Preventing conflicts among bid curves used with transactive controllers in a market-based resource allocation system

DOEpatents

Fuller, Jason C.; Chassin, David P.; Pratt, Robert G.; Hauer, Matthew; Tuffner, Francis K.

2017-03-07

Disclosed herein are representative embodiments of methods, apparatus, and systems for distributing a resource (such as electricity) using a resource allocation system. One of the disclosed embodiments is a method for operating a transactive thermostatic controller configured to submit bids to a market-based resource allocation system. According to the exemplary method, a first bid curve is determined, the first bid curve indicating a first set of bid prices for corresponding temperatures and being associated with a cooling mode of operation for a heating and cooling system. A second bid curve is also determined, the second bid curve indicating a second set of bid prices for corresponding temperatures and being associated with a heating mode of operation for a heating and cooling system. In this embodiment, the first bid curve, the second bid curve, or both the first bid curve and the second bid curve are modified to prevent overlap of any portion of the first bid curve and the second bid curve.

Structural and biochemical studies of RIG-I antiviral signaling.

PubMed

Feng, Miao; Ding, Zhanyu; Xu, Liang; Kong, Liangliang; Wang, Wenjia; Jiao, Shi; Shi, Zhubing; Greene, Mark I; Cong, Yao; Zhou, Zhaocai

2013-02-01

Retinoic acid-inducible gene I (RIG-I) is an important pattern recognition receptor that detects viral RNA and triggers the production of type-I interferons through the downstream adaptor MAVS (also called IPS-1, CARDIF, or VISA). A series of structural studies have elaborated some of the mechanisms of dsRNA recognition and activation of RIG-I. Recent studies have proposed that K63-linked ubiquitination of, or unanchored K63-linked polyubiquitin binding to RIG-I positively regulates MAVS-mediated antiviral signaling. Conversely phosphorylation of RIG-I appears to play an inhibitory role in controlling RIG-I antiviral signal transduction. Here we performed a combined structural and biochemical study to further define the regulatory features of RIG-I signaling. ATP and dsRNA binding triggered dimerization of RIG-I with conformational rearrangements of the tandem CARD domains. Full length RIG-I appeared to form a complex with dsRNA in a 2:2 molar ratio. Compared with the previously reported crystal structures of RIG-I in inactive state, our electron microscopic structure of full length RIG-I in complex with blunt-ended dsRNA, for the first time, revealed an exposed active conformation of the CARD domains. Moreover, we found that purified recombinant RIG-I proteins could bind to the CARD domain of MAVS independently of dsRNA, while S8E and T170E phosphorylation-mimicking mutants of RIG-I were defective in binding E3 ligase TRIM25, unanchored K63-linked polyubiquitin, and MAVS regardless of dsRNA. These findings suggested that phosphorylation of RIG inhibited downstream signaling by impairing RIG-I binding with polyubiquitin and its interaction with MAVS.

Negative role of RIG-I serine 8 phosphorylation in the regulation of interferon-beta production.

PubMed

Nistal-Villán, Estanislao; Gack, Michaela U; Martínez-Delgado, Gustavo; Maharaj, Natalya P; Inn, Kyung-Soo; Yang, Heyi; Wang, Rong; Aggarwal, Aneel K; Jung, Jae U; García-Sastre, Adolfo

2010-06-25

RIG-I (retinoic acid-inducible gene I) and TRIM25 (tripartite motif protein 25) have emerged as key regulatory factors to induce interferon (IFN)-mediated innate immune responses to limit viral replication. Upon recognition of viral RNA, TRIM25 E3 ligase binds the first caspase recruitment domain (CARD) of RIG-I and subsequently induces lysine 172 ubiquitination of the second CARD of RIG-I, which is essential for the interaction with downstream MAVS/IPS-1/CARDIF/VISA and, thereby, IFN-beta mRNA production. Although ubiquitination has emerged as a major factor involved in RIG-I activation, the potential contribution of other post-translational modifications, such as phosphorylation, to the regulation of RIG-I activity has not been addressed. Here, we report the identification of serine 8 phosphorylation at the first CARD of RIG-I as a negative regulatory mechanism of RIG-I-mediated IFN-beta production. Immunoblot analysis with a phosphospecific antibody showed that RIG-I serine 8 phosphorylation steady-state levels were decreased upon stimulation of cells with IFN-beta or virus infection. Substitution of serine 8 in the CARD RIG-I functional domain with phosphomimetic aspartate or glutamate results in decreased TRIM25 binding, RIG-I ubiquitination, MAVS binding, and downstream signaling. Finally, sequence comparison reveals that only primate species carry serine 8, whereas other animal species carry an asparagine, indicating that serine 8 phosphorylation may represent a primate-specific regulation of RIG-I activation. Collectively, these data suggest that the phosphorylation of RIG-I serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction, further underscoring the importance of RIG-I and TRIM25 connection in type I IFN signal transduction.

23 CFR 635.113 - Bid opening and bid tabulations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... CONSTRUCTION AND MAINTENANCE Contract Procedures § 635.113 Bid opening and bid tabulations. (a) All bids... contractors, during the period following the opening of bids and before the award of the contract shall not be...

A Hierarchical Mechanism of RIG-I Ubiquitination Provides Sensitivity, Robustness and Synergy in Antiviral Immune Responses.

PubMed

Sun, Xiaoqiang; Xian, Huifang; Tian, Shuo; Sun, Tingzhe; Qin, Yunfei; Zhang, Shoutao; Cui, Jun

2016-07-08

RIG-I is an essential receptor in the initiation of the type I interferon (IFN) signaling pathway upon viral infection. Although K63-linked ubiquitination plays an important role in RIG-I activation, the optimal modulation of conjugated and unanchored ubiquitination of RIG-I as well as its functional implications remains unclear. In this study, we determined that, in contrast to the RIG-I CARD domain, full-length RIG-I must undergo K63-linked ubiquitination at multiple sites to reach full activity. A systems biology approach was designed based on experiments using full-length RIG-I. Model selection for 7 candidate mechanisms of RIG-I ubiquitination inferred a hierarchical architecture of the RIG-I ubiquitination mode, which was then experimentally validated. Compared with other mechanisms, the selected hierarchical mechanism exhibited superior sensitivity and robustness in RIG-I-induced type I IFN activation. Furthermore, our model analysis and experimental data revealed that TRIM4 and TRIM25 exhibited dose-dependent synergism. These results demonstrated that the hierarchical mechanism of multi-site/type ubiquitination of RIG-I provides an efficient, robust and optimal synergistic regulatory module in antiviral immune responses.

A Hierarchical Mechanism of RIG-I Ubiquitination Provides Sensitivity, Robustness and Synergy in Antiviral Immune Responses

PubMed Central

Sun, Xiaoqiang; Xian, Huifang; Tian, Shuo; Sun, Tingzhe; Qin, Yunfei; Zhang, Shoutao; Cui, Jun

2016-01-01

RIG-I is an essential receptor in the initiation of the type I interferon (IFN) signaling pathway upon viral infection. Although K63-linked ubiquitination plays an important role in RIG-I activation, the optimal modulation of conjugated and unanchored ubiquitination of RIG-I as well as its functional implications remains unclear. In this study, we determined that, in contrast to the RIG-I CARD domain, full-length RIG-I must undergo K63-linked ubiquitination at multiple sites to reach full activity. A systems biology approach was designed based on experiments using full-length RIG-I. Model selection for 7 candidate mechanisms of RIG-I ubiquitination inferred a hierarchical architecture of the RIG-I ubiquitination mode, which was then experimentally validated. Compared with other mechanisms, the selected hierarchical mechanism exhibited superior sensitivity and robustness in RIG-I-induced type I IFN activation. Furthermore, our model analysis and experimental data revealed that TRIM4 and TRIM25 exhibited dose-dependent synergism. These results demonstrated that the hierarchical mechanism of multi-site/type ubiquitination of RIG-I provides an efficient, robust and optimal synergistic regulatory module in antiviral immune responses. PMID:27387525

A Hierarchical Mechanism of RIG-I Ubiquitination Provides Sensitivity, Robustness and Synergy in Antiviral Immune Responses

NASA Astrophysics Data System (ADS)

Sun, Xiaoqiang; Xian, Huifang; Tian, Shuo; Sun, Tingzhe; Qin, Yunfei; Zhang, Shoutao; Cui, Jun

2016-07-01

RIG-I is an essential receptor in the initiation of the type I interferon (IFN) signaling pathway upon viral infection. Although K63-linked ubiquitination plays an important role in RIG-I activation, the optimal modulation of conjugated and unanchored ubiquitination of RIG-I as well as its functional implications remains unclear. In this study, we determined that, in contrast to the RIG-I CARD domain, full-length RIG-I must undergo K63-linked ubiquitination at multiple sites to reach full activity. A systems biology approach was designed based on experiments using full-length RIG-I. Model selection for 7 candidate mechanisms of RIG-I ubiquitination inferred a hierarchical architecture of the RIG-I ubiquitination mode, which was then experimentally validated. Compared with other mechanisms, the selected hierarchical mechanism exhibited superior sensitivity and robustness in RIG-I-induced type I IFN activation. Furthermore, our model analysis and experimental data revealed that TRIM4 and TRIM25 exhibited dose-dependent synergism. These results demonstrated that the hierarchical mechanism of multi-site/type ubiquitination of RIG-I provides an efficient, robust and optimal synergistic regulatory module in antiviral immune responses.

Riplet/RNF135, a RING finger protein, ubiquitinates RIG-I to promote interferon-beta induction during the early phase of viral infection.

PubMed

Oshiumi, Hiroyuki; Matsumoto, Misako; Hatakeyama, Shigetsugu; Seya, Tsukasa

2009-01-09

RIG-I (retinoic acid-inducible gene-I), a cytoplasmic RNA helicase, interacts with IPS-1/MAVS/Cardif/VISA, a protein on the outer membrane of mitochondria, to signal the presence of virus-derived RNA and induce type I interferon production. Activation of RIG-I requires the ubiquitin ligase, TRIM25, which mediates lysine 63-linked polyubiquitination of the RIG-I N-terminal CARD-like region. However, how this modification proceeds for activation of IPS-1 by RIG-I remains unclear. Here we identify an alternative factor, Riplet/RNF135, that promotes RIG-I activation independent of TRIM25. The Riplet/RNF135 protein consists of an N-terminal RING finger domain, C-terminal SPRY and PRY motifs, and shows sequence similarity to TRIM25. Immunoprecipitation analyses demonstrated that the C-terminal helicase and repressor domains of RIG-I interact with the Riplet/RNF135 C-terminal region, whereas the CARD-like region of RIG-I is dispensable for this interaction. Riplet/RNF135 promotes lysine 63-linked polyubiquitination of the C-terminal region of RIG-I, modification of which differs from the N-terminal ubiquitination by TRIM25. Overexpression and knockdown analyses revealed that Riplet/RNF135 promotes RIG-I-mediated interferon-beta promoter activation and inhibits propagation of the negative-strand RNA virus, vesicular stomatitis virus. Our data suggest that Riplet/RNF135 is a novel factor of the RIG-I pathway that is involved in the evoking of human innate immunity against RNA virus infection, and activates RIG-I through ubiquitination of its C-terminal region. We infer that a variety of RIG-I-ubiquitinating molecular complexes sustain RIG-I activation to modulate RNA virus replication in the cytoplasm.

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

E Nistal-Villan; M Gack; G Martinez-Delgado

RIG-I (retinoic acid-inducible gene I) and TRIM25 (tripartite motif protein 25) have emerged as key regulatory factors to induce interferon (IFN)-mediated innate immune responses to limit viral replication. Upon recognition of viral RNA, TRIM25 E3 ligase binds the first caspase recruitment domain (CARD) of RIG-I and subsequently induces lysine 172 ubiquitination of the second CARD of RIG-I, which is essential for the interaction with downstream MAVS/IPS-1/CARDIF/VISA and, thereby, IFN-beta mRNA production. Although ubiquitination has emerged as a major factor involved in RIG-I activation, the potential contribution of other post-translational modifications, such as phosphorylation, to the regulation of RIG-I activity hasmore » not been addressed. Here, we report the identification of serine 8 phosphorylation at the first CARD of RIG-I as a negative regulatory mechanism of RIG-I-mediated IFN-beta production. Immunoblot analysis with a phosphospecific antibody showed that RIG-I serine 8 phosphorylation steady-state levels were decreased upon stimulation of cells with IFN-beta or virus infection. Substitution of serine 8 in the CARD RIG-I functional domain with phosphomimetic aspartate or glutamate results in decreased TRIM25 binding, RIG-I ubiquitination, MAVS binding, and downstream signaling. Finally, sequence comparison reveals that only primate species carry serine 8, whereas other animal species carry an asparagine, indicating that serine 8 phosphorylation may represent a primate-specific regulation of RIG-I activation. Collectively, these data suggest that the phosphorylation of RIG-I serine 8 operates as a negative switch of RIG-I activation by suppressing TRIM25 interaction, further underscoring the importance of RIG-I and TRIM25 connection in type I IFN signal transduction.« less

The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane-association and innate antiviral immunity

PubMed Central

Liu, Helene Minyi; Loo, Yueh-Ming; Horner, Stacy M.; Zornetzer, Gregory A.; Katze, Michael G.; Gale, Michael

2012-01-01

Summary RIG-I is a cytosolic pathogen recognition receptor that initiates immune responses against RNA viruses. Upon viral RNA recognition, anti-viral signalling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. Here we identify the mitochondrial targeting chaperone protein, 14-3-3ε, as a RIG-I-binding partner and essential component of a translocation complex or “translocon” containing RIG-I, 14-3-3ε, and the TRIM25 ubiquitin ligase. The RIG-I translocon directs RIG-I redistribution from the cytosol to membranes where it mediates MAVS-dependent innate immune signalling during acute RNA virus infection. 14-3-3ε is essential for the stable interaction of RIG-I with TRIM25, which facilitates RIG-I ubiquitination and initiation of innate immunity against hepatitis C virus and other pathogenic RNA viruses. Our results define 14-3-3ε as a key component of a RIG-I translocon required for innate antiviral immunity. PMID:22607805

The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity.

PubMed

Liu, Helene Minyi; Loo, Yueh-Ming; Horner, Stacy M; Zornetzer, Gregory A; Katze, Michael G; Gale, Michael

2012-05-17

RIG-I is a cytosolic pathogen recognition receptor that initiates immune responses against RNA viruses. Upon viral RNA recognition, antiviral signaling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. Here we identify the mitochondrial targeting chaperone protein, 14-3-3ε, as a RIG-I-binding partner and essential component of a translocation complex or "translocon" containing RIG-I, 14-3-3ε, and the TRIM25 ubiquitin ligase. The RIG-I translocon directs RIG-I redistribution from the cytosol to membranes where it mediates MAVS-dependent innate immune signaling during acute RNA virus infection. 14-3-3ε is essential for the stable interaction of RIG-I with TRIM25, which facilitates RIG-I ubiquitination and initiation of innate immunity against hepatitis C virus and other pathogenic RNA viruses. Our results define 14-3-3ε as a key component of a RIG-I translocon required for innate antiviral immunity. Copyright © 2012 Elsevier Inc. All rights reserved.

A distinct role of Riplet-mediated K63-Linked polyubiquitination of the RIG-I repressor domain in human antiviral innate immune responses.

PubMed

Oshiumi, Hiroyuki; Miyashita, Moeko; Matsumoto, Misako; Seya, Tsukasa

2013-01-01

The innate immune system is essential for controlling viral infections, but several viruses have evolved strategies to escape innate immunity. RIG-I is a cytoplasmic viral RNA sensor that triggers the signal to induce type I interferon production in response to viral infection. RIG-I activation is regulated by the K63-linked polyubiquitin chain mediated by Riplet and TRIM25 ubiquitin ligases. TRIM25 is required for RIG-I oligomerization and interaction with the IPS-1 adaptor molecule. A knockout study revealed that Riplet was essential for RIG-I activation. However the molecular mechanism underlying RIG-I activation by Riplet remains unclear, and the functional differences between Riplet and TRIM25 are also unknown. A genetic study and a pull-down assay indicated that Riplet was dispensable for RIG-I RNA binding activity but required for TRIM25 to activate RIG-I. Mutational analysis demonstrated that Lys-788 within the RIG-I repressor domain was critical for Riplet-mediated K63-linked polyubiquitination and that Riplet was required for the release of RIG-I autorepression of its N-terminal CARDs, which leads to the association of RIG-I with TRIM25 ubiquitin ligase and TBK1 protein kinase. Our data indicate that Riplet is a prerequisite for TRIM25 to activate RIG-I signaling. We investigated the biological importance of this mechanism in human cells and found that hepatitis C virus (HCV) abrogated this mechanism. Interestingly, HCV NS3-4A proteases targeted the Riplet protein and abrogated endogenous RIG-I polyubiquitination and association with TRIM25 and TBK1, emphasizing the biological importance of this mechanism in human antiviral innate immunity. In conclusion, our results establish that Riplet-mediated K63-linked polyubiquitination released RIG-I RD autorepression, which allowed the access of positive factors to the RIG-I protein.

A Distinct Role of Riplet-Mediated K63-Linked Polyubiquitination of the RIG-I Repressor Domain in Human Antiviral Innate Immune Responses

PubMed Central

Oshiumi, Hiroyuki; Miyashita, Moeko; Matsumoto, Misako; Seya, Tsukasa

2013-01-01

The innate immune system is essential for controlling viral infections, but several viruses have evolved strategies to escape innate immunity. RIG-I is a cytoplasmic viral RNA sensor that triggers the signal to induce type I interferon production in response to viral infection. RIG-I activation is regulated by the K63-linked polyubiquitin chain mediated by Riplet and TRIM25 ubiquitin ligases. TRIM25 is required for RIG-I oligomerization and interaction with the IPS-1 adaptor molecule. A knockout study revealed that Riplet was essential for RIG-I activation. However the molecular mechanism underlying RIG-I activation by Riplet remains unclear, and the functional differences between Riplet and TRIM25 are also unknown. A genetic study and a pull-down assay indicated that Riplet was dispensable for RIG-I RNA binding activity but required for TRIM25 to activate RIG-I. Mutational analysis demonstrated that Lys-788 within the RIG-I repressor domain was critical for Riplet-mediated K63-linked polyubiquitination and that Riplet was required for the release of RIG-I autorepression of its N-terminal CARDs, which leads to the association of RIG-I with TRIM25 ubiquitin ligase and TBK1 protein kinase. Our data indicate that Riplet is a prerequisite for TRIM25 to activate RIG-I signaling. We investigated the biological importance of this mechanism in human cells and found that hepatitis C virus (HCV) abrogated this mechanism. Interestingly, HCV NS3-4A proteases targeted the Riplet protein and abrogated endogenous RIG-I polyubiquitination and association with TRIM25 and TBK1, emphasizing the biological importance of this mechanism in human antiviral innate immunity. In conclusion, our results establish that Riplet-mediated K63-linked polyubiquitination released RIG-I RD autorepression, which allowed the access of positive factors to the RIG-I protein. PMID:23950712

Radioimmunoguided surgery for colorectal cancer.

PubMed

Bertsch, D J; Burak, W E; Young, D C; Arnold, M W; Martin, E W

1996-05-01

Operations for patients with colorectal cancer are based on traditions established by historical experience. Radioimmunoguided surgery (RIGS) provides new information that challenges these traditions. Thirty-two patients with primary colorectal cancer underwent RIGS after being injected with anti-TAG-72 murine monoclonal antibody CC49 labeled with iodine-125. Sixteen of the patients had all gross tumor and RIGS-positive tissue removed (RIGS-negative group), and 16 had only traditional extirpation of the tumor because RIGS-positive tissue was too diffuse (RIGS-positive group). In the 16 patients having all RIGS-positive tissue removed, five had traditional regional en bloc resections and 11 had additional extraregional tissues resected. Identification of extraregional disease added two liver resections and 25 lymphadenectomies: 10 of the gastrohepatic ligament, five celia axis, six retroperitoneal, and four iliac. With a median follow-up of 37 months, survival in the RIGS-negative group is 100%. In 14 of 16 patients (87.5%) there is no evidence of disease. In the RIGS-positive group, follow-up shows 14 of 16 patients are dead and two are alive with disease (p < 0.0001). These results suggest that RIGS identifies patterns of disease dissemination different from those identified by traditional staging techniques. Removal of additional RIGS-positive tissues in nontraditional areas may improve survival.

42 CFR 423.286 - Rules regarding premiums.

Code of Federal Regulations, 2011 CFR

2011-10-01

... section for the difference between the bid and the national average monthly bid amount, any supplemental... percentage as specified in paragraph (b) of this section; and (2) National average monthly bid amount... reflect difference between bid and national average bid. If the amount of the standardized bid amount...

Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses.

PubMed

Liu, Wei; Li, Jing; Zheng, Weinan; Shang, Yingli; Zhao, Zhendong; Wang, Shanshan; Bi, Yuhai; Zhang, Shuang; Xu, Chongfeng; Duan, Ziyuan; Zhang, Lianfeng; Wang, Yue L; Jiang, Zhengfan; Liu, Wenjun; Sun, Lei

2017-06-08

RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons (IFNs) against RNA virus infection. In this study, we found that cyclophilin A (CypA), a peptidyl-prolyl cis/trans isomerase, functioned as a critical positive regulator of RIG-I-mediated antiviral immune responses. Deficiency of CypA impaired RIG-I-mediated type I IFN production and promoted viral replication in human cells and mice. Upon Sendai virus infection, CypA increased the interaction between RIG-I and its E3 ubiquitin ligase TRIM25, leading to enhanced TRIM25-mediated K63-linked ubiquitination of RIG-I that facilitated recruitment of RIG-I to MAVS. In addition, CypA and TRIM25 competitively interacted with MAVS, thereby inhibiting TRIM25-induced K48-linked ubiquitination of MAVS. Taken together, our findings reveal an essential role of CypA in boosting RIG-I-mediated antiviral immune responses by controlling the ubiquitination of RIG-I and MAVS.

Design and Analysis of Tooth Impact Test Rig for Spur Gear

NASA Astrophysics Data System (ADS)

Ghazali, Wafiuddin Bin Md; Aziz, Ismail Ali Bin Abdul; Daing Idris, Daing Mohamad Nafiz Bin; Ismail, Nurazima Binti; Sofian, Azizul Helmi Bin

2016-02-01

This paper is about the design and analysis of a prototype of tooth impact test rig for spur gear. The test rig was fabricated and analysis was conducted to study its’ limitation and capabilities. The design of the rig is analysed to ensure that there will be no problem occurring during the test and reliable data can be obtained. From the result of the analysis, the maximum amount of load that can be applied, the factor of safety of the machine, the stresses on the test rig parts were determined. This is important in the design consideration of the test rig. The materials used for the fabrication of the test rig were also discussed and analysed. MSC Nastran Patran software was used to analyse the model, which was designed by using SolidWorks 2014 software. Based from the results, there were limitations found from the initial design and the test rig design needs to be improved in order for the test rig to operate properly.

48 CFR 14.202-8 - Electronic bids.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Electronic bids. 14.202-8... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-8 Electronic bids. In accordance with subpart 4.5, contracting officers may authorize use of electronic commerce for submission of bids. If...

48 CFR 14.202-8 - Electronic bids.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Electronic bids. 14.202-8... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-8 Electronic bids. In accordance with subpart 4.5, contracting officers may authorize use of electronic commerce for submission of bids. If...

48 CFR 14.202-8 - Electronic bids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Electronic bids. 14.202-8... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-8 Electronic bids. In accordance with subpart 4.5, contracting officers may authorize use of electronic commerce for submission of bids. If...

48 CFR 14.202-8 - Electronic bids.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Electronic bids. 14.202-8... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-8 Electronic bids. In accordance with subpart 4.5, contracting officers may authorize use of electronic commerce for submission of bids. If...

48 CFR 14.202-8 - Electronic bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Electronic bids. 14.202-8... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-8 Electronic bids. In accordance with subpart 4.5, contracting officers may authorize use of electronic commerce for submission of bids. If...

48 CFR 14.202-1 - Bidding time.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Bidding time. 14.202-1... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-1 Bidding time. (a) Policy. A reasonable time for prospective bidders to prepare and submit bids shall be allowed in all invitations, consistent...

48 CFR 14.202-1 - Bidding time.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Bidding time. 14.202-1... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-1 Bidding time. (a) Policy. A reasonable time for prospective bidders to prepare and submit bids shall be allowed in all invitations, consistent...

48 CFR 14.202-1 - Bidding time.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Bidding time. 14.202-1... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-1 Bidding time. (a) Policy. A reasonable time for prospective bidders to prepare and submit bids shall be allowed in all invitations, consistent...

48 CFR 14.202-1 - Bidding time.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Bidding time. 14.202-1... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-1 Bidding time. (a) Policy. A reasonable time for prospective bidders to prepare and submit bids shall be allowed in all invitations, consistent...

48 CFR 14.202-1 - Bidding time.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Bidding time. 14.202-1... AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.202-1 Bidding time. (a) Policy. A reasonable time for prospective bidders to prepare and submit bids shall be allowed in all invitations, consistent...

Health information sources accessed by college females: differences between body-image distorted and non-body-image distorted.

PubMed

Nustad, Jill; Adams, Troy; Moore, Monique

2008-01-01

This study examined and compared sources of health-related information accessed by female college students with and without body image distortions, and the believability of those sources. Survey data from the American College Health Association, National College Health Assessment were studied retrospectively (N = 27,648). Body image distorted (BID) and non-BID students' most frequent health information sources were parents (76.1% BID; 77.1% non-BID) and internet (70.3% BID; 69.5% non-BID). Believability was greatest for health educators (90.6% BID; 91.1% non-BID) and lowest for television (14.4% BID; 14.5% non-BID). Health intervention strategies for college women should market to parents and teach recognition of credible internet sources of health information.

Dynamic imaging of interaction between protein 14-3-3 and Bid in living cells

NASA Astrophysics Data System (ADS)

Chen, Tongsheng; Xing, Da; Wang, Jinjun

2006-02-01

The 14-3-3 proteins are known to sequester certain pro-apoptotic members of this family. BH3- interacting domain death agonist (Bid) may contribute to tumor necrosis factor α(TNF-α)-induced neuronal death, although regulation by 14-3-3 has not been reported. In this study we examined whether 14-3-3 proteins interact with Bid/tBid during TNF-α-induced cell death. The TNF-αtriggered Bid cleavage and tBid translocated to mitochondria. Human lung adenocarcinoma cells were co-transfected with both CFP-Bid and 14-3-3-YFP plasmids, and the dynamical interaction between the Bid/tBid and 14-3-3 were performed on laser confocal fluorescence microscope in single living cell during TNF-α-induced cell apoptosis. The Bid distribute equally only in the cytoplasm of healthy cells, and the 14-3-3 protein distribute not only in the cytoplasm but also in the nucleus of healthy cells. Our data showed that the tBid aggregate, but the 14-3-3 protein does not aggregate as the tBid, and the 14-3-3 protein separate from the aggregated tBid, implying that the 14-3-3 proteins do not interact with the aggregated tBid after TNF-αtreatment.

What Really Rigs Up RIG-I?

PubMed

Barik, Sailen

2016-01-01

RIG-I (retinoic acid-inducible gene 1) is an archetypal member of the cytoplasmic DEAD-box dsRNA helicase family (RIG-I-like receptors or RLRs), the members of which play essential roles in the innate immune response of the metazoan cell. RIG-I functions as a pattern recognition receptor that detects nonself RNA as a pathogen-associated molecular pattern (PAMP). However, the exact molecular nature of the viral RNAs that act as a RIG-I ligand has remained a mystery and a matter of debate. In this article, we offer a critical review of the actual viral RNAs that act as PAMPs to activate RIG-I, as seen from the perspective of a virologist, including a recent report that the viral Leader-read-through transcript is a novel and effective RIG-I ligand. © 2016 S. Karger AG, Basel.

Ubiquitin-like modifier FAT10 attenuates RIG-I mediated antiviral signaling by segregating activated RIG-I from its signaling platform

PubMed Central

Nguyen, Nhung T.H.; Now, Hesung; Kim, Woo-Jong; Kim, Nari; Yoo, Joo-Yeon

2016-01-01

RIG-I is a key cytosolic RNA sensor that mediates innate immune defense against RNA virus. Aberrant RIG-I activity leads to severe pathological states such as autosomal dominant multi-system disorder, inflammatory myophathies and dermatomyositis. Therefore, identification of regulators that ensure efficient defense without harmful immune-pathology is particularly critical to deal with RIG-I-associated diseases. Here, we presented the inflammatory inducible FAT10 as a novel negative regulator of RIG-I-mediated inflammatory response. In various cell lines, FAT10 protein is undetectable unless it is induced by pro-inflammatory cytokines. FAT10 non-covalently associated with the 2CARD domain of RIG-I, and inhibited viral RNA-induced IRF3 and NF-kB activation through modulating the RIG-I protein solubility. We further demonstrated that FAT10 was recruited to RIG-I-TRIM25 to form an inhibitory complex where FAT10 was stabilized by E3 ligase TRIM25. As the result, FAT10 inhibited the antiviral stress granules formation contains RIG-I and sequestered the active RIG-I away from the mitochondria. Our study presented a novel mechanism to dampen RIG-I activity. Highly accumulated FAT10 is observed in various cancers with pro-inflammatory environment, therefore, our finding which uncovered the suppressive effect of the accumulated FAT10 during virus-mediated inflammatory response may also provide molecular clue to understand the carcinogenesis related with infection and inflammation. PMID:26996158

Paramyxovirus V Proteins Interact with the RIG-I/TRIM25 Regulatory Complex and Inhibit RIG-I Signaling.

PubMed

Sánchez-Aparicio, Maria T; Feinman, Leighland J; García-Sastre, Adolfo; Shaw, Megan L

2018-03-15

Paramyxovirus V proteins are known antagonists of the RIG-I-like receptor (RLR)-mediated interferon induction pathway, interacting with and inhibiting the RLR MDA5. We report interactions between the Nipah virus V protein and both RIG-I regulatory protein TRIM25 and RIG-I. We also observed interactions between these host proteins and the V proteins of measles virus, Sendai virus, and parainfluenza virus. These interactions are mediated by the conserved C-terminal domain of the V protein, which binds to the tandem caspase activation and recruitment domains (CARDs) of RIG-I (the region of TRIM25 ubiquitination) and to the SPRY domain of TRIM25, which mediates TRIM25 interaction with the RIG-I CARDs. Furthermore, we show that V interaction with TRIM25 and RIG-I prevents TRIM25-mediated ubiquitination of RIG-I and disrupts downstream RIG-I signaling to the mitochondrial antiviral signaling protein. This is a novel mechanism for innate immune inhibition by paramyxovirus V proteins, distinct from other known V protein functions such as MDA5 and STAT1 antagonism. IMPORTANCE The host RIG-I signaling pathway is a key early obstacle to paramyxovirus infection, as it results in rapid induction of an antiviral response. This study shows that paramyxovirus V proteins interact with and inhibit the activation of RIG-I, thereby interrupting the antiviral signaling pathway and facilitating virus replication. Copyright © 2018 American Society for Microbiology.

Ubiquitin-like modifier FAT10 attenuates RIG-I mediated antiviral signaling by segregating activated RIG-I from its signaling platform.

PubMed

Nguyen, Nhung T H; Now, Hesung; Kim, Woo-Jong; Kim, Nari; Yoo, Joo-Yeon

2016-03-21

RIG-I is a key cytosolic RNA sensor that mediates innate immune defense against RNA virus. Aberrant RIG-I activity leads to severe pathological states such as autosomal dominant multi-system disorder, inflammatory myophathies and dermatomyositis. Therefore, identification of regulators that ensure efficient defense without harmful immune-pathology is particularly critical to deal with RIG-I-associated diseases. Here, we presented the inflammatory inducible FAT10 as a novel negative regulator of RIG-I-mediated inflammatory response. In various cell lines, FAT10 protein is undetectable unless it is induced by pro-inflammatory cytokines. FAT10 non-covalently associated with the 2CARD domain of RIG-I, and inhibited viral RNA-induced IRF3 and NF-kB activation through modulating the RIG-I protein solubility. We further demonstrated that FAT10 was recruited to RIG-I-TRIM25 to form an inhibitory complex where FAT10 was stabilized by E3 ligase TRIM25. As the result, FAT10 inhibited the antiviral stress granules formation contains RIG-I and sequestered the active RIG-I away from the mitochondria. Our study presented a novel mechanism to dampen RIG-I activity. Highly accumulated FAT10 is observed in various cancers with pro-inflammatory environment, therefore, our finding which uncovered the suppressive effect of the accumulated FAT10 during virus-mediated inflammatory response may also provide molecular clue to understand the carcinogenesis related with infection and inflammation.

Phosphorylation-mediated negative regulation of RIG-I antiviral activity.

PubMed

Gack, Michaela U; Nistal-Villán, Estanislao; Inn, Kyung-Soo; García-Sastre, Adolfo; Jung, Jae U

2010-04-01

Recognition of invading viruses by the host is elicited by cellular sensors which trigger signaling cascades that lead to type I interferon (IFN) gene expression. Retinoic acid-inducible gene I (RIG-I) has emerged as a key receptor for the detection of viral RNA in the cytosol, inducing IFN-mediated innate immune responses to limit viral replication through its interaction with MAVS (also called IPS-1, CARDIF, or VISA). Upon the recognition of viral RNA, the Lys-172 residue of RIG-I undergoes ubiquitination induced by tripartite motif protein 25 (TRIM25), an essential protein for antiviral signal transduction. Here we demonstrate that phosphorylation represents another regulatory mechanism for RIG-I-mediated antiviral activity. Using protein purification and mass spectrometry analysis, we identified three phosphorylation sites in the amino-terminal caspase recruitment domains (CARDs) of RIG-I. One of these residues, Thr-170, is located in close proximity to Lys-172, and we speculated that its phosphorylation may affect Lys-172 ubiquitination and functional activation of RIG-I. Indeed, a RIG-I mutant carrying a phosphomimetic Glu residue in place of Thr-170 loses TRIM25 binding, Lys-172 ubiquitination, MAVS binding, and downstream signaling ability. This suggests that phosphorylation of RIG-I at Thr-170 inhibits RIG-I-mediated antiviral signal transduction. Immunoblot analysis with a phospho-specific antibody showed that the phosphorylation of the RIG-I Thr-170 residue is present under normal conditions but rapidly declines upon viral infection. Our results indicate that Thr-170 phosphorylation and TRIM25-mediated Lys-172 ubiquitination of RIG-I functionally antagonize each other. While Thr-170 phosphorylation keeps RIG-I latent, Lys-172 ubiquitination enables RIG-I to form a stable complex with MAVS, thereby inducing IFN signal transduction.

78 FR 55254 - Information Collection Being Reviewed by the Federal Communications Commission Under Delegated...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-10

... of their bids or bidding strategies from the short-form application filing deadline to the post... communication of bids or bidding strategies is limited to one applicant's bids or bidding strategies, it may unfairly disadvantage the other bidders in the market by creating an asymmetry of information. Section 1...

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

Huttrer, G.W.

This report summarizes the investigation and evaluation of several {open_quotes}compact{close_quotes} drill rigs which could be used for drilling geothermal production wells. Use of these smaller rigs would save money by reducing mobilization costs, fuel consumption, crew sizes, and environmental impact. Advantages and disadvantages of currently-manufactured rigs are identified, and desirable characteristics for the {open_quotes}ideal{close_quotes} compact rig are defined. The report includes a detailed cost estimate of a specific rig, and an evaluation of the cost/benefit ratio of using this rig. Industry contacts for further information are given.

Study on Comparison of Bidding and Pricing Behavior Distinction between Estimate Methods

NASA Astrophysics Data System (ADS)

Morimoto, Emi; Namerikawa, Susumu

The most characteristic trend on bidding and pricing behavior distinction in recent years is the increasing number of bidders just above the criteria for low-price bidding investigations. The contractor's markup is the difference between the bidding price and the execution price. Therefore, the contractor's markup is the difference between criteria for low-price bidding investigations price and the execution price in the public works bid in Japan. Virtually, bidder's strategies and behavior have been controlled by public engineer's budgets. Estimation and bid are inseparably linked in the Japanese public works procurement system. The trial of the unit price-type estimation method begins in 2004. On another front, accumulated estimation method is one of the general methods in public works. So, there are two types of standard estimation methods in Japan. In this study, we did a statistical analysis on the bid information of civil engineering works for the Ministry of Land, Infrastructure, and Transportation in 2008. It presents several issues that bidding and pricing behavior is related to an estimation method (several estimation methods) for public works bid in Japan. The two types of standard estimation methods produce different results that number of bidders (decide on bid-no bid strategy) and distribution of bid price (decide on mark-up strategy).The comparison on the distribution of bid prices showed that the percentage of the bid concentrated on the criteria for low-price bidding investigations have had a tendency to get higher in the large-sized public works by the unit price-type estimation method, comparing with the accumulated estimation method. On one hand, the number of bidders who bids for public works estimated unit-price tends to increase significantly Public works estimated unit-price is likely to have been one of the factors for the construction companies to decide if they participate in the biddings.

Terror in the Board Room: The Bid-Opening Process

ERIC Educational Resources Information Center

Shoop, James

2009-01-01

Competitive bids and the bid-opening process are the cornerstones of public school purchasing. The bid-opening process does not begin on the day of the bid opening. It begins with good planning by the purchasing agent to ensure that the advertised bid complies with the public school contracts law. In New Jersey, that raises the following…

48 CFR 14.408-6 - Equal low bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Equal low bids. 14.408-6... AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.408-6 Equal low bids. (a) Contracts shall be awarded in the following order of priority when two or more low bids are equal in all...

TRIM25 RING-finger E3 ubiquitin ligase is essential for RIG-I-mediated antiviral activity.

PubMed

Gack, Michaela U; Shin, Young C; Joo, Chul-Hyun; Urano, Tomohiko; Liang, Chengyu; Sun, Lijun; Takeuchi, Osamu; Akira, Shizuo; Chen, Zhijian; Inoue, Satoshi; Jung, Jae U

2007-04-19

Retinoic-acid-inducible gene-I (RIG-I; also called DDX58) is a cytosolic viral RNA receptor that interacts with MAVS (also called VISA, IPS-1 or Cardif) to induce type I interferon-mediated host protective innate immunity against viral infection. Furthermore, members of the tripartite motif (TRIM) protein family, which contain a cluster of a RING-finger domain, a B box/coiled-coil domain and a SPRY domain, are involved in various cellular processes, including cell proliferation and antiviral activity. Here we report that the amino-terminal caspase recruitment domains (CARDs) of RIG-I undergo robust ubiquitination induced by TRIM25 in mammalian cells. The carboxy-terminal SPRY domain of TRIM25 interacts with the N-terminal CARDs of RIG-I; this interaction effectively delivers the Lys 63-linked ubiquitin moiety to the N-terminal CARDs of RIG-I, resulting in a marked increase in RIG-I downstream signalling activity. The Lys 172 residue of RIG-I is critical for efficient TRIM25-mediated ubiquitination and for MAVS binding, as well as the ability of RIG-I to induce antiviral signal transduction. Furthermore, gene targeting demonstrates that TRIM25 is essential not only for RIG-I ubiquitination but also for RIG-I-mediated interferon- production and antiviral activity in response to RNA virus infection. Thus, we demonstrate that TRIM25 E3 ubiquitin ligase induces the Lys 63-linked ubiquitination of RIG-I, which is crucial for the cytosolic RIG-I signalling pathway to elicit host antiviral innate immunity.

Procurement of construction services: a case study on bidding competition in Singapore public sector contracts

NASA Astrophysics Data System (ADS)

Oo, B. L.; Yan, Y.

2018-04-01

There are many variables that public clients need to consider in their bidding procedure to enhance efficiency in their procurement for construction services. This paper focusses on the competitive bidding process for public sector procurement of construction services in Singapore. A distinctive feature of the Singapore government competitive bidding process is that full bidding feedback information is released to all competing bidders (and public). The specific objectives are: (i) to examine the degree of competition in the construction markets; and (ii) to examine the bidding performance of competing bidders. Based on a collection of bidding data for a 15-month period, the results show the market environment of the Singapore public sector construction contracting is highly competitive with long bidder lists. In selection of contractors, only 50% of the contracts were awarded to lowest bidders. The results also show that the competing contractors can be broadly classified into three groups based on their bidding performance in terms of number of bidding attempts, bidding success rate and bidding competitiveness. These results provide a useful insight into the bidding competition in the Singapore public sector construction contracting, especially to new market entrants and foreign contractors who want to bid for jobs in Singapore.

COMPETITIVE BIDDING IN MEDICARE ADVANTAGE: EFFECT OF BENCHMARK CHANGES ON PLAN BIDS

PubMed Central

Song, Zirui; Landrum, Mary Beth; Chernew, Michael E.

2013-01-01

Bidding has been proposed to replace or complement the administered prices in Medicare pays to hospitals and health plans. In 2006, the Medicare Advantage program implemented a competitive bidding system to determine plan payments. In perfectly competitive models, plans bid their costs and thus bids are insensitive to the benchmark. Under many other models of competition, bids respond to changes in the benchmark. We conceptualize the bidding system and use an instrumental variable approach to study the effect of benchmark changes on bids. We use 2006–2010 plan payment data from the Centers for Medicare and Medicaid Services, published county benchmarks, actual realized fee-for-service costs, and Medicare Advantage enrollment. We find that a $1 increase in the benchmark leads to about a $0.53 increase in bids, suggesting that plans in the Medicare Advantage market have meaningful market power. PMID:24308881

Competitive bidding in Medicare Advantage: effect of benchmark changes on plan bids.

PubMed

Song, Zirui; Landrum, Mary Beth; Chernew, Michael E

2013-12-01

Bidding has been proposed to replace or complement the administered prices that Medicare pays to hospitals and health plans. In 2006, the Medicare Advantage program implemented a competitive bidding system to determine plan payments. In perfectly competitive models, plans bid their costs and thus bids are insensitive to the benchmark. Under many other models of competition, bids respond to changes in the benchmark. We conceptualize the bidding system and use an instrumental variable approach to study the effect of benchmark changes on bids. We use 2006-2010 plan payment data from the Centers for Medicare and Medicaid Services, published county benchmarks, actual realized fee-for-service costs, and Medicare Advantage enrollment. We find that a $1 increase in the benchmark leads to about a $0.53 increase in bids, suggesting that plans in the Medicare Advantage market have meaningful market power. Copyright © 2013 Elsevier B.V. All rights reserved.

Competitive bidding for Medicare Part B clinical laboratory services.

PubMed

Kautter, John; Pope, Gregory C

2014-06-01

The traditional Medicare fee-for-service program may be able to purchase clinical laboratory test services at a lower cost through competitive bidding. Demonstrations of competitive bidding for clinical laboratory tests have been twice mandated or authorized by Congress but never implemented. This article provides a summary and review of the final design of the laboratory competitive bidding demonstration mandated by the Medicare Modernization Act of 2003. The design was analogous to a sealed bid (first price), clearing price auction. Design elements presented include covered laboratory tests and beneficiaries, laboratory bidding and payment status under the demonstration, composite bids, determining bidding winners and the demonstration fee schedule, and quality under the demonstration. Expanded use of competitive bidding in Medicare, including specifically for clinical laboratory tests, has been recommended in some proposals for Medicare reform. The presented design may be a useful point of departure if Medicare clinical laboratory competitive bidding is revived in the future.

Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses

PubMed Central

Liu, Wei; Li, Jing; Zheng, Weinan; Shang, Yingli; Zhao, Zhendong; Wang, Shanshan; Bi, Yuhai; Zhang, Shuang; Xu, Chongfeng; Duan, Ziyuan; Zhang, Lianfeng; Wang, Yue L; Jiang, Zhengfan; Liu, Wenjun; Sun, Lei

2017-01-01

RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons (IFNs) against RNA virus infection. In this study, we found that cyclophilin A (CypA), a peptidyl-prolyl cis/trans isomerase, functioned as a critical positive regulator of RIG-I-mediated antiviral immune responses. Deficiency of CypA impaired RIG-I-mediated type I IFN production and promoted viral replication in human cells and mice. Upon Sendai virus infection, CypA increased the interaction between RIG-I and its E3 ubiquitin ligase TRIM25, leading to enhanced TRIM25-mediated K63-linked ubiquitination of RIG-I that facilitated recruitment of RIG-I to MAVS. In addition, CypA and TRIM25 competitively interacted with MAVS, thereby inhibiting TRIM25-induced K48-linked ubiquitination of MAVS. Taken together, our findings reveal an essential role of CypA in boosting RIG-I-mediated antiviral immune responses by controlling the ubiquitination of RIG-I and MAVS. DOI: http://dx.doi.org/10.7554/eLife.24425.001 PMID:28594325

Antiviral activity of human oligoadenylate synthetases-like (OASL) is mediated by enhancing retinoic acid-inducible gene I (RIG-I) signaling

PubMed Central

Zhu, Jianzhong; Zhang, Yugen; Ghosh, Arundhati; Cuevas, Rolando A.; Forero, Adriana; Dhar, Jayeeta; Ibsen, Mikkel Søes; Schmid-Burgk, Jonathan Leo; Schmidt, Tobias; Ganapathiraju, Madhavi K.; Fujita, Takashi; Hartmann, Rune; Barik, Sailen; Hornung, Veit; Coyne, Carolyn B.; Sarkar, Saumendra N.

2014-01-01

SUMMARY Virus infection is sensed in the cytoplasm by retinoic acid-inducible gene I (RIG-I, also known as DDX58), which requires RNA and polyubiquitin binding to induce type I interferon (IFN), and activate cellular innate immunity. We show that the human IFN-inducible oligoadenylate synthetases-like (OASL) protein had antiviral activity and mediated RIG-I activation by mimicking polyubiquitin. Loss of OASL expression reduced RIG-I signaling and enhanced virus replication in human cells. Conversely, OASL expression suppressed replication of a number of viruses in a RIG-I-dependent manner and enhanced RIG-I-mediated IFN induction. OASL interacted and colocalized with RIG-I, and through its C-terminal ubiquitin-like domain specifically enhanced RIG-I signaling. Bone marrow derived macrophages from mice deficient for Oasl2 showed that among the two mouse orthologs of human OASL; Oasl2 is functionally similar to human OASL. Our findings show a mechanism by which human OASL contributes to host antiviral responses by enhancing RIG-I activation. PMID:24931123

Structural features of influenza A virus panhandle RNA enabling the activation of RIG-I independently of 5′-triphosphate

PubMed Central

Lee, Mi-Kyung; Kim, Hee-Eun; Park, Eun-Byeol; Lee, Janghyun; Kim, Ki-Hun; Lim, Kyungeun; Yum, Seoyun; Lee, Young-Hoon; Kang, Suk-Jo; Lee, Joon-Hwa; Choi, Byong-Seok

2016-01-01

Retinoic acid-inducible gene I (RIG-I) recognizes specific molecular patterns of viral RNAs for inducing type I interferon. The C-terminal domain (CTD) of RIG-I binds to double-stranded RNA (dsRNA) with the 5′-triphosphate (5′-PPP), which induces a conformational change in RIG-I to an active form. It has been suggested that RIG-I detects infection of influenza A virus by recognizing the 5′-triphosphorylated panhandle structure of the viral RNA genome. Influenza panhandle RNA has a unique structure with a sharp helical bending. In spite of extensive studies of how viral RNAs activate RIG-I, whether the structural elements of the influenza panhandle RNA confer the ability to activate RIG-I signaling has been poorly explored. Here, we investigated the dynamics of the influenza panhandle RNA in complex with RIG-I CTD using NMR spectroscopy and showed that the bending structure of the panhandle RNA negates the requirement of a 5′-PPP moiety for RIG-I activation. PMID:27288441

30 CFR 260.130 - What criteria does MMS use for selecting bidding systems and bidding system components?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What criteria does MMS use for selecting bidding systems and bidding system components? 260.130 Section 260.130 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE OUTER CONTINENTAL SHELF OIL AND GAS LEASING Bidding Systems Bidding System Selection Criteria §...

Involvement of zebrafish RIG-I in NF-κB and IFN signaling pathways: insights into functional conservation of RIG-I in antiviral innate immunity.

PubMed

Nie, Li; Zhang, Ying-sheng; Dong, Wei-ren; Xiang, Li-xin; Shao, Jian-zhong

2015-01-01

The retinoic acid-inducible gene I (RIG-I) is a critical sensor for host recognition of RNA virus infection and initiation of antiviral signaling pathways in mammals. However, data on the occurrence and functions of this molecule in lower vertebrates are limited. In this study, we characterized an RIG-I homolog (DrRIG-I) from zebrafish. Structurally, this DrRIG-I shares a number of conserved functional domains/motifs with its mammalian counterparts, namely, caspase activation and recruitment domain, DExD/H box, a helicase domain, and a C-terminal domain. Functionally, stimulation with DrRIG-I CARD in zebrafish embryos significantly activated the NF-κB and IFN signaling pathways, leading to the expression of TNF-α, IL-8 and IFN-induced Mx, ISG15, and viperin. However, knockdown of TRIM25 (a pivotal activator for RIG-I receptors) significantly suppressed the induced activation of IFN signaling. Results suggested the functional conservation of RIG-I receptors in the NF-κB and IFN signaling pathways between teleosts and mammals, providing a perspective into the evolutionary history of RIG-I-mediated antiviral innate immunity. Copyright © 2014 Elsevier Ltd. All rights reserved.

Lapland longspur mortality at an oil well drilling rig site, Laramie County, Wyoming

USGS Publications Warehouse

Ramirez, Pedro; Dickerson, Kimberly K.; Lindstrom, Jim; Meteyer, Carol U.; Darrah, Scott

2015-01-01

Two hundred fifty-one Lapland longspur (Calcarius lapponicus) carcasses were recovered around an oil well drilling rig in Laramie County, Wyoming, USA, on December 13–14, 2010, apparent victims of a winter storm and “light entrapment” from the lights on the drilling rig during foggy conditions. We found Lapland longspur carcasses distributed around the drilling rig from 33 m to 171 m. Investigators did not find evidence of bird carcasses on the drilling rig deck or equipment immediately adjacent to the drilling rig. We ruled out chemical toxins and disease as a cause of mortality. Weather conditions, the circular depositional pattern of carcasses around the drilling rig, and bird necropsy results led investigators to conclude that the Lapland longspur mortality was the result of the migrating birds entering the area illuminated by the drilling rig lights in freezing fog and the birds repeatedly circling the drilling rig until they fell to the ground in exhaustion and dying from subsequent trauma. Further research is needed to understand how to most effectively adjust lighting of onshore drilling rigs to reduce the potential for avian light entrapment. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Gene expression profile after activation of RIG-I in 5'ppp-dsRNA challenged DF1.

PubMed

Chen, Yang; Xu, Qi; Li, Yang; Liu, Ran; Huang, Zhengyang; Wang, Bin; Chen, Guohong

2016-12-01

Retinoic acid inducible gene I (RIG-I) can recognize influenza viruses and evoke the innate immune response. RIG-I is absent in the chicken genome, but is conserved in the genome of ducks. Lack of RIG-I renders chickens more susceptible to avian influenza infection, and the clinical symptoms are more prominent than in other poultry. It is unknown whether introduction of duck RIG-I into chicken cells can establish the immunity as is seen in ducks and the role of RIG-I in established immunity is unknown. In this study, a chicken cell strain with stable expression of duRIG-I was established by lentiviral infection, giving DF1/LV5-RIG-I, and a control strain DF1/LV5 was established in parallel. To verify stable, high level expression of duRIG-I in DF1 cells, the levels of duRIG-I mRNA and protein were determined by real-time RT-PCR and Western blot, respectively. Further, 5'triphosphate double stranded RNA (5'ppp-dsRNA) was used to mimic an RNA virus infection and the infected DF1/LV5-RIG-I and DF1/LV5 cells were subjected to high-throughput RNA-sequencing, which yielded 193.46 M reads and 39.07 G bases. A total of 278 differentially expressed genes (DEGs), i.e., duRIG-I-mediated responsive genes, were identified by RNA-seq. Among the 278 genes, 120 DEGs are annotated in the KEGG database, and the most reliable KEGG pathways are likely to be the signaling pathways of RIG-I like receptors. Functional analysis by Gene ontology (GO) indicates that the functions of these DEGs are primarily related to Type I interferon (IFN) signaling, IFN-β-mediated cellular responses and up-regulation of the RIG-I signaling pathway. Based on the shared genes among different pathways, a network representing crosstalk between RIG-I and other signaling pathways was constructed using Cytoscape software. The network suggests that RIG-mediated pathway may crosstalk with the Jak-STAT signaling pathway, Toll-like receptor signaling pathway, Wnt signaling pathway, ubiquitin-mediated proteolysis and MAPK signaling pathway during the transduction of antiviral signals. After screening, a group of key responsive genes in RIG-I-mediated signaling pathways, such as ISG12-2, Mx1, IFIT5, TRIM25, USP18, STAT1, STAT2, IRF1, IRF7 and IRF8, were tested for differential expression by real-time RT-PCR. In summary, by combining our results and the current literature, we propose a RIG-I-mediated signaling network in chickens. Copyright © 2016 Elsevier Ltd. All rights reserved.

Real-time single cell analysis of Bid cleavage and translocation in cisplatin-induced apoptosis

NASA Astrophysics Data System (ADS)

Liu, Lei; Xing, Da; Pei, Yihui; Chen, Wei R.

2007-02-01

Cancer cell apoptosis can be induced by cisplatin, an efficient anticancer agent. However, its mechanism is not fully understood. Bcl-2 homology domain (BH) 3-only proteins couple stress signals to mitochondrial apoptotic pathways. Calpain-mediated cleavage of the BH3-only protein Bid into a 14 kD truncated protein (tBid) has been implicated in cisplatin-induced apoptotic pathway. We utilized a recombinant fluorescence resonance energy transfer (FRET) Bid probe to determine the kinetics of Bid cleavage during cisplatin-induced apoptosis in ASTC-a-1 cells. The cells were also co-transfected with Bid-CFP and DsRed-Mit to dynamically detect tBid translocation. Cells showed a cleavage of the Bid-FRET probe occurring at about 4-5 h after treated with 20 µM cisplatin. Cleavage of the Bid-FRET probe coincided with a translocation of tBid from the cytosolic to the mitochondria, and the translocation lasted about 1.5 h. Using real-time single-cell analysis, we first observed the kinetics of Bid cleavage and translocation to mitochondria in living cells during cisplatin-induced apoptosis.

Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways.

PubMed

Nie, Li; Xu, Xiao-Xiao; Xiang, Li-Xin; Shao, Jian-Zhong; Chen, Jiong

2017-05-27

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and retinoic acid-inducible gene I (RIG-I) are two important cytosolic pattern recognition receptors (PRRs) in the recognition of pathogen-associated molecular patterns (PAMPs), initiating innate antibacterial and antiviral signaling pathways. However, the relationship between these PRRs, especially in teleost fish models, is rarely reported. In this article, we describe the mutual regulation of zebrafish NOD2 ( Dr NOD2) and RIG-I ( Dr RIG-I) in innate immune responses. Luciferase assays were conducted to determine the activation of NF-κB and interferon signaling. Morpholino-mediated knockdown and mRNA-mediated rescue were performed to further confirm the regulatory roles between Dr NOD2 and Dr RIG-I. Results showed that Dr NOD2 and Dr RIG-I shared conserved structural hallmarks with their mammalian counterparts, and activated Dr RIG-I signaling can induce Dr NOD2 production. Surprisingly, Dr NOD2-initiated signaling can also induce Dr RIG-I expression, indicating that a mutual regulatory mechanism may exist between them. Studies conducted using HEK293T cells and zebrafish embryos showed that Dr RIG-I could negatively regulate Dr NOD2-activated NF-κB signaling, and Dr NOD2 could inhibit Dr RIG-I-induced IFN signaling. Moreover, knocking down Dr RIG-I expression by morpholino could enhance Dr NOD2-initiated NF-κB activation, and vice versa, which could be rescued by their corresponding mRNAs. Results revealed a mutual feedback regulatory mechanism underlying NOD2 and RIG-I signaling pathways in teleosts. This mechanism reflects the coordination between cytosolic antibacterial and antiviral PRRs in the complex network of innate immunity.

RIG-I overexpression decreases mortality of cigarette smoke exposed mice during influenza A virus infection.

PubMed

Wang, Xiaoqiu; Wu, Wenxin; Zhang, Wei; Leland Booth, J; Duggan, Elizabeth S; Tian, Lili; More, Sunil; Zhao, Yan D; Sawh, Ravindranauth N; Liu, Lin; Zou, Ming-Hui; Metcalf, Jordan P

2017-09-02

Retinoic acid-inducible gene I (RIG-I) is an important regulator of virus-induced antiviral interferons (IFNs) and proinflammatory cytokines which participate in clearing viral infections. Cigarette smoke (CS) exposure increases the frequency and severity of respiratory tract infections. We generated a RIG-I transgenic (TG) mouse strain that expresses the RIG-I gene product under the control of the human lung specific surfactant protein C promoter. We compared the mortality and host immune responses of RIG-I TG mice and their litter-matched wild type (WT) mice following challenge with influenza A virus (IAV). RIG-I overexpression increased survival of IAV-infected mice. CS exposure increased mortality in WT mice infected with IAV. Remarkably, the effect of RIG-I overexpression on survival during IAV infection was enhanced in CS-exposed animals. CS-exposed IAV-infected WT mice had a suppressed innate response profile in the lung compared to sham-exposed IAV-infected WT mice in terms of the protein concentration, total cell count and inflammatory cell composition in the bronchoalveolar lavage fluid. RIG-I overexpression restored the innate immune response in CS-exposed mice to that seen in sham-exposed WT mice during IAV infection, and is likely responsible for enhanced survival in RIG-I TG mice as restoration preceded death of the animals. Our results demonstrate that RIG-I overexpression in mice is protective for CS enhanced susceptibility of smokers to influenza infection, and that CS mediated RIG-I suppression may be partially responsible for the increased morbidity and mortality of the mice exposed to IAV. Thus, optimizing the RIG-I response may be an important treatment strategy for CS-enhanced lung infections, particularly those due to IAV.

Performance Evaluation of a High Bandwidth Liquid Fuel Modulation Valve for Active Combustion Control

NASA Technical Reports Server (NTRS)

Saus, Joseph R.; DeLaat, John C.; Chang, Clarence T.; Vrnak, Daniel R.

2012-01-01

At the NASA Glenn Research Center, a characterization rig was designed and constructed for the purpose of evaluating high bandwidth liquid fuel modulation devices to determine their suitability for active combustion control research. Incorporated into the rig s design are features that approximate conditions similar to those that would be encountered by a candidate device if it were installed on an actual combustion research rig. The characterized dynamic performance measures obtained through testing in the rig are planned to be accurate indicators of expected performance in an actual combustion testing environment. To evaluate how well the characterization rig predicts fuel modulator dynamic performance, characterization rig data was compared with performance data for a fuel modulator candidate when the candidate was in operation during combustion testing. Specifically, the nominal and off-nominal performance data for a magnetostrictive-actuated proportional fuel modulation valve is described. Valve performance data were collected with the characterization rig configured to emulate two different combustion rig fuel feed systems. Fuel mass flows and pressures, fuel feed line lengths, and fuel injector orifice size was approximated in the characterization rig. Valve performance data were also collected with the valve modulating the fuel into the two combustor rigs. Comparison of the predicted and actual valve performance data show that when the valve is operated near its design condition the characterization rig can appropriately predict the installed performance of the valve. Improvements to the characterization rig and accompanying modeling activities are underway to more accurately predict performance, especially for the devices under development to modulate fuel into the much smaller fuel injectors anticipated in future lean-burning low-emissions aircraft engine combustors.

Bid purchasing of pharmaceuticals.

PubMed

Swift, R G; Ryan, M R

1978-11-01

The effects of bid purchasing of drug products by hospitals and the factors to consider in bid purchasing of pharmaceuticals are reviewed; further, the prices available with bid purchasing to a specific hospital in 1974 and 1977 are presented. Factors important for a successful bid purchasing system of pharmaceuticals are: (1) use of a formulary policy, (2) an effective procedure for handling bid purchasing and (3) criteria for evaluation of drug products. Significant differences were found between prices available with and without bid purchasing for 50 nonproprietary drug products in 1974 and for 19 products in 1977. Although monetary savings to hospitals do exist with bid purchasing of pharmaceuticals, the degree of savings is dependent upon the drug usage for that hospital.

48 CFR 14.203 - Methods of soliciting bids.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Methods of soliciting bids. 14.203 Section 14.203 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.203 Methods of soliciting bids. ...

48 CFR 14.203 - Methods of soliciting bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Methods of soliciting bids. 14.203 Section 14.203 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 14.203 Methods of soliciting bids. ...

Innovative workover/drilling rigs to utilize hydraulics

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

Noran, D.

1975-09-29

While Western Gear Corp., Everett, Wash., is currently building 2 models of a hydraulic workover/drilling rig (one offshore and the other a trailer-mounted land rig), Bender Co., Bakersfield, Calif., already has an all-hydraulic servicing/drilling rig undergoing tests. The rigs are similar in that they eliminate the traveling block, crown block, draw works, chains, and sprockets found on the conventional rig. The major design innovation on the Western Gear model is the 260,000-lb-capacity hoisting system in which 2 hydraulic rams are anchored to the rig floor and carry all the pipe weight, thus eliminating the danger of the derrick's being pulledmore » in. Other changes involve the tripping system, a power swivel/elevator, and the control valves. Maintenance and labor cost reductions are expected to be substantial. The Bender Co. rig has a single-section mast that is a lever-lift-type derrick which serves as a guide for the rams and a support for the pipe-racking platform. Hoisting capacity depends on the number and size of the lifting rods (which support the crown sheaves) and the hydraulic pressure applied. Manufacturing and operating costs are expected to be less than for conventional rigs.« less

[Innate immune responses against viral infection and its suppression by viral proteins].

PubMed

Oshiumi, Hiroyuki; Matsumoto, Misako; Seya, Tsukasa

2013-01-01

Retinoic acid-inducible gene-I(RIG-I) is a cytoplasmic RNA helicase and a viral RNA sensor. RIG-I recognizes 5' triphosphate double-stranded RNA (dsRNA) and activates the IPS-1 adaptor molecule. The association of IPS-1 with RIG-I causes the formation of the prion-like structure of IPS-1. This structure is essential for activation of the signaling required for the induction of type I interferon (IFN), which possesses strong antiviral activity. Recent studies have revealed the novel factors involved in the RIG-I-dependent pathway. DDX3 and DDX60 RNA helicases associate with RIG-I and promote its binding to viral RNA. Riplet and TRIM25 ubiquitin ligase deliver Lys63-linked polyubiquitin moiety to RIG-I and result in signal activation. Several pathogenic viruses have evolved excellent systems to suppress type I IFN production. For example, NS3-4A of hepatitis C virus (HCV) cleaves IPS-1, which is the adaptor molecule of RIG-I, while the HCV core protein abrogates DDX3 function to suppress RIG-I-dependent IPS-1 activation, and the NS-1 of flu inhibits TRIM25 function to suppress RIG-I activation.

Bid Participates in Genotoxic Drug-Induced Apoptosis of HeLa Cells and Is Essential for Death Receptor Ligands' Apoptotic and Synergistic Effects

PubMed Central

Concannon, Caoimhin G.; Rehm, Markus; Kögel, Donat; Prehn, Jochen H. M.

2008-01-01

Background The BH3-only protein Bid is an important component of death receptor-mediated caspase activation. Bid is cleaved by caspase-8 or -10 into t-Bid, which translocates to mitochondria and triggers the release of caspase-activating factors. Bid has also been reported to be cleaved by other proteases. Methodology/Principal Findings To test the hypothesis that Bid is a central mediator of stress-induced apoptosis, we investigated the effects of a small molecule Bid inhibitor on stress-induced apoptosis, and generated HeLa cells deficient for Bid. Stable knockdown of bid lead to a pronounced resistance to Fas/CD95- and TRAIL-induced caspase activation and apoptosis, and significantly increased clonogenic survival. While Bid-deficient cells were equally sensitive to ER stress-induced apoptosis, they showed moderate, but significantly reduced levels of apoptosis, as well as increased clonogenic survival in response to the genotoxic drugs Etoposide, Oxaliplatin, and Doxorubicin. Similar effects were observed using the Bid inhibitor BI6C9. Interestingly, Bid-deficient cells were dramatically protected from apoptosis when subtoxic concentrations of ER stressors, Etoposide or Oxaliplatin were combined with subtoxic TRAIL concentrations. Conclusions/Significance Our data demonstrate that Bid is central for death receptor-induced cell death and participates in anti-cancer drug-induced apoptosis in human cervical cancer HeLa cells. They also show that the synergistic effects of TRAIL in combination with either ER stressors or genotoxic anti-cancer drugs are nearly exclusively mediated via an increased activation of Bid-induced apoptosis signalling. PMID:18665234

Dynamic Interaction of cBid with Detergents, Liposomes and Mitochondria

PubMed Central

Bleicken, Stephanie; García-Sáez, Ana J.; Conte, Elena; Bordignon, Enrica

2012-01-01

The BH3-only protein Bid plays a key role in the induction of mitochondrial apoptosis, but its mechanism of action is still not completely understood. Here we studied the two main activation events of Bid: Caspase-8 cleavage and interaction with the membrane bilayer. We found a striking reversible behaviour of the dissociation-association events between the Bid fragments p15 and p7. Caspase-8 cleavage does not induce per se separation of the two Bid fragments, which remain in a stable complex resembling the full length Bid. Detergents trigger a complete dissociation, which can be fully reversed by detergent removal in a range of protein concentrations from 100 µM down to 500 nM. Incubation of cBid with cardiolipin-containing liposomes leads to partial dissociation of the complex. Only p15 (tBid) fragments are found at the membrane, while p7 shows no tendency to interact with the bilayer, but complete removal of p7 strongly increases the propensity of tBid to become membrane-associated. Despite the striking structural similarities of inactive Bid and Bax, Bid does not form oligomers and reacts differently in the presence of detergents and membranes, highlighting clear differences in the modes of action of the two proteins. The partial dissociation of cBid triggered by the membrane is suggested to depend on the strong and specific interaction between p15 and p7. The reversible disassembly and re-assembly of the cBid molecules at the membrane was as well proven by EPR using spin labeled cBid in the presence of isolated mitochondria. The observed dynamic dissociation of the two Bid fragments could allow the assistance to the pore-forming Bax to occur repeatedly and may explain the proposed “hit-and-run" mode of action of Bid at the bilayer. PMID:22540011

48 CFR 14.101 - Elements of sealed bidding.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Elements of sealed bidding. 14.101 Section 14.101 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Use of Sealed Bidding 14.101 Elements of sealed bidding...

48 CFR 14.101 - Elements of sealed bidding.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 1 2014-10-01 2014-10-01 false Elements of sealed bidding. 14.101 Section 14.101 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Use of Sealed Bidding 14.101 Elements of sealed bidding...

48 CFR 14.101 - Elements of sealed bidding.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Elements of sealed bidding. 14.101 Section 14.101 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Use of Sealed Bidding 14.101 Elements of sealed bidding...

48 CFR 14.101 - Elements of sealed bidding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Elements of sealed bidding. 14.101 Section 14.101 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Use of Sealed Bidding 14.101 Elements of sealed bidding...

48 CFR 14.101 - Elements of sealed bidding.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Elements of sealed bidding. 14.101 Section 14.101 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Use of Sealed Bidding 14.101 Elements of sealed bidding...

48 CFR 2014.407 - Mistakes in bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Mistakes in bids. 2014.407 Section 2014.407 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 2014.407 Mistakes in bids. ...

Comparisons of Rig and Engine Dynamic Events in the Compressor of an Axi-Centrifugal Turboshaft Engine

NASA Technical Reports Server (NTRS)

Owen, A. Karl; Mattern, Duane L.; Le, Dzu K.

1996-01-01

Steady state and dynamic data were acquired in a T55-L-712 compressor rig. In addition, a T55-L-12 engine was instrumented and similar data were acquired. Rig and engine stall/surge data were analyzed using modal techniques. This paper compares rig and engine preliminary results for the ground idle (approximately 60% of design speed) point. The results of these analyses indicate both rig and engine dynamic event are preceded by indications of traveling wave energy in front of the compressor face. For both rig and engine, the traveling wave energy contains broad band energy with some prominent narrow peaks and, while the events are similar in many ways, some noticeable differences exist between the results of the analyses of rig data and engine data.

36 CFR 223.88 - Bidding methods.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 2 2013-07-01 2013-07-01 false Bidding methods. 223.88... Sale Contracts Advertisement and Bids § 223.88 Bidding methods. (a) Competitive sales of National Forest timber shall be offered through either sealed or oral auction bidding. The method chosen for each...

36 CFR 223.88 - Bidding methods.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 2 2012-07-01 2012-07-01 false Bidding methods. 223.88... Sale Contracts Advertisement and Bids § 223.88 Bidding methods. (a) Competitive sales of National Forest timber shall be offered through either sealed or oral auction bidding. The method chosen for each...

A Bluff-Bidding Exercise

ERIC Educational Resources Information Center

Meister, J. Patrick

2011-01-01

Consider an auction in which one potential buyer wishes to participate, but the other potential buyer would rather the bidding not start. However, once bidding starts, the reluctant firm participates (submits "bluff bids") simply to make the eventual winner pay more. This incentive exists when the marginal effect of the winning bid is to increase…

36 CFR 223.88 - Bidding methods.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 2 2014-07-01 2014-07-01 false Bidding methods. 223.88... Sale Contracts Advertisement and Bids § 223.88 Bidding methods. (a) Competitive sales of National Forest timber shall be offered through either sealed or oral auction bidding. The method chosen for each...

36 CFR 223.88 - Bidding methods.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Bidding methods. 223.88... Sale Contracts Advertisement and Bids § 223.88 Bidding methods. (a) Competitive sales of National Forest timber shall be offered through either sealed or oral auction bidding. The method chosen for each...

24 CFR 291.304 - Bidding process.

Code of Federal Regulations, 2012 CFR

2012-04-01

... DEVELOPMENT HUD-OWNED PROPERTIES DISPOSITION OF HUD-ACQUIRED SINGLE FAMILY PROPERTY Sale of HUD-Held Single... HUD in accordance with instructions in the bid package for a particular sale. (b) Effect of bid. By... bid package. Along with the bid, the bidder must submit an executed copy of the Loan Sale Agreement...

24 CFR 291.304 - Bidding process.

Code of Federal Regulations, 2014 CFR

2014-04-01

... DEVELOPMENT HUD-OWNED PROPERTIES DISPOSITION OF HUD-ACQUIRED SINGLE FAMILY PROPERTY Sale of HUD-Held Single... HUD in accordance with instructions in the bid package for a particular sale. (b) Effect of bid. By... bid package. Along with the bid, the bidder must submit an executed copy of the Loan Sale Agreement...

24 CFR 291.304 - Bidding process.

Code of Federal Regulations, 2010 CFR

2010-04-01

... DEVELOPMENT HUD-OWNED PROPERTIES DISPOSITION OF HUD-ACQUIRED SINGLE FAMILY PROPERTY Sale of HUD-Held Single... HUD in accordance with instructions in the bid package for a particular sale. (b) Effect of bid. By... bid package. Along with the bid, the bidder must submit an executed copy of the Loan Sale Agreement...

48 CFR 814.404-2 - Rejection of individual bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Rejection of individual... Rejection of individual bids. (a) When a contracting officer finds a bid that is being considered for an... nonresponsive an individual bid that is not in compliance with the Government's bid acceptance time, since...

24 CFR 291.304 - Bidding process.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 24 Housing and Urban Development 2 2011-04-01 2011-04-01 false Bidding process. 291.304 Section 291.304 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued... Family Mortgage Loans § 291.304 Bidding process. (a) Submission of bids. All bids must be submitted to...

Designing a Successful Bidding Strategy Using Fuzzy Sets and Agent Attitudes

NASA Astrophysics Data System (ADS)

Ma, Jun; Goyal, Madhu Lata

To be successful in a multi-attribute auction, agents must be capable of adapting to continuously changing bidding price. This chapter presents a novel fuzzy attitude-based bidding strategy (FA-Bid), which employs dual assessment technique, i.e., assessment of multiple attributes of the goods as well as assessment of agents' attitude (eagerness) to procure an item in automated auction. The assessment of attributes adapts the fuzzy sets technique to handle uncertainty of the bidding process as well use heuristic rules to determine the attitude of bidding agents in simulated auctions to procure goods. The overall assessment is used to determine a price range based on current bid, which finally selects the best one as the new bid.

Research on Bidding Decision-making of International Public-Private Partnership Projects

NASA Astrophysics Data System (ADS)

Hu, Zhen Yu; Zhang, Shui Bo; Liu, Xin Yan

2018-06-01

In order to select the optimal quasi-bidding project for an investment enterprise, a bidding decision-making model for international PPP projects was established in this paper. Firstly, the literature frequency statistics method was adopted to screen out the bidding decision-making indexes, and accordingly the bidding decision-making index system for international PPP projects was constructed. Then, the group decision-making characteristic root method, the entropy weight method, and the optimization model based on least square method were used to set the decision-making index weights. The optimal quasi-bidding project was thus determined by calculating the consistent effect measure of each decision-making index value and the comprehensive effect measure of each quasi-bidding project. Finally, the bidding decision-making model for international PPP projects was further illustrated by a hypothetical case. This model can effectively serve as a theoretical foundation and technical support for the bidding decision-making of international PPP projects.

32 CFR 172.5 - Procedures.

Code of Federal Regulations, 2011 CFR

2011-07-01

... SALES OF SURPLUS PERSONAL PROPERTY § 172.5 Procedures. (a) Required bid deposits. When a sale conducted... apply: (1) Term bid. This type of bid deposit is applicable when the sale involves the purchase of scrap... of 20 percent of the bid shall accompany the bid. (b) Payment terms. When a sale conducted by a DoD...

48 CFR 2052.214-72 - Bid evaluation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Bid evaluation. 2052.214-72... SOLICITATION PROVISIONS AND CONTRACT CLAUSES Text of Provisions and Clauses 2052.214-72 Bid evaluation. As... invitations for bids (paragraph “(f)” of this provision is optional): Bid Evaluation (JAN 1993) (a) Award will...

7 CFR 1780.95 - Public bidding on bonds.

Code of Federal Regulations, 2010 CFR

2010-01-01

... public bidding. The Agency will not submit a bid at the advertised sale unless required by State law, nor... 7 Agriculture 12 2010-01-01 2010-01-01 false Public bidding on bonds. 1780.95 Section 1780.95... Bonds and Bond Transcript Documents for Public Body Applicants § 1780.95 Public bidding on bonds. Bonds...

31 CFR 356.14 - What are the requirements for submitting bids for customers?

Code of Federal Regulations, 2010 CFR

2010-07-01

... submitting bids for customers? 356.14 Section 356.14 Money and Finance: Treasury Regulations Relating to... requirements for submitting bids for customers? (a) Institutions that may submit bids for customers. Only depository institutions or dealers may submit bids for customers (see definitions at § 356.2), or for...

Bidding Agents That Perpetrate Auction Fraud

NASA Astrophysics Data System (ADS)

Trevathan, Jarrod; McCabe, Alan; Read, Wayne

This paper presents a software bidding agent that inserts fake bids on the seller's behalf to inflate an auction's price. This behaviour is referred to as shill bidding. Shill bidding is strictly prohibited by online auctioneers, as it defrauds unsuspecting buyers by forcing them to pay more for the item. The malicious bidding agent was constructed to aid in developing shill detection techniques. We have previously documented a simple shill bidding agent that incrementally increases the auction price until it reaches the desired profit target, or it becomes too risky to continue bidding. This paper presents an adaptive shill bidding agent which when used over a series of auctions with substitutable items, can revise its strategy based on bidding behaviour in past auctions. The adaptive agent applies a novel prediction technique referred to as the Extremum Consistency (EC) algorithm, to determine the optimal price to aspire for. The EC algorithm has successfully been used in handwritten signature verification for determining the maximum and minimum values in an input stream. The agent's ability to inflate the price has been tested in a simulated marketplace and experimental results are presented.

Competitive Bidding in a Certain Class of Auctions

NASA Astrophysics Data System (ADS)

Johansson, Mathias

2006-11-01

We consider the problem of determining the amount to bid in a certain type of auctions in which customers submit one sealed bid. The bid reflects the price a customer is willing to pay for one unit of the offered goods. The auction is repeated and at each auction each customer requests a certain amount of goods, an amount that we call the capacity of the customer and that varies among customers and over time. At each auction, only the customer with the largest bid-capacity product obtains any goods. The price paid by the winner equals his/her bid-capacity product, and the amount of goods obtained in return equals the winner's capacity. The auction is repeated many times, with only limited information concerning winning bid-capacity products being announced to the customers. This situation is motivated in for example wireless communication networks in which a possible way of obtaining a desired service level is to use dynamic pricing and competitive bidding. In this application, the capacity is typically uncertain when the bid is made. We derive bidding rules and loss functions for a few typical service requirements.

An analysis of competitive bidding by providers for indigent medical care contracts.

PubMed Central

Kirkman-Liff, B L; Christianson, J B; Hillman, D G

1985-01-01

This article develops a model of behavior in bidding for indigent medical care contracts in which bidders set bid prices to maximize their expected utility, conditional on estimates of variables which affect the payoff associated with winning or losing a contract. The hypotheses generated by this model are tested empirically using data from the first round of bidding in the Arizona indigent health care experiment. The behavior of bidding organizations in Arizona is found to be consistent in most respects with the predictions of the model. Bid prices appear to have been influenced by estimated costs and by expectations concerning the potential loss from not securing a contract, the initial wealth of the bidding organization, and the expected number of competitors in the bidding process. PMID:4086301

Viral RNA-Unprimed Rig-I Restrains Stat3 Activation in the Modulation of Regulatory T Cell/Th17 Cell Balance.

PubMed

Yang, Hui; Guo, He-Zhou; Li, Xian-Yang; Lin, Jian; Zhang, Wu; Zhao, Jun-Mei; Zhang, Hong-Xin; Chen, Sai-Juan; Chen, Zhu; Zhu, Jiang

2017-07-01

Innate immunity activation by viral RNA-primed retinoid acid inducible gene-I (Rig-I) in CD4 + T cells antagonizes TGFβ signaling to suppress the differentiation of regulatory T cells (Tregs). However, how viral RNA-unliganded Rig-I (apo-Rig-I) modulates Treg generation remains unclear. In this article, we show that, in the absence of viral infection, Treg differentiation of Rig-I -/- CD4 + T cells was compromised, in the presence of increased generation of Th17 cells and overactivation of Stat3, a critical regulator tilting the Treg/Th17 cell balance. Mechanistically, apo-Rig-I physically associates with Stat3, thereby inhibiting Jak1's association with Stat3 while facilitating Shp2's association to inhibit p-Stat3 levels. Interestingly, inhibition of Stat3 ameliorates the Treg/Th17 imbalance and the colitis observed in Rig-I -/- mice. Collectively, these results uncover an independent functional contribution of the apo-Rig-I/Stat3 interaction in the maintenance of Treg/Th17 cell balance. Copyright © 2017 by The American Association of Immunologists, Inc.

Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein.

PubMed

Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In; Choi, Myung-Soo; Inn, Kyung-Soo

2013-07-19

RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediated IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways. Copyright © 2013 Elsevier Inc. All rights reserved.

Injury Rates on New and Old Technology Oil and Gas Rigs Operated by the Largest United States Onshore Drilling Contractor

PubMed Central

Blackley, David J.; Retzer, Kyla D.; Hubler, Warren G.; Hill, Ryan D.; Laney, A. Scott

2015-01-01

Background Occupational fatality rates among oil and gas extraction industry and specifically among drilling contractor workers are high compared to the U.S. all-industry average. There is scant literature focused on non-fatal injuries among drilling contractors, some of which have introduced engineering controls to improve rig efficiency and reduce injury risk. Methods We compared injury rates on new and old technology rigs operated by the largest U.S. drilling contractor during 2003–2012, stratifying by job type and grouping outcomes by injury severity and body part affected. Results Six hundred seventy-one injuries were recorded over 77.4 million person-hours. The rate on new rigs was 66% of that on old rigs. Roughnecks had lower injury rates on new rigs, largely through reduced limb injury rates. New rigs had lower rates in each non-fatal injury severity category. Conclusions For this company, new technology rigs appear to provide a safer environment for roughnecks. Future studies could include data from additional companies. PMID:25164118

Injury rates on new and old technology oil and gas rigs operated by the largest United States onshore drilling contractor.

PubMed

Blackley, David J; Retzer, Kyla D; Hubler, Warren G; Hill, Ryan D; Laney, A Scott

2014-10-01

Occupational fatality rates among oil and gas extraction industry and specifically among drilling contractor workers are high compared to the U.S. all-industry average. There is scant literature focused on non-fatal injuries among drilling contractors, some of which have introduced engineering controls to improve rig efficiency and reduce injury risk. We compared injury rates on new and old technology rigs operated by the largest U.S. drilling contractor during 2003-2012, stratifying by job type and grouping outcomes by injury severity and body part affected. Six hundred seventy-one injuries were recorded over 77.4 million person-hours. The rate on new rigs was 66% of that on old rigs. Roughnecks had lower injury rates on new rigs, largely through reduced limb injury rates. New rigs had lower rates in each non-fatal injury severity category. For this company, new technology rigs appear to provide a safer environment for roughnecks. Future studies could include data from additional companies. © 2014 Wiley Periodicals, Inc.

A Universal Rig for Supporting Large Hammer Drills: Reduced Injury Risk and Improved Productivity

PubMed Central

Rempel, David; Barr, Alan

2015-01-01

Drilling holes into concrete with heavy hammer and rock drills is one of the most physically demanding tasks performed in commercial construction and poses risks for musculoskeletal disorders, noise induced hearing loss, hand arm vibration syndrome and silicosis. The aim of this study was to (1) use a participatory process to develop a rig to support pneumatic rock drills or large electric hammer drills in order to reduce the health risks and (2) evaluate the usability of the rig. Seven prototype rigs for supporting large hammer drills were developed and modified with feedback from commercial contractors and construction workers. The final design was evaluated by laborers and electricians (N=29) who performed their usual concrete drilling with the usual method and the new rig. Subjective regional fatigue was significantly less in the neck, shoulders, hands and arms, and lower back) when using the universal rig compared to the usual manual method. Usability ratings for the rig were significantly better than the usual method on stability, control, drilling, accuracy, and vibration. Drilling time was reduced by approximately 50% with the rig. Commercial construction contractors, laborers and electricians who use large hammer drills for drilling many holes should consider using such a rig to prevent musculoskeletal disorders, fatigue, and silicosis. PMID:26005290

Rig-I regulates NF-κB activity through binding to Nf-κb1 3′-UTR mRNA

PubMed Central

Zhang, Hong-Xin; Liu, Zi-Xing; Sun, Yue-Ping; Lu, Shun-Yuan; Liu, Xue-Song; Huang, Qiu-Hua; Xie, Yin-Yin; Dang, Su-Ying; Zheng, Guang-Yong; Li, Yi-Xue; Kuang, Ying; Fei, Jian; Chen, Zhu; Wang, Zhu-Gang

2013-01-01

Retinoic acid inducible gene I (RIG-I) senses viral RNAs and triggers innate antiviral responses through induction of type I IFNs and inflammatory cytokines. However, whether RIG-I interacts with host cellular RNA remains undetermined. Here we report that Rig-I interacts with multiple cellular mRNAs, especially Nf-κb1. Rig-I is required for NF-κB activity via regulating Nf-κb1 expression at posttranscriptional levels. It interacts with the multiple binding sites within 3′-UTR of Nf-κb1 mRNA. Further analyses reveal that three distinct tandem motifs enriched in the 3′-UTR fragments can be recognized by Rig-I. The 3′-UTR binding with Rig-I plays a critical role in normal translation of Nf-κb1 by recruiting the ribosomal proteins [ribosomal protein L13 (Rpl13) and Rpl8] and rRNAs (18S and 28S). Down-regulation of Rig-I or Rpl13 significantly reduces Nf-κb1 and 3′-UTR–mediated luciferase expression levels. These findings indicate that Rig-I functions as a positive regulator for NF-κB signaling and is involved in multiple biological processes in addition to host antivirus immunity. PMID:23553835

Overexpression of BID in thyroids of transgenic mice increases sensitivity to iodine-induced autoimmune thyroiditis

PubMed Central

2014-01-01

Background BID functions as a bridge molecule between death-receptor and mitochondrial related apoptotic pathways to amplify apoptotic signaling. Our previous studies have demonstrated a substantial increase in BID expression in primary normal thyroid epithelia cells treated with inflammatory cytokines, including the combination of IFNγ and IL-1β or IFNγ and TNFα. The aim of this study was to determine whether an increase in BID expression in thyroid can induce autoimmune thyroiditis. Methods A transgenic mouse line that expresses human BID in thyroid cells was established by fusing a mouse thyroglobulin (Tg) promoter upstream of human BID (Tg-BID). We tested whether the increased expression of pro-apoptotic BID in thyroid would induce autoimmune thyroiditis, both in the presence and absence of 0.3% iodine water. Results Our data show that Tg-BID mice in a CBA/J (H-2 k) background do not spontaneously develop autoimmune thyroiditis for over a year. However, upon ingestion of iodine in the drinking water, autoimmune thyroiditis does develop in Tg-BID transgenic mice, as shown by a significant increase in anti-Tg antibody and mononuclear cell infiltration in the thyroid glands in 30% of mice tested. Serum T4 levels, however, were similar between iodine-treated Tg-BID transgenic mice and the wild type mice. Conclusions Our data demonstrate that increased thyroid expression of BID facilitates the development of autoimmune thyroiditis induced by iodine uptake. However, the overexpression of BID itself is not sufficient to initiate thyroiditis in CBA/J (H-2 k) mice. PMID:24957380

Activation of duck RIG-I by TRIM25 is independent of anchored ubiquitin.

PubMed

Miranzo-Navarro, Domingo; Magor, Katharine E

2014-01-01

Retinoic acid inducible gene I (RIG-I) is a viral RNA sensor crucial in defense against several viruses including measles, influenza A and hepatitis C. RIG-I activates type-I interferon signalling through the adaptor for mitochondrial antiviral signaling (MAVS). The E3 ubiquitin ligase, tripartite motif containing protein 25 (TRIM25), activates human RIG-I through generation of anchored K63-linked polyubiquitin chains attached to lysine 172, or alternatively, through the generation of unanchored K63-linked polyubiquitin chains that interact non-covalently with RIG-I CARD domains. Previously, we identified RIG-I of ducks, of interest because ducks are the host and natural reservoir of influenza viruses, and showed it initiates innate immune signaling leading to production of interferon-beta (IFN-β). We noted that K172 is not conserved in RIG-I of ducks and other avian species, or mouse. Because K172 is important for both mechanisms of activation of human RIG-I, we investigated whether duck RIG-I was activated by TRIM25, and if other residues were the sites for attachment of ubiquitin. Here we show duck RIG-I CARD domains are ubiquitinated for activation, and ubiquitination depends on interaction with TRIM25, as a splice variant that cannot interact with TRIM25 is not ubiquitinated, and cannot be activated. We expressed GST-fusion proteins of duck CARD domains and characterized TRIM25 modifications of CARD domains by mass spectrometry. We identified two sites that are ubiquitinated in duck CARD domains, K167 and K193, and detected K63 linked polyubiquitin chains. Site directed mutagenesis of each site alone, does not alter the ubiquitination profile of the duck CARD domains. However, mutation of both sites resulted in loss of all attached ubiquitin and polyubiquitin chains. Remarkably, the double mutant duck RIG-I CARD still interacts with TRIM25, and can still be activated. Our results demonstrate that anchored ubiquitin chains are not necessary for TRIM25 activation of duck RIG-I.

Pigeon RIG-I Function in Innate Immunity against H9N2 IAV and IBDV.

PubMed

Xu, Wenping; Shao, Qiang; Zang, Yunlong; Guo, Qiang; Zhang, Yongchao; Li, Zandong

2015-07-22

Retinoic acid-inducible gene I (RIG-I), a cytosolic pattern recognition receptor (PRR), can sense various RNA viruses, including the avian influenza virus (AIV) and infectious bursal disease virus (IBDV), and trigger the innate immune response. Previous studies have shown that mammalian RIG-I (human and mice) and waterfowl RIG-I (ducks and geese) are essential for type I interferon (IFN) synthesis during AIV infection. Like ducks, pigeons are also susceptible to infection but are ineffective propagators and disseminators of AIVs, i.e., "dead end" hosts for AIVs and even highly pathogenic avian influenza (HPAI). Consequently, we sought to identify pigeon RIG-I and investigate its roles in the detection of A/Chicken/Shandong/ZB/2007 (H9N2) (ZB07), Gansu/Tianshui (IBDV TS) and Beijing/CJ/1980 (IBDV CJ-801) strains in chicken DF-1 fibroblasts or human 293T cells. Pigeon mRNA encoding the putative pigeon RIG-I analogs was identified. The exogenous expression of enhanced green fluorescence protein (EGFP)-tagged pigeon RIG-I and caspase activation and recruitment domains (CARDs), strongly induced antiviral gene (IFN-β, Mx, and PKR) mRNA synthesis, decreased viral gene (M gene and VP2) mRNA expression, and reduced the viral titers of ZB07 and IBDV TS/CJ-801 virus strains in chicken DF-1 cells, but not in 293T cells. We also compared the antiviral abilities of RIG-I proteins from waterfowl (duck and goose) and pigeon. Our data indicated that waterfowl RIG-I are more effective in the induction of antiviral genes and the repression of ZB07 and IBDV TS/CJ-801 strain replication than pigeon RIG-I. Furthermore, chicken melanoma differentiation associated gene 5(MDA5)/ mitochondrial antiviral signaling (MAVS) silencing combined with RIG-I transfection suggested that pigeon RIG-I can restore the antiviral response in MDA5-silenced DF-1 cells but not in MAVS-silenced DF-1 cells. In conclusion, these results demonstrated that pigeon RIG-I and CARDs have a strong antiviral ability against AIV H9N2 and IBDV in chicken DF-1 cells but not in human 293T cells.

30 CFR 260.130 - What criteria does MMS use for selecting bidding systems and bidding system components?

Code of Federal Regulations, 2011 CFR

2011-07-01

... system or tract, or may present a conflict that we will have to resolve in the process of bidding system... bidding systems and bidding system components? 260.130 Section 260.130 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION, AND ENFORCEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE OUTER CONTINENTAL...

Auctions to Reinforce Understanding

ERIC Educational Resources Information Center

Flores, Haynet Rivera

2018-01-01

An auction is a process of buying and selling goods or services by offering them up for bid, taking bids, and then selling each good or service to the highest bidder. Participants bid openly against one another; each bid must be higher than the previous bid. In the activity described rather than goods or services, English teachers sell sentences!…

48 CFR 14.401 - Receipt and safeguarding of bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.401 Receipt and... identification, and then only by an official designated for this purpose. If a sealed bid is opened by mistake (e.g., because it is not marked as being a bid), the envelope shall be signed by the opener, whose...

30 CFR 260.111 - What conditions apply to the bidding systems that MMS uses?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false What conditions apply to the bidding systems... INTERIOR OFFSHORE OUTER CONTINENTAL SHELF OIL AND GAS LEASING Bidding Systems General Provisions § 260.111 What conditions apply to the bidding systems that MMS uses? (a) For each of the bidding systems in...

MEG-BIDS, the brain imaging data structure extended to magnetoencephalography

PubMed Central

Niso, Guiomar; Gorgolewski, Krzysztof J.; Bock, Elizabeth; Brooks, Teon L.; Flandin, Guillaume; Gramfort, Alexandre; Henson, Richard N.; Jas, Mainak; Litvak, Vladimir; T. Moreau, Jeremy; Oostenveld, Robert; Schoffelen, Jan-Mathijs; Tadel, Francois; Wexler, Joseph; Baillet, Sylvain

2018-01-01

We present a significant extension of the Brain Imaging Data Structure (BIDS) to support the specific aspects of magnetoencephalography (MEG) data. MEG measures brain activity with millisecond temporal resolution and unique source imaging capabilities. So far, BIDS was a solution to organise magnetic resonance imaging (MRI) data. The nature and acquisition parameters of MRI and MEG data are strongly dissimilar. Although there is no standard data format for MEG, we propose MEG-BIDS as a principled solution to store, organise, process and share the multidimensional data volumes produced by the modality. The standard also includes well-defined metadata, to facilitate future data harmonisation and sharing efforts. This responds to unmet needs from the multimodal neuroimaging community and paves the way to further integration of other techniques in electrophysiology. MEG-BIDS builds on MRI-BIDS, extending BIDS to a multimodal data structure. We feature several data-analytics software that have adopted MEG-BIDS, and a diverse sample of open MEG-BIDS data resources available to everyone. PMID:29917016

MEG-BIDS, the brain imaging data structure extended to magnetoencephalography.

PubMed

Niso, Guiomar; Gorgolewski, Krzysztof J; Bock, Elizabeth; Brooks, Teon L; Flandin, Guillaume; Gramfort, Alexandre; Henson, Richard N; Jas, Mainak; Litvak, Vladimir; T Moreau, Jeremy; Oostenveld, Robert; Schoffelen, Jan-Mathijs; Tadel, Francois; Wexler, Joseph; Baillet, Sylvain

2018-06-19

We present a significant extension of the Brain Imaging Data Structure (BIDS) to support the specific aspects of magnetoencephalography (MEG) data. MEG measures brain activity with millisecond temporal resolution and unique source imaging capabilities. So far, BIDS was a solution to organise magnetic resonance imaging (MRI) data. The nature and acquisition parameters of MRI and MEG data are strongly dissimilar. Although there is no standard data format for MEG, we propose MEG-BIDS as a principled solution to store, organise, process and share the multidimensional data volumes produced by the modality. The standard also includes well-defined metadata, to facilitate future data harmonisation and sharing efforts. This responds to unmet needs from the multimodal neuroimaging community and paves the way to further integration of other techniques in electrophysiology. MEG-BIDS builds on MRI-BIDS, extending BIDS to a multimodal data structure. We feature several data-analytics software that have adopted MEG-BIDS, and a diverse sample of open MEG-BIDS data resources available to everyone.

47 CFR 25.403 - Bidding application and certification procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CARRIER SERVICES SATELLITE COMMUNICATIONS Competitive Bidding Procedures for DARS § 25.403 Bidding...'s name; (b) Mailing Address (no Post Office boxes); (c) City; (d) State; (e) ZIP Code; (f) Auction...

47 CFR 25.403 - Bidding application and certification procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... CARRIER SERVICES SATELLITE COMMUNICATIONS Competitive Bidding Procedures for DARS § 25.403 Bidding...'s name; (b) Mailing Address (no Post Office boxes); (c) City; (d) State; (e) ZIP Code; (f) Auction...

Research on bidding quotation game of international project

NASA Astrophysics Data System (ADS)

Lin, Tao; Xu, Xin

2017-04-01

Bidding competition of international projects is more and more fierce currently. However, China started late relatively in the field, it is still lack of experience in the aspect of participation in bidding of international projects, and more effective bidding quotation system is not formed till present. Therefore, China can not win through systemic bidding quotation methods compared with many powerful bidding enterprises in the international field. Research on the field is also focused by many aspects as a result. It is urgent to solve related problems. Game theory is combined for analyzing the effectiveness and operability of bidding quotation models mainly based on current situation of bidding market in China international projects during research process in the paper. The research starts with the perspective of bidders for analyzing their game with tenderers and other bidders. The results have operational value aiming at bidders.

Hoisting and Rigging (Formerly Hoisting and Rigging Manual)

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

NONE

1995-06-01

This standard is intended as a reference document to be used by supervisors, line managers, safety personnel, equipment operators, and any other personnel responsible for safety of hoisting and rigging operations at DOE sites. It quotes or paraphrases the US OSHA and ANSI requirements. It also encompasses, under one cover,hoisting and rigging requirements, codes, standards, and regulations, eliminating the need to maintain extensive (and often incomplete) libraries of hoisting and rigging standards throughout DOE. The standard occasionally goes beyond the minimum general industry standards established by OSHA and ANSI, and also delineates the more stringent requirements necessary to accomplish themore » complex, diversified, critical, and often hazardous hoisting and rigging work found with the DOE complex.« less

Vapor Deposition Rig

NASA Image and Video Library

2015-01-27

The Plasma Spray-Physical Vapor Deposition (PS-PVD) Rig at NASA Glenn Research Center. The rig helps develop coatings for next-generation aircraft turbine components and create more efficient engines.

46 CFR Sec. 2 - Description of NSA-WORKSMALREP Contract.

Code of Federal Regulations, 2010 CFR

2010-10-01

... competitive bids, spot bids, or by negotiation for the performance of ship repair work. NSA Order No. 46 (SRM... bids, spot bids or negotiation, therefore, further reference thereto will not be made herein. ...

Developing Medicare Competitive Bidding: A Study of Clinical Laboratories

PubMed Central

Hoerger, Thomas J.; Meadow, Ann

1997-01-01

Competitive bidding to derive Medicare fees promises several advantages over administered fee systems. The authors show how incentives for cost savings, quality, and access can be incorporated into bidding schemes, and they report on a study of the clinical laboratory industry conducted in preparation for a bidding demonstration. The laboratory industry is marked by variable concentration across geographic markets and, among firms themselves, by social and economic heterogeneity. The authors conclude that these conditions can be accommodated by available bidding design options and by careful selection of bidding markets. PMID:10180003

Trophic and reproductive ecology of Red Snapper, Lutjanus campechanus, on natural and artificial reefs in the western Gulf of Mexico

NASA Astrophysics Data System (ADS)

Ajemian, M. J.; Wetz, J. J.; Brewton, R. A.; Downey, C. H.; Stunz, G. W.

2016-02-01

Energy exploration in the Gulf of Mexico (Gulf) has resulted in the addition of numerous oil and gas production rigs that have added structurally complex habitat to an area otherwise dominated by bare bottom. The impact of these artificial structures on fish populations is largely unknown and there is ongoing debate about their functionality. Red Snapper (Lutjanus campechanus), an ecologically and economically important sportfish to the region, use natural as well as the artificial reefs created by standing and reefed (toppled or cutoff) oil and gas rigs. However, little is known about how trophic and reproductive characteristics of Red Snapper vary over these multiple habitat types. We analyzed stable isotopic composition (δ13C, δ 15N) of epaxial muscle and compared reproductive potential of Red Snapper (155-855 mm TL) from standing rigs, reefed rigs, and natural hard-bottom habitats off Texas. Red Snapper from standing rig sites were isotopically enriched in δ 15N compared to lower relief habitats, suggesting they were feeding at a higher trophic level on standing rigs. While gonadosomatic indices (GSI) and comparative histology implied a similar spawning season among structure types, GSI was highest for both sexes at standing rigs. These initial results suggest that while standing rigs appear to provide more enriched food resources leading to higher Red Snapper reproductive capacity, the productivity of this species is similar between currently permitted rig decommissioning options (i.e., cutoff and toppled rigs) and natural hard-bottom habitats in the Gulf of Mexico.

Negative regulation of RIG-I-mediated antiviral signaling by TRK-fused gene (TFG) protein

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

Lee, Na-Rae; Shin, Han-Bo; Kim, Hye-In

2013-07-19

Highlights: •TRK-fused gene product (TFG) interacts with TRIM25 upon viral infection. •TFG negatively regulates RIG-I mediated antiviral signaling. •TFG depletion leads to enhanced viral replication. •TFG act downstream of MAVS. -- Abstract: RIG-I (retinoic acid inducible gene I)-mediated antiviral signaling serves as the first line of defense against viral infection. Upon detection of viral RNA, RIG-I undergoes TRIM25 (tripartite motif protein 25)-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that TRK-fused gene (TFG) protein, previously identified as a TRIM25-interacting protein, binds TRIM25 upon virus infection and negatively regulates RIG-I-mediated type-I IFN signaling. RIG-I-mediatedmore » IFN production and nuclear factor (NF)-κB signaling pathways were upregulated by the suppression of TFG expression. Furthermore, vesicular stomatitis virus (VSV) replication was significantly inhibited by small inhibitory hairpin RNA (shRNA)-mediated knockdown of TFG, supporting the suppressive role of TFG in RIG-I-mediated antiviral signaling. Interestingly, suppression of TFG expression increased not only RIG-I-mediated signaling but also MAVS (mitochondrial antiviral signaling protein)-induced signaling, suggesting that TFG plays a pivotal role in negative regulation of RNA-sensing, RIG-I-like receptor (RLR) family signaling pathways.« less

Hepatitis B virus inhibits intrinsic RIG-I and RIG-G immune signaling via inducing miR146a

PubMed Central

Hou, Zhaohua; Zhang, Jian; Han, Qiuju; Su, Chenhe; Qu, Jing; Xu, Dongqing; Zhang, Cai; Tian, Zhigang

2016-01-01

Previous studies showed that hepatitis B virus (HBV), as a latency invader, attenuated host anti-viral immune responses. miRNAs were shown to be involved in HBV infection and HBV-related diseases, however, the precise role of miRNAs in HBV-mediated immunosuppression remains unclear. Here, we observed that down-regulated RIG-I like receptors might be one critical mechanism of HBV-induced suppression of type I IFN transcription in both HBV+ hepatoma cell lines and liver cancer tissues. Then, miR146a was demonstrated to negatively regulate the expression of RIG-I-like receptors by directly targeting both RIG-I and RIG-G. Further investigation showed that antagonizing miR146a by anti-sense inhibitors or sponge approach accelerated HBV clearance and reduced HBV load both in vitro and in a HBV-carrying mouse model. Therefore, our findings indicated that HBV-induced miR146a attenuates cell-intrinsic anti-viral innate immunity through targeting RIG-I and RIG-G, and silencing miR146a might be an effective target to reverse HBV-induced immune suppression. PMID:27210312

A calibration rig for multi-component internal strain gauge balance using the new design-of-experiment (DOE) approach

NASA Astrophysics Data System (ADS)

Nouri, N. M.; Mostafapour, K.; Kamran, M.

2018-02-01

In a closed water-tunnel circuit, the multi-component strain gauge force and moment sensor (also known as balance) are generally used to measure hydrodynamic forces and moments acting on scaled models. These balances are periodically calibrated by static loading. Their performance and accuracy depend significantly on the rig and the method of calibration. In this research, a new calibration rig was designed and constructed to calibrate multi-component internal strain gauge balances. The calibration rig has six degrees of freedom and six different component-loading structures that can be applied separately and synchronously. The system was designed based on the applicability of formal experimental design techniques, using gravity for balance loading and balance positioning and alignment relative to gravity. To evaluate the calibration rig, a six-component internal balance developed by Iran University of Science and Technology was calibrated using response surface methodology. According to the results, calibration rig met all design criteria. This rig provides the means by which various methods of formal experimental design techniques can be implemented. The simplicity of the rig saves time and money in the design of experiments and in balance calibration while simultaneously increasing the accuracy of these activities.

RIG-I antiviral signaling drives interleukin-23 production and psoriasis-like skin disease.

PubMed

Zhu, Huiyuan; Lou, Fangzhou; Yin, Qianqian; Gao, Yuanyuan; Sun, Yang; Bai, Jing; Xu, Zhenyao; Liu, Zhaoyuan; Cai, Wei; Ke, Fang; Zhang, Lingyun; Zhou, Hong; Wang, Hong; Wang, Gang; Chen, Xiang; Zhang, Hongxin; Wang, Zhugang; Ginhoux, Florent; Lu, Chuanjian; Su, Bing; Wang, Honglin

2017-05-01

Retinoic acid inducible-gene I (RIG-I) functions as one of the major sensors of RNA viruses. DDX58 , which encodes the RIG-I protein, has been newly identified as a susceptibility gene in psoriasis. Here, we show that the activation of RIG-I by 5'ppp-dsRNA, its synthetic ligand, directly causes the production of IL-23 and triggers psoriasis-like skin disease in mice. Repeated injections of IL-23 to the ears failed to induce IL-23 production and a full psoriasis-like skin phenotype, in either germ-free or RIG-I-deficient mice. RIG-I is also critical for a full development of skin inflammation in imiquimod (IMQ)-induced psoriasis-like mouse model. Furthermore, RIG-I-mediated endogenous IL-23 production was mainly confined to the CD11c + dendritic cells (DCs) via nuclear factor-kappa B (NF-κB) signaling, and stimulated RIG-I expression in an auto-regulatory feedback loop. Thus, our data suggest that the dysregulation in the antiviral immune responses of hosts through the innate pattern recognition receptors may trigger the skin inflammatory conditions in the pathophysiology of psoriasis. © 2017 The Authors. Published under the terms of the CC BY 4.0 license.

New capacity bidding in Hungary

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

Bakacs, I.

The paper gives a description of the regulatory and legal fundamentals of the new capacity bidding launched in 1997 in Hungary by MVM Rt, the transmission system operator. Some details of the regulations relevant to new generating capacity licensing are discussed with regard to the implementation of the new formal competitive bidding for the right to establish new or retrofitted (repowered) generating capacity. The paper presents the major tender rules and conditions. The bidding has attracted considerable interest. Because of the confidentiality of information no details are given on individual Bidders or bids, only some general statistical information is available.more » Due to the unexpectedly large interest and number of bids in the first stage of the bidding closed in January 1998 and some other events MVM has to change slightly some of the tender rules for the second stage announced in February. Final bids should be submitted by September 1998.« less

Special experimental project (SEP-14) alternate surfacing bidding.

DOT National Transportation Integrated Search

2008-03-01

This report contains a discussion of the alternate bidding process used on a highway project in Kansas. : It discusses the background, bidding process, evaluation of the bids, and conclusions drawn from the : experience. It also includes a customer s...

Competitive bidding in Medicare: who benefits from competition?

PubMed

Song, Zirui; Landrum, Mary Beth; Chernew, Michael E

2012-09-01

To conduct the first empirical study of competitive bidding in Medicare. We analyzed 2006-2010 Medicare Advantage data from the Centers for Medicare and Medicaid Services using longitudinal models adjusted for market and plan characteristics. A $1 increase in Medicare's payment to health maintenance organization (HMO) plans led to a $0.49 (P <.001) increase in plan bids, with $0.34 (P <.001) going to beneficiaries in the form of extra benefits or lower cost sharing. With preferred provider organization and private fee-for-service plans included, higher Medicare payments increased bids less ($0.33 per dollar), suggesting more competition among these latter plans. As a market-based alternative to cost control through administrative pricing, competitive bidding relies on private insurance plans proposing prices they are willing to accept for insuring a beneficiary. However, competition is imperfect in the Medicare bidding market. As much as half of every dollar in increased plan payment went to higher bids rather than to beneficiaries. While having more insurers in a market lowered bids, the design of any bidding system for Medicare should recognize this shortcoming of competition.

Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes

PubMed Central

Sánchez-Aparicio, M. T.; Ayllón, J.; Leo-Macias, A.; Wolff, T.

2016-01-01

ABSTRACT The retinoic acid-inducible gene 1 (RIG-I) signaling pathway is essential for the recognition of viruses and the initiation of host interferon (IFN)-mediated antiviral responses. Once activated, RIG-I interacts with polyubiquitin chains generated by TRIM25 and binds mitochondrial antiviral signaling protein (MAVS), leading to the production of type I IFN. We now show specific interactions among these key partners in the RLR pathway through the use of bimolecular fluorescence complementation (BiFC) and super-resolution microscopy. Dimers of RIG-I, TRIM25, and MAVS localize into different compartments. Upon activation, we show that TRIM25 is redistributed into cytoplasmic dots associated with stress granules, while RIG-I associates with TRIM25/stress granules and with mitochondrial MAVS. In addition, MAVS competes with TRIM25 for RIG-I binding, and this suggests that upon TRIM25-mediated activation of RIG-I, RIG-I moves away from TRIM25 to interact with MAVS at the mitochondria. For the first time, the distribution of these three proteins was analyzed at the same time in virus-infected cells. We also investigated how specific viral proteins modify some of the protein complexes in the pathway. The protease NS3/4A from hepatitis C virus redistributes the complexes RIG-I/MAVS and MAVS/MAVS but not RIG-I/TRIM25. In contrast, the influenza A virus NS1 protein interacts with RIG-I and TRIM25 in specific areas in the cell cytoplasm and inhibits the formation of TRIM25 homocomplexes but not the formation of RIG-I/TRIM25 heterocomplexes, preventing the formation of RIG-I/MAVS complexes. Thus, we have localized spatially in the cell different complexes formed between RIG-I, TRIM25, and MAVS, in the presence or absence of two viral IFN antagonistic proteins. IMPORTANCE The first line of defense against viral infections is the innate immune response. Viruses are recognized by pathogen recognition receptors, such as the RIG-I like receptor family, that activate a signaling cascade that induces IFN production. In the present study, we visualized, for the first time in cells, both in overexpression and endogenous levels, complexes formed among key proteins involved in this innate immune signaling pathway. Through different techniques we were able to analyze how these proteins are distributed and reorganized spatially within the cell in order to transmit the signal, leading to an efficient antiviral state. In addition, this work presents a new means by how, when, and where viral proteins can target these pathways and act against the host immune system in order to counteract the activation of the immune response. PMID:27807226

Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes.

PubMed

Sánchez-Aparicio, M T; Ayllón, J; Leo-Macias, A; Wolff, T; García-Sastre, A

2017-01-15

The retinoic acid-inducible gene 1 (RIG-I) signaling pathway is essential for the recognition of viruses and the initiation of host interferon (IFN)-mediated antiviral responses. Once activated, RIG-I interacts with polyubiquitin chains generated by TRIM25 and binds mitochondrial antiviral signaling protein (MAVS), leading to the production of type I IFN. We now show specific interactions among these key partners in the RLR pathway through the use of bimolecular fluorescence complementation (BiFC) and super-resolution microscopy. Dimers of RIG-I, TRIM25, and MAVS localize into different compartments. Upon activation, we show that TRIM25 is redistributed into cytoplasmic dots associated with stress granules, while RIG-I associates with TRIM25/stress granules and with mitochondrial MAVS. In addition, MAVS competes with TRIM25 for RIG-I binding, and this suggests that upon TRIM25-mediated activation of RIG-I, RIG-I moves away from TRIM25 to interact with MAVS at the mitochondria. For the first time, the distribution of these three proteins was analyzed at the same time in virus-infected cells. We also investigated how specific viral proteins modify some of the protein complexes in the pathway. The protease NS3/4A from hepatitis C virus redistributes the complexes RIG-I/MAVS and MAVS/MAVS but not RIG-I/TRIM25. In contrast, the influenza A virus NS1 protein interacts with RIG-I and TRIM25 in specific areas in the cell cytoplasm and inhibits the formation of TRIM25 homocomplexes but not the formation of RIG-I/TRIM25 heterocomplexes, preventing the formation of RIG-I/MAVS complexes. Thus, we have localized spatially in the cell different complexes formed between RIG-I, TRIM25, and MAVS, in the presence or absence of two viral IFN antagonistic proteins. The first line of defense against viral infections is the innate immune response. Viruses are recognized by pathogen recognition receptors, such as the RIG-I like receptor family, that activate a signaling cascade that induces IFN production. In the present study, we visualized, for the first time in cells, both in overexpression and endogenous levels, complexes formed among key proteins involved in this innate immune signaling pathway. Through different techniques we were able to analyze how these proteins are distributed and reorganized spatially within the cell in order to transmit the signal, leading to an efficient antiviral state. In addition, this work presents a new means by how, when, and where viral proteins can target these pathways and act against the host immune system in order to counteract the activation of the immune response. Copyright © 2017 American Society for Microbiology.

Engine-Scale Combustor Rig Designed, Fabricated, and Tested for Combustion Instability Control Research

NASA Technical Reports Server (NTRS)

DeLaat, John C.; Breisacher, Kevin J.

2000-01-01

Low-emission combustor designs are prone to combustor instabilities. Because active control of these instabilities may allow future combustors to meet both stringent emissions and performance requirements, an experimental combustor rig was developed for investigating methods of actively suppressing combustion instabilities. The experimental rig has features similar to a real engine combustor and exhibits instabilities representative of those in aircraft gas turbine engines. Experimental testing in the spring of 1999 demonstrated that the rig can be tuned to closely represent an instability observed in engine tests. Future plans are to develop and demonstrate combustion instability control using this experimental combustor rig. The NASA Glenn Research Center at Lewis Field is leading the Combustion Instability Control program to investigate methods for actively suppressing combustion instabilities. Under this program, a single-nozzle, liquid-fueled research combustor rig was designed, fabricated, and tested. The rig has many of the complexities of a real engine combustor, including an actual fuel nozzle and swirler, dilution cooling, and an effusion-cooled liner. Prior to designing the experimental rig, a survey of aircraft engine combustion instability experience identified an instability observed in a prototype engine as a suitable candidate for replication. The frequency of the instability was 525 Hz, with an amplitude of approximately 1.5-psi peak-to-peak at a burner pressure of 200 psia. The single-nozzle experimental combustor rig was designed to preserve subcomponent lengths, cross sectional area distribution, flow distribution, pressure-drop distribution, temperature distribution, and other factors previously found to be determinants of burner acoustic frequencies, mode shapes, gain, and damping. Analytical models were used to predict the acoustic resonances of both the engine combustor and proposed experiment. The analysis confirmed that the test rig configuration and engine configuration had similar longitudinal acoustic characteristics, increasing the likelihood that the engine instability would be replicated in the rig. Parametric analytical studies were performed to understand the influence of geometry and condition variations and to establish a combustion test plan. Cold-flow experiments verified that the design values of area and flow distributions were obtained. Combustion test results established the existence of a longitudinal combustion instability in the 500-Hz range with a measured amplitude approximating that observed in the engine. Modifications to the rig configuration during testing also showed the potential for injector independence. The research combustor rig was developed in partnership with Pratt & Whitney of West Palm Beach, Florida, and United Technologies Research Center of East Hartford, Connecticut. Experimental testing of the combustor rig took place at United Technologies Research Center.

Function of duck RIG-I in induction of antiviral response against IBDV and avian influenza virus on chicken cells.

PubMed

Shao, Qiang; Xu, Wenpin; Yan, Li; Liu, Jinhua; Rui, Lei; Xiao, Xiao; Yu, Xiaoxue; Lu, Yanan; Li, Zandong

2014-10-13

The avian influenza (AI) H9N2 virus and IBDV are two major problems in the poultry industry. They have been prevalent among domestic poultry in Asia for many years and have caused considerable economic losses. Retinoic-acid-induced gene I (RIG-I) is a cytoplasmic sensor of dsRNA and ssRNA. It can detect Encephalomyocarditis virus (EMCV) and vesicular stomatitis virus (VSV) in human cells, influenza virus in duck leads to production of IFN-β and IFN-stimulated antiviral genes and reductions in the replication of RNA virus. Chickens, which lack RIG-I, are more sensitive to influenza virus than ducks. However, little is known about the roles of duck RIG-I (dRIG-I) in the detection of IBDV and AI H9N2 in chicken cells DF-1. The purpose of this study was to examine the function of dRIG-I in the recognition of IBDV Ts strain and H9N2 A/Chicken/Shandong/ZB/2007(ZB07) and in the induction of antiviral gene expression to gain an understanding of antiviral ability of dRIG-I in chicken cells against dsRNA virus IBDV and ssRNA virus ZB07. After challenge with the IBDV Ts strain and ZB07 the expression levels of Type I IFN (IFN-β and IFN-α) and IFN-induced antiviral genes (Mx and PKR) were significantly up-regulated in dRIG-I-transfected DF-1cells compared with the empty-vector-transfected control. dRIG-I knockdown experiments further proved that dRIG-I is essential to sensing IBDV and ZB07 in duck embryo fibroblasts (DEF). Growth curves showed that dRIG-I repressed the replication of IBDV and almost blunted the growth of ZB07 in DF-1. Apoptosis analysis revealed that dRIG-I increase the number of the survival cells after IBDV Ts strain or ZB07 infection relative to the empty-vector-transfected control. These results indicate that dRIG-I can up-regulates type I IFN and reduce viral gene expression and viral replication and protect chicken cells from virus-induced apoptosis during ZB07 and IBDV infection. Copyright © 2014 Elsevier B.V. All rights reserved.

46 CFR 162.050-17 - Separator test rig.

Code of Federal Regulations, 2014 CFR

2014-10-01

... diagram of a typical test rig is shown in Figure 162.050-17(a). FIGURE 162.050-17(a)—SEPARATOR TEST RIG... discharge side. (c) The inlet piping of the test rig must be sized so that— (1) Influent water flows at a Reynolds Number of at least 10,000; (2) The influent flow rate is between one and three meters per second...

46 CFR 162.050-17 - Separator test rig.

Code of Federal Regulations, 2011 CFR

2011-10-01

... diagram of a typical test rig is shown in Figure 162.050-17(a). FIGURE 162.050-17(a)—SEPARATOR TEST RIG... discharge side. (c) The inlet piping of the test rig must be sized so that— (1) Influent water flows at a Reynolds Number of at least 10,000; (2) The influent flow rate is between one and three meters per second...

46 CFR 162.050-17 - Separator test rig.

Code of Federal Regulations, 2010 CFR

2010-10-01

... diagram of a typical test rig is shown in Figure 162.050-17(a). FIGURE 162.050-17(a)—SEPARATOR TEST RIG... discharge side. (c) The inlet piping of the test rig must be sized so that— (1) Influent water flows at a Reynolds Number of at least 10,000; (2) The influent flow rate is between one and three meters per second...

46 CFR 162.050-17 - Separator test rig.

Code of Federal Regulations, 2013 CFR

2013-10-01

... diagram of a typical test rig is shown in Figure 162.050-17(a). FIGURE 162.050-17(a)—SEPARATOR TEST RIG... discharge side. (c) The inlet piping of the test rig must be sized so that— (1) Influent water flows at a Reynolds Number of at least 10,000; (2) The influent flow rate is between one and three meters per second...

46 CFR 162.050-17 - Separator test rig.

Code of Federal Regulations, 2012 CFR

2012-10-01

... diagram of a typical test rig is shown in Figure 162.050-17(a). FIGURE 162.050-17(a)—SEPARATOR TEST RIG... discharge side. (c) The inlet piping of the test rig must be sized so that— (1) Influent water flows at a Reynolds Number of at least 10,000; (2) The influent flow rate is between one and three meters per second...

Robust Lys63-Linked Ubiquitination of RIG-I Promotes Cytokine Eruption in Early Influenza B Virus Infection

PubMed Central

Jiang, Jingwen; Fan, Wenhui; Zheng, Weinan; Yu, Meng; Chen, Can; Sun, Lei; Bi, Yuhai; Ding, Chan; Gao, George F.

2016-01-01

ABSTRACT Influenza A and B virus infections both cause a host innate immunity response. Here, we report that the robust production of type I and III interferons (IFNs), IFN-stimulated genes, and proinflammatory factors can be induced by influenza B virus rather than influenza A virus infection in alveolar epithelial (A549) cells during early infection. This response is mainly dependent on the retinoic acid-inducible gene I (RIG-I)-mediated signaling pathway. Infection by influenza B virus promotes intense Lys63-linked ubiquitination of RIG-I, resulting in cytokine eruption. It is known that the influenza A virus NS1 protein (NS1-A) interacts with RIG-I and TRIM25 to suppress the activation of RIG-I-mediated signaling. However, the present results indicate that the influenza B virus NS1 protein (NS1-B) is unable to interact with RIG-I but engages in the formation of a RIG-I/TRIM25/NS1-B ternary complex. Furthermore, we demonstrate that the N-terminal RNA-binding domain (RBD) of NS1-B is responsible for interaction with TRIM25 and that this interaction blocks the inhibitory effect of the NS1-B C-terminal effector domain (TED) on RIG-I ubiquitination. Our findings reveal a novel mechanism for the host cytokine response to influenza B virus infection through regulatory interplay between host and viral proteins. IMPORTANCE Influenza B virus generally causes local mild epidemics but is occasionally lethal to individuals. Existing studies describe the broad characteristics of influenza B virus epidemiology and pathology. However, to develop better prevention and treatments for the disease, determining the concrete molecular mechanisms of pathogenesis becomes pivotal to understand how the host reacts to the challenge of influenza B virus. Thus, we aimed to characterize the host innate immune response to influenza B virus infection. Here, we show that vigorous Lys63-linked ubiquitination of RIG-I and cytokine eruption dependent on RIG-I-mediated signal transduction are induced by virus infection. Additionally, TRIM25 positively regulates RIG-I-mediated signaling by ablating the inhibitory function of NS1-B on RIG-I ubiquitination. PMID:27122586

Activation of Duck RIG-I by TRIM25 Is Independent of Anchored Ubiquitin

PubMed Central

Miranzo-Navarro, Domingo; Magor, Katharine E.

2014-01-01

Retinoic acid inducible gene I (RIG-I) is a viral RNA sensor crucial in defense against several viruses including measles, influenza A and hepatitis C. RIG-I activates type-I interferon signalling through the adaptor for mitochondrial antiviral signaling (MAVS). The E3 ubiquitin ligase, tripartite motif containing protein 25 (TRIM25), activates human RIG-I through generation of anchored K63-linked polyubiquitin chains attached to lysine 172, or alternatively, through the generation of unanchored K63-linked polyubiquitin chains that interact non-covalently with RIG-I CARD domains. Previously, we identified RIG-I of ducks, of interest because ducks are the host and natural reservoir of influenza viruses, and showed it initiates innate immune signaling leading to production of interferon-beta (IFN-β). We noted that K172 is not conserved in RIG-I of ducks and other avian species, or mouse. Because K172 is important for both mechanisms of activation of human RIG-I, we investigated whether duck RIG-I was activated by TRIM25, and if other residues were the sites for attachment of ubiquitin. Here we show duck RIG-I CARD domains are ubiquitinated for activation, and ubiquitination depends on interaction with TRIM25, as a splice variant that cannot interact with TRIM25 is not ubiquitinated, and cannot be activated. We expressed GST-fusion proteins of duck CARD domains and characterized TRIM25 modifications of CARD domains by mass spectrometry. We identified two sites that are ubiquitinated in duck CARD domains, K167 and K193, and detected K63 linked polyubiquitin chains. Site directed mutagenesis of each site alone, does not alter the ubiquitination profile of the duck CARD domains. However, mutation of both sites resulted in loss of all attached ubiquitin and polyubiquitin chains. Remarkably, the double mutant duck RIG-I CARD still interacts with TRIM25, and can still be activated. Our results demonstrate that anchored ubiquitin chains are not necessary for TRIM25 activation of duck RIG-I. PMID:24466302

48 CFR 6.401 - Sealed bidding and competitive proposals.

Code of Federal Regulations, 2010 CFR

2010-10-01

... competitive proposals. 6.401 Section 6.401 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING COMPETITION REQUIREMENTS Sealed Bidding and Competitive Proposals 6.401 Sealed bidding and competitive proposals. Sealed bidding and competitive proposals, as described in Parts...

48 CFR 6.401 - Sealed bidding and competitive proposals.

Code of Federal Regulations, 2011 CFR

2011-10-01

... competitive proposals. 6.401 Section 6.401 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION ACQUISITION PLANNING COMPETITION REQUIREMENTS Sealed Bidding and Competitive Proposals 6.401 Sealed bidding and competitive proposals. Sealed bidding and competitive proposals, as described in Parts...

47 CFR 1.2103 - Competitive bidding design options.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 1 2010-10-01 2010-10-01 false Competitive bidding design options. 1.2103 Section 1.2103 Telecommunication FEDERAL COMMUNICATIONS COMMISSION GENERAL PRACTICE AND PROCEDURE Competitive Bidding Proceedings General Procedures § 1.2103 Competitive bidding design options. (a) The...

Expression levels of the innate response gene RIG-I and its regulators RNF125 and TRIM25 in HIV-1-infected adult and pediatric individuals.

PubMed

Britto, Alan M A; Amoedo, Nívea D; Pezzuto, Paula; Afonso, Adriana O; Martínez, Ana M B; Silveira, Jussara; Sion, Fernando S; Machado, Elizabeth S; Soares, Marcelo A; Giannini, Ana L M

2013-07-31

TLRs (Toll-like receptors) and RLRs (RIG-I-like receptors) mediate innate immune responses by detecting microorganism invasion. RIG-I activation results in the production of interferon (IFN) type 1 and IFN responsive genes (ISGs). As the ubiquitin ligases RNF125 and TRIM25 are involved in regulating RIG-I function, our aim was to assess whether the levels of these three genes vary between healthy and HIV-infected individuals and whether these levels are related to disease progression. Gene expression analyses for RIG-I, RNF125, and TRIM25 were performed for HIV-infected adults and the children's peripheral blood mononuclear cells (PBMCs). Reverse transcription-quantitative PCRs (RT-qPCRs) were performed in order to quantify the expression levels of RIG-I, RNF125 and TRIM25 from PBMCs purified from control or HIV-infected individuals. Controls express higher levels of the three genes when compared to HIV-infected patients. These expressions are clearly distinct between healthy and progressors, and are reproduced in adults and children. In controls, RNF125 is the highest expressed gene, whereas in progressors, RIG-I is either the highest expressed gene or is expressed similarly to RNF125 and TRIM25. A pattern of expression of RIG-I, RNF125, and TRIM25 genes in HIV patients is evident. The high expression of RNF125 in healthy individuals reflects the importance of keeping RIG-I function off, inhibiting unnecessary IFN production. Consistent with this assumption, RNF125 levels are lower in HIV patients and importantly, the RNF125/RIG-I ratio is lower in patients who progress to AIDS. Our results might help to predict disease progression and unveil the role of poorly characterized host genes during HIV infection.

47 CFR 54.603 - Competitive bid requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 3 2011-10-01 2011-10-01 false Competitive bid requirements. 54.603 Section 54...) UNIVERSAL SERVICE Universal Service Support for Health Care Providers § 54.603 Competitive bid requirements. (a) Competitive bidding requirement. To select the telecommunications carriers that will provide...

RIG-I in RNA virus recognition

PubMed Central

Kell, Alison M.; Gale, Michael

2015-01-01

Antiviral immunity is initiated upon host recognition of viral products via non-self molecular patterns known as pathogen-associated molecular patterns (PAMPs). Such recognition initiates signaling cascades that induce intracellular innate immune defenses and an inflammatory response that facilitates development of the acquired immune response. The retinoic acid-inducible gene I (RIG-I) and the RIG-I-like receptor (RLR) protein family are key cytoplasmic pathogen recognition receptors that are implicated in the recognition of viruses across genera and virus families, including functioning as major sensors of RNA viruses, and promoting recognition of some DNA viruses. RIG-I, the charter member of the RLR family, is activated upon binding to PAMP RNA. Activated RIG-I signals by interacting with the adapter protein MAVS leading to a signaling cascade that activates the transcription factors IRF3 and NF-κB. These actions induce the expression of antiviral gene products and the production of type I and III interferons that lead to an antiviral state in the infected cell and surrounding tissue. RIG-I signaling is essential for the control of infection by many RNA viruses. Recently, RIG-I crosstalk with other pathogen recognition receptors and components of the inflammasome has been described. In this review, we discuss the current knowledge regarding the role of RIG-I in recognition of a variety of virus families and its role in programming the adaptive immune response through cross-talk with parallel arms of the innate immune system, including how RIG-I can be leveraged for antiviral therapy. PMID:25749629

The BCL-2 family protein Bid is critical for pro-inflammatory signaling in astrocytes.

PubMed

König, Hans-Georg; Coughlan, Karen S; Kinsella, Sinéad; Breen, Bridget A; Prehn, Jochen H M

2014-10-01

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motoneurons in the spinal cord, brainstem and motor cortex. Mutations in the superoxide dismutase 1 (SOD1) gene represent a frequent genetic determinant and recapitulate a disease phenotype similar to ALS when expressed in mice. Previous studies using SOD1(G93A) transgenic mice have suggested a paracrine mechanism of neuronal loss, in which cytokines and other toxic factors released from astroglia or microglia trigger motoneuron degeneration. Several pro-inflammatory cytokines activate death receptors and may downstream from this activate the Bcl-2 family protein, Bid. We here sought to investigate the role of Bid in astrocyte activation and non-cell autonomous motoneuron degeneration. We found that spinal cord Bid protein levels increased significantly during disease progression in SOD1(G93A) mice. Subsequent experiments in vitro indicated that Bid was expressed at relatively low levels in motoneurons, but was enriched in astrocytes and microglia. Bid was strongly induced in astrocytes in response to pro-inflammatory cytokines or exposure to lipopolysaccharide. Experiments in bid-deficient astrocytes or astrocytes treated with a small molecule Bid inhibitor demonstrated that Bid was required for the efficient activation of transcription factor nuclear factor-κB in response to these pro-inflammatory stimuli. Finally, we found that conditioned medium from wild-type astrocytes, but not from bid-deficient astrocytes, was toxic when applied to primary motoneuron cultures. Collectively, our data demonstrate a new role for the Bcl-2 family protein Bid as a mediator of astrocyte activation during neuroinflammation, and suggest that Bid activation may contribute to non-cell autonomous motoneuron degeneration in ALS. Copyright © 2014 Elsevier Inc. All rights reserved.

Analysis and design of trial well mooring in deepwater of the South China Sea

NASA Astrophysics Data System (ADS)

Guo, Yongfeng; Ji, Shaojun; Tang, Changquan; Li, Jiansong; Zhong, Huiquan; Ian, Ong Chin Yam

2012-06-01

Mooring systems play an important role for semi-submersible rigs that drill in deepwater. A detailed analysis was carried out on the mooring of a semi-submersible rig that conducted a trial well drilling at a deepwater location in the South China Sea in 2009. The rig was 30 years old and had a shallow platform with a designed maximum operating water depth of 457 m. Following the mooring analysis, a mooring design was given that requires upgrading of the rig's original mooring system. The upgrade included several innovations, such as installing eight larger anchors, i.e. replacing the original anchors and inserting an additional 600 m of steel wires with the existing chains. All this was done to enhance the mooring capability of the rig in order for the rig to be held in position to conduct drilling at a water depth of 476 m. The overall duration of the drilling was 50 days and the upgraded mooring system proved to be efficient in achieving the goal of keeping the rig stationary while it was drilling the trial well in the South China Sea. This successful campaign demonstrates that an older semi-submersible rig can take on drilling in deep water after careful design and proper upgrading and modification to the original mooring system.

42 CFR 422.254 - Submission of bids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... part or may choose not to renew the contract. (4) Substantial differences between bids. An MA organization's bid submissions must reflect differences in benefit packages or plan costs that CMS determines to represent substantial differences relative to a sponsor's other bid submissions. (5) CMS may...

42 CFR 422.254 - Submission of bids.

Code of Federal Regulations, 2012 CFR

2012-10-01

... this part or may choose not to renew the contract. (4) Substantial differences between bids. An MA organization's bid submissions must reflect differences in benefit packages or plan costs that CMS determines to represent substantial differences relative to a sponsor's other bid submissions. (5) CMS may...

42 CFR 422.254 - Submission of bids.

Code of Federal Regulations, 2013 CFR

2013-10-01

... this part or may choose not to renew the contract. (4) Substantial differences between bids. An MA organization's bid submissions must reflect differences in benefit packages or plan costs that CMS determines to represent substantial differences relative to a sponsor's other bid submissions. (5) CMS may...

48 CFR 2014.201 - Preparation of invitation for bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Preparation of invitation for bids. 2014.201 Section 2014.201 Federal Acquisition Regulations System NUCLEAR REGULATORY COMMISSION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Solicitation of Bids 2014.201 Preparation of...

Marginal Bidding: An Application of the Equimarginal Principle to Bidding in TAC SCM

NASA Astrophysics Data System (ADS)

Greenwald, Amy; Naroditskiy, Victor; Odean, Tyler; Ramirez, Mauricio; Sodomka, Eric; Zimmerman, Joe; Cutler, Clark

We present a fast and effective bidding strategy for the Trading Agent Competition in Supply Chain Management (TAC SCM). In TAC SCM, manufacturers compete to procure computer parts from suppliers (the procurement problem), and then sell assembled computers to customers in reverse auctions (the bidding problem). This paper is concerned only with bidding, in which an agent must decide how many computers to sell and at what prices to sell them. We propose a greedy solution, Marginal Bidding, inspired by the Equimarginal Principle, which states that revenue is maximized among possible uses of a resource when the return on the last unit of the resource is the same across all areas of use. We show experimentally that certain variations of Marginal Bidding can compute bids faster than our ILP solution, which enables Marginal Bidders to consider future demand as well as current demand, and hence achieve greater revenues when knowledge of the future is valuable.

Establish a Data Transmission Platform of the Rig Based on the Distributed Network

NASA Astrophysics Data System (ADS)

Bao, Zefu; Li, Tao

In order to control in real-time ,closed-loop feedback the information, saving the money and labor,we distribute a platform of network data. It through the establishment of the platform in the oil drilling to achieve the easiest route of each device of the rig that conveying timely. The design proposed the platform to transfer networking data by PA which allows the rig control for optimal use. Against the idea,achieving first through on-site cabling and the establishment of data transmission module in the rig monitoring system. The results of standard field application show that the platform solve the problem of rig control.

Pharmacokinetics and tolerability of eslicarbazepine acetate and oxcarbazepine at steady state in healthy volunteers.

PubMed

Elger, Christian; Bialer, Meir; Falcão, Amílcar; Vaz-da-Silva, Manuel; Nunes, Teresa; Almeida, Luís; Soares-da-Silva, Patrício

2013-08-01

Investigate the pharmacokinetics of once-daily (QD; 900 mg) and twice-daily (BID; 450 mg) regimens of eslicarbazepine acetate (ESL) and BID (450 mg) regimen of oxcarbazepine (OXC) at steady state in healthy volunteers. Single-center, open-label, randomized, three-way (n = 12) crossover studies in healthy volunteers. Mean eslicarbazepine Cmax,ss (in μm) following ESL QD (87.3) was 33.3% higher (p < 0.05) compared to ESL BID (65.5) and 82.1% higher (p < 0.05) compared to OXC BID (48.0). The mean area under the curve (AUC)ss,0-τ (in μmol h/L) following the last dose of an 8-day repeated dosing was 1156.3, 1117.6, and 968.4 for ESL QD, ESL BID, and OXC BID, respectively. The ratio eslicarbazepine plasma exposure (μmol h/L) to ESL daily-dose (μmol) was 0.381 (1156.3:3037.3), 0.368 (1117.6:3037.3), and 0.271 (968.4:3567.6) for ESL-QD, ESL-BID, and OXC-BID, respectively, which translates into a 40.6% increase in the ability of ESL-QD compared to OXC-BID to deliver into the plasma their major active entity eslicarbazepine. The extent of plasma exposure to ESL minor metabolites: (R)-licarbazepine and oxcarbazepine after ESL-QD was 71.5% and 61.1% lower, respectively, than after OXC-BID. Twenty, 24 and 38 treatment emergent adverse events were reported with ESL-QD, ESL-BID, and OXC-BID, respectively. ESL-QD resulted in 33.3% higher peak plasma concentration (Cmax,ss ) of eslicarbazepine and similar extent of plasma exposure (AUCss,0-τ ) when compared to ESL-BID, which may contribute to the efficacy profile reported with once-daily ESL. In comparison to OXC-BID, administration of ESL-QD resulted in 40.6% increase in the delivery of eslicarbazepine into the plasma as well as a significantly lower systemic exposure to (R)-licarbazepine and oxcarbazepine. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Competitive Bidding in Medicare: Who Benefits From Competition?

PubMed Central

Song, Zirui; Landrum, Mary Beth; Chernew, Michael E.

2012-01-01

Objectives To conduct the first empirical study of competitive bidding in Medicare. Study Design and Methods We analyzed 2006–2010 Medicare Advantage data from the Centers for Medicare & Medicaid Services using longitudinal models adjusted for market and plan characteristics. Results A $1 increase in Medicare's payment to health maintenance organization (HMO) plans led to a $0.49 (P <.001) increase in plan bids, with $0.34 (P <.001) going to beneficiaries in the form of extra benefits or lower cost sharing. With preferred provider organization and private fee-for-service plans included, higher Medicare payments increased bids less ($0.33 per dollar), suggesting more competition among these latter plans. Conclusions As a market-based alternative to cost control through administrative pricing, competitive bidding relies on private insurance plans proposing prices they are willing to accept for insuring a beneficiary. However, competition is imperfect in the Medicare bidding market. As much as half of every dollar in increased plan payment went to higher bids rather than to beneficiaries. While having more insurers in a market lowered bids, the design of any bidding system for Medicare should recognize this shortcoming of competition. PMID:23009305

Novel approach for the refractive index gradient measurement in microliter volumes using fiber-optic technology

NASA Astrophysics Data System (ADS)

Synovec, Robert E.; Renn, Curtiss N.

1991-07-01

The refractive index gradient (RIG) of hydrodynamically controlled profiles can be universally, yet sensitively, measured by carefully probing the radial RIG passing through a z-configuration flow cell. Fiber optic technology is applied in order to provide a narrow, collimated probe beam (100 micrometers diameter) that is deflected by a RIG and measured by a position sensitive detector. The fiber optic construction allows one to probe very small volumes (1 (mu) L to 3 (mu) L) amenable to microbore liquid chromatography ((mu) LC). The combination of (mu) LC and RIG detection is very useful for the analysis of trace quantities (ng injected amounts) of chemical species that are generally difficult to measure, i.e., species that are not amenable to absorbance detection or related techniques. Furthermore, the RIG detector is compatible with conventional mobile phase gradient and thermal gradient (mu) LC, unlike traditional RI detectors. A description of the RIG detector coupled with (mu) LC for the analysis of complex polymer samples is reported. Also, exploration into using the RIG detector for supercritical fluid chromatography is addressed.

[Innate immune response to RNA virus infection].

PubMed

Oshiumi, Hiroyuki; Matsumoto, Misako; Seya, Tsukasa

2011-12-01

Viral RNA is recognized by RIG-I-like receptors and Toll-like receptors. RIG-I is a cytoplasmic viral RNA sensor. High Mobility Group Box (HMGB) proteins and DExD/H box RNA helicases, such as DDX3 and 60, associate with viral RNA. Those proteins promotes the RIG-I binding to viral RNA. RIG-I triggers the signal via IPS-1 adaptor molecule to induce type I IFN. RIG-I harbors Lys63-linked polyubiquitination by Riplet and TRIM25 ubiquitin ligases. The polyubiquitination is essential for RIG-I-mediated signaling. Toll-like receptors are located in endosome. TLR3 recognizes viral double-stranded RNA, and TLR7 and 8 recognize single-strand RNA. Virus has the ability to suppress these innate immune response. For example, to inhibit RIG-I-mediated signaling, HCV core protein suppresses the function of DDX3. In addition, HCV NS3-4A protein cleaves IPS-1 to inhibit the signal. Molecular mechanism of how viral RNA is recognized by innate immune system will make great progress on our understanding of how virus escapes from host immune system.

Structural and functional insights into 5'-ppp RNA pattern recognition by the innate immune receptor RIG-I.

PubMed

Wang, Yanli; Ludwig, Janos; Schuberth, Christine; Goldeck, Marion; Schlee, Martin; Li, Haitao; Juranek, Stefan; Sheng, Gang; Micura, Ronald; Tuschl, Thomas; Hartmann, Gunther; Patel, Dinshaw J

2010-07-01

RIG-I is a cytosolic helicase that senses 5'-ppp RNA contained in negative-strand RNA viruses and triggers innate antiviral immune responses. Calorimetric binding studies established that the RIG-I C-terminal regulatory domain (CTD) binds to blunt-end double-stranded 5'-ppp RNA a factor of 17 more tightly than to its single-stranded counterpart. Here we report on the crystal structure of RIG-I CTD bound to both blunt ends of a self-complementary 5'-ppp dsRNA 12-mer, with interactions involving 5'-pp clearly visible in the complex. The structure, supported by mutation studies, defines how a lysine-rich basic cleft within the RIG-I CTD sequesters the observable 5'-pp of the bound RNA, with a stacked phenylalanine capping the terminal base pair. Key intermolecular interactions observed in the crystalline state are retained in the complex of 5'-ppp dsRNA 24-mer and full-length RIG-I under in vivo conditions, as evaluated from the impact of binding pocket RIG-I mutations and 2'-OCH(3) RNA modifications on the interferon response.

Mitochondrially localised MUL1 is a novel modulator of antiviral signaling.

PubMed

Jenkins, Kristie; Khoo, Jing Jing; Sadler, Anthony; Piganis, Rebecca; Wang, Die; Borg, Natalie A; Hjerrild, Kathryn; Gould, Jodee; Thomas, Belinda J; Nagley, Phillip; Hertzog, Paul J; Mansell, Ashley

2013-04-01

The innate immune response to virus must be balanced to eliminate infection yet limit damaging inflammation. A critical arm of the antiviral response is launched by the retinoic acid-inducible-gene I (RIG-I) protein. RIG-I is activated by viral RNA then associates with the mitochondrial antiviral signaling (MAVS) protein to subsequently induce potent inflammatory cytokines. Here, we demonstrate the mitochondrial E3 ubiquitin protein ligase 1 (MUL1) is a crucial moderator of RIG-I signaling. MUL1 is localized to the mitochondria where it interacts with MAVS and catalyzes RIG-I post-translational modifications that inhibit RIG-I-dependent cell signaling. Accordingly, depletion of MUL1 potentiated RIG-I mediated nuclear factor-kappa B (NF-κB) and interferon (IFN) β reporter activity. Moreover, depletion of MUL1 boosted the antiviral response and increased proinflammatory cytokines following challenge with the RNA mimetic poly I:C and Sendai virus. We therefore submit that MUL1 is a novel regulator of the RIG-I-like receptor-dependent antiviral response, that otherwise functions to limit inflammation.

36 CFR 223.231 - Bidding methods.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Bidding methods. 223.231... methods. The Contracting Officer or designated forest officer shall offer advertised sales of special forest products through sealed bid or sealed bid followed by oral auction. The method selected shall: (a...

43 CFR 3923.10 - Minimum bid.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Minimum bid. 3923.10 Section 3923.10 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL SHALE LEASING Minimum Bid § 3923.10 Minimum bid...

43 CFR 3923.10 - Minimum bid.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 2 2012-10-01 2012-10-01 false Minimum bid. 3923.10 Section 3923.10 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL SHALE LEASING Minimum Bid § 3923.10 Minimum bid...

43 CFR 3923.10 - Minimum bid.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Minimum bid. 3923.10 Section 3923.10 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR MINERALS MANAGEMENT (3000) OIL SHALE LEASING Minimum Bid § 3923.10 Minimum bid...

48 CFR 814.304 - Submission, modification, and withdrawal of bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Submission, modification, and withdrawal of bids. 814.304 Section 814.304 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Submission of Bids 814.304...

36 CFR 223.51 - Bid monitoring.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Bid monitoring. 223.51 Section 223.51 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE SALE AND... Bid monitoring. Each Regional Forester shall monitor bidding patterns on timber sales to determine if...

48 CFR 3414.406 - Mistakes in bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 7 2010-10-01 2010-10-01 false Mistakes in bids. 3414.406 Section 3414.406 Federal Acquisition Regulations System DEPARTMENT OF EDUCATION ACQUISITION REGULATION CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 3414.406 Mistakes...

Application of BIM technology in construction bidding

NASA Astrophysics Data System (ADS)

wei, Li

2017-12-01

bidding is a very important step of construction project. For the owners, bidding is the key link of selecting the best construction plan and saving the project cost to the maximum extent. For Construction Corporation, it is the key to show their construction technology which can improve the probability of winning the bid. this paper researches on the application of BIM technology in bidding process of construction project in detail, and discussesthe application of BIM technology in construction field comprehensively.

Pro-apoptotic Bid induces membrane perturbation by inserting selected lysolipids into the bilayer.

PubMed

Goonesinghe, Alexander; Mundy, Elizabeth S; Smith, Melanie; Khosravi-Far, Roya; Martinou, Jean-Claude; Esposti, Mauro D

2005-04-01

Bid is a BH3-only member of the Bcl-2 family that regulates cell death at the level of mitochondrial membranes. Bid appears to link the mitochondrial pathway with the death receptor-mediated pathway of cell death. It is generally assumed that the f.l. (full-length) protein becomes activated after proteolytic cleavage, especially by apical caspases like caspase 8. The cleaved protein then relocates to mitochondria and promotes membrane permeabilization, presumably by interaction with mitochondrial lipids and other Bcl-2 proteins that facilitate the release of apoptogenic proteins like cytochrome c. Although the major action may reside in the C-terminus part, tBid (cleaved Bid), un-cleaved Bid also has pro-apoptotic potential when ectopically expressed in cells or in vitro. This pro-apoptotic action of f.l. Bid has remained unexplained, especially at the biochemical level. In the present study, we show that f.l. (full-length) Bid can insert specific lysolipids into the membrane surface, thereby priming mitochondria for the release of apoptogenic factors. This is most effective for lysophosphatidylcholine species that we report to accumulate in mitochondria during apoptosis induction. A Bid mutant that is not pro-apoptotic in vivo is defective in lysophosphatidylcholine-mediated membrane perturbation in vitro. Our results thus provide a biochemical explanation for the pro-apoptotic action of f.l. Bid.

Improving the design of competitive bidding in Medicare Advantage.

PubMed

Cawley, John H; Whitford, Andrew B

2007-04-01

In 2003, Congress passed the Medicare Prescription Drug, Improvement, and Modernization Act, which required that in 2006 the Centers for Medicare and Medicaid Services (CMS) implement a system of competitive bids to set payments for the Medicare Advantage program. Managed care plans now bid for the right to enroll Medicare beneficiaries. Data from the first year of bidding suggest that imperfect competition is limiting the success of the bidding system. This article offers suggestions to improve this system based on findings from auction theory and previous government-run auctions. In particular, CMS can benefit by adjusting its system of competitive bids in four ways: credibly committing to regulations governing bidding; limiting the scope for collusion, entry deterrence, and predatory behavior among bidders; adjusting how benchmark reimbursement rates are set; and accounting for asymmetric information among bidders.

Improved Main Shaft Seal Life in Gas Turbines Using Laser Surface Texturing

NASA Astrophysics Data System (ADS)

McNickle, Alan D.; Etsion, Izhak

2002-10-01

This paper presents a general overview of the improved main shaft seal life in gas turbines using laser surface texturing (LST). The contents include: 1) Laser Surface Texturing System; 2) Seal Schematic with LST applied; 3) Dynamic Rig Tests; 4) Surface Finish Definitions; 5) Wear Test Rig; 6) Dynamic Test Rig; 7) Seal Cross Section-Rig Test; and 8) Typical Test Results. This paper is in viewgraph form.

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

Bradonjic, Milan; Hagberg, Aric; Hengartner, Nick

We analyze component evolution in general random intersection graphs (RIGs) and give conditions on existence and uniqueness of the giant component. Our techniques generalize the existing methods for analysis on component evolution in RIGs. That is, we analyze survival and extinction properties of a dependent, inhomogeneous Galton-Watson branching process on general RIGs. Our analysis relies on bounding the branching processes and inherits the fundamental concepts from the study on component evolution in Erdos-Renyi graphs. The main challenge becomes from the underlying structure of RIGs, when the number of offsprings follows a binomial distribution with a different number of nodes andmore » different rate at each step during the evolution. RIGs can be interpreted as a model for large randomly formed non-metric data sets. Besides the mathematical analysis on component evolution, which we provide in this work, we perceive RIGs as an important random structure which has already found applications in social networks, epidemic networks, blog readership, or wireless sensor networks.« less

Structural basis for m7G recognition and 2'-O-methyl discrimination in capped RNAs by the innate immune receptor RIG-I

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

Devarkar, Swapnil C.; Wang, Chen; Miller, Matthew T.

The cytosolic innate immune receptor Retinoic Acid Inducible Gene-I (RIG-I) is the principal detector of pathogenic RNAs carrying a 5'-triphosphate (5'ppp). Self RNAs like mRNAs evade recognition by RIG-I due to posttranscriptional modifications like 5'-end capping with 7-methyl guanosine (m7G) and 2'-O-methylation of 5'-end nucleotides. Viruses have also evolved mechanisms to mimic these modifications, which in part is believed to aid in immune evasion. Currently, it is unclear how these modifications modulate RIG-I recognition. This paper provides structural and mechanistic insights into the roles of the m7G cap and 2'-O-methylation in RIG-I evasion. We show that RIG-I accommodates the m7Gmore » base while maintaining the 5'ppp contacts and can recognize Cap-0 RNAs but not Cap-1.« less

42 CFR 423.265 - Submission of bids and related information.

Code of Federal Regulations, 2014 CFR

2014-10-01

... to offer in the subsequent calendar year. (2) Substantial differences between bids. Potential Part D sponsors' bid submissions must reflect differences in benefit packages or plan costs that CMS determines to...) Bid submission—(1) General. Not later than the first Monday in June, each potential Part D sponsor...

42 CFR 423.265 - Submission of bids and related information.

Code of Federal Regulations, 2013 CFR

2013-10-01

... to offer in the subsequent calendar year. (2) Substantial differences between bids. Potential Part D sponsors' bid submissions must reflect differences in benefit packages or plan costs that CMS determines to...) Bid submission—(1) General. Not later than the first Monday in June, each potential Part D sponsor...

42 CFR 423.265 - Submission of bids and related information.

Code of Federal Regulations, 2012 CFR

2012-10-01

... to offer in the subsequent calendar year. (2) Substantial differences between bids. Potential Part D sponsors' bid submissions must reflect differences in benefit packages or plan costs that CMS determines to...) Bid submission—(1) General. Not later than the first Monday in June, each potential Part D sponsor...

42 CFR 423.265 - Submission of bids and related information.

Code of Federal Regulations, 2010 CFR

2010-10-01

... calendar year. (2) Substantial differences between bids. Potential Part D sponsors' bid submissions must reflect differences in benefit packages or plan costs that CMS determines to represent substantial...) General. Not later than the first Monday in June, each potential Part D sponsor must submit bids and...

42 CFR 423.265 - Submission of bids and related information.

Code of Federal Regulations, 2011 CFR

2011-10-01

... calendar year. (2) Substantial differences between bids. Potential Part D sponsors' bid submissions must reflect differences in benefit packages or plan costs that CMS determines to represent substantial...) General. Not later than the first Monday in June, each potential Part D sponsor must submit bids and...

77 FR 61001 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-05

... currently approved collection; Title of Information Collection: Bid Pricing Tool (BPT) for Medicare... organizations (MAO) and Prescription Drug Plans (PDP) are required to submit an actuarial pricing ``bid'' for... PDPs use the Bid Pricing Tool (BPT) software to develop their actuarial pricing bid. The information...

36 CFR 223.231 - Bidding methods.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 36 Parks, Forests, and Public Property 2 2013-07-01 2013-07-01 false Bidding methods. 223.231... Forest Products Advertisement and Bids § 223.231 Bidding methods. The Contracting Officer or designated... followed by oral auction. The method selected shall: (a) Ensure open and fair competition; (b) Ensure that...

36 CFR 223.231 - Bidding methods.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 36 Parks, Forests, and Public Property 2 2012-07-01 2012-07-01 false Bidding methods. 223.231... Forest Products Advertisement and Bids § 223.231 Bidding methods. The Contracting Officer or designated... followed by oral auction. The method selected shall: (a) Ensure open and fair competition; (b) Ensure that...

36 CFR 223.231 - Bidding methods.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Bidding methods. 223.231... Forest Products Advertisement and Bids § 223.231 Bidding methods. The Contracting Officer or designated... followed by oral auction. The method selected shall: (a) Ensure open and fair competition; (b) Ensure that...

36 CFR 223.231 - Bidding methods.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 36 Parks, Forests, and Public Property 2 2014-07-01 2014-07-01 false Bidding methods. 223.231... Forest Products Advertisement and Bids § 223.231 Bidding methods. The Contracting Officer or designated... followed by oral auction. The method selected shall: (a) Ensure open and fair competition; (b) Ensure that...

48 CFR 252.236-7008 - Contract prices-bidding schedules.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 3 2010-10-01 2010-10-01 false Contract prices-bidding... of Provisions And Clauses 252.236-7008 Contract prices—bidding schedules. As prescribed in 236.570(b)(6), use the following provision: Contract Prices—Bidding Schedules (DEC 1991) (a) The Government's...

43 CFR 3923.10 - Minimum bid.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Minimum bid. 3923.10 Section 3923.10 Public Lands: Interior Regulations Relating to Public Lands (Continued) BUREAU OF LAND MANAGEMENT, DEPARTMENT OF THE INTERIOR RANGE MANAGEMENT (4000) OIL SHALE LEASING Minimum Bid § 3923.10 Minimum bid. The...

47 CFR 90.801 - 900 MHz SMR spectrum subject to competitive bidding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Competitive Bidding Procedures for 900 MHz Specialized Mobile Radio Service § 90.801 900 MHz SMR spectrum subject to competitive bidding. Mutually exclusive initial applications for 900 MHz SMR service licenses are subject to competitive bidding. The...

78 FR 25444 - Federal Acquisition Regulation; Submission for OMB Review; Bid Guarantees, Performance and...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-01

...; Submission for OMB Review; Bid Guarantees, Performance and Payment Bonds, and Alternative Payment Protections... concerning bid guarantees, performance and payment bonds, and alternative payment protections. A notice was...- 0045, Bid Guarantees, Performance, and Payment Bonds, and Alternative Payment Protections by any of the...

7 CFR 1435.502 - Bid selection procedures.

Code of Federal Regulations, 2013 CFR

2013-01-01

... OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS SUGAR PROGRAM Processor Sugar Payment-In-Kind... acreage of sugar beets or sugarcane from production, CCC will rank bids on the basis of the bid amount as a percentage of the expected sugar produced from the retired acreage. Bids with the lowest of such...

48 CFR 14.401 - Receipt and safeguarding of bids.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 1 2012-10-01 2012-10-01 false Receipt and safeguarding of bids. 14.401 Section 14.401 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... bids shall be kept secure. Except as provided in paragraph (b) of this section, the bids shall not be...

48 CFR 14.401 - Receipt and safeguarding of bids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Receipt and safeguarding of bids. 14.401 Section 14.401 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... bids shall be kept secure. Except as provided in paragraph (b) of this section, the bids shall not be...

10 CFR 452.5 - Bidding procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... cellulosic biofuels producers during the open window established in the solicitation. The open window shall.... (d) All bids will be confidential until 45 days after the close of the window for submission of bids... following: (1) After DOE evaluates the bids received during the open window, it shall, within 45 days...

75 FR 4701 - In the Matter of Procedural Amendments to Commission Part 1 Competitive Bidding Rules

Federal Register 2010, 2011, 2012, 2013, 2014

2010-01-29

... Procedural Amendments to Commission Part 1 Competitive Bidding Rules AGENCY: Federal Communications... bidding rules. The Commission amends the rule specifying how to report potential violations of the prohibition on certain communications in order to reduce the risk that bidding-related information might be...

48 CFR 28.001 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... surety (see also power of attorney at 2.101). Bid means any response to a solicitation, including a... acquisition. Bid guarantee means a form of security assuring that the bidder (1) will not withdraw a bid... bid, unless a longer time is allowed, after receipt of the specified forms. Bond means a written...

48 CFR 52.219-2 - Equal Low Bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Equal Low Bids. 52.219-2 Section 52.219-2 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION (CONTINUED) CLAUSES... Low Bids. As prescribed in 19.308(c), insert the following provision: Equal Low Bids (OCT 1995) (a...

Learning Inverse Rig Mappings by Nonlinear Regression.

PubMed

Holden, Daniel; Saito, Jun; Komura, Taku

2017-03-01

We present a framework to design inverse rig-functions-functions that map low level representations of a character's pose such as joint positions or surface geometry to the representation used by animators called the animation rig. Animators design scenes using an animation rig, a framework widely adopted in animation production which allows animators to design character poses and geometry via intuitive parameters and interfaces. Yet most state-of-the-art computer animation techniques control characters through raw, low level representations such as joint angles, joint positions, or vertex coordinates. This difference often stops the adoption of state-of-the-art techniques in animation production. Our framework solves this issue by learning a mapping between the low level representations of the pose and the animation rig. We use nonlinear regression techniques, learning from example animation sequences designed by the animators. When new motions are provided in the skeleton space, the learned mapping is used to estimate the rig controls that reproduce such a motion. We introduce two nonlinear functions for producing such a mapping: Gaussian process regression and feedforward neural networks. The appropriate solution depends on the nature of the rig and the amount of data available for training. We show our framework applied to various examples including articulated biped characters, quadruped characters, facial animation rigs, and deformable characters. With our system, animators have the freedom to apply any motion synthesis algorithm to arbitrary rigging and animation pipelines for immediate editing. This greatly improves the productivity of 3D animation, while retaining the flexibility and creativity of artistic input.

Robust Lys63-Linked Ubiquitination of RIG-I Promotes Cytokine Eruption in Early Influenza B Virus Infection.

PubMed

Jiang, Jingwen; Li, Jing; Fan, Wenhui; Zheng, Weinan; Yu, Meng; Chen, Can; Sun, Lei; Bi, Yuhai; Ding, Chan; Gao, George F; Liu, Wenjun

2016-07-15

Influenza A and B virus infections both cause a host innate immunity response. Here, we report that the robust production of type I and III interferons (IFNs), IFN-stimulated genes, and proinflammatory factors can be induced by influenza B virus rather than influenza A virus infection in alveolar epithelial (A549) cells during early infection. This response is mainly dependent on the retinoic acid-inducible gene I (RIG-I)-mediated signaling pathway. Infection by influenza B virus promotes intense Lys63-linked ubiquitination of RIG-I, resulting in cytokine eruption. It is known that the influenza A virus NS1 protein (NS1-A) interacts with RIG-I and TRIM25 to suppress the activation of RIG-I-mediated signaling. However, the present results indicate that the influenza B virus NS1 protein (NS1-B) is unable to interact with RIG-I but engages in the formation of a RIG-I/TRIM25/NS1-B ternary complex. Furthermore, we demonstrate that the N-terminal RNA-binding domain (RBD) of NS1-B is responsible for interaction with TRIM25 and that this interaction blocks the inhibitory effect of the NS1-B C-terminal effector domain (TED) on RIG-I ubiquitination. Our findings reveal a novel mechanism for the host cytokine response to influenza B virus infection through regulatory interplay between host and viral proteins. Influenza B virus generally causes local mild epidemics but is occasionally lethal to individuals. Existing studies describe the broad characteristics of influenza B virus epidemiology and pathology. However, to develop better prevention and treatments for the disease, determining the concrete molecular mechanisms of pathogenesis becomes pivotal to understand how the host reacts to the challenge of influenza B virus. Thus, we aimed to characterize the host innate immune response to influenza B virus infection. Here, we show that vigorous Lys63-linked ubiquitination of RIG-I and cytokine eruption dependent on RIG-I-mediated signal transduction are induced by virus infection. Additionally, TRIM25 positively regulates RIG-I-mediated signaling by ablating the inhibitory function of NS1-B on RIG-I ubiquitination. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Medical evacuations from oil rigs off the Gulf Coast of the United States from 2008 to 2012: reasons and cost implications.

PubMed

Thibodaux, Donald P; Bourgeois, Robert M; Loeppke, Ronald R; Konicki, Doris L; Hymel, Pamela A; Dreger, Marianne

2014-07-01

To identify reasons for air medical evacuations from oil rigs/platforms. Retrospective review of data of medical calls from 102 rigs/platforms in the US Gulf Coast from 2008 through 2012 with specific analysis of medevacs. On average, 1609 total calls per year relating to illness or injury on the 102 oil rigs/platforms with 4% to 7% requiring medical air evacuation. On average, 77% of medevacs were for nonoccupational medical injury or illness. Illness, not occupational injuries, is identified as the major reason for medical evacuations from oil rigs. Heart disease is the leading cause of chronic health conditions resulting in a medevac.

Toscana Virus NSs Protein Inhibits the Induction of Type I Interferon by Interacting with RIG-I

PubMed Central

Gori-Savellini, Gianni; Valentini, Melissa

2013-01-01

Toscana virus (TOSV) is a phlebovirus, of the Bunyaviridae family, that is responsible for central nervous system (CNS) injury in humans. Previous data have shown that the TOSV NSs protein is a gamma interferon (IFN-β) antagonist when transiently overexpressed in mammalian cells, inhibiting IRF-3 induction (G. Gori Savellini, F. Weber, C. Terrosi, M. Habjan, B. Martorelli, and M. G. Cusi, J. Gen. Virol. 92:71–79, 2011). In this study, we investigated whether an upstream sensor, which has a role in the signaling cascade leading to the production of type I IFN, was involved. We found a significant decrease in RIG-I protein levels in cells overexpressing TOSV NSs, suggesting that the nonstructural protein interacts with RIG-I and targets it for proteasomal degradation. In fact, the MG-132 proteasome inhibitor was able to restore IFN-β promoter activation in cells expressing NSs, demonstrating the existence of an evasion mechanism based on inhibition of the RIG-I sensor. Furthermore, a C-terminal truncated NSs protein (ΔNSs), although able to interact with RIG-I, did not affect the RIG-I-mediated IFN-β promoter activation, suggesting that the NSs domains responsible for RIG-I-mediated signaling and interaction with RIG-I are mapped on different regions. These results contribute to identify a novel mechanism for bunyaviruses by which TOSV NSs counteracts the early IFN response. PMID:23552410

Toscana virus NSs protein inhibits the induction of type I interferon by interacting with RIG-I.

PubMed

Gori-Savellini, Gianni; Valentini, Melissa; Cusi, Maria Grazia

2013-06-01

Toscana virus (TOSV) is a phlebovirus, of the Bunyaviridae family, that is responsible for central nervous system (CNS) injury in humans. Previous data have shown that the TOSV NSs protein is a gamma interferon (IFN-β) antagonist when transiently overexpressed in mammalian cells, inhibiting IRF-3 induction (G. Gori Savellini, F. Weber, C. Terrosi, M. Habjan, B. Martorelli, and M. G. Cusi, J. Gen. Virol. 92:71-79, 2011). In this study, we investigated whether an upstream sensor, which has a role in the signaling cascade leading to the production of type I IFN, was involved. We found a significant decrease in RIG-I protein levels in cells overexpressing TOSV NSs, suggesting that the nonstructural protein interacts with RIG-I and targets it for proteasomal degradation. In fact, the MG-132 proteasome inhibitor was able to restore IFN-β promoter activation in cells expressing NSs, demonstrating the existence of an evasion mechanism based on inhibition of the RIG-I sensor. Furthermore, a C-terminal truncated NSs protein (ΔNSs), although able to interact with RIG-I, did not affect the RIG-I-mediated IFN-β promoter activation, suggesting that the NSs domains responsible for RIG-I-mediated signaling and interaction with RIG-I are mapped on different regions. These results contribute to identify a novel mechanism for bunyaviruses by which TOSV NSs counteracts the early IFN response.

48 CFR 970.3102-05-18 - Independent research and development and bid and proposal costs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... development and bid and proposal costs. 970.3102-05-18 Section 970.3102-05-18 Federal Acquisition Regulations... Contract Cost Principles and Procedures 970.3102-05-18 Independent research and development and bid and proposal costs. (c) Independent Research and Development and Bid and Proposal costs are unallowable...

23 CFR 635.113 - Bid opening and bid tabulations.

Code of Federal Regulations, 2013 CFR

2013-04-01

... permitted. (b) The STD shall prepare and forward tabulations of bids to the Division Administrator. These tabulations shall be certified by a responsible STD official and shall show: (1) Bid item details for at least... opened and reviewed in accordance with the terms of the solicitation. The STD must use its own procedures...

23 CFR 635.113 - Bid opening and bid tabulations.

Code of Federal Regulations, 2014 CFR

2014-04-01

... permitted. (b) The STD shall prepare and forward tabulations of bids to the Division Administrator. These tabulations shall be certified by a responsible STD official and shall show: (1) Bid item details for at least... opened and reviewed in accordance with the terms of the solicitation. The STD must use its own procedures...

23 CFR 635.113 - Bid opening and bid tabulations.

Code of Federal Regulations, 2012 CFR

2012-04-01

... permitted. (b) The STD shall prepare and forward tabulations of bids to the Division Administrator. These tabulations shall be certified by a responsible STD official and shall show: (1) Bid item details for at least... opened and reviewed in accordance with the terms of the solicitation. The STD must use its own procedures...

23 CFR 635.113 - Bid opening and bid tabulations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... permitted. (b) The STD shall prepare and forward tabulations of bids to the Division Administrator. These tabulations shall be certified by a responsible STD official and shall show: (1) Bid item details for at least... opened and reviewed in accordance with the terms of the solicitation. The STD must use its own procedures...

48 CFR 1303.104-4 - Disclosure, protection and marking of contractor bid or proposal information and source selection...

Code of Federal Regulations, 2010 CFR

2010-10-01

... marking of contractor bid or proposal information and source selection information. 1303.104-4 Section... PRACTICES AND PERSONAL CONFLICTS OF INTEREST Safeguards 1303.104-4 Disclosure, protection and marking of contractor bid or proposal information and source selection information. Contractor bid or proposal...

42 CFR 422.256 - Review, negotiation, and approval of bids.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 42 Public Health 3 2013-10-01 2013-10-01 false Review, negotiation, and approval of bids. 422.256..., and Related Information and Plan Approval § 422.256 Review, negotiation, and approval of bids. (a... aggregate bid amounts submitted under § 422.252 and conduct negotiations with MA organizations regarding...

42 CFR 422.256 - Review, negotiation, and approval of bids.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 42 Public Health 3 2012-10-01 2012-10-01 false Review, negotiation, and approval of bids. 422.256..., and Related Information and Plan Approval § 422.256 Review, negotiation, and approval of bids. (a... aggregate bid amounts submitted under § 422.252 and conduct negotiations with MA organizations regarding...

42 CFR 422.256 - Review, negotiation, and approval of bids.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 42 Public Health 3 2014-10-01 2014-10-01 false Review, negotiation, and approval of bids. 422.256..., and Related Information and Plan Approval § 422.256 Review, negotiation, and approval of bids. (a... aggregate bid amounts submitted under § 422.252 and conduct negotiations with MA organizations regarding...

42 CFR 422.256 - Review, negotiation, and approval of bids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 42 Public Health 3 2011-10-01 2011-10-01 false Review, negotiation, and approval of bids. 422.256... Information and Plan Approval § 422.256 Review, negotiation, and approval of bids. (a) Authority. Subject to... submitted under § 422.252 and conduct negotiations with MA organizations regarding these bids (including the...

42 CFR 422.256 - Review, negotiation, and approval of bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 3 2010-10-01 2010-10-01 false Review, negotiation, and approval of bids. 422.256... Information and Plan Approval § 422.256 Review, negotiation, and approval of bids. (a) Authority. Subject to... submitted under § 422.252 and conduct negotiations with MA organizations regarding these bids (including the...

48 CFR 603.104-4 - Disclosure, protection, and marking of contractor bid or proposal information and source...

Code of Federal Regulations, 2010 CFR

2010-10-01

..., and marking of contractor bid or proposal information and source selection information. 603.104-4... contractor bid or proposal information and source selection information. (a) The following classes of persons may be authorized to receive contractor bid or proposal information or source selection information by...

43 CFR 3422.3-1 - Bidding systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 2 2013-10-01 2013-10-01 false Bidding systems. 3422.3-1 Section 3422.3-1... systems. (a) The provisions of 10 CFR part 378 1 are not applicable to this part. 1 Redesignated as 30 CFR... cash bonus—fixed royalty bidding systems or any other bidding system adopted through rulemaking...

43 CFR 3422.3-1 - Bidding systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 2 2014-10-01 2014-10-01 false Bidding systems. 3422.3-1 Section 3422.3-1... systems. (a) The provisions of 10 CFR part 378 1 are not applicable to this part. 1 Redesignated as 30 CFR... cash bonus—fixed royalty bidding systems or any other bidding system adopted through rulemaking...

48 CFR 14.302 - Bid submission.

Code of Federal Regulations, 2010 CFR

2010-10-01

... paragraphs (b) and (c) below as the designated office) not later than the exact time set for opening of bids... later than the time set for the bid opening; (4) The telegraph office that received the telegraphic bid... indicates on its face that it was received in the telegraph office before the telephone call was received by...

75 FR 57052 - Notice of Single Family Loan Sale (SFLS 2010)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-17

... submitted and determine the successful bid or bids, in terms of the best value to HUD, in its sole and... Sale (SFLS 2010) AGENCY: Office of the Assistant Secretary for Housing--Federal Housing Commissioner... insurance, in a competitive, sealed bid sale (SFLS 2010). This notice also generally describes the bidding...

23 CFR 635.112 - Advertising for bids and proposals.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false Advertising for bids and proposals. 635.112 Section 635... OPERATIONS CONSTRUCTION AND MAINTENANCE Contract Procedures § 635.112 Advertising for bids and proposals. (a) No work shall be undertaken on any Federal-aid project, nor shall any project be advertised for bids...

47 CFR 22.217 - Bidding credit for small businesses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Bidding credit for small businesses. 22.217... Bidding credit for small businesses. A winning bidder that qualifies as a small business, as defined in § 22.223(b)(1), or a consortium of small businesses may use a bidding credit of thirty-five (35...

43 CFR 5442.3 - Rejection of bids; waiver of minor deficiencies.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 2 2011-10-01 2011-10-01 false Rejection of bids; waiver of minor... Procedure § 5442.3 Rejection of bids; waiver of minor deficiencies. When the authorized officer determines... minor deficiencies in the bids or the timber sale advertisement. [38 FR 6280, Mar. 8, 1973] ...

47 CFR 22.217 - Bidding credit for small businesses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 2 2013-10-01 2013-10-01 false Bidding credit for small businesses. 22.217... Bidding credit for small businesses. A winning bidder that qualifies as a small business, as defined in § 22.223(b)(1), or a consortium of small businesses may use a bidding credit of thirty-five (35...

47 CFR 22.217 - Bidding credit for small businesses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 2 2011-10-01 2011-10-01 false Bidding credit for small businesses. 22.217... Bidding credit for small businesses. A winning bidder that qualifies as a small business, as defined in § 22.223(b)(1), or a consortium of small businesses may use a bidding credit of thirty-five (35...

47 CFR 22.217 - Bidding credit for small businesses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 2 2014-10-01 2014-10-01 false Bidding credit for small businesses. 22.217... Bidding credit for small businesses. A winning bidder that qualifies as a small business, as defined in § 22.223(b)(1), or a consortium of small businesses may use a bidding credit of thirty-five (35...

47 CFR 22.217 - Bidding credit for small businesses.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 2 2012-10-01 2012-10-01 false Bidding credit for small businesses. 22.217... Bidding credit for small businesses. A winning bidder that qualifies as a small business, as defined in § 22.223(b)(1), or a consortium of small businesses may use a bidding credit of thirty-five (35...

22 CFR 201.25 - Bid and performance bonds and guaranties.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Bid and performance bonds and guaranties. 201... § 201.25 Bid and performance bonds and guaranties. Whenever the importer requires the posting of a bid bond or guaranty or performance bond or guaranty, the type of bond or guaranty (certified check...

rigor mortis encodes a novel nuclear receptor interacting protein required for ecdysone signaling during Drosophila larval development.

PubMed

Gates, Julie; Lam, Geanette; Ortiz, José A; Losson, Régine; Thummel, Carl S

2004-01-01

Pulses of the steroid hormone ecdysone trigger the major developmental transitions in Drosophila, including molting and puparium formation. The ecdysone signal is transduced by the EcR/USP nuclear receptor heterodimer that binds to specific response elements in the genome and directly regulates target gene transcription. We describe a novel nuclear receptor interacting protein encoded by rigor mortis (rig) that is required for ecdysone responses during larval development. rig mutants display defects in molting, delayed larval development, larval lethality, duplicated mouth parts, and defects in puparium formation--phenotypes that resemble those seen in EcR, usp, E75A and betaFTZ-F1 mutants. Although the expression of these nuclear receptor genes is essentially normal in rig mutant larvae, the ecdysone-triggered switch in E74 isoform expression is defective. rig encodes a protein with multiple WD-40 repeats and an LXXLL motif, sequences that act as specific protein-protein interaction domains. Consistent with the presence of these elements and the lethal phenotypes of rig mutants, Rig protein interacts with several Drosophila nuclear receptors in GST pull-down experiments, including EcR, USP, DHR3, SVP and betaFTZ-F1. The ligand binding domain of betaFTZ-F1 is sufficient for this interaction, which can occur in an AF-2-independent manner. Antibody stains reveal that Rig protein is present in the brain and imaginal discs of second and third instar larvae, where it is restricted to the cytoplasm. In larval salivary gland and midgut cells, however, Rig shuttles between the cytoplasm and nucleus in a spatially and temporally regulated manner, at times that correlate with the major lethal phase of rig mutants and major switches in ecdysone-regulated gene expression. Taken together, these data indicate that rig exerts essential functions during larval development through gene-specific effects on ecdysone-regulated transcription, most likely as a cofactor for one or more nuclear receptors. Furthermore, the dynamic intracellular redistribution of Rig protein suggests that it may act to refine spatial and temporal responses to ecdysone during development.

Structural basis of RNA recognition and activation by innate immune receptor RIG-I

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

Jiang, Fuguo; Ramanathan, Anand; Miller, Matthew T.

Retinoic-acid-inducible gene-I (RIG-I; also known as DDX58) is a cytoplasmic pathogen recognition receptor that recognizes pathogen-associated molecular pattern (PAMP) motifs to differentiate between viral and cellular RNAs. RIG-I is activated by blunt-ended double-stranded (ds)RNA with or without a 5'-triphosphate (ppp), by single-stranded RNA marked by a 5'-ppp and by polyuridine sequences. Upon binding to such PAMP motifs, RIG-I initiates a signalling cascade that induces innate immune defences and inflammatory cytokines to establish an antiviral state. The RIG-I pathway is highly regulated and aberrant signalling leads to apoptosis, altered cell differentiation, inflammation, autoimmune diseases and cancer. The helicase and repressor domainsmore » (RD) of RIG-I recognize dsRNA and 5'-ppp RNA to activate the two amino-terminal caspase recruitment domains (CARDs) for signalling. Here, to understand the synergy between the helicase and the RD for RNA binding, and the contribution of ATP hydrolysis to RIG-I activation, we determined the structure of human RIG-I helicase-RD in complex with dsRNA and an ATP analogue. The helicase-RD organizes into a ring around dsRNA, capping one end, while contacting both strands using previously uncharacterized motifs to recognize dsRNA. Small-angle X-ray scattering, limited proteolysis and differential scanning fluorimetry indicate that RIG-I is in an extended and flexible conformation that compacts upon binding RNA. These results provide a detailed view of the role of helicase in dsRNA recognition, the synergy between the RD and the helicase for RNA binding and the organization of full-length RIG-I bound to dsRNA, and provide evidence of a conformational change upon RNA binding. The RIG-I helicase-RD structure is consistent with dsRNA translocation without unwinding and cooperative binding to RNA. The structure yields unprecedented insight into innate immunity and has a broader impact on other areas of biology, including RNA interference and DNA repair, which utilize homologous helicase domains within DICER and FANCM.« less

Central Gulf of Mexico lease sale draws weak industry response

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

Koen, A.D.

This paper reports that interest in oil and gas leases in the Gulf of Mexico continued spiraling downward at the latest Minerals Management Service offshore sale. Companies participating in Outer Continental Shelf Sale 139 last week in New Orleans offered 196 bids for 151 blocks in the central Gulf of Mexico. MMS offered 5,213 blocks for lease. The number of tracts receiving bids was the fewest at a central gulf lease sale since 114 tracts garnered high bids totaling $146.4 million at Sale 104 in April 1986. Apparent high bids in Sale 139 totaled $56,195,552, and all bids offered totaledmore » just $65,300,864. Both bidding totals were the lowest in a Gulf of Mexico lease sale since MMS began area-wide gulf leasing at Sale 72 in May 1983. Only 64 of 93 qualified companies participated in Sale 139. Fifty-five companies offered apparent winning bids. By comparison, 123 companies at central gulf lease Sale 131 in March 1991 offered 637 bids totaling $320.5 million for 464 tracts. Apparent high bids last spring totaled $259.9 million. At central gulf lease Sale 123 in March 1990, high bids totaled $427.4 million for 538 tracts. In that sale, BP Exploration Inc. led all bidders, exposing $78 million in 79 high bids, including 60 for deepwater tracts. Since then, interest in deepwater tracts has waned in part because of sagging oil and gas prices as U.S. operators sought bigger prospects outside the U.S. Ironically, Sale 139 was dominated by the U.S. subsidiary of an Italian holding company.« less

Antimicrobial susceptibility testing before first-line treatment for Helicobacter pylori infection in patients with dual or triple antibiotic resistance.

PubMed

Cosme, Angel; Montes, Milagrosa; Ibarra, Begoña; Tamayo, Esther; Alonso, Horacio; Mendarte, Usua; Lizasoan, Jacobo; Herreros-Villanueva, Marta; Bujanda, Luis

2017-05-14

To evaluate the efficacy of antimicrobial susceptibility-guided therapy before first-line treatment for infection in patients with dual or triple antibiotic resistance. A total of 1034 patients infected by Helicobacter pylori ( H. pylori ) during 2013-2014 were tested for antimicrobial susceptibility. 157 of 1034 (15%) patients showed resistance to two (127/1034; 12%) and to three (30/1034; 3%) antibiotics. Sixty-eight patients with dual H. pylori -resistance (clarithromycin, metronidazole or levofloxacin) were treated for 10 d with triple therapies: OAL (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and levofloxacin 500 mg b.i.d.) 43 cases, OAM (omeprazole 20 mg b.i.d., amoxicillin 1 g b.i.d., and metronidazole 500 mg b.i.d.) 12 cases and OAC (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and clarithromycin 500 mg b.i.d.) 13 cases based on the antimicrobial susceptibility testing. Twelve patients showed triple H. pylori -resistance (clarithromycin, metronidazole and levofloxacin) and received for 10 d triple therapy with OAR (omeprazole 20 mg b.id., amoxicillin 1 g b.i.d., and rifabutin 150 mg b.i.d.). Eradication was confirmed by 13C-urea breath test. Adverse effects and compliance were assessed by a questionnaire. Intention-to-treat eradication rates were: OAL (97.6%), OAM (91.6%), OAC (92.3%) and OAR (58.3%). Cure rate was significantly higher in naïve patients treated with OAR-10 compared to patients who had two or three previous treatment failures (83% vs 33%). Adverse events rates for OAL, OAM, OAC and OAR were 22%, 25%, 23% and 17%, respectively, all of them mild-moderate. Antimicrobial susceptibility-guided triple therapies during 10 d for first-line treatment leads to an eradication rate superior to 90% in patients with dual antibiotic H. pylori resistance.

Pharmacoeconomic comparison of Helicobacter pylori eradication regimens.

PubMed

Sancar, Mesut; Izzettin, Fikret Vehbi; Apikoglu-Rabus, Sule; Besisik, Fatih; Tozun, Nurdan; Dulger, Gul

2006-08-01

Helicobacter pylori is the most important etiologic agent for development of peptic ulcer, chronic gastritis and gastric carcinomas. It is now well established that H. pylori eradication treatment is more cost-effective than acid suppressing therapies alone for the treatment of peptic ulcer disease. However, the comparative cost-effectiveness of various H. pylori eradication regimens is still not clear. This study was designed to make a pharmacoeconomic comparison of different H. pylori eradication regimens in patients with peptic ulcer disease or chronic gastritis, using real-world cost and effectiveness data. Istanbul University Hospital and Marmara University Hospital. A total of 75 patients diagnosed as H. pylori (+) by endoscopy were randomized to receive one of the seven H. pylori treatment protocols. These protocols were as follows: (LAC) = 'lansoprazole 30 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid' for 7 days and (OCM) = 'omeprazole 20 mg bid + clarithromycin 250 mg bid + metronidazole 500 mg bid'; (OAM) = 'omeprazole 40 mg qd + amoxicillin 500 mg tid + metronidazole 500 mg tid'; (MARB) = 'metronidazole 250 mg tid + amoxicillin 500 mg qid + ranitidine 300 mg hs + bismuth 300 mg qid'; (OAC) = omeprazole 20 mg bid + amoxicillin 1 g bid + clarithromycin 500 mg bid'; (OCA) = omeprazole 40 mg bid + clarithromycin 500 mg bid + amoxicillin 1 g bid'; (OAB) = 'omeprazole 20 mg bid + amoxicillin 500 mg tid + bismuth 300 mg qid' each for 14 days. Only direct costs were included in the analysis. Effectiveness was measured in terms of "successful eradication". The cost-effectiveness ratios of the regimens were calculated using these effectiveness and cost data. The perspective of the study was assumed as the Government's perspective. Cost-effectiveness ratios of eradication regimens. MARB and OCA regimens were found to be more cost-effective than the other treatment regimens. The eradication rates and cost-effectiveness ratios calculated for these protocols were 90% (158.7 euros) for MARB and 90% (195.8 euros) for OCA regimen. This study confirms the importance of using local pharmacoeconomic data. Analyses such as this give decision-makers the tools to choose a better treatment option which is both highly effective yet and has a low cost.

Linear ubiquitin assembly complex negatively regulates RIG-I and TRIM25 mediated type-I interferon induction

PubMed Central

Inn, Kyung-Soo; Gack, Michaela U.; Tokunaga, Fuminori; Shi, Mude; Wong, Lai-Yee; Iwai, Kazuhiro; Jung, Jae U.

2011-01-01

Summary Upon detection of viral RNA, retinoic acid inducible gene I (RIG-I) undergoes TRIM25-mediated Lys-63 linked ubiquitination, leading to type-I interferon (IFN) production. In this study, we demonstrate that the linear ubiquitin assembly complex (LUBAC), comprised of two RING-IBR-RING (RBR)-containing E3 ligases HOIL-1L and HOIP, independently targets TRIM25 and RIG-I to effectively suppress virus-induced IFN production. RBR E3 ligase domains of HOIL-1L and HOIP bind and induce proteosomal degradation of TRIM25, whereas the NZF domain of HOIL-1L competes with TRIM25 for RIG-I binding. Consequently, both actions by the HOIL-1L/HOIP LUBAC potently inhibit RIG-I ubiquitination and anti-viral activity, but in a mechanistically separate manner. Conversely, the genetic deletion or depletion of HOIL-1L and HOIP robustly enhances virus-induced type-I IFN production. Taken together, the HOIL-1L/HOIP LUBAC specifically suppresses RIG-I ubiquitination and activation by inducing TRIM25 degradation and inhibiting TRIM25 interaction with RIG-I, resulting in the comprehensive suppression of the IFN-mediated anti-viral signaling pathway. PMID:21292167

Linear ubiquitin assembly complex negatively regulates RIG-I- and TRIM25-mediated type I interferon induction.

PubMed

Inn, Kyung-Soo; Gack, Michaela U; Tokunaga, Fuminori; Shi, Mude; Wong, Lai-Yee; Iwai, Kazuhiro; Jung, Jae U

2011-02-04

Upon detection of viral RNA, retinoic acid-inducible gene I (RIG-I) undergoes TRIM25-mediated K63-linked ubiquitination, leading to type I interferon (IFN) production. In this study, we demonstrate that the linear ubiquitin assembly complex (LUBAC), comprised of two RING-IBR-RING (RBR)-containing E3 ligases, HOIL-1L and HOIP, independently targets TRIM25 and RIG-I to effectively suppress virus-induced IFN production. RBR E3 ligase domains of HOIL-1L and HOIP bind and induce proteasomal degradation of TRIM25, whereas the NZF domain of HOIL-1L competes with TRIM25 for RIG-I binding. Consequently, both actions by the HOIL-1L/HOIP LUBAC potently inhibit RIG-I ubiquitination and antiviral activity, but in a mechanistically separate manner. Conversely, the genetic deletion or depletion of HOIL-1L and HOIP robustly enhances virus-induced type I IFN production. Taken together, the HOIL-1L/HOIP LUBAC specifically suppresses RIG-I ubiquitination and activation by inducing TRIM25 degradation and inhibiting TRIM25 interaction with RIG-I, resulting in the comprehensive suppression of the IFN-mediated antiviral signaling pathway. Copyright © 2011 Elsevier Inc. All rights reserved.

Insight into Buffalo (Bubalus bubalis) RIG1 and MDA5 Receptors: A Comparative Study on dsRNA Recognition and In-Vitro Antiviral Response

PubMed Central

Singh, Manvender; Brahma, Biswajit; Maharana, Jitendra; Patra, Mahesh Chandra; Kumar, Sushil; Mishra, Purusottam; Saini, Megha; De, Bidhan Chandra; Mahanty, Sourav; Datta, Tirtha Kumar; De, Sachinandan

2014-01-01

RIG1 and MDA5 have emerged as important intracellular innate pattern recognition receptors that recognize viral RNA and mediate cellular signals controlling Type I interferon (IFN-I) response. Buffalo RIG1 and MDA5 genes were investigated to understand the mechanism of receptor induced antiviral response. Sequence analysis revealed that RIG1 and MDA5 maintain a domain arrangement that is common in mammals. Critical binding site residues of the receptors are evolutionary conserved among mammals. Molecular dynamics simulations suggested that RIG1 and MDA5 follow a similar, if not identical, dsRNA binding pattern that has been previously reported in human. Moreover, binding free energy calculation revealed that MDA5 had a greater affinity towards dsRNA compared to RIG1. Constitutive expressions of RLR genes were ubiquitous in different tissues without being specific to immune organs. Poly I:C stimulation induced elevated expressions of IFN-β and IFN-stimulated genes (ISGs) through interferon regulatory factors (IRFs) mediated pathway in buffalo foetal fibroblast cells. The present study provides crucial insights into the structure and function of RIG1 and MDA5 receptors in buffalo. PMID:24587036

Ceramic applications in turbine engines

NASA Technical Reports Server (NTRS)

Byrd, J. A.; Janovicz, M. A.; Thrasher, S. R.

1981-01-01

Development testing activities on the 1900 F-configuration ceramic parts were completed, 2070 F-configuration ceramic component rig and engine testing was initiated, and the conceptual design for the 2265 F-configuration engine was identified. Fabrication of the 2070 F-configuration ceramic parts continued, along with burner rig development testing of the 2070 F-configuration metal combustor in preparation for 1132 C (2070 F) qualification test conditions. Shakedown testing of the hot engine simulator (HES) rig was also completed in preparation for testing of a spin rig-qualified ceramic-bladed rotor assembly at 1132 C (2070 F) test conditions. Concurrently, ceramics from new sources and alternate materials continued to be evaluated, and fabrication of 2070 F-configuration ceramic component from these new sources continued. Cold spin testing of the critical 2070 F-configuration blade continued in the spin test rig to qualify a set of ceramic blades at 117% engine speed for the gasifier turbine rotor. Rig testing of the ceramic-bladed gasifier turbine rotor assembly at 108% engine speed was also performed, which resulted in the failure of one blade. The new three-piece hot seal with the nickel oxide/calcium fluoride wearface composition was qualified in the regenerator rig and introduced to engine operation wiwth marginal success.

Rich burn combustor technology at Pratt and Whitney

NASA Technical Reports Server (NTRS)

Lohmann, Robert P.; Rosfjord, T. J.

1992-01-01

The topics covered include the following: near term objectives; rich burn quick quench combustor (RBQC); RBQC critical technology areas; cylindrical RBQQ combustor rig; modular RBQQ combustor; cylindrical rig objectives; quench zone mixing; noneffusive cooled liner; variable geometry requirements; and sector combustor rig.

25 CFR 166.221 - How do I acquire an advertised permit through competitive bidding?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false How do I acquire an advertised permit through competitive... permit through competitive bidding? (a) As part of the negotiation of a permit, Indian landowners may... responsible bidder(s), which may require further competitive bidding after the bid opening; and (4) Prepare...

25 CFR 166.221 - How do I acquire an advertised permit through competitive bidding?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false How do I acquire an advertised permit through competitive... permit through competitive bidding? (a) As part of the negotiation of a permit, Indian landowners may... responsible bidder(s), which may require further competitive bidding after the bid opening; and (4) Prepare...

76 FR 73654 - Notice of Single Family Loan Sales (SFLS 2012-1)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-29

... will evaluate the bids submitted and determine the successful bid, in terms of the best value to HUD... Sales (SFLS 2012-1) AGENCY: Office of the Assistant Secretary for Housing--Federal Housing Commissioner... describes the bidding process for the sale and certain persons who are ineligible to bid. This first sale of...

76 FR 55936 - Notice of Single Family Loan Sales (SFLS 2011-3)

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-09

... will evaluate the bids submitted and determine the successful bid, in terms of the best value to HUD... Sales (SFLS 2011-3) AGENCY: Office of the Assistant Secretary for Housing--Federal Housing Commissioner... describes the bidding process for the sale and certain persons who are ineligible to bid. This third sale of...

26 CFR 403.61 - Sale on open, competitive bids.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 26 Internal Revenue 18 2013-04-01 2013-04-01 false Sale on open, competitive bids. 403.61 Section... open, competitive bids. If forfeited property is to be sold at public auction to the highest bidder on open, competitive bids, the notice of sale shall so specify, and state the date, hour, and place of...

26 CFR 403.61 - Sale on open, competitive bids.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 26 Internal Revenue 18 2010-04-01 2010-04-01 false Sale on open, competitive bids. 403.61 Section... open, competitive bids. If forfeited property is to be sold at public auction to the highest bidder on open, competitive bids, the notice of sale shall so specify, and state the date, hour, and place of...

26 CFR 403.61 - Sale on open, competitive bids.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 26 Internal Revenue 18 2012-04-01 2012-04-01 false Sale on open, competitive bids. 403.61 Section... open, competitive bids. If forfeited property is to be sold at public auction to the highest bidder on open, competitive bids, the notice of sale shall so specify, and state the date, hour, and place of...

26 CFR 403.61 - Sale on open, competitive bids.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 26 Internal Revenue 18 2011-04-01 2011-04-01 false Sale on open, competitive bids. 403.61 Section... open, competitive bids. If forfeited property is to be sold at public auction to the highest bidder on open, competitive bids, the notice of sale shall so specify, and state the date, hour, and place of...

26 CFR 403.61 - Sale on open, competitive bids.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 26 Internal Revenue 18 2014-04-01 2014-04-01 false Sale on open, competitive bids. 403.61 Section... open, competitive bids. If forfeited property is to be sold at public auction to the highest bidder on open, competitive bids, the notice of sale shall so specify, and state the date, hour, and place of...

25 CFR 215.8 - Submission of bids.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false Submission of bids. 215.8 Section 215.8 Indians BUREAU OF INDIAN AFFAIRS, DEPARTMENT OF THE INTERIOR ENERGY AND MINERALS LEAD AND ZINC MINING OPERATIONS AND LEASES, QUAPAW AGENCY § 215.8 Submission of bids. At the time of public auction bidders may submit their bids in...

47 CFR 101.1208 - Bidding credits for small businesses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Bidding credits for small businesses. 101.1208... Bidding credits for small businesses. A winning bidder that qualifies as a small business or a consortium of small businesses, (as defined in § 101.1209(b)(1)(i) may use a bidding credit of 25 percent to...

47 CFR 90.810 - Bidding credits for small businesses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Bidding credits for small businesses. 90.810... Radio Service § 90.810 Bidding credits for small businesses. A winning bidder that qualifies as a small business, as defined in § 90.814(b)(1), or a consortium of small businesses may use a bidding credit of 15...

47 CFR 1.2105 - Bidding application and certification procedures; prohibition of certain communications.

Code of Federal Regulations, 2010 CFR

2010-10-01

....2110, a statement to that effect and a declaration, under penalty of perjury, that the applicant is... the post-auction market structure. (ix) Certification under penalty of perjury that it has not entered... amount of their bids, bidding strategies or the particular licenses on which they will or will not bid...

47 CFR 90.810 - Bidding credits for small businesses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Bidding credits for small businesses. 90.810... Radio Service § 90.810 Bidding credits for small businesses. A winning bidder that qualifies as a small business, as defined in § 90.814(b)(1), or a consortium of small businesses may use a bidding credit of 15...

47 CFR 90.810 - Bidding credits for small businesses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Bidding credits for small businesses. 90.810... Radio Service § 90.810 Bidding credits for small businesses. A winning bidder that qualifies as a small business, as defined in § 90.814(b)(1), or a consortium of small businesses may use a bidding credit of 15...

47 CFR 101.1208 - Bidding credits for small businesses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Bidding credits for small businesses. 101.1208... Bidding credits for small businesses. A winning bidder that qualifies as a small business or a consortium of small businesses, (as defined in § 101.1209(b)(1)(i) may use a bidding credit of 25 percent to...

47 CFR 90.810 - Bidding credits for small businesses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Bidding credits for small businesses. 90.810... Radio Service § 90.810 Bidding credits for small businesses. A winning bidder that qualifies as a small business, as defined in § 90.814(b)(1), or a consortium of small businesses may use a bidding credit of 15...

47 CFR 101.1208 - Bidding credits for small businesses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Bidding credits for small businesses. 101.1208... Bidding credits for small businesses. A winning bidder that qualifies as a small business or a consortium of small businesses, (as defined in § 101.1209(b)(1)(i) may use a bidding credit of 25 percent to...

47 CFR 90.810 - Bidding credits for small businesses.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Bidding credits for small businesses. 90.810... Radio Service § 90.810 Bidding credits for small businesses. A winning bidder that qualifies as a small business, as defined in § 90.814(b)(1), or a consortium of small businesses may use a bidding credit of 15...

47 CFR 101.1208 - Bidding credits for small businesses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Bidding credits for small businesses. 101.1208... Bidding credits for small businesses. A winning bidder that qualifies as a small business or a consortium of small businesses, (as defined in § 101.1209(b)(1)(i) may use a bidding credit of 25 percent to...

47 CFR 101.1208 - Bidding credits for small businesses.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Bidding credits for small businesses. 101.1208... Bidding credits for small businesses. A winning bidder that qualifies as a small business or a consortium of small businesses, (as defined in § 101.1209(b)(1)(i) may use a bidding credit of 25 percent to...

Hospital materials managers need to be aware of actions that constitute legal acceptance.

PubMed

Decker, R

1990-12-01

A hospital invited bids for building materials for a hospital construction project. A supplier submitted a bid which asked the hospital to sign and return a trade association form contract. The hospital didn't return the form but used the supplier's bid as part of the general contract for the entire project and notified the supplier and the general contractor. Later, the supplier submitted a higher bid for the same material contending that the hospital hadn't accepted the first bid as they hadn't followed the instructions. The hospital materials manager feels that the bid was properly accepted. In this dialogue, Dr. Decker reviews the legal issues involved in the different ways of accepting an offer.

Temporal and spatial patterns of habitat use by juveniles of a small coastal shark (Mustelus lenticulatus) in an estuarine nursery.

PubMed

Francis, Malcolm P

2013-01-01

Juvenile rig (Mustelus lenticulatus) were internally tagged with acoustic transmitters and tracked with acoustic receivers deployed throughout two arms of Porirua Harbour, a small (7 km(2)) estuary in New Zealand. Ten rig were tracked for up to four months during summer-autumn to determine their spatial and temporal use of the habitat. The overall goal was to estimate the size of Marine Protected Areas required to protect rig nursery areas from direct human impacts. Rig showed clear site preferences, but those preferences varied among rig and over time. They spent most of their time in large basins and on shallow sand and mud flats around the margins, and avoided deep channels. Habitat range increased during autumn for many of the rig. Only one shark spent time in both harbour arms, indicating that there was little movement between the two. Rig home ranges were 2-7 km(2), suggesting that an effective MPA would need to cover the entire Porirua Harbour. They moved to outer harbour sites following some high river flow rates, and most left the harbour permanently during or soon after a river spike, suggesting that they were avoiding low salinity water. Rig showed strong diel movements during summer, although the diel pattern weakened in autumn. Persistent use of the same day and night sites indicates that diel movements are directed rather than random. Further research is required to determine the sizes of rig home ranges in larger harbours where nursery habitat is more extensive. Marine Protected Areas do not control land-based impacts such as accelerated sedimentation and heavy metal pollution, so integration of marine and terrestrial management tools across a range of government agencies is essential to fully protect nursery areas.

Low Frequency Noise Contamination in Fan Model Testing

NASA Technical Reports Server (NTRS)

Brown, Clifford A.; Schifer, Nicholas A.

2008-01-01

Aircraft engine noise research and development depends on the ability to study and predict the noise created by each engine component in isolation. The presence of a downstream pylon for a model fan test, however, may result in noise contamination through pylon interactions with the free stream and model exhaust airflows. Additionally, there is the problem of separating the fan and jet noise components generated by the model fan. A methodology was therefore developed to improve the data quality for the 9 15 Low Speed Wind Tunnel (LSWT) at the NASA Glenn Research Center that identifies three noise sources: fan noise, jet noise, and rig noise. The jet noise and rig noise were then measured by mounting a scale model of the 9 15 LSWT model fan installation in a jet rig to simulate everything except the rotating machinery and in duct components of fan noise. The data showed that the spectra measured in the LSWT has a strong rig noise component at frequencies as high as 3 kHz depending on the fan and airflow fan exit velocity. The jet noise was determined to be significantly lower than the rig noise (i.e., noise generated by flow interaction with the downstream support pylon). A mathematical model for the rig noise was then developed using a multi-dimensional least squares fit to the rig noise data. This allows the rig noise to be subtracted or removed, depending on the amplitude of the rig noise relative to the fan noise, at any given frequency, observer angle, or nozzle pressure ratio. The impact of isolating the fan noise with this method on spectra, overall power level (OAPWL), and Effective Perceived Noise Level (EPNL) is studied.

Temporal and Spatial Patterns of Habitat Use by Juveniles of a Small Coastal Shark (Mustelus lenticulatus) in an Estuarine Nursery

PubMed Central

Francis, Malcolm P.

2013-01-01

Juvenile rig (Mustelus lenticulatus) were internally tagged with acoustic transmitters and tracked with acoustic receivers deployed throughout two arms of Porirua Harbour, a small (7 km2) estuary in New Zealand. Ten rig were tracked for up to four months during summer–autumn to determine their spatial and temporal use of the habitat. The overall goal was to estimate the size of Marine Protected Areas required to protect rig nursery areas from direct human impacts. Rig showed clear site preferences, but those preferences varied among rig and over time. They spent most of their time in large basins and on shallow sand and mud flats around the margins, and avoided deep channels. Habitat range increased during autumn for many of the rig. Only one shark spent time in both harbour arms, indicating that there was little movement between the two. Rig home ranges were 2–7 km2, suggesting that an effective MPA would need to cover the entire Porirua Harbour. They moved to outer harbour sites following some high river flow rates, and most left the harbour permanently during or soon after a river spike, suggesting that they were avoiding low salinity water. Rig showed strong diel movements during summer, although the diel pattern weakened in autumn. Persistent use of the same day and night sites indicates that diel movements are directed rather than random. Further research is required to determine the sizes of rig home ranges in larger harbours where nursery habitat is more extensive. Marine Protected Areas do not control land-based impacts such as accelerated sedimentation and heavy metal pollution, so integration of marine and terrestrial management tools across a range of government agencies is essential to fully protect nursery areas. PMID:23437298

Five-Axis, Three-Magnetic-Bearing Dynamic Spin Rig

NASA Technical Reports Server (NTRS)

Morrison, Carlos R.; Provenza, Andrew; Kurkov, Anatole; Mehmed, Oral; Johnson, Dexter; Montague, Gerald; Duffy, Kirsten; Jansen, Ralph

2005-01-01

The Five-Axis, Three-Magnetic-Bearing Dynamic Spin Rig is an apparatus for vibration testing of turbomachine blades in a vacuum at rotational speeds from 0 to 40,000 rpm. This rig includes (1) a vertically oriented shaft on which is mounted an assembly comprising a rotor holding the blades to be tested, (2) two actively controlled heteropolar radial magnetic bearings at opposite ends of the shaft, and (3) an actively controlled magnetic thrust bearing at the upper end of the shaft. This rig is a more capable successor to a prior apparatus, denoted the Dynamic Spin Rig (DSR), that included a vertically oriented shaft with a mechanical thrust bearing at the upper end and a single actively controlled heteropolar radial magnetic bearing at the lower end.

New drilling rigs

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

Tubb, M.

1983-03-01

Petronas recently commissioned its first offshore jack-up drilling rig at Promet, Singapore. The $49 million jack-up Parameswara will undertake both exploration and development activities in Petronas Carigali's exploration block off the eastern coast of Malaysia. The block measures 19,800 sq. km. Initially, the rig will be located at the Duyong gas field. Based on Baker Marine Corporation's BMC 300 design, the 65 X 64 X 8 m rig is capable of working in water depths of up to 91.4 m and is able to drill to a depth of 7,600 m. It has three triangular open-lattice truss-type legs, each 131more » m long. Prominent features include four-tier living quarters which can house 90 men, three cranes of boom length 30.48 m each, a helideck, mess hall, galley, and recreation room. The rig is built to American Bureau of Shipping standards. This paper describes the transport, installation and ballast operations involved in situating the Petronas rig in the Duyong field.« less

Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway

PubMed Central

Sanchez, Jacint G.; Chiang, Jessica J.; Sparrer, Konstantin M.J.; Alam, Steven L.; Chi, Michael; Roganowicz, Marcin D.; Sankaran, Banumathi; Gack, Michaela U.; Pornillos, Owen

2016-01-01

SUMMARY Antiviral response pathways induce interferon by higher-order assembly of signaling complexes called signalosomes. Assembly of the RIG-I signalosome is regulated by K63-linked polyubiquitin chains, which are synthesized by the E3 ubiquitin ligase, TRIM25. We have previously shown that the TRIM25 coiled-coil domain is a stable, antiparallel dimer that positions two catalytic RING domains on opposite ends of an elongated rod. We now show that the RING domain is a separate self-association motif that engages ubiquitin-conjugated E2 enzymes as a dimer. RING dimerization is required for catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, and antiviral activity. We also provide evidence that RING dimerization and E3 ligase activity are promoted by binding of the TRIM25 SPRY domain to the RIG-I effector domain. These results indicate that TRIM25 actively participates in higher-order assembly of the RIG-I signalosome and helps to fine-tune the efficiency of the RIG-I-mediated antiviral response. PMID:27425606

Multi-Axis Test Facility

NASA Image and Video Library

1959-11-01

Multi-Axis Test Facility, Space Progress Report, November 1, 1959: The Multi Axis Space Test Inertia Facility [MASTIF], informally referred to as the Gimbal Rig, was installed inside the Altitude Wind Tunnel. The rig, which spun on three axis simultaneously, was used to train the Mercury astronauts on how to bring a spinning spacecraft under control and to determine the effects of rapid spinning on the astronaut's eyesight and psyche. Small gaseous nitrogen jets were operated by the pilot to gain control of the rig after it had been set in motion. Part 1 shows pilot Joe Algranti in the rig as it rotates over one, two, and three axis. It also has overall views of the test set-up with researchers and technicians on the test platform. Part 2 shows Algranti being secured in the rig prior to the test. The rig is set in motion and the pilot slowly brings it under control. The Mercury astronauts trained on the MASTIF in early spring of 1960.

The HARMONY Trial: Combined Ranolazine and Dronedarone in the Management of Paroxysmal Atrial Fibrillation: Mechanistic and Therapeutic Synergism.

PubMed

Reiffel, James A; Camm, A John; Belardinelli, Luiz; Zeng, Dewan; Karwatowska-Prokopczuk, Ewa; Olmsted, Ann; Zareba, Wojciech; Rosero, Spencer; Kowey, Peter

2015-10-01

Atrial fibrillation (AF) requires arrhythmogenic changes in atrial ion channels/receptors and usually altered atrial structure. AF is commonly treated with antiarrhythmic drugs; the most effective block many ion channels/receptors. Modest efficacy, intolerance, and safety concerns limit current antiarrhythmic drugs. We hypothesized that combining agents with multiple anti-AF mechanisms at reduced individual drug doses might produce synergistic efficacy plus better tolerance/safety. HARMONY tested midrange ranolazine (750 mg BID) combined with 2 reduced dronedarone doses (150 mg BID and 225 mg BID; chosen to reduce dronedarone's negative inotropic effect-see text below) over 12 weeks in 134 patients with paroxysmal AF and implanted pacemakers where AF burden (AFB) could be continuously assessed. Patients were randomized double-blind to placebo, ranolazine alone (750 mg BID), dronedarone alone (225 mg BID), or one of the combinations. Neither placebo nor either drugs alone significantly reduced AFB. Conversely, ranolazine 750 mg BID/dronedarone 225 mg BID reduced AFB by 59% versus placebo (P=0.008), whereas ranolazine 750 mg BID/dronedarone 150 mg BID reduced AFB by 43% (P=0.072). Both combinations were well tolerated. HARMONY showed synergistic AFB reduction by moderate dose ranolazine plus reduced dose dronedarone, with good tolerance/safety, in the population enrolled. ClinicalTrials.gov; Unique identifier: NCT01522651. © 2015 American Heart Association, Inc.

The association between obesity, depression, and educational attainment in women: The mediating role of body image dissatisfaction

PubMed Central

Gavin, Amelia R.; Simon, Greg E.; Ludman, Evette J.

2011-01-01

Objective We examine the mediating role of body image dissatisfaction (BID) on the association between obesity and depression and the variation of this association as a function of years of education among a population-based sample of women aged 40–65 years. Methods A series of sample-weighted logistic regression models were used to estimate the associations between obesity, BID, and depression, stratified by educational attainment. Data were obtained from a structured telephone interview of 4543 female health plan enrollees, including self-reported height and weight, the Patient Health Questionnaire assessment of depression, and a single-item measure of BID. Results Among those with <16 years of education, in both the unadjusted and adjusted models, obesity and BID were significantly associated with depression. Similarly, among those with ≥16 years of education, obesity and BID were significantly associated with depression in the unadjusted models. However, in the adjusted model, only BID was associated with depression. A formal test for mediation suggests that the association between obesity and depression was mediated by BID regardless of level of education. Conclusions Our data suggest that BID-mediated the obesity-depression association. In addition, obesity and BID may be salient risk factors for depression among middle-aged women as a function of the level of education. PMID:21109045

Evolutionary Dynamics of Biological Auctions

PubMed Central

Chatterjee, Krishnendu; Reiter, Johannes G.; Nowak, Martin A.

2011-01-01

Many scenarios in the living world, where individual organisms compete for winning positions (or resources), have properties of auctions. Here we study the evolution of bids in biological auctions. For each auction n individuals are drawn at random from a population of size N. Each individual makes a bid which entails a cost. The winner obtains a benefit of a certain value. Costs and benefits are translated into reproductive success (fitness). Therefore, successful bidding strategies spread in the population. We compare two types of auctions. In “biological all-pay auctions” the costs are the bid for every participating individual. In “biological second price all-pay auctions” the cost for everyone other than the winner is the bid, but the cost for the winner is the second highest bid. Second price all-pay auctions are generalizations of the “war of attrition” introduced by Maynard Smith. We study evolutionary dynamics in both types of auctions. We calculate pairwise invasion plots and evolutionarily stable distributions over the continuous strategy space. We find that the average bid in second price all-pay auctions is higher than in all-pay auctions, but the average cost for the winner is similar in both auctions. In both cases the average bid is a declining function of the number of participants, n. The more individuals participate in an auction the smaller is the chance of winning, and thus expensive bids must be avoided. PMID:22120126

77 FR 33235 - Notice of Realty Action: Modified Competitive Sale of Public Lands in Becker County, MN

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-05

... bid is received or the sale is cancelled. Sealed bid envelopes must be clearly marked on the front lower left-hand corner with ``SEALED BID BLM LAND SALE, MNES-056512''. The bid envelope must contain a... of Land Management. Personal checks will not be accepted. Failure to submit the remainder of the full...

46 CFR Sec. 4 - Procedure for securing competitive bids.

Code of Federal Regulations, 2013 CFR

2013-10-01

... not subject to the Davis-Bacon Act. (g) The Invitations for Bids shall also include a statement of the... Authority may orally contact as many qualified contractors as is feasible, in order to obtain written “Spot... contractor shall be verbally advised of a time and place for the submission of the “Spot Bids.” If such bids...

46 CFR Sec. 4 - Procedure for securing competitive bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... not subject to the Davis-Bacon Act. (g) The Invitations for Bids shall also include a statement of the... Authority may orally contact as many qualified contractors as is feasible, in order to obtain written “Spot... contractor shall be verbally advised of a time and place for the submission of the “Spot Bids.” If such bids...

46 CFR Sec. 4 - Procedure for securing competitive bids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... not subject to the Davis-Bacon Act. (g) The Invitations for Bids shall also include a statement of the... Authority may orally contact as many qualified contractors as is feasible, in order to obtain written “Spot... contractor shall be verbally advised of a time and place for the submission of the “Spot Bids.” If such bids...

46 CFR Sec. 4 - Procedure for securing competitive bids.

Code of Federal Regulations, 2014 CFR

2014-10-01

... not subject to the Davis-Bacon Act. (g) The Invitations for Bids shall also include a statement of the... Authority may orally contact as many qualified contractors as is feasible, in order to obtain written “Spot... contractor shall be verbally advised of a time and place for the submission of the “Spot Bids.” If such bids...

46 CFR Sec. 4 - Procedure for securing competitive bids.

Code of Federal Regulations, 2012 CFR

2012-10-01

... not subject to the Davis-Bacon Act. (g) The Invitations for Bids shall also include a statement of the... Authority may orally contact as many qualified contractors as is feasible, in order to obtain written “Spot... contractor shall be verbally advised of a time and place for the submission of the “Spot Bids.” If such bids...

48 CFR 52.214-25 - Step Two of Two-Step Sealed Bidding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Step Two of Two-Step... Clauses 52.214-25 Step Two of Two-Step Sealed Bidding. As prescribed in 14.201-6(t), insert the following provision: Step Two of Two-Step Sealed Bidding (APR 1985) (a) This invitation for bids is issued to initiate...

78 FR 31616 - Self-Regulatory Organizations; The NASDAQ Stock Market LLC; Notice of Filing and Immediate...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-24

... current National Best Bid and National Best Offer, or if no National Best Bid or National Best Offer, at... the System to the Designated Percentage away from the then current National Best Bid and National Best Offer, or, if no National Best Bid or National Best Offer, to the Designated Percentage away from the...

Observation of interaction between bid and 14-3-3 proteins by FRET in living cell during TNF-a-induced apoptosis

NASA Astrophysics Data System (ADS)

Wang, Jinjun; Chen, Tongsheng; Xing, Da; Wang, Fang

2005-01-01

Caspase8 is activated and cleaves Bid into two fragments when cells are exposed to death-inducing molecules such as tumor necrosis factor-α (TNF-α). Then the C-terminal fragment relocates from cytosol to mitochondria and promotes the release of cytochrome c, in the final cellular apoptosis is induced. Despite recent progress in the study of Bid during apoptosis induction, it remains unclear how C-terminal fragment of Bid cleaved moves to mitochondria and then induces the release of cytochrome c and so on. The 14-3-3 proteins are known to sequester certain pro-apoptotic members of Bcl-2 family. In order to further study the biological action of Bid during apoptosis, especially under physiological condition of living cell, the plasmids pBid-CFP and pYFP-14-3-3 were constructed. By the transient transfection of pBid-CFP and pYFP-14-3-3, the dynamic process of interaction of Bid and 14-3-3 protein in individual living cell during the apoptosis was primarily investigated with FRET (fluorescent resonance energy transfer) technique by the use of fluorescence microscopy.

The effect of business improvement districts on the incidence of violent crimes

PubMed Central

Golinelli, Daniela; Stokes, Robert J; Bluthenthal, Ricky

2010-01-01

Objective To examine whether business improvement districts (BID) contributed to greater than expected declines in the incidence of violent crimes in affected neighbourhoods. Method A Bayesian hierarchical model was used to assess the changes in the incidence of violent crimes between 1994 and 2005 and the implementation of 30 BID in Los Angeles neighbourhoods. Results The implementation of BID was associated with a 12% reduction in the incidence of robbery (95% posterior probability interval −2 to 24) and an 8% reduction in the total incidence of violent crimes (95% posterior probability interval −5 to 21). The strength of the effect of BID on robbery crimes varied by location. Conclusion These findings indicate that the implementation of BID can reduce the incidence of violent crimes likely to result in injury to individuals. The findings also indicate that the establishment of a BID by itself is not a panacea, and highlight the importance of targeting BID efforts to crime prevention interventions that reduce violence exposure associated with criminal behaviours. PMID:20587814

The effect of business improvement districts on the incidence of violent crimes.

PubMed

MacDonald, John; Golinelli, Daniela; Stokes, Robert J; Bluthenthal, Ricky

2010-10-01

To examine whether business improvement districts (BID) contributed to greater than expected declines in the incidence of violent crimes in affected neighbourhoods. A Bayesian hierarchical model was used to assess the changes in the incidence of violent crimes between 1994 and 2005 and the implementation of 30 BID in Los Angeles neighbourhoods. The implementation of BID was associated with a 12% reduction in the incidence of robbery (95% posterior probability interval -2 to 24) and an 8% reduction in the total incidence of violent crimes (95% posterior probability interval -5 to 21). The strength of the effect of BID on robbery crimes varied by location. These findings indicate that the implementation of BID can reduce the incidence of violent crimes likely to result in injury to individuals. The findings also indicate that the establishment of a BID by itself is not a panacea, and highlight the importance of targeting BID efforts to crime prevention interventions that reduce violence exposure associated with criminal behaviours.

49 CFR 230.111 - Spring rigging.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Spring rigging. 230.111 Section 230.111... Tenders Trucks, Frames and Equalizing System § 230.111 Spring rigging. (a) Arrangement of springs and equalizers. Springs and equalizers shall be arranged to ensure the proper distribution of weight to the...

49 CFR 230.111 - Spring rigging.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Spring rigging. 230.111 Section 230.111... Tenders Trucks, Frames and Equalizing System § 230.111 Spring rigging. (a) Arrangement of springs and equalizers. Springs and equalizers shall be arranged to ensure the proper distribution of weight to the...

49 CFR 230.111 - Spring rigging.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Spring rigging. 230.111 Section 230.111... Tenders Trucks, Frames and Equalizing System § 230.111 Spring rigging. (a) Arrangement of springs and equalizers. Springs and equalizers shall be arranged to ensure the proper distribution of weight to the...

49 CFR 230.111 - Spring rigging.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Spring rigging. 230.111 Section 230.111... Tenders Trucks, Frames and Equalizing System § 230.111 Spring rigging. (a) Arrangement of springs and equalizers. Springs and equalizers shall be arranged to ensure the proper distribution of weight to the...

The Human Papillomavirus E6 Oncoprotein Targets USP15 and TRIM25 To Suppress RIG-I-Mediated Innate Immune Signaling.

PubMed

Chiang, Cindy; Pauli, Eva-Katharina; Biryukov, Jennifer; Feister, Katharina F; Meng, Melissa; White, Elizabeth A; Münger, Karl; Howley, Peter M; Meyers, Craig; Gack, Michaela U

2018-03-15

Retinoic acid-inducible gene I (RIG-I) is a key pattern recognition receptor that senses viral RNA and interacts with the mitochondrial adaptor MAVS, triggering a signaling cascade that results in the production of type I interferons (IFNs). This signaling axis is initiated by K63-linked ubiquitination of RIG-I mediated by the E3 ubiquitin ligase TRIM25, which promotes the interaction of RIG-I with MAVS. USP15 was recently identified as an upstream regulator of TRIM25, stabilizing the enzyme through removal of degradative K48-linked polyubiquitin, ultimately promoting RIG-I-dependent cytokine responses. Here, we show that the E6 oncoprotein of human papillomavirus type 16 (HPV16) as well as of other HPV types form a complex with TRIM25 and USP15 in human cells. In the presence of E6, the K48-linked ubiquitination of TRIM25 was markedly increased, and in line with this, TRIM25 degradation was enhanced. Our results further showed that E6 inhibited the TRIM25-mediated K63-linked ubiquitination of RIG-I and its CARD-dependent interaction with MAVS. HPV16 E6, but not E7, suppressed the RIG-I-mediated induction of IFN-β, chemokines, and IFN-stimulated genes (ISGs). Finally, CRISPR-Cas9 gene targeting in human keratinocytes showed that the TRIM25-RIG-I-MAVS triad is important for eliciting an antiviral immune response to HPV16 infection. Our study thus identifies a novel immune escape mechanism that is conserved among different HPV strains and further indicates that the RIG-I signaling pathway plays an important role in the innate immune response to HPV infection. IMPORTANCE Persistent infection and tumorigenesis by HPVs are known to require viral manipulation of a variety of cellular processes, including those involved in innate immune responses. Here, we show that the HPV E6 oncoprotein antagonizes the activation of the cytoplasmic innate immune sensor RIG-I by targeting its upstream regulatory enzymes TRIM25 and USP15. We further show that the RIG-I signaling cascade is important for an antiviral innate immune response to HPV16 infection, providing evidence that RIG-I, whose role in sensing RNA virus infections has been well characterized, also plays a crucial role in the antiviral host response to small DNA viruses of the Papillomaviridae family. Copyright © 2018 American Society for Microbiology.

Bidding process in online auctions and winning strategy: Rate equation approach

NASA Astrophysics Data System (ADS)

Yang, I.; Kahng, B.

2006-06-01

Online auctions have expanded rapidly over the last decade and have become a fascinating new type of business or commercial transaction in this digital era. Here we introduce a master equation for the bidding process that takes place in online auctions. We find that the number of distinct bidders who bid k times up to the t th bidding progresses, called the k -frequent bidder, seems to scale as nk(t)˜tk-2.4 . The successfully transmitted bidding rate by the k -frequent bidder is likely to scale as qk(t)˜k-1.4 , independent of t for large t . This theoretical prediction is close to empirical data. These results imply that bidding at the last moment is a rational and effective strategy to win in an eBay auction.

Increased A20-E3 ubiquitin ligase interactions in bid-deficient glia attenuate TLR3- and TLR4-induced inflammation.

PubMed

Kinsella, Sinéad; Fichtner, Michael; Watters, Orla; König, Hans-Georg; Prehn, Jochen H M

2018-05-02

Chronic pro-inflammatory signaling propagates damage to neural tissue and affects the rate of disease progression. Increased activation of Toll-like receptors (TLRs), master regulators of the innate immune response, is implicated in the etiology of several neuropathologies including amyotrophic lateral sclerosis, Alzheimer's disease, and Parkinson's disease. Previously, we identified that the Bcl-2 family protein BH3-interacting domain death agonist (Bid) potentiates the TLR4-NF-κB pro-inflammatory response in glia, and specifically characterized an interaction between Bid and TNF receptor associated factor 6 (TRAF6) in microglia in response to TLR4 activation. We assessed the activation of mitogen-activated protein kinase (MAPK) and interferon regulatory factor 3 (IRF3) inflammatory pathways in response to TLR3 and TLR4 agonists in wild-type (wt) and bid-deficient microglia and macrophages, using Western blot and qPCR, focusing on the response of the E3 ubiquitin ligases Pellino 1 (Peli1) and TRAF3 in the absence of microglial and astrocytic Bid. Additionally, by Western blot, we investigated the Bid-dependent turnover of Peli1 and TRAF3 in wt and bid -/- microglia using the proteasome inhibitor Bortezomib. Interactions between the de-ubiquitinating Smad6-A20 and the E3 ubiquitin ligases, TRAF3 and TRAF6, were determined by FLAG pull-down in TRAF6-FLAG or Smad6-FLAG overexpressing wt and bid-deficient mixed glia. We elucidated a positive role of Bid in both TIR-domain-containing adapter-inducing interferon-β (TRIF)- and myeloid differentiation primary response 88 (MyD88)-dependent pathways downstream of TLR4, concurrently implicating TLR3-induced inflammation. We identified that Peli1 mRNA levels were significantly reduced in PolyI:C- and lipopolysaccharide (LPS)-stimulated bid-deficient microglia, suggesting disturbed IRF3 activation. Differential regulation of TRAF3 and Peli1, both essential E3 ubiquitin ligases facilitating TRIF-dependent signaling, was observed between wt and bid -/- microglia and astrocytes. bid deficiency resulted in increased A20-E3 ubiquitin ligase protein interactions in glia, specifically A20-TRAF6 and A20-TRAF3, implicating enhanced de-ubiquitination as the mechanism of action by which E3 ligase activity is perturbed. Furthermore, Smad6-facilitated recruitment of the de-ubiquitinase A20 to E3-ligases occurred in a bid-dependent manner. This study demonstrates that Bid promotes E3 ubiquitin ligase-mediated signaling downstream of TLR3 and TLR4 and provides further evidence for the potential of Bid inhibition as a therapeutic for the attenuation of the robust pro-inflammatory response culminating in TLR activation.

Procurement and Contracting, Transportation & Public Facilities, State of

Science.gov Websites

Calendar Bid Opening Results Contract Award Status AASHTOWare Project Vendor List Contractor Bidding List Contractor Bidding Information Requests for Proposals Professional Services Request for Proposals

Reconfigurable Image Generator

NASA Technical Reports Server (NTRS)

Archdeacon, John L. (Inventor); Iwai, Nelson H. (Inventor); Kato, Kenji H. (Inventor); Sweet, Barbara T. (Inventor)

2017-01-01

A RiG may simulate visual conditions of a real world environment, and generate the necessary amount of pixels in a visual simulation at rates up to 120 frames per second. RiG may also include a database generation system capable of producing visual databases suitable to drive the visual fidelity required by the RiG.

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

Suchanecki, Z.; Antoniou, I.; Tasaki, S.

We consider the problem of rigging for the Koopman operators of the Renyi and the baker maps. We show that the rigged Hilbert space for the Renyi maps has some of the properties of a strict inductive limit and give a detailed description of the rigged Hilbert space for the baker maps. {copyright} {ital 1996 American Institute of Physics.}

29 CFR 1926.1431 - Hoisting personnel.

Code of Federal Regulations, 2011 CFR

2011-07-01

... hook, load line and rigging) must not exceed 50 percent of the rated capacity for the radius and... pursuant to paragraph (b)(2) of this section, the total load (including the hook, load line, rigging and... number required to perform the work, whichever is less. (g) Attachment and rigging. (1) Hooks and other...

49 CFR 229.65 - Spring rigging.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Spring rigging. 229.65 Section 229.65....65 Spring rigging. (a) Protective construction or safety hangers shall be provided to prevent spring planks, spring seats or bolsters from dropping to track structure in event of a hanger or spring failure...

49 CFR 229.65 - Spring rigging.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Spring rigging. 229.65 Section 229.65....65 Spring rigging. (a) Protective construction or safety hangers shall be provided to prevent spring planks, spring seats or bolsters from dropping to track structure in event of a hanger or spring failure...

49 CFR 229.65 - Spring rigging.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Spring rigging. 229.65 Section 229.65....65 Spring rigging. (a) Protective construction or safety hangers shall be provided to prevent spring planks, spring seats or bolsters from dropping to track structure in event of a hanger or spring failure...

49 CFR 229.65 - Spring rigging.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Spring rigging. 229.65 Section 229.65....65 Spring rigging. (a) Protective construction or safety hangers shall be provided to prevent spring planks, spring seats or bolsters from dropping to track structure in event of a hanger or spring failure...

49 CFR 229.65 - Spring rigging.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Spring rigging. 229.65 Section 229.65....65 Spring rigging. (a) Protective construction or safety hangers shall be provided to prevent spring planks, spring seats or bolsters from dropping to track structure in event of a hanger or spring failure...

16 CFR Figure 1 to Part 1512 - Bicycle Front Fork Cantilever Bending Test Rig

Code of Federal Regulations, 2010 CFR

2010-01-01

... 16 Commercial Practices 2 2010-01-01 2010-01-01 false Bicycle Front Fork Cantilever Bending Test Rig 1 Figure 1 to Part 1512 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS... Fork Cantilever Bending Test Rig EC03OC91.070 ...

16 CFR Figure 1 to Part 1512 - Bicycle Front Fork Cantilever Bending Test Rig

Code of Federal Regulations, 2011 CFR

2011-01-01

... 16 Commercial Practices 2 2011-01-01 2011-01-01 false Bicycle Front Fork Cantilever Bending Test Rig 1 Figure 1 to Part 1512 Commercial Practices CONSUMER PRODUCT SAFETY COMMISSION FEDERAL HAZARDOUS... Fork Cantilever Bending Test Rig EC03OC91.070 ...

Injecting rabies immunoglobulin (RIG) into wounds only: A significant saving of lives and costly RIG.

PubMed

Bharti, Omesh Kumar; Madhusudana, Shampur Narayan; Wilde, Henry

2017-04-03

An increasing number of dog bite victims were being presented to public hospitals in Himachal Pradesh in 2014 amidst virtual non availability of any rabies immunoglobulin (RIG). Only a small quantity of equine rabies immunoglobulin (eRIG) was available from the government owned Central Research Institute (CRI) Kasauli. This available eRIG was used in 269 patients as an emergency response and only for local infiltration of severe bite wounds by suspected rabid dogs. This was followed by rabies vaccination, using the WHO approved intra-dermal Thai Red Cross Society vaccination schedule. A subgroup of 26 patients were later identified who had been severely bitten by laboratory confirmed rabid dogs. They were followed for more than one year and all were found to be alive.

A comparison of pay-as-bid and marginal pricing in electricity markets

NASA Astrophysics Data System (ADS)

Ren, Yongjun

This thesis investigates the behaviour of electricity markets under marginal and pay-as-bid pricing. Marginal pricing is believed to yield the maximum social welfare and is currently implemented by most electricity markets. However, in view of recent electricity market failures, pay-as-bid has been extensively discussed as a possible alternative to marginal pricing. In this research, marginal and pay-as-bid pricing have been analyzed in electricity markets with both perfect and imperfect competition. The perfect competition case is studied under both exact and uncertain system marginal cost prediction. The comparison of the two pricing methods is conducted through two steps: (i) identify the best offer strategy of the generating companies (gencos); (ii) analyze the market performance under these optimum genco strategies. The analysis results together with numerical simulations show that pay-as-bid and marginal pricing are equivalent in a perfect market with exact system marginal cost prediction. In perfect markets with uncertain demand prediction, the two pricing methods are also equivalent but in an expected value sense. If we compare from the perspective of second order statistics, all market performance measures exhibit much lower values under pay-as-bid than under marginal pricing. The risk of deviating from the mean is therefore much higher under marginal pricing than under pay-as-bid. In an imperfect competition market with exact demand prediction, the research shows that pay-as-bid pricing yields lower consumer payments and lower genco profits. This research provides quantitative evidence that challenges some common claims about pay-as-bid pricing. One is that under pay-as-bid, participants would soon learn how to offer so as to obtain the same or higher profits than what they would have obtained under marginal pricing. This research however shows that, under pay-as-bid, participants can at best earn the same profit or expected profit as under marginal pricing. A second common claim refuted by this research is that pay-as-bid does not provide correct price signals if there is a scarcity of generation resources. We show that pay-as-bid does provide a price signal with such characteristics and furthermore argue that the price signal under marginal pricing with gaming may not necessarily be correct since it would then not reflect a lack of generation capacity but a desire to increase profit.

Therapeutic efficacy of improved α-fetoprotein promoter-mediated tBid delivered by folate-PEI600-cyclodextrin nanopolymer vector in hepatocellular carcinoma

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

Hu, Bao-guang; Department of Gastrointestinal Surgery, the Affiliated Hospital of Binzhou Medical University, Binzhou, Shandong; Liu, Li-ping

SNPs in human AFP promoter are associated with serum AFP levels in hepatocellular carcinoma (HCC), suggesting that AFP promoter variants may generate better transcriptional activities while retaining high specificity to AFP-producing cells. We sequenced human AFP promoters, cloned 15 different genotype promoters and tested their reporter activities in AFP-producing and non-producing cells. Among various AFP variant fragments tested, EA4D exhibited the highest reporter activity and thus was selected for the further study. EA4D was fused with tBid and coupled with nano-particle vector (H1) to form pGL3-EA4D-tBid/H1. pGL3-EA4D-tBid/H1 could express a high level of tBid while retain the specificity to AFP-producingmore » cells. In a HCC tumor model, application of pGL3-EA4D-tBid/H1 significantly inhibited the growth of AFP-producing-implanted tumors with minimal side-effects, but had no effect on non-AFP-producing tumors. Furthermore, pGL3-EA4D-tBid/H1 could significantly sensitize HCC cells to sorafenib, an approved anti-HCC agent. Collectively, pGL3-EA4D-tBid/H1, a construct with the AFP promoter EA4D and the novel H1 delivery system, can specifically target and effectively suppress the AFP-producing HCC. This new therapeutic tool shows little toxicity in vitro and in vivo and it should thus be safe for further clinical tests. - Highlights: • The nano-particle vector H1 has advantages in mediating gene therapy construct pGL3-EA4D-tBid for HCC treatment. • pGL3-EA4D-tBid/H1, a construct with the AFP promoter EA4D, can specifically target the AFP-producing HCC. • pGL3-EA4D-tBid/H1effectively suppresses the proliferation and growth of AFP-producing HCC. • This novel pGL3-EA4D-tBid/H1 therapeutic tool shows little toxicity in vitro and in vivo.« less

Twice-daily dosing of a repaglinide/metformin fixed-dose combination tablet provides glycaemic control comparable to rosiglitazone/metformin tablet.

PubMed

Raskin, P; Lewin, A; Reinhardt, R; Lyness, W

2009-09-01

To assess the use of a new repaglinide/metformin fixed-dose combination (FDC) tablet for the treatment of type 2 diabetes. In this 26-week, multicentre, open-label, parallel-group trial, subjects poorly controlled with mono- or dual-oral antidiabetic therapy were randomized 1 : 1 : 1 to receive a repaglinide/metformin FDC tablet either two times daily (BID) or three times daily (TID) or a rosiglitazone/metformin FDC tablet BID. The primary objective comprised two hypotheses tested in a hierarchical order: (i) that treatment with the repaglinide/metformin FDC BID is non-inferior to that of a rosiglitazone/metformin FDC tablet BID as measured by changes in haemoglobin A1c (HbA1c) (results presented here) and (ii) if true, that treatment with the repaglinide/metformin FDC BID was non-inferior to that of the repaglinide/metformin FDC TID as measured by changes in HbA1c (results presented in a companion paper). Additional efficacy and safety end-points were also assessed. Of the 561 subjects randomized, 383 completed the study. Reductions in HbA1c values became apparent at earlier times for repaglinide/metformin FDC BID treatment than rosiglitazone/metformin FDC BID, and final changes in HbA1c were not significantly different between treatment arms (p = 0.8186); thus, the predefined statistical criterion for non-inferiority was met. Overall adverse event profiles were comparable between treatment groups, and no major hypoglycaemic episodes were reported during the study. The repaglinide/metformin FDC BID regimen showed efficacy that was non-inferior to that of the rosiglitazone/metformin FDC BID regimen currently in clinical use and a more rapid reduction of HbA1c values. Thus, repaglinide/metformin FDC BID is a clinically feasible alternative to rosiglitazone/metformin FDC BID.

47 CFR 22.228 - Cellular rural service area licenses subject to competitive bidding.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) COMMON CARRIER SERVICES PUBLIC MOBILE SERVICES Licensing Requirements and Procedures Competitive Bidding... initial applications for Cellular Rural Service Area licenses are subject to competitive bidding. The...

Human islet cells are killed by BID-independent mechanisms in response to FAS ligand.

PubMed

Joglekar, Mugdha V; Trivedi, Prerak M; Kay, Thomas W; Hawthorne, Wayne J; O'Connell, Philip J; Jenkins, Alicia J; Hardikar, Anandwardhan A; Thomas, Helen E

2016-04-01

Cell death via FAS/CD95 can occur either by activation of caspases alone (extrinsic) or by activation of mitochondrial death signalling (intrinsic) depending on the cell type. The BH3-only protein BID is activated in the BCL-2-regulated or mitochondrial apoptosis pathway and acts as a switch between the extrinsic and intrinsic cell death pathways. We have previously demonstrated that islets from BID-deficient mice are protected from FAS ligand-mediated apoptosis in vitro. However, it is not yet known if BID plays a similar role in human beta cell death. We therefore aimed to test the role of BID in human islet cell apoptosis immediately after isolation from human cadaver donors, as well as after de-differentiation in vitro. Freshly isolated human islets or 10-12 day cultured human islet cells exhibited BID transcript knockdown after BID siRNA transfection, however they were not protected from FAS ligand-mediated cell death in vitro as determined by DNA fragmentation analysis using flow cytometry. On the other hand, the same cells transfected with siRNA for FAS-associated via death domain (FADD), a molecule in the extrinsic cell death pathway upstream of BID, showed significant reduction in cell death. De-differentiated islets (human islet-derived progenitor cells) also demonstrated similar results with no difference in cell death after BID knockdown as compared to scramble siRNA transfections. Our results indicate that BID-independent pathways are responsible for FAS-dependent human islet cell death. These results are different from those observed in mouse islets and therefore demonstrate potentially alternate pathways of FAS ligand-induced cell death in human and mouse islet cells.

Citizen science data suggest that a novel rig improves landing rate and reduces injury and handling time in recreational angling with artificial lures in Baltic pike (Esox lucius).

PubMed

Bursell, Jens Jakob; Arlinghaus, Robert

2018-01-01

The optimal terminal gear in hook-and-line recreational fishing maximizes landing rates and minimizes injury to the fish because some fish will be released after capture. We designed a novel rig configuration in artificial lure fishing for top predators and examined its effectiveness in angling for Baltic northern pike ( Esox lucius ) using a citizen science approach based on observational data collected from volunteer anglers in the field. The novel rig included two changes to traditional rig designs common to artificial lure angling. First, hooks were mounted in a way giving better hook exposure and eliminating lever-arm effects from the lure to the hooks once a fish is hooked. This construction allowed the second change, being a shift to hooks 4-5 sizes smaller than those used on traditional hook mounts. We analysed observational data collected by volunteer anglers using either the novel rig or a standard rig mount in two types of artificial lures (softbait and hardbait) of the same size (about 17 cm). Using N  = 768 pike contacts as input data, we showed the landing rates of pike targeted with artificial lures significantly and substantially increased from 45% with normal-rigs to 85% when the same lure types were fished with the novel rig configuration. Lure type and water temperature had no effects on landing rates. Moreover, hardbaits on normal-rigs produced significantly more injury, bleeding and elevated unhooking time compared to fish captured on hardbaits with release-rigs. We conclude that simple changes to traditional hook sizes and mounts in lure fishing may benefit both anglers and the fishes that are to be released and that citizen science projects with volunteer anglers are able to provide good data in proof-of-concept studies. Further experimental studies are needed to differentiate hook size from hook mount effects because both variables were confounded in the results of the observational data presented here.

Design and commission of an experimental test rig to apply a full-scale pressure load on composite sandwich panels representative of an aircraft secondary structure

NASA Astrophysics Data System (ADS)

Crump, D. A.; Dulieu-Barton, J. M.; Savage, J.

2010-01-01

This paper describes the design of a test rig, which is used to apply a representative pressure load to a full-scale composite sandwich secondary aircraft structure. A generic panel was designed with features to represent those in the composite sandwich secondary aircraft structure. To provide full-field strain data from the panels, the test rig was designed for use with optical measurement techniques such as thermoelastic stress analysis (TSA) and digital image correlation (DIC). TSA requires a cyclic load to be applied to a structure for the measurement of the strain state; therefore, the test rig has been designed to be mounted on a standard servo-hydraulic test machine. As both TSA and DIC require an uninterrupted view of the surface of the test panel, an important consideration in the design is facilitating the optical access for the two techniques. To aid the test rig design a finite element (FE) model was produced. The model provides information on the deflections that must be accommodated by the test rig, and ensures that the stress and strain levels developed in the panel when loaded in the test rig would be sufficient for measurement using TSA and DIC. Finally, initial tests using the test rig have shown it to be capable of achieving the required pressure and maintaining a cyclic load. It was also demonstrated that both TSA and DIC data can be collected from the panels under load, which are used to validate the stress and deflection derived from the FE model.

Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells

PubMed Central

Besch, Robert; Poeck, Hendrik; Hohenauer, Tobias; Senft, Daniela; Häcker, Georg; Berking, Carola; Hornung, Veit; Endres, Stefan; Ruzicka, Thomas; Rothenfusser, Simon; Hartmann, Gunther

2009-01-01

The retinoic acid–inducible gene I (RIG-I) and melanoma differentiation–associated antigen 5 (MDA-5) helicases sense viral RNA in infected cells and initiate antiviral responses such as the production of type I IFNs. Here we have shown that RIG-I and MDA-5 also initiate a proapoptotic signaling pathway that is independent of type I IFNs. In human melanoma cells, this signaling pathway required the mitochondrial adapter Cardif (also known as IPS-1) and induced the proapoptotic BH3-only proteins Puma and Noxa. RIG-I– and MDA-5–initiated apoptosis required Noxa but was independent of the tumor suppressor p53. Triggering this pathway led to efficient activation of mitochondrial apoptosis, requiring caspase-9 and Apaf-1. Surprisingly, this proapoptotic signaling pathway was also active in nonmalignant cells, but these cells were much less sensitive to apoptosis than melanoma cells. Endogenous Bcl-xL rescued nonmalignant, but not melanoma, cells from RIG-I– and MDA-5–mediated apoptosis. In addition, we confirmed the results of the in vitro studies, demonstrating that RIG-I and MDA-5 ligands both reduced human tumor lung metastasis in immunodeficient NOD/SCID mice. These results identify an IFN-independent antiviral signaling pathway initiated by RIG-I and MDA-5 that activates proapoptotic signaling and, unless blocked by Bcl-xL, results in apoptosis. Due to their immunostimulatory and proapoptotic activity, RIG-I and MDA-5 ligands have therapeutic potential due to their ability to overcome the characteristic resistance of melanoma cells to apoptosis. PMID:19620789

36 CFR 18.7 - How are lease proposals solicited and selected if the Director issues a Request for Bids?

Code of Federal Regulations, 2010 CFR

2010-07-01

... solicited and selected if the Director issues a Request for Bids? 18.7 Section 18.7 Parks, Forests, and... § 18.7 How are lease proposals solicited and selected if the Director issues a Request for Bids? (a) If the amount of the rent is the only criterion for award of a lease, the Director may solicit bids...

BID Mediates Oxygen-Glucose Deprivation-Induced Neuronal Injury in Organotypic Hippocampal Slice Cultures and Modulates Tissue Inflammation in a Transient Focal Cerebral Ischemia Model without Changing Lesion Volume

PubMed Central

Martin, Nellie Anne; Bonner, Helena; Elkjær, Maria Louise; D’Orsi, Beatrice; Chen, Gang; König, Hans Georg; Svensson, Martina; Deierborg, Tomas; Pfeiffer, Shona; Prehn, Jochen H.; Lambertsen, Kate Lykke

2016-01-01

The BH3 interacting-domain death agonist (BID) is a pro-apoptotic protein involved in death receptor-induced and mitochondria-mediated apoptosis. Recently, it has also been suggested that BID is involved in the regulation of inflammatory responses in the central nervous system. We found that BID deficiency protected organotypic hippocampal slice cultures in vitro from neuronal injury induced by oxygen-glucose deprivation. In vivo, BID-knockout (KO) mice and wild type (WT) mice were subjected to 60 min of transient middle cerebral artery occlusion (tMCAO) to induce focal cerebral ischemia, and allowed to recover for 24 h. Infarct volumes and functional outcome were assessed and the inflammatory response was evaluated using immunofluorescence, Western blotting, quantitative PCR (qPCR) and Mesoscale multiplex analysis. We observed no difference in the infarct volume or neurological outcome between BID-KO and WT mice. The inflammatory response was reduced by BID deficiency as indicated by a change in microglial/leukocyte response. In conclusion, our data suggest that BID deficiency is neuroprotective in an in vitro model and modulates the inflammatory response to focal cerebral ischemia in vivo. However, this is not translated into a robust neuroprotection in vivo. PMID:26869884

Body Image Disturbance in 1000 Male Appearance and Performance Enhancing Drug Users

PubMed Central

Hildebrandt, Tom; Alfano, Lauren; Langenbucher, James W.

2010-01-01

Body image disturbance (BID) among men has only recently become a phenomenon of clinical significance with noted heterogeneity in the behavioral consequences of these disturbances. The degree of heterogeneity among appearance and performance enhancing drug (APED) users is unknown and an empirically derived framework for studying BID is necessary. 1000 APED users were recruited via the Internet and they completed a comprehensive online assessment APED use patterns, motivations, consequences, and BID. Data were evaluated using latent trait, latent class, and factor mixture models. Model results were validated using a range of covariates including cycle characteristics, age, APED history, and APED risk. A 1-Factor, 4-Class model provided the best fit to the data with Class 1 scoring the highest on all measures of BID and Class 4 the lowest on all measures. Class 2 differed in their preference for being lean over muscular and Class 3 preferred adding mass and size. Each class was associated with unique risks, APED history, and training identity. Not all APED users suffer from significant BID and there are unique profiles for those with elevated BID. Future research on male BID should account for this structure in order to better define relevant diagnostic categories and evaluate the clinical significance of BID. PMID:20110092

29 CFR 1926.753 - Hoisting and rigging.

Code of Federal Regulations, 2010 CFR

2010-07-01

... lift rigging procedure. (1) A multiple lift shall only be performed if the following criteria are met: (i) A multiple lift rigging assembly is used; (ii) A maximum of five members are hoisted per lift... multiple lift have been trained in these procedures in accordance with § 1926.761(c)(1). (v) No crane is...

Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway.

PubMed

Sanchez, Jacint G; Chiang, Jessica J; Sparrer, Konstantin M J; Alam, Steven L; Chi, Michael; Roganowicz, Marcin D; Sankaran, Banumathi; Gack, Michaela U; Pornillos, Owen

2016-08-02

Antiviral response pathways induce interferon by higher-order assembly of signaling complexes called signalosomes. Assembly of the RIG-I signalosome is regulated by K63-linked polyubiquitin chains, which are synthesized by the E3 ubiquitin ligase, TRIM25. We have previously shown that the TRIM25 coiled-coil domain is a stable, antiparallel dimer that positions two catalytic RING domains on opposite ends of an elongated rod. We now show that the RING domain is a separate self-association motif that engages ubiquitin-conjugated E2 enzymes as a dimer. RING dimerization is required for catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, and antiviral activity. We also provide evidence that RING dimerization and E3 ligase activity are promoted by binding of the TRIM25 SPRY domain to the RIG-I effector domain. These results indicate that TRIM25 actively participates in higher-order assembly of the RIG-I signalosome and helps to fine-tune the efficiency of the RIG-I-mediated antiviral response. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

Comparative analysis of viral RNA signatures on different RIG-I-like receptors

PubMed Central

Sanchez David, Raul Y; Combredet, Chantal; Sismeiro, Odile; Dillies, Marie-Agnès; Jagla, Bernd; Coppée, Jean-Yves; Mura, Marie; Guerbois Galla, Mathilde; Despres, Philippe; Tangy, Frédéric; Komarova, Anastassia V

2016-01-01

The RIG-I-like receptors (RLRs) play a major role in sensing RNA virus infection to initiate and modulate antiviral immunity. They interact with particular viral RNAs, most of them being still unknown. To decipher the viral RNA signature on RLRs during viral infection, we tagged RLRs (RIG-I, MDA5, LGP2) and applied tagged protein affinity purification followed by next-generation sequencing (NGS) of associated RNA molecules. Two viruses with negative- and positive-sense RNA genome were used: measles (MV) and chikungunya (CHIKV). NGS analysis revealed that distinct regions of MV genome were specifically recognized by distinct RLRs: RIG-I recognized defective interfering genomes, whereas MDA5 and LGP2 specifically bound MV nucleoprotein-coding region. During CHIKV infection, RIG-I associated specifically to the 3’ untranslated region of viral genome. This study provides the first comparative view of the viral RNA ligands for RIG-I, MDA5 and LGP2 in the presence of infection. DOI: http://dx.doi.org/10.7554/eLife.11275.001 PMID:27011352

Truncation of the C-terminal region of Toscana Virus NSs protein is critical for interferon-β antagonism and protein stability.

PubMed

Gori Savellini, Gianni; Gandolfo, Claudia; Cusi, Maria Grazia

2015-12-01

Toscana Virus (TOSV) is a Phlebovirus responsible for central nervous system (CNS) injury in humans. The TOSV non-structural protein (NSs), which interacting with RIG-I leads to its degradation, was analysed in the C terminus fragment in order to identify its functional domains. To this aim, two C-terminal truncated NSs proteins, Δ1C-NSs (aa 1-284) and Δ2C-NSs (aa 1-287) were tested. Only Δ1C-NSs did not present any inhibitory effect on RIG-I and it showed a greater stability than the whole NSs protein. Moreover, the deletion of the TLQ aa sequence interposed between the two ΔC constructs caused a greater accumulation of the protein with a weak inhibitory effect on RIG-I, indicating some involvement of these amino acids in the NSs activity. Nevertheless, all the truncated proteins were still able to interact with RIG-I, suggesting that the domains responsible for RIG-I signaling and RIG-I interaction are mapped on different regions of the protein. Copyright © 2015 Elsevier Inc. All rights reserved.

Dynamic Spin Rig Upgraded With a Five- Axis-Controlled Three-Magnetic-Bearing Support System With Forward Excitation

NASA Technical Reports Server (NTRS)

Morrison, Carlos R.; Mehmed, Oral

2003-01-01

The NASA Glenn Research Center Dynamic Spin Rig is used for experimental evaluation of vibration analysis methods and dynamic characteristics for rotating systems. Measurements are made while rotors are spun and vibrated in a vacuum chamber. The rig has been upgraded with a new active magnetic bearing rotor support and excitation system. This design is expected to provide operational improvements over the existing rig. The rig will be able to be operated in either the old or new configuration. In the old configuration, two ball bearings support the vertical shaft of the rig, with the test article located between the bearings. Because the bearings operate in a vacuum, lubrication is limited to grease. This limits bearing life and speed. In addition, the old configuration employs two voice-coil electromagnetic shakers to apply oscillatory axial forces or transverse moments to the rotor shaft through a thrust bearing. The excitation amplitudes that can be imparted to the test article with this system are not adequate for components that are highly damped. It is expected that the new design will overcome these limitations.

Validation of the Small Hot Jet Acoustic Rig for Jet Noise Research

NASA Technical Reports Server (NTRS)

Bridges, James; Brown, Clifford A.

2005-01-01

The development and acoustic validation of the Small Hot Jet Aeroacoustic Rig (SHJAR) is documented. Originally conceived to support fundamental research in jet noise, the rig has been designed and developed using the best practices of the industry. While validating the rig for acoustic work, a method of characterizing all extraneous rig noise was developed. With this in hand, the researcher can know when the jet data being measured is being contaminated and design the experiment around this limitation. Also considered is the question of uncertainty, where it is shown that there is a fundamental uncertainty of 0.5dB or so to the best experiments, confirmed by repeatability studies. One area not generally accounted for in the uncertainty analysis is the variation which can result from differences in initial condition of the nozzle shear layer. This initial condition was modified and the differences in both flow and sound were documented. The bottom line is that extreme caution must be applied when working on small jet rigs, but that highly accurate results can be made independent of scale.

Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway

DOE PAGES

Sanchez, Jacint G.; Chiang, Jessica J.; Sparrer, Konstantin M. J.; ...

2016-07-14

Antiviral response pathways induce interferon by higher-order assembly of signaling complexes called signalosomes. Assembly of the RIG-I signalosome is regulated by K63-linked polyubiquitin chains, which are synthesized by the E3 ubiquitin ligase, TRIM25. We have previously shown that the TRIM25 coiled-coil domain is a stable, antiparallel dimer that positions two catalytic RING domains on opposite ends of an elongated rod. We now show that the RING domain is a separate self-association motif that engages ubiquitin-conjugated E2 enzymes as a dimer. RING dimerization is required for catalysis, TRIM25-mediated RIG-I ubiquitination, interferon induction, and antiviral activity. We also provide evidence that RINGmore » dimerization and E3 ligase activity are promoted by binding of the TRIM25 SPRY domain to the RIG-I effector domain. These results indicate that TRIM25 actively participates in higher-order assembly of the RIG-I signalosome and helps to fine-tune the efficiency of the RIG-I-mediated antiviral response.« less

Kinematic perturbation in the flexion-extension axis for two lumbar rigs during a high impact jump task.

PubMed

Portus, Marc R; Lloyd, David G; Elliott, Bruce C; Trama, Neil L

2011-05-01

The measurement of lumbar spine motion is an important step for injury prevention research during complex and high impact activities, such as cricket fast bowling or javelin throwing. This study examined the performance of two designs of a lumbar rig, previously used in gait research, during a controlled high impact bench jump task. An 8-camera retro-reflective motion analysis system was used to track the lumbar rig. Eleven athletes completed the task wearing the two different lumbar rig designs. Flexion extension data were analyzed using a fast Fourier transformation to assess the signal power of these data during the impact phase of the jump. The lumbar rig featuring an increased and pliable base of support recorded moderately less signal power through the 0-60 Hz spectrum, with statistically less magnitudes at the 0-5 Hz (p = .039), 5-10 Hz (p = .005) and 10-20 Hz (p = .006) frequency bins. A lumbar rig of this design would seem likely to provide less noisy lumbar motion data during high impact tasks.

Mutual antagonism between the Ebola virus VP35 protein and the RIG-I activator PACT determines infection outcome.

PubMed

Luthra, Priya; Ramanan, Parameshwaran; Mire, Chad E; Weisend, Carla; Tsuda, Yoshimi; Yen, Benjamin; Liu, Gai; Leung, Daisy W; Geisbert, Thomas W; Ebihara, Hideki; Amarasinghe, Gaya K; Basler, Christopher F

2013-07-17

The cytoplasmic pattern recognition receptor RIG-I is activated by viral RNA and induces type I IFN responses to control viral replication. The cellular dsRNA binding protein PACT can also activate RIG-I. To counteract innate antiviral responses, some viruses, including Ebola virus (EBOV), encode proteins that antagonize RIG-I signaling. Here, we show that EBOV VP35 inhibits PACT-induced RIG-I ATPase activity in a dose-dependent manner. The interaction of PACT with RIG-I is disrupted by wild-type VP35, but not by VP35 mutants that are unable to bind PACT. In addition, PACT-VP35 interaction impairs the association between VP35 and the viral polymerase, thereby diminishing viral RNA synthesis and modulating EBOV replication. PACT-deficient cells are defective in IFN induction and are insensitive to VP35 function. These data support a model in which the VP35-PACT interaction is mutually antagonistic and plays a fundamental role in determining the outcome of EBOV infection. Copyright © 2013 Elsevier Inc. All rights reserved.

A Robust Open Ascending-price Multi-unit Auction Protocol against False-name Bids

NASA Astrophysics Data System (ADS)

Iwasaki, Atsushi; Yokoo, Makoto; Terada, Kenji

This paper develops a new ascending-price multi-unit auction protocol that has following characteristics: (i) it has an open format, (ii) sincere bidding is an equilibrium strategy even if the marginal utilities of each agent can increase and agents can submit false-name bids. False-name bids are bids submitted under fictitious names such as multiple e-mail addresses, which can be done easily in the Internet. This is the first protocol that has these two characteristics. We show that our new protocol outperforms an existing protocol, which satisfies (ii), with respect to the social surplus and the seller's revenue.

Alternative contracting research : [project summary].

DOT National Transportation Integrated Search

2016-09-01

To conserve taxpayer money, many governmental agencies use a low-bid process for design : and construction services. The Florida Department of Transportations (FDOT) Design-Bid-Build : process falls in this category. However, a low-bid approach do...

Emerging Role of Ubiquitination in Antiviral RIG-I Signaling

PubMed Central

Maelfait, Jonathan

2012-01-01

Summary: Detection of viruses by the innate immune system involves the action of specialized pattern recognition receptors. Intracellular RIG-I receptors sense the presence of viral nucleic acids in infected cells and trigger signaling pathways that lead to the production of proinflammatory and antiviral proteins. Over the past few years, posttranslational modification of RIG-I and downstream signaling proteins by different types of ubiquitination has been found to be a key event in the regulation of RIG-I-induced NF-κB and interferon regulatory factor 3 (IRF3) activation. Multiple ubiquitin ligases, deubiquitinases, and ubiquitin binding scaffold proteins contribute to both positive and negative regulation of the RIG-I-induced antiviral immune response. A better understanding of the function and activity of these proteins might eventually lead to the development of novel therapeutic approaches for management of viral diseases. PMID:22390971

BIDS apps: Improving ease of use, accessibility, and reproducibility of neuroimaging data analysis methods

PubMed Central

Auer, Tibor; Churchill, Nathan W.; Flandin, Guillaume; Guntupalli, J. Swaroop; Raffelt, David; Quirion, Pierre-Olivier; Smith, Robert E.; Strother, Stephen C.; Varoquaux, Gaël

2017-01-01

The rate of progress in human neurosciences is limited by the inability to easily apply a wide range of analysis methods to the plethora of different datasets acquired in labs around the world. In this work, we introduce a framework for creating, testing, versioning and archiving portable applications for analyzing neuroimaging data organized and described in compliance with the Brain Imaging Data Structure (BIDS). The portability of these applications (BIDS Apps) is achieved by using container technologies that encapsulate all binary and other dependencies in one convenient package. BIDS Apps run on all three major operating systems with no need for complex setup and configuration and thanks to the comprehensiveness of the BIDS standard they require little manual user input. Previous containerized data processing solutions were limited to single user environments and not compatible with most multi-tenant High Performance Computing systems. BIDS Apps overcome this limitation by taking advantage of the Singularity container technology. As a proof of concept, this work is accompanied by 22 ready to use BIDS Apps, packaging a diverse set of commonly used neuroimaging algorithms. PMID:28278228

Welfare Impact of Virtual Trading on Wholesale Electricity Markets

NASA Astrophysics Data System (ADS)

Giraldo, Juan S.

Virtual bidding has become a standard feature of multi-settlement wholesale electricity markets in the United States. Virtual bids are financial instruments that allow market participants to take financial positions in the Day-Ahead (DA) market that are automatically reversed/closed in the Real-Time (RT) market. Most U.S. wholesale electricity markets only have two types of virtual bids: a decrement bid (DEC), which is virtual load, and an increment offer (INC), which is virtual generation. In theory, financial participants create benefits by seeking out profitable bidding opportunities through arbitrage or speculation. Benefits have been argued to take the form of increased competition, price convergence, increased market liquidity, and a more efficient dispatch of generation resources. Studies have found that price convergence between the DA and RT markets improved following the introduction of virtual bidding into wholesale electricity markets. The improvement in price convergence was taken as evidence that market efficiency had increased and many of the theoretical benefits realized. Persistent price differences between the DA and RT markets have led to calls to further expand virtual bidding as a means to address remaining market inefficiencies. However, the argument that price convergence is beneficial is extrapolated from the study of commodity and financial markets and the role of futures for increasing market efficiency in that context. This viewpoint largely ignores details that differentiate wholesale electricity markets from other commodity markets. This dissertation advances the understanding of virtual bidding by evaluating the impact of virtual bidding based on the standard definition of economic efficiency which is social welfare. In addition, an examination of the impacts of another type of virtual bid, up-to-congestion (UTC) transactions is presented. This virtual product significantly increased virtual bidding activity in the PJM interconnection market since it became available to be used by financial traders in September 2010. Stylized models are used to determine the optimal bidding strategy for the different virtual bids under different scenarios. The welfare analysis shows that the main impact of virtual bidding is surplus reallocation and that the impact on market efficiency is small by comparison. The market structure is such that it is more likely to see surplus transfers from consumers to producers. The results also show that outcomes with greater price convergence as a result of virtual bidding activity were not necessarily more efficient, nor do they always correct surplus distribution distortions that result from bias in the DA expectation of RT load. Compared to INCs and DECs, the UTC analysis showed that UTCs do not have the same self-corrective incentives towards price convergence and are less likely to lead to nodal price convergence or correct for surplus distribution distortions caused by uncertainty and bias in the DA expectation of RT load. Additionally, the analysis showed that UTCs allow financial traders to engage in low risk high volume trading strategies that, while profitable, may have little to no impact on price convergence or market efficiency.

41 CFR 102-38.225 - What are the additional requirements in the bid process?

Code of Federal Regulations, 2010 CFR

2010-07-01

... bid process? All sales except fixed price sales must contain a certification of independent price... matter to the Department of Justice or your agency's Office of the Inspector General. Bid Deposits ...

48 CFR 14.304 - Submission, modification, and withdrawal of bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... transmitted bid, the data received must not be viewed and, where practicable, must be purged from primary and backup data storage systems. (f) The contracting officer must promptly notify any bidder if its bid...

48 CFR 14.304 - Submission, modification, and withdrawal of bids.

Code of Federal Regulations, 2014 CFR

2014-10-01

... transmitted bid, the data received must not be viewed and, where practicable, must be purged from primary and backup data storage systems. (f) The contracting officer must promptly notify any bidder if its bid...

48 CFR 14.303 - Modification or withdrawal of bids.

Code of Federal Regulations, 2013 CFR

2013-10-01

... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not be viewed and shall be purged from primary and backup data storage systems. [48 FR 42171, Sept. 19, 1983, as...

48 CFR 14.303 - Modification or withdrawal of bids.

Code of Federal Regulations, 2012 CFR

2012-10-01

... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not be viewed and shall be purged from primary and backup data storage systems. [48 FR 42171, Sept. 19, 1983, as...

48 CFR 14.304 - Submission, modification, and withdrawal of bids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... transmitted bid, the data received must not be viewed and, where practicable, must be purged from primary and backup data storage systems. (f) The contracting officer must promptly notify any bidder if its bid...

48 CFR 14.304 - Submission, modification, and withdrawal of bids.

Code of Federal Regulations, 2013 CFR

2013-10-01

... transmitted bid, the data received must not be viewed and, where practicable, must be purged from primary and backup data storage systems. (f) The contracting officer must promptly notify any bidder if its bid...

48 CFR 14.304 - Submission, modification, and withdrawal of bids.

Code of Federal Regulations, 2012 CFR

2012-10-01

... transmitted bid, the data received must not be viewed and, where practicable, must be purged from primary and backup data storage systems. (f) The contracting officer must promptly notify any bidder if its bid...

48 CFR 14.303 - Modification or withdrawal of bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not be viewed and shall be purged from primary and backup data storage systems. [48 FR 42171, Sept. 19, 1983, as...

48 CFR 14.303 - Modification or withdrawal of bids.

Code of Federal Regulations, 2014 CFR

2014-10-01

... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not be viewed and shall be purged from primary and backup data storage systems. [48 FR 42171, Sept. 19, 1983, as...

48 CFR 14.303 - Modification or withdrawal of bids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... for the bid. (c) Upon withdrawal of an electronically transmitted bid, the data received shall not be viewed and shall be purged from primary and backup data storage systems. [48 FR 42171, Sept. 19, 1983, as...

An Assessment of the Armed Forces of the Philippines Modernization Program

DTIC Science & Technology

2007-12-14

Sayaff Group BAC Bids and Awards Committee BCDA Bases Conversion and Development Authority BEP Bid Evaluation Plan BIR Bureau of Internal Revenue...contractor execute the requirements of the contract with regard to cost, schedule and performance (Sammet and Green 1990, 136) Bid Evaluation Plan or BEP is...adopted in the evaluation and assessment of bidders’ statements and the method and criteria for the evaluation and assessment of bids. The BEP also

Advertising and Sealed Bid Auctions in a Transshipment Game

DTIC Science & Technology

1996-06-01

distributors promote their sales by advertising . While the maximum quantity demanded by each customer is fixed and given, his bids on the various...brands are determined by the advertising and other promotional efforts. The bid response function for each consumer is supposed to be given and known. The...the optimal distribution of the product, and the bids of the consumers . A numerical example is provided and the solution routine is discussed.

Smarter than others? Conjectures in lowest unique bid auctions.

PubMed

Zhou, Cancan; Dong, Hongguang; Hu, Rui; Chen, Qinghua

2015-01-01

Research concerning various types of auctions, such as English auctions, Dutch auctions, highest-price sealed-bid auctions, and second-price sealed-bid auctions, is always a topic of considerable interest in interdisciplinary fields. The type of auction, known as a lowest unique bid auction (LUBA), has also attracted significant attention. Various models have been proposed, but they often fail to explain satisfactorily the real bid-distribution characteristics. This paper discusses LUBA bid-distribution characteristics, including the inverted-J shape and the exponential decrease in the upper region. The authors note that this type of distribution, which initially increases and later decreases, cannot be derived from the symmetric Nash equilibrium framework based on perfect information that has previously been used. A novel optimization model based on non-perfect information is presented. The kernel of this model is the premise that agents make decisions to achieve maximum profit based on imaginary information or assumptions regarding the behavior of others.

Molecular characterisation of RIG-I-like helicases in the black flying fox, Pteropus alecto.

PubMed

Cowled, Christopher; Baker, Michelle L; Zhou, Peng; Tachedjian, Mary; Wang, Lin-Fa

2012-04-01

The RIG-I like helicases, RIG-I, mda5 and LGP2 are an evolutionarily conserved family of cytosolic pattern recognition receptors important in the recognition of viral RNA, and responsible for the innate induction of interferons and proinflammatory cytokines upon viral infection. Bats are natural reservoir hosts to a variety of RNA viruses that cause significant morbidity and mortality in other species; however the mechanisms responsible for the control of viral replication in bats are not understood. This report describes the molecular cloning and expression analysis of RIG-I, mda5 and LGP2 genes in the fruit bat Pteropus alecto, and is the first description of RIG-I like helicases from any species of bat. Our results demonstrate that P. alecto RIG-I, mda5 and LGP2 have similar primary structures and tissue expression patterns to their counterparts in humans and other mammals. Stimulation of bat kidney cells with synthetic dsRNA (poly I:C) induced high levels of interferon β and rapid upregulation of all three helicases. These findings reveal that the cytoplasmic virus sensing machinery is present and intact in P. alecto. This study provides the foundation for further investigations into the interactions between bat RIG-I-like helicases and viruses to elucidate the mechanisms responsible for the asymptomatic nature of viral infections in bats. Crown Copyright © 2011. Published by Elsevier Ltd. All rights reserved.

Increasing Geothermal Energy Demand: The Need for Urbanization of the Drilling Industry

ERIC Educational Resources Information Center

Teodoriu, Catalin; Falcone, Gioia

2008-01-01

Drilling wells in urban spaces requires special types of rigs that do not conflict with the surrounding environment. For this, a mutation of the current drilling equipment is necessary into what can be defined as an "urbanized drilling rig." Noise reduction, small footprint, and "good looking" rigs all help persuade the general public to accept…

Minimizing forced outage risk in generator bidding

NASA Astrophysics Data System (ADS)

Das, Dibyendu

Competition in power markets has exposed the participating companies to physical and financial uncertainties. Generator companies bid to supply power in a day-ahead market. Once their bids are accepted by the ISO they are bound to supply power. A random outage after acceptance of bids forces a generator to buy power from the expensive real-time hourly spot market and sell to the ISO at the set day-ahead market clearing price, incurring losses. A risk management technique is developed to assess this financial risk associated with forced outages of generators and then minimize it. This work presents a risk assessment module which measures the financial risk of generators bidding in an open market for different bidding scenarios. The day-ahead power market auction is modeled using a Unit Commitment algorithm and a combination of Normal and Cauchy distributions generate the real time hourly spot market. Risk profiles are derived and VaRs are calculated at 98 percent confidence level as a measure of financial risk. Risk Profiles and VaRs help the generators to analyze the forced outage risk and different factors affecting it. The VaRs and the estimated total earning for different bidding scenarios are used to develop a risk minimization module. This module will develop a bidding strategy of the generator company such that its estimated total earning is maximized keeping the VaR below a tolerable limit. This general framework of a risk management technique for the generating companies bidding in competitive day-ahead market can also help them in decisions related to building new generators.

Hybrid promoters directed tBid gene expression to breast cancer cells by transcriptional targeting.

PubMed

Farokhimanesh, Samila; Rahbarizadeh, Fatemeh; Rasaee, Mohammad J; Kamali, Abbas; Mashkani, Baratali

2010-01-01

Developing cancer gene therapy constructs based on transcriptional targeting of genes to cancer cells is a new and promising modality for treatment of cancer. Introducing truncated Bid (tBid), a recently known member of the Bcl-2 family, eradicates cancer cells efficiently. For transcriptional targeting of tBid, two dual-specificity promoters, combining cancer specific core promoters and response modules, were designed. These two core promoter modules contained cancer specific promoters of MUC1 and Survivin genes accompanied by hypoxia-responsive elements and estrogen responsive elements (microenvironment condition of breast cancer cells) which were employed to achieve a higher and more specific level of tBid expression in breast cancer cells. Correlation of the level of tBid expression in normal and cancer cell lines with promoter activity was measured by RT-PCR after treatment with hypoxia and estrogen. The level of tBid expression under control of new hybrid promoters was compared with its expression under control of cytomegalovirus (CMV) promoter as a control. Our data revealed that the level of tBid expression in breast cancer cells were nearly 11 times more than normal cells because of the cancer specific promoters, although tBid expression under control of CMV promoter was almost the same in normal and cancer cell lines. Increased apoptosis was detected in the transfected breast cancer cell lines by the Caspase-3 activity assay. The application of these promoters may prove to have the advantage of tumor selective gene therapy in breast cancer cells and low-potential toxicity for normal tissues.

48 CFR 614.402-70 - Waiver of public opening of bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of public opening of bids. Overseas posts may request waiver of the public opening of bids if that activity is inconsistent with local law or legal practice, or with post security. For that purpose, the...

47 CFR 90.910 - Bidding credits.

Code of Federal Regulations, 2011 CFR

2011-10-01

... cost of its winning bid on Spectrum Blocks A through V. A winning bidder that qualifies as a small... percent to lower the cost of its winning bid on Spectrum Blocks A through V. [68 FR 43001, July 21, 2003] ...

47 CFR 90.910 - Bidding credits.

Code of Federal Regulations, 2014 CFR

2014-10-01

... cost of its winning bid on Spectrum Blocks A through V. A winning bidder that qualifies as a small... percent to lower the cost of its winning bid on Spectrum Blocks A through V. [68 FR 43001, July 21, 2003] ...

47 CFR 90.910 - Bidding credits.

Code of Federal Regulations, 2013 CFR

2013-10-01

... cost of its winning bid on Spectrum Blocks A through V. A winning bidder that qualifies as a small... percent to lower the cost of its winning bid on Spectrum Blocks A through V. [68 FR 43001, July 21, 2003] ...

47 CFR 90.910 - Bidding credits.

Code of Federal Regulations, 2012 CFR

2012-10-01

... cost of its winning bid on Spectrum Blocks A through V. A winning bidder that qualifies as a small... percent to lower the cost of its winning bid on Spectrum Blocks A through V. [68 FR 43001, July 21, 2003] ...

24 CFR 891.535 - Requirements for awarding construction contracts.

Code of Federal Regulations, 2012 CFR

2012-04-01

... be an opportunity for minority owned and women owned businesses to be awarded a contract. (1) Bids... the right to reject any or all bids and to waive any informality. (3) The bid form, which must be...

A method for testing railway wheel sets on a full-scale roller rig

NASA Astrophysics Data System (ADS)

Liu, Binbin; Bruni, Stefano

2015-09-01

Full-scale roller rigs for tests on a single axle enable the investigation of several dynamics and durability problems related with the design and operation of the railway rolling stock. In order to exploit the best potential of this test equipment, appropriate test procedures need to be defined, particularly in terms of actuators' references, to make sure that meaningful wheel -rail contact conditions can be reproduced. The aim of this paper is to propose a new methodology to define the forces to be generated by the actuators in the rig in order to best reproduce the behaviour of a wheel set and especially the wheel -rail contact forces in a running condition of interest as obtained either from multi-body system (MBS) simulation or from on-track measurements. The method is supported by the use of a mathematical model of the roller rig and uses an iterative correction scheme, comparing the time histories of the contact force components from the roller rig test as predicted by the mathematical model to a set of target contact force time histories. Two methods are introduced, the first one considering a standard arrangement of the roller rig, the second one assuming that a differential gear is introduced in the rig, allowing different rolling speeds of the two rollers. Results are presented showing that the deviation of the roller rig test results from the considered targets can be kept within low tolerances (1% approximately) as far as the vertical and lateral contact forces on both wheels are concerned. For the longitudinal forces, larger deviations are obtained except in the case where a differential gear is introduced.

Development of a low cost test rig for standalone WECS subject to electrical faults.

PubMed

Himani; Dahiya, Ratna

2016-11-01

In this paper, a contribution to the development of low-cost wind turbine (WT) test rig for stator fault diagnosis of wind turbine generator is proposed. The test rig is developed using a 2.5kW, 1750 RPM DC motor coupled to a 1.5kW, 1500 RPM self-excited induction generator interfaced with a WT mathematical model in LabVIEW. The performance of the test rig is benchmarked with already proven wind turbine test rigs. In order to detect the stator faults using non-stationary signals in self-excited induction generator, an online fault diagnostic technique of DWT-based multi-resolution analysis is proposed. It has been experimentally proven that for varying wind conditions wavelet decomposition allows good differentiation between faulty and healthy conditions leading to an effective diagnostic procedure for wind turbine condition monitoring. Copyright © 2016 ISA. Published by Elsevier Ltd. All rights reserved.

Regenerative Fuel Cell Test Rig at Glenn Research Center

NASA Technical Reports Server (NTRS)

Chang, Bei-Jiann; Johnson, Donald W.; Garcia, Christopher P.; Jakupca, Ian J.; Scullin, Vincent J.; Bents, David J.

2003-01-01

The regenerative fuel cell development effort at Glenn Research Center (GRC) involves the integration of a dedicated fuel cell and electrolyzer into an energy storage system test rig. The test rig consists of a fuel cell stack, an electrolysis stack, cooling pumps, a water transfer pump, gas recirculation pumps, phase separators, storage tanks for oxygen (O2) and hydrogen (H2), heat exchangers, isolation valves, pressure regulators, interconnecting tubing, nitrogen purge provisions, and instrumentation for control and monitoring purposes. The regenerative fuel cell (RFC) thus formed is a completely closed system which is capable of autonomous cyclic operation. The test rig provides direct current (DC) load and DC power supply to simulate power consumption and solar power input. In addition, chillers are used as the heat sink to dissipate the waste heat from the electrochemical stack operation. Various vents and nitrogen (N2) sources are included in case inert purging is necessary to safe the RFC test rig.

NASA Lewis Research Center lean-, rich-burn materials test burner rig

NASA Technical Reports Server (NTRS)

Stearns, C. A.; Robinson, R. C.

1994-01-01

The lean-, rich-burn materials test burner rig at NASA LeRC is used to evaluate the high temperature environmental durability of aerospace materials. The rig burns jet fuel and pressurized air, and sample materials can be subjected to both lean-burn and rich-burn environments. As part of NASA's Enabling Propulsion Materials (EPM) program, an existing rig was adapted to simulate the rich-burn quick-quench lean-burn (RQL) combustor concept which is being considered for the HSCT (high speed civil transport) aircraft. RQL materials requirements exceed that of current superalloys, thus ceramic matrix composites (CMC's) emerged as the leading candidate materials. The performance of these materials in the quasi reducing environment of the rich-burn section of the RQL is of fundamental importance to materials development. This rig was developed to conduct such studies, and its operation and capabilities are described.

Advanced Control Surface Seal Development at NASA GRC for Future Space Launch Vehicles

NASA Technical Reports Server (NTRS)

Dunlap, Patrick H., Jr.; Steinetz, Bruce M.; DeMange, Jeffrey J.

2003-01-01

NASA s Glenn Research Center (GRC) is developing advanced control surface seal technologies for future space launch vehicles as part of the Next Generation Launch Technology project (NGLT). New resilient seal designs are currently being fabricated and high temperature seal preloading devices are being developed as a means of improving seal resiliency. GRC has designed several new test rigs to simulate the temperatures, pressures, and scrubbing conditions that seals would have to endure during service. A hot compression test rig and hot scrub test rig have been developed to perform tests at temperatures up to 3000 F. Another new test rig allows simultaneous seal flow and scrub tests at room temperature to evaluate changes in seal performance with scrubbing. These test rigs will be used to evaluate the new seal designs. The group is also performing tests on advanced TPS seal concepts for Boeing using these new test facilities.

A New High-Speed Oil-Free Turbine Engine Rotordynamic Simulator Test Rig

NASA Technical Reports Server (NTRS)

Howard, Samuel A.

2007-01-01

A new test rig has been developed for simulating high-speed turbomachinery rotor systems using Oil-Free foil air bearing technology. Foil air bearings have been used in turbomachinery, primarily air cycle machines, for the past four decades to eliminate the need for oil lubrication. The goal of applying this bearing technology to other classes of turbomachinery has prompted the fabrication of this test rig. The facility gives bearing designers the capability to test potential bearing designs with shafts that simulate the rotating components of a target machine without the high cost of building "make-and-break" hardware. The data collected from this rig can be used to make design changes to the shaft and bearings in subsequent design iterations. This paper describes the new test rig and demonstrates its capabilities through the initial run with a simulated shaft system.

A review of turbulent-boundary-layer heat transfer research at Stanford, 1958-1983

NASA Technical Reports Server (NTRS)

Moffat, R. J.; Kays, W. M.

1984-01-01

For the past 25 years, there has existed in the Thermosciences Laboratory of the Mechanical Engineering Department of Stanford University a research program, primarily experimental, concerned with heat transfer through turbulent boundary layers. In the early phases of the program, the topics considered were the simple zero-pressure-gradient turbulent boundary layer with constant and with varying surface temperature, and the accelerated boundary layer. Later equilibrium boundary layers were considered along with factors affecting the boundary layer, taking into account transpired flows, flows with axial pressure gradients, transpiration, acceleration, deceleration, roughness, full-coverage film cooling, surface curvature, free convection, and mixed convection. A description is provided of the apparatus and techniques used, giving attention to the smooth plate rig, the rough plate rig, the full-coverage film cooling rig, the curvature rig, the concave wall rig, the mixed convection tunnel, and aspects of data reduction and uncertainty analysis.

Myths, Misconceptions, and Realities about Public Procurement Automation.

ERIC Educational Resources Information Center

Bonner, Larry

1989-01-01

Meaningful public procurement and inventory management automation encompasses all purchasing and materials management processes, including bidder selection; bidder responsiveness tracking; preparation of bid solicitations; bid tabulation; the tracking of requisitions, bid solicitations, and deliveries; and item purchasing history reports. (MLH)

43 CFR 2710.0-6 - Policy.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of public lands under this section shall be conducted under competitive bidding procedures... competitive bidding or without competitive bidding. In recognizing public policies, the Secretary shall give... considered in determining the method of sale. These factors include, but are not limited to: Competitive...

47 CFR 90.1021 - Definitions concerning competitive bidding process.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Definitions concerning competitive bidding process. 90.1021 Section 90.1021 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY... 220 MHz Service § 90.1021 Definitions concerning competitive bidding process. (a) Scope. The...

48 CFR 245.7304 - Informal bid procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Inventory 245.7304 Informal bid procedures. (a) Upon approval of the plant clearance officer, the contractor...— (1) Maximum practical competition is maintained; (2) Sources solicited are recorded; and (3) Informal... plant clearance officer prior to soliciting bids from other prospective bidders. ...

The effects of exenatide twice daily compared to insulin lispro added to basal insulin in Latin American patients with type 2 diabetes: A retrospective analysis of the 4B trial.

PubMed

de Lapertosa, Silvia Beatriz Gorban; Frechtel, Gustavo; Hardy, Elise; Sauque-Reyna, Leobardo

2016-12-01

Socioeconomic changes in Latin American countries have led to an increased prevalence of type 2 diabetes (T2D). We examined the effects of exenatide twice daily (BID) or insulin lispro, each added to insulin glargine, in Latin American patients with T2D. This was a subgroup analysis of patients from Argentina and Mexico in the 4B study (N=114). Patients with glycated hemoglobin (HbA1c) of 7.0-10.0% (53-86mmol/mol) after 12weeks of intensive basal insulin optimization were randomized to exenatide BID or thrice-daily insulin lispro added to insulin glargine and metformin. After 30weeks, addition of exenatide BID or insulin lispro resulted in significant (P<0.0001) reductions in HbA1c (exenatide BID: -0.9% [-10mmol/mol]; insulin lispro: -1.2% [-13mmol/mol]). Weight was stable in the exenatide BID group (-0.1kg) and increased significantly (+3.4kg; P<0.0001) with insulin lispro. Major and minor hypoglycemia occurred less frequently (40 vs. 253 events) with exenatide BID compared with insulin lispro. Gastrointestinal adverse events of nausea, diarrhea, and vomiting occurred more frequently with exenatide BID than with insulin lispro. Both exenatide BID and prandial insulin lispro, each added to basal insulin glargine, were effective at reducing HbA1c in Latin American patients. Treatment with exenatide BID resulted in stable weight but more gastrointestinal adverse events. Treatment with insulin lispro resulted in weight gain and an increased risk of hypoglycemia. These findings support the addition of exenatide BID to insulin glargine as an option for Latin American patients unable to achieve glycemic control on basal insulin alone. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Bad and Bid - potential background players in preneoplastic to neoplastic shift in human endometrium.

PubMed

Driak, D; Dvorska, M; Bolehovska, P; Svandova, I; Novotny, J; Halaska, M

2014-01-01

The most common malignancies of the female genital tract are endometrial carcinomas, whose are generally proceeded by hyperplasia. The maintenance of tissue homeostasis is to great extent governed by apoptosis, whose defects can lead to the preneoplastic and/or cancerous changes. Endometrial apoptosis involves among others three groups of proteins of the Bcl-2 family. First group contains anti-apoptotic proteins (e. g. Bcl-2, Bcl-xL). The other two groups belong to the pro-apoptotic proteins with three (e. g. Bax, Bak) or one (e. g. Bad, Bid) so-called BH domains. Bad and Bid trigger the oligomerization of Bak and Bax protein, which permeabilize the outer mitochondrial wall. Unlike Bid, Bad cannot directly trigger apoptosis. Instead, Bad lowers the threshold at which apoptosis is induced, by binding anti-apoptotic Bcl-2 proteins. However, their mutual counterbalance or synergism in the human endometrium has not been reported yet.In this study, the levels of Bid and Bad were measured using SDS-PAGE and Western blotting with specific antibodies, with the aim to analyse expression of Bid and Bad proteins in normal (NE), hyperplastic (HE) and cancerous (CE) endometrium. We demonstrated that Bid expression in CE reached only 47% and 50% of this observed in NE and HE. Conversely, Bad expression in HE reached only 40% and 36% of this observed in NE and CE, respectively. We detected no significant changes of Bid expression between HE and NE, and levels of Bad protein were not different between CE and NE.Trend of Bid and Bad protein expression is clearly opposite in HE and CE. We hypothesise that disrupted apoptotic program in CE seems to be reduced further by lowering levels of direct apoptotic trigger protein Bid. We suggest that the adenocarcinoma tissue of human endometrium thus tries to strengthen its apoptotic effort by lowering the apoptotic threshold via higher Bad levels.

New drilling rigs

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

Tubb, M.

1981-03-01

Rig builders maintain their frantic work pace to meet drilling contractors' orders for new mobile units - principally the jack-up and semis now so popular. Leading new rig client is Santa Fe Drilling, which has ordered its seventh new offshore unit. The order includes two Enhanced 9500 Pacesetter Series semis, each scheduled to cost $80 million, to be built by Daewoo Shipbuilding and Heavy Machinery in Korea.

[Body image dissatisfaction as a mediator of the association between BMI, self-esteem and mental health in early adolescents: a multiple-group path analysis across gender].

PubMed

Jang, Mi Heui; Lee, Gyungjoo

2013-04-01

This study was done to examine not only the relationships between body mass index (BMI), self-esteem, body image dissatisfaction (BID) and mental health, according to gender, but the mediating role of BID on mental health in relation to BMI and self-esteem among early adolescents. Data from 576 (296 boys and 280 girls) elementary school students in grades 5 to 6 were collected. A multiple-group path analysis was utilized to examine the relationships between BMI, self-esteem, BID and mental health by gender. In the path analysis for all students, poor mental health was related directly to BID, while it was indirectly related to BMI and self-esteem. In the multiple-group path analysis of both genders, BID was found to have a significant direct and indirect effect on mental health for girls alone. The findings suggested that BID should be examined early to prevent poor mental health in early adolescent girls. This study helps to elucidate the role of early adolescent BID on mental health and provides insight for further prevention and intervention programs in school and community mental health settings.

Switch from type II to I Fas/CD95 death signaling upon in vitro culturing of primary hepatocytes

PubMed Central

Walter, Dorothée; Schmich, Kathrin; Vogel, Sandra; Pick, Robert; Kaufmann, Thomas; Hochmuth, Florian Christoph; Haber, Angelika; Neubert, Karin; McNelly, Sabine; von Weizsäcker, Fritz; Merfort, Irmgard; Maurer, Ulrich; Strasser, Andreas; Borner, Christoph

2010-01-01

Fas/CD95-induced apoptosis of hepatocytes in vivo proceeds through the so-called type II pathway, requiring the pro-apoptotic BH3-only Bcl-2 family member Bid for mitochondrial death signaling. Consequently, Bid-deficient mice are protected from anti-Fas antibody injection induced fatal hepatitis. Here we report the unexpected finding that freshly isolated mouse hepatocytes, cultured on collagen or Matrigel™, become independent of Bid for Fas-induced apoptosis, thereby switching death signaling from type II to type I. In such in vitro cultures, FasL activates caspase-3 without Bid cleavage, Bax/Bak activation or cytochrome c release, and neither Bid ablation nor Bcl-2 overexpression is protective. The type II to type I switch depends on extracellular matrix adhesion, as primary hepatocytes in suspension die in a Bid-dependent manner. Moreover, the switch is specific for FasL-induced apoptosis as collagen-plated Bid-deficient hepatocytes are protected from TNFα/ActD-induced apoptosis. Conclusion Our data suggest a selective crosstalk between extracellular matrix and Fas-mediated signaling which favours mitochondria-independent type I apoptosis induction. PMID:19003879

Switch from type II to I Fas/CD95 death signaling on in vitro culturing of primary hepatocytes.

PubMed

Walter, Dorothée; Schmich, Kathrin; Vogel, Sandra; Pick, Robert; Kaufmann, Thomas; Hochmuth, Florian Christoph; Haber, Angelika; Neubert, Karin; McNelly, Sabine; von Weizsäcker, Fritz; Merfort, Irmgard; Maurer, Ulrich; Strasser, Andreas; Borner, Christoph

2008-12-01

Fas/CD95-induced apoptosis of hepatocytes in vivo proceeds through the so-called type II pathway, requiring the proapoptotic BH3-only Bcl-2 family member Bid for mitochondrial death signaling. Consequently, Bid-deficient mice are protected from anti-Fas antibody injection induced fatal hepatitis. We report the unexpected finding that freshly isolated mouse hepatocytes, cultured on collagen or Matrigel, become independent of Bid for Fas-induced apoptosis, thereby switching death signaling from type II to type I. In such in vitro cultures, Fas ligand (FasL) activates caspase-3 without Bid cleavage, Bax/Bak activation or cytochrome c release, and neither Bid ablation nor Bcl-2 overexpression is protective. The type II to type I switch depends on extracellular matrix adhesion, as primary hepatocytes in suspension die in a Bid-dependent manner. Moreover, the switch is specific for FasL-induced apoptosis as collagen-plated Bid-deficient hepatocytes are protected from tumor necrosis factor alpha/actinomycin D (TNFalpha/ActD)-induced apoptosis. Our data suggest a selective crosstalk between extracellular matrix and Fas-mediated signaling that favors mitochondria-independent type I apoptosis induction.

[Brain activitivation of euthymic patients with Type I bipolar disorder in resting state Default Mode Network].

PubMed

Vargas, Cristian; Pineda, Julián; Calvo, Víctor; López-Jaramillo, Carlos

2014-01-01

As there are still doubts about brain connectivity in type I bipolar disorder (BID), resting-state functional magnetic resonance imaging (RS-fMRI) studies are necessary during euthymia for a better control of confounding factors. To evaluate the differences in brain activation between euthymic BID patients and control subjects using resting state- functional-magnetic resonance imaging (RS-fMRI), and to identify the lithium effect in these activations. A cross-sectional study was conducted on 21 BID patients (10 receiving lithium only, and 11 non-medicated) and 12 healthy control subjects, using RS fMRI and independent component analysis (ICA). Increased activation was found in the right hippocampus (P=.049) and posterior cingulate (P=.040) within the Default Mode Network (DMN) when BID and control group were compared. No statistically significant differences were identified between BID on lithium only therapy and non-medicated BID patients. The results suggest that there are changes in brain activation and connectivity in BID even during euthymic phase and mainly within the DMN network, which could be relevant in affect regulation. Copyright © 2013 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.

Laboratory facility for testing electric-vehicle batteries Test rig for simulating duty cycles with different discharge modes

NASA Astrophysics Data System (ADS)

Hamilton, J. A.; Rand, D. A. J.

1983-03-01

A test rig has been designed and constructed to examine the performance of batteries under laboratory conditions that simulate the power characteristics of electric vehicles. Each station in the rig subjects a battery to continuous charge/discharge cycles, with an equalising charge every eighth cycle. The battery discharge follows the current-verse-time profile of a given vehicle operating under a driving schedule normal to road service. The test rig allows both smooth- and pulsed-current discharge to be investigated. Data collection is accomplished either with multi-pen recorders or with a computer-based information logger.

Regulation of WNT Signaling at the Neuromuscular Junction by the Immunoglobulin Superfamily Protein RIG-3 in Caenorhabditis elegans

PubMed Central

Pandey, Pratima; Bhardwaj, Ashwani; Babu, Kavita

2017-01-01

Perturbations in synaptic function could affect the normal behavior of an animal, making it important to understand the regulatory mechanisms of synaptic signaling. Previous work has shown that in Caenorhabditis elegans an immunoglobulin superfamily protein, RIG-3, functions in presynaptic neurons to maintain normal acetylcholine receptor levels at the neuromuscular junction (NMJ). In this study, we elucidate the molecular and functional mechanism of RIG-3. We demonstrate by genetic and BiFC (Bi-molecular Fluorescence Complementation) assays that presynaptic RIG-3 functions by directly interacting with the immunoglobulin domain of the nonconventional Wnt receptor, ROR receptor tyrosine kinase (RTK), CAM-1, which functions in postsynaptic body-wall muscles. This interaction in turn inhibits Wnt/LIN-44 signaling through the ROR/CAM-1 receptor, and allows for maintenance of normal acetylcholine receptor, AChR/ACR-16, levels at the neuromuscular synapse. Further, this work reveals that RIG-3 and ROR/CAM-1 function through the β-catenin/HMP-2 at the NMJ. Taken together, our results demonstrate that RIG-3 functions as an inhibitory molecule of the Wnt/LIN-44 signaling pathway through the RTK, CAM-1. PMID:28515212

Large Eddy Simulations of the Tilted Rig Experiment: A Two-dimensional Rayleigh-Taylor Instability Case

NASA Astrophysics Data System (ADS)

Rollin, Bertrand; Denissen, Nicholas A.; Reisner, Jon M.; Andrews, Malcolm J.

2012-11-01

The tilted rig experiment is a derivative of the rocket rig experiment designed to investigate turbulent mixing induced by the Rayleigh-Taylor (RT) instability. A tank containing two fluids of different densities is accelerated downwards between two parallel guiding rods by rocket motors. The acceleration is such that the pressure and density gradients face opposite directions at the fluids interface, creating a Rayleigh-Taylor unstable configuration. The rig is tilted such that the tank is initially at an angle and the acceleration is not perpendicular to the fluids interface when the rockets fire. This results in a two dimensional Rayleigh-Taylor instability case where the fluids experience RT mixing and a bulk overturning motion. The tilted rig is therefore a valuable experiment to help calibrating two-dimensional mixing models. Large Eddy Simulations of the tilted rig experiments will be compared to available experimental results. A study of the behavior of turbulence variables relevant to turbulence modeling will be presented. LA-UR 12-23829. This work was performed for the U.S. Department of Energy by Los Alamos National Laboratory under Contract No.DEAC52- 06NA2-5396.

Towards the control of the modal energy transfer in transverse mode instabilities

NASA Astrophysics Data System (ADS)

Stihler, Christoph; Jauregui, Cesar; Tünnermann, Andreas; Limpert, Jens

2018-02-01

Thermally-induced refractive index gratings (RIG) in high-power fiber laser systems lead to transverse mode instabilities (TMI) above a certain average power threshold. The effect of TMI is currently the main limitation for the further average power scaling of fiber lasers and amplifiers with nearly diffraction-limited beam quality. In this work we experimentally investigate, for the first time, the growth of the RIG strength by introducing a phase-shift between the RIG and the modal interference pattern in a fiber amplifier. The experiments reveal that the RIG is strong enough to couple energy between different transverse modes even at powers significantly below the TMI threshold, provided that the introduced phase-shift is high enough. This indicates that, as the strength of the RIG further increases with increasing average output power, the RIG becomes more and more sensitive to even small noise-induced phase-shifts, which ultimately trigger TMI. Furthermore, it is shown that a beam cleaning also occurs when a positive phase-shift is introduced, even above the TMI threshold. This finding will pave the way for the development of a new class of mitigation strategies for TMI, which key feature is the control of the introduced phase-shift.

Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity.

PubMed

Chiang, Jessica J; Sparrer, Konstantin M J; van Gent, Michiel; Lässig, Charlotte; Huang, Teng; Osterrieder, Nikolaus; Hopfner, Karl-Peter; Gack, Michaela U

2018-01-01

The sensor RIG-I detects double-stranded RNA derived from RNA viruses. Although RIG-I is also known to have a role in the antiviral response to DNA viruses, physiological RNA species recognized by RIG-I during infection with a DNA virus are largely unknown. Using next-generation RNA sequencing (RNAseq), we found that host-derived RNAs, most prominently 5S ribosomal RNA pseudogene 141 (RNA5SP141), bound to RIG-I during infection with herpes simplex virus 1 (HSV-1). Infection with HSV-1 induced relocalization of RNA5SP141 from the nucleus to the cytoplasm, and virus-induced shutoff of host protein synthesis downregulated the abundance of RNA5SP141-interacting proteins, which allowed RNA5SP141 to bind RIG-I and induce the expression of type I interferons. Silencing of RNA5SP141 strongly dampened the antiviral response to HSV-1 and the related virus Epstein-Barr virus (EBV), as well as influenza A virus (IAV). Our findings reveal that antiviral immunity can be triggered by host RNAs that are unshielded following depletion of their respective binding proteins by the virus.

Local infiltration of rabies immunoglobulins without systemic intramuscular administration: An alternative cost effective approach for passive immunization against rabies

PubMed Central

Bharti, Omesh Kumar; Madhusudana, Shampur Narayan; Gaunta, Pyare Lal; Belludi, Ashwin Yajaman

2016-01-01

ABSTRACT Presently the dose of rabies immunoglobulin (RIG) which is an integral part of rabies post exposure prophylaxis (PEP) is calculated based on body weight though the recommendation is to infiltrate the wound(s). This practice demands large quantities of RIG which may be unaffordable to many patients. In this background, we conducted this study to know if the quantity and cost of RIG can be reduced by restricting passive immunization to local infiltration alone and avoiding systemic intramuscular administration based on the available scientific evidence. Two hundred and sixty nine category III patients bitten by suspect or confirmed rabid dogs/animals were infiltrated with equine rabies immunoglobulin (ERIGs) in and around the wound. The quantity of ERIG used was proportionate to the size and number of wounds irrespective of their body weight. They were followed with a regular course of rabies vaccination by intra-dermal route. As against 363 vials of RIGs required for all these cases as per current recommendation based on body weight, they required only 42 vials of 5ml RIG. Minimum dose of RIGs given was 0.25 ml and maximum dose given was 8 ml. On an average 1.26 ml of RIGs was required per patient that costs Rs. 150 ($3). All the patients were followed for 9 months and they were healthy and normal at the end of observation period. With local infiltration, that required small quantities of RIG, the RIGs could be made available to all patients in times of short supply in the market. A total of 30 (11%) serum samples of patients were tested for rabies virus neutralizing antibodies by the rapid fluorescent focus inhibition test (RFFIT) and all showed antibody titers >0.5 IU/mL by day 14. In no case the dose was higher than that required based on body weight and no immunosuppression resulted. To conclude, this pilot study shows that local infiltration of RIG need to be considered in times of non-availability in the market or unaffordability by poor patients. This preliminary study needs to be done on larger scale in other centers with long term follow up to substantiate the results of our study. PMID:26317441

Estimating procedure for major highway construction bid item cost : final report.

DOT National Transportation Integrated Search

1978-06-01

The present procedure for estimating construction bid item cost makes use of the quarterly weighted average unit price report coupled with engineering judgement. The limitation to this method is that this report format provides only the lowest bid da...

42 CFR 414.422 - Terms of contracts.

Code of Federal Regulations, 2011 CFR

2011-10-01

...) MEDICARE PROGRAM PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES Competitive Bidding for Certain... exercised by CMS, for the full duration of the contract period. (b) Recompeting competitive bidding contracts. CMS recompetes competitive bidding contracts at least once every 3 years. (c) Nondiscrimination...

42 CFR 414.422 - Terms of contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

...) MEDICARE PROGRAM PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES Competitive Bidding for Certain... exercised by CMS, for the full duration of the contract period. (b) Recompeting competitive bidding contracts. CMS recompetes competitive bidding contracts at least once every 3 years. (c) Nondiscrimination...

7 CFR 1726.201 - Formal competitive bidding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Procurement Procedures § 1726.201 Formal... formal competitive bidding: (a) Selection of qualified bidders. The borrower (acting through its engineer... § 1726.23). (b) Invitations to bid. The borrower (acting through its engineer, if applicable) is...

7 CFR 1726.201 - Formal competitive bidding.

Code of Federal Regulations, 2013 CFR

2013-01-01

... AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Procurement Procedures § 1726.201 Formal... formal competitive bidding: (a) Selection of qualified bidders. The borrower (acting through its engineer... § 1726.23). (b) Invitations to bid. The borrower (acting through its engineer, if applicable) is...

7 CFR 1726.201 - Formal competitive bidding.

Code of Federal Regulations, 2014 CFR

2014-01-01

... AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Procurement Procedures § 1726.201 Formal... formal competitive bidding: (a) Selection of qualified bidders. The borrower (acting through its engineer... § 1726.23). (b) Invitations to bid. The borrower (acting through its engineer, if applicable) is...

7 CFR 1726.201 - Formal competitive bidding.

Code of Federal Regulations, 2012 CFR

2012-01-01

... AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Procurement Procedures § 1726.201 Formal... formal competitive bidding: (a) Selection of qualified bidders. The borrower (acting through its engineer... § 1726.23). (b) Invitations to bid. The borrower (acting through its engineer, if applicable) is...

7 CFR 1726.201 - Formal competitive bidding.

Code of Federal Regulations, 2011 CFR

2011-01-01

... AGRICULTURE ELECTRIC SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Procurement Procedures § 1726.201 Formal... formal competitive bidding: (a) Selection of qualified bidders. The borrower (acting through its engineer... § 1726.23). (b) Invitations to bid. The borrower (acting through its engineer, if applicable) is...

47 CFR 1.2203 - Competitive bidding mechanisms.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Random Selection Competitive Bidding Proceedings Broadcast Television Spectrum Reverse Auction § 1.2203... forward auction assigning new spectrum licenses will occur. (2) Reserve price. Reserve prices, either... winning bid. A winning bidder will relinquish spectrum usage rights pursuant to the terms of any winning...

Bidding: Getting the Best Price for School Foodservice.

ERIC Educational Resources Information Center

DiBella, Cecilia M.

1998-01-01

Sharon (Massachusetts) Public Schools developed an alternative procurement process for school food services that complies with state public bidding laws while evading "low-bid" constraints. The new process features evaluative criteria covering nutrition education, community outreach, management expertise, site visits, and price…

Tofacitinib induction and maintenance therapy in East Asian patients with active ulcerative colitis: subgroup analyses from three phase 3 multinational studies.

PubMed

Motoya, Satoshi; Watanabe, Mamoru; Kim, Hyo Jong; Kim, Young Ho; Han, Dong Soo; Yuasa, Hirotoshi; Tabira, Junichi; Isogawa, Naoki; Arai, Shoko; Kawaguchi, Isao; Hibi, Toshifumi

2018-04-01

Tofacitinib is an oral, small-molecule Janus kinase inhibitor being investigated for ulcerative colitis (UC). In OCTAVE Induction 1 and 2, patients with moderately to severely active UC received placebo or tofacitinib 10 mg twice daily (BID) for 8 weeks. Clinical responders in OCTAVE Induction were re-randomized to 52 weeks' therapy with placebo, tofacitinib 5 mg BID, or tofacitinib 10 mg BID. We conducted post-hoc efficacy and safety analyses of East Asian patients in OCTAVE Induction 1 and 2 and OCTAVE Sustain. A total of 121 East Asian (Japan, Korea, and Taiwan) patients were randomized in OCTAVE Induction 1 and 2 (placebo, n=26; tofacitinib 10 mg BID, n=95), and 63 in OCTAVE Sustain (placebo, n=20; tofacitinib 5 mg BID, n=22; tofacitinib 10 mg BID, n=21). At week 8 of OCTAVE Induction 1 and 2, 18.9% of patients (18/95) achieved remission with tofacitinib 10 mg BID versus 3.8% (1/26) with placebo. In OCTAVE Sustain, the week 52 remission rates were 45.5% (10/22), 47.6% (10/21), and 15.0% (3/20) with 5 mg BID, 10 mg BID, and placebo, respectively. Adverse event rates were similar between groups in OCTAVE Induction and numerically higher with tofacitinib in OCTAVE Sustain. Serious adverse event rates were similar across groups in all studies. Infections were numerically more frequent with tofacitinib than placebo. Increases in serum lipid levels were observed with tofacitinib. In East Asian patients with UC, tofacitinib demonstrated numerically greater efficacy versus placebo as induction and maintenance therapy, with a safety profile consistent with the global study population. ClinicalTrials.gov: NCT01465763; NCT01458951; NCT01458574.

Adenovirus-mediated truncated Bid overexpression induced by the Cre/LoxP system promotes the cell apoptosis of CD133+ ovarian cancer stem cells.

PubMed

Long, Qifang; Yang, Ru; Lu, Weixian; Zhu, Weipei; Zhou, Jundong; Zheng, Cui; Zhou, Dongmei; Yu, Ling; Wu, Jinchang

2017-01-01

Cancer stem cells are a small subset of cancer cells that contribute to cancer progression, metastasis, chemoresistance and recurrence. CD133-positive (CD133+) ovarian cancer cells have been identified as ovarian cancer stem cells. Adenovirus-mediated gene therapy is an innovative therapeutic method for cancer treatment. In the present study, we aimed to develop a new gene therapy to specifically eliminate CD133+ ovarian cancer stem cells by targeting CD133. We used the Cre/LoxP system to augment the selective expression of the truncated Bid (tBid) gene as suicide gene therapy in CD133+ ovarian cancer stem cells. The adenovirus (Ad)-CD133-Cre expressing Cre recombinase under the control of the CD133 promoter and Ad-CMV-LoxP-Neo-LoxP-tBid expressing tBid under the control of the CMV promoter were successfully constructed using the Cre/LoxP switching system. The co-infection of Ad-CMV-LoxP-Neo-LoxP-tBid and Ad-CD133-Cre selectively induced tBid overexpression, which inhibited cell growth and triggered the cell apoptosis of CD133+ ovarian cancer stem cells. The Cre/LoxP system-mediated tBid overexpression activated the pro-apoptotic signaling pathway and augmented the cytotoxic effect of cisplatin in CD133+ ovarian cancer stem cells. Furthermore, in xenograft experiments, co-infection with the two recombinant adenoviruses markedly suppressed tumor growth in vivo and promoted cell apoptosis in tumor tissues. Taken together, the present study provides evidence that the adenovirus-mediated tBid overexpression induced by the Cre/LoxP system can effectively eliminate CD133+ ovarian cancer stem cells, representing a novel therapeutic strategy for the treatment of ovarian cancer.

Apixaban 5 and 2.5 mg twice-daily versus warfarin for stroke prevention in nonvalvular atrial fibrillation patients: Comparative effectiveness and safety evaluated using a propensity-score-matched approach.

PubMed

Li, Xiaoyan; Keshishian, Allison; Hamilton, Melissa; Horblyuk, Ruslan; Gupta, Kiran; Luo, Xuemei; Mardekian, Jack; Friend, Keith; Nadkarni, Anagha; Pan, Xianying; Lip, Gregory Y H; Deitelzweig, Steve

2018-01-01

Prior real-world studies have shown that apixaban is associated with a reduced risk of stroke/systemic embolism (stroke/SE) and major bleeding versus warfarin. However, few studies evaluated the effectiveness and safety of apixaban according to its dosage, and most studies contained limited numbers of patients prescribed 2.5 mg twice-daily (BID) apixaban. Using pooled data from 4 American claims database sources, baseline characteristics and outcomes for patients prescribed 5 mg BID and 2.5 mg BID apixaban versus warfarin were compared. After 1:1 propensity-score matching, 31,827 5 mg BID apixaban-matched warfarin patients and 6600 2.5 mg BID apixaban-matched warfarin patients were identified. Patients prescribed 2.5 mg BID apixaban were older, had clinically more severe comorbidities, and were more likely to have a history of stroke and bleeding compared with 5 mg BID apixaban patients. Compared with warfarin, 5 mg BID apixaban was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.70, 95% confidence interval [CI]: 0.60-0.81) and major bleeding (HR: 0.59, 95% CI: 0.53-0.66). Compared with warfarin, 2.5 mg BID apixaban was also associated with a lower risk of stroke/SE (HR: 0.63, 95% CI: 0.49-0.81) and major bleeding (HR: 0.59, 95% CI: 0.49-0.71). In this real-world study, both apixaban doses were assessed in 2 patient groups differing in age and clinical characteristics. Each apixaban dose was associated with a lower risk of stroke/SE and major bleeding compared with warfarin in the distinct population for which it is being prescribed in United States clinical practice. Clinicaltrials.Gov Identifier: NCT03087487.

The autoinhibitory CARD2-Hel2i Interface of RIG-I governs RNA selection.

PubMed

Ramanathan, Anand; Devarkar, Swapnil C; Jiang, Fuguo; Miller, Matthew T; Khan, Abdul G; Marcotrigiano, Joseph; Patel, Smita S

2016-01-29

RIG-I (Retinoic Acid Inducible Gene-I) is a cytosolic innate immune receptor that detects atypical features in viral RNAs as foreign to initiate a Type I interferon signaling response. RIG-I is present in an autoinhibited state in the cytoplasm and activated by blunt-ended double-stranded (ds)RNAs carrying a 5' triphosphate (ppp) moiety. These features found in many pathogenic RNAs are absent in cellular RNAs due to post-transcriptional modifications of RNA ends. Although RIG-I is structurally well characterized, the mechanistic basis for RIG-I's remarkable ability to discriminate between cellular and pathogenic RNAs is not completely understood. We show that RIG-I's selectivity for blunt-ended 5'-ppp dsRNAs is ≈3000 times higher than non-blunt ended dsRNAs commonly found in cellular RNAs. Discrimination occurs at multiple stages and signaling RNAs have high affinity and ATPase turnover rate and thus a high katpase/Kd. We show that RIG-I uses its autoinhibitory CARD2-Hel2i (second CARD-helicase insertion domain) interface as a barrier to select against non-blunt ended dsRNAs. Accordingly, deletion of CARDs or point mutations in the CARD2-Hel2i interface decreases the selectivity from ≈3000 to 150 and 750, respectively. We propose that the CARD2-Hel2i interface is a 'gate' that prevents cellular RNAs from generating productive complexes that can signal. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Testing for voter rigging in small polling stations

PubMed Central

Jimenez, Raúl; Hidalgo, Manuel; Klimek, Peter

2017-01-01

Nowadays, a large number of countries combine formal democratic institutions with authoritarian practices. Although in these countries the ruling elites may receive considerable voter support, they often use several manipulation tools to control election outcomes. A common practice of these regimes is the coercion and mobilization of large numbers of voters. This electoral irregularity is known as voter rigging, distinguishing it from vote rigging, which involves ballot stuffing or stealing. We develop a statistical test to quantify the extent to which the results of a particular election display traces of voter rigging. Our key hypothesis is that small polling stations are more susceptible to voter rigging because it is easier to identify opposing individuals, there are fewer eyewitnesses, and interested parties might reasonably expect fewer visits from election observers. We devise a general statistical method for testing whether voting behavior in small polling stations is significantly different from the behavior in their neighbor stations in a way that is consistent with the widespread occurrence of voter rigging. On the basis of a comparative analysis, the method enables third parties to conclude that an explanation other than simple variability is needed to explain geographic heterogeneities in vote preferences. We analyze 21 elections in 10 countries and find significant statistical anomalies compatible with voter rigging in Russia from 2007 to 2011, in Venezuela from 2006 to 2013, and in Uganda in 2011. Particularly disturbing is the case of Venezuela, where the smallest polling stations were decisive to the outcome of the 2013 presidential elections. PMID:28695193

Type I IFN triggers RIG-I/TLR3/NLRP3-dependent inflammasome activation in influenza A virus infected cells.

PubMed

Pothlichet, Julien; Meunier, Isabelle; Davis, Beckley K; Ting, Jenny P-Y; Skamene, Emil; von Messling, Veronika; Vidal, Silvia M

2013-01-01

Influenza A virus (IAV) triggers a contagious and potentially lethal respiratory disease. A protective IL-1β response is mediated by innate receptors in macrophages and lung epithelial cells. NLRP3 is crucial in macrophages; however, which sensors elicit IL-1β secretion in lung epithelial cells remains undetermined. Here, we describe for the first time the relative roles of the host innate receptors RIG-I (DDX58), TLR3, and NLRP3 in the IL-1β response to IAV in primary lung epithelial cells. To activate IL-1β secretion, these cells employ partially redundant recognition mechanisms that differ from those described in macrophages. RIG-I had the strongest effect through a MAVS/TRIM25/Riplet-dependent type I IFN signaling pathway upstream of TLR3 and NLRP3. Notably, RIG-I also activated the inflammasome through interaction with caspase 1 and ASC in primary lung epithelial cells. Thus, NS1, an influenza virulence factor that inhibits the RIG-I/type I IFN pathway, strongly modulated the IL-1β response in lung epithelial cells and in ferrets. The NS1 protein derived from a highly pathogenic strain resulted in increased interaction with RIG-I and inhibited type I IFN and IL-1β responses compared to the least pathogenic virus strains. These findings demonstrate that in IAV-infected lung epithelial cells RIG-I activates the inflammasome both directly and through a type I IFN positive feedback loop.

Testing for voter rigging in small polling stations.

PubMed

Jimenez, Raúl; Hidalgo, Manuel; Klimek, Peter

2017-06-01

Nowadays, a large number of countries combine formal democratic institutions with authoritarian practices. Although in these countries the ruling elites may receive considerable voter support, they often use several manipulation tools to control election outcomes. A common practice of these regimes is the coercion and mobilization of large numbers of voters. This electoral irregularity is known as voter rigging, distinguishing it from vote rigging, which involves ballot stuffing or stealing. We develop a statistical test to quantify the extent to which the results of a particular election display traces of voter rigging. Our key hypothesis is that small polling stations are more susceptible to voter rigging because it is easier to identify opposing individuals, there are fewer eyewitnesses, and interested parties might reasonably expect fewer visits from election observers. We devise a general statistical method for testing whether voting behavior in small polling stations is significantly different from the behavior in their neighbor stations in a way that is consistent with the widespread occurrence of voter rigging. On the basis of a comparative analysis, the method enables third parties to conclude that an explanation other than simple variability is needed to explain geographic heterogeneities in vote preferences. We analyze 21 elections in 10 countries and find significant statistical anomalies compatible with voter rigging in Russia from 2007 to 2011, in Venezuela from 2006 to 2013, and in Uganda in 2011. Particularly disturbing is the case of Venezuela, where the smallest polling stations were decisive to the outcome of the 2013 presidential elections.

GUCY2C Signaling Opposes the Acute Radiation-Induced GI Syndrome.

PubMed

Li, Peng; Wuthrick, Evan; Rappaport, Jeff A; Kraft, Crystal; Lin, Jieru E; Marszalowicz, Glen; Snook, Adam E; Zhan, Tingting; Hyslop, Terry M; Waldman, Scott A

2017-09-15

High doses of ionizing radiation induce acute damage to epithelial cells of the gastrointestinal (GI) tract, mediating toxicities restricting the therapeutic efficacy of radiation in cancer and morbidity and mortality in nuclear disasters. No approved prophylaxis or therapy exists for these toxicities, in part reflecting an incomplete understanding of mechanisms contributing to the acute radiation-induced GI syndrome (RIGS). Guanylate cyclase C (GUCY2C) and its hormones guanylin and uroguanylin have recently emerged as one paracrine axis defending intestinal mucosal integrity against mutational, chemical, and inflammatory injury. Here, we reveal a role for the GUCY2C paracrine axis in compensatory mechanisms opposing RIGS. Eliminating GUCY2C signaling exacerbated RIGS, amplifying radiation-induced mortality, weight loss, mucosal bleeding, debilitation, and intestinal dysfunction. Durable expression of GUCY2C, guanylin, and uroguanylin mRNA and protein by intestinal epithelial cells was preserved following lethal irradiation inducing RIGS. Oral delivery of the heat-stable enterotoxin (ST), an exogenous GUCY2C ligand, opposed RIGS, a process requiring p53 activation mediated by dissociation from MDM2. In turn, p53 activation prevented cell death by selectively limiting mitotic catastrophe, but not apoptosis. These studies reveal a role for the GUCY2C paracrine hormone axis as a novel compensatory mechanism opposing RIGS, and they highlight the potential of oral GUCY2C agonists (Linzess; Trulance) to prevent and treat RIGS in cancer therapy and nuclear disasters. Cancer Res; 77(18); 5095-106. ©2017 AACR . ©2017 American Association for Cancer Research.

47 CFR 80.1251 - Maritime communications subject to competitive bidding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Maritime communications subject to competitive... AND SPECIAL RADIO SERVICES STATIONS IN THE MARITIME SERVICES Competitive Bidding Procedures § 80.1251 Maritime communications subject to competitive bidding. Mutually exclusive initial applications for VPCSA...

32 CFR 274.8 - Bids-revocations-rejections-postponements.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 2 2011-07-01 2011-07-01 false Bids-revocations-rejections-postponements. 274.8 Section 274.8 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS REGULATIONS GOVERNING COMPETITIVE BIDDING ON U.S. GOVERNMENT GUARANTEED MILITARY...

32 CFR 274.8 - Bids-revocations-rejections-postponements.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false Bids-revocations-rejections-postponements. 274.8 Section 274.8 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS REGULATIONS GOVERNING COMPETITIVE BIDDING ON U.S. GOVERNMENT GUARANTEED MILITARY...

48 CFR 1814.302 - Bid submission. (NASA supplements paragraph (b))

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 6 2012-10-01 2012-10-01 false Bid submission. (NASA supplements paragraph (b)) 1814.302 Section 1814.302 Federal Acquisition Regulations System NATIONAL... 1814.302 Bid submission. (NASA supplements paragraph (b)) (b) NASA contracting officers shall not...

48 CFR 1814.302 - Bid submission. (NASA supplements paragraph (b))

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 6 2011-10-01 2011-10-01 false Bid submission. (NASA supplements paragraph (b)) 1814.302 Section 1814.302 Federal Acquisition Regulations System NATIONAL... 1814.302 Bid submission. (NASA supplements paragraph (b)) (b) NASA contracting officers shall not...

48 CFR 1814.302 - Bid submission. (NASA supplements paragraph (b))

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 6 2010-10-01 2010-10-01 true Bid submission. (NASA supplements paragraph (b)) 1814.302 Section 1814.302 Federal Acquisition Regulations System NATIONAL... 1814.302 Bid submission. (NASA supplements paragraph (b)) (b) NASA contracting officers shall not...

48 CFR 1814.302 - Bid submission. (NASA supplements paragraph (b))

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 6 2013-10-01 2013-10-01 false Bid submission. (NASA supplements paragraph (b)) 1814.302 Section 1814.302 Federal Acquisition Regulations System NATIONAL... 1814.302 Bid submission. (NASA supplements paragraph (b)) (b) NASA contracting officers shall not...

48 CFR 1814.302 - Bid submission. (NASA supplements paragraph (b))

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 6 2014-10-01 2014-10-01 false Bid submission. (NASA supplements paragraph (b)) 1814.302 Section 1814.302 Federal Acquisition Regulations System NATIONAL... 1814.302 Bid submission. (NASA supplements paragraph (b)) (b) NASA contracting officers shall not...

48 CFR 314.103 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CONTRACT TYPES SEALED BIDDING Use of Sealed Bidding 314.103 Policy. EIT products and services, including EIT deliverables such as electronic documents and reports, acquired using sealed-bid procedures shall... determinations for EIT products and services that do not meet some or all of the applicable Section 508...

13 CFR 305.10 - Bid underrun.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Bid underrun. 305.10 Section 305.10 Business Credit and Assistance ECONOMIC DEVELOPMENT ADMINISTRATION, DEPARTMENT OF COMMERCE PUBLIC WORKS AND ECONOMIC DEVELOPMENT INVESTMENTS Requirements for Approved Projects § 305.10 Bid underrun. If...

47 CFR 101.1101 - LMDS service subject to competitive bidding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false LMDS service subject to competitive bidding. 101.1101 Section 101.1101 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Competitive Bidding Procedures for LMDS § 101.1101 LMDS...

47 CFR 101.1101 - LMDS service subject to competitive bidding.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false LMDS service subject to competitive bidding. 101.1101 Section 101.1101 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Competitive Bidding Procedures for LMDS § 101.1101 LMDS...

47 CFR 101.1101 - LMDS service subject to competitive bidding.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false LMDS service subject to competitive bidding. 101.1101 Section 101.1101 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Competitive Bidding Procedures for LMDS § 101.1101 LMDS...

47 CFR 101.1101 - LMDS service subject to competitive bidding.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false LMDS service subject to competitive bidding. 101.1101 Section 101.1101 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Competitive Bidding Procedures for LMDS § 101.1101 LMDS...

47 CFR 101.1101 - LMDS service subject to competitive bidding.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false LMDS service subject to competitive bidding. 101.1101 Section 101.1101 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Competitive Bidding Procedures for LMDS § 101.1101 LMDS...

Rationality, irrationality and escalating behavior in lowest unique bid auctions.

PubMed

Radicchi, Filippo; Baronchelli, Andrea; Amaral, Luís A N

2012-01-01

Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions--lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of "bid space". The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets.

Issues in bidding for contracts for occupational therapy services.

PubMed

Harms, S; Law, M

2001-06-01

There is an increasing number of occupational therapists in Canada who are involved in bidding for contracts to deliver occupational therapy services. Occupational therapists working in an institutional or community-based setting may not have had the responsibility of developing a proposal or a marketing plan for bidding purposes. However, the responsibility of developing a bid to compete for a service delivery contract often rests on occupational therapists who are sole practitioners in a private practice setting. The purpose of this paper is to highlight issues in the literature such as service delivery plans, marketing strategies and costing of services that can assist the occupational therapist in the development of a contractual bid. A specific clinical example, school therapy services, has been used to illustrate how these strategies can be applied to practice. Success in contractual bids appears to be primarily influenced by cost of the service, the expertise of the service provider, ability to provide coordinated care, ease of access for clients, and inclusion of methods to measure client outcome.

Rationality, Irrationality and Escalating Behavior in Lowest Unique Bid Auctions

PubMed Central

Radicchi, Filippo; Baronchelli, Andrea; Amaral, Luís A. N.

2012-01-01

Information technology has revolutionized the traditional structure of markets. The removal of geographical and time constraints has fostered the growth of online auction markets, which now include millions of economic agents worldwide and annual transaction volumes in the billions of dollars. Here, we analyze bid histories of a little studied type of online auctions – lowest unique bid auctions. Similarly to what has been reported for foraging animals searching for scarce food, we find that agents adopt Lévy flight search strategies in their exploration of “bid space”. The Lévy regime, which is characterized by a power-law decaying probability distribution of step lengths, holds over nearly three orders of magnitude. We develop a quantitative model for lowest unique bid online auctions that reveals that agents use nearly optimal bidding strategies. However, agents participating in these auctions do not optimize their financial gain. Indeed, as long as there are many auction participants, a rational profit optimizing agent would choose not to participate in these auction markets. PMID:22279553

Effect of Lorcaserin Alone and in Combination with Phentermine on Food Cravings After 12-Week Treatment: A Randomized Substudy.

PubMed

Rebello, Candida J; Nikonova, Elena V; Zhou, Sharon; Aronne, Louis J; Fujioka, Ken; Garvey, W Timothy; Smith, Steven R; Coulter, Ann A; Greenway, Frank L

2018-02-01

This study evaluated the effect of lorcaserin 10 mg twice daily (LOR BID), or with phentermine 15 mg once daily (LOR BID + PHEN QD) and 15 mg twice daily (LOR BID + PHEN BID), in conjunction with energy restriction on food cravings. Two hundred and thirty-five patients without diabetes but with obesity or overweight and ≥ 1 comorbidity received LOR BID, LOR BID + PHEN QD, or LOR BID + PHEN BID for 12 weeks in a randomized double-blind study. The Food Craving Inventory (FCI) and the Control of Eating Questionnaire (COEQ) were administered over 12 weeks. The FCI total score and the subscale scores reduced from baseline in all groups. The least squares means (95% confidence intervals) for the total scores were -0.65 (-0.75 to -0.55), -0.75 (-0.84 to -0.65), and -0.84 (-0.95 to -0.74) in the LOR BID, LOR BID + PHEN QD, and LOR BID + PHEN BID groups, respectively. Cravings assessed by COEQ reduced from baseline in all groups. In general, the combination treatments were more effective than lorcaserin alone. At week 12, except for fruit juice and dairy products, general and specific cravings reduced in LOR BID + PHEN BID compared with LOR BID (P < 0.05). Lorcaserin in combination with phentermine improves control of food cravings during short-term energy restriction. © 2018 The Obesity Society.

Evaluation of a novel helium ionization detector within the context of (low-)flow modulation comprehensive two-dimensional gas chromatography.

PubMed

Franchina, Flavio A; Maimone, Mariarosa; Sciarrone, Danilo; Purcaro, Giorgia; Tranchida, Peter Q; Mondello, Luigi

2015-07-10

The present research is focused on the use and evaluation of a novel helium ionization detector, defined as barrier discharge ionization detector (BID), within the context of (low-)flow modulation comprehensive two-dimensional gas chromatography (FM GC×GC). The performance of the BID device was compared to that of a flame ionization detector (FID), under similar FM GC×GC conditions. Following development and optimization of the FM GC×GC method, the BID was subjected to fine tuning in relation to acquisition frequency and discharge flow. Moreover, the BID performance was measured and compared to that of the FID, in terms of extra-column band broadening, sensitivity and dynamic range. The comparative study was carried out by using standard compounds belonging to different chemical classes, along with a sample of diesel fuel. Advantages and disadvantages of the BID system, also within the context of FM GC×GC, are critically discussed. In general, the BID system was characterized by a more limited dynamic range and increased sensitivity, compared to the FID. Additionally, BID and FID contribution to band broadening was found to be similar under the operational conditions applied. Particular attention was devoted to the behaviour of the FM GC×GC-BID system toward saturated and aromatic hydrocarbons, for a possible future use in the field of mineral-oil food contamination research. Copyright © 2015 Elsevier B.V. All rights reserved.

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

McCann, D.; White, D.

This paper reports on a smart alarm system installed on a number of offshore rigs and one land rig which can detect kicks more quickly than conventional systems. This rapid kick detection improves rig safety because the smaller the detected influx, the easier it is to control the well. The extensive computerized monitoring system helps drilling personnel detect fluid influxes and fluid losses before the changes in flow would normally be apparent.

The Effect of Applied Tensile Stress on Localized Corrosion in Sensitized AA5083

DTIC Science & Technology

2015-09-01

of stainless steel 4-point bending rig used to apply elastic stress to aluminum plate samples. (Bottom) Stress- strain data based on displacement and...ASTM-G39, from [25]. ..........................20 Figure 13. Photograph of stainless steel 4-point bending rig used to apply elastic stress to...aluminum plate samples, from [8]. ....................................................20 Figure 14. Photograph of stainless steel 4-point bending rig

A numerical model of a HIL scaled roller rig for simulation of wheel-rail degraded adhesion condition

NASA Astrophysics Data System (ADS)

Conti, Roberto; Meli, Enrico; Pugi, Luca; Malvezzi, Monica; Bartolini, Fabio; Allotta, Benedetto; Rindi, Andrea; Toni, Paolo

2012-05-01

Scaled roller rigs used for railway applications play a fundamental role in the development of new technologies and new devices, combining the hardware in the loop (HIL) benefits with the reduction of the economic investments. The main problem of the scaled roller rig with respect to the full scale ones is the improved complexity due to the scaling factors. For this reason, before building the test rig, the development of a software model of the HIL system can be useful to analyse the system behaviour in different operative conditions. One has to consider the multi-body behaviour of the scaled roller rig, the controller and the model of the virtual vehicle, whose dynamics has to be reproduced on the rig. The main purpose of this work is the development of a complete model that satisfies the previous requirements and in particular the performance analysis of the controller and of the dynamical behaviour of the scaled roller rig when some disturbances are simulated with low adhesion conditions. Since the scaled roller rig will be used to simulate degraded adhesion conditions, accurate and realistic wheel-roller contact model also has to be included in the model. The contact model consists of two parts: the contact point detection and the adhesion model. The first part is based on a numerical method described in some previous studies for the wheel-rail case and modified to simulate the three-dimensional contact between revolute surfaces (wheel-roller). The second part consists in the evaluation of the contact forces by means of the Hertz theory for the normal problem and the Kalker theory for the tangential problem. Some numerical tests were performed, in particular low adhesion conditions were simulated, and bogie hunting and dynamical imbalance of the wheelsets were introduced. The tests were devoted to verify the robustness of control system with respect to some of the more frequent disturbances that may influence the roller rig dynamics. In particular we verified that the wheelset imbalance could significantly influence system performance, and to reduce the effect of this disturbance a multistate filter was designed.

24 CFR 891.535 - Requirements for awarding construction contracts.

Code of Federal Regulations, 2010 CFR

2010-04-01

... bidding (formal advertising) in selecting a construction contractor or the negotiated noncompetitive... be an opportunity for minority owned and women owned businesses to be awarded a contract. (1) Bids... forth for opening of bids. In addition, the invitation shall be publicly advertised. (2) The invitation...

24 CFR 891.535 - Requirements for awarding construction contracts.

Code of Federal Regulations, 2011 CFR

2011-04-01

... bidding (formal advertising) in selecting a construction contractor or the negotiated noncompetitive... be an opportunity for minority owned and women owned businesses to be awarded a contract. (1) Bids... forth for opening of bids. In addition, the invitation shall be publicly advertised. (2) The invitation...

47 CFR 1.2113 - Construction prior to grant of application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Competitive Bidding Proceedings General Procedures § 1.2113 Construction prior to grant of application. Subject to the provisions of this section, applicants for licenses awarded by competitive bidding may..., applicants must not begin to construct facilities for licenses subject to competitive bidding. (a) When...

47 CFR 1.2113 - Construction prior to grant of application.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Competitive Bidding Proceedings General Procedures § 1.2113 Construction prior to grant of application. Subject to the provisions of this section, applicants for licenses awarded by competitive bidding may..., applicants must not begin to construct facilities for licenses subject to competitive bidding. (a) When...

48 CFR 52.214-16 - Minimum Bid Acceptance Period.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Minimum Bid Acceptance Period. 52.214-16 Section 52.214-16 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... date specified in this solicitation for receipt of bids. (b) This provision supersedes any language...

47 CFR 27.209 - Designated entities; bidding credits; unjust enrichment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 2 2010-10-01 2010-10-01 false Designated entities; bidding credits; unjust enrichment. 27.209 Section 27.209 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON... 2305-2320 MHz and 2345-2360 MHz Bands § 27.209 Designated entities; bidding credits; unjust enrichment...

32 CFR 274.6 - Submission of bids.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false Submission of bids. 274.6 Section 274.6 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS REGULATIONS GOVERNING COMPETITIVE BIDDING ON U.S. GOVERNMENT GUARANTEED MILITARY EXPORT LOAN AGREEMENTS § 274...

32 CFR 274.7 - Acceptance of bids.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 2 2011-07-01 2011-07-01 false Acceptance of bids. 274.7 Section 274.7 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS REGULATIONS GOVERNING COMPETITIVE BIDDING ON U.S. GOVERNMENT GUARANTEED MILITARY EXPORT LOAN AGREEMENTS § 274...

32 CFR 274.7 - Acceptance of bids.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false Acceptance of bids. 274.7 Section 274.7 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS REGULATIONS GOVERNING COMPETITIVE BIDDING ON U.S. GOVERNMENT GUARANTEED MILITARY EXPORT LOAN AGREEMENTS § 274...

32 CFR 274.6 - Submission of bids.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 2 2011-07-01 2011-07-01 false Submission of bids. 274.6 Section 274.6 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS REGULATIONS GOVERNING COMPETITIVE BIDDING ON U.S. GOVERNMENT GUARANTEED MILITARY EXPORT LOAN AGREEMENTS § 274...

48 CFR 52.214-16 - Minimum Bid Acceptance Period.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 2 2012-10-01 2012-10-01 false Minimum Bid Acceptance Period. 52.214-16 Section 52.214-16 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... date specified in this solicitation for receipt of bids. (b) This provision supersedes any language...

48 CFR 52.214-16 - Minimum Bid Acceptance Period.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 2 2013-10-01 2013-10-01 false Minimum Bid Acceptance Period. 52.214-16 Section 52.214-16 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... date specified in this solicitation for receipt of bids. (b) This provision supersedes any language...

48 CFR 52.214-16 - Minimum Bid Acceptance Period.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Minimum Bid Acceptance Period. 52.214-16 Section 52.214-16 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... date specified in this solicitation for receipt of bids. (b) This provision supersedes any language...

48 CFR 52.214-16 - Minimum Bid Acceptance Period.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 2 2014-10-01 2014-10-01 false Minimum Bid Acceptance Period. 52.214-16 Section 52.214-16 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION... date specified in this solicitation for receipt of bids. (b) This provision supersedes any language...

48 CFR 14.202-3 - Bid envelopes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Bid envelopes. 14.202-3 Section 14.202-3 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION CONTRACTING METHODS... envelopes bearing Postage and Fees Paid indicia shall not be distributed with the invitation for bids or...

47 CFR 101.1107 - Bidding credits for very small businesses, small businesses and entrepreneurs.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Bidding credits for very small businesses, small businesses and entrepreneurs. 101.1107 Section 101.1107 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Competitive Bidding...

47 CFR 101.1107 - Bidding credits for very small businesses, small businesses and entrepreneurs.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Bidding credits for very small businesses, small businesses and entrepreneurs. 101.1107 Section 101.1107 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Competitive Bidding...

47 CFR 101.1107 - Bidding credits for very small businesses, small businesses and entrepreneurs.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Bidding credits for very small businesses, small businesses and entrepreneurs. 101.1107 Section 101.1107 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Competitive Bidding...

47 CFR 101.1107 - Bidding credits for very small businesses, small businesses and entrepreneurs.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Bidding credits for very small businesses, small businesses and entrepreneurs. 101.1107 Section 101.1107 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES FIXED MICROWAVE SERVICES Competitive Bidding...

Overcoming codon bias: a method for high-level overexpression of Plasmodium and other AT-rich parasite genes in Escherichia coli.

PubMed

Baca, A M; Hol, W G

2000-02-01

Parasite genes often use codons which are rarely used in the highly expressed genes of Escherichia coli, possibly resulting in translational stalling and lower yields of recombinant protein. We have constructed the "RIG" plasmid to overcome the potential codon-bias problem seen in Plasmodium genes. RIG contains the genes that encode three tRNAs (Arg, Ile, Gly), which recognise rare codons found in parasite genes. When co-transformed into E. coli along with expression plasmids containing parasite genes, RIG can greatly increase levels of overexpressed protein. Codon frequency analysis suggests that RIG may be applied to a variety of protozoan and helminth genes.

Energy efficient engine: High pressure turbine uncooled rig technology report

NASA Technical Reports Server (NTRS)

Gardner, W. B.

1979-01-01

Results obtained from testing five performance builds (three vane cascades and two rotating rigs of the Energy Efficient Engine uncooled rig have established the uncooled aerodynamic efficiency of the high-pressure turbine at 91.1 percent. This efficiency level was attained by increasing the rim speed and annulus area (AN(2)), and by increasing the turbine reaction level. The increase in AN(2) resulted in a performance improvement of 1.15 percent. At the design point pressure ratio, the increased reaction level rig demonstrated an efficiency of 91.1 percent. The results of this program have verified the aerodynamic design assumptions established for the Energy Efficient Engine high-pressure turbine component.

Stratified charge rotary aircraft engine technology enablement program

NASA Technical Reports Server (NTRS)

Badgley, P. R.; Irion, C. E.; Myers, D. M.

1985-01-01

The multifuel stratified charge rotary engine is discussed. A single rotor, 0.7L/40 cu in displacement, research rig engine was tested. The research rig engine was designed for operation at high speeds and pressures, combustion chamber peak pressure providing margin for speed and load excursions above the design requirement for a high is advanced aircraft engine. It is indicated that the single rotor research rig engine is capable of meeting the established design requirements of 120 kW, 8,000 RPM, 1,379 KPA BMEP. The research rig engine, when fully developed, will be a valuable tool for investigating, advanced and highly advanced technology components, and provide an understanding of the stratified charge rotary engine combustion process.

47 CFR 24.717 - Bidding credits for licenses for frequency Block F.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Block F. 24.717 Section 24.717 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PERSONAL COMMUNICATIONS SERVICES Competitive Bidding Procedures for Broadband PCS § 24... closed bidding in auctions that begin after March 23, 1999, a winning bidder that qualifies as a small...

47 CFR 24.712 - Bidding credits for licenses won for frequency Block C.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Block C. 24.712 Section 24.712 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES PERSONAL COMMUNICATIONS SERVICES Competitive Bidding Procedures for Broadband PCS § 24... closed bidding in auctions that begin after March 23, 1999, a winning bidder that qualifies as a small...

7 CFR 1753.27 - Bidding procedure.

Code of Federal Regulations, 2010 CFR

2010-01-01

... AGRICULTURE TELECOMMUNICATIONS SYSTEM CONSTRUCTION POLICIES AND PROCEDURES Construction of Buildings § 1753.27.... (b) The borrower shall determine that title to the real estate has been approved by RUS before the invitations to bid are released. (c) The borrower shall set the time for opening of bids, allowing ample time...

31 CFR 356.11 - How are bids submitted in an auction?

Code of Federal Regulations, 2012 CFR

2012-07-01

..., our computer time stamp will establish the receipt time. You are bound by your bids after the closing... failures or disruptions of equipment or communications facilities used for participating in Treasury auctions. (4) Submitters are responsible for bids submitted using computer equipment on their premises...

31 CFR 356.11 - How are bids submitted in an auction?

Code of Federal Regulations, 2011 CFR

2011-07-01

..., our computer time stamp will establish the receipt time. You are bound by your bids after the closing... failures or disruptions of equipment or communications facilities used for participating in Treasury auctions. (4) Submitters are responsible for bids submitted using computer equipment on their premises...

36 CFR 223.88 - Bidding methods.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Bidding methods. 223.88... methods. (a) Competitive sales of National Forest timber shall be offered through either sealed or oral auction bidding. The method chosen for each sale will: (1) Insure open and fair competition, (2) Insure...

48 CFR 14.203-2 - Dissemination of information concerning invitations for bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 14.203-2 Dissemination of information concerning invitations for bids. Procedures concerning display... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Dissemination of information concerning invitations for bids. 14.203-2 Section 14.203-2 Federal Acquisition Regulations System...

30 CFR 581.18 - Bidding system.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 30 Mineral Resources 2 2012-07-01 2012-07-01 false Bidding system. 581.18 Section 581.18 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE LEASING OF MINERALS OTHER THAN OIL, GAS, AND SULPHUR IN THE OUTER CONTINENTAL SHELF Leasing Procedures § 581.18 Bidding system...

30 CFR 581.18 - Bidding system.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 30 Mineral Resources 2 2014-07-01 2014-07-01 false Bidding system. 581.18 Section 581.18 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE LEASING OF MINERALS OTHER THAN OIL, GAS, AND SULPHUR IN THE OUTER CONTINENTAL SHELF Leasing Procedures § 581.18 Bidding system...

30 CFR 581.18 - Bidding system.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 30 Mineral Resources 2 2013-07-01 2013-07-01 false Bidding system. 581.18 Section 581.18 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, DEPARTMENT OF THE INTERIOR OFFSHORE LEASING OF MINERALS OTHER THAN OIL, GAS, AND SULPHUR IN THE OUTER CONTINENTAL SHELF Leasing Procedures § 581.18 Bidding system...

7 CFR 1753.48 - Procurement procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

...' qualifications for all types of construction and for the required information on the bidder and subcontractors... qualified to submit bids, RUS written approval must be obtained to proceed with requesting bids. (4) Bid...) Materials on hand to be furnished by the borrower shall be released to the contractor at the start of...

30 CFR 281.18 - Bidding system.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 2 2010-07-01 2010-07-01 false Bidding system. 281.18 Section 281.18 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT OF THE INTERIOR OFFSHORE LEASING OF MINERALS OTHER THAN OIL, GAS, AND SULPHUR IN THE OUTER CONTINENTAL SHELF Leasing Procedures § 281.18 Bidding system. (a...

47 CFR 1.2109 - License grant, denial, default, and disqualification.

Code of Federal Regulations, 2010 CFR

2010-10-01

... PROCEDURE Competitive Bidding Proceedings General Procedures § 1.2109 License grant, denial, default, and... has declared competitive bidding closed or fails to remit the required down payment within ten (10) business days after the Commission has declared competitive bidding closed, the bidder will be deemed to...

47 CFR 1.2109 - License grant, denial, default, and disqualification.

Code of Federal Regulations, 2011 CFR

2011-10-01

... PROCEDURE Competitive Bidding Proceedings General Procedures § 1.2109 License grant, denial, default, and... has declared competitive bidding closed or fails to remit the required down payment within ten (10) business days after the Commission has declared competitive bidding closed, the bidder will be deemed to...

48 CFR 14.404-1 - Cancellation of invitations after opening.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., the agency head determines in writing that— (1) Inadequate or ambiguous specifications were cited in...) Should administrative difficulties be encountered after bid opening that may delay award beyond bidders... period specified in the bid) should be requested, before expiration of their bids, to extend in writing...

48 CFR 14.404-1 - Cancellation of invitations after opening.

Code of Federal Regulations, 2012 CFR

2012-10-01

..., the agency head determines in writing that— (1) Inadequate or ambiguous specifications were cited in...) Should administrative difficulties be encountered after bid opening that may delay award beyond bidders... period specified in the bid) should be requested, before expiration of their bids, to extend in writing...

48 CFR 14.404-1 - Cancellation of invitations after opening.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., the agency head determines in writing that— (1) Inadequate or ambiguous specifications were cited in...) Should administrative difficulties be encountered after bid opening that may delay award beyond bidders... period specified in the bid) should be requested, before expiration of their bids, to extend in writing...

48 CFR 14.404-1 - Cancellation of invitations after opening.

Code of Federal Regulations, 2010 CFR

2010-10-01

..., the agency head determines in writing that— (1) Inadequate or ambiguous specifications were cited in...) Should administrative difficulties be encountered after bid opening that may delay award beyond bidders... period specified in the bid) should be requested, before expiration of their bids, to extend in writing...

48 CFR 14.404-1 - Cancellation of invitations after opening.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., the agency head determines in writing that— (1) Inadequate or ambiguous specifications were cited in...) Should administrative difficulties be encountered after bid opening that may delay award beyond bidders... period specified in the bid) should be requested, before expiration of their bids, to extend in writing...

32 CFR 274.5 - Notice of intent to bid.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 2 2011-07-01 2011-07-01 false Notice of intent to bid. 274.5 Section 274.5 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS REGULATIONS GOVERNING COMPETITIVE BIDDING ON U.S. GOVERNMENT GUARANTEED MILITARY EXPORT LOAN...

32 CFR 274.5 - Notice of intent to bid.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 2 2010-07-01 2010-07-01 false Notice of intent to bid. 274.5 Section 274.5 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS REGULATIONS GOVERNING COMPETITIVE BIDDING ON U.S. GOVERNMENT GUARANTEED MILITARY EXPORT LOAN...

7 CFR 1726.202 - Informal competitive bidding.

Code of Federal Regulations, 2010 CFR

2010-01-01

... persons or organizations on its qualified bidder list for the specific project (see § 1726.23). (b... a responsive bid. (d) Evaluation basis. Any factors, other than lowest dollar amount of the bid, which are to be considered in evaluating the proposals of qualified bidders (e.g., power consumption...

47 CFR 90.801 - 900 MHz SMR spectrum subject to competitive bidding.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false 900 MHz SMR spectrum subject to competitive bidding. 90.801 Section 90.801 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... Specialized Mobile Radio Service § 90.801 900 MHz SMR spectrum subject to competitive bidding. Mutually...

47 CFR 90.801 - 900 MHz SMR spectrum subject to competitive bidding.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false 900 MHz SMR spectrum subject to competitive bidding. 90.801 Section 90.801 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... Specialized Mobile Radio Service § 90.801 900 MHz SMR spectrum subject to competitive bidding. Mutually...

47 CFR 90.801 - 900 MHz SMR spectrum subject to competitive bidding.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false 900 MHz SMR spectrum subject to competitive bidding. 90.801 Section 90.801 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... Specialized Mobile Radio Service § 90.801 900 MHz SMR spectrum subject to competitive bidding. Mutually...

47 CFR 90.801 - 900 MHz SMR spectrum subject to competitive bidding.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false 900 MHz SMR spectrum subject to competitive bidding. 90.801 Section 90.801 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND... Specialized Mobile Radio Service § 90.801 900 MHz SMR spectrum subject to competitive bidding. Mutually...

48 CFR 852.247-70 - Determining transportation costs for bid evaluation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... costs for bid evaluation. 852.247-70 Section 852.247-70 Federal Acquisition Regulations System DEPARTMENT OF VETERANS AFFAIRS CLAUSES AND FORMS SOLICITATION PROVISIONS AND CONTRACT CLAUSES Texts of Provisions and Clauses 852.247-70 Determining transportation costs for bid evaluation. As prescribed in 847...

Schoolhouse Systems Project: SSP. 3rd Report.

ERIC Educational Resources Information Center

Florida State Dept. of Education, Tallahassee.

This brochure provides statistical bid breakdown for Programs 1A and 2 of the Florida Schoolhouse Systems Project. Tabular information is provided on bidders, compatible building subsystems, bid tabulation by compatibility, "per school" building subsystems, nominated bidders and lump sums, and a comparison of programs 1A and 2 bids. Data…

47 CFR 90.901 - 800 MHz SMR spectrum subject to competitive bidding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... SPECIAL RADIO SERVICES PRIVATE LAND MOBILE RADIO SERVICES Competitive Bidding Procedures for 800 MHz Specialized Mobile Radio Service § 90.901 800 MHz SMR spectrum subject to competitive bidding. Mutually exclusive initial applications for 800 MHz band licenses in Spectrum Blocks A through V are subject to...

48 CFR 14.407-2 - Apparent clerical mistakes.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.407-2 Apparent... contracting officer before award. The contracting officer first shall obtain from the bidder a verification of the bid intended. Examples of apparent mistakes are— (1) Obvious misplacement of a decimal point; (2...

48 CFR 14.407-2 - Apparent clerical mistakes.

Code of Federal Regulations, 2011 CFR

2011-10-01

... CONTRACTING METHODS AND CONTRACT TYPES SEALED BIDDING Opening of Bids and Award of Contract 14.407-2 Apparent... contracting officer before award. The contracting officer first shall obtain from the bidder a verification of the bid intended. Examples of apparent mistakes are— (1) Obvious misplacement of a decimal point; (2...

47 CFR 90.1017 - Bidding credits for small businesses and very small businesses.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 5 2010-10-01 2010-10-01 false Bidding credits for small businesses and very small businesses. 90.1017 Section 90.1017 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... the 220 MHz Service § 90.1017 Bidding credits for small businesses and very small businesses. A...

48 CFR 14.405 - Minor informalities or irregularities in bids.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Minor informalities or... Minor informalities or irregularities in bids. A minor informality or irregularity is one that is merely... cure any deficiency resulting from a minor informality or irregularity in a bid or waive the deficiency...

48 CFR 14.405 - Minor informalities or irregularities in bids.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Minor informalities or... Minor informalities or irregularities in bids. A minor informality or irregularity is one that is merely... cure any deficiency resulting from a minor informality or irregularity in a bid or waive the deficiency...

23 CFR 635.110 - Licensing and qualification of contractors.

Code of Federal Regulations, 2010 CFR

2010-04-01

... TRAFFIC OPERATIONS CONSTRUCTION AND MAINTENANCE Contract Procedures § 635.110 Licensing and qualification... licensing contractors, who may bid for, be awarded, or perform Federal-aid highway contracts, shall be... of a bid or before the bid may be considered for award of a contract. This, however, is not intended...

40 CFR 35.936-22 - Bonding and insurance.

Code of Federal Regulations, 2010 CFR

2010-07-01

... sewer system rehabilitation exceeding $100,000, each bidder must furnish a bid guarantee equivalent to 5 percent of the bid price. In addition, the contractor awarded a construction contract for the building and... contracts less than $100,000 shall be subject to State and local requirements for bid guarantees...

7 CFR 1753.8 - Contract construction procedures.

Code of Federal Regulations, 2010 CFR

2010-01-01

... of all bids including “Buy American” evaluations, if any, and all other evaluations required by law... Contract construction procedures. (a) Sealed, competitive bidding—(1) Bid opening date. The borrower is responsible for scheduling the bid opening date. If RUS review of P&S is required by § 1753.7, the borrower...

47 CFR 73.5007 - Designated entity provisions.

Code of Federal Regulations, 2013 CFR

2013-10-01

... lower the cost of its winning bid on any broadcast construction permit. Any winning bidder claiming new... underlying its new entrant bidding credit eligibility claim, or that of any attributable interest-holder in... of the new entrant bidding credit claimed in the applicant's FCC Form 175 application, if the change...

47 CFR 73.5007 - Designated entity provisions.

Code of Federal Regulations, 2012 CFR

2012-10-01

... lower the cost of its winning bid on any broadcast construction permit. Any winning bidder claiming new... underlying its new entrant bidding credit eligibility claim, or that of any attributable interest-holder in... of the new entrant bidding credit claimed in the applicant's FCC Form 175 application, if the change...

47 CFR 73.5007 - Designated entity provisions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... lower the cost of its winning bid on any broadcast construction permit. Any winning bidder claiming new... underlying its new entrant bidding credit eligibility claim, or that of any attributable interest-holder in... of the new entrant bidding credit claimed in the applicant's FCC Form 175 application, if the change...

47 CFR 73.5007 - Designated entity provisions.

Code of Federal Regulations, 2011 CFR

2011-10-01

... lower the cost of its winning bid on any broadcast construction permit. Any winning bidder claiming new... underlying its new entrant bidding credit eligibility claim, or that of any attributable interest-holder in... of the new entrant bidding credit claimed in the applicant's FCC Form 175 application, if the change...

47 CFR 73.5007 - Designated entity provisions.

Code of Federal Regulations, 2014 CFR

2014-10-01

... lower the cost of its winning bid on any broadcast construction permit. Any winning bidder claiming new... underlying its new entrant bidding credit eligibility claim, or that of any attributable interest-holder in... of the new entrant bidding credit claimed in the applicant's FCC Form 175 application, if the change...

47 CFR 90.910 - Bidding credits.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) SAFETY AND SPECIAL RADIO SERVICES PRIVATE LAND....910 Bidding credits. A winning bidder that qualifies as a very small business, as defined in § 90.912(b)(2), or a consortium of very small businesses may use a bidding credit of 35 percent to lower the...

47 CFR 1.2105 - Bidding application and certification procedures; prohibition of certain communications.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... (6) Any applicant that makes or receives a communication of bids or bidding strategies prohibited under paragraph (c)(1) of this section shall report such communication in writing to the Commission... procedures; prohibition of certain communications. 1.2105 Section 1.2105 Telecommunication FEDERAL...

47 CFR 90.1017 - Bidding credits for small businesses and very small businesses.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 5 2014-10-01 2014-10-01 false Bidding credits for small businesses and very small businesses. 90.1017 Section 90.1017 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... the 220 MHz Service § 90.1017 Bidding credits for small businesses and very small businesses. A...

47 CFR 90.1017 - Bidding credits for small businesses and very small businesses.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 5 2012-10-01 2012-10-01 false Bidding credits for small businesses and very small businesses. 90.1017 Section 90.1017 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... the 220 MHz Service § 90.1017 Bidding credits for small businesses and very small businesses. A...

47 CFR 90.1017 - Bidding credits for small businesses and very small businesses.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 5 2013-10-01 2013-10-01 false Bidding credits for small businesses and very small businesses. 90.1017 Section 90.1017 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... the 220 MHz Service § 90.1017 Bidding credits for small businesses and very small businesses. A...

47 CFR 90.1017 - Bidding credits for small businesses and very small businesses.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 5 2011-10-01 2011-10-01 false Bidding credits for small businesses and very small businesses. 90.1017 Section 90.1017 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED... the 220 MHz Service § 90.1017 Bidding credits for small businesses and very small businesses. A...

48 CFR 225.870-3 - Submission of offers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... sealed bids in terms of U.S. currency. Do not adjust contracts awarded under sealed bidding for losses or gains from fluctuation in exchange rates. (d) Except for sealed bids, the Canadian Commercial Corporation normally will submit offers and quotations in terms of Canadian currency. The Corporation may, at...

Competition in the economic crisis: Analysis of procurement auctions.

PubMed

Gugler, Klaus; Weichselbaumer, Michael; Zulehner, Christine

2015-01-01

We study the effects of the recent economic crisis on firms׳ bidding behavior and markups in sealed bid auctions. Using data from Austrian construction procurements, we estimate bidders׳ construction costs within a private value auction model. We find that markups of all bids submitted decrease by 1.5 percentage points in the recent economic crisis, markups of winning bids decrease by 3.3 percentage points. We also find that without the government stimulus package this decrease would have been larger. These two pieces of evidence point to pro-cyclical markups.

Competitive bidding for home care under the channeling demonstration

PubMed Central

Christianson, Jon B.

1987-01-01

Competitive bidding is a relatively new strategy for setting rates and choosing providers for public medical care programs. In this article, the experience in competitive bidding by home health care providers and homemaker agencies in the National Long-Term Care Channeling Demonstration is described. Particular attention is paid to contrasting approaches that select a single winning bidder with those that select multiple winning bidders for the same service. Results are discussed with respect to bid prices, characteristics of winning bidders, administrative demands, and service delivery. PMID:10312190

Standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori eradication

PubMed Central

Gao, Xiao-Zhong; Qiao, Xiu-Li; Song, Wen-Chong; Wang, Xiao-Feng; Liu, Feng

2010-01-01

AIM: To compare the effectiveness of standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori (H. pylori) eradication in a randomized, double-blinded, comparative clinical trial in China. METHODS: A total of 215 H. pylori-positive patients were enrolled in the study and randomly allocated into three groups: group A (n = 72) received a 10-d bismuth pectin quadruple therapy (20 mg rabeprazole bid, 1000 mg amoxicillin bid, 100 mg bismuth pectin qid, and 500 mg levofloxacin qd); group B (n = 72) received the sequential therapy (20 mg omeprazole bid, 1000 mg amoxicillin bid, in 5 d, followed by 20 mg omeprazole bid, 500 mg tinidazole bid, 500 mg clarithromycin bid, for another 5 d); group C (n = 71) received a standard 1-wk triple therapy (20 mg omeprazole bid, 1000 mg amoxicillin bid, 500 mg clarithromycin bid). After all these treatments, 20 mg omeprazole bid was administrated for 3 wk. H. pylori status was assessed by histology, 13C-urea breath test and rapid urease test at baseline and 4-6 wk after completion of treatment. Ulcer cicatrization was assessed by gastroscopy. χ2 test (P < 0.05) was used to compare the eradication rates and ulcer cicatrisation rates among the three groups. RESULTS: The eradication rate was 83.33% (60/72) in group A, 88.89% (64/72) in group B, and 80.56% (58/71) in group C. The ulcer cicatrisation rate was 86.44% (51/59) in group A, 90.16% (55/61) in group B, and 84.91% (45/53) in group C. The sequential therapy yielded a higher eradication rate and ulcer cicatrisation rate than the standard triple and bismuth pectin quadruple therapies. Statistically, the eradication rate of group B was significantly different from groups A and C (P < 0.05), but the difference of ulcer cicatrisation rate and side effects was not statistically significant among the three groups (P > 0.05). The three protocols were generally well tolerated. CONCLUSION: The sequential therapy has achieved a significantly higher eradication rate, and is a more suitable first-line alternative protocol for anti-H. pylori infection compared with the standard triple and bismuth pectin quadruple therapies. PMID:20818821

Vibrio vulnificus quorum-sensing molecule cyclo(Phe-Pro) inhibits RIG-I-mediated antiviral innate immunity.

PubMed

Lee, Wooseong; Lee, Seung-Hoon; Kim, Minwoo; Moon, Jae-Su; Kim, Geon-Woo; Jung, Hae-Gwang; Kim, In Hwang; Oh, Ji Eun; Jung, Hi Eun; Lee, Heung Kyu; Ku, Keun Bon; Ahn, Dae-Gyun; Kim, Seong-Jun; Kim, Kun-Soo; Oh, Jong-Won

2018-04-23

The recognition of pathogen-derived ligands by pattern recognition receptors activates the innate immune response, but the potential interaction of quorum-sensing (QS) signaling molecules with host anti-viral defenses remains largely unknown. Here we show that the Vibrio vulnificus QS molecule cyclo(Phe-Pro) (cFP) inhibits interferon (IFN)-β production by interfering with retinoic-acid-inducible gene-I (RIG-I) activation. Binding of cFP to the RIG-I 2CARD domain induces a conformational change in RIG-I, preventing the TRIM25-mediated ubiquitination to abrogate IFN production. cFP enhances susceptibility to hepatitis C virus (HCV), as well as Sendai and influenza viruses, each known to be sensed by RIG-I but did not affect the melanoma-differentiation-associated gene 5 (MDA5)-recognition of norovirus. Our results reveal an inter-kingdom network between bacteria, viruses and host that dysregulates host innate responses via a microbial quorum-sensing molecule modulating the response to viral infection.

Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by RIG-I

PubMed Central

Gack, Michaela Ulrike; Albrecht, Randy Allen; Urano, Tomohiko; Inn, Kyung-Soo; Huang, I-Chueh; Carnero, Elena; Farzan, Michael; Inoue, Satoshi; Jung, Jae Ung; García-Sastre, Adolfo

2009-01-01

SUMMARY TRIM25 mediates Lys 63-linked ubiquitination of the N-terminal CARDs of the viral RNA sensor RIG-I, leading to type I interferon (IFN) production. Here, we report that the influenza A virus non-structural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing RIG-I signal transduction. A novel domain in NS1 comprising E96/E97 residues mediates its interaction with the coiled-coil domain of TRIM25, thus blocking TRIM25 multimerization and RIG-I CARD ubiquitination. Furthermore, a recombinant influenza A virus expressing an E96A/E97A NS1 mutant is defective in blocking TRIM25-mediated anti-viral IFN response and loses virulence in mice. Our findings reveal a novel mechanism of influenza virus to inhibit host IFN response and also emphasize the vital role of TRIM25 in modulating viral infections. PMID:19454348

Influenza A virus NS1 targets the ubiquitin ligase TRIM25 to evade recognition by the host viral RNA sensor RIG-I.

PubMed

Gack, Michaela Ulrike; Albrecht, Randy Allen; Urano, Tomohiko; Inn, Kyung-Soo; Huang, I-Chueh; Carnero, Elena; Farzan, Michael; Inoue, Satoshi; Jung, Jae Ung; García-Sastre, Adolfo

2009-05-08

The ubiquitin ligase TRIM25 mediates Lysine 63-linked ubiquitination of the N-terminal CARD domains of the viral RNA sensor RIG-I to facilitate type I interferon (IFN) production and antiviral immunity. Here, we report that the influenza A virus nonstructural protein 1 (NS1) specifically inhibits TRIM25-mediated RIG-I CARD ubiquitination, thereby suppressing RIG-I signal transduction. A novel domain in NS1 comprising E96/E97 residues mediates its interaction with the coiled-coil domain of TRIM25, thus blocking TRIM25 multimerization and RIG-I CARD domain ubiquitination. Furthermore, a recombinant influenza A virus expressing an E96A/E97A NS1 mutant is defective in blocking TRIM25-mediated antiviral IFN response and loses virulence in mice. Our findings reveal a mechanism by which influenza virus inhibits host IFN response and also emphasize the vital role of TRIM25 in modulating antiviral defenses.

ECSIT bridges RIG-I-like receptors to VISA in signaling events of innate antiviral responses.

PubMed

Lei, Cao-Qi; Zhang, Yu; Li, Mi; Jiang, Li-Qun; Zhong, Bo; Kim, Yong Ho; Shu, Hong-Bing

2015-01-01

Upon binding to RNA structures from invading viruses, RIG-I and MDA5 are recruited to mitochondria to interact with VISA and initiate antiviral type I interferon (IFN) responses. How this process is mediated is less understood. In this report, we demonstrate that ECSIT is an essential scaffolding protein that mediates the association of VISA and RIG-I or MDA5. Overexpression of ECSIT potentiated virus-triggered activation of IFN-regulatory factor 3 (IRF3) and expression of IFNB1, whereas knockdown of ECSIT impaired viral infection-induced activation of IRF3 and expression of IFNB1 as well as cellular antiviral responses. Mechanistically, ECSIT was associated with VISA on mitochondria and important for bridging RIG-I and MDA5 to VISA. Our findings suggest that ECSIT mediates virus-triggered type I IFN induction by bridging RIG-I and MDA5 to the VISA complex, and provide new insights into the molecular events of innate antiviral immune responses. © 2014 S. Karger AG, Basel.

Cholera on a Gulf Coast oil rig.

PubMed

Johnston, J M; Martin, D L; Perdue, J; McFarland, L M; Caraway, C T; Lippy, E C; Blake, P A

1983-09-01

A single case of severe diarrhea on a floating Texas oil rig was followed two days later by what proved to be the largest outbreak of cholera in the United States in over a century. After isolation of toxigenic Vibrio cholerae El Tor Inaba of the typical United States phage type from the index patient's stool, the ensuing investigation detected 14 additional cases of cholera and one asymptomatic infection serologically. Infection was associated with eating rice on the oil rig on a particular day (P = 0.03) when an open valve permitted the rig's drinking-water system to be contaminated by canal water containing sewage (including that from the index patient) discharged from the rig. The rice had been rinsed in the contaminated water after cooking, and before being served it had been maintained at a temperature that allows V. cholerae 01 to multiply. Toxigenic V. cholerae 01 is persisting in the United States, and large common-source outbreaks of cholera can occur if proper sanitation is not maintained.

Oil rigs and offshore sport fishing in Louisiana

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

Dugas, R.; Guillory, V.; Fischer, M.

Forty years ago, offshore sport fishing in Louisiana was almost nonexistent. Offshore oil drilling platforms are the primary cause of the present increase in sport fishing in this area. Algae and other organisms forming the first step in the food chain cluster around the subsurface structures of the rigs, attracting fish that seek food and shelter. Major game species frequenting these rigs are identified. (3 photos, 22 references, 2 tables)

Burner Rig Laboratory

NASA Image and Video Library

2015-05-12

The Fuel Burner Rig is a test laboratory at NASA Glenn, which subjects new jet engine materials, treated with protective coatings, to the hostile, high temperature, high velocity environment found inside aircraft turbine engines. These samples face 200-mile per hour flames to simulate the temperatures of aircraft engines in flight. The rig can also simulate aircraft carrier and dusty desert operations where salt and sand can greatly reduce engine life and performance.

New drilling rigs

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

Tubb, M.

1981-02-01

Friede and Goldman Ltd. of New Orleans, Louisiana has a successful drilling rig, the L-780 jack-up series. The triangular-shaped drilling vessel measures 180 x 176 ft. and is equipped with three 352 ft legs including spud cans. It is designed to work in up to 250 ft waters and drill to 20,000 ft depths. The unit is scheduled to begin initial drilling operations in the Gulf of Mexico for Arco. Design features are included for the unit. Davie Shipbuilding Ltd. has entered the Mexican offshore market with the signing of a $40,000,000 Canadian contract for a jack-up to work inmore » 300 ft water depths. Baker Marine Corporation has contracted with the People's Republic of China for construction of two self-elevating jack-ups. The units will be built for Magnum Marine, headquartered in Houston. Details for the two rigs are given. Santa Fe International Corporation has ordered a new jack-up rig to work initially in the Gulf of Suez. The newly ordered unit, Rig 136, will be the company's fourth offshore drilling rig now being built in the Far East. Temple Drilling Company has signed a construction contract with Bethlehem Steel for a jack-up to work in 200 ft water depths. Penrod Drilling Company has ordered two additional cantilever type jack-ups for Hitachi Shipbuilding and Engineering Co. Ltd. of Japan. Two semi-submersibles, capable of working in up to 2000 ft water depths, have been ordered by two Liberian companies. Details for these rigs are included. (DP)« less