vaccination 28 days before challenge resulted in significantly (P < 0.05) decreased amounts of PCV2 in tissues and sera and significantly (P < 0.05) reduced macroscopic and microscopic lesions. The results of this study indicate that the experimental live-attenuated chimeric PCV2 vaccine, although transmissible to contact pigs, remains attenuated in pigs concurrently infected with PRRSV and PPV and induces protective immunity against PCV2b when it is administered 28 days before PCV2 exposure.

Involvement of I-A-restricted B-B cell interaction in the polyclonal B cell differentiation induced by lipopolysaccharide

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

Takahama, Y.; Ono, S.; Ishihara, K.

1990-01-01

The present study has examined a functional role of Ia molecules expressed on murine B cells in polyclonal B cell differentiation induced by lipopolysaccharide (LPS). Reverse, IgM PFC responses of unprimed B cells induced by LPS in the apparent absence of T cells and adherent accessory cells were markedly inhibited in a haplotype-specific manner by Fab monomer fragment of anti-class II (Ia) but not anti-class I MHC monoclonal antibody (mAb). However, the degree of inhibition of LPS responses of H-2-heterozygous F1 B cells expressing both parental I-A products by either one of anti-I-A mAb was at best half that ofmore » the parental B cells. Interestingly, when (B10 x B10.-BR)F1 (H-2b/k) B cells were fractionated into adherent and nonadherent populations by their ability to bind to parental B10 B cell monolayers, LPS responses of F1 B cells adherent to and nonadherent to the B10 B cell monolayers were selectively inhibited by anti-I-Ab and anti-I-Ak mAb, respectively. These results suggest that LPS-responsive F1 B cells comprise at least two separate populations with restriction specificity for only one of the parental I-A products expressed on B cells. In addition, it was demonstrated that the I-A-restriction specificity of LPS-responsive B cells is plastic and determined by H-2-genotype of bone marrow cells present during B cell ontogeny but not by that of radiation-resistant host elements. Namely, the LPS responses of B10-derived B cells from (B10 + B10.BR) (H-2b x H - 2k)F1 radiation bone marrow chimeras but not from B10 (H-2b x H-2k)F1 chimeras became sensitive to the inhibition of anti-I-Ak mAb in the presence of mitomycin C-treated I-Ak-positive B cells, supporting a notion of receptor-Ia molecules interactions rather than like-like interactions.« less

Stronger enhancer II/core promoter activities of hepatitis B virus isolates of B2 subgenotype than those of C2 subgenotype

PubMed Central

Qin, Yanli; Zhou, Xueshi; Jia, Haodi; Chen, Chaoyang; Zhao, Weifeng; Zhang, Jiming; Tong, Shuping

2016-01-01

Hepatitis B virus (HBV) genotype C causes prolonged chronic infection and increased risk for liver cancer than genotype B. Our previous work revealed lower replication capacity of wild-type genotype C2 than B2 isolates. HBV DNA replication is driven by pregenomic RNA, which is controlled by core promoter (CP) and further augmented by enhancer I (ENI) and enhancer II (ENII). DNA fragments covering these regulatory elements were amplified from B2 and C2 isolates to generate luciferase reporter constructs. As ENII is fully embedded in CP, we inserted HBV DNA fragments in the sense orientation to determine their combined activities, and in the antisense orientation to measure enhancer activities alone. Genotype B2 isolates displayed higher ENI+ENII+CP, ENII+CP, and ENII activities, but not ENI or ENI+ENII activity, than C2 isolates. The higher ENII+CP activity was partly attributable to 4 positions displaying genotype-specific variability. Exchanging CP region was sufficient to revert the replication phenotypes of several B2 and C2 clones tested. These results suggest that a weaker ENII and/or CP at least partly accounts for the lower replication capacities of wild-type C2 isolates, which could drive the subsequent acquisition of CP mutations. Such mutations increase genome replication and are implicated in liver cancer development. PMID:27461034

Stronger enhancer II/core promoter activities of hepatitis B virus isolates of B2 subgenotype than those of C2 subgenotype.

PubMed

Qin, Yanli; Zhou, Xueshi; Jia, Haodi; Chen, Chaoyang; Zhao, Weifeng; Zhang, Jiming; Tong, Shuping

2016-07-27

Hepatitis B virus (HBV) genotype C causes prolonged chronic infection and increased risk for liver cancer than genotype B. Our previous work revealed lower replication capacity of wild-type genotype C2 than B2 isolates. HBV DNA replication is driven by pregenomic RNA, which is controlled by core promoter (CP) and further augmented by enhancer I (ENI) and enhancer II (ENII). DNA fragments covering these regulatory elements were amplified from B2 and C2 isolates to generate luciferase reporter constructs. As ENII is fully embedded in CP, we inserted HBV DNA fragments in the sense orientation to determine their combined activities, and in the antisense orientation to measure enhancer activities alone. Genotype B2 isolates displayed higher ENI+ENII+CP, ENII+CP, and ENII activities, but not ENI or ENI+ENII activity, than C2 isolates. The higher ENII+CP activity was partly attributable to 4 positions displaying genotype-specific variability. Exchanging CP region was sufficient to revert the replication phenotypes of several B2 and C2 clones tested. These results suggest that a weaker ENII and/or CP at least partly accounts for the lower replication capacities of wild-type C2 isolates, which could drive the subsequent acquisition of CP mutations. Such mutations increase genome replication and are implicated in liver cancer development.

ST2 suppresses IL-6 production via the inhibition of I{kappa}B degradation induced by the LPS signal in THP-1 cells

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

Takezako, Naoki; Hayakawa, Morisada; Hayakawa, Hiroko

2006-03-10

LPS induces the production of inflammatory cytokines via the stimulation of Toll-like receptors. In this study, we demonstrated that a soluble secreted form of the ST2 gene product (ST2), a member of the interleukin-1 receptor family, suppressed the production of IL-6 in an LPS-stimulated human monocytic leukemia cell line, THP-1. Immunofluorescence confocal microscopy revealed the binding of ST2 to the surface of the THP-1 cells, in which ST2 led to decreased binding of nuclear factor-{kappa}B to the IL-6 promoter. Furthermore, the degradation of I{kappa}B in the cytoplasm after LPS stimulation was reduced by pretreatment with ST2. These results demonstrated thatmore » ST2 negatively regulates LPS-induced IL-6 production via the inhibition of I{kappa}B degradation in THP-1 cells.« less

Optical population of iodine molecule ion-pair states via MI2 vdW complexes, M = I2, Xe, of valence states correlating with the third, I(2 P 1/2) + I(2 P 1/2), dissociation limit

NASA Astrophysics Data System (ADS)

Lukashov, S. S.; Poretsky, S. A.; Pravilov, A. M.; Khadikova, E. I.; Shevchenko, E. V.

2010-10-01

The first results of measurements and analysis of excitation spectra of the λlum = 3250 Å luminescence corresponding to I2( D0{/u +} → X0{/g +}) transition as well as luminescence at λlum = 3400 Å, where I2( D'2 g → A'2 u and/or β1 g → A1 u ) transitions occur, observed after three-step, λ1 + λ f + λ1, λ1 = 5321-5508.2 Å, λ f = 10644.0 Å, laser excitation of pure iodine vapour and I2 + Xe mixtures at room temperature via MI2 vdW complexes, M = I2, Xe, of the I2(0{/g +}, 1 u ( bb)) valence states correlating with the third, I(2 P 1/2) + I(2 P 1/2) (I2( bb)), dissociation limit are presented. Luminescence spectra in the λlum = 2200-3500 Å spectral range are also analyzed. Strong luminescence from the I2(D) and, probably, I2(D' and β) states is observed. We discuss three alternative mechanisms of optical population of the IP state. In our opinion, the mechanism including the MI2 complexes is the most probable.

Direct visualization of soliton stripes in the Cu O2 plane and oxygen interstitials in B i2(S r2 -xL ax) Cu O6 +δ superconductors

NASA Astrophysics Data System (ADS)

Guo, C.; Tian, H. F.; Yang, H. X.; Zhang, B.; Sun, K.; Sun, X.; Peng, Y. Y.; Zhou, X. J.; Li, J. Q.

2017-11-01

Microstructure features in correlation with the incommensurate modulation and oxygen interstitials in B i2(S r2 -xL ax) Cu O6 +δ superconducting materials were studied by Cs-corrected scanning transmission electron microscopy. Atomic displacements following the modulation wave were well characterized by a sinusoidal wave for each atomic layer, which highlighted clear changes resulting from increases in the La concentration. Careful investigations of the alterations in the local atomic structure revealed that remarkable microstructural features, i.e., notable soliton lines, which arise from the prominent interplay between incommensurate modulation and the basic lattice, appear at the Cu O2 sheets yielding visible structural anomalies for x ranging from 0.40 to 0.85. The interstitial oxygen atoms between the SrO-BiO layers became clearly visible for X ≥0.73 and showed well-defined ordered states in the x =1.10 sample. These structural features, in particular the strong structural effects of the soliton lines on the Cu O2 sheets, could evidently affect the physical properties of layered La-Bi2201 systems.

Cross Talk in HEK293 Cells Between Nrf2, HIF, and NF-κB Activities upon Challenges with Redox Therapeutics Characterized with Single-Cell Resolution.

PubMed

Johansson, Katarina; Cebula, Marcus; Rengby, Olle; Dreij, Kristian; Carlström, Karl E; Sigmundsson, Kristmundur; Piehl, Fredrik; Arnér, Elias S J

2017-02-20

Many transcription factors with importance in health and disease are redox regulated. However, how their activities may be intertwined in responses to redox-perturbing stimuli is poorly understood. To enable in-depth characterization of this aspect, we here developed a methodology for simultaneous determination of nuclear factor E2-related factor 2 (Nrf2), hypoxia-inducible factor (HIF), and nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) activation at single-cell resolution, using a new tool named pTRAF (plasmid for transcription factor reporter activation based upon fluorescence). The pTRAF allowed determination of Nrf2, HIF, and NF-κB activities in a high-resolution and high-throughput manner, and we here assessed how redox therapeutics affected the activities of these transcription factors in human embryonic kidney cells (HEK293). Cross talk was detected between the three signaling pathways upon some types of redox therapeutics, also by using inducers typically considered specific for Nrf2, such as sulforaphane or auranofin, hypoxia for HIF activation, or tumor necrosis factor alpha (TNFα) for NF-κB stimulation. Doxorubicin, at low nontoxic doses, potentiated TNFα-induced activation of NF-κB and HIF, without effects in stand-alone treatment. Stochastic activation patterns in cell cultures were also considerable upon challenges with several redox stimuli. A novel strategy was here used to study simultaneous activation of Nrf2, HIF, and NF-κB in single cells. The method can also be adapted for studies of other transcription factors. The pTRAF provides new opportunities for in-depth studies of transcription factor activities. In this study, we found that upon challenges of cells with several redox-perturbing conditions, Nrf2, HIF, and NF-κB are uniquely responsive to separate stimuli, but can also display marked cross talk to each other within single cells. Antioxid. Redox Signal. 26, 229-246.

Scratch Testing of Hot-Pressed Monolithic Chromium Diboride (CrB2) and CrB2 + MoSi2 Composite

NASA Astrophysics Data System (ADS)

Bhatt, B.; Murthy, T. S. R. Ch.; Singh, K.; Sashanka, A.; Vishwanadh, B.; Sonber, J. K.; Sairam, K.; Nageswara Rao, G. V. S.; Srinivasa Rao, T.; Kain, Vivekanand

2017-10-01

The tribological performance of hot-pressed monolithic CrB2 and a newly developed CrB2 + 20 vol.% MoSi2 composite was investigated by using scratch test. The test was carried out under progressive loading ranging from 0.9 to 30 N over a scratch distance of 3 mm. In situ values of coefficient of friction (COF), depth of penetration and acoustic emission were recorded. The wear volume and fracture toughness were also calculated. COF of both materials is increased with increasing the scratch length and progressive load. COF of the composite was observed to be slightly higher compared to the monolithic CrB2. The wear volume of the composite is 60% higher compared to monolithic CrB2. Fracture toughness values of 2.48 and 2.81 MPa m1/2 were calculated for monolithic CrB2 and CrB2 + 20 vol.% MoSi2 composite, respectively. Microstructural characterization indicates that the abrasive wear is the dominant wear mechanism in both the materials.

Synthesis, Structure, Bonding, and Reactivity of Metal Complexes Comprising Diborane(4) and Diborene(2): [{Cp*Mo(CO)2 }2 {μ-η2 :η2 -B2 H4 }] and [{Cp*M(CO)2 }2 B2 H2 M(CO)4 ], M=Mo,W.

PubMed

Mondal, Bijan; Bag, Ranjit; Ghorai, Sagar; Bakthavachalam, K; Jemmis, Eluvathingal D; Ghosh, Sundargopal

2018-07-02

The reaction of [(Cp*Mo) 2 (μ-Cl) 2 B 2 H 6 ] (1) with CO at room temperature led to the formation of the highly fluxional species [{Cp*Mo(CO) 2 } 2 {μ-η 2 :η 2 -B 2 H 4 }] (2). Compound 2, to the best of our knowledge, is the first example of a bimetallic diborane(4) conforming to a singly bridged C s structure. Theoretical studies show that 2 mimics the Cotton dimolybdenum-alkyne complex [{CpMo(CO) 2 } 2 C 2 H 2 ]. In an attempt to replace two hydrogen atoms of diborane(4) in 2 with a 2e [W(CO) 4 ] fragment, [{Cp*Mo(CO) 2 } 2 B 2 H 2 W(CO) 4 ] (3) was isolated upon treatment with [W(CO) 5 ⋅thf]. Compound 3 shows the intriguing presence of [B 2 H 2 ] with a short B-B length of 1.624(4) Å. We isolated the tungsten analogues of 3, [{Cp*W(CO) 2 } 2 B 2 H 2 W(CO) 4 ] (4) and [{Cp*W(CO) 2 } 2 B 2 H 2 Mo(CO) 4 ] (5), which provided direct proof of the existence of the tungsten analogue of 2. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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.

Lattice Thermal Conductivity from Atomistic Simulations: ZrB2 and HfB2

NASA Technical Reports Server (NTRS)

Lawson, John W.; Daw, Murray S.; Bauschlicher, Charles W.

2012-01-01

Ultra high temperature ceramics (UHTC) including ZrB2 and HfB2 have a number of properties that make them attractive for applications in extreme environments. One such property is their high thermal conductivity. Computational modeling of these materials will facilitate understanding of fundamental mechanisms, elucidate structure-property relationships, and ultimately accelerate the materials design cycle. Progress in computational modeling of UHTCs however has been limited in part due to the absence of suitable interatomic potentials. Recently, we developed Tersoff style parameterizations of such potentials for both ZrB2 and HfB2 appropriate for atomistic simulations. As an application, Green-Kubo molecular dynamics simulations were performed to evaluate the lattice thermal conductivity for single crystals of ZrB2 and HfB2. The atomic mass difference in these binary compounds leads to oscillations in the time correlation function of the heat current, in contrast to the more typical monotonic decay seen in monoatomic materials such as Silicon, for example. Results at room temperature and at elevated temperatures will be reported.

Crystal structures of functional building blocks derived from bis(benzo[b]thiophen-2-yl)methane.

PubMed

Katzsch, Felix; Gruber, Tobias; Weber, Edwin

2016-09-01

The syntheses of three bis(benzo[b]thiophen-2-yl)methane derivatives, namely bis(benzo[b]thiophen-2-yl)methanone, C17H10OS2, (I), 1,1-bis(benzo[b]thiophen-2-yl)-3-(trimethylsilyl)prop-2-yn-1-ol, C22H20OS2Si, (II), and 1,1-bis(benzo[b]thiophen-2-yl)prop-2-yn-1-ol, C19H12OS2, (III), are described and their crystal structures discussed comparatively. The conformation of ketone (I) and the respective analogues are rather similar for most of the compounds compared. This is true for the interplanar angles, the Caryl-Cbridge-Caryl angles and the dihedral angles. The best resemblance is found for a bioisotere of (I), viz. 2,2'-dinaphthyl ketone, (VII). By way of interest, the crystal packings also reveal similarities between (I) and (VII). In (I), the edge-to-face interactions seen between two napthyl residues in (VII) are substituted by S...π contacts between the benzo[b]thiophen-2-yl units in (I). In the structures of the bis(benzo[b]thiophen-2-yl)methanols, i.e. (II) and (III), the interplanar angles are also quite similar compared with analogues and related active pharmaceutical ingredients (APIs) containing the dithiophen-2-ylmethane scaffold, though the dihedral angles show a larger variability and produce unsymmetrical molecules.

A 2-D Array of Superconducting Magnesium Diboride (MgB2) Far-IR Thermal Detectors for Planetary Exploration

NASA Technical Reports Server (NTRS)

Lakew, Brook

2009-01-01

A 2-D array of superconducting Magnesium Diboride(MgB2) far IR thermal detectors has been fabricated. Such an array is intended to be at the focal plane of future generation thermal imaging far-IR instruments that will investigate the outer planets and their icy moons. Fabrication and processing of the pixels of the array as well as noise characterization of architectured MgB2 thin films will be presented. Challenges and solutions for improving the performance of the array will be discussed.

Glutaredoxin 2 prevents H(2)O(2)-induced cell apoptosis by protecting complex I activity in the mitochondria.

PubMed

Wu, Hongli; Xing, Kuiyi; Lou, Marjorie F

2010-10-01

Glutaredoxin 2 (Grx2) belongs to the oxidoreductase family and is an isozyme of glutaredoxin 1 (Grx1) present in the mitochondria, however its function is not well understood. The purpose of this study is to evaluate the potential anti-apoptotic function of Grx2 by examining its ability to protect complex I in the mitochondrial electron transport system using human lens epithelial cells as a model. We found that cells treated with 200muM hydrogen peroxide (H(2)O(2)) for 24h exhibited decreased viability and became apoptotic with corresponding Bax up-regulation, Bcl-2 down-regulation, caspase 3 activation and mitochondrial cytochrome c leakage. Grx2 over-expression (OE) could protect cells against H(2)O(2)-induced damage while Grx2 knockdown (KD) showed the opposite effect. Under the same conditions, H(2)O(2) treatment caused 50% inactivation of complex I activity in control cells (vector only), 75% in Grx2 KD cells but only 20% in Grx2 OE cells. Furthermore, the inactivated complex I in the H(2)O(2)-treated cells could be protected mostly by importing the purified nascent Grx2 protein, but not the Grx2 protein mutated at the active site with C70S, or C73S, or with C70S plus C73S. Immunoprecipitation study also revealed that Grx2 co-precipitated with complex I, but not complex II, in the mitochondrial lysate. Thus, the mechanism of Grx2 protection against H(2)O(2)-induced apoptosis is likely associated with its ability to preserve complex I. Published by Elsevier B.V.

Word Frequency Analysis. MOS: 95B. Skill Levels 1 & 2.

DTIC Science & Technology

1981-05-01

uU N D 1 A C P A C K1 ? G .I A 2 1 A’J Kt I S , 1 K L S 1 BaRp IF S I ~t2iIAED 5. 1.T’ 6 BATTERY 9!j 2 BECAUSE 17 67EI 2 BEHIND 13 IL 2 RE l1󈧱 3 b1...T S :t cTt lIION 5 U It :,4t 5 F L 1%T5 &:, JC.L ME NT 5 ESTIMS4EO 5 F -4 U0 . F- "CL5 UJ 7 "S 5 F-.[377 7i (, ID󈧏CAlN5.C1DEINTS 5 I’%SER71NkG .0

Magnetospheric Multiscale Mission (MMS) Phase 2B Navigation Performance

NASA Technical Reports Server (NTRS)

Scaperoth, Paige Thomas; Long, Anne; Carpenter, Russell

2009-01-01

The Magnetospheric Multiscale (MMS) formation flying mission, which consists of four spacecraft flying in a tetrahedral formation, has challenging navigation requirements associated with determining and maintaining the relative separations required to meet the science requirements. The baseline navigation concept for MMS is for each spacecraft to independently estimate its position, velocity and clock states using GPS pseudorange data provided by the Goddard Space Flight Center-developed Navigator receiver and maneuver acceleration measurements provided by the spacecraft's attitude control subsystem. State estimation is performed onboard in real-time using the Goddard Enhanced Onboard Navigation System flight software, which is embedded in the Navigator receiver. The current concept of operations for formation maintenance consists of a sequence of two maintenance maneuvers that is performed every 2 weeks. Phase 2b of the MMS mission, in which the spacecraft are in 1.2 x 25 Earth radii orbits with nominal separations at apogee ranging from 30 km to 400 km, has the most challenging navigation requirements because, during this phase, GPS signal acquisition is restricted to less than one day of the 2.8-day orbit. This paper summarizes the results from high-fidelity simulations to determine if the MMS navigation requirements can be met between and immediately following the maintenance maneuver sequence in Phase 2b.

TEES 2.2: Biomedical Event Extraction for Diverse Corpora

PubMed Central

2015-01-01

Background The Turku Event Extraction System (TEES) is a text mining program developed for the extraction of events, complex biomedical relationships, from scientific literature. Based on a graph-generation approach, the system detects events with the use of a rich feature set built via dependency parsing. The TEES system has achieved record performance in several of the shared tasks of its domain, and continues to be used in a variety of biomedical text mining tasks. Results The TEES system was quickly adapted to the BioNLP'13 Shared Task in order to provide a public baseline for derived systems. An automated approach was developed for learning the underlying annotation rules of event type, allowing immediate adaptation to the various subtasks, and leading to a first place in four out of eight tasks. The system for the automated learning of annotation rules is further enhanced in this paper to the point of requiring no manual adaptation to any of the BioNLP'13 tasks. Further, the scikit-learn machine learning library is integrated into the system, bringing a wide variety of machine learning methods usable with TEES in addition to the default SVM. A scikit-learn ensemble method is also used to analyze the importances of the features in the TEES feature sets. Conclusions The TEES system was introduced for the BioNLP'09 Shared Task and has since then demonstrated good performance in several other shared tasks. By applying the current TEES 2.2 system to multiple corpora from these past shared tasks an overarching analysis of the most promising methods and possible pitfalls in the evolving field of biomedical event extraction are presented. PMID:26551925

TEES 2.2: Biomedical Event Extraction for Diverse Corpora.

PubMed

Björne, Jari; Salakoski, Tapio

2015-01-01

The Turku Event Extraction System (TEES) is a text mining program developed for the extraction of events, complex biomedical relationships, from scientific literature. Based on a graph-generation approach, the system detects events with the use of a rich feature set built via dependency parsing. The TEES system has achieved record performance in several of the shared tasks of its domain, and continues to be used in a variety of biomedical text mining tasks. The TEES system was quickly adapted to the BioNLP'13 Shared Task in order to provide a public baseline for derived systems. An automated approach was developed for learning the underlying annotation rules of event type, allowing immediate adaptation to the various subtasks, and leading to a first place in four out of eight tasks. The system for the automated learning of annotation rules is further enhanced in this paper to the point of requiring no manual adaptation to any of the BioNLP'13 tasks. Further, the scikit-learn machine learning library is integrated into the system, bringing a wide variety of machine learning methods usable with TEES in addition to the default SVM. A scikit-learn ensemble method is also used to analyze the importances of the features in the TEES feature sets. The TEES system was introduced for the BioNLP'09 Shared Task and has since then demonstrated good performance in several other shared tasks. By applying the current TEES 2.2 system to multiple corpora from these past shared tasks an overarching analysis of the most promising methods and possible pitfalls in the evolving field of biomedical event extraction are presented.

The rat ErbB2 tyrosine kinase receptor produced in plants is immunogenic in mice and confers protective immunity against ErbB2(+) mammary cancer.

PubMed

Matić, Slavica; Quaglino, Elena; Arata, Lucia; Riccardo, Federica; Pegoraro, Mattia; Vallino, Marta; Cavallo, Federica; Noris, Emanuela

2016-01-01

The rat ErbB2 (rErbB2) protein is a 185-kDa glycoprotein belonging to the epidermal growth factor-related proteins (ErbB) of receptor tyrosine kinases. Overexpression and mutations of ErbB proteins lead to several malignancies including breast, lung, pancreatic, bladder and ovary carcinomas. ErbB2 is immunogenic and is an ideal candidate for cancer immunotherapy. We investigated the possibility of expressing the extracellular (EC) domain of rErbB2 (653 amino acids, aa) in Nicotiana benthamiana plants, testing the influence of the 23 aa transmembrane (TM) sequence on protein accumulation. Synthetic variants of the rErbB2 gene portion encoding the EC domain, optimized with a human codon usage and either linked to the full TM domain (rErbB2_TM, 676 aa), to a portion of it (rErbB2-pTM, 662 aa), or deprived of it (rErbB2_noTM, 653 aa) were cloned in the pEAQ-HT expression vector as 6X His tag fusions. All rErbB2 variants (72-74.5 kDa) were transiently expressed, but the TM was detrimental for rErbB2 EC accumulation. rERbB2_noTM was the most expressed protein; it was solubilized and purified with Nickel affinity resin. When crude soluble extracts expressing rErbB2_noTM were administered to BALB/c mice, specific rErbB2 immune responses were triggered. A potent antitumour activity was induced when vaccinated mice were challenged with syngeneic transplantable ErbB2(+) mammary carcinoma cells. To our knowledge, this is the first report of expression of rErbB2 in plants and of its efficacy in inducing a protective antitumour immune response, opening interesting perspectives for further immunological testing. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Photophysics of indole-2-carboxylic acid (I2C) and indole-5-carboxylic acid (I5C): heavy atom effect.

PubMed

Kowalska-Baron, Agnieszka; Gałęcki, Krystian; Wysocki, Stanisław

2013-12-01

triplet states has been expressed in Arrhenius form. The linearity of the obtained Arrhenius plots clearly indicated the existence of one temperature-dependent non-radiative process for the de-excitation of I2C and I5C triplet state in the presence of iodide. This process may be attributed to the solute-quenching by iodide and, most probably, proceeds via reversibly formed exciplex. The activation energies obtained from linear Arrhenius plots (1.89 kcal/mol for I5 C; 2.55 kcal/mol for I2 C) are smaller as compared to that for diffusion controlled reactions in aqueous solution (about 4 kcal/mol), which may indicate the great importance of the electrostatic interactions between solute and iodide ions in lowering the energy barrier needed for the formation of the triplet-quencher complex. Based on the theoretical predictions (at the DFT(CAM-B3LYP)/6-31+G(d,p) level of theory) and careful analysis of the obtained FTIR spectra it may be concluded that in the solid state I2 C and I5 C molecules form associates by intermolecular NH · · · OC and OH · · · OC hydrogen bonding interactions, whereas the existence of intramolecular NH · · · OC interactions in the solid state of I2C and I5C is highly unlikely. Copyright © 2013 Elsevier B.V. All rights reserved.

Crystal growth, crystal structure of new polymorphic modification, β-Bi 2B 8O 15 and thermal expansion of α-Bi 2B 8O 15

NASA Astrophysics Data System (ADS)

Bubnova, R. S.; Alexandrova, J. V.; Krivovichev, S. V.; Filatov, S. K.; Egorysheva, A. V.

2010-02-01

Single crystals of α- and β-polymorphs of Bi 2B 8O 15 were grown by Czochralski method from a charge of the stoichiometric composition. The crystal structure of β-Bi 2B 8O 15 was solved by direct methods from a twinned crystal and refined to R1=0.081 (w R=0.198) on the basis of 1584 unique observed reflections ( I>2 σ( I)). The compound is triclinic, space group P1¯, a=4.3159(8), b=6. 4604(12), c=22.485(4) Å, α=87.094(15)°, β=86.538(15)°, γ=74.420(14)°, V=602.40(19) Å 3, Z=2. The B-O layered anion of β-Bi 2B 8O 15 is topologically identical to the anion of α-Bi 2B 8O 15 but the orientation of neighboring layers is different. Thermal expansion of α-Bi 2B 8O 15 has been investigated by X-ray powder diffraction in air in temperature range from 20 to 700 °C. It is strongly anisotropic, which can be explained by the hinge mechanism applied to chains of Bi-O polyhedra. While the anisotropy of thermal expansion is rather high, the volume thermal expansion coefficient α V=40×10 6 °C -1 for α-Bi 2B 8O 15 is close to those of other bismuth borates.

77 FR 59670 - Electronic Filing of H-2A and H-2B Labor Certification Applications Through the iCERT Visa Portal...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-28

... DEPARTMENT OF LABOR Employment and Training Administration Electronic Filing of H-2A and H-2B... certification applications under the H-2A and H-2B visa programs through the Department of Labor's (Department... will be able to submit H-2B applications electronically beginning on October 15, 2012, and H-2A...

GS143, an I{kappa}B ubiquitination inhibitor, inhibits allergic airway inflammation in mice

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

Hirose, Koichi; Wakashin, Hidefumi; Oki, Mie

2008-09-26

Asthma is characterized by airway inflammation with intense eosinophil infiltration and mucus hyper-production, in which antigen-specific Th2 cells play critical roles. Nuclear factor-{kappa}B (NF-{kappa}B) pathway has been demonstrated to be essential for the production of Th2 cytokines and chemokines in the airways in murine asthma models. In the present study, we examined the effect of GS143, a novel small-molecule inhibitor of I{kappa}B ubiquitination, on antigen-induced airway inflammation and Th2 cytokine production in mice. Intranasal administration of GS143 prior to antigen challenge suppressed antigen-induced NF-{kappa}B activation in the lung of sensitized mice. Intranasal administration of GS143 also inhibited antigen-induced eosinophil andmore » lymphocyte recruitment into the airways as well as the expression of Th2 cytokines and eotaxin in the airways. Moreover, GS143 inhibited antigen-induced differentiation of Th2 cells but not of Th1 cells in vitro. Taken together, these results suggest that I{kappa}B ubiquitination inhibitor may have therapeutic potential against asthma.« less

B2 and G2 Toda systems on compact surfaces: A variational approach

NASA Astrophysics Data System (ADS)

Battaglia, Luca

2017-01-01

We consider the B2 and G2 Toda systems on a compact surface (Σ, g), namely, systems of two Liouville-type PDEs coupled with a matrix of coefficients A = ( a i j ) = 2 - 1 - 2 2 ) or (2 - 1 - 3 2) . We attack the problem using variational techniques, following the previous work [Battaglia, L. et al., Adv. Math. 285, 937-979 (2015)] concerning the A2 Toda system, namely, the case A = 2 - 1 - 1 2 ) . We get the existence and multiplicity of solutions as long as χ(Σ) ≤ 0 and a generic choice of the parameters. We also extend some of the results to the case of general systems.

Finding 'Evidence of Absence' in Medical Notes: Using NLP for Clinical Inferencing.

PubMed

Carter, Marjorie E; Divita, Guy; Redd, Andrew; Rubin, Michael A; Samore, Matthew H; Gupta, Kalpana; Trautner, Barbara W; Gundlapalli, Adi V

2016-01-01

Extracting evidence of the absence of a target of interest from medical text can be useful in clinical inferencing. The purpose of our study was to develop a natural language processing (NLP) pipelineto identify the presence of indwelling urinary catheters from electronic medical notes to aid in detection of catheter-associated urinary tract infections (CAUTI). Finding clear evidence that a patient does not have an indwelling urinary catheter is useful in making a determination regarding CAUTI. We developed a lexicon of seven core concepts to infer the absence of a urinary catheter. Of the 990,391 concepts extractedby NLP from a large corpus of 744,285 electronic medical notes from 5589 hospitalized patients, 63,516 were labeled as evidence of absence.Human review revealed three primary causes for false negatives. The lexicon and NLP pipeline were refined using this information, resulting in outputs with an acceptable false positive rate of 11%.

Boosting Up Performance of Inverted Photovoltaic Cells from Bis(alkylthien-2-yl)dithieno[2,3-d:2',3'-d']benzo[1,2-b:4',5'-b']di thiophene-Based Copolymers by Advantageous Vertical Phase Separation.

PubMed

Guo, Pengzhi; Luo, Guoping; Su, Qiang; Li, Jianfeng; Zhang, Peng; Tong, Junfeng; Yang, Chunyan; Xia, Yangjun; Wu, Hongbin

2017-03-29

The photovoltaic cells (PVCs) from conjugated copolymers of PDTBDT-BT and PDTBDT-FBT with 5,10-bis(4,5-didecylthien-2-yl)dithieno[2,3-d:2',3'-d']benzo[1,2-b:4,5-b']dithiophene as electron donor moieties and benzothiadiazole and/or 5,6-difluorobenzothiadiazole as electron acceptor moieties are optimized by employing alcohol-soluble PFN (poly(9,9-bis(3'-(N,N-dimethylamino)propyl)-2,7-fluorene)-alt-2,7-(9,9-dioctylfluorene)) as cathode modification interlayer. The power conversion efficiencies (PCEs) of inverted PVCs (i-PVCs) from PDTBDT-BT and PDTBDT-FBT with devices configuration as ITO/PFN/active layer/MoO 3 /Ag are increased from 4.97% to 8.54% and 5.92% to 8.74%, in contrast to those for the regular PVCs (r-PVCs) with devices configuration as ITO/PEDOT:PSS/active layer/Ca/Al under 100 mW/cm 2 AM 1.5 illumination. The optical modeling calculations and X-ray photoelectron spectroscopy (XPS) investigations reveal that the r-PVCs and i-PVCs from the copolymers exhibit similar light harvesting characteristics, and the enhancements of the PCEs of the i-PVCs from the copolymers are mainly contributed to the favorable vertical phase separation as the strongly polymer-enriched top surface layers and slightly PC 71 BM (phenyl-C 71 -butyric acid methyl ester)-enriched bottom surface layers are correspondingly connected to the anodes and cathodes of the i-PVCs, while they are opposite in the r-PVCs. As we known, it is the first time to experimentally verify that the i-PVCs with alcohol-soluble conjugated polymers cathode modification layers enjoy favorable vertical phase separation.

Enhanced expression of rat hepatic CYP2B1/2B2 and 2E1 by pyridine: differential induction kinetics and molecular basis of expression.

PubMed

Kim, H; Putt, D; Reddy, S; Hollenberg, P F; Novak, R F

1993-11-01

Expression of the cytochrome P450 (CYP) 2B subfamily in rat and rabbit hepatic tissues after pyridine (PY) treatment has been examined, and the molecular basis for enhanced 2B1/2B2 expression has been determined. P450 expression was monitored using metabolic activity, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblot analyses, and the identity of the proteins was confirmed through N-terminus microsequence analysis. PY caused a dose-dependent elevation of hepatic CYP2B1/B2B levels in rats, which ranged from 4- to 22-fold over the dosing regimen of 100 to 400 mg PY/kg/day, for 3 days, respectively. PY at low dose failed to induce CYP2B in rabbit hepatic tissue, suggesting a species-dependent response in 2B expression. Anti-2B1 IgG addition to PY-induced microsomes inhibited benzphetamine N-demethylase activity by only approximately 15%, in sharp contrast to the approximately 73% inhibition observed for phenobarbital-induced microsomes, suggesting the induction of other form(s) of P450 having benzphetamine N-demethylase activity. Northern blot analysis revealed that PY treatment increased 2B1 and 2B2 poly(A)+ RNA levels approximately 69- and approximately 34-fold, respectively, whereas the 2E1 poly(A)+ RNA levels failed to increase. The results of this study show that PY induces CYP2B1/2B2 and that induction is species-dependent and kinetically distinguishable from 2E1 induction. Moreover, 2B1/2B2 induction occurs as a result of elevated mRNA levels associated with either transcriptional activation or mRNA stabilization, and it differs from the mechanism of hepatic 2E1 induction by PY.

Quenching of I(2P1/2) by NO2, N2O4, and N2O.

PubMed

Kabir, Md Humayun; Azyazov, Valeriy N; Heaven, Michael C

2007-10-11

Quenching of excited iodine atoms (I(5p5, 2P1/2)) by nitrogen oxides are processes of relevance to discharge-driven oxygen iodine lasers. Rate constants at ambient and elevated temperatures (293-380 K) for quenching of I(2P1/2) atoms by NO2, N2O4, and N2O have been measured using time-resolved I(2P1/2) --> I(2P3/2) 1315 nm emission. The excited atoms were generated by pulsed laser photodissociation of CF3I at 248 nm. The rate constants for I(2P1/2) quenching by NO2 and N2O were found to be independent of temperature over the range examined with average values of (2.9 +/- 0.3) x 10(-15) and (1.4 +/- 0.1) x 10(-15) cm3 s(-1), respectively. The rate constant for quenching of I(2P1/2) by N2O4 was found to be (3.5 +/- 0.5) x 10(-13) cm3 s(-1) at ambient temperature.

B2B Models for DoD Acquisition

DTIC Science & Technology

2007-07-30

Internet, extranets, intranets, or private networks • In 2003 it represented about 11% of total B2B trade estimated at $13.5 trillion • Predicted to... B2B Models for DoD Acquisition 30 July 2007 by Magdi N. Kamel, Associate Professor Graduate School of Operational & Information Sciences...number. 1. REPORT DATE 30 JUL 2007 2. REPORT TYPE 3. DATES COVERED 00-00-2007 to 00-00-2007 4. TITLE AND SUBTITLE B2B Models for DoD

Bu-2470, a new peptide antibiotic complex. II. Structure determination of Bu-2470 A, B1, B2a and B2b.

PubMed

Sugawara, K; Yonemoto, T; Konishi, M; Matsumoto, K; Miyaki, T; Kawaguchi, H

1983-06-01

The structures of Bu-2470 A, B1, B2a, and B2b have been determined. Bu-2470 A is a simple octapeptide having no fatty acid moiety, while Bu-2470 B1, B2a and B2b are octapeptides that have been acylated with a beta-hydroxy C11 or C10 fatty acid. The octapeptide structure of Bu-2470 components was found identical with that of octapeptin C1, hence generic names of octapeptin C0, C2, C3 and C4 are proposed for Bu-2470 A, B1, B2a and B2b, respectively.

Textured Nd2Fe14B flakes with enhanced coercivity

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

Cui, BZ; Zheng, LY; Marinescu, M

2012-04-01

Morphology, structure, and magnetic properties of the [001] textured Nd2Fe14B nanocrystalline flakes prepared by surfactant-assisted high energy ball milling (HEBM) and subsequent annealing were studied. These flakes have a thickness of 80-200 nm, a length of 0.5-10 mu m, and an average grain size of 10-14nm. The addition of some amount of Dy, Nd70Cu30 alloy, and an appropriate post annealing increased the coercivity H-i(c) of the Nd2Fe14B flakes. iHc was 3.7, 4.3, and 5.7 kOe for the Nd15.5Fe78.5B6, Nd14Dy1.5Fe78.5B6 and 83.3wt.% Nd14Dy1.5Fe78.5B6+16.7 wt.% Nd70Cu30 flakes prepared by HEBM for 5 h in heptane with 20 wt.% oleylamine, respectively. After annealingmore » at 450 degrees C for 0.5h, their iHc increased to 5.1, 6.2, and 7.0 kOe, respectively. Anisotropic magnetic behavior was found in all of the as-milled and annealed flakes. Both, the thickening of Nd-rich phase at grain boundaries via diffusion of Nd70Cu30 and the surface modification of the Nd2Fe14B flake could be the main reasons for the coercivity enhancement in the as-milled and annealed Nd70Cu30-added Nd2Fe14B flakes. (C) 2012 American Institute of Physics. [doi: 10.1063/1.3679425]« less

Olfactomedin-like 2 A and B (OLFML2A and OLFML2B) expression profile in primates (human and baboon).

PubMed

Pérez-Ibave, Diana Cristina; González-Alvarez, Rafael; de La Luz Martinez-Fierro, Margarita; Ruiz-Ayma, Gabriel; Luna-Muñoz, Maricela; Martínez-De-Villarreal, Laura Elia; De Lourdes Garza-Rodríguez, María; Reséndez-Pérez, Diana; Mohamed-Noriega, Jibran; Garza-Guajardo, Raquel; Bautista-De-Lucío, Víctor Manuel; Mohamed-Noriega, Karim; Barboza-Quintana, Oralia; Arámburo-De-La-Hoz, Carlos; Barrera-Saldaña, Hugo Alberto; Rodríguez-Sánchez, Irám Pablo

2016-11-08

The olfactomedin-like domain (OLFML) is present in at least four families of proteins, including OLFML2A and OLFML2B, which are expressed in adult rat retina cells. However, no expression of their orthologous has ever been reported in human and baboon. The aim of this study was to investigate the expression of OLFML2A and OLFML2B in ocular tissues of baboons (Papio hamadryas) and humans, as a key to elucidate OLFML function in eye physiology. OLFML2A and OLFML2B cDNA detection in ocular tissues of these species was performed by RT-PCR. The amplicons were cloned and sequenced, phylogenetically analyzed and their proteins products were confirmed by immunofluorescence assays. OLFML2A and OLFML2B transcripts were found in human cornea, lens and retina and in baboon cornea, lens, iris and retina. The baboon OLFML2A and OLFML2B ORF sequences have 96% similarity with their human's orthologous. OLFML2A and OLFML2B evolution fits the hypothesis of purifying selection. Phylogenetic analysis shows clear orthology in OLFML2A genes, while OLFML2B orthology is not clear. Expression of OLFML2A and OLFML2B in human and baboon ocular tissues, including their high similarity, make the baboon a powerful model to deduce the physiological and/or metabolic function of these proteins in the eye.

Speaker Recognition Through NLP and CWT Modeling

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

Brown-VanHoozer, S.A.; Kercel, S.W.; Tucker, R.W.

The objective of this research is to develop a system capable of identifying speakers on wiretaps from a large database (>500 speakers) with a short search time duration (<30 seconds), and with better than 90% accuracy. Much previous research in speaker recognition has led to algorithms that produced encouraging preliminary results, but were overwhelmed when applied to populations of more than a dozen or so different speakers. The authors are investigating a solution to the "large population" problem by seeking two completely different kinds of characterizing features. These features are he techniques of Neuro-Linguistic Programming (NLP) and the continuous waveletmore » transform (CWT). NLP extracts precise neurological, verbal and non-verbal information, and assimilates the information into useful patterns. These patterns are based on specific cues demonstrated by each individual, and provide ways of determining congruency between verbal and non-verbal cues. The primary NLP modalities are characterized through word spotting (or verbal predicates cues, e.g., see, sound, feel, etc.) while the secondary modalities would be characterized through the speech transcription used by the individual. This has the practical effect of reducing the size of the search space, and greatly speeding up the process of identifying an unknown speaker. The wavelet-based line of investigation concentrates on using vowel phonemes and non-verbal cues, such as tempo. The rationale for concentrating on vowels is there are a limited number of vowels phonemes, and at least one of them usually appears in even the shortest of speech segments. Using the fast, CWT algorithm, the details of both the formant frequency and the glottal excitation characteristics can be easily extracted from voice waveforms. The differences in the glottal excitation waveforms as well as the formant frequency are evident in the CWT output. More significantly, the CWT reveals significant detail of the glottal

Speaker recognition through NLP and CWT modeling.

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

Brown-VanHoozer, A.; Kercel, S. W.; Tucker, R. W.

The objective of this research is to develop a system capable of identifying speakers on wiretaps from a large database (>500 speakers) with a short search time duration (<30 seconds), and with better than 90% accuracy. Much previous research in speaker recognition has led to algorithms that produced encouraging preliminary results, but were overwhelmed when applied to populations of more than a dozen or so different speakers. The authors are investigating a solution to the ''huge population'' problem by seeking two completely different kinds of characterizing features. These features are extracted using the techniques of Neuro-Linguistic Programming (NLP) and themore » continuous wavelet transform (CWT). NLP extracts precise neurological, verbal and non-verbal information, and assimilates the information into useful patterns. These patterns are based on specific cues demonstrated by each individual, and provide ways of determining congruency between verbal and non-verbal cues. The primary NLP modalities are characterized through word spotting (or verbal predicates cues, e.g., see, sound, feel, etc.) while the secondary modalities would be characterized through the speech transcription used by the individual. This has the practical effect of reducing the size of the search space, and greatly speeding up the process of identifying an unknown speaker. The wavelet-based line of investigation concentrates on using vowel phonemes and non-verbal cues, such as tempo. The rationale for concentrating on vowels is there are a limited number of vowels phonemes, and at least one of them usually appears in even the shortest of speech segments. Using the fast, CWT algorithm, the details of both the formant frequency and the glottal excitation characteristics can be easily extracted from voice waveforms. The differences in the glottal excitation waveforms as well as the formant frequency are evident in the CWT output. More significantly, the CWT reveals significant detail of

Bu-2470, a new peptide antibiotic complex. I. Production, isolation and properties of Bu-2470 A, B1 and B2.

PubMed

Konishi, M; Sugawara, K; Tomita, K; Matsumoto, K; Miyaki, T; Fujisawa, K; Tsukiura, H; Kawaguchi, H

1983-06-01

A strain of Bacillus circulans produced a complex of basic peptide antibiotics designated Bu-2470, which was found to contain four active components, A, B1, B2a and B2b. Bu-2470 A specifically inhibited various Pseudomonas species including P. aeruginosa, P. maltophilia and P. putida, but otherwise its antibacterial spectrum was limited to certain Gram-negative organisms. Bu-2470 B1 and B2 (B2a + B2b) showed broad antibiotic activity against Gram-positive and Gram-negative bacteria including Pseudomonas species. The physicochemical and biological properties of Bu-2470 B1 and B2 are very similar to those of the octapeptin group of antibiotics.

Deliberate and Crisis Action Planning and Execution Segments Increment 2B (DCAPES Inc 2B)

DTIC Science & Technology

2016-03-01

2016 Major Automated Information System Annual Report Deliberate and Crisis Action Planning and Execution Segments Increment 2B (DCAPES Inc 2B...Defense Acquisition Management Information Retrieval (DAMIR) UNCLASSIFIED DCAPES Inc 2B 2016 MAR UNCLASSIFIED 2 Table of Contents Common...Logistics DCAPES Inc 2B 2016 MAR UNCLASSIFIED 3 Lt Col Christopher Thrower 201 East Moore Drive Building 856, Room 154 Maxwell Air Force Base-Gunter

Absence of B1-B2 structural transition in lithium halides under hydrostatic pressure

NASA Astrophysics Data System (ADS)

de Coss, Romeo; Murrieta, Gabriel

2005-03-01

We have investigated the B1-B2 structural transition in LiF, LiCl, LiBr, and LiI under hydrostatic pressure by means of first-principles total-energy calculations using the Full- Potential LAPW method. In order to analyze the gradient effects, we have performed calculations using the local density approximation (LDA) and the generalized gradient approximation (GGA), for the exchange and correlation potential. In agreement with the experimental observations, we find that even for pressures higher than 100 GPa, the Li halides do not present the B1-B2 structural transition. In order to understand this behavior, we have calculated the distribution of the electron densities. From the analysis of the distribution of electron densities for the Li halides in the B1 and B2 phases, we find that for this group of ionic compounds the B1 phase have a distribution of electron densities more homogeneous than in the B2 phase, preventing the B1-B2 structural transition. This work was partially supported by Consejo Nacional de Ciencia y Tecnolog'ia (CONACYT, M'exico) under Grant No. 43830-F.

PolyI:C and mouse survivin artificially embedding human 2B peptide induce a CD4+ T cell response to autologous survivin in HLA-A*2402 transgenic mice.

PubMed

Kasamatsu, Jun; Takahashi, Shojiro; Azuma, Masahiro; Matsumoto, Misako; Morii-Sakai, Akiko; Imamura, Masahiro; Teshima, Takanori; Takahashi, Akari; Hirohashi, Yoshihiko; Torigoe, Toshihiko; Sato, Noriyuki; Seya, Tsukasa

2015-01-01

CD4(+) T cell effectors are crucial for establishing antitumor immunity. Dendritic cell maturation by immune adjuvants appears to facilitate subset-specific CD4(+) T cell proliferation, but the adjuvant effect for CD4 T on induction of cytotoxic T lymphocytes (CTLs) is largely unknown. Self-antigenic determinants with low avidity are usually CD4 epitopes in mutated proteins with tumor-associated class I-antigens (TAAs). In this study, we made a chimeric version of survivin, a target of human CTLs. The chimeric survivin, where human survivin-2B containing a TAA was embedded in the mouse survivin frame (MmSVN2B), was used to immunize HLA-A-2402/K(b)-transgenic (HLA24(b)-Tg) mice. Subcutaneous administration of MmSVN2B or xenogeneic human survivin (control HsSNV2B) to HLA24(b)-Tg mice failed to induce an immune response without co-administration of an RNA adjuvant polyI:C, which was required for effector induction in vivo. Although HLA-A-2402/K(b) presented the survivin-2B peptide in C57BL/6 mice, 2B-specific tetramer assays showed that no CD8(+) T CTLs specific to survivin-2B proliferated above the detection limit in immunized mice, even with polyI:C treatment. However, the CD4(+) T cell response, as monitored by IFN-γ, was significantly increased in mice given polyI:C+MmSVN2B. The Th1 response and antibody production were enhanced in the mice with polyI:C. The CD4 epitope responsible for effector function was not Hs/MmSNV13-27, a nonconserved region between human and mouse survivin, but region 53-67, which was identical between human and mouse survivin. These results suggest that activated, self-reactive CD4(+) helper T cells proliferate in MmSVN2B+polyI:C immunization and contribute to Th1 polarization followed by antibody production, but hardly participate in CTL induction. Copyright © 2014 Elsevier GmbH. All rights reserved.

Novel high pressure hexagonal OsB2 by mechanochemistry

NASA Astrophysics Data System (ADS)

Xie, Zhilin; Graule, Moritz; Orlovskaya, Nina; Andrew Payzant, E.; Cullen, David A.; Blair, Richard G.

2014-07-01

Hexagonal OsB2, a theoretically predicted high-pressure phase, has been synthesized for the first time by a mechanochemical method, i.e., high energy ball milling. X-ray diffraction indicated that formation of hexagonal OsB2 begins after 2.5 h of milling, and the reaction reaches equilibrium after 18 h of milling. Rietveld refinement of the powder data indicated that hexagonal OsB2 crystallizes in the P63/mmc space group (No. 194) with lattice parameters of a=2.916 Å and c=7.376 Å. Transmission electron microscopy confirmed the appearance of the hexagonal OsB2 phase after high energy ball milling. in situ X-ray diffraction experiments showed that the phase is stable from -225 °C to 1050 °C. The hexagonal OsB2 powder was annealed at 1050 °C for 6 days in vacuo to improve crystallinity and remove strain induced during the mechanochemical synthesis. The structure partially converted to the orthorhombic phase (20 wt%) after fast current assisted sintering of hexagonal OsB2 at 1500 °C for 5 min. Mechanochemical approaches to the synthesis of hard boride materials allow new phases to be produced that cannot be prepared using conventional methods.

B2B Models for DoD Acquisition

DTIC Science & Technology

2008-01-15

unlimited. Prepared for: Naval Postgraduate School, Monterey, California 93943 B2B Models for DoD Acquisition 15 January 2008 by Magdi N...TYPE AND DATES COVERED 1 Oct 2006 through 30 Sept 2007 4. TITLE AND SUBTITLE B2B Models for DoD Acquisition 5. FUNDING 6. AUTHOR (S...public release; distribution is unlimited 12b. DISTRIBUTION CODE 13. ABSTRACT (Maximum 200 words.) A central vision of B2B e-commerce is that

The protein phosphatase 2A catalytic subunit StPP2Ac2b acts as a positive regulator of tuberization induction in Solanum tuberosum L.

PubMed

Muñiz García, María Noelia; Muro, María Catalina; Mazzocchi, Luciana Carla; País, Silvia Marina; Stritzler, Margarita; Schlesinger, Mariana; Capiati, Daniela Andrea

2017-02-01

This study provides the first genetic evidence for the role of PP2A in tuberization, demonstrating that the catalytic subunit StPP2Ac2b positively modulates tuber induction, and that its function is related to the regulation of gibberellic acid metabolism. The results contribute to a better understanding of the molecular mechanism controlling tuberization induction, which remains largely unknown. The serine/threonine protein phosphatases type 2A (PP2A) are implicated in several physiological processes in plants, playing important roles in hormone responses. In cultivated potato (Solanum tuberosum), six PP2A catalytic subunits (StPP2Ac) were identified. The PP2Ac of the subfamily I (StPP2Ac1, 2a and 2b) were suggested to be involved in the tuberization signaling in leaves, where the environmental and hormonal signals are perceived and integrated. The aim of this study was to investigate the role of PP2A in the tuberization induction in stolons. We selected one of the catalytic subunits of the subfamily I, StPP2Ac2b, to develop transgenic plants overexpressing this gene (StPP2Ac2b-OE). Stolons from StPP2Ac2b-OE plants show higher tuber induction rates in vitro, as compared to wild type stolons, with no differences in the number of tubers obtained at the end of the process. This effect is accompanied by higher expression levels of the gibberellic acid (GA) catabolic enzyme StGA2ox1. GA up-regulates StPP2Ac2b expression in stolons, possibly as part of the feedback system by which the hormone regulates its own level. Sucrose, a tuber-promoting factor in vitro, increases StPP2Ac2b expression. We conclude that StPP2Ac2b acts in stolons as a positive regulator tuber induction, integrating different tuberization-related signals mainly though the modulation of GA metabolism.

Competing E2 and SN2 Mechanisms for the F- + CH3CH2I Reaction.

PubMed

Yang, Li; Zhang, Jiaxu; Xie, Jing; Ma, Xinyou; Zhang, Linyao; Zhao, Chenyang; Hase, William L

2017-02-09

Anti-E2, syn-E2, inv-, and ret-S N 2 reaction channels for the gas-phase reaction of F - + CH 3 CH 2 I were characterized with a variety of electronic structure calculations. Geometrical analysis confirmed synchronous E2-type transition states for the elimination of the current reaction, instead of nonconcerted processes through E1cb-like and E1-like mechanisms. Importantly, the controversy concerning the reactant complex for anti-E2 and inv-S N 2 paths has been clarified in the present work. A positive barrier of +19.2 kcal/mol for ret-S N 2 shows the least feasibility to occur at room temperature. Negative activation energies (-16.9, -16.0, and -4.9 kcal/mol, respectively) for inv-S N 2, anti-E2, and syn-E2 indicate that inv-S N 2 and anti-E2 mechanisms significantly prevail over the eclipsed elimination. Varying the leaving group for a series of reactions F - + CH 3 CH 2 Y (Y = F, Cl, Br, and I) leads to monotonically decreasing barriers, which relates to the gradually looser TS structures following the order F > Cl > Br > I. The reactivity of each channel nearly holds unchanged except for the perturbation between anti-E2 and inv-S N 2. RRKM calculation reveals that the reaction of the fluorine ion with ethyl iodide occurs predominately via anti-E2 elimination, and the inv-S N 2 pathway is suppressed, although it is energetically favored. This phenomenon indicates that, in evaluating the competition between E2 and S N 2 processes, the kinetic or dynamical factors may play a significant role. By comparison with benchmark CCSD(T) energies, MP2, CAM-B3LYP, and M06 methods are recommended to perform dynamics simulations of the title reaction.

Using the Natural Language Paradigm (NLP) to Increase Vocalizations of Older Adults with Cognitive Impairments

ERIC Educational Resources Information Center

LeBlanc, Linda A.; Geiger, Kaneen B.; Sautter, Rachael A.; Sidener, Tina M.

2007-01-01

The Natural Language Paradigm (NLP) has proven effective in increasing spontaneous verbalizations for children with autism. This study investigated the use of NLP with older adults with cognitive impairments served at a leisure-based adult day program for seniors. Three individuals with limited spontaneous use of functional language participated…

An Au(I)-catalyzed rearrangement/cyclization cascade toward the synthesis of 2-substituted-1,4,5,6-tetrahydrocyclopenta[b]pyrrole.

PubMed

Mou, Xue-Qing; Xu, Zheng-Liang; Wang, Shao-Hua; Zhu, Dao-Yong; Wang, Jie; Bao, Wen; Zhou, Shi-Jiang; Yang, Chao; Zhang, Di

2015-08-04

An Au(I)-catalyzed tandem reaction for the synthesis of 2-phenyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole derivatives from 1-(1-hydroxy-3-phenylprop-2-yn-1-yl)cyclobutanol and primary amines or NH4OAc has been developed to afford a series of polysubstituted pyrroles in moderate to good yields.

B-2 Extremely High Frequency SATCOM and Computer Increment 1 (B-2 EHF Inc 1)

DTIC Science & Technology

2015-12-01

Confidence Level Confidence Level of cost estimate for current APB: 55% This APB reflects cost and funding data based on the B-2 EHF Increment I SCP...This cost estimate was quantified at the Mean (~55%) confidence level . Total Quantity Quantity SAR Baseline Production Estimate Current APB...Production Estimate Econ Qty Sch Eng Est Oth Spt Total 33.624 -0.350 1.381 0.375 0.000 -6.075 0.000 -0.620 -5.289 28.335 Current SAR Baseline to Current

Limited MHC class I intron 2 repertoire variation in bonobos.

PubMed

de Groot, Natasja G; Heijmans, Corrine M C; Helsen, Philippe; Otting, Nel; Pereboom, Zjef; Stevens, Jeroen M G; Bontrop, Ronald E

2017-10-01

Common chimpanzees (Pan troglodytes) experienced a selective sweep, probably caused by a SIV-like virus, which targeted their MHC class I repertoire. Based on MHC class I intron 2 data analyses, this selective sweep took place about 2-3 million years ago. As a consequence, common chimpanzees have a skewed MHC class I repertoire that is enriched for allotypes that are able to recognise conserved regions of the SIV proteome. The bonobo (Pan paniscus) shared an ancestor with common chimpanzees approximately 1.5 to 2 million years ago. To investigate whether the signature of this selective sweep is also detectable in bonobos, the MHC class I gene repertoire of two bonobo panels comprising in total 29 animals was investigated by Sanger sequencing. We identified 14 Papa-A, 20 Papa-B and 11 Papa-C alleles, of which eight, five and eight alleles, respectively, have not been reported previously. Within this pool of MHC class I variation, we recovered only 2 Papa-A, 3 Papa-B and 6 Papa-C intron 2 sequences. As compared to humans, bonobos appear to have an even more diminished MHC class I intron 2 lineage repertoire than common chimpanzees. This supports the notion that the selective sweep may have predated the speciation of common chimpanzees and bonobos. The further reduction of the MHC class I intron 2 lineage repertoire observed in bonobos as compared to the common chimpanzee may be explained by a founding effect or other subsequent selective processes.

Drosophila TAP/p32 is a core histone chaperone that cooperates with NAP-1, NLP, and nucleophosmin in sperm chromatin remodeling during fertilization

PubMed Central

Emelyanov, Alexander V.; Rabbani, Joshua; Mehta, Monika; Vershilova, Elena; Keogh, Michael C.

2014-01-01

Nuclear DNA in the male gamete of sexually reproducing animals is organized as sperm chromatin compacted primarily by sperm-specific protamines. Fertilization leads to sperm chromatin remodeling, during which protamines are expelled and replaced by histones. Despite our increased understanding of the factors that mediate nucleosome assembly in the nascent male pronucleus, the machinery for protamine removal remains largely unknown. Here we identify four Drosophila protamine chaperones that mediate the dissociation of protamine–DNA complexes: NAP-1, NLP, and nucleophosmin are previously characterized histone chaperones, and TAP/p32 has no known function in chromatin metabolism. We show that TAP/p32 is required for the removal of Drosophila protamine B in vitro, whereas NAP-1, NLP, and Nph share roles in the removal of protamine A. Embryos from P32-null females show defective formation of the male pronucleus in vivo. TAP/p32, similar to NAP-1, NLP, and Nph, facilitates nucleosome assembly in vitro and is therefore a histone chaperone. Furthermore, mutants of P32, Nlp, and Nph exhibit synthetic-lethal genetic interactions. In summary, we identified factors mediating protamine removal from DNA and reconstituted in a defined system the process of sperm chromatin remodeling that exchanges protamines for histones to form the nucleosome-based chromatin characteristic of somatic cells. PMID:25228646

Optical population of iodine molecule ion-pair states via valence states correlating with the third, I(2 P 1/2) + I(2 P 1/2), dissociation limit and their MI2 vdW complexes, M = I2, Xe

NASA Astrophysics Data System (ADS)

Lukashov, S. S.; Poretsky, S. A.; Pravilov, A. M.; Khadikova, E. I.; Shevchenko, E. V.

2010-10-01

The first results of measurements and analysis of excitation spectra of the I2( D0{/u +} → X0{/g +}) and I2( D0{/u +} → X0{/g +} and/or β1 g → A1 u ) luminescence, observed after three-step, λ1 + λ f + λ1, λ1 = 5508-5530 Å, λ f = 10644.0 Å, laser excitation of pure iodine vapour and I2 + Xe mixtures at room temperature via bound parts of the I2(0{/g +}, 1 u ( bb)) valence states correlating with the third, I(2 P 1/2) + I(2 P 1/2), dissociation limit and their MI2 vdW complexes, M = I2, Xe, are presented. Luminescence spectra in the λlum = 2200-5000 Å spectral range are also analyzed. Strong luminescence from the I2( D, γ, D', and/or β) states is observed, though the two latter may be populated in optical transitions in a free iodine molecule if hyperfine coupling of the I2(0{/g +} and 1 u ( bb)) state rovibronic levels occurs. We discuss possible mechanisms of optical population of the IP state.

Inelastic scattering matrix elements for the nonadiabatic collision B(2P1/2)+H2(1Sigmag+,j)<-->B(2P3/2)+H2(1Sigmag+,j').

PubMed

Weeks, David E; Niday, Thomas A; Yang, Sang H

2006-10-28

Inelastic scattering matrix elements for the nonadiabatic collision B(2P1/2)+H2(1Sigmag+,j)<-->B(2P3/2)+H2(1Sigmag+,j') are calculated using the time dependent channel packet method (CPM). The calculation employs 1 2A', 2 2A', and 1 2A" adiabatic electronic potential energy surfaces determined by numerical computation at the multireference configuration-interaction level [M. H. Alexander, J. Chem. Phys. 99, 6041 (1993)]. The 1 2A' and 2 2A', adiabatic electronic potential energy surfaces are transformed to yield diabatic electronic potential energy surfaces that, when combined with the total B+H2 rotational kinetic energy, yield a set of effective potential energy surfaces [M. H. Alexander et al., J. Chem. Phys. 103, 7956 (1995)]. Within the framework of the CPM, the number of effective potential energy surfaces used for the scattering matrix calculation is then determined by the size of the angular momentum basis used as a representation. Twenty basis vectors are employed for these calculations, and the corresponding effective potential energy surfaces are identified in the asymptotic limit by the H2 rotor quantum numbers j=0, 2, 4, 6 and B electronic states 2Pja, ja=1/2, 3/2. Scattering matrix elements are obtained from the Fourier transform of the correlation function between channel packets evolving in time on these effective potential energy surfaces. For these calculations the H2 bond length is constrained to a constant value of req=1.402 a.u. and state to state scattering matrix elements corresponding to a total angular momentum of J=1/2 are discussed for j=0<-->j'=0,2,4 and 2P1/2<-->2P1/2, 2P3/2 over a range of total energy between 0.0 and 0.01 a.u.

Using the Natural Language Paradigm (NLP) to increase vocalizations of older adults with cognitive impairments.

PubMed

Leblanc, Linda A; Geiger, Kaneen B; Sautter, Rachael A; Sidener, Tina M

2007-01-01

The Natural Language Paradigm (NLP) has proven effective in increasing spontaneous verbalizations for children with autism. This study investigated the use of NLP with older adults with cognitive impairments served at a leisure-based adult day program for seniors. Three individuals with limited spontaneous use of functional language participated in a multiple baseline design across participants. Data were collected on appropriate and inappropriate vocalizations with appropriate vocalizations coded as prompted or unprompted during baseline and treatment sessions. All participants experienced increases in appropriate speech during NLP with variable response patterns. Additionally, the two participants with substantial inappropriate vocalizations showed decreases in inappropriate speech. Implications for intervention in day programs are discussed.

Recent Progress in the Design of Advanced Cathode Materials and Battery Models for High-Performance Lithium-X (X = O2 , S, Se, Te, I2 , Br2 ) Batteries.

PubMed

Xu, Jiantie; Ma, Jianmin; Fan, Qinghua; Guo, Shaojun; Dou, Shixue

2017-07-01

Recent advances and achievements in emerging Li-X (X = O 2 , S, Se, Te, I 2 , Br 2 ) batteries with promising cathode materials open up new opportunities for the development of high-performance lithium-ion battery alternatives. In this review, we focus on an overview of recent important progress in the design of advanced cathode materials and battery models for developing high-performance Li-X (X = O 2 , S, Se, Te, I 2 , Br 2 ) batteries. We start with a brief introduction to explain why Li-X batteries are important for future renewable energy devices. Then, we summarize the existing drawbacks, major progress and emerging challenges in the development of cathode materials for Li-O 2 (S) batteries. In terms of the emerging Li-X (Se, Te, I 2 , Br 2 ) batteries, we systematically summarize their advantages/disadvantages and recent progress. Specifically, we review the electrochemical performance of Li-Se (Te) batteries using carbonate-/ether-based electrolytes, made with different electrode fabrication techniques, and of Li-I 2 (Br 2 ) batteries with various cell designs (e.g., dual electrolyte, all-organic electrolyte, with/without cathode-flow mode, and fuel cell/solar cell integration). Finally, the perspective on and challenges for the development of cathode materials for the promising Li-X (X = O 2 , S, Se, Te, I 2 , Br 2 ) batteries is presented. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.