47 CFR 63.65 - Closure of public toll station where another toll station of applicant in the community will...

Code of Federal Regulations, 2014 CFR

2014-10-01

... 47 Telecommunication 3 2014-10-01 2014-10-01 false Closure of public toll station where another toll station of applicant in the community will continue service. 63.65 Section 63.65 Telecommunication... of public toll station where another toll station of applicant in the community will continue service...

47 CFR 63.65 - Closure of public toll station where another toll station of applicant in the community will...

Code of Federal Regulations, 2011 CFR

2011-10-01

... 47 Telecommunication 3 2011-10-01 2011-10-01 false Closure of public toll station where another toll station of applicant in the community will continue service. 63.65 Section 63.65 Telecommunication... of public toll station where another toll station of applicant in the community will continue service...

47 CFR 63.65 - Closure of public toll station where another toll station of applicant in the community will...

Code of Federal Regulations, 2012 CFR

2012-10-01

... 47 Telecommunication 3 2012-10-01 2012-10-01 false Closure of public toll station where another toll station of applicant in the community will continue service. 63.65 Section 63.65 Telecommunication... of public toll station where another toll station of applicant in the community will continue service...

47 CFR 63.65 - Closure of public toll station where another toll station of applicant in the community will...

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Closure of public toll station where another toll station of applicant in the community will continue service. 63.65 Section 63.65 Telecommunication... of public toll station where another toll station of applicant in the community will continue service...

47 CFR 63.65 - Closure of public toll station where another toll station of applicant in the community will...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Closure of public toll station where another toll station of applicant in the community will continue service. 63.65 Section 63.65 Telecommunication... of public toll station where another toll station of applicant in the community will continue service...

47 CFR 63.504 - Contents of applications to close a public toll station where no other such toll station of the...

Code of Federal Regulations, 2010 CFR

2010-10-01

... 47 Telecommunication 3 2010-10-01 2010-10-01 false Contents of applications to close a public toll station where no other such toll station of the applicant in the community will continue service and where telephone toll service is not otherwise available to the public through a telephone exchange connected with the toll lines of a carrier....

47 CFR 52.111 - Toll free number assignment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 47 Telecommunication 3 2013-10-01 2013-10-01 false Toll free number assignment. 52.111 Section 52.111 Telecommunication FEDERAL COMMUNICATIONS COMMISSION (CONTINUED) COMMON CARRIER SERVICES (CONTINUED) NUMBERING Toll Free Numbers § 52.111 Toll free number assignment. Toll free numbers shall be made available...

Effects of an HOV-2 to HOT-3 conversion on traveler behavior : evidence from a panel study of the I-85 corridor in Atlanta.

DOT National Transportation Integrated Search

2014-04-01

This paper uses a two-stage panel survey approach, with roughly 1,600 respondent : households, to analyze the impacts of a federally sponsored variable tolling : program on the I-85 corridor northeast of Atlanta. The focus is on corridor : users d...

2004-2006 Puget Sound Traffic Choices Study | Transportation Secure Data

Science.gov Websites

Center | NREL 04-2006 Puget Sound Traffic Choices Study 2004-2006 Puget Sound Traffic Choices Study The 2004-2006 Puget Sound Traffic Choices Study tested the hypothesis that time-of-day variable Administration for a pilot project on congestion-based tolling. Methodology To test the hypothesis, the study

The Toll pathway is required in the epidermis for muscle development in the Drosophila embryo

NASA Technical Reports Server (NTRS)

Halfon, M. S.; Keshishian, H.

1998-01-01

The Toll signaling pathway functions in several Drosophila processes, including dorsal-ventral pattern formation and the immune response. Here, we demonstrate that this pathway is required in the epidermis for proper muscle development. Previously, we showed that the zygotic Toll protein is necessary for normal muscle development; in the absence of zygotic Toll, close to 50% of hemisegments have muscle patterning defects consisting of missing, duplicated and misinserted muscle fibers (Halfon, M.S., Hashimoto, C., and Keshishian, H., Dev. Biol. 169, 151-167, 1995). We have now also analyzed the requirements for easter, spatzle, tube, and pelle, all of which function in the Toll-mediated dorsal-ventral patterning pathway. We find that spatzle, tube, and pelle, but not easter, are necessary for muscle development. Mutations in these genes give a phenotype identical to that seen in Toll mutants, suggesting that elements of the same pathway used for Toll signaling in dorsal-ventral development are used during muscle development. By expressing the Toll cDNA under the control of distinct Toll enhancer elements in Toll mutant flies, we have examined the spatial requirements for Toll expression during muscle development. Expression of Toll in a subset of epidermal cells that includes the epidermal muscle attachment cells, but not Toll expression in the musculature, is necessary for proper muscle development. Our results suggest that signals received by the epidermis early during muscle development are an important part of the muscle patterning process.

Queue theory for triangular and weibull arrival distribution models (case study of Banyumanik toll)

NASA Astrophysics Data System (ADS)

Sugito; Rahmawati, Rita; Kusuma Wardhani, Jenesia

2018-05-01

Queuing is one of the most common phenomena in daily life. Queued also happens on highway during busy time. The Electronic Toll Collection (ETC) was the new system of the Banyumanik toll gate which operates in 2014. Before ETC, Banyumanik toll gate users got regular service (regular toll gate) by paying in cash only. The ETC benefits more than regular service, but automatic toll gate (ETC) users are still few compared to regular toll gate users. To know the effectiveness of substance service, this paper used analysis of queuing system. The research was conducted at Toll Gate Banyumanik with the implementation time on 26-28 December 2016 for Ungaran-Semarang direction, and 29-31 December 2016 for Semarang- Ungaran direction. In one day, observation was done for 11 hours. That was at 07.00 a.m. until 06.00 p.m. There are 4 models of queues at Banyumanik toll gate. Here the four models will be used on the number of arrival and service time. Based on the simulation with Arena, the result showed that queue model regular toll gate in Ugaran-Semarang direction is (Tria/G/3):(GD/∞/∞) and the queue model for automatic toll gate is (G/G/3):(GD/∞/∞). While the queue model for the direction of Semarang-Ungaran regular toll gate is (G/G/3):(GD/∞/∞) and the queue model of automatic toll gate is (Weib/G/3):(GD/∞/∞).

2011 Atlanta and Seattle Tolling Impact Survey | Transportation Secure Data

Science.gov Websites

Center | NREL Atlanta and Seattle Tolling Impact Survey 2011 Atlanta and Seattle Tolling Impact Survey The 2011 Tolling Impact Survey measured the impact of tolling on travel behavior in Atlanta Transportation and the Urban Partnership Agreement, the Volpe Center conducted the survey. Methodology The

47 CFR 42.6 - Retention of telephone toll records.

Code of Federal Regulations, 2010 CFR

2010-10-01

... telephone toll calls: the name, address, and telephone number of the caller, telephone number called, date, time and length of the call. Each carrier shall retain this information for toll calls that it bills whether it is billing its own toll service customers for toll calls or billing customers for another...

Mincle suppresses Toll-like receptor 4 activation.

PubMed

Greco, Stephanie H; Mahmood, Syed Kashif; Vahle, Anne-Kristin; Ochi, Atsuo; Batel, Jennifer; Deutsch, Michael; Barilla, Rocky; Seifert, Lena; Pachter, H Leon; Daley, Donnele; Torres-Hernandez, Alejandro; Hundeyin, Mautin; Mani, Vishnu R; Miller, George

2016-07-01

Regulation of Toll-like receptor responses is critical for limiting tissue injury and autoimmunity in both sepsis and sterile inflammation. We found that Mincle, a C-type lectin receptor, regulates proinflammatory Toll-like receptor 4 signaling. Specifically, Mincle ligation diminishes Toll-like receptor 4-mediated inflammation, whereas Mincle deletion or knockdown results in marked hyperresponsiveness to lipopolysaccharide in vitro, as well as overwhelming lipopolysaccharide-mediated inflammation in vivo. Mechanistically, Mincle deletion does not up-regulate Toll-like receptor 4 expression or reduce interleukin 10 production after Toll-like receptor 4 ligation; however, Mincle deletion decreases production of the p38 mitogen-activated protein kinase-dependent inhibitory intermediate suppressor of cytokine signaling 1, A20, and ABIN3 and increases expression of the Toll-like receptor 4 coreceptor CD14. Blockade of CD14 mitigates the increased sensitivity of Mincle(-/-) leukocytes to Toll-like receptor 4 ligation. Collectively, we describe a major role for Mincle in suppressing Toll-like receptor 4 responses and implicate its importance in nonmycobacterial models of inflammation. © Society for Leukocyte Biology.

Innate Immune Regulation by Toll-Like Receptors in the Brain

PubMed Central

Mallard, Carina

2012-01-01

The innate immune system plays an important role in cerebral health and disease. In recent years the role of innate immune regulation by toll-like receptors in the brain has been highlighted. In this paper the expression of toll-like receptors and endogenous toll-like receptor ligands in the brain and their role in cerebral ischemia will be discussed. Further, the ability of systemic toll-like receptor ligands to induce cerebral inflammation will be reviewed. Finally, the capacity of toll-like receptors to both increase (sensitization) and decrease (preconditioning/tolerance) the vulnerability of the brain to damage will be disclosed. Studies investigating the role of toll-like receptors in the developing brain will be emphasized. PMID:23097717

Toll motorway accessibility for wheelchair users: a survey.

PubMed

Prigent, Hélène; Roche, Nicolas; Guillon, Bruno; Hurand, Anne; Moreau, Bernadette; Dufresne, Jean Pierre; Ravaud, Jean-François; Lofaso, Frédéric

2008-09-01

To identify difficulties encountered by wheelchair users who travel on toll motorways, with the goal of defining areas for improvement. Survey. After observing a wheelchair user travelling on a toll motorway and using the associated services, we designed a self-questionnaire on perceptions by wheelchair users of toll motorway accessibility. Toll motorway and rehabilitation hospital in France. We recruited 167 wheelchair users by advertisement and, to assess selection bias, 19 consecutive outpatients who visited our hospital's wheelchair showroom. None. Of the 186 included subjects, 91 (49%) were used to driving independently on toll motorways. Among them, only 16% used automatic toll booths and 32% reported difficulties at toll booths. Furthermore, 53% routinely asked for help at filling stations, and only 27% were aware of the availability of a free-of-charge assistance service for disabled people at some filling stations. Among the 186 toll motorway users, only 84 (45%) reported never encountering difficulties in lay-bys; 162 (87%) felt that toilet accessibility was the most important feature of lay-bys and 143 (77%) preferred the locked toilets reserved for disabled people. Wheelchair users reported difficulties on toll motorways that could be corrected fairly easily.

Cloning and characterisation of the SpToll gene from green mud crab, Scylla paramamosain.

PubMed

Lin, Zhongyang; Qiao, Jie; Zhang, Yueling; Guo, Lingling; Huang, He; Yan, Fang; Li, Yuanyou; Wang, Xiuying

2012-05-01

Toll/Toll-like receptors (TLRs), one of the most important pattern recognition receptors (PRRs), play a crucial role in innate immune responses in both invertebrates and vertebrates. In this study, we cloned and characterised a Toll gene from Scylla paramamosain (SpToll). Bioinformatic analysis predicted that SpToll contained one open reading frame of 3018bp and encoded a single-pass transmembrane domain protein of 1005 amino acids. Further, SpToll could be clustered into one branch along with other arthropod Tolls in a phylogenetic tree. SpToll transcripts could be detected by RT-PCR from all tissues examined including the heart, gill, hepatopancreas, stomach, intestine, muscle, eyestalk and hemocytes. Infection by Vibrio parahemolyticus up-regulated SpToll mRNA expression in hemocytes after 48h. The profile of single nucleotide polymorphisms (SNPs) in the leucine-rich repeats (LRRs) domain of SpToll in three healthy crabs was then evaluated. Two hundred and twenty SNPs with a frequency of about 1.0-4.0% were identified in hemocyte DNA/cDNA. Surprisingly, the adenine to guanine transition at position 1372 (c.1372A>G) had a frequency of about 50%. Finally, the results showed that challenge with V. parahemolyticus stimulated the appearance of two sets of SNPs in crabs. More importantly, the c.1372A>G mutation could contribute to a low mortality after V. parahemolyticus infection and introduce variation of charge and secondary structure into the SpToll polypeptide. In summary, these studies suggested a novel Toll homologue in crab and identified a SNP with potential pathogen-resistant activities. The result will be important for the investigation of crab immune defense mechanisms. Copyright © 2011 Elsevier Ltd. All rights reserved.

8. INTERIOR OF TOLL PLAZA OBSERVATION TOWER, LOOKING NORTH. ARTELUAR ...

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

8. INTERIOR OF TOLL PLAZA OBSERVATION TOWER, LOOKING NORTH. ARTELUAR COOK, ACTING SUPERVISOR, IS AT THE HELM. - Chicago Skyway Toll Bridge, Toll Plaza & Service Building, 8801 South Anthony Avenue, Chicago, Cook County, IL

23 CFR 950.3 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-04-01

... HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION INTELLIGENT TRANSPORTATION SYSTEMS ELECTRONIC TOLL... Express Lanes Demonstration Program, and the Interstate System Construction Toll Pilot Program. Electronic toll collection means the ability for vehicle operators to pay tolls automatically without slowing down...

Are outbreaks of emerging pathogens correlated with construction of wetlands? Report 2 : amphibian breeding and disease outbreaks during 2014-2015 and possible correlates with environmental variables : research report.

DOT National Transportation Integrated Search

2016-10-01

A study of wetlands near the Intercounty Connector construction site (now a toll facility MD 200) in Maryland, : found that an emerging pathogen known as Ranavirus was having a significant impact on at least two species of : amphibians as well as...

Missouri toll feasibility study : phase I

DOT National Transportation Integrated Search

2002-05-01

The purpose of this toll feasibility study is to estimate the potential revenue that could be generated from several candidate toll projects within the state. Potential toll revenue may then be considered in combination with other possible funding me...

Historic American Buildings Survey, A.S. Burns, Photographer December, 1933 TOLL ...

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

Historic American Buildings Survey, A.S. Burns, Photographer December, 1933 TOLL HOUSE (DETAIL OF PLAQUE SHOWING TOLL RATES) - Structures on Old National Trail, Toll House, U.S. Route 40, Pittsburgh, Allegheny County, PA

PcToll3 was involved in anti-Vibrio response by regulating the expression of antimicrobial peptides in red swamp crayfish, Procambarus clarkii.

PubMed

Lan, Jiang-Feng; Wei, Shun; Wang, Yu-Qing; Dai, Yun-Jia; Tu, Jia-Gang; Zhao, Li-Juan; Li, Xin-Cang; Qin, Qi-Wei; Chen, Nan; Lin, Li

2016-10-01

Tolls and Toll-like receptors (TLRs) play an important role in host immune defenses by regulating the expression of antimicrobial peptides (AMPs) and cytokines, but the functional differences of crustacean Tolls from Drosophila Tolls or Mammal TLRs are largely unknown. A novel Toll receptor, named PcToll3, was identified from red swamp crayfish, Procambarus clarkii. It was widely expressed in all detected tissues, and its transcript in hemocytes was up-regulated at 12 h after Vibrio parahemolyticus (Vibrio) injection or at 24 h post white spot syndrome virus (WSSV) challenge. After knockdown of PcToll3, the activity of bacterial clearance was inhibited, and the expression levels of AMPs including Crustin1 (Cru1), Anti-lippopolysaccharide factor 1 (ALF1), and Lysozymes1 (Lys1), which could be up-regulated by Vibrio, were all affected. Meanwhile, PcToll3 silencing influenced the expression of myeloid differentiation factor 88 (PcMyd88), tumor necrosis factor-associated factor 6 (PcTRAF6), and PcDorsal, which were the counterparts of Drosophila Toll signaling pathway. Interestingly, PcToll3 silencing inhibited translocation of PcDorsal from cytoplasm to nucleus. Furthermore, the knockdown of PcDorsal also impaired the expression of AMPs after Vibrio challenge. Hence, we concluded that, besides participating in antiviral immunity, PcToll3 might also regulate the expression of Cru1 and Lys1 to participate in anti-Vibrio immune responses by promoting PcDorsal translocation into nucleus. Copyright © 2016 Elsevier Ltd. All rights reserved.

miR-958 inhibits Toll signaling and Drosomycin expression via direct targeting of Toll and Dif in Drosophila melanogaster.

PubMed

Li, Shengjie; Li, Yao; Shen, Li; Jin, Ping; Chen, Liming; Ma, Fei

2017-02-01

Drosophila melanogaster is widely used as a model system to study innate immunity and signaling pathways related to innate immunity, including the Toll signaling pathway. Although this pathway is well studied, the precise mechanisms of posttranscriptional regulation of key components of the Toll signaling pathway by microRNAs (miRNAs) remain obscure. In this study, we used an in silico strategy in combination with the Gal80 ts -Gal4 driver system to identify microRNA-958 (miR-958) as a candidate Toll pathway regulating miRNA in Drosophila We report that overexpression of miR-958 significantly reduces the expression of Drosomycin, a key antimicrobial peptide involved in Toll signaling and the innate immune response. We further demonstrate in vitro and in vivo that miR-958 targets the Toll and Dif genes, key components of the Toll signaling pathway, to negatively regulate Drosomycin expression. In addition, a miR-958 sponge rescued the expression of Toll and Dif, resulting in increased expression of Drosomycin. These results, not only revealed a novel function and modulation pattern of miR-958, but also provided a new insight into the underlying molecular mechanisms of Toll signaling in regulation of innate immunity. Copyright © 2017 the American Physiological Society.

Design And Evaluation Of Toll Plaza Systems

DOT National Transportation Integrated Search

2001-01-01

This mini-project supported the effort for some preliminary studies of several design issues in the toll plazas of highway systems. Particular attention is paid to the toll plaza on the Garden State Parkway (GST), one of two major toll highways in Ne...

Characteristics of the auto users and non-users of central Texas toll roads.

DOT National Transportation Integrated Search

2009-08-01

As toll road usage increases to finance new road infrastructure or add capacity to existing road infrastructure, the : question of who does and does not use toll roads becomes increasingly important to toll road developers, financiers, : Traffic and ...

An investigation of toll plaza capacity and level of service.

DOT National Transportation Integrated Search

1991-01-01

This study was undertaken to accomplish two objectives pertinent to traffic characteristics at toll plaza areas: (1) to develop a methodology for evaluating the capacity of a toll plaza, and (2) to establish level-of-service criteria for toll area tr...

Toll-like receptors 3, 7, and 9 in Juvenile nasopharyngeal angiofibroma.

PubMed

Renkonen, Suvi; Cardell, Lars-Olaf; Mattila, Petri; Lundberg, Marie; Haglund, Caj; Hagström, Jaana; Mäkitie, Antti A

2015-05-01

Juvenile nasopharyngeal angiofibroma (JNA) is a rare, benign tumor affecting adolescent males. The etiology of JNA as well as the causes determining the variable growth patterns of individual tumors remains unknown. Toll-like receptors (TLRs) are part of the innate immune response to microbes; by recognition of distinct features, they link to induction of pro-inflammatory signaling pathways. We immunostained TLR 3, 7, and 9 in 27 JNA specimens of patients treated at the Helsinki University Central Hospital, Helsinki, Finland, during the years 1970-2009. TLR 3, 7, and 9 expressions were found in stromal and endothelial cells of JNA, and their expression levels varied from negative to very strong positive. TLR 3 expression was found to have a significant correlation with the clinical stage of JNA. The present results propose a putative role of TLRs in the growth process of JNA. © 2015 APMIS. Published by John Wiley & Sons Ltd.

Characteristics of the truck users and non-users of Texas toll roads.

DOT National Transportation Integrated Search

2009-08-01

As the use of toll roads increase to finance new road infrastructure or add capacity to existing road infrastructure, the : question of who use and do not use toll roads becomes increasingly important to toll road developers, financiers, : Traffic an...

Exploring the equity impacts of two road pricing implementations using a traveler behavior panel survey : full facility pricing on SR 520 in Seattle and the I-85 HOV-2 to HOT-3 conversion in Atlanta.

DOT National Transportation Integrated Search

2014-04-01

This paper reports survey findings on the equity impacts of variable tolling programs implemented on SR 520 in Seattle (Urban Partnership Agreement) and on I-85 in Atlanta(Congestion Reduction Demonstration Program). The analysis utilizes data from p...

40 CFR 52.111 - Toll free number assignment.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 3 2013-07-01 2013-07-01 false Toll free number assignment. 52.111... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Arizona § 52.111 Toll free number assignment. Toll free numbers shall be made available on a first-come, first-served basis unless otherwise directed...

40 CFR 52.111 - Toll free number assignment.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 3 2010-07-01 2010-07-01 false Toll free number assignment. 52.111... (CONTINUED) APPROVAL AND PROMULGATION OF IMPLEMENTATION PLANS Arizona § 52.111 Toll free number assignment. Toll free numbers shall be made available on a first-come, first-served basis unless otherwise directed...

77 FR 67735 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-13

... Toll-Free Phone Line Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of Meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee will be held Monday, December 3rd, 2012...

Strategic plan for the electronic toll collection system : FasTrak on the San Francisco Bay Area state-owned toll bridges : executive summary

DOT National Transportation Integrated Search

2003-02-01

This report summarizes the findings and recommendations of the utilization and operational analysis of the electronic toll collection (ETC) - FasTrak - system on the seven state-owned bridges in the Bay Area. At present, there are a total of 68 toll ...

77 FR 30590 - Open meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee.

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-23

... Toll-Free Project Committee. AGENCY: Internal Revenue Service (IRS) Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee will be conducted. The.... (1988) that an open meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee will be held...

77 FR 37102 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

... Toll-Free Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee will be conducted. The.... (1988) that an open meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee will be held...

33 CFR 402.10 - Schedule of tolls.

Code of Federal Regulations, 2013 CFR

2013-07-01

... TRANSPORTATION TARIFF OF TOLLS § 402.10 Schedule of tolls. Item Column 1 Description of Charges Column 2 Rate ($) Montreal to or from Lake Ontario (5 locks) Column 3 Rate ($) Welland Canal—Lake Ontario to or from Lake Erie (8 locks) 1. Subject to item 3, for complete transit of the Seaway, a composite toll, comprising...

PcToll2 positively regulates the expression of antimicrobial peptides by promoting PcATF4 translocation into the nucleus.

PubMed

Lan, Jiang-Feng; Zhao, Li-Juan; Wei, Shun; Wang, Yuan; Lin, Li; Li, Xin-Cang

2016-11-01

Drosophila Toll and mammalian Toll-like receptors (TLRs) are a family of evolutionarily conserved immune receptors that play a crucial role in the first-line defense against intruded pathogens. Activating transcription factor 4 (ATF4), a member of the ATF/CREB transcription factor family, is an important factor that participates in TLR signaling and other physiological processes. However, in crustaceans, whether ATF4 homologs were involved in TLR signaling remains unclear. In the current study, we identified a Toll homolog PcToll2 and a novel ATF4 homolog PcATF4 from Procambarus clarkii, and analyzed the likely regulatory activity of PcATF4 in PcToll2 signaling. The complete cDNA sequence of PcToll2 was 4175 bp long containing an open reading frame of 2820 bp encoding a 939-amino acid protein, and the cDNA sequence of PcATF4 was 2027 bp long with an open reading frame of 1296 bp encoding a 431-amino acid protein. PcToll2 and human TLR4 shared the high identity and they were grouped into a cluster. Furthermore, PcToll2 had a close relationship with other shrimp TLRs that possessed potential antibacterial activity. PcToll2 was highly expressed in the hemocytes, heart and gills, while PcATF4 mainly distributed in gills. Upon challenge with Vibrio parahemolyticus, PcToll2 and PcATF4 together with the antimicrobial peptides of ALF1 and ALF2 were significantly up-regulated in the hemocytes, and the PcATF4 was translocated into the nucleus. After PcToll2 silencing and challenge with Vibrio, the translocation of PcATF4 into the nucleus was inhibited and the expression of ALF1 and ALF2 was reduced, but the expression of PcDorsal and PcSTAT was not affected. Furthermore, after PcATF4 knockdown and challenge with or without Vibrio, the expression of ALF1 and ALF2 was also decreased while the expression of PcToll2 was upregulated. These results suggested that PcToll2 might regulate the expression of ALF1 and ALF2 by promoting the import of PcATF4, instead of the routine transcription factor PcDorsal, into the nucleus participating in the immune defense against Gram-negative bacteria. Copyright © 2016 Elsevier Ltd. All rights reserved.

78 FR 36304 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-17

... Toll-Free Phone Line Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of Meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Act, 5 U.S.C. App. (1988) that an open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line...

78 FR 3500 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee.

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... Toll-Free Phone Line Project Committee. AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Toll-Free Phone Line Project Committee will be held Tuesday, February 19, 2013 at 11:00 a.m. Eastern...

77 FR 74920 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-18

... Toll-Free Phone Line Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Advocacy Panel Toll-Free Phone Line Project Committee will be held Tuesday, January 15, 2013 at 11:00 a.m...

33 CFR 402.11 - Schedule of tolls.

Code of Federal Regulations, 2014 CFR

2014-07-01

... TRANSPORTATION TARIFF OF TOLLS § 402.11 Schedule of tolls. Item Column 1 Description of charges Column 2 Rate ($)Montreal to or from Lake Ontario (5 locks) Column 3 Rate ($)Welland Canal—Lake Ontario to or from Lake Erie (8 locks) 1 Subject to item 3, for complete transit of the Seaway, a composite toll, comprising: (1...

25 CFR 170.130 - How can tribes use Federal highway funds for toll and ferry facilities?

Code of Federal Regulations, 2010 CFR

2010-04-01

... 25 Indians 1 2010-04-01 2010-04-01 false How can tribes use Federal highway funds for toll and... Toll, Ferry and Airport Facilities § 170.130 How can tribes use Federal highway funds for toll and ferry facilities? (a) A tribe can use Federal-aid highway funds, including IRR Program funds, to study...

25 CFR 170.130 - How can tribes use Federal highway funds for toll and ferry facilities?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 25 Indians 1 2014-04-01 2014-04-01 false How can tribes use Federal highway funds for toll and... Toll, Ferry and Airport Facilities § 170.130 How can tribes use Federal highway funds for toll and ferry facilities? (a) A tribe can use Federal-aid highway funds, including IRR Program funds, to study...

25 CFR 170.130 - How can tribes use Federal highway funds for toll and ferry facilities?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 25 Indians 1 2012-04-01 2011-04-01 true How can tribes use Federal highway funds for toll and... Toll, Ferry and Airport Facilities § 170.130 How can tribes use Federal highway funds for toll and ferry facilities? (a) A tribe can use Federal-aid highway funds, including IRR Program funds, to study...

25 CFR 170.130 - How can tribes use Federal highway funds for toll and ferry facilities?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 1 2011-04-01 2011-04-01 false How can tribes use Federal highway funds for toll and... Toll, Ferry and Airport Facilities § 170.130 How can tribes use Federal highway funds for toll and ferry facilities? (a) A tribe can use Federal-aid highway funds, including IRR Program funds, to study...

25 CFR 170.130 - How can tribes use Federal highway funds for toll and ferry facilities?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 25 Indians 1 2013-04-01 2013-04-01 false How can tribes use Federal highway funds for toll and... Toll, Ferry and Airport Facilities § 170.130 How can tribes use Federal highway funds for toll and ferry facilities? (a) A tribe can use Federal-aid highway funds, including IRR Program funds, to study...

A Geography-Specific Approach to Estimating the Distributional Impact of Highway Tolls: An Application to the Puget Sound Region of Washington State

PubMed Central

Plotnick, Robert D.; Romich, Jennifer; Thacker, Jennifer; Dunbar, Matthew

2011-01-01

This study contributes to the debate about tolls’ equity impacts by examining the potential economic costs of tolling for low-income and non-low-income households. Using data from the Puget Sound metropolitan region in Washington State and GIS methods to map driving routes from home to work, we examine car ownership and transportation patterns among low-income and non-low-income households. We follow standard practice of estimating tolls’ potential impact only on households with workers who would drive on tolled and non-tolled facilities. We then redo the analysis including broader groups of households. We find that the degree of regressivity is quite sensitive to the set of households included in the analysis. The results suggest that distributional analyses of tolls should estimate impacts on all households in the relevant region in addition to impacts on just users of roads that are currently tolled or likely to be tolled. PMID:21818172

Monthly means of selected climate variables for 1985 - 1989

NASA Technical Reports Server (NTRS)

Schubert, S.; Wu, C.-Y.; Zero, J.; Schemm, J.-K.; Park, C.-K.; Suarez, M.

1992-01-01

Meteorologists are accustomed to viewing instantaneous weather maps, since these contain the most relevant information for the task of producing short-range weather forecasts. Climatologists, on the other hand, tend to deal with long-term means, which portray the average climate. The recent emphasis on dynamical extended-range forecasting and, in particular measuring and predicting short term climate change makes it important that we become accustomed to looking at variations on monthly and longer time scales. A convenient toll for researchers to familiarize themselves with the variability which occurs in selected parameters on these time scales is provided. The format of the document was chosen to help facilitate the intercomparison of various parameters and highlight the year-to-year variability in monthly means.

Toll-like receptor 4 promotes proliferation and apoptosis resistance in human papillomavirus-related cervical cancer cells through the Toll-like receptor 4/nuclear factor-κB pathway.

PubMed

Jiang, Ninghong; Xie, Feng; Guo, Qisang; Li, Ming-Qing; Xiao, Jingjing; Sui, Long

2017-06-01

Toll-like receptor 4 is overexpressed in various tumors, including cervical carcinoma. However, the role of Toll-like receptor 4 in cervical cancer remains controversial, and the underlying mechanisms are largely elusive. Therefore, Toll-like receptor 4 in cervical cancer and related mechanisms were investigated in this study. Quantitative reverse transcription polymerase chain reaction and western blot analyses were used to detect messenger RNA and protein levels in HeLa, Caski, and C33A cells with different treatments. Proliferation was quantified using Cell Counting Kit-8. Cell cycle distribution and apoptosis were assessed by flow cytometry. Higher levels of Toll-like receptor 4 expression were found in human papillomavirus-positive cells compared to human papillomavirus-negative cells. Proliferation of HeLa and Caski cells was promoted in lipopolysaccharide-stimulated groups but suppressed in short hairpin RNA-transfected groups. Apoptosis rates were lower in lipopolysaccharide-stimulated groups relative to short hairpin RNA-transfected groups. In addition, G2-phase distribution was enhanced when Toll-like receptor 4 was downregulated. Moreover, the pNF-κBp65 level was positively correlated with the Toll-like receptor 4 level in HeLa and Caski cells, though when an nuclear factor-κB inhibitor was applied to lipopolysaccharide-stimulated groups, the patterns of proliferation and apoptosis were opposite to those of the lipopolysaccharide-stimulated groups without inhibitor treatment. In conclusion, these data suggest that Toll-like receptor 4 promotes proliferation and apoptosis resistance in human papillomavirus-related cervical cancer cells at least in part through the Toll-like receptor 4/nuclear factor-κB pathway, which may be correlated with the occurrence and development of cervical carcinoma.

Toll pathway is required for wound-induced expression of barrier repair genes in the Drosophila epidermis

PubMed Central

Capilla, Amalia; Karachentsev, Dmitry; Patterson, Rachel A.; Hermann, Anita; Juarez, Michelle T.; McGinnis, William

2017-01-01

The epidermis serves as a protective barrier in animals. After epidermal injury, barrier repair requires activation of many wound response genes in epidermal cells surrounding wound sites. Two such genes in Drosophila encode the enzymes dopa decarboxylase (Ddc) and tyrosine hydroxylase (ple). In this paper we explore the involvement of the Toll/NF-κB pathway in the localized activation of wound repair genes around epidermal breaks. Robust activation of wound-induced transcription from ple and Ddc requires Toll pathway components ranging from the extracellular ligand Spätzle to the Dif transcription factor. Epistasis experiments indicate a requirement for Spätzle ligand downstream of hydrogen peroxide and protease function, both of which are known activators of wound-induced transcription. The localized activation of Toll a few cell diameters from wound edges is reminiscent of local activation of Toll in early embryonic ventral hypoderm, consistent with the hypothesis that the dorsal–ventral patterning function of Toll arose from the evolutionary cooption of a morphogen-responsive function in wound repair. Furthermore, the combinatorial activity of Toll and other signaling pathways in activating epidermal barrier repair genes can help explain why developmental activation of the Toll, ERK, or JNK pathways alone fail to activate wound repair loci. PMID:28289197

The expression of Toll-like receptors 2, 4, 5, 7 and 9 in Merkel cell carcinoma.

PubMed

Jouhi, Lauri; Koljonen, Virve; Böhling, Tom; Haglund, Caj; Hagström, Jaana

2015-04-01

We sought to clarify whether the expression of toll-like receptors (TLR) in Merkel cell carcinoma (MCC) is linked to tumor and patient characteristics, especially the presence of Merkel cell polyoma virus (MCV). The study comprised of 128 patients with data on Merkel cell polyomavirus (MCV) status and clinical features were included in the study. Immunohistochemistry for TLR expression was performed on tissue microarray (TMA) slides. TLR 2, 4, 5, 7 and 9 expression was noted in most of the tumor specimens. Decreased expression of TLR 9 correlated strongly with MCV positivity. Cytoplasmic TLR 2 expression correlated with small tumor size, while nuclear TLR 2 and TLR 5 expressions with larger tumors. Increased nuclear TLR 4 expression and decreased TLR 7 expression were associated with older age. TLR 2, 4, 5, 7 and 9 appear to reflect certain clinicopathological variables and prognostic markers of MCC tumors. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Investigate attractiveness of toll roads.

DOT National Transportation Integrated Search

2015-03-01

HOT facilities are used as a solution for congestion mitigation instead of constructing or expanding the capacity of : existing roadways. Although toll roads modeling has been researched for a long time, High Occupancy Toll (HOT) : modeling is relati...

Technology scan for electronic toll collection.

DOT National Transportation Integrated Search

2008-06-01

The purpose of this project was to identify and assess available technologies and methodologies for electronic toll collection (ETC) and to develop recommendations for the best way(s) to implement toll collection in the Louisville metropolitan area. ...

78 FR 19105 - Tariff of Tolls

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-29

... revised to read as follows: Sec. 402.10 Schedule of tolls. Column 1 Column 2 Column 3 Rate ($) Welland... Lake Erie (8 (5 locks) locks) 1 Subject to item 3, for complete transit of the Seaway, a composite toll...

Toll-Booth Purification

NASA Technical Reports Server (NTRS)

1977-01-01

NASA's Technology Application Team at Stanford Research Institute searched available information and suggested a transfer of clean-room technology employing the use of the same laminar flow techniques found in environmental control systems of clean rooms used for contamination-free assembly of precision aerospace equipment. That information, from technology originally developed by NASA and the Energy Research & Development Administration was incorporated in the design of a prototype toll booth purifier. The draft-free design includes a "diffusor", which blows clean air out the toll booth doorway, thus retarding the infiltration of contaminated air. The net effect is a decrease in the toll collector's inhalation of exhaust fumes. The Washington Department of Highways installed the prototype system in a toll booth at the Evergreen Point Bridge near Seattle. After a successful two-year test, the department now has equipped all 10 of the bridge's toll booths with the air purifiers.

Conventional and Non-Conventional Drosophila Toll Signaling

PubMed Central

Lindsay, Scott A.; Wasserman, Steven A.

2013-01-01

The discovery of Toll in Drosophila and of the remarkable conservation in pathway composition and organization catalyzed a transformation in our understanding of innate immune recognition and response. At the center of that picture is a cascade of interactions in which specific microbial cues activate Toll receptors, which then transmit signals driving transcription factor nuclear localization and activity. Experiments gave substance to the vision of pattern recognition receptors, linked phenomena in development, gene regulation, and immunity into a coherent whole, and revealed a rich set of variations for identifying non-self and responding effectively. More recently, research in Drosophila has illuminated the positive and negative regulation of Toll activation, the organization of signaling events at and beneath membranes, the sorting of information flow, and the existence of non-conventional signaling via Toll-related receptors. Here, we provide an overview of the Toll pathway of flies and highlight these ongoing realms of research. PMID:23632253

Selenium and Other Elements in Water and Adjacent Rock and Sediment of Toll Gate Creek, Aurora, Arapahoe County, Colorado, December 2003 through March 2004

USGS Publications Warehouse

Herring, J.R.; Walton-Day, Katherine

2007-01-01

Streamwater and solid samples (rock, unconsolidated sediment, stream sediment, and efflorescent material) in the Toll Gate Creek watershed, Colorado, were collected and analyzed for major and trace elements to determine trace-element concentrations and stream loads from December 2003 through March 2004, a period of seasonally low flow. Special emphasis was given to selenium (Se) concentrations because historic Se concentrations exceeded current (2004) stream standards. The goal of the project was to assess the distribution of Se concentration and loads in Toll Gate Creek and to determine the potential for rock and unconsolidated sediment in the basin to be sources of Se to the streamwater. Streamwater samples and discharge measurements were collected during December 2003 and March 2004 along Toll Gate Creek and its two primary tributaries - West Toll Gate Creek and East Toll Gate Creek. During both sampling periods, discharge ranged from 2.5 liters per second to 138 liters per second in the watershed. Discharge was greater in March 2004 than December 2003, but both periods represent low flow in Toll Gate Creek, and results of this study should not be extended to periods of higher flow. Discharge decreased moving downstream in East Toll Gate Creek but increased moving downstream along West Toll Gate Creek and the main stem of Toll Gate Creek, indicating that these two streams gain flow from ground water. Se concentrations in streamwater samples ranged from 7 to 70 micrograms per liter, were elevated in the upstream-most samples, and were greater than the State stream standard of 4.6 micrograms per liter. Se loads ranged from 6 grams per day to 250 grams per day, decreased in a downstream direction along East Toll Gate Creek, and increased in a downstream direction along West Toll Gate Creek and Toll Gate Creek. The largest Se-load increases occurred between two sampling locations on West Toll Gate Creek during both sampling periods and between the two sampling locations on the main stem of Toll Gate Creek during the December 2003 sampling. These load increases may indicate that sources of Se exist between these two locations; however, Se loading along West Toll Gate Creek and Toll Gate Creek primarily was characterized by gradual downstream increases in load. Linear regressions between Se load and discharge for both sampling periods had large, significant values of r2 (r2 > 0.96, p < 0.0001) because increases in Se load (per unit of flow increase) were generally constant. This relation is evidence for a constant addition of water having a relatively constant Se concentration over much of the length of Toll Gate Creek, a result which is consistent with a ground-water source for the Se loads. Rock outcroppings along the stream were highly weathered, and Se concentrations in rock and other solid samples ranged from below detection (1 part per million) to 25 parts per million. One sample of efflorescence (a surface encrustation produced by evaporation) had the greatest selenium concentration of all solid samples, was composed of thenardite (sodium sulfate), gypsum (calcium sulfate) and minor halite (sodium chloride), and released all of its Se during a 30-minute water-leaching procedure. Calculations indicate there was an insufficient amount of this material present throughout the watershed to account for the observed Se load in the stream. However, this material likely indicates zones of ground-water discharge that contain Se. This report did not identify an unequivocal source of Se in Toll Gate Creek. However, multiple lines of evidence indicate that ground-water discharge supplies Se to Toll Gate Creek: (1) the occurrence of elevated Se concentrations in the stream throughout the watershed and in the headwater regions, upstream from industrial sources; (2) the progressive increase in Se loads moving downstream, which indicates a continuous input of Se along the stream rather than input from point sources; (3) the occurr

The Toll-Dorsal Pathway Is Required for Resistance to Viral Oral Infection in Drosophila

PubMed Central

Ferreira, Álvaro Gil; Naylor, Huw; Esteves, Sara Santana; Pais, Inês Silva; Martins, Nelson Eduardo; Teixeira, Luis

2014-01-01

Pathogen entry route can have a strong impact on the result of microbial infections in different hosts, including insects. Drosophila melanogaster has been a successful model system to study the immune response to systemic viral infection. Here we investigate the role of the Toll pathway in resistance to oral viral infection in D. melanogaster. We show that several Toll pathway components, including Spätzle, Toll, Pelle and the NF-kB-like transcription factor Dorsal, are required to resist oral infection with Drosophila C virus. Furthermore, in the fat body Dorsal is translocated from the cytoplasm to the nucleus and a Toll pathway target gene reporter is upregulated in response to Drosophila C Virus infection. This pathway also mediates resistance to several other RNA viruses (Cricket paralysis virus, Flock House virus, and Nora virus). Compared with control, viral titres are highly increased in Toll pathway mutants. The role of the Toll pathway in resistance to viruses in D. melanogaster is restricted to oral infection since we do not observe a phenotype associated with systemic infection. We also show that Wolbachia and other Drosophila-associated microbiota do not interact with the Toll pathway-mediated resistance to oral infection. We therefore identify the Toll pathway as a new general inducible pathway that mediates strong resistance to viruses with a route-specific role. These results contribute to a better understanding of viral oral infection resistance in insects, which is particularly relevant in the context of transmission of arboviruses by insect vectors. PMID:25473839

Development of an early-stage toll revenue estimation model.

DOT National Transportation Integrated Search

2012-05-01

With agencies and states increasingly considering tolls as a means to finance transportation infrastructure, : there is an increasing need to quickly assess the feasibility of potential tolling projects. In the early stages : of a project when an age...

A self-adaptive toll rate algorithm for high occupancy toll (HOT) lane operations.

DOT National Transportation Integrated Search

2009-12-01

Dramatically increasing travel demands and insufficient traffic facility supplies have resulted in severe : traffic congestion. High Occupancy Toll (HOT) lane operations have been proposed as one of the most : applicable and cost-effective countermea...

The design of a toll plaza

NASA Astrophysics Data System (ADS)

Dong, Haibin

2017-04-01

In this paper, a model is established to find the optimal shape, size and merging pattern of the toll plaza. The main work is how to take the aspects such as the accident prevention, throughput and cost into consideration to make the model of the toll plaza optimal. By analyzing the match of the number of tollbooths (B) and travel lanes (L) considering safety and cost, the optimal toll plaza model is established when the traffic flow is given.

Logit and probit model in toll sensitivity analysis of Solo-Ngawi, Kartasura-Palang Joglo segment based on Willingness to Pay (WTP)

NASA Astrophysics Data System (ADS)

Handayani, Dewi; Cahyaning Putri, Hera; Mahmudah, AMH

2017-12-01

Solo-Ngawi toll road project is part of the mega project of the Trans Java toll road development initiated by the government and is still under construction until now. PT Solo Ngawi Jaya (SNJ) as the Solo-Ngawi toll management company needs to determine the toll fare that is in accordance with the business plan. The determination of appropriate toll rates will affect progress in regional economic sustainability and decrease the traffic congestion. These policy instruments is crucial for achieving environmentally sustainable transport. Therefore, the objective of this research is to find out how the toll fare sensitivity of Solo-Ngawi toll road based on Willingness To Pay (WTP). Primary data was obtained by distributing stated preference questionnaires to four wheeled vehicle users in Kartasura-Palang Joglo artery road segment. Further data obtained will be analysed with logit and probit model. Based on the analysis, it is found that the effect of fare change on the amount of WTP on the binomial logit model is more sensitive than the probit model on the same travel conditions. The range of tariff change against values of WTP on the binomial logit model is 20% greater than the range of values in the probit model . On the other hand, the probability results of the binomial logit model and the binary probit have no significant difference (less than 1%).

β-Arrestins Negatively Regulate the Toll Pathway in Shrimp by Preventing Dorsal Translocation and Inhibiting Dorsal Transcriptional Activity*

PubMed Central

Sun, Jie-Jie; Lan, Jiang-Feng; Shi, Xiu-Zhen; Yang, Ming-Chong; Niu, Guo-Juan; Ding, Ding; Zhao, Xiao-Fan; Yu, Xiao-Qiang; Wang, Jin-Xing

2016-01-01

The Toll signaling pathway plays an important role in the innate immunity of Drosophila melanogaster and mammals. The activation and termination of Toll signaling are finely regulated in these animals. Although the primary components of the Toll pathway were identified in shrimp, the functions and regulation of the pathway are seldom studied. We first demonstrated that the Toll signaling pathway plays a central role in host defense against Staphylococcus aureus by regulating expression of antimicrobial peptides in shrimp. We then found that β-arrestins negatively regulate Toll signaling in two different ways. β-Arrestins interact with the C-terminal PEST domain of Cactus through the arrestin-N domain, and Cactus interacts with the RHD domain of Dorsal via the ankyrin repeats domain, forming a heterotrimeric complex of β-arrestin·Cactus·Dorsal, with Cactus as the bridge. This complex prevents Cactus phosphorylation and degradation, as well as Dorsal translocation into the nucleus, thus inhibiting activation of the Toll signaling pathway. β-Arrestins also interact with non-phosphorylated ERK (extracellular signal-regulated protein kinase) through the arrestin-C domain to inhibit ERK phosphorylation, which affects Dorsal translocation into the nucleus and phosphorylation of Dorsal at Ser276 that impairs Dorsal transcriptional activity. Our study suggests that β-arrestins negatively regulate the Toll signaling pathway by preventing Dorsal translocation and inhibiting Dorsal phosphorylation and transcriptional activity. PMID:26846853

Novel approaches for road congestion mitigation.

DOT National Transportation Integrated Search

2012-07-02

Transportation planning is usually aiming to solve two problems: the traffic assignment and the toll pricing problems. The latter one utilizes information from the first one, in order to find the optimal set of tolls that is the set of tolls that lea...

Novel approaches for road congestion minimization.

DOT National Transportation Integrated Search

2012-07-01

Transportation planning is usually aiming to solve two problems: the traffic assignment and the toll pricing problems. The latter one utilizes information from the first one, in order to find the optimal set of tolls that is the set of tolls that lea...

Electronic Toll And Traffic Management Systems, National Cooperative Highway Research Program Synthesis

DOT National Transportation Integrated Search

1993-01-01

ELECTRONIC TOLL COLLECTION OR ETC AND TRAFFIC MANAGEMENT OR ETTM, AUTOMATIC VEHICLE IDENTIFICATION OR AVI : ELECTRONIC TOLL COLLECTION AND TRAFFIC MANAGEMENT (ETTM) SYSTEMS ARE NOT A FUTURISTIC DREAM, THEY ARE OPERATING OR ARE BEING TESTED TODAY I...

Automatic vehicle identification technology applications to toll collection services

DOT National Transportation Integrated Search

1997-01-01

Intelligent transportation systems technologies are being developed and applied through transportation systems in the United States. An example of this type of innovation can be seen on toll roads where a driver is required to deposit a toll in order...

Suicide in the Guard and Reserve: Variables in Mental Health Access and Support

DTIC Science & Technology

2016-06-01

I’ve served for almost ten years in the Air National Guard. My career has consisted of serving in two states, both as a traditional Guardsman working...balancing two careers . Not to mention in recent years, the National Guard and Reserve forces have often faced multiple deployments, which can easily...take a toll on family stability and civilian careers . In response to these predicted stressors, the DoD implemented numerous programs in recent

Alcohol resistance in Drosophila is modulated by the Toll innate immune pathway.

PubMed

Troutwine, B R; Ghezzi, A; Pietrzykowski, A Z; Atkinson, N S

2016-04-01

A growing body of evidence has shown that alcohol alters the activity of the innate immune system and that changes in innate immune system activity can influence alcohol-related behaviors. Here, we show that the Toll innate immune signaling pathway modulates the level of alcohol resistance in Drosophila. In humans, a low level of response to alcohol is correlated with increased risk of developing an alcohol use disorder. The Toll signaling pathway was originally discovered in, and has been extensively studied in Drosophila. The Toll pathway is a major regulator of innate immunity in Drosophila, and mammalian Toll-like receptor signaling has been implicated in alcohol responses. Here, we use Drosophila-specific genetic tools to test eight genes in the Toll signaling pathway for effects on the level of response to ethanol. We show that increasing the activity of the pathway increases ethanol resistance whereas decreasing the pathway activity reduces ethanol resistance. Furthermore, we show that gene products known to be outputs of innate immune signaling are rapidly induced following ethanol exposure. The interaction between the Toll signaling pathway and ethanol is rooted in the natural history of Drosophila melanogaster. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Pelle kinase is activated by autophosphorylation during Toll signaling in Drosophila.

PubMed

Shen, Baohe; Manley, James L

2002-04-01

The Drosophila Pelle kinase plays a key role in the evolutionarily conserved Toll signaling pathway, but the mechanism responsible for its activation has been unknown. We present in vivo and in vitro evidence establishing an important role for concentration-dependent autophosphorylation in the signaling process. We first show that Pelle phosphorylation can be detected transiently in early embryos, concomitant with activation of signaling. Importantly, Pelle phosphorylation is enhanced in a gain-of-function Toll mutant (Toll(10b)), but decreased by loss-of-function Toll alleles. Next we found that Pelle is phosphorylated in transfected Schneider L2 cells in a concentration-dependent manner such that significant modification is observed only at high Pelle concentrations, which coincide with levels required for phosphorylation and activation of the downstream target, Dorsal. Pelle phosphorylation is also enhanced in L2 cells co-expressing Toll(10b), and is dependent on Pelle kinase activity. In vitro kinase assays revealed that recombinant, autophosphorylated Pelle is far more active than unphosphorylated Pelle. Importantly, unphosphorylated Pelle becomes autophosphorylated, and activated, by incubation at high concentrations. We discuss these results in the context of Toll-like receptor mediated signaling in both flies and mammals.

Toll facilities in the United States : bridges, roads, tunnels, ferries

DOT National Transportation Integrated Search

2007-12-01

This report contains selected information on toll facilities in the United States that has been provided to FHWA by the States and/or various toll authorities. The information is based on a survey of facilities in operation, financed, or under constr...

Toll facilities in the United States : bridges, roads, tunnels, ferries

DOT National Transportation Integrated Search

1997-02-01

The first section of this report presents a discussion of the history and current policy regarding toll roads in the United States. The second section contains selected information on toll facilities in the United States that has been provided to FHW...

47 CFR 52.105 - Warehousing.

Code of Federal Regulations, 2014 CFR

2014-10-01

... the Service Management System database without having an actual toll free subscriber for whom those... database; or (2) The Responsible Organization does not have an identified toll free subscriber agreeing to... database shall serve as that Responsible Organization's certification that there is an identified toll free...

47 CFR 52.105 - Warehousing.

Code of Federal Regulations, 2011 CFR

2011-10-01

... the Service Management System database without having an actual toll free subscriber for whom those... database; or (2) The Responsible Organization does not have an identified toll free subscriber agreeing to... database shall serve as that Responsible Organization's certification that there is an identified toll free...

47 CFR 52.105 - Warehousing.

Code of Federal Regulations, 2013 CFR

2013-10-01

... the Service Management System database without having an actual toll free subscriber for whom those... database; or (2) The Responsible Organization does not have an identified toll free subscriber agreeing to... database shall serve as that Responsible Organization's certification that there is an identified toll free...

47 CFR 52.105 - Warehousing.

Code of Federal Regulations, 2010 CFR

2010-10-01

... the Service Management System database without having an actual toll free subscriber for whom those... database; or (2) The Responsible Organization does not have an identified toll free subscriber agreeing to... database shall serve as that Responsible Organization's certification that there is an identified toll free...

47 CFR 52.105 - Warehousing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... the Service Management System database without having an actual toll free subscriber for whom those... database; or (2) The Responsible Organization does not have an identified toll free subscriber agreeing to... database shall serve as that Responsible Organization's certification that there is an identified toll free...

A dynamic feedback-control toll pricing methodology : a case study on Interstate 95 managed lanes.

DOT National Transportation Integrated Search

2013-06-01

Recently, congestion pricing emerged as a cost-effective and efficient strategy to mitigate the congestion problem on freeways. This study develops a feedback-control based dynamic toll approach to formulate and solve for optimal tolls. The study com...

Impact of transportation demand management (TDM) elements on managed lanes toll prices : [summary].

DOT National Transportation Integrated Search

2015-04-01

The 95 Express in Miami, Florida, is a set of dynamically tolled, managed lanes on I-95. : Single occupant vehicles must pay a toll to use 95 Express, but registered carpools, vanpools, : motorcycles, inherently low emission vehicles (ILEV; generally...

Simulation-Based Testbed Development for Analyzing Toll Impacts on Freeway Travel

DOT National Transportation Integrated Search

2012-06-01

Traffic congestion has been a world-wide problem in metropolitan areas all over the world. Toll-based traffic management is one of the most applicable solutions against freeway congestion. This research chooses two toll roads, the SR-167 HOT Lane and...

Toll immune signal activates cellular immune response via eicosanoids.

PubMed

Shafeeq, Tahir; Ahmed, Shabbir; Kim, Yonggyun

2018-07-01

Upon immune challenge, insects recognize nonself. The recognition signal will propagate to nearby immune effectors. It is well-known that Toll signal pathway induces antimicrobial peptide (AMP) gene expression. Eicosanoids play crucial roles in mediating the recognition signal to immune effectors by enhancing humoral immune response through activation of AMP synthesis as well as cellular immune responses, suggesting a functional cross-talk between Toll and eicosanoid signals. This study tested a cross-talk between these two signals. Two signal transducing factors (MyD88 and Pelle) of Toll immune pathway were identified in Spodoptera exigua. RNA interference (RNAi) of either SeMyD88 or SePelle expression interfered with the expression of AMP genes under Toll signal pathway. Bacterial challenge induced PLA 2 enzyme activity. However, RNAi of these two immune factors significantly suppressed the induction of PLA 2 enzyme activity. Furthermore, RNAi treatment prevented gene expression of cellular PLA 2 . Inhibition of PLA 2 activity reduced phenoloxidase activity and subsequent suppression in cellular immune response measured by hemocyte nodule formation. However, immunosuppression induced by RNAi of Toll signal molecules was significantly reversed by addition of arachidonic acid (AA), a catalytic product of PLA 2 . The addition also significantly reduced the enhanced fungal susceptibility of S. exigua treated by RNAi against two Toll signal molecules. These results indicate that there is a cross-talk between Toll and eicosanoid signals in insect immunity. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Grassroots Public/Private Toll Movement - The Lake of the Ozarks Community Bridge

DOT National Transportation Integrated Search

1999-01-01

From the 1930's through the 1960's, most of the toll-financed transportation : facilities in the U.S. were large, statewide initiatives, such as the New Jersey, : Massachusetts, and Kansas Turnpikes. When the toll movement was reborn in the : form of...

47 CFR 36.124 - Tandem switching equipment-Category 2.

Code of Federal Regulations, 2014 CFR

2014-10-01

... circuits with each other or with local or tandem telephone central office trunks, intertoll dial selector equipment, or intertoll trunk equipment in No. 5 type electronic offices. Equipment, including switchboards... interconnection of: Toll center to toll center circuits; toll center to tributary circuits; tributary to tributary...

47 CFR 36.124 - Tandem switching equipment-Category 2.

Code of Federal Regulations, 2012 CFR

2012-10-01

... circuits with each other or with local or tandem telephone central office trunks, intertoll dial selector equipment, or intertoll trunk equipment in No. 5 type electronic offices. Equipment, including switchboards... interconnection of: Toll center to toll center circuits; toll center to tributary circuits; tributary to tributary...

47 CFR 36.124 - Tandem switching equipment-Category 2.

Code of Federal Regulations, 2011 CFR

2011-10-01

... circuits with each other or with local or tandem telephone central office trunks, intertoll dial selector equipment, or intertoll trunk equipment in No. 5 type electronic offices. Equipment, including switchboards... interconnection of: Toll center to toll center circuits; toll center to tributary circuits; tributary to tributary...

47 CFR 36.124 - Tandem switching equipment-Category 2.

Code of Federal Regulations, 2013 CFR

2013-10-01

... circuits with each other or with local or tandem telephone central office trunks, intertoll dial selector equipment, or intertoll trunk equipment in No. 5 type electronic offices. Equipment, including switchboards... interconnection of: Toll center to toll center circuits; toll center to tributary circuits; tributary to tributary...

47 CFR 36.124 - Tandem switching equipment-Category 2.

Code of Federal Regulations, 2010 CFR

2010-10-01

... circuits with each other or with local or tandem telephone central office trunks, intertoll dial selector equipment, or intertoll trunk equipment in No. 5 type electronic offices. Equipment, including switchboards... interconnection of: Toll center to toll center circuits; toll center to tributary circuits; tributary to tributary...

Alaska Job Center Network

Science.gov Websites

Job Centers Toll-free in Alaska (877)724-2539 *Workshop Schedules are linked under participating Job : midtown.jobcenter@alaska.gov Employers: anchorage.employers@alaska.gov Toll free Anchorage Employer Phone: 1-888-830 -1149 Phone: 842-5579 Fax: 842-5679, Toll Free: 1-800-478-5579 Job Seekers & Employers

Genetic polymorphism in postoperative sepsis after open heart surgery in infants.

PubMed

Fakhri, Dicky; Djauzi, Samsuridjal; Murni, Tri Wahyu; Rachmat, Jusuf; Harahap, Alida Roswita; Rahayuningsih, Sri Endah; Mansyur, Muchtaruddin; Santoso, Anwar

2016-05-01

Sepsis is one of the complications following open heart surgery. Toll-like receptor 2 and toll-interacting protein polymorphism influence the immune response after open heart surgery. This study aimed to assess the genetic distribution of toll-like receptor 2 N199N and toll-interacting protein rs5743867 polymorphism in the development of postoperative sepsis. A prospective cohort study was conducted in 108 children <1-year old who underwent open heart surgery with a Basic Aristotle score ≥6. Patients with an accompanying congenital anomaly, human immunodeficiency virus infection, or history of previous open heart surgery were excluded. The patients' nutritional status and genetic polymorphism were assessed prior to surgery. The results of genetic polymorphism were obtained through genotyping. Patients' ages on the day of surgery and cardiopulmonary bypass times were recorded. The diagnosis of sepsis was established according to Surviving Sepsis Campaign criteria. Postoperative sepsis was observed in 21% of patients. There were 92.6% patients with toll-like receptor 2 N199N polymorphism and 52.8% with toll-interacting protein rs5743867 polymorphism. Toll-like receptor 2 N199N polymorphism tends to increase the risk of sepsis (odds ratio = 1.974; 95% confidence interval: 0.23-16.92; p = 0.504), while toll-interacting protein rs5743867 polymorphism tends to decrease the risk of sepsis (odds ratio = 0.496; 95% confidence interval: 0.19-1.27; p = 0.139) in infants <1-year old undergoing complex open heart surgery. © The Author(s) 2016.

23 CFR 661.49 - Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges?

Code of Federal Regulations, 2011 CFR

2011-04-01

..., and Toll Road IRR bridges? 661.49 Section 661.49 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS INDIAN RESERVATION ROAD BRIDGE PROGRAM § 661.49 Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges? Yes. Interstate...

Alaska State Legislature

Science.gov Websites

image description Tom Begich City: Anchorage Party: Democrat District: J Phone: 907-465-3704 Toll-Free : Republican District: C Phone: 907-465-2327 Toll-Free: 800-336-7383 Email Me image description John Coghill City: North Pole Party: Republican District: B Phone: 907-465-3719 Toll-Free: 877-465-3719 Fax: 907-465

Alaska State Legislature

Science.gov Websites

District: 26 Phone: 907-465-4931 Toll-Free: 800-870-4931 Email Me image description Mike Chenault City : Nikiski Party: Republican District: 29 Phone: 907-465-3779 Toll-Free: 800-469-3779 Email Me image description Matt Claman City: Anchorage Party: Democrat District: 21 Phone: 907-465-4919 Toll-Free: 888-465

76 FR 46897 - Open Meeting of the Taxpayer Advocacy Panel Small Business/Self Employed Correspondence Exam Toll...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-03

... Small Business/Self Employed Correspondence Exam Toll Free Project Committee AGENCY: Internal Revenue... Panel Small Business/ Self Employed Correspondence Exam Toll Free Project Committee will be conducted....C. App. (1988) that an open meeting of the Taxpayer Advocacy Panel Small Business/Self Employed...

76 FR 37893 - Open Meeting of the Taxpayer Advocacy Panel Small Business/Self Employed Correspondence Exam Toll...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-28

... Small Business/Self Employed Correspondence Exam Toll Free Project Committee AGENCY: Internal Revenue... Panel Small Business/ Self Employed Correspondence Exam Toll Free Project Committee will be conducted....C. App. (1988) that an open meeting of the Taxpayer Advocacy Panel Small Business/Self Employed...

76 FR 17996 - Open Meeting of the Taxpayer Advocacy Panel Small Business/Self Employed Correspondence Exam Toll...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-31

... Small Business/Self Employed Correspondence Exam Toll Free Project Committee AGENCY: Internal Revenue... Small Business/ Self Employed Correspondence Exam Toll Free Project Committee will be conducted. The... Act, 5 U.S.C. App. (1988) that an open meeting of the Taxpayer Advocacy Panel Small Business/Self...

76 FR 6190 - Open Meeting of the Taxpayer Advocacy Panel Small Business/Self Employed Correspondence Exam Toll...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-03

... Small Business/Self Employed Correspondence Exam Toll Free Project Committee AGENCY: Internal Revenue... Panel Small Business/ Self Employed Correspondence Exam Toll Free Project Committee will be conducted....C. App. (1988) that an open meeting of the Taxpayer Advocacy Panel Small Business/Self Employed...

76 FR 10942 - Open Meeting of the Taxpayer Advocacy Panel Small Business/Self Employed Correspondence Exam Toll...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-28

... Small Business/Self Employed Correspondence Exam Toll Free Project Committee AGENCY: Internal Revenue... Panel Small Business/ Self Employed Correspondence Exam Toll Free Project Committee will be conducted....C. App. (1988) that an open meeting of the Taxpayer Advocacy Panel Small Business/Self Employed...

77 FR 47165 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-07

... Toll-Free Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee will be conducted. The... at the Internal Revenue Service. DATES: The meeting will be held Tuesday, September 4, 2012. FOR...

23 CFR 661.49 - Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges?

Code of Federal Regulations, 2010 CFR

2010-04-01

..., and Toll Road IRR bridges? 661.49 Section 661.49 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS INDIAN RESERVATION ROAD BRIDGE PROGRAM § 661.49 Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges? Yes. Interstate...

Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila

PubMed Central

Phizacklea, Mark; Gay, Nicholas J.

2017-01-01

Cell number plasticity is coupled to circuitry in the nervous system, adjusting cell mass to functional requirements. In mammals, this is achieved by neurotrophin (NT) ligands, which promote cell survival via their Trk and p75NTR receptors and cell death via p75NTR and Sortilin. Drosophila NTs (DNTs) bind Toll receptors instead to promote neuronal survival, but whether they can also regulate cell death is unknown. In this study, we show that DNTs and Tolls can switch from promoting cell survival to death in the central nervous system (CNS) via a three-tier mechanism. First, DNT cleavage patterns result in alternative signaling outcomes. Second, different Tolls can preferentially promote cell survival or death. Third, distinct adaptors downstream of Tolls can drive either apoptosis or cell survival. Toll-6 promotes cell survival via MyD88–NF-κB and cell death via Wek-Sarm-JNK. The distribution of adaptors changes in space and time and may segregate to distinct neural circuits. This novel mechanism for CNS cell plasticity may operate in wider contexts. PMID:28373203

Analysis of potential diverted of passenger car to the new toll road (case study: Cileunyi - Sumedang, West Java)

NASA Astrophysics Data System (ADS)

Prahara, Eduardi; Suangga, Made; Lutfi Ansori, Ahmad

2017-12-01

This study aims to determine of potential of passenger car divert from national road to on-construction Cisumdawu Toll Road. The study was conducted by traffic count survey and followed by a roadside interview survey. Stated Preference method was used in order to analyse trip forecasting value. Mode choice model of new trip mode plans (Cisumdawu Toll Road) and current intercity road for Cileunyi - Sumedang is (UJT -UJR ) = 0.1079-0.507726x 1-0.8953764x 2, while Sumedang - Cileunyi is (UJT -UJR ) = 0.0790-0.301341x 1-0.548446x 2. Multiple linear regression analysis was used to obtain the forecasting of private vehicle that diverts to the new toll road (Cisumdawu Toll Road). Trip characteristics such as trip origin and destination, types of trips, occupations, salary, and others become a motive for respondents to choose a new trip mode. Results of the new trip mode forecasting that prefer to divert to the toll road in terms of the value of cost and time for Cileunyi - Sumedang are 74.11% and 86.62% respectively, while for Sumedang - Cileunyi are 69.60% and 76.48% respectively. These results are relatively high compare to toll planning document. The impact of this results can be determined such as lower overall fuel consumption, lower pollution and more important is the maintenance cost of national road will be decrease.

TLR and IMD signaling pathways from Caligus rogercresseyi (Crustacea: Copepoda): in silico gene expression and SNPs discovery.

PubMed

Valenzuela-Muñoz, V; Gallardo-Escárate, C

2014-02-01

The Toll and IMD signaling pathways represent one of the first lines of innate immune defense in invertebrates like Drosophila. However, for crustaceans like Caligus rogercresseyi, there is very little genomic information and, consequently, understanding of immune mechanisms. Massive sequencing data obtained for three developmental stages of C. rogercresseyi were used to evaluate in silico the expression patterns and presence of SNPs variants in genes involved in the Toll and IMD pathways. Through RNA-seq analysis, which used 20 contigs corresponding to relevant genes of the Toll and IMD pathways, an overexpression of genes linked to the Toll pathway, such as toll3 and Dorsal, were observed in the copepod stage. For the chalimus and adult stages, overexpression of genes in both pathways, such as Akirin and Tollip and IAP and Toll9, respectively, were observed. On the other hand, PCA statistical analysis inferred that in the chalimus and adult stages, the immune response mechanism was more developed, as evidenced by a relation between these two stages and the genes of both pathways. Moreover, 136 SNPs were identified for 20 contigs in genes of the Toll and IMD pathways. This study provides transcriptomic information about the immune response mechanisms of Caligus, thus providing a foundation for the development of new control strategies through blocking the innate immune response. Copyright © 2013 Elsevier Ltd. All rights reserved.

78 FR 2684 - Notice of Proposed Information Collection for Public Comment: Annual Progress Report (APR) for...

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2013-01-14

..., Washington, DC 20410-5000; telephone (202) 402-3400, (this is not a toll-free number) or email Ms. Pollard at... or speech impairments may access this number through TTY by calling the toll-free Federal Information... is not a toll-free number.) SUPPLEMENTARY INFORMATION: The Department will submit the proposed...

78 FR 15126 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee

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2013-03-08

... Toll-Free Phone Line Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of Meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Phone Line Project Committee will be held Tuesday, April 16, 2013 at 11:00 a.m. Eastern Time via...

78 FR 41193 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee

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2013-07-09

... Toll-Free Phone Line Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Phone Line Project Committee will be held Tuesday, August 20, 2013 at 11:00 a.m. Eastern Time via...

78 FR 11277 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee

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2013-02-15

... Toll-Free Phone Line Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of Meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Phone Line Project Committee will be held Tuesday, March 19, 2013 at 11:00 a.m. Eastern Time via...

78 FR 78517 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee

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2013-12-26

... Toll-Free Phone Line Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of Meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Phone Line Project Committee will be held Tuesday, January 21, 2014 at 11:00 a.m. Eastern Time via...

78 FR 64063 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee

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2013-10-25

... Toll-Free Phone Line Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Phone Line Project Committee will be held Tuesday, November 19, 2013 at 11:00 a.m. Eastern Time via...

78 FR 56269 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee

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2013-09-12

... Toll-Free Phone Line Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of Meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Phone Line Project Committee will be held Tuesday, October 15, 2013 at 11:00 a.m. Eastern Time via...

78 FR 69939 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project Committee

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2013-11-21

... Toll-Free Phone Line Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of Meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Phone Line Project Committee will be held Tuesday, December 17, 2013 at 11:00 a.m. Eastern Time via...

76 FR 2196 - Open Meeting of the Taxpayer Advocacy Panel Small Business/Self Employed Correspondence Exam Toll...

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2011-01-12

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76 FR 56880 - Open Meeting of the Taxpayer Advocacy Panel Small Business/Self Employed Correspondence Exam Toll...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-14

... Small Business/Self Employed Correspondence Exam Toll Free Project Committee AGENCY: Internal Revenue... Small Business/ Self Employed Correspondence Exam Toll Free Project Committee will be conducted. The...: Notice is hereby given pursuant to Section 10(a)(2) of the Federal Advisory Committee Act, 5 U.S.C. App...

76 FR 22170 - Open Meeting of the Taxpayer Advocacy Panel Small Business/Self Employed Correspondence Exam Toll...

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2011-04-20

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76 FR 63716 - Open Meeting of the Taxpayer Advocacy Panel Small Business/Self Employed Correspondence Exam Toll...

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2011-10-13

... Small Business/Self Employed Correspondence Exam Toll Free Project Committee AGENCY: Internal Revenue... Small Business/ Self Employed Correspondence Exam Toll Free Project Committee will be conducted. The...: Notice is hereby given pursuant to Section 10(a)(2) of the Federal Advisory Committee Act, 5 U.S.C. App...

75 FR 1685 - HOPE for Homeowners Program; Statutory Transfer of Program Authority to HUD and Conforming...

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2010-01-12

... by calling the Regulations Division at 202-708-3055 (this is not a toll-free number). Individuals with speech or hearing impairments may access this number through TTY by calling the toll-free Federal... a toll-free number). Persons with hearing or speech impairments may access this number through TTY...

32 CFR 536.26 - Identification of a proper claim.

Code of Federal Regulations, 2010 CFR

2010-07-01

... this section tolls the two-year statute of limitations (SOL) even though the documents required to... this part. (f) Receipt of a claim by another federal agency does not toll the SOL. Receipt of a U.S. Army claim by DOD, Navy, or Air Force does toll the SOL. (g) The guidelines set forth in federal FTCA...

Tractor-trailers, other commercial vehicles are in more multiple-vehicle crashes on most toll roads : single-vehicle crash rate is lower for commercials

DOT National Transportation Integrated Search

1999-07-17

Article discusses the findings of a study that compared data on commercial and passenger motor vehicle crashes on toll roads. This analysis is based on data from toll roads in Florida, Illinois, Indiana, Kansas, New York, Ohio, and Pennsylvania. In a...

Postconditioning: "Toll-erating" mesenteric ischemia-reperfusion injury?

PubMed

Rosero, Olivér; Ónody, Péter; Kovács, Tibor; Molnár, Dávid; Fülöp, András; Lotz, Gábor; Harsányi, László; Szijártó, Attila

2017-04-01

Postconditioning may prove to be a suitable method to decrease ischemia-reperfusion injury of intestine after mesenteric arterial occlusion. Toll-like-receptor-4 is involved in the pathophysiology of organ damage after ischemia-reperfusion; therefore, the aim of our study was to investigate the effect of postconditioning on the mucosal expression of toll-like-receptor-4. Male Wistar rats (n = 10/group) underwent 60 minutes of superior mesenteric artery occlusion followed by 6 hours of reperfusion in 3 groups: sham-operated, ischemia-reperfusion, and a postconditioned group. Postconditioning was performed by 6 alternating cycles of 10 seconds of reperfusion/reocclusion. Blood and tissue samples were collected at the end of reperfusion. Intestinal histopathologic changes and immunohistochemical expression of mucosal caspase-3, antioxidant status, and protein levels of high-mobility group box-1 and toll-like-receptor-4 were assessed. Immunofluorescent labeling and confocal microscopic analysis of toll-like-receptor-4 were performed. Mucosal and serum levels of interleukin-6 and tumor necrosis factor-α protein were measured. Histologic alterations in the postconditioned group were associated with decreased caspase-3 positivity, less toll-like-receptor-4 mRNA, and less protein expression of high-mobility group box-1 and toll-like-receptor-4 in the intestinal villi compared with the ischemia-reperfusion group. Furthermore, a significantly improved antioxidant state of the intestinal mucosa and less mucosal and serum protein levels of interleukin-6 and tumor necrosis factor-α were detected in the postconditioned group. Small intestinal ischemia-reperfusion injury in male Wistar rats caused by the occlusion of the superior mesenteric artery was ameliorated by the use of postconditioning, showing a more favorable inflammatory response, which may be attributed to the decreased mucosal expression of toll-like-receptor-4. Copyright © 2016 Elsevier Inc. All rights reserved.

Proteolytic Cascade for the Activation of the Insect Toll Pathway Induced by the Fungal Cell Wall Component

PubMed Central

Roh, Kyung-Baeg; Kim, Chan-Hee; Lee, Hanna; Kwon, Hyun-Mi; Park, Ji-Won; Ryu, Ji-Hwan; Kurokawa, Kenji; Ha, Nam-Chul; Lee, Won-Jae; Lemaitre, Bruno; Söderhäll, Kenneth; Lee, Bok-Luel

2009-01-01

The insect Toll signaling pathway is activated upon recognition of Gram-positive bacteria and fungi, resulting in the expression of antimicrobial peptides via NF-κB-like transcription factor. This activation is mediated by a serine protease cascade leading to the processing of Spätzle, which generates the functional ligand of the Toll receptor. Recently, we identified three serine proteases mediating Toll pathway activation induced by lysine-type peptidoglycan of Gram-positive bacteria. However, the identities of the downstream serine protease components of Gram-negative-binding protein 3 (GNBP3), a receptor for a major cell wall component β-1,3-glucan of fungi, and their order of activation have not been characterized yet. Here, we identified three serine proteases that are required for Toll activation by β-1,3-glucan in the larvae of a large beetle, Tenebrio molitor. The first one is a modular serine protease functioning immediately downstream of GNBP3 that proteolytically activates the second one, a Spätzle-processing enzyme-activating enzyme that in turn activates the third serine protease, a Spätzle-processing enzyme. The active form of Spätzle-processing enzyme then cleaves Spätzle into the processed Spätzle as Toll ligand. In addition, we show that injection of β-1,3-glucan into Tenebrio larvae induces production of two antimicrobial peptides, Tenecin 1 and Tenecin 2, which are also inducible by injection of the active form of Spätzle-processing enzyme-activating enzyme or processed Spätzle. These results demonstrate a three-step proteolytic cascade essential for the Toll pathway activation by fungal β-1,3-glucan in Tenebrio larvae, which is shared with lysine-type peptidoglycan-induced Toll pathway activation. PMID:19473968

Sex Differences in the Response to Viral Infections: TLR8 and TLR9 Ligand Stimulation Induce Higher IL10 Production in Males

PubMed Central

Torcia, Maria Gabriella; Nencioni, Lucia; Clemente, Ann Maria; Civitelli, Livia; Celestino, Ignacio; Limongi, Dolores; Fadigati, Giulia; Perissi, Eloisa; Cozzolino, Federico; Garaci, Enrico; Palamara, Anna Teresa

2012-01-01

Background Susceptibility to viral infections as well as their severity are higher in men than in women. Heightened antiviral responses typical of women are effective for rapid virus clearance, but if excessively high or prolonged, can result in chronic/inflammatory pathologies. We investigated whether this variability could be in part attributable to differences in the response to the Toll-Like Receptors (TLR) more involved in the virus recognition. Methods Cytokine production by peripheral blood mononuclear cells (PBMCs) from male and female healthy donors after stimulation with Toll-like receptors (TLR) 3, 7, 8, 9 ligands or with viruses (influenza and Herpes-simplex-1) was evaluated. Results Compared to females, PBMCs from males produced not only lower amounts of IFN-α in response to TLR7 ligands but also higher amounts of the immunosuppressive cytokine IL10 after stimulation with TLR8 and TLR9 ligands or viruses. IL10 production after TLR9 ligands or HSV-1 stimulation was significantly related with plasma levels of sex hormones in both groups, whereas no correlation was found in cytokines produced following TLR7 and TLR8 stimulation. Conclusions Given the role of an early production of IL10 by cells of innate immunity in modulating innate and adaptive immune response to viruses, we suggest that sex-related difference in its production following viral nucleic acid stimulation of TLRs may be involved in the sex-related variability in response to viral infections. PMID:22768144

77 FR 23756 - Agency Information Collection Activities; Submission for OMB Review; Comment Request...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-20

... this notice or by contacting Michel Smyth by telephone at 202-693-4129 (this is not a toll-free number... 10235, Washington, DC 20503, Telephone: 202-395-6929/Fax: 202-395-6881 (these are not toll-free numbers...-693- 4129 (this is not a toll-free number) or by email at [email protected] . SUPPLEMENTARY...

76 FR 10053 - Changes to the Public Housing Assessment System (PHAS): Capital Fund Scoring Notice

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2011-02-23

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76 FR 10050 - Changes to the Public Housing Assessment System (PHAS): Management Operations Scoring Notice

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2011-02-23

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23 CFR 661.49 - Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges?

Code of Federal Regulations, 2012 CFR

2012-04-01

... 23 Highways 1 2012-04-01 2012-04-01 false Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges? 661.49 Section 661.49 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT... Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges? Yes. Interstate...

23 CFR 661.49 - Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges?

Code of Federal Regulations, 2014 CFR

2014-04-01

... 23 Highways 1 2014-04-01 2014-04-01 false Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges? 661.49 Section 661.49 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT... Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges? Yes. Interstate...

23 CFR 661.49 - Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges?

Code of Federal Regulations, 2013 CFR

2013-04-01

... 23 Highways 1 2013-04-01 2013-04-01 false Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges? 661.49 Section 661.49 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT... Can IRRBP funds be spent on Interstate, State Highway, and Toll Road IRR bridges? Yes. Interstate...

Serpin Facilitates Tumor-Suppressive Cell Competition by Blocking Toll-Mediated Yki Activation in Drosophila.

PubMed

Katsukawa, Mitsuko; Ohsawa, Shizue; Zhang, Lina; Yan, Yan; Igaki, Tatsushi

2018-06-04

Normal epithelial tissue exerts an intrinsic tumor-suppressive effect against oncogenically transformed cells. In Drosophila imaginal epithelium, clones of oncogenic polarity-deficient cells mutant for scribble (scrib) or discs large (dlg) are eliminated by cell competition when surrounded by wild-type cells. Here, through a genetic screen in Drosophila, we identify Serpin5 (Spn5), a secreted negative regulator of Toll signaling, as a crucial factor for epithelial cells to eliminate scrib mutant clones from epithelium. Downregulation of Spn5 in wild-type cells leads to elevation of Toll signaling in neighboring scrib cells. Strikingly, forced activation of Toll signaling or Toll-related receptor (TRR) signaling in scrib clones transforms scrib cells from losers to supercompetitors, resulting in tumorous overgrowth of mutant clones. Mechanistically, Toll activation in scrib clones leads to c-Jun N-terminal kinase (JNK) activation and F-actin accumulation, which cause strong activation of the Hippo pathway effector Yorkie that blocks cell death and promotes cell proliferation. Our data suggest that Spn5 secreted from normal epithelial cells acts as a component of the extracellular surveillance system that facilitates elimination of pre-malignant cells from epithelium. Copyright © 2018 Elsevier Ltd. All rights reserved.

Linear signaling in the Toll-Dorsal pathway of Drosophila: activated Pelle kinase specifies all threshold outputs of gene expression while the bHLH protein Twist specifies a subset.

PubMed

Stathopoulos, Angelike; Levine, Michael

2002-07-01

Differential activation of the Toll receptor leads to the formation of a broad Dorsal nuclear gradient that specifies at least three patterning thresholds of gene activity along the dorsoventral axis of precellular embryos. We investigate the activities of the Pelle kinase and Twist basic helix-loop-helix (bHLH) transcription factor in transducing Toll signaling. Pelle functions downstream of Toll to release Dorsal from the Cactus inhibitor. Twist is an immediate-early gene that is activated upon entry of Dorsal into nuclei. Transgenes misexpressing Pelle and Twist were introduced into different mutant backgrounds and the patterning activities were visualized using various target genes that respond to different thresholds of Toll-Dorsal signaling. These studies suggest that an anteroposterior gradient of Pelle kinase activity is sufficient to generate all known Toll-Dorsal patterning thresholds and that Twist can function as a gradient morphogen to establish at least two distinct dorsoventral patterning thresholds. We discuss how the Dorsal gradient system can be modified during metazoan evolution and conclude that Dorsal-Twist interactions are distinct from the interplay between Bicoid and Hunchback, which pattern the anteroposterior axis.

An effector Peptide family required for Drosophila toll-mediated immunity.

PubMed

Clemmons, Alexa W; Lindsay, Scott A; Wasserman, Steven A

2015-04-01

In Drosophila melanogaster, recognition of an invading pathogen activates the Toll or Imd signaling pathway, triggering robust upregulation of innate immune effectors. Although the mechanisms of pathogen recognition and signaling are now well understood, the functions of the immune-induced transcriptome and proteome remain much less well characterized. Through bioinformatic analysis of effector gene sequences, we have defined a family of twelve genes - the Bomanins (Boms) - that are specifically induced by Toll and that encode small, secreted peptides of unknown biochemical activity. Using targeted genome engineering, we have deleted ten of the twelve Bom genes. Remarkably, inactivating these ten genes decreases survival upon microbial infection to the same extent, and with the same specificity, as does eliminating Toll pathway function. Toll signaling, however, appears unaffected. Assaying bacterial load post-infection in wild-type and mutant flies, we provide evidence that the Boms are required for resistance to, rather than tolerance of, infection. In addition, by generating and assaying a deletion of a smaller subset of the Bom genes, we find that there is overlap in Bom activity toward particular pathogens. Together, these studies deepen our understanding of Toll-mediated immunity and provide a new in vivo model for exploration of the innate immune effector repertoire.

76 FR 59162 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Federal...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-23

... contacting Michel Smyth by telephone at 202-693-4129 (this is not a toll-free number) or sending an e-mail to...: 202-395-6881 (these are not toll-free numbers), e-mail: [email protected] . FOR FURTHER INFORMATION CONTACT: Michel Smyth by telephone at 202-693- 4129 (this is not a toll-free number) or by e-mail...

The Toll pathway underlies host sexual dimorphism in resistance to both Gram-negative and Gram-positive bacteria in mated Drosophila.

PubMed

Duneau, David F; Kondolf, Hannah C; Im, Joo Hyun; Ortiz, Gerardo A; Chow, Christopher; Fox, Michael A; Eugénio, Ana T; Revah, J; Buchon, Nicolas; Lazzaro, Brian P

2017-12-21

Host sexual dimorphism is being increasingly recognized to generate strong differences in the outcome of infectious disease, but the mechanisms underlying immunological differences between males and females remain poorly characterized. Here, we used Drosophila melanogaster to assess and dissect sexual dimorphism in the innate response to systemic bacterial infection. We demonstrated sexual dimorphism in susceptibility to infection by a broad spectrum of Gram-positive and Gram-negative bacteria. We found that both virgin and mated females are more susceptible than mated males to most, but not all, infections. We investigated in more detail the lower resistance of females to infection with Providencia rettgeri, a Gram-negative bacterium that naturally infects D. melanogaster. We found that females have a higher number of phagocytes than males and that ablation of hemocytes does not eliminate the dimorphism in resistance to P. rettgeri, so the observed dimorphism does not stem from differences in the cellular response. The Imd pathway is critical for the production of antimicrobial peptides in response to Gram-negative bacteria, but mutants for Imd signaling continued to exhibit dimorphism even though both sexes showed strongly reduced resistance. Instead, we found that the Toll pathway is responsible for the dimorphism in resistance. The Toll pathway is dimorphic in genome-wide constitutive gene expression and in induced response to infection. Toll signaling is dimorphic in both constitutive signaling and in induced activation in response to P. rettgeri infection. The dimorphism in pathway activation can be specifically attributed to Persephone-mediated immune stimulation, by which the Toll pathway is triggered in response to pathogen-derived virulence factors. We additionally found that, in absence of Toll signaling, males become more susceptible than females to the Gram-positive Enterococcus faecalis. This reversal in susceptibility between male and female Toll pathway mutants compared to wildtype hosts highlights the key role of the Toll pathway in D. melanogaster sexual dimorphism in resistance to infection. Altogether, our data demonstrate that Toll pathway activity differs between male and female D. melanogaster in response to bacterial infection, thus identifying innate immune signaling as a determinant of sexual immune dimorphism.

Spätzle-Processing Enzyme-independent Activation of the Toll Pathway in Drosophila Innate Immunity.

PubMed

Yamamoto-Hino, Miki; Goto, Satoshi

2016-05-07

The Toll pathway regulates innate immunity in insects and vertebrates. The Drosophila Toll receptor is activated by a processed form of a ligand, Spätzle. Spätzle-processing enzyme (SPE) is the only enzyme identified to date that functions in converting Spätzle to an active form during the immune response. In the present study, Toll activation induced by immune challenge was almost suppressed in spätzle mutant larvae and adults, whereas it was present in SPE mutant larvae challenged with Micrococcus luteus and adults challenged with Bacillus subtilis. Our data suggest that an unidentified protease besides SPE processes Spätzle under conditions of microbial challenge.

Structure of the Toll-Spatzle complex, a molecular hub in Drosophila development and innate immunity.

PubMed

Parthier, Christoph; Stelter, Marco; Ursel, Christian; Fandrich, Uwe; Lilie, Hauke; Breithaupt, Constanze; Stubbs, Milton T

2014-04-29

Drosophila Toll receptors are involved in embryonic development and the immune response of adult flies. In both processes, the only known Toll receptor ligand is the human nerve growth factor-like cystine knot protein Spätzle. Here we present the crystal structure of a 1:1 (nonsignaling) complex of the full-length Toll receptor ectodomain (ECD) with the Spätzle cystine knot domain dimer. The ECD is divided into two leucine-rich repeat (LRR) domains, each of which is capped by cysteine-rich domains. Spätzle binds to the concave surface of the membrane-distal LRR domain, in contrast to the flanking ligand interactions observed for mammalian Toll-like receptors, with asymmetric contributions from each Spätzle protomer. The structure allows rationalization of existing genetic and biochemical data and provides a framework for targeting the immune systems of insects of economic importance, as well as a variety of invertebrate disease vectors.

A novel function for the IκB inhibitor Cactus in promoting Dorsal nuclear localization and activity in the Drosophila embryo.

PubMed

Cardoso, Maira Arruda; Fontenele, Marcio; Lim, Bomyi; Bisch, Paulo Mascarello; Shvartsman, Stanislav Y; Araujo, Helena Marcolla

2017-08-15

The evolutionarily conserved Toll signaling pathway controls innate immunity across phyla and embryonic patterning in insects. In the Drosophila embryo, Toll is required to establish gene expression domains along the dorsal-ventral axis. Pathway activation induces degradation of the IκB inhibitor Cactus, resulting in a ventral-to-dorsal nuclear gradient of the NFκB effector Dorsal. Here, we investigate how cactus modulates Toll signals through its effects on the Dorsal gradient and on Dorsal target genes. Quantitative analysis using a series of loss- and gain-of-function conditions shows that the ventral and lateral aspects of the Dorsal gradient can behave differently with respect to Cactus fluctuations. In lateral and dorsal embryo domains, loss of Cactus allows more Dorsal to translocate to the nucleus. Unexpectedly, cactus loss-of-function alleles decrease Dorsal nuclear localization ventrally, where Toll signals are high. Overexpression analysis suggests that this ability of Cactus to enhance Toll stems from the mobilization of a free Cactus pool induced by the Calpain A protease. These results indicate that Cactus acts to bolster Dorsal activation, in addition to its role as a NFκB inhibitor, ensuring a correct response to Toll signals. © 2017. Published by The Company of Biologists Ltd.

Uncovering the 2010 Haiti earthquake death toll

NASA Astrophysics Data System (ADS)

Daniell, J. E.; Khazai, B.; Wenzel, F.

2013-05-01

Casualties are estimated for the 12 January 2010 earthquake in Haiti using various reports calibrated by observed building damage states from satellite imagery and reconnaissance reports on the ground. By investigating various damage reports, casualty estimates and burial figures, for a one year period from 12 January 2010 until 12 January 2011, there is also strong evidence that the official government figures of 316 000 total dead and missing, reported to have been caused by the earthquake, are significantly overestimated. The authors have examined damage and casualties report to arrive at their estimation that the median death toll is less than half of this value (±137 000). The authors show through a study of historical earthquake death tolls, that overestimates of earthquake death tolls occur in many cases, and is not unique to Haiti. As death toll is one of the key elements for determining the amount of aid and reconstruction funds that will be mobilized, scientific means to estimate death tolls should be applied. Studies of international aid in recent natural disasters reveal that large distributions of aid which do not match the respective needs may cause oversupply of help, aggravate corruption and social disruption rather than reduce them, and lead to distrust within the donor community.

Streamflow and water-quality conditions including geologic sources and processes affecting selenium loading in the Toll Gate Creek watershed, Aurora, Arapahoe County, Colorado, 2007

USGS Publications Warehouse

Paschke, Suzanne S.; Runkel, Robert L.; Walton-Day, Katherine; Kimball, Briant A.; Schaffrath, Keelin R.

2013-01-01

Toll Gate Creek is a perennial stream draining a suburban area in Aurora, Colorado, where selenium concentrations have consistently exceeded the State of Colorado aquatic-life standard for selenium of 4.6 micrograms per liter since the early 2000s. In cooperation with the City of Aurora, Colorado, Utilities Department, a synoptic water-quality study was performed along an 18-kilometer reach of Toll Gate Creek extending from downstream from Quincy Reservoir to the confluence with Sand Creek to develop a detailed understanding of streamflow and concentrations and loads of selenium in Toll Gate Creek. Streamflow and surface-water quality were characterized for summer low-flow conditions (July–August 2007) using four spatially overlapping synoptic-sampling subreaches. Mass-balance methods were applied to the synoptic-sampling and tracer-injection results to estimate streamflow and develop spatial profiles of concentration and load for selenium and other chemical constituents in Toll Gate Creek surface water. Concurrent groundwater sampling determined concentrations of selenium and other chemical constituents in groundwater in areas surrounding the Toll Gate Creek study reaches. Multivariate principal-component analysis was used to group samples and to suggest common sources for dissolved selenium and major ions. Hydrogen and oxygen stable-isotope ratios, groundwater-age interpretations, and chemical analysis of water-soluble paste extractions from core samples are presented, and interpretation of the hydrologic and geochemical data support conclusions regarding geologic sources of selenium and the processes affecting selenium loading in the Toll Gate Creek watershed.

Public expenditure for plasma-derived and recombinant medicinal products in Italy.

PubMed

Lanzoni, Monica; Candura, Fabio; Calizzani, Gabriele; Biffoli, Claudia; Grazzini, Giuliano

2013-09-01

In Italy, the supply of plasma-derived medicinal products funded by the National Health Service can be through public healthcare facilities, accredited pharmacies or toll fractionation agreements between Regions and the manufacturer. Pharmaceutical public expenditure includes the supply related to the first two channels and costs can significantly vary because of channel-specific price reductions. This paper describes 2011 public expenditure for plasma-derived medicinal products purchased on the market, as well as the cost analysis per active substance. Analysis of the usage of plasma-derived medicinal products and of the related expenditure in public facilities has been carried out using medicinal product traceability data. The analysis related to the accredited pharmacies channel has been carried out using quantities for every medicinal package recorded by Pharmacy Associations and applying reference prices in force on March 1(st), 2012 as well as discounts for the accredited pharmaceutical expenditure imposed by law. At national and regional level, total and total per capita expenditures on plasma-derived medicinal products by market channel and funded by the National Health Service are shown. Analysis was conducted considering the active substances in three groups: substances included in toll fractionation agreements, recombinant coagulation factors, and other substances not included in toll fractionation agreements. In 2011, the national expenditure estimate for plasma-derived and recombinant medicinal product acquisition on the market was about € 535 million. The purchased volumes and mean purchased prices per unit of each substance have a significant influence on the observed regional variability of the pharmaceutical public expenditure. A strategy of regional comparison aimed at both sharing a national range of reference for purchase prices and evaluating modalities for centralised purchasing is desirable.

Two White Spot Syndrome Virus MicroRNAs Target the Dorsal Gene To Promote Virus Infection in Marsupenaeus japonicus Shrimp

PubMed Central

Ren, Qian; Huang, Xin; Cui, Yalei; Sun, Jiejie; Wang, Wen

2017-01-01

ABSTRACT In eukaryotes, microRNAs (miRNAs) serve as regulators of many biological processes, including virus infection. An miRNA can generally target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs has not yet been extensively explored during virus infection. This study found that the Spaztle (Spz)-Toll-Dorsal-antilipopolysaccharide factor (ALF) signaling pathway plays a very important role in antiviral immunity against invasion of white spot syndrome virus (WSSV) in shrimp (Marsupenaeus japonicus). Dorsal, the central gene in the Toll pathway, was targeted by two viral miRNAs (WSSV-miR-N13 and WSSV-miR-N23) during WSSV infection. The regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo, leading to virus infection. Our study contributes novel insights into the viral miRNA-mediated Toll signaling pathway during the virus-host interaction. IMPORTANCE An miRNA can target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs during virus infection has not yet been extensively explored. The results of this study indicated that the shrimp Dorsal gene, the central gene in the Toll pathway, was targeted by two viral miRNAs during infection with white spot syndrome virus. Regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo, leading to virus infection. Our study provides new insight into the viral miRNA-mediated Toll signaling pathway in virus-host interactions. PMID:28179524

Two White Spot Syndrome Virus MicroRNAs Target the Dorsal Gene To Promote Virus Infection in Marsupenaeus japonicus Shrimp.

PubMed

Ren, Qian; Huang, Xin; Cui, Yalei; Sun, Jiejie; Wang, Wen; Zhang, Xiaobo

2017-04-15

In eukaryotes, microRNAs (miRNAs) serve as regulators of many biological processes, including virus infection. An miRNA can generally target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs has not yet been extensively explored during virus infection. This study found that the Spaztle (Spz)-Toll-Dorsal-antilipopolysaccharide factor (ALF) signaling pathway plays a very important role in antiviral immunity against invasion of white spot syndrome virus (WSSV) in shrimp ( Marsupenaeus japonicus ). Dorsal , the central gene in the Toll pathway, was targeted by two viral miRNAs (WSSV-miR-N13 and WSSV-miR-N23) during WSSV infection. The regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo , leading to virus infection. Our study contributes novel insights into the viral miRNA-mediated Toll signaling pathway during the virus-host interaction. IMPORTANCE An miRNA can target diverse genes during virus-host interactions. However, the regulation of gene expression by multiple miRNAs during virus infection has not yet been extensively explored. The results of this study indicated that the shrimp Dorsal gene, the central gene in the Toll pathway, was targeted by two viral miRNAs during infection with white spot syndrome virus. Regulation of Dorsal expression by viral miRNAs suppressed the Spz-Toll-Dorsal-ALF signaling pathway in shrimp in vivo , leading to virus infection. Our study provides new insight into the viral miRNA-mediated Toll signaling pathway in virus-host interactions. Copyright © 2017 American Society for Microbiology.

Serum oxidant and antioxidant levels in diesel exposed toll collectors.

PubMed

Arbak, Peri; Yavuz, Ozlem; Bukan, Neslihan; Balbay, Oner; Ulger, Füsun; Annakkaya, Ali Nihat

2004-07-01

It has been suggested that exposure to diesel exhaust may lead to adverse effects due to the generation of oxidants. To evaluate the end products of oxidative stress in DE exposure, toll collectors who are considered a high risk group in regard to occupational toxins were compared to controls who had office-based occupations in the same company in this cross sectional study. A total of 38 toll collectors constituted the study group. All subjects were male. The toll collectors and 29 controls were similar regarding age, smoking status and duration of work. All subjects underwent a clinical examination and an interviewer-administrated questionnaire regarding respiratory symptoms, past medical and occupational history, and pulmonary function tests were performed in all subjects. Serum malondialdehyde (MDA), nitrite+nitrate and vitamin E levels were measured. Toll collectors showed higher serum MDA (5.76 +/- 2.15 micromol/L vs. 3.07 +/- 0.76 micromol/L, p=0.0001) and nitrite+nitrate levels (96.50 +/- 45.54 micromol/L vs. 19.32 +/- 11.77 micromol/L, p=0.0001) than controls. Vitamin E levels were similar in toll collectors and controls (10.57 +/- 3.44 mg/L and 9.72 +/- 2.44 mg/L, respectively, p=0.267). There was no difference between groups in terms of the findings of clinical examinations and respiratory symptoms. In pulmonary function parameters, only peak expiratory flow (PEF) in toll collectors was significantly lower than that of controls (88.9% predicted and 104.2% predicted, respectively, p=0.012). In conclusion, we suggest that serum MDA and nitrite+nitrate levels may be used as biological markers of oxidative stress related to DE exposure, but prospective controlled clinical studies are necessary to clarify the possible association between concentrations of MDA and nitrite+nitrate and pulmonary diseases related to DE exposure.

Enrichment assessment of multiple virtual screening strategies for Toll-like receptor 8 agonists based on a maximal unbiased benchmarking data set.

PubMed

Pei, Fen; Jin, Hongwei; Zhou, Xin; Xia, Jie; Sun, Lidan; Liu, Zhenming; Zhang, Liangren

2015-11-01

Toll-like receptor 8 agonists, which activate adaptive immune responses by inducing robust production of T-helper 1-polarizing cytokines, are promising candidates for vaccine adjuvants. As the binding site of toll-like receptor 8 is large and highly flexible, virtual screening by individual method has inevitable limitations; thus, a comprehensive comparison of different methods may provide insights into seeking effective strategy for the discovery of novel toll-like receptor 8 agonists. In this study, the performance of knowledge-based pharmacophore, shape-based 3D screening, and combined strategies was assessed against a maximum unbiased benchmarking data set containing 13 actives and 1302 decoys specialized for toll-like receptor 8 agonists. Prior structure-activity relationship knowledge was involved in knowledge-based pharmacophore generation, and a set of antagonists was innovatively used to verify the selectivity of the selected knowledge-based pharmacophore. The benchmarking data set was generated from our recently developed 'mubd-decoymaker' protocol. The enrichment assessment demonstrated a considerable performance through our selected three-layer virtual screening strategy: knowledge-based pharmacophore (Phar1) screening, shape-based 3D similarity search (Q4_combo), and then a Gold docking screening. This virtual screening strategy could be further employed to perform large-scale database screening and to discover novel toll-like receptor 8 agonists. © 2015 John Wiley & Sons A/S.

Hoarseness

MedlinePlus

... MD 20892-3456 Toll-free voice: (800) 241-1044 Toll-free TTY: (800) 241-1055 Email: nidcdinfo@ ... questions in English or Spanish. Voice: (800) 241-1044 TTY: (800) 241-1055 nidcdinfo@nidcd.nih.gov ...

Apraxia of Speech

MedlinePlus

... MD 20892-3456 Toll-free voice: (800) 241-1044 Toll-free TTY: (800) 241-1055 Email: nidcdinfo@ ... questions in English or Spanish. Voice: (800) 241-1044 TTY: (800) 241-1055 nidcdinfo@nidcd.nih.gov ...

Vocal Fold Paralysis

MedlinePlus

... MD 20892-3456 Toll-free voice: (800) 241-1044 Toll-free TTY: (800) 241-1055 Email: nidcdinfo@ ... questions in English or Spanish. Voice: (800) 241-1044 TTY: (800) 241-1055 nidcdinfo@nidcd.nih.gov ...

Toll-like receptor 4 promotes autonomic dysfunction, inflammation and microglia activation in the hypothalamic paraventricular nucleus: role of endoplasmic reticulum stress.

PubMed

Masson, Gustavo S; Nair, Anand R; Dange, Rahul B; Silva-Soares, Pedro Paulo; Michelini, Lisete C; Francis, Joseph

2015-01-01

Toll-like receptor 4 (TLR4) signaling induces tissue pro-inflammatory cytokine release and endoplasmic reticulum (ER) stress. We examined the role of TLR4 in autonomic dysfunction and the contribution of ER stress. Our study included animals divided in 6 experimental groups: rats treated with saline (i.v., 0.9%), LPS (i.v., 10mg/kg), VIPER (i.v., 0.1 mg/kg), or 4-PBA (i.p., 10 mg/kg). Two other groups were pretreated either with VIPER (TLR4 viral inhibitory peptide) LPS + VIPER (i.v., 0.1 mg/kg) or 4-Phenyl butyric acid (4-PBA) LPS + PBA (i.p., 10 mg/kg). Arterial pressure (AP) and heart rate (HR) were measured in conscious Sprague-Dawley rats. AP, HR variability, as well as baroreflex sensitivity (BrS), was determined after LPS or saline treatment for 2 hours. Immunofluorescence staining for NeuN, Ib1a, TLR4 and GRP78 in the hypothalamic paraventricular nucleus (PVN) was performed. TNF-α, TLR4 and GRP78 protein expression in the PVN were evaluated by western blot. Plasma norepinephrine levels were determined by ELISA. Acute LPS treatment increased HR and plasma norepinephrine concentration. It also decreased HR variability and high frequency (HF) components of HR variability, as well BrS. Acute LPS treatment increased TLR4 and TNF-α protein expression in the PVN. These hemodynamic and molecular effects were partially abrogated with TLR4 blocker or ER stress inhibitor pretreatment. In addition, immunofluorescence study showed that TLR4 is co-localized with GRP78in the neurons. Further inhibition of TLR4 or ER stress was able to attenuate the LPS-induced microglia activation. TLR4 signaling promotes autonomic dysfunction, inflammation and microglia activation, through neuronal ER stress, in the PVN.

TSCA Chemical Data Reporting Fact Sheet: Toll Manufacturing

EPA Pesticide Factsheets

This fact sheet provides information on existing Chemical Data Reporting (CDR) regulations to persons who are involved in toll manufacturing of chemical substances which may be subject to the CDR rule.

Health sciences librarians, patient contact, and secondary traumatic stress.

PubMed

Becker, Rachel W; McCrillis, Aileen

2015-04-01

The purpose of this study was to determine the prevalence of secondary traumatic stress (STS) in health sciences librarians (HSLs) who have direct contact with traumatized individuals and their families. A twenty-five-item survey and the Secondary Traumatic Stress Scale (STSS) were distributed via email to three Medical Library Association email discussion lists. A total of fifty-five HSLs responded to the survey. Survey results indicate moderate levels of STS and variability of symptoms among participants. Library and employee assistance program managers should be aware of the emotional toll of patient and/or family contact for HSLs.

Equity of tolling : myths and realities

DOT National Transportation Integrated Search

2010-02-26

This presentation discusses the equity and efficiency of tolling and the increases in efficiency from efficiency gains. Efficiency and equity are inextricably related, and they are not inherently in conflict. Congestion pricing generates positive net...

Toll Mediated Infection Response Is Altered by Gravity and Spaceflight in Drosophila

PubMed Central

Taylor, Katherine; Kleinhesselink, Kurt; George, Michael D.; Morgan, Rachel; Smallwood, Tangi; Hammonds, Ann S.; Fuller, Patrick M.; Saelao, Perot; Alley, Jeff; Gibbs, Allen G.; Hoshizaki, Deborah K.; von Kalm, Laurence; Fuller, Charles A.; Beckingham, Kathleen M.; Kimbrell, Deborah A.

2014-01-01

Space travel presents unlimited opportunities for exploration and discovery, but requires better understanding of the biological consequences of long-term exposure to spaceflight. Immune function in particular is relevant for space travel. Human immune responses are weakened in space, with increased vulnerability to opportunistic infections and immune-related conditions. In addition, microorganisms can become more virulent in space, causing further challenges to health. To understand these issues better and to contribute to design of effective countermeasures, we used the Drosophila model of innate immunity to study immune responses in both hypergravity and spaceflight. Focusing on infections mediated through the conserved Toll and Imd signaling pathways, we found that hypergravity improves resistance to Toll-mediated fungal infections except in a known gravitaxis mutant of the yuri gagarin gene. These results led to the first spaceflight project on Drosophila immunity, in which flies that developed to adulthood in microgravity were assessed for immune responses by transcription profiling on return to Earth. Spaceflight alone altered transcription, producing activation of the heat shock stress system. Space flies subsequently infected by fungus failed to activate the Toll pathway. In contrast, bacterial infection produced normal activation of the Imd pathway. We speculate on possible linkage between functional Toll signaling and the heat shock chaperone system. Our major findings are that hypergravity and spaceflight have opposing effects, and that spaceflight produces stress-related transcriptional responses and results in a specific inability to mount a Toll-mediated infection response. PMID:24475130

Genome-wide miRNA screening reveals miR-310 family members negatively regulate the immune response in Drosophila melanogaster via co-targeting Drosomycin.

PubMed

Li, Yao; Li, Shengjie; Li, Ruimin; Xu, Jiao; Jin, Ping; Chen, Liming; Ma, Fei

2017-03-01

Although innate immunity mediated by Toll signaling has been extensively studied in Drosophila melanogaster, the role of miRNAs in regulating the Toll-mediated immune response remains largely unknown. In this study, following Gram-positive bacterial challenge, we identified 93 differentially expressed miRNAs via genome-wide miRNA screening. These miRNAs were regarded as immune response related (IRR). Eight miRNAs were confirmed to be involved in the Toll-mediated immune response upon Gram-positive bacterial infection through genetic screening of 41 UAS-miRNA lines covering 60 miRNAs of the 93 IRR miRNAs. Interestingly, four out of these eight miRNAs, miR-310, miR-311, miR-312 and miR-313, are clustered miRNAs and belong to the miR-310 family. These miR-310 family members were shown to target and regulate the expression of Drosomycin, an antimicrobial peptide produced by Toll signaling. Taken together, our study implies important regulatory roles of miRNAs in the Toll-mediated innate immune response of Drosophila upon Gram-positive bacterial infection. Copyright © 2016 Elsevier Ltd. All rights reserved.

Simulation of investment returns of toll projects.

DOT National Transportation Integrated Search

2013-08-01

This research develops a methodological framework to illustrate key stages in applying the simulation of investment returns of toll projects, acting as an example process of helping agencies conduct numerical risk analysis by taking certain uncertain...

New York City bicycle master plan

DOT National Transportation Integrated Search

1997-05-01

IVHS Electronic Toll and Traffic Management (ETTM) Systems will involve very large numbers of electronic equipment in vehicles and along the roadside. These systems and others will be used for communication, toll collection, traffic management, vehic...

23 CFR 950.7 - Interoperability requirements.

Code of Federal Regulations, 2013 CFR

2013-04-01

... Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION INTELLIGENT TRANSPORTATION SYSTEMS... receive the FHWA's concurrence that the facility's toll collection system's standards and design meet the... system design shall include the communications requirements between roadside equipment and toll...

23 CFR 950.7 - Interoperability requirements.

Code of Federal Regulations, 2012 CFR

2012-04-01

... Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION INTELLIGENT TRANSPORTATION SYSTEMS... receive the FHWA's concurrence that the facility's toll collection system's standards and design meet the... system design shall include the communications requirements between roadside equipment and toll...

23 CFR 950.7 - Interoperability requirements.

Code of Federal Regulations, 2010 CFR

2010-04-01

... Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION INTELLIGENT TRANSPORTATION SYSTEMS... receive the FHWA's concurrence that the facility's toll collection system's standards and design meet the... system design shall include the communications requirements between roadside equipment and toll...

23 CFR 950.7 - Interoperability requirements.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION INTELLIGENT TRANSPORTATION SYSTEMS... receive the FHWA's concurrence that the facility's toll collection system's standards and design meet the... system design shall include the communications requirements between roadside equipment and toll...

23 CFR 950.7 - Interoperability requirements.

Code of Federal Regulations, 2011 CFR

2011-04-01

... Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION INTELLIGENT TRANSPORTATION SYSTEMS... receive the FHWA's concurrence that the facility's toll collection system's standards and design meet the... system design shall include the communications requirements between roadside equipment and toll...

Structural complementarity of Toll/interleukin-1 receptor domains in Toll-like receptors and the adaptors Mal and MyD88.

PubMed

Dunne, Aisling; Ejdeback, Mikael; Ludidi, Phumzile L; O'Neill, Luke A J; Gay, Nicholas J

2003-10-17

The Toll/interleukin 1 receptor (TIR) domain is a region found in the cytoplasmic tails of members of the Toll-like receptor/interleukin-1 receptor superfamily. The domain is essential for signaling and is also found in the adaptor proteins Mal (MyD88 adaptor-like) and MyD88, which function to couple activation of the receptor to downstream signaling components. Experimental structures of two Toll/interleukin 1 receptor domains reveal a alpha-beta-fold similar to that of the bacterial chemotaxis protein CheY, and other evidence suggests that the adaptors can make heterotypic interactions with both the receptors and themselves. Here we show that the purified TIR domains of Mal and MyD88 can form stable heterodimers and also that Mal homodimers and oligomers are dissociated in the presence of ATP. To identify structural features that may contribute to the formation of signaling complexes, we produced models of the TIR domains from human Toll-like receptor 4 (TLR4), Mal, and MyD88. We found that although the overall fold is conserved the electrostatic surface potentials are quite distinct. Docking studies of the models suggest that Mal and MyD88 bind to different regions in TLRs 2 and 4, a finding consistent with a cooperative role of the two adaptors in signaling. Mal and MyD88 are predicted to interact at a third non-overlapping site, suggesting that the receptor and adaptors may form heterotetrameric complexes. The theoretical model of the interactions is supported by experimental data from glutathione S-transferase pull-downs and co-immunoprecipitations. Neither theoretical nor experimental data suggest a direct role for the conserved proline in the BB-loop in the association of TLR4, Mal, and MyD88. Finally we show a sequence relationship between the Drosophila protein Tube and Mal that may indicate a functional equivalence of these two adaptors in the Drosophila and vertebrate Toll pathways.

Evaluating the Impacts of Time-of-Day Tolling on Indiana Roadways

DOT National Transportation Integrated Search

2017-06-01

In recent decades, several agencies have implemented tolls on their highway, bridge, or tunnel infrastructure for purposes that include mitigation and revenue generation. The Indiana Department of Transportation (INDOT) sought to investigate the feas...

33 CFR 402.10 - Schedule of tolls.

Code of Federal Regulations, 2011 CFR

2011-07-01

... orfrom Lake Ontario (5 locks) Rate ($) Welland Canal—Lake Ontario to or from Lake Erie(8 locks) Column 1 Column 2 Column 3 1. Subject to item 3, for complete transit of the Seaway, a composite toll, comprising...

33 CFR 402.10 - Schedule of tolls.

Code of Federal Regulations, 2010 CFR

2010-07-01

... orfrom Lake Ontario (5 locks) Rate ($) Welland Canal—Lake Ontario to or from Lake Erie(8 locks) Column 1 Column 2 Column 3 1. Subject to item 3, for complete transit of the Seaway, a composite toll, comprising...

33 CFR 402.10 - Schedule of tolls.

Code of Federal Regulations, 2012 CFR

2012-07-01

... orfrom Lake Ontario (5 locks) Rate ($) Welland Canal—Lake Ontario to or from Lake Erie(8 locks) Column 1 Column 2 Column 3 1. Subject to item 3, for complete transit of the Seaway, a composite toll, comprising...

The IRAK homolog Pelle is the functional counterpart of IκB kinase in the Drosophila Toll pathway.

PubMed

Daigneault, Jessica; Klemetsaune, Liv; Wasserman, Steven A

2013-01-01

Toll receptors transduce signals that activate Rel-family transcription factors, such as NF-κB, by directing proteolytic degradation of inhibitor proteins. In mammals, the IκB Kinase (IKK) phosphorylates the inhibitor IκBα. A βTrCP protein binds to phosphorylated IκBα, triggering ubiquitination and proteasome mediated degradation. In Drosophila, Toll signaling directs Cactus degradation via a sequence motif that is highly similar to that in IκBα, but without involvement of IKK. Here we show that Pelle, the homolog of a mammalian regulator of IKK, acts as a Cactus kinase. We further find that the fly βTrCP protein Slimb is required in cultured cells to mediate Cactus degradation. These findings enable us for the first time to trace an uninterrupted pathway from the cell surface to the nucleus for Drosophila Toll signaling.

The IRAK Homolog Pelle Is the Functional Counterpart of IκB Kinase in the Drosophila Toll Pathway

PubMed Central

Daigneault, Jessica; Klemetsaune, Liv; Wasserman, Steven A.

2013-01-01

Toll receptors transduce signals that activate Rel-family transcription factors, such as NF-κB, by directing proteolytic degradation of inhibitor proteins. In mammals, the IκB Kinase (IKK) phosphorylates the inhibitor IκBα. A βTrCP protein binds to phosphorylated IκBα, triggering ubiquitination and proteasome mediated degradation. In Drosophila, Toll signaling directs Cactus degradation via a sequence motif that is highly similar to that in IκBα, but without involvement of IKK. Here we show that Pelle, the homolog of a mammalian regulator of IKK, acts as a Cactus kinase. We further find that the fly βTrCP protein Slimb is required in cultured cells to mediate Cactus degradation. These findings enable us for the first time to trace an uninterrupted pathway from the cell surface to the nucleus for Drosophila Toll signaling. PMID:24086459

Robust Pricing of Transportation Networks Under Uncertainty

DOT National Transportation Integrated Search

2010-09-01

Both public and private entities are concerned with the impacts of future toll revenue, and the effects of tolled facilities on system congestion. Due to the inherent complexity of transportation systems, it is impossible to predict travel demand and...

Toll facilities in the United States : bridges, roads, tunnels, ferries

DOT National Transportation Integrated Search

2005-06-01

This report contains selected information on toll facilities in the United States. The information is based on a survey of facilities in operation, financed, or under construction as of January 1, 2005. /Abstract from report, p. xi/

Toll Facilities in the United States : Bridges, Roads, Tunnels, Ferries

DOT National Transportation Integrated Search

2003-06-01

This report contains selected information on toll facilities in the United States. The information is based on a survey of facilities in operation, financed, or under construction as of January 1, 2003. /Abstract from report, p. x/

Alaska Workforce Investment Board

Science.gov Websites

! Looking for a job? Click here. About Us Board Member Documents Phone: (907) 269-7485 Toll Free: (888) 412 : 907-269-7485 Toll Free: 888-412-4742 Fax: 907-269-7489 State of Alaska myAlaska My Government Resident

Home, Department of Administration, State of Alaska

Science.gov Websites

anytime, toll-free at 1-877-266-4357 State Office Closures Office Closure Information and Links Office Closure Policy and Procedures (pdf) For recorded alerts: Toll-Free 877-326-5551 In Juneau 465-5551 Popular

Electronic toll collection/electronic screening interoperability pilot project : final report synthesis

DOT National Transportation Integrated Search

2005-12-02

In 1998, ITS America established a Blue Ribbon Panel on electronic commerce to study the convergence of transportation and electronic payment systems. Panel members included senior managers from government, toll agencies, motor carrier industry, and ...

23 CFR 655.603 - Standards.

Code of Federal Regulations, 2011 CFR

2011-04-01

... includes toll roads and roads within shopping centers, airports, sports arenas, and other similar business... without access restrictions. Except for gated toll roads, roads within private gated properties where... period. (c) Color specifications. Color determinations and specifications of sign and pavement marking...

23 CFR 655.603 - Standards.

Code of Federal Regulations, 2012 CFR

2012-04-01

... includes toll roads and roads within shopping centers, airports, sports arenas, and other similar business... without access restrictions. Except for gated toll roads, roads within private gated properties where... period. (c) Color specifications. Color determinations and specifications of sign and pavement marking...

23 CFR 655.603 - Standards.

Code of Federal Regulations, 2014 CFR

2014-04-01

... includes toll roads and roads within shopping centers, airports, sports arenas, and other similar business... without access restrictions. Except for gated toll roads, roads within private gated properties where... period. (c) Color specifications. Color determinations and specifications of sign and pavement marking...

23 CFR 655.603 - Standards.

Code of Federal Regulations, 2013 CFR

2013-04-01

... includes toll roads and roads within shopping centers, airports, sports arenas, and other similar business... without access restrictions. Except for gated toll roads, roads within private gated properties where... period. (c) Color specifications. Color determinations and specifications of sign and pavement marking...

Nonlinear road pricing for congestion and the environment.

DOT National Transportation Integrated Search

2012-03-30

Under nonlinear road pricing (or tolling), the price charged is not strictly proportional to the distance travelled inside a tolling area, the generalized travel cost is not link-wise additive, and finding a user equilibrium distribution is typically...

Delivering Career Information on a Toll-Free Hotline.

ERIC Educational Resources Information Center

Snipes, Juanita K.; McDaniels, Carl

1982-01-01

Reviews some of the uses of the phone in crisis situations and describes a popular toll-free career information hotline in Virginia. Provides a profile of the mostly adult users along with a user evaluation of the service. (Author)

Risk neutral second best toll pricing.

DOT National Transportation Integrated Search

2011-08-01

We propose a risk-neutral second best toll pricing scheme to account for the possible no uniqueness : of user equilibrium solutions. The scheme is designed to optimize for the expected objective value : as the UE solution varies within the solution s...

Geometric design and operational factors that impact truck use of toll roads.

DOT National Transportation Integrated Search

2010-09-01

This purpose of this project was to identify the potential factors that could impact truck use of toll roads or : managed lanes. The researchers outlined the trucking and freight industry needs through synthesis of : existing literature. Identificati...

Toll bridge report to the California legislature, FY 2001 - 02

DOT National Transportation Integrated Search

2002-01-01

In the San Francisco Bay Area, eight toll bridges serve as essential transportation arteries for the traveling public. Seven of the bridges are state-owned: the Antioch Bridge, the Benicia-Martinez Bridge, the Carquinez Bridge, the Richmond-San Rafae...

Sandia Corporate Ombuds Office

Science.gov Websites

(925) 294-2065 (925) 294-2072 Fax (800) 472-6342 ext. 4-2065 Toll-Free PO Box 969, MS 9911 Livermore -9763 (505) 845-0608 FAX (866) 236-9874 Toll-Free PO Box 5800, MS0918 Albuquerque, NM, 87185-0918 Sandia

Estimation of toll road users value of time

DOT National Transportation Integrated Search

2008-02-01

This research examines a new methodology for prospectively estimating the willingness of travelers to use a toll road by combining travel time saved with the income of the prospective customer base. The purpose of the research is to facilitate networ...

Minnesota urban partnership agreement national evaluation : tolling test plan.

DOT National Transportation Integrated Search

2009-11-17

This report presents the test plan for collecting and analyzing toll data for the Minnesota Urban Partnership Agreement (UPA) under the United States Department of Transportation (U.S. DOT) UPA Program. The Minnesota UPA projects focus on reducing co...

23 CFR 950.9 - Enforcement.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Enforcement. 950.9 Section 950.9 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION INTELLIGENT TRANSPORTATION SYSTEMS ELECTRONIC TOLL COLLECTION § 950.9 Enforcement. (a) The tolling authority of any facility operating pursuant to authority...

14. Toll Plaza and approach signage on 180 looking north ...

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

14. Toll Plaza and approach signage on 1-80 looking north (East 1-80). Photo taken from 250 feet north of 1959 bridge (east-bound 1-80). - Carquinez Bridge, Spanning Carquinez Strait at Interstate 80, Vallejo, Solano County, CA

Concentrations of ultrafine particles at a highway toll collection booth and exposure implications for toll collectors.

PubMed

Cheng, Yu-Hsiang; Huang, Cheng-Hsiung; Huang, Hsiao-Lin; Tsai, Chuen-Jinn

2010-12-15

Research regarding the magnitude of ultrafine particle levels at highway toll stations is limited. This study measured ambient concentrations of ultrafine particles at a highway toll station from October 30 to November 1 and November 5 to November 6, 2008. A scanning mobility particle sizer was used to measure ultrafine particle concentrations at a ticket/cash tollbooth. Levels of hourly average ultrafine particles at the tollbooth were about 3-6 times higher than those in urban backgrounds, indicating that a considerable amount of ultrafine particles are exhausted from passing vehicles. A bi-modal size distribution pattern with a dominant mode at about <6 nm and a minor mode at about 40 nm was observed at the tollbooth. The high amounts of nanoparticles in this study can be attributed to gas-to-particle reactions in fresh fumes emitted directly from vehicles. The influences of traffic volume, wind speed, and relative humidity on ultrafine particle concentrations were also determined. High ambient concentrations of ultrafine particles existed under low wind speed, low relative humidity, and high traffic volume. Although different factors account for high ambient concentrations of ultrafine particles at the tollbooth, measurements indicate that toll collectors who work close to traffic emission sources have a high exposure risk. Copyright © 2010 Elsevier B.V. All rights reserved.

Silencing of Apis mellifera dorsal genes reveals their role in expression of the antimicrobial peptide defensin-1.

PubMed

Lourenço, Anete Pedro; Florecki, Mônica Mazzei; Simões, Zilá Luz Paulino; Evans, Jay Daniel

2018-04-17

Like all other insects, two key signaling pathways (Toll and Imd) regulate the induction of honey bee immune effectors that target microbial pathogens. Among these effectors are antimicrobial peptides (AMPs) that are presumed to be produced by the NF-κB factors Dorsal and Relish from the Toll and Imd pathways, respectively. Using in silico analysis, we previously proposed that the honey bee AMP defensin-1 was regulated by the Toll pathway, while hymenoptaecin was regulated by Imd and abaecin by both the Toll and Imd pathways. Here we use an RNA interference (RNAi) assay to determine the role of Dorsal in regulating abaecin and defensin-1. Honey bees have two dorsal genes (dorsal-1 and dorsal-2) and two splicing isoforms of dorsal-1 (dorsal-1A and dorsal-1B). Accordingly, we used both single and multiple (double or triple) isoform knockdown strategies to clarify the roles of dorsal proteins and their isoforms. Down-regulation of defensin-1 was observed for dorsal-1A and dorsal-2 knockdowns, but abaecin expression was not affected by dorsal RNAi. We conclude that defensin-1 is regulated by Dorsal (Toll pathway). This article is protected by copyright. All rights reserved. © 2018 The Royal Entomological Society.

[Application of artificial neural networks in forecasting the number of circulatory system diseases death toll].

PubMed

Zhang, Ying; Shao, Yi; Shang, Kezheng; Wang, Shigong; Wang, Jinyan

2014-09-01

Set up the model of forecasting the number of circulatorys death toll based on back-propagation (BP) artificial neural networks discuss the relationship between the circulatory system diseases death toll meteorological factors and ambient air pollution. The data of tem deaths, meteorological factors, and ambient air pollution within the m 2004 to 2009 in Nanjing were collected. On the basis of analyzing the ficient between CSDDT meteorological factors and ambient air pollution, leutral network model of CSDDT was built for 2004 - 2008 based on factors and ambient air pollution within the same time, and the data of 2009 est the predictive power of the model. There was a closely system diseases relationship between meteorological factors, ambient air pollution and the circulatory system diseases death toll. The ANN model structure was 17 -16 -1, 17 input notes, 16 hidden notes and 1 output note. The training precision was 0. 005 and the final error was 0. 004 999 42 after 487 training steps. The results of forecast show that predict accuracy over 78. 62%. This method is easy to be finished with smaller error, and higher ability on circulatory system death toll on independent prediction, which can provide a new method for forecasting medical-meteorological forecast and have the value of further research.

Airport Pricing Strategies

NASA Technical Reports Server (NTRS)

Pels, Eric; Verhoef, Erik T.

2003-01-01

Conventional economic wisdom suggests that congestion pricing would be an appropriate response to cope with the growing congestion levels currently experienced at many airports. Several characteristics of aviation markets, however, may make naive congestion prices equal to the value of marginal travel delays a non-optimal response. This paper has developed a model of airport pricing that captures a number of these features. The model in particular reflects that airlines typically have market power and are engaged in oligopolistic competition at different sub-markets; that part of external travel delays that aircraft impose are internal to an operator and hence should not be accounted for in congestion tolls. We presented an analytical treatment for a simple bi-nodal symmetric network, which through the use of 'hyper-networks' would be readily applicable to dynamic problems (in discrete time) such as peak - off-peak differences, and some numerical exercises for the same symmetric network, which was only designed to illustrate the possible comparative static impacts of tolling, in addition to marginal equilibrium conditions as could be derived for the general model specification. Some main conclusions are that second-best optimal tolls are typically lower than what would be suggested by congestion costs alone and may even be negative, and that the toll as derived by Brueckner (2002) may not lead to an increase in total welfare. While Brueckner (2002) has made clear that congestion tolls on airports may be smaller than expected when congestion costs among aircraft are internal for a firm, our analysis adds to this that a further downward adjustment may be in order due to market power. The presence of market power (which causes prices to exceed marginal costs) may cause the pure congestion toll to be suboptimal, because the resulting decrease in demand is too high (the pure congestion tall does not take into account the decrease in consumer surplus). The various downward adjustments in welfare maximizing tolls may well cause the optimal values of these to be negative. Insofar as subsidization is considered unacceptable for whichever reason, our results warn that the most efficient among the non-negative tolls may actually be a zero toll; the pure congestion toll may actually decrease welfare compared to the base case. The model in this paper contains a few simplifying assumptions that may be relaxed in future work. Load factors and aircraft capacity are fixed in this model for simplicity. In a more advanced version of this model, load factors and aircraft capacity can be endogenized. This makes the derivation of the optimality conditions far more complicated, but it should be feasible in a numerical experiment. One can also add a fourth layer to the model, describing the airport's optimization problem. For example, the airport can maximize profits under a cost recovery constraint. The model then deals with interactions between four types of agents. No distinction is made between peak and off-peak traffic in this paper. Finally, the results of the numerical exercise in this paper need to be checked against an asymmetric equilibrium.

Network-optimized congestion pricing : a parable, model and algorithm

DOT National Transportation Integrated Search

1995-05-31

This paper recites a parable, formulates a model and devises an algorithm for optimizing tolls on a road network. Such tolls induce an equilibrium traffic flow that is at once system-optimal and user-optimal. The parable introduces the network-wide c...

Considerations for high occupancy vehicle (HOV) to high occupancy toll (HOT) lanes conversions primer.

DOT National Transportation Integrated Search

2007-09-01

This primer presents key issues and challenges related to the conversion of high occupancy vehicle (HOV) lanes to high occupancy toll (HOT) lanes. The primer is intended for community leaders, administrators, : the public, and other stakeholders resp...

78 FR 75245 - Civilian Health and Medical Program of the Uniformed Services (CHAMPUS)/TRICARE: Pilot Program...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-11

... will ensure that a pharmacist is available at all times through the toll-free telephone number to... program. (vii) The PBM will ensure that a pharmacist is available at all times through the toll-free...

Impact of transportation demand management (TDM) elements on managed lanes toll prices.

DOT National Transportation Integrated Search

2015-03-01

This research involved a simulation comparing three days of actual traffic data for the I-95 Express : Lanes and General Purpose Lanes in Miami, Florida to a hypothetical scenario where all transportation : demand management (TDM) activities and toll...

Sandia Corporate Ombuds Office

Science.gov Websites

maramos@sandia.gov (925) 294-2065 (925) 294-2072 Fax (800) 472-6342 ext. 4-2065 Toll-Free PO Box 969, MS or (505) 844-9763 (505) 845-0608 FAX (866) 236-9874 Toll-Free PO Box 5800, MS0918 Albuquerque, NM

Attachment 1 : appendices : electronic toll collection/electronic screening interoperability pilot project, supplement to the final report

DOT National Transportation Integrated Search

2005-07-29

In 1998, ITS America established a Blue Ribbon Panel on electronic commerce to study the convergence of transportation and electronic payment systems. Panel members included senior managers from government, toll agencies, motor carrier industry, and ...

CHOOSING CONGESTION PRICING POLICY: CORDON TOLLS VS. LINK-BASED TOLLS. (R831450)

EPA Science Inventory

The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

Quantifying the effects of network improvement actions on the value of new and existing toll road projects.

DOT National Transportation Integrated Search

2010-02-01

Development, delivery, and operation of public infrastructure are becoming increasingly dependent on : participation of the private sector. While revenue generating projects, such as toll roads, were traditionally : developed and funded from the publ...

Modeling Single Occupant Vehicle Behavior in High-Occupancy Toll (HOT) Facilities

DOT National Transportation Integrated Search

2009-12-14

High-occupancy toll (HOT) lanes are in operation, under construction, and planned for in several major metropolitan areas. The premise behind HOT lanes is to allow single occupant vehicles (SOVs) to access high occupancy vehicle (HOV) lanes (and theo...

23 CFR 950.1 - Purpose.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 23 Highways 1 2010-04-01 2010-04-01 false Purpose. 950.1 Section 950.1 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION INTELLIGENT TRANSPORTATION SYSTEMS ELECTRONIC TOLL COLLECTION § 950.1 Purpose. The purpose of this part is to establish interoperability requirements for toll...

Investigation of the feasibility of toll and transit agency equity sharing : white paper.

DOT National Transportation Integrated Search

2010-04-12

This research project frames the institutional constraints and opportunities for equity sharing that currently exist in the highway, transit and toll agency realms and identifies statutory, regulatory and/or policy changes that may be requried. It al...

The relationship between emotional labor status and workplace violence among toll collectors.

PubMed

Joo, Yosub; Rhie, Jeongbae

2017-01-01

This study aimed to identify the emotional labor and workplace violence status among toll collectors by assessing and comparing the same with that in workers in other service occupation. It also aimed to analyze the relationship between emotional labor and workplace violence. This study examined emotional labor and workplace violence status in 264 female toll collectors from August 20 to September 4, 2015. The emotional labor was assessed using the Korean Emotional Labor Scale (K-ELS), and a questionnaire was used to examine the presence or absence, and type and frequency of workplace violence experienced by the subjects. A linear regression analysis was also performed to analyze the relationship between workplace violence and emotional labor. The scores on "emotional demanding and regulation ( p  < 0.001)," "overload and conflict in customer service ( p  = 0.005)," "emotional disharmony and hurt ( p  < 0.001)," and "organizational surveillance and monitoring ( p  < 0.001)" among the sub-categories of emotional labor were significantly high and indicated "at-risk" levels of emotional labor in those who experienced workplace violence, whereas they were "normal" of emotional labor in those who did not. Even after being adjusted in the linear regression analysis, the emotional labor scores for the above 4 sub-categories were still significantly high in those who experienced workplace violence. On comparing the present scores with 13 other service occupations, it was found that toll collectors had the highest level in "emotional disharmony and hurt," "organizational surveillance and monitoring," and "organizational supportive and protective system". This study found that the toll collectors engaged in a high level of emotional labor. Additionally, there was a significant relationship between emotional labor and the experience of workplace violence among the toll collectors.

Toll facilities in the United States : Bridges, Roads, Tunnels, Ferries

DOT National Transportation Integrated Search

1993-02-01

Selected information on toll facilities in the United States open to the public are contained in this report. The information is based on a survey of facilities in operation, financed, or under construction as of January 1, 1993. The information is p...

Guide for geometric design and operational factors that impact truck use of toll roads.

DOT National Transportation Integrated Search

2010-09-01

Texas has approximately 300 miles of toll roads, predominantly in the three largest and : most congested urban areas of Austin, Dallas, and Houston. The Texas Turnpike Authority : (TTA) Division of the Texas Department of Transportation (TxDOT) and t...

Toll facilities in the United States : bridges, roads, tunnels, ferries

DOT National Transportation Integrated Search

1995-02-01

This report contains selected information on toll facilities in the United States. The information is based on a survey of facilities in operation, financed, or under construction as of January 1, 1995, and is presented in four tables. Table T-1 cont...

Enhancing CORSIM for simulating high occupancy/toll lane operations.

DOT National Transportation Integrated Search

2012-03-15

Congestion pricing has been advocated as an efficient way to mitigate traffic congestion : since 1920s. A prevalent form of congestion pricing in the U.S. is high occupancy/toll (HOT) : lanes. The operating objective of HOT lanes is to improve the th...

Electronic toll collection interoperability study in Brazil. Task 4 : recommendations and final report

DOT National Transportation Integrated Search

1998-05-01

The report examines the potential for developing electronic toll collection systems in Brazil. This is Volume III and it is 'Task-Recommendations and Final Report'. The report is made up of the following subtasks: (1) Issue Recommended Installation S...

Electronic toll collection interoperability study in Brazil. Task 1 : data collection

DOT National Transportation Integrated Search

1998-05-01

The report, conducted by Parsons Bricknerhoff International, was funded by the U.S. Trade and Development Agency. The report examines the potential for developing electronic toll collection systems in Brazil. This is volume I and it is Task 1, the da...

Toll Facilities in the United States : Bridges, Roads, Tunnels, Ferries

DOT National Transportation Integrated Search

1999-02-01

This report contains selected information on toll facilities in the United States. The information is based on a survey of facilities in operation, financed, or under construction as of January 1, 1999, and is presented in six tables. Table T-1 conta...

Impact of removal of tolls on travel in Tidewater Virginia.

DOT National Transportation Integrated Search

1977-01-01

The purpose of the first report was to monitor and report the effects that the removal of the tolls on the Hampton Roads Bridge-Tunnel had upon travel activity in the Tidewater area. Before and after questionnaire surveys were utilized to gather data...

Understanding Traveler Behavior : The Psychology Behind Managed Lane Use

DOT National Transportation Integrated Search

2012-07-01

Recent analysis of Katy Freeway/Managed Lane (ML) travelers and I-394 Freeway/High : Occupancy Toll (HOT) lane traveler data has found that many travelers pay to use these HOT : lanes and MLs when adjacent toll-free lanes are operating at nearly the ...

Consumer reaction to call boxes on the Dulles toll road in Virginia

DOT National Transportation Integrated Search

2001-06-01

This study represents the first part of an assessment of consumer reactions to the introduction of call boxes on the Dulles Toll Road (Northern Virginia). It initially looks at the existing experiences with call boxes in the US. Despite their adoptio...

Global earthquake fatalities and population

USGS Publications Warehouse

Holzer, Thomas L.; Savage, James C.

2013-01-01

Modern global earthquake fatalities can be separated into two components: (1) fatalities from an approximately constant annual background rate that is independent of world population growth and (2) fatalities caused by earthquakes with large human death tolls, the frequency of which is dependent on world population. Earthquakes with death tolls greater than 100,000 (and 50,000) have increased with world population and obey a nonstationary Poisson distribution with rate proportional to population. We predict that the number of earthquakes with death tolls greater than 100,000 (50,000) will increase in the 21st century to 8.7±3.3 (20.5±4.3) from 4 (7) observed in the 20th century if world population reaches 10.1 billion in 2100. Combining fatalities caused by the background rate with fatalities caused by catastrophic earthquakes (>100,000 fatalities) indicates global fatalities in the 21st century will be 2.57±0.64 million if the average post-1900 death toll for catastrophic earthquakes (193,000) is assumed.

Amyloid-beta mediates the receptor of advanced glycation end product-induced pro-inflammatory response via toll-like receptor 4 signaling pathway in retinal ganglion cell line RGC-5.

PubMed

Lee, Jong-Jer; Wang, Pei-Wen; Yang, I-Hui; Wu, Chia-Lin; Chuang, Jiin-Haur

2015-07-01

Patients with diabetes mellitus have an increased risk of developing Alzheimer's disease. Amyloid-β, a product of amyloid precursor protein, is associated with neuro-inflammation in patients with Alzheimer's diseases. The correlation between amyloid-beta and advanced glycation end products, which accumulate in tissue of diabetic patients, is not clear. The aims of this study were to determine the effect of advanced glycation end product on the expression of amyloid precursor protein/amyloid-beta and associated pro-inflammatory responses in retinal ganglion cell line RGC-5. Treatment with advanced glycation end product produced upregulation of amyloid precursor protein and increased secretion of amyloid-β(1-40). Additionally, amyloid-β(1-40) induced toll-like receptor 4-dependent phosphorylation of tyrosine in myeloid differentiation primary response gene (88). We found that N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester, a γ-secretase inhibitor, reduced the secretion of amyloid-β(1-40) and inhibited the advanced glycation end product-induced activation of myeloid differentiation primary response gene (88). Amyloid-β(1-40) induced the activation of NF-κB and the expression of TNFα mRNA. Knockdown of toll-like receptor 4 inhibited the amyloid-β(1-40)-induced phosphorylation of p65 in NF-κB. Additionally, the nuclear translocation of p65 and transcriptions of TNFα were inhibited by siRNA knockdown of receptor of advanced glycation end product or toll-like receptor 4. The advanced glycation end product-induced secretion of VEGF-A was also reduced by knockdown of toll-like receptor 4. Taken together, our data suggested that amyloid-β(1-40) mediates the interaction between receptor of advanced glycation end product and toll-like receptor 4. Inhibition of the toll-like receptor 4 is an effective method for suppressing the amyloid-β(1-40)-induced pro-inflammatory responses in RGC-5 cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

Induction of Direct Antimicrobial Activity Through Mammalian Toll-Like Receptors

NASA Astrophysics Data System (ADS)

Thoma-Uszynski, Sybille; Stenger, Steffen; Takeuchi, Osamu; Ochoa, Maria Teresa; Engele, Matthias; Sieling, Peter A.; Barnes, Peter F.; Röllinghoff, Martin; Bölcskei, Pal L.; Wagner, Manfred; Akira, Shizuo; Norgard, Michael V.; Belisle, John T.; Godowski, Paul J.; Bloom, Barry R.; Modlin, Robert L.

2001-02-01

The mammalian innate immune system retains from Drosophila a family of homologous Toll-like receptors (TLRs) that mediate responses to microbial ligands. Here, we show that TLR2 activation leads to killing of intracellular Mycobacterium tuberculosis in both mouse and human macrophages, through distinct mechanisms. In mouse macrophages, bacterial lipoprotein activation of TLR2 leads to a nitric oxide-dependent killing of intracellular tubercle bacilli, but in human monocytes and alveolar macrophages, this pathway was nitric oxide-independent. Thus, mammalian TLRs respond (as Drosophila Toll receptors do) to microbial ligands and also have the ability to activate antimicrobial effector pathways at the site of infection.

47 CFR 54.601 - Eligibility.

Code of Federal Regulations, 2011 CFR

2011-10-01

...). (2) Internet access and limited toll-free access to internet. (i) For purposes of this subpart, eligible Internet access is an information service that enables rural health care providers to post their...) Internet access shall be eligible for universal service support under § 54.621(a). (iii) Limited toll-free...

Toll Facilities in the United States : Bridges, Roads, Tunnels, Ferries

DOT National Transportation Integrated Search

1989-04-01

Selected data on highway toll facilities in the United States are contained in Table T-1 of this report based on a survey of facilities in operation, financed, or under construction as of January 1, 1989. The data include information such as the name...

Self Care for Educators

ERIC Educational Resources Information Center

National Child Traumatic Stress Network, 2008

2008-01-01

Trauma takes a toll on children, families, schools, and communities. Trauma can also take a toll on school professionals. Any educator who works directly with traumatized children and adolescents is vulnerable to the effects of trauma--referred to as "compassion fatigue" or "secondary traumatic stress"--being physically, mentally, or emotionally…

47 CFR 52.107 - Hoarding.

Code of Federal Regulations, 2010 CFR

2010-10-01

... use for the provision of toll free service. The definition of hoarding also includes number brokering... free database access tariffs: [T]he Federal Communications Commission (“FCC”) has concluded that hoarding, defined as the acquisition of more toll free numbers than one intends to use for the provision of...

Trucking industry response in a changing world of tolling and rising fuel prices

DOT National Transportation Integrated Search

2007-12-01

Direct user fees based options are gaining further momentum all across the United States and particularly in the state of TX. The success of such ventures or projects requires a clear assessment of demand for toll roads among the potential user group...

Toll Facilities in the United States: Bridges - Roads - Tunnels - Ferries

DOT National Transportation Integrated Search

1987-04-01

Selected data on highway toll facilities in the United States are contained in Table T-1 of this report based on a survey of facilities in operation, financed, or under construction as of January 1, 1987. The data includes information such as the nam...

78 FR 48231 - Internal Revenue Service

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-07

... Toll-Free Phone Line Project Committee. AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of Meeting. SUMMARY: An open meeting of the Taxpayer Advocacy Panel Toll-Free Phone Line Project... Phone Line Project Committee will be held Tuesday, September 17, 2013 at 11:00 a.m. Eastern Time via...

78 FR 45973 - Brookwood-Sago Mine Safety Grants

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-30

... to Robert Glatter at [email protected] or at 202-693-9570 (this is not a toll-free number) or... toll-free number). SUPPLEMENTARY INFORMATION: This solicitation provides background information and the... requirements for drug-free workplace (financial assistance). 29 CFR Part 95, Grants and agreements with...

33 CFR 402.2 - Title.

Code of Federal Regulations, 2010 CFR

1999-07-01

... 33 Navigation and Navigable Waters 3 1999-07-01 1999-07-01 false Title. 402.2 Section 402.2 Navigation and Navigable Waters SAINT LAWRENCE SEAWAYDEVELOPMENT CORPORATION, DEPARTMENT OF TRANSPORTATION TARIFF OF TOLLS § 402.2 Title. This tariff may be cited as the St. Lawrence Seaway Tariff of Tolls. ...

Consumer Experiences Calling Toll-Free Corporate Hotlines.

ERIC Educational Resources Information Center

Martin, Charles L.; Smart, Denise T.

1994-01-01

Finds that dimensions that contribute to caller satisfaction (of toll-free corporate hotlines) included operator characteristics such as knowledge, courtesy, and interest; specific behaviors such as apologizing for a problem, thanking the consumer for calling, and encouraging them to call again; and reducing time placed on "hold." (SR)

Smart Cards for Transit : Multi-Use Remotely Interrogated Stored-Data Cards for Fare and Toll Payment

DOT National Transportation Integrated Search

1995-04-01

This project developed relevant information on existing and future, stored readable/writable data card technology for fare and toll payments. The project supports the FTA objective of developing a plan for a common standard card-based fare payment sy...

Evaluation of implementation viability gap funding (VGF) policy on toll road investment in Indonesia

NASA Astrophysics Data System (ADS)

Mahani, Iris; Tamin, Rizal Z.; Pribadi, Krishna S.; Wibowo, Andreas

2017-11-01

VGF policy for toll road investment in Indonesia must be reviewed. Since 2012 the Government of Indonesia (GOI) has issued viability gap funding (VGF) policy for PPP infrastructure project through ministry of finance decision (PMK) No.223/2012. One of VGF purpose is to improve the financial feasibility. In the toll road investment in Indonesia, the implementation of this policy has some problems. This study aimed to evaluate the policy by seeking implementation constraints so can be given an alternative. This research was conducted qualitatively, included aspects of implementation process VGF policy. The analysis process is based on literature study and in-depth interviews to related parties include business entity, ministry of finance, and the ministry of public works, Indonesia Toll Road Authority (BPJT) and professional societies. The literature review conducted by reviewing existing policies and best practices in countries that already practice VGF. The conclusion of this study are 1) There is a conflict of regulation in viability gap funding (VGF) for toll road investment in Indonesia; 2) If Government of Indonesia (GOI) want implement construction grant as VGF, so the regulation must improve in time limited for submission and clearly define limited given in regulation; 3) If GOI want implement partial construction as VGF, so the regulation must be improve in guideline for submission and given.

Phase II : operational and safety-based analyses of varied toll lane configurations.

DOT National Transportation Integrated Search

2016-08-01

The Puerto Rico Dynamic Toll Lane (DTL) is a 6.44 mi (10.4 km) reversible facility within a stretch of freeway PR-22 that operates a congestion pricing system; the first of its kind in the Commonwealth of Puerto Rico. This managed lane system is shar...

Electronic toll collection interoperability study in Brazil. Task 2 : economic and financial analysis and Task 3 : environmental/societal analysis

DOT National Transportation Integrated Search

1998-05-01

This report, conducted by Parsons Bricknerhoff International, was funded by the U.S. Trade and Development Agency. The report examines the potential for developing electronic toll collection systems in Brazil. This is Volume II and it contains "Task ...

75 FR 58443 - Submission for OMB Review: Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-24

... toll-free number)/e-mail: [email protected] . Interested parties are encouraged to send comments to...-395-6929/Fax: 202-395-6974 (these are not toll-free numbers), E-mail: [email protected], Resource Justification Model, to the Office of Management and Budget (OMB) for review and approval in...

Taking Care of Your Behavioral Health: Tips for Social Distancing, Quarantine, and Isolation

MedlinePlus

... REDUCE FINANCIAL STRESS If you’re unable to work during this time, you may experience stress related to your job status or financial situation. 2 Toll-Free: 1-877-SAMHSA-7 ... you are away from work. ƒ Contact the U.S. Department of Labor toll- free ...

DIESEL EXHAUST ENHANCES TOLL-LIKE RECEPTOR 3 EXPRESSION AND SIGNALING IN RESPIRATORY EPITHELIAL CELLS

EPA Science Inventory

Our previous studies have shown that prior exposure of respiratory epithelial cells to an aqueous-trapped solution of DE (DEas) enhances the susceptibility to Influenza infections. Here we examined the effect of DEas on the toll-like receptor 3 (TLR3) pathway, which is responsib...

77 FR 55492 - Mortgagee Review Board: Administrative Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-10

...; telephone (202) 708-2224 (this is not a toll-free number). Persons with hearing or speech impairments may access this number through TTY by calling the toll-free Federal Information Service at (800) 877-8339... to December 31, 2011. I. Settlement Agreements, Civil Money Penalties, Withdrawals of FHA Approval...

78 FR 21618 - Mortgagee Review Board: Administrative Actions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-11

..., Washington, DC 20410-8000; telephone number 202-708-2224 (this is not a toll-free number). Persons with hearing or speech impairments may access this number through TTY by calling the toll-free Federal... the Board in its meetings from January 1, 2012 to September 30, 2012. I. Civil Money Penalties...

78 FR 16159 - Application Procedures and Criteria for Approval of Providers of a Personal Financial Management...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-14

...: Doreen Solomon, Assistant Director for Oversight on (202) 307-2829 (not a toll-free number), Wendy Tien, Deputy Assistant Director for Oversight on (202) 307-3698 (not a toll- free number), or Larry Wahlquist, Office of the General [[Page 16160

77 FR 61052 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-05

... Taxpayer Advocacy Panel is soliciting public comments, ideas and suggestions on improving customer service... DEPARTMENT OF THE TREASURY Internal Revenue Service Open Meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of meeting...

77 FR 21156 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-09

... Taxpayer Advocacy Panel is soliciting public comments, ideas and suggestions on improving customer service... DEPARTMENT OF THE TREASURY Internal Revenue Service Open Meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice of Meeting...

77 FR 8328 - Open Meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-14

... Taxpayer Advocacy Panel is soliciting public comments, ideas and suggestions on improving customer service... DEPARTMENT OF THE TREASURY Internal Revenue Service Open Meeting of the Taxpayer Advocacy Panel Toll-Free Project Committee AGENCY: Internal Revenue Service (IRS) Treasury. ACTION: Notice of meeting...

33 CFR 402.2 - Title.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Title. 402.2 Section 402.2 Navigation and Navigable Waters SAINT LAWRENCE SEAWAY DEVELOPMENT CORPORATION, DEPARTMENT OF TRANSPORTATION TARIFF OF TOLLS § 402.2 Title. This tariff may be cited as the St. Lawrence Seaway Tariff of Tolls...

33 CFR 402.2 - Title.

Code of Federal Regulations, 2010 CFR

2009-07-01

... 33 Navigation and Navigable Waters 3 2009-07-01 2009-07-01 false Title. 402.2 Section 402.2 Navigation and Navigable Waters SAINT LAWRENCE SEAWAY DEVELOPMENT CORPORATION, DEPARTMENT OF TRANSPORTATION TARIFF OF TOLLS § 402.2 Title. This tariff may be cited as the St. Lawrence Seaway Tariff of Tolls...

An integrated system model for evaluating the impact of the dynamic ICC toll policy on the regional network mobility.

DOT National Transportation Integrated Search

2011-12-01

Road pricing has been advocated as an efficient travel demand management to alleviate congestion since the : seminal work by Pigou (1920) and Knight (1924) (see Lindsey, 2006, for recent reviews). More specifically, dynamic : toll pricing has receive...

Managed lane operations--adjusted time of day pricing vs. near-real time dynamic pricing : summary.

DOT National Transportation Integrated Search

2012-01-01

In 2008, the Florida Department of Transportation began implementing the 95 Express, a segment of I-95 in Miami with high occupancy toll (HOT) lanes. Some vehicles use HOT lanes free, but most vehicles pay a toll based on real-time traffic conditions...

How Can the Science Community Support Reality Based Policies to Reducing the Escalating Toll of Natural Hazards?

NASA Astrophysics Data System (ADS)

Thomas, E. A.

2012-12-01

Worldwide, the toll of disaster damage caused by foreseeable natural hazards is growing, despite the fact that science is increasingly able to quantify the risk and foresee the likely location of natural events (NCDC 2012; NHC 2010). Those events can cause disastrous consequences if human built infrastructure is not properly designed for both the current state and future events (IBHS, 2012). Our existing approaches are not working at reducing the mounting toll of disasters which follow foreseeable natural events. Rather, even if the climate were not changing, current land use decisions coupled with development, engineering, design, and construction practices are significantly contributing to further increasing an unsustainable toll from disasters (Pielke, Gratz et al. 2007). Safe and proper construction practices developed to reduce flood losses (e.g. Design for Flooding, Watson, Adams et al., 2010) are all too often thought of as a zero sum situation where the community wins and the developer loses. In reality, the United States and the rest of the world often can find win-win solutions based on sound economics, law, ethics, and environmental sustainability that will benefit communities, developers, and natural hazard risk mitigation practitioners. While such solutions are being implemented in a fragmentary manner throughout the United States, communities implementing these solutions are increasingly working together in peer networks, such as the Natural Hazard Mitigation Association (NHMA)'s Resilient Neighbors Network. Examples include the Urban Drainage and Flood Control District that covers the metropolitan Denver area and recent work in Tulsa, Oklahoma. This presentation will set forth the scientific, ethical, and legal basis of higher development standards which, when combined with good negotiations techniques, can significantly decrease the terrible misery from wildfires, tornadoes, floods, and other natural disasters. Communities clearly have the legal right to implement safe design standards (Thomas, Riley Medlock 2008); yet all too often do not (NOAA, 2010). The required negotiations techniques must include outreach even to those who believe the topics of climate change and sustainability are some sort of plot against property rights and the free enterprise system. The presentation will also challenge the scientific community to support reasoned efforts to better prepare society for the even greater challenges posed by climate variability, uncertainty, and change: to work with practitioners who seek to build a safe and sustainable future to identify gaps in scientific knowledge and help develop workable solutions at the local level. Edward A. Thomas Esq. President Natural Hazard Mitigation Association

The evaluation model of the design of toll

NASA Astrophysics Data System (ADS)

Feng, Shuting

2018-04-01

In recent years, the dramatic increase in traffic burden has highlighted the necessity of rational allocation of toll plaza. At the same time, the need to consider a lot of factors has enhanced the design requirements. In this background, we carry out research on this subject. We propose a reasonable assumption, and abstract the toll plaza into a model only related to B and L. By using the queuing theory and traffic flow theory, we define the throughput, cost and accident prevent with B and L to acquire the base model. By using the method of linear weighting in economics to calculate this model, the optimal B and L strategies are obtained.

Low-dose radiation induces Drosophila innate immunity through Toll pathway activation.

PubMed

Seong, Ki Moon; Kim, Cha Soon; Lee, Byung-Sub; Nam, Seon Young; Yang, Kwang Hee; Kim, Ji-Young; Park, Joong-Jean; Min, Kyung-Jin; Jin, Young-Woo

2012-01-01

Numerous studies report that exposing certain organisms to low-dose radiation induces beneficial effects on lifespan, tumorigenesis, and immunity. By analyzing survival after bacterial infection and antimicrobial peptide gene expression in irradiated flies, we demonstrate that low-dose irradiation of Drosophila enhances innate immunity. Low-dose irradiation of flies significantly increased resistance against gram-positive and gram-negative bacterial infections, as well as expression of several antimicrobial peptide genes. Additionally, low-dose irradiation also resulted in a specific increase in expression of key proteins of the Toll signaling pathway and phosphorylated forms of p38 and JNK. These results indicate that innate immunity is activated after low-dose irradiation through Toll signaling pathway in Drosophila.

12 CFR 334.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2011 CFR

2011-01-01

... or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing... by calling a single toll-free telephone number. (2) Opt-out methods that are not reasonable and...

12 CFR 717.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2011 CFR

2011-01-01

... an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing consumers to... single toll-free telephone number. (2) Opt-out methods that are not reasonable and simple. Reasonable and...

16 CFR 680.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2011 CFR

2011-01-01

... a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that...-out under the Act, by a single method, such as by calling a single toll-free telephone number. (2) Opt...

16 CFR 680.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2012 CFR

2012-01-01

... a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that...-out under the Act, by a single method, such as by calling a single toll-free telephone number. (2) Opt...

12 CFR 717.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2012 CFR

2012-01-01

... an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing consumers to... single toll-free telephone number. (2) Opt-out methods that are not reasonable and simple. Reasonable and...

24 CFR 35.1330 - Interim controls.

Code of Federal Regulations, 2013 CFR

2013-04-01

... on the Internet at http://www.hud.gov/offices/lead, or by mail or fax from the HUD Office of Healthy Homes and Lead Hazard Control at (202) 755-1785, extension 104 (this is not a toll-free number). Persons... the toll-free Federal Information Relay Service at (800) 877-8339. (iv) “The Remodeler's and Renovator...

12 CFR 334.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2012 CFR

2012-01-01

... or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing... by calling a single toll-free telephone number. (2) Opt-out methods that are not reasonable and...

12 CFR 717.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2013 CFR

2013-01-01

... an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing consumers to... single toll-free telephone number. (2) Opt-out methods that are not reasonable and simple. Reasonable and...

47 CFR 64.2401 - Truth-in-Billing Requirements.

Code of Federal Regulations, 2014 CFR

2014-10-01

..., charges on the bill. Common carriers must prominently display on each bill a toll-free number or numbers by which subscribers may inquire or dispute any charges on the bill. A carrier may list a toll-free... her telephone bill, but instead accesses that bill only by e-mail or internet, the carrier may comply...

16 CFR 680.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2013 CFR

2013-01-01

... a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that...-out under the Act, by a single method, such as by calling a single toll-free telephone number. (2) Opt...

47 CFR 64.611 - Internet-based TRS registration.

Code of Federal Regulations, 2012 CFR

2012-10-01

... number assigned or issued to any Registered Internet-based TRS User. (e) Toll free numbers. A VRS or IP... effective date of this Order remove from the Internet-based TRS Numbering Directory any toll free number... 47 Telecommunication 3 2012-10-01 2012-10-01 false Internet-based TRS registration. 64.611 Section...

47 CFR 64.2401 - Truth-in-Billing Requirements.

Code of Federal Regulations, 2013 CFR

2013-10-01

..., charges on the bill. Common carriers must prominently display on each bill a toll-free number or numbers by which subscribers may inquire or dispute any charges on the bill. A carrier may list a toll-free... her telephone bill, but instead accesses that bill only by e-mail or internet, the carrier may comply...

24 CFR 35.1330 - Interim controls.

Code of Federal Regulations, 2014 CFR

2014-04-01

... on the Internet at http://www.hud.gov/offices/lead, or by mail or fax from the HUD Office of Healthy Homes and Lead Hazard Control at (202) 755-1785, extension 104 (this is not a toll-free number). Persons... the toll-free Federal Information Relay Service at (800) 877-8339. (iv) “The Remodeler's and Renovator...

12 CFR 334.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2013 CFR

2013-01-01

... or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing... by calling a single toll-free telephone number. (2) Opt-out methods that are not reasonable and...

12 CFR 717.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2014 CFR

2014-01-01

... an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing consumers to... single toll-free telephone number. (2) Opt-out methods that are not reasonable and simple. Reasonable and...

12 CFR 334.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2014 CFR

2014-01-01

... or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing... by calling a single toll-free telephone number. (2) Opt-out methods that are not reasonable and...

12 CFR 717.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2010 CFR

2010-01-01

... an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing consumers to... single toll-free telephone number. (2) Opt-out methods that are not reasonable and simple. Reasonable and...

12 CFR 334.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2010 CFR

2010-01-01

... or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing... by calling a single toll-free telephone number. (2) Opt-out methods that are not reasonable and...

42 CFR 423.128 - Dissemination of Part D plan information.

Code of Federal Regulations, 2011 CFR

2011-10-01

... plan sponsor's toll free customer service line or by accessing the plan sponsor's internet Web site. (8... redetermination processes via an Internet Web site; and (iii) A system that transmits codes to network pharmacies...— (1) A toll-free customer call center that— (i) Is open during usual business hours. (ii) Provides...

16 CFR 680.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2010 CFR

2010-01-01

... a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that...-out under the Act, by a single method, such as by calling a single toll-free telephone number. (2) Opt...

16 CFR 680.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2014 CFR

2014-01-01

... a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that...-out under the Act, by a single method, such as by calling a single toll-free telephone number. (2) Opt...

A Review of "Life Cycle: How We Grow and Change"

ERIC Educational Resources Information Center

Digioia, Melissa Keyes

2010-01-01

Sexuality education curricula designed for youths with special needs are sparse. "Life Cycle: How We Grow and Change" (Vavricheck & Tolle, 2008) is a new curriculum by clinical social workers Sherrie Mansfield Vavricheck and R. Kay Tolle. Each chapter addresses a particular developmental stage between birth and death. Lessons within each chapter…

33 CFR 402.10 - Coming into force.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 false Coming into force. 402.10 Section... TRANSPORTATION TARIFF OF TOLLS § 402.10 Coming into force. In Canada, this Tariff and the tolls set forth herein come into force from the date on which this Tariff is filed with the Canadian Transportation Agency...

33 CFR 402.9 - Coming into force.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Coming into force. 402.9 Section... TRANSPORTATION TARIFF OF TOLLS § 402.9 Coming into force. In Canada, this Tariff and the tolls set forth herein come into force from the date on which this Tariff is filed with the Canadian Transportation Agency...

33 CFR 402.9 - Coming into force.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 33 Navigation and Navigable Waters 3 2013-07-01 2013-07-01 false Coming into force. 402.9 Section... TRANSPORTATION TARIFF OF TOLLS § 402.9 Coming into force. In Canada, this Tariff and the tolls set forth herein come into force from the date on which this Tariff is filed with the Canadian Transportation Agency...

33 CFR 402.9 - Coming into force.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 33 Navigation and Navigable Waters 3 2012-07-01 2012-07-01 false Coming into force. 402.9 Section... TRANSPORTATION TARIFF OF TOLLS § 402.9 Coming into force. In Canada, this Tariff and the tolls set forth herein come into force from the date on which this Tariff is filed with the Canadian Transportation Agency...

Contact Information

Science.gov Websites

Employee Directory Toll Free & Emergency Numbers Questions regarding safe food handling practices: 1-87 Telephone: 907-465-5105; Toll Free 866-241-2805 Fax Number: 907-465-5129 Email: denise.koch@alaska.gov Air Free In-state 800-478-2577 Solid Waste 555 Cordova Street Anchorage, AK 99501 907-269-7802 State

76 FR 36811 - Representation-Case Procedures

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

... delivered comments by contacting (202) 273-1067 (this is not a toll-free number). Individuals with hearing... Board, 1099 14th Street, NW., Washington, DC 20570, (202) 273-1067 (this is not a toll-free number), 1... to insure the fair and free choice of bargaining representatives by employees.'' NLRB v. A.J. Tower...

GENES, IN ADDITION TO TOLL-LIKE RECEPTOR 2, PLAY A ROLE IN ANTIBACTERIAL DEFENSE TO STREPTOCOCCAL PNEUMONIA

EPA Science Inventory

Streptococcus infection in human populations continues to be a major cause of morbidity and mortality. To evaluate the effect of genetic background and toll-like receptor 2 (TLR2) on antibacterial defense to streptococcal infection, eight genetically diverse strains of mic...

75 FR 64985 - Agenda and Notice of Public Meeting of the Utah Advisory Committee

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-21

...-Discrimination and Labor Division Audit and next steps in developing a resource directory of human rights... the public through the following toll- free call-in and conference ID numbers: 1-(800) [[Page 64986... land-line connections to the toll-free telephone number. Persons with hearing impairments may also...

Effects of Air Pollutants on Innate Immunity: The Role of Toll-like receptors and nucleotide-binding oligomerization domain-like receptors

EPA Science Inventory

Interactions between exposure to ambient air pollutants and respiratory pathogens have been shown to modify respiratory immune responses. Emerging data suggest key roles for toll-like receptor (TLR) and NOD-like receptor (NLR) signaling in pathogen-induced immune responses. Simil...

Toll Bar on Sea

ERIC Educational Resources Information Center

Hunter, Dave

2008-01-01

In the summer of 2007 the United Kingdom experienced some of the heaviest rainfall since records began. Toll Bar in South Yorkshire featured prominently in media coverage as the village and the homes surrounding it began to flood. Many people lost everything: their homes, their furniture, their possessions. In an effort to come to terms with what…

33 CFR 402.9 - Coming into force.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Coming into force. 402.9 Section... TRANSPORTATION TARIFF OF TOLLS § 402.9 Coming into force. In Canada, this Tariff and the tolls set forth herein come into force from the date on which this Tariff is filed with the Canadian Transportation Agency...

75 FR 5620 - Notice of Proposed Information Collection for Public Comment; Public Housing Contracting With...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-03

... hearing or speech impairments may access this number through TTY by calling the toll-free Federal... documents (this is not a toll-free number.) SUPPLEMENTARY INFORMATION: The Department will submit the... exceed a combined dollar value of $1,000,000. The alternative procurement method requires PHAs to collect...

78 FR 69704 - 60-Day Notice of Proposed Information Collection: HUD Conditional Commitment/Statement of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... Information Collection: HUD Conditional Commitment/Statement of Appraised Value AGENCY: Office of the... toll-free number) or email at [email protected] for a copy of the proposed forms or other... calling the toll-free Federal Relay Service at (800) 877-8339. FOR FURTHER INFORMATION CONTACT: Robert...

77 FR 75184 - Notice of Proposed Information Collection: Survey and Collection of Information From HUD Healthy...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-19

... a toll-free number) for copies of the proposed survey and other available documents. Hearing- or speech-challenged individuals may access this number through TTY by calling the toll-free Federal Relay... AGENCY: Office of Healthy Homes and Lead Hazard Control (OHHLHC), HUD. ACTION: Notice. SUMMARY: The...

78 FR 43221 - Federal Property Suitable as Facilities To Assist the Homeless

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-19

... speech-impaired (202) 708-2565 (these telephone numbers are not toll-free), or call the toll-free Title V... the Homeless v. Veterans Administration, No. 88-2503-OG (D.D.C.). Properties reviewed are listed in... Assistant Secretary for Special Needs. TITLE V, FEDERAL SURPLUS PROPERTY PROGRAM FEDERAL REGISTER REPORT FOR...

26 CFR 49.4252-2 - Toll telephone service.

Code of Federal Regulations, 2011 CFR

2011-04-01

... telephone message or conversation. (2) The tax attaches to the total charge made to a hotel or similar subscriber for toll telephone service furnished to the hotel or its guests, but no tax attaches to any charge made by the hotel for service rendered in placing the calls for its guests. (c) Cross reference. For...

78 FR 46240 - Delegation of Procurement Authority and Chief Acquisition Officer Functions

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-30

...; telephone number 202-708-0294 (this is not a toll-free number). Persons with hearing or speech impairments may access this number through TTY by calling the toll-free Federal Relay Service at 800-877-8339... agencywide strategic sourcing vehicles to save money and reduce duplication; (2) Identifying goals for...

Hepatocyte Toll-like receptor 4 regulates obesity-induced inflammation and insulin resistance

USDA-ARS?s Scientific Manuscript database

Chronic low-grade inflammation is a hallmark of obesity and thought to contribute to the development of obesity-related insulin resistance. Toll-like receptor 4 (Tlr4) is a key mediator of pro-inflammatory responses. Mice lacking Tlr4s are protected from diet-induced insulin resistance and inflammat...

78 FR 69705 - 60-Day Notice of Proposed Information Collection: Mortgagee's Application for Partial Settlement

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-20

... calling the toll-free Federal Relay Service at (800) 877-8339. FOR FURTHER INFORMATION CONTACT: Steve... through TTY by calling the toll-free Federal Relay Service at (800) 877-8339. Copies of available... techniques or other forms of information technology, e.g., permitting electronic submission of responses. HUD...

78 FR 75367 - 60-Day Notice of Proposed Information Collection: The Multifamily Accelerated Processing Guide

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-11

... TTY by calling the toll-free Federal Relay Service at (800) 877-8339. FOR FURTHER INFORMATION CONTACT... access this number through TTY by calling the toll-free Federal Relay Service at (800) 877-8339. Copies... forms of information technology, e.g., permitting electronic submission of responses. HUD encourages...

78 FR 49280 - 30-Day Notice of Proposed Information Collection: Third-Party Documentation Facsimile Transmittal...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-13

... calling the toll-free Federal Relay Service at (800) 877-8339. This is not a toll- free number. Copies of... produces an electronic version of the document that will be matched with the electronic application....g., permitting electronic submission of responses. HUD encourages interested parties to submit...

77 FR 19010 - Zone J Tolling Co., LLC; Supplemental Notice That Initial Market-Based Rate Filing Includes...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-29

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. ER12-1301-000] Zone J Tolling Co., LLC; Supplemental Notice That Initial Market- Based Rate Filing Includes Request for Blanket Section 204 Authorization This is a supplemental notice in the above-referenced proceeding of Zone J...

26 CFR 49.4252-2 - Toll telephone service.

Code of Federal Regulations, 2010 CFR

2010-04-01

... telephone message or conversation. (2) The tax attaches to the total charge made to a hotel or similar subscriber for toll telephone service furnished to the hotel or its guests, but no tax attaches to any charge made by the hotel for service rendered in placing the calls for its guests. (c) Cross reference. For...

47 CFR 64.1504 - Restrictions on the use of toll-free numbers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... CARRIER SERVICES (CONTINUED) MISCELLANEOUS RULES RELATING TO COMMON CARRIERS Interstate Pay-Per-Call and... advertised or widely understood to be toll-free, in a manner that would result in: (a) The calling party or the subscriber to the originating line being assessed, by virtue of completing the call, a charge for...

77 FR 75433 - Information Collection Being Reviewed by the Federal Communications Commission

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-20

... services must include information detailing consumers' rights and responsibilities with respect to these... requirements are intended to ensure that consumers know when charges will be levied for calls to toll-free..., carriers handling pay-per-call services must establish a toll-free number that consumers may call to...

78 FR 68858 - Federal Property Suitable as Facilities To Assist the Homeless

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-15

... speech-impaired (202) 708-2565, (these telephone numbers are not toll- free), or call the toll-free Title... Facilities To Assist the Homeless AGENCY: Office of the Assistant Secretary for Community Planning and... surplus Federal property reviewed by HUD for suitability for possible use to assist the homeless. FOR...

Sci-Hub provides access to nearly all scholarly literature

PubMed Central

Romero, Ariel Rodriguez; Levernier, Jacob G; Munro, Thomas Anthony; McLaughlin, Stephen Reid; Greshake Tzovaras, Bastian

2018-01-01

The website Sci-Hub enables users to download PDF versions of scholarly articles, including many articles that are paywalled at their journal’s site. Sci-Hub has grown rapidly since its creation in 2011, but the extent of its coverage has been unclear. Here we report that, as of March 2017, Sci-Hub’s database contains 68.9% of the 81.6 million scholarly articles registered with Crossref and 85.1% of articles published in toll access journals. We find that coverage varies by discipline and publisher, and that Sci-Hub preferentially covers popular, paywalled content. For toll access articles, we find that Sci-Hub provides greater coverage than the University of Pennsylvania, a major research university in the United States. Green open access to toll access articles via licit services, on the other hand, remains quite limited. Our interactive browser at https://greenelab.github.io/scihub allows users to explore these findings in more detail. For the first time, nearly all scholarly literature is available gratis to anyone with an Internet connection, suggesting the toll access business model may become unsustainable. PMID:29424689

Toll Receptor-Mediated Hippo Signaling Controls Innate Immunity in Drosophila.

PubMed

Liu, Bo; Zheng, Yonggang; Yin, Feng; Yu, Jianzhong; Silverman, Neal; Pan, Duojia

2016-01-28

The Hippo signaling pathway functions through Yorkie to control tissue growth and homeostasis. How this pathway regulates non-developmental processes remains largely unexplored. Here, we report an essential role for Hippo signaling in innate immunity whereby Yorkie directly regulates the transcription of the Drosophila IκB homolog, Cactus, in Toll receptor-mediated antimicrobial response. Loss of Hippo pathway tumor suppressors or activation of Yorkie in fat bodies, the Drosophila immune organ, leads to elevated cactus mRNA levels, decreased expression of antimicrobial peptides, and vulnerability to infection by Gram-positive bacteria. Furthermore, Gram-positive bacteria acutely activate Hippo-Yorkie signaling in fat bodies via the Toll-Myd88-Pelle cascade through Pelle-mediated phosphorylation and degradation of the Cka subunit of the Hippo-inhibitory STRIPAK PP2A complex. Our studies elucidate a Toll-mediated Hippo signaling pathway in antimicrobial response, highlight the importance of regulating IκB/Cactus transcription in innate immunity, and identify Gram-positive bacteria as extracellular stimuli of Hippo signaling under physiological settings. Copyright © 2016 Elsevier Inc. All rights reserved.

Toll-like receptor 5 in obesity: the role of gut microbiota and adipose tissue inflammation.

PubMed

Pekkala, Satu; Munukka, Eveliina; Kong, Lingjia; Pöllänen, Eija; Autio, Reija; Roos, Christophe; Wiklund, Petri; Fischer-Posovszky, Pamela; Wabitsch, Martin; Alen, Markku; Huovinen, Pentti; Cheng, Sulin

2015-03-01

This study aimed at establishing bacterial flagellin-recognizing toll-like receptor 5 (TLR5) as a novel link between gut microbiota composition, adipose tissue inflammation, and obesity. An adipose tissue microarray database was used to compare women having the highest (n = 4, H-TLR) and lowest (n = 4, L-TLR) expression levels of TLR5-signaling pathway genes. Gut microbiota composition was profiled using flow cytometry and FISH. Standard laboratory techniques were used to determine anthropometric and clinical variables. In vivo results were verified using cultured human adipocytes. The H-TLR group had higher flagellated Clostridium cluster XIV abundance and Firmicutes-to-Bacteroides ratio. H-TLR subjects had obese phenotype characterized by greater waist circumference, fat %, and blood pressure (P < 0.05 for all). They also had higher leptin and lower adiponectin levels (P < 0.05 for both). Six hundred and sixty-eight metabolism- and inflammation-related adipose tissue genes were differentially expressed between the groups. In vitro studies confirmed that flagellin activated TLR5 inflammatory pathways, decreased insulin signaling, and increased glycerol secretion. The in vivo findings suggest that flagellated Clostridium cluster XIV bacteria contribute to the development of obesity through distorted adipose tissue metabolism and inflammation. The in vitro studies in adipocytes show that the underlying mechanisms of the human findings may be due to flagellin-activated TLR5 signaling. © 2015 The Obesity Society.

Toll-like receptor 2 deficiency increases resistance to Pseudomonas aeruginosa pneumonia in the setting of sepsis-induced immune dysfunction.

PubMed

Pène, Frédéric; Grimaldi, David; Zuber, Benjamin; Sauneuf, Bertrand; Rousseau, Christophe; El Hachem, Carole; Martin, Clémence; Belaïdouni, Nadia; Balloy, Viviane; Mira, Jean-Paul; Chiche, Jean-Daniel

2012-09-15

Sepsis is characterized by a dysregulated inflammatory response followed by immunosuppression that favors the development of secondary infections. Toll-like receptors (TLRs) are major regulators of the host's response to infections. How variability in TLR signaling may impact the development of sepsis-induced immune dysfunction has not been established. We sought to establish the role of TLR2, TLR4, and TLR5 in postseptic mice with Pseudomonas aeruginosa pneumonia. We used an experimental model of sublethal polymicrobial sepsis induced by cecal ligation and puncture (CLP). Wild-type, tlr2(-/-), tlr4(-/-), tlr5(-/-), tlr2 4(-/-) mice that underwent CLP were secondarily subjected to P. aeruginosa pulmonary infection. Postseptic wild-type and tlr4(-/-) and tlr5(-/-) mice displayed high susceptibility to P. aeruginosa pneumonia. In contrast, TLR2-deficient mice, either tlr2(-/-)or tlr2 4(-/-), that underwent CLP were resistant to the secondary pulmonary infection. As compared to wild-type mice, tlr2(-/-) mice displayed improvement in bacterial clearance, decreased bacteremic dissemination, and attenuated lung damage. Furthermore, tlr2(-/-) mice exhibited a pulmonary proinflammatory cytokine balance, with increased production of tumor necrosis factor α and decreased release of interleukin 10. In a model of secondary P. aeruginosa pneumonia in postseptic mice, TLR2 deficiency improves survival by promoting efficient bacterial clearance and restoring a proinflammatory cytokine balance in the lung.

The toll of traffic-related fatalities in a metropolitan Italian area through the experience of the Department of Legal Medicine.

PubMed

Amadasi, Alberto; Cerutti, Elisa; Spagnoli, Laura; Blandino, Alberto; Rancati, Alessandra; Gallo, Carlotta; Mancini, Elisabetta; Rizzi, Vittorio; Cattaneo, Cristina

2016-01-01

Despite the introduction of new traffic laws in Italy, traffic-related deaths are still a huge burden. The study presents data and medico-legal issues behind traffic deaths in Milan between 2001 and 2012 (1506 traffic-related deaths). Data were collected from the database of the Department of Legal Medicine: 79.4% males and 20.6% females (mean age 44.14). The target group concerned traumatic deaths as a consequence of the accident as well as deaths not directly related to an accident. Although 6.1% were non-traumatic deaths (cause of death unconnected to the accident, i.e. because of a heart attack, or when death occurred after survival and cause of death was not related certainly to the accident), multiple skeletal/visceral injuries were the main cause of death (57.9%), occurring in motorcyclists the most (63.7%). Injuries to the skull and brain were the second cause of death (25.9%). Victims were mostly males (79.4%) and drivers (77.6%). Fifty-five per cent were deaths on-scene, while 45% survived. Other variables were also considered: medications, medical history, and drugs/alcohol/smoke. A downward trend in traffic-related fatalities was evident, but the toll is still high. This study should be a glimpse at the actual situation, since it is indicative of a metropolitan area where autopsies are systematically performed.

Genetic Screen in Drosophila Larvae Links ird1 Function to Toll Signaling in the Fat Body and Hemocyte Motility

PubMed Central

Schmid, Martin R.; Anderl, Ines; Vo, Hoa T. M.; Valanne, Susanna; Yang, Hairu; Kronhamn, Jesper; Rämet, Mika; Rusten, Tor Erik

2016-01-01

To understand how Toll signaling controls the activation of a cellular immune response in Drosophila blood cells (hemocytes), we carried out a genetic modifier screen, looking for deletions that suppress or enhance the mobilization of sessile hemocytes by the gain-of-function mutation Toll10b (Tl10b). Here we describe the results from chromosome arm 3R, where five regions strongly suppressed this phenotype. We identified the specific genes immune response deficient 1 (ird1), headcase (hdc) and possibly Rab23 as suppressors, and we studied the role of ird1 in more detail. An ird1 null mutant and a mutant that truncates the N-terminal kinase domain of the encoded Ird1 protein affected the Tl10b phenotype, unlike mutations that affect the C-terminal part of the protein. The ird1 null mutant suppressed mobilization of sessile hemocytes, but enhanced other Tl10b hemocyte phenotypes, like the formation of melanotic nodules and the increased number of circulating hemocytes. ird1 mutants also had blood cell phenotypes on their own. They lacked crystal cells and showed aberrant formation of lamellocytes. ird1 mutant plasmatocytes had a reduced ability to spread on an artificial substrate by forming protrusions, which may explain why they did not go into circulation in response to Toll signaling. The effect of the ird1 mutation depended mainly on ird1 expression in hemocytes, but ird1-dependent effects in other tissues may contribute. Specifically, the Toll receptor was translocated from the cell membrane to intracellular vesicles in the fat body of the ird1 mutant, and Toll signaling was activated in that tissue, partially explaining the Tl10b-like phenotype. As ird1 is otherwise known to control vesicular transport, we conclude that the vesicular transport system may be of particular importance during an immune response. PMID:27467079

12 CFR 41.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2012 CFR

2012-01-01

... means to opt out, such as a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free... affiliate marketing opt-out under the Act, by a single method, such as by calling a single toll-free...

17 CFR 248.125 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2014 CFR

2014-04-01

... electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing..., such as by calling a single toll-free telephone number. (2) Opt out methods that are not reasonable and...

12 CFR 571.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2014 CFR

2014-01-01

... out, such as a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that...-out under the Act, by a single method, such as by calling a single toll-free telephone number. (2) Opt...

17 CFR 248.125 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2013 CFR

2013-04-01

... electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing..., such as by calling a single toll-free telephone number. (2) Opt out methods that are not reasonable and...

24 CFR 203.10 - Informed consumer choice for prospective FHA mortgagors.

Code of Federal Regulations, 2013 CFR

2013-04-01

... internet at HUD's web site at http://www.hud.gov or by contacting: Home Mortgage Insurance Division, Office... Street, SW, Washington, DC 20410-8000; telephone (202) 708-2700 (this is not a toll-free number), or the... these numbers via TTY by calling the toll-free Federal Information Relay Service at (800) 877-8339. (c...

24 CFR 203.10 - Informed consumer choice for prospective FHA mortgagors.

Code of Federal Regulations, 2012 CFR

2012-04-01

... internet at HUD's web site at http://www.hud.gov or by contacting: Home Mortgage Insurance Division, Office... Street, SW, Washington, DC 20410-8000; telephone (202) 708-2700 (this is not a toll-free number), or the... these numbers via TTY by calling the toll-free Federal Information Relay Service at (800) 877-8339. (c...

12 CFR 571.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2013 CFR

2013-01-01

... out, such as a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that...-out under the Act, by a single method, such as by calling a single toll-free telephone number. (2) Opt...

12 CFR 41.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2013 CFR

2013-01-01

... means to opt out, such as a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free... affiliate marketing opt-out under the Act, by a single method, such as by calling a single toll-free...

12 CFR 571.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2011 CFR

2011-01-01

... out, such as a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that...-out under the Act, by a single method, such as by calling a single toll-free telephone number. (2) Opt...

17 CFR 248.125 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2012 CFR

2012-04-01

... electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing..., such as by calling a single toll-free telephone number. (2) Opt out methods that are not reasonable and...

24 CFR 203.10 - Informed consumer choice for prospective FHA mortgagors.

Code of Federal Regulations, 2011 CFR

2011-04-01

... internet at HUD's web site at http://www.hud.gov or by contacting: Home Mortgage Insurance Division, Office... Street, SW, Washington, DC 20410-8000; telephone (202) 708-2700 (this is not a toll-free number), or the... these numbers via TTY by calling the toll-free Federal Information Relay Service at (800) 877-8339. (c...

12 CFR 41.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2014 CFR

2014-01-01

... means to opt out, such as a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free... affiliate marketing opt-out under the Act, by a single method, such as by calling a single toll-free...

17 CFR 248.125 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2010 CFR

2010-04-01

... electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing..., such as by calling a single toll-free telephone number. (2) Opt out methods that are not reasonable and...

12 CFR 41.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2010 CFR

2010-01-01

... means to opt out, such as a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free... affiliate marketing opt-out under the Act, by a single method, such as by calling a single toll-free...

17 CFR 248.125 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2011 CFR

2011-04-01

... electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing..., such as by calling a single toll-free telephone number. (2) Opt out methods that are not reasonable and...

47 CFR 64.2401 - Truth-in-Billing Requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... Common carriers must prominently display on each bill a toll-free number or numbers by which subscribers may inquire or dispute any charges on the bill. A carrier may list a toll-free number for a billing... telephone bill, but instead accesses that bill only by e-mail or internet, the carrier may comply with this...

24 CFR 203.10 - Informed consumer choice for prospective FHA mortgagors.

Code of Federal Regulations, 2010 CFR

2010-04-01

... internet at HUD's web site at http://www.hud.gov or by contacting: Home Mortgage Insurance Division, Office... Street, SW, Washington, DC 20410-8000; telephone (202) 708-2700 (this is not a toll-free number), or the... these numbers via TTY by calling the toll-free Federal Information Relay Service at (800) 877-8339. (c...

12 CFR 571.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2010 CFR

2010-01-01

... out, such as a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that...-out under the Act, by a single method, such as by calling a single toll-free telephone number. (2) Opt...

24 CFR 203.10 - Informed consumer choice for prospective FHA mortgagors.

Code of Federal Regulations, 2014 CFR

2014-04-01

... internet at HUD's web site at http://www.hud.gov or by contacting: Home Mortgage Insurance Division, Office... Street, SW, Washington, DC 20410-8000; telephone (202) 708-2700 (this is not a toll-free number), or the... these numbers via TTY by calling the toll-free Federal Information Relay Service at (800) 877-8339. (c...

12 CFR 571.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2012 CFR

2012-01-01

... out, such as a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that...-out under the Act, by a single method, such as by calling a single toll-free telephone number. (2) Opt...

12 CFR 222.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2010 CFR

2010-01-01

... electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing... by calling a single toll-free telephone number. (2) Opt-out methods that are not reasonable and...

12 CFR 222.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2014 CFR

2014-01-01

... electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing... by calling a single toll-free telephone number. (2) Opt-out methods that are not reasonable and...

12 CFR 222.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2012 CFR

2012-01-01

... electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing... by calling a single toll-free telephone number. (2) Opt-out methods that are not reasonable and...

12 CFR 41.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2011 CFR

2011-01-01

... means to opt out, such as a form that can be electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free... affiliate marketing opt-out under the Act, by a single method, such as by calling a single toll-free...

12 CFR 222.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2013 CFR

2013-01-01

... electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing... by calling a single toll-free telephone number. (2) Opt-out methods that are not reasonable and...

12 CFR 222.25 - Reasonable and simple methods of opting out.

Code of Federal Regulations, 2011 CFR

2011-01-01

... electronically mailed or processed at an Internet Web site, if the consumer agrees to the electronic delivery of information; (iv) Providing a toll-free telephone number that consumers may call to opt out; or (v) Allowing... by calling a single toll-free telephone number. (2) Opt-out methods that are not reasonable and...

78 FR 38356 - 60-Day Notice of Proposed Information Collection: Notice of Proposed Information Collection for...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-26

... Information Collection: Notice of Proposed Information Collection for Disaster Recovery Grant Reporting System... impairments may access this number through TTY by calling the toll-free Federal Relay Service at (800) 877... this number through TTY by calling the toll-free Federal Relay Service at (800) 877-8339. SUPPLEMENTARY...

78 FR 9048 - Agency Information Collection Activities: Proposed Collection; Submission for OMB Review...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-07

...) 663-4070 (voice) or (202) 663-4074 (TTD). (These are not toll-free telephone numbers.) Instead of... staff at (202) 663-4630 (voice) or (202) 663-4641 (TTY). (These are not toll-free numbers.) FOR FURTHER... 4SW30F, Washington, DC 20507; (202) 663-4958 (voice) or (202) 663-7063 (TTY). SUPPLEMENTARY INFORMATION...

Online Education as a Toll Good: An Examination of the South Carolina Virtual School Program

ERIC Educational Resources Information Center

Rauh, Jonathan

2011-01-01

Education has long been considered merit good; however, inequitable distribution has made it more akin to a toll good. This was most recently demonstrated by Henry, Fortner, and Thompson (2010). Choice requirements designed to remedy the inequitable distribution of education, have largely been confined to brick and mortar schools. Subsequently,…

77 FR 14591 - Open Meeting of the Federal Advisory Committee on Insurance

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-12

... Avenue NW., Washington, DC 20220, at (202) 622-6910 (this is not a toll-free number). Persons who have difficulty hearing or speaking may access this number via TTY by calling the toll-free Federal Relay Service... on the work to date of the Federal Insurance Office. Lance Auer, Deputy Assistant Secretary Financial...

78 FR 66041 - 60-Day Notice of Proposed Information Collection: Requirements for Designating Housing Projects

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-04

... sent to: Colette Pollard, Reports Management Officer, QDAM, Department of Housing and Urban Development... information. Persons with hearing or speech impairments may access this number through TTY by calling the toll... is not a toll-free number). Persons with hearing or speech impairments may access this number via TTY...

78 FR 35045 - 60-Day Notice of Proposed Information Collection: Section 8 Management Assessment Program (SEMAP)

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-11

... sent to: Colette Pollard, Reports Management Officer, QDAM, Department of Housing and Urban Development... information. Persons with hearing or speech impairments may access this number through TTY by calling the toll... not a toll-free number. Persons with hearing or speech impairments may access this number through TTY...

76 FR 67471 - Delegation Authority for the Office of the Chief Information Officer

Federal Register 2010, 2011, 2012, 2013, 2014

2011-11-01

...) 708-0306 (this is not a toll-free number). Persons with hearing or speech impairments may access this number by calling the toll-free Federal Relay Service at 1-(800) 877-8339. SUPPLEMENTARY INFORMATION..., implement, and maintain HUD process for maximizing the value and assessing and managing the risks of IT...

76 FR 81363 - Federal Housing Administration (FHA): Temporary Exemption From Compliance With FHA's Regulation...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-28

... (202) 708-2121 (this is not a toll-free number). Persons with hearing or speech impairments may access this number through TTY by calling the toll-free Federal Information Relay Service at (800) 877-8339... is resold for a considerable profit with an artificially inflated value, often the result of a lender...

77 FR 59627 - Federal Property Suitable as Facilities To Assist the Homeless

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-28

... (202) 708-2565 (these telephone numbers are not toll- free), or call the toll-free Title V information... published in order to comply with the December 12, 1988 Court Order in National Coalition for the Homeless v... (Acting) for Special Needs. TITLE V, FEDERAL SURPLUS PROPERTY PROGRAM FEDERAL REGISTER REPORT FOR 09/28...

76 FR 67104 - Child Labor Regulations, Orders and Statements of Interpretation; Child Labor Violations-Civil...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-10-31

... Regulations, Orders and Statements of Interpretation; Child Labor Violations--Civil Money Penalties AGENCY..., DC 20210; telephone: (202) 693-0072 (this is not a toll free number). Copies of this notice of...), upon request, by calling (202) 693-0023. TTY/TDD callers may dial toll-free (877) 889-5627 to obtain...

78 FR 48543 - Veterans Health Administration Fund Availability Under the VA's Homeless Providers Grant and Per...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

..., Department of Veterans Affairs, 10770 N. 46th Street, Suite C-200, Tampa, FL 33617; (toll-free) (877) 332... vocational development, benefits management, fiduciary or money management services, medication compliance..., Department of Veterans Affairs, 10770 N. 46th Street, Suite C-200, Tampa, FL 33617; (toll- free) (877) 332...

78 FR 70957 - 60-Day Notice of Proposed Information Collection: HUD-Owned Real Estate Good Neighbor Next Door...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-27

... calling the toll-free Federal Relay Service at (800) 877-8339. FOR FURTHER INFORMATION CONTACT: Ivery W... number through TTY by calling the toll-free Federal Relay Service at (800) 877-8339. Copies of available... automated collection techniques or other forms of information technology, e.g., permitting electronic...

78 FR 67384 - 60-Day Notice of Proposed Information Collection: FHA-Insured Mortgage Loan Servicing Involving...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-11-12

... hearing or speech impairments may access this number through TTY by calling the toll-free Federal Relay... calling the toll-free Federal Relay Service at (800) 877-8339. Copies of available documents submitted to... techniques or other forms of information technology, e.g., permitting electronic submission of responses. HUD...

78 FR 75364 - 60-Day Notice of Proposed Information Collection: Application for FHA Insured Mortgages

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-11

... through TTY by calling the toll-free Federal Relay Service at (800) 877-8339. FOR FURTHER INFORMATION... through TTY by calling the toll-free Federal Relay Service at (800) 877-8339. Copies of available... techniques or other forms of information technology, e.g., permitting electronic submission of responses. HUD...

The effects of administration of ligands for Toll-like receptor 4 and 21 against Marek’s disease in chickens

USDA-ARS?s Scientific Manuscript database

Ligands for Toll-like receptors (TLRs) are known to stimulate immune responses, leading to protection against bacterial and viral pathogens. Here, we aimed to examine the effects of various TLR ligands on the development of Marek’s disease in chickens. Specific-pathogen free chickens were treated wi...

For Whom Does "The Bell Curve" Toll"? It Tolls for You.

ERIC Educational Resources Information Center

Sternberg, Robert J.

Although British psychologist Francis Galton lost the battle for the definition of intelligence in his own time, his views live on in the work of Richard Herrnstein and Charles Murray. They argue that the Intelligence Quotient (IQ) is an adequate measure of intelligence, and that IQ is highly heritable. They contend that there are racial and…

Managed lane operations--adjusted time of day pricing vs. near-real time dynamic pricing : volume I, dynamic pricing and operations of managed lanes.

DOT National Transportation Integrated Search

2012-02-12

In 2008, the Florida Department of Transportation began implementing the 95 Express, a segment of I-95 in Miami with high occupancy toll (HOT) lanes. Some vehicles use HOT lanes free, but most vehicles pay a toll based on real-time traffic conditions...

ROLE OF TOLL LIKE RECEPTORS ON PULMONARY INFLAMMATORY RESPONSES TO SIZE FRACTIONATED COMBUSTION AND AMBIENT AIR PARTICLES.

EPA Science Inventory

C3H/HeJ mice feature a single point mutation in the Toll like receptor 4 gene which renders these animals resistant to a number of pro-inflammatory agents including lipopolysaccharide and ozone. This study compared pulmonary inflammatory responses in endotoxin resistant (C3H/HeJ...

37 CFR 41.40 - Tolling of time period to file a reply brief.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 37 Patents, Trademarks, and Copyrights 1 2013-07-01 2013-07-01 false Tolling of time period to file a reply brief. 41.40 Section 41.40 Patents, Trademarks, and Copyrights UNITED STATES PATENT AND TRADEMARK OFFICE, DEPARTMENT OF COMMERCE PRACTICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex Parte Appeals...

An Estimation of Mobile Emissions Reduction from Using Electronic Toll Collection in the Baltimore Metropolitan Area: A Case Study of the Fort McHenry Tunnel Toll Plaza

DOT National Transportation Integrated Search

2000-03-01

The Baltimore Metropolitan Area is classified as a severe nonattainment area under the Clean Air Act Amendments of 1990. Consequently, it operates on a stringent emissions budget and is mandated to embark on mitigation measures. The area has been agg...

77 FR 28741 - The Housing and Economic Recovery Act of 2008 (HERA): Changes to the Section 8 Tenant-Based...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-15

... (this is not a toll-free number). Individuals with speech or hearing impairments may access this number... listed telephone number is not a toll-free number. Persons with hearing or speech impairments may access... identify and consider regulatory approaches that reduce burdens and maintain flexibility and freedom of...

78 FR 59414 - Environmental Impact Statement; King County, Washington

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-26

... Island, and partial tolls collected on trips within a segment. In addition to these three tolling... improvements on I-90. The total length of the corridor is approximately seven (7) miles. The scoping period for... centers over Lake Washington, a 22-mile-long body of water. The FHWA is issuing this notice to advise the...

Toll-like receptor activation in the pathogenesis of lupus nephritis.

PubMed

Lorenz, Georg; Lech, Maciej; Anders, Hans-Joachim

2017-12-01

The pathogenesis of systemic lupus erythematosus (SLE) and lupus nephritis is complex but no longer enigmatic. Much progress has been made to on the polygenetic origin of lupus in identifying gene variants that permit the loss of tolerance against nuclear autoantigens. Along the same line in about 50% of lupus patients additional genetic weaknesses promote immune complex glomerulonephritis and filtration barrier dysfunction. Here we briefly summarize the pathogenesis of SLE with a focus on loss of tolerance and the role of toll-like receptors in the "pseudo"-antiviral immunity concept of systemic lupus. In addition, we discuss the local role of Toll-like receptors in intrarenal inflammation and kidney remodeling. Copyright © 2016 Elsevier Inc. All rights reserved.

Defining Toll Fee of Wheeling Renewable with Reference to a Gas Pipeline in Indonesia

NASA Astrophysics Data System (ADS)

Hakim, Amrullah

2017-07-01

Indonesia has a huge number of renewable energy sources (RE) however; the utilization of these is currently very low. The main challenge of power production is its alignment with consumption levels; supply should equal demand at all times. There is a strong initiative from corporations with high energy demand, compared to other sectors, to apply a renewable portfolio standard for their energy input, e.g. 15% of their energy consumption requirement must come from a renewable energy source. To support this initiative, the utilization of power wheeling will help large factories on industrial estates to source firm and steady renewables from remote sites. The wheeling renewable via PLN’s transmission line has been regulated under the Ministry Decree in 2015 however; the tariff or toll fee has not yet been defined. The potential project to apply wheeling renewable will obtain power supply from a geothermal power plant, with power demand from the scattered factories under one company. This is the concept driving the application of power wheeling in the effort to push the growth of renewable energy in Indonesia. Given that the capacity of PLN’s transmission line are normally large and less congested compared to distribution line, the wheeling renewable can accommodate the scattered factories locations which then results in the cheaper toll fee of the wheeling renewable. Defining the best toll fee is the main topic of this paper with comparison of the toll fee of the gas pipeline infrastructure in Indonesia, so that it can be applied massively to achieve COP21’s commitment.

76 FR 28426 - Withdrawal of Notice Inviting Applications for New Awards for Fiscal Year (FY) 2011...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-17

... the FRS, toll free, at 1--800--877--8339. Electronic Access to This Document: The official version of this document is the document published in the Federal Register. Free Internet access to the official... or by e-mail: [email protected] . If you use a TDD, call the Federal Relay Service (FRS), toll free...

File a Consumer Complaint with the Alaska Attorney Generals Office

Science.gov Websites

. You can call our office if you have any questions at 907-269-5200, or toll free outside Anchorage at 1 -888-576-2529. Some documents on this page require Adobe Reader (available as a free download) to view Telemarketing Travel & Shopping Vehicles Contact Information Consumer Protection Unit 907-269-5200 Toll free

75 FR 17333 - Addition of National Toxicology Program Carcinogens; Community Right-to-Know Toxic Chemical...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-06

... encryption, and be free of any defects or viruses. Docket: All documents in the docket are listed in the www... Community Right-to-Know Hotline, toll free at (800) 424-9346 or (703) 412-9810 in Virginia and Alaska or toll free, TDD (800) 553-7672, http://www.epa.gov/epaoswer/hotline/ . SUPPLEMENTARY INFORMATION: I...

Toll-like receptors and intestinal defence: molecular basis and therapeutic implications.

PubMed

Cario, Elke

2003-07-07

Toll-like receptors (TLRs) play a principle role in distinct pathogen recognition and in the initiation of innate immune responses of the intestinal mucosa. Activated innate immunity interconnects downstream with adaptive immunity in complex feedback regulatory loops. Intestinal disease might result from inappropriate activation of the mucosal immune system driven by TLRs in response to normal luminal flora.

78 FR 31451 - Pet Ownership for the Elderly or Persons With Disabilities in Multifamily Rental Housing...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-24

... must be scheduled by calling the Regulations Division at 202-708-3055 (this is not a toll-free number). Individuals with speech or hearing impairments may access this number via TTY by calling the toll-free Federal...). Persons with hearing or speech impairments may access this telephone number through TTY by calling the...

76 FR 36849 - Adjustment of Civil Money Penalty Amount for Inflation

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-22

..., telephone number 202-402-7687 (this is not a toll-free number). Hearing- or speech- impaired individuals may access this number via TTY by calling the toll-free Federal Relay Service at 800-877-8339. SUPPLEMENTARY.../special.requests/cpi/cpiai.txt . For June 2010 and June 1996, the CPI-U values are 217.965 and 156.7...

75 FR 31334 - Real Estate Settlement Procedures Act (RESPA): Strengthening and Clarifying RESPA's “Required Use...

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Fatal accident reporting system : a review of information on fatal traffic accidents in the U.S. in 1983

DOT National Transportation Integrated Search

1984-03-01

During 1983, 42,584 men, women, and children died in motor vehicle traffic accidents. That's more than 116 people per day. This is a 3.1 percent decline from the 1982 death toll of 43,945, and a 16.7 percent decline from the 1980 death toll of 51,091...

Analysis of a National Toll Free Suicide Crisis Line in South Africa

ERIC Educational Resources Information Center

Meehan, Sue-Ann; Broom, Yvonne

2007-01-01

The first national toll free suicide crisis line for South Africa was launched in October 2003 with the aim of providing a service dedicated to the prevention of suicide in this country. The intervention was motivated by South Africa's suicide rate which had risen higher than the global suicide rate, with the majority of attempted suicides…

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Differential expression of Toll-like receptor pathway genes in chicken embryo fibroblasts from chickens resistant and susceptible to Marek’s disease

USDA-ARS?s Scientific Manuscript database

The Toll-like receptor (TLR) signaling pathway is one of the innate immune defense mechanisms against pathogens in vertebrates and invertebrates. However, the role of TLR in non-MHC genetic resistance or susceptibility to Marek’s disease (MD) in the chicken is yet to be elucidated. Chicken embryo fi...

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Bovine viral diarrhea virus type 2 impairs macrophage responsiveness to toll-like receptor ligation with the exception of toll-like receptor 7

USDA-ARS?s Scientific Manuscript database

Bovine viral diarrhea virus (BVDV) is a member of the Flaviviradae family. BVDV isolates are classified into two biotypes based on the development of cytopathic (cp) or non-cytopathic (ncp) effects in epithelial cell culture. In addition, BVDV isolates are further separated into species, BVDV1 and 2...

29 CFR 2520.102-3 - Contents of summary plan description.

Code of Federal Regulations, 2011 CFR

2011-07-01

... users may call the federal relay service toll-free at 1-800-877-8339 and ask to be connected to 202-326... number). TTY/TDD users may call the federal relay service toll-free at 1-800-877-8339 and ask to be... certain rights and protections under the Employee Retirement Income Security Act of 1974 (ERISA). ERISA...

Unpacking Constructs: A Network Approach for Studying War Exposure, Daily Stressors and Post-Traumatic Stress Disorder

PubMed Central

De Schryver, Maarten; Vindevogel, Sofie; Rasmussen, Andrew E.; Cramer, Angélique O. J.

2015-01-01

Conflict-affected populations are exposed to stressful events during and after war, and it is well established that both take a substantial toll on individuals’ mental health. Exactly how exposure to events during and after war affect mental health is a topic of considerable debate. Various hypotheses have been put forward on the relation between stressful war exposure (SWE), daily stressors (DS) and the development of post-traumatic stress disorder (PTSD). This paper seeks to contribute to this debate by critically reflecting upon conventional modeling approaches and by advancing an alternative model to studying interrelationships between SWE, DS, and PTSD variables. The network model is proposed as an innovative and comprehensive modeling approach in the field of mental health in the context of war. It involves a conceptualization and representation of variables and relationships that better approach reality, hence improving methodological rigor. It also promises utility in programming and delivering mental health support for war-affected populations. PMID:26733901

Assembly of oligomeric death domain complexes during Toll receptor signaling.

PubMed

Moncrieffe, Martin C; Grossmann, J Günter; Gay, Nicholas J

2008-11-28

The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling.

Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*

PubMed Central

Moncrieffe, Martin C.; Grossmann, J. Günter; Gay, Nicholas J.

2008-01-01

The Drosophila Toll receptor is activated by the endogenous protein ligand Spätzle in response to microbial stimuli in immunity and spatial cues during embryonic development. Downstream signaling is mediated by the adaptor proteins Tube, the kinase Pelle, and the Drosophila homologue of myeloid differentiation primary response protein (dMyD88). Here we have characterized heterodimeric (dMyD88-Tube) and heterotrimeric (dMyD88-Tube-Pelle) death domain complexes. We show that both the heterodimeric and heterotrimeric complexes form kidney-shaped structures and that Tube is bivalent and has separate high affinity binding sites for dMyD88 and Pelle. Additionally we found no interaction between the isolated death domains of Pelle and dMyD88. These results indicate that the mode of assembly of the heterotrimeric dMyD88-Tube-Pelle complex downstream of the activated Toll receptor is unique. The measured dissociation constants for the interaction between the death domains of dMyD88 and Tube and of Pelle and a preformed dMyD88-Tube complex are used to propose a model of the early postreceptor events in Drosophila Toll receptor signaling. PMID:18829464

Sci-Hub provides access to nearly all scholarly literature.

PubMed

Himmelstein, Daniel S; Romero, Ariel Rodriguez; Levernier, Jacob G; Munro, Thomas Anthony; McLaughlin, Stephen Reid; Greshake Tzovaras, Bastian; Greene, Casey S

2018-03-01

The website Sci-Hub enables users to download PDF versions of scholarly articles, including many articles that are paywalled at their journal's site. Sci-Hub has grown rapidly since its creation in 2011, but the extent of its coverage has been unclear. Here we report that, as of March 2017, Sci-Hub's database contains 68.9% of the 81.6 million scholarly articles registered with Crossref and 85.1% of articles published in toll access journals. We find that coverage varies by discipline and publisher, and that Sci-Hub preferentially covers popular, paywalled content. For toll access articles, we find that Sci-Hub provides greater coverage than the University of Pennsylvania, a major research university in the United States. Green open access to toll access articles via licit services, on the other hand, remains quite limited. Our interactive browser at https://greenelab.github.io/scihub allows users to explore these findings in more detail. For the first time, nearly all scholarly literature is available gratis to anyone with an Internet connection, suggesting the toll access business model may become unsustainable. © 2018, Himmelstein et al.

The interplay between dose and immune system activation determines fungal infection outcome in the African malaria mosquito, Anopheles gambiae.

PubMed

Rhodes, Victoria L; Thomas, Matthew B; Michel, Kristin

2018-08-01

The Toll pathway is a central regulator of antifungal immunity in insects. In mosquitoes, the Toll pathway affects infections with the fungal entomopathogen, Beauveria bassiana, which is considered a potential mosquito biopesticide. We report here the use of B. bassiana strain I93-825 in Anopheles gambiae to analyze the impact of Toll pathway modulation on mosquito survival. Exposure to a narrow dose range of conidia by direct contact decreased mosquito longevity and median survival. In addition, fungal exposure dose correlated positively and linearly with hazard ratio. Increased Toll signaling by knockdown of its inhibitor, cactus, decreased survivorship of uninfected females, increased mosquito survival after low dose B. bassiana exposure, but had little effect following exposure to higher doses. This observed trade-off could have implications for development of B. bassiana as a prospective vector control tool. On the one hand, selection for small increases in mosquito immune signaling across a narrow dose range could impair efficacy of B. bassiana. On the other hand, costs of immunity and the capacity for higher doses of fungus to overwhelm immune responses could limit evolution of resistance. Copyright © 2018 Elsevier Ltd. All rights reserved.

Toll-like receptors and chronic inflammation in rheumatic diseases: new developments.

PubMed

Joosten, Leo A B; Abdollahi-Roodsaz, Shahla; Dinarello, Charles A; O'Neill, Luke; Netea, Mihai G

2016-06-01

In the past few years, new developments have been reported on the role of Toll-like receptors (TLRs) in chronic inflammation in rheumatic diseases. The inhibitory function of TLR10 has been demonstrated. Receptors that enhance the function of TLRs, and several TLR inhibitors, have been identified. In addition, the role of the microbiome and TLRs in the onset of rheumatic diseases has been reported. We review novel insights on the role of TLRs in several inflammatory joint diseases, including rheumatoid arthritis, systemic lupus erythematosus, gout and Lyme arthritis, with a focus on the signalling mechanisms mediated by the Toll-IL-1 receptor (TIR) domain, the exogenous and endogenous ligands of TLRs, and the current and future therapeutic strategies to target TLR signalling in rheumatic diseases.

77 FR 40590 - Applications for New Awards: Disability and Rehabilitation Research Projects and Centers Program...

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28 CFR 50.10 - Policy with regard to the issuance of subpoenas to members of the news media, subpoenas for...

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2013-07-01

... subpoenas to members of the news media, subpoenas for telephone toll records of members of the news media, and the interrogation, indictment, or arrest of, members of the news media. 50.10 Section 50.10... to the issuance of subpoenas to members of the news media, subpoenas for telephone toll records of...

28 CFR 50.10 - Policy with regard to the issuance of subpoenas to members of the news media, subpoenas for...

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... subpoenas to members of the news media, subpoenas for telephone toll records of members of the news media, and the interrogation, indictment, or arrest of, members of the news media. 50.10 Section 50.10... to the issuance of subpoenas to members of the news media, subpoenas for telephone toll records of...

28 CFR 50.10 - Policy with regard to the issuance of subpoenas to members of the news media, subpoenas for...

Code of Federal Regulations, 2012 CFR

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... subpoenas to members of the news media, subpoenas for telephone toll records of members of the news media, and the interrogation, indictment, or arrest of, members of the news media. 50.10 Section 50.10... to the issuance of subpoenas to members of the news media, subpoenas for telephone toll records of...

28 CFR 50.10 - Policy with regard to the issuance of subpoenas to members of the news media, subpoenas for...

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... subpoenas to members of the news media, subpoenas for telephone toll records of members of the news media, and the interrogation, indictment, or arrest of, members of the news media. 50.10 Section 50.10... to the issuance of subpoenas to members of the news media, subpoenas for telephone toll records of...

Develop preliminary engineering design and study the benefits of providing an access to the Indiana toll road at State Road 327 near Orland, IN.

DOT National Transportation Integrated Search

2016-10-05

A new toll road exit is proposed at the intersection of I-80/90 and SR 327 in Orland, : Indiana. The new exit is needed to facilitate travel for a proposed manufacturing plant to be : established on a 500-acre site east of SR 327 and south of I-80/90...

75 FR 36127 - Proposed Submission of Information Collection for OMB Review; Comment Request; Annual Reporting...

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2010-06-24

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Carbon Management In the Post-Cap-and-Trade Carbon Economy

NASA Astrophysics Data System (ADS)

DeGroff, F. A.

2012-12-01

Global carbon management is a pressing issue and will remain so for the balance of the 21st century. Without a worldwide comprehensive carbon management strategy in place,the economic, social, military, and humanitarian impact of excess carbon in our biosphere will preoccupy humanity until an efficient and effective strategy for carbon pricing can be implemented. In this paper, we discuss a possible strategy and construct model for comprehensive carbon management for the balance of this century. The focus of our strategy is an economic model with a carbon construct and metric that assigns a value to all states and forms of carbon involved with any anthropogenic activity. Any changes in the state or form of carbon due to anthropogenic activity will thereby generate discrete, finite, and measurable economic costs, or tolls, for the associated activity. All activities within a jurisdiction (or between jurisdictions with equivalent carbon toll treatment) that lack any change in the state or form of carbon will be free of any carbon toll. All goods and services crossing jurisdictions with dissimilar toll treatment will be assessed (or credited) to reflect the carbon toll differential. This model has three clear advantages. First, the carbon pricing and cost scheme uses existing and generally accepted accounting and economic methodologies to ensure the veracity and verifiability of carbon management efforts with minimal effort and expense using standard, existing auditing protocols. Implementing this model will not require any new, special, unique, or additional training, tools, or systems for any entity to achieve their minimum carbon target goals within their jurisdictional framework. Second, given the wide spectrum of carbon affinities across jurisdictions worldwide, our strategy recognizes and provides for flexible carbon pricing regimes, but does not undermine or penalize domestic carbon-consuming producers subject to imports from exporters in lower carbon pricing jurisdictions. Thus, this strategy avoids a key shortcoming of cap-and-trade carbon pricing, and eliminates any incentive to shift carbon consumption to jurisdictions with lower carbon tolls. Third, the model is a comprehensive, efficient, and effective strategy that allows for the implementation of a carbon pricing structure without the complete, explicit agreement of carbon consumers worldwide.

Modelling landscape change in paddy fields using logistic regression and GIS

NASA Astrophysics Data System (ADS)

Franjaya, E. E.; Syartinilia; Setiawan, Y.

2018-05-01

Paddy field in karawang district, as an important agricultural land in west java, has been decreased since 1994. From previous study, paddy fields dominantly turned into built area. The changes were almost occured in the middle area of the district where roadways, industries, settlements, and commercial buildings were existed. These were estimated as driving forces. But, we still need to prove it. This study aimed to construct the paddy field probability change model, subsequently the driving forces will be obtained. GIS combined with logistic regression using environmental variables were used as main method in this study. Ten environmental variables were elevation 0–500 m, elevation>500 m, slope<8%, slope>8%, CBD, build up area, river, irrigation, toll and national roadway, and collector and local roadway. The result indicated that four variables were significantly played as driving forces (slope>8%, CBD area, build up area, and collector and local roadway). Paddy field has high, medium, and low probability to change which covered about 27.8%, 7.8%, and 64.4% area in Karawang respectively. Based on landscape ecology, the recommendation that suitable with landscape change is adaptive management.

Tenebrio molitor Gram-negative-binding protein 3 (TmGNBP3) is essential for inducing downstream antifungal Tenecin 1 gene expression against infection with Beauveria bassiana JEF-007.

PubMed

Yang, Yi-Ting; Lee, Mi Rong; Lee, Se Jin; Kim, Sihyeon; Nai, Yu-Shin; Kim, Jae Su

2017-05-23

The Toll signaling pathway is responsible for defense against both Gram-positive bacteria and fungi. Gram-negative binding protein 3 (GNBP3) has a strong affinity for the fungal cell wall component, β-1,3-glucan, which can activate the prophenoloxidase (proPO) cascade and induce the Toll signaling pathway. Myeloid differentiation factor 88 (MyD88) is an intracellular adaptor protein involved in the Toll signaling pathway. In this study, we monitored the response of 5 key genes (TmGNBP3, TmMyD88, and Tenecin 1, 2, and 3) in the Toll pathway of the mealworm Tenebrio molitor immune system against the fungus Beauveria bassiana JEF-007 using RT-PCR. TmGNBP3, Tenecin 1, and Tenecin 2 were significantly upregulated after fungal infection. To better understand the roles of the Toll signaling pathway in the mealworm immune system, TmGNBP3 and TmMyD88 were knocked down by RNAi silencing. Target gene expression levels decreased at 2 d postknockdown and were dramatically reduced at 6 d post-dsRNA injection. Therefore, mealworms were compromised by B. bassiana JEF-007 at 6 d post-dsRNA injection. Silencing of TmMyD88 and TmGNBP3 resulted in reduced resistance of the host to fungal infection. Particularly, reducing TmGNBP3 levels obviously downregulated Tenecin 1 and Tenecin 2 expression levels, whereas silencing TmMyD88 expression resulted in decreased Tenecin 2 expression. These results indicate that TmGNBP3 is essential to induce downstream antifungal peptide Tenecin 1 expression against B. bassiana JEF-007. © 2017 Institute of Zoology, Chinese Academy of Sciences.

Sleep deprivation and divergent toll-like receptor-4 activation of cellular inflammation in aging.

PubMed

Carroll, Judith E; Carrillo, Carmen; Olmstead, Richard; Witarama, Tuff; Breen, Elizabeth C; Yokomizo, Megumi; Seeman, Teresa; Irwin, Michael R

2015-02-01

Sleep disturbance and aging are associated with increases in inflammation, as well as increased risk of infectious disease. However, there is limited understanding of the role of sleep loss on age-related differences in immune responses. This study examines the effects of sleep deprivation on toll-like receptor activation of monocytic inflammation in younger compared to older adults. Community-dwelling adults (n = 70) who were categorized as younger (25-39 y old, n = 21) and older (60-84 y old, n = 49) participants, underwent a sleep laboratory-based experimental partial sleep deprivation (PSD) protocol including adaptation, an uninterrupted night of sleep, sleep deprivation (sleep restricted to 03:00-07:00), and recovery. Blood samples were obtained each morning to measure toll-like receptor-4 activation of monocyte intracellular production of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Partial sleep deprivation induced a significant increase in the production of IL-6 and/or TNF-α that persisted after a night of recovery sleep (F(2,121.2) = 3.8, P < 0.05). Age moderated the effects of sleep loss, such that younger adults had an increase in inflammatory cytokine production that was not present in older adults (F(2,121.2) = 4.0, P < 0.05). Older adults exhibit reduced toll-like receptor 4 stimulated cellular inflammation that, unlike in younger adults, is not activated after a night of partial sleep loss. Whereas sleep loss increases cellular inflammation in younger adults and may contribute to inflammatory disorders, blunted toll-like receptor activation in older adults may increase the risk of infectious disease seen with aging. © 2015 Associated Professional Sleep Societies, LLC.

Diversity in the Toll-Like Receptor Genes of the African Penguin (Spheniscus demersus).

PubMed

Dalton, Desiré Lee; Vermaak, Elaine; Roelofse, Marli; Kotze, Antoinette

2016-01-01

The African penguin, Spheniscus demersus, is listed as Endangered by the IUCN Red List of Threatened Species due to the drastic reduction in population numbers over the last 20 years. To date, the only studies on immunogenetic variation in penguins have been conducted on the major histocompatibility complex (MHC) genes. It was shown in humans that up to half of the genetic variability in immune responses to pathogens are located in non-MHC genes. Toll-like receptors (TLRs) are now increasingly being studied in a variety of taxa as a broader approach to determine functional genetic diversity. In this study, we confirm low genetic diversity in the innate immune region of African penguins similar to that observed in New Zealand robin that has undergone several severe population bottlenecks. Single nucleotide polymorphism (SNP) diversity across TLRs varied between ex situ and in situ penguins with the number of non-synonymous alterations in ex situ populations (n = 14) being reduced in comparison to in situ populations (n = 16). Maintaining adaptive diversity is of vital importance in the assurance populations as these animals may potentially be used in the future for re-introductions. Therefore, this study provides essential data on immune gene diversity in penguins and will assist in providing an additional monitoring tool for African penguin in the wild, as well as to monitor diversity in ex situ populations and to ensure that diversity found in the in situ populations are captured in the assurance populations.

Toll-like receptors and gastrointestinal diseases: from bench to bedside?

PubMed

Cario, Elke

2002-11-01

The family of Toll-like receptors (TLRs) plays a key role in mediating innate immune responses to numerous luminal commensal- and pathogen-derived pattern molecules by the intestinal mucosa. Recent findings have identified several ligands recognized by TLRs as well as the complex downstream signaling effects resulting from activation of these receptors. Understanding is emerging of the importance of TLRs in mucosal host defense-potentially triggering gastrointestinal diseases.

Burn Enhances Toll-Like Receptor Induced Responses by Circulating Leukocytes

DTIC Science & Technology

2012-04-30

Introduction Major burn is associated with a local and sys- temic activation of the innate immune system resulting in a profound inflammatory...plications. Previous studies have shown that responses after burn differ between fixed-tissue immune cells and circulating immune cells [15]. In the current...Abstract: Burn and toll-like receptors (TLR) are associated with innate immune system activation, but the impact of burn on TLR-induced inflammation

Absence of Toll-like receptor 4 signaling results in delayed Yersinia enterocolitica YopP-induced cell death of dendritic cells.

PubMed

Gröbner, Sabine; Schulz, Sebastian; Soldanova, Irena; Gunst, Dani S J; Waibel, Michaela; Wesselborg, Sebastian; Borgmann, Stefan; Autenrieth, Ingo B

2007-01-01

In an initial period (< or =4 h) Toll-like receptor 4 (TLR4) signaling is required for Yersinia enterocolitica YopP-induced dendritic cell (DC) death. Later (>4 h), DC die independent of TLR4 signaling. In TLR4-deficient DC caspase 8 cleavage is delayed, indicating that TLR4 signaling accelerates caspase 8 activation, leading to DC death.

Age-related alteration of expression and function of TLRs and NK activity in oral candidiasis.

PubMed

Oouchi, M; Hasebe, A; Hata, H; Segawa, T; Yamazaki, Y; Yoshida, Y; Kitagawa, Y; Shibata, K-I

2015-07-01

Roles of aging or immune responses mediated by Toll-like receptors and natural killer cell in the onset or progression of human candidiasis remain unclear. This study was designed to elucidate the roles using peripheral blood mononuclear cells from healthy donors and patients with oral candidiasis. Subjects tested were healthy volunteers and patients who visited Dental Clinical Division of Hokkaido University Hospital. The patients with oral candidiasis included 39 individuals (25-89 years of age) with major complaints on pain in oral mucosa and/or dysgeusia. Healthy volunteers include students (25-35 years of age) and teaching staffs (50-65 years of age) of Hokkaido University Graduate School of Dental Medicine. Functions of Toll-like receptors 2 and 4 were downregulated significantly and the natural killer activity was slightly, but not significantly downregulated in aged healthy volunteers compared with healthy young volunteers. Functions of Toll-like receptors 2 and 4 and the natural killer activity were significantly downregulated in patients with oral candidiasis compared with healthy volunteers. Downregulation of functions of Toll-like receptors 2 and 4 as well as natural killer activity is suggested to be associated with the onset or progression of oral candidiasis in human. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The role of hemocytes in A. gambiae antiplasmodial immunity

PubMed Central

Ramirez, Jose Luis; Garver, Lindsey S.; Brayner, Fábio André; Alves, Luiz Carlos; Rodrigues, Janneth; Molina-Cruz, Alvaro; Barillas-Mury, Carolina

2013-01-01

Hemocytes synthesize key components of the mosquito complement-like system, but their role in the activation of antiplasmodial responses has not been established. The effect of activating Toll signaling in hemocytes on Plasmodium survival was investigated by transferring hemocytes or cell-free hemolymph from donor mosquitoes in which the suppressor cactus was silenced. These transfers greatly enhanced antiplasmodial immunity, indicating that hemocytes are active players in the activation of the complement-like system, through an effector(s) regulated by the Toll pathway. A comparative analysis of hemocyte populations between susceptible (S) G3 and the refractory (R) L3-5 A. gambiae mosquito strains did not reveal significant differences under basal conditions or in response to Plasmodium berghei infection. The response of S mosquitoes to different Plasmodium species revealed similar kinetics following infection with P. berghei, P. yoelii or P. falciparum, but the strength of the priming response was stronger in less compatible mosquito-parasite pairs. The Toll, Imd, STAT or JNK signaling cascades were not essential for the production of hemocyte differentiation factor (HDF) in response to P. berghei infection, but disruption of Toll, STAT or JNK abolished hemocyte differentiation in response to HDF. We conclude that hemocytes are key mediators of A. gambiae antiplasmodial responses. PMID:23886925

Antimicrobial peptide gene induction, involvement of Toll and IMD pathways and defense against bacteria in the red flour beetle, Tribolium castaneum.

PubMed

Yokoi, Kakeru; Koyama, Hiroaki; Minakuchi, Chieka; Tanaka, Toshiharu; Miura, Ken

2012-01-01

Using Tribolium castaneum, we quantitatively investigated the induction of nine antimicrobial peptide (AMP) genes by live gram-negative bacteria (Escherichia coli and Enterobacter cloacae), gram-positive bacteria (Micrococcus luteus and Bacillus subtilis) and the budding yeast (Saccharomyces cerevisiae). Then, five representative AMP genes were selected, and the involvement of the Toll and IMD pathways in their induction by E. coli, M. luteus and S. cerevisiae was examined by utilizing RNA interference of either MyD88 or IMD. Results indicated: Robust and acute induction of three genes by the two bacterial species was mediated mainly by the IMD pathway; slow and sustained induction of one gene by the two bacteria was mediated mainly by the Toll pathway; induction of the remaining one gene by the two bacteria was mediated by both pathways; induction of the five genes by the yeast was mediated by the Toll and/or IMD pathways depending on respective genes. These results suggest that more promiscuous activation and usage of the two pathways may occur in T. castaneum than in Drosophila melanogaster. In addition, the IMD pathway was revealed to dominantly contribute to defense against two bacterial species, gram-negative E. cloacae and gram-positive B. subtilis that possesses DAP-type peptidoglycan.

Thioester-containing proteins regulate the Toll pathway and play a role in Drosophila defence against microbial pathogens and parasitoid wasps.

PubMed

Dostálová, Anna; Rommelaere, Samuel; Poidevin, Mickael; Lemaitre, Bruno

2017-09-05

Members of the thioester-containing protein (TEP) family contribute to host defence in both insects and mammals. However, their role in the immune response of Drosophila is elusive. In this study, we address the role of TEPs in Drosophila immunity by generating a mutant fly line, referred to as TEPq Δ , lacking the four immune-inducible TEPs, TEP1, 2, 3 and 4. Survival analyses with TEPq Δ flies reveal the importance of these proteins in defence against entomopathogenic fungi, Gram-positive bacteria and parasitoid wasps. Our results confirm that TEPs are required for efficient phagocytosis of bacteria, notably for the two Gram-positive species tested, Staphylococcus aureus and Enterococcus faecalis. Furthermore, we show that TEPq Δ flies have reduced Toll pathway activation upon microbial infection, resulting in lower expression of antimicrobial peptide genes. Epistatic analyses suggest that TEPs function upstream or independently of the serine protease ModSP at an initial stage of Toll pathway activation. Collectively, our study brings new insights into the role of TEPs in insect immunity. It reveals that TEPs participate in both humoral and cellular arms of immune response in Drosophila. In particular, it shows the importance of TEPs in defence against Gram-positive bacteria and entomopathogenic fungi, notably by promoting Toll pathway activation.

[The receptor theory of atherosclerosis].

PubMed

Likhoded, V G; Bondarenko, V M; Gintsburg, A L

2010-01-01

Lipopolysaccharides of Gram-negative bacteria can interact with Toll-like receptor 4 (TLR4) and induce atheroma formation. The risk of atherosclerosis is decreased in case of TLR4 mutation. Other bacterial ligands and endogenous ligands of TLRs can also be involved in induction of atherogenesis. The general concept of atherosclerosis pathogentsis is presented. According to this concept atherogenesis can be initiated by some reactions resulting from interaction of exogenous and endogenous microbial ligands with Toll-like receptors.

Pellino enhances innate immunity in Drosophila.

PubMed

Haghayeghi, Amirhossein; Sarac, Amila; Czerniecki, Stefan; Grosshans, Jörg; Schöck, Frieder

2010-01-01

The innate immune response is a defense mechanism against infectious agents in both vertebrates and invertebrates, and is in part mediated by the Toll pathway. Toll receptor activation upon exposure to bacteria causes stimulation of Pelle/IRAK kinase, eventually resulting in translocation of the transcription factor NF-kappaB to the nucleus. Here we show that Pellino, a highly conserved protein interacting with activated Pelle/IRAK, acts as a positive regulator of innate immunity in Drosophila.

Association study of Toll-like receptor 5 (TLR5) and Toll-like receptor 9 (TLR9) polymorphisms in systemic lupus erythematosus.

PubMed

Demirci, F Yesim K; Manzi, Susan; Ramsey-Goldman, Rosalind; Kenney, Margaret; Shaw, Penny S; Dunlop-Thomas, Charmayne M; Kao, Amy H; Rhew, Elisa Y; Bontempo, Franklin; Kammerer, Candace; Kamboh, M Ilyas

2007-08-01

Toll-like receptors (TLR) play an important role in both adaptive and innate immunity. Variations in TLR genes have been shown to be associated with various infectious and inflammatory diseases. We investigated the association of TLR5 (Arg392Stop, rs5744168) and TLR9 (-1237T-->C, rs5743836) single nucleotide polymorphisms (SNP) with systemic lupus erythematosus (SLE) in Caucasian American subjects. We performed a case-control association study and genotyped 409 Caucasian women with SLE and 509 Caucasian healthy female controls using TaqMan allelic discrimination (rs5744168) or polymerase chain reaction-restriction fragment length polymorphism analysis (rs5743836). None of the 2 TLR SNP showed a statistically significant association with SLE risk in our cohort. Our results do not indicate a major influence of these putative functional TLR SNP on the susceptibility to (or protection from) SLE.

Environmental lead exposure to toll booth workers in Hong Kong

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

Tan, T.C.; Wong, L.T.L.; Lam, C.W.K.

1988-01-01

A survey of workers in the Lion Rock Tunnel toll booths was conducted, as they were regarded as a high risk group in lead exposure due to high density of vehicular traffic. The exposure of the workers to lead was determined by continuous sapling of air around the breathing zone of workers inside the booths. Blood lead concentration of 50 workers showed a mean of 0.65 {mu}mol/L and the mean urine lead concentration was 0.14 {mu}mol/L. Other tests, such as urinary amino-levulinic acid (ALA), erythrocyte zinc protoporphyrin (ZnPP) and hemoglobin concentration (Hb), were also preformed. The blood lead concentrations andmore » other biological parameters of the toll-booth workers were acceptable and may be attributed to the recent legislation to lower the lead content in petrol and to the good preventive measures taken by the management.« less

Combating Biological Terrorism from Imported Food

DTIC Science & Technology

2011-03-24

2006 Lettuce 0 71 E. coli 2009 Cookie dough 0 65 E. coli 2007 Snack food 0 65 Salmonella 2010 Duck eggs 1 63 Salmonella 2007 Pet food 0 62...Eating Raw Refrigerated, Prepackaged Nestle Toll House Cookie Dough . Sixty-five people from twenty-nine states were infected with E. coli O157:H7 from...eating raw refrigerated, prepackaged Nestle Toll House cookie dough 1 March to 18 June 2009 (CDC, “Multistate”, 2009a) Outbreak of Salmonella

Specificity in Toll-like receptor signalling through distinct effector functions of TRAF3 and TRAF6.

PubMed

Häcker, Hans; Redecke, Vanessa; Blagoev, Blagoy; Kratchmarova, Irina; Hsu, Li-Chung; Wang, Gang G; Kamps, Mark P; Raz, Eyal; Wagner, Hermann; Häcker, Georg; Mann, Matthias; Karin, Michael

2006-01-12

Toll-like receptors (TLRs) are activated by pathogen-associated molecular patterns to induce innate immune responses and production of pro-inflammatory cytokines, interferons and anti-inflammatory cytokines. TLRs activate downstream effectors through adaptors that contain Toll/interleukin-1 receptor (TIR) domains, but the mechanisms accounting for diversification of TLR effector functions are unclear. To dissect biochemically TLR signalling, we established a system for isolating signalling complexes assembled by dimerized adaptors. Using MyD88 as a prototypical adaptor, we identified TNF receptor-associated factor 3 (TRAF3) as a new component of TIR signalling complexes that is recruited along with TRAF6. Using myeloid cells from TRAF3- and TRAF6-deficient mice, we show that TRAF3 is essential for the induction of type I interferons (IFN) and the anti-inflammatory cytokine interleukin-10 (IL-10), but is dispensable for expression of pro-inflammatory cytokines. In fact, TRAF3-deficient cells overproduce pro-inflammatory cytokines owing to defective IL-10 production. Despite their structural similarity, the functions of TRAF3 and TRAF6 are largely distinct. TRAF3 is also recruited to the adaptor TRIF (Toll/IL-1 receptor domain-containing adaptor-inducing IFN-beta) and is required for marshalling the protein kinase TBK1 (also called NAK) into TIR signalling complexes, thereby explaining its unique role in activation of the IFN response.

Macrophage activation by heparanase is mediated by TLR-2 and TLR-4 and associates with plaque progression.

PubMed

Blich, Miry; Golan, Amnon; Arvatz, Gil; Sebbag, Anat; Shafat, Itay; Sabo, Edmond; Cohen-Kaplan, Victoria; Petcherski, Sirouch; Avniel-Polak, Shani; Eitan, Amnon; Hammerman, Haim; Aronson, Doron; Axelman, Elena; Ilan, Neta; Nussbaum, Gabriel; Vlodavsky, Israel

2013-02-01

Factors and mechanisms that activate macrophages in atherosclerotic plaques are incompletely understood. We examined the capacity of heparanase to activate macrophages. Highly purified heparanase was added to mouse peritoneal macrophages and macrophage-like J774 cells, and the levels of tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 were evaluated by ELISA. Gene expression was determined by RT-PCR. Cells collected from Toll-like receptor-2 and Toll-like receptor-4 knockout mice were evaluated similarly. Heparanase levels in the plasma of patients with acute myocardial infarction, stable angina, and healthy subjects were determined by ELISA. Immunohistochemistry was applied to detect the expression of heparanase in control specimens and specimens of patients with stable angina or acute myocardial infarction. Addition or overexpression of heparanase variants resulted in marked increase in tumor necrosis factor-α, matrix metalloproteinase-9, interlukin-1, and monocyte chemotactic protein-1 levels. Mouse peritoneal macrophages harvested from Toll-like receptor-2 or Toll-like receptor-4 knockout mice were not activated by heparanase. Plasma heparanase level was higher in patients with acute myocardial infarction, compared with patients with stable angina and healthy subjects. Pathologic coronary specimens obtained from vulnerable plaques showed increased heparanase staining compared with specimens of stable plaque and controls. Heparanase activates macrophages, resulting in marked induction of cytokine expression associated with plaque progression toward vulnerability.

An entomopathogenic bacterium, Xenorhabdus nematophila, suppresses expression of antimicrobial peptides controlled by Toll and Imd pathways by blocking eicosanoid biosynthesis.

PubMed

Hwang, Jihyun; Park, Youngjin; Kim, Yonggyun; Hwang, Jihyun; Lee, Daeweon

2013-07-01

Immune-associated genes of the beet armyworm, Spodoptera exigua, were predicted from 454 pyrosequencing transcripts of hemocytes collected from fifth instar larvae challenged with bacteria. Out of 22,551 contigs and singletons, 36% of the transcripts had at least one significant hit (E-value cutoff of 1e-20) and used to predict immune-associated genes implicated in pattern recognition, prophenoloxidase activation, intracellular signaling, and antimicrobial peptides (AMPs). Immune signaling and AMP genes were further confirmed in their expression patterns in response to different types of microbial challenge. To discriminate the AMP expression signaling between Toll and Imd pathways, RNA interference was applied to specifically knockdown each signal pathway; the separate silencing treatments resulted in differential suppression of AMP genes. An entomopathogenic bacterium, Xenorhabdus nematophila, suppressed expression of most AMP genes controlled by Toll and Imd pathways, while challenge with heat-killed X. nematophila induced expression of all AMPs in experimental larvae. Benzylideneacetone (BZA), a metabolite of X. nematophila, suppressed the AMP gene inductions when it was co-injected with the heat-killed X. nematophila. However, arachidonic acid, a catalytic product of PLA2 , significantly reversed the inhibitory effect of BZA on the AMP gene expression. This study suggests that X. nematophila suppresses AMP production controlled by Toll and Imd pathways by inhibiting eicosanoid biosynthesis in S. exigua. © 2013 Wiley Periodicals, Inc.

A Toll/interleukin (IL)-1 receptor domain protein from Yersinia pestis interacts with mammalian IL-1/Toll-like receptor pathways but does not play a central role in the virulence of Y. pestis in a mouse model of bubonic plague.

PubMed

Spear, Abigail M; Rana, Rohini R; Jenner, Dominic C; Flick-Smith, Helen C; Oyston, Petra C F; Simpson, Peter; Matthews, Stephen J; Byrne, Bernadette; Atkins, Helen S

2012-06-01

The Toll/interleukin (IL)-1 receptor (TIR) domain is an essential component of eukaryotic innate immune signalling pathways. Interaction between TIR domains present in Toll-like receptors and associated adaptors initiates and propagates an immune signalling cascade. Proteins containing TIR domains have also been discovered in bacteria. Studies have subsequently shown that these proteins are able to modulate mammalian immune signalling pathways dependent on TIR interactions and that this may represent an evasion strategy for bacterial pathogens. Here, we investigate a TIR domain protein from the highly virulent bacterium Yersinia pestis, the causative agent of plague. When overexpressed in vitro this protein is able to downregulate IL-1β- and LPS-dependent signalling to NFκB and to interact with the TIR adaptor protein MyD88. This interaction is dependent on a single proline residue. However, a Y. pestis knockout mutant lacking the TIR domain protein was not attenuated in virulence in a mouse model of bubonic plague. Minor alterations in the host cytokine response to the mutant were indicated, suggesting a potential subtle role in pathogenesis. The Y. pestis mutant also showed increased auto-aggregation and reduced survival in high-salinity conditions, phenotypes which may contribute to pathogenesis or survival.

Dengue serotype-specific immune response in Aedes aegypti and Aedes albopictus.

PubMed

Smartt, Chelsea T; Shin, Dongyoung; Alto, Barry W

2017-12-01

Dengue viruses (DENV) are considered one of the most important emerging pathogens and dengue disease is a global health threat. The geographic expansion of dengue viruses has led to co-circulation of all four dengue serotypes making it imperative that new DENV control strategies be devised. Here we characterize dengue serotype-specific innate immune responses in Aedes aegypti and Aedes albopictus using DENV from Puerto Rico (PR). Ae. aegypti and Ae. albopictus were infected with dengue serotype 1 and 2 isolated from Puerto Rico. DENV infected mosquito samples were collected and temporal change in expression of selected innate immune response pathway genes analyzed by quantitative real time PCR. The Toll pathway is involved in anti-dengue response in Ae. aegypti, and Ae. albopictus. Infections with PR DENV- 1 elicited a stronger response from genes of the Toll immune pathway than PR DENV-2 in Ae. aegypti but in infected Ae. albopictus expression of Toll pathway genes tended to be similar between the serotypes. Two genes (a ribosomal S5 protein gene and a nimrod-like gene) from Ae. albopictus were expressed in response to DENV. These studies revealed a role for antiviral genes in DENV serotype-specific interactions with DENV vectors, demonstrated that infections with DENV-2 can modulate the Toll immune response pathway in Ae. aegypti and elucidated candidate molecules that might be used to interfere with serotype specific vector-virus interactions.

Disasters and youth: a meta-analytic examination of posttraumatic stress.

PubMed

Furr, Jami M; Comer, Jonathan S; Edmunds, Julie M; Kendall, Philip C

2010-12-01

Meta-analyze the literature on posttraumatic stress (PTS) symptoms in youths post-disaster. Meta-analytic synthesis of the literature (k = 96 studies; Ntotal = 74,154) summarizing the magnitude of associations between disasters and youth PTS, and key factors associated with variations in the magnitude of these associations. We included peer-reviewed studies published prior to 1/1/2009 that quantitatively examined youth PTS (≤ 18 years at event) after a distinct and identifiable disaster. Despite variability across studies, disasters had a significant effect on youth PTS (small-to-medium magnitude; rpooled = .19, SEr = .03; d = 0.4). Female gender (rpooled = .14), higher death toll (disasters of death toll ≤ 25: rpooled = .09; vs. disasters with ≥ 1,000 deaths: rpooled = .22), child proximity (rpooled = .33), personal loss (rpooled = .16), perceived threat (rpooled = .34), and distress (rpooled = .38) at time of event were each associated with increased PTS. Studies conducted within 1 year post-disaster, studies that used established measures, and studies that relied on child-report data identified a significant effect. Youths are vulnerable to appreciable PTS after disaster, with pre-existing child characteristics, aspects of the disaster experience, and study methodology each associated with variations in the effect magnitude. Findings underscore the importance of measurement considerations in post-disaster research. Areas in need of research include the long-term impact of disasters, disaster-related media exposure, prior trauma and psychopathology, social support, ethnicity/race, prejudice, parental psychopathology, and the effects of disasters in developing regions of the world. Policy and clinical implications are discussed. (c) 2010 APA, all rights reserved.

Promoters, toll like receptors and microRNAs: a strange association.

PubMed

Korla, Kalyani; Arrigo, Patrizio; Mitra, Chanchal K

2013-06-01

Toll-like receptors (TLRs) are proteins that play key role in the innate immune system. In the present study, -1000 base pairs upstream are taken from the transcription start site of the various TLR genes (10 known) in human. About 40 microRNAs have been identified that share 12-19 nucleotide sequence similarity with the promoter regions of 10 TLRs. It is proposed that the microRNA performs potential role in identification of promoter sequence and initiation of transcription.

A Novel Approach for Effectively Treating SCI Pain, Improving Opioid Efficacy, and Preventing Opioid-Induced Constipation: Key Role of Toll-Like Receptor 4 (TLR4)

DTIC Science & Technology

2015-10-01

University of Colorado Boulder, CO 80303 REPORT DATE: October 2015 TYPE OF REPORT: Annual PREPARED FOR: U.S. Army Medical Research and Materiel...TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Regents of the University of Colorado Boulder, CO 80303 8...allodynia, hyperalgesia, toll-like receptor 4 OVERALL PROJECT SUMMARY Task 1. Obtain approval from the University of Colorado Institute Animal Care & Use

Toll-like receptor signaling and its relevance to intestinal inflammation.

PubMed

Cario, Elke; Podolsky, Daniel K

2006-08-01

This review discusses the current progress in the understanding of how commensal-mediated activation of toll-like receptors (TLRs) may be involved in the regulation of physiological and pathophysiological processes of the intestinal mucosa including tissue regeneration and inflammation. While regulation of TLRs and their downstream signaling mediators might be used to prevent and treat inflammatory bowel diseases, paradoxically, at this time, it remains uncertain whether this would be more effectively accomplished by enhancing or inhibiting these pathways.

U.S. Progress Reports for the Vietnam War, 1967-68. A Study of the Hamlet Evaluation System and the Enemy Order of Battle

DTIC Science & Technology

1990-08-01

foreign policy. The physical and emotional toll of executive responsibility in State, the Pentagon, the White House, and other executive agencies is...enormousl that toll is...compounded by extended service...Complaints may be few, and physical health may remain unimpaired, though emotional health is far...Category V. The enemy are reported to be in physical control of the hamlet. 2 .cV.C supremacy, except for occasional allied forays) 40 specially

Curbing gridlock: Peak-period fees to relieve traffic congestion. Volume 2. Commissioned papers. Special report

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

Not Available

1994-01-01

;Contents: Volume 2: Commissioned Papers: Congestion Trends in Metropolitan Areas; Alternative Methods for Measuring Congestion Levels; Potential of Congestion Pricing in the Metropolitan Washington Region; Transportation Pricing and Travel Behavior; Peak Pricing Strategies in Transportation, Utilities, and Telecommunications: Lessons for Road Pricing; Cashing Out Employer-Paid Parking: A Precedent for Congestion Pricing; The New York Region: First in Tolls, Last in Road Pricing; Pricing Urban Roadways: Administrative and Institutional Issues; Equity and Fairness Considerations of Congestion Pricing; The Politics of Congestion Pricing; Institutional and Political Challenges in Implementing Congestion Pricing: Case Study of the San Francisco Bay Area; How Congestion Pricingmore » Came to Be Proposed in the San Diego Region: A Case History; Urban Transportation Congestion Pricing: Effects on Urban Form; Congestion Pricing and Motor Vehicle Emissions: An Initial Review; Private Toll Roads: Acceptability of Congestion Pricing in Southern California; Potential of Next-Generation Technology; Electronic Toll Collection Systems; and Impacts of Congestion Pricing on Transit and Carpool Demand and Supply.« less

Reactive oxygen species-dependent Toll/NF-κB activation in the Drosophila hematopoietic niche confers resistance to wasp parasitism.

PubMed

Louradour, Isabelle; Sharma, Anurag; Morin-Poulard, Ismael; Letourneau, Manon; Vincent, Alain; Crozatier, Michèle; Vanzo, Nathalie

2017-11-01

Hematopoietic stem/progenitor cells in the adult mammalian bone marrow ensure blood cell renewal. Their cellular microenvironment, called 'niche', regulates hematopoiesis both under homeostatic and immune stress conditions. In the Drosophila hematopoietic organ, the lymph gland, the posterior signaling center (PSC) acts as a niche to regulate the hematopoietic response to immune stress such as wasp parasitism. This response relies on the differentiation of lamellocytes, a cryptic cell type, dedicated to pathogen encapsulation and killing. Here, we establish that Toll/NF-κB pathway activation in the PSC in response to wasp parasitism non-cell autonomously induces the lymph gland immune response. Our data further establish a regulatory network where co-activation of Toll/NF-κB and EGFR signaling by ROS levels in the PSC/niche controls lymph gland hematopoiesis under parasitism. Whether a similar regulatory network operates in mammals to control emergency hematopoiesis is an open question.

Patents for Toll-like receptor ligands as radiation countermeasures for acute radiation syndrome.

PubMed

Singh, Vijay K; Pollard, Harvey B

2015-01-01

Acute radiation exposure induces apoptosis of tissues in the hematopoietic, digestive, cutaneous, cardiovascular and nervous systems; extensive apoptosis of these tissues ultimately leads to acute radiation syndrome. A novel strategy for developing radiation countermeasures has been to imitate the genetic mechanisms acquired by radiation-resistant tumors. Two mechanisms that underlie this ability of tumor cells are the p53 and NF-κB pathways. The loss of p53 function results in the inactivation of pro-apoptotic control mechanisms, while constitutive activation of NF-κB results in the up-regulation of anti-apoptotic genes. Various Toll-like receptor ligands are capable of up regulating the NF-κB pathway, which increases radio-resistance and reduces radiation-induced apoptosis in various tissues. Several Toll-like receptor ligands have been patented and are currently under development as radiation countermeasures for acute radiation syndrome. Ongoing studies suggest that a few of these attractive agents are progressing well along the US FDA approval pathway to become radiation countermeasures.

The Boundaries of Genocide: Quantifying the Uncertainty of the Death Toll During the Pol Pot Regime (1975-1979)

PubMed Central

Heuveline, Patrick

2015-01-01

Estimates of excess deaths under Pol Pot's rule of Cambodia (1975-79) range from under one million to over three million. The more plausible among those, methodologically, still vary from one to two million deaths, but this range of independent point estimates has no particular statistical meaning. Stochastically reconstructing population dynamics in Cambodia from extant historical and demographic data yields interpretable distributions of the death toll and other demographic indicators. The resulting 95-percent simulation interval (1.2 to 2.8 million excess deaths) demonstrates substantial uncertainty with regards to the exact scale of mortality, yet still excludes nearly half of the previous death-toll estimates. The 1.5 to 2.25 million interval contains 69 per cent of the simulations for the actual number of excess death, more than the wider (one to two million) range of previous plausible estimates. The median value of 1.9 million excess deaths represents 21 percent of the population at risk. PMID:26218856

Patents for Toll-like receptor ligands as radiation countermeasures for acute radiation syndrome

PubMed Central

Singh, Vijay K; Pollard, Harvey B

2015-01-01

Acute radiation exposure induces apoptosis of tissues in the hematopoietic, digestive, cutaneous, cardiovascular and nervous systems; extensive apoptosis of these tissues ultimately leads to acute radiation syndrome. A novel strategy for developing radiation countermeasures has been to imitate the genetic mechanisms acquired by radiation-resistant tumors. Two mechanisms that underlie this ability of tumor cells are the p53 and NF-κB pathways. The loss of p53 function results in the inactivation of pro-apoptotic control mechanisms, while constitutive activation of NF-κB results in the up-regulation of anti-apoptotic genes. Various Toll-like receptor ligands are capable of up regulating the NF-κB pathway, which increases radio-resistance and reduces radiation-induced apoptosis in various tissues. Several Toll-like receptor ligands have been patented and are currently under development as radiation countermeasures for acute radiation syndrome. Ongoing studies suggest that a few of these attractive agents are progressing well along the US FDA approval pathway to become radiation countermeasures. PMID:26135043

Taking a Toll on human disease: Toll-like receptor 4 agonists as vaccine adjuvants and monotherapeutic agents.

PubMed

Baldridge, Jory R; McGowan, Patrick; Evans, Jay T; Cluff, Christopher; Mossman, Sally; Johnson, David; Persing, David

2004-07-01

Toll-like receptor (TLR) agonists are being developed for use as vaccine adjuvants and as stand-alone immunomodulators because of their ability to stimulate innate and adaptive immune responses. Among the most thoroughly studied TLR agonists are the lipid A molecules that target the TLR4 complex. One promising candidate, monophosphoryl lipid A, which is a derivative of lipid A from Salmonella minnesota, has proven to be safe and effective as a vaccine adjuvant in > 120,000 human doses. A new class of synthetic lipid A mimetics, the aminoalkyl glucosaminide 4-phosphates (AGPs), have been engineered specifically to target human TLR4 and are showing promise as vaccine adjuvants and as monotherapeutic agents capable of eliciting nonspecific protection against a wide range of infectious pathogens. In this review, the authors provide an update of the preclinical and clinical experiences with the TLR4 agonists, MPL (Corixa Corporation) adjuvant and the AGPs.

The role of MAPK in CD4{sup +} T cells toll-like receptor 9-mediated signaling following HHV-6 infection

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

Chi, Jing; Wang, Fang; Li, Lingyun

2012-01-05

Human herpesvirus-6 (HHV-6) is an important immunosuppressive and immunomodulatory virus that primarily infects immune cells (mainly CD4{sup +} T cells) and strongly suppresses the proliferation of infected cells. Toll-like receptors are pattern-recognition receptors essential for the development of an appropriate innate immune defense against infection. To understand the role of CD4{sup +} T cells in the innate response to HHV-6 infection and the involvement of TLRs, we used an in vitro infection model and observed that the infection of CD4{sup +} T cells resulted in the activation of JNK/SAPK via up-regulation of toll-like receptor 9 (TLR9). Associated with JNK activation,more » annexin V-PI staining indicated that HHV-6A was a strong inducer of apoptosis. Apoptotic response associated cytokines, IL-6 and TNF-{alpha} also induced by HHV-6A infection.« less

The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae. aegypti strains and against multiple dengue virus serotypes

PubMed Central

Ramirez, Jose L.; Dimopoulos, George

2010-01-01

Dengue virus has become one of the most important arboviral pathogens affecting the world today. The virus is transmitted among humans by the mosquitoes Aedes aegypti and Ae. albopictus. Like other vector-borne pathogens, this virus encounters innate immune defenses within the mosquito vector that limit infection. We have previously demonstrated the involvement of the Toll pathway in the anti-dengue defense at 7 days after infection. In the present study, we have investigated the activity of this immune signaling pathway against different dengue virus serotypes at the early stages of infection in laboratory and field-derived mosquito strains. Our studies corroborate the importance of the Toll pathway in the anti-dengue defense repertoire at 3 days after an infectious blood meal, when new virions are released from the midgut for dissemination and infection of other mosquito tissues. These immune defenses are furthermore conserved among different Ae. aegypti strains and can act against a broad range of dengue virus serotypes. PMID:20079370

Postmarketing surveillance of new food ingredients: results from the program with the fat replacer olestra.

PubMed

Allgood, G S; Kuter, D J; Roll, K T; Taylor, S L; Zorich, N L

2001-04-01

Market introduction of savory snacks containing olestra offered an opportunity to evaluate the safety of olestra in a free-living population and thereby compare the outcome to the previously established safety profile determined in clinical trials in which subjects were required to eat predetermined amounts at prescribed intervals. Therefore, a multifaceted postmarketing surveillance program was designed to evaluate consumer experience and safety of olestra in the marketplace. Customer comments were solicited through toll-free telephone numbers. Collected data were evaluated by both internal and external medical experts. About 10% of toll-free telephone calls reported health effects, most of which were gastrointestinal (GI) in nature. Clinical studies were designed and conducted to determine potential GI effects under the range of consumption patterns reported by toll-free calls. Health effects reported were those found commonly in the general population and analyses of the data found no biological reason to conclude that serious or meaningful health effects were the result of olestra consumption. Copyright 2001 Academic Press.

Heat shock proteins and toll-like receptors.

PubMed

Asea, Alexzander

2008-01-01

Researchers have only just begun to elucidate the relationship between heat shock proteins (HSP) and Toll-like receptors (TLR). HSP were originally described as an intracellular molecular chaperone of naïve, aberrantly folded, or mutated proteins and primarily implicated as a cytoprotective protein when cells are exposed to stressful stimuli. However, recent studies have ascribed novel functions to the Hsp70 protein depending on its localization: Surface-bound Hsp70 specifically activate natural killer (NK) cells, while Hsp70 released into the extracellular milieu specifically bind to Toll-like receptors (TLR) 2 and 4 on antigen-presenting cells (APC) and exerts immunoregulatory effects, including upregulation of adhesion molecules, co-stimulatory molecule expression, and cytokine and chemokine release-a process known as the chaperokine activity of Hsp70. This chapter discusses the most recent advances in the understanding of heat shock protein (HSP) and TLR interactions in general and highlights recent findings that demonstrate Hsp70 is a ligand for TLR and its biological significance.

Bacterial Stimulation of Toll-Like Receptor 4 Drives Macrophages To Hemophagocytose

PubMed Central

McDonald, Erin M.; Pilonieta, M. Carolina; Nick, Heidi J.

2015-01-01

During acute infection with bacteria, viruses or parasites, a fraction of macrophages engulf large numbers of red and white blood cells, a process called hemophagocytosis. Hemophagocytes persist into the chronic stage of infection and have an anti-inflammatory phenotype. Salmonella enterica serovar Typhimurium infection of immunocompetent mice results in acute followed by chronic infection, with the accumulation of hemophagocytes. The mechanism(s) that triggers a macrophage to become hemophagocytic is unknown, but it has been reported that the proinflammatory cytokine gamma interferon (IFN-γ) is responsible. We show that primary macrophages become hemophagocytic in the absence or presence of IFN-γ upon infection with Gram-negative bacterial pathogens or prolonged exposure to heat-killed Salmonella enterica, the Gram-positive bacterium Bacillus subtilis, or Mycobacterium marinum. Moreover, conserved microbe-associated molecular patterns are sufficient to stimulate macrophages to hemophagocytose. Purified bacterial lipopolysaccharide (LPS) induced hemophagocytosis in resting and IFN-γ-pretreated macrophages, whereas lipoteichoic acid and synthetic unmethylated deoxycytidine-deoxyguanosine dinucleotides, which mimic bacterial DNA, induced hemophagocytosis only in IFN-γ-pretreated macrophages. Chemical inhibition or genetic deletion of Toll-like receptor 4, a pattern recognition receptor responsive to LPS, prevented both Salmonella- and LPS-stimulated hemophagocytosis. Inhibition of NF-κB also prevented hemophagocytosis. These results indicate that recognition of microbial products by Toll-like receptors stimulates hemophagocytosis, a novel outcome of prolonged Toll-like receptor signaling, suggesting hemophagocytosis is a highly conserved innate immune response. PMID:26459510

Distributions of observed death tolls govern sensitivity to human fatalities

PubMed Central

Olivola, Christopher Y.; Sagara, Namika

2009-01-01

How we react to humanitarian crises, epidemics, and other tragic events involving the loss of human lives depends largely on the extent to which we are moved by the size of their associated death tolls. Many studies have demonstrated that people generally exhibit a diminishing sensitivity to the number of human fatalities and, equivalently, a preference for risky (vs. sure) alternatives in decisions under risk involving human losses. However, the reason for this tendency remains unknown. Here we show that the distributions of event-related death tolls that people observe govern their evaluations of, and risk preferences concerning, human fatalities. In particular, we show that our diminishing sensitivity to human fatalities follows from the fact that these death tolls are approximately power-law distributed. We further show that, by manipulating the distribution of mortality-related events that people observe, we can alter their risk preferences in decisions involving fatalities. Finally, we show that the tendency to be risk-seeking in mortality-related decisions is lower in countries in which high-mortality events are more frequently observed. Our results support a model of magnitude evaluation based on memory sampling and relative judgment. This model departs from the utility-based approaches typically encountered in psychology and economics in that it does not rely on stable, underlying value representations to explain valuation and choice, or on choice behavior to derive value functions. Instead, preferences concerning human fatalities emerge spontaneously from the distributions of sampled events and the relative nature of the evaluation process. PMID:20018778

Dengue serotype-specific immune response in Aedes aegypti and Aedes albopictus

PubMed Central

Smartt, Chelsea T; Shin, Dongyoung; Alto, Barry W

2017-01-01

BACKGROUND Dengue viruses (DENV) are considered one of the most important emerging pathogens and dengue disease is a global health threat. The geographic expansion of dengue viruses has led to co-circulation of all four dengue serotypes making it imperative that new DENV control strategies be devised. OBJECTIVES Here we characterize dengue serotype-specific innate immune responses in Aedes aegypti and Aedes albopictus using DENV from Puerto Rico (PR). METHODS Ae. aegypti and Ae. albopictus were infected with dengue serotype 1 and 2 isolated from Puerto Rico. DENV infected mosquito samples were collected and temporal change in expression of selected innate immune response pathway genes analyzed by quantitative real time PCR. FINDINGS The Toll pathway is involved in anti-dengue response in Ae. aegypti, and Ae. albopictus. Infections with PR DENV- 1 elicited a stronger response from genes of the Toll immune pathway than PR DENV-2 in Ae. aegypti but in infected Ae. albopictus expression of Toll pathway genes tended to be similar between the serotypes. Two genes (a ribosomal S5 protein gene and a nimrod-like gene) from Ae. albopictus were expressed in response to DENV. MAIN CONCLUSIONS These studies revealed a role for antiviral genes in DENV serotype-specific interactions with DENV vectors, demonstrated that infections with DENV-2 can modulate the Toll immune response pathway in Ae. aegypti and elucidated candidate molecules that might be used to interfere with serotype specific vector-virus interactions. PMID:29211244

The innate immune repertoire in cnidaria--ancestral complexity and stochastic gene loss.

PubMed

Miller, David J; Hemmrich, Georg; Ball, Eldon E; Hayward, David C; Khalturin, Konstantin; Funayama, Noriko; Agata, Kiyokazu; Bosch, Thomas C G

2007-01-01

Characterization of the innate immune repertoire of extant cnidarians is of both fundamental and applied interest--it not only provides insights into the basic immunological 'tool kit' of the common ancestor of all animals, but is also likely to be important in understanding the global decline of coral reefs that is presently occurring. Recently, whole genome sequences became available for two cnidarians, Hydra magnipapillata and Nematostella vectensis, and large expressed sequence tag (EST) datasets are available for these and for the coral Acropora millepora. To better understand the basis of innate immunity in cnidarians, we scanned the available EST and genomic resources for some of the key components of the vertebrate innate immune repertoire, focusing on the Toll/Toll-like receptor (TLR) and complement pathways. A canonical Toll/TLR pathway is present in representatives of the basal cnidarian class Anthozoa, but neither a classic Toll/TLR receptor nor a conventional nuclear factor (NF)-kappaB could be identified in the anthozoan Hydra. Moreover, the detection of complement C3 and several membrane attack complex/perforin domain (MAC/PF) proteins suggests that a prototypic complement effector pathway may exist in anthozoans, but not in hydrozoans. Together with data for several other gene families, this implies that Hydra may have undergone substantial secondary gene loss during evolution. Such losses are not confined to Hydra, however, and at least one MAC/PF gene appears to have been lost from Nematostella. Consideration of these patterns of gene distribution underscores the likely significance of gene loss during animal evolution whilst indicating ancient origins for many components of the vertebrate innate immune system.

TACI deficiency leads to alternatively activated macrophage phenotype and susceptibility to Leishmania infection

PubMed Central

Allman, Windy R.; Dey, Ranadhir; Liu, Lunhua; Siddiqui, Shafiuddin; Coleman, Adam S.; Bhattacharya, Parna; Yano, Masahide; Uslu, Kadriye; Takeda, Kazuyo; Nakhasi, Hira L.; Akkoyunlu, Mustafa

2015-01-01

The TNF family member, transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI), is a key molecule for plasma cell maintenance and is required in infections where protection depends on antibody response. Here, we report that compared with WT mouse, TACI KO Μϕs expressed lower levels of Toll-like receptors (TLRs), CD14, myeloid differentiation primary response protein 88, and adaptor protein Toll/IL-1 receptor domain-containing adapter-inducing IFN-β and responded poorly to TLR agonists. Analysis of Μϕ phenotype revealed that, in the absence of TACI, Μϕs adapt the alternatively activated (M2) phenotype. Steady-state expression levels for M2 markers IL-4Rα, CD206, CCL22, IL-10, Arg1, IL1RN, and FIZZ1 were significantly higher in TACI KO Μϕ than in WT cells. Confirming their M2 phenotype, TACI-KO Mϕs were unable to control Leishmania major infection in vitro, and intradermal inoculation of Leishmania resulted in a more severe manifestation of disease than in the resistant C57BL/6 strain. Transfer of WT Μϕs to TACI KO mice was sufficient to significantly reduce disease severity. TACI is likely to influence Mϕ phenotype by mediating B cell-activating factor belonging to the TNF family (BAFF) and a proliferation inducing ligand (APRIL) signals because both these ligands down-regulated M2 markers in WT but not in TACI-deficient Μϕs. Moreover, treatment of Μϕs with BAFF or APRIL enhanced the clearance of Leishmania from cells only when TACI is expressed. These findings may have implications for understanding the shortcomings of host response in newborns where TACI expression is reduced and in combined variable immunodeficiency patients where TACI signaling is ablated. PMID:26170307

Cow-to-cow variation in fibroblast response to a toll-like receptor 2/6 agonist and its relation to mastitis caused by intramammary challenge with Staphylococcus aureus.

PubMed

Benjamin, A L; Green, B B; Hayden, L R; Barlow, J W; Kerr, D E

2015-03-01

Staphylococcus aureus is a common cause of chronic mammary gland infections in dairy cattle. However, the inflammatory response and duration of infection following pathogen exposure is variable between individual animals. To investigate interanimal differences in immune response, dermal fibroblast cultures were established from skin biopsies collected from 50 early lactation Holstein cows. The fibroblasts ability to produce IL-8 in response to a 24-h treatment with a synthetic toll-like receptor 2/6 agonist (Pam2CSK4) was used to assign a response phenotype to the animals. Five high-responding and 5 low-responding animals were then selected for an intramammary challenge with S. aureus to evaluate differences in the inflammatory response, chronicity of infection, and development of antibodies to the pathogen. All animals exhibited clinical symptoms of mastitis at 24h postchallenge. Animals previously classified as high responders experienced a greater inflammatory response characterized by elevated levels of milk somatic cell count, IL-8, and BSA following the challenge compared with low responders. In addition, antibodies toward the challenge strain of S. aureus reached higher levels in whey from the challenged gland of high responders compared with low responders. Despite the antibody response, all 5 high responders were chronically infected for the 6-wk duration of the study, whereas 2 of the low responders cleared the infection, although 1 of these did become reinfected. The observed differences between animals classified as low and high responders based on their fibroblast responsiveness suggests that this cell type can be used to further examine the causes of interanimal variation in response to mammary infection. Copyright © 2015 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Genetic variations in toll-like receptor 4 in Mexican-Mestizo patients with intra-abdominal infection and/or pneumonia.

PubMed

Rodriguez-Osorio, Carlos A; Lima, Guadalupe; Herrera-Caceres, Jaime O; Villegas-Torres, Beatriz E; Zuñiga, Joaquin; Ponce-de-Leon, Sergio; Llorente, Luis; Sifuentes-Osornio, Jose

2013-06-01

Sepsis is a leading cause of death around the world, and 73-83% of all sepsis cases requiring attention in intensive care units are linked to intra-abdominal infection (IAI) or pneumonia. The activation of innate immunity is central to the manifestation of sepsis, and toll-like receptor (TLR) 4 plays an important role in this activation process. The 299G and 399I alleles of TLR4 have been linked with an increased risk of Gram-negative bacteria (GNB) infections and septic shock in some populations. This case-control study evaluated the prevalence of D299G/T399I polymorphisms in Mexican patients with IAI and/or pneumonia and in healthy controls. Genotyping revealed that 1 in 44 patients (2.3%; CI 95%: 0.05-12.0%) and 4 in 126 controls (3.2%; CI 95%: 0.9-7.9%) were heterozygous for both the D299G and T399l polymorphisms (OR: 0.71, CI 95%: 0.01-7.44, p = NS), confirming the co-segregation of these alleles in this population. Furthermore, the patients with a GNB infection and severe sepsis were not carriers of the risk alleles. In summary, this report shows that the frequency of the D299G and T399I polymorphisms in Mexican-Mestizos is lower than anticipated in comparison with other ethnic groups, emphasizing the variable distribution of TLR4 polymorphisms among different populations. Consequently, this study was not able to detect associations between TLR4 polymorphisms and sepsis in this population. Copyright © 2013 Elsevier B.V. All rights reserved.

Association of TLR2 S450S and ICAM1 K469E polymorphisms with polycystic ovary syndrome (PCOS) and obesity.

PubMed

Ojeda-Ojeda, Miriam; Martínez-García, M Ángeles; Alpañés, Macarena; Luque-Ramírez, Manuel; Escobar-Morreale, Héctor F

2016-02-01

Toll-like receptors (TLRs) are activated by inflammatory stimuli and influence endothelial functions, contributing to the pathogenesis of atherosclerosis. We investigate the influence of polymorphisms in the genes encoding toll-like receptor 2 (TLR2) and 4 (TLR4) and endothelial adhesion molecules on polycystic ovary syndrome (PCOS) and its interaction with obesity. Ten single nucleotide polymorphisms were genotyped in 305 women with PCOS and 166 non-hyperandrogenic control women. In obese women, TLR2 S450S and ICAM1 K469E polymorphisms differently influenced metabolic variables and PCOS, respectively. Irrespective of PCOS, variant alleles of TLR2 S450S increased triglycerides, fasting insulin levels, and insulin resistance in obese women. TLR2 S450S interacted with obesity and PCOS on androstenedione levels, mutant alleles were associated with increased androstenedione concentrations in all women, with the exception of obese patients with PCOS (P=0.034). Regarding ICAM1 K469E, homozygosis for K469 alleles was more frequent in PCOS, but only in obese women (P=0.014). K469 alleles were also related to increased body mass index (P=0.017) and diastolic blood pressure (P=0.034). Moreover, ICAM1 K469E interacted with obesity and PCOS on serum triglyceride levels (P=0.019) and with PCOS on serum sex hormone-binding globulin concentrations (P=0.006). In conclusion, TLR2 S450S and ICAM1 K469E polymorphisms may be associated with PCOS and metabolic comorbidities in obese women. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Sustained activation of toll-like receptor 9 induces an invasive phenotype in lung fibroblasts: possible implications in idiopathic pulmonary fibrosis.

PubMed

Kirillov, Varvara; Siler, Jonathan T; Ramadass, Mahalakshmi; Ge, Lingyin; Davis, James; Grant, Geraldine; Nathan, Steven D; Jarai, Gabor; Trujillo, Glenda

2015-04-01

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive scarring of the lung parenchyma, resulting in a steady decline of lung function and ultimately respiratory failure. The disease course of IPF is extremely variable, with some patients exhibiting stability of symptoms for prolonged periods of time, whereas others exhibit rapid progression and loss of lung function. Viral infections have been implicated in IPF and linked to disease severity; however, whether they directly contribute to progression is unclear. We previously classified patients as rapid and slow progressors on the basis of clinical features and expression of the pathogen recognition receptor, Toll-like receptor 9 (TLR9). Activation of TLR9 in vivo exacerbated IPF in mice and induced differentiation of myofibroblasts in vitro, but the mechanism of TLR9 up-regulation and progression of fibrosis are unknown. Herein, we investigate whether transforming growth factor (TGF)-β, a pleiotropic cytokine central to IPF pathogenesis, regulates TLR9 in lung myofibroblasts. Results showed induction of TLR9 expression by TGF-β in lung myofibroblasts and a distinct profibrotic myofibroblast phenotype driven by stimulation with the TLR9 agonist, CpG-DNA. Chronic TLR9 stimulation resulted in stably differentiated α-smooth muscle actin(+)/platelet-derived growth factor receptor α(+)/CD44(+)/matrix metalloproteinase-14(+)/matrix metalloproteinase-2(+) myofibroblasts, which secrete inflammatory cytokines, invade Matrigel toward platelet-derived growth factor, and resist hypoxia-induced apoptosis. These results suggest a mechanism by which TGF-β and TLR9 responses in myofibroblasts collaborate to drive rapid progression of IPF. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

Toll-like receptor 4 gene polymorphism modulates phenotypic expression in patients with hereditary hemochromatosis.

PubMed

Krayenbuehl, Pierre-Alexandre; Hersberger, Martin; Truninger, Kaspar; Müllhaupt, Beat; Maly, Friedrich E; Bargetzi, Mario; Schulthess, Georg

2010-07-01

Clinical penetrance of hereditary hemochromatosis is highly variable. We hypothesized that it might be modified by factors involved in the cellular immune response, such as toll-like receptors (TLRs) or nucleotide oligomerization domain proteins (NODs). Clinical expression of hemochromatosis was assessed as a function of TLR4, TLR9, and NOD2 polymorphisms in 99 homozygous carriers of the HFE C282Y mutation with mild-to-severe iron overload. Thirteen (13%) of the 99 hemochromatosis patients were heterozygous for a TLR4 Asp299Gly polymorphism and 86 (87%) were TLR4 wild-type-only carriers. Clinical expression of hemochromatosis was observed more frequently in carriers of the TLR4 polymorphism (100%) than in TLR4 wild-type carriers (56%, P = 0.002). This was based on higher prevalences of liver disease (92 vs. 45%, P = 0.002) and arthropathy of metacarpophalangeal joints (69 vs. 35%, P = 0.018) in TLR4 polymorphism carriers. The finding was strengthened by the strong association of TLR4 polymorphism with liver fibrosis in the subgroup of 52 patients who underwent a liver biopsy (P = 0.011). The TLR4 polymorphism did, however, not correlate with body iron overload. The study results remained significant in multiple regression analyses after excluding possible confounding effects, such as age, sex, alcohol, or meat intake, and in the subgroup of 84 patients presenting as the first members of their families. TLR4 Asp299Gly polymorphism modulates clinical expression in patients with hereditary hemochromatosis. The polymorphism does not correlate with iron overload suggesting that TLR4 plays a role in an inflammatory process arising from toxic effects of iron accumulation.

Comparison of gene expression of Toll-like receptors and cytokines between Piau and Commercial line (Landrace×Large White crossbred) pigs vaccinated against Pasteurella multocida type D.

PubMed

Sousa, Katiene Régia Silva; Ribeiro, André Mauric Frossard; Dantas, Waleska de Melo Ferreira; Oliveira, Leandro Licursi de; Gasparino, Eliane; Guimarães, Simone Eliza Facioni

2017-10-01

We aimed to compare Toll-like receptors (TLR) and cytokines expression in local Piau breed and a Commercial line (Landrace×Large White crossbred) pigs in response to vaccination against Pasteurella multocida type D. Seronegative gilts for Pasteurella multocida type D and Mycoplasma hyopneumoniae were used, from which peripheral blood mononuclear cells (PBMC) were collected in four time points (T0, T1, T2 and T3; before and after each vaccination dose). For bronchoalveolar lavage fluid cells (BALF), we set groups of vaccinated and unvaccinated animals for both genetic groups. Gene expression was evaluated on PBMC and BALF. In PBMC, when we analyzed time points within breeds, significant differences in expression for TLRs and cytokines, except TGFβ, were observed for Commercial animals. For the Piau pigs, only TGFβ showed differential expression. Comparing the expression among genetic groups, the Commercial pigs showed higher expression for TLRs after first vaccination dose, while for IL2, IL6, IL12 and IL13, higher expression was also observed in T3 and IL8 and IL10, in T1 and T3. Still comparing the breeds, the crossbred animals showed higher expression for TNFα in T1 and T2, while for TGFβ only in T2. For gene expression in BALF, vaccinated Commercial pigs showed higher expression of TLR6, TLR10, IL6, IL8, IL10, TNFα and TGFβ genes than vaccinated Piau pigs. The Commercial line pigs showed higher sensitivity to vaccination, while in local Piau breed lower responsiveness, which may partly explain genetic variability in immune response and will let us better understand the tolerance/susceptibility for pasteurellosis. Copyright © 2017 Elsevier Ltd. All rights reserved.

Single-cell systems level analysis of human Toll-Like-Receptor activation defines a chemokine signature in Systemic Lupus Erythematosus

PubMed Central

O'Gorman, William E.; Hsieh, Elena W.Y.; Savig, Erica S.; Gherardini, Pier Federico; Hernandez, Joseph D.; Hansmann, Leo; Balboni, Imelda M.; Utz, Paul J.; Bendall, Sean C.; Fantl, Wendy J.; Lewis, David B.; Nolan, Garry P.; Davis, Mark M.

2015-01-01

Background Activation of Toll-Like Receptors (TLRs) induces inflammatory responses involved in immunity to pathogens and autoimmune pathogenesis, such as in Systemic Lupus Erythematosus (SLE). Although TLRs are differentially expressed across the immune system, a comprehensive analysis of how multiple immune cell subsets respond in a system-wide manner has previously not been described. Objective To characterize TLR activation across multiple immune cell subsets and individuals, with the goal of establishing a reference framework against which to compare pathological processes. Methods Peripheral whole blood samples were stimulated with TLR ligands, and analyzed by mass cytometry simultaneously for surface marker expression, activation states of intracellular signaling proteins, and cytokine production. We developed a novel data visualization tool to provide an integrated view of TLR signaling networks with single-cell resolution. We studied seventeen healthy volunteer donors and eight newly diagnosed untreated SLE patients. Results Our data revealed the diversity of TLR-induced responses within cell types, with TLR ligand specificity. Subsets of NK and T cells selectively induced NF-κB in response to TLR2 ligands. CD14hi monocytes exhibited the most polyfunctional cytokine expression patterns, with over 80 distinct cytokine combinations. Monocytic TLR-induced cytokine patterns were shared amongst a group of healthy donors, with minimal intra- and inter- individual variability. Furthermore, autoimmune disease altered baseline cytokine production, as newly diagnosed untreated SLE patients shared a distinct monocytic chemokine signature, despite clinical heterogeneity. Conclusion Mass cytometry analysis defined a systems-level reference framework for human TLR activation, which can be applied to study perturbations in inflammatory disease, such as SLE. PMID:26037552

Toll-like Receptor 4 and Comorbid Pain in Interstitial Cystitis/Bladder Pain Syndrome: A Multidisciplinary Approach to the Study of Chronic Pelvic Pain Research Network Study

PubMed Central

Schrepf, Andrew; Bradley, Catherine S.; O'Donnell, Michael; Luo, Yi; Harte, Steven E.; Kreder, Karl; Lutgendorf, Susan

2015-01-01

Background Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS) is a condition characterized by pelvic pain and urinary symptoms. Some IC/BPS patients have pain confined to the pelvic region, while others suffer widespread pain. Inflammatory processes have previously been linked to pelvic pain in IC/BPS, but their association with widespread pain in IC/BPS has not been characterized. Methods Sixty-six women meeting criteria for IC/BPS completed self-report measures of pain as part of the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP), collected 3 days of saliva for cortisol assays, and provided blood samples. Peripheral blood mononuclear cells (PBMCs) were stimulated with Toll-Like Receptor (TLR) 2 and 4 agonists and cytokines were measured in supernatant; IL-6 was also measured in plasma. Associations between inflammatory variables and the likelihood of endorsing extra-pelvic pain, or the presence of a comorbid syndrome, were tested by logistic regression and General Linear Models, respectively. A subset of patients (n=32) completed Quantitative Sensory Testing. Results A one standard deviation increase in TLR-4 inflammatory response was associated with a 1.59 greater likelihood of endorsing extra-pelvic pain (p = .019). Participants with comorbid syndromes also had higher inflammatory responses to TLR-4 stimulation in PBMCs (p = .016). Lower pressure pain thresholds were marginally associated with higher TLR-4 inflammatory responses (p = .062), and significantly associated with higher IL-6 in plasma (p = .031). Conclusions TLR-4 inflammatory responses in PBMCs are a marker of widespread pain in IC/BPS, and should be explored in other conditions characterized by medically unexplained pain. PMID:25771510

Typhoid fever as cellular microbiological model.

PubMed

de Andrade, Dahir Ramos; de Andrade Júnior, Dahir Ramos

2003-01-01

The knowledge about typhoid fever pathogenesis is growing in the last years, mainly about the cellular and molecular phenomena that are responsible by clinical manifestations of this disease. In this article are discussed several recent discoveries, as follows: a) Bacterial type III protein secretion system; b) The five virulence genes of Salmonella spp. that encoding Sips (Salmonella invasion protein) A, B, C, D and E, which are capable of induce apoptosis in macrophages; c) The function of Toll R2 and Toll R4 receptors present in the macrophage surface (discovered in the Drosophila). The Toll family receptors are critical in the signalizing mediated by LPS in macrophages in association with LBP and CD14; d) The lines of immune defense between intestinal lumen and internal organs; e) The fundamental role of the endothelial cells in the inflammatory deviation from bloodstream into infected tissues by bacteria. In addition to above subjects, the authors comment the correlation between the clinical features of typhoid fever and the cellular and molecular phenomena of this disease, as well as the therapeutic consequences of this knowledge.

Toll-like receptor 4 stimulation with the detoxified ligand monophosphoryl lipid A improves Alzheimer’s disease-related pathology

PubMed Central

Michaud, Jean-Philippe; Hallé, Maxime; Lampron, Antoine; Thériault, Peter; Préfontaine, Paul; Filali, Mohammed; Tribout-Jover, Pascale; Lanteigne, Anne-Marie; Jodoin, Rachel; Cluff, Christopher; Brichard, Vincent; Palmantier, Rémi; Pilorget, Anthony; Larocque, Daniel; Rivest, Serge

2013-01-01

Alzheimer’s disease (AD) is the most common cause of dementia worldwide. The pathogenesis of this neurodegenerative disease, currently without curative treatment, is associated with the accumulation of amyloid β (Aβ) in brain parenchyma and cerebral vasculature. AD patients are unable to clear this toxic peptide, leading to Aβ accumulation in their brains and, presumably, the pathology associated with this devastating disease. Compounds that stimulate the immune system to clear Aβ may therefore have great therapeutic potential in AD patients. Monophosphoryl lipid A (MPL) is an LPS-derived Toll-like receptor 4 agonist that exhibits unique immunomodulatory properties at doses that are nonpyrogenic. We show here that repeated systemic injections of MPL, but not LPS, significantly improved AD-related pathology in APPswe/PS1 mice. MPL treatment led to a significant reduction in Aβ load in the brain of these mice, as well as enhanced cognitive function. MPL induced a potent phagocytic response by microglia while triggering a moderate inflammatory reaction. Our data suggest that the Toll-like receptor 4 agonist MPL may be a treatment for AD. PMID:23322736

[Association of polymorphisms in toll-like receptor genes with atopic dermatitis in the Republic of Bashkortostan].

PubMed

Gimalova, G F; Karunas, A S; Fedorova, Iu Iu; Gumennaia, É R; Levasheva, S V; Khismatullina, Z R; Prans, E; Koks, S; Étkina, É I; Khusnutdinova, É K

2014-01-01

Atopic dermatitis (AD) is a prevalent chronic inflammatory skin disease developing as a result of the interaction between genetic predisposition and environmental factors. Considerable role in allergic diseases development is played by polymorphisms of genes of pattern-recognition receptors (PRR) which are capable of recognizing conservative standard molecular structures (patterns) unique for large pathogen groups. In this study polymorphic variants of PRR genes--Toll-like receptors (TLR1, TLR2, TLR4, TLR5, TLR6, TLR9, TLR10), NOD-like receptors (NOD1, NOD2), lipopolysaccharide receptor CD14 gene, and C11orf30 and LRRC32 genes, located in 11q13.5 region, have been investigated in AD patients and control subjects from the Republic of Bashkortostan. An association of TLR1 (rs5743571 and rs5743604), TLR6 (rs5743794) and TLR10 (rs11466617) with AD was found. Our results confirm an important role of the innate immune system in the pathogenesis of AD and the significance of polymorphisms within the Toll-like receptor 2 subfamily genes in AD development.

Physical and functional interactions between Drosophila TRAF2 and Pelle kinase contribute to Dorsal activation.

PubMed

Shen, B; Liu, H; Skolnik, E Y; Manley, J L

2001-07-17

Signaling through the Toll receptor is required for dorsal/ventral polarity in Drosophila embryos, and also plays an evolutionarily conserved role in the immune response. Upon ligand binding, Toll appears to multimerize and activate the associated kinase, Pelle. However, the immediate downstream targets of Pelle have not been identified. Here we show that Drosophila tumor necrosis factor receptor-associated factor 2 (dTRAF2), a homologue of human TRAF6, physically and functionally interacts with Pelle, and is phosphorylated by Pelle in vitro. Importantly, dTRAF2 and Pelle cooperate to activate Dorsal synergistically in cotransfected Schneider cells. Deletion of the C-terminal TRAF domain of dTRAF2 enhances Dorsal activation, perhaps reflecting the much stronger interaction of the mutant protein with phosphorylated, active Pelle. Taken together, our results indicate that Pelle and dTRAF2 physically and functionally interact, and that the TRAF domain acts as a regulator of this interaction. dTRAF2 thus appears to be a downstream target of Pelle. We discuss these results in the context of Toll signaling in flies and mammals.

Mesenchymal stem cells cannot affect mRNA expression of toll-like receptors in different tissues during sepsis.

PubMed

Pedrazza, Leonardo; Pereira, Talita Carneiro Brandão; Abujamra, Ana Lucia; Nunes, Fernanda Bordignon; Bogo, Maurício Reis; de Oliveira, Jarbas Rodrigues

2017-07-01

Experimental animal models and human clinical studies support a crucial role for TLRs in infectious diseases. The aim of this study was to test the ability of MSCs, which have immunomodulatory effects, of altering the mRNA expression of toll-like receptors during a experimental model of sepsis in different tissues. Three experimental groups (male C57BL/6 mice) were formed for the test: control group, untreated septic group and septic group treated with MSCs (1 × 10 6 cells/animal). Lungs, cortex, kidney, liver and colon tissue were dissected after 12 h of sepsis induction and TLR2/3/4/9 mRNA were evaluated by RT-qPCR. We observed a decrease of TLR2 and 9 mRNA expression in the liver of the sepsis group, while TLR3 was decreased in the lung and liver. No change was found between the sepsis group and the sepsis + MSC group. In this model of experimental sepsis the MSCs were unable to modify the mRNA expression of the different toll-like receptors evaluated.

Human Milk Components Modulate Toll-Like Receptor-Mediated Inflammation.

PubMed

He, YingYing; Lawlor, Nathan T; Newburg, David S

2016-01-01

Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2'-fucosyllactose attenuate TLR4 signaling; 3'-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling. © 2016 American Society for Nutrition.

Mannose-Binding Lectin and Toll-Like Receptor Polymorphisms and Chagas Disease in Chile

PubMed Central

Zulantay, Inés; Danquah, Ina; Hamann, Lutz; Schumann, Ralf R.; Apt, Werner; Mockenhaupt, Frank P.

2012-01-01

Mannose-binding lectin (MBL) and Toll-like receptor (TLR) polymorphisms may influence susceptibility and manifestation of Trypanosoma cruzi infection. In northern Chile, we examined 61 asymptomatic patients with chronic Chagas disease (CD), 64 patients with chronic Chagas cardiomyopathy (CCC), and 45 healthy individuals. Low-producer MBL2*B genotypes were more common in CD patients (48%) than healthy individuals (31%; adjusted odds ratio = 2.3, 95% confidence interval = 1.01–5.4, P = 0.047) but did not differ with manifestation. In contrast, the heterozygous Toll-like receptor 4 (TLR4)-deficiency genotype D299G/T399I occurred more frequently in asymptomatic (14.8%) than CCC patients (3.1%; P = 0.02). TLR1-I602S, TLR2-R753Q, TLR6-S249P, and MAL/TIRAP-S180L did not associate with CD or CCC. These findings support the complement system to be involved in defense against Trypanosoma cruzi infection and indicate that curbed TLR4 activation might be beneficial in preventing CCC. PMID:22302853

Human Milk Components Modulate Toll-Like Receptor–Mediated Inflammation12

PubMed Central

He, YingYing; Lawlor, Nathan T

2016-01-01

Toll-like receptor (TLR) signaling is central to innate immunity. Aberrant expression of TLRs is found in neonatal inflammatory diseases. Several bioactive components of human milk modulate TLR expression and signaling pathways, including soluble toll-like receptors (sTLRs), soluble cluster of differentiation (sCD) 14, glycoproteins, small peptides, and oligosaccharides. Some milk components, such as sialyl (α2,3) lactose and lacto-N-fucopentaose III, are reported to increase TLR signaling; under some circumstances this might contribute toward immunologic balance. Human milk on the whole is strongly anti-inflammatory, and contains abundant components that depress TLR signaling pathways: sTLR2 and sCD14 inhibit TLR2 signaling; sCD14, lactadherin, lactoferrin, and 2′-fucosyllactose attenuate TLR4 signaling; 3′-galactosyllactose inhibits TLR3 signaling, and β-defensin 2 inhibits TLR7 signaling. Feeding human milk to neonates decreases their risk of sepsis and necrotizing enterocolitis. Thus, the TLR regulatory components found in human milk hold promise as benign oral prophylactic and therapeutic treatments for the many gastrointestinal inflammatory disorders mediated by abnormal TLR signaling. PMID:26773018

Burma’s 2010 Elections: Implications of the New Constitution and Election Laws

DTIC Science & Technology

2010-04-29

10,000,’” BBC, May 5, 2008; “Burma’s Cyclone Death Toll Soars,” BBC, May 6, 2008, and Aung Hla Tun , “Myanmar Cyclone Toll Climbs to Nearly 22,500...Aftermath,” December 20, 2007, by Michael F. Martin. 22 Aung Hla Tun , “Suu Kyi’s Party Says Won’t Stand in Myanmar Polls,” Reuters, March 30, 2010. Burma’s...part of her name. 27 U.S. Department of State, “Daily Press Briefing,” press release, March 10, 2010. 28 Ibid. 29 Aung Zaw , “Hipocrisy Replaces

Virtual Screening Approaches towards the Discovery of Toll-Like Receptor Modulators

PubMed Central

Pérez-Regidor, Lucía; Zarioh, Malik; Ortega, Laura; Martín-Santamaría, Sonsoles

2016-01-01

This review aims to summarize the latest efforts performed in the search for novel chemical entities such as Toll-like receptor (TLR) modulators by means of virtual screening techniques. This is an emergent research field with only very recent (and successful) contributions. Identification of drug-like molecules with potential therapeutic applications for the treatment of a variety of TLR-regulated diseases has attracted considerable interest due to the clinical potential. Additionally, the virtual screening databases and computational tools employed have been overviewed in a descriptive way, widening the scope for researchers interested in the field. PMID:27618029

Carbon Management In the Post-Cap-and-Trade Carbon Economy: An Economic Model for Limiting Climate Change by Managing Anthropogenic Carbon Flux

NASA Astrophysics Data System (ADS)

DeGroff, F. A.

2013-05-01

In this paper, we discuss an economic model for comprehensive carbon management that focuses on changes in carbon flux in the biosphere due to anthropogenic activity. The two unique features of the model include: 1. A shift in emphasis from primarily carbon emissions, toward changes in carbon flux, mainly carbon extraction, and 2. A carbon price vector (CPV) to express the value of changes in carbon flux, measured in changes in carbon sequestration, or carbon residence time. The key focus with the economic model is the degree to which carbon flux changes due to anthropogenic activity. The economic model has three steps: 1. The CPV metric is used to value all forms of carbon associated with any anthropogenic activity. In this paper, the CPV used is a logarithmic chronological scale to gauge expected carbon residence (or sequestration) time. In future economic models, the CPV may be expanded to include other factors to value carbon. 2. Whenever carbon changes form (and CPV) due to anthropogenic activity, a carbon toll is assessed as determined by the change in the CPV. The standard monetary unit for carbon tolls are carbon toll units, or CTUs. The CTUs multiplied by the quantity of carbon converted (QCC) provides the total carbon toll, or CT. For example, CT = (CTU /mole carbon) x (QCC moles carbon). 3. Whenever embodied carbon (EC) attributable to a good or service moves via trade to a jurisdiction with a different CPV metric, a carbon toll (CT) is assessed representing the CPV difference between the two jurisdictions. This economic model has three clear advantages. First, the carbon pricing and cost scheme use existing and generally accepted accounting methodologies to ensure the veracity and verifiability of carbon management efforts with minimal effort and expense using standard, existing auditing protocols. Implementing this economic model will not require any new, special, unique, or additional training, tools, or systems for any entity to achieve their minimum carbon target goals within their jurisdictional framework. Second, given the wide spectrum of carbon affinities across jurisdictions worldwide, the economic model recognizes and provides for flexible carbon pricing regimes, but does not undermine or penalize domestic carbon-consuming producers subject to imports from exporters in lower carbon pricing jurisdictions. Thus, the economic model avoids a key shortcoming of cap-and-trade carbon pricing, and eliminates any incentive to shift carbon consumption to jurisdictions with lower carbon tolls. Third, the economic model is a comprehensive, efficient, and effective strategy that allows for the implementation of a carbon pricing structure without the complete, explicit agreement of carbon consumers worldwide.

The association between trauma and chronic medical conditions in individuals with severe mental illness.

PubMed

Raab, Phillip Andrew; Claypoole, Keith Harvey; Hayashi, Kentaro; Baker, Charlene

2012-10-01

Based on the concept of allostatic load, this study proposed and evaluated a model for the relationship between childhood trauma, chronic medical conditions, and intervening variables affecting this relationship in individuals with severe mental illness. Childhood trauma, adult trauma, major depressive disorder symptoms, posttraumatic stress disorder symptoms, health risk factors, and chronic medical conditions were retrospectively assessed using a cross-sectional survey design in a sample of 117 individuals with severe mental illness receiving public mental health services. Path analyses produced a good-fitting model, with significant pathways from childhood to adult trauma and from adult trauma to chronic medical conditions. Multisample path analyses revealed the equivalence of the model across sex. The results support a model for the relationship between childhood and adult trauma and chronic medical conditions, which highlights the pathophysiological toll of cumulative trauma experienced across the life span and the pressing need to prevent retraumatization in this population.

Childhood Adversity and Mental Health Correlates of Obesity in a Population at Risk.

PubMed

Brewer-Smyth, Kathleen; Cornelius, Monica; Pohlig, Ryan T

2016-10-01

The staggering prevalence of obesity and obesity-related health conditions takes exorbitant tolls on health care resources. This cross-sectional study with private evaluations of 636 adult inmates in a southern state prison was conducted with regressions comparing obese (body mass index [BMI] ≥ 30) to nonobese individuals to define obesity risk factors. Obese individuals more likely were female, were victims of childhood sexual abuse, suffered greater severity of childhood sexual abuse, attempted suicide, reported drug dependency, were non-Caucasian, and were older than nonobese. Psychopathy predicted lower BMI. Though obesity might be expected in victims of childhood physical abuse, traumatic brain injury, or other mental health conditions due to mobility or decision-making deficits, neither were significant. Adjusting for related variables, childhood sexual abuse remained significant. Females attempted suicide more frequently and suffered greater childhood sexual abuse. © The Author(s) 2016.

Childhood Adversity and Mental Health Correlates of Obesity in a Population at Risk

PubMed Central

Brewer-Smyth, Kathleen; Cornelius, Monica; Pohlig, Ryan T.

2017-01-01

The staggering prevalence of obesity and obesity-related health conditions takes exorbitant tolls on health care resources. This cross-sectional study with private evaluations of 636 adult inmates in a southern state prison was conducted with regressions comparing obese (body mass index [BMI] ≥ 30) to nonobese individuals to define obesity risk factors. Obese individuals more likely were female, were victims of childhood sexual abuse, suffered greater severity of childhood sexual abuse, attempted suicide, reported drug dependency, were non-Caucasian, and were older than non-obese. Psychopathy predicted lower BMI. Though obesity might be expected in victims of childhood physical abuse, traumatic brain injury, or other mental health conditions due to mobility or decision-making deficits, neither were significant. Adjusting for related variables, childhood sexual abuse remained significant. Females attempted suicide more frequently and suffered greater childhood sexual abuse. PMID:27742859

A narrow repertoire of transcriptional modules responsive to pyogenic bacteria is impaired in patients carrying loss-of-function mutations in MYD88 or IRAK4

PubMed Central

Alsina, L; Israelsson, E; Altman, MC; Dang, KK; Ghandil, P; Israel, L; von Bernuth, H; Baldwin, N; Qin, H; Jin, Z; Banchereau, R; Anguiano, E; Ionan, A; Abel, L; Puel, A; Picard, C; Pascual, V; Casanova, JL; Chaussabel, D

2014-01-01

Loss of function in the kinase IRAK-4 or the adapter MyD88 in humans interrupts a pathway critical for pathogen sensing and ignition of inflammation. Yet patients with loss of function mutations are surprisingly only susceptible to a limited range of pathogens. We employed a systems approach to investigate transcriptome responses following in vitro exposure of patients’ blood to Toll-like receptor and interleukin-1 receptor agonists, and whole pathogens. Responses to purified agonists were globally abolished but variable residual responses were present following exposure to whole pathogens. Further dissection of the latter responses identified a narrow repertoire of immune transcriptional programs affected by loss of MyD88 or IRAK-4 function. This work introduces the use of a systems approach for the global assessment of innate immune responses, and the characterization of human primary immunodeficiencies. PMID:25344726

Mangroves protected villages and reduced death toll during Indian super cyclone

PubMed Central

Das, Saudamini; Vincent, Jeffrey R.

2009-01-01

Protection against coastal disasters has been identified as an important service of mangrove ecosystems. Empirical studies on this service have been criticized, however, for using small samples and inadequately controlling for confounding factors. We used data on several hundred villages to test the impact of mangroves on human deaths during a 1999 super cyclone that struck Orissa, India. We found that villages with wider mangroves between them and the coast experienced significantly fewer deaths than ones with narrower or no mangroves. This finding was robust to the inclusion of a wide range of other variables to our statistical model, including controls for the historical extent of mangroves. Although mangroves evidently saved fewer lives than an early warning issued by the government, the retention of remaining mangroves in Orissa is economically justified even without considering the many benefits they provide to human society besides storm-protection services. PMID:19380735

Occupational exposure assessment of highway toll station workers to vehicle engine exhaust.

PubMed

Belloc-Santaliestra, Miriam; van der Haar, Rudolf; Molinero-Ruiz, Emilia

2015-01-01

Toll station workers are occupationally exposed to vehicle engine exhaust, a complex mixture of different chemical substances, including carcinogenic compounds. Therefore, a study was carried out on attendants of two highway toll stations to describe their occupational exposure to vehicle engine exhaust, based on a worst-case scenario approach. Personal sampling was conducted during the day shift for all attendants, testing for three groups of chemical substances: polycyclic aromatic hydrocarbons (PAHs), volatile organic compounds (VOCs) and aldehydes (formaldehyde and acrolein). Concentrations of total PAH, BTEX (benzene, toluene, ethylbenzene, and xylenes) and formaldehyde content varied between 97.60-336.08 ng/m3, 5.01-40.52 μg/m3, and 0.06-19.13 μg/m3, respectively. No clear relationships could be established between exposure levels and the number of vehicles. Furthermore, no differences were found between truck versus car lanes, or inside versus outside the tollbooth. Not all the detected VOCs were related to vehicle exhaust; some were consistent with the use of cleaning products. The measured concentrations were far below the established occupational exposure limits, but tended to be higher than values reported for outdoor urban environments. There are very few international studies assessing occupational exposures among toll station workers, and this is the first such study to be conducted in Spain. The results suggest that further, more detailed studies are necessary to characterize exposure properly, and ones which include other airborne pollutants, such as ultrafine particles. The comparison of the results to other similar studies was difficult, since no data related to some important exposure determinants have been provided. Therefore, it is recommended that these determinants be considered in future studies.

The innate immune repertoire in Cnidaria - ancestral complexity and stochastic gene loss

PubMed Central

Miller, David J; Hemmrich, Georg; Ball, Eldon E; Hayward, David C; Khalturin, Konstantin; Funayama, Noriko; Agata, Kiyokazu; Bosch, Thomas CG

2007-01-01

Background Characterization of the innate immune repertoire of extant cnidarians is of both fundamental and applied interest - it not only provides insights into the basic immunological 'tool kit' of the common ancestor of all animals, but is also likely to be important in understanding the global decline of coral reefs that is presently occurring. Recently, whole genome sequences became available for two cnidarians, Hydra magnipapillata and Nematostella vectensis, and large expressed sequence tag (EST) datasets are available for these and for the coral Acropora millepora. Results To better understand the basis of innate immunity in cnidarians, we scanned the available EST and genomic resources for some of the key components of the vertebrate innate immune repertoire, focusing on the Toll/Toll-like receptor (TLR) and complement pathways. A canonical Toll/TLR pathway is present in representatives of the basal cnidarian class Anthozoa, but neither a classic Toll/TLR receptor nor a conventional nuclear factor (NF)-κB could be identified in the anthozoan Hydra. Moreover, the detection of complement C3 and several membrane attack complex/perforin domain (MAC/PF) proteins suggests that a prototypic complement effector pathway may exist in anthozoans, but not in hydrozoans. Together with data for several other gene families, this implies that Hydra may have undergone substantial secondary gene loss during evolution. Such losses are not confined to Hydra, however, and at least one MAC/PF gene appears to have been lost from Nematostella. Conclusion Consideration of these patterns of gene distribution underscores the likely significance of gene loss during animal evolution whilst indicating ancient origins for many components of the vertebrate innate immune system. PMID:17437634

Three Pairs of Protease-Serpin Complexes Cooperatively Regulate the Insect Innate Immune Responses*

PubMed Central

Jiang, Rui; Kim, Eun-Hye; Gong, Ji-Hee; Kwon, Hyun-Mi; Kim, Chan-Hee; Ryu, Kyoung-Hwa; Park, Ji-Won; Kurokawa, Kenji; Zhang, Jinghai; Gubb, David; Lee, Bok-Luel

2009-01-01

Serpins are known to be necessary for the regulation of several serine protease cascades. However, the mechanisms of how serpins regulate the innate immune responses of invertebrates are not well understood due to the uncertainty of the identity of the serine proteases targeted by the serpins. We recently reported the molecular activation mechanisms of three serine protease-mediated Toll and melanin synthesis cascades in a large beetle, Tenebrio molitor. Here, we purified three novel serpins (SPN40, SPN55, and SPN48) from the hemolymph of T. molitor. These serpins made specific serpin-serine protease pairs with three Toll cascade-activating serine proteases, such as modular serine protease, Spätzle-processing enzyme-activating enzyme, and Spätzle-processing enzyme and cooperatively blocked the Toll signaling cascade and β-1,3-glucan-mediated melanin biosynthesis. Also, the levels of SPN40 and SPN55 were dramatically increased in vivo by the injection of a Toll ligand, processed Spätzle, into Tenebrio larvae. This increase in SPN40 and SPN55 levels indicates that these serpins function as inducible negative feedback inhibitors. Unexpectedly, SPN55 and SPN48 were cleaved at Tyr and Glu residues in reactive center loops, respectively, despite being targeted by trypsin-like Spätzle-processing enzyme-activating enzyme and Spätzle-processing enzyme. These cleavage patterns are also highly similar to those of unusual mammalian serpins involved in blood coagulation and blood pressure regulation, and they may contribute to highly specific and timely inactivation of detrimental serine proteases during innate immune responses. Taken together, these results demonstrate the specific regulatory evidences of innate immune responses by three novel serpins. PMID:19858208

Diversity of Innate Immune Recognition Mechanism for Bacterial Polymeric meso-Diaminopimelic Acid-type Peptidoglycan in Insects

PubMed Central

Yu, Yang; Park, Ji-Won; Kwon, Hyun-Mi; Hwang, Hyun-Ok; Jang, In-Hwan; Masuda, Akiko; Kurokawa, Kenji; Nakayama, Hiroshi; Lee, Won-Jae; Dohmae, Naoshi; Zhang, Jinghai; Lee, Bok Luel

2010-01-01

In Drosophila, the synthesis of antimicrobial peptides in response to microbial infections is under the control of the Toll and immune deficiency (Imd) signaling pathway. The Toll signaling pathway responds mainly to the lysine-type peptidoglycan of Gram-positive bacteria and fungal β-1,3-glucan, whereas the Imd pathway responds to the meso-diaminopimelic acid (DAP)-type peptidoglycan of Gram-negative bacteria and certain Gram-positive bacilli. Recently we determined the activation mechanism of a Toll signaling pathway biochemically using a large beetle, Tenebrio molitor. However, DAP-type peptidoglycan recognition mechanism and its signaling pathway are still unclear in the fly and beetle. Here, we show that polymeric DAP-type peptidoglycan, but not its monomeric form, formed a complex with Tenebrio peptidoglycan recognition protein-SA, and this complex activated the three-step proteolytic cascade to produce processed Spätzle, a Toll receptor ligand, and induced Drosophila defensin-like antimicrobial peptide in Tenebrio larvae similarly to polymeric lysine-type peptidoglycan. Monomeric DAP-type peptidoglycan induced Drosophila diptericin-like antimicrobial peptide in Tenebrio hemocytes. In addition, both polymeric and monomeric DAP-type peptidoglycans induced expression of Tenebrio peptidoglycan recognition protein-SC2, which is DAP-type peptidoglycan-selective N-acetylmuramyl-l-alanine amidase that functions as a DAP-type peptidoglycan scavenger, appearing to function as a negative regulator of the DAP-type peptidoglycan signaling by cleaving DAP-type peptidoglycan in Tenebrio larvae. Taken together, these results demonstrate that molecular recognition mechanism for polymeric DAP-type peptidoglycan is different between Tenebrio larvae and Drosophila adults, providing biochemical evidences of biological diversity of innate immune responses in insects. PMID:20702416

Toll-like receptor-associated keratitis and strategies for its management.

PubMed

Kaur, Amandeep; Kumar, Vijay; Singh, Simranjeet; Singh, Joginder; Upadhyay, Niraj; Datta, Shivika; Singla, Sourav; Kumar, Virender

2015-10-01

Keratitis is an inflammatory condition, characterized by involvement of corneal tissues. Most recurrent challenge of keratitis is infection. Bacteria, virus, fungus and parasitic organism have potential to cause infection. TLR are an important class of protein which has a major role in innate immune response to combat with pathogens. In last past years, extensive research efforts have provided considerable abundance information regarding the role of TLR in various types of keratitis. This paper focuses to review the recent literature illustrating amoebic, bacterial, fungal and viral keratitis associated with Toll-like receptor molecules and summarize existing thoughts on pathogenesis and treatment besides future probabilities for prevention against TLR-associated keratitis.

Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2.

PubMed

Cario, E

2005-08-01

Toll-like receptors (TLR) and NOD2 are emerging as key mediators of innate host defence in the intestinal mucosa, crucially involved in maintaining mucosal as well as commensal homeostasis. Recent observations suggest new (patho-) physiological mechanisms of how functional versus dysfunctional TLRx/NOD2 pathways may oppose or favour inflammatory bowel disease (IBD). In health, TLRx signalling protects the intestinal epithelial barrier and confers commensal tolerance whereas NOD2 signalling exerts antimicrobial activity and prevents pathogenic invasion. In disease, aberrant TLRx and/or NOD2 signalling may stimulate diverse inflammatory responses leading to acute and chronic intestinal inflammation with many different clinical phenotypes.

Discovery and Structure-Activity Relationships of the Neoseptins: A New Class of Toll-like Receptor-4 (TLR4) Agonists.

PubMed

Morin, Matthew D; Wang, Ying; Jones, Brian T; Su, Lijing; Surakattula, Murali M R P; Berger, Michael; Huang, Hua; Beutler, Elliot K; Zhang, Hong; Beutler, Bruce; Boger, Dale L

2016-05-26

Herein, we report studies leading to the discovery of the neoseptins and a comprehensive examination of the structure-activity relationships (SARs) of this new class of small-molecule mouse Toll-like receptor 4 (mTLR4) agonists. The compounds in this class, which emerged from screening an α-helix mimetic library, stimulate the immune response, act by a well-defined mechanism (mouse TLR4 agonist), are easy to produce and structurally manipulate, exhibit exquisite SARs, are nontoxic, and elicit improved and qualitatively different responses compared to lipopolysaccharide, even though they share the same receptor.

In silico analysis of Schmidtea mediterranea TIR domain-containing proteins.

PubMed

Tsoumtsa, Landry Laure; Sougoufora, Seynabou; Torre, Cedric; Lemichez, Emmanuel; Pontarotti, Pierre; Ghigo, Eric

2018-09-01

While genetic evidence points towards an absence of Toll-Like Receptors (TLRs) in Platyhelminthes, the Toll/IL-1 Receptor (TIR)-domains that drive the assembly of signalling complexes downstream TLR are present in these organisms. Here, we undertook the characterisation of the repertoire of TIR-domain containing proteins in Schmidtea mediterranea in order to gain valuable information on TLR evolution in metazoan. We report the presence of twenty proteins containing between one and two TIR domains. In addition, our phylogenetic-based reconstruction approach identified Smed-SARM and Smed-MyD88 as conserved TLR adaptors. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Toll-like receptor in lung response to pathogens].

PubMed

Rivas-Santiago, Bruno; Juárez, Esmeralda

2007-01-01

Innate immunity plays a central role in antimicrobial defense. Advances in the understanding of pathogen recognition systems of innate cells have yielded the identification of Toll like receptors (TLR) as key elements of the lung defense mechanisms which is heavily exposed to a variety of stimuli. TLR recognition of several microbial compounds induces proinflammatory cytokines production whose contribution to the host may be either protective or detrimental. Human immune response diversity may explain the differences observed between patients facing bacterial, viral and fungal lung infections. New strategies designs that modify innate immune response may be useful to limit detrimental consequences of inflammatory processes in the lung.

Regulation of dendritic cell function through toll-like receptors.

PubMed

Kaisho, Tsuneyasu; Akira, Shizuo

2003-12-01

Higher animals establish host defense by orchestrating innate and adaptive immunity. This is mediated by professional antigen presenting cells, i.e. dendritic cells (DCs). DCs can incorporate pathogens, produce a variety of cytokines, maturate, and present pathogen-derived peptides to T cells, thereby inducing T cell activation and differentiation. These responses are triggered by microbial recognition through type I transmembrane proteins, Toll-like receptors (TLRs) on DCs. TLRs consist of ten members and each TLR is involved in recognizing a variety of microorganism-derived molecular structures. TLR ligands include cell wall components, proteins, nucleic acids, and synthetic chemical compounds, all of which can activate DCs as immune adjuvants.

Changes in fatal and nonfatal crash rates on a toll highway.

PubMed

Doege, T C; Levy, P S

1976-02-01

Rates of crashes, crashes with injuries, and crashes with fatalities were lower during the 6 months of March 1-August 31, 1974, following a 5-15 mph (8-24 kph) decrease in speed limits on the Illinois Tollway, than the corresponding rates for any of the 6 preceding years, 1968-1973. During the same months of 1968-1974, rates of crashes and of crashes with injuries showed peaks without consistent trends, but rates and percentages of fatal crashes decreased. The data agree with the hypothesis that reducing speed limits on toll roads may lead to substantial reductions in rate of crashes and injuries.

Mucosal interplay among commensal and pathogenic bacteria: lessons from flagellin and Toll-like receptor 5.

PubMed

Rumbo, Martin; Nempont, Clément; Kraehenbuhl, Jean-Pierre; Sirard, Jean-Claude

2006-05-22

Toll-like receptors (TLR) detect pathogen-associated molecular patterns (PAMP) and play a crucial role in triggering immunity. Due to their large surfaces in direct contact with the environment, mucosal tissues are the major sites of PAMP-TLR signalling. How innate and adaptive immunity are triggered through flagellin-TLR5 interaction is the main focus of the review. In view of recent reports on genetic polymorphism, we will summarize the impact of TLR5 on the susceptibility to mucosal infections and on various immuno-pathologies. Finally, the contribution of TLRs in the induction and maintenance of mucosal homeostasis and commensal discrimination is discussed.

The fruit fly Drosophila melanogaster unfolds the secrets of innate immunity.

PubMed

Rämet, Mika

2012-09-01

In 2011, the Nobel Prize in Physiology and Medicine was rewarded, in part, for research on the Drosophila immune response. The research described the role of the Drosophila Toll receptor in antifungal resistance, and the subsequent characterization of Toll-like receptors in mammals reshaped our understanding of the immune system. This review summarizes the potential of the Drosophila model and describes the path that has lead Drosophila to become an important model to study immunity. Drosophila melanogaster has been one of the most fruitful models to study innate immunity. © 2012 The Author(s)/Acta Paediatrica © 2012 Foundation Acta Paediatrica.

Flow Perturbation Mediates Neutrophil Recruitment and Potentiates Endothelial Injury via TLR2 in Mice: Implications for Superficial Erosion.

PubMed

Franck, Grégory; Mawson, Thomas; Sausen, Grasiele; Salinas, Manuel; Masson, Gustavo Santos; Cole, Andrew; Beltrami-Moreira, Marina; Chatzizisis, Yiannis; Quillard, Thibault; Tesmenitsky, Yevgenia; Shvartz, Eugenia; Sukhova, Galina K; Swirski, Filip K; Nahrendorf, Matthias; Aikawa, Elena; Croce, Kevin J; Libby, Peter

2017-06-23

Superficial erosion currently causes up to a third of acute coronary syndromes; yet, we lack understanding of its mechanisms. Thrombi because of superficial intimal erosion characteristically complicate matrix-rich atheromata in regions of flow perturbation. This study tested in vivo the involvement of disturbed flow and of neutrophils, hyaluronan, and Toll-like receptor 2 ligation in superficial intimal injury, a process implicated in superficial erosion. In mouse carotid arteries with established intimal lesions tailored to resemble the substrate of human eroded plaques, acute flow perturbation promoted downstream endothelial cell activation, neutrophil accumulation, endothelial cell death and desquamation, and mural thrombosis. Neutrophil loss-of-function limited these findings. Toll-like receptor 2 agonism activated luminal endothelial cells, and deficiency of this innate immune receptor decreased intimal neutrophil adherence in regions of local flow disturbance, reducing endothelial cell injury and local thrombosis ( P <0.05). These results implicate flow disturbance, neutrophils, and Toll-like receptor 2 signaling as mechanisms that contribute to superficial erosion, a cause of acute coronary syndrome of likely growing importance in the statin era. © 2017 American Heart Association, Inc.

Differential immune responses of Monochamus alternatus against symbiotic and entomopathogenic fungi.

PubMed

Zhang, Wei; Meng, Jie; Ning, Jing; Qin, Peijun; Zhou, Jiao; Zou, Zhen; Wang, Yanhong; Jiang, Hong; Ahmad, Faheem; Zhao, Lilin; Sun, Jianghua

2017-08-01

Monochamus alternatus, the main vector beetles of invasive pinewood nematode, has established a symbiotic relationship with a native ectotrophic fungal symbiont, Sporothrix sp. 1, in China. The immune response of M. alternatus to S. sp. 1 in the coexistence of beetles and fungi is, however, unknown. Here, we report that immune responses of M. alternatus pupae to infection caused by ectotrophic symbiotic fungus S. sp. 1 and entomopathogenic fungus Beauveria bassiana differ significantly. The S. sp. 1 did not kill the beetles while B. bassiana killed all upon injection. The transcriptome results showed that the numbers of differentially expressed genes in M. alternatus infected with S. sp. 1 were 2-fold less than those infected with B. bassiana at 48 hours post infection. It was noticed that Toll and IMD pathways played a leading role in the beetle's immune system when infected by symbiotic fungus, but upon infection by entomopathogenic fungus, only the Toll pathway gets triggered actively. Furthermore, the beetles could tolerate the infection of symbiotic fungi by retracing their Toll and IMD pathways at 48 h. This study provided a comprehensive sequence resource of M. alternatus transcriptome for further study of the immune interactions between host and associated fungi.

Anti-viral role of toll like receptor 4 in hepatitis B virus infection: An in vitro study.

PubMed

Das, Dipanwita; Sarkar, Neelakshi; Sengupta, Isha; Pal, Ananya; Saha, Debraj; Bandopadhyay, Manikankana; Das, Chandrima; Narayan, Jimmy; Singh, Shivram Prasad; Chakravarty, Runu

2016-12-21

Toll like receptors plays a significant anti-viral role in different infections. The aim of this study was to look into the role of toll like receptor 4 (TLR4) in hepatitis B virus (HBV) infection. Real time PCR was used to analyze the transcription of TLR4 signaling molecules, cell cycle regulators and HBV DNA viral load after triggering the HepG2.2.15 cells with TLR4 specific ligand. Nuclear factor (NF)-κB translocation on TLR4 activation was analyzed using microscopic techniques. Protein and cell cycle analysis was done using Western Blot and FACS respectively. The present study shows that TLR4 activation represses HBV infection. As a result of HBV suppression, there are several changes in host factors which include partial release in G1/S cell cycle arrest and changes in host epigenetic marks. Finally, it was observed that anti-viral action of TLR4 takes place through the NF-κB pathway. The study shows that TLR4 activation in HBV infection brings about changes in hepatocyte microenvironment and can be used for developing a promising therapeutic target in future.

The impact of anti-congestion policies on fuel consumption, carbon dioxide emissions and urban sprawl: Application of RELU-TRAN2, a CGE model

NASA Astrophysics Data System (ADS)

Hiramatsu, Tomoru

RELU-TRAN (Regional Economy and Land Use and Transportation) is a numerically solvable general equilibrium model (Anas and Liu, 2007), which treats in a unified manner the regional economy, urban land use and urban personal transportation sectors. In this dissertation, the model is extended by adding the consumer-workers' choice of private vehicle type according to the vehicle's fuel economy, by treating congestion on local roads as well as on major roads and by introducing car fuel consumption as a function of congested vehicle speed. By making the extensions, the model becomes more suitable to analyze the fuel consumption and CO2 emission consequences of urban development. The model is calibrated and simulated for the Chicago metropolitan area. By adjusting the model to the longer time span gradually, the shortand long-run price elasticities of fuel consumption are examined. As the time span becomes longer, fuel consumption becomes more elastic with respect to gasoline price, but when technological improvements in car fuel economy over comparable time spans are introduced exogenously, then the elasticity of fuel with respect to gasoline price becomes similar to that estimated in the econometric literature. Comparative statics exercises show that, if travel by auto becomes relatively more attractive in terms of travel time or travel cost than travel by public transit, then the Chicago MSA becomes more sprawled in total developed land area, whereas if public transit travel becomes relatively more attractive, then the Chicago MSA becomes more centralized. To mitigate fuel consumption and CO2 emissions, relative effectiveness of quasi-Pigouvian congestion tolls, a fuel tax on gasoline, a cordon toll around the downtown and a downtown parking fee are tested. All of these policies successfully reduce the aggregate fuel consumption and CO2. The urban growth boundary (UGB) is an alternative policy tested by the model. The UGB directly makes the Chicago MSA more centralized by prohibiting the development into urban use of a part of the vacant land in the suburban areas. The UGB also reduces aggregate fuel and CO2 emissions, but the impact is much smaller than the quasi-Pigouvian toll. Although Chicago MSA is centralized by both the UGB and the quasi-Pigouvian toll, the auto travel is directly discouraged by quasi-Pigouvian toll and but not by the UGB.

Disseminated cysticercosis: clinical spectrum, Toll-like receptor-4 gene polymorphisms and role of albendazole: A prospective follow-up of 60 cases with a review of 56 published cases.

PubMed

Qavi, Abdul; Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Jain, Amita; Kumar, Neeraj; Malhotra, Kiran Preet; Srivastava, Pradeep Kumar; Verma, Rajesh; Sharma, Praveen Kumar

2016-09-01

In this study, we describe clinical and imaging spectrum, and the natural course of patients with disseminated cysticercosis. How albendazole affects the course of disease has also been evaluated. We assessed the Toll-like receptor-4 gene polymorphisms, to know the reason for the apparently higher prevalence of disseminated cysticercosis in India.Sixty consecutive patients with disseminated cysticercosis were enrolled. Sixty age-and-sex-matched healthy controls were also enrolled for the purpose of genetic study. Twenty patients, who gave consent, were treated with albendazole along with corticosteroids. Forty patients did not give consent for antiparasitic therapy. Assessment for Toll-like receptor-4 gene polymorphisms (Asp299Gly and Thr399Ile genes) was done. Patients were followed for 6 months. We also performed a literature search of cases published in English language using PubMed electronic database and analyzed 56 cases thus available.There was an increased risk (6.63 fold and 4.61 fold) of disseminated cysticercosis in the presence of Asp299Gly and Thr399Ile polymorphisms in Toll-like receptor-4, respectively. The allelic frequency of Gly (11% vs. 3%, P = 0.024, odds ratio [OR] = 3.52) and Ile alleles (11% vs. 2%, P = 0.009, OR = 4.738) in disseminated cysticercosis was high. Albendazole resulted in complete disappearance of all cerebral lesions in 35% (7/20) patients and reduction in lesion load in remaining 65% (13/20) patients. No significant change in number of cysticercal lesion was noted in patients who did not receive albendazole. No major adverse reaction following antiparasitic treatment was noted. Three deaths were recorded in patients who did not receive antiparasitic treatment.Of the 56 cases reported in PubMed, 33 patients received antiparasitic treatment with follow-up data available for 31 patients. Most (24) of these patients received albendazole. A significant clinical and/or imaging improvements, on follow up, were observed in 27 patients. Of the 4 deaths recorded, 3 had a heavy parasitic load and died after praziquantel therapy.Toll-like receptor-4 gene polymorphisms are associated with an increased susceptibility to disseminated cysticercosis, in the Indian population. Albendazole treatment seems to reduce the lesion load and improve symptoms.

Disseminated cysticercosis: clinical spectrum, Toll-like receptor-4 gene polymorphisms and role of albendazole

PubMed Central

Qavi, Abdul; Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Jain, Amita; Kumar, Neeraj; Malhotra, Kiran Preet; Srivastava, Pradeep Kumar; Verma, Rajesh; Sharma, Praveen Kumar

2016-01-01

Abstract In this study, we describe clinical and imaging spectrum, and the natural course of patients with disseminated cysticercosis. How albendazole affects the course of disease has also been evaluated. We assessed the Toll-like receptor-4 gene polymorphisms, to know the reason for the apparently higher prevalence of disseminated cysticercosis in India. Sixty consecutive patients with disseminated cysticercosis were enrolled. Sixty age-and-sex-matched healthy controls were also enrolled for the purpose of genetic study. Twenty patients, who gave consent, were treated with albendazole along with corticosteroids. Forty patients did not give consent for antiparasitic therapy. Assessment for Toll-like receptor-4 gene polymorphisms (Asp299Gly and Thr399Ile genes) was done. Patients were followed for 6 months. We also performed a literature search of cases published in English language using PubMed electronic database and analyzed 56 cases thus available. There was an increased risk (6.63 fold and 4.61 fold) of disseminated cysticercosis in the presence of Asp299Gly and Thr399Ile polymorphisms in Toll-like receptor-4, respectively. The allelic frequency of Gly (11% vs. 3%, P = 0.024, odds ratio [OR] = 3.52) and Ile alleles (11% vs. 2%, P = 0.009, OR = 4.738) in disseminated cysticercosis was high. Albendazole resulted in complete disappearance of all cerebral lesions in 35% (7/20) patients and reduction in lesion load in remaining 65% (13/20) patients. No significant change in number of cysticercal lesion was noted in patients who did not receive albendazole. No major adverse reaction following antiparasitic treatment was noted. Three deaths were recorded in patients who did not receive antiparasitic treatment. Of the 56 cases reported in PubMed, 33 patients received antiparasitic treatment with follow-up data available for 31 patients. Most (24) of these patients received albendazole. A significant clinical and/or imaging improvements, on follow up, were observed in 27 patients. Of the 4 deaths recorded, 3 had a heavy parasitic load and died after praziquantel therapy. Toll-like receptor-4 gene polymorphisms are associated with an increased susceptibility to disseminated cysticercosis, in the Indian population. Albendazole treatment seems to reduce the lesion load and improve symptoms. PMID:27684822

A Method for Estimation of Death Tolls in Disastrous Earthquake

NASA Astrophysics Data System (ADS)

Pai, C.; Tien, Y.; Teng, T.

2004-12-01

Fatality tolls caused by the disastrous earthquake are the one of the most important items among the earthquake damage and losses. If we can precisely estimate the potential tolls and distribution of fatality in individual districts as soon as the earthquake occurrences, it not only make emergency programs and disaster management more effective but also supply critical information to plan and manage the disaster and the allotments of disaster rescue manpower and medicine resources in a timely manner. In this study, we intend to reach the estimation of death tolls caused by the Chi-Chi earthquake in individual districts based on the Attributive Database of Victims, population data, digital maps and Geographic Information Systems. In general, there were involved many factors including the characteristics of ground motions, geological conditions, types and usage habits of buildings, distribution of population and social-economic situations etc., all are related to the damage and losses induced by the disastrous earthquake. The density of seismic stations in Taiwan is the greatest in the world at present. In the meantime, it is easy to get complete seismic data by earthquake rapid-reporting systems from the Central Weather Bureau: mostly within about a minute or less after the earthquake happened. Therefore, it becomes possible to estimate death tolls caused by the earthquake in Taiwan based on the preliminary information. Firstly, we form the arithmetic mean of the three components of the Peak Ground Acceleration (PGA) to give the PGA Index for each individual seismic station, according to the mainshock data of the Chi-Chi earthquake. To supply the distribution of Iso-seismic Intensity Contours in any districts and resolve the problems for which there are no seismic station within partial districts through the PGA Index and geographical coordinates in individual seismic station, the Kriging Interpolation Method and the GIS software, The population density depends on whether the districts are more urbanized or not. As the present researches are concerned, there were not a good and reliable relationship between the mortality and the characteristics of ground motions. We propose the concept of Equal Population Gaps to resolve the influence of mortality in a rural or urban district and decision of the weighting function to each district. The relationship between PGA Index and the mortality determined in this study can be expressed as:\\[M=28.9/[1+exp{(1.67-0.0029 \\times PGA)}] \\] Here M is mortality in %, and PGA is PGA Index in gals. The corresponding curve matches the data reasonably well, with R2=0.91. We process the estimation for districts in different scales to verify the feasibility of the method. The mortality-based on PGA Index is particularly useful in real-time application for death tolls prediction and assessment--a piece of information most critical for post earthquake emergency response operation.

Toll-like receptor 2 and type 2 diabetes.

PubMed

Sepehri, Zahra; Kiani, Zohre; Nasiri, Ali Akbar; Kohan, Farhad

2016-01-01

Innate immunity plays a crucial role in the pathogenesis of type 2 diabetes and related complications. Since the toll-like receptors (TLRs) are central to innate immunity, it appears that they are important participants in the development and pathogenesis of the disease. Previous investigations demonstrated that TLR2 homodimers and TLR2 heterodimers with TLR1 or TLR6 activate innate immunity upon recognition of damage-associated molecular patterns (DAMPs). Several DAMPs are released during type 2 diabetes, so it may be hypothesized that TLR2 is significantly involved in its progression. Here, we review recent data on the important roles and status of TLR2 in type 2 diabetes and related complications.

Microglial cells and peritoneal macrophages release activin A upon stimulation with Toll-like receptor agonists.

PubMed

Ebert, Sandra; Zeretzke, Moritz; Nau, Roland; Michel, Uwe

2007-02-21

Activin A levels are elevated in the cerebrospinal fluid (CSF) of patients with meningitis and in the sera of patients with sepsis. The source(s) of the elevated concentrations of activin A in CSF and serum have not yet been discovered. Here we demonstrate that primary mouse microglial cells and peritoneal macrophages release activin A after treatment with agonists of Toll-like receptor (TLR) 2, 4, and 9. These findings provide further evidence for a role of activin in the innate immune response and suggest that microglial cells and macrophages are a source of elevated activin A concentrations observed in the CSF during bacterial meningitis and in the systemic circulation during sepsis.

Immunoregulation of GVHD by triggering the innate immune system with CpG.

PubMed

Morecki, Shoshana; Slavin, Shimon

2009-08-01

Stimulation of Toll-like receptors by oligodeoxynucleotide sequences containing a CpG motif provides signals capable of triggering the innate and adaptive immune systems, thereby leading either to stimulation or suppression of immunoreactivities. Similar immunoregulatory capabilities are necessary for achieving the fine balance between engraftment and graft-versus-host disease required in the setup of allogeneic cell therapy. Ligation of CpG to its Toll-like receptors can be accomplished by treatment of the host or pretransplant treatment of the donor in vivo. These different strategies are presented in this review, which summarizes the attempts to maximize beneficial alloreactivity against malignant or other undesirable host cells, while controlling graft-versus-host disease.

Bench-to-bedside review: Toll-like receptors and their role in septic shock

PubMed Central

Opal, Steven M; Huber, Christian E

2002-01-01

The Toll-like receptors (TLRs) are essential transmembrane signaling receptors of the innate immune system that alert the host to the presence of a microbial invader. The recent discovery of the TLRs has rapidly expanded our knowledge of molecular events that initiate host–pathogen interactions. These functional attributes of the cellular receptors provide insights into the nature of pattern recognition receptors that activate the human antimicrobial defense systems. The fundamental significance of the TLRs in the generation of systemic inflammation and the pathogenesis of septic shock is reviewed. The potential clinical implications of therapeutic modulation of these recently characterized receptors of innate immunity are also discussed. PMID:11983038

Near-toll quality digital speech transmission in the mobile satellite service

NASA Technical Reports Server (NTRS)

Townes, S. A.; Divsalar, D.

1986-01-01

This paper discusses system considerations for near-toll quality digital speech transmission in a 5 kHz mobile satellite system channel. Tradeoffs are shown for power performance versus delay for a 4800 bps speech compression system in conjunction with a 16 state rate 2/3 trellis coded 8PSK modulation system. The suggested system has an additional 150 ms of delay beyond the propagation delay and requires an E(b)/N(0) of about 7 dB for a Ricean channel assumption with line-of-sight to diffuse component ratio of 10 assuming ideal synchronization. An additional loss of 2 to 3 dB is expected for synchronization in fading environment.

Toll-like receptor activation by helminths or helminth products to alleviate inflammatory bowel disease.

PubMed

Sun, ShuMin; Wang, XueLin; Wu, XiuPing; Zhao, Ying; Wang, Feng; Liu, XiaoLei; Song, Yanxia; Wu, ZhiLiang; Liu, MingYuan

2011-09-27

Helminth infection may modulate the expression of Toll like receptors (TLR) in dendritic cells (DCs) and modify the responsiveness of DCs to TLR ligands. This may regulate aberrant intestinal inflammation in humans with helminthes and may thus help alleviate inflammation associated with human inflammatory bowel disease (IBD). Epidemiological and experimental data provide further evidence that reducing helminth infections increases the incidence rate of such autoimmune diseases. Fine control of inflammation in the TLR pathway is highly desirable for effective host defense. Thus, the use of antagonists of TLR-signaling and agonists of their negative regulators from helminths or helminth products should be considered for the treatment of IBD.

The Drosophila imd signaling pathway.

PubMed

Myllymäki, Henna; Valanne, Susanna; Rämet, Mika

2014-04-15

The fruit fly, Drosophila melanogaster, has helped us to understand how innate immunity is activated. In addition to the Toll receptor and the Toll signaling pathway, the Drosophila immune response is regulated by another evolutionarily conserved signaling cascade, the immune deficiency (Imd) pathway, which activates NF-κB. In fact, the Imd pathway controls the expression of most of the antimicrobial peptides in Drosophila; thus, it is indispensable for normal immunity in flies. In this article, we review the current literature on the Drosophila Imd pathway, with special emphasis on its role in the (patho)physiology of different organs. We discuss the systemic response, as well as local responses, in the epithelial and mucosal surfaces and the nervous system.

Toll-like receptor activation by helminths or helminth products to alleviate inflammatory bowel disease

PubMed Central

2011-01-01

Helminth infection may modulate the expression of Toll like receptors (TLR) in dendritic cells (DCs) and modify the responsiveness of DCs to TLR ligands. This may regulate aberrant intestinal inflammation in humans with helminthes and may thus help alleviate inflammation associated with human inflammatory bowel disease (IBD). Epidemiological and experimental data provide further evidence that reducing helminth infections increases the incidence rate of such autoimmune diseases. Fine control of inflammation in the TLR pathway is highly desirable for effective host defense. Thus, the use of antagonists of TLR-signaling and agonists of their negative regulators from helminths or helminth products should be considered for the treatment of IBD. PMID:21943110

Speech Perception in Noise by Children With Cochlear Implants

PubMed Central

Caldwell, Amanda; Nittrouer, Susan

2013-01-01

Purpose Common wisdom suggests that listening in noise poses disproportionately greater difficulty for listeners with cochlear implants (CIs) than for peers with normal hearing (NH). The purpose of this study was to examine phonological, language, and cognitive skills that might help explain speech-in-noise abilities for children with CIs. Method Three groups of kindergartners (NH, hearing aid wearers, and CI users) were tested on speech recognition in quiet and noise and on tasks thought to underlie the abilities that fit into the domains of phonological awareness, general language, and cognitive skills. These last measures were used as predictor variables in regression analyses with speech-in-noise scores as dependent variables. Results Compared to children with NH, children with CIs did not perform as well on speech recognition in noise or on most other measures, including recognition in quiet. Two surprising results were that (a) noise effects were consistent across groups and (b) scores on other measures did not explain any group differences in speech recognition. Conclusions Limitations of implant processing take their primary toll on recognition in quiet and account for poor speech recognition and language/phonological deficits in children with CIs. Implications are that teachers/clinicians need to teach language/phonology directly and maximize signal-to-noise levels in the classroom. PMID:22744138

Transcriptomics of cortical gray matter thickness decline during normal aging

PubMed Central

Kochunov, P; Charlesworth, J; Winkler, A; Hong, LE; Nichols, T; Curran, JE; Sprooten, E; Jahanshad, N; Thompson, PM; Johnson, MP; Kent, JW; Landman, BA; Mitchell, B; Cole, SA; Dyer, TD; Moses, EK; Goring, HHH; Almasy, L; Duggirala, R; Olvera, RL; Glahn, DC; Blangero, J

2013-01-01

Introduction We performed a whole-transcriptome correlation analysis, followed by the pathway enrichment and testing of innate immune response pathways analyses to evaluate the hypothesis that transcriptional activity can predict cortical gray matter thickness (GMT) variability during normal cerebral aging Methods Transcriptome and GMT data were availabe for 379 individuals (age range=28–85) community-dwelling members of large extended Mexican-American families. Collection of transcriptome data preceded that of neuroimaging data by 17 years. Genome-wide gene transcriptome data consisted of 20,413 heritable lymphocytes-based transcripts. GMT measurements were performed from high-resolution (isotropic 800µm) T1-weighted MRI. Transcriptome-wide and pathway enrichment analysis was used to classify genes correlated with GMT. Transcripts for sixty genes from seven innate immune pathways were tested as specific predictors of GMT variability. Results Transcripts for eight genes (IGFBP3, LRRN3, CRIP2, SCD, IDS, TCF4, GATA3, HN1) passed the transcriptome-wide significance threshold. Four orthogonal factors extracted from this set predicted 31.9% of the variability in the whole-brain and between 23.4 and 35% of regional GMT measurements. Pathway enrichment analysis identified six functional categories including cellular proliferation, aggregation, differentiation, viral infection, and metabolism. The integrin signaling pathway was significantly (p<10−6) enriched with GMT. Finally, three innate immune pathways (complement signaling, toll-receptors and scavenger and immunoglobulins) were significantly associated with GMT. Conclusion Expression activity for the genes that regulate cellular proliferation, adhesion, differentiation and inflammation can explain a significant proportion of individual variability in cortical GMT. Our findings suggest that normal cerebral aging is the product of a progressive decline in regenerative capacity and increased neuroinflammation. PMID:23707588

Transcriptomics of cortical gray matter thickness decline during normal aging.

PubMed

Kochunov, P; Charlesworth, J; Winkler, A; Hong, L E; Nichols, T E; Curran, J E; Sprooten, E; Jahanshad, N; Thompson, P M; Johnson, M P; Kent, J W; Landman, B A; Mitchell, B; Cole, S A; Dyer, T D; Moses, E K; Goring, H H H; Almasy, L; Duggirala, R; Olvera, R L; Glahn, D C; Blangero, J

2013-11-15

We performed a whole-transcriptome correlation analysis, followed by the pathway enrichment and testing of innate immune response pathway analyses to evaluate the hypothesis that transcriptional activity can predict cortical gray matter thickness (GMT) variability during normal cerebral aging. Transcriptome and GMT data were available for 379 individuals (age range=28-85) community-dwelling members of large extended Mexican American families. Collection of transcriptome data preceded that of neuroimaging data by 17 years. Genome-wide gene transcriptome data consisted of 20,413 heritable lymphocytes-based transcripts. GMT measurements were performed from high-resolution (isotropic 800 μm) T1-weighted MRI. Transcriptome-wide and pathway enrichment analysis was used to classify genes correlated with GMT. Transcripts for sixty genes from seven innate immune pathways were tested as specific predictors of GMT variability. Transcripts for eight genes (IGFBP3, LRRN3, CRIP2, SCD, IDS, TCF4, GATA3, and HN1) passed the transcriptome-wide significance threshold. Four orthogonal factors extracted from this set predicted 31.9% of the variability in the whole-brain and between 23.4 and 35% of regional GMT measurements. Pathway enrichment analysis identified six functional categories including cellular proliferation, aggregation, differentiation, viral infection, and metabolism. The integrin signaling pathway was significantly (p<10(-6)) enriched with GMT. Finally, three innate immune pathways (complement signaling, toll-receptors and scavenger and immunoglobulins) were significantly associated with GMT. Expression activity for the genes that regulate cellular proliferation, adhesion, differentiation and inflammation can explain a significant proportion of individual variability in cortical GMT. Our findings suggest that normal cerebral aging is the product of a progressive decline in regenerative capacity and increased neuroinflammation. Copyright © 2013 Elsevier Inc. All rights reserved.

Toll-Like Receptor–2/6 and Toll-Like Receptor–9 Agonists Suppress Viral Replication but Not Airway Hyperreactivity in Guinea Pigs

PubMed Central

Evans, Scott E.; Dickey, Burton F.; Fryer, Allison D.; Jacoby, David B.

2013-01-01

Respiratory virus infections cause airway hyperreactivity (AHR). Preventative strategies for virus-induced AHR remain limited. Toll-like receptors (TLRs) have been suggested as a therapeutic target because of their central role in triggering antiviral immune responses. Previous studies showed that concurrent treatment with TLR2/6 and TLR9 agonists reduced lethality and the microbial burden in murine models of bacterial and viral pneumonia. This study investigated the effects of TLR2/6 and TLR9 agonist pretreatment on parainfluenza virus pneumonia and virus-induced AHR in guinea pigs in vivo. Synthetic TLR2/6 lipopeptide agonist Pam2CSK4 and Class C oligodeoxynucleotide TLR9 agonist ODN2395, administered in combination 24 hours before virus infection, significantly reduced viral replication in the lung. Despite a fivefold reduction in viral titers, concurrent TLR2/6 and TLR9 agonist pretreatment did not prevent virus-induced AHR or virus-induced inhibitory M2 muscarinic receptor dysfunction. Interestingly, the TLR agonists independently caused non–M2-dependent AHR. These data confirm the therapeutic antiviral potential of TLR agonists, while suggesting that virus inhibition may be insufficient to prevent virus-induced airway pathophysiology. Furthermore, TLR agonists independently cause AHR, albeit through a distinctly different mechanism from that of parainfluenza virus. PMID:23449736

TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy

DOE PAGES

Lim, So-Yon; Osuna, Christa E.; Hraber, Peter T.; ...

2018-05-02

Antiretroviral therapy can halt HIV-1 replication, but fails to target the long-lived latent viral reservoir. Several pharmacological compounds have been evaluated for their ability to reverse HIV-1 latency, but none have demonstrably reduced the latent HIV-1 reservoir, or impacted viral rebound following the interruption of antiretroviral therapy. Here, we evaluate orally administered selective tolllike receptor 7 agonists GS-986 and GS-9620 for their ability to induce transient viremia in simian immunodeficiency virus-infected rhesus monkeys on suppressive antiretroviral therapy. In an initial doseescalation study, and a subsequent dose-optimization study, we found that toll-like receptor 7 agonists activate multiple innate and adaptive immunemore » cell populations in addition to inducing SIV RNA. We also observed toll-like receptor 7 agonist-induced reductions in SIV DNA and ex vivo inducible virus from treated animals. In a second study, after stopping antiretroviral therapy, two of nine treated animals have remained aviremic for more than two years, even after in vivo CD8+ lymphocyte depletion. Moreover, adoptive transfer of cells from aviremic animals could not induce de novo infection in naive recipient macaques. These findings suggest that toll-like receptor agonists may facilitate reservoir reduction in a subset of individuals.« less

Systematic Review of the Relation Between Intestinal Microbiota and Toll-Like Receptors in the Metabolic Syndrome: What Do We Know So Far?

PubMed

Portela-Cidade, José Pedro; Borges-Canha, Marta; Leite-Moreira, Adelino Ferreira; Pimentel-Nunes, Pedro

2015-01-01

Metabolic syndrome is an emerging problem in developed countries and presents itself as a potential threat worldwide. The role of diabetes, dyslipidaemia and hepatic steatosis as pivotal components of the metabolic syndrome is well known. However, their common persistent chronic inflammation and its potential cause still elude. This systematic review aims to present evidence of the mechanisms that link the intestinal microbioma, innate immunity and metabolic syndrome. A comprehensive research was made using PubMed database and 35 articles were selected. We found that metabolic syndrome is associated to increased levels of innate immunity receptors, namely, Toll-like receptors, both in intestine and systemically and its polymorphisms may change the risk of metabolic syndrome development. Microbioma dysbiosis is also present in metabolic syndrome, with lower prevalence of Bacteroidetes and increased prevalence of Firmicutes populations. The data suggest that the link between intestinal microbiota and Toll-like receptors can negatively endanger the metabolic homeostasis. Current evidence suggests that innate immunity and intestinal microbiota may be the hidden link in the metabolic syndrome development mechanisms. In the near future, this can be the key in the development of new prophylactic and therapeutic strategies to treat metabolic syndrome patients.

Toll/Interleukin-1 Receptor Domain Derived from TcpC (TIR-TcpC) Ameliorates Experimental Autoimmune Arthritis by Down-modulating Th17 Cell Response*

PubMed Central

Pasi, Shweta; Kant, Ravi; Surolia, Avadhesha

2016-01-01

Evasion through immunomodulation is one of the several strategies adopted by pathogens to prolong their survival within the host. One such pathogen, Escherichia coli CFT073, utilizes an immunomodulatory protein, TcpC, to combat the host's innate immune defense. TcpC abrogates the function of MyD88 in macrophages, thus perturbing all the signaling processes that involve this adaptor protein. Although central to various signaling pathways initiated by IL-1, IL-18, and toll-like receptors, the precise contribution of MyD88 to the development of autoimmunity, particularly rheumatoid arthritis, still needs extensive exploration. Herein, by using the toll/interleukin-1 receptor (TIR) domain homologous C-terminal motif of TcpC, i.e. TIR-TcpC, we found MyD88 to be critical for the induction and progression of rheumatoid arthritis through its pivotal role in the development of Th17 cells, the subset of CD4+ T-cells widely implicated in various autoimmune disorders. The TIR-TcpC mediated inhibition of signaling through MyD88, and subsequent amelioration of experimental autoimmune arthritis was observed to be an outcome of perturbations in the NFκB-RORγt (RAR-related orphan receptor γt) axis. PMID:27022030

Toll-like receptor signaling: a perspective to develop vaccine against leishmaniasis.

PubMed

Singh, Rakesh K; Srivastava, Ankita; Singh, Nisha

2012-09-06

The toll-like receptors (TLRs) are the sentinel factor of the innate immunity, which are essential for host defense. These receptors detect the presence of conserved molecular patterns of potentially pathogenic microorganisms and contribute in both, cellular as well as humoral immune responses. Leishmania is an intracellular pathogen that silently invades host immune system. After phagocytosis, it divides and proliferates in the harmful environment of host macrophages by down-regulating its vital effector functions. In leishmaniasis, the outcome of the infection basically relies on the skewed balance between Th1/Th2 immune responses. Lots of work have been done and on progress but still characterization of either preventive or prophylactic candidate antigen/s is far from satisfactory. How does Leishmania regulate host innate immune system? Still it is unanswered. TLRs play very important role during inflammatory process of various diseases such as cancer, bacterial and viral infections but TLR signaling is comparatively less explained in leishmanial infection. In the context to Th1/Th2 dichotomy, identification of leishmanial antigens that modulate toll-like receptor signaling will certainly help in the development of future vaccine. This review will initially describe global properties of TLRs, and later will discuss their role in the pathogenesis of leishmaniasis. Copyright © 2012 Elsevier GmbH. All rights reserved.

Association of Toll-Like Receptor 3 and Toll-Like Receptor 9 Single Nucleotide Polymorphisms with Hepatitis C Virus Infection and Hepatic Fibrosis in Egyptian Patients

PubMed Central

Zayed, Rania A.; Omran, Dalia; Mokhtar, Doha A.; Zakaria, Zinab; Ezzat, Sameera; Soliman, Mohamed A.; Mobarak, Lamiaa; El-Sweesy, Hossam; Emam, Ghada

2017-01-01

Toll-like receptors (TLRs) are recognized as fundamental contributors to the immune system function against infections. Hepatitis C virus (HCV) infection represents a global health problem especially in Egypt having the highest HCV prevalence worldwide where HCV infection is a continuing epidemic. The aim of the present study was to investigate the possible association between genetic variation in TLR-3 and TLR-9 and HCV infection and hepatic fibrosis in chronic HCV-positive Egyptian patients. The present study included 100 naïve chronic HCV-positive patients and 100 age- and sex-matched healthy controls. Genotyping of TLR-3 (_7 C/A [rs3775296]), TLR-3 (c.1377C/T [rs3775290]) and TLR-9 (1237T/C [rs5743836]) were done by polymerase chain reaction restriction fragment length polymorphism technique. Frequency of polymorphic genotypes in TLR-3 (_7 C/A), TLR-3 (c.1377C/T) and TLR-9 (1237T/C) were not significantly different between studied HCV-positive patients and controls with P values 0.121, 0.112, and 0.683, respectively. TLR-3 c.1377 T-allele was associated with advanced stage of hepatic fibrosis (P = 0.003). PMID:28093541