ICN_Atlas: Automated description and quantification of functional MRI activation patterns in the framework of intrinsic connectivity networks.

PubMed

Kozák, Lajos R; van Graan, Louis André; Chaudhary, Umair J; Szabó, Ádám György; Lemieux, Louis

2017-12-01

Generally, the interpretation of functional MRI (fMRI) activation maps continues to rely on assessing their relationship to anatomical structures, mostly in a qualitative and often subjective way. Recently, the existence of persistent and stable brain networks of functional nature has been revealed; in particular these so-called intrinsic connectivity networks (ICNs) appear to link patterns of resting state and task-related state connectivity. These networks provide an opportunity of functionally-derived description and interpretation of fMRI maps, that may be especially important in cases where the maps are predominantly task-unrelated, such as studies of spontaneous brain activity e.g. in the case of seizure-related fMRI maps in epilepsy patients or sleep states. Here we present a new toolbox (ICN_Atlas) aimed at facilitating the interpretation of fMRI data in the context of ICN. More specifically, the new methodology was designed to describe fMRI maps in function-oriented, objective and quantitative way using a set of 15 metrics conceived to quantify the degree of 'engagement' of ICNs for any given fMRI-derived statistical map of interest. We demonstrate that the proposed framework provides a highly reliable quantification of fMRI activation maps using a publicly available longitudinal (test-retest) resting-state fMRI dataset. The utility of the ICN_Atlas is also illustrated on a parametric task-modulation fMRI dataset, and on a dataset of a patient who had repeated seizures during resting-state fMRI, confirmed on simultaneously recorded EEG. The proposed ICN_Atlas toolbox is freely available for download at http://icnatlas.com and at http://www.nitrc.org for researchers to use in their fMRI investigations. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Estimation of water absorption coefficient using the TDR method

NASA Astrophysics Data System (ADS)

Suchorab, Zbigniew; Majerek, Dariusz; Brzyski, Przemysław; Sobczuk, Henryk; Raczkowski, Andrzej

2017-07-01

Moisture accumulation and transport in the building barriers is an important feature that influences building performance, causing serious exploitation problems as increased energy use, mold and bacteria growth, decrease of indoor air parameters that may lead to sick building syndrome (SBS). One of the parameters that is used to describe moisture characteristic of the material is water absorption coefficient being the measure of capillary behavior of the material as a function of time and the surface area of the specimen. As usual it is determined using gravimetric methods according to EN 1925:1999 standard. In this article we demonstrate the possibility of determination of water absorption coefficient of autoclaved aerated concrete (AAC) using the Time Domain Reflectometry (TDR) method. TDR is an electric technique that had been adopted from soil science and can be successfully used for real-time monitoring of moisture transport in building materials and envelopes. Data achieved using TDR readouts show high correlation with standard method of moisture absorptivity coefficient determination.

NBS1 Phosphorylation Status Dictates Repair Choice of Dysfunctional Telomeres.

PubMed

Rai, Rekha; Hu, Chunyi; Broton, Cayla; Chen, Yong; Lei, Ming; Chang, Sandy

2017-03-02

Telomeres employ TRF2 to protect chromosome ends from activating the DNA damage sensor MRE11-RAD50-NBS1 (MRN), thereby repressing ATM-dependent DNA damage checkpoint responses. How TRF2 prevents MRN activation at dysfunctional telomeres is unclear. Here, we show that the phosphorylation status of NBS1 determines the repair pathway choice of dysfunctional telomeres. The crystal structure of the TRF2-NBS1 complex at 3.0 Å resolution shows that the NBS1 429 YQLSP 433 motif interacts specifically with the TRF2 TRFH domain. Phosphorylation of NBS1 serine 432 by CDK2 in S/G2 dissociates NBS1 from TRF2, promoting TRF2-Apollo/SNM1B complex formation and the protection of leading-strand telomeres. Classical-NHEJ-mediated repair of telomeres lacking TRF2 requires phosphorylated NBS1 S432 to activate ATM, while interaction of de-phosphorylated NBS1 S432 with TRF2 promotes alternative-NHEJ repair of telomeres lacking POT1-TPP1. Our work advances understanding of how the TRF2 TRFH domain orchestrates telomere end protection and reveals how the phosphorylation status of the NBS1 S432 dictates repair pathway choice of dysfunctional telomeres. Copyright © 2017 Elsevier Inc. All rights reserved.

Performance comparison of TDR-based systems for permanent and diffused detection of water content and leaks

NASA Astrophysics Data System (ADS)

Cataldo, A.; De Benedetto, E.; Cannazza, G.; Huebner, C.; Trebbels, D.

2017-01-01

In this work, the performance of three time domain reflectometry (TDR) instruments (with different hardware architectures, specifications and costs) is comparatively assessed. The goal is to evaluate the performance of low-cost TDR instrumentation, in view of the development of a completely permanent TDR-based monitoring solution, wherein the costs of the instrument is so low, that it can be left on-site, even unguarded, and controlled remotely. Without losing generality, the applications considered for the comparative experiments are the TDR-based detection of leaks in underground pipes and, more in general, of soil water content variations. For this reason, both laboratory and in-the-field experiments are carried out by comparatively using three TDR instruments, in conjunction with wire-like sensing elements (SEs).

Genome-Wide Comparative Analysis Reveals Similar Types of NBS Genes in Hybrid Citrus sinensis Genome and Original Citrus clementine Genome and Provides New Insights into Non-TIR NBS Genes

PubMed Central

Wang, Yunsheng; Zhou, Lijuan; Li, Dazhi; Dai, Liangying; Lawton-Rauh, Amy; Srimani, Pradip K.; Duan, Yongping; Luo, Feng

2015-01-01

In this study, we identified and compared nucleotide-binding site (NBS) domain-containing genes from three Citrus genomes (C. clementina, C. sinensis from USA and C. sinensis from China). Phylogenetic analysis of all Citrus NBS genes across these three genomes revealed that there are three approximately evenly numbered groups: one group contains the Toll-Interleukin receptor (TIR) domain and two different Non-TIR groups in which most of proteins contain the Coiled Coil (CC) domain. Motif analysis confirmed that the two groups of CC-containing NBS genes are from different evolutionary origins. We partitioned NBS genes into clades using NBS domain sequence distances and found most clades include NBS genes from all three Citrus genomes. This suggests that three Citrus genomes have similar numbers and types of NBS genes. We also mapped the re-sequenced reads of three pomelo and three mandarin genomes onto the C. sinensis genome. We found that most NBS genes of the hybrid C. sinensis genome have corresponding homologous genes in both pomelo and mandarin genomes. The homologous NBS genes in pomelo and mandarin suggest that the parental species of C. sinensis may contain similar types of NBS genes. This explains why the hybrid C. sinensis and original C. clementina have similar types of NBS genes in this study. Furthermore, we found that sequence variation amongst Citrus NBS genes were shaped by multiple independent and shared accelerated mutation accumulation events among different groups of NBS genes and in different Citrus genomes. Our comparative analyses yield valuable insight into the structure, organization and evolution of NBS genes in Citrus genomes. Furthermore, our comprehensive analysis showed that the non-TIR NBS genes can be divided into two groups that come from different evolutionary origins. This provides new insights into non-TIR genes, which have not received much attention. PMID:25811466

Genome-wide comparative analysis reveals similar types of NBS genes in hybrid Citrus sinensis genome and original Citrus clementine genome and provides new insights into non-TIR NBS genes.

PubMed

Wang, Yunsheng; Zhou, Lijuan; Li, Dazhi; Dai, Liangying; Lawton-Rauh, Amy; Srimani, Pradip K; Duan, Yongping; Luo, Feng

2015-01-01

In this study, we identified and compared nucleotide-binding site (NBS) domain-containing genes from three Citrus genomes (C. clementina, C. sinensis from USA and C. sinensis from China). Phylogenetic analysis of all Citrus NBS genes across these three genomes revealed that there are three approximately evenly numbered groups: one group contains the Toll-Interleukin receptor (TIR) domain and two different Non-TIR groups in which most of proteins contain the Coiled Coil (CC) domain. Motif analysis confirmed that the two groups of CC-containing NBS genes are from different evolutionary origins. We partitioned NBS genes into clades using NBS domain sequence distances and found most clades include NBS genes from all three Citrus genomes. This suggests that three Citrus genomes have similar numbers and types of NBS genes. We also mapped the re-sequenced reads of three pomelo and three mandarin genomes onto the C. sinensis genome. We found that most NBS genes of the hybrid C. sinensis genome have corresponding homologous genes in both pomelo and mandarin genomes. The homologous NBS genes in pomelo and mandarin suggest that the parental species of C. sinensis may contain similar types of NBS genes. This explains why the hybrid C. sinensis and original C. clementina have similar types of NBS genes in this study. Furthermore, we found that sequence variation amongst Citrus NBS genes were shaped by multiple independent and shared accelerated mutation accumulation events among different groups of NBS genes and in different Citrus genomes. Our comparative analyses yield valuable insight into the structure, organization and evolution of NBS genes in Citrus genomes. Furthermore, our comprehensive analysis showed that the non-TIR NBS genes can be divided into two groups that come from different evolutionary origins. This provides new insights into non-TIR genes, which have not received much attention.

Genome-Wide Identification and Expression Analysis of NBS-Encoding Genes in Malus x domestica and Expansion of NBS Genes Family in Rosaceae

PubMed Central

Arya, Preeti; Kumar, Gulshan; Acharya, Vishal; Singh, Anil K.

2014-01-01

Nucleotide binding site leucine-rich repeats (NBS-LRR) disease resistance proteins play an important role in plant defense against pathogen attack. A number of recent studies have been carried out to identify and characterize NBS-LRR gene families in many important plant species. In this study, we identified NBS-LRR gene family comprising of 1015 NBS-LRRs using highly stringent computational methods. These NBS-LRRs were characterized on the basis of conserved protein motifs, gene duplication events, chromosomal locations, phylogenetic relationships and digital gene expression analysis. Surprisingly, equal distribution of Toll/interleukin-1 receptor (TIR) and coiled coil (CC) (1∶1) was detected in apple while the unequal distribution was reported in majority of all other known plant genome studies. Prediction of gene duplication events intriguingly revealed that not only tandem duplication but also segmental duplication may equally be responsible for the expansion of the apple NBS-LRR gene family. Gene expression profiling using expressed sequence tags database of apple and quantitative real-time PCR (qRT-PCR) revealed the expression of these genes in wide range of tissues and disease conditions, respectively. Taken together, this study will provide a blueprint for future efforts towards improvement of disease resistance in apple. PMID:25232838

The ICN Leadership For Change™ Programme--20 years of growing influence.

PubMed

Ferguson, Stephanie L; Al Rifai, Fatima; Maay'a, Maisa; Nguyen, Luu Bich; Qureshi, Kristine; Tse, Alice M; Casken, John; Parsons, Teresa; Shannon, Maureen; Napa, Maria Diana; Samson-Langidrik, Malia; Jeadrik, Glorine

2016-03-01

The aim of this article was to present experiences from the field in the context of the International Council of Nurses' Leadership for Change™ programme, which celebrates 20 years of excellence in 2016 for developing the leadership and management capacity of nurses worldwide. The programme was launched in 1996 in order to boost nurse participation in the healthcare policy-making process, globally, and to foster within the nursing profession the requisite skills for nurses to lobby for and assume a greater responsibility in the leadership and management of health care services. Over the course of two decades, the programme has been implemented in cooperation between ICN, national nurses associations, the World Health Organization, Ministries of Health and a variety of donor organizations such as the W.K. Kellogg Foundation and development agencies such as USAID and AUSAID. The programme has been implemented in more than 60 nations throughout Africa, Asia, Europe, the Middle East, Latin America and the Pacific Islands, to name a few regions. This article offers an overview of the impact that certified ICN LFC nurse trainers and their colleagues have had in the United Arab Emirates, Vietnam and the United States of America and is affiliated islands and the North Pacific Islands. Twenty years of growth and empowerment are now the ongoing legacy of the ICN LFC Program, which has graduated and deployed nurse trainers around the world and achieved significant advances in the professional development of nurse leaders on an international scale. Nurse leaders can improve the health and well-being of their nations in collaboration with consumers and other key stakeholders. Nurse leaders are critical in improving health systems, their work places and broader societal challenges through sound nursing practice, education, research and evidence-based health and social policy change. © 2016 International Council of Nurses.

Framework for city planning including nature-based solutions (NBS)

NASA Astrophysics Data System (ADS)

Alkan Olsson, Johanna; Sörensen, Johanna; Persson, Anna

2017-04-01

A common strategy to lower the demand for intense land use and energy consumption is the densification of urban areas. While this might be a fruitful strategy for its main objectives, one concern is that space for green areas and surface water will be decreased. Therefore, densification increases the need of strategies to develop and increase the quality of nature-based solutions (NBS) in urban areas. Smarter city planning strategies are needed, both for maintenance of existing NBS and for implementation of NBS in new developments. City planning must be based on well-evaluated solutions, which in turn must be based on a decent data material for each city. Today there is however several type of difficulties related to adequate provision of data to ensure a better implementation of NBS. The challenges arise from issues such as lack of information about for example costs of maintenance of existing NBS, citizens' perceptions and preferred use of NBS to difficulties of a more technical character such as the format of available GIS information. This study focuses on this information gap regarding NBS that persists in most cities today. The project aims to develop a framework that can help city planners to overcome the gaps and facilitate the inclusion of high quality nature-based solutions where developed or maintained. The framework, which is detailed by identifying information gaps through a literature review and selected interviews with urban planners and experts in the area of NBS, is based on the idea that well-structured and user-friendly data supporting city-planning strategies are essential to facilitate the implementation of NBS. What can be understood as well structured and user-friendly data depends on the goals and needs expressed in the strategic plans, which mean that there is a need for a close interaction between the development data and the strategic political goals expressed in the plans.

Bioinformatics Analysis of NBS-LRR Encoding Resistance Genes in Setaria italica.

PubMed

Zhao, Yan; Weng, Qiaoyun; Song, Jinhui; Ma, Hailian; Yuan, Jincheng; Dong, Zhiping; Liu, Yinghui

2016-06-01

In plants, resistance (R) genes are involved in pathogen recognition and subsequent activation of innate immune responses. The nucleotide-binding site-leucine-rich repeat (NBS-LRR) genes family forms the largest R-gene family among plant genomes and play an important role in plant disease resistance. In this paper, comprehensive analysis of NBS-encoding genes is performed in the whole Setaria italica genome. A total of 96 NBS-LRR genes are identified, and comprehensive overview of the NBS-LRR genes is undertaken, including phylogenetic analysis, chromosome locations, conserved motifs of proteins, and gene expression. Based on the domain, these genes are divided into two groups and distributed in all Setaria italica chromosomes. Most NBS-LRR genes are located at the distal tip of the long arms of the chromosomes. Setaria italica NBS-LRR proteins share at least one nucleotide-biding domain and one leucine-rich repeat domain. Our results also show the duplication of NBS-LRR genes in Setaria italica is related to their gene structure.

Monitoring stream stage, channel profile, and aqueous conductivity with time domain reflectometry (TDR).

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

Brainard, James Robert; Tidwell, Vincent Carroll; Coplen, Amy K.

2004-11-01

Time domain reflectometry (TDR) operates by propagating a radar frequency electromagnetic pulse down a transmission line while monitoring the reflected signal. As the electromagnetic pulse propagates along the transmission line, it is subject to impedance by the dielectric properties of the media along the transmission line (e.g., air, water, sediment), reflection at dielectric discontinuities (e.g., air-water or water-sediment interface), and attenuation by electrically conductive materials (e.g., salts, clays). Taken together, these characteristics provide a basis for integrated stream monitoring; specifically, concurrent measurement of stream stage, channel profile and aqueous conductivity. Here, we make novel application of TDR within the contextmore » of stream monitoring. Efforts toward this goal followed three critical phases. First, a means of extracting the desired stream parameters from measured TDR traces was required. Analysis was complicated by the fact that interface location and aqueous conductivity vary concurrently and multiple interfaces may be present at any time. For this reason a physically based multisection model employing the S11 scatter function and Cole-Cole parameters for dielectric dispersion and loss was developed to analyze acquired TDR traces. Second, we explored the capability of this multisection modeling approach for interpreting TDR data acquired from complex environments, such as encountered in stream monitoring. A series of laboratory tank experiments were performed in which the depth of water, depth of sediment, and conductivity were varied systematically. Comparisons between modeled and independently measured data indicate that TDR measurements can be made with an accuracy of {+-}3.4x10{sup -3} m for sensing the location of an air/water or water/sediment interface and {+-}7.4% of actual for the aqueous conductivity. Third, monitoring stations were sited on the Rio Grande and Paria rivers to evaluate performance of the TDR

TDR water content inverse profiling in layered soils during infiltration and evaporation

NASA Astrophysics Data System (ADS)

Greco, R.; Guida, A.

2009-04-01

During the last three decades, time domain reflectometry (TDR) has become one of the most commonly used tools for soil water content measurements either in laboratory or in the field. Indeed, TDR provides easy and cheap water content estimations with relatively small disturbance to the investigated soil. TDR measurements of soil water content are based on the strong correlation between relative dielectric permittivity of wet soil and its volumetric water content. Several expressions of the relationship between relative dielectric permittivity and volumetric water content have been proposed, empirically stated (Topp et al., 1980) as well as based on semi-analytical approach to dielectric mixing models (Roth et al., 1990; Whalley, 1993). So far, TDR field applications suffered the limitation due to the capability of the technique of estimating only the mean water content in the volume investigated by the probe. Whereas the knowledge of non homogeneous vertical water content profiles was needed, it was necessary to install either several vertical probes of different length or several horizontal probes placed in the soil at different depths, in both cases strongly increasing soil disturbance as well as the complexity of the measurements. Several studies have been recently dedicated to the development of inversion methods aimed to extract more information from TDR waveforms, in order to estimate non homogeneous moisture profiles along the axis of the metallic probe used for TDR measurements. A common feature of all these methods is that electromagnetic transient through the wet soil along the probe is mathematically modelled, assuming that the unknown soil water content distribution corresponds to the best agreement between simulated and measured waveforms. In some cases the soil is modelled as a series of small layers with different dielectric properties, and the waveform is obtained as the result of the superposition of multiple reflections arising from impedance

Testing of the Japanese Experimental Module in NBS

NASA Technical Reports Server (NTRS)

1993-01-01

This photograph was taken in the Marshall Space Flight Center (MSFC) Neutral Buoyancy Simulator (NBS) during the testing of the Japanese Experimental Module. The NBS provided the weightless environment encountered in space needed for testing and the practices of extra-vehicular activities.

Accuracy improvement in the TDR-based localization of water leaks

NASA Astrophysics Data System (ADS)

Cataldo, Andrea; De Benedetto, Egidio; Cannazza, Giuseppe; Monti, Giuseppina; Demitri, Christian

A time domain reflectometry (TDR)-based system for the localization of water leaks has been recently developed by the authors. This system, which employs wire-like sensing elements to be installed along the underground pipes, has proven immune to the limitations that affect the traditional, acoustic leak-detection systems. Starting from the positive results obtained thus far, in this work, an improvement of this TDR-based system is proposed. More specifically, the possibility of employing a low-cost, water-absorbing sponge to be placed around the sensing element for enhancing the accuracy in the localization of the leak is addressed. To this purpose, laboratory experiments were carried out mimicking a water leakage condition, and two sensing elements (one embedded in a sponge and one without sponge) were comparatively used to identify the position of the leak through TDR measurements. Results showed that, thanks to the water retention capability of the sponge (which maintains the leaked water more localized), the sensing element embedded in the sponge leads to a higher accuracy in the evaluation of the position of the leak.

Rock Slide Monitoring by Using TDR Inclinometers

NASA Astrophysics Data System (ADS)

Drusa, Marián; Bulko, Roman

2016-12-01

The geotechnical monitoring of the slope deformations is widespread at present time. In many geological localities and civil engineering construction areas, monitoring is a unique tool for controlling of negative factors and processes, also inform us about actual state of rock environment or interacting structures. It is necessary for risk assessment. In our case, geotechnical monitoring is controlling rockslide activity around in the future part of motorway. The construction of new highway route D1 from Bratislava to Košice crosses the territory which is affected by a massive rockslide close to Kraľovany village. There was a need to monitor the activity of a large unstable rockslide with deep shear planes. In this case of underground movement activity, the Department of Geotechnics of the University of Žilina installed inclinometers at the unstable area which worked on Time Domain Reflectometry (TDR) principle. Based on provided measurements, effectivity and suitability of TDR inclinometers for monitoring of deep underground movement activity is demonstrated.

A New Non-Destructive TDR System Combined with a Piezoelectric Stack for Measuring Properties of Geomaterials

PubMed Central

Choi, Chanyong; Song, Minwoo; Kim, Daehyeon; Yu, Xiong

2016-01-01

Dry density and water content are two important factors affecting the degree of soil compaction. Conventional methods such as the sand cone test and the plate load test are used to measure such properties for evaluating the degree of compaction and the stiffness of soil in the field. However, these tests are generally very time-consuming and are inherent with some errors depending on the operator (in particular for the sand cone test). Elastic modulus is an indicator to describe the stress-strain behavior of soil and in some cases is used as a design input parameter. Although a rod type TDR (Time Domain Reflectometry) system has been recently proposed to overcome some shortcomings of the conventional methods (particularly the sand cone test), it requires driving the probes into the ground, thus implying that it is still a time-consuming and destructive testing method. This study aims to develop a new non-destructive TDR system that can rapidly measure the dry density, water content, and elastic modulus of soil on the surface of compacted soil, without disturbing the ground. In this study, the Piezoelectric Stack, which is an instrument for measuring the elastic modulus of soil, has been added to the TDR system with a flat type probe, leading to a non-destructive TDR system that is capable of measuring the dry density, water content, and elastic modulus of soil. The new TDR system developed is light enough for an engineer to carry. Results of the standard compaction and TDR tests on sand showed that the dry densities and the moisture contents measured with the new TDR system were in good agreement with those measured with the standard compaction test, respectively. Consequently, it appears that the new TDR system developed will be very useful to advance the current practice of compaction quality control. PMID:28773563

A New Non-Destructive TDR System Combined with a Piezoelectric Stack for Measuring Properties of Geomaterials.

PubMed

Choi, Chanyong; Song, Minwoo; Kim, Daehyeon; Yu, Xiong

2016-06-02

Dry density and water content are two important factors affecting the degree of soil compaction. Conventional methods such as the sand cone test and the plate load test are used to measure such properties for evaluating the degree of compaction and the stiffness of soil in the field. However, these tests are generally very time-consuming and are inherent with some errors depending on the operator (in particular for the sand cone test). Elastic modulus is an indicator to describe the stress-strain behavior of soil and in some cases is used as a design input parameter. Although a rod type TDR (Time Domain Reflectometry) system has been recently proposed to overcome some shortcomings of the conventional methods (particularly the sand cone test), it requires driving the probes into the ground, thus implying that it is still a time-consuming and destructive testing method. This study aims to develop a new non-destructive TDR system that can rapidly measure the dry density, water content, and elastic modulus of soil on the surface of compacted soil, without disturbing the ground. In this study, the Piezoelectric Stack, which is an instrument for measuring the elastic modulus of soil, has been added to the TDR system with a flat type probe, leading to a non-destructive TDR system that is capable of measuring the dry density, water content, and elastic modulus of soil. The new TDR system developed is light enough for an engineer to carry. Results of the standard compaction and TDR tests on sand showed that the dry densities and the moisture contents measured with the new TDR system were in good agreement with those measured with the standard compaction test, respectively. Consequently, it appears that the new TDR system developed will be very useful to advance the current practice of compaction quality control.

Study on Elastic Helical TDR Sensing Cable for Distributed Deformation Detection

PubMed Central

Tong, Renyuan; Li, Ming; Li, Qing

2012-01-01

In order to detect distributed ground surface deformation, an elastic helical structure Time Domain Reflectometry (TDR) sensing cable is shown in this paper. This special sensing cable consists of three parts: a silicone rubber rope in the center; a couple of parallel wires coiling around the rope; a silicone rubber pipe covering the sensing cable. By analyzing the relationship between the impedance and the structure of the sensing cable, the impedance model shows that the sensing cable impedance will increase when the cable is stretched. This specific characteristic is verified in the cable stretching experiment which is the base of TDR sensing technology. The TDR experiment shows that a positive reflected signal is created at the stretching deformation point on the sensing cable. The results show that the deformation section length and the stretching elongation will both affect the amplitude of the reflected signal. Finally, the deformation locating experiments show that the sensing cable can accurately detect the deformation point position on the sensing cable. PMID:23012560

The TDR: A Repository for Long Term Storage of Geophysical Data and Metadata

NASA Astrophysics Data System (ADS)

Wilson, A.; Baltzer, T.; Caron, J.

2006-12-01

For many years Unidata has provided easy, low cost data access to universities and research labs. Historically Unidata technology provided access to data in near real time. In recent years Unidata has additionally turned to providing middleware to serve longer term data and associated metadata via its THREDDS technology, the most recent offering being the THREDDS Data Server (TDS). The TDS provides middleware for metadata access and management, OPeNDAP data access, and integration with the Unidata Integrated Data Viewer (IDV), among other benefits. The TDS was designed to support rolling archives of data, that is, data that exist only for a relatively short, predefined time window. Now we are creating an addition to the TDS, called the THREDDS Data Repository (TDR), which allows users to store and retrieve data and other objects for an arbitrarily long time period. Data in the TDR can also be served by the TDS. The TDR performs important functions of locating storage for the data, moving the data to and from the repository, assigning unique identifiers, and generating metadata. The TDR framework supports pluggable components that allow tailoring an implementation for a particular application. The Linked Environments for Atmospheric Discovery (LEAD) project provides an excellent use case for the TDR. LEAD is a multi-institutional Large Information Technology Research project funded by the National Science Foundation (NSF). The goal of LEAD is to create a framework based on Grid and Web Services to support mesoscale meteorology research and education. This includes capabilities such as launching forecast models, mining data for meteorological phenomena, and dynamic workflows that are automatically reconfigurable in response to changing weather. LEAD presents unique challenges in managing and storing large data volumes from real-time observational systems as well as data that are dynamically created during the execution of adaptive workflows. For example, in order to

Jernigan and Wolf in Neutral Buoyancy Simulator (NBS)

NASA Technical Reports Server (NTRS)

1995-01-01

Astronauts Tamara Jernigan (#1) and David Wolf (#2) are training in the Neutral Buoyancy Simulator (NBS) at Marshall Space Flight center with an exercise for International Space Station Alpha. The NBS provided the weightless environment encountered in space needed for testing and the practices of Extravehicular Activities (EVA).

The ICN Leadership For Change™ Programme – 20 years of growing influence

PubMed Central

Ferguson, Stephanie L.; Rifai, Fatima Al; Maay'a, Maisa; Nguyen, Luu Bich; Qureshi, Kristine; Tse, Alice M.; Casken, John; Parsons, Teresa; Shannon, Maureen; Napa, Maria Diana; Samson-Langidrik, Malia; Jeadrik, Glorine

2017-01-01

Aim The aim of this article was to present experiences from the field in the context of the International Council of Nurses' Leadership for Change™ programme, which celebrates 20 years of excellence in 2016 for developing the leadership and management capacity of nurses worldwide. Background The programme was launched in 1996 in order to boost nurse participation in the healthcare policy-making process, globally, and to foster within the nursing profession the requisite skills for nurses to lobby for and assume a greater responsibility in the leadership and management of health care services. Introduction Over the course of two decades, the programme has been implemented in cooperation between ICN, national nurses associations, the World Health Organization, Ministries of Health and a variety of donor organizations such as the W.K. Kellogg Foundation and development agencies such as USAID and AUSAID. The programme has been implemented in more than 60 nations throughout Africa, Asia, Europe, the Middle East, Latin America and the Pacific Islands, to name a few regions. Methods This article offers an overview of the impact that certified ICN LFC nurse trainers and their colleagues have had in the United Arab Emirates, Vietnam and the United States of America and is affiliated islands and the North Pacific Islands. Results Twenty years of growth and empowerment are now the ongoing legacy of the ICN LFC Program, which has graduated and deployed nurse trainers around the world and achieved significant advances in the professional development of nurse leaders on an international scale. Implications for nursing and health policy Nurse leaders can improve the health and well-being of their nations in collaboration with consumers and other key stakeholders. Nurse leaders are critical in improving health systems, their work places and broader societal challenges through sound nursing practice, education, research and evidence-based health and social policy change. PMID

Design and Calibration of the NBS Isotropic Electric-Field Monitor (EFM- 5), 0.2 to 1000 MHz

DTIC Science & Technology

1981-03-01

34 "’" ^^ Up t0 about 5° ™<<« (316 V/m). and a There are th * "P t0 M dBV/m (10°° V/m)’ teen designated "IT"’"’ ^^^ ^^ *""* ’" the meter1n9 un1t...investigation. However, NBS personnel have analyzed •v ■ v" .*U^O> IV ***» • ts* M .h jnj hjve nude preliminary evaluations of new types of

3. WIDE ANGLE OF NEUTRAL BUOYANCY SIMULATOR (NBS) FROM WITHIN ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

3. WIDE ANGLE OF NEUTRAL BUOYANCY SIMULATOR (NBS) FROM WITHIN NBS HIGHBAY DOORS. DIVE BELL IN FOREGROUND. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

A verification of the gyrokinetic microstability codes GEM, GYRO, and GS2

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

Bravenec, R. V.; Chen, Y.; Wan, W.

2013-10-15

A previous publication [R. V. Bravenec et al., Phys. Plasmas 18, 122505 (2011)] presented favorable comparisons of linear frequencies and nonlinear fluxes from the Eulerian gyrokinetic codes gyro[J. Candy and R. E. Waltz, J. Comput. Phys. 186, 545 (2003)] and gs2[W. Dorland et al., Phys. Rev. Lett. 85, 5579 (2000)]. The motivation was to verify the codes, i.e., demonstrate that they correctly solve the gyrokinetic-Maxwell equations. The premise was that it is highly unlikely for both codes to yield the same incorrect results. In this work, we add the Lagrangian particle-in-cell code gem[Y. Chen and S. Parker, J. Comput. Phys.more » 220, 839 (2007)] to the comparisons, not simply to add another code, but also to demonstrate that the codes' algorithms do not matter. We find good agreement of gem with gyro and gs2 for the plasma conditions considered earlier, thus establishing confidence that the codes are verified and that ongoing validation efforts for these plasma parameters are warranted.« less

Quantification of soil water retention parameters using multi-section TDR-waveform analysis

NASA Astrophysics Data System (ADS)

Baviskar, S. M.; Heimovaara, T. J.

2017-06-01

Soil water retention parameters are important for describing flow in variably saturated soils. TDR is one of the standard methods used for determining water content in soil samples. In this study, we present an approach to estimate water retention parameters of a sample which is initially saturated and subjected to an incremental decrease in boundary head causing it to drain in a multi-step fashion. TDR waveforms are measured along the height of the sample at assumed different hydrostatic conditions at daily interval. The cumulative discharge outflow drained from the sample is also recorded. The saturated water content is obtained using volumetric analysis after the final step involved in multi-step drainage. The equation obtained by coupling the unsaturated parametric function and the apparent dielectric permittivity is fitted to a TDR wave propagation forward model. The unsaturated parametric function is used to spatially interpolate the water contents along TDR probe. The cumulative discharge outflow data is fitted with cumulative discharge estimated using the unsaturated parametric function. The weight of water inside the sample estimated at the first and final boundary head in multi-step drainage is fitted with the corresponding weights calculated using unsaturated parametric function. A Bayesian optimization scheme is used to obtain optimized water retention parameters for these different objective functions. This approach can be used for samples with long heights and is especially suitable for characterizing sands with a uniform particle size distribution at low capillary heads.

Estimation of Soil-Water Characteristic Curves in Multiple-Cycles Using Membrane and TDR System

PubMed Central

Hong, Won-Taek; Jung, Young-Seok; Kang, Seonghun; Lee, Jong-Sub

2016-01-01

The objective of this study is to estimate multiple-cycles of the soil-water characteristic curve (SWCC) using an innovative volumetric pressure plate extractor (VPPE), which is incorporated with a membrane and time domain reflectometry (TDR). The pressure cell includes the membrane to reduce the experimental time and the TDR probe to automatically estimate the volumetric water content. For the estimation of SWCC using the VPPE system, four specimens with different grain size and void ratio are prepared. The volumetric water contents of the specimens according to the matric suction are measured by the burette system and are estimated in the TDR system during five cycles of SWCC tests. The volumetric water contents estimated by the TDR system are almost identical to those determined by the burette system. The experimental time significantly decreases with the new VPPE. The hysteresis in the SWCC is largest in the first cycle and is nearly identical after 1.5 cycles. As the initial void ratio decreases, the air entry value increases. This study suggests that the new VPPE may effectively estimate multiple-cycles of the SWCC of unsaturated soils. PMID:28774139

pyNBS: A Python implementation for network-based stratification of tumor mutations.

PubMed

Huang, Justin K; Jia, Tongqiu; Carlin, Daniel E; Ideker, Trey

2018-03-28

We present pyNBS: a modularized Python 2.7 implementation of the network-based stratification (NBS) algorithm for stratifying tumor somatic mutation profiles into molecularly and clinically relevant subtypes. In addition to release of the software, we benchmark its key parameters and provide a compact cancer reference network that increases the significance of tumor stratification using the NBS algorithm. The structure of the code exposes key steps of the algorithm to foster further collaborative development. The package, along with examples and data, can be downloaded and installed from the URL http://www.github.com/huangger/pyNBS/. jkh013@ucsd.edu.

TDR Targets: a chemogenomics resource for neglected diseases.

PubMed

Magariños, María P; Carmona, Santiago J; Crowther, Gregory J; Ralph, Stuart A; Roos, David S; Shanmugam, Dhanasekaran; Van Voorhis, Wesley C; Agüero, Fernán

2012-01-01

The TDR Targets Database (http://tdrtargets.org) has been designed and developed as an online resource to facilitate the rapid identification and prioritization of molecular targets for drug development, focusing on pathogens responsible for neglected human diseases. The database integrates pathogen specific genomic information with functional data (e.g. expression, phylogeny, essentiality) for genes collected from various sources, including literature curation. This information can be browsed and queried using an extensive web interface with functionalities for combining, saving, exporting and sharing the query results. Target genes can be ranked and prioritized using numerical weights assigned to the criteria used for querying. In this report we describe recent updates to the TDR Targets database, including the addition of new genomes (specifically helminths), and integration of chemical structure, property and bioactivity information for biological ligands, drugs and inhibitors and cheminformatic tools for querying and visualizing these chemical data. These changes greatly facilitate exploration of linkages (both known and predicted) between genes and small molecules, yielding insight into whether particular proteins may be druggable, effectively allowing the navigation of chemical space in a genomics context.

Genome-wide comparative analysis of NBS-encoding genes between Brassica species and Arabidopsis thaliana.

PubMed

Yu, Jingyin; Tehrim, Sadia; Zhang, Fengqi; Tong, Chaobo; Huang, Junyan; Cheng, Xiaohui; Dong, Caihua; Zhou, Yanqiu; Qin, Rui; Hua, Wei; Liu, Shengyi

2014-01-03

Plant disease resistance (R) genes with the nucleotide binding site (NBS) play an important role in offering resistance to pathogens. The availability of complete genome sequences of Brassica oleracea and Brassica rapa provides an important opportunity for researchers to identify and characterize NBS-encoding R genes in Brassica species and to compare with analogues in Arabidopsis thaliana based on a comparative genomics approach. However, little is known about the evolutionary fate of NBS-encoding genes in the Brassica lineage after split from A. thaliana. Here we present genome-wide analysis of NBS-encoding genes in B. oleracea, B. rapa and A. thaliana. Through the employment of HMM search and manual curation, we identified 157, 206 and 167 NBS-encoding genes in B. oleracea, B. rapa and A. thaliana genomes, respectively. Phylogenetic analysis among 3 species classified NBS-encoding genes into 6 subgroups. Tandem duplication and whole genome triplication (WGT) analyses revealed that after WGT of the Brassica ancestor, NBS-encoding homologous gene pairs on triplicated regions in Brassica ancestor were deleted or lost quickly, but NBS-encoding genes in Brassica species experienced species-specific gene amplification by tandem duplication after divergence of B. rapa and B. oleracea. Expression profiling of NBS-encoding orthologous gene pairs indicated the differential expression pattern of retained orthologous gene copies in B. oleracea and B. rapa. Furthermore, evolutionary analysis of CNL type NBS-encoding orthologous gene pairs among 3 species suggested that orthologous genes in B. rapa species have undergone stronger negative selection than those in B .oleracea species. But for TNL type, there are no significant differences in the orthologous gene pairs between the two species. This study is first identification and characterization of NBS-encoding genes in B. rapa and B. oleracea based on whole genome sequences. Through tandem duplication and whole genome

TIR-NBS-LRR genes are rare in monocots: evidence from diverse monocot orders

PubMed Central

Tarr, D Ellen K; Alexander, Helen M

2009-01-01

Background Plant resistance (R) gene products recognize pathogen effector molecules. Many R genes code for proteins containing nucleotide binding site (NBS) and C-terminal leucine-rich repeat (LRR) domains. NBS-LRR proteins can be divided into two groups, TIR-NBS-LRR and non-TIR-NBS-LRR, based on the structure of the N-terminal domain. Although both classes are clearly present in gymnosperms and eudicots, only non-TIR sequences have been found consistently in monocots. Since most studies in monocots have been limited to agriculturally important grasses, it is difficult to draw conclusions. The purpose of our study was to look for evidence of these sequences in additional monocot orders. Findings Using degenerate PCR, we amplified NBS sequences from four monocot species (C. blanda, D. marginata, S. trifasciata, and Spathiphyllum sp.), a gymnosperm (C. revoluta) and a eudicot (C. canephora). We successfully amplified TIR-NBS-LRR sequences from dicot and gymnosperm DNA, but not from monocot DNA. Using databases, we obtained NBS sequences from additional monocots, magnoliids and basal angiosperms. TIR-type sequences were not present in monocot or magnoliid sequences, but were present in the basal angiosperms. Phylogenetic analysis supported a single TIR clade and multiple non-TIR clades. Conclusion We were unable to find monocot TIR-NBS-LRR sequences by PCR amplification or database searches. In contrast to previous studies, our results represent five monocot orders (Poales, Zingiberales, Arecales, Asparagales, and Alismatales). Our results establish the presence of TIR-NBS-LRR sequences in basal angiosperms and suggest that although these sequences were present in early land plants, they have been reduced significantly in monocots and magnoliids. PMID:19785756

A Scientometric Evaluation of the Chagas Disease Implementation Research Programme of the PAHO and TDR

PubMed Central

Carbajal-de-la-Fuente, Ana Laura; Yadón, Zaida E.

2013-01-01

The Special Programme for Research and Training in Tropical Diseases (TDR) is an independent global programme of scientific collaboration cosponsored by the United Nations Children's Fund, the United Nations Development Program, the World Bank, and the World Health Organization. TDR's strategy is based on stewardship for research on infectious diseases of poverty, empowerment of endemic countries, research on neglected priority needs, and the promotion of scientific collaboration influencing global efforts to combat major tropical diseases. In 2001, in view of the achievements obtained in the reduction of transmission of Chagas disease through the Southern Cone Initiative and the improvement in Chagas disease control activities in some countries of the Andean and the Central American Initiatives, TDR transferred the Chagas Disease Implementation Research Programme (CIRP) to the Communicable Diseases Unit of the Pan American Health Organization (CD/PAHO). This paper presents a scientometric evaluation of the 73 projects from 18 Latin American and European countries that were granted by CIRP/PAHO/TDR between 1997 and 2007. We analyzed all final reports of the funded projects and scientific publications, technical reports, and human resource training activities derived from them. Results about the number of projects funded, countries and institutions involved, gender analysis, number of published papers in indexed scientific journals, main topics funded, patents inscribed, and triatomine species studied are presented and discussed. The results indicate that CIRP/PAHO/TDR initiative has contributed significantly, over the 1997–2007 period, to Chagas disease knowledge as well as to the individual and institutional-building capacity. PMID:24244761

Turbulence and turbulent drag reduction in swirling flow: Inertial versus viscous forcing

NASA Astrophysics Data System (ADS)

Burnishev, Yuri; Steinberg, Victor

2015-08-01

We report unexpected results of a drastic difference in the transition to fully developed turbulent and turbulent drag reduction (TDR) regimes and in their properties in a von Karman swirling flow with counter-rotating disks of water-based polymer solutions for viscous (by smooth disks) as well as inertial (by bladed disks) forcing and by tracking just torque Γ (t ) and pressure p (t ) . For the viscous forcing, just a single TDR regime is found with the transition values of the Reynolds number (Re) Recturb=RecTDR≃(4.8 ±0.2 ) ×105 independent of ϕ , whereas for the inertial forcing two turbulent regimes are revealed. The first transition is to fully developed turbulence, and the second one is to the TDR regime with both Recturb and RecTDR depending on polymer concentration ϕ . Both regimes differ by the values of Cf and Cp, by the scaling exponents of the fundamental turbulent characteristics, by the nonmonotonic dependencies of skewness and flatness of the pressure PDFs on Re, and by the different frequency power spectra of p with the different dependencies of the main vortex peak frequency in the p power spectra on ϕ and Re. Thus our experimental results show the transition to the TDR regime in a von Karman swirling flow for the viscous and inertial forcings in a sharp contrast to the recent experiments [Phys. Fluids 10, 426 (1998), 10.1063/1.869532; Phys. Rev. E 47, R28(R) (1993), 10.1103/PhysRevE.47.R28; and J. Phys.: Condens. Matter 17, S1195 (2005), 10.1088/0953-8984/17/14/008] where the transition to TDR is observed in the same swirling flow with counter-rotating disks only for the viscous forcing. The latter result has led its authors to the wrong conclusion that TDR is a solely boundary effect contrary to the inertial forcing associated with the bulk effect, and this conception is currently rather widely accepted in literature.

TDR Targets: a chemogenomics resource for neglected diseases

PubMed Central

Magariños, María P.; Carmona, Santiago J.; Crowther, Gregory J.; Ralph, Stuart A.; Roos, David S.; Shanmugam, Dhanasekaran; Van Voorhis, Wesley C.; Agüero, Fernán

2012-01-01

The TDR Targets Database (http://tdrtargets.org) has been designed and developed as an online resource to facilitate the rapid identification and prioritization of molecular targets for drug development, focusing on pathogens responsible for neglected human diseases. The database integrates pathogen specific genomic information with functional data (e.g. expression, phylogeny, essentiality) for genes collected from various sources, including literature curation. This information can be browsed and queried using an extensive web interface with functionalities for combining, saving, exporting and sharing the query results. Target genes can be ranked and prioritized using numerical weights assigned to the criteria used for querying. In this report we describe recent updates to the TDR Targets database, including the addition of new genomes (specifically helminths), and integration of chemical structure, property and bioactivity information for biological ligands, drugs and inhibitors and cheminformatic tools for querying and visualizing these chemical data. These changes greatly facilitate exploration of linkages (both known and predicted) between genes and small molecules, yielding insight into whether particular proteins may be druggable, effectively allowing the navigation of chemical space in a genomics context. PMID:22116064

Functionalized NbS2 as cathode for Li- and Na-ion batteries

NASA Astrophysics Data System (ADS)

Zhu, Jiajie; Alshareef, Husam N.; Schwingenschlögl, Udo

2017-07-01

Cathodes of Li- and Na-ion batteries usually have capacities <200 mAh/g, significantly less than the anodes. Two-dimensional materials can overcome this limitation but suffer from low voltages. In this context, we investigate NbS2 functionalized by O, F, and Cl as a cathode material by first-principles calculations, considering both the conversion and intercalation mechanisms. NbS2O2 shows a higher voltage than NbS2 for both Li and Na, but the voltage decreases drastically for increasing ion coverage. Even higher voltages and favorable dependences on the ion coverage are achieved by F and Cl functionalization. We obtain NbS2F2 and NbS2Cl2 energy densities of 1223 mW h/g and 823 mW h/g for lithiation and 1086 mW h/g and 835 mW h/g for sodiation, respectively. These values are higher than those for most state-of-the-art cathode materials ( ˜600 mW h/g). In addition, low diffusion barriers enable high cycling rates.

Proceedings of the Fifth Integrated Communications, Navigation, and Surveillance (ICNS) Conference and Workshop

NASA Technical Reports Server (NTRS)

Fujikawa, Gene (Compiler)

2005-01-01

Contents includes papers on the following: JPDO: Inter-Agency Cooperation for the Next Generation ATS; R&T Programs; Integrated CNS Systems and Architectures; Datalink Communication Systems; Navigation, System Demonstrations and Operations; Safety and Security Initiatives Impacting CNS; Global Communications Initiatives; Airborne Internet; Avionics for System-Level Enhancements; SWIM (System Wide Information Management); Weather Products and Data Dissemination Technologies; Airsapce Communication Networks; Surveillance Systems; Workshop Breakouts Sessions and ; ICNS Conference Information.

Sandia National Laboratories, Tonopah Test Range Askania Tower (Building 02-00): Photographs and Written Historical and Descriptive Data

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

Ullrich, Rebecca A.

The Askania Tower (Building 02-00) was built in 1956 as part of the first wave of construction at the newly established Tonopah Test Range (TTR). Located at Station 2, near the primary target area at the range, the tower was one of the first four built to house Askania phototheodolites used in tracking test units dropped from aircraft. This report includes historical information, architectural information, sources of information, project information, maps, blueprints, and photographs.

Oral ezatiostat HCl (Telintra®, TLK199) and Idiopathic Chronic Neutropenia (ICN): a case report of complete response of a patient with G-CSF resistant ICN following treatment with ezatiostat, a glutathione S-transferase P1-1 (GSTP1-1) inhibitor

PubMed Central

2011-01-01

Idiopathic chronic neutropenia (ICN) describes a heterogeneous group of hematologic diseases characterized by low circulating neutrophil levels often associated with recurrent fevers, chronic mucosal inflammation, and severe systemic infections. The severity and risk of complications, including serious infections, are inversely proportional to the absolute neutrophil count (ANC), with the greatest problems occurring in patients with an ANC of less than 0.5 × 109/L. This case report describes a 64-year-old female with longstanding rheumatoid arthritis who subsequently developed ICN with frequent episodes of sepsis requiring hospitalization and prolonged courses of antibiotics over a 4-year period. She was treated with granulocyte colony stimulating factors (G-CSF) but had a delayed, highly variable, and volatile response. She was enrolled in a clinical trial evaluating the oral investigational agent ezatiostat. Ezatiostat, a glutathione S-transferase P1-1 inhibitor, activates Jun kinase, promoting the growth and maturation of hematopoietic progenitor stem cells. She responded by the end of the first month of treatment with stabilization of her ANC (despite tapering and then stopping G-CSF), clearing of fever, and healing of areas of infection. This ANC response to ezatiostat treatment has now been sustained for over 8 months and continues. These results suggest potential roles for ezatiostat in the treatment of patients with ICN who are not responsive to G-CSF, as an oral therapy alternative, or as an adjunct to G-CSF, and further studies are warranted. PMID:22047626

Dynamic Biomechanical Examination of the Lumbar Spine with Implanted Total Disc Replacement (TDR) Utilizing a Pendulum Testing System

PubMed Central

Daniels, Alan H; Paller, David J; Koruprolu, Sarath; McDonnell, Matthew; Palumbo, Mark A; Crisco, Joseph J

2013-01-01

Study Design Biomechanical cadaver investigation Objective To examine dynamic bending stiffness and energy absorption of the lumbar spine with and without implanted Total Disc Replacement (TDR) under simulated physiologic motion. Summary of background data The pendulum testing system is capable of applying physiologic compressive loads without constraining motion of functional spinal units (FSUs). The number of cycles to equilibrium observed under pendulum testing is a measure of the energy absorbed by the FSU. Methods Five unembalmed, frozen human lumbar FSUs were tested on the pendulum system with axial compressive loads of 181N, 282N, 385N, and 488N before and after Synthes ProDisc-L TDR implantation. Testing in flexion, extension, and lateral bending began by rotating the pendulum to 5° resulting in unconstrained oscillatory motion. The number of rotations to equilibrium was recorded and bending stiffness (N-m/°) was calculated and compared for each testing mode. Results In flexion/extension, the TDR constructs reached equilibrium with significantly (p<0.05) fewer cycles than the intact FSU with compressive loads of 282N, 385N and 488N. Mean dynamic bending stiffness in flexion, extension, and lateral bending increased significantly with increasing load for both the intact FSU and TDR constructs (p<0.001). In flexion, with increasing compressive loading from 181N to 488N, the bending stiffness of the intact FSUs increased from 4.0N-m/° to 5.5N-m/°, compared to 2.1N-m/° to 3.6N-m/° after TDR implantation. At each compressive load, the intact FSU was significantly more stiff than the TDR (p<0.05). Conclusion Lumbar FSUs with implanted TDR were found to be less stiff, but also absorbed more energy during cyclic loading with an unconstrained pendulum system. Although the effects on clinical performance of motion preserving devices are not fully known, these results provide further insight into the biomechanical behavior of this device under approximated

An anther development F-box (ADF) protein regulated by tapetum degeneration retardation (TDR) controls rice anther development.

PubMed

Li, Li; Li, Yixing; Song, Shufeng; Deng, Huafeng; Li, Na; Fu, Xiqin; Chen, Guanghui; Yuan, Longping

2015-01-01

In this study, we reported that a F-box protein, OsADF, as one of the direct targets of TDR , plays a critical role in rice tapetum cell development and pollen formation. The tapetum, the innermost sporophytic tissue of anther, plays an important supportive role in male reproduction in flowering plants. After meiosis, tapetal cells undergo programmed cell death (PCD) and provide nutrients for pollen development. Previously we showed that tapetum degeneration retardation (TDR), a basic helix-loop-helix transcription factor, can trigger tapetal PCD and control pollen wall development during anther development. However, the comprehensive regulatory network of TDR remains to be investigated. In this study, we cloned and characterized a panicle-specific expression F-box protein, anther development F-box (OsADF). By qRT-PCR and RNA in situ hybridization, we further confirmed that OsADF expressed specially in tapetal cells from stage 9 to stage 12 during anther development. In consistent with this specific expression pattern, the RNAi transgenic lines of OsADF exhibited abnormal tapetal degeneration and aborted microspores development, which eventually grew pollens with reduced fertility. Furthermore, we demonstrated that the TDR, a key regulator in controlling rice anther development, could regulate directly the expression of OsADF by binding to E-box motifs of its promoter. Therefore, this work highlighted the possible regulatory role of TDR, which regulates tapetal cell development and pollen formation via triggering the possible ADF-mediated proteolysis pathway.

PCR Cloning of Partial "nbs" Sequences from Grape ("Vitis aestivalis" Michx)

ERIC Educational Resources Information Center

Chang, Ming-Mei; DiGennaro, Peter; Macula, Anthony

2009-01-01

Plants defend themselves against pathogens via the expressions of disease resistance (R) genes. Many plant R gene products contain the characteristic nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains. There are highly conserved motifs within the NBS domain which could be targeted for polymerase chain reaction (PCR) cloning of R…

Polymer Research at NBS-NIST

NASA Astrophysics Data System (ADS)

Han, Charles

2001-03-01

Research on Polymers at NBS-NIST can be traced back to the World War I era.. During World War II, rubber and other organic materials testing and characterization started to play an important role in the nation's war effort. Since the 1940's, the rubber and plastic industry has transformed our lives. Rubber and plastic becomes a part of nearly every aspect of our daily life, including clothing, housing, transportation, and even food. The standards, testing methods, and basic physics research results produced at NBS-NIST had extensive influences and impacts on science and technology development during the post WWII period. Although sometimes controversial, the research in polymer crystallization, in linear and non-linear visco-elasticity, in surface adsorption, in piezoelectrical and pyroelectrical properties, in light scattering and neutron scattering, in polymer blends and alloys, and in dental applications, has made important contributions in the establishment of the current technology base. The challenge is to set the correct course in the future. We can learn many things by simply looking back at our past.

A Model-Based Probabilistic Inversion Framework for Wire Fault Detection Using TDR

NASA Technical Reports Server (NTRS)

Schuet, Stefan R.; Timucin, Dogan A.; Wheeler, Kevin R.

2010-01-01

Time-domain reflectometry (TDR) is one of the standard methods for diagnosing faults in electrical wiring and interconnect systems, with a long-standing history focused mainly on hardware development of both high-fidelity systems for laboratory use and portable hand-held devices for field deployment. While these devices can easily assess distance to hard faults such as sustained opens or shorts, their ability to assess subtle but important degradation such as chafing remains an open question. This paper presents a unified framework for TDR-based chafing fault detection in lossy coaxial cables by combining an S-parameter based forward modeling approach with a probabilistic (Bayesian) inference algorithm. Results are presented for the estimation of nominal and faulty cable parameters from laboratory data.

Theseus: tethered distributed robotics (TDR)

NASA Astrophysics Data System (ADS)

Digney, Bruce L.; Penzes, Steven G.

2003-09-01

The Defence Research and Development Canada's (DRDC) Autonomous Intelligent System's program conducts research to increase the independence and effectiveness of military vehicles and systems. DRDC-Suffield's Autonomous Land Systems (ALS) is creating new concept vehicles and autonomous control systems for use in outdoor areas, urban streets, urban interiors and urban subspaces. This paper will first give an overview of the ALS program and then give a specific description of the work being done for mobility in urban subspaces. Discussed will be the Theseus: Thethered Distributed Robotics (TDR) system, which will not only manage an unavoidable tether but exploit it for mobility and navigation. Also discussed will be the prototype robot called the Hedgehog, which uses conformal 3D mobility in ducts, sewer pipes, collapsed rubble voids and chimneys.

The Rice Basic Helix-Loop-Helix Transcription Factor TDR INTERACTING PROTEIN2 Is a Central Switch in Early Anther Development[C][W

PubMed Central

Fu, Zhenzhen; Yu, Jing; Cheng, Xiaowei; Zong, Xu; Xu, Jie; Chen, Mingjiao; Li, Zongyun; Zhang, Dabing; Liang, Wanqi

2014-01-01

In male reproductive development in plants, meristemoid precursor cells possessing transient, stem cell–like features undergo cell divisions and differentiation to produce the anther, the male reproductive organ. The anther contains centrally positioned microsporocytes surrounded by four distinct layers of wall: the epidermis, endothecium, middle layer, and tapetum. Here, we report that the rice (Oryza sativa) basic helix-loop-helix (bHLH) protein TDR INTERACTING PROTEIN2 (TIP2) functions as a crucial switch in the meristemoid transition and differentiation during early anther development. The tip2 mutants display undifferentiated inner three anther wall layers and abort tapetal programmed cell death, causing complete male sterility. TIP2 has two paralogs in rice, TDR and EAT1, which are key regulators of tapetal programmed cell death. We revealed that TIP2 acts upstream of TDR and EAT1 and directly regulates the expression of TDR and EAT1. In addition, TIP2 can interact with TDR, indicating a role of TIP2 in later anther development. Our findings suggest that the bHLH proteins TIP2, TDR, and EAT1 play a central role in regulating differentiation, morphogenesis, and degradation of anther somatic cell layers, highlighting the role of paralogous bHLH proteins in regulating distinct steps of plant cell–type determination. PMID:24755456

Large-scale synthesis of NbS2 nanosheets with controlled orientation on graphene by ambient pressure CVD.

PubMed

Ge, Wanyin; Kawahara, Kenji; Tsuji, Masaharu; Ago, Hiroki

2013-07-07

We report ambient pressure chemical vapor deposition (CVD) growth of single-crystalline NbS2 nanosheets with controlled orientation. On Si and SiO2 substrates, NbS2 nanosheets grow almost perpendicular to the substrate surface. However, when we apply transferred CVD graphene on SiO2 as a substrate, NbS2 sheets grow laterally lying on the graphene. The NbS2 sheets show the triangular and hexagonal shapes with a thickness of about 20-200 nm and several micrometres in the lateral dimension. Analyses based on X-ray diffraction and Raman spectroscopy indicate that the NbS2 nanosheets are single crystalline 3R-type with a rhombohedral structure of R3m space group. Our findings on the formation of highly aligned NbS2 nanosheets on graphene give new insight into the formation mechanism of NbS2 and would contribute to the templated growth of various layered materials.

Genome-wide comparative analysis reveals similar types of NBS genes in hybrid Citrus sinensis genome and original Citrus clementine genome and provides new insights into non-TIR NBS genes

USDA-ARS?s Scientific Manuscript database

In this study, we identified and compared nucleotide-binding site (NBS) domain-containing genes from three Citrus genomes (C. clementina, C. sinensis from USA and C. sinensis from China). Phylogenetic analysis of all Citrus NBS genes across these three genomes revealed that there are three approxima...

17. NBS TOOL ROOM. MISCELLANEOUS TOOLS USED DURING EXTRA VEHICULAR ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

17. NBS TOOL ROOM. MISCELLANEOUS TOOLS USED DURING EXTRA VEHICULAR ACTIVITY (EVA) MISSIONS AND NBS TRAINING. FROM LEFT TO RIGHT THE TOOLS ARE: SHUTTLE TRANSPORTATION SYSTEM (STS) PORTABLE FOOT RESTRAINT (PFR), ESSEX WRENCH, SOCKET WRENCH, SAFETY TETHER REEL (LEFT REAR), MINI WORKSTATION (CENTER REAR), TETHERS (FRONT CENTER), HUBBLE SPACE TELESCOPE (HST) POWER TOOL (FRONT RIGHT), HUBBLE SPACE TELESCOPE & PORTABLE FOOT RESTRAINT (REAR RIGHT). - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

Genome-Wide Association Study Identifies NBS-LRR-Encoding Genes Related with Anthracnose and Common Bacterial Blight in the Common Bean.

PubMed

Wu, Jing; Zhu, Jifeng; Wang, Lanfen; Wang, Shumin

2017-01-01

Nucleotide-binding site and leucine-rich repeat (NBS-LRR) genes represent the largest and most important disease resistance genes in plants. The genome sequence of the common bean ( Phaseolus vulgaris L.) provides valuable data for determining the genomic organization of NBS-LRR genes. However, data on the NBS-LRR genes in the common bean are limited. In total, 178 NBS-LRR-type genes and 145 partial genes (with or without a NBS) located on 11 common bean chromosomes were identified from genome sequences database. Furthermore, 30 NBS-LRR genes were classified into Toll/interleukin-1 receptor (TIR)-NBS-LRR (TNL) types, and 148 NBS-LRR genes were classified into coiled-coil (CC)-NBS-LRR (CNL) types. Moreover, the phylogenetic tree supported the division of these PvNBS genes into two obvious groups, TNL types and CNL types. We also built expression profiles of NBS genes in response to anthracnose and common bacterial blight using qRT-PCR. Finally, we detected nine disease resistance loci for anthracnose (ANT) and seven for common bacterial blight (CBB) using the developed NBS-SSR markers. Among these loci, NSSR24, NSSR73, and NSSR265 may be located at new regions for ANT resistance, while NSSR65 and NSSR260 may be located at new regions for CBB resistance. Furthermore, we validated NSSR24, NSSR65, NSSR73, NSSR260, and NSSR265 using a new natural population. Our results provide useful information regarding the function of the NBS-LRR proteins and will accelerate the functional genomics and evolutionary studies of NBS-LRR genes in food legumes. NBS-SSR markers represent a wide-reaching resource for molecular breeding in the common bean and other food legumes. Collectively, our results should be of broad interest to bean scientists and breeders.

Genome-Wide Association Study Identifies NBS-LRR-Encoding Genes Related with Anthracnose and Common Bacterial Blight in the Common Bean

PubMed Central

Wu, Jing; Zhu, Jifeng; Wang, Lanfen; Wang, Shumin

2017-01-01

Nucleotide-binding site and leucine-rich repeat (NBS-LRR) genes represent the largest and most important disease resistance genes in plants. The genome sequence of the common bean (Phaseolus vulgaris L.) provides valuable data for determining the genomic organization of NBS-LRR genes. However, data on the NBS-LRR genes in the common bean are limited. In total, 178 NBS-LRR-type genes and 145 partial genes (with or without a NBS) located on 11 common bean chromosomes were identified from genome sequences database. Furthermore, 30 NBS-LRR genes were classified into Toll/interleukin-1 receptor (TIR)-NBS-LRR (TNL) types, and 148 NBS-LRR genes were classified into coiled-coil (CC)-NBS-LRR (CNL) types. Moreover, the phylogenetic tree supported the division of these PvNBS genes into two obvious groups, TNL types and CNL types. We also built expression profiles of NBS genes in response to anthracnose and common bacterial blight using qRT-PCR. Finally, we detected nine disease resistance loci for anthracnose (ANT) and seven for common bacterial blight (CBB) using the developed NBS-SSR markers. Among these loci, NSSR24, NSSR73, and NSSR265 may be located at new regions for ANT resistance, while NSSR65 and NSSR260 may be located at new regions for CBB resistance. Furthermore, we validated NSSR24, NSSR65, NSSR73, NSSR260, and NSSR265 using a new natural population. Our results provide useful information regarding the function of the NBS-LRR proteins and will accelerate the functional genomics and evolutionary studies of NBS-LRR genes in food legumes. NBS-SSR markers represent a wide-reaching resource for molecular breeding in the common bean and other food legumes. Collectively, our results should be of broad interest to bean scientists and breeders. PMID:28848595

Genome-Wide Identification and Mapping of NBS-Encoding Resistance Genes in Solanum tuberosum Group Phureja

PubMed Central

Lozano, Roberto; Ponce, Olga; Ramirez, Manuel; Mostajo, Nelly; Orjeda, Gisella

2012-01-01

The majority of disease resistance (R) genes identified to date in plants encode a nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domain containing protein. Additional domains such as coiled-coil (CC) and TOLL/interleukin-1 receptor (TIR) domains can also be present. In the recently sequenced Solanum tuberosum group phureja genome we used HMM models and manual curation to annotate 435 NBS-encoding R gene homologs and 142 NBS-derived genes that lack the NBS domain. Highly similar homologs for most previously documented Solanaceae R genes were identified. A surprising ∼41% (179) of the 435 NBS-encoding genes are pseudogenes primarily caused by premature stop codons or frameshift mutations. Alignment of 81.80% of the 577 homologs to S. tuberosum group phureja pseudomolecules revealed non-random distribution of the R-genes; 362 of 470 genes were found in high density clusters on 11 chromosomes. PMID:22493716

12. NBS LOWER ROOM. BEHIND FAR GLASS WALL IS VIDEO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

12. NBS LOWER ROOM. BEHIND FAR GLASS WALL IS VIDEO TAPE EQUIPMENT AND VOICE INTERCOM EQUIPMENT. THE MONITORS ABOVE GLASS WALL DISPLAY UNDERWATER TEST VIDEO TO CONTROL ROOM. FARTHEST CONSOLE ROW CONTAINS CAMERA SWITCHING, PANNING, TILTING, FOCUSING, AND ZOOMING. MIDDLE CONSOLE ROW CONTAINS TEST CONDUCTOR CONSOLES FOR MONITORING TEST ACTIVITIES AND DATA. THE CLOSEST CONSOLE ROW IS NBS FACILITY CONSOLES FOR TEST DIRECTOR, SAFETY AND QUALITY ASSURANCE REPRESENTATIVES. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

A reevaluation of TDR propagation time determination in soils and geological media

USDA-ARS?s Scientific Manuscript database

Time domain reflectometry (TDR) is an established method for the determination of apparent dielectric permittivity and water content in soils. Using current waveform interpretation procedures, signal attenuation and variation in dielectric media properties along the transmission line can significant...

The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage

PubMed Central

Larsen, Dorthe H; Hari, Flurina; Clapperton, Julie A; Gwerder, Myriam; Gutsche, Katrin; Altmeyer, Matthias; Jungmichel, Stephanie; Toledo, Luis I; Fink, Daniel; Rask, Maj-Britt; Grøfte, Merete; Lukas, Claudia; Nielsen, Michael L; Smerdon, Stephen J; Lukas, Jiri; Stucki, Manuel

2016-01-01

Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in-trans signaling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identified TCOF1-Treacle, a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle-dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in-trans in the presence of distant chromosome breaks. PMID:25064736

The NBS1-Treacle complex controls ribosomal RNA transcription in response to DNA damage.

PubMed

Larsen, Dorthe H; Hari, Flurina; Clapperton, Julie A; Gwerder, Myriam; Gutsche, Katrin; Altmeyer, Matthias; Jungmichel, Stephanie; Toledo, Luis I; Fink, Daniel; Rask, Maj-Britt; Grøfte, Merete; Lukas, Claudia; Nielsen, Michael L; Smerdon, Stephen J; Lukas, Jiri; Stucki, Manuel

2014-08-01

Chromosome breakage elicits transient silencing of ribosomal RNA synthesis, but the mechanisms involved remained elusive. Here we discover an in trans signalling mechanism that triggers pan-nuclear silencing of rRNA transcription in response to DNA damage. This is associated with transient recruitment of the Nijmegen breakage syndrome protein 1 (NBS1), a central regulator of DNA damage responses, into the nucleoli. We further identify TCOF1 (also known as Treacle), a nucleolar factor implicated in ribosome biogenesis and mutated in Treacher Collins syndrome, as an interaction partner of NBS1, and demonstrate that NBS1 translocation and accumulation in the nucleoli is Treacle dependent. Finally, we provide evidence that Treacle-mediated NBS1 recruitment into the nucleoli regulates rRNA silencing in trans in the presence of distant chromosome breaks.

Productive replication of human papillomavirus 31 requires DNA repair factor Nbs1.

PubMed

Anacker, Daniel C; Gautam, Dipendra; Gillespie, Kenric A; Chappell, William H; Moody, Cary A

2014-08-01

Activation of the ATM (ataxia telangiectasia-mutated kinase)-dependent DNA damage response (DDR) is necessary for productive replication of human papillomavirus 31 (HPV31). We previously found that DNA repair and homologous recombination (HR) factors localize to sites of HPV replication, suggesting that ATM activity is required to recruit factors to viral genomes that can productively replicate viral DNA in a recombination-dependent manner. The Mre11-Rad50-Nbs1 (MRN) complex is an essential component of the DDR that is necessary for ATM-mediated HR repair and localizes to HPV DNA foci. In this study, we demonstrate that the HPV E7 protein is sufficient to increase levels of the MRN complex and also interacts with MRN components. We have found that Nbs1 depletion blocks productive viral replication and results in decreased localization of Mre11, Rad50, and the principal HR factor Rad51 to HPV DNA foci upon differentiation. Nbs1 contributes to the DDR by acting as an upstream activator of ATM in response to double-strand DNA breaks (DSBs) and as a downstream effector of ATM activity in the intra-S-phase checkpoint. We have found that phosphorylation of ATM and its downstream target Chk2, as well as SMC1 (structural maintenance of chromosome 1), is maintained upon Nbs1 knockdown in differentiating cells. Given that ATM and Chk2 are required for productive replication, our results suggest that Nbs1 contributes to viral replication outside its role as an ATM activator, potentially through ensuring localization of DNA repair factors to viral genomes that are necessary for efficient productive replication. The mechanisms that regulate human papillomavirus (HPV) replication during the viral life cycle are not well understood. Our finding that Nbs1 is necessary for productive replication even in the presence of ATM (ataxia telangiectasia-mutated kinase) and Chk2 phosphorylation offers evidence that Nbs1 contributes to viral replication downstream of facilitating ATM

Productive Replication of Human Papillomavirus 31 Requires DNA Repair Factor Nbs1

PubMed Central

Anacker, Daniel C.; Gautam, Dipendra; Gillespie, Kenric A.; Chappell, William H.

2014-01-01

ABSTRACT Activation of the ATM (ataxia telangiectasia-mutated kinase)-dependent DNA damage response (DDR) is necessary for productive replication of human papillomavirus 31 (HPV31). We previously found that DNA repair and homologous recombination (HR) factors localize to sites of HPV replication, suggesting that ATM activity is required to recruit factors to viral genomes that can productively replicate viral DNA in a recombination-dependent manner. The Mre11-Rad50-Nbs1 (MRN) complex is an essential component of the DDR that is necessary for ATM-mediated HR repair and localizes to HPV DNA foci. In this study, we demonstrate that the HPV E7 protein is sufficient to increase levels of the MRN complex and also interacts with MRN components. We have found that Nbs1 depletion blocks productive viral replication and results in decreased localization of Mre11, Rad50, and the principal HR factor Rad51 to HPV DNA foci upon differentiation. Nbs1 contributes to the DDR by acting as an upstream activator of ATM in response to double-strand DNA breaks (DSBs) and as a downstream effector of ATM activity in the intra-S-phase checkpoint. We have found that phosphorylation of ATM and its downstream target Chk2, as well as SMC1 (structural maintenance of chromosome 1), is maintained upon Nbs1 knockdown in differentiating cells. Given that ATM and Chk2 are required for productive replication, our results suggest that Nbs1 contributes to viral replication outside its role as an ATM activator, potentially through ensuring localization of DNA repair factors to viral genomes that are necessary for efficient productive replication. IMPORTANCE The mechanisms that regulate human papillomavirus (HPV) replication during the viral life cycle are not well understood. Our finding that Nbs1 is necessary for productive replication even in the presence of ATM (ataxia telangiectasia-mutated kinase) and Chk2 phosphorylation offers evidence that Nbs1 contributes to viral replication downstream of

Newborn Screening (NBS): Answers to Frequently Asked Questions

MedlinePlus

... states consider the NBS recommendations made by the Secretary’s Advisory Committee on Heritable Disorders in Newborns and Children, a federal panel that reports to the Secretary of Health and Human Services. Some states may ...

In sickness or in health: TDR's partners. 6. The French Development Research Institute (ORSTOM).

PubMed

1997-10-01

One of the partner agencies working with the UN Development Program/World Bank/World Health Organization Special Programme for Research and Training in Tropical Diseases (TDR) is the French development research agency, ORSTOM. ORSTOM has been conducting research in intertropical regions for approximately 50 years with a particular focus on entomoparasitological aspects of vector-borne diseases. ORSTOM's close collaboration with TDR since the TDR Special Program was launched in 1975 has led to 1) improved knowledge about various aspects of trypanosomiasis that allowed identification of ways to control the epidemic; 2) reappraisal of the taxonomy of the parasitic protozoa responsible for Chagas disease and leishmaniasis; 3) improvements in the strategy to fight malaria; 4) assessment of the efficacy of ivermectin as a form of mass treatment for onchocerciasis; 5) improved knowledge about dracunculiasis that contributed to an eradication campaign; 6) expansion of the scope of biological control of bancroftian filariasis and other parasites; and 7) improved knowledge about ways to control two schistosome species. ORSTOM also participated in a training and structural enhancement initiative that resulted in creation of the Boake Medical and Veterinary Entomology Training Center. ORSTOM is currently undergoing a complete restructuring to respond to changes in international tropical disease research and to changing priorities that focus on vector-borne diseases, nutrition, AIDS, and health systems.

Did Rev-1 small ruminants vaccination helped improve cattle brucellosis prevalence status in Algeria?

PubMed

Kardjadj, Moustafa

2017-12-01

In 2006, the Algerian authorities started the Rev-1 vaccination of sheep and goats; consequently, there was a significant improvement of small ruminant brucellosis sanitary status. In this paper, we attempt to study the effect of Rev-1 small ruminants' vaccination on cattle brucellosis prevalence in Algeria. Our results showed an overall cattle herd seroprevalence of 12% (9 positive herds of 75). The risk factor analysis using a logistic regression model indicated that the presence of small ruminants along with cattle in the herd (mixed herds) decreased the odds for brucellosis seropositivity by 1.69 [95% CI 0.54-2.84; P = 0.042] compared to the cattle herds only. Likewise, the present study showed that the presence of Rev-1 vaccinated small ruminants in the herd decreased also the odds for brucellosis seropositivity by 4.10 [95% CI 3.20-5.00; P = 0.003] compared to other herds. This result lead to the assumption that the small ruminants Rev-1 vaccination diminish Brucella microbisme pressure in the mixed herds and help decrease the cattle brucellosis prevalence in these herds.

Plant GSK3 proteins regulate xylem cell differentiation downstream of TDIF-TDR signalling

NASA Astrophysics Data System (ADS)

Kondo, Yuki; Ito, Tasuku; Nakagami, Hirofumi; Hirakawa, Yuki; Saito, Masato; Tamaki, Takayuki; Shirasu, Ken; Fukuda, Hiroo

2014-03-01

During plant radial growth typically seen in trees, procambial and cambial cells act as meristematic cells in the vascular system to self-proliferate and differentiate into xylem cells. These two processes are regulated by a signalling pathway composed of a peptide ligand and its receptor; tracheary element differentiation inhibitory factor (TDIF) and TDIF RECEPTOR (TDR). Here we show that glycogen synthase kinase 3 proteins (GSK3s) are crucial downstream components of the TDIF signalling pathway suppressing xylem differentiation from procambial cells. TDR interacts with GSK3s at the plasma membrane and activates GSK3s in a TDIF-dependent fashion. Consistently, a specific inhibitor of plant GSK3s strongly induces xylem cell differentiation through BRI1-EMS SUPPRESSOR 1 (BES1), a well-known target transcription factor of GSK3s. Our findings provide insight into the regulation of cell fate determination in meristem maintenance.

Disruption of NBS1 gene leads to early embryonic lethality in homozygous null mice and induces specific cancer in heterozygous mice

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

Kurimasa, Akihiro; Burma, Sandeep; Henrie, Melinda

2002-04-15

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosome instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition, with cellular features similar to that of ataxia telangiectasia (AT). NBS results from mutations in the mammalian gene Nbs1 that codes for a 95-kDa protein called nibrin, NBS1, or p95. To establish an animal model for NBS, we attempted to generate NBS1 knockout mice. However, NBS1 gene knockouts were lethal at an early embryonic stage. NBS1 homozygous(-/-) blastocyst cells cultured in vitro showed retarded growth and subsequently underwent growth arrest within 5 days of culture. Apoptosis, assayed by TUNELmore » staining, was observed in NBSI homozygous(-/-) blastocyst cells cultured for four days. NBSI heterozygous(+/-) mice were normal, and exhibited no specific phenotype for at least one year. However, fibroblast cells from NBSI heterozygous(+/-) mice displayed an enhanced frequency of spontaneous transformation to anchorage-independent growth as compared to NBS1 wild-type(+/+) cells. Furthermore, heterozygous(+/-) mice exhibited a high incidence of hepatocellular carcinoma after one year compared to wild-type mice, even though no significant differences in the incidence of other tumors such as lung adenocarcinoma and lymphoma were observed. Taken together, these results strongly suggest that NBS1 heterozygosity and reduced NBSI expression induces formation of specific tumors in mice.« less

Dr. von Braun Tries Out the NBS

NASA Technical Reports Server (NTRS)

1967-01-01

Marshall Space Flight Center (MSFC) Director, Dr. von Braun, is shown fitted with suit and diving equipment as he prepares for a tryout in the MSFC Neutral Buoyancy Simulator (NBS). Weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

Clinical ascertainment of Nijmegen breakage syndrome (NBS) and prevalence of the major mutation, 657del5, in three Slav populations.

PubMed

Varon, R; Seemanova, E; Chrzanowska, K; Hnateyko, O; Piekutowska-Abramczuk, D; Krajewska-Walasek, M; Sykut-Cegielska, J; Sperling, K; Reis, A

2000-11-01

Nijmegen breakage syndrome (NBS) is a chromosomal instability disorder, clinically characterised by microcephaly, immunodeficiency, radiosensitivity and a very high predisposition to lymphoid malignancy. Recently, it was demonstrated that mutations in the NBS1 gene are responsible for NBS. Most of the NBS patients known so far are of Slav origin and carry a major founder mutation 657del5 in exon 6 of the NBS1 gene. In this study we estimated the prevalence of the 657del5 mutation in the Czech Republic, Poland and the Ukraine. We found an unexpectedly high carrier frequency of the 657del5 mutation (1/177) in the three Slav populations, a factor that may contribute to cancer frequency in those countries. In addition, we show that NBS patients are often diagnosed late and therefore receive inappropriate therapy.

A brief review of intermediate controlled nuclear syntheses (ICNS) without harmful radiations

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

Lanjewar, R. B.

Hadronic mechanics gave birth to new magnecular fuels. The present day demand is of clean energy source that is cheap and abundant. Clean energy can be obtained by harnessing renewable energy sources like solar, wind etc. Nuclear energy conventionally produced by fission reactions emits hazardous radiation and radioactive waste. The requirements of clean and safe energy gets fulfilled by novel fuel that achieved by elevating the traditional quantum mechanics to hadronic mechanics and to hadronic chemistry. In the present paper, a comprehensive review on both the theoretical and experimental aspect of the Intermediate Controlled Nuclear Synthesis (ICNS) as developed bymore » Italian American Scientist Professor R. M. Santilli.« less

Radiosensitization of head/neck sqaumous cell carcinoma by adenovirus-mediated expression of the Nbs1 protein

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

Rhee, Juong G.; Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore, MD; Li, Daqing

2007-01-01

Purpose: Local failure and toxicity to adjacent critical structures is a significant problem in radiation therapy of cancers of the head and neck. We are developing a gene therapy based method of sensitizing head/neck squamous cell carcinoma (HNSCC) to radiation treatment. As patients with the rare hereditary disorder, Nijmegen breakage syndrome, show radiation sensitivity we hypothesized that tumor-specific disruption of the function of the Nbs1 protein would lead to enhanced cellular sensitivity to ionizing radiation. Experimental Procedures: We constructed two recombinant adenoviruses by cloning the full-length Nbs1 cDNA as well as the C-terminal 300 amino acids of Nbs1 into anmore » adenovirus backbone under the control of a CMV promoter. The resulting adenoviruses were used to infect HNSCC cell line JHU011. These cells were evaluated for expression of the viral based constructs and assayed for clonogenic survival following radiation exposure. Results: Exposure of cells expressing Nbs1-300 to ionizing radiation resulted in a small reduction in survival relative to cells infected with control virus. Surprisingly, expression of full-length Nbs1 protein resulted in markedly enhanced sensitivity to ionizing radiation. Furthermore, the use of a fractionated radiation scheme following virus infection demonstrates that expression of full-length Nbs1 protein results in significant reduction in cell survival. Conclusions: These results provide a proof of principle that disruption of Nbs1 function may provide a means of enhancing the radiosensitivity of head and neck tumors. Additionally, this work highlights the Mre11 complex as an attractive target for development of radiation sensitizers.« less

Functional markers based molecular characterization and cloning of resistance gene analogs encoding NBS-LRR disease resistance proteins in finger millet (Eleusine coracana).

PubMed

Panwar, Preety; Jha, Anand Kumar; Pandey, P K; Gupta, Arun K; Kumar, Anil

2011-06-01

Magnaporthe grisea, the blast fungus is one of the main pathological threats to finger millet crop worldwide. A systematic search for the blast resistance gene analogs was carried out, using functional molecular markers. Three-fourths of the recognition-dependent disease resistance genes (R-genes) identified in plants encodes nucleotide binding site (NBS) leucine-rich repeat (LRR) proteins. NBS-LRR homologs have only been isolated on a limited scale from Eleusine coracana. Genomic DNA sequences sharing homology with NBS region of resistance gene analogs were isolated and characterized from resistant genotypes of finger millet using PCR based approach with primers designed from conserved regions of NBS domain. Attempts were made to identify molecular markers linked to the resistance gene and to differentiate the resistant bulk from the susceptible bulk. A total of 9 NBS-LRR and 11 EST-SSR markers generated 75.6 and 73.5% polymorphism respectively amongst 73 finger millet genotypes. NBS-5, NBS-9, NBS-3 and EST-SSR-04 markers showed a clear polymorphism which differentiated resistant genotypes from susceptible genotypes. By comparing the banding pattern of different resistant and susceptible genotypes, five DNA amplifications of NBS and EST-SSR primers (NBS-05(504,) NBS-09(711), NBS-07(688), NBS-03(509) and EST-SSR-04(241)) were identified as markers for the blast resistance in resistant genotypes. Principal coordinate plot and UPGMA analysis formed similar groups of the genotypes and placed most of the resistant genotypes together showing a high level of genetic relatedness and the susceptible genotypes were placed in different groups on the basis of differential disease score. Our results provided a clue for the cloning of finger millet blast resistance gene analogs which not only facilitate the process of plant breeding but also molecular characterization of blast resistance gene analogs from Eleusine coracana.

Production of a compound against methicillin resistant Staphylococcus aureus (MRSA) from Streptomyces rubrolavendulae ICN3 & its evaluation in zebrafish embryos

PubMed Central

Kannan, Rajaretinam Rajesh; Iniyan, Appadurai Muthamil; Vincent, Samuel Gnana Prakash

2014-01-01

Background & objectives: Antibiotic resistance in pathogens has become a serious problem worldwide. Therefore, the search for new antibiotics for drug resistanct pathogens is an important endeavor. The present study deals with the production of anti-methicillin resistant Staphylococcus aureus (MRSA) potential of Streptomyces rubrolavendulae ICN3 and evaluation of anti-MRSA compound in zebrafish embryos. Methods: The antibiotic production from S. rubrolavendulae ICN3 was optimized in solid state fermentation and extracted. The antagonistic activity was confirmed against MRSA and purified in silica gel column and reverse phase - HPLC with an absorption maximum at 215 nm. Minimal inhibitory concentration of the compound was determined by broth microdilution method. Zebrafish embryos were used to evaluate the extract/compound for its minimal inhibition studies, influences on heart beat rates, haematopoietic blood cell count and lethal dose values. Results: Streptomyces rubrolavendulae ICN3 showed potent antagonistic activity against MRSA with a zone of 42 mm. The minimum inhibitory concentration was calculated as 500 μg/ml of the crude extract and the purified C23 exhibited 2.5 μg/ml in in vitro assay. The LC50 value of the anti MRSA compound C23 was calculated as 60.49 μg/ml and the MRSA treated embryos survived in the presence of purified compound C23 at a dose of 10 μg/ml. Interpretation & conclusions: Our results suggested that the compound was potent with less toxic effects in zebrafish embryonic model system for MRSA infection. Further structural evaluation and analysis in higher mammalian model system may lead to a novel drug candidate for drug resistant Staphylococcus aureus. PMID:25109726

Cloning of novel rice blast resistance genes from two rapidly evolving NBS-LRR gene families in rice.

PubMed

Guo, Changjiang; Sun, Xiaoguang; Chen, Xiao; Yang, Sihai; Li, Jing; Wang, Long; Zhang, Xiaohui

2016-01-01

Most rice blast resistance genes (R-genes) encode proteins with nucleotide-binding site (NBS) and leucine-rich repeat (LRR) domains. Our previous study has shown that more rice blast R-genes can be cloned in rapidly evolving NBS-LRR gene families. In the present study, two rapidly evolving R-gene families in rice were selected for cloning a subset of genes from their paralogs in three resistant rice lines. A total of eight functional blast R-genes were identified among nine NBS-LRR genes, and some of these showed resistance to three or more blast strains. Evolutionary analysis indicated that high nucleotide diversity of coding regions served as important parameters in the determination of gene resistance. We also observed that amino-acid variants (nonsynonymous mutations, insertions, or deletions) in essential motifs of the NBS domain contribute to the blast resistance capacity of NBS-LRR genes. These results suggested that the NBS regions might also play an important role in resistance specificity determination. On the other hand, different splicing patterns of introns were commonly observed in R-genes. The results of the present study contribute to improving the effectiveness of R-gene identification by using evolutionary analysis method and acquisition of novel blast resistance genes.

ATM activation and its recruitment to damaged DNA require binding to the C terminus of Nbs1.

PubMed

You, Zhongsheng; Chahwan, Charly; Bailis, Julie; Hunter, Tony; Russell, Paul

2005-07-01

ATM has a central role in controlling the cellular responses to DNA damage. It and other phosphoinositide 3-kinase-related kinases (PIKKs) have giant helical HEAT repeat domains in their amino-terminal regions. The functions of these domains in PIKKs are not well understood. ATM activation in response to DNA damage appears to be regulated by the Mre11-Rad50-Nbs1 (MRN) complex, although the exact functional relationship between the MRN complex and ATM is uncertain. Here we show that two pairs of HEAT repeats in fission yeast ATM (Tel1) interact with an FXF/Y motif at the C terminus of Nbs1. This interaction resembles nucleoporin FXFG motif binding to HEAT repeats in importin-beta. Budding yeast Nbs1 (Xrs2) appears to have two FXF/Y motifs that interact with Tel1 (ATM). In Xenopus egg extracts, the C terminus of Nbs1 recruits ATM to damaged DNA, where it is subsequently autophosphorylated. This interaction is essential for ATM activation. A C-terminal 147-amino-acid fragment of Nbs1 that has the Mre11- and ATM-binding domains can restore ATM activation in an Nbs1-depleted extract. We conclude that an interaction between specific HEAT repeats in ATM and the C-terminal FXF/Y domain of Nbs1 is essential for ATM activation. We propose that conformational changes in the MRN complex that occur upon binding to damaged DNA are transmitted through the FXF/Y-HEAT interface to activate ATM. This interaction also retains active ATM at sites of DNA damage.

NBS1 knockdown by small interfering RNA increases ionizing radiation mutagenesis and telomere association in human cells

NASA Technical Reports Server (NTRS)

Zhang, Ying; Lim, Chang U K.; Williams, Eli S.; Zhou, Junqing; Zhang, Qinming; Fox, Michael H.; Bailey, Susan M.; Liber, Howard L.

2005-01-01

Hypomorphic mutations which lead to decreased function of the NBS1 gene are responsible for Nijmegen breakage syndrome, a rare autosomal recessive hereditary disorder that imparts an increased predisposition to development of malignancy. The NBS1 protein is a component of the MRE11/RAD50/NBS1 complex that plays a critical role in cellular responses to DNA damage and the maintenance of chromosomal integrity. Using small interfering RNA transfection, we have knocked down NBS1 protein levels and analyzed relevant phenotypes in two closely related human lymphoblastoid cell lines with different p53 status, namely wild-type TK6 and mutated WTK1. Both TK6 and WTK1 cells showed an increased level of ionizing radiation-induced mutation at the TK and HPRT loci, impaired phosphorylation of H2AX (gamma-H2AX), and impaired activation of the cell cycle checkpoint regulating kinase, Chk2. In TK6 cells, ionizing radiation-induced accumulation of p53/p21 and apoptosis were reduced. There was a differential response to ionizing radiation-induced cell killing between TK6 and WTK1 cells after NBS1 knockdown; TK6 cells were more resistant to killing, whereas WTK1 cells were more sensitive. NBS1 deficiency also resulted in a significant increase in telomere association that was independent of radiation exposure and p53 status. Our results provide the first experimental evidence that NBS1 deficiency in human cells leads to hypermutability and telomere associations, phenotypes that may contribute to the cancer predisposition seen among patients with this disease.

Matter-Wave Optics of Diatomic Molecules

DTIC Science & Technology

2012-10-23

81.013802 10/11/2012 32.00 Swati Singh , Pierre Meystre. Atomic probe Wigner tomography of a nanomechanical system, Physical Review A, (04 2010): 41804...PhysRevA.78.041801 10/11/2012 3.00 S. Singh , M. Bhattacharya, O. Dutta, P. Meystre. Coupling Nanomechanical Cantilevers to Dipolar Molecules...degenerate matter waves, Physical Review A, (02 2009): 0. doi: 10.1103/PhysRevA.79.023622 10/11/2012 10.00 M. Bhattacharya, S. Singh , P. -L. Giscard

Laboratory testing of the (Japan Storage Battery) traction batteries GS E75A and GS E150H

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

Not Available

This report describes the testing of the GS E75A and GS E150H flooded lead-acid 12-volt traction batteries and compares the selected batteries to U.S.-made electric vehicle batteries. The results and conclusions of the testing are presented.

Rapid Percolation of Water through Soil Macropores Affects Reading and Calibration of Large Encapsulated TDR Sensors

NASA Astrophysics Data System (ADS)

Matula, Svatopluk; Dolezal, Frantisek; Moreira Barradas, Joao Manuel

2015-04-01

The electromagnetic soil water content sensors are invaluable tools because of their selective sensitivity to water, versatility, ease of automation and large resolution. A common drawback of most their types is their preferential sensitivity to water near to their surfaces. The ways in which the drawback manifests itself were explored for the case of large Time-Domain Reflectometry (TDR) sensors Aqua-Tel-TDR (Automata, Inc., now McCrometer CONNECT). Their field performance was investigated and compared with the results of field and laboratory calibration. The field soil was loamy Chernozem on a carbonate-rich loess substrate, while the laboratory calibration was done in fine quartz sand. In the field, the sensors were installed horizontally into pre-bored holes after being wrapped in slurry of native soil or fine earth. Large sensor-to-sensor variability of readings was observed. It was partially removed by field calibration. The occurrence of percolation events could be easily recognised, because they made the TDR readings suddenly rising and sometimes considerably exceeding the saturated water content. After the events, the TDR readings fell, usually equally suddenly, remaining afterwards at the levels somewhat higher than those before the event. These phenomena can be explained by the preferential flow of water in natural and artificial soil macropores around the sensors. It is hypothesised that the percolating water which enters the gaps and other voids around the sensors accumulates there for short time, being hindered by the sensors themselves. This water also has a enlarged opportunity to get absorbed by the adjacent soil matrix. The variance of TDR readings obtained during the field calibration does not differ significantly from the variance of the corresponding gravimetric sampling data. This suggests that the slope of the field calibration equation is close to unity, in contrast to the laboratory calibration in quartz sand. This difference in slopes can

Isolation and characterization of NBS-LRR- resistance gene candidates in turmeric (Curcuma longa cv. surama).

PubMed

Joshi, R K; Mohanty, S; Subudhi, E; Nayak, S

2010-09-08

Turmeric (Curcuma longa), an important asexually reproducing spice crop of the family Zingiberaceae is highly susceptible to bacterial and fungal pathogens. The identification of resistance gene analogs holds great promise for development of resistant turmeric cultivars. Degenerate primers designed based on known resistance genes (R-genes) were used in combinations to elucidate resistance gene analogs from Curcuma longa cultivar surama. The three primers resulted in amplicons with expected sizes of 450-600 bp. The nucleotide sequence of these amplicons was obtained through sequencing; their predicted amino acid sequences compared to each other and to the amino acid sequences of known R-genes revealed significant sequence similarity. The finding of conserved domains, viz., kinase-1a, kinase-2 and hydrophobic motif, provided evidence that the sequences belong to the NBS-LRR class gene family. The presence of tryptophan as the last residue of kinase-2 motif further qualified them to be in the non-TIR-NBS-LRR subfamily of resistance genes. A cluster analysis based on the neighbor-joining method was carried out using Curcuma NBS analogs together with several resistance gene analogs and known R-genes, which classified them into two distinct subclasses, corresponding to clades N3 and N4 of non-TIR-NBS sequences described in plants. The NBS analogs that we isolated can be used as guidelines to eventually isolate numerous R-genes in turmeric.

Identification of RFLP and NBS/PK profiling markers for disease resistance loci in genetic maps of oats.

PubMed

Sanz, M J; Loarce, Y; Fominaya, A; Vossen, J H; Ferrer, E

2013-01-01

Two of the domains most widely shared among R genes are the nucleotide binding site (NBS) and protein kinase (PK) domains. The present study describes and maps a number of new oat resistance gene analogues (RGAs) with two purposes in mind: (1) to identify genetic regions that contain R genes and (2) to determine whether RGAs can be used as molecular markers for qualitative loci and for QTLs affording resistance to Puccinia coronata. Such genes have been mapped in the diploid A. strigosa × A. wiestii (Asw map) and the hexaploid MN841801-1 × Noble-2 (MN map). Genomic and cDNA NBS-RGA probes from oat, barley and wheat were used to produce RFLPs and to obtain markers by motif-directed profiling based on the NBS (NBS profiling) and PK (PK profiling) domains. The efficiency of primers used in NBS/PK profiling to amplify RGA fragments was assessed by sequencing individual marker bands derived from genomic and cDNA fragments. The positions of 184 markers were identified in the Asw map, while those for 99 were identified in the MN map. Large numbers of NBS and PK profiling markers were found in clusters across different linkage groups, with the PK profiling markers more evenly distributed. The location of markers throughout the genetic maps and the composition of marker clusters indicate that NBS- and PK-based markers cover partly complementary regions of oat genomes. Markers of the different classes obtained were found associated with the two resistance loci, PcA and R-284B-2, mapped on Asw, and with five out of eight QTLs for partial resistance in the MN map. 53 RGA-RFLPs and 187 NBS/PK profiling markers were also mapped on the hexaploid map A. byzantina cv. Kanota × A. sativa cv. Ogle. Significant co-localization was seen between the RGA markers in the KO map and other markers closely linked to resistance loci, such as those for P. coronata and barley yellow dwarf virus (Bydv) that were previously mapped in other segregating populations.

ProUCL version 4.00.04 Documentation Downloads

EPA Pesticide Factsheets

ProUCL Version 4.00.04 is an upgrade of ProUCL Version 4.0 (EPA, 2007). ProUCL 4.00.02 contains statistical methods to address various environmental issues for both full data sets without nondetects and for data sets with NDs (also known as left-censored d

Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response.

PubMed

Ciccia, Alberto; Huang, Jen-Wei; Izhar, Lior; Sowa, Mathew E; Harper, J Wade; Elledge, Stephen J

2014-12-30

The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage.

Treacher Collins syndrome TCOF1 protein cooperates with NBS1 in the DNA damage response

PubMed Central

Ciccia, Alberto; Huang, Jen-Wei; Izhar, Lior; Sowa, Mathew E.; Harper, J. Wade; Elledge, Stephen J.

2014-01-01

The signal transduction pathway of the DNA damage response (DDR) is activated to maintain genomic integrity following DNA damage. The DDR promotes genomic integrity by regulating a large network of cellular activities that range from DNA replication and repair to transcription, RNA splicing, and metabolism. In this study we define an interaction between the DDR factor NBS1 and TCOF1, a nucleolar protein that regulates ribosomal DNA (rDNA) transcription and is mutated in Treacher Collins syndrome. We show that NBS1 relocalizes to nucleoli after DNA damage in a manner dependent on TCOF1 and on casein kinase II and ATM, which are known to modify TCOF1 by phosphorylation. Moreover, we identify a putative ATM phosphorylation site that is required for NBS1 relocalization to nucleoli in response to DNA damage. Last, we report that TCOF1 promotes cellular resistance to DNA damaging agents. Collectively, our findings identify TCOF1 as a DDR factor that could cooperate with ATM and NBS1 to suppress inappropriate rDNA transcription and maintain genomic integrity after DNA damage. PMID:25512513

Proceedings of the Sixth Integrated Communications, Navigation and Surveillance (ICNS) Conference & Workshop 2006

NASA Technical Reports Server (NTRS)

Ponchak, Denise (Compiler)

2006-01-01

The Integrated Communications, Navigation and Surveillance (ICNS) Technologies Conference and Workshop provides a forum for government, industry, and academic communities performing research and technology development for advanced digital communications, navigation, and surveillance security systems and associated applications supporting the national and global air transportation systems. The event s goals are to understand current efforts and recent results in near- and far-term research and technology demonstration; identify integrated digital communications, navigation and surveillance research requirements necessary for a safe, high-capacity, advanced air transportation system; foster collaboration and coordination among all stakeholders; and discuss critical issues and develop recommendations to achieve the future integrated CNS vision for the national and global air transportation system.

Proceedings of the Fourth Integrated Communications, Navigation, and Surveillance (ICNS) Conference and Workshop

NASA Technical Reports Server (NTRS)

Fujikawa, Gene (Compiler)

2004-01-01

The Integrated Communications, Navigational and Surveillance (ICNS) Technologies Conference and Workshop provides a forum for Government, industry, and academic communities performing research and technology development for advanced digital communications, navigation, and surveillance security systems and associated applications supporting the national and global air transportation systems. The event's goals are to understand current efforts and recent results in near-and far-term research and technology demonstration; identify integrated digital communications, navigation and surveillance research requirements necessary for a safe, high-capacity, advanced air transportation system; foster collaboration and coordination among all stakeholders; and discuss critical issues and develop recommendations to achieve the future integrated CNS vision for the national and global air transportation system.

21. NBS SUIT LAB. THREE GLOVES, HELMET, AND SCREW DRIVER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

21. NBS SUIT LAB. THREE GLOVES, HELMET, AND SCREW DRIVER TORQUE WRENCH FOR ASSEMBLY AND REPAIR OF BOTH. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

High profile backing for GS1 drive.

PubMed

Hodgson, Glen

2016-09-01

At the 2016 GS1 UK Healthcare Conference in London, delegates heard from speakers including Pat Mills, the Department of Health's commercial director, on the ongoing work to embed GS1 standards throughout the NHS in England in line with the DH's eProcurement Strategy, published in April 2014. This mandated that any service or product procured by an English NHS acute Trust comply with the standards--one of the most obvious representations of which is on barcodes--'to enable Trusts to manage their non-pay spending by adopting master procurement data, automating the exchange of such data, and benchmarking their procurement against other Trusts and healthcare providers'. One of six 'demonstrator site' Trusts to provide a speaker at the 2016 GS1 UK national conference to report on their progress to date was Leeds Teaching Hospitals NHS Trust. Shortly after, HEJ editor, Jonathan Baillie, spoke to the Trust's associate director, Commercial and Procurement, Chris Slater, and to head of Healthcare at GS1 UK, Glen Hodgson.

Quantitative profiling of drug-associated proteomic alterations by combined 2-nitrobenzenesulfenyl chloride (NBS) isotope labeling and 2DE/MS identification.

PubMed

Ou, Keli; Kesuma, Djohan; Ganesan, Kumaresan; Yu, Kun; Soon, Sou Yen; Lee, Suet Ying; Goh, Xin Pei; Hooi, Michelle; Chen, Wei; Jikuya, Hiroyuki; Ichikawa, Tetsuo; Kuyama, Hiroki; Matsuo, Ei-ichi; Nishimura, Osamu; Tan, Patrick

2006-09-01

The identification of drug-responsive biomarkers in complex protein mixtures is an important goal of quantitative proteomics. Here, we describe a novel approach for identifying such drug-induced protein alterations, which combines 2-nitrobenzenesulfenyl chloride (NBS) tryptophan labeling with two-dimensional gel electrophoresis (2DE)/mass spectrometry (MS). Lysates from drug-treated and control samples are labeled with light or heavy NBS moiety and separated on a common 2DE gel, and protein alterations are identified by MS through the differential intensity of paired NBS peptide peaks. Using NBS/2DE/MS, we profiled the proteomic alterations induced by tamoxifen (TAM) in the estrogen receptor (ER) positive MCF-7 breast cancer cell line. Of 88 protein spots that significantly changed upon TAM treatment, 44 spots representing 23 distinct protein species were successfully identified with NBS-paired peptides. Of these 23 TAM-altered proteins, 16 (70%) have not been previously associated with TAM or ER activity. We found the NBS labeling procedure to be both technically and biologically reproducible, and the NBS/2DE/MS alterations exhibited good concordance with conventional 2DE differential protein quantitation, with discrepancies largely due to the comigration of distinct proteins in the regular 2DE gels. To validate the NBS/2DE/MS results, we used immunoblotting to confirm GRP78, CK19, and PA2G4 as bona fide TAM-regulated proteins. Furthermore, we demonstrate that PA2G4 expression can serve as a novel prognostic factor for disease-free survival in two independent breast cancer patient cohorts. To our knowledge, this is the first report describing the proteomic changes in breast cancer cells induced by TAM, the most commonly used selective estrogen receptor modulator (SERM). Our results indicate that NBS/2DE/MS may represent a more reliable approach for cellular protein quantitation than conventional 2DE approaches.

Storing, Browsing, Querying, and Sharing Data: the THREDDS Data Repository (TDR)

NASA Astrophysics Data System (ADS)

Wilson, A.; Lindholm, D.; Baltzer, T.

2005-12-01

The Unidata Internet Data Distribution (IDD) network delivers gigabytes of data per day in near real time to sites across the U.S. and beyond. The THREDDS Data Server (TDS) supports public browsing of metadata and data access via OPeNDAP enabled URLs for datasets such as these. With such large quantities of data, sites generally employ a simple data management policy, keeping the data for a relatively short term on the order of hours to perhaps a week or two. In order to save interesting data in longer term storage and make it available for sharing, a user must move the data herself. In this case the user is responsible for determining where space is available, executing the data movement, generating any desired metadata, and setting access control to enable sharing. This task sequence is generally based on execution of a sequence of low level operating system specific commands with significant user involvement. The LEAD (Linked Environments for Atmospheric Discovery) project is building a cyberinfrastructure to support research and education in mesoscale meteorology. LEAD orchestrations require large, robust, and reliable storage with speedy access to stage data and store both intermediate and final results. These requirements suggest storage solutions that involve distributed storage, replication, and interfacing to archival storage systems such as mass storage systems and tape or removable disks. LEAD requirements also include metadata generation and access in order to support querying. In support of both THREDDS and LEAD requirements, Unidata is designing and prototyping the THREDDS Data Repository (TDR), a framework for a modular data repository to support distributed data storage and retrieval using a variety of back end storage media and interchangeable software components. The TDR interface will provide high level abstractions for long term storage, controlled, fast and reliable access, and data movement capabilities via a variety of technologies such as

Statement of the ICN on the World Health Assembly technical discussions on strategies for Health for All in the face of rapid urbanization (May 1991).

PubMed

1991-01-01

National associations of nurses are represented by the International Council of Nurses (ICN). This ICN statement reaffirms a commitment to primary health care (PHC) and the WHO "Health for All" goals. Support for environmental and health programs in urban areas is reaffirmed, and attention is paid to the needs of the poorest and most disadvantaged people. Specific directions of the ICN include: 1) overcoming economic and social barriers in order to improve primary health care in cities (rural approaches which by-pass first level care may be successful in cities), 2) holding health care workers responsible for promoting health and environmental consciousness, and 3) involving and educating women for work in community health and environmental projects. Family health can be improved by improving literacy among women. In some developing countries, efforts have been directed to community mobilization in PHC programs. The results of such efforts have been positive for enhancing health in cities. On May 12th of every year, nurses celebrate International Nurses Day. The focus this year is on mental health. Another area of activity is involvement in interdisciplinary and government programs. One such collaborative project with the WHO AIDS groups in Africa is training trainers in workshops. The outcome is a well-informed health care population which can train other health workers and the public about HIV transmission and patient care. A project which has been ongoing for 4 years is overcoming the legal barriers which inhibit nurses from full participation in PHC. ICN recommends that health care workers be educated better in PHC and in intersectoral cooperation, community participation, and disease prevention. Healthy lifestyles, proper nutrition, and disease prevention need to be promoted in school health programs. Children can be taught to be responsible for their own health. Health education can benefit from the use of media such as radio and television. Interdisciplinary

Flurbiprofen benzyl nitrate (NBS-242) inhibits the growth of A-431 human epidermoid carcinoma cells and targets β-catenin.

PubMed

Nath, Niharika; Liu, Xiaoping; Jacobs, Lloydine; Kashfi, Khosrow

2013-01-01

The Wnt/β-catenin/T cell factor (TCF) signaling pathway is important in the development of nonmelanoma skin cancers (NMSCs). Nitric-oxide-releasing nonsteroidal anti-inflammatory drugs (NO-NSAIDs) are chemopreventive agents consisting of a traditional NSAID attached to an NO-releasing moiety through a chemical spacer. Previously we showed that an aromatic spacer enhanced the potency of a particular NO-NSAID compared to an aliphatic spacer. We synthesized an NO-releasing NSAID with an aromatic spacer (flurbiprofen benzyl nitrate, NBS-242), and using the human skin cancer cell line A-431, we evaluated its effects on cell kinetics, Wnt/β-catenin, cyclin D1, and caspase-3. NBS-242 inhibited the growth of A-431 cancer cells, being ~15-fold more potent than flurbiprofen and up to 5-fold more potent than NO-flurbiprofen with an aliphatic spacer, the half maximal inhibitory concentrations (IC50) for growth inhibition being 60 ± 4 μM, 320 ± 20 μM, and 880 ± 65 μM for NBS-242, NO-flurbiprofen, and flurbiprofen, respectively. This effect was associated with inhibition of proliferation, accumulation of cells in the G0/G1 phase of the cell cycle, and an increase in apoptotic cell population. NBS-242 cleaved β-catenin both in the cytoplasm and the nucleus of A-431 cells. NBS-242 activated caspase-3 whose activation was reflected in the cleavage of procaspase-3. To test the functional consequence of β-catenin cleavage, we determined the expression of cyclin D1, a Wnt-response gene. NBS-242 reduced cyclin D1 levels in a concentration dependent manner. These findings establish a strong inhibitory effect of NBS-242 in A-431 human epidermoid carcinoma cells. NBS-242 modulates parameters that are important in determining cellular mass.

Caution on the use of NBS 30 biotite for hydrogen-isotope measurements with on-line high-temperature conversion systems

USGS Publications Warehouse

Qi, Haiping; Coplen, Tyler B.; Olack, Gerard; Vennemann, Torsten W.

2014-01-01

RATIONALEThe supply of NBS 30 biotite is nearly exhausted. During measurements of NBS 30 and potential replacements, reproducible δ2HVSMOW-SLAP values could not be obtained by three laboratories using high-temperature conversion (HTC) systems. The cause of this issue has been investigated using the silver-tube technique for hydrogen-isotope measurements of water.METHODSThe δ2HVSMOW-SLAP values of NBS 30 biotite, other biotites, muscovites, and kaolinite with different particle sizes, along with IAEA-CH-7 polyethylene, and reference waters and NBS 22 oil that were sealed in silver-tube segments, were measured. The effect of absorbed water on mineral surfaces was investigated with waters both enriched and depleted in 2H. The quantitative conversion of hydrogen from biotite into gaseous hydrogen as a function of mass and particle size was also investigated.RESULTSThe δ2HVSMOW-SLAP values of NBS 30 obtained by three laboratories were as much as 21 ‰ too high compared with the accepted value of −65.7 ‰, determined by conventional off-line measurements. The experiments showed a strong correlation between grain size and the δ2HVSMOW-SLAP value of NBS 30 biotite, but not of biotites with lower iron content. The δ2HVSMOW-SLAP values of NBS 30 as a function of particle size show a clear trend toward −65.7 ‰ with finer grain size.CONCLUSIONSDetermination of the δ2HVSMOW-SLAP values of hydrous minerals and of NBS 30 biotite by on-line HTC systems coupled to isotope-ratio mass spectrometers may be unreliable because hydrogen in this biotite may not be converted quantitatively into molecular hydrogen. Extreme caution in the use and interpretation of δ2HVSMOW-SLAP on-line measurements of hydrous minerals is recommended.

Predictors of Gleason Score (GS) upgrading on subsequent prostatectomy: a single Institution study in a cohort of patients with GS 6

PubMed Central

Mehta, Vikas; Rycyna, Kevin; Baesens, Bart MM; Barkan, Güliz A; Paner, Gladell P; Flanigan, Robert C; Wojcik, Eva M; Venkataraman, Girish

2012-01-01

Background Biopsy Gleason score (bGS) remains an important prognostic indicator for adverse outcomes in Prostate Cancer (PCA). In the light of recent studies purporting difference in prognostic outcomes for the subgroups of GS7 group (primary Gleason pattern 4 vs. 3), upgrading of a bGS of 6 to a GS≥7 has serious implications. We sought to identify pre-operative factors associated with upgrading in a cohort of GS6 patients who underwent prostatectomy. Design We identified 281 cases of GS6 PCA on biopsy with subsequent prostatectomies. Using data on pre-operative variables (age, PSA, biopsy pathology parameters), logistic regression models (LRM) were developed to identify factors that could be used to predict upgrading to GS≥7 on subsequent prostatectomy. A decision tree (DT) was constructed. Results 92 of 281 cases (32.7%) were upgraded on subsequent prostatectomy. LRM identified a model with two variables with statistically significant ability to predict upgrading, including pre-biopsy PSA (Odds Ratio 8.66; 2.03-37.49, 95% CI) and highest percentage of cancer at any single biopsy site (Odds Ratio 1.03, 1.01-1.05, 95% CI). This two-parameter model yielded an area under curve of 0.67. The decision tree was constructed using only 3 leave nodes; with a test set classification accuracy of 70%. Conclusions A simplistic model using clinical and biopsy data is able to predict the likelihood of upgrading of GS with an acceptable level of certainty. External validation of these findings along with development of a nomogram will aid in better stratifying the cohort of low risk patients as based on the GS. PMID:22949931

1. NEUTRAL BUOYANCY SIMULATOR BUILDING (NBS) EXTERIOR ELEVATION LOOKING NORTH; ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

1. NEUTRAL BUOYANCY SIMULATOR BUILDING (NBS) EXTERIOR ELEVATION LOOKING NORTH; TANK BUILDING TO LEFT, CONTROL ROOM ETC. TO RIGHT OF CONNECTING BAY. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

TDR measurements looking for complex dielectric permittivity and complex magnetic permeability in lossy materials

NASA Astrophysics Data System (ADS)

Persico, Raffaele

2017-04-01

TDR probes can be exploited for the measure of the electromagnetic characteristics of the soil, or of any penetrable material. They are commonly exploited as instruments for the measure of the propagation velocity of the electromagnetic waves in the probed medium [1], in its turn useful for the proper focusing of GPR data [2-5]. However, a more refined hardware and processing can allow to extrapolate from these probes also the discrimination between dielectric and magnetic characteristics of the material under test, which can be relevant for a better interpretation of the buried scenario or in order to infer physical-chemical characteristics of the material at hand. This requires a TDR probe that can work in frequency domain, and in particular that allows to retrieve the reflection coefficient at the air soil interface. It has been already shown [6] that in lossless cases this can be promising. In the present contribution, it will be shown at the EGU conference that it is possible to look for both the relative complex permittivity and the relative magnetic permeability of the probed material, on condition that the datum has an acceptable SNR and that some diversity of information is guaranteed, either by multifrequency data or by a TDR that can prolong its arms in the soil. References [1] F. Soldovieri, G. Prisco, R. Persico, Application of Microwave Tomography in Hydrogeophysics: some examples, Vadose Zone Journal, vol. 7, n. 1 pp. 160-170, Feb. 2008. [2] I. Catapano, L. Crocco, R. Persico, M. Pieraccini, F. Soldovieri, "Linear and Nonlinear Microwave Tomography Approaches for Subsurface Prospecting: Validation on Real Data", IEEE Trans. on Antennas and Wireless Propagation Letters, vol. 5, pp. 49-53, 2006. [3] G. Leucci, N. Masini, R. Persico, F. Soldovieri." GPR and sonic tomography for structural restoration : the case of the Cathedral of Tricarico", Journal of Geophysics and Engineering, vol. 8, pp. S76-S92, Aug. 2011. [4] S. Piscitelli, E. Rizzo, F. Cristallo

Functional differentiation and spatial-temporal co-expression networks of the NBS-encoding gene family in Jilin ginseng, Panax ginseng C.A. Meyer.

PubMed

Yin, Rui; Zhao, Mingzhu; Wang, Kangyu; Lin, Yanping; Wang, Yanfang; Sun, Chunyu; Wang, Yi; Zhang, Meiping

2017-01-01

Ginseng, Panax ginseng C.A. Meyer, is one of the most important medicinal plants for human health and medicine. It has been documented that over 80% of genes conferring resistance to bacteria, viruses, fungi and nematodes are contributed by the nucleotide binding site (NBS)-encoding gene family. Therefore, identification and characterization of NBS genes expressed in ginseng are paramount to its genetic improvement and breeding. However, little is known about the NBS-encoding genes in ginseng. Here we report genome-wide identification and systems analysis of the NBS genes actively expressed in ginseng (PgNBS genes). Four hundred twelve PgNBS gene transcripts, derived from 284 gene models, were identified from the transcriptomes of 14 ginseng tissues. These genes were classified into eight types, including TNL, TN, CNL, CN, NL, N, RPW8-NL and RPW8-N. Seven conserved motifs were identified in both the Toll/interleukine-1 receptor (TIR) and coiled-coil (CC) typed genes whereas six were identified in the RPW8 typed genes. Phylogenetic analysis showed that the PgNBS gene family is an ancient family, with a vast majority of its genes originated before ginseng originated. In spite of their belonging to a family, the PgNBS genes have functionally dramatically differentiated and been categorized into numerous functional categories. The expressions of the across tissues, different aged roots and the roots of different genotypes. However, they are coordinating in expression, forming a single co-expression network. These results provide a deeper understanding of the origin, evolution and functional differentiation and expression dynamics of the NBS-encoding gene family in plants in general and in ginseng particularly, and a NBS gene toolkit useful for isolation and characterization of disease resistance genes and for enhanced disease resistance breeding in ginseng and related species.

Functional differentiation and spatial-temporal co-expression networks of the NBS-encoding gene family in Jilin ginseng, Panax ginseng C.A. Meyer

PubMed Central

Wang, Kangyu; Lin, Yanping; Wang, Yanfang; Sun, Chunyu; Wang, Yi

2017-01-01

Ginseng, Panax ginseng C.A. Meyer, is one of the most important medicinal plants for human health and medicine. It has been documented that over 80% of genes conferring resistance to bacteria, viruses, fungi and nematodes are contributed by the nucleotide binding site (NBS)-encoding gene family. Therefore, identification and characterization of NBS genes expressed in ginseng are paramount to its genetic improvement and breeding. However, little is known about the NBS-encoding genes in ginseng. Here we report genome-wide identification and systems analysis of the NBS genes actively expressed in ginseng (PgNBS genes). Four hundred twelve PgNBS gene transcripts, derived from 284 gene models, were identified from the transcriptomes of 14 ginseng tissues. These genes were classified into eight types, including TNL, TN, CNL, CN, NL, N, RPW8-NL and RPW8-N. Seven conserved motifs were identified in both the Toll/interleukine-1 receptor (TIR) and coiled-coil (CC) typed genes whereas six were identified in the RPW8 typed genes. Phylogenetic analysis showed that the PgNBS gene family is an ancient family, with a vast majority of its genes originated before ginseng originated. In spite of their belonging to a family, the PgNBS genes have functionally dramatically differentiated and been categorized into numerous functional categories. The expressions of the across tissues, different aged roots and the roots of different genotypes. However, they are coordinating in expression, forming a single co-expression network. These results provide a deeper understanding of the origin, evolution and functional differentiation and expression dynamics of the NBS-encoding gene family in plants in general and in ginseng particularly, and a NBS gene toolkit useful for isolation and characterization of disease resistance genes and for enhanced disease resistance breeding in ginseng and related species. PMID:28727829

Facile fabrication of 3D porous MnO@GS/CNT architecture as advanced anode materials for high-performance lithium-ion battery.

PubMed

Wang, Junyong; Deng, Qinglin; Li, Mengjiao; Wu, Cong; Jiang, Kai; Hu, Zhigao; Chu, Junhao

2018-08-03

To overcome inferior rate capability and cycle stability of MnO-based anode materials for lithium-ion batteries (LIBs), we reported a novel 3D porous MnO@GS/CNT composite, consisting of MnO nanoparticles homogeneously distributed on the conductive interconnected framework based on 2D graphene sheets (GS) and 1D carbon nanotubes (CNTs). The distinctive architecture offers highly interpenetrated network along with efficient porous channels for fast electron transfer and ionic diffusion as well as abundant stress buffer space to accommodate the volume expansion of the MnO nanoparticles. The MnO@GS/CNT anode exhibits an ultrahigh capacity of 1115 mAh g -1 at 0.2 A g -1 after 150 cycles and outstanding rate capacity of 306 mAh g -1 at 10.0 A g -1 . Moreover, a stable capacity of 405 mAh g -1 after 3200 cycles can still be achieved, even at a large current density of 5.0 A g -1 . When coupled with LiMn 2 O 4 (LMO) cathode, the LMO [Formula: see text] MnO@GS/CNT full cell characterizes an excellent cycling stability and rate capability, indicating the promising application of MnO@GS/CNT anode in the next-generation LIBs.

Thermoelectric Properties of Ca1−xGdxMnO3−δ (0.00, 0.02, and 0.05) Systems

PubMed Central

Bhaskar, Ankam; Liu, Chia-Jyi; Yuan, J. J.

2012-01-01

Polycrystalline samples of Ca1−xGdxMnO3−δ (x = 0.00, 0.02, and 0.05) have been studied by X-ray diffraction (XRD), electrical resistivity (ρ), thermoelectric power (S), and thermal conductivity (κ). All the samples were single phase with an orthorhombic structure. The Seebeck coefficient of all the samples was negative, indicating that the predominant carriers are electrons over the entire temperature range. The iodometric titration measurements indicate that the electrical resistivity of Ca1−xGdxMnO3−δ correlated well with the average valence of Mnv+ and oxygen deficiency. Among the doped samples, Ca0.98Gd0.02MnO3−δ had the highest dimensionless figure of merit 0.018 at 300 K, representing an improvement of about 125% with respect to the undoped GaMnO3−δ sample at the same temperature. PMID:22997488

Turbulence and turbulent drag reduction in swirling flow: Inertial versus viscous forcing.

PubMed

Burnishev, Yuri; Steinberg, Victor

2015-08-01

We report unexpected results of a drastic difference in the transition to fully developed turbulent and turbulent drag reduction (TDR) regimes and in their properties in a von Karman swirling flow with counter-rotating disks of water-based polymer solutions for viscous (by smooth disks) as well as inertial (by bladed disks) forcing and by tracking just torque Γ(t) and pressure p(t) . For the viscous forcing, just a single TDR regime is found with the transition values of the Reynolds number (Re) Re turb c =Re TDR c ≃(4.8±0.2)×10(5) independent of ϕ , whereas for the inertial forcing two turbulent regimes are revealed. The first transition is to fully developed turbulence, and the second one is to the TDR regime with both Re turb c and Re TDR c depending on polymer concentration ϕ . Both regimes differ by the values of C f and C p , by the scaling exponents of the fundamental turbulent characteristics, by the nonmonotonic dependencies of skewness and flatness of the pressure PDFs on Re, and by the different frequency power spectra of p with the different dependencies of the main vortex peak frequency in the p power spectra on ϕ and Re. Thus our experimental results show the transition to the TDR regime in a von Karman swirling flow for the viscous and inertial forcings in a sharp contrast to the recent experiments [Phys. Fluids 10, 426 (1998); Phys. Rev. E 47, R28(R) (1993); and J. Phys.: Condens. Matter 17, S1195 (2005)] where the transition to TDR is observed in the same swirling flow with counter-rotating disks only for the viscous forcing. The latter result has led its authors to the wrong conclusion that TDR is a solely boundary effect contrary to the inertial forcing associated with the bulk effect, and this conception is currently rather widely accepted in literature.

Recollections on Sixty Years of NBS Ionizing Radiation Programs for Energetic X Rays and Electrons1

PubMed Central

Koch, H. William

2006-01-01

These recollections are on ionizing radiation programs at the National Bureau of Standards (NBS) that started in 1928 and ended in 1988 when NBS became the National Institute of Standards and Technology (NIST). The independent Council on Ionizing Radiation Measurements and Standards (CIRMS) was formed in 1992. This article focuses on how measurements and standards for x rays, gamma rays, and electrons with energies above 1 MeV began at NBS and how they progressed. It also suggests how the radiation processors of materials and foods, the medical radiographic and radiological industries, and the radiological protection interests of the government (including homeland security) represented in CIRMS can benefit from NIST programs. PMID:27274947

18. NBS SUIT LAB. OVERALL VIEW. ALL WORK TABLES WITH ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

18. NBS SUIT LAB. OVERALL VIEW. ALL WORK TABLES WITH MISCELLANEOUS SUIT COMPONENTS AND SUPPLIES. TERRY WEST TO LEFT, AND PAUL DUMBACHER TO RIGHT. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

Accumulated Expression Level of Cytosolic Glutamine Synthetase 1 Gene (OsGS1;1 or OsGS1;2) Alter Plant Development and the Carbon-Nitrogen Metabolic Status in Rice

PubMed Central

Bao, Aili; Zhao, Zhuqing; Ding, Guangda; Shi, Lei; Xu, Fangsen; Cai, Hongmei

2014-01-01

Maintaining an appropriate balance of carbon to nitrogen metabolism is essential for rice growth and yield. Glutamine synthetase is a key enzyme for ammonium assimilation. In this study, we systematically analyzed the growth phenotype, carbon-nitrogen metabolic status and gene expression profiles in GS1;1-, GS1;2-overexpressing rice and wildtype plants. Our results revealed that the GS1;1-, GS1;2-overexpressing plants exhibited a poor plant growth phenotype and yield and decreased carbon/nitrogen ratio in the stem caused by the accumulation of nitrogen in the stem. In addition, the leaf SPAD value and photosynthetic parameters, soluble proteins and carbohydrates varied greatly in the GS1;1-, GS1;2-overexpressing plants. Furthermore, metabolite profile and gene expression analysis demonstrated significant changes in individual sugars, organic acids and free amino acids, and gene expression patterns in GS1;1-, GS1;2-overexpressing plants, which also indicated the distinct roles that these two GS1 genes played in rice nitrogen metabolism, particularly when sufficient nitrogen was applied in the environment. Thus, the unbalanced carbon-nitrogen metabolic status and poor ability of nitrogen transportation from stem to leaf in GS1;1-, GS1;2-overexpressing plants may explain the poor growth and yield. PMID:24743556

Increased cancer risk of heterozygotes with NBS1 germline mutations in Poland.

PubMed

Steffen, Jan; Varon, Raymonda; Mosor, Maria; Maneva, Galina; Maurer, Martin; Stumm, Markus; Nowakowska, Dorota; Rubach, Maryna; Kosakowska, Ewa; Ruka, Włodzimierz; Nowecki, Zbigniew; Rutkowski, Piotr; Demkow, Tomasz; Sadowska, Małgorzata; Bidziński, Mariusz; Gawrychowski, Krzysztof; Sperling, Karl

2004-08-10

It has been suggested based on familial data that Nijmegen breakage syndrome (NBS) heterozygotes have an increased risk of malignant tumors. We found 15 carriers of the 657del5 mutation and 8 carriers of the R215W molecular variant of the NBS1 gene among 1,289 consecutive patients from Central Poland with various cancers and only 10 and 4 such carriers, respectively, in 1,620 controls from this region. Most of the 657del5 mutation carriers were found among patients with melanoma (4/105), non-Hodgkin lymphoma (2/42) and breast cancer (4/224) and of the 234 patients with colorectal carcinoma 3 carried the 657del5 mutation and 3 others the R215W molecular variant. The frequencies of 657del5 mutation carriers among patients with melanoma and non-Hodgkin lymphoma and of R215W carriers in patients with colorectal cancer were significantly higher than in controls (p < 0.01, < 0.05 and < 0.05 respectively). The pooled frequencies of 657del5 and R215W mutations in all cancer patients were also significantly higher than in controls (p < 0.05). Two carriers of the 657del5 mutation had second primary tumors. Malignant tumors among parents and siblings of 657del5 mutation carriers (14/77) were twice more frequent than in population controls. Three carriers of this mutation (2 probands with melanoma) reported melanoma in relatives. These results suggest strongly that NBS1 heterozygosity may be associated with elevated risk of some cancers. Larger studies are needed to evaluate the impact of the high frequency of germline NBS1 mutations on the cancer burden in the Slav populations. Copyright 2004 Wiley-Liss, Inc.

NBS/NIST Gas Thermometry From 0 to 660 °C

PubMed Central

Schooley, J. F.

1990-01-01

In the NBS/NIST Gas Thermometry program, constant-volume gas thermometers, a unique mercury manometer, and a highly accurate thermal expansion apparatus have been employed to evaluate temperatures on the Kelvin Thermodynamic Temperature Scale (KTTS) that correspond to particular temperatures on the 1968 International Practical Temperature Scale (IPTS-68). In this paper, we present a summary of the NBS/NIST Gas Thermometry project, which originated with planning activities in the late 1920s and was completed by measurements of the differences t(KTTS)-t(IPTS-68) in the range 0 to 660 °C. Early results of this project were the first to demonstrate the surprisingly large inaccuracy of the IPTS-68 with respect to the KTTS above 0 °C. Advances in several different measurement techniques, development of new, specialized instruments, and two distinct sets of gas thermometry observations have resulted from the project. PMID:28179778

Mining whole genomes and transcriptomes of Jatropha (Jatropha curcas) and Castor bean (Ricinus communis) for NBS-LRR genes and defense response associated transcription factors.

PubMed

Sood, Archit; Jaiswal, Varun; Chanumolu, Sree Krishna; Malhotra, Nikhil; Pal, Tarun; Chauhan, Rajinder Singh

2014-11-01

Jatropha (Jatropha curcas L.) and Castor bean (Ricinus communis) are oilseed crops of family Euphorbiaceae with the potential of producing high quality biodiesel and having industrial value. Both the bioenergy plants are becoming susceptible to various biotic stresses directly affecting the oil quality and content. No report exists as of today on analysis of Nucleotide Binding Site-Leucine Rich Repeat (NBS-LRR) gene repertoire and defense response transcription factors in both the plant species. In silico analysis of whole genomes and transcriptomes identified 47 new NBS-LRR genes in both the species and 122 and 318 defense response related transcription factors in Jatropha and Castor bean, respectively. The identified NBS-LRR genes and defense response transcription factors were mapped onto the respective genomes. Common and unique NBS-LRR genes and defense related transcription factors were identified in both the plant species. All NBS-LRR genes in both the species were characterized into Toll/interleukin-1 receptor NBS-LRRs (TNLs) and coiled-coil NBS-LRRs (CNLs), position on contigs, gene clusters and motifs and domains distribution. Transcript abundance or expression values were measured for all NBS-LRR genes and defense response transcription factors, suggesting their functional role. The current study provides a repertoire of NBS-LRR genes and transcription factors which can be used in not only dissecting the molecular basis of disease resistance phenotype but also in developing disease resistant genotypes in Jatropha and Castor bean through transgenic or molecular breeding approaches.

Physical properties and phase diagram of the magnetic compound Cr0.26NbS1.74 at high pressures

NASA Astrophysics Data System (ADS)

Sidorov, V. A.; Petrova, A. E.; Pinyagin, A. N.; Kolesnikov, N. N.; Khasanov, S. S.; Stishov, S. M.

2016-06-01

We report the results of a study of magnetic, electrical, and thermodynamic properties of a single crystal of the magnetic compound Cr0.26NbS1.74 at ambient and high pressures. Results of the measurements of magnetization as a function of temperature reveal the existence of a ferromagnetic phase transition in Cr0.26NbS1.74. The effective number of Bohr magnetons per Cr atom in the paramagnetic phase of Cr0.26NbS1.74 is µeff ≈ 4.6µB, which matches the literature data for Cr1/3NbS2. Similarly, the effective number of Bohr magnetons per Cr atom in the saturation fields is rather close in both substances and corresponds to the number of magnetons in the Cr+3 ion. In contrast to the stoichiometric compound, Cr0.26NbS1.74 does not show a metamagnetic transition, that indicates the lack of a magnetic soliton. A high-pressure phase diagram of the compound reveals the quantum phase transition at T = 0 and P ≈ 4.2 GPa and the triple point situated at T ≈ 20 K and P ≈ 4.2 GPa.

Dr. von Braun Tries Out the Neutral Buoyancy Simulator (NBS)

NASA Technical Reports Server (NTRS)

1967-01-01

Marshall Space Flight Center (MSFC) Director, Dr. von Braun, submerges after spending some time under water in the MSFC Neutral Buoyancy Simulator (NBS). Weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

JCPDS-ICDD Research Associateship (Cooperative Program with NBS/NIST)

PubMed Central

Wong-Ng, W.; McMurdie, H. F.; Hubbard, C. R.; Mighell, A. D.

2001-01-01

The Research Associateship program of the Joint Committee on Powder Diffraction-International Centre for Diffraction Data (JCPDS-ICDD, now known as the ICDD) at NBS/NIST was a long standing (over 35 years) successful industry-government cooperation. The main mission of the Associateship was to publish high quality x-ray reference patterns to be included in the Powder Diffraction File (PDF). The PDF is a continuing compilation of patterns gathered from many sources, compiled and published by the ICDD. As a result of this collaboration, more than 1500 high quality powder diffraction patterns, which have had a significant impact on the scientific community, were reported. In addition, various research collaborations with NBS/NIST also led to the development of several standard reference materials (SRMs) for instrument calibration and quantitative analyses, and computer software for data collection, calibration, reduction, for the editorial process of powder pattern publication, analysis of powder data, and for quantitative analyses. This article summarizes information concerning the JCPDS-ICDD organization, the Powder Diffraction File (PDF), history and accomplishments of the JCPDS-ICDD Research Associateship. PMID:27500061

51g-s-219

NASA Image and Video Library

2011-04-25

51G-S-219 (June 1985) --- Public Affairs Office (PAO) commentator Janet K. Ross is pictured at her console in the Mission Operations Control Room (MOCR) in the Mission Control Center at NASA's Johnson Space Center during the STS-51G mission. Photo credit: NASA

51g-s-213

NASA Image and Video Library

2011-04-25

51G-S-213 (June 1985) --- Public Affairs Office (PAO) commentator Janet K. Ross is pictured at her console in the Mission Operations Control Room (MOCR) in the Mission Control Center at NASA's Johnson Space Center during the STS-51G mission. Photo credit: NASA

Differential CLE peptide perception by plant receptors implicated from structural and functional analyses of TDIF-TDR interactions

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

Li, Zhijie; Chakraborty, Sayan; Xu, Guozhou

Tracheary Element Differentiation Inhibitory Factor (TDIF) belongs to the family of post-translationally modified CLE (CLAVATA3/embryo surrounding region (ESR)-related) peptide hormones that control root growth and define the delicate balance between stem cell proliferation and differentiation in SAM (shoot apical meristem) or RAM (root apical meristem). In Arabidopsis, Tracheary Element Differentiation Inhibitory Factor Receptor (TDR) and its ligand TDIF signaling pathway is involved in the regulation of procambial cell proliferation and inhibiting its differentiation into xylem cells. Here we present the crystal structures of the extracellular domains (ECD) of TDR alone and in complex with its ligand TDIF resolved at 2.65more » Åand 2.75 Å respectively. These structures provide insights about the ligand perception and specific interactions between the CLE peptides and their cognate receptors. Our in vitro biochemical studies indicate that the interactions between the ligands and the receptors at the C-terminal anchoring site provide conserved binding. While the binding interactions occurring at the N-terminal anchoring site dictate differential binding specificities between different ligands and receptors. Our studies will open different unknown avenues of TDR-TDIF signaling pathways that will enhance our knowledge in this field highlighting the receptor ligand interaction, receptor activation, signaling network, modes of action and will serve as a structure function relationship model between the ligand and the receptor for various similar leucine-rich repeat receptor-like kinases (LRR-RLKs).« less

Electronic structure of the chiral helimagnet and 3d-intercalated transition metal dichalcogenide Cr 1/3NbS 2

DOE PAGES

Sirca, N.; Mo, S. -K.; Bondino, F.; ...

2016-08-18

The electronic structure of the chiral helimagnet Cr 1/3NbS 2 has been studied with core level and angle-resolved photoemission spectroscopy (ARPES). Intercalated Cr atoms are found to be effective in donating electrons to the NbS 2 layers but also cause significant modifications of the electronic structure of the host NbS 2 material. Specifically, the data provide evidence that a description of the electronic structure of Cr 1/3NbS 2 on the basis of a simple rigid band picture is untenable. The data also reveal substantial inconsistencies with the predictions of standard density functional theory. In conclusion, the relevance of these resultsmore » to the attainment of a correct description of the electronic structure of chiral helimagnets, magnetic thin films/multilayers, and transition metal dichalcogenides intercalated with 3d magnetic elements is discussed.« less

NBS (National Bureau of Standards): Materials measurements

NASA Technical Reports Server (NTRS)

Manning, J. R.

1985-01-01

NBS work for NASA in support of NASA's Microgravity Science and Applications Program under NASA Government Order H-27954B (Properties of Electronic Materials) covering the period April 1, 1984 to March 31, 1985 is described. The work has been carried out in three independent tasks: Task 1--Surface Tensions and Their Variations with Temperature and Impurities; Task 2--Convention during Unidirectional Solidification; Task 3--Measurement of High Temperature Thermodynamic Properties. The results for each task are given separately in the body of the report.

19. NBS SUIT LAB. STORAGE SHELF WITH LIQUID COOLING VENTILATION ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

19. NBS SUIT LAB. STORAGE SHELF WITH LIQUID COOLING VENTILATION GARMENT (LCVG), SUIT GLOVES, WAIST INSERTS, UPPER AND LOWER ARMS (LEFT, FROM TOP TO BOTTOM), LOWER TORSO ASSEMBLIES (LTA) (MIDDLE RIGHT TO LOWER RIGHT). - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

A waveguide-on-access-tube (WOAT) TDR sensor for deep soil water content and bulk EC

USDA-ARS?s Scientific Manuscript database

A waveguide-on-access-tube (WOAT) TDR sensor was invented and the design optimized through a combination of electromagnetic modeling and several rounds of prototyping and testing in air, water, mixtures of water and ethylene glycol, sand, and silty clay loam soils over a range of water contents and ...

Gsα deficiency in the paraventricular nucleus of the hypothalamus partially contributes to obesity associated with Gsα mutations.

PubMed

Chen, Min; Berger, Alta; Kablan, Ahmed; Zhang, Jiandi; Gavrilova, Oksana; Weinstein, Lee S

2012-09-01

The G protein α-subunit G(s)α mediates receptor-stimulated cAMP generation. Heterozygous inactivating G(s)α mutations on the maternal allele result in obesity primarily due to reduced energy expenditure in Albright hereditary osteodystrophy patients and in mice. We previously showed that mice with central nervous system (CNS)-specific G(s)α deletion on the maternal allele (mBrGs KO) also develop severe obesity with reduced energy expenditure and that G(s)α is primarily expressed from the maternal allele in the paraventricular nucleus (PVN) of the hypothalamus, an important site of energy balance regulation. We now generated mice with PVN-specific G(s)α deficiency by mating Single-minded 1-cre and G(s)α-floxed mice. Homozygous G(s)α deletion produced early lethality. Heterozygotes with maternal G(s)α deletion (mPVNGsKO) also developed obesity and had small reductions in energy expenditure. However, this effect was much milder than that found in mBrGsKO mice and was more prominent in males. We previously showed mBrGsKO mice to have significant reductions in melanocortin receptor agonist-stimulated energy expenditure and now show that mBrGsKO mice have impaired cold-induced brown adipose tissue stimulation. In contrast, these effects were absent in mPVNGsKO mice. mPVNGsKO mice also had minimal effects on glucose metabolism as compared with mBrGsKO mice. Consistent with the presence of G(s)α imprinting, paternal heterozygotes showed no changes in energy or glucose metabolism. These results indicate that although G(s)α deficiency in PVN partially contributes to the metabolic phenotype resulting from maternal G(s)α mutations, G(s)α imprinting in other CNS regions is also important in mediating the CNS effects of G(s)α mutations on energy and glucose metabolism.

Proflavine acts as a Rev inhibitor by targeting the high-affinity Rev binding site of the Rev responsive element of HIV-1.

PubMed

DeJong, Eric S; Chang, Chia-en; Gilson, Michael K; Marino, John P

2003-07-08

Rev is an essential regulatory HIV-1 protein that binds the Rev responsive element (RRE) within the env gene of the HIV-1 RNA genome, activating the switch between viral latency and active viral replication. Previously, we have shown that selective incorporation of the fluorescent probe 2-aminopurine (2-AP) into a truncated form of the RRE sequence (RRE-IIB) allowed the binding of an arginine-rich peptide derived from Rev and aminoglycosides to be characterized directly by fluorescence methods. Using these fluorescence and nuclear magnetic resonance (NMR) methods, proflavine has been identified, through a limited screen of selected small heterocyclic compounds, as a specific and high-affinity RRE-IIB binder which inhibits the interaction of the Rev peptide with RRE-IIB. Direct and competitive 2-AP fluorescence binding assays reveal that there are at least two classes of proflavine binding sites on RRE-IIB: a high-affinity site that competes with the Rev peptide for binding to RRE-IIB (K(D) approximately 0.1 +/- 0.05 microM) and a weaker binding site(s) (K(D) approximately 1.1 +/- 0.05 microM). Titrations of RRE-IIB with proflavine, monitored using (1)H NMR, demonstrate that the high-affinity proflavine binding interaction occurs with a 2:1 (proflavine:RRE-IIB) stoichiometry, and NOEs observed in the NOESY spectrum of the 2:1 proflavine.RRE-IIB complex indicate that the two proflavine molecules bind specifically and close to each other within a single binding site. NOESY data further indicate that formation of the 2:1 proflavine.RRE-IIB complex stabilizes base pairing and stacking within the internal purine-rich bulge of RRE-IIB in a manner analogous to what has been observed in the Rev peptide.RRE-IIB complex. The observation that proflavine competes with Rev for binding to RRE-IIB by binding as a dimer to a single high-affinity site opens the possibility for rational drug design based on linking and modifying it and related compounds.

Relay NBS Graft with the Plus Delivery System to Improve Deployment in Aortic Arch with Small Radius Curve

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

Ferro, Carlo; Rossi, Umberto G., E-mail: urossi76@hotmail.com; Seitun, Sara

The purpose of this report is to describe deployment of the Relay NBS Thoracic Stent Graft with the Plus Delivery System (Bolton Medical, Sunrise, FL) in a flexible resin arch model with a 15-mm radius curve as well as our preliminary clinical results. The Relay NBS graft with the Plus Delivery System was evaluated by way of bench testing, which was performed with stent grafts with diameters ranging from 24 to 46 mm and lengths ranging from 100 to 250 mm in flexible resin arch models with a 15-mm arch radius of curvature. The deployment sequence was analyzed. The Relaymore » NBS graft with the Plus Delivery System was deployed in two patients, respectively, having a 6.5-cm penetrating aortic ulcer of the proximal third of the descending thoracic aorta and a DeBakey type-I aortic dissection with chronic false lumen dilatation after surgery due to an entry site at the distal thoracic aorta. Bench tests showed proper conformation and apposition of the Relay NBS graft with the Plus Delivery System in the flexible resin model. This stent graft was deployed successfully into the two patients with a correct orientation of the first stent and without early or late complications. The Relay NBS graft with the Plus Delivery System ensures an optimal conformation and apposition of the first stent in the aortic arch with a small radius of curvature.« less

Dr. von Braun Tries Out the Neutral Buoyancy Simulator (NBS)

NASA Technical Reports Server (NTRS)

1967-01-01

Marshall Space Flight Center (MSFC) Director, Dr. von Braun, is shown leaving the suiting-up van wearing a pressure suit prepared for a tryout in the MSFC Neutral Buoyancy Simulator (NBS). Weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

Origin of Superconductivity and Latent Charge Density Wave in NbS2

NASA Astrophysics Data System (ADS)

Heil, Christoph; Poncé, Samuel; Lambert, Henry; Schlipf, Martin; Margine, Elena R.; Giustino, Feliciano

2017-08-01

We elucidate the origin of the phonon-mediated superconductivity in 2 H -NbS2 using the ab initio anisotropic Migdal-Eliashberg theory including Coulomb interactions. We demonstrate that superconductivity is associated with Fermi surface hot spots exhibiting an unusually strong electron-phonon interaction. The electron-lattice coupling is dominated by low-energy anharmonic phonons, which place the system on the verge of a charge density wave instability. We also provide definitive evidence for two-gap superconductivity in 2 H -NbS2 , and show that the low- and high-energy peaks observed in tunneling spectra correspond to the Γ - and K -centered Fermi surface pockets, respectively. The present findings call for further efforts to determine whether our proposed mechanism underpins superconductivity in the whole family of metallic transition metal dichalcogenides.

Spatial distribution of soil moisture obtained from gravimetric and TDR methods for SMOS validation, at the Polesie test site SVRT 3275, in Poland

NASA Astrophysics Data System (ADS)

Usowicz, B.; Marczewski, W.; Lipiec, J.; Usowicz, J. B.; Sokolowska, Z.; Dabkowska-Naskret, H.; Hajnos, M.; Lukowski, M. I.

2009-04-01

The purpose is obtaining trustful ground based measurement data of SM (Soil Moisture) for validating SMOS, respectively to spatial and temporal distribution and variations. A use of Time Domain Reflectometric (TDR) method is fast, simple and less destructive, to the soil matter, than a usual standard gravimetric method. TDR tools operate efficiently, enable nearly instant measurements, and allow on collecting many measurements from numerous sites, even when operated manually in short time intervals. The method enables also very frequent sampling of SM at few selected fixed sites, when long terms of temporal variations are needed. In effect one obtains reasonably large data base for determining spatial and temporal distributions of SM. The study is devoted to determining a plan on collecting TDR data, in the scales of small and large field areas, and checking their relevance to those available from gravimetric methods. Finally, the ground based SM distributions are needed for validating other SM distributions, available remotely in larger scales, from the satellite data of ENVISAT-ASAR, and from SMOS (Soil Moisture and Ocean Salinity Mission) when it becomes operational. The ground based evaluations are served mainly by geo-statistical analysis. The space borne estimations are retrieved by image processing and physical models, proper to relevant Remote Sensing (RS) instruments on the orbit. Finally, validation must engage again the geo-statistical evaluations, to assess the agreement between direct and remote sensing means, and provide a measure of trust for extending the limited scales of the ground based data, on concluding the agreement in scales proper to the satellite data. The study is focused mainly on trustful evaluating data from the ground, provided independently on satellite data sources. SM ground based data are collected permanently at 2 selected tests sites, and temporary in areas around the tests sites, in one day sessions, repeated several times per

Lignin metabolism involves Botrytis cinerea BcGs1- induced defense response in tomato.

PubMed

Yang, Chenyu; Liang, Yingbo; Qiu, Dewen; Zeng, Hongmei; Yuan, Jingjing; Yang, Xiufen

2018-06-04

BcGs1, a cell wall-degrading enzyme (CWDE), was originally derived from Botrytis cinerea. Our previous study revealed that BcGs1 could trigger defense responses and protect plants against various pathogens. We researched the defense response mechanism underlying this BcGs1 elicitation in tomato. We revealed that the two domains were required for BcGs1's full necrosis activity. According to analysis and quantitative real-time PCR of the up-regulated proteins and genes filtered by iTRAQ-based quantitative proteome approach, oxidative metabolism and phenylpropanoid metabolism were speculated to be involved in BcGs1-triggered defense response in tomato. Furthermore, experimental evidence showed that BcGs1 triggered reactive oxygen species (ROS) burst and increased the level of phenylalanine-ammonia lyase (PAL) and peroxidase (POD) enzyme activity, as well as lignin accumulation. Moreover, histochemical analysis revealed that infiltration of BcGs1 in tomato leaves exhibited cell wall thickening compared with untreated plants. The results suggested that BcGs1 activated the basal defense response included lignin metabolism contributed to BcGs1-induced resistance to Botrytis. cinerea infection in tomato.

NBS1 plays a synergistic role with telomerase in the maintenance of telomeres in Arabidopsis thaliana.

PubMed

Najdekrova, Lucie; Siroky, Jiri

2012-09-17

Telomeres, as elaborate nucleo-protein complexes, ensure chromosomal stability. When impaired, the ends of linear chromosomes can be recognised by cellular repair mechanisms as double-strand DNA breaks and can be healed by non-homologous-end-joining activities to produce dicentric chromosomes. During cell divisions, particularly during anaphase, dicentrics can break, thus producing naked chromosome tips susceptible to additional unwanted chromosome fusion. Many telomere-building protein complexes are associated with telomeres to ensure their proper capping function. It has been found however, that a number of repair complexes also contribute to telomere stability. We used Arabidopsis thaliana to study the possible functions of the DNA repair subunit, NBS1, in telomere homeostasis using knockout nbs1 mutants. The results showed that although NBS1-deficient plants were viable, lacked any sign of developmental aberration and produced fertile seeds through many generations upon self-fertilisation, plants also missing the functional telomerase (double mutants), rapidly, within three generations, displayed severe developmental defects. Cytogenetic inspection of cycling somatic cells revealed a very early onset of massive genome instability. Molecular methods used for examining the length of telomeres in double homozygous mutants detected much faster telomere shortening than in plants deficient in telomerase gene alone. Our findings suggest that NBS1 acts in concert with telomerase and plays a profound role in plant telomere renewal.

[Construction of genetic linkage map and localization of NBS-LRR like resistance gene analogues in cauliflower (Brassica oleracea var. botrytis)].

PubMed

Gu, Yu; Zhao, Qian-Cheng; Sun, De-Ling; Song, Wen-Qin

2007-06-01

Nucleotide binding site (NBS) profiling, a new method was used to map resistance gene analogues (RGAs) in cauliflower (Brassica oleracea var. botrytis). This method allows amplification and the mapping of genetic markers anchored in the conserved NBS encoding domain of plant disease resistance genes. AFLP was also performed to construct the cauliflower intervarietal genetic map. The aim of constructing genetic map was to identify potential molecular markers linked to important agronomic traits that would be particularly useful for development and improving the species. Using 17 AFLP primer combinations and two degeneration primer/enzyme combinations, a total of 234 AFLP markers and 21 NBS markers were mapped in the F2 population derived from self-pollinating a single F1 plant of the cross AD White Flower x C-8. The markers were mapped in 9 of major linkage groups spanning 668.4 cM, with an average distance of 2.9 cM between adjacent mapped markers. The AFLP markers were well distributed throughout the linkage groups. The linkage groups contained from 12 to 47 loci each and the distance between two consecutive loci ranged from 0 to 14.9 cM. NBS markers were mapped on 8 of the 9 linkage groups of the genetic map. Most of these markers were organized in clusters. This result demonstrates the feasibility of the NBS-profiling method for generating NBS markers for resistance loci in cauliflower. The clustering of the markers mapped in this study adds to the evidence that most of them could be real RGAs.

Tracking the career development of scientists in low- and middle-income countries trained through TDR's research capacity strengthening programmes: Learning from monitoring and impact evaluation.

PubMed

Halpaap, Béatrice; Vahedi, Mahnaz; Certain, Edith; Alvarado, Tini; Saint Martin, Caroline; Merle, Corinne; Mihut, Michael; Launois, Pascal

2017-12-01

The Special Programme for Research and Training in Tropical Diseases (TDR) co-sponsored by UNICEF, UNDP, World Bank and WHO has been supporting research capacity strengthening in low- and middle-income countries for over 40 years. In order to assess and continuously optimize its capacity strengthening approaches, an evaluation of the influence of TDR training grants on research career development was undertaken. The assessment was part of a larger evaluation conducted by the European Science Foundation. A comprehensive survey questionnaire was developed and sent to a group of 117 trainees supported by TDR who had completed their degree (masters or PhD) between 2000 and 2012; of these, seventy seven (77) responded. Most of the respondents (80%) rated TDR support as a very important factor that influenced their professional career achievements. The "brain drain" phenomenon towards high-income countries was particularly low amongst TDR grantees: the rate of return to their region of origin upon completion of their degree was 96%. A vast majority of respondents are still working in research (89%), with 81% of respondents having participated in multidisciplinary research activities; women engaged in multidisciplinary collaboration to a higher extent than men. However, only a minority of all have engaged in intersectoral collaboration, an aspect that would require further study. The post-degree career choices made by the respondents were strongly influenced by academic considerations. At the time of the survey, 92% of all respondents hold full-time positions, mainly in the public sector. Almost 25% of the respondents reported that they had influenced policy and practice changes. Some of the challenges and opportunities faced by trainees at various stages of their research career have been identified. Modalities to overcome these will require further investigation. The survey evidenced how TDR's research capacity grant programmes made a difference on researchers' career

The novel sodium channel modulator GS-458967 (GS967) is an effective treatment in a mouse model of SCN8A encephalopathy.

PubMed

Baker, Erin M; Thompson, Christopher H; Hawkins, Nicole A; Wagnon, Jacy L; Wengert, Eric R; Patel, Manoj K; George, Alfred L; Meisler, Miriam H; Kearney, Jennifer A

2018-06-01

De novo mutations of SCN8A, encoding the voltage-gated sodium channel Na V 1.6, have been associated with a severe infant onset epileptic encephalopathy. Individuals with SCN8A encephalopathy have a mean age of seizure onset of 4-5 months, with multiple seizure types that are often refractory to treatment with available drugs. Anecdotal reports suggest that high-dose phenytoin is effective for some patients, but there are associated adverse effects and potential for toxicity. Functional characterization of several SCN8A encephalopathy variants has shown that elevated persistent sodium current is one of several common biophysical defects. Therefore, specifically targeting elevated persistent current may be a useful therapeutic strategy in some cases. The novel sodium channel modulator GS967 has greater preference for persistent as opposed to peak current and nearly 10-fold greater potency than phenytoin. We evaluated the therapeutic effect of GS967 in the Scn8a N1768D/+ mouse model carrying an SCN8A patient mutation that results in elevated persistent sodium current. We also performed patch clamp recordings to assess the effect of GS967 on peak and persistent sodium current and excitability in hippocampal neurons from Scn8a N1768D/+ mice. GS967 potently blocked persistent sodium current without affecting peak current, normalized action potential morphology, and attenuated excitability in neurons from heterozygous Scn8a N1768D/+ mice. Acute treatment with GS967 provided dose-dependent protection against maximal electroshock-induced seizures in Scn8a N1768D/+ and wild-type mice. Chronic treatment of Scn8a N1768D/+ mice with GS967 resulted in lower seizure burden and complete protection from seizure-associated lethality observed in untreated Scn8a N1768D/+ mice. Protection was achieved at a chronic dose that did not cause overt behavioral toxicity or sedation. Persistent sodium current modulators like GS967 may be an effective precision targeting strategy for SCN8A

657del5 mutation in the NBS1 gene is associated with Nijmegen breakage syndrome in a Turkish family.

PubMed

Tekin, Mustafa; Doğu, F; Taçyíldiz, N; Akar, E; Ikincioğullari, A; Oğur, G; Yavuz, G; Babacan, E; Akar, N

2002-07-01

We report on a consanguineous Turkish family whose first son died of anal atresia and whose second son presented with severe pre- and post-natal growth retardation as well as striking microcephaly, immunodeficiency, congenital heart disease, chromosomal instability and rhabdomyosarcoma in the anal region. The proband was found to carry the homozygous 657del5 mutation in the NBS1 gene, which is responsible for Nijmegen breakage syndrome (NBS) in most of the Slav populations. Our family, the first diagnosed with NBS in the Turkish population, represents one of the most severely affected examples of the syndrome, with profound pre- and post-natal growth retardation associated with structural abnormalities, and expands the clinical spectrum of this rare disorder.

Detection of an organic-non volatile compound in variable-contaminated volcanic soil samples via Time Domain Reflectometry (TDR) technique: Preliminary results

NASA Astrophysics Data System (ADS)

comegna, alessandro; coppola, antonio; dragonetti, giovanna; chaali, nesrine; sommella, angelo

2014-05-01

Hydrocarbons may be present in soils as non-aqueous phase liquids (NAPLs), which means that these organic compounds, exist as a separate and immiscible phase with respect to water and air commonly present in the soil. NAPLs, which can be accidentally introduced in the environment (for example by waste disposal sites, industrial spills, gasoline stations, etc), constitutes a serious geo-environmental problem, given the toxicity level and the high mobility. Time domain reflectometry (TDR) has became, over several decades, an important technique for water estimation in soils. In order to expand the potentiality of the TDR technique, the main objective of this study is to explore the capacity of dielectric response to detect the presence of NAPLs in volcanic soils. In laboratory, soil samples were oven dried at 105° C and passed through a 2 mm sieve. Known quantities of soil, water and NAPL (corn oil, a non-volatile and non-toxic organic compound) were mixed and repacked into plastic cylinders (16 cm high and 9.5 cm in diameter); in order to obtain forty different volumetric combinations of water and oil (i.e. θfg = θwater + θNAPL), with θNAPL varying from 0.05 to 0.40 by 0.05 cm3/cm3 increments. Data collected were employed to implement a multiphase mixing model which permitted conversion from a dielectric permittivity domain into a θf domain and vice versa. The results of this study show that, the TDR device is NAPL-sensitive, especially for θf values greater than 0.20. Further works will be built on this initial study, concentrating on improving the dielectric response-database, in order to: i) enhancing the model efficiency in terms of NAPL capability detention, and ii) validating the developed TDR interpretation tool with field results.

Evaluation of Two Guralp Preamplifiers for GS13 Seismometer Application.

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

Merchant, Bion J.

Sandia National Laboratories has tested and evaluated a new preamplifier, the Guralp Preamplifier for GS13, manufactured by Guralp. These preamplifiers are used to interface between Guralp digitizers and Geotech GS13 Seismometers. The purpose of the preamplifier evaluation was to measure the performance characteristics in such areas as power consumption, input impedance, sensitivity, full scale, self-noise, dynamic range, system noise, response, passband, and timing. The Guralp GS13 Preamplifiers are being evaluated for potential use in the International Monitoring System (IMS) of the Comprehensive Nuclear Test-Ban-Treaty Organization (CTBTO).

5 CFR 531.217 - Special conversion rules for certain non-GS employees.

Code of Federal Regulations, 2012 CFR

2012-01-01

... be converted to GS-equivalent rates immediately before leaving the non-GS system, the employee is... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Special conversion rules for certain non... Appointment Or Position Changes § 531.217 Special conversion rules for certain non-GS employees. When an...

5 CFR 531.217 - Special conversion rules for certain non-GS employees.

Code of Federal Regulations, 2014 CFR

2014-01-01

... be converted to GS-equivalent rates immediately before leaving the non-GS system, the employee is... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Special conversion rules for certain non... Appointment Or Position Changes § 531.217 Special conversion rules for certain non-GS employees. When an...

5 CFR 531.217 - Special conversion rules for certain non-GS employees.

Code of Federal Regulations, 2011 CFR

2011-01-01

... be converted to GS-equivalent rates immediately before leaving the non-GS system, the employee is... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Special conversion rules for certain non... Appointment Or Position Changes § 531.217 Special conversion rules for certain non-GS employees. When an...

5 CFR 531.217 - Special conversion rules for certain non-GS employees.

Code of Federal Regulations, 2013 CFR

2013-01-01

... be converted to GS-equivalent rates immediately before leaving the non-GS system, the employee is... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Special conversion rules for certain non... Appointment Or Position Changes § 531.217 Special conversion rules for certain non-GS employees. When an...

5 CFR 531.217 - Special conversion rules for certain non-GS employees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... be converted to GS-equivalent rates immediately before leaving the non-GS system, the employee is... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Special conversion rules for certain non... Appointment Or Position Changes § 531.217 Special conversion rules for certain non-GS employees. When an...

Comparison of revision surgeries for one- to two-level cervical TDR and ACDF from 2002 to 2011.

PubMed

Nandyala, Sreeharsha V; Marquez-Lara, Alejandro; Fineberg, Steven J; Singh, Kern

2014-12-01

Cervical total disc replacement (TDR) and anterior cervical discectomy and fusion (ACDF) provide comparable outcomes for degenerative cervical pathology. However, revisions of these procedures are not well characterized. The purpose of this study is to examine the rates, epidemiology, perioperative complications, and costs between the revision procedures and to compare these outcomes with those of primary cases. This study is a retrospective database analysis. A total of 3,792 revision and 183,430 primary cases from the Nationwide Inpatient Sample (NIS) database from 2002 to 2011 were included. Incidence of revision cases, patient demographics, length of stay (LOS), in-hospital costs, mortality, and perioperative complications. Patients who underwent revision for either one- to two-level cervical TDR or ACDF were identified. SPSS v.20 was used for statistical analysis with χ(2) test for categorical data and independent sample t test for continuous data. The relative risk for perioperative complications with revisions was calculated in comparison with primary cases using a 95% confidence interval. An alpha level of less than 0.05 denoted statistical significance. There were 3,536 revision one- to two-level ACDFs and 256 revision cervical TDRs recorded in the NIS database from 2002 to 2011. The revision cervical TDR cohort demonstrated a significantly greater LOS (3.18 vs. 2.25, p<.001), cost ($16,998 vs. $15,222, p=.03), and incidence of perioperative wound infections (13.6 vs. 5.3 per 1,000, p<.001) compared with the ACDF revision cohort (p<.001). There were no differences in mortality between the revision surgical cohorts. Compared with primary cases, both revision cohorts demonstrated a significantly greater LOS and cost. Furthermore, patients who underwent revision demonstrated a greater incidence and risk for perioperative wound infections, hematomas, dysphagia, and neurologic complications relative to the primary procedures. This study demonstrated a

Traces of charge density waves in NbS 2

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

Leroux, Maxime; Cario, Laurent; Bosak, Alexei

Among transition metal dichalcogenides (TMD), NbS 2 is often considered as the archetypal compound that does not have a charge density wave (CDW) in any of its polytypes. By comparison, close isoelectronic compounds such as NbSe 2, TaS 2, and TaSe 2 all have CDW in at least one polytype. Here we report traces of CDW in the 2H polytype of NbS 2, using diffuse x-ray scattering measurements at 77 K and room temperature. We observe 12 extremely weak satellite peaks located at ±13.9° from →a* and →b* around each Bragg peak in the (h,k,0) plane. These satellite peaks aremore » commensurate with the lattice via 3 →q– →q'= →a*, where →q' is the 120° rotation of →q, and define two √13a × √13a superlattices in real space. These commensurate wave vectors and tilt angle are identical to those of the CDW observed in the 1T polytype of TaS 2 and TaSe 2. In conclusion, to understand this similarity and the faintness of the peaks, we discuss possible sources of local 1T polytype environment in bulk 2H-NbS 2 crystals.« less

Traces of charge density waves in NbS2

NASA Astrophysics Data System (ADS)

Leroux, Maxime; Cario, Laurent; Bosak, Alexei; Rodière, Pierre

2018-05-01

Among transition metal dichalcogenides (TMD), NbS2 is often considered as the archetypal compound that does not have a charge density wave (CDW) in any of its polytypes. By comparison, close isoelectronic compounds such as NbSe2, TaS2, and TaSe2 all have CDW in at least one polytype. Here we report traces of CDW in the 2H polytype of NbS2, using diffuse x-ray scattering measurements at 77 K and room temperature. We observe 12 extremely weak satellite peaks located at ±13.9° from a⃗* and b⃗* around each Bragg peak in the (h ,k ,0 ) plane. These satellite peaks are commensurate with the lattice via 3 q ⃗-q ⃗'=a⃗*,where q ⃗' is the 120° rotation of q ⃗, and define two √{13 }a ×√{13 }a superlattices in real space. These commensurate wave vectors and tilt angle are identical to those of the CDW observed in the 1T polytype of TaS2 and TaSe2. To understand this similarity and the faintness of the peaks, we discuss possible sources of local 1T polytype environment in bulk 2H-NbS2 crystals.

Traces of charge density waves in NbS 2

DOE PAGES

Leroux, Maxime; Cario, Laurent; Bosak, Alexei; ...

2018-05-15

Among transition metal dichalcogenides (TMD), NbS 2 is often considered as the archetypal compound that does not have a charge density wave (CDW) in any of its polytypes. By comparison, close isoelectronic compounds such as NbSe 2, TaS 2, and TaSe 2 all have CDW in at least one polytype. Here we report traces of CDW in the 2H polytype of NbS 2, using diffuse x-ray scattering measurements at 77 K and room temperature. We observe 12 extremely weak satellite peaks located at ±13.9° from →a* and →b* around each Bragg peak in the (h,k,0) plane. These satellite peaks aremore » commensurate with the lattice via 3 →q– →q'= →a*, where →q' is the 120° rotation of →q, and define two √13a × √13a superlattices in real space. These commensurate wave vectors and tilt angle are identical to those of the CDW observed in the 1T polytype of TaS 2 and TaSe 2. In conclusion, to understand this similarity and the faintness of the peaks, we discuss possible sources of local 1T polytype environment in bulk 2H-NbS 2 crystals.« less

Dr. von Braun Tries Out the Neutral Buoyancy Simulator (NBS)

NASA Technical Reports Server (NTRS)

1967-01-01

Astronaut L. Gordon Cooper checks the neck ring of a space suit worn by Marshall Space Flight Center (MSFC) Director, Dr. von Braun before he submerges into the water of the MSFC Neutral Buoyancy Simulator (NBS). Wearing a pressurized suit and weighted to a neutrally buoyant condition, Dr. von Braun was able to perform tasks underwater which simulated weightless conditions found in space.

Suppression of atherosclerosis by synthetic REV-ERB agonist

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

Sitaula, Sadichha; Billon, Cyrielle; Kamenecka, Theodore M.

2015-05-08

The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks comparedmore » to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. - Highlights: • Synthetic REV-ERB agonist treatment reduced atherosclerosis in a mouse model. • Pharmacological activation of REV-ERB decreased M1 macrophage polarization. • Pharmacological activation of REV-ERB increased M2 macrophage polarization.« less

Multiplex single-tube screening for mutations in the Nijmegen Breakage Syndrome (NBS1) gene in Hodgkin's and non-Hodgkin's lymphoma patients of Slavic origin.

PubMed

Soucek, Pavel; Gut, Ivan; Trneny, Marek; Skovlund, Eva; Grenaker Alnaes, Grethe; Kristensen, Tom; Børresen-Dale, Anne-Lise; Kristensen, Vessela N

2003-05-01

Patients with Nijmegen Breakage Syndrome (NBS) have a high risk to develop malignant diseases, most frequently B-cell lymphomas. It has been demonstrated that this chromosomal breakage syndrome results from mutations in the NBS1 gene that cause either a loss of full-length protein expression or expression of a variant protein. A large proportion of the known NBS patients are of Slavic origin who carry a major founder mutation 657del5 in exon 6 of the NBS1 gene. The prevalence of this mutation in Slav populations is reported to be high, possibly contributing to higher cancer risk in these populations. Therefore, if mutations in NBS1 are associated with higher risk of developing lymphoid cancers it would be most likely to be observed in these populations. A multiplex assay for four of the most frequent NBS1 mutations was designed and a series of 119 lymphoma patients from Slavic origin as well as 177 healthy controls were tested. One of the patients was a heterozygote carrier of the ACAAA deletion mutation in exon 6 (1/119). No mutation was observed in the control group, despite the reported high frequency (1/177). The power of this study was 30% to detect a relative risk of 2.0.

NBS work on neutron resonance radiography

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

Schrack, R.A.

1987-01-01

NBS has been engaged in a wide-ranging program in Neutron Resonance Radiography utilizing both one- and two-dimensional position-sensitive neutron detectors. The ability to perform a position-sensitive assay of up to 16 isotopes in a complex matrix has been demonstrated for a wide variety of sample types, including those with high gamma activity. A major part of the program has been the development and application of the microchannel-plate-based position-sensitive neutron detector. This detector system has high resolution and sensitivity, together with adequate speed of response to be used with neutron time-of-flight techniques. This system has demonstrated the ability to simultaneously imagemore » three isotopes in a sample with no interference.« less

Genome-wide comparative analysis of NBS-encoding genes in four Gossypium species

USDA-ARS?s Scientific Manuscript database

Nucleotide binding site (NBS) genes encode a large family of disease resistance (R) proteins in plants. The availability of genomic data of the two diploid cotton species, Gossypium arboreum and Gossypium raimondii, and the two allotetraploid cotton species, Gossypium hirsutum (TM-1) and Gossypium ...

Time to take action to meet GS1 mandate.

PubMed

Doyle, Chris

2014-10-01

A recent paper, NHS eProcurement Strategy,(1) published earlier this year by the Department of Health, mandated the use of GS1 standards throughout the NHS in England. The Strategy requires all NHS Trusts in England to produce a Board-approved adoption plan. Chris Doyle, head of Healthcare at independent global supply chain standards organization, GS1 UK, explains the next steps to becoming compliant.

Intermediate clinical and radiological results of cervical TDR (Mobi-C®) with up to 2 years of follow-up

PubMed Central

Beaurain, J.; Bernard, P.; Dufour, T.; Fuentes, J. M.; Hovorka, I.; Huppert, J.; Steib, J. P.; Vital, J. M.; Aubourg, L.

2009-01-01

The interest in cervical total disc replacement (TDR) as an alternative to the so-far gold standard in the surgical treatment of degenerative disc disease (DDD), e.g anterior cervical discectomy and fusion (ACDF), is growing very rapidly. Many authors have established the fact that ACDF may result in progressive degeneration in adjacent segments. On the contrary, but still theoretically, preservation of motion with TDR at the surgically treated level may potentially reduce the occurrence of adjacent-level degeneration (ALD). The authors report the intermediate results of an undergoing multicentre prospective study of TDR with Mobi-C® prosthesis. The aim of the study was to assess the safety and efficacy of the device in the treatment of DDD and secondary to evaluate the radiological status of adjacent levels and the occurrence of ossifications, at 2-year follow-up (FU). 76 patients have performed their 2-year FU visit and have been analyzed clinically and radiologically. Clinical outcomes (NDI, VAS, SF-36) and ROM measurements were analyzed pre-operatively and at the different post-operative time-points. Complications and re-operations were also assessed. Occurrences of heterotopic ossifications (HOs) and of adjacent disc degeneration radiographic changes have been analyzed from 2-year FU X-rays. The mean NDI and VAS scores for arm and neck are reduced significantly at each post-operative time-point compared to pre-operative condition. Motion is preserved over the time at index levels (mean ROM = 9° at 2 years) and 85.5% of the segments are mobile at 2 years. HOs are responsible for the fusion of 6/76 levels at 2 years. However, presence of HO does not alter the clinical outcomes. The occurrence rate of radiological signs of ALD is very low at 2 years (9.1%). There has been no subsidence, no expulsion and no sub-luxation of the implant. Finally, after 2 years, 91% of the patients assume that they would undergo the procedure again. These intermediate

Chromatin modification contributes to the expression divergence of three TaGS2 homoeologs in hexaploid wheat

PubMed Central

Zhang, Wei; Fan, Xiaoli; Gao, Yingjie; Liu, Lei; Sun, Lijing; Su, Qiannan; Han, Jie; Zhang, Na; Cui, Fa; Ji, Jun; Tong, Yiping; Li, Junming

2017-01-01

Plastic glutamine synthetase (GS2) is responsible for ammonium assimilation. The reason that TaGS2 homoeologs in hexaploid wheat experience different selection pressures in the breeding process remains unclear. TaGS2 were minimally expressed in roots but predominantly expressed in leaves, and TaGS2-B had higher expression than TaGS2-A and TaGS2-D. ChIP assays revealed that the activation of TaGS2-B expression in leaves was correlated with increased H3K4 trimethylation. The transcriptional silencing of TaGS2 in roots was correlated with greater cytosine methylation and less H3K4 trimethylation. Micrococcal nuclease and DNase I accessibility experiments indicated that the promoter region was more resistant to digestion in roots than leaves, which indicated that the closed nucleosome conformation of the promoter region was important to the transcription initiation for the spatial-temporal expression of TaGS2. In contrast, the transcribed regions possess different nuclease accessibilities of three TaGS2 homoeologs in the same tissue, suggesting that nucleosome conformation of the transcribed region was part of the fine adjustment of TaGS2 homoeologs. This study provides evidence that histone modification, DNA methylation and nuclease accessibility coordinated the control of the transcription of TaGS2 homoeologs. Our results provided important evidence that TaGS2-B experienced the strongest selection pressures during the breeding process. PMID:28300215

HSV-1 Genome Subnuclear Positioning and Associations with Host-Cell PML-NBs and Centromeres Regulate LAT Locus Transcription during Latency in Neurons

PubMed Central

Catez, Frédéric; Picard, Christel; Held, Kathrin; Gross, Sylvain; Rousseau, Antoine; Theil, Diethilde; Sawtell, Nancy; Labetoulle, Marc; Lomonte, Patrick

2012-01-01

Major human pathologies are caused by nuclear replicative viruses establishing life-long latent infection in their host. During latency the genomes of these viruses are intimately interacting with the cell nucleus environment. A hallmark of herpes simplex virus type 1 (HSV-1) latency establishment is the shutdown of lytic genes expression and the concomitant induction of the latency associated (LAT) transcripts. Although the setting up and the maintenance of the latent genetic program is most likely dependent on a subtle interplay between viral and nuclear factors, this remains uninvestigated. Combining the use of in situ fluorescent-based approaches and high-resolution microscopic analysis, we show that HSV-1 genomes adopt specific nuclear patterns in sensory neurons of latently infected mice (28 days post-inoculation, d.p.i.). Latent HSV-1 genomes display two major patterns, called “Single” and “Multiple”, which associate with centromeres, and with promyelocytic leukemia nuclear bodies (PML-NBs) as viral DNA-containing PML-NBs (DCP-NBs). 3D-image reconstruction of DCP-NBs shows that PML forms a shell around viral genomes and associated Daxx and ATRX, two PML partners within PML-NBs. During latency establishment (6 d.p.i.), infected mouse TGs display, at the level of the whole TG and in individual cells, a substantial increase of PML amount consistent with the interferon-mediated antiviral role of PML. “Single” and “Multiple” patterns are reminiscent of low and high-viral genome copy-containing neurons. We show that LAT expression is significantly favored within the “Multiple” pattern, which underlines a heterogeneity of LAT expression dependent on the viral genome copy number, pattern acquisition, and association with nuclear domains. Infection of PML-knockout mice demonstrates that PML/PML-NBs are involved in virus nuclear pattern acquisition, and negatively regulate the expression of the LAT. This study demonstrates that nuclear domains

Nuclear Expression of GS28 Protein: A Novel Biomarker that Predicts Prognosis in Colorectal Cancers

PubMed Central

Lee, Sung Hak; Yoo, Hyung Jae; Rim, Do Eun; Cui, Yinji; Lee, Ahwon; Jung, Eun Sun; Oh, Seung Taek; Kim, Jun Gi; Kwon, Oh-Joo; Kim, Su Young; Jeong, Seong-Whan

2017-01-01

Aims: GS28 (Golgi SNARE protein, 28 kDa), a member of the soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) protein family, plays a critical role in mammalian endoplasmic reticulum (ER)-Golgi or intra-Golgi vesicle transport. To date, few researches on the GS28 protein in human cancer tissues have been reported. In this study, we assessed the prognostic value of GS28 in patients with colorectal cancer (CRC). Methods and results: We screened for GS28 expression using immunohistochemistry in 230 surgical CRC specimens. The CRCs were right-sided and left-sided in 28.3% (65/230) and 71.3% (164/230) of patients, respectively. GS28 staining results were available in 214 cases. Among these, there were 26 nuclear predominant cases and 188 non-nuclear predominant cases. Stromal GS28 expression was noted in 152 cases of CRC. GS28 nuclear predominant immunoreactivity was significantly associated with advanced tumour stage (p = 0.045) and marginally associated with perineural invasion (p = 0.064). Decreased GS28 expression in the stromal cells was significantly associated with lymph node metastasis (N stage; p = 0.036). GS28 expression was not associated with epidermal growth factor receptor (EGFR) immunohistochemical positivity or KRAS mutation status. Investigation of the prognostic value of GS28 with Kaplan-Meier analysis revealed a correlation with overall survival (p = 0.004). Cases with GS28 nuclear predominant expression had significantly poorer overall survival than those with a non-nuclear predominant pattern. Conclusions: Taken together, these results indicate that GS28 nuclear predominant expression could serve as a prognostic marker for CRC and may help in identifying aggressive forms of CRC. PMID:28638266

The 2015 hard-state only outburst of GS 1354-64

NASA Astrophysics Data System (ADS)

Stiele, H.; Kong, A. K. H.

2016-07-01

Since its outburst in 1997, GS 1354-64 stayed in quiescence. In 2015 June, renewed activity of GS 1354-64 was observed. Based on our analysis of energy spectra and timing properties obtained from Swift/X-ray telescope monitoring data, we found that GS 1354-64 stayed in the hard state during the entire outburst. Such a hard state only (or `failed' outburst) has also been observed in 1997. In addition, we analysed an XMM-Newton observation taken on August 6th. We compared variability on long and short time-scales using covariance ratio and found that the ratio showed a decrease towards lower energies instead of the increase that has been found in other black hole X-ray binaries. There are now two sources (H1743-322 and GS 1354-64) that do not show an increase towards lower energies in their covariance ratio. Both sources have been observed during `failed' outbursts and showed photon indices much harder than what is usually observed in black hole X-ray binaries.

Optimized Chemical Probes for REV-ERBα

PubMed Central

Trump, Ryan P.; Bresciani, Stefano; Cooper, Anthony W. J.; Tellam, James P.; Wojno, Justyna; Blaikley, John; Orband-Miller, Lisa A.; Kashatus, Jennifer A.; Dawson, Helen C.; Loudon, Andrew; Ray, David; Grant, Daniel; Farrow, Stuart N.; Willson, Timothy M.; Tomkinson, Nicholas C. O.

2015-01-01

REV-ERBα has emerged as an important target for regulation of circadian rhythm and its associated physiology. Herein, we report on the optimization of a series of REV-ERBα agonists based on GSK4112 (1) for potency, selectivity, and bioavailability. Potent REV-ERBα agonists 4, 10, 16, and 23 are detailed for their ability to suppress BMAL and IL-6 expression from human cells while also demonstrating excellent selectivity over LXRα. Amine 4 demonstrated in vivo bioavailability after either IV or oral dosing. PMID:23656296

Docosahexaenoic acid alters Gsα localization in lipid raft and potentiates adenylate cyclase.

PubMed

Zhu, Zhuoran; Tan, Zhoubin; Li, Yan; Luo, Hongyan; Hu, Xinwu; Tang, Ming; Hescheler, Jürgen; Mu, Yangling; Zhang, Lanqiu

2015-01-01

Supplementation with docosahexaenoic acid (DHA), an ω-3 polyunsaturated fatty acid (PUFA), recently has become popular for the amelioration of depression; however the molecular mechanism of DHA action remains unclear. The aim of this study was to investigate the mechanism underlying the antidepressant effect of DHA by evaluating Gsα localization in lipid raft and the activity of adenylate cyclase in an in vitro glioma cell model. Lipid raft fractions from C6 glioma cells treated chronically with DHA were isolated by sucrose gradient ultracentrifugation. The content of Gsα in lipid raft was analyzed by immunoblotting and colocalization of Gsα with lipid raft was subjected to confocal microscopic analysis. The intracellular cyclic adenosine monophosphate (cAMP) level was determined by cAMP immunoassay kit. DHA decreased the amount of Gsα in lipid raft, whereas whole cell lysate Gsα was not changed. Confocal microscopic analysis demonstrated that colocalization of Gsα with lipid raft was decreased, whereas DHA increased intracellular cAMP accumulation in a dose-dependent manner. Interestingly, we found that DHA increased the lipid raft level, instead of disrupting it. The results of this study suggest that DHA may exert its antidepressant effect by translocating Gsα from lipid raft and potentiating the activity of adenylate cyclase. Importantly, the reduced Gsα in lipid raft by DHA is independent of disruption of lipid raft. Overall, the study provides partial preclinical evidence supporting a safe and effective therapy using DHA for depression. Copyright © 2015 Elsevier Inc. All rights reserved.

Suppression of atherosclerosis by synthetic REV-ERB agonist

PubMed Central

Sitaula, Sadichha; Billon, Cyrielle; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

2015-01-01

The nuclear receptors for heme, REV-ERBα and REV-ERBβ, play important roles in the regulation of metabolism and inflammation. Recently it was demonstrated that reduced REV-ERBα expression in hematopoetic cells in LDL receptor null mice led to increased atherosclerosis. We sought to determine if synthetic REV-ERB agonists that we have developed might have the ability to suppress atherosclerosis in this model. A previously characterized synthetic REV-ERB agonist, SR9009, was used to determine if activation of REV-ERB activity would affect atherosclerosis in LDL receptor deficient mice. Atherosclerotic plaque size was significantly reduced (p < 0.05) in mice administered SR9009 (100 mg/kg) for seven weeks compared to control mice (n = 10 per group). SR9009 treatment of bone marrow-derived mouse macrophages (BMDM) reduced the polarization of BMDMs to proinflammatory M1 macrophage while increasing the polarization of BMDMs to anti-inflammatory M2 macrophages. Our results suggest that pharmacological targeting of REV-ERBs may be a viable therapeutic option for treatment of atherosclerosis. PMID:25800870

A TDR-Based Soil Moisture Monitoring System with Simultaneous Measurement of Soil Temperature and Electrical Conductivity

PubMed Central

Skierucha, Wojciech; Wilczek, Andrzej; Szypłowska, Agnieszka; Sławiński, Cezary; Lamorski, Krzysztof

2012-01-01

Elements of design and a field application of a TDR-based soil moisture and electrical conductivity monitoring system are described with detailed presentation of the time delay units with a resolution of 10 ps. Other issues discussed include the temperature correction of the applied time delay units, battery supply characteristics and the measurement results from one of the installed ground measurement stations in the Polesie National Park in Poland. PMID:23202009

Deconstruction of the (Paleo)Polyploid Grapevine Genome Based on the Analysis of Transposition Events Involving NBS Resistance Genes

PubMed Central

Cestaro, Alessandro; Sterck, Lieven; Fontana, Paolo; Van de Peer, Yves; Viola, Roberto; Velasco, Riccardo; Salamini, Francesco

2012-01-01

Plants have followed a reticulate type of evolution and taxa have frequently merged via allopolyploidization. A polyploid structure of sequenced genomes has often been proposed, but the chromosomes belonging to putative component genomes are difficult to identify. The 19 grapevine chromosomes are evolutionary stable structures: their homologous triplets have strongly conserved gene order, interrupted by rare translocations. The aim of this study is to examine how the grapevine nucleotide-binding site (NBS)-encoding resistance (NBS-R) genes have evolved in the genomic context and to understand mechanisms for the genome evolution. We show that, in grapevine, i) helitrons have significantly contributed to transposition of NBS-R genes, and ii) NBS-R gene cluster similarity indicates the existence of two groups of chromosomes (named as Va and Vc) that may have evolved independently. Chromosome triplets consist of two Va and one Vc chromosomes, as expected from the tetraploid and diploid conditions of the two component genomes. The hexaploid state could have been derived from either allopolyploidy or the separation of the Va and Vc component genomes in the same nucleus before fusion, as known for Rosaceae species. Time estimation indicates that grapevine component genomes may have fused about 60 mya, having had at least 40–60 mya to evolve independently. Chromosome number variation in the Vitaceae and related families, and the gap between the time of eudicot radiation and the age of Vitaceae fossils, are accounted for by our hypothesis. PMID:22253773

The GS (genetic selection) Principle.

PubMed

Abel, David L

2009-01-01

The GS (Genetic Selection) Principle states that biological selection must occur at the nucleotide-sequencing molecular-genetic level of 3'5' phosphodiester bond formation. After-the-fact differential survival and reproduction of already-living phenotypic organisms (ordinary natural selection) does not explain polynucleotide prescription and coding. All life depends upon literal genetic algorithms. Even epigenetic and "genomic" factors such as regulation by DNA methylation, histone proteins and microRNAs are ultimately instructed by prior linear digital programming. Biological control requires selection of particular configurable switch-settings to achieve potential function. This occurs largely at the level of nucleotide selection, prior to the realization of any integrated biofunction. Each selection of a nucleotide corresponds to the setting of two formal binary logic gates. The setting of these switches only later determines folding and binding function through minimum-free-energy sinks. These sinks are determined by the primary structure of both the protein itself and the independently prescribed sequencing of chaperones. The GS Principle distinguishes selection of existing function (natural selection) from selection for potential function (formal selection at decision nodes, logic gates and configurable switch-settings).

Identification and distribution of the NBS-LRR gene family in the cassava genome

USDA-ARS?s Scientific Manuscript database

Plant resistance genes (R genes) exist in large families and usually contain both a nucleotide-binding site domain and a leucine-rich repeat domain, denoted NBS-LRR. The genome sequence of cassava (Manihot esculenta) is a valuable resource for analyzing the genomic organization of resistance genes i...

Genome wide re-sequencing of newly developed Rice Lines from common wild rice (Oryza rufipogon Griff.) for the identification of NBS-LRR genes.

PubMed

Liu, Wen; Ghouri, Fozia; Yu, Hang; Li, Xiang; Yu, Shuhong; Shahid, Muhammad Qasim; Liu, Xiangdong

2017-01-01

Common wild rice (Oryza rufipogon Griff.) is an important germplasm for rice breeding, which contains many resistance genes. Re-sequencing provides an unprecedented opportunity to explore the abundant useful genes at whole genome level. Here, we identified the nucleotide-binding site leucine-rich repeat (NBS-LRR) encoding genes by re-sequencing of two wild rice lines (i.e. Huaye 1 and Huaye 2) that were developed from common wild rice. We obtained 128 to 147 million reads with approximately 32.5-fold coverage depth, and uniquely covered more than 89.6% (> = 1 fold) of reference genomes. Two wild rice lines showed high SNP (single-nucleotide polymorphisms) variation rate in 12 chromosomes against the reference genomes of Nipponbare (japonica cultivar) and 93-11 (indica cultivar). InDels (insertion/deletion polymorphisms) count-length distribution exhibited normal distribution in the two lines, and most of the InDels were ranged from -5 to 5 bp. With reference to the Nipponbare genome sequence, we detected a total of 1,209,308 SNPs, 161,117 InDels and 4,192 SVs (structural variations) in Huaye 1, and 1,387,959 SNPs, 180,226 InDels and 5,305 SVs in Huaye 2. A total of 44.9% and 46.9% genes exhibited sequence variations in two wild rice lines compared to the Nipponbare and 93-11 reference genomes, respectively. Analysis of NBS-LRR mutant candidate genes showed that they were mainly distributed on chromosome 11, and NBS domain was more conserved than LRR domain in both wild rice lines. NBS genes depicted higher levels of genetic diversity in Huaye 1 than that found in Huaye 2. Furthermore, protein-protein interaction analysis showed that NBS genes mostly interacted with the cytochrome C protein (Os05g0420600, Os01g0885000 and BGIOSGA038922), while some NBS genes interacted with heat shock protein, DNA-binding activity, Phosphoinositide 3-kinase and a coiled coil region. We explored abundant NBS-LRR encoding genes in two common wild rice lines through genome wide re

Genome wide re-sequencing of newly developed Rice Lines from common wild rice (Oryza rufipogon Griff.) for the identification of NBS-LRR genes

PubMed Central

Yu, Hang; Li, Xiang; Yu, Shuhong; Shahid, Muhammad Qasim

2017-01-01

Common wild rice (Oryza rufipogon Griff.) is an important germplasm for rice breeding, which contains many resistance genes. Re-sequencing provides an unprecedented opportunity to explore the abundant useful genes at whole genome level. Here, we identified the nucleotide-binding site leucine-rich repeat (NBS-LRR) encoding genes by re-sequencing of two wild rice lines (i.e. Huaye 1 and Huaye 2) that were developed from common wild rice. We obtained 128 to 147 million reads with approximately 32.5-fold coverage depth, and uniquely covered more than 89.6% (> = 1 fold) of reference genomes. Two wild rice lines showed high SNP (single-nucleotide polymorphisms) variation rate in 12 chromosomes against the reference genomes of Nipponbare (japonica cultivar) and 93–11 (indica cultivar). InDels (insertion/deletion polymorphisms) count-length distribution exhibited normal distribution in the two lines, and most of the InDels were ranged from -5 to 5 bp. With reference to the Nipponbare genome sequence, we detected a total of 1,209,308 SNPs, 161,117 InDels and 4,192 SVs (structural variations) in Huaye 1, and 1,387,959 SNPs, 180,226 InDels and 5,305 SVs in Huaye 2. A total of 44.9% and 46.9% genes exhibited sequence variations in two wild rice lines compared to the Nipponbare and 93–11 reference genomes, respectively. Analysis of NBS-LRR mutant candidate genes showed that they were mainly distributed on chromosome 11, and NBS domain was more conserved than LRR domain in both wild rice lines. NBS genes depicted higher levels of genetic diversity in Huaye 1 than that found in Huaye 2. Furthermore, protein-protein interaction analysis showed that NBS genes mostly interacted with the cytochrome C protein (Os05g0420600, Os01g0885000 and BGIOSGA038922), while some NBS genes interacted with heat shock protein, DNA-binding activity, Phosphoinositide 3-kinase and a coiled coil region. We explored abundant NBS-LRR encoding genes in two common wild rice lines through genome wide re

GOES-R GS Product Generation Infrastructure Operations

NASA Astrophysics Data System (ADS)

Blanton, M.; Gundy, J.

2012-12-01

GOES-R GS Product Generation Infrastructure Operations: The GOES-R Ground System (GS) will produce a much larger set of products with higher data density than previous GOES systems. This requires considerably greater compute and memory resources to achieve the necessary latency and availability for these products. Over time, new algorithms could be added and existing ones removed or updated, but the GOES-R GS cannot go down during this time. To meet these GOES-R GS processing needs, the Harris Corporation will implement a Product Generation (PG) infrastructure that is scalable, extensible, extendable, modular and reliable. The primary parts of the PG infrastructure are the Service Based Architecture (SBA), which includes the Distributed Data Fabric (DDF). The SBA is the middleware that encapsulates and manages science algorithms that generate products. The SBA is divided into three parts, the Executive, which manages and configures the algorithm as a service, the Dispatcher, which provides data to the algorithm, and the Strategy, which determines when the algorithm can execute with the available data. The SBA is a distributed architecture, with services connected to each other over a compute grid and is highly scalable. This plug-and-play architecture allows algorithms to be added, removed, or updated without affecting any other services or software currently running and producing data. Algorithms require product data from other algorithms, so a scalable and reliable messaging is necessary. The SBA uses the DDF to provide this data communication layer between algorithms. The DDF provides an abstract interface over a distributed and persistent multi-layered storage system (memory based caching above disk-based storage) and an event system that allows algorithm services to know when data is available and to get the data that they need to begin processing when they need it. Together, the SBA and the DDF provide a flexible, high performance architecture that can meet

Quicklook overview of model changes in Melcor 2.2: Rev 6342 to Rev 9496

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

Humphries, Larry L.

2017-05-01

MELCOR 2.2 is a significant official release of the MELCOR code with many new models and model improvements. This report provides the code user with a quick review and characterization of new models added, changes to existing models, the effect of code changes during this code development cycle (rev 6342 to rev 9496), a preview of validation results with this code version. More detailed information is found in the code Subversion logs as well as the User Guide and Reference Manuals.

Absolute 1* quantum yields for the ICN A state by diode laser gain versus absorption spectroscopy

NASA Technical Reports Server (NTRS)

Hess, Wayne P.; Leone, Stephen R.

1987-01-01

Absolute I* quantum yields were measured as a function of wavelength for room temperature photodissociation of the ICN A state continuum. The temperature yields are obtained by the technique of time-resolved diode laser gain-versus-absorption spectroscopy. Quantum yields are evaluated at seven wavelengths from 248 to 284 nm. The yield at 266 nm is 66.0 +/- 2% and it falls off to 53.4 +/- 2% and 44.0 +/- 4% at 284 and 248 respectively. The latter values are significantly higher than those obtained by previous workers using infrared fluorescence. Estimates of I* quantum yields obtained from analysis of CN photofragment rotational distributions, as discussed by other workers, are in good agreement with the I* yields. The results are considered in conjunction with recent theoretical and experimental work on the CN rotational distributions and with previous I* yield results.

A Rare Allele of GS2 Enhances Grain Size and Grain Yield in Rice.

PubMed

Hu, Jiang; Wang, Yuexing; Fang, Yunxia; Zeng, Longjun; Xu, Jie; Yu, Haiping; Shi, Zhenyuan; Pan, Jiangjie; Zhang, Dong; Kang, Shujing; Zhu, Li; Dong, Guojun; Guo, Longbiao; Zeng, Dali; Zhang, Guangheng; Xie, Lihong; Xiong, Guosheng; Li, Jiayang; Qian, Qian

2015-10-05

Grain size determines grain weight and affects grain quality. Several major quantitative trait loci (QTLs) regulating grain size have been cloned; however, our understanding of the underlying mechanism that regulates the size of rice grains remains fragmentary. Here, we report the cloning and characterization of a dominant QTL, grain size on chromosome 2 (GS2), which encodes Growth-Regulating Factor 4 (OsGRF4), a transcriptional regulator. GS2 localizes to the nucleus and may act as a transcription activator. A rare mutation of GS2 affecting the binding site of a microRNA, OsmiR396c, causes elevated expression of GS2/OsGRF4. The increase in GS2 expression leads to larger cells and increased numbers of cells, which thus enhances grain weight and yield. The introduction of this rare allele of GS2/OsGRF4 into rice cultivars could significantly enhance grain weight and increase grain yield, with possible applications in breeding high-yield rice varieties. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

Analysis of Chromosomal Aberrations after Low and High Dose Rate Gamma Irradiation in ATM or NBS Suppressed Human Fibroblast Cells

NASA Technical Reports Server (NTRS)

Hada, M.; Huff, J. L.; Patel, Z.; Pluth, J. M.; George, K. A.; Cucinotta, F. A.

2009-01-01

A detailed understanding of the biological effects of heavy nuclei is needed for space radiation protection and for cancer therapy. High-LET radiation produces more complex DNA lesions that may be non-repairable or that may require additional processing steps compared to endogenous DSBs, increasing the possibility of misrepair. Interplay between radiation sensitivity, dose, and radiation quality has not been studied extensively. Previously we studied chromosome aberrations induced by low- and high- LET radiation in several cell lines deficient in ATM (ataxia telangactasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. We found that the yields of both simple and complex chromosomal aberrations were significantly increased in the DSB repair defective cells compared to normal cells. The increased aberrations observed for the ATM and NBS defective lines was due to a significantly larger quadratic dose-response term compared to normal fibroblasts for both simple and complex aberrations, while the linear dose-response term was significantly higher in NBS cells only for simple exchanges. These results point to the importance of the functions of ATM and NBS in chromatin modifications that function to facilitate correct DSB repair and minimize aberration formation. To further understand the sensitivity differences that were observed in ATM and NBS deficient cells, in this study, chromosomal aberration analysis was performed in normal lung fibroblast cells treated with KU-55933, a specific ATM kinase inhibitor, or Mirin, an MRN complex inhibitor involved in activation of ATM. We are also testing siRNA knockdown of these proteins. Normal and ATM or NBS suppressed cells were irradiated with gamma-rays and chromosomes were collected with a premature chromosome

Ovarian cancer therapeutic potential of glutamine depletion based on GS expression.

PubMed

Furusawa, Akiko; Miyamoto, Morikazu; Takano, Masashi; Tsuda, Hitoshi; Song, Yong Sang; Aoki, Daisuke; Miyasaka, Naoyuki; Inazawa, Johji; Inoue, Jun

2018-05-28

Amino acids (AAs) are biologically important nutrient compounds necessary for the survival of any cell. Of the 20 AAs, cancer cells depend on the uptake of several extracellular AAs for survival. However, which extracellular AA is indispensable for the survival of cancer cells and the molecular mechanism involved have not been fully defined. In this study, we found that the reduction of cell survival caused by glutamine (Gln) depletion is inversely correlated with the expression level of glutamine synthetase (GS) in ovarian cancer (OVC) cells. GS expression was downregulated in 45 of 316 OVC cases (14.2%). The depletion of extracellular Gln by treatment with l-asparaginase, in addition to inhibiting Gln uptake via the knockdown of a Gln transporter, led to the inhibition of cell growth in OVC cells with low expression of GS (GSlow-OVC cells). Furthermore, the re-expression of GS in GSlow-OVC cells induced the inhibition of tumor growth in vitro and in vivo. Thus, these findings provide novel insight into the development of an OVC therapy based on the requirement of Gln.

13. NBS LOWER ROOM. BEHIND FAR GLASS WALL IS VIDEO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

13. NBS LOWER ROOM. BEHIND FAR GLASS WALL IS VIDEO TAPE EQUIPMENT AND VOICE INTERCOM EQUIPMENT. THE MONITORS ABOVE GLASS WALL DISPLAY UNDERWATER TEST VIDEO TO CONTROL ROOM. FARTHEST CONSOLE ROW CONTAINS CAMERA SWITCHING, PANNING, TILTING, FOCUSING, AND ZOOMING. MIDDLE CONSOLE ROW CONTAINS TEST CONDUCTOR CONSOLES FOR MONITORING TEST ACTIVITIES AND DATA. THE CLOSEST CONSOLE ROW IS NBC FACILITY CONSOLES FOR TEST DIRECTOR, SAFETY AND QUALITY ASSURANCE REPRESENTATIVES. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

TDR method for determine IC's parameters

NASA Astrophysics Data System (ADS)

Timoshenkov, V.; Rodionov, D.; Khlybov, A.

2016-12-01

Frequency domain simulation is a widely used approach for determine integrated circuits parameters. This approach can be found in most of software tools used in IC industry. Time domain simulation approach shows intensive usage last years due to some advantages. In particular it applicable for analysis of nonlinear and nonstationary systems where frequency domain is inapplicable. Resolution of time domain systems allow see heterogeneities on distance 1mm, determine it parameters and properties. Authors used approach based on detecting reflected signals from heterogeneities - time domain reflectometry (TDR). Field effect transistor technology scaling up to 30-60nm gate length and 10nm gate dielectric, heterojunction bi-polar transistors with 10-30nm base width allows fabricate digital IC's with 20GHz clock frequency and RF-IC's with tens GHz bandwidth. Such devices and operation speed suppose transit signal by use microwave lines. There are local heterogeneities can be found inside of the signal path due to connections between different parts of signal lines (stripe line-RF-connector pin, stripe line - IC package pin). These heterogeneities distort signals that cause bandwidth decrease for RF-devices. Time domain research methods of transmission and reflected signals give the opportunities to determine heterogeneities, it properties, parameters and built up equivalent circuits. Experimental results are provided and show possibility for inductance and capacitance measurement up to 25GHz. Measurements contains result of signal path research on IC and printed circuit board (PCB) used for 12GHz RF chips. Also dielectric constant versus frequency was measured up to 35GHz.

Dynamic Solidification in Nanoconfined Water Films

DTIC Science & Technology

2010-06-16

C . Ramanujan , H. O. Ozer, and A. Oral, Phys. Rev. B, 70, 054114 (2004). [6] T. D. Li, J. P. Gao...unclassified c . THIS PAGE unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Water is the fundamental solvent of all...Displacement (nm) 0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4 D a m p in g c o e ff ic ie n t (m N s /m ) 0.0 0.5 1.0 1.5 0 1 2 3 4 5 6 7 R e la x a ti o n t

TaGS5-3A, a grain size gene selected during wheat improvement for larger kernel and yield.

PubMed

Ma, Lin; Li, Tian; Hao, Chenyang; Wang, Yuquan; Chen, Xinhong; Zhang, Xueyong

2016-05-01

Grain size is a dominant component of grain weight in cereals. Earlier studies have shown that OsGS5 plays a major role in regulating both grain size and weight in rice via promotion of cell division. In this study, we isolated TaGS5 homoeologues in wheat and mapped them on chromosomes 3A, 3B and 3D. Temporal and spatial expression analysis showed that TaGS5 homoeologues were preferentially expressed in young spikes and developing grains. Two alleles of TaGS5-3A, TaGS5-3A-T and TaGS5-3A-G were identified in wheat accessions, and a functional marker was developed to discriminate them. Association analysis revealed that TaGS5-3A-T was significantly correlated with larger grain size and higher thousand kernel weight. Biochemical assays showed that TaGS5-3A-T possesses a higher enzymatic activity than TaGS5-3A-G. Transgenic rice lines overexpressing TaGS5-3A-T also exhibited larger grain size and higher thousand kernel weight than TaGS5-3A-G lines, and the transcript levels of cell cycle-related genes in TaGS5-3A-T lines were higher than those in TaGS5-3A-G lines. Furthermore, systematic evolution analysis in diploid, tetraploid and hexaploid wheat showed that TaGS5-3A underwent strong artificial selection during wheat polyploidization events and the frequency changes of two alleles demonstrated that TaGS5-3A-T was favoured in global modern wheat cultivars. These results suggest that TaGS5-3A is a positive regulator of grain size and its favoured allele TaGS5-3A-T exhibits a larger potential application in wheat high-yield breeding. © 2015 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Ectopic Expression of GsSRK in Medicago sativa Reveals Its Involvement in Plant Architecture and Salt Stress Responses.

PubMed

Sun, Mingzhe; Qian, Xue; Chen, Chao; Cheng, Shufei; Jia, Bowei; Zhu, Yanming; Sun, Xiaoli

2018-01-01

Receptor-like kinases (RLK) play fundamental roles in plant growth and stress responses. Compared with other RLKs, little information is provided concerning the S-locus LecRLK subfamily, which is characterized by an extracellular G-type lectin domain and an S-locus-glycop domain. Until now, the function of the G-type lectin domain is still unknown. In a previous research, we identified a Glycine soja S-locus LecRLK gene GsSRK , which conferred increased salt stress tolerance in transgenic Arabidopsis . In this study, to investigate the role of the G-type lectin domain and to breed transgenic alfalfa with superior salt stress tolerance, we transformed the full-length GsSRK ( GsSRK-f ) and a truncated version of GsSRK ( GsSRK-t ) deleting the G-type lectin domain into alfalfa. Our results showed that overexpression of GsSRK-t , but not GsSRK-f , resulted in changes of plant architecture, as evidenced by more branches but shorter shoots of GsSRK-t transgenic alfalfa, indicating a potential role of the extracellular G-type lectin domain in regulating plant architecture. Furthermore, we also found that transgenic alfalfa overexpressing either GsSRK-f or GsSRK-t showed increased salt stress tolerance, and GsSRK-t transgenic alfalfa displayed better growth (more branches and higher fresh weight) than GsSRK-f lines under salt stress. In addition, our results suggested that both GsSRK-f and GsSRK-t were involved in ion homeostasis, ROS scavenging, and osmotic regulation. Under salt stress, the Na + content in the transgenic lines was significantly lower, while the K + content was slightly higher than that in WT. Moreover, the transgenic lines displayed reduced ion leakage and MDA content, but increased SOD activity and proline content than WT. Notably, no obvious difference in these physiological indices was observed between GsSRK-f and GsSRK-t transgenic lines, implying that deletion of the GsSRK G-type lectin domain does not affect its physiological function in salt

New biotite and muscovite isotopic reference materials, USGS57 and USGS58, for δ2H measurements–A replacement for NBS 30

USGS Publications Warehouse

Qi, Haiping; Coplen, Tyler B.; Gehre, Matthias; Vennemann, Torsten W.; Brand, Willi A.; Geilmann, Heike; Olack, Gerard; Bindeman, Ilya N.; Palandri, Jim; Huang, Li; Longstaffe, Fred J.

2017-01-01

The advent of continuous-flow isotope-ratio mass spectrometry (CF-IRMS) coupled with a high temperature conversion (HTC) system enabled faster, more cost effective, and more precise δ2H analysis of hydrogen-bearing solids. Accurate hydrogen isotopic analysis by on-line or off-line techniques requires appropriate isotopic reference materials (RMs). A strategy of two-point calibrations spanning δ2H range of the unknowns using two RMs is recommended. Unfortunately, the supply of the previously widely used isotopic RM, NBS 30 biotite, is exhausted. In addition, recent measurements have shown that the determination of δ2H values of NBS 30 biotite on the VSMOW-SLAP isotope-delta scale by on-line HTC systems with CF-IRMS may be unreliable because hydrogen in this biotite may not be converted quantitatively to molecular hydrogen. The δ2HVSMOW-SLAP values of NBS 30 biotite analyzed by on-line HTC systems can be as much as 21 mUr (or ‰) too positive compared to the accepted value of − 65.7 mUr, determined by only a few conventional off-line measurements. To ensure accurate and traceable on-line hydrogen isotope-ratio determinations in mineral samples, we here propose two isotopically homogeneous, hydrous mineral RMs with well-characterized isotope-ratio values, which are urgently needed. The U.S. Geological Survey (USGS) has prepared two such RMs, USGS57 biotite and USGS58 muscovite. The δ2H values were determined by both glassy carbon-based on-line conversion and chromium-based on-line conversion, and results were confirmed by off-line conversion. The quantitative conversion of hydrogen from the two RMs using the on-line HTC method was carefully evaluated in this study. The isotopic compositions of these new RMs with 1-σ uncertainties and mass fractions of hydrogen are:USGS57 (biotite)δ2HVSMOW-SLAP = − 91.5 ± 2.4 mUr (n = 24)Mass fraction hydrogen = 0.416 ± 0.002% (n = 4)Mass fraction water = 3.74 ± 0.02% (n = 4)USGS58 (muscovite

20. NBS SUIT LAB. TABLE WITH MISCELLANEOUS SUIT PARTS AND ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. NBS SUIT LAB. TABLE WITH MISCELLANEOUS SUIT PARTS AND TERRY WEST, A SPACE SUIT ASSEMBLY TECHNICIAN LOGGING SUIT PART DATA. PARTS ON THE TABLE ARE A HARD UPPER TORSO (HUT) (REAR LEFT), FULL HELMET (FRONT LEFT), TWO HELMETS WITHOUT PROTECTIVE VISORS, A PAIR OF GLOVES, AND A BACKPACK WITHOUT VOLUMETRIC COVER (REAR RIGHT). THE BACKPACK ATTACHES TO THE HUT TO MAKE-UP THE UPPER TORSO COMPONENTS OF THE SUIT. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

Morphological features of different polyploids for adaptation and molecular characterization of CC-NBS-LRR and LEA gene families in Agave L.

PubMed

Tamayo-Ordóñez, M C; Rodriguez-Zapata, L C; Narváez-Zapata, J A; Tamayo-Ordóñez, Y J; Ayil-Gutiérrez, B A; Barredo-Pool, F; Sánchez-Teyer, L F

2016-05-20

Polyploidy has been widely described in many Agave L. species, but its influence on environmental response to stress is still unknown. With the objective of knowing the morphological adaptations and regulation responses of genes related to biotic (LEA) and abiotic (NBS-LRR) stress in species of Agave with different levels of ploidy, and how these factors contribute to major response of Agave against environmental stresses, we analyzed 16 morphological trials on five accessions of three species (Agave tequilana Weber, Agave angustifolia Haw. and Agave fourcroydes Lem.) with different ploidy levels (2n=2x=60 2n=3x=90, 2n=5x=150, 2n=6x=180) and evaluated the expression of NBS-LRR and LEA genes regulated by biotic and abiotic stress. It was possible to associate some morphological traits (spines, nuclei, and stomata) to ploidy level. The genetic characterization of stress-related genes NBS-LRR induced by pathogenic infection and LEA by heat or saline stresses indicated that amino acid sequence analysis in these genes showed more substitutions in higher ploidy level accessions of A. fourcroydes Lem. 'Sac Ki' (2n=5x=150) and A. angustifolia Haw. 'Chelem Ki' (2n=6x=180), and a higher LEA and NBS-LRR representativeness when compared to their diploid and triploid counterparts. In all studied Agave accessions expression of LEA and NBS-LRR genes was induced by saline or heat stresses or by infection with Erwinia carotovora, respectively. The transcriptional activation was also higher in A. angustifolia Haw. 'Chelem Ki' (2n=6x=180) and A. fourcroydes 'Sac Ki' (2n=5x=150) than in their diploid and triploid counterparts, which suggests higher adaptation to stress. Finally, the diploid accession A. tequilana Weber 'Azul' showed a differentiated genetic profile relative to other Agave accessions. The differences include similar or higher genetic representativeness and transcript accumulation of LEA and NBS-LRR genes than in polyploid (2n=5x=150 and 2n=6x=180) Agave accessions

Co-Expression analysis of miRNAs and target NBS-LRR genes in Cucumis sativus

USDA-ARS?s Scientific Manuscript database

Plants react against their biological enemies by activating the innate immune system. Their defense system comprises of various R-protein, which usually contain NBS-LRR domain. MicroRNAs (miRNAs) are important molecules of 2nd layer of plant defense and play pivotal role behind the scene. To support...

The powdery mildew resistance gene REN1 co-segregates with an NBS-LRR gene cluster in two Central Asian grapevines

PubMed Central

2009-01-01

Background Grape powdery mildew is caused by the North American native pathogen Erysiphe necator. Eurasian Vitis vinifera varieties were all believed to be susceptible. REN1 is the first resistance gene naturally found in cultivated plants of Vitis vinifera. Results REN1 is present in 'Kishmish vatkana' and 'Dzhandzhal kara', two grapevines documented in Central Asia since the 1920's. These cultivars have a second-degree relationship (half sibs, grandparent-grandchild, or avuncular), and share by descent the chromosome on which the resistance allele REN1 is located. The REN1 interval was restricted to 1.4 cM using 38 SSR markers distributed across the locus and the segregation of the resistance phenotype in two progenies of collectively 461 offspring, derived from either resistant parent. The boundary markers delimit a 1.4-Mbp sequence in the PN40024 reference genome, which contains 27 genes with known functions, 2 full-length coiled-coil NBS-LRR genes, and 9 NBS-LRR pseudogenes. In the REN1 locus of PN40024, NBS genes have proliferated through a mixture of segmental duplications, tandem gene duplications, and intragenic recombination between paralogues, indicating that the REN1 locus has been inherently prone to producing genetic variation. Three SSR markers co-segregate with REN1, the outer ones confining the 908-kb array of NBS-LRR genes. Kinship and clustering analyses based on genetic distances with susceptible cultivars representative of Central Asian Vitis vinifera indicated that 'Kishmish vatkana' and 'Dzhandzhal kara' fit well into local germplasm. 'Kishmish vatkana' also has a parent-offspring relationship with the seedless table grape 'Sultanina'. In addition, the distant genetic relatedness to rootstocks, some of which are derived from North American species resistant to powdery mildew and have been used worldwide to guard against phylloxera since the late 1800's, argues against REN1 being infused into Vitis vinifera from a recent interspecific

The Nuclear Receptor Rev-erbα Controls Circadian Thermogenic Plasticity

PubMed Central

Gerhart-Hines, Zachary; Everett, Logan J.; Loro, Emanuele; Briggs, Erika R.; Bugge, Anne; Hou, Catherine; Ferrara, Christine; Seale, Patrick; Pryma, Daniel A.; Khurana, Tejvir S.; Lazar, Mitchell A.

2013-01-01

Circadian oscillation of body temperature is a basic, evolutionary-conserved feature of mammalian biology1. Additionally, homeostatic pathways allow organisms to protect their core temperatures in response to cold exposure2. However, the mechanism responsible for coordinating daily body temperature rhythm and adaptability to environmental challenges is unknown. Here we show that the nuclear receptor Rev-erbα, a powerful transcriptional repressor, links circadian and thermogenic networks through the regulation of brown adipose tissue (BAT) function. Mice exposed to cold fare dramatically better at 5 AM (Zeitgeber time 22) when Rev-erbα is barely expressed than at 5 PM (ZT10) when Rev-erbα is abundant. Deletion of Rev-erbα markedly improves cold tolerance at 5 PM, indicating that overcoming Rev-erbα-dependent repression is a fundamental feature of the thermogenic response to cold. Physiological induction of uncoupling protein 1 (UCP1) by cold temperatures is preceded by rapid down-regulation of Rev-erbα in BAT. Rev-erbα represses UCP1 in a brown adipose cell-autonomous manner and BAT UCP1 levels are high in Rev-erbα-null mice even at thermoneutrality. Genetic loss of Rev-erbα also abolishes normal rhythms of body temperature and BAT activity. Thus, Rev-erbα acts as a thermogenic focal point required for establishing and maintaining body temperature rhythm in a manner that is adaptable to environmental demands. PMID:24162845

Circadian clock component REV-ERBα controls homeostatic regulation of pulmonary inflammation.

PubMed

Pariollaud, Marie; Gibbs, Julie E; Hopwood, Thomas W; Brown, Sheila; Begley, Nicola; Vonslow, Ryan; Poolman, Toryn; Guo, Baoqiang; Saer, Ben; Jones, D Heulyn; Tellam, James P; Bresciani, Stefano; Tomkinson, Nicholas Co; Wojno-Picon, Justyna; Cooper, Anthony Wj; Daniels, Dion A; Trump, Ryan P; Grant, Daniel; Zuercher, William; Willson, Timothy M; MacDonald, Andrew S; Bolognese, Brian; Podolin, Patricia L; Sanchez, Yolanda; Loudon, Andrew Si; Ray, David W

2018-06-01

Recent studies reveal that airway epithelial cells are critical pulmonary circadian pacemaker cells, mediating rhythmic inflammatory responses. Using mouse models, we now identify the rhythmic circadian repressor REV-ERBα as essential to the mechanism coupling the pulmonary clock to innate immunity, involving both myeloid and bronchial epithelial cells in temporal gating and determining amplitude of response to inhaled endotoxin. Dual mutation of REV-ERBα and its paralog REV-ERBβ in bronchial epithelia further augmented inflammatory responses and chemokine activation, but also initiated a basal inflammatory state, revealing a critical homeostatic role for REV-ERB proteins in the suppression of the endogenous proinflammatory mechanism in unchallenged cells. However, REV-ERBα plays the dominant role, as deletion of REV-ERBβ alone had no impact on inflammatory responses. In turn, inflammatory challenges cause striking changes in stability and degradation of REV-ERBα protein, driven by SUMOylation and ubiquitination. We developed a novel selective oxazole-based inverse agonist of REV-ERB, which protects REV-ERBα protein from degradation, and used this to reveal how proinflammatory cytokines trigger rapid degradation of REV-ERBα in the elaboration of an inflammatory response. Thus, dynamic changes in stability of REV-ERBα protein couple the core clock to innate immunity.

GS6, a member of the GRAS gene family, negatively regulates grain size in rice.

PubMed

Sun, Lianjun; Li, Xiaojiao; Fu, Yongcai; Zhu, Zuofeng; Tan, Lubin; Liu, Fengxia; Sun, Xianyou; Sun, Xuewen; Sun, Chuanqing

2013-10-01

Grain size is an important yield-related trait in rice. Intensive artificial selection for grain size during domestication is evidenced by the larger grains of most of today's cultivars compared with their wild relatives. However, the molecular genetic control of rice grain size is still not well characterized. Here, we report the identification and cloning of Grain Size 6 (GS6), which plays an important role in reducing grain size in rice. A premature stop at the +348 position in the coding sequence (CDS) of GS6 increased grain width and weight significantly. Alignment of the CDS regions of GS6 in 90 rice materials revealed three GS6 alleles. Most japonica varieties (95%) harbor the Type I haplotype, and 62.9% of indica varieties harbor the Type II haplotype. Association analysis revealed that the Type I haplotype tends to increase the width and weight of grains more than either of the Type II or Type III haplotypes. Further investigation of genetic diversity and the evolutionary mechanisms of GS6 showed that the GS6 gene was strongly selected in japonica cultivars. In addition, a "ggc" repeat region identified in the region that encodes the GRAS domain of GS6 played an important historic role in the domestication of grain size in rice. Knowledge of the function of GS6 might aid efforts to elucidate the molecular mechanisms that control grain development and evolution in rice plants, and could facilitate the genetic improvement of rice yield. © 2013 Institute of Botany, Chinese Academy of Sciences.

RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs

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

Huang, Feng; Zhang, Junsong; Zhang, Yijun

Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-boxmore » of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. - Highlights: • MOV10 can function as a co-factor of HIV-1 Rev. • MOV10 facilitates Rev/RRE-dependent transport of viral mRNAs. • MOV10 interacts with Rev in an RNA-independent manner. • The DEAG-box of MOV10 is required for the enhancement of Rev/RRE-dependent export.« less

NOSH-aspirin (NBS-1120), a novel nitric oxide- and hydrogen sulfide-releasing hybrid has enhanced chemo-preventive properties compared to aspirin, is gastrointestinal safe with all the classic therapeutic indications

PubMed Central

Kodela, Ravinder; Chattopadhyay, Mitali; Velázquez-Martínez, Carlos A.; Kashfi, Khosrow

2015-01-01

Aspirin is chemopreventive; however, side effects preclude its long-term use. NOSH-aspirin (NBS-1120), a novel hybrid that releases nitric oxide and hydrogen sulfide, was designed to be a safer alternative. Here we compare the gastrointestinal safety, anti-inflammatory, analgesic, antipyretic, anti-platelet, and chemopreventive properties of aspirin and NBS-1120 administered orally to rats at equimolar doses. Gastrointestinal safety: 6h post-administration, the number and size of hemorrhagic lesions in stomachs were counted; tissue samples were frozen for PGE2, SOD, and MDA determination. Anti-inflammatory: 1h after drug administration, the volume of carrageenan-induced rat paw edemas was measured for 5h. Anti-pyretic: fever was induced by LPS (ip) an hour before administration of the test drugs, core body temperature was measured hourly for 5h. Analgesic: time-dependent analgesic effects were evaluated by carrageenan-induced hyperalgesia. Antiplatelet: anti-aggregatory effects were studied on collagen-induced platelet aggregation of human platelet-rich plasma. Chemoprevention: Nude mice were gavaged daily for 25 days with vehicle, aspirin or NBS-1120. After one week, each mouse was inoculated subcutaneously in the right flank with HT-29 human colon cancer cells. Both agents reduced PGE2 levels in stomach tissue; however, NBS-1120 did not cause any stomach ulcers, whereas aspirin caused significant bleeding. Lipid peroxidation induced by aspirin was higher than that exerted by NBS-1120. SOD activity was significantly inhibited by aspirin but increased by NBS-1120. Both agents showed similar anti-inflammatory, analgesic, anti-pyretic, and anti-platelet activities. Aspirin increased plasma TNFα more than NBS-1120-treated animals. NBS-1120 was better than aspirin as a chemopreventive agent; it dose-dependently inhibited tumor growth and tumor mass. PMID:26394025

Methionine sulfoximine supplementation enhances productivity in GS-CHOK1SV cell lines through glutathione biosynthesis.

PubMed

Feary, Marc; Racher, Andrew J; Young, Robert J; Smales, C Mark

2017-01-01

In Lonza Biologics' GS Gene Expression System™, recombinant protein-producing GS-CHOK1SV cell lines are generated by transfection with an expression vector encoding both GS and the protein product genes followed by selection in MSX and glutamine-free medium. MSX is required to inhibit endogenous CHOK1SV GS, and in effect create a glutamine auxotrophy in the host that can be complemented by the expression vector encoded GS in selected cell lines. However, MSX is not a specific inhibitor of GS as it also inhibits the activity of GCL (a key enzyme in the glutathione biosynthesis pathway) to a similar extent. Glutathione species (GSH and GSSG) have been shown to provide both oxidizing and reducing equivalents to ER-resident oxidoreductases, raising the possibility that selection for transfectants with increased GCL expression could result in the isolation of GS-CHOKISV cell lines with improved capacity for recombinant protein production. In this study we have begun to address the relationship between MSX supplementation, the amount of intracellular GCL subunit and mAb production from a panel of GS-CHOK1SV cell lines. We then evaluated the influence of reduced GCL activity on batch culture of an industrially relevant mAb-producing GS-CHOK1SV cell line. To the best of our knowledge, this paper describes for the first time the change in expression of GCL subunits and recombinant mAb production in these cell lines with the degree of MSX supplementation in routine subculture. Our data also shows that partial inhibition of GCL activity in medium containing 75 µM MSX increases mAb productivity, and its more specific inhibitor BSO used at a concentration of 80 µM in medium increases the specific rate of mAb production eight-fold and the concentration in harvest medium by two-fold. These findings support a link between the inhibition of glutathione biosynthesis and recombinant protein production in industrially relevant systems and provide a process-driven method for

NMR Structure and Dynamics of the C-terminal Domain from Human Rev1 and its Complex with Rev1 Interacting Region of DNA Polymerase η

PubMed Central

Pozhidaeva, Alexandra; Pustovalova, Yulia; D'Souza, Sanjay; Bezsonova, Irina; Walker, Graham C.; Korzhnev, Dmitry M.

2013-01-01

Rev1 is a translesion synthesis (TLS) DNA polymerase essential for DNA damage tolerance in eukaryotes. In the process of TLS stalled high-fidelity replicative DNA polymerases are temporarily replaced by specialized TLS enzymes that can bypass sites of DNA damage (lesions), thus allowing replication to continue or postreplicational gaps to be filled. Despite its limited catalytic activity, human Rev1 plays a key role in TLS by serving as a scaffold that provides an access of Y-family TLS polymerases polη, ι, and κ to their cognate DNA lesions and facilitates their subsequent exchange to polζ that extends the distorted DNA primer-template. Rev1 interaction with the other major human TLS polymerases, polη, ι, κ and the regulatory subunit Rev7 of polζ, is mediated by Rev1 C-terminal domain (Rev1-CT). We used NMR spectroscopy to determine the spatial structure of the Rev1-CT domain (residues 1157-1251) and its complex with Rev1 interacting region (RIR) from polη (residues 524-539). The domain forms a four-helix bundle with a well-structured N-terminal β-hairpin docking against helices 1 and 2, creating a binding pocket for the two conserved Phe residues of the RIR motif that upon binding folds into an α-helix. NMR spin-relaxation and NMR relaxation dispersion measurements suggest that free Rev1-CT and Rev1-CT/polη-RIR complex exhibit μs-ms conformational dynamics encompassing the RIR binding site, which might facilitate selection of the molecular configuration optimal for binding. These results offer new insights into the control of TLS in human cells by providing a structural basis for understanding the recognition of the Rev1-CT by Y-family DNA polymerases. PMID:22691049

Spiritual Experiences of Muslim Critical Care Nurses.

PubMed

Bakir, Ercan; Samancioglu, Sevgin; Kilic, Serap Parlar

2017-12-01

The purpose of this study was to determine the experiences and perceptions of intensive care nurses (ICNs) about spirituality and spiritual care, as well as the effective factors, and increase the sensitivity to the subject. In this study, we examined spiritual experiences, using McSherry et al. (Int J Nurs Stud 39:723-734, 2002) Spirituality and spiritual care rating scale (SSCRS), among 145 ICNs. 44.8% of the nurses stated that they received spiritual care training and 64.1% provided spiritual care to their patients. ICNs had a total score average of 57.62 ± 12.00 in SSCRS. As a consequence, it was determined that intensive care nurses participating in the study had insufficient knowledge about spirituality and spiritual care, but only the nurses with sufficient knowledge provided the spiritual care to their patients.

49 CFR 1242.29 - Fringe benefits (accounts 12-17-00, 12-18-00, and 12-19-00).

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 9 2010-10-01 2010-10-01 false Fringe benefits (accounts 12-17-00, 12-18-00, and... RAILROADS 1 Operating Expenses-Way and Structures § 1242.29 Fringe benefits (accounts 12-17-00, 12-18-00, and 12-19-00). Separate common expenses in the running subactivity in the same proportion as the...

Binding and thermodynamics of REV peptide-ctDNA interaction.

PubMed

Upadhyay, Santosh Kumar

2017-03-01

The thermodynamics of DNA-ligand binding is important as it provides useful information to understand the details of binding processes. HIV-1 REV response element (RRE) located in the env coding region of the viral genome is reported to be well conserved across different HIV-1 isolates. In this study, the binding characteristics of Calf thymus DNA (ctDNA) and REV peptide from HIV-1 were investigated using spectroscopic (UV-visible, fluorescence, and circular dichroism (CD)) and isothermal titration calorimetric (ITC) techniques. Thermal stability and ligand binding properties of the ctDNA revealed that native ctDNA had a T m of 75.5 °C, whereas the ctDNA-REV peptide complex exhibited an incremental shift in the T m by 8 °C, indicating thermal stability of the complex. CD data indicated increased ellipticity due to large conformational changes in ctDNA molecule upon binding with REV peptide and two binding stoichiometric modes are apparent. The ctDNA experienced condensation due to large conformational changes in the presence of REV peptide and positive B→Ψ transition was observed at higher molar charge ratios. Fluorescence studies performed at several ligand concentrations revealed a gradual decrease in the fluorescence intensity of EtBr-bound ctDNA in response to increasing ligand concentrations. The fluorescence data further confirmed two stoichiometric modes of binding for ctDNA-REV peptide complex as previously observed with CD studies. The binding enthalpies were determined using ITC in the temperature range of 293 K-308 K. The ITC binding isotherm was exothermic at all temperatures examined, with low ΔH values indicating that the ctDNA-REV peptide interaction is driven largely by entropy. The heat capacity change (ΔC p ) was insignificant, an unusual finding in the area of DNA-peptide interaction studies. The variation in the values obtained for ΔH, ΔS, and ΔG with temperature further suggests that ctDNA-REV peptide interaction is entropically

RevManHAL: towards automatic text generation in systematic reviews.

PubMed

Torres Torres, Mercedes; Adams, Clive E

2017-02-09

Systematic reviews are a key part of healthcare evaluation. They involve important painstaking but repetitive work. A major producer of systematic reviews, the Cochrane Collaboration, employs Review Manager (RevMan) programme-a software which assists reviewers and produces XML-structured files. This paper describes an add-on programme (RevManHAL) which helps auto-generate the abstract, results and discussion sections of RevMan-generated reviews in multiple languages. The paper also describes future developments for RevManHAL. RevManHAL was created in Java using NetBeans by a programmer working full time for 2 months. The resulting open-source programme uses editable phrase banks to envelop text/numbers from within the prepared RevMan file in formatted readable text of a chosen language. In this way, considerable parts of the review's 'abstract', 'results' and 'discussion' sections are created and a phrase added to 'acknowledgements'. RevManHAL's output needs to be checked by reviewers, but already, from our experience within the Cochrane Schizophrenia Group (200 maintained reviews, 900 reviewers), RevManHAL has saved much time which is better employed thinking about the meaning of the data rather than restating them. Many more functions will become possible as review writing becomes increasingly automated.

Controlling the Topological Sector of Magnetic Solitons in Exfoliated Cr 1 / 3 NbS 2 Crystals

DOE PAGES

Wang, Lin; Chepiga, N.; Ki, D. -K.; ...

2017-06-23

Here, we investigate manifestations of topological order in monoaxial helimagnet Cr 1/3NbS 2 by performing transport measurements on ultrathin crystals. Upon sweeping the magnetic field perpendicularly to the helical axis, crystals thicker than one helix pitch (48 nm) but much thinner than the magnetic domain size (similar to 1 mu m) are found to exhibit sharp and hysteretic resistance jumps. We also show that these phenomena originate from transitions between topological sectors with a different number of magnetic solitons. This is confirmed by measurements on crystals thinner than 48 nm-in which the topological sector cannot change-that do not exhibit anymore » jump or hysteresis. These results show the ability to deterministically control the topological sector of finite-size Cr 1/3NbS 2 and to detect intersector transitions by transport measurements.« less

Controlling the Topological Sector of Magnetic Solitons in Exfoliated Cr 1 / 3 NbS 2 Crystals

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

Wang, Lin; Chepiga, N.; Ki, D. -K.

Here, we investigate manifestations of topological order in monoaxial helimagnet Cr 1/3NbS 2 by performing transport measurements on ultrathin crystals. Upon sweeping the magnetic field perpendicularly to the helical axis, crystals thicker than one helix pitch (48 nm) but much thinner than the magnetic domain size (similar to 1 mu m) are found to exhibit sharp and hysteretic resistance jumps. We also show that these phenomena originate from transitions between topological sectors with a different number of magnetic solitons. This is confirmed by measurements on crystals thinner than 48 nm-in which the topological sector cannot change-that do not exhibit anymore » jump or hysteresis. These results show the ability to deterministically control the topological sector of finite-size Cr 1/3NbS 2 and to detect intersector transitions by transport measurements.« less

Pharmacological Targeting the REV-ERBs in Sleep/Wake Regulation

PubMed Central

Amador, Ariadna; Huitron-Resendiz, Salvador; Roberts, Amanda J.; Kamenecka, Theodore M.; Solt, Laura A.; Burris, Thomas P.

2016-01-01

The circadian clock maintains appropriate timing for a wide range of behaviors and physiological processes. Circadian behaviors such as sleep and wakefulness are intrinsically dependent on the precise oscillation of the endogenous molecular machinery that regulates the circadian clock. The identical core clock machinery regulates myriad endocrine and metabolic functions providing a link between sleep and metabolic health. The REV-ERBs (REV-ERBα and REV-ERBβ) are nuclear receptors that are key regulators of the molecular clock and have been successfully targeted using small molecule ligands. Recent studies in mice suggest that REV-ERB-specific synthetic agonists modulate metabolic activity as well as alter sleep architecture, inducing wakefulness during the light period. Therefore, these small molecules represent unique tools to extensively study REV-ERB regulation of sleep and wakefulness. In these studies, our aim was to further investigate the therapeutic potential of targeting the REV-ERBs for regulation of sleep by characterizing efficacy, and optimal dosing time of the REV-ERB agonist SR9009 using electroencephalographic (EEG) recordings. Applying different experimental paradigms in mice, our studies establish that SR9009 does not lose efficacy when administered more than once a day, nor does tolerance develop when administered once a day over a three-day dosing regimen. Moreover, through use of a time response paradigm, we determined that although there is an optimal time for administration of SR9009 in terms of maximal efficacy, there is a 12-hour window in which SR9009 elicited a response. Our studies indicate that the REV-ERBs are potential therapeutic targets for treating sleep problems as those encountered as a consequence of shift work or jet lag. PMID:27603791

Software Measurement Guidebook. Version 02.00.02

DTIC Science & Technology

1992-12-01

Compatibility Testing Process .............................. 9-5 Figure 9-3. Development Effort Planning Curve ................................. 9-7 Figure 10-1...requirements, design, code, and test and for analyzing this data. "* Proposal Manager. The person responsible for describing and supporting the estimated...designed, build/elease ranges, variances, and comparisons size growth; costs; completions; and content, units completing test , units with historical

Selective excitation of LG 00, LG 01, and LG 02 modes by a solid core PCF based mode selector in MDM-Ro-FSO transmission systems

NASA Astrophysics Data System (ADS)

Chaudhary, Sushank; Amphawan, Angela

2018-07-01

Radio over free space (Ro-FSO) provides an ambitious platform for seamless integration of radio networks to optical networks. Three independent channels, each carrying 2.5 Gbps–5 GHz data, are successfully transmitted over a free space link of 2.5 km by using mode division multiplexing (MDM) of three modes LG 00, LG 01, and LG 02 modes in conjunction with solid core photonic crystal fibers (SC-PCFs). Moreover, SC-PCFs are used as a mode selector in the proposed MDM-Ro-FSO system. The results are reported in terms of bit error rate, mode spectrum, and spatial profiles. The performance of the proposed Ro-FSO system is also evaluated under the influence of atmospheric turbulence in the form of different levels of fog, namely, light fog, thin fog, and heavy fog.

Highly efficient antibody immobilization with multimeric protein Gs coupled magnetic silica nanoparticles

NASA Astrophysics Data System (ADS)

Lee, J. H.; Choi, H. K.; Chang, J. H.

2011-10-01

This work reports the immobilization of monomeric, dimeric and trimer protein Gs onto silica magnetic nanoparticles for self-oriented antibody immobilization. To achieve this, we initially prepared the silica-coated magnetic nanoparticle having about 170 nm diameters. The surface of the silica coated magnetic nanoparticles was modified with 3- aminopropyl-trimethoxysilane (APTMS) to chemically link to multimeric protein Gs. The conjugation of amino groups on the SiO2-MNPs to cysteine tagged in multimeric protein Gs was performed using a sulfo-SMCC coupling procedure. The binding efficiencies of monomer, dimer and trimer were 77 %, 67 % and 55 % respectively. However, the efficiencies of antibody immobilization were 70 %, 83 % and 95 % for monomeric, dimeric and trimeric protein G, respectively. To prove the enhancement of accessibility by using multimeric protein G, FITC labeled goat-anti-mouse IgG was treated to mouse IgG immobilized magnetic silica nanoparticles through multimeric protein G. FITC labeled goat anti-mouse IgGs were more easily bound to mouse IgG immobilized by trimeric protein G than others. Finally protein G bound silica magnetic nanoparticles were utilized to develop highly sensitive immunoassay to detect hepatitis B antigen.

FLiGS Score: A New Method of Outcome Assessment for Lip Carcinoma–Treated Patients

PubMed Central

Grassi, Rita; Toia, Francesca; Di Rosa, Luigi; Cordova, Adriana

2015-01-01

Background: Lip cancer and its treatment have considerable functional and cosmetic effects with resultant nutritional and physical detriments. As we continue to investigate new treatment regimens, we are simultaneously required to assess postoperative outcomes to design interventions that lessen the adverse impact of this disease process. We wish to introduce Functional Lip Glasgow Scale (FLiGS) score as a new method of outcome assessment to measure the effect of lip cancer and its treatment on patients’ daily functioning. Methods: Fifty patients affected by lip squamous cell carcinoma were recruited between 2009 and 2013. Patients were asked to fill the FLiGS questionnaire before surgery, 1 month, 6 months, and 1 year after surgery. The subscores were used to calculate a total FLiGS score of global oral disability. Statistical analysis was performed to test validity and reliability. Results: FLiGS scores improved significantly from preoperative to 12 months postoperative values (P = 0.000). Statistical evidence of validity was provided through rs (Spearman correlation coefficient) that resulted >0.30 for all surveys and for which P < 0.001. FLiGS score reliability was shown through examination of internal consistency and test-retest reliability. Conclusions: FLiGS score is a simple way of assessing functional impairment related to lip cancer before and after surgery; it is sensitive, valid, reliable, and clinically relevant: it provides useful information to orient the physician in the postoperative management and in the rehabilitation program. PMID:26034652

Altered Sleep Homeostasis in Rev-erbα Knockout Mice

PubMed Central

Mang, Géraldine M.; La Spada, Francesco; Emmenegger, Yann; Chappuis, Sylvie; Ripperger, Jürgen A.; Albrecht, Urs; Franken, Paul

2016-01-01

Study Objectives: The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep. Methods: EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline. Results: Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1–4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain. Conclusions: Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context. Citation: Mang GM, La Spada F, Emmenegger Y, Chappuis S, Ripperger JA, Albrecht U, Franken P. Altered sleep homeostasis in Rev

PIF1 disruption or NBS1 hypomorphism does not affect chromosome healing or fusion resulting from double-strand breaks near telomeres in murine embryonic stem cells.

PubMed

Reynolds, Gloria E; Gao, Qing; Miller, Douglas; Snow, Bryan E; Harrington, Lea A; Murnane, John P

2011-11-10

Telomerase serves to maintain telomeric repeat sequences at the ends of chromosomes. However, telomerase can also add telomeric repeat sequences at DNA double-strand breaks (DSBs), a process called chromosome healing. Here, we employed a method of inducing DSBs near telomeres to query the role of two proteins, PIF1 and NBS1, in chromosome healing in mammalian cells. PIF1 was investigated because the PIF1 homolog in Saccharomyces cerevisiae inhibits chromosome healing, as shown by a 1000-fold increase in chromosome in PIF1-deficient cells. NBS1 was investigated because the functional homolog of NBS1 in S. cerevisiae, Xrs2, is part of the Mre11/Rad50/Xrs2 complex that is required for chromosome healing due to its role in the processing of DSBs and recruitment of telomerase. We found that disruption of mPif1 had no detectable effect on the frequency of chromosome healing at DSBs near telomeres in murine embryonic stem cells. Moreover, the Nbs1(ΔB) hypomorph, which is defective in the processing of DSBs, also had no detectable effect on the frequency of chromosome healing, DNA degradation, or gross chromosome rearrangements (GCRs) that result from telomeric DSBs. Although we cannot rule out small changes in chromosome healing using this system, it is clear from our results that knockout of PIF1 or the Nbs1(ΔB) hypomorph does not result in large differences in chromosome healing in murine cells. These results represent the first genetic assessment of the role of these proteins in chromosome healing in mammals, and suggest that murine cells have evolved mechanisms to ensure the functional redundancy of Pif1 or Nbs1 in the regulation of chromosome healing. Copyright © 2011 Elsevier B.V. All rights reserved.

Altered Sleep Homeostasis in Rev-erbα Knockout Mice.

PubMed

Mang, Géraldine M; La Spada, Francesco; Emmenegger, Yann; Chappuis, Sylvie; Ripperger, Jürgen A; Albrecht, Urs; Franken, Paul

2016-03-01

The nuclear receptor REV-ERBα is a potent, constitutive transcriptional repressor critical for the regulation of key circadian and metabolic genes. Recently, REV-ERBα's involvement in learning, neurogenesis, mood, and dopamine turnover was demonstrated suggesting a specific role in central nervous system functioning. We have previously shown that the brain expression of several core clock genes, including Rev-erbα, is modulated by sleep loss. We here test the consequences of a loss of REV-ERBα on the homeostatic regulation of sleep. EEG/EMG signals were recorded in Rev-erbα knockout (KO) mice and their wild type (WT) littermates during baseline, sleep deprivation, and recovery. Cortical gene expression measurements after sleep deprivation were contrasted to baseline. Although baseline sleep/wake duration was remarkably similar, KO mice showed an advance of the sleep/wake distribution relative to the light-dark cycle. After sleep onset in baseline and after sleep deprivation, both EEG delta power (1-4 Hz) and sleep consolidation were reduced in KO mice indicating a slower increase of homeostatic sleep need during wakefulness. This slower increase might relate to the smaller increase in theta and gamma power observed in the waking EEG prior to sleep onset under both conditions. Indeed, the increased theta activity during wakefulness predicted delta power in subsequent NREM sleep. Lack of Rev-erbα increased Bmal1, Npas2, Clock, and Fabp7 expression, confirming the direct regulation of these genes by REV-ERBα also in the brain. Our results add further proof to the notion that clock genes are involved in sleep homeostasis. Because accumulating evidence directly links REV-ERBα to dopamine signaling the altered homeostatic regulation of sleep reported here are discussed in that context. © 2016 Associated Professional Sleep Societies, LLC.

The Glycine soja NAC transcription factor GsNAC019 mediates the regulation of plant alkaline tolerance and ABA sensitivity.

PubMed

Cao, Lei; Yu, Yang; Ding, Xiaodong; Zhu, Dan; Yang, Fan; Liu, Beidong; Sun, Xiaoli; Duan, Xiangbo; Yin, Kuide; Zhu, Yanming

2017-10-01

Overexpression of Gshdz4 or GsNAC019 enhanced alkaline tolerance in transgenic Arabidopsis. We proved that Gshdz4 up-regulated both GsNAC019 and GsRD29B but GsNAC019 may repress the GsRD29B expression under alkaline stress. Wild soybean (Glycine soja) has a high tolerance to environmental challenges. It is a model species for dissecting the molecular mechanisms of salt-alkaline stresses. Although many NAC transcription factors play important roles in response to multiple abiotic stresses, such as salt, osmotic and cold, their mode of action in alkaline stress resistance is largely unknown. In our study, we identified a G. soja NAC gene, GsNAC019, which is a homolog of the Arabidopsis AtNAC019 gene. GsNAC019 was highly up-regulated by 50 mM NaHCO 3 treatment in the roots of wild soybean. Further investigation showed that a well-characterized transcription factor, Gshdz4 protein, bound the cis-acting element sequences (CAATA/TA), which are located in the promoter of the AtNAC019/GsNAC019 genes. Overexpression of Gshdz4 positively regulated AtNAC019 expression in transgenic Arabidopsis, implying that AtNAC019/GsNAC019 may be the target genes of Gshdz4. GsNAC019 was demonstrated to be a nuclear-localized protein in onion epidermal cells and possessed transactivation activity in yeast cells. Moreover, overexpression of GsNAC019 in Arabidopsis resulted in enhanced tolerance to alkaline stress at the seedling and mature stages, but reduced ABA sensitivity. The closest Arabidopsis homolog mutant plants of Gshdz4, GsNAC019 and GsRD29B containing athb40, atnac019 and atrd29b were sensitive to alkaline stress. Overexpression or the closest Arabidopsis homolog mutant plants of the GsNAC019 gene in Arabidopsis positively or negatively regulated the expression of stress-related genes, such as AHA2, RD29A/B and KIN1. Moreover, this mutation could phenotypically promoted or compromised plant growth under alkaline stress, implying that GsNAC019 may contribute to alkaline stress

Our trial to develop a risk assessment tool for CO2 geological storage (GERAS-CO2GS)

NASA Astrophysics Data System (ADS)

Tanaka, A.; Sakamoto, Y.; Komai, T.

2012-12-01

We will introduce our researches about to develop a risk assessment tool named 'GERAS-CO2GS' (Geo-environmental Risk Assessment System, CO2 Geological Storage Risk Assessment System) for 'Carbon Dioxide Geological Storage (Geological CCS)'. It aims to facilitate understanding of size of impact of risks related with upper migration of injected CO2. For gaining public recognition about feasibility of Geological CCS, quantitative estimation of risks is essential, to let public knows the level of the risk: whether it is negligible or not. Generally, in preliminary hazard analysis procedure, potential hazards could be identified within Geological CCS's various facilities such as: reservoir, cap rock, upper layers, CO2 injection well, CO2 injection plant and CO2 transport facilities. Among them, hazard of leakage of injected C02 is crucial, because it is the clue to estimate risks around a specific injection plan in terms of safety, environmental protection effect and economy. Our risk assessment tool named GERAS-CO2GS evaluates volume and rate of retention and leakage of injected CO2 in relation with fractures and/or faults, and then it estimates impact of seepages on the surface of the earth. GERAS-CO2GS has four major processing segments: (a) calculation of CO2 retention and leakage volume and rate, (b) data processing of CO2 dispersion on the surface and ambient air, (c) risk data definition and (d) evaluation of risk. Concerning to the injection site, we defined a model, which is consisted from an injection well and a geological strata model: which involves a reservoir, a cap rock, an upper layer, faults, seabed, sea, the surface of the earth and the surface of the sea. For retention rate of each element of CO2 injection site model, we use results of our experimental and numerical studies on CO2 migration within reservoirs and faults with specific lithological conditions. For given CO2 injection rate, GERAS-CO2GS calculates CO2 retention and leakage of each segment

Distinct kinetics of DNA repair protein accumulation at DNA lesions and cell cycle-dependent formation of γH2AX- and NBS1-positive repair foci.

PubMed

Suchánková, Jana; Kozubek, Stanislav; Legartová, Soňa; Sehnalová, Petra; Küntziger, Thomas; Bártová, Eva

2015-12-01

The DNA damage response is a fundamental, well-regulated process that occurs in the genome to recognise DNA lesions. Here, we studied kinetics of proteins involved in DNA repair pathways and their recruitment to DNA lesions during the cell cycle. In non-irradiated and irradiated cells, we analysed the distribution pattern and spatiotemporal dynamics of γH2AX, 53BP1, BMI1, MDC1, NBS1, PCNA, coilin and BRCA1 proteins. We observed that spontaneous and irradiation-induced foci (IRIF) demonstrated a high abundance of phosphorylated H2AX, which was consistent with 53BP1 and BMI1 protein accumulation. However, NBS1 and MDC1 proteins were recruited to nuclear bodies (NBs) to a lesser extent. Irradiation by γ-rays significantly increased the number of 53BP1- and γH2AX-positive IRIF, but cell cycle-dependent differences were only observed for γH2AX-positive foci in both non-irradiated and γ-irradiated cells. In non-irradiated cells, the G2 phase was characterised by an increased number of spontaneous γH2AX-foci; this increase was more pronounced after γ-irradiation. Cells in G2 phase had the highest number of γH2AX-positive foci. Similarly, γ-irradiation increased the number of NBS1-positive NBs only in G2 phase. Moreover, NBS1 accumulated in nucleoli after γ-irradiation showed the slowest recovery after photobleaching. Analysis of protein accumulation kinetics at locally induced DNA lesions showed that in HeLa cells, BMI1, PCNA and coilin were rapidly recruited to the lesions, 10-15 s after UVA-irradiation, whereas among the other proteins studied, BRCA1 demonstrated the slowest recruitment: BRCA1 appeared at the lesion 20 min after local micro-irradiation by UVA laser. We show that the kinetics of the accumulation of selected DNA repair-related proteins is protein specific at locally induced DNA lesions, and that the formation of γH2AX- and NBS1-positive foci, but not 53BP1-positive NBs, is cell cycle dependent in HeLa cells. Moreover, γH2AX is the most

NbS2 Nanosheets with M/Se (M = Fe, Co, Ni) Codopants for Li+ and Na+ Storage.

PubMed

Zhang, Jianli; Du, Chengfeng; Dai, Zhengfei; Chen, Wei; Zheng, Yun; Li, Bing; Zong, Yun; Wang, Xin; Zhu, Junwu; Yan, Qingyu

2017-10-24

Transition metal (M = Fe, Co, Ni) and Se codoped two-dimensional uniform NbS 2 (M x Nb 1-x S 2-y Se y ) nanosheets were synthesized via a facile oil-phase synthetic process. The morphology of M x Nb 1-x S 2-y Se y can be adjusted by tuning the amount of metal and Se introduced into NbS 2 . Among them, the optimized Fe 0.3 Nb 0.7 S 1.6 Se 0.4 nanosheets, with lateral sizes of 1-2 μm and approximately 5 nm thick, achieve the best Li-ion and Na-ion storage properties. For example, the Fe 0.3 Nb 0.7 S 1.6 Se 0.4 nanosheets depict excellent rate capabilities with fifth-cycle specific capacities of 461.3 mAh g -1 at 10 A g -1 for Li storage and 136 mAh g -1 at 5 A g -1 for Na storage. More significantly, ultralong cyclic stabilities were achieved with reversible specific capacities of 444 mAh g -1 at 5 A g -1 during the 3000th cycle for Li storage and 250 mAh g -1 at 1 A g -1 during the 750th cycle for Na storage. Post-treatment high-resolution transmission electron microscopy was studied to prove that the reversible Li-ion storage in NbS 2 was based on a conversion reaction mechanism.

Ectopic Expression of GsPPCK3 and SCMRP in Medicago sativa Enhances Plant Alkaline Stress Tolerance and Methionine Content

PubMed Central

Zhao, Yang; Zhao, Chaoyue; DuanMu, Huizi; Yu, Yang; Ji, Wei; Zhu, Yanming

2014-01-01

So far, it has been suggested that phosphoenolpyruvate carboxylases (PEPCs) and PEPC kinases (PPCKs) fulfill several important non-photosynthetic functions. However, the biological functions of soybean PPCKs, especially in alkali stress response, are not yet well known. In previous studies, we constructed a Glycine soja transcriptional profile, and identified three PPCK genes (GsPPCK1, GsPPCK2 and GsPPCK3) as potential alkali stress responsive genes. In this study, we confirmed the induced expression of GsPPCK3 under alkali stress and investigated its tissue expression specificity by using quantitative real-time PCR analysis. Then we ectopically expressed GsPPCK3 in Medicago sativa and found that GsPPCK3 overexpression improved plant alkali tolerance, as evidenced by lower levels of relative ion leakage and MDA content and higher levels of chlorophyll content and root activity. In this respect, we further co-transformed the GsPPCK3 and SCMRP genes into alfalfa, and demonstrated the increased alkali tolerance of GsPPCK3-SCMRP transgenic lines. Further investigation revealed that GsPPCK3-SCMRP co-overexpression promoted the PEPC activity, net photosynthetic rate and citric acid content of transgenic alfalfa under alkali stress. Moreover, we also observed the up-regulated expression of PEPC, CS (citrate synthase), H+-ATPase and NADP-ME genes in GsPPCK3-SCMRP transgenic alfalfa under alkali stress. As expected, we demonstrated that GsPPCK3-SCMRP transgenic lines displayed higher methionine content than wild type alfalfa. Taken together, results presented in this study supported the positive role of GsPPCK3 in plant response to alkali stress, and provided an effective way to simultaneously improve plant alkaline tolerance and methionine content, at least in legume crops. PMID:24586886

Broad-spectrum antiviral GS-5734 inhibits both epidemic and zoonotic coronaviruses

PubMed Central

Sheahan, Timothy P.; Sims, Amy C.; Graham, Rachel L.; Menachery, Vineet D.; Gralinski, Lisa E.; Case, James B.; Leist, Sarah R.; Pyrc, Krzysztof; Feng, Joy Y.; Trantcheva, Iva; Bannister, Roy; Park, Yeojin; Babusis, Darius; Clarke, Michael O.; Mackman, Richard L.; Spahn, Jamie E.; Palmiotti, Christopher A.; Siegel, Dustin; Ray, Adrian S.; Cihlar, Tomas; Jordan, Robert; Denison, Mark R.; Baric, Ralph S.

2017-01-01

Emerging viral infections are difficult to control as heterogeneous members periodically cycle in and out of humans and zoonotic hosts, complicating the development of specific antiviral therapies and vaccines. Coronaviruses (CoVs) have a proclivity to spread rapidly into new host species causing severe disease. SARS-CoV and MERS-CoV successively emerged causing severe epidemic respiratory disease in immunologically naïve human populations throughout the globe. Broad-spectrum therapies capable of inhibiting CoV infections would address an immediate unmet medical need and could be invaluable in the treatment of emerging and endemic CoV infections. Here we show that a nucleotide prodrug GS-5734, currently in clinical development for treatment of Ebola virus disease, can inhibit SARS-CoV and MERS-CoV replication in multiple in vitro systems including primary human airway epithelial cell cultures with submicromolar IC50 values. GS-5734 was also effective against bat-CoVs, prepandemic bat-CoVs and circulating contemporary human CoV in primary human lung cells, thus demonstrating broad-spectrum anti-CoV activity. In a mouse model of SARS-CoV pathogenesis, prophylactic and early therapeutic administration of GS-5734 significantly reduced lung viral load and improved clinical signs of disease as well as respiratory functions. These data provide substantive evidence that GS-5734 may prove effective against endemic MERS-CoV in the Middle East, circulating human CoV, and possibly most importantly, emerging CoV of the future. PMID:28659436

Absolute I(asterisk) quantum yields for the ICN A state by diode laser gain-vs-absorption spectroscopy

NASA Technical Reports Server (NTRS)

Hess, Wayne P.; Leone, Stephen R.

1987-01-01

Absolute I(asterisk) quantum yields have been measured as a function of wavelength for room temperature photodissociation of the ICN A state continuum. The yields are obtained by the technique of time-resolved diode laser gain-vs-absorption spectroscopy. Quantum yields are evaluated at seven wavelengths from 248 to 284 nm. The yield at 266 nm is 66.0 + or - 2 percent and it falls off to 53.4 + or - 2 percent and 44.0 + or - 4 percent at 284 and 248 nm, respectively. The latter values are significantly higher than those obtained by previous workers using infrared fluorescence. Estimates of I(asterisk) quantum yields obtained from analysis of CN photofragment rotational distributions, as discussed by other workers, are in good agreement with the I(asterisk) yields reported here. The results are considered in conjunction with recent theoretical and experimental work on the CN rotational distributions and with previous I(asterisk) quantum yield results.

REV-ERB and ROR nuclear receptors as drug targets

PubMed Central

Kojetin, Douglas J.; Burris, Thomas P.

2016-01-01

The nuclear receptors REV-ERB (consisting of REV-ERBα and REV-ERBβ) and retinoic acid receptor-related orphan receptors (RORs; consisting of RORα, RORβ and RORγ) are involved in many physiological processes, including regulation of metabolism, development and immunity as well as the circadian rhythm. The recent characterization of endogenous ligands for these former orphan nuclear receptors has stimulated the development of synthetic ligands and opened up the possibility of targeting these receptors to treat several diseases, including diabetes, atherosclerosis, autoimmunity and cancer. This Review focuses on the latest developments in ROR and REV-ERB pharmacology indicating that these nuclear receptors are druggable targets and that ligands targeting these receptors may be useful in the treatment of several disorders. PMID:24577401

Variability among Cucurbitaceae species (melon, cucumber and watermelon) in a genomic region containing a cluster of NBS-LRR genes.

PubMed

Morata, Jordi; Puigdomènech, Pere

2017-02-08

Cucurbitaceae species contain a significantly lower number of genes coding for proteins with similarity to plant resistance genes belonging to the NBS-LRR family than other plant species of similar genome size. A large proportion of these genes are organized in clusters that appear to be hotspots of variability. The genomes of the Cucurbitaceae species measured until now are intermediate in size (between 350 and 450 Mb) and they apparently have not undergone any genome duplications beside those at the origin of eudicots. The cluster containing the largest number of NBS-LRR genes has previously been analyzed in melon and related species and showed a high degree of interspecific and intraspecific variability. It was of interest to study whether similar behavior occurred in other cluster of the same family of genes. The cluster of NBS-LRR genes located in melon chromosome 9 was analyzed and compared with the syntenic regions in other cucurbit genomes. This is the second cluster in number within this species and it contains nine sequences with a NBS-LRR annotation including two genes, Fom1 and Prv, providing resistance against Fusarium and Ppapaya ring-spot virus (PRSV). The variability within the melon species appears to consist essentially of single nucleotide polymorphisms. Clusters of similar genes are present in the syntenic regions of the two species of Cucurbitaceae that were sequenced, cucumber and watermelon. Most of the genes in the syntenic clusters can be aligned between species and a hypothesis of generation of the cluster is proposed. The number of genes in the watermelon cluster is similar to that in melon while a higher number of genes (12) is present in cucumber, a species with a smaller genome than melon. After comparing genome resequencing data of 115 cucumber varieties, deletion of a group of genes is observed in a group of varieties of Indian origin. Clusters of genes coding for NBS-LRR proteins in cucurbits appear to have specific variability in

Applying the silver-tube introduction method for thermal conversion elemental analyses and a new δ2H value for NBS 22 oil

USGS Publications Warehouse

Coplen, Tyler B.; Qi, Haiping

2010-01-01

The δ2HVSMOW–SLAP value of total hydrogen of the international measurement standard NBS 22 oil was determined by a new method of sealing water in silver tubes for use in a thermal conversion elemental analysis (TC/EA) reduction unit. The isotopic fractionation of water due to evaporation is virtually non-existent in this silver-tube method. A new value for the δ2HVSMOW–SLAP of NBS 22 oil, calibrated with isotopic reference waters, was determined to be −116.9 ± 0.8‰ (1σ and n = 31).

Therapeutic efficacy of the small molecule GS-5734 against Ebola virus in rhesus monkeys.

PubMed

Warren, Travis K; Jordan, Robert; Lo, Michael K; Ray, Adrian S; Mackman, Richard L; Soloveva, Veronica; Siegel, Dustin; Perron, Michel; Bannister, Roy; Hui, Hon C; Larson, Nate; Strickley, Robert; Wells, Jay; Stuthman, Kelly S; Van Tongeren, Sean A; Garza, Nicole L; Donnelly, Ginger; Shurtleff, Amy C; Retterer, Cary J; Gharaibeh, Dima; Zamani, Rouzbeh; Kenny, Tara; Eaton, Brett P; Grimes, Elizabeth; Welch, Lisa S; Gomba, Laura; Wilhelmsen, Catherine L; Nichols, Donald K; Nuss, Jonathan E; Nagle, Elyse R; Kugelman, Jeffrey R; Palacios, Gustavo; Doerffler, Edward; Neville, Sean; Carra, Ernest; Clarke, Michael O; Zhang, Lijun; Lew, Willard; Ross, Bruce; Wang, Queenie; Chun, Kwon; Wolfe, Lydia; Babusis, Darius; Park, Yeojin; Stray, Kirsten M; Trancheva, Iva; Feng, Joy Y; Barauskas, Ona; Xu, Yili; Wong, Pamela; Braun, Molly R; Flint, Mike; McMullan, Laura K; Chen, Shan-Shan; Fearns, Rachel; Swaminathan, Swami; Mayers, Douglas L; Spiropoulou, Christina F; Lee, William A; Nichol, Stuart T; Cihlar, Tomas; Bavari, Sina

2016-03-17

The most recent Ebola virus outbreak in West Africa, which was unprecedented in the number of cases and fatalities, geographic distribution, and number of nations affected, highlights the need for safe, effective, and readily available antiviral agents for treatment and prevention of acute Ebola virus (EBOV) disease (EVD) or sequelae. No antiviral therapeutics have yet received regulatory approval or demonstrated clinical efficacy. Here we report the discovery of a novel small molecule GS-5734, a monophosphoramidate prodrug of an adenosine analogue, with antiviral activity against EBOV. GS-5734 exhibits antiviral activity against multiple variants of EBOV and other filoviruses in cell-based assays. The pharmacologically active nucleoside triphosphate (NTP) is efficiently formed in multiple human cell types incubated with GS-5734 in vitro, and the NTP acts as an alternative substrate and RNA-chain terminator in primer-extension assays using a surrogate respiratory syncytial virus RNA polymerase. Intravenous administration of GS-5734 to nonhuman primates resulted in persistent NTP levels in peripheral blood mononuclear cells (half-life, 14 h) and distribution to sanctuary sites for viral replication including testes, eyes, and brain. In a rhesus monkey model of EVD, once-daily intravenous administration of 10 mg kg(-1) GS-5734 for 12 days resulted in profound suppression of EBOV replication and protected 100% of EBOV-infected animals against lethal disease, ameliorating clinical disease signs and pathophysiological markers, even when treatments were initiated three days after virus exposure when systemic viral RNA was detected in two out of six treated animals. These results show the first substantive post-exposure protection by a small-molecule antiviral compound against EBOV in nonhuman primates. The broad-spectrum antiviral activity of GS-5734 in vitro against other pathogenic RNA viruses, including filoviruses, arenaviruses, and coronaviruses, suggests the

Influence of polymer additives on turbulence in von Karman swirling flow between two disks. II

NASA Astrophysics Data System (ADS)

Burnishev, Yuri; Steinberg, Victor

2016-03-01

We present the experimental studies of the influence of polymer additives on the statistical and scaling properties of the fully developed turbulent regime in a von Karman swirling flow driven either by the smooth or bladed disks using only the global measurements of torque Γ and pressure p fluctuations in water- and water-sugar-based solutions of different viscosities, or elasticity El, and different polymer concentrations ϕ as a function of Re in the same apparatus. There are three highlights achieved and reported in the paper: (i) An observation of turbulent drag reduction (TDR) at both the inertial and viscous flow forcing, in a contradiction to a currently accepted opinion that only the viscous forcing leads to TDR, and the unexpected drastic difference in the transition to the fully developed turbulent and TDR regimes in von Karman swirling flow of water-based polymer solutions depending on the way of the forcing; (ii) a continuous transition to TDR in both the normalized torque drop and the rms pressure fluctuations drop and universality in scaling behavior of Cf in an agreement with theoretical predictions; and (iii) the dramatic differences in the appearance of the frequency power spectra of Γ and in particular p due to the different ways of the forcing are also observed. We discuss and summarize further the results in accordance with these three main achievements. The main message of these studies is that both the inertial forcing and viscous forcing of von Karman swirling flow between two counter-rotating disks lead to TDR in the sharp contrast to the currently accepted opinion [O. Cadot et al., "Turbulent drag reduction in a closed flow system: Boundary layer versus bulk effects," Phys. Fluids 10, 426 (1998); D. Bonn et al., "From scale scales to large scales in three-dimensional turbulence: The effect of diluted polymers," Phys. Rev. E 47, R28 (1993); and D. Bonn et al., "Turbulent drag reduction by polymers," J. Phys.: Condens. Matter 17, S1195

Primary versus secondary hypertension in children followed up at an outpatient tertiary unit.

PubMed

Gomes, Romina S; Quirino, Isabel G; Pereira, Regina M; Vitor, Breno M; Leite, Alysson F; Oliveira, Eduardo A; Simões e Silva, Ana Cristina

2011-03-01

Childhood hypertension has classically been recognized as a secondary disease. However, primary hypertension also occurs in children. The aim of this study was to compare clinical features of pediatric patients with elevated blood pressure, which were referred to an outpatient tertiary unit, and to detect variables associated with the identification of primary hypertension. The records of 220 patients with hypertension followed between 1996 and 2006 were analyzed. The variable of interest was primary hypertension. Logistic regression analysis was applied to identify clinical variables that were independently associated with primary hypertension. Of 220 patients, 33 (15%) had primary hypertension, and 187 (85%) exhibited secondary hypertension. No statistically significant differences were detected in gender, race, age at diagnosis, and systolic/diastolic blood pressure levels between both groups. After adjustment, four variables at baseline remained independently associated with primary hypertension: absence of signs/symptoms (OR 18.87, 95% CI 6.32-56.29), normal serum creatinine (OR 0.02, 95% CI 0.00-0.27), family history of hypertension (OR 3.03, 95% CI 1.04-8.79), and elevated body weight (OR 1.06, 95% CI 1.02-1.10). The absence of signs/symptoms, normal serum creatinine, family history of hypertension, and overweight/obesity at admission are clues to diagnose primary hypertension in childhood.

Magnetocaloric effect and critical field analysis in Eu substituted La0.7-xEuxSr0.3MnO3 (x = 0.0, 0.1, 0.2, 0.3) manganites

NASA Astrophysics Data System (ADS)

Vadnala, Sudharshan; Asthana, Saket

2018-01-01

In this study, we have investigated magnetic behavior, magnetocaloric effect and critical exponent analysis of La0.7-xEuxSr0.3MnO3 (x = 0.0, 0.1, 0.2, 0.3) manganites synthesized through solid state reaction route. The crystallographic data obtained from refinement of X-ray diffraction patterns reveal that crystal structure changes from rhombohedral (for x = 0.0) to orthorhombic (for x ≥ 0.1). The average ionic radius of A-site is decreased from 1.384 Å (for x = 0.0) to 1.360 Å (for x = 0.3) with Eu3+ substitution which in turn decreases the Mn-O-Mn bond angles. Magnetization measurements are performed in the vicinity of TC to determine magnetocaloric effect (MCE) and critical field behavior. The maximum magnetic entropy change (Δ SMmax) (for μ0ΔH = 6T) increases with the Eu3+ substitution from 3.88 J/kg K (for x = 0.0) to 5.03 J/kg K (for x = 0.3) at the transition temperature. The critical field behaviour of compounds was analysed using various methods such as modified Arrott plots, Kouvel-Fisher method and critical isotherm to determine critical temperature and critical exponents (β, γ and δ). The obtained critical exponents are in good accordance with scaling relation. The temperature dependence of the order parameter n, for different magnetic fields, is studied using the relation ΔSMαHn. The values of n are found to obey the Curie-Weiss law for temperatures above the transition temperature. The rescaled change in entropy data for all compounds collapses into the same universal curve, revealing a second order phase transition.

The NBS-LRR architectures of plant R-proteins and metazoan NLRs evolved in independent events

PubMed Central

Urbach, Jonathan M.; Ausubel, Frederick M.

2017-01-01

There are intriguing parallels between plants and animals, with respect to the structures of their innate immune receptors, that suggest universal principles of innate immunity. The cytosolic nucleotide binding site–leucine rich repeat (NBS-LRR) resistance proteins of plants (R-proteins) and the so-called NOD-like receptors of animals (NLRs) share a domain architecture that includes a STAND (signal transduction ATPases with numerous domains) family NTPase followed by a series of LRRs, suggesting inheritance from a common ancestor with that architecture. Focusing on the STAND NTPases of plant R-proteins, animal NLRs, and their homologs that represent the NB-ARC (nucleotide-binding adaptor shared by APAF-1, certain R gene products and CED-4) and NACHT (named for NAIP, CIIA, HET-E, and TEP1) subfamilies of the STAND NTPases, we analyzed the phylogenetic distribution of the NBS-LRR domain architecture, used maximum-likelihood methods to infer a phylogeny of the NTPase domains of R-proteins, and reconstructed the domain structure of the protein containing the common ancestor of the STAND NTPase domain of R-proteins and NLRs. Our analyses reject monophyly of plant R-proteins and NLRs and suggest that the protein containing the last common ancestor of the STAND NTPases of plant R-proteins and animal NLRs (and, by extension, all NB-ARC and NACHT domains) possessed a domain structure that included a STAND NTPase paired with a series of tetratricopeptide repeats. These analyses reject the hypothesis that the domain architecture of R-proteins and NLRs was inherited from a common ancestor and instead suggest the domain architecture evolved at least twice. It remains unclear whether the NBS-LRR architectures were innovations of plants and animals themselves or were acquired by one or both lineages through horizontal gene transfer. PMID:28096345

Biallelic inactivation of REV7 is associated with Fanconi anemia.

PubMed

Bluteau, Dominique; Masliah-Planchon, Julien; Clairmont, Connor; Rousseau, Alix; Ceccaldi, Raphael; Dubois d'Enghien, Catherine; Bluteau, Olivier; Cuccuini, Wendy; Gachet, Stéphanie; Peffault de Latour, Régis; Leblanc, Thierry; Socié, Gérard; Baruchel, André; Stoppa-Lyonnet, Dominique; D'Andrea, Alan D; Soulier, Jean

2016-09-01

Fanconi anemia (FA) is a recessive genetic disease characterized by congenital abnormalities, chromosome instability, progressive bone marrow failure (BMF), and a strong predisposition to cancer. Twenty FA genes have been identified, and the FANC proteins they encode cooperate in a common pathway that regulates DNA crosslink repair and replication fork stability. We identified a child with severe BMF who harbored biallelic inactivating mutations of the translesion DNA synthesis (TLS) gene REV7 (also known as MAD2L2), which encodes the mutant REV7 protein REV7-V85E. Patient-derived cells demonstrated an extended FA phenotype, which included increased chromosome breaks and G2/M accumulation upon exposure to DNA crosslinking agents, γH2AX and 53BP1 foci accumulation, and enhanced p53/p21 activation relative to cells derived from healthy patients. Expression of WT REV7 restored normal cellular and functional phenotypes in the patient's cells, and CRISPR/Cas9 inactivation of REV7 in a non-FA human cell line produced an FA phenotype. Finally, silencing Rev7 in primary hematopoietic cells impaired progenitor function, suggesting that the DNA repair defect underlies the development of BMF in FA. Taken together, our genetic and functional analyses identified REV7 as a previously undescribed FA gene, which we term FANCV.

Biallelic inactivation of REV7 is associated with Fanconi anemia

PubMed Central

Masliah-Planchon, Julien; Clairmont, Connor; Rousseau, Alix; Ceccaldi, Raphael; Dubois d’Enghien, Catherine; Bluteau, Olivier; Cuccuini, Wendy; Gachet, Stéphanie; Peffault de Latour, Régis; Leblanc, Thierry; Socié, Gérard; Baruchel, André; Stoppa-Lyonnet, Dominique; D’Andrea, Alan D.

2016-01-01

Fanconi anemia (FA) is a recessive genetic disease characterized by congenital abnormalities, chromosome instability, progressive bone marrow failure (BMF), and a strong predisposition to cancer. Twenty FA genes have been identified, and the FANC proteins they encode cooperate in a common pathway that regulates DNA crosslink repair and replication fork stability. We identified a child with severe BMF who harbored biallelic inactivating mutations of the translesion DNA synthesis (TLS) gene REV7 (also known as MAD2L2), which encodes the mutant REV7 protein REV7-V85E. Patient-derived cells demonstrated an extended FA phenotype, which included increased chromosome breaks and G2/M accumulation upon exposure to DNA crosslinking agents, γH2AX and 53BP1 foci accumulation, and enhanced p53/p21 activation relative to cells derived from healthy patients. Expression of WT REV7 restored normal cellular and functional phenotypes in the patient’s cells, and CRISPR/Cas9 inactivation of REV7 in a non-FA human cell line produced an FA phenotype. Finally, silencing Rev7 in primary hematopoietic cells impaired progenitor function, suggesting that the DNA repair defect underlies the development of BMF in FA. Taken together, our genetic and functional analyses identified REV7 as a previously undescribed FA gene, which we term FANCV. PMID:27500492

Growing Global Migration and Its Implications for the United States

DTIC Science & Technology

2001-03-01

Growing Global Migration and Its Implications for the United States NIE 2001-02D March 2001 Report Documentation Page Form ApprovedOMB No. 0704-0188...00-00-2001 4. TITLE AND SUBTITLE Growing Global Migration and Its Implications for the United States 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c...unclassified Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std Z39-18 Growing Global Migration and Its Implications for the United States This

Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export.

PubMed

Behrens, Ryan T; Aligeti, Mounavya; Pocock, Ginger M; Higgins, Christina A; Sherer, Nathan M

2017-02-01

HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks its NES peptide

Nuclear Export Signal Masking Regulates HIV-1 Rev Trafficking and Viral RNA Nuclear Export

PubMed Central

Behrens, Ryan T.; Aligeti, Mounavya; Pocock, Ginger M.; Higgins, Christina A.

2016-01-01

ABSTRACT HIV-1's Rev protein forms a homo-oligomeric adaptor complex linking viral RNAs to the cellular CRM1/Ran-GTP nuclear export machinery through the activity of Rev's prototypical leucine-rich nuclear export signal (NES). In this study, we used a functional fluorescently tagged Rev fusion protein as a platform to study the effects of modulating Rev NES identity, number, position, or strength on Rev subcellular trafficking, viral RNA nuclear export, and infectious virion production. We found that Rev activity was remarkably tolerant of diverse NES sequences, including supraphysiological NES (SNES) peptides that otherwise arrest CRM1 transport complexes at nuclear pores. Rev's ability to tolerate a SNES was both position and multimerization dependent, an observation consistent with a model wherein Rev self-association acts to transiently mask the NES peptide(s), thereby biasing Rev's trafficking into the nucleus. Combined imaging and functional assays also indicated that NES masking underpins Rev's well-known tendency to accumulate at the nucleolus, as well as Rev's capacity to activate optimal levels of late viral gene expression. We propose that Rev multimerization and NES masking regulates Rev's trafficking to and retention within the nucleus even prior to RNA binding. IMPORTANCE HIV-1 infects more than 34 million people worldwide causing >1 million deaths per year. Infectious virion production is activated by the essential viral Rev protein that mediates nuclear export of intron-bearing late-stage viral mRNAs. Rev's shuttling into and out of the nucleus is regulated by the antagonistic activities of both a peptide-encoded N-terminal nuclear localization signal and C-terminal nuclear export signal (NES). How Rev and related viral proteins balance strong import and export activities in order to achieve optimal levels of viral gene expression is incompletely understood. We provide evidence that multimerization provides a mechanism by which Rev transiently masks

Overexpression of GsZFP1 enhances salt and drought tolerance in transgenic alfalfa (Medicago sativa L.).

PubMed

Tang, Lili; Cai, Hua; Ji, Wei; Luo, Xiao; Wang, Zhenyu; Wu, Jing; Wang, Xuedong; Cui, Lin; Wang, Yang; Zhu, Yanming; Bai, Xi

2013-10-01

GsZFP1 encodes a Cys2/His2-type zinc-finger protein. In our previous study, when GsZFP1 was heterologously expressed in Arabidopsis, the transgenic Arabidopsis plants exhibited enhanced drought and cold tolerance. However, it is still unknown whether GsZFP1 is also involved in salt stress. GsZFP1 is from the wild legume Glycine soja. Therefore, the aims of this study were to further elucidate the functions of the GsZFP1 gene under salt and drought stress in the forage legume alfalfa and to investigate its biochemical and physiological functions under these stress conditions. Our data showed that overexpression of GsZFP1 in alfalfa resulted in enhanced salt tolerance. Under high salinity stress, greater relative membrane permeability and malondialdehyde (MDA) content were observed and more free proline and soluble sugars accumulated in transgenic alfalfa than in the wild-type (WT) plants; in addition, the transgenic lines accumulated less Na(+) and more K(+) in both the shoots and roots. Overexpression of GsZFP1 also enhanced the drought tolerance of alfalfa. The fold-inductions of stress-responsive marker gene expression, including MtCOR47, MtRAB18, MtP5CS, and MtRD2, were greater in transgenic alfalfa than those of WT under drought stress conditions. In conclusion, the transgenic alfalfa plants generated in this study could be used for farming in salt-affected as well as arid and semi-arid areas. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Oxycodone Plus Ultra-Low-Dose Naltrexone Attenuates Neuropathic Pain and Associated μ-Opioid Receptor–Gs Coupling

PubMed Central

Largent-Milnes, Tally M.; Guo, Wenhong; Wang, Hoau-Yan; Burns, Lindsay H.; Vanderah, Todd W.

2017-01-01

Both peripheral nerve injury and chronic opioid treatment can result in hyperalgesia associated with enhanced excitatory neurotransmission at the level of the spinal cord. Chronic opioid administration leads to a shift in μ-opioid receptor (MOR)–G protein coupling from Gi/o to Gs that can be prevented by cotreatment with an ultra-low-dose opioid antagonist. In this study, using lumbar spinal cord tissue from rats with L5/L6 spinal nerve ligation (SNL), we demonstrated that SNL injury induces MOR linkage to Gs in the damaged (ipsilateral) spinal dorsal horn. This MOR-Gs coupling occurred without changing Gi/o coupling levels and without changing the expression of MOR or Gα proteins. Repeated administration of oxycodone alone or in combination with ultra-low-dose naltrexone (NTX) was assessed on the SNL-induced MOR-Gs coupling as well as on neuropathic pain behavior. Repeated spinal oxycodone exacerbated the SNL-induced MOR-Gs coupling, whereas ultra-low-dose NTX cotreatment slightly but significantly attenuated this Gs coupling. Either spinal or oral administration of oxycodone plus ultra-low-dose NTX markedly enhanced the reductions in allodynia and thermal hyperalgesia produced by oxycodone alone and minimized tolerance to these effects. The MOR-Gs coupling observed in response to SNL may in part contribute to the excitatory neurotransmission in spinal dorsal horn in neuropathic pain states. The antihyperalgesic and antiallodynic effects of oxycodone plus ultra-low-dose NTX (Oxytrex, Pain Therapeutics, Inc., San Mateo, CA) suggest a promising new treatment for neuropathic pain. PMID:18468954

Ceramic R and D Programs. Part III. NASA, ARPA, AEC, NBS, Bureau of Mines, and National Science Foundation.

DTIC Science & Technology

The report is a DCIC compilation of current R and D programs that are supported by NASA, ARPA, AEC, NBS, Bureau of Mines, and National Science Foundation in the field of ceramics and related materials. (Author)

Double heterozygotes among breast cancer patients analyzed for BRCA1, CHEK2, ATM, NBN/NBS1, and BLM germ-line mutations.

PubMed

Sokolenko, Anna P; Bogdanova, Natalia; Kluzniak, Wojciech; Preobrazhenskaya, Elena V; Kuligina, Ekatherina S; Iyevleva, Aglaya G; Aleksakhina, Svetlana N; Mitiushkina, Natalia V; Gorodnova, Tatiana V; Bessonov, Alexandr A; Togo, Alexandr V; Lubiński, Jan; Cybulski, Cezary; Jakubowska, Anna; Dörk, Thilo; Imyanitov, Evgeny N

2014-06-01

17 double heterozygous (DH) breast cancer (BC) patients were identified upon the analysis of 5,391 affected women for recurrent Slavic mutations in BRCA1, CHEK2, NBN/NBS1, ATM, and BLM genes. Double heterozygosity was found for BRCA1 and BLM (4 patients), BRCA1 and CHEK2 (4 patients), CHEK2 and NBS1 (3 patients), BRCA1 and ATM (2 patients), CHEK2 and BLM (2 patients), CHEK2 and ATM (1 patient), and NBS1 and BLM (1 patient). DH BC patients were on average not younger than single mutation carriers and did not have an excess of bilateral BC; an additional non-breast tumor was documented in two BRCA1/BLM DH patients (ovarian cancer and lymphoplasmacytic lymphoma). Loss-of-heterozygosity (LOH) analysis of involved genes was performed in 5 tumors, and revealed a single instance of somatic loss of the wild-type allele (LOH at CHEK2 locus in BRCA1/CHEK2 double heterozygote). Distribution of mutations in patients and controls favors the hypothesis on multiplicative interaction between at least some of the analyzed genes. Other studies on double heterozygosity for BC-predisposing germ-line mutations are reviewed.

Specificity of RSG-1.2 Peptide Binding to RRE-IIB RNA Element of HIV-1 over Rev Peptide Is Mainly Enthalpic in Origin

PubMed Central

Kumar, Santosh; Bose, Debojit; Suryawanshi, Hemant; Sabharwal, Harshana; Mapa, Koyeli; Maiti, Souvik

2011-01-01

Rev is an essential HIV-1 regulatory protein which binds to the Rev responsive element (RRE) present within the env gene of HIV-1 RNA genome. This binding facilitates the transport of the RNA to the cytoplasm, which in turn triggers the switch between viral latency and active viral replication. Essential components of this complex have been localized to a minimal arginine rich Rev peptide and stem IIB region of RRE. A synthetic peptide known as RSG-1.2 binds with high binding affinity and specificity to the RRE-IIB than the Rev peptide, however the thermodynamic basis of this specificity has not yet been addressed. The present study aims to probe the thermodynamic origin of this specificity of RSG-1.2 over Rev Peptide for RRE-IIB. The temperature dependent melting studies show that RSG-1.2 binding stabilizes the RRE structure significantly (ΔT m = 4.3°C), in contrast to Rev binding. Interestingly the thermodynamic signatures of the binding have also been found to be different for both the peptides. At pH 7.5, RSG-1.2 binds RRE-IIB with a Ka = 16.2±0.6×107 M−1 where enthalpic change ΔH = −13.9±0.1 kcal/mol is the main driving force with limited unfavorable contribution from entropic change TΔS = −2.8±0.1 kcal/mol. A large part of ΔH may be due to specific stacking between U72 and Arg15. In contrast binding of Rev (Ka = 3.1±0.4×107 M−1) is driven mainly by entropy (ΔH = 0 kcal/mol and TΔS = 10.2±0.2 kcal/mol) which arises from major conformational changes in the RNA upon binding. PMID:21853108

Specificity of RSG-1.2 peptide binding to RRE-IIB RNA element of HIV-1 over Rev peptide is mainly enthalpic in origin.

PubMed

Kumar, Santosh; Bose, Debojit; Suryawanshi, Hemant; Sabharwal, Harshana; Mapa, Koyeli; Maiti, Souvik

2011-01-01

Rev is an essential HIV-1 regulatory protein which binds to the Rev responsive element (RRE) present within the env gene of HIV-1 RNA genome. This binding facilitates the transport of the RNA to the cytoplasm, which in turn triggers the switch between viral latency and active viral replication. Essential components of this complex have been localized to a minimal arginine rich Rev peptide and stem IIB region of RRE. A synthetic peptide known as RSG-1.2 binds with high binding affinity and specificity to the RRE-IIB than the Rev peptide, however the thermodynamic basis of this specificity has not yet been addressed. The present study aims to probe the thermodynamic origin of this specificity of RSG-1.2 over Rev Peptide for RRE-IIB. The temperature dependent melting studies show that RSG-1.2 binding stabilizes the RRE structure significantly (ΔT(m) = 4.3°C), in contrast to Rev binding. Interestingly the thermodynamic signatures of the binding have also been found to be different for both the peptides. At pH 7.5, RSG-1.2 binds RRE-IIB with a K(a) = 16.2±0.6×10(7) M(-1) where enthalpic change ΔH = -13.9±0.1 kcal/mol is the main driving force with limited unfavorable contribution from entropic change TΔS = -2.8±0.1 kcal/mol. A large part of ΔH may be due to specific stacking between U72 and Arg15. In contrast binding of Rev (K(a) = 3.1±0.4×10(7) M(-1)) is driven mainly by entropy (ΔH = 0 kcal/mol and TΔS = 10.2±0.2 kcal/mol) which arises from major conformational changes in the RNA upon binding.

Heterologous expression of the cotton NBS-LRR gene GbaNA1 enhances Verticillium wilt resistance in Arabidopsis

USDA-ARS?s Scientific Manuscript database

Verticillium wilt caused by Verticillium dahliae results in severe losses in cotton, and is economically the most destructive disease of this crop. Improving genetic resistance is the cleanest and least expensive option to manage Verticillium wilt. Previously, we identified the island cotton NBS-LRR...

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

RNA helicase MOV10 functions as a co-factor of HIV-1 Rev to facilitate Rev/RRE-dependent nuclear export of viral mRNAs.

PubMed

Huang, Feng; Zhang, Junsong; Zhang, Yijun; Geng, Guannan; Liang, Juanran; Li, Yingniang; Chen, Jingliang; Liu, Chao; Zhang, Hui

2015-12-01

Human immunodeficiency virus type 1 (HIV-1) exploits multiple host factors during its replication. The REV/RRE-dependent nuclear export of unspliced/partially spliced viral transcripts needs the assistance of host proteins. Recent studies have shown that MOV10 overexpression inhibited HIV-1 replication at various steps. However, the endogenous MOV10 was required in certain step(s) of HIV-1 replication. In this report, we found that MOV10 potently enhances the nuclear export of viral mRNAs and subsequently increases the expression of Gag protein and other late products through affecting the Rev/RRE axis. The co-immunoprecipitation analysis indicated that MOV10 interacts with Rev in an RNA-independent manner. The DEAG-box of MOV10 was required for the enhancement of Rev/RRE-dependent nuclear export and the DEAG-box mutant showed a dominant-negative activity. Our data propose that HIV-1 utilizes the anti-viral factor MOV10 to function as a co-factor of Rev and demonstrate the complicated effects of MOV10 on HIV-1 life cycle. Copyright © 2015 Elsevier Inc. All rights reserved.

Interaction between the Rev1 C-terminal Domain and the PolD3 Subunit of Polζ Suggests a Mechanism of Polymerase Exchange upon Rev1/Polζ-Dependent Translesion Synthesis

PubMed Central

Pustovalova, Yulia; Magalhães, Mariana T. Q.; D’Souza, Sanjay; Rizzo, Alessandro A.; Korza, George; Walker, Graham C.; Korzhnev, Dmitry M.

2016-01-01

Translesion synthesis (TLS) is a mutagenic branch of cellular DNA damage tolerance that enables bypass replication over DNA lesions carried out by specialized low-fidelity DNA polymerases. The replicative bypass of most types of DNA damage is performed in a two-step process of Rev1/Polζ-dependent TLS. In the first step, a Y-family TLS enzyme, typically Polη, Polι or Polκ, inserts a nucleotide across DNA lesion. In the second step, a four-subunit B-family DNA polymerase Polζ (Rev3/Rev7/PolD2/PolD3 complex) extends the distorted DNA primer-template. The coordinated action of error-prone TLS enzymes is regulated through their interactions with the two scaffold proteins, the sliding clamp PCNA and the TLS polymerase Rev1. Rev1 interactions with all other TLS enzymes are mediated by its C-terminal domain (Rev1-CT), which can simultaneously bind the Rev7 subunit of Polζ and Rev1-interacting regions (RIRs) from Polη, Polι or Polκ. In this work, we identified a previously unknown RIR motif in the C-terminal part of PolD3 subunit of Polζ whose interaction with the Rev1-CT is among the tightest mediated by RIR motifs. Three-dimensional structure of the Rev1-CT/PolD3-RIR complex determined by NMR spectroscopy revealed a structural basis for the relatively high affinity of this interaction. The unexpected discovery of PolD3-RIR motif suggests a mechanism of 'inserter' to 'extender' DNA polymerase switch upon Rev1/Polζ-dependent TLS, in which the PolD3-RIR binding to the Rev1-CT (i) helps displace the 'inserter' Polη, Polι or Polκ from its complex with Rev1, and (ii) facilitates assembly of the four-subunit 'extender' Polζ through simultaneous interaction of Rev1-CT with Rev7 and PolD3 subunits. PMID:26982350

NBS/EPA (NATIONAL BUREAU OF STANDARDS/ENVIRONMENTAL PROTECTION AGENCY) CERTIFIED REFERENCE MATERIAL PERFORMANCE AUDIT PROGRAM: STATUS REPORT 1

EPA Science Inventory

A traceability procedure has been established which allows specialty gas producers to prepare gaseous pollutant Certified Reference Materials (CRMs). The accuracy, stability and homogeneity of the CRMs approach those of NBS Standard Reference Materials (SRMs). Part of this proced...

NBS/EPA (NATIONAL BUREAU OF STANDARDS/ENVIRONMENTAL PROTECTION AGENCY) CERTIFIED REFERENCE MATERIAL PERFORMANCE AUDIT PROGRAM: STATUS REPORT 2

EPA Science Inventory

A traceability procedure has been established which allows specialty gas producers to prepare gaseous pollutant Certified Reference Materials (CRM's). The accuracy, stability and homogeneity of the CRM's approach those of NBS Standard Reference Materials (SRM's). As of October 19...

NBS computerized carpool matching system: users' guide. Final technical report

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

Gilsinn, J.F.; Landau, S.

1974-12-01

The report includes flowcharts, input/output formats, and program listings for the programs, plus details of the manual process for coordinate coding. The matching program produces, for each person desiring it, a list of others residing within a pre-specified distance of him, and is thus applicable to a single work destination having primarily one work schedule. The system is currently operational on the National Bureau of Standards' UNIVAC 1108 computer and was run in March of 1974, producing lists for about 950 employees in less than four minutes computer time. Subsequent maintenance of the system will be carried out by themore » NBS Management and Organization Division. (GRA)« less

14. NBS REMOTE MANIPULATOR SIMULATOR (RMS) CONTROL ROOM. THE RMS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

14. NBS REMOTE MANIPULATOR SIMULATOR (RMS) CONTROL ROOM. THE RMS CONTROL PANEL IS IDENTICAL TO THE SHUTTLE ORBITER AFT FLIGHT DECK WITH ALL RMS SWITCHES AND CONTROL KNOBS FOR INVOKING ANY POSSIBLE FLIGHT OPERATIONAL MODE. THIS INCLUDES ALL COMPUTER AIDED OPERATIONAL MODES, AS WELL AS FULL MANUAL MODE. THE MONITORS IN THE AFT FLIGHT DECK WINDOWS AND THE GLASSES THE OPERATOR WEARS PROVIDE A 3-D VIDEO PICTURE TO AID THE OPERATOR WITH DEPTH PERCEPTION WHILE OPERATING THE ARM. THIS IS REQUIRED BECAUSE THE RMS OPERATOR CANNOT VIEW RMS MOVEMENTS IN THE WATER WHILE AT THE CONTROL PANEL. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

Tuning Magnetic Soliton Phase via Dimensional Confinement in Exfoliated 2D Cr 1/3 NbS 2 Thin Flakes

DOE PAGES

Tang, Siwei; Fishman, Randy S.; Okamoto, Satoshi; ...

2018-05-02

Thin flakes of Cr 1/3NbS 2 are fabricated successfully via microexfoliation techniques. Temperature-dependent and field-dependent magnetizations of thin flakes with various thicknesses are investigated. When the thickness of the flake is around several hundred nanometers, the softening and eventual disappearance of the bulk soliton peak is accompanied by the appearance of other magnetic peaks at lower magnetic fields. The emergence and annihilation of the soliton peaks are explained and simulated theoretically by the change in spin spiral number inside the soliton lattice due to dimensional confinement. Compared to the conventional magnetic states in nanoscale materials, the stability and thickness tunabilitymore » of quantified spin spirals make Cr 1/3NbS 2 a potential candidate for spintronics nanodevices beyond Moore’s law.« less

Tuning Magnetic Soliton Phase via Dimensional Confinement in Exfoliated 2D Cr 1/3 NbS 2 Thin Flakes

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

Tang, Siwei; Fishman, Randy S.; Okamoto, Satoshi

Thin flakes of Cr 1/3NbS 2 are fabricated successfully via microexfoliation techniques. Temperature-dependent and field-dependent magnetizations of thin flakes with various thicknesses are investigated. When the thickness of the flake is around several hundred nanometers, the softening and eventual disappearance of the bulk soliton peak is accompanied by the appearance of other magnetic peaks at lower magnetic fields. The emergence and annihilation of the soliton peaks are explained and simulated theoretically by the change in spin spiral number inside the soliton lattice due to dimensional confinement. Compared to the conventional magnetic states in nanoscale materials, the stability and thickness tunabilitymore » of quantified spin spirals make Cr 1/3NbS 2 a potential candidate for spintronics nanodevices beyond Moore’s law.« less

solGS: a web-based tool for genomic selection

USDA-ARS?s Scientific Manuscript database

Genomic selection (GS) promises to improve accuracy in estimating breeding values and genetic gain for quantitative traits compared to traditional breeding methods. Its reliance on high-throughput genome-wide markers and statistical complexity, however, is a serious challenge in data management, ana...

Libraries and Cable TV: Plans, Proposal, and Study to Explore Ways of Serving the Community's Information Needs Using the Data Transmission Capabilities of the Institutional Communications Network (ICN) of Storer Cable in the 1980's and 1990's.

ERIC Educational Resources Information Center

Taylor, Arthur R.

A feasibility study was conducted to identify alternative demonstration projects which would involve multitype (academic, public, and school) libraries in using the data transmission capabilities of the Institutional Communications Network (ICN) of Storer Cable to meet the information needs of schools and communities in Boone, Campbell, and Kenton…

Investigation of structure and function of mitochondrial alcohol dehydrogenase isozyme III from Komagataella phaffii GS115.

PubMed

Zhang, Huaidong; Li, Qin; Wang, Lina; Chen, Yan

2018-05-01

Alcohol dehydrogenases (ADHs) catalyze the reversible oxidation of alcohol using NAD + or NADP + as cofactor. Three ADH homologues have been identified in Komagataella phaffii GS115 (also named Pichia pastoris GS115), ADH1, ADH2 and ADH3, among which adh3 is the only gene responsible for consumption of ethanol in Komagataella phaffii GS115. However, the relationship between structure and function of mitochondrial alcohol dehydrogenase isozyme III from Komagataella phaffii GS115 (KpADH3) is still not clear yet. KpADH3 was purified, identified and characterized by multiple biophysical techniques (Nano LC-MS/MS, Enzymatic activity assay, X-ray crystallography). The crystal structure of KpADH3, which was the first ADH structure from Komagataella phaffii GS115, was solved at 1.745 Å resolution. Structural analysis indicated that KpADH3 was the sole dimeric ADH structure with face-to-face orientation quaternary structure from yeast. The major structural different conformations located on residues 100-114 (the structural zinc binding loop) and residues 337-344 (the loop between α12 and β15 which covered the catalytic domain). In addition, three channels were observed in KpADH3 crystal structure, channel 2 and channel 3 may be essential for substrate specific recognition, ingress and egress, channel 1 may be the pass-through for cofactor. KpADH3 plays an important role in the metabolism of alcohols in Komagataella phaffii GS115, and its crystal structure is the only dimeric medium-chain ADH from yeast described so far. Knowledge of the relationship between structure and function of KpADH3 is crucial for understanding the role of KpADH3 in Komagataella phaffii GS115 mitochondrial metabolism. Copyright © 2018 Elsevier B.V. All rights reserved.

A Narrative Approach to Exploring TGfU-GS

ERIC Educational Resources Information Center

Stolz, Steven A.; Pill, Shane

2016-01-01

This paper uses a narrative approach in the form of a fictional dialogue between a physical education teacher educator (PETE) and an enquiring physical education teacher (EPET) in order to both contextualise the problem posed by Almond, that Teaching Games for Understanding-Game Sense (TGfU-GS) has been better accepted in academia than in the…

A novel Fe(III) dependent bioflocculant from Klebsiella oxytoca GS-4-08: culture conditions optimization and flocculation mechanism

PubMed Central

Yu, Lei; Tang, Qing-wen; Zhang, Yu-jia; Chen, Rong-ping; Liu, Xin; Qiao, Wei-chuan; Li, Wen-wei; Ruan, Hong-hua; Song, Xin

2016-01-01

In this work, the effect of cultivation factors on the flocculation efficiency (FE) of bioflocculant P-GS408 from Klebsiella oxytoca was optimized by the response surface methodology. The most significant factor, i.e. culture time, was determined by gray relational analysis. A total of 240 mg of purified P-GS408 was prepared from 1 liter of culture solution under the optimal conditions. GC-MS analysis results indicated that the polysaccharide of P-GS408 mainly contains Rhamnose and Galactose, and the existence of abundant hydroxyl, carboxyl and amino groups was evidenced by FTIR and XPS analyses. With the aid of Fe3+, the FE of kaolin solution by P-GS408 could achieve 99.48% in ten minutes. Functional groups of polysaccharide were involved in the first adsorption step and the zeta potential of kaolin solution changed from −39.0 mV to 43.4 mV in the presence of Fe3+ and P-GS408. Three-dimensional excitation-emission (EEM) fluorescence spectra demonstrates that the trivalent Fe3+ and Al3+ can bind efficiently with P-GS408, while those univalent and divalent cations cannot. With the help of SEM images, FTIR, zeta potential and EEM spectra, we proposed the P-GS408 flocculation mechanism, which consists of coordination bond combination, charge neutrality, adsorption and bridging, and net catching. PMID:27713559

A novel Fe(III) dependent bioflocculant from Klebsiella oxytoca GS-4-08: culture conditions optimization and flocculation mechanism.

PubMed

Yu, Lei; Tang, Qing-Wen; Zhang, Yu-Jia; Chen, Rong-Ping; Liu, Xin; Qiao, Wei-Chuan; Li, Wen-Wei; Ruan, Hong-Hua; Song, Xin

2016-10-07

In this work, the effect of cultivation factors on the flocculation efficiency (FE) of bioflocculant P-GS408 from Klebsiella oxytoca was optimized by the response surface methodology. The most significant factor, i.e. culture time, was determined by gray relational analysis. A total of 240 mg of purified P-GS408 was prepared from 1 liter of culture solution under the optimal conditions. GC-MS analysis results indicated that the polysaccharide of P-GS408 mainly contains Rhamnose and Galactose, and the existence of abundant hydroxyl, carboxyl and amino groups was evidenced by FTIR and XPS analyses. With the aid of Fe 3+ , the FE of kaolin solution by P-GS408 could achieve 99.48% in ten minutes. Functional groups of polysaccharide were involved in the first adsorption step and the zeta potential of kaolin solution changed from -39.0 mV to 43.4 mV in the presence of Fe 3+ and P-GS408. Three-dimensional excitation-emission (EEM) fluorescence spectra demonstrates that the trivalent Fe 3+ and Al 3+ can bind efficiently with P-GS408, while those univalent and divalent cations cannot. With the help of SEM images, FTIR, zeta potential and EEM spectra, we proposed the P-GS408 flocculation mechanism, which consists of coordination bond combination, charge neutrality, adsorption and bridging, and net catching.

Human REV3 DNA Polymerase Zeta Localizes to Mitochondria and Protects the Mitochondrial Genome.

PubMed

Singh, Bhupendra; Li, Xiurong; Owens, Kjerstin M; Vanniarajan, Ayyasamy; Liang, Ping; Singh, Keshav K

2015-01-01

To date, mitochondrial DNA polymerase γ (POLG) is the only polymerase known to be present in mammalian mitochondria. A dogma in the mitochondria field is that there is no other polymerase present in the mitochondria of mammalian cells. Here we demonstrate localization of REV3 DNA polymerase in the mammalian mitochondria. We demonstrate localization of REV3 in the mitochondria of mammalian tissue as well as cell lines. REV3 associates with POLG and mitochondrial DNA and protects the mitochondrial genome from DNA damage. Inactivation of Rev3 leads to reduced mitochondrial membrane potential, reduced OXPHOS activity, and increased glucose consumption. Conversely, inhibition of the OXPHOS increases expression of Rev3. Rev3 expression is increased in human primary breast tumors and breast cancer cell lines. Inactivation of Rev3 decreases cell migration and invasion, and localization of Rev3 in mitochondria increases survival and the invasive potential of cancer cells. Taken together, we demonstrate that REV3 functions in mammalian mitochondria and that mitochondrial REV3 is associated with the tumorigenic potential of cells.

Neutral Buoyancy Simulator - SADE NBS Test

NASA Technical Reports Server (NTRS)

1983-01-01

One of the main components of the Hubble Space Telescope (HST) is the Solar Array Drive Electronics (SADE) system. This system interfaces with the Support System Module (SSM) for exchange of operational commands and telemetry data. SADE operates and controls the Solar Array Drive Mechanisms (SADM) for the orientation of the Solar Array Drive (SAD). It also monitors the position of the arrays and the temperature of the SADM. During the first HST servicing mission, the astronauts replaced the SADE component because of some malfunctions. This turned out to be a very challenging extravehicular activity (EVA). Two transistors and two diodes had been thermally stressed with the conformal coating discolored and charred. Soldered cornections became molten and reflowed between the two diodes. The failed transistors gave no indication of defective construction. All repairs were made and the HST was redeposited into orbit. Prior to undertaking this challenging mission, the orbiter's crew trained at Marshall Space Flight Center's (MSFC) Neutral Buoyancy Simulator (NBS) to prepare themselves for working in a low gravity environment. They also practiced replacing HST parts and exercised maneuverability and equipment handling. Pictured is an astronaut practicing climbing a space platform that was necessary in making repairs on the HST.

Evaluation of Two Guralp Preamplifiers for GS21 Seismometer Application.

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

Merchant, Bion J.; Slad, George William

2015-08-01

Sandia National Laboratories has tested and evaluated two Guralp preamplifiers for use with a GS21 seismometer application. The two preamplifiers have a gain factor of 61.39. The purpose of the preamplifier evaluation was to determine a measured gain factor, transfer function, total harmonic distortion, self-noise, application passband, dynamic range, seismometer calibration pass-through, and to comment on any issues encountered during the evaluation. The test results included in this report were in response to static, tonal, and dynamic input signals. The Guralp GS21 preamplifiers are being evaluated for potential use in the International Monitoring System (IMS) of the Comprehensive Nuclear Test-Ban-Treatymore » Organization (CTBTO). Test methodologies used were based on IEEE Standards 1057 for Digitizing Waveform Recorders and 1241 for Analog to Digital Converters« less

Gsα Deficiency in the Ventromedial Hypothalamus Enhances Leptin Sensitivity and Improves Glucose Homeostasis in Mice on a High-Fat Diet.

PubMed

Berger, Alta; Kablan, Ahmed; Yao, Catherine; Ho, Thuy; Podyma, Brandon; Weinstein, Lee S; Chen, Min

2016-02-01

In both mice and patients with Albright hereditary osteodystrophy, heterozygous inactivating mutations of Gsα, a ubiquitously expressed G protein that mediates receptor-stimulated intracellular cAMP production, lead to obesity and insulin resistance but only when the mutation is present on the maternal allele. This parent-of-origin effect in mice was shown to be due to Gsα imprinting in one or more brain regions. The ventromedial hypothalamus (VMH) is involved in the regulation of energy and glucose homeostasis, but the role of Gsα in VMH on metabolic regulation is unknown. To examine this, we created VMH-specific Gsα-deficient mice by mating Gsα-floxed mice with SF1-cre mice. Heterozygotes with Gsα mutation on either the maternal or paternal allele had a normal metabolic phenotype, and there was no molecular evidence of Gsα imprinting, indicating that the parent-of-origin metabolic effects associated with Gsα mutations is not due to Gsα deficiency in VMH SF1 neurons. Homozygous VMH Gsα knockout mice (VMHGsKO) showed no changes in body weight on either a regular or high-fat diet. However, glucose metabolism (fasting glucose, glucose tolerance, insulin sensitivity) was significantly improved in male VMHGsKO mice, with the difference more dramatic on the high-fat diet. In addition, male VMHGsKO mice on the high-fat diet showed a greater anorexigenic effect and increased VMH signal transducer and activator of transcription-3 phosphorylation in response to leptin. These results indicate that VMH Gsα/cyclic AMP signaling regulates glucose homeostasis and alters leptin sensitivity in mice, particularly in the setting of excess caloric intake.

Mechanistic Characterization of GS-9190 (Tegobuvir), a Novel Nonnucleoside Inhibitor of Hepatitis C Virus NS5B Polymerase▿

PubMed Central

Shih, I-hung; Vliegen, Inge; Peng, Betty; Yang, Huiling; Hebner, Christy; Paeshuyse, Jan; Pürstinger, Gerhard; Fenaux, Martijn; Tian, Yang; Mabery, Eric; Qi, Xiaoping; Bahador, Gina; Paulson, Matthew; Lehman, Laura S.; Bondy, Steven; Tse, Winston; Reiser, Hans; Lee, William A.; Schmitz, Uli; Neyts, Johan; Zhong, Weidong

2011-01-01

GS-9190 (Tegobuvir) is a novel imidazopyridine inhibitor of hepatitis C virus (HCV) RNA replication in vitro and has demonstrated potent antiviral activity in patients chronically infected with genotype 1 (GT1) HCV. GS-9190 exhibits reduced activity against GT2a (JFH1) subgenomic replicons and GT2a (J6/JFH1) infectious virus, suggesting that the compound's mechanism of action involves a genotype-specific viral component. To further investigate the GS-9190 mechanism of action, we utilized the susceptibility differences between GT1b and GT2a by constructing a series of replicon chimeras where combinations of 1b and 2a nonstructural proteins were encoded within the same replicon. The antiviral activities of GS-9190 against the chimeric replicons were reduced to levels comparable to that of the wild-type GT2a replicon in chimeras expressing GT2a NS5B. GT1b replicons in which the β-hairpin region (amino acids 435 to 455) was replaced by the corresponding sequence of GT2a were markedly less susceptible to GS-9190, indicating the importance of the thumb subdomain of the polymerase in this effect. Resistance selection in GT1b replicon cells identified several mutations in NS5B (C316Y, Y448H, Y452H, and C445F) that contributed to the drug resistance phenotype. Reintroduction of these mutations into wild-type replicons conferred resistance to GS-9190, with the number of NS5B mutations correlating with the degree of resistance. Analysis of GS-9190 cross-resistance against previously reported NS5B drug-selected mutations showed that the resistance pattern of GS-9190 is different from other nonnucleoside inhibitors. Collectively, these data demonstrate that GS-9190 represents a novel class of nonnucleoside polymerase inhibitors that interact with NS5B likely through involvement of the β-hairpin in the thumb subdomain. PMID:21746939

15. NBS TOP SIDE CONTROL ROOM. THE SUIT SYSTEMS CONSOLE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

15. NBS TOP SIDE CONTROL ROOM. THE SUIT SYSTEMS CONSOLE IS USED TO CONTROL AIR FLOW AND WATER FLOW TO THE UNDERWATER SPACE SUIT DURING THE TEST. THE SUIT SYSTEMS ENGINEER MONITORS AIR FLOW ON THE PANEL TO THE LEFT, AND SUIT DATA ON THE COMPUTER MONITOR JUST SLIGHTLY TO HIS LEFT. WATER FLOW IS MONITORED ON THE PANEL JUST SLIGHTLY TO HIS RIGHT AND TEST VIDEO TO HIS FAR RIGHT. THE DECK CHIEF MONITORS THE DIVER'S DIVE TIMES ON THE COMPUTER IN THE UPPER RIGHT. THE DECK CHIEF LOGS THEM IN AS THEY ENTER THE WATER, AND LOGS THEM OUT AS THEY EXIT THE WATER. THE COMPUTER CALCULATES TOTAL DIVE TIME. - Marshall Space Flight Center, Neutral Buoyancy Simulator Facility, Rideout Road, Huntsville, Madison County, AL

All Prime Contract Awards by State or Country, Place and Contractor. Part 19. (Abbot, Virginia-Yorktown, Virginia)

DTIC Science & Technology

1989-01-01

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Anaerobic oxidation of toluene, phenol, and p-cresol by the dissimilatory iron-reducing organism, GS-15

USGS Publications Warehouse

Lovley, D.R.; Lonergan, D.J.

1990-01-01

The dissimilatory Fe(III) reducer, GS-15, is the first microorganism known to couple the oxidation of aromatic compounds to the reduction of Fe(III) and the first example of a pure culture of any kind known to anaerobically oxidize an aromatic hydrocarbon, toluene. In this study, the metabolism of toluene, phenol, and p-cresol by GS-15 was investigated in more detail. GS-15 grew in an anaerobic medium with toluene as the sole electron donor and Fe(III) oxide as the electron acceptor. Growth coincided with Fe(III) reduction. [ring-14C]toluene was oxidized to 14CO2, and the stoichiometry of 14CO2 production and Fe(III) reduction indicated that GS-15 completely oxidized toluene to carbon dioxide with Fe(III) as the electron acceptor. Magnetite was the primary iron end product during toluene oxidation. Phenol and p-cresol were also completely oxidized to carbon dioxide with Fe(III) as the sole electron acceptor, and GS-15 could obtain energy to support growth by oxidizing either of these compounds as the sole electron donor. p-Hydroxybenzoate was a transitory extracellular intermediate of phenol and p-cresol metabolism but not of toluene metabolism. GS-15 oxidized potential aromatic intermediates in the oxidation of toluene (benzylalcohol and benzaldehyde) and p-cresol (p-hydroxybenzylalcohol and p-hydroxybenzaldehyde). The metabolism described here provides a model for how aromatic hydrocarbons and phenols may be oxidized with the reduction of Fe(III) in contaminated aquifers and petroleum-containing sediments.

Two-Way Time Transfer via Geostationary Satellites NRC/NBS, NRC/USNO and NBS/USNO via Hermes and NRC/LPTF (France) via Symphonie

NASA Technical Reports Server (NTRS)

Costain, C.; Boulanger, J. S.; Daams, H.; Hanson, D. W.; Beehler, R. E.; Clements, A. J.; Davis, D. D.; Klepczynski, W. J.; Veenstra, L. B.; Kaiser, J.

1979-01-01

In most of the experiments, 1 pps pulses of the station atomic clocks were exchanged between the partners, and a cubic equation was fitted to the 1000 to 2000 second measurements. The equations were exchanged and substracted to obtain the time difference of the stations. The standard deviation in the fit of the equations varied, depending on conditions, from 1.5 ns to 16 ns. For the last month of the Hermes experiment, a 1 MHz signal was used, giving a standard deviation of 0.18 ns. The comparison of the time scales via satellite and via Loran-C (BIH Circular D) show clearly that some Loran-C links are very good, but that the NBS link varies by 1 micron s. Via the satellite the frequencies of the time scales can be compared with an accuracy of 2 x 10 to the minus 14 power.

Tamavidin 2-REV: an engineered tamavidin with reversible biotin-binding capability.

PubMed

Takakura, Yoshimitsu; Sofuku, Kozue; Tsunashima, Masako

2013-03-10

A biotin-binding protein with reversible biotin-binding capability is of great technical value in the affinity purification of biotinylated biomolecules. Although several proteins, chemically or genetically modified from avidin or streptavidin, with reversible biotin-binding have been reported, they have been problematic in one way or another. Tamavidin 2 is a fungal protein similar to avidin and streptavidin in biotin-binding. Here, a mutein, tamavidin 2-REV, was engineered from tamavidin 2 by replacing the serine at position 36 (S36) with alanine. S36 is thought to form a hydrogen bond with biotin in tamavidin 2/biotin complexes and two hydrogen bonds with V38 within the protein. Tamavidin 2-REV bound to biotin-agarose and was eluted with excess free biotin at a neutral pH. In addition, the model substrate biotinylated bovine serum albumin was efficiently purified from a crude extract from Escherichia coli by means of single-step affinity chromatography with tamavidin 2-REV-immobilized resin. Tamavidin 2-REV thus demonstrated reversible biotin-binding capability. The Kd value of tamavidin 2-REV to biotin was 2.8-4.4×10(-7)M.Tamavidin 2-REV retained other convenient characteristics of tamavidin 2, such as high-level expression in E. coli, resistance to proteases, and a neutral isoelectric point, demonstrating that tamavidin 2-REV is a powerful tool for the purification of biotinylated biomolecules. Copyright © 2013 Elsevier B.V. All rights reserved.

Development of breast tumors in CHEK2, NBN/NBS1 and BLM mutation carriers does not commonly involve somatic inactivation of the wild-type allele.

PubMed

Suspitsin, Evgeny N; Yanus, Grigory A; Sokolenko, Anna P; Yatsuk, Olga S; Zaitseva, Olga A; Bessonov, Alexandr A; Ivantsov, Alexandr O; Heinstein, Valeria A; Klimashevskiy, Valery F; Togo, Alexandr V; Imyanitov, Evgeny N

2014-02-01

Somatic inactivation of the remaining allele is a characteristic feature of cancers arising in BRCA1 and BRCA2 mutation carriers, which determines their unprecedented sensitivity to some DNA-damaging agents. Data on tumor-specific status of the involved gene in novel varieties of hereditary breast cancer (BC) remain incomplete. We analyzed 32 tumors obtained from 30 patients with non-BRCA1/2 BC-associated germ-line mutations: 25 women were single mutation carriers (7 BLM, 15 CHEK2 and 3 NBN/NBS1) and 5 were double mutation carriers (2 BLM/BRCA1, 1 CHEK2/BLM, 1 CHEK2/BRCA1 and 1 NBN/BLM). Losses of heterozygosity affecting the wild-type allele were detected in none of the tumors from BLM mutation carriers, 3/18 (17 %) CHEK2-associated BC and 1/4 (25 %) NBN/NBS1-driven tumors. The remaining 28 BC were subjected to the sequence analysis of entire coding region of the involved gene; no somatic mutations were identified. We conclude that the tumor-specific loss of the wild-type allele is not characteristic for BC arising in CHEK2, NBN/NBS1 and BLM mutation carriers. Rarity of "second-hit" inactivation of the involved gene in CHEK2-, NBN/NBS1- and BLM-associated BC demonstrates their substantial biological difference from BRCA1/2-driven cancers and makes them poorly suitable for the clinical trials with cisplatin and PARP inhibitors.

Mutational definition of functional domains within the Rev homolog encoded by human endogenous retrovirus K.

PubMed

Bogerd, H P; Wiegand, H L; Yang, J; Cullen, B R

2000-10-01

Nuclear export of the incompletely spliced mRNAs encoded by several complex retroviruses, including human immunodeficiency virus type 1 (HIV-1), is dependent on a virally encoded adapter protein, termed Rev in HIV-1, that directly binds both to a cis-acting viral RNA target site and to the cellular Crm1 export factor. Human endogenous retrovirus K, a family of ancient endogenous retroviruses that is not related to the exogenous retrovirus HIV-1, was recently shown to also encode a Crm1-dependent nuclear RNA export factor, termed K-Rev. Although HIV-1 Rev and K-Rev display little sequence identity, they share the ability not only to bind to Crm1 and to RNA but also to form homomultimers and shuttle between nucleus and cytoplasm. We have used mutational analysis to identify sequences in the 105-amino-acid K-Rev protein required for each of these distinct biological activities. While mutations in K-Rev that inactivate any one of these properties also blocked K-Rev-dependent nuclear RNA export, several K-Rev mutants were comparable to wild type when assayed for any of these individual activities yet nevertheless defective for RNA export. Although several nonfunctional K-Rev mutants acted as dominant negative inhibitors of K-Rev-, but not HIV-1 Rev-, dependent RNA export, these were not defined by their inability to bind to Crm1, as is seen with HIV-1 Rev. In total, this analysis suggests a functional architecture for K-Rev that is similar to, but distinct from, that described for HIV-1 Rev and raises the possibility that viral RNA export mediated by the approximately 25 million-year-old K-Rev protein may require an additional cellular cofactor that is not required for HIV-1 Rev function.

Interspecific and intraspecific gene variability in a 1-Mb region containing the highest density of NBS-LRR genes found in the melon genome.

PubMed

González, Víctor M; Aventín, Núria; Centeno, Emilio; Puigdomènech, Pere

2014-12-17

Plant NBS-LRR -resistance genes tend to be found in clusters, which have been shown to be hot spots of genome variability. In melon, half of the 81 predicted NBS-LRR genes group in nine clusters, and a 1 Mb region on linkage group V contains the highest density of R-genes and presence/absence gene polymorphisms found in the melon genome. This region is known to contain the locus of Vat, an agronomically important gene that confers resistance to aphids. However, the presence of duplications makes the sequencing and annotation of R-gene clusters difficult, usually resulting in multi-gapped sequences with higher than average errors. A 1-Mb sequence that contains the largest NBS-LRR gene cluster found in melon was improved using a strategy that combines Illumina paired-end mapping and PCR-based gap closing. Unknown sequence was decreased by 70% while about 3,000 SNPs and small indels were corrected. As a result, the annotations of 18 of a total of 23 NBS-LRR genes found in this region were modified, including additional coding sequences, amino acid changes, correction of splicing boundaries, or fussion of ORFs in common transcription units. A phylogeny analysis of the R-genes and their comparison with syntenic sequences in other cucurbits point to a pattern of local gene amplifications since the diversification of cucurbits from other families, and through speciation within the family. A candidate Vat gene is proposed based on the sequence similarity between a reported Vat gene from a Korean melon cultivar and a sequence fragment previously absent in the unrefined sequence. A sequence refinement strategy allowed substantial improvement of a 1 Mb fragment of the melon genome and the re-annotation of the largest cluster of NBS-LRR gene homologues found in melon. Analysis of the cluster revealed that resistance genes have been produced by sequence duplication in adjacent genome locations since the divergence of cucurbits from other close families, and through the

77 FR 62620 - Proposed Collection; Comment Request for Information Collection Tools

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-15

... Form 706-GS(T), Generation-Skipping Transfer Tax Return For Terminations; REG-130477-00; REG-130481-00... Terminations. OMB Number: 1545-1145. Form Number: 706-GS(T). Abstract: Form 706-GS(T) is used by trustees to.... Estimated Number of Respondents: 500. Estimated Time per Respondent: 1 hr., 22 min. Estimated Total Annual...

Differences in Outcomes between Early and Late Diagnosis of Cystic Fibrosis in the Newborn Screening Era.

PubMed

Coffey, Michael J; Whitaker, Viola; Gentin, Natalie; Junek, Rosie; Shalhoub, Carolyn; Nightingale, Scott; Hilton, Jodi; Wiley, Veronica; Wilcken, Bridget; Gaskin, Kevin J; Ooi, Chee Y

2017-02-01

To evaluate children with cystic fibrosis (CF) who had a late diagnosis of CF (LD-CF) despite newborn screening (NBS) and compare their clinical outcomes with children diagnosed after a positive NBS (NBS-CF). A retrospective review of patients with LD-CF in New South Wales, Australia, from 1988 to 2010 was performed. LD-CF was defined as NBS-negative (negative immunoreactive trypsinogen or no F508del) or NBS-positive but discharged following sweat chloride < 60 mmol/L. Cases of LD-CF were each matched 1:2 with patients with NBS-CF for age, sex, hospital, and exocrine pancreatic status. A total of 45 LD-CF cases were identified (39 NBS-negative and 6 NBS-positive) with 90 NBS-CF matched controls. Median age (IQR) of diagnosis for LD-CF and NBS-CF was 1.35 (0.4-2.8) and 0.12 (0.03-0.2) years, respectively (P <.0001). Estimated incidence of LD-CF was 1 in 45 000 live births. Compared with NBS-CF, LD-CF had more respiratory manifestations at time of diagnosis (66% vs 4%; P <.0001), a higher rate of hospital admission per year for respiratory illness (0.49 vs 0.2; P = .0004), worse lung function (forced expiratory volume in 1 second percentage of predicted, 0.88 vs 0.97; P = .007), and higher rates of chronic colonization with Pseudomonas aeruginosa (47% vs 24%; P = .01). The LD-CF cohort also appeared to be shorter than NBS-CF controls (mean height z-score -0.65 vs -0.03; P = .02). LD-CF, despite NBS, seems to be associated with worse health before diagnosis and worse later growth and respiratory outcomes, thus providing further support for NBS programs for CF. Copyright © 2016 Elsevier Inc. All rights reserved.

Alternative Fuels Data Center: New Hampshire Fleet Revs up With Natural Gas

Science.gov Websites

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The translesion polymerase Rev3L in the tolerance of alkylating anticancer drugs.

PubMed

Roos, Wynand Paul; Tsaalbi-Shtylik, Anastasia; Tsaryk, Roman; Güvercin, Fatma; de Wind, Niels; Kaina, Bernd

2009-10-01

Temozolomide and fotemustine, representing methylating and chloroethylating agents, respectively, are used in the treatment of glioma and malignant melanoma. Because chemoresistance of these tumors is a common phenomenon, identification of the underlying mechanisms is needed. Here we show that Rev3L, the catalytic subunit of the translesion DNA polymerase zeta, mediates resistance to both temozolomide and fotemustine. Rev3L knockout cells are hypersensitive to both agents. It is remarkable that cells heterozygous for Rev3L showed an intermediate sensitivity. Rev3L is not involved in the tolerance of the toxic O6-methylguanine lesion. However, a possible role of Rev3L in the tolerance of O6-chloroethylguanine or the subsequently formed N1-guanine-N3-cytosine interstrand cross-link is shown. Rev3L had no influence on base excision repair (BER) of the N-alkylation lesions but is very likely to be involved in the tolerance of N-alkylations or apurinic/apyrimidinic sites originating from them. We also show that Rev3L exerts its protective effect in replicating cells and that loss of Rev3L leads to a significant increase in DNA double-strand breaks after temozolomide and fotemustine treatment. These data show that Rev3L contributes to temozolomide and fotemustine resistance, thus acting in concert with O6-methylguanine-DNA methyltransferase, BER, mismatch repair, and double-strand break repair in defense against simple alkylating anticancer drugs.

NBS (National Bureau of Standards) calibration services users guide: Fee schedule

NASA Astrophysics Data System (ADS)

1987-04-01

The physical measurement services of the National Bureau of Standards are designed to help the makers and users of precision instruments achieve the highest possible levels of measurement quality and productivity. The hundreds of individual services found listed in the Fee Schedule constitute the highest-order calibration services available in the United States. These services directly link a customer's precision equipment or transfer standards to national measurement standards. These services are offered to public and private organizations and individuals alike. The Fee Schedule is a supplement to NBS Special Publication 250, Calibration Services Users Guide. These documents are designed to make the task of selecting and ordering an appropriate calibration service as quick and easy as possible.

Structural Basis for the Interaction of Mutasome Assembly Factor REV1 with Ubiquitin.

PubMed

Cui, Gaofeng; Botuyan, Maria Victoria; Mer, Georges

2018-05-18

REV1 is an evolutionarily conserved translesion synthesis (TLS) DNA polymerase and an assembly factor key for the recruitment of other TLS polymerases to DNA damage sites. REV1-mediated recognition of ubiquitin in the proliferative cell nuclear antigen is thought to be the trigger for TLS activation. Here we report the solution NMR structure of a 108-residue fragment of human REV1 encompassing the two putative ubiquitin-binding motifs UBM1 and UBM2 in complex with ubiquitin. While in mammals UBM1 and UBM2 are both required for optimal association of REV1 with replication factories after DNA damage, we show that only REV1 UBM2 binds ubiquitin. Structure-guided mutagenesis in Saccharomyces cerevisiae further highlights the importance of UBM2 for REV1-mediated mutagenesis and DNA damage tolerance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Amino- and carboxy-terminal deletion mutants of Gs alpha are localized to the particulate fraction of transfected COS cells

PubMed Central

1992-01-01

To elucidate the structural basis for membrane attachment of the alpha subunit of the stimulatory G protein (Gs alpha), mutant Gs alpha cDNAs with deletions of amino acid residues in the amino and/or carboxy termini were transiently expressed in COS-7 cells. The particulate and soluble fractions prepared from these cells were analyzed by immunoblot using peptide specific antibodies to monitor distribution of the expressed proteins. Transfection of mutant forms of Gs alpha with either 26 amino terminal residues deleted (delta 3-28) or with 59 amino terminal residues deleted (delta 1-59) resulted in immunoreactive proteins which localized primarily to the particulate fraction. Similarly, mutants with 10 (delta 385-394), 32 (delta 353-384), or 42 (delta 353-394) amino acid residues deleted from the carboxy terminus also localized to the particulate fraction, as did a mutant form of Gs alpha lacking amino acid residues at both the amino and carboxy termini (delta 3-28)/(delta 353-384). Mutant and wild type forms of Gs alpha demonstrated a similar degree of tightness in their binding to membranes as demonstrated by treatment with 2.5 M NaCl or 6 M urea, but some mutant forms were relatively resistant compared with wild type Gs alpha to solubilization by 15 mM NaOH or 1% sodium cholate. We conclude that: (a) deletion of significant portions of the amino and/or carboxyl terminus of Gs alpha is still compatible with protein expression; (b) deletion of these regions is insufficient to cause cytosolic localization of the expressed protein. The basis of Gs alpha membrane targeting remains to be elucidated. PMID:1400589

How human IgGs against myelin basic protein (MBP) recognize oligopeptides and MBP.

PubMed

Belov, Sergey; Buneva, Valentina N; Nevinsky, Georgy A

2017-10-01

Myelin basic protein (MBP) is a major protein of myelin-proteolipid shell of axons, and it plays an important role in pathogenesis of multiple sclerosis. In the literature, there are no data on how antibodies recognize different protein antigens including MBP. A stepwise increase in ligand complexity was used to estimate the relative contributions of virtually every amino acid residue (AA) of a specific 12-mer LSRFSWGAEGQK oligopeptide corresponding to immunodominant sequence of MBP to the light chains and to intact anti-MBP IgGs from sera of patients with multiple sclerosis. It was shown that the minimal ligands of the light chains of IgGs are many different free AAs (K d  = 0.51-0.016 M), and each free AA interacts with the specific subsite of the light chain intended for recognition of this AA in specific LSRFSW oligopeptide. A gradual transition from Leu to LSRFSWGAEGQK leads to an increase in the affinity from 10 -1 to 2.3 × 10 -4  M because of additive interactions of the light chain with 6 AAs of this oligopeptide and then the affinity reaches plateau. The contributions of 6 various AAs to the affinity of the oligopeptide are different (K d , M): 0.71 (S), 0.44 (R), 0.14 (F), 0.17 (S), and 0.62 (W). Affinity of nonspecific oligopeptides to the light chains of IgGs is significantly lower. Intact MBP interacts with both light and heavy chains of IgGs demonstrating 192-fold higher affinity than the specific oligopeptide. It is a first quantitative analysis of the mechanism of proteins recognition by antibodies. The thermodynamic model was constructed to describe the interactions of IgGs with MBP. The data obtained can be very useful for understanding how antibodies against many different proteins can recognize these proteins. Copyright © 2017 John Wiley & Sons, Ltd.

Lessons learned from the recovered heatshield of the USERS REV capsule

NASA Astrophysics Data System (ADS)

Yamada, Tetsuya; Matsuda, Seiji; Okuyama, Keiichi; Ishii, Nobuaki

2008-01-01

The USERS Reentry Vehicle (REV) capsule carried out reentry flight from the low earth orbit and was successfully recovered on the sea in May, 2003. This paper presents the post-flight analysis of the recovered heatshield of REV capsule and summarizes the lessons learned. REV capsule, totally about 670 kg, has the combined shape of the nose hemisphere and the rear cone part, and its size is about 1.5 m in diameter and 1.9 m in length. REV is thermally protected against the aerodynamic heating by the carbon phenolic ablator heatshield. The recovered REV heatshield was scrutinized based on the outside aspect and the cross-sections. In general, the temperature profiles of the heatshield have been compared between the flight data and the prediction. The origin of the surface shallow cracks and slight delamination observed in the heatshield have been investigated based on the flight data and taking account of the ablator internal pyrolysis gas pressure, the thermal stress, and the allowable stress. The heatshield has proven to satisfy thermal protection requirements, and the validity of the designing has been confirmed.

MDM Redshift of the Host of ASASSN-17gs

NASA Astrophysics Data System (ADS)

Chornock, R.; Margutti, R.

2017-06-01

The optical transient ASASSN-17gs = AT2017egv (http://www.astronomy.ohio-state.edu/ assassin/transients.html, https://wis-tns.weizmann.ac.il/object/2017egv) was associated with the new Fermi LAT source J1544-0649 and a new, bright X-ray source Swift 154419.7-064915 by Ciprini et al. (ATel #10482).

BcGs1, a glycoprotein from Botrytis cinerea, elicits defence response and improves disease resistance in host plants.

PubMed

Zhang, Yi; Zhang, Yunhua; Qiu, Dewen; Zeng, Hongmei; Guo, Lihua; Yang, Xiufen

2015-02-20

In this study, a necrosis-inducing protein was purified from the culture filtrate of the necrotrophic fungus Botrytis cinerea BC-98 strain. Secreted proteins were collected and fractionated by liquid chromatography. The fraction with the highest necrosis-inducing activity was further purified. A glycoprotein named BcGs1 was identified by 2D electrophoresis and mass spectrometry. The BcGs1 protein consisted of 672 amino acids with a theoretical molecular weight of 70.487 kDa. Functional domain analysis indicated that BcGs1 was a glucan 1,4-alpha-glucosidase, a cell wall-degrading enzyme, with a Glyco_hydro_15 domain and a CBM20_glucoamylase domain. The BcGs1 protein caused necrotic lesions that mimicked a typical hypersensitive response and H2O2 production in tomato and tobacco leaves. BcGs1-treated plants exhibited resistance to B. cinerea, Pseudomonas syringae pv. tomato DC3000 and tobacco mosaic virus in systemic leaves. In addition, BcGs1 triggered elevation of the transcript levels of the defence-related genes PR-1a, TPK1b and Prosystemin. This is the first report of a Botrytis glucan 1,4-alpha-glucosidase triggering host plant immunity as an elicitor. These results lay a foundation for further study of the comprehensive interaction between plants and necrotrophic fungi. Copyright © 2015 Elsevier Inc. All rights reserved.

Isolation and characterization of a GS2 gene in melon (Cucumis melo L.) and its expression patterns under the fertilization of different forms of N.

PubMed

Deng, Yang-Wu; Zhang, Yi-Dong; Chen, Yi; Wang, Shu; Tang, Dong-Mei; Huang, Dan-Feng

2010-01-01

We isolated a novel glutamine synthetase (GS, EC 6.3.1.2) gene M-GS2 (accession: AY773090) by the RACE approach from melon. The full-length cDNA of M-GS2 is 1807 bp and contains a 1296 bp open reading frame (ORF) encoding 432 amino acids. The deduced protein contains conserved structural domains among plant GS2 proteins and shares extensive sequence homology with GS2 enzymes from other higher plants. M-GS2 expresses with specificity in leaf, and identification of a chloroplast transit peptide (cTP) in M-GS2 suggests that it localizes to the chloroplast. As shown by real-time quantitative PCR, distinct forms of nitrogen (N) found in fertilizers transcriptionally regulated M-GS2 differently. Ammonium and nitrate feeding only significantly regulated M-GS2 transcripts in leaf; starving (0.75 mM) or moderate (3.75 mM) N levels dramatically increased M-GS2 transcripts for 1 day, decreasing to a constant low level after 2-3 days, while sufficient N level (7.5 mM) had a minor effect throughout 3 days compared to controls. Glutamate feeding, however, not only significantly regulated M-GS2 transcripts in leaf (decreased initially then increased to higher levels than controls), but also in root, where it was up-regulated continuously. Our results suggested that M-GS2 is the first GS gene cloned and characterized in melon and melon responds to the variations in N fertilization by differentially expressing M-GS2.

GsCBRLK, a calcium/calmodulin-binding receptor-like kinase, is a positive regulator of plant tolerance to salt and ABA stress.

PubMed

Yang, Liang; Ji, Wei; Zhu, Yanming; Gao, Peng; Li, Yong; Cai, Hua; Bai, Xi; Guo, Dianjing

2010-05-01

Calcium/calmodulin-dependent kinases play vital roles in protein phosphorylation in eukaryotes, yet little is known about the phosphorylation process of calcium/calmodulin-dependent protein kinase and its role in stress signal transduction in plants. A novel plant-specific calcium-dependent calmodulin-binding receptor-like kinase (GsCBRLK) has been isolated from Glycine soja. A subcellular localization study using GFP fusion protein indicated that GsCBRLK is localized in the plasma membrane. Binding assays demonstrated that calmodulin binds to GsCBRLK with an affinity of 25.9 nM in a calcium-dependent manner and the binding motif lies between amino acids 147 to169 within subdomain II of the kinase domain. GsCBRLK undergoes autophosphorylation and Myelin Basis Protein phosphorylation in the presence of calcium. It was also found that calcium/calmodulin positively regulates GsCBRLK kinase activity through direct interaction between the calmodulin-binding domain and calmodulin. So, it is likely that GsCBRLK responds to an environmental stimulus in two ways: by increasing the protein expression level and by regulating its kinase activity through the calcium/calmodulin complex. Furthermore, cold, salinity, drought, and ABA stress induce GsCBRLK gene transcripts. Over-expression of GsCBRLK in transgenic Arabidopsis resulted in enhanced plant tolerance to high salinity and ABA and increased the expression pattern of a number of stress gene markers in response to ABA and high salt. These results identify GsCBRLK as a molecular link between the stress- and ABA-induced calcium/calmodulin signal and gene expression in plant cells.

Ligand-Mediated Activation of an Engineered Gs G Protein-Coupled Receptor in Osteoblasts Increases Trabecular Bone Formation

PubMed Central

Hsiao, Edward C.; Millard, Susan M.; Louie, Alyssa; Huang, Yong; Conklin, Bruce R.; Nissenson, Robert A.

2010-01-01

Age-dependent changes in skeletal growth play important roles in regulating skeletal expansion and in the course of many diseases affecting bone. How G protein-coupled receptor (GPCR) signaling affects these changes is poorly understood. Previously, we described a mouse model expressing Rs1, an engineered receptor with constitutive Gs activity. Rs1 expression in osteoblasts from gestation induced a dramatic age-dependent increase in trabecular bone with features resembling fibrous dysplasia; however, these changes were greatly minimized if Rs1 expression was delayed until after puberty. To further investigate whether ligand-induced activation of the Gs-GPCR pathway affects bone formation in adult mice, we activated Rs1 in adult mice with the synthetic ligand RS67333 delivered continuously via an osmotic pump or intermittently by daily injections. We found that osteoblasts from adult animals can be stimulated to form large amounts of bone, indicating that adult mice are sensitive to the dramatic bone- forming actions of Gs signaling in osteoblasts. In addition, our results show that intermittent and continuous activation of Rs1 led to structurally similar but quantitatively different degrees of trabecular bone formation. These results indicate that activation of a Gs-coupled receptor in osteoblasts of adult animals by either intermittent or continuous ligand administration can increase trabecular bone formation. In addition, osteoblasts located at the bone epiphyses may be more responsive to Gs signaling than osteoblasts at the bone diaphysis. This model provides a powerful tool for investigating the effects of ligand-activated Gs-GPCR signaling on dynamic bone growth and remodeling. PMID:20150184

GsERF6, an ethylene-responsive factor from Glycine soja, mediates the regulation of plant bicarbonate tolerance in Arabidopsis.

PubMed

Yu, Yang; Liu, Ailin; Duan, Xiangbo; Wang, Sunting; Sun, Xiaoli; Duanmu, Huizi; Zhu, Dan; Chen, Chao; Cao, Lei; Xiao, Jialei; Li, Qiang; Nisa, Zaib Un; Zhu, Yanming; Ding, Xiaodong

2016-09-01

This is an original study focus on ERF gene response to alkaline stress. GsERF6 functions as transcription factor and significantly enhanced plant tolerance to bicarbonate (HCO 3 (-) ) in transgenic Arabidopsis . Alkaline stress is one of the most harmful, but little studied environmental factors, which negatively affects plant growth, development and yield. The cause of alkaline stress is mainly due to the damaging consequence of high concentration of the bicarbonate ion, high-pH, and osmotic shock to plants. The AP2/ERF family genes encode plant-specific transcription factors involved in diverse environmental stresses. However, little is known about their physiological functions, especially in alkaline stress responses. In this study, we functionally characterized a novel ERF subfamily gene, GsERF6 from alkaline-tolerant wild soybean (Glycine soja). In wild soybean, GsERF6 was rapidly induced by NaHCO3 treatment, and its overexpression in Arabidopsis enhanced transgenic plant tolerance to NaHCO3 challenge. Interestingly, GsERF6 transgenic lines also displayed increased tolerance to KHCO3 treatment, but not to high pH stress, implicating that GsERF6 may participate specifically in bicarbonate stress responses. We also found that GsERF6 overexpression up-regulated the transcription levels of bicarbonate-stress-inducible genes such as NADP-ME, H (+)-Ppase and H (+)-ATPase, as well as downstream stress-tolerant genes such as RD29A, COR47 and KINI. GsERF6 overexpression and NaHCO3 stress also altered the expression patterns of plant hormone synthesis and hormone-responsive genes. Conjointly, our results suggested that GsERF6 is a positive regulator of plant alkaline stress by increasing bicarbonate ionic resistance specifically, providing a new insight into the regulation of gene expression under alkaline conditions.

Seasonal variations measured by TDR and GPR on an anthropogenic sandy soil and the implications for utility detection

NASA Astrophysics Data System (ADS)

Curioni, Giulio; Chapman, David N.; Metje, Nicole

2017-06-01

The electromagnetic (EM) soil properties are dynamic variables that can change considerably over time, and they fundamentally affect the performance of Ground Penetrating Radar (GPR). However, long-term field studies are remarkably rare and records of the EM soil properties and their seasonal variation are largely absent from the literature. This research explores the extent of the seasonal variation of the apparent permittivity (Ka) and bulk electrical conductivity (BEC) measured by Time Domain Reflectometry (TDR) and their impact on GPR results, with a particularly important application to utility detection. A bespoke TDR field monitoring station was specifically developed and installed in an anthropogenic sandy soil in the UK for 22 months. The relationship between the temporal variation of the EM soil properties and GPR performance has been qualitatively assessed, highlighting notably degradation of the GPR images during wet periods and a few days after significant rainfall events following dry periods. Significantly, it was shown that by assuming arbitrary average values (i.e. not extreme values) of Ka and BEC which do not often reflect the typical conditions of the soil, it can lead to significant inaccuracies in the estimation of the depth of buried targets, with errors potentially up to approximately 30% even over a depth of 0.50 m (where GPR is expected to be most accurate). It is therefore recommended to measure or assess the soil conditions during GPR surveys, and if this is not possible to use typical wet and dry Ka values reported in the literature for the soil expected at the site, to improve confidence in estimations of target depths.

Discrete Functions of Nuclear Receptor Rev-erbα Couple Metabolism to the Clock

PubMed Central

Zhang, Yuxiang; Fang, Bin; Emmett, Matthew J.; Damle, Manashree; Sun, Zheng; Feng, Dan; Armour, Sean M.; Remsberg, Jarrett R.; Jager, Jennifer; Soccio, Raymond E.; Steger, David J.; Lazar, Mitchell A.

2015-01-01

SUMMARY Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbα, a transcription factor (TF) that functions both as a core repressive component of the cell autonomous clock and as a regulator of metabolic genes. Here we show that Rev-erbα modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbα to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbα regulates metabolic genes primarily by recruiting the HDAC3 corepressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erbα and ROR TFs provides a universal mechanism for self-sustained control of molecular clock across all tissues, whereas Rev-erbα utilizes lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. PMID:26044300

Improved method for reliable HMW-GS identification by RP-HPLC and SDS-PAGE in common wheat cultivars

USDA-ARS?s Scientific Manuscript database

The accurate identification of alleles for high-molecular weight glutenins (HMW-GS) is critical for wheat breeding programs targeting end-use quality. RP-HPLC methods were optimized for separation of HMW-GS, resulting in enhanced resolution of 1By and 1Dx subunits. Statistically significant differe...

Growth and photo-response of NbSe2 and NbS2 crystals

NASA Astrophysics Data System (ADS)

Patel, Kunjal; Solanki, G. K.; Pataniya, Pratik; Patel, K. D.

2018-05-01

Transition metal dichalcogenides(TMDCs) have attracted intense research efforts due to their drastic properties change as we move towards ultra-thin crystalline layers from their bulk counterparts. Many well studied members of this family such as MoS2, WS2, WSe2, WS2 etc. have shown potential for flexible electronic devices including photovoltaic applications. The TMDCs like NbSe2 and NbS2 are relatively less studied layered compounds consisting of staked sandwiches of Se-Nb-Se/S-Nb-Se tri-layers with strong covalent/ionic intra layer bonds and weak Van der Waals interlayer interactions. In the present work, author have grown the crystals of NbSe2 and NbS2 by Direct Vapour Transport (DVT) technique and the material composition is confirmed using EDAX data. Photoelectrochemical (PEC) solar cell measurements are performed under monochromatic light illumination at different intensities and various solar cell parameters are calculated. These crystalline semiconductor electrodes were also analysed by photocurrent-voltage characteristics in a PEC solar cell structure (Cu/NbSe2/(0.1M K4Fe(CN)6 + 0.1M K3Fe(CN)6) and Cu/NbS2/(0.1M K4Fe(CN)6 +0.1M K3Fe(CN)6)). Blue coloured light gave the maximum efficiency. For further analysis of photodetection properties of the grown crystals, Ag painted broad low contact resistance electrical contacts were drawn from the crystals and its transient photoresponse was studied to evaluate different detector parameters.

Power line identification of millimeter wave radar based on PCA-GS-SVM

NASA Astrophysics Data System (ADS)

Fang, Fang; Zhang, Guifeng; Cheng, Yansheng

2017-12-01

Aiming at the problem that the existing detection method can not effectively solve the security of UAV's ultra low altitude flight caused by power line, a power line recognition method based on grid search (GS) and the principal component analysis and support vector machine (PCA-SVM) is proposed. Firstly, the candidate line of Hough transform is reduced by PCA, and the main feature of candidate line is extracted. Then, upport vector machine (SVM is) optimized by grid search method (GS). Finally, using support vector machine classifier optimized parameters to classify the candidate line. MATLAB simulation results show that this method can effectively identify the power line and noise, and has high recognition accuracy and algorithm efficiency.

Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake

PubMed Central

Nakajima, Ken-ichiro; Cui, Zhenzhong; Li, Chia; Meister, Jaroslawna; Cui, Yinghong; Fu, Ou; Smith, Adam S.; Jain, Shalini; Lowell, Bradford B.; Krashes, Michael J.; Wess, Jürgen

2016-01-01

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity. PMID:26743492

Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.

PubMed

Nakajima, Ken-ichiro; Cui, Zhenzhong; Li, Chia; Meister, Jaroslawna; Cui, Yinghong; Fu, Ou; Smith, Adam S; Jain, Shalini; Lowell, Bradford B; Krashes, Michael J; Wess, Jürgen

2016-01-08

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.

The NBS Reaction: A Simple Explanation for the Predominance of Allylic Substitution over Olefin Addition by Bromine at Low Concentrations.

ERIC Educational Resources Information Center

Wamser, Carl C.; Scott, Lawrence T.

1985-01-01

Examines mechanisms related to use of N-bromosuccinimide (NBS) for bromination at an allylic position. Also presents derived rate laws for three possible reactions of molecular bromine with an alkene: (1) free radical substitution; (2) free radical addition; and (3) electrophilic addition. (JN)

[Construction of Rev-erbβ gene knockout HEK293 cell line with CRISPR/Cas9 system].

PubMed

Chen, Fang; Zhang, Weifeng; Zhao, Junli; Yang, Peiyan; Ma, Rui; Xia, Haibin

2016-11-01

Objective To prepare Rev-erbβ knockout HEK293 cells using clustered regularly interspaced short palindromic repeats/Cas 9 nuclease (CRISPR/Cas9) gene editing technology. Methods The knock-in or knockout of Rev-erbβ gene could be realized by single-guide RNA (sgRNA)-mediated Cas9 cutting of target DNA, and followed by DNA homologous recombination or non-homologous end joining-mediated DNA repair. Firstly, four sgRNAs were designed for Rev-erbβ gene. The sgRNA1 and sgRNA2 with the higher activity were respectively used to construct pCMV-hCas9-U6-Rev-erbβ sgRNA1 and pCMV-hCas9-U6-Rev-erbβ sgRNA2. Then, pCMV-hCas9-U6-Rev-erbβ sgRNA1, pCMV-hCas9-U6-Rev-erbβ sgRNA2 and pAd5-E1/hRev-erbβ donor plasmid vectors were co-transfected into HEK293 cells. Through drug screening, cloning and sequencing, the Rev-erbβ gene-knockout HEK293 (Rev-erbβ -/- ) cell lines were obtained with one chain integrated with exogenous gene fragment and the other chain for deletion mutants. Finally, the HEK293 (Rev-erbβ -/- ) cell lines (C3-6) was detected with real-time quantitative PCR and Western blotting. Results Expression of Rev-erbβ mRNA and protein was undetectable in HEK293 Rev-erbβ -/- cell line. Conclusion Using CRISPR/Cas9 technology, the HEK293 Rev-erbβ -/- cell line has been successfully constructed, which would provide an effective tool for the study on the function of Rev-erbβ.

Circadian Amplitude Regulation via FBXW7-Targeted REV-ERBα Degradation.

PubMed

Zhao, Xuan; Hirota, Tsuyoshi; Han, Xuemei; Cho, Han; Chong, Ling-Wa; Lamia, Katja; Liu, Sihao; Atkins, Annette R; Banayo, Ester; Liddle, Christopher; Yu, Ruth T; Yates, John R; Kay, Steve A; Downes, Michael; Evans, Ronald M

2016-06-16

Defects in circadian rhythm influence physiology and behavior with implications for the treatment of sleep disorders, metabolic disease, and cancer. Although core regulatory components of clock rhythmicity have been defined, insight into the mechanisms underpinning amplitude is limited. Here, we show that REV-ERBα, a core inhibitory component of clock transcription, is targeted for ubiquitination and subsequent degradation by the F-box protein FBXW7. By relieving REV-ERBα-dependent repression, FBXW7 provides an unrecognized mechanism for enhancing the amplitude of clock gene transcription. Cyclin-dependent kinase 1 (CDK1)-mediated phosphorylation of REV-ERBα is necessary for FBXW7 recognition. Moreover, targeted hepatic disruption of FBXW7 alters circadian expression of core clock genes and perturbs whole-body lipid and glucose levels. This CDK1-FBXW7 pathway controlling REV-ERBα repression defines an unexpected molecular mechanism for re-engaging the positive transcriptional arm of the clock, as well as a potential route to manipulate clock amplitude via small molecule CDK1 inhibition. Copyright © 2016 Elsevier Inc. All rights reserved.

Swift observations of GS 1826-238

NASA Astrophysics Data System (ADS)

Ji, L.; Santangelo, A.; Zhang, S.; Ducci, L.; Suleimanov, V.

2018-02-01

GS 1826-238 is a well-studied low-mass X-ray binary neutron star. This source was in a persistent hard state since its discovery in 1988 and until 2014 June. After that, the source exhibited several softer periods of enhanced intensity in the energy range 2-20 keV. We studied the long-term light curves of MAXI (Monitor of All Sky X-ray Image) and Swift/BAT, and found clearly two branches in the MAXI-BAT and hardness-intensity diagrams, which correspond to the persistent state and softer periods, respectively. We analysed 21 Swift/XRT observations, of which four were located in the persistent state while the others were in softer periods or in a state between them. The XRT spectra could be generally fitted by using an absorbed Comptonization model with no other components required. We found a peculiar relationship between the luminosity and the hardness in the energy range of 0.6-10 keV: when the luminosity is larger (smaller) than 4 per cent-6 per cent Ledd, the hardness is anti-correlated (correlated) with luminosity. We also estimated the variability for each observation by using the fractional rms in the 0.1-10 Hz range. We found that the observations in the persistent state had a large fractional rms of ˜25 per cent, similar to other low-mass X-ray binaries. However, the variability is mainly found in the range of 5 per cent-20 per cent during softer periods. We suggest that GS 1826-238 did not evolve into the soft state of atoll sources, and all the observed XRT observations during the softer periods resemble a peculiar intermediate state of atoll sources.

RevBayes: Bayesian Phylogenetic Inference Using Graphical Models and an Interactive Model-Specification Language

PubMed Central

Höhna, Sebastian; Landis, Michael J.

2016-01-01

Programs for Bayesian inference of phylogeny currently implement a unique and fixed suite of models. Consequently, users of these software packages are simultaneously forced to use a number of programs for a given study, while also lacking the freedom to explore models that have not been implemented by the developers of those programs. We developed a new open-source software package, RevBayes, to address these problems. RevBayes is entirely based on probabilistic graphical models, a powerful generic framework for specifying and analyzing statistical models. Phylogenetic-graphical models can be specified interactively in RevBayes, piece by piece, using a new succinct and intuitive language called Rev. Rev is similar to the R language and the BUGS model-specification language, and should be easy to learn for most users. The strength of RevBayes is the simplicity with which one can design, specify, and implement new and complex models. Fortunately, this tremendous flexibility does not come at the cost of slower computation; as we demonstrate, RevBayes outperforms competing software for several standard analyses. Compared with other programs, RevBayes has fewer black-box elements. Users need to explicitly specify each part of the model and analysis. Although this explicitness may initially be unfamiliar, we are convinced that this transparency will improve understanding of phylogenetic models in our field. Moreover, it will motivate the search for improvements to existing methods by brazenly exposing the model choices that we make to critical scrutiny. RevBayes is freely available at http://www.RevBayes.com. [Bayesian inference; Graphical models; MCMC; statistical phylogenetics.] PMID:27235697

First Line Treatment Response in Patients with Transmitted HIV Drug Resistance and Well Defined Time Point of HIV Infection: Updated Results from the German HIV-1 Seroconverter Study

PubMed Central

zu Knyphausen, Fabia; Scheufele, Ramona; Kücherer, Claudia; Jansen, Klaus; Somogyi, Sybille; Dupke, Stephan; Jessen, Heiko; Schürmann, Dirk; Hamouda, Osamah; Meixenberger, Karolin; Bartmeyer, Barbara

2014-01-01

Background Transmission of drug-resistant HIV-1 (TDR) can impair the virologic response to antiretroviral combination therapy. Aim of the study was to assess the impact of TDR on treatment success of resistance test-guided first-line therapy in the German HIV-1 Seroconverter Cohort for patients infected with HIV between 1996 and 2010. An update of the prevalence of TDR and trend over time was performed. Methods Data of 1,667 HIV-infected individuals who seroconverted between 1996 and 2010 were analysed. The WHO drug resistance mutations list was used to identify resistance-associated HIV mutations in drug-naïve patients for epidemiological analysis. For treatment success analysis the Stanford algorithm was used to classify a subset of 323 drug-naïve genotyped patients who received a first-line cART into three resistance groups: patients without TDR, patients with TDR and fully active cART and patients with TDR and non-fully active cART. The frequency of virologic failure 5 to 12 months after treatment initiation was determined. Results Prevalence of TDR was stable at a high mean level of 11.9% (198/1,667) in the HIV-1 Seroconverter Cohort without significant trend over time. Nucleotide reverse transcriptase inhibitor resistance was predominant (6.0%) and decreased significantly over time (OR = 0.92, CI = 0.87–0.98, p = 0.01). Non-nucleoside reverse transcriptase inhibitor (2.4%; OR = 1.00, CI = 0.92–1.09, p = 0.96) and protease inhibitor resistance (2.0%; OR = 0.94, CI = 0.861.03, p = 0.17) remained stable. Virologic failure was observed in 6.5% of patients with TDR receiving fully active cART, 5,6% of patients with TDR receiving non-fully active cART and 3.2% of patients without TDR. The difference between the three groups was not significant (p = 0.41). Conclusion Overall prevalence of TDR remained stable at a rather high level. No significant differences in the frequency of virologic failure were identified during

Rev-erb beta regulates the Srebp-1c promoter and mRNA expression in skeletal muscle cells

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

Ramakrishnan, Sathiya N.; Lau, Patrick; Crowther, Lisa M.

2009-10-30

The nuclear hormone receptor, Rev-erb beta operates as a transcriptional silencer. We previously demonstrated that exogenous expression of Rev-erb{beta}{Delta}E in skeletal muscle cells increased Srebp-1c mRNA expression. We validated these in vitro observations by injection of an expression vector driving Rev-erb{beta}{Delta}E expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. Paradoxically, Rev-erb{beta} siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erb{beta} expression was necessary for Srebp-1c expression. ChIP analysis demonstrated that Rev-erb{beta} was recruited to the Srebp-1c promoter. Moreover, Rev-erb{beta} trans-activated the Srebp-1c promoter, in contrast, Rev-erb{beta} efficiently repressed the Rev-erb{alpha} promoter, amore » previously characterized target gene. Finally, treatment with the Rev-erb agonist (hemin) (i) increased the trans-activation of the Srebp-1c promoter by Rev-erb{beta}; and (ii) increased Rev-erb{beta} and Srebp-1c mRNA expression. These data suggest that Rev-erb{beta} has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis.« less

Metal-dependent hydrolysis of myelin basic protein by IgGs from the sera of patients with multiple sclerosis.

PubMed

Polosukhina, Dar'ya I; Kanyshkova, Tat'yana G; Doronin, Boris M; Tyshkevich, Olga B; Buneva, Valentina N; Boiko, Alexey N; Gusev, Evgenii I; Nevinsky, Georgy A; Favorova, Olga O

2006-02-28

Homogeneous IgG fractions were obtained by chromatography of the sera of patients with multiple sclerosis (MS) on Protein G-Sepharose under conditions that remove non-specifically bound proteins. These IgGs contained several chelated metals, the relative amount of which decreases in the order: Fe>or=Ca>Cu>or=Zn>or=Mg>or=Mn>or=Pb>or=Co>or=Ni. In contrast to homogeneous IgGs of healthy individuals, Abs of MS patients effectively hydrolyzed human myelin basic protein (MBP). A minor metal-dependent fraction was obtained by chromatography of highly purified IgGs from MS patient on Chelex-100. This IgG fraction did not hydrolyze human MBP in the absence of Me(2+) ions but was activated after addition of Me(2+) ions: Mg(2+)>Mn(2+)>Cu(2+)>Ca(2+). Proteolytic activities of IgGs from other MS patients were also activated by other metal ions (Ni(2+), Fe(2+), Co(2+), Zn(2+), Pb(2+), and Co(2+)) and especially Ni(2+). Ni(2+)-activated IgGs were separated into distinct MBP-hydrolyzing fractions by chromatography on HiTraptrade mark Chelating Sepharose charged with Ni(2+). Detection of Mg(2+)-dependent proteolytic activity in the SDS-PAGE area corresponding only to IgG provided direct evidence that IgG from sera of MS patients possesses metal-dependent human MBP-hydrolyzing activity. Observed properties of MS abzymes distinguish them from other known mammalian metalloproteases and demonstrate their pronounced catalytic diversity. Metal-dependent IgGs from MS patients represent the first example of abzymes with metal-dependent proteolytic activity.

RevBayes: Bayesian Phylogenetic Inference Using Graphical Models and an Interactive Model-Specification Language.

PubMed

Höhna, Sebastian; Landis, Michael J; Heath, Tracy A; Boussau, Bastien; Lartillot, Nicolas; Moore, Brian R; Huelsenbeck, John P; Ronquist, Fredrik

2016-07-01

Programs for Bayesian inference of phylogeny currently implement a unique and fixed suite of models. Consequently, users of these software packages are simultaneously forced to use a number of programs for a given study, while also lacking the freedom to explore models that have not been implemented by the developers of those programs. We developed a new open-source software package, RevBayes, to address these problems. RevBayes is entirely based on probabilistic graphical models, a powerful generic framework for specifying and analyzing statistical models. Phylogenetic-graphical models can be specified interactively in RevBayes, piece by piece, using a new succinct and intuitive language called Rev. Rev is similar to the R language and the BUGS model-specification language, and should be easy to learn for most users. The strength of RevBayes is the simplicity with which one can design, specify, and implement new and complex models. Fortunately, this tremendous flexibility does not come at the cost of slower computation; as we demonstrate, RevBayes outperforms competing software for several standard analyses. Compared with other programs, RevBayes has fewer black-box elements. Users need to explicitly specify each part of the model and analysis. Although this explicitness may initially be unfamiliar, we are convinced that this transparency will improve understanding of phylogenetic models in our field. Moreover, it will motivate the search for improvements to existing methods by brazenly exposing the model choices that we make to critical scrutiny. RevBayes is freely available at http://www.RevBayes.com [Bayesian inference; Graphical models; MCMC; statistical phylogenetics.]. © The Author(s) 2016. Published by Oxford University Press, on behalf of the Society of Systematic Biologists.

Molecular interaction between K-Ras and H-REV107 in the Ras signaling pathway.

PubMed

Han, Chang Woo; Jeong, Mi Suk; Jang, Se Bok

2017-09-16

Ras proteins are small GTPases that serve as master moderators of a large number of signaling pathways involved in various cellular processes. Activating mutations in Ras are found in about one-third of cancers. H-REV107, a K-Ras binding protein, plays an important role in determining K-Ras function. H-REV107 is a member of the HREV107 family of class II tumor suppressor genes and a growth inhibitory Ras target gene that suppresses cellular growth, differentiation, and apoptosis. Expression of H-REV107 was strongly reduced in about 50% of human carcinoma cell lines. However, the specific molecular mechanism by which H-REV107 inhibits Ras is still unknown. In the present study, we suggest that H-REV107 forms a strong complex with activating oncogenic mutation Q61H K-Ras from various biochemical binding assays and modeled structures. In addition, the interaction sites between K-Ras and H-REV107 were predicted based on homology modeling. Here, we found that some structure-based mutants of the K-Ras disrupted the complex formation with H-REV107. Finally, a novel molecular mechanism describing K-Ras and H-REV107 binding is suggested and insights into new K-Ras effector target drugs are provided. Copyright © 2017 Elsevier Inc. All rights reserved.

Ectopic Expression of a Glycine soja myo-Inositol Oxygenase Gene (GsMIOX1a) in Arabidopsis Enhances Tolerance to Alkaline Stress

PubMed Central

Chen, Chen; Sun, Xiaoli; Duanmu, Huizi; Yu, Yang; Liu, Ailin; Xiao, Jialei; Zhu, Yanming

2015-01-01

Myo-inositol participates in various aspects of plant physiology, and myo-inositol oxygenase is the key enzyme of the myo-inositol oxygenation pathway. Previous studies indicated that myo-inositol oxygenase may play a role in plant responses to abiotic stresses. In this study, we focused on the functional characterization of GsMIOX1a, a remarkable alkaline stress-responsive gene of Glycine soja 07256, based on RNA-seq data. Using quantitative real-time PCR, we demonstrated that GsMIOX1a is rapidly induced by alkaline stress and expressed predominantly in flowers. We also elucidated the positive function of GsMIOX1a in the alkaline response in the wild type, atmiox1 mutant as well as GsMIOX1a-overexpressing Arabidopsis. We determined that atmiox1 mutant decreased Arabidopsis tolerance to alkaline stress, whereas GsMIOX1a overexpression increased tolerance. Moreover, the expression levels of some alkaline stress-responsive and inducible marker genes, including H+-Ppase, NADP-ME, KIN1 and RD29B, were also up-regulated in GsMIOX1a overexpression lines compared with the wild type and atmiox1 mutant. Together, these results suggest that the GsMIOX1a gene positively regulates plant tolerance to alkaline stress. This is the first report to demonstrate that ectopic expression of myo-inositol oxygenase improves alkaline tolerance in plants. PMID:26091094

Solvothermal-induced self-assembly of Fe2O3/GS aerogels for high Li-storage and excellent stability.

PubMed

Wang, Ronghua; Xu, Chaohe; Du, Meng; Sun, Jing; Gao, Lian; Zhang, Peng; Yao, Heliang; Lin, Chucheng

2014-06-12

A novel solvothermal-induced self-assembly approach, using colloid sol as precursor, is developed to construct monolithic 3D metal oxide/GS (graphene sheets) aerogels. During the solvothermal process, graphene oxide (GO) is highly reduced to GS and self-assembles into 3D macroscopic hydrogels, accompanying with in situ transformation of colloid sol to metal oxides. As a proof of concept, Fe2 O3 /GS aerogels are synthesized based on Fe(OH)3 sol, in which GS self-assemble into an interconnected macroporous framework and Fe2 O3 nanocrystals (20-50 nm) uniformly deposit on GS. Benefitting from the integration of macroporous structures, large surface area, high electrical conductivity, and good electrode homogeneity, the hybrid electrode manifests a superior rate capability (930, 660 and 520 mAh g(-1) at 500, 2000 and 4000 mA g(-1), respectively) and excellent prolonged cycling stability at high rates (733 mAh g(-1) during 1000 charge/discharge cycles at 2000 mA g(-1)), demonstrating its great potential for application in high performance lithium ion batteries. The work described here provides a versatile pathway to construct various graphene-based hybrid aerogels. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Comment on 'Precision global measurements of London penetration depth in FeTe0.58Se0.42'

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

Cho, Kyuil; Kim, Hyunsoo; Tanatar, Makariy A.

2012-08-21

We reply to the Comment by Klein, Rodière, and Marcenat [ Phys. Rev. B 86 066501 (2012)] on our paper [ Phys. Rev. B 84 174502 (2011)]. Our work was motivated by Klein et al. [ Phys. Rev. B 82 184506 (2010)]. In their paper, Klein et al. have attributed a factor of 5 difference in the value of the London penetration depth obtained from their tunnel diode resonator (TDR) measurements and calculated from the “field of first penetration”to the surface roughness, although they have not verified it experimentally. In our paper, we have studied the effects of deliberately introducedmore » surface roughness and found that its effects are minor and cannot be responsible for the difference of such magnitude. Instead, we suggest that the value of the field of first penetration measured with Hall arrays cannot be used to extract a true lower critical field due to several reasons outlined in our Reply. We emphasize that the accuracy of the calibration procedure of the TDR technique has been carefully verified in several prior studies and our work on FeTe0.58Se0.42 further confirms it. We show that in their Comment, Klein et al. use wrong arguments of the universal behavior of the superfluid density in the gapless limit, because it is inapplicable for the multiband superconductors. We also discuss the applicability of the clean-limit γ model and the influence of the disorder on the obtained results.« less

GS 455534 selectively suppresses binge eating of palatable food and attenuates dopamine release in the accumbens of sugar-bingeing rats.

PubMed

Bocarsly, Miriam E; Hoebel, Bartley G; Paredes, Daniel; von Loga, Isabell; Murray, Susan M; Wang, Miaoyuan; Arolfo, Maria P; Yao, Lina; Diamond, Ivan; Avena, Nicole M

2014-04-01

Binge eating palatable foods has been shown to have behavioral and neurochemical similarities to drug addiction. GS 455534 is a highly selective reversible aldehyde dehydrogenase 2 inhibitor that has been shown to reduce alcohol and cocaine intake in rats. Given the overlaps between binge eating and drug abuse, we examined the effects of GS 455534 on binge eating and subsequent dopamine release. Sprague-Dawley rats were maintained on a sugar (experiment 1) or fat (experiment 2) binge eating diet. After 25 days, GS 455534 was administered at 7.5 and 15 mg/kg by an intraperitoneal injection, and food intake was monitored. In experiment 3, rats with cannulae aimed at the nucleus accumbens shell were maintained on the binge sugar diet for 25 days. Microdialysis was performed, during which GS 455534 15 mg/kg was administered, and sugar was available. Dialysate samples were analyzed to determine extracellular levels of dopamine. In experiment 1, GS 455534 selectively decreased sugar intake food was made available in the Binge Sugar group but not the Ad libitum Sugar group, with no effect on chow intake. In experiment 2, GS 455534 decreased fat intake in the Binge Fat group, but not the Ad libitum Fat group, however, it also reduced chow intake. In experiment 3, GS 455534 attenuated accumbens dopamine release by almost 50% in binge eating rats compared with the vehicle injection. The findings suggest that selective reversible aldehyde dehydrogenase 2 inhibitors may have the therapeutic potential to reduce binge eating of palatable foods in clinical populations.

Astronaut Anna Fisher Suiting Up For NBS Training

NASA Technical Reports Server (NTRS)

1980-01-01

The Hubble Space Telescope (HST) is a cooperative program of the European Space Agency (ESA) and the National Aeronautical and Space Administration (NASA) to operate a long-lived space-based observatory. It was the flagship mission of NASA's Great Observatories program. The HST program began as an astronomical dream in the 1940s. During the 1970s and 1980s, the HST was finally designed and built becoming operational in the 1990s. The HST was deployed into a low-Earth orbit on April 25, 1990 from the cargo bay of the Space Shuttle Discovery (STS-31). The design of the HST took into consideration its length of service and the necessity of repairs and equipment replacement by making the body modular. In doing so, subsequent shuttle missions could recover the HST, replace faulty or obsolete parts and be re-released. Marshall Space Flight Center's (MSFC's) Neutral Buoyancy Simulator (NBS) served as the test center for shuttle astronauts training for Hubble related missions. Shown is astronaut Anna Fisher suiting up for training on a mockup of a modular section of the HST for an axial scientific instrument change out.

Astronaut Anna Fisher Suited Up For NBS Training

NASA Technical Reports Server (NTRS)

1980-01-01

The Hubble Space Telescope (HST) is a cooperative program of the European Space Agency (ESA) and the National Aeronautical and Space Administration (NASA) to operate a long-lived space-based observatory. It was the flagship mission of NASA's Great Observatories program. The HST program began as an astronomical dream in the 1940s. During the 1970s and 1980s, the HST was finally designed and built becoming operational in the 1990s. The HST was deployed into a low-Earth orbit on April 25, 1990 from the cargo bay of the Space Shuttle Discovery (STS-31). The design of the HST took into consideration its length of service and the necessity of repairs and equipment replacement by making the body modular. In doing so, subsequent shuttle missions could recover the HST, replace faulty or obsolete parts and be re-released. Marshall Space Flight Center's (MSFC's) Neutral Buoyancy Simulator (NBS) served as the test center for shuttle astronauts training for Hubble related missions. Shown is astronaut Anna Fisher suited up for training on a mockup of a modular section of the HST for an axial scientific instrument change out.

Astronaut Anna Fisher Suited Up For NBS Training

NASA Technical Reports Server (NTRS)

1980-01-01

The Hubble Space Telescope (HST) is a cooperative program of the European Space Agency (ESA) and the National Aeronautical and Space Administration (NASA) to operate a long-lived space-based observatory. It was the flagship mission of NASA's Great Observatories program. The HST program began as an astronomical dream in the 1940s. During the 1970s and 1980s, the HST was finally designed and built becoming operational in the 1990s. The HST was deployed into a low-Earth orbit on April 25, 1990 from the cargo bay of the Space Shuttle Discovery (STS-31). The design of the HST took into consideration its length of service and the necessity of repairs and equipment replacement by making the body modular. In doing so, subsequent shuttle missions could recover the HST, replace faulty or obsolete parts and be re-released. Marshall SPace Flight Center's (MSFC's) Neutral Buoyancy Simulator (NBS) served as the test center for shuttle astronauts training for Hubble related missions. Shown is astronaut Anna Fisher suited up for training on a mockup of a modular section of the HST for an axial scientific instrument change out.

Astronaut Anna Fisher Suits Up for NBS Training

NASA Technical Reports Server (NTRS)

1980-01-01

The Hubble Space Telescope (HST) is a cooperative program of the European Space Agency (ESA) and the National Aeronautical and Space Administration (NASA) to operate a long-lived space-based observatory. It was the flagship mission of NASA's Great Observatories program. The HST program began as an astronomical dream in the 1940s. During the 1970s and 1980s, the HST was finally designed and built becoming operational in the 1990s. The HST was deployed into a low-Earth orbit on April 25, 1990 from the cargo bay of the Space Shuttle Discovery (STS-31). The design of the HST took into consideration its length of service and the necessity of repairs and equipment replacement by making the body modular. In doing so, subsequent shuttle missions could recover the HST, replace faulty or obsolete parts and be re-released. Marshall Space Flight Center's (MSFC's) Neutral Buoyancy Simulator (NBS) served as the test center for shuttle astronauts training for Hubble related missions. Shown is astronaut Anna Fisher suiting up for training on a mockup of a modular section of the HST for an axial scientific instrument change out.

Astronaut Anna Fisher Suiting Up For NBS Training

NASA Technical Reports Server (NTRS)

1980-01-01

The Hubble Space Telescope (HST) is a cooperative program of the European Space Agency (ESA) and the National Aeronautical and Space Administration (NASA) to operate a long-lived space-based observatory. It was the flagship mission of NASA's Great Observatories program. The HST program began as an astronomical dream in the 1940s. During the 1970s and 1980s, the HST was finally designed and built becoming operational in the 1990s. The HST was deployed into a low-Earth orbit on April 25, 1990 from the cargo bay of the Space Shuttle Discovery (STS-31). The design of the HST took into consideration its length of service and the necessity of repairs and equipment replacement by making the body modular. In doing so, subsequent shuttle missions could recover the HST, replace faulty or obsolete parts and be re-released. MSFC's Neutral Buoyancy Simulator (NBS) served as the test center for shuttle astronauts training for Hubble related missions. Shown is astronaut Anna Fisher suiting up for training on a mockup of a modular section of the HST for an axial scientific instrument change out.

Astronaut Anna Fisher Suits Up For NBS Training

NASA Technical Reports Server (NTRS)

1980-01-01

The Hubble Space Telescope (HST) is a cooperative program of the European Space Agency (ESA) and the National Aeronautical and Space Administration (NASA) to operate a long-lived space-based observatory. It was the flagship mission of NASA's Great Observatories program. The HST program began as an astronomical dream in the 1940s. During the 1970s and 1980s, the HST was finally designed and built becoming operational in the 1990s. The HST was deployed into a low-Earth orbit on April 25, 1990 from the cargo bay of the Space Shuttle Discovery (STS-31). The design of the HST took into consideration its length of service and the necessity of repairs and equipment replacement by making the body modular. In doing so, subsequent shuttle missions could recover the HST, replace faulty or obsolete parts and be re-released. Marshall Space Flight Center's (MSFC's) Neutral Buoyancy Simulator (NBS) served as the test center for shuttle astronauts training for Hubble related missions. Shown is astronaut Anna Fisher suiting up for training on a mockup of a modular section of the HST for an axial scientific instrument change out.

The orphan receptor Rev-erbα gene is a target of the circadian clock pacemaker

PubMed Central

Triqueneaux, Gérard; Thenot, Sandrine; Kakizawa, Tomoko; Antoch, Marina P; Safi, Rachid; Takahashi, Joseph S; Delaunay, Franck; Laudet, Vincent

2013-01-01

Rev-erbα is a ubiquitously expressed orphan nuclear receptor which functions as a constitutive transcriptional repressor and is expressed in vertebrates according to a robust circadian rhythm. We report here that two Rev-erbα mRNA isoforms, namely Rev-erbα1 and Rev-erbα2, are generated through alternative promoter usage and that both show a circadian expression pattern in an in vitro system using serum-shocked fibroblasts. Both promoter regions P1 (Rev-erbα1) and P2 (Rev-erbα2) contain several E-box DNA sequences, which function as response elements for the core circadian-clock components: CLOCK and BMAL1. The CLOCK–BMAL1 heterodimer stimulates the activity of both P1 and P2 promoters in transient transfection assay by 3–6-fold. This activation was inhibited by the overexpression of CRY1, a component of the negative limb of the circadian transcriptional loop. Critical E-box elements were mapped within both promoters. This regulation is conserved in vertebrates since we found that the CLOCK–BMAL1 heterodimer also regulates the zebrafish Rev-erbα gene. In line with these data Rev-erbα circadian expression was strongly impaired in the livers of Clock mutant mice and in the pineal glands of zebrafish embryos treated with Clock and Bmal1 antisense oligonucleotides. Together these data demonstrate that CLOCK is a critical regulator of Rev-erbα circadian gene expression in evolutionarily distant vertebrates and suggest a role for Rev-erbα in the circadian clock output. PMID:15591021

Fluctuation in the Intermediate Magnetic Phase of Triangular Ising Antiferromagnet (CeS)1.16[Fe0.33(NbS2)2

NASA Astrophysics Data System (ADS)

Michioka, Chishiro; Suzuki, Kazuya; Mibu, Ko

2002-10-01

We applied 57Fe Mössbauer spectroscopy for investigating the Ising spin triangular lattice antiferromagnet (TLA) (CeS)1.16[Fe0.33(NbS2)2] between 2 and 300 K. The spectra revealed that the relaxation time of the hyperfine field markedly changes in the intermediate phase between TN1=22 K and TN2=15 K due to strong spin fluctuation. The relaxation of the hyperfine field is not sufficiently fast as a paramagnet even at 77 K, which is much higher than TN1, and the inverse susceptibility of (LaS)1.14[Fe0.33(NbS2)2] deviates from the Curie-Weiss law below 100 K. These results indicate that an unusual short-range order exists above TN1. The temperature dependence of the Mössbauer spectra can be explained by phase transition of the three-dimensional TLA model with weak interlayer exchange interactions.

Contributions of individual domains to function of the HIV-1 Rev response element.

PubMed

O'Carroll, Ina P; Thappeta, Yashna; Fan, Lixin; Ramirez-Valdez, Edric A; Smith, Sean; Wang, Yun-Xing; Rein, Alan

2017-08-16

The HIV-1 Rev response element (RRE) is a 351-base element in unspliced and partially spliced viral RNA; binding of the RRE by the viral Rev protein induces nuclear export of RRE-containing RNAs, as required for virus replication. It contains one long, imperfect double helix (domain I), one branched domain (domain II) containing a high-affinity Rev-binding site, and two or three additional domains. We previously reported that the RRE assumes an "A" shape in solution and suggested that the location of the Rev binding sites in domains I and II, opposite each other on the two legs of the A, is optimal for Rev binding and explains Rev's specificity for RRE-containing RNAs. Using SAXS and a quantitative functional assay, we have now analyzed a panel of RRE mutants. All the results support the essential role of the A shape for RRE function. Moreover, they suggest that the distal portion of domain I and the three crowning domains all contribute to the maintenance of the A shape. Domains I and II are necessary and sufficient for substantial RRE function, provided they are joined by a flexible linker that allows the two domains to face each other. IMPORTANCE Retroviral replication requires that some of the viral RNAs transcribed in the cell nucleus be exported to the cytoplasm without being spliced. To achieve this, HIV-1 encodes a protein, Rev, which binds to a complex, highly structured element within viral RNA, the Rev Response Element (RRE), and escorts RRE-containing RNAs from the nucleus. We previously reported that the RRE is "A"-shaped and suggested that this architecture, with the 2 legs opposite one another, can explain the specificity of Rev for the RRE. We have analyzed the functional contributions of individual RRE domains, and now report that several domains contribute, with some redundancy, to maintenance of the overall RRE shape. The data strongly support the hypothesis that the opposed placement of the 2 legs is essential for RRE function. Copyright © 2017

Contributions of Individual Domains to Function of the HIV-1 Rev Response Element

PubMed Central

O'Carroll, Ina P.; Thappeta, Yashna; Fan, Lixin; Ramirez-Valdez, Edric A.; Smith, Sean; Wang, Yun-Xing

2017-01-01

ABSTRACT The HIV-1 Rev response element (RRE) is a 351-base element in unspliced and partially spliced viral RNA; binding of the RRE by the viral Rev protein induces nuclear export of RRE-containing RNAs, as required for virus replication. It contains one long, imperfect double helix (domain I), one branched domain (domain II) containing a high-affinity Rev-binding site, and two or three additional domains. We previously reported that the RRE assumes an “A” shape in solution and suggested that the location of the Rev binding sites in domains I and II, opposite each other on the two legs of the A, is optimal for Rev binding and explains Rev's specificity for RRE-containing RNAs. Using small-angle X-ray scattering (SAXS) and a quantitative functional assay, we have now analyzed a panel of RRE mutants. All the results support the essential role of the A shape for RRE function. Moreover, they suggest that the distal portion of domain I and the three crowning domains all contribute to the maintenance of the A shape. Domains I and II are necessary and sufficient for substantial RRE function, provided they are joined by a flexible linker that allows the two domains to face each other. IMPORTANCE Retroviral replication requires that some of the viral RNAs transcribed in the cell nucleus be exported to the cytoplasm without being spliced. To achieve this, HIV-1 encodes a protein, Rev, which binds to a complex, highly structured element within viral RNA, the Rev response element (RRE), and escorts RRE-containing RNAs from the nucleus. We previously reported that the RRE is “A” shaped and suggested that this architecture, with the 2 legs opposite one another, can explain the specificity of Rev for the RRE. We have analyzed the functional contributions of individual RRE domains and now report that several domains contribute, with some redundancy, to maintenance of the overall RRE shape. The data strongly support the hypothesis that the opposed placement of the 2 legs

Large-scale bioinformatic analysis of the regulation of the disease resistance NBS gene family by microRNAs in Poaceae.

PubMed

Habachi-Houimli, Yosra; Khalfallah, Yosra; Makni, Hanem; Makni, Mohamed; Bouktila, Dhia

2016-01-01

In the present study, we have screened 71, 713, 525, 119 and 241 mature miRNA variants from Hordeum vulgare, Oryza sativa, Brachypodium distachyon, Triticum aestivum, and Sorghum bicolor, respectively, and classified them with respect to their conservation status and expression levels. These Poaceae non-redundant miRNA species (1,669) were distributed over a total of 625 MIR families, among which only 54 were conserved across two or more plant species, confirming the relatively recent evolutionary differentiation of miRNAs in grasses. On the other hand, we have used 257 H. vulgare, 286T. aestivum, 119 B. distachyon, 269 O. sativa, and 139 S. bicolor NBS domains, which were either mined directly from the annotated proteomes, or predicted from whole genome sequence assemblies. The hybridization potential between miRNAs and their putative NBS genes targets was analyzed, revealing that at least 454 NBS genes from all five Poaceae were potentially regulated by 265 distinct miRNA species, most of them expressed in leaves and predominantly co-expressed in additional tissues. Based on gene ontology, we could assign these probable miRNA target genes to 16 functional groups, among which three conferring resistance to bacteria (Rpm1, Xa1 and Rps2), and 13 groups of resistance to fungi (Rpp8,13, Rp3, Tsn1, Lr10, Rps1-k-1, Pm3, Rpg5, and MLA1,6,10,12,13). The results of the present analysis provide a large-scale platform for a better understanding of biological control strategies of disease resistance genes in Poaceae, and will serve as an important starting point for enhancing crop disease resistance improvement by means of transgenic lines with artificial miRNAs. Copyright © 2016 Académie des sciences. Published by Elsevier SAS. All rights reserved.

HIV-1 Rev expressed in recombinant Escherichia coli: purification, polymerization, and conformational properties.

PubMed

Wingfield, P T; Stahl, S J; Payton, M A; Venkatesan, S; Misra, M; Steven, A C

1991-07-30

The high-level expression of HIV-1 Rev in Escherichia coli is described. Protein in crude bacterial extracts was dissociated from bound nucleic acid with urea. A simple purification and renaturation protocol, monitored by circular dichroism, is described which results in high yields of pure protein. The purified protein binds with high affinity to the Rev-responsive element mRNA and has nativelike spectroscopic properties. The protein exhibits concentration-dependent self-association as judged by analytical ultracentrifugation and gel filtration measurements. Purified Rev showed reversible heat-induced aggregation over the temperature range 0-30 degrees C. This hydrophobic-driven and nonspecific protein association was inhibited by low concentrations of sulfate ions. Rev solutions at greater than 80 micrograms/mL, incubated at 0-4 degrees C, slowly polymerized to form long hollow fibers of 20-nm diameter. Filament formation occurs at a lower protein concentration and more rapidly in the presence of Rev-responsive mRNA. The nucleic acid containing filaments are about 8 nm in diameter and up to 0.4 micron in length. On the basis of physical properties of the purified protein, we have suggested that in the nucleus of infected cells, Rev binding to the Rev-responsive region of env mRNA may be followed by helical polymerization of the protein which results in coating of the nucleic acid. Coated nucleic acid could be protected from splicing in the nucleus and exported to the cytoplasm.

Two-way time transfers between NRC/NBS and NRC/USNO via the Hermes (CTS) satellite

NASA Technical Reports Server (NTRS)

Costain, C. C.; Daams, H.; Boulanger, J. S.; Hanson, D. W.; Klepczynski, W. J.

1978-01-01

At each station the differences were measured between the local UTC seconds pulse and the remote UTC pulse received by satellite. The difference between the readings, if station delays are assumed to be symmetrical, is two times the difference between the clocks at the two ground station sites. Over a 20-minute period, the precision over the satellite is better than 1 ns. The time transfer from NRC to the CRC satellite terminal near Ottawa and from NBS to the Denver HEW terminal was examined.

General Framework for Animal Food Safety Traceability Using GS1 and RFID

NASA Astrophysics Data System (ADS)

Cao, Weizhu; Zheng, Limin; Zhu, Hong; Wu, Ping

GS1 is global traceability standard, which is composed by the encoding system (EAN/UCC, EPC), the data carriers identified automatically (bar codes, RFID), electronic data interchange standards (EDI, XML). RFID is a non-contact, multi-objective automatic identification technique. Tracing of source food, standardization of RFID tags, sharing of dynamic data are problems to solve urgently for recent traceability systems. The paper designed general framework for animal food safety traceability using GS1 and RFID. This framework uses RFID tags encoding with EPCglobal tag data standards. Each information server has access tier, business tier and resource tier. These servers are heterogeneous and distributed, providing user access interfaces by SOAP or HTTP protocols. For sharing dynamic data, discovery service and object name service are used to locate dynamic distributed information servers.

REV, A BRET-Based Sensor of ERK Activity

PubMed Central

Xu, Chanjuan; Peter, Marion; Bouquier, Nathalie; Ollendorff, Vincent; Villamil, Ignacio; Liu, Jianfeng; Fagni, Laurent; Perroy, Julie

2013-01-01

Networks of signaling molecules are activated in response to environmental changes. How are these signaling networks dynamically integrated in space and time to process particular information? To tackle this issue, biosensors of single signaling pathways have been engineered. Bioluminescence resonance energy transfer (BRET)-based biosensors have proven to be particularly efficient in that matter due to the high sensitivity of this technology to monitor protein–protein interactions or conformational changes in living cells. Extracellular signal-regulated kinases (ERK) are ubiquitously expressed and involved in many diverse cellular functions that might be encoded by the strength and spatio-temporal pattern of ERK activation. We developed a BRET-based sensor of ERK activity, called Rluc8-ERKsubstrate-Venus (REV). As expected, BRET changes of REV were correlated with ERK phosphorylation, which is required for its kinase activity. In neurons, the nature of the stimuli determines the strength, the location, or the moment of ERK activation, thus highlighting how acute modulation of ERK may encode the nature of initial stimulus to specify the consequences of this activation. This study provides evidence for suitability of REV as a new biosensor to address biological questions. PMID:23908646

Molecular characterization of a novel algal glutamine synthetase (GS) and an algal glutamate synthase (GOGAT) from the colorful outer mantle of the giant clam, Tridacna squamosa, and the putative GS-GOGAT cycle in its symbiotic zooxanthellae.

PubMed

Fam, Rachel R S; Hiong, Kum C; Choo, Celine Y L; Wong, Wai P; Chew, Shit F; Ip, Yuen K

2018-05-20

Giant clams harbor symbiotic zooxanthellae (Symbiodinium), which are nitrogen-deficient, mainly in the fleshy and colorful outer mantle. This study aimed to sequence and characterize the algal Glutamine Synthetase (GS) and Glutamate Synthase (GLT), which constitute the glutamate synthase cycle (or GS-GOGAT cycle, whereby GOGAT is the protein acronym of GLT) of nitrogen assimilation, from the outer mantle of the fluted giant clam, Tridacna squamosa. We had identified a novel GS-like cDNA coding sequence of 2325 bp, and named it as T. squamosa Symbiodinium GS1 (TSSGS1). The deduced TSSGS1 sequence had 774 amino acids with a molecular mass of 85 kDa, and displayed the characteristics of GS1 and Nucleotide Diphosphate Kinase. The cDNA coding sequence of the algal GLT, named as T. squamosa Symbiodinium GLT (TSSGLT), comprised 6399 bp, encoding a protein of 2133 amino acids and 232.4 kDa. The zooxanthellal origin of TSSGS1 and TSSGOGAT was confirmed by sequence comparison and phylogenetic analyses. Indeed, TSSGS1 and TSSGOGAT were expressed predominately in the outer mantle, which contained the majority of the zooxanthellae. Immunofluorescence microscopy confirmed the expression of TSSGS1 and TSSGOGAT in the cytoplasm and the plastids, respectively, of the zooxanthellae in the outer mantle. It can be concluded that the symbiotic zooxanthellae of T. squamosa possesses a glutamate synthase (TSSGS1-TSSGOGAT) cycle that can assimilate endogenous ammonia produced by the host clam into glutamate, which can act as a substrate for amino acid syntheses. Thus, our results provide insights into why intact giant clam-zooxanthellae associations do not excrete ammonia under normal circumstances. Copyright © 2018 Elsevier B.V. All rights reserved.

Synthesis and optimization of cholesterol-based diquaternary ammonium Gemini Surfactant (Chol-GS) as a new gene delivery vector.

PubMed

Kim, Bieong-Kil; Doh, Kyung-Oh; Bae, Yun-Ui; Seu, Young-Bae

2011-01-01

Amongst a number of potential nonviral vectors, cationic liposomes have been actively researched, with both gemini surfactants and bola amphiphiles reported as being in possession of good structures in terms of cell viability and in vitro transfection. In this study, a cholesterol-based diquaternary ammonium gemini surfactant (Chol-GS) was synthesized and assessed as a novel nonviral gene vector. Chol-GS was synthesized from cholesterol by way of four reaction steps. The optimal efficiency was found to be at a weight ratio of 1:4 of lipid:DOPE (1,2-dioleoyl-L-alpha- glycero-3-phosphatidylethanolamine), and at a ratio of between 10:1~15:1 of liposome:DNA. The transfection efficiency was compared with commercial liposomes and with Lipofectamine, 1,2-dimyristyloxypropyl-3-dimethylhydroxyethylammonium bromide (DMRIE-C), and N-[1-(2,3-dioleoyloxy)propyl]- N,N,N-trimethylammonium chloride (DOTAP). The results indicate that the efficiency of Chol-GS is greater than that of all the tested commercial liposomes in COS7 and Huh7 cells, and higher than DOTAP and Lipofectamine in A549 cells. Confirmation of these findings was observed through the use of green fluorescent protein expression. Chol-GS exhibited a moderate level of cytotoxicity, at optimum concentrations for efficient transfection, indicating cell viability. Hence, the newly synthesized Chol-GS liposome has the potential of being an excellent nonviral vector for gene delivery.

Piezo channels and GsMTx4: Two milestones in our understanding of excitatory mechanosensitive channels and their role in pathology.

PubMed

Suchyna, Thomas M

2017-11-01

Discovery of Piezo channels and the reporting of their sensitivity to the inhibitor GsMTx4 were important milestones in the study of non-selective cationic mechanosensitive channels (MSCs) in normal physiology and pathogenesis. GsMTx4 had been used for years to investigate the functional role of cationic MSCs, especially in muscle tissue, but with little understanding of its target or inhibitory mechanism. The sensitivity of Piezo channels to bilayer stress and its robust mechanosensitivity when expressed in heterologous systems were keys to determining GsMTx4's mechanism of action. However, questions remain regarding Piezo's role in muscle function due to the non-selective nature of GsMTx4 inhibition toward membrane mechanoenzymes and the implication of MCS channel types by genetic knockdown. Evidence supporting Piezo like activity, at least in the developmental stages of muscle, is presented. While the MSC targets of GsMTx4 in muscle pathology are unclear, its muscle protective effects are clearly demonstrated in two recent in situ studies on normal cardiomyocytes and dystrophic skeletal muscle. The muscle protective function may be due to the combined effect of GsMTx4's inhibitory action on cationic MSCs like Piezo and TRP, and its potentiation of repolarizing K + selective MSCs like K2P and SAKCa. Paradoxically, the potent in vitro action of GsMTx4 on many physiological functions seems to conflict with its lack of in situ side-effects on normal animal physiology. Future investigations into cytoskeletal control of sarcolemma mechanics and the suspected inclusion of MSCs in membrane micro/nano sized domains with distinct mechanical properties will aide our understanding of this dichotomy. Published by Elsevier Ltd.

REV-ERBs agonism suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss partially via FABP4 upregulation.

PubMed

Song, Chao; Tan, Peng; Zhang, Zheng; Wu, Wei; Dong, Yonghui; Zhao, Liming; Liu, Huiyong; Guan, Hanfeng; Li, Feng

2018-01-22

REV-ERBs (REV-ERBα and REV-ERBβ) are transcription repressors and circadian regulators. Previous investigations have shown that REV-ERBs repress the expression of target genes, including MMP9 and CX3CR1, in macrophages. Because MMP9 and CX3CR1 reportedly participate in receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis, we inferred that REV-ERBs might play a role in osteoclastogenesis. In the present study, we found that the REV-ERBα level decreased significantly during RANKL-induced osteoclast differentiation from primary bone marrow-derived macrophages (BMMs). REV-ERBα knockdown by small interfering RNA in BMMs resulted in the enhanced formation of osteoclasts, whereas REV-ERBβ knockdown showed no effect on osteoclast differentiation. Moreover, the REV-ERB agonist SR9009 inhibited osteoclast differentiation and bone resorption. Intraperitoneal SR9009 administration prevented ovariectomy-induced bone loss; this effect was accompanied by decreased serum RANKL and C-terminal telopeptide of type I collagen levels and increased osteoprotegerin levels. Further investigation revealed that NF-κB and MAPK activation and nuclear factor of activated T cells, cytoplasmic 1, and c-fos expression were suppressed by SR9009. The level of reactive oxygen species was also decreased by SR9009, with NADPH oxidase subunits also being down-regulated. In addition, an expression microarray showed that FABP4, an intracellular lipid-binding protein, was up-regulated by REV-ERB agonism. BMS309403, an inhibitor of FABP4, partially prevented the suppression of osteoclastogenesis by SR9009 through stabilizing phosphorylation of p65. To summarize, our results proved that the REV-ERB agonism inhibited osteoclastogenesis partially via FABP4 up-regulation.-Song, C., Tan, P., Zhang, Z., Wu, W., Dong, Y., Zhao, L., Liu, H., Guan, H., Li, F. REV-ERBs agonism suppresses osteoclastogenesis and prevents ovariectomy-induced bone loss partially via FABP4 upregulation.

Genome-wide analysis of Glycine soja ubiquitin (UBQ) genes and functional analysis of GsUBQ10 in response to alkaline stress.

PubMed

Chen, Chao; Chen, Ranran; Wu, Shengyang; Zhu, Dan; Sun, Xiaoli; Liu, Beidong; Li, Qiang; Zhu, Yanming

2018-03-26

Ubiquitin is a highly conserved protein with multiple essential regulation functions through the ubiquitin-proteasome system. Even though its functions in the ubiquitin-mediated protein degradation pathway were very well characterized. The functions of ubiquitin genes in regulating alkaline stress response are not fully established. In this study, we identified 12 potential UBQ genes in Glycine soja genome, and analyzed their evolutionary relationship, conserved domains and promoter cis-elements. We also explored the expression profiles of G. soja UBQ genes under alkaline stress, based on the transcriptome sequencing. We found that the expression of GsUBQ10 was significantly induced by alkaline stress, and function of GsUBQ10 was characterized using overexpression transgenic alfalfa (Medicago sativa). Our results suggested that GsUBQ10 transgenic lines significantly improved the alkaline tolerance in alfalfa. The GsUBQ10 transgenic lines showed lower relative membrane permeability, lower malon dialdehyde content and higher catalase activity than in the wild-type plants. This indicates that GsUBQ10 is involved in regulating the reactive oxygen species accumulation under alkaline stress. Taken together, we identified an ubiquitin gene GsUBQ10 from G. soja, which plays a positive role in responses to alkaline stress in alfalfa. This article is protected by copyright. All rights reserved.

Enhanced energy storage density in lead free (Na0.5Bi0.48Eu0.02)Ti1-xNbxO3(x=0.00, 0.01 & 0.02) ceramics

NASA Astrophysics Data System (ADS)

Yanamandra, Radha; Kandula, Kumara Raja; Bandi, Posidevi; Reddy, H. Satish Kumar; Asthana, Saket; Patri, Tirupathi

2018-05-01

Eco friendly (Na0.5Bi0.48Eu0.02) Ti1-xNbxO3 ceramics were synthesized with help of conventional solid state reaction by using high energy ball milling. The room temperature XRD of Nb5+ substituted NBET ceramics were stabilized in single phase pervoskite structure without any secondary phase. Polarization study reflects long range ferroelectric order for pure NBET ceramics and coercive field enhance with the substitution of Nb5+ ion at Ti site. Further, the substitution of Nb5+ ≥ 0.02 composition induced relaxor future. The energy density calculation shows the maximum energy storage density of 1.02 J/cm3 for x=0.02 ceramics. These results confirms a small fraction of Nb5+ doped NBET ceramics should be good candidates for energy storage applications.

GENE REGULATION. Discrete functions of nuclear receptor Rev-erbα couple metabolism to the clock.

PubMed

Zhang, Yuxiang; Fang, Bin; Emmett, Matthew J; Damle, Manashree; Sun, Zheng; Feng, Dan; Armour, Sean M; Remsberg, Jarrett R; Jager, Jennifer; Soccio, Raymond E; Steger, David J; Lazar, Mitchell A

2015-06-26

Circadian and metabolic physiology are intricately intertwined, as illustrated by Rev-erbα, a transcription factor (TF) that functions both as a core repressive component of the cell-autonomous clock and as a regulator of metabolic genes. Here, we show that Rev-erbα modulates the clock and metabolism by different genomic mechanisms. Clock control requires Rev-erbα to bind directly to the genome at its cognate sites, where it competes with activating ROR TFs. By contrast, Rev-erbα regulates metabolic genes primarily by recruiting the HDAC3 co-repressor to sites to which it is tethered by cell type-specific transcription factors. Thus, direct competition between Rev-erbα and ROR TFs provides a universal mechanism for self-sustained control of the molecular clock across all tissues, whereas Rev-erbα uses lineage-determining factors to convey a tissue-specific epigenomic rhythm that regulates metabolism tailored to the specific need of that tissue. Copyright © 2015, American Association for the Advancement of Science.

RevEcoR: an R package for the reverse ecology analysis of microbiomes.

PubMed

Cao, Yang; Wang, Yuanyuan; Zheng, Xiaofei; Li, Fei; Bo, Xiaochen

2016-07-29

All species live in complex ecosystems. The structure and complexity of a microbial community reflects not only diversity and function, but also the environment in which it occurs. However, traditional ecological methods can only be applied on a small scale and for relatively well-understood biological systems. Recently, a graph-theory-based algorithm called the reverse ecology approach has been developed that can analyze the metabolic networks of all the species in a microbial community, and predict the metabolic interface between species and their environment. Here, we present RevEcoR, an R package and a Shiny Web application that implements the reverse ecology algorithm for determining microbe-microbe interactions in microbial communities. This software allows users to obtain large-scale ecological insights into species' ecology directly from high-throughput metagenomic data. The software has great potential for facilitating the study of microbiomes. RevEcoR is open source software for the study of microbial community ecology. The RevEcoR R package is freely available under the GNU General Public License v. 2.0 at http://cran.r-project.org/web/packages/RevEcoR/ with the vignette and typical usage examples, and the interactive Shiny web application is available at http://yiluheihei.shinyapps.io/shiny-RevEcoR , or can be installed locally with the source code accessed from https://github.com/yiluheihei/shiny-RevEcoR .

Glutamine synthetase and alanine transaminase expression are decreased in livers of aged vs. young beef cows and GS can be upregulated by 17β-estradiol implants.

PubMed

Miles, E D; McBride, B W; Jia, Y; Liao, S F; Boling, J A; Bridges, P J; Matthews, J C

2015-09-01

the MIXED procedure of SAS. Cow BW was not affected ( ≥ 0.96). Implant increased ( ≤ 0.02) total plasma estradiol by 220% (5.07 vs. 1.58 pg/mL) and GS protein by 300%, whereas the relative content of other proteins was not altered ( ≥ 0.16). We conclude that hepatic expression of ALT and GS are reduced in aged vs. young cows, and administration of 17β-estradiol to aged cows increases plasma estradiol and hepatic GS, but not that of other proteins that support hepatic Glu metabolism.

78 FR 27971 - Determination That REV-EYES (Dapiprazole Hydrochloride Ophthalmic Solution), 0.5%, Was Not...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-13

...] Determination That REV-EYES (Dapiprazole Hydrochloride Ophthalmic Solution), 0.5%, Was Not Withdrawn From Sale.... SUMMARY: The Food and Drug Administration (FDA) has determined that REV-EYES (dapiprazole hydrochloride... CFR 314.161)). FDA may not approve an ANDA that does not refer to a listed drug. REV-EYES (dapiprazole...

REV-ERB and ROR: therapeutic targets for treating myopathies

NASA Astrophysics Data System (ADS)

Welch, Ryan D.; Flaveny, Colin A.

2017-08-01

Muscle is primarily known for its mechanical roles in locomotion, maintenance of posture, and regulation of cardiac and respiratory function. There are numerous medical conditions that adversely affect muscle, myopathies that disrupt muscle development, regeneration and protein turnover to detrimental effect. Skeletal muscle is also a vital secretory organ that regulates thermogenesis, inflammatory signaling and directs context specific global metabolic changes in energy substrate preference on a daily basis. Myopathies differ in the causative factors that drive them but share common features including severe reduction in quality of life and significantly increased mortality all due irrefutably to the loss of muscle mass. Thus far clinically viable approaches for preserving muscle proteins and stimulating new muscle growth without unwanted side effects or limited efficacy has been elusive. Over the last few decades, evidence has emerged through in vitro and in vivo studies that suggest the nuclear receptors REV-ERB and ROR might modulate pathways involved in myogenesis and mitochondrial biogenesis. Hinting that REV-ERB and ROR might be targeted to treat myopathies. However there is still a need for substantial investigation into the roles of these nuclear receptors in in vivo rodent models of degenerative muscle diseases and acute injury. Although exciting, REV-ERB and ROR have somewhat confounding roles in muscle physiology and therefore more studies utilizing in vivo models of skeletal muscle myopathies are needed. In this review we highlight the molecular forces driving some of the major degenerative muscular diseases and showcase two promising molecular targets that may have the potential to treat myopathies: ROR and REV-ERB.

Aerodynamic Drag of Cylindrical Vehicles Moving Concentrically Within Long Tubes

DTIC Science & Technology

1988-03-09

FULLY DEVELOPED FLOW b a(zi* ( * f/ Rev b a ffd f d d apfd /apm 104 1.01 1.00505 101. 0.03902 25.09 24.51 1.03 105 1.00506 49.3 0.02004 12.32 12.00 0.97...1.22 0.01178 0.3275 0.2838 0.89 107 0.817 0.007687 0.2201 0.1892 1.01 108 0.584 0.005423 0.1574 0.1347 1.02 B-1 Nw Rev b a ffd f (ri) ’. 0 ) aPfd ...1.08433 0.02399 0.0156 1.36E5 1.164 1.0974 0.1872 0.01822 0.05722 0.03747 0.93 B-2 Rev b a ffd fM (t.) (oC ) APfd /AP .I M fd fd 104 1.2 0.2994 0.03779

Quantification and varietal variation of low molecular weight glutenin subunits (LMW-GS) using size exclusion chromatography.

PubMed

Dangi, Priya; Khatkar, B S

2018-03-01

Crude glutenin of four commercial wheat varieties viz. C 306, HI 977, HW 2004 and PBW 550 of diverse origin and breadmaking quality were fractionated by size-exclusion chromatography into three fractions of decreasing molecular weights. The relative quantity of peak II, containing LMW-GS specifically, varied considerably among the varieties as reflected from their discrete SEC profiles. The area % of peak II, containing protein of interest, was maximal for C 306 (22.08%) followed by PBW 550 (15.86%). The least proportion of LMW-GS were recovered from variety HW 2004 (9.68%). As the concentration of the sample extract injected to the column increased, the resolution of the peak declined in association with the slight shifting of retention time to the higher values. The best results were obtained for variety C 306 at 100 mg protein concentration with 3 M urea buffer. Consequently, the optimized conditions for purification of LMW-GS in appreciable amounts using SEC were established.

[An investigation of trichloroethylene-induced effects on histone methylation in L-02 hepatic cells].

PubMed

Deng, R X; Ren, X H; Ruan, J W; Zheng, J; Zhong, J C; Lu, W X; Zou, X Q; Liu, J J

2017-04-06

Objective: To further explore TCE-induced hepatotoxicity and its mechanisms by identification of trichloroethylene (TCE) induced abnormal histone methylation in human liver cells. Methods: L-02 cells were treated with 0 and 8 mmol/L TCE for 24 h. Histones were extracted by acid. Liquid chromatography electrospray ionization tandem mass spectrometry (ESI-LC-MS/MS) were used to identify and quantify TCE related histone methylations. TCE induced abnormal methylation of H3K79 me2 and H3K79 me3 were validated by Western blot analysis. The further analysis of the function of histone abnormal methylation modifications were done by single cell gel electrophoresis (SCGE) and Western blot analysis of p53 and ɤH2AX. Results: After treatment with TCE for 24 h in L-02 cells, the 36 TCE related histone methylation sites in 28 peptide segments were identified by MS. After treatment with TCE in concentrations of 0 and 8.0 mmol/L in L-02 cells for 24 h, the relative expression level of histone H3K79 me3 were 1.00±0.06, 0.70±0.09 ( t= 15.01, P= 0.015); the relative expression level of histone H3K79 me2 were 1.00±0.05, 0.74±0.07 ( t= 16.69, P= 0.018); the Olive Tail Moment about DNA damage were 1.46±0.28, 3.12± 0.68 ( t= 15.22, P= 0.018); the relative expression levels of p53 were 1.00±0.04, 1.24±0.04 ( t= 18.71, P= 0.012); and the relative expression levels of ɤH2AX were 1.00 ± 0.03, 1.56 ± 0.11 ( t= 8.32, P= 0 045). Conclusion: TCE can induce changes in the relative expression level of H3K79 me2 and H3K79 me3 in L-02 cell, and induce DNA damage, suggesting that TCE may induce changes in the relative expression level of H3K79 me2 and H3K79 me3 by DNA damage.

78 FR 10001 - Proposed Collection; Comment Request for Form 706-GS(D)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-12

... Form 706-GS(D), Generation-Skipping Transfer Tax Return for Distributions. DATES: Written comments should be received on or before April 15, 2013 to be assured of consideration. ADDRESSES: Direct all... [email protected] . SUPPLEMENTARY INFORMATION: Title: Generation-Skipping Transfer Tax Return for...

Anti-tumor efficacy study of the Bruton's tyrosine kinase (BTK) inhibitor, ONO/GS-4059, in combination with the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) demonstrates superior in vivo efficacy compared to ONO/GS-4059 in combination with rituximab.

PubMed

Yasuhiro, Tomoko; Sawada, Wako; Klein, Christian; Kozaki, Ryohei; Hotta, Shingo; Yoshizawa, Toshio

2017-03-01

The activated B-cell diffuse large B-cell-like lymphoma (ABC-DLBCL) correlates with poor prognosis. The B-cell receptor signaling pathway is known to be dysregulated in NHL/CLL and given BTK is a downstream mediator of BCR signaling, BTK constitutes an interesting and obvious therapeutic target. Given the high potency and selectivity of the BTK inhibitor, ONO/GS-4059, it was hypothesized that, the anti-tumor activity of ONO/GS-4059 could be further enhanced by combining it with the anti-CD20 Abs, rituximab (RTX) or obinutuzumab (GA101). ONO/GS-4059 combined with GA101 or RTX was significantly better than the respective monotherapy with tumor growth inhibition (TGI) of 90% for the GA101 combination and 86% for the RTX combination. In contrast, ibrutinib (PCI-32765) combined with RTX did not result in improved efficacy compared with respective monotherapy. Taken together these data indicate that the combination of ONO/GS-4059 with rituximab and particularly obinutuzumab may be an effective treatment for ABC-DLBCL.

Randomised clinical trial: a phase 1, dose-ranging study of the anti-matrix metalloproteinase-9 monoclonal antibody GS-5745 versus placebo for ulcerative colitis.

PubMed

Sandborn, W J; Bhandari, B R; Fogel, R; Onken, J; Yen, E; Zhao, X; Jiang, Z; Ge, D; Xin, Y; Ye, Z; French, D; Silverman, J A; Kanwar, B; Subramanian, G M; McHutchison, J G; Lee, S D; Shackelton, L M; Pai, R K; Levesque, B G; Feagan, B G

2016-07-01

Matrix metalloproteinase-9 is a proteolytic enzyme whose expression is increased in ulcerative colitis. To evaluate the safety and efficacy of GS-5745, a fully humanised anti-matrix metalloproteinase-9 monoclonal antibody, in moderately-to-severely active ulcerative colitis. We randomised 74 patients with ulcerative colitis to treatment with single or multiple ascending intravenous or subcutaneous doses of GS-5745 or placebo. Multiple-dose cohorts received either IV infusions (0.3, 1.0, 2.5 or 5.0 mg/kg GS-5745 or placebo) every 2 weeks (three total IV infusions) or five weekly SC injections (150 mg GS-5745 or placebo). The primary outcomes were the safety, tolerability and pharmacokinetics of escalating single and multiple doses of GS-5745. Exploratory analyses in the multiple-dose cohorts included clinical response (≥3 points or 30% decrease from baseline in Mayo Clinic score and ≥1 point decrease in the rectal bleeding subscore or a rectal bleeding subscore ≤1) and clinical remission (a complete Mayo Clinic score ≤2 with no subscore >1) at Day 36. Biological effects associated with a clinical response to GS-5745 were explored using histological and molecular approaches. Twenty-three of the 42 patients (55%) receiving multiple doses of GS-5745 had adverse events, compared with 5/8 patients (63%) receiving placebo. GS-5745 showed target-mediated drug disposition, approximately dose-proportional increases in maximum plasma concentration and more than dose-proportional increases in the area under the plasma drug concentration-time curve. Clinical response occurred in 18/42 patients (43%) receiving GS-5745 compared with 1/8 patients (13%) receiving placebo. Clinical remission occurred in 6/42 patients (14%) receiving GS-5745 and 0/8 (0%) receiving placebo. Patients with a clinical response to GS-5745 had reductions in matrix metalloproteinase-9 tissue levels (mean 48.9% decrease from baseline compared with a mean 18.5% increase in nonresponders, P = 0

Development of techniques and associated instrumentation for high temperature emissivity measurements

NASA Technical Reports Server (NTRS)

Cunnington, G. R.; Funai, A. I.

1972-01-01

The calibrating and testing procedures for the radiometric emittance measurement apparatus are described. Test results are given for the NBS platinum-rhodium standard (SRM No. 1409), the NBS oxidized Kanthal standard, and the oxidized Rene 41 materials. Results indicate that with the platinum-rhodium standard the measurement system compared with the NBS data to within 0.02 for both total and spectral normal emitttance. Data from the Kanthal strip was consistently higher than NBS values. For oxidized Rene 41, no significant changes in as prepared emittance was observed. The emittance was stable for temperatures up to 1150 K.

Rev1 Recruits Ung to Switch Regions and Enhances dU Glycosylation for Immunoglobulin Class Switch DNA Recombination

PubMed Central

Zan, Hong; White, Clayton A.; Thomas, Lisa M.; Mai, Thach; Li, Guideng; Xu, Zhenming; Zhang, Jinsong; Casali, Paolo

2012-01-01

SUMMARY By diversifying the biological effector functions of antibodies, class switch DNA recombination (CSR) plays a critical role in the maturation of the immune response. It is initiated by AID-mediated dC deamination, yielding dUs, and dU glycosylation by Ung in antibody switch (S) region DNA. Here we showed that the translesion DNA synthesis polymerase Rev1 directly interacted with Ung and targeted in an AID-dependent and Ung-independent fashion the S regions undergoing CSR. Rev1–/– Ung+/+ B cells reduced Ung recruitment to S regions, DNA-dU glycosylation and CSR. This together with an S region spectrum of mutations similar to that of Rev1+/+ Ung–/– B cells suggested that Rev1 operated in the same pathway as Ung, as emphasized by further decreased CSR in Rev1–/– Msh2–/– B cells. Rescue of CSR in Rev1–/– B cells by a catalytically inactive Rev1 mutant showed that the important role of Rev1 in CSR is mediated by Rev1 scaffold, not enzymatic function. PMID:23140944

Improved fatigue resistance in Gsα-deficient and aging mouse skeletal muscles due to adaptive increases in slow fibers

PubMed Central

Feng, Han-Zhong; Chen, Min; Weinstein, Lee S.

2011-01-01

Genetically modified mice with deficiency of the G protein α-subunit (Gsα) in skeletal muscle showed metabolic abnormality with reduced glucose tolerance, low muscle mass, and low contractile force, along with a fast-to-slow-fiber-type switch (Chen M, Feng HZ, Gupta D, Kelleher J, Dickerson KE, Wang J, Hunt D, Jou W, Gavrilova O, Jin JP, Weinstein LS. Am J Physiol Cell Physiol 296: C930–C940, 2009). Here we investigated a hypothesis that the switching to more slow fibers is an adaptive response with specific benefit. The results showed that, corresponding to the switch of myosin isoforms, the thin-filament regulatory proteins troponin T and troponin I both switched to their slow isoforms in the atrophic soleus muscle of 3-mo-old Gsα-deficient mice. This fiber-type switch involving coordinated changes of both thick- and thin-myofilament proteins progressed in the Gsα-deficient soleus muscles of 18- to 24-mo-old mice, as reflected by the expression of solely slow isoforms of myosin and troponin. Compared with age-matched controls, Gsα-deficient soleus muscles with higher proportion of slow fibers exhibited slower contractile and relaxation kinetics and lower developed force, but significantly increased resistance to fatigue, followed by a better recovery. Gsα-deficient soleus muscles of neonatal and 3-wk-old mice did not show the increase in slow fibers. Therefore, the fast-to-slow-fiber-type switch in Gsα deficiency at older ages was likely an adaptive response. The benefit of higher fatigue resistance in adaption to metabolic deficiency and aging provides a mechanism to sustain skeletal muscle function in diabetic patients and elderly individuals. PMID:21680879

Isolation of a full-length CC-NBS-LRR resistance gene analog candidate from sugar pine showing low nucleotide diversity.

Treesearch

K.D. Jermstad; L.A. Sheppard; B.B. Kinloch; A. Delfino-Mix; E.S. Ersoz; K.V. Krutovsky; D.B Neale

2006-01-01

The nucleotide-binding-site and leucine-rich-repeat (NBS–LRR) class of R proteins is abundant and widely distributed in plants. By using degenerate primers designed on the NBS domain in lettuce, we amplified sequences in sugar pine that shared sequence identity with many of the NBS–LRR class resistance genes catalogued in GenBank. The polymerase chain reaction products...

Identification of Small Molecule Translesion Synthesis Inhibitors That Target the Rev1-CT/RIR Protein-Protein Interaction.

PubMed

Sail, Vibhavari; Rizzo, Alessandro A; Chatterjee, Nimrat; Dash, Radha C; Ozen, Zuleyha; Walker, Graham C; Korzhnev, Dmitry M; Hadden, M Kyle

2017-07-21

Translesion synthesis (TLS) is an important mechanism through which proliferating cells tolerate DNA damage during replication. The mutagenic Rev1/Polζ-dependent branch of TLS helps cancer cells survive first-line genotoxic chemotherapy and introduces mutations that can contribute to the acquired resistance so often observed with standard anticancer regimens. As such, inhibition of Rev1/Polζ-dependent TLS has recently emerged as a strategy to enhance the efficacy of first-line chemotherapy and reduce the acquisition of chemoresistance by decreasing tumor mutation rate. The TLS DNA polymerase Rev1 serves as an integral scaffolding protein that mediates the assembly of the active multiprotein TLS complexes. Protein-protein interactions (PPIs) between the C-terminal domain of Rev1 (Rev1-CT) and the Rev1-interacting region (RIR) of other TLS DNA polymerases play an essential role in regulating TLS activity. To probe whether disrupting the Rev1-CT/RIR PPI is a valid approach for developing a new class of targeted anticancer agents, we designed a fluorescence polarization-based assay that was utilized in a pilot screen for small molecule inhibitors of this PPI. Two small molecule scaffolds that disrupt this interaction were identified, and secondary validation assays confirmed that compound 5 binds to Rev1-CT at the RIR interface. Finally, survival and mutagenesis assays in mouse embryonic fibroblasts and human fibrosarcoma HT1080 cells treated with cisplatin and ultraviolet light indicate that these compounds inhibit mutagenic Rev1/Polζ-dependent TLS in cells, validating the Rev1-CT/RIR PPI for future anticancer drug discovery and identifying the first small molecule inhibitors of TLS that target Rev1-CT.

Photometry of the three eclipsing novalike variables EC 21178-5417, GS Pav and V345 Pav

NASA Astrophysics Data System (ADS)

Bruch, Albert

2017-10-01

As part of a project to better characterize comparatively bright, yet little studied cataclysmic variables time resolved photometry of the three eclipsing novalike variables EC 21178-5417, GS Pav und V345 Pav is presented. Previously known orbital periods are significantly improved and long-term ephemeris are derived. Variations of eclipse profiles, occurring on time scales of days to weeks, are analyzed. Out of eclipse the light curves are characterized by low scale flickering superposed on more gradual variations with amplitudes limited to a few tenths of a magnitude and profiles which at least in EC 21178-5417 and GS Pav roughly follow the same pattern in all observed cycles. Additionally, signs for variations on the time scale of some tens of minutes are seen in GS Pav, most clearly in two subsequent nights when in the first of these a signal with a period of 15.7 min was observed over several hours. In the second night variations with twice this period were seen. While no additional insight could be gained on quasi periodic oscillations (QPOs) and dwarf nova oscillations in EC 21178-5417, previously detected by Warner et al. (2003), and while such oscillations could not be found in V345 Pav, stacked power spectra of GS Pav clearly reveal the presence of QPOs over time intervals of several hours with periods varying between 200 s and 500 s in that system.

Critical Behavior and Macroscopic Phase Diagram of the Monoaxial Chiral Helimagnet Cr 1/3NbS 2

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

Clements, Eleanor M.; Das, Raja; Li, Ling

2017-07-26

Cr 1/3NbS 2 is a unique example of a hexagonal chiral helimagnet with high crystalline anisotropy, and has generated growing interest for a possible magnetic field control of the incommensurate spin spiral. Here, we construct a comprehensive phase diagram based on detailed magnetization measurements of a high quality single crystal of Cr 1/3NbS 2 over three magnetic field regions. An analysis of the critical properties in the forced ferromagnetic region yields 3D Heisenberg exponents β = 0.3460 ± 0.040, γ = 1.344 ± 0.002, and T C = 130.78 K ± 0.044, which are consistent with the localized nature themore » of Cr 3+ moments and suggest short-range ferromagnetic interactions. We exploit the temperature and magnetic field dependence of magnetic entropy change (ΔS M) to accurately map the nonlinear crossover to the chiral soliton lattice regime from the chiral helimagnetic phase. Our observations in the low field region are consistent with the existence of chiral ordering in a temperature range above the Curie temperature, T C < T < T*, where a first-order transition has been previously predicted. An analysis of the universal behavior of ΔS M(T,H) experimentally demonstrates for the first time the first-order nature of the onset of chiral ordering.« less

Guggulsterone (GS) inhibits smokeless tobacco and nicotine-induced NF-κB and STAT3 pathways in head and neck cancer cells.

PubMed

Macha, Muzafar A; Matta, Ajay; Chauhan, S S; Siu, K W Michael; Ralhan, Ranju

2011-03-01

Understanding the molecular pathways perturbed in smokeless tobacco- (ST) associated head and neck squamous cell carcinoma (HNSCC) is critical for identifying novel complementary agents for effective disease management. Activation of nuclear factor-kappaB (NF-κB) and cyclooxygenase-2 (COX-2) was reported in ST-associated HNSCC by us [Sawhney,M. et al. (2007) Expression of NF-kappaB parallels COX-2 expression in oral precancer and cancer: association with smokeless tobacco. Int. J. Cancer, 120, 2545-2556]. In search of novel agents for treatment of HNSCC, we investigated the potential of guggulsterone (GS), (4,17(20)-pregnadiene-3,16-dione), a biosafe nutraceutical, in inhibiting ST- and nicotine-induced activation of NF-κB and signal transducer and activator of transcription (STAT) 3 pathways in HNSCC cells. GS inhibited the activation of NF-κB and STAT3 proteins in head and neck cancer cells. This inhibition of NF-κB by GS resulted from decreased phosphorylation and degradation of nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha the inhibitory subunit of NF-κB. Importantly, treatment of HNSCC cells with GS abrogated both ST- and nicotine-induced nuclear activation of NF-κB and pSTAT3 proteins and their downstream targets COX-2 and vascular endothelial growth factor. Furthermore, GS treatment decreased the levels of ST- and nicotine-induced secreted interleukin-6 in culture media of HNSCC cells. In conclusion, our findings demonstrated that GS treatment abrogates the effects of ST and nicotine on activation of NF-κB and STAT3 pathways in HNSCC cells that contribute to inflammatory and angiogenic responses as well as its progression and metastasis. These findings provide a biologic rationale for further clinical investigation of GS as an effective complementary agent for inhibiting ST-induced head and neck cancer.

NREL Fuels and Engines R&D Revs Up Vehicle Efficiency, Performance (Text

Science.gov Websites

Version) | News | NREL Fuels and Engines R&D Revs Up Vehicle Efficiency, Performance (Text Version) NREL Fuels and Engines R&D Revs Up Vehicle Efficiency, Performance (Text Version) NREL's combustion to the evolution of how fuels interact with engine and vehicle design. This is a text version of

Contract W911NF-09-1-0384 (Purdue University)

DTIC Science & Technology

2012-10-27

spin system, Physical Review A , (02 2010): 22324. doi: 10.1103/PhysRevA.81.022324 08/31/2011 8.00 Sabre Kais, Anmer Daskin . Group leaders... a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. a ...billions ) and developed new quantum algorithms to solve complex chemistry problems such as global optimization and excited states of molecules. ( a ) Papers

Assessing the osteoblast transcriptome in a model of enhanced bone formation due to constitutive Gs-G protein signaling in osteoblasts

PubMed Central

Wattanachanya, Lalita; Wang, Liping; Millard, Susan M.; Lu, Wei-Dar; O’Carroll, Dylan; Hsiao, Edward C.; Conklin, Bruce R.; Nissenson, Robert A.

2015-01-01

G protein–coupled receptor (GPCR) signaling in osteoblasts (OBs) is an important regulator of bone formation. We previously described a mouse model expressing Rs1, an engineered constitutively active Gs-coupled GPCR, under the control of the 2.3-kb Col I promoter. These mice showed a dramatic age-dependent increase in trabecular bone of femurs. Here, we further evaluated the effects of enhanced Gs signaling in OBs on intramembranous bone formation by examining calvariae of 1- and 9-week-old Col1(2.3)/Rs1 mice and characterized the in vivo gene expression specifically occurring in osteoblasts with activated Gs G protein–coupled receptor signaling, at the cellular level rather than in a whole bone. Rs1 calvariae displayed a dramatic increase in bone volume with partial loss of cortical structure. By immunohistochemistry, Osterix was detected in cells throughout the inter-trabecular space while Osteocalcin was expressed predominantly in cells along bone surfaces, suggesting the role of paracrine mediators secreted from OBs driven by 2.3-kb Col I promoter could influence early OB commitment, differentiation, and/or proliferation. Gene expression analysis of calvarial OBs revealed that genes affected by Rs1 signaling include those encoding proteins important for cell differentiation, cytokines and growth factors, angiogenesis, coagulation, and energy metabolism. The set of Gs-GPCRs and other GPCRs that may contribute to the observed skeletal phenotype and candidate paracrine mediators of the effect of Gs signaling in OBs were also determined. Our results identify novel detailed in vivo cellular changes of the anabolic response of the skeleton to Gs signaling in mature OBs. PMID:25704759

Transmitted HIV Drug Resistance Is High and Longstanding in Metropolitan Washington, DC

PubMed Central

Kassaye, Seble G.; Grossman, Zehava; Balamane, Maya; Johnston-White, Betsy; Liu, Chenglong; Kumar, Princy; Young, Mary; Sneller, Michael C.; Sereti, Irini; Dewar, Robin; Rehm, Catherine; Meyer, William; Shafer, Robert; Katzenstein, David; Maldarelli, Frank

2016-01-01

Background. Washington, DC, has 2.5% human immunodeficiency virus (HIV) prevalence, 3.9% among African Americans. Antiretrovirals (ARTs) are the cornerstone for treatment and prevention. Monitoring changes in transmitted drug resistance (TDR) is critical for effective HIV care. Methods. HIV genotype data for individuals enrolled in research studies in metropolitan Washington, D.C., were used to identify TDR using the World Health Organization mutation list [Bennett DE, Camacho RJ, Otelea D, et al. Drug resistance mutations for surveillance of transmitted HIV-1 drug-resistance: 2009 update. PloS One 2009; 4:e4724]. HIV phylogenies were reconstructed using maximum likelihood and Bayesian methods. HIV transmission clusters were supported by 1000 bootstrap values >0.70 and posterior probability >0.95 of having a common ancestor. Results. Among 710 individuals enrolled in 1994–2013, the median age was 38.6 years, 46.2% were female, and 53.3% were African-American. TDR was 22.5% among 566 treatment-naive individuals; 15.8% had nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) resistance, 9.8% had nonnucleoside reverse-transcriptase inhibitor (NNRTI) resistance, and 4.2% had protease inhibitor (PI) resistance. Single class TDR was 10.0%, 5.1%, and 1.6% to NRTIs, NNRTIs, and PIs. Dual TDR to PI and NRTI was seen in 1.6%, NRTI and NNRTI in 3.4%, and triple class TDR in 0.9%. TDR frequency decreased from 1994–2006 (27.1%) to 2007–2013 (19.4%; P = .02). Only 6/79 (7.6%) individuals within transmission clusters had evidence of TDR. Discussions. We identified high prevalence of TDR among HIV-infected individuals in metropolitan Washington, DC, regardless of gender. Active surveillance for TDR is needed to guide ART usage and analyses of risk group contributions to HIV transmission and resistance. PMID:27307507

Use of plant trait data in the ISBA-A-gs model

NASA Astrophysics Data System (ADS)

Calvet, Jean-Christophe

2014-05-01

ISBA-A-gs is a CO2-responsive LSM (Calvet et al., 1998; Gibelin et al., 2006), able to simulate the diurnal cycle of carbon and water vapour fluxes, together with LAI and soil moisture evolution. The various components of ISBA-A-gs are based to a large extent on meta-analyses of trait data. (1) Photosynthesis: ISBA-A-gs uses the model of Goudriaan et al. (1985) modified by Jacobs (1994) and Jacobs et al. (1996). The main parameter is mesophyll conductance (gm). Leaf-level photosynthesis observations were used together with canopy level flux observations to derive gm together with other key parameters of the Jacobs model, including in drought conditions. This permitted implementing detailed representations of the soil moisture stress. Two different types of drought responses are distinguished for both herbaceous vegetation (Calvet, 2000) and forests (Calvet et al., 2004), depending on the evolution of the water use efficiency (WUE) under moderate stress: WUE increases in the early soil water stress stages in the case of the drought-avoiding response, whereas WUE decreases or remains stable in the case of the drought-tolerant response. (2) Plant growth: the leaf biomass is provided by a growth model (Calvet et al., 1998; Calvet and Soussana, 2001) driven by photosynthesis. In contrast to other land surface models, no GDD-based phenology model is used in ISBA-A-gs, as the vegetation growth and senescence are entirely driven by photosynthesis. The leaf biomass is supplied with the carbon assimilated by photosynthesis, and decreased by a turnover and a respiration term. Turnover is increased by a deficit in photosynthesis. The leaf onset is triggered by sufficient photosynthesis levels and a minimum LAI value is prescribed. The maximum annual value of LAI is prognostic, i.e. it can be predicted by the model. LAI is derived from leaf biomass using SLA values. The latter are derived from the leaf nitrogen concentration using plasticity parameters. (3) CO2 effect: the

B23/nucleophosmin interacts with bovine immunodeficiency virus Rev protein and facilitates viral replication.

PubMed

Passos-Castilho, Ana Maria; Marchand, Claude; Archambault, Denis

2018-02-01

The bovine immunodeficiency virus (BIV) Rev shuttling protein contains nuclear/nucleolar localization signals and nuclear import/export mechanisms that are novel among lentivirus Rev proteins. Several viral proteins localize to the nucleolus, which may play a role in processes that are essential to the outcome of viral replication. Although BIV Rev localizes to the nucleoli of transfected/infected cells and colocalizes with one of its major proteins, nucleophosmin (NPM1, also known as B23), the role of the nucleolus and B23 in BIV replication remains to be determined. Here, we demonstrate for the first time that BIV Rev interacts with nucleolar phosphoprotein B23 in cells. Using small interfering RNA (siRNA) technology, we show that depletion of B23 expression inhibits virus production by BIV-infected cells, indicating that B23 plays an important role in BIV replication. The interaction between Rev and B23 may represent a potential new target for the development of antiviral drugs against lentiviruses. Copyright © 2017 Elsevier Inc. All rights reserved.

Preparation and characterization of a novel silicon-modified nanobubble

PubMed Central

Li, Maotong; Zhou, Meijun; Li, Fei; Huang, Xiuxian; Pan, Min; Xue, Li

2017-01-01

Nanobubbles (NBs) opened a new field of ultrasound imaging. There is still no practical method to control the diameter of bubbles. In this study, we developed a new method to control the size by incorporating of silicon hybrid lipids into the bubble membrane. The range of particle size of resulting NBs is between 523.02 ± 46.45 to 857.18 ± 82.90, smaller than the conventional microbubbles. The size of resulting NBs increased with the decrease in amount of silicon hybrid lipids, indicating the diameter of NBs can be regulated through modulating the ratio of silicon hybrid lipids in the bubble shell. Typical harmonic signals could be detected. The in vitro and in vivo ultrasound imaging experiments demonstrated these silicon-modified NBs had significantly improved ultrasound contrast enhancement abilities. Cytotoxicity assays revealed that these NBs had no obvious cytotoxicity to the 293 cell line at the tested bubble concentration. Our results showed that the novel NBs could use as nanoscale ultrasound contrast agents, providing the foundation for NBs in future applications including contrast-enhanced imaging and drug/gene delivery. PMID:28557995

UV-induced reversion of his4 frameshift mutations in rad6, rev1, and rev3 mutants of yeast.

PubMed

Lawrence, C W; O'Brien, T; Bond, J

1984-01-01

The UV-induced reversion of two his4 frameshift alleles was much reduced in rad6 mutants of Saccharomyces cerevisiae, an observation that is consistent with the hypothesis that RAD6 function is required for the induction of all types of genetic alteration in misrepair mutagenesis. The reversion of these his4 alleles, together with two others of the same type, was also reduced in rev1 and rev3 mutant strains; in these, however, the extent of the reduction varied considerably with test allele used, in a manner analogous to the results in these strains for base repair substitution test alleles. The general features of UV-induced frameshift and substitution mutagenesis therefore appear quite similar, indicating that they may depend on related processes. If this conclusion is correct, greater attention must be given to integrating models which account for the production of nucleotide additions and deletions into those concerning misrepair mutagenesis.

Growth hormone-releasing hormone resistance in pseudohypoparathyroidism type ia: new evidence for imprinting of the Gs alpha gene.

PubMed

Mantovani, Giovanna; Maghnie, Mohamad; Weber, Giovanna; De Menis, Ernesto; Brunelli, Valeria; Cappa, Marco; Loli, Paola; Beck-Peccoz, Paolo; Spada, Anna

2003-09-01

Heterozygous inactivating mutations in the Gs alpha gene cause Albright's hereditary osteodystrophy. Consistent with the observation that only maternally inherited mutations lead to resistance to hormone action [pseudohypoparathyroidism type Ia (PHP Ia)], recent studies provided evidence for a predominant maternal origin of Gs alpha transcripts in endocrine organs, such as thyroid, gonad, and pituitary. The aim of this study was to investigate the presence of pituitary resistance to hypothalamic hormones acting via Gs alpha-coupled receptors in patients with PHP Ia. Six of nine patients showed an impaired GH responsiveness to GHRH plus arginine, consistent with a complete GH deficiency (GH peak from 2.6-8.6 microg/liter, normal > 16.5), and partial (GH peak 13.9 and 13.6 microg/liter) and normal responses were found in two and one patient, respectively. Accordingly, IGF-I levels were below and in the low-normal range in seven and two patients. All patients had a normal cortisol response to 1 microg ACTH test, suggesting a normal corticotroph function that was confirmed by a normal ACTH and cortisol response to CRH test in three patients. In conclusion, we report that in addition to PTH and TSH resistance, patients with PHP Ia display variable degrees of GHRH resistance, consistent with Gs alpha imprinting in human pituitary.

Identification and characterization of potential NBS-encoding resistance genes and induction kinetics of a putative candidate gene associated with downy mildew resistance in Cucumis

PubMed Central

2010-01-01

Background Due to the variation and mutation of the races of Pseudoperonospora cubensis, downy mildew has in recent years become the most devastating leaf disease of cucumber worldwide. Novel resistance to downy mildew has been identified in the wild Cucumis species, C. hystrix Chakr. After the successful hybridization between C. hystrix and cultivated cucumber (C. sativus L.), an introgression line (IL5211S) was identified as highly resistant to downy mildew. Nucleotide-binding site and leucine-rich repeat (NBS-LRR) genes are the largest class of disease resistance genes cloned from plant with highly conserved domains, which can be used to facilitate the isolation of candidate genes associated with downy mildew resistance in IL5211S. Results Degenerate primers that were designed based on the conserved motifs in the NBS domain of resistance (R) proteins were used to isolate NBS-type sequences from IL5211S. A total of 28 sequences were identified and named as cucumber (C. sativus = CS) resistance gene analogs as CSRGAs. Polygenetic analyses separated these sequences into four different classes. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis showed that these CSRGAs expressed at different levels in leaves, roots, and stems. In addition, introgression from C. hystrix induced expression of the partial CSRGAs in cultivated cucumber, especially CSRGA23, increased four-fold when compared to the backcross parent CC3. Furthermore, the expression of CSRGA23 under P. cubensis infection and abiotic stresses was also analyzed at different time points. Results showed that the P. cubensis treatment and four tested abiotic stimuli, MeJA, SA, ABA, and H2O2, triggered a significant induction of CSRGA23 within 72 h of inoculation. The results indicate that CSRGA23 may play a critical role in protecting cucumber against P. cubensis through a signaling the pathway triggered by these molecules. Conclusions Four classes of NBS-type RGAs were successfully isolated

Potent inhibitory effects of D-tagatose on the acid production and water-insoluble glucan synthesis of Streptococcus mutans GS5 in the presence of sucrose.

PubMed

Sawada, Daijo; Ogawa, Takaaki; Miyake, Minoru; Hasui, Yoshinori; Yamaguchi, Fuminori; Izumori, Ken; Tokuda, Masaaki

2015-01-01

We examined and compared the inhibitory effects of D-tagatose on the growth, acid production, and water-insoluble glucan synthesis of GS5, a bacterial strain of Streptococcus mutans, with those of xylitol, D-psicose, L-psicose and L-tagatose. GS5 was cultured for 12h in a medium containing 10% (w/v) of xylitol, D-psicose, L-psicose, D-tagatose or L-tagatose, and the inhibitory effect of GS5 growth was assessed. Each sugar showed different inhibitory effects on GS5. Both D-tagatose and xylitol significantly inhibited the acid production and water-insoluble glucan synthesis of GS5 in the presence of 1% (w/v) sucrose. However, the inhibitory effect of acid production by D-tagatose was significantly stronger than that of xylitol in presence of sucrose.

GsLRPK, a novel cold-activated leucine-rich repeat receptor-like protein kinase from Glycine soja, is a positive regulator to cold stress tolerance.

PubMed

Yang, Liang; Wu, Kangcheng; Gao, Peng; Liu, Xiaojuan; Li, Guangpu; Wu, Zujian

2014-02-01

Plant LRR-RLKs serve as protein interaction platforms, and as regulatory modules of protein activation. Here, we report the isolation of a novel plant-specific LRR-RLK from Glycine soja (termed GsLRPK) by differential screening. GsLRPK expression was cold-inducible and shows Ser/Thr protein kinase activity. Subcellular localization studies using GFP fusion protein indicated that GsLRPK is localized in the plasma membrane. Real-time PCR analysis indicated that temperature, salt, drought, and ABA treatment can alter GsLRPK gene transcription in G. soja. However, just protein induced by cold stress not by salinity and ABA treatment in tobacco was found to possess kinase activity. Furthermore, we found that overexpression of GsLRPK in yeast and Arabidopsis can enhance resistance to cold stress and increase the expression of a number of cold responsive gene markers. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Impact of concurrent overexpression of cytosolic glutamine synthetase (GS1) and sucrose phosphate synthase (SPS) on growth and development in transgenic tobacco.

PubMed

Seger, Mark; Gebril, Sayed; Tabilona, Jules; Peel, Amanda; Sengupta-Gopalan, Champa

2015-01-01

The outcome of simultaneously increasing SPS and GS activities in transgenic tobacco, suggests that sucrose is the major determinant of growth and development, and is not affected by changes in N assimilation. Carbon (C) and nitrogen (N) are the major components required for plant growth and the metabolic pathways for C and N assimilation are very closely interlinked. Maintaining an appropriate balance or ratio of sugar to nitrogen metabolites in the cell, is important for the regulation of plant growth and development. To understand how C and N metabolism interact, we manipulated the expression of key genes in C and N metabolism individually and concurrently and checked for the repercussions. Transgenic tobacco plants with a cytosolic soybean glutamine synthetase (GS1) gene and a sucrose phosphate synthase (SPS) gene from maize, both driven by the CaMV 35S promoter were produced. Co-transformants, with both the transgenes were produced by sexual crosses. While GS is the key enzyme in N assimilation, involved in the synthesis of glutamine, SPS plays a key role in C metabolism by catalyzing the synthesis of sucrose. Moreover, to check if nitrate has any role in this interaction, the plants were grown under both low and high nitrogen. The SPS enzyme activity in the SPS and SPS/GS1 co-transformants were the same under both nitrogen regimens. However, the GS activity was lower in the co-transformants compared to the GS1 transformants, specifically under low nitrogen conditions. The GS1/SPS transformants showed a phenotype similar to the SPS transformants, suggesting that sucrose is the major determinant of growth and development in tobacco, and its effect is only marginally affected by increased N assimilation. Sucrose may be functioning in a metabolic capacity or as a signaling molecule.

Multiplexed direct genomic selection (MDiGS): a pooled BAC capture approach for highly accurate CNV and SNP/INDEL detection.

PubMed

Alvarado, David M; Yang, Ping; Druley, Todd E; Lovett, Michael; Gurnett, Christina A

2014-06-01

Despite declining sequencing costs, few methods are available for cost-effective single-nucleotide polymorphism (SNP), insertion/deletion (INDEL) and copy number variation (CNV) discovery in a single assay. Commercially available methods require a high investment to a specific region and are only cost-effective for large samples. Here, we introduce a novel, flexible approach for multiplexed targeted sequencing and CNV analysis of large genomic regions called multiplexed direct genomic selection (MDiGS). MDiGS combines biotinylated bacterial artificial chromosome (BAC) capture and multiplexed pooled capture for SNP/INDEL and CNV detection of 96 multiplexed samples on a single MiSeq run. MDiGS is advantageous over other methods for CNV detection because pooled sample capture and hybridization to large contiguous BAC baits reduces sample and probe hybridization variability inherent in other methods. We performed MDiGS capture for three chromosomal regions consisting of ∼ 550 kb of coding and non-coding sequence with DNA from 253 patients with congenital lower limb disorders. PITX1 nonsense and HOXC11 S191F missense mutations were identified that segregate in clubfoot families. Using a novel pooled-capture reference strategy, we identified recurrent chromosome chr17q23.1q23.2 duplications and small HOXC 5' cluster deletions (51 kb and 12 kb). Given the current interest in coding and non-coding variants in human disease, MDiGS fulfills a niche for comprehensive and low-cost evaluation of CNVs, coding, and non-coding variants across candidate regions of interest. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Investigating the Temporal Patterns within and between Intrinsic Connectivity Networks under Eyes-Open and Eyes-Closed Resting States: A Dynamical Functional Connectivity Study Based on Phase Synchronization

PubMed Central

Wang, Xun-Heng; Li, Lihua; Xu, Tao; Ding, Zhongxiang

2015-01-01

The brain active patterns were organized differently under resting states of eyes open (EO) and eyes closed (EC). The altered voxel-wise and regional-wise resting state active patterns under EO/EC were found by static analysis. More importantly, dynamical spontaneous functional connectivity has been observed in the resting brain. To the best of our knowledge, the dynamical mechanisms of intrinsic connectivity networks (ICNs) under EO/EC remain largely unexplored. The goals of this paper were twofold: 1) investigating the dynamical intra-ICN and inter-ICN temporal patterns during resting state; 2) analyzing the altered dynamical temporal patterns of ICNs under EO/EC. To this end, a cohort of healthy subjects with scan conditions of EO/EC were recruited from 1000 Functional Connectomes Project. Through Hilbert transform, time-varying phase synchronization (PS) was applied to evaluate the inter-ICN synchrony. Meanwhile, time-varying amplitude was analyzed as dynamical intra-ICN temporal patterns. The results found six micro-states of inter-ICN synchrony. The medial visual network (MVN) showed decreased intra-ICN amplitude during EC relative to EO. The sensory-motor network (SMN) and auditory network (AN) exhibited enhanced intra-ICN amplitude during EC relative to EO. Altered inter-ICN PS was found between certain ICNs. Particularly, the SMN and AN exhibited enhanced PS to other ICNs during EC relative to EO. In addition, the intra-ICN amplitude might influence the inter-ICN synchrony. Moreover, default mode network (DMN) might play an important role in information processing during EO/EC. Together, the dynamical temporal patterns within and between ICNs were altered during different scan conditions of EO/EC. Overall, the dynamical intra-ICN and inter-ICN temporal patterns could benefit resting state fMRI-related research, and could be potential biomarkers for human functional connectome. PMID:26469182

GS-2, a pyrazolo[1,5-a]indole derivative with inhibitory activity of topoisomerases, exerts its potent cytotoxic activity by ROS generation.

PubMed

Ji, Yuan Yuan; Zhu, Yong Ming; Wang, Jian Wen

2013-11-01

Pyrazolo[1,5-a]indole derivatives, a new type of topoisomerase (topo) inhibitor, demonstrate a broad spectrum of antitumor activities. However, the mechanism underlying the induced cytotoxicity remains unclear. In this study, we investigated whether GS-2, one of the derivatives, altered the levels of ROS in breast cancer MDA-231 cells and whether these ROS contributed to the observed antitumoral activity. Our data revealed that GS-2 caused a time- and dose-dependent elevation of intracellular ROS level in MDA-231 cells. GS-2 subsequently elicited notable inhibition on the expression of topos, DNA damage, activation of caspase-3, -9. The loss of mitochondrial membrane potential (MMP) was observed during the induction. The addition of N-acetyl cysteine (NAC, a well-known antioxidant) could effectively attenuate the GS-2-induced ROS enhancement and subsequent apoptosis. NAC attenuated the induced inhibition on expression of topos, indicating that topos might be the target of GS-2-induced ROS. The finding of the induced ROS provides new evidence for the molecular mechanisms of antitumor activity of pyrazolo[1,5-a]indole derivatives. Copyright © 2013 Elsevier B.V. All rights reserved.

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

PubMed

Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George; Sloan, Derek D; Murry, Jeffrey P

2017-04-15

Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is persistently

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy

PubMed Central

Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George

2017-01-01

ABSTRACT Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is

Anti-EBOV GP IgGs Lacking α1-3-Galactose and Neu5Gc Prolong Survival and Decrease Blood Viral Load in EBOV-Infected Guinea Pigs

PubMed Central

Reynard, Olivier; Jacquot, Frédéric; Evanno, Gwénaëlle; Mai, Hoa Le; Martinet, Bernard; Duvaux, Odile; Bach, Jean-Marie; Conchon, Sophie; Judor, Jean-Paul; Perota, Andrea; Lagutina, Irina; Duchi, Roberto; Lazzari, Giovanna; Le Berre, Ludmilla; Perreault, Hélène; Lheriteau, Elsa; Raoul, Hervé; Volchkov, Viktor; Galli, Cesare; Soulillou, Jean-Paul

2016-01-01

Polyclonal xenogenic IgGs, although having been used in the prevention and cure of severe infectious diseases, are highly immunogenic, which may restrict their usage in new applications such as Ebola hemorrhagic fever. IgG glycans display powerful xenogeneic antigens in humans, for example α1–3 Galactose and the glycolyl form of neuraminic acid Neu5Gc, and IgGs deprived of these key sugar epitopes may represent an advantage for passive immunotherapy. In this paper, we explored whether low immunogenicity IgGs had a protective effect on a guinea pig model of Ebola virus (EBOV) infection. For this purpose, a double knock-out pig lacking α1–3 Galactose and Neu5Gc was immunized against virus-like particles displaying surface EBOV glycoprotein GP. Following purification from serum, hyper-immune polyclonal IgGs were obtained, exhibiting an anti-EBOV GP titer of 1:100,000 and a virus neutralizing titer of 1:100. Guinea pigs were injected intramuscularly with purified IgGs on day 0 and day 3 post-EBOV infection. Compared to control animals treated with IgGs from non-immunized double KO pigs, the anti-EBOV IgGs-treated animals exhibited a significantly prolonged survival and a decreased virus load in blood on day 3. The data obtained indicated that IgGs lacking α1–3 Galactose and Neu5Gc, two highly immunogenic epitopes in humans, have a protective effect upon EBOV infection. PMID:27280712

HR-LC-MS based analysis of two antibacterial metabolites from a marine sponge symbiont Streptomyces pharmamarensis ICN40.

PubMed

Joseph, Francis-Joseph Rosemary Sharmila; Iniyan, Appadurai Muthamil; Vincent, Samuel Gnana Prakash

2017-10-01

On the effort to screen antibiotics against Methicillin resistant Staphylococcus aureus (MRSA), an actinomycete strain which can produce bactericidal compound was isolated from a marine sponge of Kanyakumari Coast, India. Two anti-MRSA compounds (PVI401 and PVI402) were isolated from the fermentation plates of Streptomyces pharmamarensis ICN40. TLC bioautography analysis yielded two active spots with Rf value of 0.75 (PVI401) and 0.8 (PVI402) from the crude extract. Both the compounds were characterized by HR-LC-MS analysis. LC-MS based de-replication analysis found out the compound PVI401 with an exact mass of 376.09435 Da and PVI402 with an exact mass of 273.26795 Da were found to be unidentified. Antibacterial spectrum showed significant minimal inhibitory concentration as 0.5 μg/ml of PVI401 and 2 μg/ml of PVI402 against MRSA. The whole organism zebrafish safety evaluation exhibited the compound PVI402 is safe upto 1 mg/ml 40 μg/ml of PVI401 exhibited thrombosis in cardiac chamber and this compound exhibited 44 μg/ml of LC 50 against HepG2 hepatic carcinoma cell line. Both the compounds may be identified further for its structural novelty and clinical studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of novel interactors and potential phosphorylation substrates of GsSnRK1 from wild soybean (Glycine soja).

PubMed

Song, Yu; Zhang, Hang; You, Hongguang; Liu, Yuanming; Chen, Chao; Feng, Xu; Yu, Xingyu; Wu, Shengyang; Wang, Libo; Zhong, Shihua; Li, Qiang; Zhu, Yanming; Ding, Xiaodong

2018-04-17

The plant sucrose nonfermenting kinase 1 (SnRK1) kinases play the central roles in the processes of energy balance, hormone perception, stress resistance, metabolism, growth, and development. However, the functions of these kinases are still elusive. In this study, we used GsSnRK1 of wild soybean as bait to perform library-scale screens by the means of yeast two-hybrid to identify its interacting proteins. The putative interactions were verified by yeast retransformation and β-galactosidase assays, and the selected interactions were further confirmed in planta by bimolecular fluorescence complementation and biochemical Co-IP assays. Protein phosphorylation analyses were carried out by phos-tag assay and anti-phospho-(Ser/Thr) substrate antibodies. Finally, we obtained 24 GsSnRK1 interactors and several putative substrates that can be categorized into SnRK1 regulatory β subunit, protein modification, biotic and abiotic stress-related, hormone perception and signalling, gene expression regulation, water and nitrogen transport, metabolism, and unknown proteins. Intriguingly, we first discovered that GsSnRK1 interacted with and phosphorylated the components of soybean nodulation and symbiotic nitrogen fixation. The interactions and potential functions of GsSnRK1 and its associated proteins were extensively discussed and analysed. This work provides plausible clues to elucidate the novel functions of SnRK1 in response to variable environmental, metabolic, and physiological requirements. © 2018 John Wiley & Sons Ltd.

A HIV-1 Tat mutant protein disrupts HIV-1 Rev function by targeting the DEAD-box RNA helicase DDX1.

PubMed

Lin, Min-Hsuan; Sivakumaran, Haran; Jones, Alun; Li, Dongsheng; Harper, Callista; Wei, Ting; Jin, Hongping; Rustanti, Lina; Meunier, Frederic A; Spann, Kirsten; Harrich, David

2014-12-14

Previously we described a transdominant negative mutant of the HIV-1 Tat protein, termed Nullbasic, that downregulated the steady state levels of unspliced and singly spliced viral mRNA, an activity caused by inhibition of HIV-1 Rev activity. Nullbasic also altered the subcellular localizations of Rev and other cellular proteins, including CRM1, B23 and C23 in a Rev-dependent manner, suggesting that Nullbasic may disrupt Rev function and trafficking by intervening with an unidentified component of the Rev nucleocytoplasmic transport complex. To seek a possible mechanism that could explain how Nullbasic inhibits Rev activity, we used a proteomics approach to identify host cellular proteins that interact with Nullbasic. Forty-six Nullbasic-binding proteins were identified by mass spectrometry including the DEAD-box RNA helicase, DDX1. To determine the effect of DDX1 on Nullbasic-mediated Rev activity, we performed cell-based immunoprecipitation assays, Rev reporter assays and bio-layer interferometry (BLI) assays. Interaction between DDX1 and Nullbasic was observed by co-immunoprecipitation of Nullbasic with endogenous DDX1 from cell lysates. BLI assays showed a direct interaction between Nullbasic and DDX1. Nullbasic affected DDX1 subcellular distribution in a Rev-independent manner. Interestingly overexpression of DDX1 in cells not only restored Rev-dependent mRNA export and gene expression in a Rev reporter assay but also partly reversed Nullbasic-induced Rev subcellular mislocalization. Moreover, HIV-1 wild type Tat co-immunoprecipitated with DDX1 and overexpression of Tat could rescue the unspliced viral mRNA levels inhibited by Nullbasic in HIV-1 expressing cells. Nullbasic was used to further define the complex mechanisms involved in the Rev-dependent nuclear export of the 9 kb and 4 kb viral RNAs. All together, these data indicate that DDX1 can be sequestered by Nullbasic leading to destabilization of the Rev nucleocytoplasmic transport complex and decreased

Mössbauer spectroscopy of MgxCu0.5-xZn0.5Fe2O4 (x = 0.0, 0.2 and 0.5) ferrites system irradiated by γ-rays

NASA Astrophysics Data System (ADS)

Ahmed, M. A.; Hassan, H. E.; Eltabey, M. M.; Latka, K.; Tatarchuk, T. R.

2018-02-01

The effect of the Mg-content on the cation distribution of cubic MgxCu0.5-xZn0.5Fe2O4(x = 0.0, 0.2, 0.3, 0.5) prepared by conventional ceramic method was investigated using Mössbauer spectroscopy at room temperature. We aimed to estimate the enhanced changes in the inversion parameter of MgxCu0.5-xZn0.5Fe2O4 system due to γ-ray irradiation as a function of the Mg-content in the range 0.5 ≥ x ≥ 0.0. The samples were irradiated by 1173 keV + 1332.5 keV γ-rays emitted from 60Co radioactive source. The total absorbed dose was 1.9 MGy with dose rate 5 kGy/h. The observed superposition of more than one sextet that belong to either octahedral [B] or tetrahedral (A) sites in the Mössbauer spectra before and after γ-irradiation was interpreted by the effect of spin canting. Moreover, there is an evidence on the presence of the Fe2+ charge state at A-sites in the irradiated samples. The quadrupole splittings showed that the orientation of the magnetic hyperfine field with respect to the principle axes of the electric field gradient was random. The magnetic hyperfine field values indicated also that the A sites had more A-O-B super exchange interactions than the B sites. New antistructure modeling for the pristine and irradiated MgxCu0.5-xZn0.5Fe2O4 samples at different γ-doses was used for describing of the lattice defects and surface centers.

HIV-1 Rev protein specifies the viral RNA export pathway by suppressing TAP/NXF1 recruitment

PubMed Central

Taniguchi, Ichiro; Mabuchi, Naoto; Ohno, Mutsuhito

2014-01-01

Nuclear RNA export pathways in eukaryotes are often linked to the fate of a given RNA. Therefore, the choice of export pathway should be well-controlled to avoid an unfavorable effect on gene expression. Although some RNAs could be exported by more than one pathway, little is known about how the choice is regulated. This issue is highlighted when the human immunodeficiency virus type 1 (HIV-1) Rev protein induces the export of singly spliced and unspliced HIV-1 transcripts. How these RNAs are exported is not well understood because such transcripts should have the possibility of utilizing CRM1-dependent export via Rev or cellular TAP/NXF1-dependent export via the transcription/export (TREX) complex, or both. Here we found that Rev suppressed TAP/NXF1-dependent export of model RNA substrates that recapitulated viral transcripts. In this effect, Rev interacted with the cap-binding complex and inhibited the recruitment of the TREX complex. Thus, Rev controls the identity of the factor occupying the cap-proximal region that determines the RNA export pathway. This ribonucleoprotein remodeling activity of Rev may favor viral gene expression. PMID:24753416

Anti-HBV response to toll-like receptor 7 agonist GS-9620 is associated with intrahepatic aggregates of T cells and B cells.

PubMed

Li, Li; Barry, Vivian; Daffis, Stephane; Niu, Congrong; Huntzicker, Erik; French, Dorothy M; Mikaelian, Igor; Lanford, Robert E; Delaney, William E; Fletcher, Simon P

2018-05-01

GS-9620, an oral agonist of toll-like receptor 7, is in clinical development for the treatment of chronic hepatitis B (CHB). GS-9620 was previously shown to induce prolonged suppression of serum viral DNA and antigens in the chimpanzee and woodchuck models of CHB. Herein, we investigated the immunomodulatory mechanisms underlying these antiviral effects. Archived liver biopsies and paired peripheral blood mononuclear cell samples from a previous chimpanzee study were analyzed by RNA sequencing, quantitative reverse transcription PCR, immunohistochemistry (IHC) and in situ hybridization (ISH). GS-9620 treatment of CHB chimpanzees induced an intrahepatic transcriptional profile significantly enriched with genes associated with hepatitis B virus (HBV) clearance in acutely infected chimpanzees. Type I and II interferon, CD8 + T cell and B cell transcriptional signatures were associated with treatment response, together with evidence of hepatocyte death and liver regeneration. IHC and ISH confirmed an increase in intrahepatic CD8 + T cell and B cell numbers during treatment, and revealed that GS-9620 transiently induced aggregates predominantly comprised of CD8 + T cells and B cells in portal regions. There were no follicular dendritic cells or IgG-positive cells in these lymphoid aggregates and very few CD11b + myeloid cells. There was no change in intrahepatic natural killer cell number during GS-9620 treatment. The antiviral response to GS-9620 treatment in CHB chimpanzees was associated with an intrahepatic interferon response and formation of lymphoid aggregates in the liver. Our data indicate these intrahepatic structures are not fully differentiated follicles containing germinal center reactions. However, the temporal correlation between development of these T and B cell aggregates and the antiviral response to treatment suggests they play a role in promoting an effective immune response against HBV. New therapies to treat chronic hepatitis B (CHB) are urgently

48 CFR 970.0808-00 - Scope.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Scope. 970.0808-00 Section 970.0808-00 Federal Acquisition Regulations System DEPARTMENT OF ENERGY AGENCY SUPPLEMENTARY REGULATIONS DOE MANAGEMENT AND OPERATING CONTRACTS Required sources of supplies and services 970.0808-00 Scope...

Half molecular exchange of IgGs in the blood of healthy humans: chimeric lambda-kappa-immunoglobulins containing HL fragments of antibodies of different subclasses (IgG1-IgG4).

PubMed

Sedykh, Sergey E; Lekchnov, Evgenii A; Prince, Viktor V; Buneva, Valentina N; Nevinsky, Georgy A

2016-10-20

In the classic paradigm, immunoglobulins represent products of clonal B cell populations, each producing antibodies recognizing a single antigen (monospecific). There is a common belief that IgGs in mammalian biological fluids are monospecific molecules having stable structures and two identical antigen-binding sites. But the issue concerning the possibility of exchange by HL-fragments between the antibody molecules in human blood is still unexplored. Different physico-chemical and immunological methods for analysis of half-molecule exchange between human blood IgGs were used. Using eighteen blood samples of healthy humans we have shown unexpected results for the first time: blood antibodies undergo extensive post-transcriptional half-molecule exchange and IgG pools on average consist of 62.4 ± 6.5% IgGs containing kappa light chains (kappa-kappa-IgGs), 29.8.6 ± 5.4% lambda light chains (lambda-lambda-IgGs), and 8.8 ± 2.7% (range 2.6-16.8%) IgGs containing both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained on average (%): IgG1 (36.0 and 32.3), IgG2 (50.9 and 51.4), IgG3 (9.7 and 9.9), and IgG4 (6.5 and 5.7), while chimeric kappa-lambda-IgGs consisted of (%): 25.5 ± 4.2 IgG1, 50.8 ± 3.9 IgG2, 9.1 ± 2.1 IgG3, and 14.5 ± 2.2 IgG4. Our unexpected data are indicative of the possibility of half-molecule exchange between blood IgGs of various subclasses, raised against different antigens. The existence of blood chimeric bifunctional IgGs with different binding sites destroys the classic paradigm. Due to the phenomenon of polyspecificity and cross-reactivity of bifunctional IgGs containing HL-fragments of different types to different antigens, such IgGs may be important in human blood for widening their different biological functions.

Astronaut Anna Fisher in NBS Training For Hubble Space Telescope

NASA Technical Reports Server (NTRS)

1980-01-01

The Hubble Space Telescope (HST) is a cooperative program of the European Space Agency (ESA) and the National Aeronautical and Space Administration (NASA) to operate a long-lived space-based observatory. It was the flagship mission of NASA's Great Observatories program. The HST program began as an astronomical dream in the 1940s. During the 1970s and 1980s, the HST was finally designed and built becoming operational in the 1990s. The HST was deployed into a low-Earth orbit on April 25, 1990 from the cargo bay of the Space Shuttle Discovery (STS-31). The design of the HST took into consideration its length of service and the necessity of repairs and equipment replacement by making the body modular. In doing so, subsequent shuttle missions could recover the HST, replace faulty or obsolete parts and be re-released. Marshall Space Flight Center's (MSFC's) Neutral Buoyancy Simulator (NBS) served as the test center for shuttle astronauts training for Hubble related missions. Shown is astronaut Anna Fisher training on a mock-up of a modular section of the HST for an axial scientific instrument change out.

Clean Cities Conference to Rev Up Alternative Fuels Market

Science.gov Websites

Cities Conference to Rev Up Alternative Fuels Market For more information contact: George Douglas , 303-275-4096 email: George Douglas Golden, Colo., Jan. 26, 2001 - Cleaner air and greater energy

User Instructions for the Systems Assessment Capability, Rev. 1, Computer Codes Volume 3: Utility Codes

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

Eslinger, Paul W.; Aaberg, Rosanne L.; Lopresti, Charles A.

2004-09-14

This document contains detailed user instructions for a suite of utility codes developed for Rev. 1 of the Systems Assessment Capability. The suite of computer codes for Rev. 1 of Systems Assessment Capability performs many functions.

rs2735383, located at a microRNA binding site in the 3’UTR of NBS1, is not associated with breast cancer risk

PubMed Central

Liu, Jingjing; Lončar, Ivona; Collée, J. Margriet; Bolla, Manjeet K.; Dennis, Joe; Michailidou, Kyriaki; Wang, Qin; Andrulis, Irene L.; Barile, Monica; Beckmann, Matthias W.; Behrens, Sabine; Benitez, Javier; Blomqvist, Carl; Boeckx, Bram; Bogdanova, Natalia V.; Bojesen, Stig E.; Brauch, Hiltrud; Brennan, Paul; Brenner, Hermann; Broeks, Annegien; Burwinkel, Barbara; Chang-Claude, Jenny; Chen, Shou-Tung; Chenevix-Trench, Georgia; Cheng, Ching Y.; Choi, Ji-Yeob; Couch, Fergus J.; Cox, Angela; Cross, Simon S.; Cuk, Katarina; Czene, Kamila; Dörk, Thilo; dos-Santos-Silva, Isabel; Fasching, Peter A.; Figueroa, Jonine; Flyger, Henrik; García-Closas, Montserrat; Giles, Graham G.; Glendon, Gord; Goldberg, Mark S.; González-Neira, Anna; Guénel, Pascal; Haiman, Christopher A.; Hamann, Ute; Hart, Steven N.; Hartman, Mikael; Hatse, Sigrid; Hopper, John L.; Ito, Hidemi; Jakubowska, Anna; Kabisch, Maria; Kang, Daehee; Kosma, Veli-Matti; Kristensen, Vessela N.; Le Marchand, Loic; Lee, Eunjung; Li, Jingmei; Lophatananon, Artitaya; Jan Lubinski; Mannermaa, Arto; Matsuo, Keitaro; Milne, Roger L.; Sahlberg, Kristine K.; Ottestad, Lars; Kåresen, Rolf; Langerød, Anita; Schlichting, Ellen; Holmen, Marit Muri; Sauer, Toril; Haakensen, Vilde; Engebråten, Olav; Naume, Bjørn; Kiserud, Cecile E.; Reinertsen, Kristin V.; Helland, åslaug; Riis, Margit; Bukholm, Ida; Lønning, Per Eystein; Børresen-Dale, Anne-Lise; Grenaker Alnæs, Grethe I.; Neuhausen, Susan L.; Nevanlinna, Heli; Orr, Nick; Perez, Jose I. A.; Peto, Julian; Putti, Thomas C.; Pylkäs, Katri; Radice, Paolo; Sangrajrang, Suleeporn; Sawyer, Elinor J.; Schmidt, Marjanka K.; Schneeweiss, Andreas; Shen, Chen-Yang; Shrubsole, Martha J.; Shu, Xiao-Ou; Simard, Jacques; Southey, Melissa C.; Swerdlow, Anthony; Teo, Soo H.; Tessier, Daniel C.; Thanasitthichai, Somchai; Tomlinson, Ian; Torres, Diana; Truong, Thérèse; Tseng, Chiu-Chen; Vachon, Celine; Winqvist, Robert; Wu, Anna H.; Yannoukakos, Drakoulis; Zheng, Wei; Hall, Per; Dunning, Alison M.; Easton, Douglas F.; Hooning, Maartje J.; van den Ouweland, Ans M. W.; Martens, John W. M.; Hollestelle, Antoinette

2016-01-01

NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3′-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936–1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r2 > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969–1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905–1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility. PMID:27845421

Glutathione Preservation during Storage of Rat Lenses in Optisol-GS and Castor Oil

PubMed Central

Holm, Thomas; Brøgger-Jensen, Martin Rocho; Johnson, Leif; Kessel, Line

2013-01-01

Background Glutathione concentration in the lens decreases in aging and cataractous lenses, providing a marker for tissue condition. Experimental procedures requiring unfrozen lenses from donor banks rely on transportation in storage medium, affecting lens homeostasis and alterations in glutathione levels. The aim of the study was to examine the effects of Optisol-GS and castor oil on lens condition, determined from their ability to maintain glutathione concentrations. Methodology/Principal Findings Rat lenses were stored in the two types of storage media at varying time intervals up to 3 days. Glutathione concentration was afterwards determined in an enzymatic detection assay, specific for both reduced and oxidized forms. Lenses removed immediately after death exhibited a glutathione concentration of 4.70±0.29 mM. In vitro stored lenses in Optisol-GS lost glutathione quickly, ending with a concentration of 0.60±0.34 mM after 3 days while castor oil stored lenses exhibited a slower decline and ended at 3 times the concentration. A group of lenses were additionally stored under post mortem conditions within the host for 6 hours before its removal. Total glutathione after 6 hours was similar to that of lenses removed immediately after death, but with altered GSH and GSSG concentrations. Subsequent storage of these lenses in media showed changes similar to those in the first series of experiments, albeit to a lesser degree. Conclusions/Significance It was determined that storage in Optisol-GS resulted in a higher loss of glutathione than lenses stored in castor oil. Storage for more than 12 hours reduced glutathione to half its original concentration, and was considered unusable after 24 hours. PMID:24260265

Identification of Brucella melitensis Rev.1 vaccine-strain genetic markers: Towards understanding the molecular mechanism behind virulence attenuation.

PubMed

Issa, Mohammad Nouh; Ashhab, Yaqoub

2016-09-22

Brucella melitensis Rev.1 is an avirulent strain that is widely used as a live vaccine to control brucellosis in small ruminants. Although an assembled draft version of Rev.1 genome has been available since 2009, this genome has not been investigated to characterize this important vaccine. In the present work, we used the draft genome of Rev.1 to perform a thorough genomic comparison and sequence analysis to identify and characterize the panel of its unique genetic markers. The draft genome of Rev.1 was compared with genome sequences of 36 different Brucella melitensis strains from the Brucella project of the Broad Institute of MIT and Harvard. The comparative analyses revealed 32 genetic alterations (30 SNPs, 1 single-bp insertion and 1 single-bp deletion) that are exclusively present in the Rev.1 genome. In silico analyses showed that 9 out of the 17 non-synonymous mutations are deleterious. Three ABC transporters are among the disrupted genes that can be linked to virulence attenuation. Out of the 32 mutations, 11 Rev.1 specific markers were selected to test their potential to discriminate Rev.1 using a bi-directional allele-specific PCR assay. Six markers were able to distinguish between Rev.1 and a set of control strains. We succeeded in identifying a panel of 32 genome-specific markers of the B. melitensis Rev.1 vaccine strain. Extensive in silico analysis showed that a considerable number of these mutations could severely affect the function of the associated genes. In addition, some of the discovered markers were able to discriminate Rev.1 strain from a group of control strains using practical PCR tests that can be applied in resource-limited settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

EXO1 is critical for embryogenesis and the DNA damage response in mice with a hypomorphic Nbs1 allele.

PubMed

Rein, Katrin; Yanez, Diana A; Terré, Berta; Palenzuela, Lluís; Aivio, Suvi; Wei, Kaichun; Edelmann, Winfried; Stark, Jeremy M; Stracker, Travis H

2015-09-03

The maintenance of genome stability is critical for the suppression of diverse human pathologies that include developmental disorders, premature aging, infertility and predisposition to cancer. The DNA damage response (DDR) orchestrates the appropriate cellular responses following the detection of lesions to prevent genomic instability. The MRE11 complex is a sensor of DNA double strand breaks (DSBs) and plays key roles in multiple aspects of the DDR, including DNA end resection that is critical for signaling and DNA repair. The MRE11 complex has been shown to function both upstream and in concert with the 5'-3' exonuclease EXO1 in DNA resection, but it remains unclear to what extent EXO1 influences DSB responses independently of the MRE11 complex. Here we examine the genetic relationship of the MRE11 complex and EXO1 during mammalian development and in response to DNA damage. Deletion of Exo1 in mice expressing a hypomorphic allele of Nbs1 leads to severe developmental impairment, embryonic death and chromosomal instability. While EXO1 plays a minimal role in normal cells, its loss strongly influences DNA replication, DNA repair, checkpoint signaling and damage sensitivity in NBS1 hypomorphic cells. Collectively, our results establish a key role for EXO1 in modulating the severity of hypomorphic MRE11 complex mutations. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

EXO1 is critical for embryogenesis and the DNA damage response in mice with a hypomorphic Nbs1 allele

PubMed Central

Rein, Katrin; Yanez, Diana A.; Terré, Berta; Palenzuela, Lluís; Aivio, Suvi; Wei, Kaichun; Edelmann, Winfried; Stark, Jeremy M.; Stracker, Travis H.

2015-01-01

The maintenance of genome stability is critical for the suppression of diverse human pathologies that include developmental disorders, premature aging, infertility and predisposition to cancer. The DNA damage response (DDR) orchestrates the appropriate cellular responses following the detection of lesions to prevent genomic instability. The MRE11 complex is a sensor of DNA double strand breaks (DSBs) and plays key roles in multiple aspects of the DDR, including DNA end resection that is critical for signaling and DNA repair. The MRE11 complex has been shown to function both upstream and in concert with the 5′-3′ exonuclease EXO1 in DNA resection, but it remains unclear to what extent EXO1 influences DSB responses independently of the MRE11 complex. Here we examine the genetic relationship of the MRE11 complex and EXO1 during mammalian development and in response to DNA damage. Deletion of Exo1 in mice expressing a hypomorphic allele of Nbs1 leads to severe developmental impairment, embryonic death and chromosomal instability. While EXO1 plays a minimal role in normal cells, its loss strongly influences DNA replication, DNA repair, checkpoint signaling and damage sensitivity in NBS1 hypomorphic cells. Collectively, our results establish a key role for EXO1 in modulating the severity of hypomorphic MRE11 complex mutations. PMID:26160886

Low Temperature Power Coating (LTPC) Phase 2 Laboratory Test Plan and Procedures for PACAF (Rev D)

DTIC Science & Technology

2018-03-20

Δa*, LTPC Phase II Laboratory Test Plan and Procedures Rev D (CDRL A004) BATTELLE | 20 March 2018 | 6 Δb* and ΔE will be calculated post ...BATTELLE | CONTRACT NUMBER: FA8532-17-C-0008 (CDRL A004) LTPC Phase II Laboratory Test Plan and Procedures (Rev D) Prepared by... Test Plan and Procedures Rev D (CDRL A004) BATTELLE | 20 March 2018 | i List of Acronyms AGE Aircraft Ground Equipment ASTM American

Forkhead-Associated Domain of Yeast Xrs2, a Homolog of Human Nbs1, Promotes Nonhomologous End Joining Through Interaction With a Ligase IV Partner Protein, Lif1

PubMed Central

Matsuzaki, Kenichiro; Shinohara, Akira; Shinohara, Miki

2008-01-01

DNA double-strand breaks (DSB) are repaired through two different pathways, homologous recombination (HR) and nonhomologous end joining (NHEJ). Yeast Xrs2, a homolog of human Nbs1, is a component of the Mre11-Rad50-Xrs2 (MRX) complex required for both HR and NHEJ. Previous studies showed that the N-terminal forkhead-associated (FHA) domain of Xrs2/Nbs1 in yeast is not involved in HR, but is likely to be in NHEJ. In this study, we showed that the FHA domain of Xrs2 plays a critical role in efficient DSB repair by NHEJ. The FHA domain of Xrs2 specifically interacts with Lif1, a component of the ligase IV complex, Dnl4-Nej1-Lif1 (DNL). Lif1, which is phosphorylated in vivo, contains two Xrs2-binding regions. Serine 383 of Lif1 plays an important role in the interaction with Xrs2 as well as in NHEJ. Interestingly, the phospho-mimetic substitutions of serine 383 enhance the NHEJ activity of Lif1. Our results suggest that the phosphorylation of Lif1 at serine 383 is recognized by the Xrs2 FHA domain, which in turn may promote recruitment of the DNL complex to DSB for NHEJ. The interaction between Xrs2 and Lif1 through the FHA domain is conserved in humans; the FHA domain Nbs1 interacts with Xrcc4, a Lif1 homolog of human. PMID:18458108

40 CFR 192.00 - Applicability.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 25 2014-07-01 2014-07-01 false Applicability. 192.00 Section 192.00 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) RADIATION PROTECTION PROGRAMS HEALTH AND ENVIRONMENTAL PROTECTION STANDARDS FOR URANIUM AND THORIUM MILL TAILINGS Standards for the Control...

Photochemistry of Surface-Confined Organometallics: Photochemical Release of a Surface-Confined Cobalt Carbonyl Catalyst.

DTIC Science & Technology

1981-06-08

a r~ 2,2 3 ai ey, -. ar.ger, S.. :.hem. Rev., , 2, ¢9 5 Hartley, F.R.; Vezey, P.. Aav . Organo’et. , em., 1977, 7, 139. 6. Grusnka, E.; Kikta, E.J...sooctane- 1.2- hSC (C)zSIt 996 1.0 - 1991 sh 75min hzu wL 30min hzu ~0.8- 0 0.6- < 2027 0.475 11lmin hu 30 0.2- 0.0 2050 2000 1950 1900 WAVENUMBERS (cm𔃻) Q

Differential expression of multiple glutamine synthetase genes in air-breathing magur catfish, Clarias magur and their induction under hyper-ammonia stress.

PubMed

Banerjee, Bodhisattwa; Koner, Debaprasad; Bhuyan, Gitalee; Saha, Nirmalendu

2018-06-01

The present study demonstrates the unique presence of three different gs genes (cmgs01, cmgs02, and cmgs03) in air-breathing ureogenic magur catfish (Clarias magur), which is otherwise reported to be encoded by a single gene in higher vertebrates. Of these three genes, two (cmgs01and cmgs03) were identified as 'liver' form, predominantly expressed in liver cells, and the third one as 'brain' form (cmgs02), expressed chiefly in brain cells. Molecular characterization studies have revealed conservation of homologous active site residues in all the three gs genes. In silico analysis, accompanied by GS enzyme assay and Western blot analysis of different GS isoforms in different subcellular fractions indicated the mitochondrial localization of cmGS01 and cmGS03 in liver and kidney cells and cytosolic localization of cmGS02 in brain cells. Further, exposure of magur catfish to high external ammonia (HEA; 25 mM NH 4 Cl) led to a significant induction of multiple gs genes as evidenced by higher expression of different gs mRNAs at variable levels in different tissues. The cmgs01 and cmgs03 mRNA levels elevated significantly in liver, kidney, muscle, and gills, whereas the cmgs02 mRNA level increased considerably in the brain after 14 days of exposure to HEA. These increases in mRNA levels were associated with a significant rise in cmGS01 and cmGS03 proteins in liver, kidney, muscle, and gills, and the cmGS02 protein in the brain after 14 days of exposure to HEA. Therefore, it can be concluded that the unique differential expression of three gs genes and their induction under high ammonia level probably helps in detoxification of ammonia to glutamine and further to urea via the ornithine-urea cycle in ureogenic as well as non-ureogenic tissues of these magur catfish. Copyright © 2017. Published by Elsevier B.V.

75 FR 27840 - NUREG-0654/FEMA-REP-1, Rev. 1, Supplement 3, Guidance for Protective Action Recommendations for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-18

... NUCLEAR REGULATORY COMMISSION [NRC-2010-0080] NUREG-0654/FEMA-REP-1, Rev. 1, Supplement 3...: ``NUREG-0654/FEMA-REP-1, Rev. 1, Supplement 3, Guidance for Protective Action Recommendations for General... the existing guidance contained in Supplement 3 to NUREG- 0654/FEMA-REP-1, Rev. 1, ``Criteria for...

Synchrotron radiation calibration of the EUVE variable line-spaced diffraction gratings at the NBS SURF II facility

NASA Technical Reports Server (NTRS)

Jelinsky, P.; Jelinsky, S. R.; Miller, A.; Vallerga, J.; Malina, R. F.

1988-01-01

The Extreme Ultraviolet Explorer (EUVE) has a spectrometer which utilizes variable line-spaced, plane diffraction gratings in the converging beam of a Wolter-Schwarzschild type II mirror. The gratings, microchannel plate detector, and thin film filters have been calibrated with continuum radiation provided by the NBS SURF II facility. These were calibrated in a continuum beam to find edges or other sharp spectral features in the transmission of the filters, quantum efficiency of the microchannel plate detector, and efficiency of the gratings. The details of the calibration procedure and the results of the calibration are presented.

75 FR 72952 - Safety Zone; 1000-yard radius from position 29°48.77′ N 091°33.02′ W, Charenton Drainage and...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-29

...-AA00 Safety Zone; 1000-yard radius from position 29[deg]48.77' N 091[deg]33.02' W, Charenton Drainage... position 29[deg]48.77' N 091[deg]33.02' W, Charenton Drainage and Navigation Canal, St. Mary Parish, LA... associated hazards in position 29[deg]48.77' N 091[deg]33.02' W, in the Charenton Drainage and Navigation...

Tracking and data relay satellite system (TDRSS) capabilities

NASA Astrophysics Data System (ADS)

Spearing, R. E.

1985-10-01

The Tracking and Data Relay Satellite System (TDRSS) is the latest implementation to tracking and data acquisition network for near-earth orbiting satellite support designed to meet the requirements of the current and projected (to the year 2000) satellite user community. The TDRSS consists of a space segment (SS) and a ground segment (GS) that fit within NASA's Space Network (SN) complex controlled at the Goddard Space Flight Center. The SS currently employs a single satellite, TDRS-1, with two additional satellites to be deployed in January 1986 and July 1986. The GS contains the communications and equipment required to manage the three TDR satellites and to transmit and receive information to and from TDRSS user satellites. Diagrams and tables illustrating the TDRSS signal characteristics, the situation of TDRSS within the SN, the SN operations and element interrelationships, as well as future plans for new missions are included.

Tracking and data relay satellite system (TDRSS) capabilities

NASA Technical Reports Server (NTRS)

Spearing, R. E.

1985-01-01

The Tracking and Data Relay Satellite System (TDRSS) is the latest implementation to tracking and data acquisition network for near-earth orbiting satellite support designed to meet the requirements of the current and projected (to the year 2000) satellite user community. The TDRSS consists of a space segment (SS) and a ground segment (GS) that fit within NASA's Space Network (SN) complex controlled at the Goddard Space Flight Center. The SS currently employs a single satellite, TDRS-1, with two additional satellites to be deployed in January 1986 and July 1986. The GS contains the communications and equipment required to manage the three TDR satellites and to transmit and receive information to and from TDRSS user satellites. Diagrams and tables illustrating the TDRSS signal characteristics, the situation of TDRSS within the SN, the SN operations and element interrelationships, as well as future plans for new missions are included.

Prospective, Randomized Comparison of One-level Mobi-C Cervical Total Disc Replacement vs. Anterior Cervical Discectomy and Fusion: Results at 5-year Follow-up

PubMed Central

Zigler, Jack E.; Jackson, Robert; Nunley, Pierce D.; Bae, Hyun W.; Kim, Kee D.; Ohnmeiss, Donna D.

2016-01-01

Introduction There is increasing interest in the role of cervical total disc replacement (TDR) as an alternative to anterior cervical discectomy and fusion (ACDF). Multiple prospective randomized studies with minimum 2 year follow-up have shown TDR to be at least as safe and effective as ACDF in treating symptomatic degenerative disc disease at a single level. The purpose of this study was to compare outcomes of cervical TDR using the Mobi-C® with ACDF at 5-year follow-up. Methods This prospective, randomized, controlled trial was conducted as a Food and Drug Administration regulated Investigational Device Exemption trial across 23 centers with 245 patients randomized (2:1) to receive TDR with Mobi-C® Cervical Disc Prosthesis or ACDF with anterior plate and allograft. Outcome assessments included a composite overall success score, Neck Disability Index (NDI), visual analog scales (VAS) assessing neck and arm pain, Short Form-12 (SF-12) health survey, patient satisfaction, major complications, subsequent surgery, segmental range of motion, and adjacent segment degeneration. Results The 60-month follow-up rate was 85.5% for the TDR group and 78.9% for the ACDF group. The composite overall success was 61.9% with TDR vs. 52.2% with ACDF, demonstrating statistical non-inferiority. Improvements in NDI, VAS neck and arm pain, and SF-12 scores were similar between groups and were maintained from earlier follow-up through 60 months. There was no significant difference between TDR and ACDF in adverse events or major complications. Range of motion was maintained with TDR through 60 months. Device-related subsequent surgeries (TDR: 3.0%, ACDF: 11.1%, p<0.02) and adjacent segment degeneration at the superior level (TDR: 37.1%, ACDF: 54.7%, p<0.03) were significantly lower for TDR patients. Conclusions Five-year results demonstrate the safety and efficacy of TDR with the Mobi-C as a viable alternative to ACDF with the potential advantage of lower rates of reoperation and

Copper Oxide Precipitates in NBS Standard Reference Material 482

PubMed Central

Windsor, Eric S.; Carlton, Robert A.; Gillen, Greg; Wight, Scott A.; Bright, David S.

2002-01-01

Copper oxide has been detected in the copper containing alloys of NBS Standard Reference Material (SRM) 482. This occurrence is significant because it represents heterogeneity within a standard reference material that was certified to be homogeneous on a micrometer scale. Oxide occurs as elliptically to spherically shaped precipitates whose size differs with alloy composition. The largest precipitates occur in the Au20-Cu80 alloy and range in size from submicrometer up to 2 μm in diameter. Precipitates are observed using light microscopy, electron microscopy, and secondary ion mass spectrometry (SIMS). SIMS has demonstrated that the precipitates are present within all the SRM 482 wires that contain copper. Only the pure gold wire is precipitate free. Initial results from the analysis of the Au20-Cu80 alloy indicate that the percentage of precipitates is less than 1 % by area. Electron probe microanalysis (EPMA) of large (2 μm) precipitates in this same alloy indicates that precipitates are detectable by EPMA and that their composition differs significantly from the certified alloy composition. The small size and low percentage of these oxide precipitates minimizes the impact that they have upon the intended use of this standard for electron probe microanalysis. Heterogeneity caused by these oxide precipitates may however preclude the use of this standard for automated EPMA analyses and other microanalysis techniques. PMID:27446759

Correlation of gas dynamics and dust in the evolved filament G82.65-02.00

NASA Astrophysics Data System (ADS)

Saajasto, M.; Juvela, M.; Dobashi, K.; Shimoikura, T.; Ristorcelli, I.; Montillaud, J.; Marshall, D. J.; Malinen, J.; Pelkonen, V.-M.; Fehér, O.; Rivera-Ingraham, A.; Toth, L. V.; Montier, L.; Bernard, J.-Ph.; Onishi, T.

2017-12-01

Context. The combination of line and continuum observations can provide vital insight into the formation and fragmentation of filaments and the initial conditions for star formation. We have carried out line observations to map the kinematics of an evolved, actively star forming filament G82.65-2.00. The filament was first identified from the Planck data as a region of particularly cold dust emission and was mapped at 100-500 μm as a part of the Herschel key program Galactic Cold Cores. The Herschel observations cover the central part of the filament, corresponding to a filament length of 12 pc at the assumed distance of 620 pc. Aims: CO observations show that the filament has an intriguing velocity field with several velocity components around the filament. In this paper, we study the velocity structure in detail, to quantify possible mass accretion rate onto the filament, and study the masses of the cold cores located in the filament. Methods: We have carried out line observations of several molecules, including CO isotopologues, HCO+, HCN, and CS with the Osaka 1.85 m telescope and the Nobeyama 45 m telescope. The spectral line data are used to derive velocity and column density information. Results: The observations reveal several velocity components in the field, with strongest line emission concentrated to velocity range [3,5] km s-1. The column density of molecular hydrogen along the filament varies from 1.0 to 2.3 × 1022cm2. We have examined six cold clumps from the central part of the filament. The clumps have masses in the range 10-20M⊙ ( 70 M⊙ in total) and are close to or above the virial mass. Furthermore, the main filament is heavily fragmented and most of the substructures have a mass lower than or close to the virial mass, suggesting that the filament is dispersing as a whole. Position-velocity maps of 12CO and 13CO lines indicate that at least one of the striations is kinematically connected to two of the clumps, potentially indicating mass

Cooperativity among Rev-Associated Nuclear Export Signals Regulates HIV-1 Gene Expression and Is a Determinant of Virus Species Tropism

PubMed Central

Aligeti, Mounavya; Behrens, Ryan T.; Pocock, Ginger M.; Schindelin, Johannes; Dietz, Christian; Eliceiri, Kevin W.; Swanson, Chad M.; Malim, Michael H.; Ahlquist, Paul

2014-01-01

ABSTRACT Murine cells exhibit a profound block to HIV-1 virion production that was recently mapped to a species-specific structural attribute of the murine version of the chromosomal region maintenance 1 (mCRM1) nuclear export receptor and rescued by the expression of human CRM1 (hCRM1). In human cells, the HIV-1 Rev protein recruits hCRM1 to intron-containing viral mRNAs encoding the Rev response element (RRE), thereby facilitating viral late gene expression. Here we exploited murine 3T3 fibroblasts as a gain-of-function system to study hCRM1's species-specific role in regulating Rev's effector functions. We show that Rev is rapidly exported from the nucleus by mCRM1 despite only weak contributions to HIV-1's posttranscriptional stages. Indeed, Rev preferentially accumulates in the cytoplasm of murine 3T3 cells with or without hCRM1 expression, in contrast to human HeLa cells, where Rev exhibits striking en masse transitions between the nuclear and cytoplasmic compartments. Efforts to bias Rev's trafficking either into or out of the nucleus revealed that Rev encoding a second CRM1 binding domain (Rev-2xNES) or Rev-dependent viral gag-pol mRNAs bearing tandem RREs (GP-2xRRE), rescue virus particle production in murine cells even in the absence of hCRM1. Combined, these results suggest a model wherein Rev-associated nuclear export signals cooperate to regulate the number or quality of CRM1's interactions with viral Rev/RRE ribonucleoprotein complexes in the nucleus. This mechanism regulates CRM1-dependent viral gene expression and is a determinant of HIV-1's capacity to produce virions in nonhuman cell types. IMPORTANCE Cells derived from mice and other nonhuman species exhibit profound blocks to HIV-1 replication. Here we elucidate a block to HIV-1 gene expression attributable to the murine version of the CRM1 (mCRM1) nuclear export receptor. In human cells, hCRM1 regulates the nuclear export of viral intron-containing mRNAs through the activity of the viral Rev

Comparisons of 'Identical' Simulations by the Eulerian Gyrokinetic Codes GS2 and GYRO

NASA Astrophysics Data System (ADS)

Bravenec, R. V.; Ross, D. W.; Candy, J.; Dorland, W.; McKee, G. R.

2003-10-01

A major goal of the fusion program is to be able to predict tokamak transport from first-principles theory. To this end, the Eulerian gyrokinetic code GS2 was developed years ago and continues to be improved [1]. Recently, the Eulerian code GYRO was developed [2]. These codes are not subject to the statistical noise inherent to particle-in-cell (PIC) codes, and have been very successful in treating electromagnetic fluctuations. GS2 is fully spectral in the radial coordinate while GYRO uses finite-differences and ``banded" spectral schemes. To gain confidence in nonlinear simulations of experiment with these codes, ``apples-to-apples" comparisons (identical profile inputs, flux-tube geometry, two species, etc.) are first performed. We report on a series of linear and nonlinear comparisons (with overall agreement) including kinetic electrons, collisions, and shaped flux surfaces. We also compare nonlinear simulations of a DIII-D discharge to measurements of not only the fluxes but also the turbulence parameters. [1] F. Jenko, et al., Phys. Plasmas 7, 1904 (2000) and refs. therein. [2] J. Candy, J. Comput. Phys. 186, 545 (2003).

U.S. EPA, Pesticide Product Label, RANGE CATTLE LIVESTOCK & SHEEP DIP CONCENTRATE, 03/02/1984

EPA Pesticide Factsheets

2011-04-21

... CiSDc~e of in a ~an,tdr.f ~arCf1:1 )r lnc~'1erd~~cn, crt 1~ d~~owe~:'/ sta~e ~nc :oca1 aLJt~ori~ies. ~~ :urp~~c. :; Jur··~~, s:a, :~~ ~f ;~~~e. ...

Outcomes and genotype-phenotype correlations in 52 individuals with VLCAD deficiency diagnosed by NBS and enrolled in the IBEM-IS database

PubMed Central

Pena, Loren D.M.; van Calcar, Sandra C.; Hansen, Joyanna; Edick, Mathew J.; Vockley, Cate Walsh; Leslie, Nancy; Cameron, Cynthia; Mohsen, Al-Walid; Berry, Susan A; Arnold, Georgianne L; Vockley, Jerry

2016-01-01

Very long chain acyl-CoA dehydrogenase (VLCAD) deficiency can present at various ages from the neonatal period to adulthood, and poses the greatest risk of complications during intercurrent illness or after prolonged fasting. Early diagnosis, treatment, and surveillance can reduce mortality; hence, the disorder is included in the newborn Recommended Uniform Screening Panel (RUSP) in the United States. The Inborn Errors of Metabolism Information System (IBEM-IS) was established in 2007 to collect longitudinal information on individuals with inborn errors of metabolism included in newborn screening (NBS) programs, including VLCAD deficiency. We retrospectively analyzed early outcomes for individuals who were diagnosed with VLCAD deficiency by NBS and describe initial presentations, diagnosis, clinical outcomes and treatment in a cohort of 52 individuals ages 1–18 years. Maternal prenatal symptoms were not reported, and most newborns remained asymptomatic. Cardiomyopathy was uncommon in the cohort, diagnosed in 2/52 cases. Elevations in creatine kinase were a common finding, and usually first occurred during the toddler period (1–3 years of age). Diagnostic evaluations required several testing modalities, most commonly plasma acylcarnitine profiles and molecular testing. Functional testing, including fibroblast acylcarnitine profiling and white blood cell or fibroblast enzyme assay, is a useful diagnostic adjunct if uncharacterized mutations are identified. PMID:27209629

Hvr-Gs at MT. Graham:. Optical Turbulence Vertical Distribution with Standard and High Resolution

NASA Astrophysics Data System (ADS)

Masciadri, E.; Stoesz, J.; Lascaux, F.; Hagelin, S.

2009-09-01

Since a few years measurements of the optical turbulence vertical distribution have been done at Mt. Graham with a Generalized Scidar (GS) located at the focus of the 1.75 m Vatican Advance Technological Telescope (VATT). Such a telescope is placed on the summit of Mt. Graham (Arizona) at around 250 m far away from the Large Binocular Telescope (LBT). Thanks to a new technique1 that we recently proposed based on the GS observations of wide-binaries (30-35 arcsec), measurements of CN2 profiles characterized by a vertical resolution as high as 20-30 m in the first 600 m have been also collected. The statistic sample of measurements consists, at present, of 43 nights distributed in different periods of the year. In this contribution we present the main scientific motivations as well as the analysis of this extended survey and new insights into the turbulence characterization achieved so far by this on-going activity.

Potent Inhibition of Human Immunodeficiency Virus Type 1 Replication by an Intracellular Anti-Rev Single-Chain Antibody

NASA Astrophysics Data System (ADS)

Duan, Lingxun; Bagasra, Omar; Laughlin, Mark A.; Oakes, Joseph W.; Pomerantz, Roger J.

1994-05-01

Human immunodeficiency virus type 1 (HIV-1) has a complex life cycle, which has made it a difficult target for conventional therapeutic modalities. A single-chain antibody moiety, directed against the HIV-1 regulatory protein Rev, which rescues unspliced viral RNA from the nucleus of infected cells, has now been developed. This anti-Rev single-chain construct (SFv) consists of both light and heavy chain variable regions of an anti-Rev monoclonal antibody, which, when expressed intracellularly within human cells, potently inhibits HIV-1 replication. This intracellular SFv molecule is demonstrated to specifically antagonize Rev function. Thus, intracellular SFv expression, against a retroviral regulatory protein, may be useful as a gene therapeutic approach to combat HIV-1 infections.

Necessary and sufficient liveness condition of GS3PR Petri nets

NASA Astrophysics Data System (ADS)

Liu, GaiYun; Barkaoui, Kamel

2015-05-01

Structural analysis is one of the most important and efficient methods to investigate the behaviour of Petri nets. Liveness is a significant behavioural property of Petri nets. Siphons, as structural objects of a Petri net, are closely related to its liveness. Many deadlock control policies for flexible manufacturing systems (FMS) modelled by Petri nets are implemented via siphon control. Most of the existing methods design liveness-enforcing supervisors by adding control places for siphons based on their controllability conditions. To compute a liveness-enforcing supervisor with as much as permissive behaviour, it is both theoretically and practically significant to find an exact controllability condition for siphons. However, the existing conditions, max, max‧, and max″-controllability of siphons are all overly restrictive and generally sufficient only. This paper develops a new condition called max*-controllability of the siphons in generalised systems of simple sequential processes with resources (GS3PR), which are a net subclass that can model many real-world automated manufacturing systems. We show that a GS3PR is live if all its strict minimal siphons (SMS) are max*-controlled. Compared with the existing conditions, i.e., max-, max‧-, and max″-controllability of siphons, max*-controllability of the SMS is not only sufficient but also necessary. An example is used to illustrate the proposed method.

REV7 counteracts DNA double-strand break resection and impacts PARP inhibition

PubMed Central

Xu, Guotai; Yuan, Jingsong; Mistrik, Martin; Bouwman, Peter; Bartkova, Jirina; Gogola, Ewa; Warmerdam, Daniël; Barazas, Marco; Jaspers, Janneke E.; Watanabe, Kenji; Pieterse, Mark; Kersbergen, Ariena; Sol, Wendy; Celie, Patrick H. N.; Schouten, Philip C.; van den Broek, Bram; Salman, Ahmed; Nieuwland, Marja; de Rink, Iris; de Ronde, Jorma; Jalink, Kees; Boulton, Simon J.; Chen, Junjie; van Gent, Dik C.; Bartek, Jiri; Jonkers, Jos; Borst, Piet; Rottenberg, Sven

2015-01-01

Summary Error-free repair of DNA double-strand breaks (DSB) is achieved by homologous recombination (HR), and BRCA1 is an important factor for this repair pathway1. In the absence of BRCA1-mediated HR, administration of PARP inhibitors induces synthetic lethality of tumor cells of patients with breast or ovarian cancers2,3. Despite the benefit of this tailored therapy, drug resistance can occur by HR restoration4. Genetic reversion of BRCA1-inactivating mutations can be the underlying mechanism of drug resistance, but this does not explain resistance in all cases5. In particular, little is known about BRCA1-independent restoration of HR. Here, we show that loss of REV7 (also known as MAD2L2) re-establishes CtIP-dependent end resection of DSBs in BRCA1-deficient cells, leading to HR restoration and PARP inhibitor resistance, reversed by ATM kinase inhibition. REV7 is recruited to DSBs in a manner dependent on the H2AX-MDC1-RNF8-RNF168-53BP1 chromatin pathway, and appears to block HR and promote end joining in addition to its regulatory role in DNA damage tolerance6. Finally, we establish that REV7 blocks DSB resection to promote non-homologous end-joining (NHEJ) during immunoglobulin class switch recombination. Our results reveal an unexpected critical function of REV7 downstream of 53BP1 in coordinating pathological DSB repair pathway choices in BRCA1-deficient cells. PMID:25799992

Charge Transfer in Saturation Doping of Double-Wall Carbon Nanotubes

NASA Astrophysics Data System (ADS)

Tchernatinsky, Alexander; Jayanthi, Chakram; Sumanasekera, Gamini; Wu, Shi-Yu

2004-03-01

Recent experimental evidences suggest that the outer tube of a double-wall carbon nanotube (DWCNT) may serve as a 'Faraday' cage (G. Chen, et al., Phys. Rev. Lett., 90, 257403 (2003)). In this presentation, we report the result of our systematic study of the effect of saturation doping of a (10,10) single-wall carbon nanotube, a (5,5)@(10,10) DWCNT, and a C_60@(10,10) peapod using DFT-based VASP computational package (G. Kresse and J. Hafner, Phys. Rev. B, 47, 558 (1993)). By comparing the resulting charge transfer of the above mentioned cases we shall provide the physics underlying the Faraday cage behavior of DWCNTs. Acknowledgments: This work was supported by the NSF (DMR-0112824) and the U.S.DOE (DE-FG02-00ER45832).

Computational Study on the Different Ligands Induced Conformation Change of β2 Adrenergic Receptor-Gs Protein Complex

PubMed Central

Bai, Qifeng; Zhang, Yang; Ban, Yihe; Liu, Huanxiang; Yao, Xiaojun

2013-01-01

β2 adrenergic receptor (β2AR) regulated many key physiological processes by activation of a heterotrimeric GTP binding protein (Gs protein). This process could be modulated by different types of ligands. But the details about this modulation process were still not depicted. Here, we performed molecular dynamics (MD) simulations on the structures of β2AR-Gs protein in complex with different types of ligands. The simulation results demonstrated that the agonist BI-167107 could form hydrogen bonds with Ser2035.42, Ser2075.46 and Asn2936.55 more than the inverse agonist ICI 118,551. The different binding modes of ligands further affected the conformation of β2AR. The energy landscape profiled the energy contour map of the stable and dissociated conformation of Gαs and Gβγ when different types of ligands bound to β2AR. It also showed the minimum energy pathway about the conformational change of Gαs and Gβγ along the reaction coordinates. By using interactive essential dynamics analysis, we found that Gαs and Gβγ domain of Gs protein had the tendency to separate when the inverse agonist ICI 118,551 bound to β2AR. The α5-helix had a relatively quick movement with respect to transmembrane segments of β2AR when the inverse agonist ICI 118,551 bound to β2AR. Besides, the analysis of the centroid distance of Gαs and Gβγ showed that the Gαs was separated from Gβγ during the MD simulations. Our results not only could provide details about the different types of ligands that induced conformational change of β2AR and Gs protein, but also supplied more information for different efficacies of drug design of β2AR. PMID:23922653

Complete genome sequence of Streptococcus mutans GS-5, a serotype c strain.

PubMed

Biswas, Saswati; Biswas, Indranil

2012-09-01

Streptococcus mutans, a principal causative agent of dental caries, is considered to be the most cariogenic among all oral streptococci. Of the four S. mutans serotypes (c, e, f, and k), serotype c strains predominate in the oral cavity. Here, we present the complete genome sequence of S. mutans GS-5, a serotype c strain originally isolated from human carious lesions, which is extensively used as a laboratory strain worldwide.

Computational investigation of the HIV-1 Rev multimerization using molecular dynamics simulations and binding free energy calculations.

PubMed

Venken, Tom; Daelemans, Dirk; De Maeyer, Marc; Voet, Arnout

2012-06-01

The HIV Rev protein mediates the nuclear export of viral mRNA, and is thereby essential for the production of late viral proteins in the replication cycle. Rev forms a large organized multimeric protein-protein complex for proper functioning. Recently, the three-dimensional structures of a Rev dimer and tetramer have been resolved and provide the basis for a thorough structural analysis of the binding interaction. Here, molecular dynamics (MD) and binding free energy calculations were performed to elucidate the forces thriving dimerization and higher order multimerization of the Rev protein. It is found that despite the structural differences between each crystal structure, both display a similar behavior according to our calculations. Our analysis based on a molecular mechanics-generalized Born surface area (MM/GBSA) and a configurational entropy approach demonstrates that the higher order multimerization site is much weaker than the dimerization site. In addition, a quantitative hot spot analysis combined with a mutational analysis reveals the most contributing amino acid residues for protein interactions in agreement with experimental results. Additional residues were found in each interface, which are important for the protein interaction. The investigation of the thermodynamics of the Rev multimerization interactions performed here could be a further step in the development of novel antiretrovirals using structure based drug design. Moreover, the variability of the angle between each Rev monomer as measured during the MD simulations suggests a role of the Rev protein in allowing flexibility of the arginine rich domain (ARM) to accommodate RNA binding. Copyright © 2012 Wiley Periodicals, Inc.

REV-ERB-ALPHA circadian gene variant associates with obesity in two independent populations: Mediterranean and North American.

PubMed

Garaulet, Marta; Smith, Caren E; Gomez-Abellán, Purificación; Ordovás-Montañés, María; Lee, Yu-Chi; Parnell, Laurence D; Arnett, Donna K; Ordovás, José M

2014-04-01

Despite the solid connection between REV-ERB and obesity, the information about whether genetic variations at this locus may be associated with obesity traits is scarce. Therefore our objective was to study the association between REV-ERB-ALPHA1 rs2314339 and obesity in two independent populations. Participants were 2214 subjects from Spanish Mediterranean (n = 1404) and North American (n = 810) populations. Anthropometric, biochemical, dietary, and genotype analyses were performed. We found novel associations between the REV-ERB-ALPHA1 rs2314339 genotype and obesity in two independent populations: in Spanish Mediterranean and North American groups, the frequency of the minor-allele-carriers (AA+ AG) was significantly lower in the "abdominally obese" group than in those of the "nonabdominally obese" group (p < 0.05). Minor allele carriers had lower probability of abdominal obesity than noncarriers, and the effect was of similar magnitude for both populations (OR ≈ 1.50). There were consistent associations between REV-ERB-ALPHA1 genotype and obesity-related traits (p < 0.05). Energy intake was not significantly associated with REV-ERB-ALPHA1 rs2314339. However, physical activity significantly differed by genotype. A significant interaction between the REV-ERB-ALPHA1 variant and monounsaturated-fatty-acids (MUFA) intake for obesity was also detected in the Mediterranean population. This new discovery highlights the importance of REV-ERB-ALPHA1 in obesity and provides evidence for the connection between our biological clock and obesity-related traits. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tier One Performance Screen Initial Operational Test and Evaluation: 2014 Annual Report

DTIC Science & Technology

2017-07-01

selecting applicants into the Army, comprises the Verbal Expression5 (VE), Arithmetic Reasoning (AR), and Math Knowledge (MK) tests (AFQT = 2*VE + AR...135,013 49.45 9.00 16 84 General Science (GS) 418,620 50.99 8.29 19 76 135,013 50.26 8.31 20 76 Math Knowledge (MK) 418,620 53.24 6.80 25 73 135,013...7.02 20 76 Math Knowledge (MK) 396,164 53.43 6.81 25 73 22,456 49.76 5.57 26 73 Mechanical Comprehension (MC) 396,161 52.35 8.37 23 82 22,456

Roles of Rev1, Pol ζ, Pol32 and Pol η in the bypass of chromosomal abasic sites in Saccharomyces cerevisiae

PubMed Central

Auerbach, Paul A.; Demple, Bruce

2010-01-01

Translesion synthesis (TLS) on DNA is a process by which potentially cytotoxic replication-blocking lesions are bypassed, but at the risk of increased mutagenesis. The exact in vivo role of the individual TLS enzymes in Saccharomyces cerevisiae has been difficult to determine from previous studies due to differing results from the variety of systems used. We have generated a series of S.cerevisiae strains in which each of the TLS-related genes REV1, REV3, REV7, RAD30 and POL32 was deleted, and in which chromosomal apyrimidinic sites were generated during normal cell growth by the activity of altered forms of human uracil-DNA glycosylase that remove undamaged cytosines or thymines. Deletion of REV1, REV3 or REV7 resulted in slower growth dependent on (rev3Δ and rev7Δ) or enhanced by (rev1Δ) expression of the mutator glycosylases and a nearly complete abolition of glycosylase-induced mutagenesis. Deletion of POL32 resulted in cell death when the mutator glycosylases were expressed and, in their absence, diminished spontaneous mutagenesis. RAD30 appeared to be unnecessary for mutagenesis in response to abasic sites, as deleting this gene caused no significant change in either the mutation rates or the mutational spectra due to glycosylase expression. PMID:19901007

Oxycodone plus ultra-low-dose naltrexone attenuates neuropathic pain and associated mu-opioid receptor-Gs coupling.

PubMed

Largent-Milnes, Tally M; Guo, Wenhong; Wang, Hoau-Yan; Burns, Lindsay H; Vanderah, Todd W

2008-08-01

Both peripheral nerve injury and chronic opioid treatment can result in hyperalgesia associated with enhanced excitatory neurotransmission at the level of the spinal cord. Chronic opioid administration leads to a shift in mu-opioid receptor (MOR)-G protein coupling from G(i/o) to G(s) that can be prevented by cotreatment with an ultra-low-dose opioid antagonist. In this study, using lumbar spinal cord tissue from rats with L(5)/L(6) spinal nerve ligation (SNL), we demonstrated that SNL injury induces MOR linkage to G(s) in the damaged (ipsilateral) spinal dorsal horn. This MOR-G(s) coupling occurred without changing G(i/o) coupling levels and without changing the expression of MOR or Galpha proteins. Repeated administration of oxycodone alone or in combination with ultra-low-dose naltrexone (NTX) was assessed on the SNL-induced MOR-G(s) coupling as well as on neuropathic pain behavior. Repeated spinal oxycodone exacerbated the SNL-induced MOR-G(s) coupling, whereas ultra-low-dose NTX cotreatment slightly but significantly attenuated this G(s) coupling. Either spinal or oral administration of oxycodone plus ultra-low-dose NTX markedly enhanced the reductions in allodynia and thermal hyperalgesia produced by oxycodone alone and minimized tolerance to these effects. The MOR-G(s) coupling observed in response to SNL may in part contribute to the excitatory neurotransmission in spinal dorsal horn in neuropathic pain states. The antihyperalgesic and antiallodynic effects of oxycodone plus ultra-low-dose NTX (Oxytrex, Pain Therapeutics, Inc., San Mateo, CA) suggest a promising new treatment for neuropathic pain. The current study investigates whether Oxytrex (oxycodone with an ultra-low dose of naltrexone) alleviates mechanical and thermal hypersensitivities in an animal model of neuropathic pain over a period of 7 days, given locally or systemically. In this report, we first describe an injury-induced shift in mu-opioid receptor coupling from G(i/o) to G(s), suggesting

Involvement of the Clock Gene Rev-erb alpha in the Regulation of Glucagon Secretion in Pancreatic Alpha-Cells

PubMed Central

Vieira, Elaine; Marroquí, Laura; Figueroa, Ana Lucia C.; Merino, Beatriz; Fernandez-Ruiz, Rebeca; Nadal, Angel; Burris, Thomas P.; Gomis, Ramon; Quesada, Ivan

2013-01-01

Disruption of pancreatic clock genes impairs pancreatic beta-cell function, leading to the onset of diabetes. Despite the importance of pancreatic alpha-cells in the regulation of glucose homeostasis and in diabetes pathophysiology, nothing is known about the role of clock genes in these cells. Here, we identify the clock gene Rev-erb alpha as a new intracellular regulator of glucagon secretion. Rev-erb alpha down-regulation by siRNA (60–70% inhibition) in alphaTC1-9 cells inhibited low-glucose induced glucagon secretion (p<0.05) and led to a decrease in key genes of the exocytotic machinery. The Rev-erb alpha agonist GSK4112 increased glucagon secretion (1.6 fold) and intracellular calcium signals in alphaTC1-9 cells and mouse primary alpha-cells, whereas the Rev-erb alpha antagonist SR8278 produced the opposite effect. At 0.5 mM glucose, alphaTC1-9 cells exhibited intrinsic circadian Rev-erb alpha expression oscillations that were inhibited by 11 mM glucose. In mouse primary alpha-cells, glucose induced similar effects (p<0.001). High glucose inhibited key genes controlled by AMPK such as Nampt, Sirt1 and PGC-1 alpha in alphaTC1-9 cells (p<0.05). AMPK activation by metformin completely reversed the inhibitory effect of glucose on Nampt-Sirt1-PGC-1 alpha and Rev-erb alpha. Nampt inhibition decreased Sirt1, PGC-1 alpha and Rev-erb alpha mRNA expression (p<0.01) and glucagon release (p<0.05). These findings identify Rev-erb alpha as a new intracellular regulator of glucagon secretion via AMPK/Nampt/Sirt1 pathway. PMID:23936124

Glycation of polyclonal IgGs: Effect of sugar excipients during stability studies.

PubMed

Leblanc, Y; Bihoreau, N; Jube, M; Andre, M-H; Tellier, Z; Chevreux, G

2016-05-01

A number of intravenous immunoglobulin preparations are stabilized with sugar additives that may lead over time to undesirable glycation reactions especially in liquid formulation. This study aimed to evaluate the reactivity of sugar excipients on such preparations in condition of temperature, formulation and concentration commonly used for pharmaceutical products. Through an innovative LC-MS method reported to characterize post-translational modifications of IgGs Fc/2 fragments, a stability study of IVIg formulated with reducing and non-reducing sugars has been undertaken. The rate of polyclonal IgGs glycation was investigated during 6months at 5, 25, 30 and 40°C. High levels of glycation were observed with reducing sugars such as glucose and maltose in the first months of the stability study from 25°C. Non-reducing sugars presented a low reactivity even at the highest tested temperature (40°C). Furthermore, a site by site analysis was performed by MS/MS to determine the glycation sites which were mainly identified at Lys246, Lys248 and Lys324. This work points out the high probability of glycation reactions in some commercialized products and describes a useful method to characterize IVIg glycated products issued from reducing sugar excipients. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Roles of infection control nurses in Royal Thai Army hospitals.

PubMed

Chaisombat, Yawares; Moongtui, Wanchai; Soparat, Poonsap; Buppanharan, Wanchai; Danchaivijitr, Somwang

2005-12-01

To study the performance according to the assigned roles of infection control nurses (ICNs) in Royal Thai Army hospitals. Interviewing ICNs in 6 hospitals. During April and May 2002, 11 ICNs in 6 hospitals were interviewed. Two hospitals had been accredited and 4 were applying for hospital accreditation. Full-time ICNs were identified in 5 and part-time in 6. The ICNs were graduated with bachelor and master degrees in 5 and 6 respectively. Two ICNs graduated with master degree in IC. All could perform their roles in administration, education, surveillance, personnel health, consultation and quality improvement. Only 7 ICNs had experience in outbreak investigation. None were principle investigators in research except for their master degrees. The main problem was the absence of ICNs posts in all except 1 hospital. Infection control nurses in Royal Thai Army hospitals in the present study could perform their roles according to assignment except involvement in outbreak investigation in some and in research as the principle investigators in all.

[Gymnema sylvestre leaf extract: a 52-week dietary toxicity study in Wistar rats].

PubMed

Ogawa, Yukio; Sekita, Kiyoshi; Umemura, Takashi; Saito, Minoru; Ono, Atsushi; Kawasaki, Yasushi; Uchida, Osayuki; Matsushima, Yuko; Inoue, Tohru; Kanno, Jun

2004-02-01

A 52-week study of oral-repeated-dose toxicity for the extraction powder of Gymnema sylvestre (GS), Indian-native genus, Metaplexis japonica, was conducted in both genders of Wistar rats. The rats were administered a graded dose of GS at 0.01, 0.10 and 1.00% of basal powder diet, along with a group fed solely with the basal powder diet without GS, for 52 weeks. General conditions were recorded daily. Body weights and food consumptions were recorded weekly up to 12 weeks, and thereafter at longer intervals. At 26 weeks, for an intermediate examination, and 52 weeks, for the final examination, animals were subjected to hematology, serum chemistry, and pathological examination. None of the animals died in the period up to 52 weeks. No exposure-related changes in body-weight, in the food consumption, in the hematological examinations, or in the serum biochemical examinations were recognized. No histopathological alterations were seen. Thus, it was concluded that there was no toxic effect in rats treated with GS at up to 1.00% in the diet for 52 weeks. The no-observable-effect level from this study is 1.00% GS, i.e., 504 mg/kg/day for male and 563 mg/kg/day for female as mean daily intake, for 52 weeks.

Innocuity and immune response to Brucella melitensis Rev.1 vaccine in camels (Camelus dromedarius)

PubMed Central

Benkirane, A.; Idrissi, A.H. El; Doumbia, A.; de Balogh, K.

2014-01-01

A field trial was conducted in a camel brucellosis-free herd to evaluate antibody response to the Brucella melitensis Rev.1 vaccine in camels and assess shedding of the vaccine strain in milk. Twenty eight camels were divided into four groups according to their age and vaccination route. Groups A (n=3) and B (n=3) consisted of non-pregnant lactating female camels, vaccinated through subcutaneous and conjunctival routes, respectively. Groups C (n=10) consisted of 8-11 months old calves vaccinated through conjunctival route. The rest of the herd (n=12) composed of female and young camels were not vaccinated and were considered as the control group. Each animal from groups A, B and C was given the recommended dose of 2 × 109 colony forming units of Rev.1 vaccine irrespective of age or route of vaccination. Blood samples were collected from all the animals at the time of vaccination and at weekly, bi-weekly and monthly interval until 32 weeks post vaccination and from controls at weeks 8 and 24. The serological tests used were modified Rose Bengal Test, sero-agglutination test, and an indirect Enzyme Linked Immunosorbent Assay. Milk samples were collected from all vaccinated female camels and tested for the presence of Rev.1 vaccine strain. Most vaccinated animals started to show an antibody response at week 2 and remained positive until week 16. By week 20 post-vaccination all animals in the three groups were tested negative for Brucella antibodies. Bacteriological analysis of milk samples did not allow any isolation of Brucella melitensis. All samples were found Brucella negative in PCR analysis. The results of this study indicate that the Rev.1 vaccine induces seroconversion in camels. Rev.1 vaccine strain is not excreted in the milk of camels. These findings are promising as to the safe use of the Rev.1 vaccine in camels. PMID:26623347

Human protein Staufen-2 promotes HIV-1 proliferation by positively regulating RNA export activity of viral protein Rev.

PubMed

Banerjee, Atoshi; Benjamin, Ronald; Balakrishnan, Kannan; Ghosh, Payel; Banerjee, Sharmistha

2014-02-13

The export of intron containing viral RNAs from the nucleus to the cytoplasm is an essential step in the life cycle of Human Immunodeficiency Virus-1 (HIV-1). As the eukaryotic system does not permit the transport of intron containing RNA out of the nucleus, HIV-1 makes a regulatory protein, Rev, that mediates the transportation of unspliced and partially spliced viral mRNA from the nucleus to the cytoplasm, thereby playing a decisive role in the generation of new infectious virus particles. Therefore, the host factors modulating the RNA export activity of Rev can be major determinants of virus production in an infected cell. In this study, human Staufen-2 (hStau-2) was identified as a host factor interacting with HIV-1 Rev through affinity chromatography followed by MALDI analyses. Our experiments involving transient expressions, siRNA mediated knockdowns and infection assays conclusively established that hStau-2 is a positive regulator of HIV-1 pathogenesis. We demonstrated that Rev-hStau-2 interactions positively regulated the RNA export activity of Rev and promoted progeny virus synthesis. The Rev-hStau-2 interaction was independent of RNA despite both being RNA binding proteins. hStau-2 mutant, with mutations at Q314R-A318F-K319E, deficient of binding Rev, failed to promote hStau-2 dependent Rev activity and viral production, validating the essentiality of this protein-protein interaction. The expression of this positive regulator was elevated upon HIV-1 infection in both human T-lymphocyte and astrocyte cell lines. With this study, we establish that human Staufen-2, a host factor which is up-regulated upon HIV-1 infection, interacts with HIV-1 Rev, thereby promoting its RNA export activity and progeny virus formation. Altogether, our study provides new insights into the emerging role of the Staufen family of mRNA transporters in host-pathogen interaction and supports the notion that obliterating interactions between viral and host proteins that positively

Reuse Adoption Guidebook. Version 02.00.05

DTIC Science & Technology

1993-11-01

Oriented Domain Analysis ( FODA ) Feasibiity Study, W Novak, and S. Peterson CMU/SEI-90-TR-21 Pittsburgh, Pennsylvania: Software 1990 Engineering Institute...Mettala and Graham 1992). " SEI has developed domain analysis techniques (Kang et al. 1990) and other reuse technology. Additionally, the SEI is in the...continue to build on your success. Figure 2-1 illustrates the Reuse Adoption process using a Structured Analysis and Design Thchmque (SADT) diagram

High Pressure X-Ray Crystallography With the Diamond Cell at NIST/NBS

PubMed Central

Piermarini, Gasper J.

2001-01-01

Scientists in the Crystallography Section at NIST/NBS made several outstanding contributions which greatly promoted the development and advancement of high pressure x-ray crystallography during the second-half of the 20th century. These milestone achievements or “firsts” included: (1) the invention of the lever-arm type diamond anvil cell (DAC) in 1958; (2) the development of DAC technology for powder x-ray diffraction at high pressure in 1960; (3) the introduction of DAC methodology for single crystal x-ray diffraction at high pressure in 1964; (4) the invention of the optical fluorescence ruby method of pressure measurement in 1971; and (5) the discovery of hydrostatic pressure-transmitting media useful to unprecedented pressures for that time. These achievements provided the spark that ignited the explosion of activity in high pressure research that occurred in laboratories throughout the world during the latter part of the 20th century. It is still going on, unabated, today. An estimated 5000 DACs were built during the last 40 years. PMID:27500054

An atlas of stellar spectra between 2.00 and 2.45 micrometers (Arnaud, Gilmore, and Collier Cameron 1989)

NASA Technical Reports Server (NTRS)

Warren, Wayne N., Jr.

1990-01-01

The machine-readable version of the atlas, as it is currently being distributed from the Astronomical Data Center, is described. The atlas represent a collection of spectra in the wavelength range 2.00 to 2.45 micros having a resolution of approximately 0.02 micron. The sample of 73 stars includes a supergiant, giants, dwarfs, and subdwarfs with a chemical abundance range of about -2 to +0.5 dex.

Immunocytochemical localization of glutamic acid decarboxylase (GAD) and glutamine synthetase (GS) in the area postrema of the cat. Light and electron microscopy

NASA Technical Reports Server (NTRS)

D'Amelio, Fernando E.; Mehler, William R.; Gibbs, Michael A.; Eng, Lawrence F.; Wu, Jang-Yen

1987-01-01

Morphological evidence is presented of the existence of the putative neurotransmitter gamma-aminobutyric acid (GABA) in axon terminals and of glutamine synthetase (GS) in ependymoglial cells and astroglial components of the area postrema (AP) of the cat. Purified antiserum directed against the GABA biosynthetic enzyme glutamic acid decarboxylase (GAD) and GS antiserum were used. The results showed that punctate structures of variable size corresponding to axon terminals exhibited GAD-immunoreactivity and were distributed in varying densities. The greatest accumulation occurred in the caudal and middle segment of the AP and particularly in the area subpostrema, where the aggregation of terminals was extremely dense. The presence of both GAD-immunoreactive profiles and GS-immunostained ependymoglial cells and astrocytes in the AP provide further evidence of the functional correlation between the two enzymes.

Treatment with the fusion inhibitor enfuvirtide influences the appearance of mutations in the human immunodeficiency virus type 1 regulatory protein rev.

PubMed

Svicher, Valentina; Alteri, Claudia; D'Arrigo, Roberta; Laganà, Alessandro; Trignetti, Maria; Lo Caputo, Sergio; Callegaro, Anna Paola; Maggiolo, Franco; Mazzotta, Francesco; Ferro, Alfredo; Dimonte, Salvatore; Aquaro, Stefano; di Perri, Giovanni; Bonora, Stefano; Tommasi, Chiara; Trotta, Maria Paola; Narciso, Pasquale; Antinori, Andrea; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca

2009-07-01

The gp41-encoding sequence of the env gene contains in two separate regions the Rev-responsive elements (RRE) and the alternative open reading frame of the second exon of the regulatory protein Rev. The binding of Rev to the RRE allows the transport of unspliced/singly spliced viral mRNAs out of the nucleus, an essential step in the life cycle of human immunodeficiency virus type 1 (HIV-1). In this study, we have investigated whether the fusion-inhibitor enfuvirtide (ENF) can induce mutations in Rev and if these mutations correlate with the classical ENF resistance gp41 mutations and with viremia and CD4 cell count. Specific Rev mutations were positively associated with ENF treatment and significantly correlated with classical ENF resistance gp41 mutations. In particular, a cluster was observed for the Rev mutations E57A (E57A(rev)) and N86S(rev) with the ENF resistance gp41 mutations Q40H (Q40H(gp41)) and L45M(gp41). In addition, the presence at week 48 of the E57A(rev) correlates with a significant viremia increase from baseline to week 48 and with a CD4 cell count loss from baseline to week 48. By modeling the RRE structure, we found that the Q40(gp41) and L45(gp41) codons form complementary base pairs in a region of the RRE involved in Rev binding. The conformation of this Rev-binding site is disrupted when Q40H(gp41) and L45M(gp41) occur alone while it is restored when both mutations are present. In conclusion, our study shows that ENF pressure may also affect both Rev and RRE structures and can provide an excellent example of compensatory evolution. This highlights the multiple roles of ENF (and perhaps other entry inhibitors) in modulating the correct interplay between the different HIV-1 genes and proteins during the HIV-1 life cycle.

Attenuation of Quorum Sensing Regulated Virulence of Pectobacterium carotovorum subsp. carotovorum through an AHL Lactonase Produced by Lysinibacillus sp. Gs50

PubMed Central

Garge, Sneha S.; Nerurkar, Anuradha S.

2016-01-01

Quorum sensing (QS) is a mechanism in which Gram negative bacterial pathogens sense their population density through acyl homoserine lactones (AHLs) and regulate the expression of virulence factors. Enzymatic degradation of AHLs by lactonases, known as quorum quenching (QQ), is thus a potential strategy for attenuating QS regulated bacterial infections. We characterised the QQ activity of soil isolate Lysinibacillus sp. Gs50 and explored its potential for controlling bacterial soft rot of crop plants. Lysinibacillus sp. Gs50 inactivated AHL, which could be restored upon acidification, suggested that inactivation was due to the lactone ring hydrolysis of AHL. Heterologous expression of cloned gene for putative hydrolase (792 bp) designated adeH from Lysinibacillus sp. Gs50 produced a ~29 kDa protein which degraded AHLs of varying chain length. Mass spectrometry analysis of AdeH enzymatic reaction product revealed that AdeH hydrolyses the lactone ring of AHL and hence is an AHL lactonase. Multiple sequence alignment of the amino acid sequence of AdeH showed that it belongs to the metallo- β- lactamase superfamily, has a conserved “HXHXDH” motif typical of AHL lactonases. KM for AdeH for C6HSL was found to be 3.089 μM and the specific activity was 0.8 picomol min-1μg-1. AdeH has not so far been reported from any Lysinibacillus sp. and has less than 40% identity with known AHL lactonases. Finally we found that Lysinibacillus sp. Gs50 can degrade AHL produced by Pectobacterium carotovorum subsp. carotovorum (Pcc), a common cause of soft rot. This QQ activity causes a decrease in production of plant cell wall degrading enzymes of Pcc and attenuates symptoms of soft rot in experimental infection of potato, carrot and cucumber. Our results demonstrate the potential of Lysinibacillus sp. Gs50 as a preventive and curative biocontrol agent. PMID:27911925

A phase 1 clinical trial of the selective BTK inhibitor ONO/GS-4059 in relapsed and refractory mature B-cell malignancies.

PubMed

Walter, Harriet S; Rule, Simon A; Dyer, Martin J S; Karlin, Lionel; Jones, Ceri; Cazin, Bruno; Quittet, Philippe; Shah, Nimish; Hutchinson, Claire V; Honda, Hideyuki; Duffy, Kevin; Birkett, Joseph; Jamieson, Virginia; Courtenay-Luck, Nigel; Yoshizawa, Toshio; Sharpe, John; Ohno, Tomoya; Abe, Shinichiro; Nishimura, Akihisa; Cartron, Guillaume; Morschhauser, Franck; Fegan, Christopher; Salles, Gilles

2016-01-28

We report the results of a multicenter phase 1 dose-escalation study of the selective Bruton tyrosine kinase (BTK) inhibitor ONO/GS-4059 in 90 patients with relapsed/refractory B-cell malignancies. There were 9 dose-escalation cohorts ranging from 20 mg to 600 mg once daily with twice-daily regimens of 240 mg and 300 mg. Twenty-four of 25 evaluable chronic lymphocytic leukemia (CLL) patients (96%) responded to ONO/GS-4059, with a median treatment duration of 80 weeks; 21 CLL patients remain on treatment. Lymph node responses were rapid and associated with a concurrent lymphocytosis. Eleven of 12 evaluable patients with mantle cell lymphoma (92%) responded (median treatment duration, 40 weeks). Eleven of 31 non-germinal center B-cell diffuse large B-cell lymphoma patients (35%) responded but median treatment duration was 12 weeks due to development of progressive disease. ONO/GS-4059 was very well tolerated with 75% of adverse events (AEs) being Common Toxicity Criteria for Adverse Events version 4.0 grade 1 or grade 2. Grade 3/4 AEs were mainly hematologic and recovered spontaneously during therapy. One CLL patient experienced a grade 3 treatment-related bleeding event (spontaneous muscle hematoma) but no clinically significant diarrhea, cardiac dysrhythmias, or arthralgia were observed. No maximal tolerated dose (MTD) was reached in the CLL cohort. In the non-Hodgkin lymphoma cohort, 4 patients developed a dose-limiting toxicity, yielding an MTD of 480 mg once daily. ONO/GS-4059 has significant activity in relapsed/refractory B-cell malignancies without major drug-related toxicity. The selectivity of ONO/GS-4059 should confer advantages in combination therapies. This trial was registered at www.clinicaltrials.gov as #NCT01659255. © 2016 by The American Society of Hematology.

MAXI/GSC detection of a hard-to-soft transition of NS-LMXB GS 1826-238

NASA Astrophysics Data System (ADS)

Nakahira, S.; Mihara, T.; Sugizaki, M.; Serino, M.; Morii, M.; Sugimoto, J.; Takagi, T.; Yoshikawa, A.; Matsuoka, M.; Kawai, N.; Yoshii, T.; Tachibana, Y.; Ueno, S.; Tomida, H.; Kimura, M.; Ishikawa, M.; Nakagawa, Y. E.; Negoro, H.; Nakajima, M.; Fukushima, K.; Onodera, T.; Suzuki, K.; Fujita, M.; Namba, T.; Honda, F.; Yoshida, A.; Sakamoto, T.; Kawakubo, Y.; Ohtsuki, H.; Tsunemi, H.; Uchida, D.; Ueda, Y.; Shidatsu, M.; Kawamuro, T.; Hori, T.; Kawagoe, A.; Tsuboi, Y.; Yamauchi, M.; Morooka, Y.; Yamaoka, K.

2014-06-01

We report on a hard-to-soft spectral transition of an X-ray burster GS 1826-238 detected with MAXI/GSC. This source had been consistently observed in the hard state for more than 25 years since the discovery in 1988 (Tanaka 1989, Barret et al. ...

Endo-symbiont mediated synthesis of gold nanobactericides and their activity against human pathogenic bacteria.

PubMed

Syed, Baker; M N, Nagendra Prasad; K, Mohan Kumar; B L, Dhananjaya; Satish, Sreedharamurthy

2017-06-01

Synthesis of gold nanobactericides (AuNBs) were achieved by treating 1mM chloroaurate with cell free supernatant of Aneurinibacillus migulanus. Formation of AuNBs was initially was monitored with change in colour to ruby red. Further confirmation was assessed with UV-visible spectra with maximum absorption occurring at 510nm. Transmission electron microscopy (TEM) analysis revealed the polydispersity of AuNBs with size distribution ranging from 10 to 60nm with an average size of 30nm. Crystalline nature was studied using X-ray diffraction which exhibited characteristic peaks indexed to Bragg's reflection at 2θ angle which confers (111), (200), (220), and (311) planes suggesting AuNBs were face-centred cubic. Fourier transform infrared spectroscopy (FTIR) analysis revealed absorption peaks occurring at 3341cm -1 , 1635cm -1 and 670cm -1 which corresponds to functional groups attributing to synthesis. The antibacterial efficacy of AuNBs was tested against selective human pathogenic bacteria and activity was measured as zone of inhibition by using disc and well diffusion. Bactericidal activity was interpreted with standard antibiotics gentamicin and kanamycin. Micro broth dilution assay expressed the minimal concentration of AuNBs to inhibit the growth of test pathogens. Highest activity was observed against Pseudomonas aeruginosa (MTCC 7903) with 21.00±0.57mm compared to other pathogens. The possible mode of action of AuNBs on DNA was carried out with in vitro assay as preliminary test against pathogenic DNA isolated from P. aeruginosa. Further studies will be interesting enough to reveal the exact interactive mechanism of AuNBs with DNA. Overall study contributes towards biogenic synthesis of AuNBs as one of the alternative in combating drug resistant pathogens. Copyright © 2017 Elsevier B.V. All rights reserved.

Biological Characterization of CVRM2-BAC, A Recombinant CV1988 Virus Containing an REV LTR Insertion

USDA-ARS?s Scientific Manuscript database

It has been previously reported that avian retroviruses, i.e. avian leukosis virus (ALV) and reticoloendotheliosis virus (REV), integrate in the Marek’s disease virus genome affecting MDV pathogenicity. RM-2 is an attenuated serotype 1 MDV virus generated by insertion of the REV LTR in the genome of...

Genetic divergence for high-molecular weight glutenin subunits (HMW-GS) in indigenous landraces and commercial cultivars of bread wheat of Pakistan.

PubMed

Yasmeen, F; Khurshid, H; Ghafoor, A

2015-05-11

Wheat flour quality is an important consideration in the breeding and development of new cultivars. A strong association between high-molecular weight glutenin subunits (HMW-GS) and bread making quality has resulted in the widespread utilization of HMW-GS in wheat breeding. In this study, we analyzed 242 lines of wheat, including landraces from the provinces of Punjab and Baluchistan, as well as the commercial varieties of Pakistan, to determine allelic variation in the Glu-A1, Glu-B1, and Glu-D1 loci encoding HMW-GS. Higher genetic diversity was observed for HMW-GS in landraces from Baluchistan, followed by landraces collected from Punjab and then commercial varieties. Rare and uncommon subunits were observed in Glu-B1, whereas Glu-A1 was less polymorphic. However, Glu-B1 was the highest contributor to overall diversity (78%), with a total of 31 rare alleles, followed by Glu-D1 (20%) with the high quality 5+10 allele and other variants. Commercial cultivars possessed favorable alleles, potentially from indirect selection for wheat flour quality by the breeders; however, this indirect selection has decreased the pedigree base of commercial cultivars. The allelic combinations, including 2*, 5+10, and 17+18, showing high quality scores were frequent among landraces, indicating their usefulness in future crop improvement and breeding programs.

Improved stress tolerance and productivity in transgenic rice plants constitutively expressing the Oryza sativa glutathione synthetase OsGS under paddy field conditions.

PubMed

Park, Seong-Im; Kim, Young-Saeng; Kim, Jin-Ju; Mok, Ji-Eun; Kim, Yul-Ho; Park, Hyang-Mi; Kim, Il-Sup; Yoon, Ho-Sung

2017-08-01

Reactive oxygen species, which increase under various environmental stresses, have deleterious effects on plants. An important antioxidant, glutathione, is used to detoxify reactive oxygen species in plant cells and is mainly produced by two enzymes: gamma-glutamylcysteine synthetase (γ-ECS) and glutathione synthetase (GS). To evaluate the functional roles of the glutathione synthetase gene (OsGS) in rice, we generated four independent transgenic rice plants (TG1-TG4) that overexpressed OsGS under the control of the constitutively expressed OsCc1 promoter. When grown under natural paddy field conditions, the TG rice plants exhibited greater growth development, higher chlorophyll content, and higher GSH/GSSH ratios than control wild-type (WT) rice plants. Subsequently, the TG rice plants enhanced redox homeostasis by preventing hydroperoxide-mediated membrane damage, which improved their adaptation to environmental stresses. As a result, TG rice plants improved rice grain yield and total biomass following increases in panicle number and number of spikelets per panicle, despite differences in climate during the cultivation periods of 2014 and 2015. Overall, our results indicate that OsGS overexpression improved redox homeostasis by enhancing the glutathione pool, which resulted in greater tolerance to environmental stresses in the paddy fields. Copyright © 2017. Published by Elsevier GmbH.

Stimulation of nuclear receptor REV-ERBs regulates tumor necrosis factor-induced expression of proinflammatory molecules in C6 astroglial cells

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

Morioka, Norimitsu, E-mail: mnori@hiroshima-u.ac.jp; Tomori, Mizuki; Zhang, Fang Fang

Under physiological conditions, astrocytes maintain homeostasis in the CNS. Following inflammation and injury to the CNS, however, activated astrocytes produce neurotoxic molecules such as cytokines and chemokines, amplifying the initial molecular-cellular events evoked by inflammation and injury. Nuclear receptors REV-ERBα and REV-ERBβ (REV-ERBs) are crucial in the regulation of inflammation- and metabolism-related gene transcription. The current study sought to elucidate a role of REV-ERBs in rat C6 astroglial cells on the expression of inflammatory molecules following stimulation with the neuroinflammatory cytokine tumor necrosis factor (TNF). Stimulation of C6 cells with TNF (10 ng/ml) significantly increased the mRNA expression of CCL2, interleukin-6more » (IL-6), inducible nitric oxide synthase (iNOS), and matrix metalloprotease (MMP)-9, but not fibroblast growth factor-2 (FGF-2), cyclooxygenase-2 (COX-2) and MMP-2. Treatment with either REV-ERB agonists GSK4112 or SR9009 significantly blocked TNF-induced upregulation of CCL2 mRNA and MMP-9 mRNA, but not IL-6 mRNA and iNOS mRNA expression. Furthermore, treatment with RGFP966, a selective histone deacetylase 3 (HDAC3) inhibitor, potently reversed the inhibitory effects of GSK4112 on TNF-induced expression of MMP-9 mRNA, but not CCL2 mRNA. Expression of Rev-erbs mRNA in C6 astroglial cells, primary cultured rat cortical and spinal astrocytes was confirmed by reverse transcription polymerase chain reaction. Together, the findings demonstrate an anti-inflammatory effect, downregulating of MMP-9 and CCL2 transcription, of astroglial REV-ERBs activation through HDAC3-dependent and HDAC3-independent mechanisms. - Highlights: • Rev-erbα mRNA and Rev-erbβ mRNA are expressed in C6 astroglial cells. • TNF increases the expression of CCL2, IL-6, MMP-9 and iNOS mRNA. • REV-ERB activation inhibits CCL2 mRNA and MMP-9 mRNA expression. • HDAC3 activity is involved in the inhibitory effect of REV-ERB on MMP-9

Shadoo/PrP (Sprn0/0/Prnp0/0) double knockout mice

PubMed Central

Daude, Nathalie; Westaway, David

2012-01-01

Shadoo (Sho) is a brain glycoprotein with similarities to the unstructured region of PrPC. Frameshift alleles of the Sho gene, Sprn, are reported in variant Creutzfeldt-Jakob disease (vCJD) patients while Sprn mRNA knockdown in PrP-null (Prnp0/0) embryos produces lethality, advancing Sho as the hypothetical PrP-like “pi” protein. Also, Sho levels are reduced as misfolded PrP accumulates during prion infections. To penetrate these issues we created Sprn null alleles (Daude et al., Proc. Natl. Acad. Sci USA 2012; 109(23): 9035–40). Results from the challenge of Sprn null and TgSprn transgenic mice with rodent-adapted prions coalesce to define downregulation of Sho as a “tracer” for the formation of misfolded PrP. However, classical BSE and rodent-adapted BSE isolates may behave differently, as they do for other facets of the pathogenic process, and this intriguing variation warrants closer scrutiny. With regards to physiological function, double knockout mice (Sprn0/0/Prnp0/0) mice survived to over 600 d of age. This suggests that Sho is not pi, or, given the accumulating data for many activities for PrPC, that the pi hypothesis invoking a discrete signaling pathway to maintain neuronal viability is no longer tenable. PMID:22929230

THE FAST DECLINING TYPE Ia SUPERNOVA 2003gs, AND EVIDENCE FOR A SIGNIFICANT DISPERSION IN NEAR-INFRARED ABSOLUTE MAGNITUDES OF FAST DECLINERS AT MAXIMUM LIGHT

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

Krisciunas, Kevin; Marion, G. H.; Suntzeff, Nicholas B.

2009-12-15

We obtained optical photometry of SN 2003gs on 49 nights, from 2 to 494 days after T(B {sub max}). We also obtained near-IR photometry on 21 nights. SN 2003gs was the first fast declining Type Ia SN that has been well observed since SN 1999by. While it was subluminous in optical bands compared to more slowly declining Type Ia SNe, it was not subluminous at maximum light in the near-IR bands. There appears to be a bimodal distribution in the near-IR absolute magnitudes of Type Ia SNe at maximum light. Those that peak in the near-IR after T(B {sub max})more » are subluminous in the all bands. Those that peak in the near-IR prior to T(B {sub max}), such as SN 2003gs, have effectively the same near-IR absolute magnitudes at maximum light regardless of the decline rate {delta}m {sub 15}(B). Near-IR spectral evidence suggests that opacities in the outer layers of SN 2003gs are reduced much earlier than for normal Type Ia SNe. That may allow {gamma} rays that power the luminosity to escape more rapidly and accelerate the decline rate. This conclusion is consistent with the photometric behavior of SN 2003gs in the IR, which indicates a faster than normal decline from approximately normal peak brightness.« less

a KA-BAND Chirped-Pulse Fourier Transform Microwave Spectrometer.

NASA Astrophysics Data System (ADS)

Zaleski, Daniel P.; Neill, Justin L.; Muckle, Matthew T.; Pate, Brooks H.; Carroll, P. Brandon; Weaver, Susanna L. Widicus

2010-06-01

The design and performance of a new chirped-pulse Fourier transform microwave (CP-FTMW) spectrometer operating from 25-40 GHz will be discussed. A 10.5-3 GHz linear frequency sweep, generated by a 24 GS/s arbitrary waveform generator, is upconverted by a 23.00 GHz phase-locked oscillator, then fed into an active doubler to create a 25-40 GHz chirped pulse. After amplification with a 60-80 W pulsed traveling wave tube amplifier, the pulse is broadcast across a molecular beam chamber where it interacts with a molecular sample. The molecular FID signal is downconverted with the 23 GHz oscillator so that it can be digitized on a 50 GS/s oscilloscope with 16 GHz hardware bandwidth. The sensitivity and phase stability of this spectrometer is comparable to that of the previously reported 6.5-18.5 CP-FTMW spectrometer. On propyne (μ=0.78 D), a single-shot signal to noise ratio of approximately 200:1 is observed on the J=2-1 rotational transition at 34183 MHz when the full bandwidth is swept; optimal excitation is observed for this transition with a 250 MHz bandwidth sweep. The emission has a T_2 lifetime of 4 μs. Early results from this spectrometer, particularly in the study of species of astrochemical interest, will be presented. G.G. Brown et al., Rev. Sci. Instrum. 79 (2008) 053103.

Chimeric RNase H–Competent Oligonucleotides Directed to the HIV-1 Rev Response Element

PubMed Central

Prater, Chrissy E.; Saleh, Anthony D.; Wear, Maggie P.; Miller, Paul S.

2007-01-01

Chimeric oligo-2′-O-methylribonucleotides containing centrally located patches of contiguous 2′-deoxyribonucleotides and terminating in a nuclease resistant 3′-methylphosphonate internucleotide linkage were prepared. The oligonucleotides were targeted to the 3′-side of HIV Rev response element (RRE) stem-loop IIB RNA, which is adjacent to the high affinity Rev protein binding site and is critical to virus function. Thermal denaturation experiments showed that chimeric oligonucleotides form very stable duplexes with a complementary single-stranded RNA, and gel electrophoretic mobility shift assays (EMSA) showed that they bind with high affinity and specificity to RRE stem-loop II RNA (KD approximately 200 nM). The chimeric oligonucleotides promote RNase H-mediated hydrolysis of RRE stem-loop II RNA and have half lives exceeding 24 h when incubated in cell culture medium containing 10% fetal calf serum. One of the chimeric oligonucleotides inhibited RRE mediated expression of chloramphenicol acetyl transferase (CAT) approximately 60% at a concentration of 300 nM in HEK 293T cells co-transfected with p-RRE/CAT and p-Rev mammalian expression vectors. PMID:17566743

Comparative Proteome Analysis of Brucella melitensis Vaccine Strain Rev 1 and a Virulent Strain, 16M

PubMed Central

Eschenbrenner, Michel; Wagner, Mary Ann; Horn, Troy A.; Kraycer, Jo Ann; Mujer, Cesar V.; Hagius, Sue; Elzer, Philip; DelVecchio, Vito G.

2002-01-01

The genus Brucella consists of bacterial pathogens that cause brucellosis, a major zoonotic disease characterized by undulant fever and neurological disorders in humans. Among the different Brucella species, Brucella melitensis is considered the most virulent. Despite successful use in animals, the vaccine strains remain infectious for humans. To understand the mechanism of virulence in B. melitensis, the proteome of vaccine strain Rev 1 was analyzed by two-dimensional gel electrophoresis and compared to that of virulent strain 16M. The two strains were grown under identical laboratory conditions. Computer-assisted analysis of the two B. melitensis proteomes revealed proteins expressed in either 16M or Rev 1, as well as up- or down-regulation of proteins specific for each of these strains. These proteins were identified by peptide mass fingerprinting. It was found that certain metabolic pathways may be deregulated in Rev 1. Expression of an immunogenic 31-kDa outer membrane protein, proteins utilized for iron acquisition, and those that play a role in sugar binding, lipid degradation, and amino acid binding was altered in Rev 1. PMID:12193611

Comparative proteome analysis of Brucella melitensis vaccine strain Rev 1 and a virulent strain, 16M.

PubMed

Eschenbrenner, Michel; Wagner, Mary Ann; Horn, Troy A; Kraycer, Jo Ann; Mujer, Cesar V; Hagius, Sue; Elzer, Philip; DelVecchio, Vito G

2002-09-01

The genus Brucella consists of bacterial pathogens that cause brucellosis, a major zoonotic disease characterized by undulant fever and neurological disorders in humans. Among the different Brucella species, Brucella melitensis is considered the most virulent. Despite successful use in animals, the vaccine strains remain infectious for humans. To understand the mechanism of virulence in B. melitensis, the proteome of vaccine strain Rev 1 was analyzed by two-dimensional gel electrophoresis and compared to that of virulent strain 16M. The two strains were grown under identical laboratory conditions. Computer-assisted analysis of the two B. melitensis proteomes revealed proteins expressed in either 16M or Rev 1, as well as up- or down-regulation of proteins specific for each of these strains. These proteins were identified by peptide mass fingerprinting. It was found that certain metabolic pathways may be deregulated in Rev 1. Expression of an immunogenic 31-kDa outer membrane protein, proteins utilized for iron acquisition, and those that play a role in sugar binding, lipid degradation, and amino acid binding was altered in Rev 1.

Is the coverage of google scholar enough to be used alone for systematic reviews

PubMed Central

2013-01-01

Background In searches for clinical trials and systematic reviews, it is said that Google Scholar (GS) should never be used in isolation, but in addition to PubMed, Cochrane, and other trusted sources of information. We therefore performed a study to assess the coverage of GS specifically for the studies included in systematic reviews and evaluate if GS was sensitive enough to be used alone for systematic reviews. Methods All the original studies included in 29 systematic reviews published in the Cochrane Database Syst Rev or in the JAMA in 2009 were gathered in a gold standard database. GS was searched for all these studies one by one to assess the percentage of studies which could have been identified by searching only GS. Results All the 738 original studies included in the gold standard database were retrieved in GS (100%). Conclusion The coverage of GS for the studies included in the systematic reviews is 100%. If the authors of the 29 systematic reviews had used only GS, no reference would have been missed. With some improvement in the research options, to increase its precision, GS could become the leading bibliographic database in medicine and could be used alone for systematic reviews. PMID:23302542

A Sequence of Outbursts from the Transient X-Ray Pulsar GS 0834-430

NASA Technical Reports Server (NTRS)

Wilson, Colleen A.; Finger, Mark H.; Harmon, B.Alan; Scott, D. Matthew; Wilson, Robert B.; Bildsten, Lars; Chakrabarty, Deepto; Prince, Thomas A.

1997-01-01

GS 0834-430, a 12.3 s accretion-powered pulsar, has been observed in seven outbursts with the BATSE large-area detectors on the Compton Gamma Ray Observatory. The first five outbursts observed by BATSE occurred at intervals of about 107 days, while the final two outbursts were separated by about 140 days. The photon energy spectrum, measured by Earth occultation in the 20 100 keV band, can be fitted by a power law with photon index alpha approximately equals -3.7 or by an exponential spectrum with temperature kT approximately equals 15 keV, with some variations within outbursts. The source has a low pulse fraction, less than or equal to 0.15 in the 20-50 keV band. We have observed significant temporal and energy-dependent variations in epoch folded pulse profiles. Because the intrinsic torque effects for this system are at least comparable to orbital effects, pulse timing analysis did not produce a unique orbital solution. However, confidence regions for the orbital elements yielded the following 1 sigma limits: orbital period P(sub orb) = 105.8 +/- 0.4 days and eccentricity 0.10 less than or approximately equals epsilon less than or approximately equals 0.17. GS 0834-430 is most likely a Be/X-ray binary.

A 10 GS/s time-interleaved ADC in 0.25 micrometer CMOS technology

NASA Astrophysics Data System (ADS)

Aytar, Oktay; Tangel, Ali; Afacan, Engin

2017-11-01

This paper presents design and simulation of a 4-bit 10 GS/s time interleaved ADC in 0.25 micrometer CMOS technology. The designed TI-ADC has 4 channels including 4-bit flash ADC in each channel, in which area and power efficiency are targeted. Therefore, basic standard cell logic gates are preferred. Meanwhile, the aspect ratios in the gate designs are kept as small as possible considering the speed performance. In the literature, design details of the timing control circuits have not been provided, whereas the proposed timing control process is comprehensively explained and design details of the proposed timing control process are clearly presented in this study. The proposed circuits producing consecutive pulses for timing control of the input S/H switches (ie the analog demultiplexer front-end circuitry) and the very fast digital multiplexer unit at the output are the main contributions of this study. The simulation results include +0.26/-0.22 LSB of DNL and +0.01/-0.44 LSB of INL, layout area of 0.27 mm2, and power consumption of 270 mW. The provided power consumption, DNL and INL measures are observed at 100 MHz input with 10 GS/s sampling rate.

Experimental Investigation of Widespread Delamination Damage to Composite Materials Caused by Radiant Heating

DTIC Science & Technology

2013-06-30

Rev. E) 2002. 7. RM-3002 Bismaleimide (BMI) Prepreg , Product Information, Renegade Materials Corporation, Revision Date: 16-May-2012 KOA 16... prepregs /polyimide- prepregs . Renegade Materials Corporation Website, Accessed June 20, 2013. 9. Shen, C. and G.S. Springer, “Moisture Absorption and

20. FOUR 4B17Gs BEING CONVERTED TO F9Cs. Photographic copy of ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

20. FOUR 4B-17Gs BEING CONVERTED TO F-9Cs. Photographic copy of historic photograph. Jan.-June 1947 OAMA (original print located at Ogden Air Logistics Center, Hill Air Force Base, Utah). Photographer unknown. - Hill Field, Airplane Repair Hangars No. 1-No. 4, 5875 Southgate Avenue, Layton, Davis County, UT

REV-ERB-ALPHA circadian gene variant associates with obesity in two independent populations: Mediterranean and North American

USDA-ARS?s Scientific Manuscript database

Despite the solid connection between REV-ERB and obesity, the information about whether genetic variations at this locus may be associated with obesity traits is scarce. Therefore our objective was to study the association between REV-ERB-ALPHA1 rs2314339 and obesity in two independent populations. ...

Effect of total lumbar disc replacement on lumbosacral lordosis.

PubMed

Kasliwal, Manish K; Deutsch, Harel

2012-10-01

Original article : To study effect of lumbar disc replacement on lumbosacral lordosis. There has been a growing interest in total disc replacement (TDR) for back pain with the rising concern of adjacent segment degeneration. Lumbar fusion surgery has been shown to lead to decrease in lumbar lordosis, which may account for postfusion pain resulting in less acceptable clinical outcome after successful fusion. TDR has recently emerged as an alternative treatment for back pain. There have been very few studies reporting lumbar sagittal outcome after TDR. Retrospective study of radiographic data of 17 patients who underwent TDR for single level degenerative disc disease at the author's institution was carried out. Study included measurement of preoperative and postoperative segmental and global lumbar lordosis and angle of lordosis. Patients age varied from 19 to 54 (mean, 35) years. Follow-up ranged from 12 to 24 months. TDR was performed at L4-5 level in 3 patients and L5-S1 level in 14 patients. The average values for segmental lordosis, global lordosis, and angle of lordosis at the operated level before and after surgery were 17.3, 49.7, and 8.6 degrees and 21.6, 54, and 9.5 degrees, respectively. There was a trend toward significant (P=0.02) and near significant (P=0.057) increase in segmental and global lordosis, respectively after TDR. Although prosthesis increased angle of lordosis at the level implanted in majority of the patients, the difference in preoperative and postoperative angle of lordosis was not significant (P=0.438). In addition, there was no correlation between the angle of implant of chosen and postoperative angle of lordosis at the operated level. The effect of TDR on sagittal balance appears favorable with an increase in global and segmental lumbar lordosis after single level TDR for degenerative disc disease. The degree of postoperative angle of lordosis was not affected by the angle of implant chosen at the operated level and varied

Unprecedented NES non-antagonistic inhibitor for nuclear export of Rev from Sida cordifolia.

PubMed

Tamura, Satoru; Kaneko, Masafumi; Shiomi, Atsushi; Yang, Guang-Ming; Yamaura, Toshiaki; Murakami, Nobutoshi

2010-03-15

Bioassay-guided separation from the MeOH extract of the South American medicinal plant Sida cordifolia resulted in isolation of (10E,12Z)-9-hydroxyoctadeca-10,12-dienoic acid (1) as an unprecedented NES non-antagonistic inhibitor for nuclear export of Rev. This mechanism of action was established by competitive experiment by the biotinylated probe derived from leptomycin B, the known NES antagonistic inhibitor. Additionally, structure-activity relationship analysis by use of the synthesized analogs clarified cooperation of several functionalities in the Rev-export inhibitory activity of 1. Copyright 2010 Elsevier Ltd. All rights reserved.

05/04 VIG Seminar @ 3:00 pm - 4:00 pm Bldg 50/2328 | Center for Cancer Research

Cancer.gov

Please join us for the next VIG seminar on Thursday, May 4th from 3:00-4:00 in Building 50, Room 2328.   Presenter: Gustavo Palacios, Ph.D. Director, Genomic Center, USAMRIID Title: How Genomic Tools could improve our Biopreparedness?: Pathogen Discovery, Near Real-Time Advanced characterization and Immunomics  

Documentation for the machine-readable version of A Finding List for the Multiplet Tables of NSRDS-NBS 3, Sections 1-10 (Adelman, Adelman, Fischel and Warren 1984)

NASA Technical Reports Server (NTRS)

Warren, W. H., Jr.

1984-01-01

The machine-readable finding list, as it is currently being distributed from the Astronomical Data Center, is described. This version of the list supersedes an earlier one (1977) containing only Sections 1 through 7 of the NSRDS-NBS 3 multiplet tables publications. Additional sections are to be incorporated into this list as they are published.

Field gamma-ray spectrometer GS256: measurements stability

NASA Astrophysics Data System (ADS)

Mojzeš, Andrej

2009-01-01

The stability of in situ readings of the portable gamma-ray spectrometer GS256 during the field season of 2006 was studied. The instrument is an impulse detector of gamma rays based on NaI(Tl) 3" × 3" scintillation unit and 256-channel spectral analyzer which allows simultaneous assessment of up to 8 radioisotopes in rocks. It is commonly used in surface geophysical survey for the measurement of natural 40K, 238U and 232Th but also artificial 137Cs quantities. The statistical evaluation is given of both repeated measurements - in the laboratory and at several field control points in different survey areas. The variability of values shows both the instrument stability and also the relative influence of some meteorological factors, mainly rainfalls. The analysis shows an acceptable level of instrument measurements stability, the necessity to avoid measurement under unfavourable meteorological conditions and to keep detailed field book information about time, position and work conditions.

Molecular typing of Brucella melitensis endemic strains and differentiation from the vaccine strain Rev-1.

PubMed

Noutsios, Georgios T; Papi, Rigini M; Ekateriniadou, Loukia V; Minas, Anastasios; Kyriakidis, Dimitrios A

2012-03-01

In the present study forty-four Greek endemic strains of Br. melitensis and three reference strains were genotyped by Multi locus Variable Number Tandem Repeat (ML-VNTR) analysis based on an eight-base pair tandem repeat sequence that was revealed in eight loci of Br. melitensis genome. The forty-four strains were discriminated from the vaccine strain Rev-1 by Restriction Fragment Length Polymorphism (RFLP) and Denaturant Gradient Gel Electrophoresis (DGGE). The ML-VNTR analysis revealed that endemic, reference and vaccine strains are genetically closely related, while most of the loci tested (1, 2, 4, 5 and 7) are highly polymorphic with Hunter-Gaston Genetic Diversity Index (HGDI) values in the range of 0.939 to 0.775. Analysis of ML-VNTRs loci stability through in vitro passages proved that loci 1 and 5 are non stable. Therefore, vaccine strain can be discriminated from endemic strains by allele's clusters of loci 2, 4, 6 and 7. RFLP and DGGE were also employed to analyse omp2 gene and reveled different patterns among Rev-1 and endemic strains. In RFLP, Rev-1 revealed three fragments (282, 238 and 44 bp), while endemic strains two fragments (238 and 44 bp). As for DGGE, the electrophoretic mobility of Rev-1 is different from the endemic strains due to heterologous binding of DNA chains of omp2a and omp2b gene. Overall, our data show clearly that it is feasible to genotype endemic strains of Br. melitensis and differentiate them from vaccine strain Rev-1 with ML-VNTR, RFLP and DGGE techniques. These tools can be used for conventional investigations in brucellosis outbreaks.

Influence of fogging lenses and cycloplegia on open-field automatic refraction.

PubMed

Queirós, A; González-Méijome, J; Jorge, J

2008-07-01

To compare refractive values measured with and without cycloplegia, or with fogging lenses, using an open-field auto-refractor. One hundred and forty-two young adults were enrolled from a university population; 96 were female (67.6%) and 46 were male (32.4%), the age range was 18-26 years (mean 22.3 +/- 3.7 years). The refraction measurement was obtained for the right eye of each subject with the Grand Seiko Auto Ref/Keratometer WAM-5500 (GS) under three conditions, always in this sequence: (1) without cycloplegia (GS), (2) without cycloplegia but using a + 2.00 D fogging lens (GS_2D) and (3) with cycloplegia (GS_cycl). When the average values of spherical equivalent were compared, both accommodation control strategies were almost equally successful: GS, M = -0.85 +/- 2.21 D; GC_2D, M = -0.53 +/- 2.10 D and GS_cycl, M = -0.57 +/- 2.24 D (Kruskal-Wallis test, p < 0.001). When the results were analysed separately for different refractive groups, emmetropes and hyperopes show statistically significant differences while myopes did not. When both accommodation strategies were compared there was a trend for more myopic subjects to display more negative values under cycloplegia, while low myopes, emmetropes and hyperopes tend to display more negative values with the +2.00 D fogging lenses, suggesting this was less effective for accommodation control. Over-refraction through +2.00 D fogging lenses is useful to achieve additional relaxation of the accommodative response in a similar way to cycloplegia when open-field autorefraction is performed in young adults.

Simultaneous mutation and copy number variation (CNV) detection by multiplex PCR-based GS-FLX sequencing.

PubMed

Goossens, Dirk; Moens, Lotte N; Nelis, Eva; Lenaerts, An-Sofie; Glassee, Wim; Kalbe, Andreas; Frey, Bruno; Kopal, Guido; De Jonghe, Peter; De Rijk, Peter; Del-Favero, Jurgen

2009-03-01

We evaluated multiplex PCR amplification as a front-end for high-throughput sequencing, to widen the applicability of massive parallel sequencers for the detailed analysis of complex genomes. Using multiplex PCR reactions, we sequenced the complete coding regions of seven genes implicated in peripheral neuropathies in 40 individuals on a GS-FLX genome sequencer (Roche). The resulting dataset showed highly specific and uniform amplification. Comparison of the GS-FLX sequencing data with the dataset generated by Sanger sequencing confirmed the detection of all variants present and proved the sensitivity of the method for mutation detection. In addition, we showed that we could exploit the multiplexed PCR amplicons to determine individual copy number variation (CNV), increasing the spectrum of detected variations to both genetic and genomic variants. We conclude that our straightforward procedure substantially expands the applicability of the massive parallel sequencers for sequencing projects of a moderate number of amplicons (50-500) with typical applications in resequencing exons in positional or functional candidate regions and molecular genetic diagnostics. 2008 Wiley-Liss, Inc.

Juxta-articular myxoma and intramuscular myxoma are two distinct entities. Activating Gs alpha mutation at Arg 201 codon does not occur in juxta-articular myxoma.

PubMed

Okamoto, Sumika; Hisaoka, Masanori; Meis-Kindblom, Jeanne M; Kindblom, Lars-Gunnar; Hashimoto, Hiroshi

2002-01-01

Juxta-articular myxoma is a rare myxoid tumor of soft tissue that bears a close histologic resemblance to intramuscular myxoma but is distinguished from the latter by its clinical setting and behavior. Activating missense mutations at the Arg 201 codon of the Gs alpha gene ultimately leading to increased levels of cyclic adenosine monophosphate have been implicated in McCune-Albright syndrome and sporadic fibrous dysplasia of bone. Recently, we have demonstrated that the same Gs alpha mutations occur in intramuscular myxomas associated with fibrous dysplasia of bone (Mazabraud's syndrome) as well as in sporadic intramuscular myxoma. The overlapping histologic appearances of juxta-articular myxoma and intramuscular myxoma prompted us to investigate whether there is a relationship between the two entities. We studied this possibility by looking for Gs alpha mutations in juxta-articular myxoma using polymerase chain reaction (PCR) to amplify appropriate genomic DNA fragments extracted from formalin-fixed, paraffin-embedded specimens of five juxta-articular myxomas, followed by single-strand conformation polymorphism analysis. Using these techniques, no aberrant bands were detected in any of the five juxta-articular myxomas, indicating that they lack Gs alpha mutations. Moreover, DNA sequencing of the PCR products of two JAMs showed no abnormalities. We conclude that juxta-articular myxomas, in contrast to intramuscular myxomas, do not involve Arg 201 mutations of the Gs alpha gene, indicating that they represent distinct entities with different underlying molecular mechanisms.

Observations of whitecaps during HiWinGS, their dependence on wave field, and relation to gas transfer velocities

NASA Astrophysics Data System (ADS)

Brumer, S. E.; Zappa, C. J.; Fairall, C. W.; Blomquist, B.; Brooks, I. M.; Tamura, H.; Yang, M.; Huebert, B. J.

2016-02-01

The High Wind Gas exchange Study (HiWinGS) presents the unique opportunity to gain new insights on the poorly understood aspects of air-sea interaction under high winds. The HiWinGS cruise took place in the North Atlantic during October and November 2013. Wind speeds exceeded 15 m s-1 25% of the time, including 48 hrs with U10 > 20 m s-1. Continuous measurements of turbulent fluxes of heat, momentum, and gas were taken from the bow of the R/V Knorr. Visible imagery was acquired from the port and starboard side of the flying bridge during daylight hours at 20Hz and directional wave spectra were obtained when on station from a wave rider buoy. Additional wave field statistics were computed from a laser altimeter as well as from a Wavewatch III hindcast. Taking advantage of the range of physical forcing and wave conditions sampled during HiWinGS, we investigate how the fractional whitecap coverage (W) and gas transfer velocity (K) vary with sea state. We distinguish between windseas and swell based on a separation algorithm applied to directional wave spectra, allowing contrasting pure windseas to swell dominated periods. For mixed seas, system alignment is considered when interpreting results. The four gases sampled during HiWinGS ranged from being mostly waterside controlled to almost entirely airside controlled. While bubble-mediated transfer appears to be small for moderately soluble gases like DMS, the importance of wave breaking turbulence transport has yet to be determined for all gases regardless of their solubility. This will be addressed by correlating measured K to estimates of active whitecap fraction (WA) and turbulent kinetic energy dissipation rate (ɛ). WA and ɛ are estimated from moments of the breaking crest length distribution derived from the imagery, focusing on young seas, when it is likely that large-scale breaking waves (i.e., whitecapping) will dominate the ɛ.

40 CFR 86.131-00 - Vehicle preparation.

Code of Federal Regulations, 2010 CFR

2010-07-01

... controls dynamometer dynamic inertia weight adjustments (see §§ 86.108-00(b)(2)(ii) and 86.129-00(f)(2)). If a manufacturer chooses not to implement dynamic inertia adjustments for a portion or all of their...

40 CFR 86.131-00 - Vehicle preparation.

Code of Federal Regulations, 2013 CFR

2013-07-01

... controls dynamometer dynamic inertia weight adjustments (see §§ 86.108-00(b)(2)(ii) and 86.129-00(f)(2)). If a manufacturer chooses not to implement dynamic inertia adjustments for a portion or all of their...

40 CFR 86.131-00 - Vehicle preparation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... controls dynamometer dynamic inertia weight adjustments (see §§ 86.108-00(b)(2)(ii) and 86.129-00(f)(2)). If a manufacturer chooses not to implement dynamic inertia adjustments for a portion or all of their...

Determining the Complexity of the Quantum Adiabatic Algorithm using Quantum Monte Carlo Simulations

DTIC Science & Technology

2012-12-18

of this printing. List the papers, including journal references, in the following categories: Received Paper 12/06/2012 4.00 Itay Hen, A. Young...PhysRevLett.104.020502 12/06/2012 3.00 A. P. Young, Itay Hen. Exponential complexity of the quantum adiabatic algorithm for certain satisfiability problems...Physical Review E, (12 2011): 0. doi: 10.1103/PhysRevE.84.061152 12/06/2012 5.00 Edward Farhi, David Gosset, Itay Hen, A. Sandvik, Peter Shor, A

Investigating univariate temporal patterns for intrinsic connectivity networks based on complexity and low-frequency oscillation: a test-retest reliability study.

PubMed

Wang, X; Jiao, Y; Tang, T; Wang, H; Lu, Z

2013-12-19

Intrinsic connectivity networks (ICNs) are composed of spatial components and time courses. The spatial components of ICNs were discovered with moderate-to-high reliability. So far as we know, few studies focused on the reliability of the temporal patterns for ICNs based their individual time courses. The goals of this study were twofold: to investigate the test-retest reliability of temporal patterns for ICNs, and to analyze these informative univariate metrics. Additionally, a correlation analysis was performed to enhance interpretability. Our study included three datasets: (a) short- and long-term scans, (b) multi-band echo-planar imaging (mEPI), and (c) eyes open or closed. Using dual regression, we obtained the time courses of ICNs for each subject. To produce temporal patterns for ICNs, we applied two categories of univariate metrics: network-wise complexity and network-wise low-frequency oscillation. Furthermore, we validated the test-retest reliability for each metric. The network-wise temporal patterns for most ICNs (especially for default mode network, DMN) exhibited moderate-to-high reliability and reproducibility under different scan conditions. Network-wise complexity for DMN exhibited fair reliability (ICC<0.5) based on eyes-closed sessions. Specially, our results supported that mEPI could be a useful method with high reliability and reproducibility. In addition, these temporal patterns were with physiological meanings, and certain temporal patterns were correlated to the node strength of the corresponding ICN. Overall, network-wise temporal patterns of ICNs were reliable and informative and could be complementary to spatial patterns of ICNs for further study. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Enhancement of heterogeneous alkaline xylanase production in Pichia pastoris GS115

NASA Astrophysics Data System (ADS)

Zheng, Wei

2017-08-01

A series of strategies were applied to improve expression level of the recombinant alkaline xylanase from Bacillus pumilus G1-3 in Pichia pastoris GS115. Codon optimization of xylanase gene xynG1-3 from B. pumilus G1-3 were carried out for its heterogeneous expression in P. pastoris. The activity of xylanase encoded by optimized gene (xynG1-3-opt) was up to 33641 U/mL, which was 37% higher than that by wild-type (xynG1-3) gene. The results will greatly contribute to increasing the production of recombinant proteins in P. pastoris and improving the industrial production of the alkaline xylanase.

NICER Discovers mHz Oscillations and Marginally Stable Burning in GS 1826-24

NASA Astrophysics Data System (ADS)

Strohmayer, Tod E.; Gendreau, Keith C.; Keek, Laurens; Bult, Peter; Mahmoodifar, Simin; Chakrabarty, Deepto; Arzoumanian, Zaven; NICER Science Team

2018-01-01

To date, marginally stable thermonuclear burning, evidenced as mHz X-ray flux oscillations, has been observed in only five accreting neutron star binaries, 4U 1636-536, 4U 1608-52, Aql X-1, 4U 1323-619 and Terzan 5 X-2. Here we report the discovery with NASA's Neutron Star Interior Composition Explorer (NICER) of such oscillations from the well-known X-ray burster GS 1826-24. NICER observed GS 1826-24 on 9 September, 2017 for a total exposure of about 4 ksec. Timing analysis revealed highly significant oscillations at a frequency of 8.2 mHz in two successive pointings. The oscillations have a fractional modulation amplitude of approximately 3% for photon energies less than 6 keV. The observed frequency is consistent with the range observed in the other mHz QPO systems, and indeed is slightly higher than the frequency measured in 4U 1636-536 below which mHz oscillations ceased and unstable burning (X-ray bursts) resumed. We discuss the mass accretion rate dependence of the oscillations as well as the X-ray spectrum as a function of pulsation phase. We place the observations in the context of the current theory of marginally stable burning and briefly discuss the potential for constraining neutron star properties using mHz oscillations.

International Space Station Research Plan, Assembly Sequence Rev., F

DTIC Science & Technology

2000-08-01

muscles ü Higher risk for bone fracture upon return to Earth ü Potential for “slipped discs” ü Diminished ability to quickly respond to emergencies...Office of Biological and Physical Research International Space Station Research Plan Assembly Sequence Rev. F, Aug. 2000l . , . Report...Organization Name(s) and Address(es) NASA, Office of Biological and Physical Research Performing Organization Report Number Sponsoring/Monitoring Agency

A truncated form of CD9-partner 1 (CD9P-1), GS-168AT2, potently inhibits in vivo tumour-induced angiogenesis and tumour growth

PubMed Central

Colin, S; Guilmain, W; Creoff, E; Schneider, C; Steverlynck, C; Bongaerts, M; Legrand, E; Vannier, J P; Muraine, M; Vasse, M; Al-Mahmood, S

2011-01-01

Background: Tetraspanins are transmembrane proteins known to contribute to angiogenesis. CD9 partner-1 (CD9P-1/EWI-F), a glycosylated type 1 transmembrane immunoglobulin, is a member of the tetraspanin web, but its role in angiogenesis remains to be elucidated. Methods: We measured the expression of CD9P-1 under angiogenic and angiostatic conditions, and the influence of its knockdown onto capillary structures formation by human endothelial cells (hECs). A truncated form of CDP-1, GS-168AT2, was produced and challenged vs hEC proliferation, migration and capillaries' formation. Its association with CD9P-1, CD9, CD81 and CD151 and the expressions of these later at hEC surface were analysed. Finally, its effects onto in vivo tumour-induced angiogenesis and tumour growth were investigated. Results: Vascular endothelial growth factor (VEGF)-induced capillary tube-like formation was inhibited by tumour necrosis factor α and was associated with a rise in CD9P-1 mRNA expression (P<0.05); accordingly, knockdown of CD9P-1 inhibited VEGF-dependent in vitro angiogenesis. GS-168AT2 dose-dependently inhibited in vitro angiogenesis, hEC migration and proliferation (P<0.05). Co-precipitation experiments suggest that GS-168AT2 corresponds to the sequence by which CD9P-1 physiologically associates with CD81. GS-168AT2 induced the depletion of CD151, CD9 and CD9P-1 from hEC surface, correlating with GS-168AT2 degradation. Finally, in vivo injections of GS-168AT2 inhibited tumour-associated angiogenesis by 53.4±9.5% (P=0.03), and reduced tumour growth of Calu 6 tumour xenografts by 73.9±16.4% (P=0.007) without bodyweight loss. Conclusion: The truncated form of CD9P-1, GS-168AT2, potently inhibits angiogenesis and cell migration by at least the downregulation of CD151 and CD9, which provides the first evidences for the central role of CD9P-1 in tumour-associated angiogenesis and tumour growth. PMID:21863033

76 FR 4532 - Safety Zone; 500 Yards North and South, Bank to Bank, of Position 29°48.77′ N 091°33.02′ W...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-26

...-AA00 Safety Zone; 500 Yards North and South, Bank to Bank, of Position 29[deg]48.77' N 091[deg]33.02' W... and South, bank to bank, of position 29[deg]48.77' N 091[deg]33.02' W, Charenton Drainage and Navigation Canal, St. Mary Parish, LA. This Safety Zone is needed to protect the general public, vessels and...

A canopy radiative transfer scheme with explicit FAPAR for the ISBA-A-gs land surface model: impact on carbon fluxes

NASA Astrophysics Data System (ADS)

Calvet, Jean-Christophe; Carrer, Dominique; Roujean, Jean-Louis; Lafont, Sébastien

2013-04-01

The ISBA-A-gs land surface model is a component of the SURFEX modeling platform developed by Meteo-France, used for research and operational applications in meteorology, hydrology, and climate modeling. ISBA-A-gs simulates hourly water and CO2 fluxes together with soil moisture. An option of the model permits the simulation of the vegetation biomass and of the leaf area index (LAI). The simulated photosynthesis depends on atmospheric CO2 concentration, air temperature and humidity, soil moisture, radiant solar energy, the photosynthetic capacity of the leaves and on factors that condition the distribution of solar radiation over the leaves. In the original version of the model (Jacobs et al. (Agr. Forest Meteorol., 1996), Calvet et al. (Agr. Forest Meteorol., 1998)), the radiative transfer scheme within the canopy was implemented according to a self shading approach. The incident fluxes at the top of the canopy go through a multi-layer vegetation cover. Then, the attenuated flux in the PAR wavelength domain of each layer is used by the photosynthesis model to calculate the leaf net assimilation of CO2 (An). The leaf-level An values are then integrated at the canopy level. In this study, an upgraded version of the radiative transfer model is implemented. An assessment of the vegetation transmittance functions and of various canopy light-response curves is made. The fluxes produced by the new version of ISBA-A-gs are evaluated using data from a number of FLUXNET forest sites. The new model presents systematically better scores than the previous version. Moreover, ISBA-A-gs is now able to simulate prognostic values of the fraction of absorbed PAR (FAPAR). As FAPAR can be observed from space, this new capability permits the validation of the model simulations at a global scale, and the integration of measured FAPAR values in the model through data assimilation techniques.

In-silico mining, type and frequency analysis of genic microsatellites of finger millet (Eleusine coracana (L.) Gaertn.): a comparative genomic analysis of NBS-LRR regions of finger millet with rice.

PubMed

Kalyana Babu, B; Pandey, Dinesh; Agrawal, P K; Sood, Salej; Kumar, Anil

2014-05-01

In recent years, the increased availability of the DNA sequences has given the possibility to develop and explore the expressed sequence tags (ESTs) derived SSR markers. In the present study, a total of 1956 ESTs of finger millet were used to find the microsatellite type, distribution, frequency and developed a total of 545 primer pairs from the ESTs of finger millet. Thirty-two EST sequences had more than two microsatellites and 1357 sequences did not have any SSR repeats. The most frequent type of repeats was trimeric motif, however the second place was occupied by dimeric motif followed by tetra-, hexa- and penta repeat motifs. The most common dimer repeat motif was GA and in case of trimeric SSRs, it was CGG. The EST sequences of NBS-LRR region of finger millet and rice showed higher synteny and were found on nearly same positions on the rice chromosome map. A total of eight, out of 15 EST based SSR primers were polymorphic among the selected resistant and susceptible finger millet genotypes. The primer FMBLEST5 could able to differentiate them into resistant and susceptible genotypes. The alleles specific to the resistant and susceptible genotypes were sequenced using the ABI 3130XL genetic analyzer and found similarity to NBS-LRR regions of rice and finger millet and contained the characteristic kinase-2 and kinase 3a motifs of plant R-genes belonged to NBS-LRR region. The In-silico and comparative analysis showed that the genes responsible for blast resistance can be identified, mapped and further introgressed through molecular breeding approaches for enhancing the blast resistance in finger millet.

40 CFR 86.132-00 - Vehicle preconditioning.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 18 2010-07-01 2010-07-01 false Vehicle preconditioning. 86.132-00 Section 86.132-00 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS...] (iii) If a manufacturer has concerns about fuel effects on adaptive memory systems, a manufacturer may...

LLNL Radiation Protection Program (RPP) Rev 9.2, Implementation of 10 CFR 835, 'Occupational Radiation Protection'

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

Shingleton, K. L.

2011-06-15

The Department of Energy (DOE) originally issued Part 10 CFR 835, Occupational Radiation Protection, on January 1, 1994. This regulation, hereafter referred to as “the Rule”, required DOE contractors to develop and maintain a DOE-approved Radiation Protection Program (RPP); DOE approved the initial Lawrence Livermore National Laboratory (LLNL) RPP (Rev 2) on 6/29/95. DOE issued a revision to the Rule on December 4, 1998 and approved LLNL’s revised RPP (Rev 7.1) on 11/18/99. DOE issued a second Rule revision on June 8, 2007 (effective July 9, 2007) and on June 13, 2008 approved LLNL’s RPP (Rev 9.0) which contained plansmore » and measures for coming into compliance with the 2007 Rule changes. DOE issued a correction to the Rule on April 21, 2009.« less

Preliminary experiments about the measure of the magnetic properties of a material by means of TDR probes

NASA Astrophysics Data System (ADS)

Persico, Raffaele

2016-04-01

In this contribution, the possibility of measuring possible magnetic properties of materials by means of a TDR probe is studied. A transmission line model is adopted and data in time and frequency domain are exploited together. Simulation results are shown, at the moment based on a bifilar line model. Magnetic properties of materials can be of interest for several applications. In particular, the presence of magnetic features in the soil or in any substance, might be associated to some contaminant (presumably containing some metallic element as iron, nickel or chromium [1]). This kind of pollution might occur close to some farms, especially regarding the dying of dresses, the production of some medicines, the tanning of leather issues. Moreover, modern agriculture puts in the soil several fertilizing substances, and there is a debate about the quantity of heavy metals spread in the terrain by these activities [2]. Still, some depuration-mud can be affected by an excessive presence of metallic elements, because of the presence of batteries, skins, varnishes, cosmetics, and so on [2]. Moreover, it is thought that the soil on the planet Mars might show magnetic properties [3]. Finally, in GPR prospecting, possible magnetic characteristics of the soil or of the targets might be of interest too [4], but they cannot be retrieved by means of only GPR data [5]. In the present paper, the results of a preliminary study are exposed with regard to the possibility to measure the magnetic properties of a material by mean of a TDR probe [6-7]. In particular a TDR probe is essentially a transmission line (a bifilar model will be exploited in this work) open at the end, form which most of the impinging energy (ideally the whole of thi energy in a lossless medium) is back reflected. In particular, this allows a customary measure of the propagation velocity in the medium if an impulsive signal is generated. In fact, the return time along a path of known length is measured. The

Determination of Flux rope axis for GS reconstruction

NASA Astrophysics Data System (ADS)

Tian, A.; Shi, Q.; Bai, S.; Zhang, S.

2016-12-01

It is important to give the axis direction and velocity of a magnetic flux ropes before employing Grad-Shafranov reconstruction. The ability of single-satellite based MVA (MVAB and CMVA) and multi-satellite based MDD methods in finding the invariant axis are tested by a model. The choice of principal axis given by MVA along the aimed direction is dependent on the distance of the path from the flux-rope axis. The MDD results are influenced by the ratio of Noise level/separation to the gradient of the structure. An accurate axial direction will be obtained when the ratio is less than 1. By a model, an example with failed HT method is displayed indicating the importance of the STD method in obtaining the velocity of such a structure. The applicability of trial and error method by Hu and Sonnerup(2012) was also used and discussed. Finally, all above methods were applied to a flux-rope observed by Cluster. It shows that the GS method can be easily carried out in the case of clearly known dimensionality and velocity.

Genome-Wide Analysis of Mycoplasma bovirhinis GS01 Reveals Potential Virulence Factors and Phylogenetic Relationships.

PubMed

Chen, Shengli; Hao, Huafang; Zhao, Ping; Liu, Yongsheng; Chu, Yuefeng

2018-05-04

Mycoplasma bovirhinis is a significant etiology in bovine pneumonia and mastitis, but our knowledge about the genetic and pathogenic mechanisms of M. bovirhinis is very limited. In this study, we sequenced the complete genome of M. bovirhinis strain GS01 isolated from the nasal swab of pneumonic calves in Gansu, China, and we found that its genome forms a 847,985 bp single circular chromosome with a GC content of 27.57% and with 707 protein-coding genes. The putative virulence determinants of M. bovirhinis were then analyzed. Results showed that three genomic islands and 16 putative virulence genes, including one adhesion gene enolase, seven surface lipoproteins, proteins involved in glycerol metabolism, and cation transporters, might be potential virulence factors. Glycerol and pyruvate metabolic pathways were defective. Comparative analysis revealed remarkable genome variations between GS01 and a recently reported HAZ141_2 strain, and extremely low homology with others mycoplasma species. Phylogenetic analysis demonstrated that M. bovirhinis was most genetically close to M. canis , distant from other bovine Mycoplasma species. Genomic dissection may provide useful information on the pathogenic mechanisms and genetics of M. bovirhinis . Copyright © 2018 Chen et al.

Dynamic release of gentamicin sulfate (GS) from alginate dialdehyde (AD)-crosslinked casein (CAS) films for antimicrobial applications

PubMed Central

Bajpai, S. K.; Shah, Farhan Ferooz; Bajpai, M.

2017-01-01

Abstract In the present work, antibiotic drug gentamicin sulfate (GS) has been loaded into alginate dialdehyde-crosslinked casein (CAS) films for wound dressing applications. The films have been characterized by Fourier transform infrared spectroscopy, X-ray diffraction analysis and scanning electron microscopy. The dynamic release of model drug GS has been investigated in the physiological fluid at 37 °C. The drug release data has been interpreted in the terms of various kinetic models such as Power function model, first order model and Schott model. The release data was found to be well fitted by Schott model. The various diffusion coefficients are also evaluated. The adsorption of model therapeutic protein BSA on the film has been investigated. The maximum adsorption is found to be 5.7 mg/cm2.The films were tested for their antibacterial and anti-fungal action. Finally, the in vivo wound healing study was carried out on Albino wistar rats. PMID:29491776

Pharmacokinetic study of isocorynoxeine metabolites mediated by cytochrome P450 enzymes in rat and human liver microsomes.

PubMed

Zhao, Lizhu; Zang, Bin; Qi, Wen; Chen, Fangfang; Wang, Haibo; Kano, Yoshihiro; Yuan, Dan

2016-06-01

Isocorynoxeine (ICN) is one of the major bioactive tetracyclic oxindole alkaloids found in Uncaria rhynchophylla (Miq.) Jacks. that is widely used for the treatment of hypertension, vascular dementia, and stroke. The present study was undertaken to assess the plasma pharmacokinetic characteristics of major ICN metabolites, and the role of simulated gastric and intestinal fluid (SGF and SIF), human and rat liver microsomes (HLMs and RLMs), and seven recombinant human CYP enzymes in the major metabolic pathway of ICN. A rapid, sensitive and accurate UHPLC/Q-TOF MS method was validated for the simultaneous determination of ICN and its seven metabolites in rat plasma after oral administration of ICN at 40mg/kg. It was found that 18.19-dehydrocorynoxinic acid (DCA) and 5-oxoisocorynoxeinic acid (5-O-ICA) were both key and predominant metabolites, rather than ICN itself, due to the rapid and extensive metabolism of ICN in vivo. The further study indicated that ICN was mainly metabolized in human or rat liver, and CYPs 2C19, 3A4 and 2D6 were the major enzymes responsible for the biotransformation of ICN to DCA and 5-O-ICA in human. These findings are of significance in understanding of the pharmacokinetic nature of tetracyclic oxindole alkaloids, and provide helpful information for the clinical co-administration of the herbal preparations containing U. rhynchophylla with antihypertensive drugs that are mainly metabolized by CYP3A4 and CYP2C19. Copyright © 2016 Elsevier B.V. All rights reserved.

Efficacy and tolerance of enzymatic hydrolysed collagen (EHC) vs. glucosamine sulphate (GS) in the treatment of knee osteoarthritis (KOA).

PubMed

Trč, Tomáš; Bohmová, Jana

2011-03-01

This was a 13-week, multicentre, randomised, parallel, double-blind study. One hundred men and women volunteers aged ≥ 40 years with knee osteoarthritis (KOA) were randomised to once daily enzymatic hydrolysed collagen (EHC) 10 g or glucosamine sulphate (GS) 1.5 g for 90 consecutive days. Follow-up took place after two weeks and after one, two and three months. Primary [visual analogue scale (VAS), Western Ontario and McMaster Universities (WOMAC Index)] and secondary outcomes variables, assessed at weeks two, four, eight and 12, were KOA pain intensity measured by quadruple visual analogue scales in the target knee, the WOMAC total score index, patient's and investigator's global assessments of disease activity, joint assessment, use of rescue medication (ibuprofen 400 mg tablets) and assessment of Quality of Life index (SF-36 Questionnaire). Safety and tolerability were also evaluated. Clear improvement was observed in both joint pain and symptoms in patients with KOA treated with EHC (Colatech®) and significant differences were observed. Mean reductions from baseline for EHC 10 g daily and GS 1.5 g, respectively, were KOA pain intensity reduction in the target knee for Colatech® (p < 0.05): WOMAC index decrease ≤ 15 points at the last visit (day 90) for Colatech® in 16 patients (34.04%) (p < 0.05) and for glucosamine in six patients (13.04%); total score index for painful joints: Colatech® 1.6 (p < 0.05) and glucosamine 1.8; total score index for swollen joints: Colatech® 0.5 (p < 0.05) and glucosamine 0.7; patient's global assessment of efficacy as the sum of improvement good + ideal: 80.8% for Colatech® and 46.6% for glucosamine (p < 0.05). EHC (Colatech®) showed superior improvement over GS in the SF-36 Questionnaire in the Physical Health Index (42.0 for Colatech and 40.0 for glucosamine). The incidence of adverse events was similar in both groups. Both EHC and GS were well tolerated.

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Federal Register 2010, 2011, 2012, 2013, 2014

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The positive impact of simultaneous implementation of the BD FocalPoint GS Imaging System and lean principles on the operation of gynecologic cytology.

PubMed

Wong, Rebecca; Levi, Angelique W; Harigopal, Malini; Schofield, Kevin; Chhieng, David C

2012-02-01

Our cytology laboratory, like many others, is under pressure to improve quality and provide test results faster while decreasing costs. We sought to address these issues by introducing new technology and lean principles. To determine the combined impact of the FocalPoint Guided Screener (GS) Imaging System (BD Diagnostics-TriPath, Burlington, North Carolina) and lean manufacturing principles on the turnaround time (TAT) and productivity of the gynecologic cytology operation. We established a baseline measure of the TAT for Papanicolaou tests. We then compared that to the performance after implementing the FocalPoint GS Imaging System and lean principles. The latter included value-stream mapping, workflow modification, and a first in-first out policy. The mean (SD) TAT for Papanicolaou tests before and after the implementation of FocalPoint GS Imaging System and lean principles was 4.38 (1.28) days and 3.20 (1.32) days, respectively. This represented a 27% improvement in the average TAT, which was statistically significant (P < .001). In addition, the productivity of staff improved 17%, as evidenced by the increase in slides screened from 8.85/h to 10.38/h. The false-negative fraction decreased from 1.4% to 0.9%, representing a 36% improvement. In our laboratory, the implementation of FocalPoint GS Imaging System in conjunction with lean principles resulted in a significant decrease in the average TAT for Papanicolaou tests and a substantial increase in the productivity of cytotechnologists while maintaining the diagnostic quality of gynecologic cytology.

DOE-FG02-00ER62797 Final Report

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

Sweedler, J.V.

2004-12-01

Specific Aims The overall goal of this proposal has been to develop and interface a new technology, molecular gates, with microfabricated systems to add an important capability to microfabricated DNA measurement systems. This project specifically focused on demonstrating how molecular gates could be used to capture a single analyte band, among a stream of bands from a separation or a flow injection analysis experiment, and release it for later measurement, thus allowing further manipulations on the selected analyte. Since the original proposal, the molecular gate concept has been greatly expanded to allow the gates to be used as externally controllablemore » intelligent interconnects in multilayer microfluidic networks. We have demonstrated: (1) the ability of the molecular gates to work with a much wider range of biological molecules including DNA, proteins and small metabolites; and (2) the capability of performing an electrophoretic separation and sequestering individual picoliter volume components (or even classes of components) into separate channels for further analysis. Both capabilities will enable characterization of small mass amounts of complex mixtures of DNA, proteins and even small molecules--allowing them to be further separated and chemically characterized.« less

Evaluation of instant cup noodle, irradiated for immuno-compromised patients

NASA Astrophysics Data System (ADS)

Lee, Ji-Hye; Kim, Jae-Kyung; Park, Jae-Nam; Yoon, Young-Min; Sung, Nak-Yun; Kim, Jae-Hun; Song, Beom-Seok; Yook, Hong-Sun; Kim, Byeong-Keun; Lee, Ju-Woon

2012-08-01

In the present study, initial microbial load of instant cup noodle (ICN) was investigated and gamma irradiation applied to develop immuno-compromised patients food for their safe consumption. The initial microbial population of dried vegetable and meat, and noodle was below the detection limit (1 log CFU/g); however, that of seasoning powder was just above 4 log CFU/g. Moreover, rehydrated-ICN with water at 100 °C still show above 3 log CFU/g of microbial load, which indicates the need for an additional process to control microbial safety of the seasoning powder. The total aerobic bacteria in seasoning powder and rehydrated-ICN could be controlled with 17 kGy gamma irradiation. This result referred 17 kGy gamma irradiation could reach 'practical sterility' of ICN. The overall difference in sensory properties between the non-irradiated and irradiated ICN was insignificant. Thus, gamma irradiation could improve the microbial quality of ICN, and reduce the risk of infection posed by the seasoning powder, without any adverse effects on their sensory quality. These results suggest that gamma-irradiated ICN can be used as a snack food for immuno-compromised patients.