Sample records for task request ttr

  1. Therapeutic Oligonucleotides Targeting Liver Disease: TTR Amyloidosis.

    PubMed

    Niemietz, Christoph; Chandhok, Gursimran; Schmidt, Hartmut

    2015-09-30

    The liver has become an increasingly interesting target for oligonucleotide therapy. Mutations of the gene encoding transthyretin (TTR), expressed in vast amounts by the liver, result in a complex degenerative disease, termed familial amyloid polyneuropathy (FAP). Misfolded variants of TTR are linked to the establishment of extracellular protein deposition in various tissues, including the heart and the peripheral nervous system. Recent progress in the chemistry and formulation of antisense (ASO) and small interfering RNA (siRNA) designed for a knockdown of TTR mRNA in the liver has allowed to address the issue of gene-specific molecular therapy in a clinical setting of FAP. The two therapeutic oligonucleotides bind to RNA in a sequence specific manner but exploit different mechanisms. Here we describe major developments that have led to the advent of therapeutic oligonucleotides for treatment of TTR-related disease.

  2. Non-coding variants contribute to the clinical heterogeneity of TTR amyloidosis.

    PubMed

    Iorio, Andrea; De Lillo, Antonella; De Angelis, Flavio; Di Girolamo, Marco; Luigetti, Marco; Sabatelli, Mario; Pradotto, Luca; Mauro, Alessandro; Mazzeo, Anna; Stancanelli, Claudia; Perfetto, Federico; Frusconi, Sabrina; My, Filomena; Manfellotto, Dario; Fuciarelli, Maria; Polimanti, Renato

    2017-09-01

    Coding mutations in TTR gene cause a rare hereditary form of systemic amyloidosis, which has a complex genotype-phenotype correlation. We investigated the role of non-coding variants in regulating TTR gene expression and consequently amyloidosis symptoms. We evaluated the genotype-phenotype correlation considering the clinical information of 129 Italian patients with TTR amyloidosis. Then, we conducted a re-sequencing of TTR gene to investigate how non-coding variants affect TTR expression and, consequently, phenotypic presentation in carriers of amyloidogenic mutations. Polygenic scores for genetically determined TTR expression were constructed using data from our re-sequencing analysis and the GTEx (Genotype-Tissue Expression) project. We confirmed a strong phenotypic heterogeneity across coding mutations causing TTR amyloidosis. Considering the effects of non-coding variants on TTR expression, we identified three patient clusters with specific expression patterns associated with certain phenotypic presentations, including late onset, autonomic neurological involvement, and gastrointestinal symptoms. This study provides novel data regarding the role of non-coding variation and the gene expression profiles in patients affected by TTR amyloidosis, also putting forth an approach that could be used to investigate the mechanisms at the basis of the genotype-phenotype correlation of the disease.

  3. Transthyretin familial amyloid polyneuropathy (TTR-FAP): Parameters for early diagnosis.

    PubMed

    Escolano-Lozano, Fabiola; Barreiros, Ana Paula; Birklein, Frank; Geber, Christian

    2018-01-01

    Familial transthyretin amyloidosis is a life-threatening disease presenting with sensorimotor and autonomic polyneuropathy. Delayed diagnosis has a detrimental effect on treatment and prognosis. To facilitate diagnosis, we analyzed data patterns of patients with transthyretin familial amyloid polyneuropathy (TTR-FAP) and compared them to polyneuropathies of different etiology for clinical and electrophysiological discriminators. Twenty-four patients with TTR-FAP and 48 patients with diabetic polyneuropathy (dPNP) were investigated (neurological impairment score NIS; neurological disability score NDS) in a cross-sectional design. Both groups were matched for gender and presence of pain. Quantitative sensory testing (QST), sympathetic skin response (SSR), heart rate variability (HRV), and nerve conduction studies (NCV) were performed. Both groups were compared using univariate analysis. In a stepwise discriminant analysis, discriminators between both neuropathies were identified. These discriminators were validated comparing TTR-FAP patients with a cohort of patients with chemotherapy-induced polyneuropathy (CIN) and chronic inflammatory demyelinating neuropathy (CIDP). TTR-FAP patients scored higher in NDS and NIS and had impaired cold detection (CDT, p  = .024), cold-warm discrimination (TSL, p  = .019) and mechanical hyperalgesia (MPT, p  = .029) at the hands, SSR (upper limb, p  = .022) HRV and ulnar and sural NCS (all p  < .05) were more affected in TTR-FAP. Ulnar nerve sensory NCV, CDT, and the MPT but not the other parameters discriminated TTR-FAP from dPNP (82% of cases), from CIN (86.7%) and from CIDP (68%; only ulnar sNCV). Low ulnar SNCV, impaired cold perception, and mechanical hyperalgesia at the hands seem to characterize TTR-FAP and might help to differentiate from other polyneuropathies.

  4. Sixty years of transthyretin familial amyloid polyneuropathy (TTR-FAP) in Europe: where are we now? A European network approach to defining the epidemiology and management patterns for TTR-FAP.

    PubMed

    Parman, Yesim; Adams, David; Obici, Laura; Galán, Lucía; Guergueltcheva, Velina; Suhr, Ole B; Coelho, Teresa

    2016-02-01

    Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a highly disabling, life-threatening disease characterized by progressive sensorimotor and autonomic neuropathy. The profile of the disease across Europe is inadequately understood at present. The incidence and clinical presentation of TTR-FAP varies widely within Europe, with early and late-onset disease subtypes. In those regions in which the disease is endemic (Portugal, Sweden, Cyprus, and Majorca), a Val30Met substitution in the TTR gene is the predominant genetic cause, whereas in the rest of Europe, cases of TTR-FAP are mainly sporadic with genetic heterogeneity. Current management strategies lack cohesion and patients can experience years of misdiagnosis and suboptimal treatment. The article aims to disseminate the findings and recommendations from two recent meetings of the European Network for TTR-FAP (ATTReuNET), a panel comprising representatives from 10 European countries (Bulgaria, Cyprus, France, Germany, Italy, the Netherlands, Portugal, Spain, Sweden, and Turkey) with expertise in the diagnosis and management of TTR-FAP. We explore the epidemiology and genetic mark of TTR-FAP across Europe and assess current management strategies, with a view to developing an alternative framework - a networked approach to disease management with an emphasis on collaboration and sharing of best practice.

  5. Human TTR conformation altered by rhenium tris-carbonyl derivatives.

    PubMed

    Ciccone, Lidia; Policar, Clotilde; Stura, Enrico A; Shepard, William

    2016-09-01

    Transthyretin (TTR) is a 54 kDa homotetrameric serum protein that transports thyroxine (T4) and retinol. TTR is potentially amyloidogenic due to homotetramer dissociation into monomeric intermediates that self-assemble as amyloid deposits and insoluble fibrils. Most crystallographic structures, including those of amyloidogenic variants show the same tetramer without major variations in the monomer-monomer interface nor in the volume of the interdimeric cavity. Soaking TTR crystals in a solution containing rhenium tris-carbonyl derivatives yields a TTR conformer never observed before. Only one of the two monomers of the crystallographic dimer is significantly altered, and the inner part of the T4 binding cavity is expanded at one end and shrunk at the other. The result redefines the mechanism of allosteric communication between the two sites, suggesting that negative cooperativity is a function of dimer asymmetry, which can be induced through internal or external binding. An aspect that remains unexplained is why the conformational changes are ubiquitous throughout the crystal although the heavy metal content of the derivatized crystals is relatively low. The conformational changes observed, which include Leu(82), may represent a form of TTR better at scavenging β-Amyloid. At a resolution of 1.69Å, with excellent refinement statistics and well defined electron density for all parts of the structure, it is possible to envisage answering important questions that range from protein cooperative behavior to heavy atom induced protein conformational modifications that can result in crystallographic non-isomorphism. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. Inhibition of TTR Aggregation-Induced Cell Death – A New Role for Serum Amyloid P Component

    PubMed Central

    Dacklin, Ingrid; Lundgren, Erik

    2013-01-01

    Background Serum amyloid P component (SAP) is a glycoprotein that is universally found associated with different types of amyloid deposits. It has been suggested that it stabilizes amyloid fibrils and therefore protects them from proteolytic degradation. Methodology/Principal Findings In this paper, we show that SAP binds not only to mature amyloid fibrils but also to early aggregates of amyloidogenic mutants of the plasma protein transthyretin (TTR). It does not inhibit fibril formation of TTR mutants, which spontaneously form amyloid in vitro at physiological pH. We found that SAP prevents cell death induced by mutant TTR, while several other molecules that are also known to decorate amyloid fibrils do not have such effect. Using a Drosophila model for TTR-associated amyloidosis, we found a new role for SAP as a protective factor in inhibition of TTR-induced toxicity. Overexpression of mutated TTR leads to a neurological phenotype with changes in wing posture. SAP-transgenic flies were crossed with mutated TTR-expressing flies and the results clearly confirmed a protective effect of SAP on TTR-induced phenotype, with an almost complete reduction in abnormal wing posture. Furthermore, we found in vivo that binding of SAP to mutated TTR counteracts the otherwise detrimental effects of aggregation of amyloidogenic TTR on retinal structure. Conclusions/Significance Together, these two approaches firmly establish the protective effect of SAP on TTR-induced cell death and degenerative phenotypes, and suggest a novel role for SAP through which the toxicity of early amyloidogenic aggregates is attenuated. PMID:23390551

  7. Photogrammetric Deflection Measurements for the Tiltrotor Test Rig (TTR) Multi-Component Rotor Balance Calibration

    NASA Technical Reports Server (NTRS)

    Solis, Eduardo; Meyn, Larry

    2016-01-01

    Calibrating the internal, multi-component balance mounted in the Tiltrotor Test Rig (TTR) required photogrammetric measurements to determine the location and orientation of forces applied to the balance. The TTR, with the balance and calibration hardware attached, was mounted in a custom calibration stand. Calibration loads were applied using eleven hydraulic actuators, operating in tension only, that were attached to the forward frame of the calibration stand and the TTR calibration hardware via linkages with in-line load cells. Before the linkages were installed, photogrammetry was used to determine the location of the linkage attachment points on the forward frame and on the TTR calibration hardware. Photogrammetric measurements were used to determine the displacement of the linkage attachment points on the TTR due to deflection of the hardware under applied loads. These measurements represent the first photogrammetric deflection measurements to be made to support 6-component rotor balance calibration. This paper describes the design of the TTR and the calibration hardware, and presents the development, set-up and use of the photogrammetry system, along with some selected measurement results.

  8. Results from the interim salt disposition program macrobatch 10 tank 21H qualification samples

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

    Peters, T. B.; Bannochie, C. J.

    2017-02-23

    Savannah River National Laboratory (SRNL) analyzed samples from Tank 21H in support of qualification of Macrobatch (Salt Batch) 10 for the Interim Salt Disposition Program (ISDP). This document reports characterization data on the samples of Tank 21H and fulfills the requirements of Deliverable 3 of the Technical Task Request (TTR). Further work will report the results of the Extraction-Scrub-Strip (ESS) testing (Task 5 of the TTR) using the Tank 21H material. Task 4 of the TTR (MST Strike) will not be completed for Salt Batch 10.

  9. Impairment of autophagy by TTR V30M aggregates: in vivo reversal by TUDCA and curcumin.

    PubMed

    Teixeira, Cristina A; Almeida, Maria do Rosário; Saraiva, Maria João

    2016-09-01

    Transthyretin (TTR)-related amyloidoses are diseases characterized by extracellular deposition of amyloid fibrils and aggregates in tissues composed of insoluble misfolded TTR that becomes toxic. Previous studies have demonstrated the ability of small compounds in preventing and reversing TTR V30M deposition in transgenic mice gastrointestinal (GI) tract as well as lowering biomarkers associated with cellular stress and apoptotic mechanisms. In the present study we aimed to study TTR V30M aggregates effect in autophagy, a cellular mechanism crucial for cell survival that has been implicated in the development of several neurodegenerative diseases. We were able to demonstrate in cell culture that TTR V30M aggregates cause a partial impairment of the autophagic machinery as shown by p62 accumulation, whereas early steps of the autophagic flux remain unaffected as shown by autophagosome number evaluation and LC3 turnover assay. Our studies performed in TTR V30M transgenic animals demonstrated that tauroursodeoxycholic acid (TUDCA) and curcumin effectively reverse p62 accumulation in the GI tract pointing to the ability of both compounds to modulate autophagy additionally to mitigate apoptosis. Overall, our in vitro and in vivo studies establish an association between TTR V30M aggregates and autophagy impairment and suggest the use of autophagy modulators as an additional and alternative therapeutic approach for the treatment of TTR V30M-related amyloidosis. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  10. Geodetic positioning of the Aerospace Electronics Research Lab (ERL) Osborne Time Transfer Receiver (TTR) using the GPS NAVSTAR Block I satellites

    NASA Technical Reports Server (NTRS)

    Liu, Anthony S.

    1990-01-01

    Aerospace has routinely processed the Osborne Time Transfer Receiver (TTR) data for the purpose of monitoring the performance of ground and GPS atomic clocks in near real-time with on-line residual displays and characterizing clock stability with Allan Variance calculations. Recently, Aerospace added the ability to estimate the TTR's location by differentially correcting the TTR's location in the WGS84 reference system. This new feature is exercised on a set of TTR clock phase data and Sub-meter accurate station location estimates of the TTR at the Aerospace Electronic Research Lab (ERL) are obtained.

  11. Epigallocatechin-3-gallate as a potential therapeutic drug for TTR-related amyloidosis: "in vivo" evidence from FAP mice models.

    PubMed

    Ferreira, Nelson; Saraiva, Maria João; Almeida, Maria Rosário

    2012-01-01

    Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disease caused by the extracellular deposition of mutant transthyretin (TTR), with special involvement of the peripheral nervous system (PNS). Currently, hepatic transplantation is considered the most efficient therapy to halt the progression of clinical symptoms in FAP since more than 95% of TTR is produced by the liver. However, less invasive and more reliable therapeutic approaches have been proposed for FAP therapy, namely based on drugs acting as inhibitors of amyloid formation or as amyloid disruptors. We have recently reported that epigallocatechin-3-gallate (EGCG), the most abundant catechin in green tea, is able to inhibit TTR aggregation and fibril formation, "in vitro" and in a cellular system, and is also able to disrupt pre-formed amyloid fibrils "in vitro". In the present study, we assessed the effect of EGCG subchronic administration on TTR amyloidogenesis "in vivo", using well characterized animal models for FAP. Semiquantitative immunohistochemistry (SQ-IHC) and Western blot analysis of mice tissues after treatment demonstrated that EGCG inhibits TTR toxic aggregates deposition in about 50% along the gastrointestinal tract (GI) and peripheral nervous system (PNS). Moreover EGCG treatment considerably lowered levels of several biomarkers associated with non-fibrillar TTR deposition, namely endoplasmic reticulum (ER)-stress, protein oxidation and apoptosis markers. Treatment of old FAP mice with EGCG resulted not only in the decrease of non-fibrillar TTR deposition but also in disaggregation of amyloid deposits. Consistently, matrix metalloproteinase (MMP)-9 and serum amyloid P component (SAP), both markers of amyloid deposition, were also found reduced in treated old FAP mice. The dual effect of EGCG both as TTR aggregation inhibitor and amyloid fibril disruptor together with the high tolerability and low toxicity of EGCG in humans, point towards the potential use of this compound, or

  12. Diagnostic pitfalls in sporadic transthyretin familial amyloid polyneuropathy (TTR-FAP).

    PubMed

    Planté-Bordeneuve, V; Ferreira, A; Lalu, T; Zaros, C; Lacroix, C; Adams, D; Said, G

    2007-08-14

    Transthyretin familial amyloid polyneuropathies (TTR-FAPs) are autosomal dominant neuropathies of fatal outcome within 10 years after inaugural symptoms. Late diagnosis in patients who present as nonfamilial cases delays adequate management and genetic counseling. Clinical data of the 90 patients who presented as nonfamilial cases of the 300 patients of our cohort of patients with TTR-FAP were reviewed. They were 21 women and 69 men with a mean age at onset of 61 (extremes: 38 to 78 years) and 17 different mutations of the TTR gene including Val30Met (38 cases), Ser77Tyr (16 cases), Ile107Val (15 cases), and Ser77Phe (5 cases). Initial manifestations included mainly limb paresthesias (49 patients) or pain (17 patients). Walking difficulty and weakness (five patients) and cardiac or gastrointestinal manifestations (five patients), were less common at onset. Mean interval to diagnosis was 4 years (range 1 to 10 years); 18 cases were mistaken for chronic inflammatory demyelinating polyneuropathy, which was the most common diagnostic error. At referral a length-dependent sensory loss affected the lower limbs in 2, all four limbs in 20, and four limbs and anterior trunk in 77 patients. All sensations were affected in 60 patients (67%), while small fiber dysfunction predominated in the others. Severe dysautonomia affected 80 patients (90%), with postural hypotension in 52, gastrointestinal dysfunction in 50, impotence in 58 of 69 men, and sphincter disturbance in 31. Twelve patients required a cardiac pacemaker. Nerve biopsy was diagnostic in 54 of 65 patients and salivary gland biopsy in 20 of 30. Decreased nerve conduction velocity, increased CSF protein, negative biopsy findings, and false immunolabeling of amyloid deposits were the main causes of diagnostic errors. We conclude that DNA testing, which is the most reliable test for TTR-FAP, should be performed in patients with a progressive length-dependent small fiber polyneuropathy of unknown origin, especially when

  13. Retrospective study of a TTR FAP cohort to modify NIS+7 for therapeutic trials.

    PubMed

    Suanprasert, N; Berk, J L; Benson, M D; Dyck, P J B; Klein, C J; Gollob, J A; Bettencourt, B R; Karsten, V; Dyck, P J

    2014-09-15

    Protein stabilization and oligonucleotide therapies are being tested in transthyretin amyloid polyneuropathy (TTR FAP) trials. From retrospective analysis of 97 untreated TTR FAP patients, we test the adequacy of Neuropathy Impairment Score+7 tests (NIS+7) and modifications to comprehensively score impairments for use in such therapeutic trials. Our data confirms that TTR FAP usually is a sensorimotor polyneuropathy with autonomic features which usually is symmetric, length dependent, lower limb predominant and progressive. NIS+7 adequately assesses weakness and muscle stretch reflexes without ceiling effects but not sensation loss, autonomic dysfunction or nerve conduction abnormalities. Three modifications of NIS+7 are suggested: 1) use of Smart Somatotopic Quantitative Sensation Testing (S ST QSTing); 2) choice of new autonomic assessments, e.g., sudomotor testing of distributed anatomical sites; and 3) use of only compound muscle action potential amplitudes (of ulnar, peroneal and tibial nerves) and sensory nerve action potentials of ulnar and sural nerve - than the previously recommended attributes suggested for the sensitive detection of diabetic sensorimotor polyneuropathy. These modifications of NIS+7 if used in therapeutic trials should improve characterization and quantification of sensation and autonomic impairment in TTR FAP and provide better nerve conduction tests. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Teaching Children with Autism to Request Help with Difficult Tasks

    ERIC Educational Resources Information Center

    Rodriguez, Nicole M.; Levesque, Megan A.; Cohrs, Victoria L.; Niemeier, Jessica J.

    2017-01-01

    We taught three children diagnosed with autism spectrum disorder to request help using an interrupted chain procedure during which we manipulated task materials such that the child was either incapable or capable of independently completing a link of a behavior chain. We initially observed undesirable generalization of requests for help during…

  15. Gene therapy approach to FAP: in vivo influence of T119M in TTR deposition in a transgenic V30M mouse model.

    PubMed

    Batista, A R; Gianni, D; Ventosa, M; Coelho, A V; Almeida, M R; Sena-Esteves, M; Saraiva, M J

    2014-12-01

    Familial amyloidotic polyneuropathy (FAP) is a neurodegenerative disorder characterized by extracellular deposition of amyloid fibrils composed by mutated transthyretin (TTR) mainly in the peripheral nervous system. At present, liver transplantation is still the standard treatment to halt the progression of clinical symptoms in FAP, but new therapeutic strategies are emerging, including the use of TTR stabilizers. Here we propose to establish a new gene therapy approach using adeno-associated virus (AAV) vectors to deliver the trans-suppressor TTR T119M variant to the liver of transgenic TTR V30M mice at different ages. This TTR variant is known for its ability to stabilize the tetrameric protein. Analysis of the gastrointestinal tract of AAV-treated animals revealed a significant reduction in deposition of TTR non-fibrillar aggregates in as much as 34% in stomach and 30% in colon, as well as decreased levels of biomarkers associated with TTR deposition, namely the endoplasmic reticulum stress marker BiP and the extracellular matrix protein MMP-9. Moreover, we showed with different studies that our approach leads to an increase in tetrameric and more stable forms of TTR, in favor of destabilized monomers. Altogether our data suggest the possibility to use this gene therapy approach in a prophylactic manner to prevent FAP pathology.

  16. [Comparison of TTR and CMV promoters in vivo and in vitro via a secreted luciferase reporter system].

    PubMed

    Luo, Shun-Tao; Tian, Wen-Hong; Wang, Gang; Dong, Xiao-Yan; Yang, Li; Wu, Xiao-Bing

    2009-11-01

    GLuc (Gaussia luciferase) is a secreted luciferase with high sensitivity. In this study, we primarily compared expression character of PTTR with that of PCMV, relied on easy secretion, high sensitivity and simple and fast detection of GLuc. We firstly constructed two plasmids pAAV2-neo-TTR-GLuc and pAAV2-neo-CMV-GLuc. Then, 4 cell lines were transfected with the two plasmids in aid of Lipofectamine 2000, including Huh7 and HepG2, which are derived from liver cells, as well as HEK293 and HeLaS3 cells, which are non-liver cell lines. We monitored the expression of GLuc in the supernatant of these cell cultures at different time points post-transfection. Furthermore, we injected the two plasmids with different doses into BALB/c mice by the means of hydrodynamic delivery and monitored the GLuc expression in vivo with 2.5 microl tail tip blood since 2 h post-injection. The cell assay results suggested that the expression of GLuc driven by CMV promoter was significantly higher than that of GLuc driven by TTR promoter. And, the luciferase activity of GLuc driven by CMV promoter was 50-300 times higher than that of GLuc driven by TTR promoter in HEK293 and HeLaS3 cell lines, but less than 10 times higher than that of GLuc driven by TTR promoter in the HepG2 and Huh7 cell lines, indicating the relative liver-specificity of TTR promoter. In the animal assay, the higher luciferase activity was determined in CMV promoter group than in TTR promoter group at different doses of the two plasmids. But the expression patterns for the two promoters differed obviously. The expression of GLuc driven by CMV promoter reached the maximum 10 hours post-injection and declined rapidly; while the expression of GLuc driven by TTR promoter reached the maximum 48 hours after delivery, and declined very slowly. These results implied that PTTR could keep expression of driven gene in a long time although its expression intensity is lower than PCMV's. Thus, it is more suitable for maintaining longer

  17. Transthyretin-Related Familial Amyloid Polyneuropathy (TTR-FAP): A Single-Center Experience in Sicily, an Italian Endemic Area.

    PubMed

    Mazzeo, Anna; Russo, Massimo; Di Bella, Gianluca; Minutoli, Fabio; Stancanelli, Claudia; Gentile, Luca; Baldari, Sergio; Carerj, Scipione; Toscano, Antonio; Vita, Giuseppe

    2015-07-22

    Familial amyloid polyneuropathy related to transthyretin gene (TTR-FAP) is a life-threatening disease transmitted as an autosomal dominant trait. Val30Met mutation accounts for the majority of the patients with large endemic foci especially in Portugal, Sweden and Japan. However, more than one hundred other mutations have been described worldwide. A great phenotypic variability among patients with late- and early-onset has been reported. To present a detailed report of TTR-FAP patients diagnosed in our tertiary neuromuscular center, in a 20-year period. Clinical informations were gathered through the database of our center. The study involved 76 individuals carrying a TTR-FAP mutation. Three phenotypes were identified, each corresponding to a different TTR variant, homogeneous within and heterogeneous between each other: i) Glu89Gln mutation, characterised by 5th - 6th decade onset, neuropathy as presenting symptoms, early heart dysfunction, cardiomyopathy as major cause of mortality followed by dysautonomia and cachexia; ii) Phe64Leu mutation, marked by familiarity reported in one-half of cases, late onset, severe peripheral neuropathy, moderate dysautonomia and mild cardiomyopathy, death for wasting syndrome; iii) Thr49Ala mutation, distinguished by onset in the 5th decade, autonomic disturbances as inaugural symptoms which may remain isolated for many years, moderate polyneuropathy, cachexia as major cause of mortality followed by cardiomyopathy. This survey highlighted a prevalence of 8.8/1,000,000 in Sicily Island. Good knowledge of the natural history of the disease according to different TTR mutations allow clinicians to optimise multiprofessional care for patients and to offer carriers a personalized follow-up to reveal first signs of the disease.

  18. 76 FR 54258 - Request for Comments-Fiscal Oversight Task Force Report and Recommendations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-31

    ... LEGAL SERVICES CORPORATION Request for Comments--Fiscal Oversight Task Force Report and... Fiscal Oversight Task Force, which reviewed and made recommendations regarding how LSC conducts fiscal... territories. By Resolution adopted on July 21, 2010, the Board established the Fiscal Oversight Task Force...

  19. Ecological studies of small vertebrates in Pu-contaminated study areas of NTS and TTR

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

    Bradley, W.G.; Moor, K.S.; White, M.G.

    Ecological studies of vertebrates in plutonium-contaminated areas of the Nevada Test Site (NTS) were initiated in March 1972, and have continued to date. In September 1973, standard census methods were also employed to derive a qualitative and quantitative inventory of vertebrate biota of four Nevada Applied Ecology Group (NAEG) study areas of the Tonopah Test Range (TTR). A checklist of vertebrates of NAEG study areas of NTS and TTR is presented. Data are presented on vertebrate composition, relative abundance, and seasonal status in the study areas. Concentrations of $sup 239$Pu and $sup 241$Am were determined in pelt or skin, GImore » tract, and carcass of 13 lizards and 16 mammals resident on Clean Slate 2, TTR, and Area 11, NTS. A total of 71 animals were collected for radioanalysis. However, the data were not available at the time this report was written. Pu tissue burdens were highest in lizards from Area 11 GZ. Maximum values obtained in nCi/g ash were 30.9, 42.2, and 0.43 for the pelt, GI tract, and carcass, respectively. Maximum $sup 239$Pu values in tissues of small rodents from Area 11 (not from GZ) were 11.4, 6.49, and 0.20 nCi/g ash for pelt, GI tract, and carcass, respectively. Pu/Am ratios were relatively consistent in tissue samples of lizards and small mammals from Area 11 (approximately 6:1, Pu/Am). Pu/Am ratios were not consistent in vertebrates of Clean Slate 2, TTR, and appeared to be lower in carcass (28:1, Pu/Am in mammals) than GI tract (9:1, Pu/Am in mammals). Although this trend was more conspicuous in mammals, it was also evident in reptiles. (auth)« less

  20. 78 FR 10127 - Request for Nominations to the Agricultural Air Quality Task Force

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-13

    ... Conservation Service Request for Nominations to the Agricultural Air Quality Task Force AGENCY: Natural... Nominations to the Agricultural Air Quality Task Force. SUMMARY: The Secretary of Agriculture invites... Force (AAQTF) which was established by the Federal Agriculture Improvement and Reform Act of 1996 to...

  1. Bleeding complications and mortality in warfarin-treated VTE patients, dependence of INR variability and iTTR.

    PubMed

    Sandén, Per; Renlund, Henrik; Svensson, Peter J; Själander, Anders

    2017-01-05

    High quality of warfarin treatment is important to prevent recurrence of venous thromboembolism (VTE) without bleeding complications. The aim of this study was to examine the effect of individual time in therapeutic range (iTTR) and International Normalised Ratio (INR) variability on bleeding risk and mortality in a large cohort of well-managed patients with warfarin due to VTE. A cohort of 16612 patients corresponding to 19502 treatment periods with warfarin due to VTE between January 1, 2006 and December 31, 2011 was retrieved from the Swedish national quality register AuriculA and matched with the Swedish National Patient Register for bleeding complications and background characteristics and the Cause of death register for occurrence and date of death. The rate of bleeding was 1.79 (confidence interval (CI) 95 % 1.66-1.93) per 100 treatment years among all patients. Those with poor warfarin treatment quality had a higher rate of clinically relevant bleeding, both when measured as iTTR below 70 %, 2.91 (CI 95 % 2.61-3.21) or as INR variability over the mean value 0.85, 2.61 (CI 95 % 2.36-2.86). Among those with both high INR variability and low iTTR the risk of clinically relevant bleeding was clearly increased hazard ratio (HR) 3.47 (CI 95 % 2.89-4.17). A similar result was found for all-cause mortality with a HR of 3.67 (CI 95 % 3.02-4.47). Both a low iTTR and a high INR variability increase the risk of bleeding complications or mortality. When combining the two treatment quality indicators patients at particular high risk of bleeding or death can be identified.

  2. 75 FR 12493 - Task Force on Childhood Obesity: Request for Information

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-16

    ... Force on Childhood Obesity: Request for Information AGENCY: U.S. Department of Agriculture, U.S.... SUMMARY: Across the country, childhood obesity has reached epidemic rates. On February 9, 2010, President Obama signed a Presidential Memo establishing a Task Force on Childhood Obesity that directs Federal...

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

    Peters, T. B.; Bannochie, C. J.

    Savannah River National Laboratory (SRNL) analyzed samples from Tank 21H in support of verification of Macrobatch (Salt Batch) 11 for the Interim Salt Disposition Program (ISDP) for processing. This document reports characterization data on the samples of Tank 21H and fulfills the requirements of Deliverable 3 of the Technical Task Request (TTR).

  4. ENDEAVOUR: Phase 3 Multicenter Study of Revusiran (ALN-TTRSC) in Patients With Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC)

    ClinicalTrials.gov

    2017-12-08

    Transthyretin (TTR) Mediated Familial Amyloidotic Cardiomyopathy (FAC); Amyloidosis, Hereditary; Amyloid Neuropathies, Familial; Amyloid Neuropathies; Amyloidosis, Hereditary, Transthyretin-Related; Familial Transthyretin Cardiac Amyloidosis

  5. 78 FR 9928 - Food and Drug Administration Drug Shortages Task Force and Strategic Plan; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0124] Food and Drug Administration Drug Shortages Task Force and Strategic Plan; Request for Comments AGENCY: Food and Drug Administration, HHS. ACTION: Notice; request for comments. SUMMARY: To assist the Food...

  6. Levels and distributions of organic pollutants in subtidal sediments from the Loire estuary: Are there any relationships with TTR-binding activity?

    NASA Astrophysics Data System (ADS)

    Couderc, M.; Gandolfi, F.; Zalouk-Vergnoux, A.; Beyeler, N.; Malleret, L.; Ambidina, I.; Kamari, A.; Blanchet-Letrouvé, I.; Mouneyrac, C.; Hamers, T.; Poirier, L.

    2016-12-01

    The Loire estuary runs through important urban sites with shipping, industrial and agricultural activities, being the receptacle of diffusive pollutants comprising, a mixture of contaminants such as persistent organic pollutants (POPs). This work was set out to evaluate the occurrence of thyroid endocrine disruptors in sediments of this estuary. Sediments were collected in September 2012 and April 2013, in subtidal zones along the estuary. Targeted chemical analyses of five classes of pollutants, i.e. polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs), polycyclic aromatic hydrocarbons (PAHs), alkylphenols (APs), and bisphenol A (BPA) were performed in sediment extracts. Extracts were further tested for their thyroid hormone (TH) disrupting potency to compete with TH for binding to its transporter protein transthyretin (TTR). The Haute-Indre site was characterized by a significant PAH contamination whereas Saint-Nazaire, Bellevue and Rezé would be particularly contaminated by PCBs. These observations could be linked to the different type of anthropogenic activities taking place close to these sites. Donges, Mindin and Paimboeuf were the sampling sites displaying the lowest contamination in PAHs, APs, PCBs and PBDEs. No inter-site difference could be observed for TTR-binding activity, which should be attributed to different compounds than the chemically analyzed compounds, as confirmed by PCA analyses. Furthermore, the TTR-binding potencies of the extracts were relatively low compared to data from literature. More investigations on the quantification of PCB and PBDE hydroxylated metabolites and other known endocrine disruptors such as pesticides or perfluorinated compounds could be considered, as well as bioassays highlighting other endocrine disrupting effects.

  7. MODELING CST ION EXCHANGE FOR CESIUM REMOVAL FROM SCIX BATCHES 1 - 4

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

    Smith, F.

    2011-04-25

    The objective of this work is, through modeling, to predict the performance of Crystalline Silicotitinate (CST) for the removal of cesium from Small Column Ion Exchange (SCIX) Batches 1-4 (as proposed in Revision 16 of the Liquid Waste System Plan). The scope of this task is specified in Technical Task Request (TTR) 'SCIX Feed Modeling', HLE-TTR-2011-003, which specified using the Zheng, Anthony, Miller (ZAM) code to predict CST isotherms for six given SCIX feed compositions and the VErsatile Reaction and SEparation simulator for Liquid Chromatography (VERSE-LC) code to predict ion-exchange column behavior. The six SCIX feed compositions provided in themore » TTR represent SCIX Batches 1-4 and Batches 1 and 2 without caustic addition. The study also investigated the sensitivity in column performance to: (1) Flow rates of 5, 10, and 20 gpm with 10 gpm as the nominal flow; and (2) Temperatures of 25, 35, and 45 C with 35 C as the nominal temperature. The isotherms and column predictions presented in this report reflect the expected performance of engineered CST IE-911. This form of CST was used in experiments conducted at the Savannah River National Laboratory (SRNL) that formed the basis for estimating model parameters (Hamm et al., 2002). As has been done previously, the engineered resin capacity is estimated to be 68% of the capacity of particulate CST without binder.« less

  8. Promoting Task-Based Pragmatics Instruction in EFL Classroom Contexts: The Role of Task Complexity

    ERIC Educational Resources Information Center

    Kim, Youjin; Taguchi, Naoko

    2015-01-01

    Robinson's (2001) Cognition Hypothesis claims that more complex tasks promote interaction and language development. This study examined the effect of task complexity in the learning of request-making expressions. Task complexity was operationalized as [+/- reasoning] following Robinson's framework. The study employed a pretest-posttest research…

  9. Performance Assessment of Hazardous Air Pollutant (HAP)Free Chemical Paint Strippers on Military Coatings for Validation to Federal Specification TT-R-2918A

    DTIC Science & Technology

    2016-03-01

    ARL-TN-0742 ● MAR 2016 US Army Research Laboratory Performance Assessment of Hazardous Air Pollutant (HAP)–Free Chemical Paint ...Free Chemical Paint Strippers on Military Coatings for Validation to Federal Specification TT-R-2918A by Lindsey Blohm Oak Ridge Institute for...COVERED (From - To) 1–30 April 2014 4. TITLE AND SUBTITLE Performance Assessment of Hazardous Air Pollutant (HAP)–Free Chemical Paint Strippers

  10. TANK 18-F AND 19-F TANK FILL GROUT SCALE UP TEST SUMMARY

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

    Stefanko, D.; Langton, C.

    2012-01-03

    High-level waste (HLW) tanks 18-F and 19-F have been isolated from FTF facilities. To complete operational closure the tanks will be filled with grout for the purpose of: (1) physically stabilizing the tanks, (2) limiting/eliminating vertical pathways to residual waste, (3) entombing waste removal equipment, (4) discouraging future intrusion, and (5) providing an alkaline, chemical reducing environment within the closure boundary to control speciation and solubility of select radionuclides. This report documents the results of a four cubic yard bulk fill scale up test on the grout formulation recommended for filling Tanks 18-F and 19-F. Details of the scale upmore » test are provided in a Test Plan. The work was authorized under a Technical Task Request (TTR), HLE-TTR-2011-008, and was performed according to Task Technical and Quality Assurance Plan (TTQAP), SRNL-RP-2011-00587. The bulk fill scale up test described in this report was intended to demonstrate proportioning, mixing, and transportation, of material produced in a full scale ready mix concrete batch plant. In addition, the material produced for the scale up test was characterized with respect to fresh properties, thermal properties, and compressive strength as a function of curing time.« less

  11. Closure Report for Corrective Action Unit 408: Bomblet Target Area Tonopah Test Range (TTR), Nevada, Revision 0

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

    Mark Krauss

    2010-09-01

    This Closure Report (CR) presents information supporting the closure of Corrective Action Unit (CAU) 408: Bomblet Target Area (TTR), Tonopah Test Range, Nevada. This CR complies with the requirements of the Federal Facility Agreement and Consent Order that was agreed to by the State of Nevada; U.S. Department of Energy (DOE), Environmental Management; U.S. Department of Defense; and DOE, Legacy Management. Corrective Action Unit 408 is located at the Tonopah Test Range, Nevada, and consists of Corrective Action Site (CAS) TA-55-002-TAB2, Bomblet Target Areas. This CAS includes the following seven target areas: • Mid Target • Flightline Bomblet Location •more » Strategic Air Command (SAC) Target Location 1 • SAC Target Location 2 • South Antelope Lake • Tomahawk Location 1 • Tomahawk Location 2 The purpose of this CR is to provide documentation supporting the completed corrective actions and data confirming that the closure objectives for the CAS within CAU 408 were met. To achieve this, the following actions were performed: • Review the current site conditions, including the concentration and extent of contamination. • Implement any corrective actions necessary to protect human health and the environment. • Properly dispose of corrective action and investigation wastes. • Document Notice of Completion and closure of CAU 408 issued by the Nevada Division of Environmental Protection. From July 2009 through August 2010, closure activities were performed as set forth in the Streamlined Approach for Environmental Restoration Plan for CAU 408: Bomblet Target Area, Tonopah Test Range (TTR), Nevada. The purposes of the activities as defined during the data quality objectives process were as follows: • Identify and remove munitions of explosive concern (MEC) associated with DOE activities. • Investigate potential disposal pit locations. • Remove depleted uranium-contaminated fragments and soil. • Determine whether contaminants of concern

  12. Beads task vs. box task: The specificity of the jumping to conclusions bias.

    PubMed

    Balzan, Ryan P; Ephraums, Rachel; Delfabbro, Paul; Andreou, Christina

    2017-09-01

    Previous research involving the probabilistic reasoning 'beads task' has consistently demonstrated a jumping-to-conclusions (JTC) bias, where individuals with delusions make decisions based on limited evidence. However, recent studies have suggested that miscomprehension may be confounding the beads task. The current study aimed to test the conventional beads task against a conceptually simpler probabilistic reasoning "box task" METHODS: One hundred non-clinical participants completed both the beads task and the box task, and the Peters et al. Delusions Inventory (PDI) to assess for delusion-proneness. The number of 'draws to decision' was assessed for both tasks. Additionally, the total amount of on-screen evidence was manipulated for the box task, and two new box task measures were assessed (i.e., 'proportion of evidence requested' and 'deviation from optimal solution'). Despite being conceptually similar, the two tasks did not correlate, and participants requested significantly less information on the beads task relative to the box task. High-delusion-prone participants did not demonstrate hastier decisions on either task; in fact, for box task, this group was observed to be significantly more conservative than low-delusion-prone group. Neither task was incentivized; results need replication with a clinical sample. Participants, and particularly those identified as high-delusion-prone, displayed a more conservative style of responding on the novel box task, relative to the beads task. The two tasks, whilst conceptually similar, appear to be tapping different cognitive processes. The implications of these results are discussed in relation to the JTC bias and the theoretical mechanisms thought to underlie it. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

    Williams, M. S.; Miller, D. H.; Fowley, M. D.

    The Savannah River National Laboratory (SRNL) was tasked to support validation of the Defense Waste Processing Facility (DWPF) melter offgas flammability model for the nitric-glycolic (NG) flowsheet. The work supports Deliverable 4 of the DWPF & Saltstone Facility Engineering Technical Task Request (TTR)1 and is supplemental to the Cold Cap Evaluation Furnace (CEF) testing conducted in 2014.2 The Slurry-fed Melt Rate Furnace (SMRF) was selected for the supplemental testing as it requires significantly less resources than the CEF and could provide a tool for more rapid analysis of melter feeds in the future. The SMRF platform has been used previouslymore » to evaluate melt rate behavior of DWPF glasses, but was modified to accommodate analysis of the offgas stream. Additionally, the Melt Rate Furnace (MRF) and Quartz Melt Rate Furnace (QMRF) were utilized for evaluations. MRF data was used exclusively for melt behavior observations and REDuction/OXidation (REDOX) prediction comparisons and will be briefly discussed in conjunction with its support of the SMRF testing. The QMRF was operated similarly to the SMRF for the same TTR task, but will be discussed in a separate future report. The overall objectives of the SMRF testing were to; 1) Evaluate the efficacy of the SMRF as a platform for steady state melter testing with continuous feeding and offgas analysis; and 2) Generate supplemental melter offgas flammability data to support the melter offgas flammability modelling effort for DWPF implementation of the NG flowsheet.« less

  14. 21 CFR 20.50 - Nonspecific and overly burdensome requests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... policy reasons justifying the requests. A decision on the processing of such a request for information... PUBLIC INFORMATION Procedures and Fees § 20.50 Nonspecific and overly burdensome requests. The Food and... taking into account the staff-hours required, the tasks from which these resources must be diverted, the...

  15. Closure Report for Corrective Action Unit 412: Clean Slate I Plutonium Dispersion (TTR) Tonopah Test Range, Nevada, Revision 0

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

    Matthews, Patrick

    This Closure Report (CR) presents information supporting the clean closure of Corrective Action Unit (CAU) 412: Clean Slate I Plutonium Dispersion (TTR), located on the Tonopah Test Range, Nevada. CAU 412 consists of a release of radionuclides to the surrounding soil from a storage–transportation test conducted on May 25, 1963. Corrective action investigation (CAI) activities were performed in April and May 2015, as set forth in the Streamlined Approach for Environmental Restoration (SAFER) Plan for Corrective Action Unit 412: Clean Slate I Plutonium Dispersion (TTR), Tonopah Test Range, Nevada; and in accordance with the Soils Activity Quality Assurance Plan. Themore » purpose of the CAI was to fulfill data needs as defined during the data quality objectives process. The CAU 412 dataset of investigation results was evaluated based on a data quality assessment. This assessment demonstrated the dataset is complete and acceptable for use in fulfilling the data needs identified by the data quality objectives process. This CR provides documentation and justification for the clean closure of CAU 412 under the FFACO without further corrective action. This justification is based on historical knowledge of the site, previous site investigations, implementation of the 1997 interim corrective action, and the results of the CAI. The corrective action of clean closure was confirmed as appropriate for closure of CAU 412 based on achievement of the following closure objectives: Radiological contamination at the site is less than the final action level using the ground troops exposure scenario (i.e., the radiological dose is less than the final action level): Removable alpha contamination is less than the high contamination area criterion: No potential source material is present at the site, and any impacted soil associated with potential source material has been removed so that remaining soil contains contaminants at concentrations less than the final action levels: and

  16. ISOLOK VALVE ACCEPTANCE TESTING FOR DWPF SME SAMPLING PROCESS

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

    Edwards, T.; Hera, K.; Coleman, C.

    2011-12-05

    Evaluation of the Defense Waste Processing Facility (DWPF) Chemical Process Cell (CPC) cycle time identified several opportunities to improve the CPC processing time. Of the opportunities, a focus area related to optimizing the equipment and efficiency of the sample turnaround time for DWPF Analytical Laboratory was identified. The Mechanical Systems & Custom Equipment Development (MS&CED) Section of the Savannah River National Laboratory (SRNL) evaluated the possibility of using an Isolok{reg_sign} sampling valve as an alternative to the Hydragard{reg_sign} valve for taking process samples. Previous viability testing was conducted with favorable results using the Isolok sampler and reported in SRNL-STI-2010-00749 (1).more » This task has the potential to improve operability, reduce maintenance time and decrease CPC cycle time. This report summarizes the results from acceptance testing which was requested in Task Technical Request (TTR) HLW-DWPF-TTR-2010-0036 (2) and which was conducted as outlined in Task Technical and Quality Assurance Plan (TTQAP) SRNL-RP-2011-00145 (3). The Isolok to be tested is the same model which was tested, qualified, and installed in the Sludge Receipt Adjustment Tank (SRAT) sample system. RW-0333P QA requirements apply to this task. This task was to qualify the Isolok sampler for use in the DWPF Slurry Mix Evaporator (SME) sampling process. The Hydragard, which is the current baseline sampling method, was used for comparison to the Isolok sampling data. The Isolok sampler is an air powered grab sampler used to 'pull' a sample volume from a process line. The operation of the sampler is shown in Figure 1. The image on the left shows the Isolok's spool extended into the process line and the image on the right shows the sampler retracted and then dispensing the liquid into the sampling container. To determine tank homogeneity, a Coliwasa sampler was used to grab samples at a high and low location within the mixing tank. Data from the two

  17. Results of initial analyses of the salt (macro) batch 10 tank 21H qualification samples

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

    Peters, T. B.

    2017-01-01

    Savannah River National Laboratory (SRNL) analyzed samples from Tank 21H in support of qualification of Interim Salt Disposition Project (ISDP) Salt (Macro) Batch 10 for processing through the Actinide Removal Process (ARP) and the Modular Caustic-Side Solvent Extraction Unit (MCU). This document reports the initial results of the analyses of samples of Tank 21H. Analysis of the Tank 21H Salt (Macro) Batch 10 composite sample indicates that the material does not display any unusual characteristics or observations, such as floating solids, the presence of large amount of solids, or unusual colors. Further sample results will be reported in a futuremore » document. This memo satisfies part of Deliverable 3 of the Technical Task Request (TTR).« less

  18. Results of initial analyses of the salt (macro) batch 11 Tank 21H qualification samples

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

    Peters, T. B.

    Savannah River National Laboratory (SRNL) analyzed samples from Tank 21H in support of qualification of Interim Salt Disposition Project (ISDP) Salt (Macro) Batch 11 for processing through the Actinide Removal Process (ARP) and the Modular Caustic-Side Solvent Extraction Unit (MCU). This document reports the initial results of the analyses of samples of Tank 21H. Analysis of the Tank 21H Salt (Macro) Batch 11 composite sample indicates that the material does not display any unusual characteristics or observations, such as floating solids, the presence of large amounts of solids, or unusual colors. Further sample results will be reported in a futuremore » document. This memo satisfies part of Deliverable 3 of the Technical Task Request (TTR).« less

  19. 75 FR 16577 - Gulf War Veterans' Illnesses Task Force

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-01

    ... DEPARTMENT OF VETERANS AFFAIRS Gulf War Veterans' Illnesses Task Force AGENCY: Department of Veterans Affairs (VA). ACTION: Notice with request for comments. SUMMARY: The Secretary Department of Veterans Affairs (VA) established the Gulf War Veterans' Illnesses Task Force (GWVI-TF) in August 2009 to...

  20. 78 FR 28292 - Gulf War Veterans' Illnesses Task Force

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-14

    ... DEPARTMENT OF VETERANS AFFAIRS Gulf War Veterans' Illnesses Task Force AGENCY: Department of Veterans Affairs (VA). ACTION: Notice with request for comments. SUMMARY: The Secretary, Department of Veterans Affairs (VA) established the Gulf War Veterans' Illnesses Task Force (GWVI-TF) in August 2009 to...

  1. 76 FR 65321 - Gulf War Veterans' Illnesses Task Force

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-20

    ... DEPARTMENT OF VETERANS AFFAIRS Gulf War Veterans' Illnesses Task Force AGENCY: Department of Veterans Affairs (VA). ACTION: Notice with request for comments. SUMMARY: The Secretary, Department of Veterans Affairs (VA) established the Gulf War Veterans' Illnesses Task Force (GWVI-TF) in August 2009 to...

  2. Trojan Tour and Rendezvous (TTR): A New Frontiers Mission to Explore the Origin and Evolution of the Early Solar System

    NASA Astrophysics Data System (ADS)

    Bell, J. F., III; Olkin, C.; Castillo, J. C.

    2015-12-01

    The orbital properties, compositions, and physical properties of the diverse populations of small outer solar system bodies provide a forensic map of how our solar system formed and evolved. Perhaps the most potentially diagnostic, but least explored, of those populations are the Jupiter Trojan asteroids, which orbit at ~5 AU in the L4 and L5 Lagrange points of Jupiter. More than 6200 Jupiter Trojans are presently known, but these are predicted to be only a small fraction of the 500,000 to 1 million Trojans >1 km in size. The Trojans are hypothesized to be either former Kuiper Belt Objects (KBOs) that were scattered into the inner solar system by early giant planet migration and then trapped in the 1:1 Jupiter mean motion resonance, or bodies formed near 5 AU in a much more quiescent early solar system, and then trapped at L4 and L5. The 2011 Planetary Science Decadal Survey identified important questions about the origin and evolution of the solar system that can be addressed by studying of the Trojan asteroids, including: (a) How did the giant planets and their satellite systems accrete, and is there evidence that they migrated to new orbital positions? (b) What is the relationship between large and small KBOs? Is the small population derived by impact disruption of the large one? (c) What kinds of surface evolution, radiation chemistry, and surface-atmosphere interactions occur on distant icy primitive bodies? And (d) What are the sources of asteroid groups (Trojans and Centaurs) that remain to be explored by spacecraft? The Trojan Tour and Rendezvous (TTR) is a New Frontiers-class mission designed to answer these questions, and to test hypotheses for early giant planet migration and solar system evolution. Via close flybys of a large number of these objects,, and orbital characterization of at least one large Trojan, TTR will enable the first-time exploration of this population. Our primary mission goals are to characterize the overall surface geology

  3. Trojan Tour and Rendezvous (TTR): A New Frontiers Mission to Conduct the First Detailed Reconnaissance of the Jupiter Trojan Asteroids

    NASA Astrophysics Data System (ADS)

    Bell, James F.; Olkin, Cathy; Castillo-Rogez, Julie

    2015-11-01

    Among the most potentially diagnostic but least explored populations of small bodies are the Jupiter Trojan asteroids, which orbit at ~5 AU in the L4 and L5 Lagrange points of Jupiter. The Trojans provide a unique perspective on solar system history, because their locations and physical, compositional, and mineralogic properties preserve evidence for important gravitational interactions among the giant planets. The locations and orbital properties of more than 6200 Jupiter Trojans are now known, but that is likely only a small fraction of a population of up to ~1e6 Trojans >1 km in size. The Trojans are hypothesized to be either former KBOs scattered into the inner solar system by early giant planet migration and then trapped in L4 and L5, or bodies formed near 5 AU in a more quiescent early solar system.Important Planetary Decadal Survey questions that can be addressed by studying the Trojans include: (a) How did the giant planets and their satellite systems accrete, and is there evidence that they migrated to new orbital positions? (b) What is the relationship between large and small KBOs? Is the small population derived by impact disruption of the large one? (c) What kinds of surface evolution, radiation chemistry, and surface-atmosphere interactions occur on distant icy primitive bodies? And (d) What are the sources of asteroid groups (Trojans and Centaurs) that remain to be explored by spacecraft?Here we describe the Trojan Tour and Rendezvous (TTR) New Frontiers mission concept, which is designed to answer these Decadal questions and to test hypotheses for early giant planet migration and solar system evolution. Via close flybys of many of these objects, and orbital characterization of at least one large Trojan, TTR will enable the initial up-close exploration of this population. Our primary mission goals are to characterize the overall surface geology, geochemistry and mineralogy of these worlds; to characterize their internal structure and dynamical

  4. The approach to engineering tasks composition on knowledge portals

    NASA Astrophysics Data System (ADS)

    Novogrudska, Rina; Globa, Larysa; Schill, Alexsander; Romaniuk, Ryszard; Wójcik, Waldemar; Karnakova, Gaini; Kalizhanova, Aliya

    2017-08-01

    The paper presents an approach to engineering tasks composition on engineering knowledge portals. The specific features of engineering tasks are highlighted, their analysis makes the basis for partial engineering tasks integration. The formal algebraic system for engineering tasks composition is proposed, allowing to set the context-independent formal structures for engineering tasks elements' description. The method of engineering tasks composition is developed that allows to integrate partial calculation tasks into general calculation tasks on engineering portals, performed on user request demand. The real world scenario «Calculation of the strength for the power components of magnetic systems» is represented, approving the applicability and efficiency of proposed approach.

  5. The use of the AOA TTR-4P GPS receiver in operation at the BIPM for real-time restitution of GPS time

    NASA Technical Reports Server (NTRS)

    Thomas, Claudine

    1994-01-01

    The Global Positioning System is an outstanding tool for the dissemination of time. Using mono-channel C/A-code GPS time receivers, the restitution of GPS time through the satellite constellation presents a peak-to-peak discrepancy of several tens of nanoseconds without SA but may be as high as several hundreds of nanoseconds with SA. As a consequence, civil users are more and more interested in implementing hardware and software methods for efficient restitution of GPS time, especially in the framework of the project of a real-time prediction of UTC (UTCp) which could be available in the form of time differences (UTCp - GPS time). Previous work, for improving the real-time restitution of GPS time with SA, to the level obtained without SA, focused on the implementation of a Kalman filter based on past data and updated at each new observation. An alternative solution relies upon the statistical features of the noise brought about by SA; it has already been shown that the SA noise is efficiently reduced by averaging data from numerous satellites observed simultaneously over a sufficiently long time. This method was successfully applied to data from a GPS time receiver, model AOA TTR-4P, connected to the cesium clock kept at the BIPM. This device, a multi-channel, dual frequency, P-code GPS time receiver, is one of the first TTR-4P units in operation in a civil laboratory. Preliminary comparative studies of this new equipment with conventional GPS time receivers are described in this paper. The results of an experimental restitution of GPS time, obtained in June 1993, are also detailed: 3 to 6 satellites were observed simultaneously with a sample interval of 15 s, an efficient smoothing of SA noise was realized by averaging data on all observed satellites over more than 1 hour. When the GPS system is complete in 1994, 8 satellites will be observable continuously from anywhere in the world and the same level of uncertainty will be obtained using a shorter averaging

  6. In Health-Related Tasks, Where Does the School Nurse Function?

    ERIC Educational Resources Information Center

    Berg, Beryl; And Others

    1973-01-01

    The study provided a composite picture of health-related tasks performed in one school district. Nurses were able to evaluate their current practices and recommend specific improvements in nursing actions. Other school districts seeking a profile of their involvement in health-related tasks may request copies of the questionnaire or the entire…

  7. Teaching an Individual with Severe Intellectual Delay to Request Assistance Conditionally

    ERIC Educational Resources Information Center

    Reichle, Joe; McComas, Jennifer; Dahl, Norm; Solberg, Gina; Pierce, Sarah; Smith, David

    2005-01-01

    The purpose of this study was to evaluate intervention procedures to teach conditional use of a communicative request for assistance and independent task performance. A 40-year-old man with autism and severe mental retardation with a history of escape-related problems was taught to use a graphic symbol to request assistance and to engage…

  8. Social motivation in prospective memory: higher importance ratings and reported performance rates for social tasks.

    PubMed

    Penningroth, Suzanna L; Scott, Walter D; Freuen, Margaret

    2011-03-01

    Few studies have addressed social motivation in prospective memory (PM). In a pilot study and two main studies, we examined whether social PM tasks possess a motivational advantage over nonsocial PM tasks. In the pilot study and Study 1, participants listed their real-life important and less important PM tasks. Independent raters categorized the PM tasks as social or nonsocial. Results from both studies showed a higher proportion of tasks rated as social when important tasks were requested than when less important tasks were requested. In Study 1, participants also reported whether they had remembered to perform each PM task. Reported performance rates were higher for tasks rated as social than for those rated as nonsocial. Finally, in Study 2, participants rated the importance of two hypothetical PM tasks, one social and one nonsocial. The social PM task was rated higher in importance. Overall, these findings suggest that social PM tasks are viewed as more important than nonsocial PM tasks and they are more likely to be performed. We propose that consideration of the social relevance of PM will lead to a more complete and ecologically valid theoretical description of PM performance. (PsycINFO Database Record (c) 2011 APA, all rights reserved).

  9. Timing of gazes in child dialogues: a time-course analysis of requests and back channelling in referential communication.

    PubMed

    Sandgren, Olof; Andersson, Richard; van de Weijer, Joost; Hansson, Kristina; Sahlén, Birgitta

    2012-01-01

    This study investigates gaze behaviour in child dialogues. In earlier studies the authors have investigated the use of requests for clarification and responses in order to study the co-creation of understanding in a referential communication task. By adding eye tracking, this line of research is now expanded to include non-verbal contributions in conversation. To investigate the timing of gazes in face-to-face interaction and to relate the gaze behaviour to the use of requests for clarification. Eight conversational pairs of typically developing 10-15 year olds participated. The pairs (director and executor) performed a referential communication task requiring the description of faces. During the dialogues both participants wore head-mounted eye trackers. All gazes were recorded and categorized according to the area fixated (Task, Face, Off). The verbal context for all instances of gaze at the partner's face was identified and categorized using time-course analysis. The results showed that the executor spends almost 90% of the time fixating the gaze on the task, 10% on the director's face and less than 0.5% elsewhere. Turn shift, primarily requests for clarification, and back channelling significantly predicted the executors' gaze to the face of the task director. The distribution of types of requests showed that requests for previously unmentioned information were significantly more likely to be associated with gaze at the director. The study shows that the executors' gaze at the director accompanies important dynamic shifts in the dialogue. The association with requests for clarification indicates that gaze at the director can be used to monitor the response with two modalities. Furthermore, the significantly higher association with requests for previously unmentioned information indicates that gaze may be used to emphasize the verbal content. The results will be used as a reference for studies of gaze behaviour in clinical populations with hearing and language

  10. 75 FR 47624 - U.S. Coral Reef Task Force Public Meeting and Public Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-06

    ... DEPARTMENT OF THE INTERIOR Fish and Wildlife Service U.S. Coral Reef Task Force Public Meeting and... (Service), announce a public meeting of the U.S. Coral Reef Task Force (USCRTF) and a request for written.... Coral Reef Task Force Department of the Interior Liaison, U.S. Department of the Interior, MS-3530-MIB...

  11. Handbook for Strategic Air Command (SAC) Management Engineering Officers (MEOs)

    DTIC Science & Technology

    1985-04-01

    JACK D. MARTIN, USAF FACULTY ADVISOR« MAJOR ROBERT M. WEIS, ACSC/ EDX SPONSOR« COLONEL DENNIS D. GRAVES, HQ SAC/XPM Submitted to the...8217^^^!^^^’T^^T^^TTT^"?,^w, Fr ’,^’TTrT^TTrTT,Tr,T^’ in AFR 25-5, then close the book and perform the task satisfac- tcsrily? The key to...Command and Staff College, Air University (ATC), Maxwell AFB, Alabama, 1981. 130 o.V ^^^^^^ WWW ^^^^T^^^^^^^I^^^^^^^^^^^^^W»^»>T»>il)’»M’j MJM ■iii.ii

  12. Experimental Model for Successful Liver Cell Therapy by Lenti TTR-YapERT2 Transduced Hepatocytes with Tamoxifen Control of Yap Subcellular Location

    PubMed Central

    Yovchev, Mladen; Jaber, Fadi L.; Lu, Zhonglei; Patel, Shachi; Locker, Joseph; Rogler, Leslie E.; Murray, John W.; Sudol, Marius; Dabeva, Mariana D.; Zhu, Liang; Shafritz, David A.

    2016-01-01

    Liver repopulation by transplanted hepatocytes has not been achieved previously in a normal liver microenvironment. Here we report that adult rat hepatocytes transduced ex vivo with a lentivirus expressing a human YapERT2 fusion protein (hYapERT2) under control of the hepatocyte-specific transthyretin (TTR) promoter repopulate normal rat liver in a tamoxifen-dependent manner. Transplanted hepatocytes expand very slowly but progressively to produce 10% repopulation at 6 months, showing clusters of mature hepatocytes that are fully integrated into hepatic parenchyma, with no evidence for dedifferentiation, dysplasia or malignant transformation. Thus, we have developed the first vector designed to regulate the growth control properties of Yap that renders it capable of producing effective cell therapy. The level of liver repopulation achieved has significant translational implications, as it is 2-3x the level required to cure many monogenic disorders of liver function that have no underlying hepatic pathology and is potentially applicable to diseases of other tissues and organs. PMID:26763940

  13. 78 FR 1918 - Public-Private Partnerships Public Meeting and Request for Comment

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-09

    ... complexities in P3 agreements, tasked the USDOT, via the Moving Ahead for Progress in the 21st Century Act (MAP...), DOT. ACTION: Public meeting notice; request for comment. SUMMARY: The USDOT/FHWA is tasked by MAP-21... be conducted on Wednesday, January 16, 2013, from 12:00 p.m. to 4:00 p.m., e.t. ADDRESSES: Comment...

  14. In-Space Crew-Collaborative Task Scheduling

    NASA Technical Reports Server (NTRS)

    Jaap, John; Meyer, Patrick; Davis, Elizabeth; Richardson, Lea

    2007-01-01

    For all past and current human space missions, the final scheduling of tasks to be done in space has been devoid of crew control, flexibility, and insight. Ground controllers, with minimal input from the crew, schedule the tasks and uplink the timeline to the crew or uplink the command sequences to the hardware. Prior to the International Space Station (ISS), the crew could make requests about tomorrow s timeline, they could omit a task, or they could request that something in the timeline be delayed. This lack of control over one's own schedule has had negative consequences. There is anecdotal consensus among astronauts that control over their own schedules will mitigate the stresses of long duration missions. On ISS, a modicum of crew control is provided by the job jar. Ground controllers prepare a task list (a.k.a. "job jar") of non-conflicting tasks from which jobs can be chosen by the in space crew. Because there is little free time and few interesting non-conflicting activities, the task-list approach provides little relief from the tedium of being micro-managed by the timeline. Scheduling for space missions is a complex and laborious undertaking which usually requires a large cadre of trained specialists and suites of complex software tools. It is a giant leap from today s ground prepared timeline (with a job jar) to full crew control of the timeline. However, technological advances, currently in-work or proposed, make it reasonable to consider scheduling a collaborative effort by the ground-based teams and the in-space crew. Collaboration would allow the crew to make minor adjustments, add tasks according to their preferences, understand the reasons for the placement of tasks on the timeline, and provide them a sense of control. In foreseeable but extraordinary situations, such as a quick response to anomalies and extended or unexpected loss of signal, the crew should have the autonomous ability to make appropriate modifications to the timeline, extend the

  15. 32 CFR 1900.21 - Processing of requests for records.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Information Act Amendments of 1996. (b) Database of “officially released information.” As an alternative to extensive tasking and as an accommodation to many requesters, the Agency maintains a database of “officially released information” which contains copies of documents released by this Agency. Searches of this database...

  16. 75 FR 11893 - Food and Drug Administration Transparency Task Force; Request for Comments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-12

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2009-N-0247... Administration, HHS. ACTION: Notice; request for comments. SUMMARY: The Food and Drug Administration (FDA) is soliciting comments from interested persons on ways in which FDA can increase transparency between FDA and...

  17. Report of the Task Force on De-Regulation Initiatives.

    ERIC Educational Resources Information Center

    Fishbein, Estelle A.; Blumer, Dennis H.

    In response to a request by the Presidential Task Force on Regulatory Relief, this report offers specific recommendations for reform of federal regulations. A cover letter explains the constraints imposed by the recommended format: that the report is unable to address adequately the area of federal regulatory activity generating the most adverse…

  18. Evaluation of quartz melt rate furnace with the nitric-glycolic flowsheet

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

    Williams, M. S.; Miller, D. H.

    The Savannah River National Laboratory (SRNL) was tasked to support validation of the Defense Waste Processing Facility (DWPF) melter offgas flammability model for the Nitric-Glycolic (NG) flowsheet. The work is supplemental to the Cold Cap Evaluation Furnace (CEF) testing conducted in 20141 and the Slurry-fed Melt Rate Furnace (SMRF) testing conducted in 20162 that supported Deliverable 4 of the DWPF & Saltstone Facility Engineering Technical Task Request (TTR).3 The Quartz Melt Rate Furnace (QMRF) was evaluated as a bench-scale scoping tool to potentially be used in lieu of or simply prior to the use of the larger-scale SMRF or CEF.more » The QMRF platform has been used previously to evaluate melt rate behavior and offgas compositions of DWPF glasses prepared from the Nitric-Formic (NF) flowsheet but not for the NG flowsheet and not with continuous feeding.4 The overall objective of the 2016-2017 testing was to evaluate the efficacy of the QMRF as a lab-scale platform for steady state, continuously fed melter testing with the NG flowsheet as an alternative to more expensive and complex testing with the SMRF or CEF platforms.« less

  19. U.S. Marine Corps Study of Establishing Time Criteria for Logistics Tasks

    DTIC Science & Technology

    2004-09-30

    STATISTICS FOR REQUESTS PER DAY FOR TWO BATTALIONS II-25 II-6 SUMMARY STATISTICS IN HOURS FOR RESOURCE REQUIREMENTS PER DAY FOR TWO BATTALIONS II-26 II-7...SUMMARY STATISTICS FOR INDIVIDUALS FOR RESOURCE REQUIREMENTS PER DAY FOR TWO BATTALIONS II-27 Study of Establishing Time Criteria for Logistics...developed and run to provide statistical information for analysis. In Task Four, the study team used Task Three findings to determine data requirements

  20. Drug Information Requests at the Philadelphia College of Pharmacy and Science.

    ERIC Educational Resources Information Center

    Snow, Bonnie

    1979-01-01

    Analysis of requests received at the Pharmaceutical Information Center of the Philadelphia College of Pharmacy and Science contributes to: (1) the task of educational planning for health-science professionals, (2) identification of pharmaceutical literature retrieval skills needed, and (3) identification of sources which contain information…

  1. What Lies Beneath?: Verbal Report in Interlanguage Requests in English

    ERIC Educational Resources Information Center

    Woodfield, Helen

    2010-01-01

    The present study investigates the role of concurrent and retrospective verbal report in exploring the cognitive processes of six pairs of advanced ESL learners engaged on a written discourse completion task eliciting status-unequal requests in English. Qualitative analysis of the concurrent data indicate that (i) social contextual aspects of the…

  2. Task Management in the New ATLAS Production System

    NASA Astrophysics Data System (ADS)

    De, K.; Golubkov, D.; Klimentov, A.; Potekhin, M.; Vaniachine, A.; Atlas Collaboration

    2014-06-01

    This document describes the design of the new Production System of the ATLAS experiment at the LHC [1]. The Production System is the top level workflow manager which translates physicists' needs for production level processing and analysis into actual workflows executed across over a hundred Grid sites used globally by ATLAS. As the production workload increased in volume and complexity in recent years (the ATLAS production tasks count is above one million, with each task containing hundreds or thousands of jobs) there is a need to upgrade the Production System to meet the challenging requirements of the next LHC run while minimizing the operating costs. In the new design, the main subsystems are the Database Engine for Tasks (DEFT) and the Job Execution and Definition Interface (JEDI). Based on users' requests, DEFT manages inter-dependent groups of tasks (Meta-Tasks) and generates corresponding data processing workflows. The JEDI component then dynamically translates the task definitions from DEFT into actual workload jobs executed in the PanDA Workload Management System [2]. We present the requirements, design parameters, basics of the object model and concrete solutions utilized in building the new Production System and its components.

  3. Freedom of Information Act Requests: Six Keys to Handling Them

    DTIC Science & Technology

    2016-01-01

    Defense AT&L: January–February 2016 50 Freedom of Information Act Requests Six Keys to Handling Them Michael A. Rodgers Rodgers is a professor of...crucial mission tasks. Understanding and using the six steps and keys provided above will free you from FOIA-induced distractions. The author can be contacted at michael.rodgers@dau.mil.

  4. Development of Physical Employment Standards for the Royal Australian Navy: Validation of Identified Whole-of-ship Tasks

    DTIC Science & Technology

    2014-11-01

    to determining individual CS tasks, this partially satisfied Navy’s request to quantify the physical demands of the course in order to draw parity ...will enable comparison between task demands on the course and during on-board duties. These data will be used to determine whether there is parity ...between the physical and physiological demands of the ACSC (or components of it) and CS tasks performed on-board each platform. If parity is drawn

  5. Physiological IgM Class Catalytic Antibodies Selective for Transthyretin Amyloid*

    PubMed Central

    Planque, Stephanie A.; Nishiyama, Yasuhiro; Hara, Mariko; Sonoda, Sari; Murphy, Sarah K.; Watanabe, Kenji; Mitsuda, Yukie; Brown, Eric L.; Massey, Richard J.; Primmer, Stanley R.; O'Nuallain, Brian; Paul, Sudhir

    2014-01-01

    Peptide bond-hydrolyzing catalytic antibodies (catabodies) could degrade toxic proteins, but acquired immunity principles have not provided evidence for beneficial catabodies. Transthyretin (TTR) forms misfolded β-sheet aggregates responsible for age-associated amyloidosis. We describe nucleophilic catabodies from healthy humans without amyloidosis that degraded misfolded TTR (misTTR) without reactivity to the physiological tetrameric TTR (phyTTR). IgM class B cell receptors specifically recognized the electrophilic analog of misTTR but not phyTTR. IgM but not IgG class antibodies hydrolyzed the particulate and soluble misTTR species. No misTTR-IgM binding was detected. The IgMs accounted for essentially all of the misTTR hydrolytic activity of unfractionated human serum. The IgMs did not degrade non-amyloidogenic, non-superantigenic proteins. Individual monoclonal IgMs (mIgMs) expressed variable misTTR hydrolytic rates and differing oligoreactivity directed to amyloid β peptide and microbial superantigen proteins. A subset of the mIgMs was monoreactive for misTTR. Excess misTTR was dissolved by a hydrolytic mIgM. The studies reveal a novel antibody property, the innate ability of IgMs to selectively degrade and dissolve toxic misTTR species as a first line immune function. PMID:24648510

  6. Request queues for interactive clients in a shared file system of a parallel computing system

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

    Bent, John M.; Faibish, Sorin

    Interactive requests are processed from users of log-in nodes. A metadata server node is provided for use in a file system shared by one or more interactive nodes and one or more batch nodes. The interactive nodes comprise interactive clients to execute interactive tasks and the batch nodes execute batch jobs for one or more batch clients. The metadata server node comprises a virtual machine monitor; an interactive client proxy to store metadata requests from the interactive clients in an interactive client queue; a batch client proxy to store metadata requests from the batch clients in a batch client queue;more » and a metadata server to store the metadata requests from the interactive client queue and the batch client queue in a metadata queue based on an allocation of resources by the virtual machine monitor. The metadata requests can be prioritized, for example, based on one or more of a predefined policy and predefined rules.« less

  7. EVALUATION OF ARG-1 SAMPLES PREPARED BY CESIUM CARBONATE DISSOLUTION DURING THE ISOLOK SME ACCEPTABILITY TESTING

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

    Edwards, T.; Hera, K.; Coleman, C.

    2011-12-05

    Evaluation of Defense Waste Processing Facility (DWPF) Chemical Process Cell (CPC) cycle time identified several opportunities to improve the CPC processing time. The Mechanical Systems & Custom Equipment Development (MS&CED) Section of the Savannah River National Laboratory (SRNL) recently completed the evaluation of one of these opportunities - the possibility of using an Isolok sampling valve as an alternative to the Hydragard valve for taking DWPF process samples at the Slurry Mix Evaporator (SME). The use of an Isolok for SME sampling has the potential to improve operability, reduce maintenance time, and decrease CPC cycle time. The SME acceptability testingmore » for the Isolok was requested in Task Technical Request (TTR) HLW-DWPF-TTR-2010-0036 and was conducted as outlined in Task Technical and Quality Assurance Plan (TTQAP) SRNLRP-2011-00145. RW-0333P QA requirements applied to the task, and the results from the investigation were documented in SRNL-STI-2011-00693. Measurement of the chemical composition of study samples was a critical component of the SME acceptability testing of the Isolok. A sampling and analytical plan supported the investigation with the analytical plan directing that the study samples be prepared by a cesium carbonate (Cs{sub 2}CO{sub 3}) fusion dissolution method and analyzed by Inductively Coupled Plasma - Optical Emission Spectroscopy (ICP-OES). The use of the cesium carbonate preparation method for the Isolok testing provided an opportunity for an additional assessment of this dissolution method, which is being investigated as a potential replacement for the two methods (i.e., sodium peroxide fusion and mixed acid dissolution) that have been used at the DWPF for the analysis of SME samples. Earlier testing of the Cs{sub 2}CO{sub 3} method yielded promising results which led to a TTR from Savannah River Remediation, LLC (SRR) to SRNL for additional support and an associated TTQAP to direct the SRNL efforts. A technical report

  8. Quantification of the Thermodynamically Linked Quaternary and Tertiary Structural Stabilities of Transthyretin and its Disease-Associated Variants–the Relationship between Stability and Amyloidosis†

    PubMed Central

    Hurshman Babbes, Amy R.; Powers, Evan T.; Kelly, Jeffery W.

    2009-01-01

    Urea denaturation studies were carried out as a function of transthyretin (TTR) concentration to quantify the thermodynamically linked quaternary and tertiary structural stability and to better understand the relationship between mutant folding energetics and amyloid disease phenotype. Urea denaturation of TTR involves at least two equilibria—dissociation of tetramers into folded monomers, and monomer unfolding. To deal with the thermodynamic linkage of these equilibria, we analyzed concentration-dependent denaturation data by global fitting to an equation that simultaneously accounts for the two-step denaturation process. Using this method, the quaternary and tertiary structural stabilities of well-behaved TTR sequences, wild type (WT) TTR and the disease-associated variant V122I, were scrutinized. The V122I variant is linked to late onset familial amyloid cardiomyopathy, the most common familial TTR amyloid disease. V122I TTR exhibits a destabilized quaternary structure and a stable tertiary structure relative to WT TTR. Three other variants of TTR were also examined, L55P, V30M, and A25T TTR. The L55P mutation is associated with the most aggressive familial TTR amyloid disease. L55P TTR has a complicated denaturation pathway that includes dimers and trimers, and so globally fitting its concentration-dependent urea denaturation data yielded error-laden estimates of stability parameters. Nevertheless, it is clear that L55P TTR is substantially less stable than WT TTR, primarily because its tertiary structure is unstable, although its quaternary structure is destabilized as well. V30M is the most common mutation associated with neuropathic forms of TTR amyloid disease. V30M TTR is certainly destabilized relative to WT TTR, but like L55P TTR it has a complex denaturation pathway that cannot be fit to the aforementioned two-step denaturation model. Literature data suggest that V30M TTR has stable quaternary structure but unstable tertiary structure. The A25T mutant

  9. Repositioning tolcapone as a potent inhibitor of transthyretin amyloidogenesis and associated cellular toxicity

    PubMed Central

    Sant'Anna, Ricardo; Gallego, Pablo; Robinson, Lei Z.; Pereira-Henriques, Alda; Ferreira, Nelson; Pinheiro, Francisca; Esperante, Sebastian; Pallares, Irantzu; Huertas, Oscar; Rosário Almeida, Maria; Reixach, Natàlia; Insa, Raul; Velazquez-Campoy, Adrian; Reverter, David; Reig, Núria; Ventura, Salvador

    2016-01-01

    Transthyretin (TTR) is a plasma homotetrameric protein implicated in fatal systemic amyloidoses. TTR tetramer dissociation precedes pathological TTR aggregation. Native state stabilizers are promising drugs to treat TTR amyloidoses. Here we repurpose tolcapone, an FDA-approved molecule for Parkinson's disease, as a potent TTR aggregation inhibitor. Tolcapone binds specifically to TTR in human plasma, stabilizes the native tetramer in vivo in mice and humans and inhibits TTR cytotoxicity. Crystal structures of tolcapone bound to wild-type TTR and to the V122I cardiomyopathy-associated variant show that it docks better into the TTR T4 pocket than tafamidis, so far the only drug on the market to treat TTR amyloidoses. These data indicate that tolcapone, already in clinical trials for familial amyloid polyneuropathy, is a strong candidate for therapeutic intervention in these diseases, including those affecting the central nervous system, for which no small-molecule therapy exists. PMID:26902880

  10. The validation of procedures to assess prevocational task preferences in retarded adults.

    PubMed

    Mithaug, D E; Hanawalt, D A

    1978-01-01

    Three severely retarded young adults between the ages of 19 and 21 years participated in a prevocational training program, and worked regularly on six different tasks during the scheduled six-hour day. The study attempted to assess each subject's preferences for the six tasks: collating, stuffing, sorting, pulley assembly, flour-sifter assembly, and circuit-board stuffing. In Phase I, the procedure consisted of randomly pairing each task with all other tasks in a two-choice situation that required the subjects to select one task from each pair combination to work for a seven-minute period. The selection procedure consisted of presenting two representative task objects on a tray and requesting the subject to pick up one object and place it on the work table. The object selected represented the task worked for that period. The 15 possible pair combinations were presented randomly every two days for a period of 34 days to determine the preferences. During the validation phase (Phase II), each subject's least- and most-preferred tasks were paired separately with moderately-preferred tasks. As expected, these manipulations confirmed the baseline data, as choices for the moderately-preferred tasks decreased when consistently paired with the preferred tasks and increased when consistently paired with the least-preferred tasks.

  11. Selective binding to transthyretin and tetramer stabilization in serum from patients with familial amyloidotic polyneuropathy by an iodinated diflunisal derivative

    PubMed Central

    2004-01-01

    In familial amyloidotic polyneuropathy, TTR (transthyretin) variants are deposited as amyloid fibrils. It is thought that this process involves TTR tetramer dissociation, which leads to partially unfolded monomers that aggregate and polymerize into amyloid fibrils. This process can be counteracted by stabilization of the tetramer. Several small compounds, such as diclofenac, diflunisal and flufenamic acid, have been reported to bind to TTR in vitro, in the T4 (thyroxine) binding channel that runs through the TTR tetramer, and consequently are considered to stabilize TTR. However, if these agents bind plasma proteins other than TTR, decreased drug availability will occur, compromising their use as therapeutic agents for TTR amyloidosis. In the present work, we compared the action of these compounds and of new derivatives designed to increase both selectivity of binding to TTR and inhibitory potency in relation to TTR amyloid fibril formation. We found two diflunisal derivatives that, in contrast with diclofenac, flufenamic acid and diflunisal, displaced T4 from TTR in plasma preferentially over binding to albumin and thyroxine binding globulin. The same diflunisal derivatives also had a stabilizing effect on TTR tetramers in plasma, as studied by isoelectric focusing of whole plasma under semi-denaturing conditions. In addition, by transmission electron microscopy, we demonstrated that, in contrast with other proposed TTR stabilizers (namely diclofenac, flufenamic acid and diflunisal), one of the diflunisal derivatives tested efficiently inhibited TTR aggregation. Taken together, our ex vivo and in vitro studies present evidence for the selectivity and efficiency of novel diflunisal derivates as TTR stabilizers and as inhibitors of fibril formation. PMID:15080795

  12. Million Hearts 2022: Understanding the Links between Environmental Pollutant Exposure and Cardiovascular and Cerebrovascular Events - Justus-Warren Heart Disease and Stroke Prevention Task Force

    EPA Science Inventory

    The webinar was requested by the Justus-Warren Heart Disease and Stroke Prevention Task Force. From their website, “The task force was established in 1995 in North Carolina to provide statewide leadership for the prevention and management of cardiovascular disease. Meetings are...

  13. A strategic stakeholder approach for addressing further analysis requests in whole genome sequencing research.

    PubMed

    Thornock, Bradley Steven O

    2016-01-01

    Whole genome sequencing (WGS) can be a cost-effective and efficient means of diagnosis for some children, but it also raises a number of ethical concerns. One such concern is how researchers derive and communicate results from WGS, including future requests for further analysis of stored sequences. The purpose of this paper is to think about what is at stake, and for whom, in any solution that is developed to deal with such requests. To accomplish this task, this paper will utilize stakeholder theory, a common method used in business ethics. Several scenarios that connect stakeholder concerns and WGS will also posited and analyzed. This paper concludes by developing criteria composed of a series of questions that researchers can answer in order to more effectively address requests for further analysis of stored sequences.

  14. Cultural Influences on Toddlers' Prosocial Behavior: How Maternal Task Assignment Relates to Helping Others

    ERIC Educational Resources Information Center

    Köster, Moritz; Cavalcante, Lilia; Vera Cruz de Carvalho, Rafael; Dôgo Resende, Briseida; Kärtner, Joscha

    2016-01-01

    This cross-cultural study investigates how maternal task assignment relates to toddlers' requested behavior and helping between 18 and 30 months. One hundred seven mother-child dyads were assessed in three different cultural contexts (rural Brazil, urban Germany, and urban Brazil). Brazilian mothers showed assertive scaffolding (serious and…

  15. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, for Calendar Year 2012

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

    NSTec Environmental Restoration

    2013-01-28

    This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2012 and includes inspection and repair activities completed at the following CAUs: · CAU 400: Bomblet Pit and Five Points Landfill (TTR) · CAU 407: Roller Coaster RadSafe Area (TTR) · CAU 424: Area 3 Landfill Complexes (TTR) · CAU 453: Area 9 UXO Landfill (TTR) · CAU 487: Thunderwell Site (TTR)

  16. Research of GIS-services applicability for solution of spatial analysis tasks.

    NASA Astrophysics Data System (ADS)

    Terekhin, D. A.; Botygin, I. A.; Sherstneva, A. I.; Sherstnev, V. S.

    2017-01-01

    Experiments for working out the areas of applying various gis-services in the tasks of spatial analysis are discussed in this paper. Google Maps, Yandex Maps, Microsoft SQL Server are used as services of spatial analysis. All services have shown a comparable speed of analyzing the spatial data when carrying out elemental spatial requests (building up the buffer zone of a point object) as well as the preferences of Microsoft SQL Server in operating with more complicated spatial requests. When building up elemental spatial requests, internet-services show higher efficiency due to cliental data handling with JavaScript-subprograms. A weak point of public internet-services is an impossibility to handle data on a server side and a barren variety of spatial analysis functions. Microsoft SQL Server offers a large variety of functions needed for spatial analysis on the server side. The authors conclude that when solving practical problems, the capabilities of internet-services used in building up routes and completing other functions with spatial analysis with Microsoft SQL Server should be involved.

  17. 77 FR 27801 - Request for Comments-LSC Budget Request for FY 2014

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... LEGAL SERVICES CORPORATION Request for Comments--LSC Budget Request for FY 2014 AGENCY: Legal Services Corporation. ACTION: Request for Comments--LSC Budget Request for FY 2014. SUMMARY: The Legal Services Corporation is beginning the process of developing its FY 2014 budget request to Congress and is...

  18. 76 FR 34102 - Request for Comments-LSC Budget Request for FY 2013

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-10

    ... LEGAL SERVICES CORPORATION Request for Comments--LSC Budget Request for FY 2013 AGENCY: Legal Services Corporation. ACTION: Request for Comments--LSC Budget Request for FY 2013. SUMMARY: The Legal Services Corporation is beginning the process of developing its FY 2013 budget request to Congress and is...

  19. 75 FR 54389 - Request for Comments-LSC Budget Request for FY 2012

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-07

    ... LEGAL SERVICES CORPORATION Request for Comments--LSC Budget Request for FY 2012 AGENCY: Legal Services Corporation. ACTION: Request for Comments--LSC Budget Request for FY 2012. SUMMARY: The Legal Services Corporation is beginning the process of developing its FY 2012 budget request to Congress and is...

  20. Supervisory Control of a Humanoid Robot in Microgravity for Manipulation Tasks

    NASA Technical Reports Server (NTRS)

    Farrell, Logan C.; Strawser, Phil; Hambuchen, Kimberly; Baker, Will; Badger, Julia

    2017-01-01

    Teleoperation is the dominant form of dexterous robotic tasks in the field. However, there are many use cases in which direct teleoperation is not feasible such as disaster areas with poor communication as posed in the DARPA Robotics Challenge, or robot operations on spacecraft a large distance from Earth with long communication delays. Presented is a solution that combines the Affordance Template Framework for object interaction with TaskForce for supervisory control in order to accomplish high level task objectives with basic autonomous behavior from the robot. TaskForce, is a new commanding infrastructure that allows for optimal development of task execution, clear feedback to the user to aid in off-nominal situations, and the capability to add autonomous verification and corrective actions. This framework has allowed the robot to take corrective actions before requesting assistance from the user. This framework is demonstrated with Robonaut 2 removing a Cargo Transfer Bag from a simulated logistics resupply vehicle for spaceflight using a single operator command. This was executed with 80% success with no human involvement, and 95% success with limited human interaction. This technology sets the stage to do any number of high level tasks using a similar framework, allowing the robot to accomplish tasks with minimal to no human interaction.

  1. 43 CFR 4.1363 - Contents of request; amendment of request; responses.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Request for Review of Approval Or Disapproval of Applications for New Permits, Permit Revisions, Permit Renewals, the Transfer, Assignment Or Sale of Rights Granted Under Permit (federal Program; Federal Lands... Contents of request; amendment of request; responses. (a) The request for review shall include— (1) A clear...

  2. The WorkQueue project - a task queue for the CMS workload management system

    NASA Astrophysics Data System (ADS)

    Ryu, S.; Wakefield, S.

    2012-12-01

    We present the development and first experience of a new component (termed WorkQueue) in the CMS workload management system. This component provides a link between a global request system (Request Manager) and agents (WMAgents) which process requests at compute and storage resources (known as sites). These requests typically consist of creation or processing of a data sample (possibly terabytes in size). Unlike the standard concept of a task queue, the WorkQueue does not contain fully resolved work units (known typically as jobs in HEP). This would require the WorkQueue to run computationally heavy algorithms that are better suited to run in the WMAgents. Instead the request specifies an algorithm that the WorkQueue uses to split the request into reasonable size chunks (known as elements). An advantage of performing lazy evaluation of an element is that expanding datasets can be accommodated by having job details resolved as late as possible. The WorkQueue architecture consists of a global WorkQueue which obtains requests from the request system, expands them and forms an element ordering based on the request priority. Each WMAgent contains a local WorkQueue which buffers work close to the agent, this overcomes temporary unavailability of the global WorkQueue and reduces latency for an agent to begin processing. Elements are pulled from the global WorkQueue to the local WorkQueue and into the WMAgent based on the estimate of the amount of work within the element and the resources available to the agent. WorkQueue is based on CouchDB, a document oriented NoSQL database. The WorkQueue uses the features of CouchDB (map/reduce views and bi-directional replication between distributed instances) to provide a scalable distributed system for managing large queues of work. The project described here represents an improvement over the old approach to workload management in CMS which involved individual operators feeding requests into agents. This new approach allows for a

  3. Caenorhabditis elegans as a model system to study post-translational modifications of human transthyretin

    NASA Astrophysics Data System (ADS)

    Henze, Andrea; Homann, Thomas; Rohn, Isabelle; Aschner, Michael; Link, Christopher D.; Kleuser, Burkhard; Schweigert, Florian J.; Schwerdtle, Tanja; Bornhorst, Julia

    2016-11-01

    The visceral protein transthyretin (TTR) is frequently affected by oxidative post-translational protein modifications (PTPMs) in various diseases. Thus, better insight into structure-function relationships due to oxidative PTPMs of TTR should contribute to the understanding of pathophysiologic mechanisms. While the in vivo analysis of TTR in mammalian models is complex, time- and resource-consuming, transgenic Caenorhabditis elegans expressing hTTR provide an optimal model for the in vivo identification and characterization of drug-mediated oxidative PTPMs of hTTR by means of matrix assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS). Herein, we demonstrated that hTTR is expressed in all developmental stages of Caenorhabditis elegans, enabling the analysis of hTTR metabolism during the whole life-cycle. The suitability of the applied model was verified by exposing worms to D-penicillamine and menadione. Both drugs induced substantial changes in the oxidative PTPM pattern of hTTR. Additionally, for the first time a covalent binding of both drugs with hTTR was identified and verified by molecular modelling.

  4. Quantification of Transthyretin Kinetic Stability in Human Plasma Using Subunit Exchange

    PubMed Central

    2015-01-01

    The transthyretin (TTR) amyloidoses are a group of degenerative diseases caused by TTR aggregation, requiring rate-limiting tetramer dissociation. Kinetic stabilization of TTR, by preferential binding of a drug to the native tetramer over the dissociative transition state, dramatically slows the progression of familial amyloid polyneuropathy. An established method for quantifying the kinetic stability of recombinant TTR tetramers in buffer is subunit exchange, in which tagged TTR homotetramers are added to untagged homotetramers at equal concentrations to measure the rate at which the subunits exchange. Herein, we report a subunit exchange method for quantifying the kinetic stability of endogenous TTR in human plasma. The subunit exchange reaction is initiated by the addition of a substoichiometric quantity of FLAG-tagged TTR homotetramers to endogenous TTR in plasma. Aliquots of the subunit exchange reaction, taken as a function of time, are then added to an excess of a fluorogenic small molecule, which immediately arrests further subunit exchange. After binding, the small molecule reacts with the TTR tetramers, rendering them fluorescent and detectable in human plasma after subsequent ion exchange chromatography. The ability to report on the extent of TTR kinetic stabilization resulting from treatment with oral tafamidis is important, especially for selection of the appropriate dose for patients carrying rare mutations. This method could also serve as a surrogate biomarker for the prediction of the clinical outcome. Subunit exchange was used to quantify the stabilization of WT TTR from senile systemic amyloidosis patients currently being treated with tafamidis (20 mg orally, once daily). TTR kinetic stability correlated with the tafamidis plasma concentration. PMID:24661308

  5. Serum transthyretin levels in senile systemic amyloidosis: effects of age, gender and ethnicity

    PubMed Central

    Buxbaum, Joel; Koziol, James; Connors, Lawreen H.

    2017-01-01

    Serum transthyretin (TTR) levels are reduced in familial amyloidotic polyneuropathy (FAP). A single study of patients with senile systemic amyloidosis (SSA) in Sweden found that those individuals also had a significantly lower mean serum TTR concentration than age- and gender-matched controls. To determine if the same phenomenon prevailed in an ethnically more heterogeneous population, we compared the serum TTR levels, as determined by ELISA, in 45 documented SSA patients with congestive heart failure, 20 AL patients with congestive heart failure and population controls. Serum TTR concentrations in the controls were influenced in a statistically significant manner by age, gender and ethnicity. Although it is unlikely that such differences are clinically relevant, they must be considered when assessing the meaning of serum TTR concentrations in any clinically defined population. The serum concentrations in patients with SSA did not differ from age, gender and ethnically matched controls or from a group of AL patients with significant clinical cardiac involvement. We also compared TTR concentrations in 12 African-Americans carrying the TTR V122I allele with those in 826 African-Americans who were homozygous wild type at the TTR locus. The TTR V122I carriers had significantly lower serum TTR concentrations than appropriate controls even though the majority of such individuals had not reached the age of clinical or anatomic risk, i.e. over 60. Thus, as in carriers of other TTR mutations the serum TTR level is lower than normal, despite having a much later appearance of clinical disease. PMID:19065297

  6. Closure Letter Report for Corrective Action Unit 496: Buried Rocket Site - Antelope Lake

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

    NSTec Environmental Restoration

    A Streamlined Approach for Environmental Restoration (SAFER) Plan for investigation and closure of CAU 496, Corrective Action Site (CAS) TA-55-008-TAAL (Buried Rocket), at the Tonopah Test Range (TTR), was approved by the Nevada Department of Environmental Protection (NDEP) on July 21,2004. Approval to transfer CAS TA-55-008-TAAL from CAU 496 to CAU 4000 (No Further Action Sites) was approved by NDEP on December 21, 2005, based on the assumption that the rocket did not present any environmental concern. The approval letter included the following condition: ''NDEP understands, from the NNSA/NSO letter dated November 30,2005, that a search will be conducted formore » the rocket during the planned characterization of other sites at the Tonopah Test Range and, if found, the rocket will be removed as a housekeeping measure''. NDEP and U.S. Department of Energy, National Nuclear Security Administration Nevada Site Office personnel located the rocket on Mid Lake during a site visit to TTR, and a request to transfer CAS TA-55-008-TAAL from CAU 4000 back to CAU 496 was approved by NDEP on September 11,2006. CAS TA-55-008-TAAL was added to the ''Federal Facility Agreement and Consent Order'' of 1996, based on an interview with a retired TTR worker in 1993. The original interview documented that a rocket was launched from Area 9 to Antelope Lake and was never recovered due to the high frequency of rocket tests being conducted during this timeframe. The interviewee recalled the rocket being an M-55 or N-55 (the M-50 ''Honest John'' rocket was used extensively at TTR from the 1960s to early 1980s). A review of previously conducted interviews with former TTR personnel indicated that the interviewees confused information from several sites. The location of the CAU 496 rocket on Mid Lake is directly south of the TTR rocket launch facility in Area 9 and is consistent with information gathered on the lost rocket during recent interviews. Most pertinently, an interview in 2005 with

  7. Self-identified Obese People Request Less Money: A Field Experiment.

    PubMed

    Proestakis, Antonios; Brañas-Garza, Pablo

    2016-01-01

    Empirical evidence suggests that obese people are discriminated in different social environments, such as the work place. Yet, the degree to which obese people are internalizing and adjusting their own behavior as a result of this discriminatory behavior has not been thoroughly studied. We develop a proxy for measuring experimentally the "self-weight bias" by giving to both self-identified obese ( n = 90) and non-obese ( n = 180) individuals the opportunity to request a positive amount of money after having performed an identical task. Consistent with the System Justification Theory, we find that self-identified obese individuals, due to a preexisting false consciousness , request significantly lower amounts of money than non-obese ones. A within subject comparison between self-reports and external monitors' evaluations reveals that the excessive weight felt by the "self" but not reported by evaluators captures the self-weight bias not only for obese but also for non-obese individuals. Linking our experimental results to the supply side of the labor market, we argue that self-weight bias, as expressed by lower salary requests, enhances discriminatory behavior against individuals who feel, but may not actually be, obese and consequently exacerbates the wage gap across weight.

  8. Warfarin time in therapeutic range and its impact on healthcare resource utilization and costs among patients with nonvalvular atrial fibrillation.

    PubMed

    Deitelzweig, Steve; Evans, Michael; Hillson, Eric; Trocio, Jeffrey; Bruno, Amanda; Tan, Wilson; Lingohr-Smith, Melissa; Singh, Prianka; Lin, Jay

    2016-01-01

    Warfarin is efficacious for reducing stroke risk among patients with nonvalvular atrial fibrillation (NVAF). However, the efficacy and safety of warfarin are influenced by its time in therapeutic range (TTR). To assess differences in healthcare resource utilization and costs among NVAF patients with low (<60%) and high (≥60%) warfarin TTRs in an integrated delivery network (IDN) setting. Patients with NVAF were identified from an electronic medical record database. Patients were required to have ≥6 international normalized prothrombin time ratio (INR) tests. NVAF patients were grouped into two cohorts: those with warfarin TTR <60% (low TTR) and those with warfarin TTR ≥60% (high TTR). Healthcare resource utilization and costs were evaluated during a 12 month follow-up period. Multivariable regressions were used to assess the impact of different warfarin TTRs on healthcare costs. Among the study population, greater than half (54%, n = 1595) had a low TTR, and 46% (n = 1356) had a high TTR. Total all-cause healthcare resource utilization was higher among patients in the low TTR cohort vs. the high TTR cohort (number of encounters: 70.2 vs. 56.1, p < 0.001). After adjusting for patient characteristics, total all-cause healthcare costs and stroke-related healthcare costs were $2398 (p < 0.001) and $687 (p = 0.02) higher, respectively, for patients in the low TTR cohort vs. the high TTR cohort. In this retrospective study, we were only able to evaluate the association and not the causality between healthcare resource utilization and costs with the different warfarin TTRs. Many warfarin-treated NVAF patients have a low warfarin TTR. NVAF patients with low vs. patients with high warfarin TTR used healthcare resources to a greater extent, which was reflected in higher healthcare costs.

  9. 77 FR 58143 - Interagency Task Force on Antimicrobial Resistance (ITFAR): An Update of A Public Health Action...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-19

    ...-2012-0011] Interagency Task Force on Antimicrobial Resistance (ITFAR): An Update of A Public Health...), Department of Health and Human Services (HHS). ACTION: Notice of public meeting and request for comments... Federal agencies in accomplishing activities outlined in ``A Public Health Action Plan to Combat...

  10. REQUEST A COLOR GUARD

    Science.gov Websites

    EMERGENCY PREPAREDNESS CONTACT REQUEST A SPEAKER REQUEST A COLOR GUARD OPERATIONAL CONTRACT SUPPORT HomeCONTACTREQUEST A COLOR GUARD Request a Color Guard Please take a moment to fill out the document at the link one month to process your request, but no more than three. Color Guard Request Form For Community

  11. 40 CFR 57.804 - Request for hearing; request to participate in hearing.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 5 2010-07-01 2010-07-01 false Request for hearing; request to participate in hearing. 57.804 Section 57.804 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... of Continuous Emission Reduction Technology § 57.804 Request for hearing; request to participate in...

  12. Central transthyretin acts to decrease food intake and body weight

    PubMed Central

    Zheng, Fenping; Kim, Yonwook J.; Moran, Timothy H.; Li, Hong; Bi, Sheng

    2016-01-01

    Transthyretin (TTR) is a blood and cerebrospinal fluid transporter of thyroxine and retinol. Gene expression profiling revealed an elevation of Ttr expression in the dorsomedial hypothalamus (DMH) of rats with exercise-induced anorexia, implying that central TTR may also play a functional role in modulating food intake and energy balance. To test this hypothesis, we have examined the effects of brain TTR on food intake and body weight and have further determined hypothalamic signaling that may underlie its feeding effect in rats. We found that intracerebroventricular (icv) administration of TTR in normal growing rats decreased food intake and body weight. This effect was not due to sickness as icv TTR did not cause a conditioned taste aversion. ICV TTR decreased neuropeptide Y (NPY) levels in the DMH and the paraventricular nucleus (P < 0.05). Chronic icv infusion of TTR in Otsuka Long-Evans Tokushima Fatty rats reversed hyperphagia and obesity and reduced DMH NPY levels. Overall, these results demonstrate a previously unknown anorectic action of central TTR in the control of energy balance, providing a potential novel target for treating obesity and its comorbidities. PMID:27053000

  13. The Oklahoma Attorney General's Task Force report on the State of End-of-Life Health Care, 2005.

    PubMed

    Edmondson, W A Drew

    2005-05-01

    This article includes the recommendations submitted by the 15 members of the Oklahoma Attorney General's Task Force in their Report on the State of End-of-Life Health Care. The task force was created on April 21, 2004, and their report was accepted by Attorney General W.A. Drew Edmondson at a press conference April 11, 2005. It has been forwarded to members of the Oklahoma Legislature, relevant state agencies and organizations with an invitation to join with members of the task force to continue efforts to improve end-of-life care for Oklahomans. Copies of the report are available upon request to the Office of Attorney General.

  14. Lessons Learned from Crowdsourcing Complex Engineering Tasks.

    PubMed

    Staffelbach, Matthew; Sempolinski, Peter; Kijewski-Correa, Tracy; Thain, Douglas; Wei, Daniel; Kareem, Ahsan; Madey, Gregory

    2015-01-01

    Crowdsourcing is the practice of obtaining needed ideas, services, or content by requesting contributions from a large group of people. Amazon Mechanical Turk is a web marketplace for crowdsourcing microtasks, such as answering surveys and image tagging. We explored the limits of crowdsourcing by using Mechanical Turk for a more complicated task: analysis and creation of wind simulations. Our investigation examined the feasibility of using crowdsourcing for complex, highly technical tasks. This was done to determine if the benefits of crowdsourcing could be harnessed to accurately and effectively contribute to solving complex real world engineering problems. Of course, untrained crowds cannot be used as a mere substitute for trained expertise. Rather, we sought to understand how crowd workers can be used as a large pool of labor for a preliminary analysis of complex data. We compared the skill of the anonymous crowd workers from Amazon Mechanical Turk with that of civil engineering graduate students, making a first pass at analyzing wind simulation data. For the first phase, we posted analysis questions to Amazon crowd workers and to two groups of civil engineering graduate students. A second phase of our experiment instructed crowd workers and students to create simulations on our Virtual Wind Tunnel website to solve a more complex task. With a sufficiently comprehensive tutorial and compensation similar to typical crowd-sourcing wages, we were able to enlist crowd workers to effectively complete longer, more complex tasks with competence comparable to that of graduate students with more comprehensive, expert-level knowledge. Furthermore, more complex tasks require increased communication with the workers. As tasks become more complex, the employment relationship begins to become more akin to outsourcing than crowdsourcing. Through this investigation, we were able to stretch and explore the limits of crowdsourcing as a tool for solving complex problems.

  15. Lessons Learned from Crowdsourcing Complex Engineering Tasks

    PubMed Central

    Kijewski-Correa, Tracy; Thain, Douglas; Kareem, Ahsan; Madey, Gregory

    2015-01-01

    Crowdsourcing Crowdsourcing is the practice of obtaining needed ideas, services, or content by requesting contributions from a large group of people. Amazon Mechanical Turk is a web marketplace for crowdsourcing microtasks, such as answering surveys and image tagging. We explored the limits of crowdsourcing by using Mechanical Turk for a more complicated task: analysis and creation of wind simulations. Harnessing Crowdworkers for Engineering Our investigation examined the feasibility of using crowdsourcing for complex, highly technical tasks. This was done to determine if the benefits of crowdsourcing could be harnessed to accurately and effectively contribute to solving complex real world engineering problems. Of course, untrained crowds cannot be used as a mere substitute for trained expertise. Rather, we sought to understand how crowd workers can be used as a large pool of labor for a preliminary analysis of complex data. Virtual Wind Tunnel We compared the skill of the anonymous crowd workers from Amazon Mechanical Turk with that of civil engineering graduate students, making a first pass at analyzing wind simulation data. For the first phase, we posted analysis questions to Amazon crowd workers and to two groups of civil engineering graduate students. A second phase of our experiment instructed crowd workers and students to create simulations on our Virtual Wind Tunnel website to solve a more complex task. Conclusions With a sufficiently comprehensive tutorial and compensation similar to typical crowd-sourcing wages, we were able to enlist crowd workers to effectively complete longer, more complex tasks with competence comparable to that of graduate students with more comprehensive, expert-level knowledge. Furthermore, more complex tasks require increased communication with the workers. As tasks become more complex, the employment relationship begins to become more akin to outsourcing than crowdsourcing. Through this investigation, we were able to stretch and

  16. Cysteinylated transthyretin as a discriminator of cardiovascular risk in patients with diabetes mellitus.

    PubMed

    Wakabayashi, Ichiro; Marumo, Mikio; Nonaka, Daisuke; Lee, Lyang-Ja; Mukai, Jun; Ohki, Makoto; Tanaka, Kenji; Uchida, Kagehiro

    2017-07-01

    The cysteine residue on transthyretin (TTR) is susceptible to be oxidized, and serum cysteinylated TTR (Cys-TTR) level is thought to reflect oxidative stress. The purpose of this study was to elucidate the relationship between Cys-TTR and arterial stiffness, a known predictor of cardiovascular disease, in patients with type 2 diabetes. The subjects were 105 male outpatients with type 2 diabetes. Arterial stiffness was evaluated by measuring cardio-ankle vascular index (CAVI). The relationship between CAVI and ratio of Cys-TTR to total TTR (Cys-TTR ratio) was analyzed. Cys-TTR ratio was significantly correlated with CAVI (Pearson's correlation coefficient: 0.316, p<0.01), and CAVI was significantly higher in the 3rd tertile group for Cys-TTR ratio than in its 1st tertile group. These relationships were also significant after adjusting for age, smoking, alcohol drinking, body mass index, mean arterial pressure, hemoglobin A1c, LDL cholesterol-to-HDL cholesterol ratio and eGFR. Prevalence of high CAVI (≥10.0) was significantly higher in the 3rd tertile for Cys-TTR ratio than in its 1st tertile and tended to be higher with an increase in tertile (28.6% in the 1st tertile, 42.9% in the 2nd tertile and 60.0% in the 3rd tertile). Odds ratio (OR) for high CAVI of the 3rd vs. 1st tertile groups for Cys-TTR ratio was significantly higher than the reference level of 1.00 both before and after adjustment for the above cardiovascular risk factors (crude OR, 3.75 [1.38-10.17]; adjusted OR, 5.09 [1.39-18.64]). Cys-TTR ratio is associated with arterial stiffness in patients with diabetes and is proposed as a new discriminator of cardiovascular risk. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Use of Serum Transthyretin as a Prognostic Indicator and Predictor of Outcome in Cardiac Amyloid Disease Associated With Wild-Type Transthyretin.

    PubMed

    Hanson, Jacquelyn L S; Arvanitis, Marios; Koch, Clarissa M; Berk, John L; Ruberg, Frederick L; Prokaeva, Tatiana; Connors, Lawreen H

    2018-02-01

    Wild-type transthyretin amyloidosis (ATTRwt), an underappreciated cause of heart failure in older adults, is challenging to diagnose and monitor in the absence of validated, disease-specific biomarkers. We examined the prognostic use and survival association of serum TTR (transthyretin) concentration in ATTRwt. Patients with biopsy-proven ATTRwt were retrospectively identified. Serum TTR, cardiac biomarkers, and echocardiographic parameters were assessed at baseline and follow-up evaluations. Statistical analyses included Kaplan-Meier method, Cox proportional hazard survival models, and receiver-operating characteristic curve analysis. Median serum TTR concentration at presentation was 23 mg/dL (n=116). Multivariate predictors of shorter overall survival were decreased TTR, left ventricular ejection fraction and elevated cTn-I (cardiac troponin I); an inclusive model demonstrated superior accuracy in 4-year survival prediction by receiver-operating characteristic curve analysis (area under the curve, 0.77). TTR values lower than the normal limit, <18 mg/dL, were associated with shorter survival (2.8 versus 4.1 years; P =0.03). Further, TTR values at 1- and 2-year follow-ups were significantly lower ( P <0.001) in untreated patients (n=23) compared with those treated with TTR stabilizer, diflunisal (n=12), after baseline evaluation. During 2-year follow-up, unchanged TTR corresponded to increased cTn-I ( P =0.006) in untreated patients; conversely, the diflunisal-treated group showed increased TTR ( P =0.001) and stabilized cTn-I and left ventricular ejection fraction at 1 year. In this series of biopsy-proven ATTRwt, lower baseline serum TTR concentration was associated with shorter survival as an independent predictor of outcome. Longitudinal analysis demonstrated that decreasing TTR corresponded to worsening cardiac function. These data suggest that TTR may be a useful prognostic marker and predictor of outcome in ATTRwt. © 2018 American Heart Association, Inc.

  18. 78 FR 66382 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Request by...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-05

    ... Information Collection Activities; Proposed Collection; Comments Requested: Request by Organization for... Information Collection: New Voluntary Collection. (2) Title of the Form/Collection: Request by Organization... information collection request to the Office of Management and Budget (OMB) for review and approval in...

  19. Constructing a Scale to Assess L2 Written Speech Act Performance: WDCT and E-Mail Tasks

    ERIC Educational Resources Information Center

    Chen, Yuan-shan; Liu, Jianda

    2016-01-01

    This study reports the development of a scale to evaluate the speech act performance by intermediate-level Chinese learners of English. A qualitative analysis of the American raters' comments was conducted on learner scripts in response to a total of 16 apology and request written discourse completion task (WDCT) situations. The results showed…

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

    Buxbaum, J.; Pastore, R.; Yaghoubian, R.

    Point mutations in the protein transthyretin (TTR) cause familial amyloidosis involving mainly the heart and peripheral nerves. To determine the TTR Ile 122 gene frequency in African Americans, the allele encoding TTR Ile 122 was identified by PCR-Primer Introduced Restriction Analysis of TTR exon 4 and FokI digestion on 1659 control DNA samples from 1659 African Americans: 64 were heterozygous and one homozygous (allele frequency .02). To determine the risk to gene carriers of developing cardiac amyloidosis, immunohistochemical and genetic studies were performed on amyloid-containing samples identified among 52,370 autopsy samples examined over 32 years. In autopsy samples from patientsmore » over age 60, isolated cardiac amyloidosis was more common in African Americans (1.6%) than in White Americans (.40%), suggesting a genetic risk factor. All 29 samples from African Americans were immunohistochemically TTR-positive, and 5 were heterozygous for the TTR Ile 122 allele (17%), as compared with 5/108 heterozygotes (4.6%) among age-matched (over age 60) African American controls without amyloidosis from the same autopsy study (one-tailed P value < .03). Among the 29 amyloid-positive samples were 16 with 1+ or 2+ deposition and 13 with 3+ or 4+ deposition. All 5 TTR Ile 122 heterozygotes had 3+ or 4+ deposition. None of 15 samples from White Americans with cardiac amyloidosis was TTR Ile 122-positive. Extrapolating from the 5/29 samples from which we were able to obtain genetic data, we estimate that 9/54 samples containing cardiac amyloid were TTR Ile 122 heterozygotes. We conclude that heterozygosity for TTR Ile 122 is associated with a greater frequency (relative risk 5.8) and greater severity of cardiac amyloid deposition than in non-carriers of the TTR Ile 122 gene. Of over 40 TTR point mutations associated with amyloidosis described to date, TTR Ile 122 appears to be the most common worldwide and to have the lowest penetrance in causing disease.« less

  1. Recommendations for presymptomatic genetic testing and management of individuals at risk for hereditary transthyretin amyloidosis.

    PubMed

    Obici, Laura; Kuks, Jan B; Buades, Juan; Adams, David; Suhr, Ole B; Coelho, Teresa; Kyriakides, Theodore

    2016-02-01

    These recommendations highlight recent experience in genetic counselling for the severe autosomal-dominant, late-onset transthyretin familial amyloid polyneuropathy (TTR-FAP) disease, and present a structured approach towards identification and monitoring of asymptomatic carriers of the mutated gene. The effectiveness of current treatment options is still limited in patients with TTR-FAP beyond stage I. Diagnosis in the early stages of TTR-FAP is essential to prevent or delay the progression of disease. Existing legal and cultural issues differ among countries within Europe. Experts of the European Network for TTR-FAP (ATTReuNET) concluded that genetic counselling for diagnosed individuals and at-risk family members is mostly beneficial and should be carried out with care by trained professionals. Systematic and regular monitoring of an asymptomatic carrier is necessary to detect early signs of TTR-FAP and maximize the effectiveness of treatment. This includes five areas of assessment: history/clinical examination, sensorimotor function, autonomic dysfunction, cardiac function, and renal function. At least two related symptoms and positive biopsy findings are required to confirm diagnosis of TTR-FAP. Early detection of TTR-FAP is essential to improve the prognosis of TTR-FAP. ATTReuNET recommends genetic counselling and routine monitoring for asymptomatic carriers of TTR-FAP.

  2. The evolutionary and integrative roles of transthyretin in thyroid hormone homeostasis.

    PubMed

    Schreiber, G

    2002-10-01

    In larger mammals, thyroid hormone-binding plasma proteins are albumin, transthyretin (TTR) and thyroxine (T4)-binding globulin. They differ characteristically in affinities and release rates for T4 and triiodothyronine (T3). Together, they form a 'buffering' system counteracting thyroid hormone permeation from aqueous to lipid phases. Evolution led to important differences in the expression pattern of these three proteins in tissues. In adult liver, TTR is only made in eutherians and herbivorous marsupials. During development, it is also made in tadpole and fish liver. More intense TTR synthesis than in liver is found in the choroid plexus of reptilians, birds and mammals, but none in the choroid plexus of amphibians and fish, i.e. species without a neocortex. All brain-made TTR is secreted into the cerebrospinal fluid, where it becomes the major thyroid hormone-binding protein. During ontogeny, the maximum TTR synthesis in the choroid plexus precedes that of the growth rate of the brain and occurs during the period of maximum neuroblast replication. TTR is only one component in a network of factors determining thyroid hormone distribution. This explains why, under laboratory conditions, TTR-knockout mice show no major abnormalities. The ratio of TTR affinity for T4 over affinity for T3 is higher in eutherians than in reptiles and birds. This favors T4 transport from blood to brain providing more substrate for conversion of the biologically less active T4 into the biologically more active T3 by the tissue-specific brain deiodinases. The change in affinity of TTR during evolution involves a shortening and an increase in the hydrophilicity of the N-terminal regions of the TTR subunits. The molecular mechanism for this change is a stepwise shift of the splice site at the intron 1/exon 2 border of the TTR gene. The shift probably results from a sequence of single base mutations. Thus, TTR evolution provides an example for a molecular mechanism of positive Darwinian

  3. Putting ROSE to Work: A Proposed Application of a Request-Oriented Scheduling Engine for Space Station Operations

    NASA Technical Reports Server (NTRS)

    Jaap, John; Muery, Kim

    2000-01-01

    Scheduling engines are found at the core of software systems that plan and schedule activities and resources. A Request-Oriented Scheduling Engine (ROSE) is one that processes a single request (adding a task to a timeline) and then waits for another request. For the International Space Station, a robust ROSE-based system would support multiple, simultaneous users, each formulating requests (defining scheduling requirements), submitting these requests via the internet to a single scheduling engine operating on a single timeline, and immediately viewing the resulting timeline. ROSE is significantly different from the engine currently used to schedule Space Station operations. The current engine supports essentially one person at a time, with a pre-defined set of requirements from many payloads, working in either a "batch" scheduling mode or an interactive/manual scheduling mode. A planning and scheduling process that takes advantage of the features of ROSE could produce greater customer satisfaction at reduced cost and reduced flow time. This paper describes a possible ROSE-based scheduling process and identifies the additional software component required to support it. Resulting changes to the management and control of the process are also discussed.

  4. Transthyretin-binding activity of contaminants in blood from polar bear (Ursus maritimus) cubs.

    PubMed

    Bytingsvik, Jenny; Simon, Eszter; Leonards, Pim E G; Lamoree, Marja; Lie, Elisabeth; Aars, Jon; Derocher, Andrew E; Wiig, Oystein; Jenssen, Bjørn M; Hamers, Timo

    2013-05-07

    We determined the transthyretin (TTR)-binding activity of blood-accumulating contaminants in blood plasma samples of approximately 4-months-old polar bear (Ursus maritimus) cubs from Svalbard sampled in 1998 and 2008. The TTR-binding activity was measured as thyroxine (T4)-like equivalents (T4-EQMeas). Our findings show that the TTR-binding activity related to contaminant levels was significantly lower (45%) in 2008 than in 1998 (mean ± standard error of mean: 1998, 2265 ± 231 nM; 2008, 1258 ± 170 nM). Although we cannot exclude a potential influence of between-year differences in capture location and cub body mass, our findings most likely reflect reductions of TTR-binding contaminants or their precursors in the arctic environment (e.g., polychlorinated biphenyls [PCBs]). The measured TTR-binding activity correlated positively with the cubs' plasma levels of hydroxylated PCBs (OH-PCBs). No such association was found between TTR-binding activity and the plasma levels of perfluoroalkyl substances (PFASs). The OH-PCBs explained 60 ± 7% and 54 ± 4% of the TTR-binding activity in 1998 and 2008, respectively, and PFASs explained ≤1.2% both years. Still, almost half the TTR-binding activity could not be explained by the contaminants we examined. The considerable levels of TTR-binding contaminants warrant further effect directed analysis (EDA) to identify the contaminants responsible for the unexplained part of the observed TTR-binding activity.

  5. Fourth Report of the Task Force on the Shuttle-Mir Rendezvous and Docking Missions

    NASA Technical Reports Server (NTRS)

    1995-01-01

    On December 6, 1994, the NASA Administrator, Mr. Daniel Goldin, requested that Lt. Gen. Thomas P. Stafford, in his role as the Chairman of the NASA Advisory Council Task Force on the Shuttle-Mir Rendezvous and Docking Missions, lead a team composed of several Task Force members and technical advisors' to Russia with the goal of reviewing preparations and readiness for the upcoming international Space Station Phase 1 missions. In his directions to Gen. Stafford, Mr. Goldin requested that the review team focus its initial efforts on safety of flight issues for the following Phase 1A missions: the Soyuz TM-21 mission which will carry U.S. astronaut Dr. Norman Thagard and cosmonauts Lt. Col. Vladimir Dezhurov and Mr. Gennady Strekalov aboard a Soyuz spacecraft to the Mir Station; the Mir 18 Main Expedition during which Thagard and his fellow cosmonauts, Dezhurov and Strokalov, will spend approximately three months aboard the Mir Station; the STS-71 Space Shuttle mission which will perform the first Shuttle-Mir docking, carry cosmonauts Col. Anatoly SoloViev and Mr. Nikolai Budarin to the Mir Station, and return Thagard, Dezhurov, and Strekalov to Earth.

  6. Load Balancing in Cloud Computing Environment Using Improved Weighted Round Robin Algorithm for Nonpreemptive Dependent Tasks.

    PubMed

    Devi, D Chitra; Uthariaraj, V Rhymend

    2016-01-01

    Cloud computing uses the concepts of scheduling and load balancing to migrate tasks to underutilized VMs for effectively sharing the resources. The scheduling of the nonpreemptive tasks in the cloud computing environment is an irrecoverable restraint and hence it has to be assigned to the most appropriate VMs at the initial placement itself. Practically, the arrived jobs consist of multiple interdependent tasks and they may execute the independent tasks in multiple VMs or in the same VM's multiple cores. Also, the jobs arrive during the run time of the server in varying random intervals under various load conditions. The participating heterogeneous resources are managed by allocating the tasks to appropriate resources by static or dynamic scheduling to make the cloud computing more efficient and thus it improves the user satisfaction. Objective of this work is to introduce and evaluate the proposed scheduling and load balancing algorithm by considering the capabilities of each virtual machine (VM), the task length of each requested job, and the interdependency of multiple tasks. Performance of the proposed algorithm is studied by comparing with the existing methods.

  7. Load Balancing in Cloud Computing Environment Using Improved Weighted Round Robin Algorithm for Nonpreemptive Dependent Tasks

    PubMed Central

    Devi, D. Chitra; Uthariaraj, V. Rhymend

    2016-01-01

    Cloud computing uses the concepts of scheduling and load balancing to migrate tasks to underutilized VMs for effectively sharing the resources. The scheduling of the nonpreemptive tasks in the cloud computing environment is an irrecoverable restraint and hence it has to be assigned to the most appropriate VMs at the initial placement itself. Practically, the arrived jobs consist of multiple interdependent tasks and they may execute the independent tasks in multiple VMs or in the same VM's multiple cores. Also, the jobs arrive during the run time of the server in varying random intervals under various load conditions. The participating heterogeneous resources are managed by allocating the tasks to appropriate resources by static or dynamic scheduling to make the cloud computing more efficient and thus it improves the user satisfaction. Objective of this work is to introduce and evaluate the proposed scheduling and load balancing algorithm by considering the capabilities of each virtual machine (VM), the task length of each requested job, and the interdependency of multiple tasks. Performance of the proposed algorithm is studied by comparing with the existing methods. PMID:26955656

  8. Self-identified Obese People Request Less Money: A Field Experiment

    PubMed Central

    Proestakis, Antonios; Brañas-Garza, Pablo

    2016-01-01

    Empirical evidence suggests that obese people are discriminated in different social environments, such as the work place. Yet, the degree to which obese people are internalizing and adjusting their own behavior as a result of this discriminatory behavior has not been thoroughly studied. We develop a proxy for measuring experimentally the “self-weight bias” by giving to both self-identified obese (n = 90) and non-obese (n = 180) individuals the opportunity to request a positive amount of money after having performed an identical task. Consistent with the System Justification Theory, we find that self-identified obese individuals, due to a preexisting false consciousness, request significantly lower amounts of money than non-obese ones. A within subject comparison between self-reports and external monitors' evaluations reveals that the excessive weight felt by the “self” but not reported by evaluators captures the self-weight bias not only for obese but also for non-obese individuals. Linking our experimental results to the supply side of the labor market, we argue that self-weight bias, as expressed by lower salary requests, enhances discriminatory behavior against individuals who feel, but may not actually be, obese and consequently exacerbates the wage gap across weight. PMID:27721803

  9. Effects of Non-Driving Related Task Modalities on Takeover Performance in Highly Automated Driving.

    PubMed

    Wandtner, Bernhard; Schömig, Nadja; Schmidt, Gerald

    2018-04-01

    Aim of the study was to evaluate the impact of different non-driving related tasks (NDR tasks) on takeover performance in highly automated driving. During highly automated driving, it is allowed to engage in NDR tasks temporarily. However, drivers must be able to take over control when reaching a system limit. There is evidence that the type of NDR task has an impact on takeover performance, but little is known about the specific task characteristics that account for performance decrements. Thirty participants drove in a simulator using a highly automated driving system. Each participant faced five critical takeover situations. Based on assumptions of Wickens's multiple resource theory, stimulus and response modalities of a prototypical NDR task were systematically manipulated. Additionally, in one experimental group, the task was locked out simultaneously with the takeover request. Task modalities had significant effects on several measures of takeover performance. A visual-manual texting task degraded performance the most, particularly when performed handheld. In contrast, takeover performance with an auditory-vocal task was comparable to a baseline without any task. Task lockout was associated with faster hands-on-wheel times but not altered brake response times. Results showed that NDR task modalities are relevant factors for takeover performance. An NDR task lockout was highly accepted by the drivers and showed moderate benefits for the first takeover reaction. Knowledge about the impact of NDR task characteristics is an enabler for adaptive takeover concepts. In addition, it might help regulators to make decisions on allowed NDR tasks during automated driving.

  10. 78 FR 20102 - Proposed Information Collection Request; Comment Request; Reformulated Gasoline Commingling...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-03

    ... Request; Comment Request; Reformulated Gasoline Commingling Provisions AGENCY: Environmental Protection... information collection request (ICR), ``Reformulated Gasoline Commingling Provisions'' (EPA ICR No.2228.04.... Abstract: EPA would like to continue collecting notifications from gasoline retailers and wholesale...

  11. 76 FR 24912 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-03

    ... for OMB Review; Comment Request; Request for Examination and/or Treatment ACTION: Notice. SUMMARY: The... information collection request (ICR) titled, ``Request for Examination and/or Treatment,'' Form LS-1, to the... Request for Examination and/or Treatment, Form LS-1, is used by employers to authorize medical treatment...

  12. Iodine Atoms: A New Molecular Feature for the Design of Potent Transthyretin Fibrillogenesis Inhibitors

    PubMed Central

    Pinto, Marta; Almeida, Maria Rosário; Gales, Luis; Ballesteros, Alfredo; Barluenga, José; Pérez, Juan J.; Vázquez, Jesús T.; Centeno, Nuria B.; Saraiva, Maria Joao; Damas, Ana M.; Planas, Antoni; Arsequell, Gemma; Valencia, Gregorio

    2009-01-01

    The thyroid hormone and retinol transporter protein known as transthyretin (TTR) is in the origin of one of the 20 or so known amyloid diseases. TTR self assembles as a homotetramer leaving a central hydrophobic channel with two symmetrical binding sites. The aggregation pathway of TTR into amiloid fibrils is not yet well characterized but in vitro binding of thyroid hormones and other small organic molecules to TTR binding channel results in tetramer stabilization which prevents amyloid formation in an extent which is proportional to the binding constant. Up to now, TTR aggregation inhibitors have been designed looking at various structural features of this binding channel others than its ability to host iodine atoms. In the present work, greatly improved inhibitors have been designed and tested by taking into account that thyroid hormones are unique in human biochemistry owing to the presence of multiple iodine atoms in their molecules which are probed to interact with specific halogen binding domains sitting at the TTR binding channel. The new TTR fibrillogenesis inhibitors are based on the diflunisal core structure because diflunisal is a registered salicylate drug with NSAID activity now undergoing clinical trials for TTR amyloid diseases. Biochemical and biophysical evidence confirms that iodine atoms can be an important design feature in the search for candidate drugs for TTR related amyloidosis. PMID:19125186

  13. Quality of warfarin control in atrial fibrillation patients in South East Queensland, Australia.

    PubMed

    Bernaitis, N; Badrick, T; Davey, A K; Anoopkumar-Dukie, S

    2016-08-01

    Warfarin is widely prescribed to decrease the risk of stroke in atrial fibrillation (AF) patients. Due to patient variability in response, regular monitoring is required, and time in therapeutic range (TTR) used to indicate quality of warfarin control with a TTR>60% is recommended. Recently, an Australian Government review of anticoagulants identified the need to establish current warfarin control and determine the potential place of the newer oral anticoagulants. To determine warfarin control by a pathology practice in Queensland, Australia and identify factors influencing TTR. Retrospective data were collected from Sullivan Nicolaides Pathology, a major pathology practice offering a warfarin care programme in Australia. Patients enrolled in their programme as of September 2014 were included in the study. TTR was calculated using INR test results, and test dates using the Rosendaal method with mean patient TTR were used for analysis and comparison. Exclusions were target therapeutic range outside 2.0-3.0, less than two INR tests and programme treatment time of less than 30 days. The eligible 3692 AF patients had 73.6% of INR tests within the therapeutic range. The mean TTR was 81%, with 97% of patients above a TTR of 60%. TTR was not significantly influenced by age, gender or socioeconomic factors. The observed mean TTR of over 80% is superior to the minimum recommended threshold of 60%. The TTR achieved by the Queensland pathology practice demonstrates that dedicated warfarin programmes can produce high-quality warfarin care, ensuring the full benefit of warfarin for Australian patients. © 2016 Royal Australasian College of Physicians.

  14. Comparing the Cost Effectiveness of Non-vitamin K Antagonist Oral Anticoagulants with Well-Managed Warfarin for Stroke Prevention in Atrial Fibrillation Patients at High Risk of Bleeding.

    PubMed

    Hospodar, Alexa R; Smith, Kenneth J; Zhang, Yuting; Hernandez, Inmaculada

    2018-05-09

    Several studies have compared the cost effectiveness of non-vitamin K antagonist oral anticoagulants (NOACs) and warfarin using results from clinical trials evaluating NOACs. However, the time in therapeutic range (TTR) of warfarin groups ranged across clinical trials, and all were below the therapeutic goal of 70%. We compared the cost effectiveness of edoxaban 60 mg, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, rivaroxaban 20 mg, and well-managed warfarin with a TTR of 70% in preventing stroke among patients with atrial fibrillation at high risk of bleeding. For the six treatments, we used a Markov state-transition model to quantify lifetime costs in $US and effectiveness in quality-adjusted life-years (QALYs). We simulated relative risk ratios of clinical events with each NOAC versus warfarin with a TTR of 70% using published regression models that predict how the incidence of thrombotic or hemorrhagic events changes for each unit change in TTR. We re-ran our analysis for two other estimates of TTR: 65 and 75%. Treatment with edoxaban 60 mg cost $US127,520/QALY gained compared with warfarin with a TTR of 70% and cost $US41,860/QALY gained compared with warfarin with a TTR of 65%. However, warfarin with a TTR of 75% was more effective and less expensive than all NOACs. For three levels of TTR, apixaban 5 mg, dabigatran 150 mg, dabigatran 110 mg, and rivaroxaban 20 mg were dominated strategies. The comparative cost effectiveness of edoxaban and warfarin is highly sensitive to TTR. At the $US100,000/QALY willingness-to-pay threshold, our results suggest that warfarin is the most cost-effective treatment for patients who can achieve a TTR of 70%.

  15. Transthyretin Protects against A-Beta Peptide Toxicity by Proteolytic Cleavage of the Peptide: A Mechanism Sensitive to the Kunitz Protease Inhibitor

    PubMed Central

    Costa, Rita; Ferreira-da-Silva, Frederico; Saraiva, Maria J.; Cardoso, Isabel

    2008-01-01

    Alzheimer's disease (AD) is a neurodegenerative disorder characterized by the deposition of amyloid β-peptide (A-Beta) in the brain. Transthyretin (TTR) is a tetrameric protein of about 55 kDa mainly produced in the liver and choroid plexus of the brain. The known physiological functions of TTR are the transport of thyroid hormone T4 and retinol, through binding to the retinol binding protein. TTR has also been established as a cryptic protease able to cleave ApoA-I in vitro. It has been described that TTR is involved in preventing A-Beta fibrilization, both by inhibiting and disrupting A-Beta fibrils, with consequent abrogation of toxicity. We further characterized the nature of the TTR/A-Beta interaction and found that TTR, both recombinant or isolated from human sera, was able to proteolytically process A-Beta, cleaving the peptide after aminoacid residues 1, 2, 3, 10, 13, 14,16, 19 and 27, as determined by mass spectrometry, and reversed phase chromatography followed by N-terminal sequencing. A-Beta peptides (1–14) and (15–42) showed lower amyloidogenic potential than the full length counterpart, as assessed by thioflavin binding assay and ultrastructural analysis by transmission electron microscopy. A-Beta cleavage by TTR was inhibited in the presence of an αAPP peptide containing the Kunitz Protease Inhibitor (KPI) domain but not in the presence of the secreted αAPP derived from the APP isoform 695 without the KPI domain. TTR was also able to degrade aggregated forms of A-Beta peptide. Our results confirmed TTR as a protective molecule in AD, and prompted A-Beta proteolysis by TTR as a protective mechanism in this disease. TTR may prove to be a useful therapeutic agent for preventing or retarding the cerebral amyloid plaque formation implicated in AD pathology. PMID:18682830

  16. Analysis of transthyretin in human serum by capillary zone electrophoresis electrospray ionization time-of-flight mass spectrometry. Application to familial amyloidotic polyneuropathy type I.

    PubMed

    Pont, Laura; Benavente, Fernando; Barbosa, José; Sanz-Nebot, Victoria

    2015-06-01

    Transthyretin (TTR) is known to misfold and aggregate, causing different types of amyloidosis. Familial amyloidotic polyneuropathy type I (FAP-I), which is the most common hereditary systemic amyloidosis, is associated with a TTR variant that presents a single amino acid substitution of valine for methionine at position 30 (Met 30). To screen for TTR-related amyloidosis rapidly and reliably, we have developed a novel procedure based on the analysis of monomers from the homotetrameric protein (∼56 kDa). First, we established a CZE-ESI-TOF-MS method to detect wild-type (normal) TTR with or without several PTMs, as well as an extra minor isoform in TTR standard solutions. Later, a sample pretreatment based on immunoprecipitation (IP) and centrifugal filtration was optimized to analyze serum samples from healthy controls and FAP-I patients (including an asymptomatic patient, a symptomatic patient, a liver-transplanted patient with the specific mutation, and a patient originally without the mutation who received a liver transplant from an FAP-I patient (iatrogenic FAP-I)). The mutant TTR (Met 30) variant with a relative molecular mass 32.07 higher than the wild-type TTR was found in the asymptomatic, the symptomatic and the iatrogenic FAP-I patients, who interestingly also presented the same concentration ratio between both variants of TTR (abnormal and normal). In contrast, as in the healthy controls, the abnormal TTR variant was not detected in the liver-transplanted patient with the specific mutation, which confirms the effectiveness of the treatment. The proposed procedure could be regarded as a suitable screening system for individuals with suspected TTR amyloidosis, and to gain insight into TTR structure, to understand the mechanism underlying the disease. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Characterization of little skate (Leucoraja erinacea) recombinant transthyretin: Zinc-dependent 3,3',5-triiodo-l-thyronine binding.

    PubMed

    Suzuki, Shunsuke; Kasai, Kentaro; Yamauchi, Kiyoshi

    2015-01-01

    Transthyretin (TTR) diverged from an ancestral 5-hydroxyisourate hydrolase (HIUHase) by gene duplication at some early stage of chordate evolution. To clarify how TTR had participated in the thyroid system as an extracellular thyroid hormone (TH) binding protein, TH binding properties of recombinant little skate Leucoraja erinacea TTR was investigated. At the amino acid level, skate TTR showed 37-46% identities with the other vertebrate TTRs. Because the skate TTR had a unique histidine-rich segment in the N-terminal region, it could be purified by Ni-affinity chromatography. The skate TTR was a 46-kDa homotetramer of 14.5kDa subunits, and had one order of magnitude higher affinity for 3,3',5-triiodo-l-thyronine (T3) and some halogenated phenols than for l-thyroxine. However, the skate TTR had no HIUHase activity. Ethylenediaminetetraacetic acid (EDTA) treatment inhibited [(125)I]T3 binding activity whereas the addition of Zn(2+) to the EDTA-treated TTR recovered [(125)I]T3 binding activity in a Zn(2+) concentration-dependent manner. Scatchard analysis revealed the presence of two classes of binding site for T3, with dissociation constants of 0.24 and 17nM. However, the high-affinity sites were completely abolished with 1mM EDTA, whereas the remaining low-affinity sites decreased binding capacity. The number of zinc per TTR was quantified to be 4.5-6.3. Our results suggest that skate TTR has tight Zn(2+)-binding sites, which are essential for T3 binding to at least the high-affinity sites. Zn(2+) binding to the N-terminal histidine-rich segment may play an important role in acquisition or reinforcement of TH binding ability during early evolution of TTR. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. 78 FR 55252 - Proposed Information Collection Request; Comment Request; State Review Framework

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-10

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OECA-2010-0291; FRL-9900-88-OECA] Proposed Information Collection Request; Comment Request; State Review Framework AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The Environmental Protection Agency is planning to submit a request to renew an...

  19. 76 FR 20987 - Agency Information Collection Request; 60-Day Public Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-14

    ... Information Collection Request; 60-Day Public Comment Request AGENCY: Office of the Secretary, HHS. In... of a proposed information collection request for public comment. Interested persons are invited to send comments regarding this burden estimate or any other aspect of this collection of information...

  20. Feedback is the breakfast of champions: the significance of self-controlled formal feedback for autonomous task engagement.

    PubMed

    Meng, Liang; Yang, Zijing

    2018-01-03

    With the aim of examining the positive effect of the formal feedback mechanism itself beyond its informational aspect, we engaged participants in the stopwatch task and recorded their electroencephalogram throughout the experiment. This task requires a button press to stop the watch within a given time interval, the completion of which is simultaneously accompanied by adequate information on task performance. In the self-controlled feedback mode, participants could freely choose whether to request formal feedback after completing the task. In another mode, additional feedback was not provided. The 'non-choice' cue was found to elicit a more negative cue-elicited feedback negativity compared with 'choice', suggesting that the opportunity to solicit formal feedback was perceived as more desirable. In addition, a more enhanced stimulus-preceding negativity was observed prior to the task initiation cue in the self-controlled feedback condition, indicating that participants paid more sustained anticipatory attention during task preparation. Taken together, these electrophysiological results suggested an inherent reward within the formal feedback mechanism itself and the significance of self-controlled formal feedback for autonomous task engagement.

  1. Fiscal Year 2010 Budget Request. Summary Justification

    DTIC Science & Technology

    2009-05-01

    FISCAL YEAR 2010 BUDGET REQUEST S U M M A R Y J U S T I F I C A T I O N • M A Y 2 0 0 9 U N I T E D S T A T E S D E P A R T M E N T O F D...E F E N S E Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average...Justification 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR( S ) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7

  2. 75 FR 67975 - Agency Information Collection Request; 30-Day Public Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-11-04

    ... Information Request Form. The Civil Rights Information Request Form is designed to collect data from health... of the Medicare certification process, health care facilities must receive a civil rights clearance... regulations. The civil rights information is requested only when a health care provider applies for Medicare...

  3. 12 CFR 1402.27 - Aggregating requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Information § 1402.27 Aggregating requests. A requester may not file multiple requests at the same time, each... in concert, is attempting to break a request down into a series of requests for the purpose of... reasonable is the time period over which the requests have occurred. ...

  4. 12 CFR 1402.27 - Aggregating requests.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Information § 1402.27 Aggregating requests. A requester may not file multiple requests at the same time, each... in concert, is attempting to break a request down into a series of requests for the purpose of... reasonable is the time period over which the requests have occurred. ...

  5. 12 CFR 1402.27 - Aggregating requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Information § 1402.27 Aggregating requests. A requester may not file multiple requests at the same time, each... in concert, is attempting to break a request down into a series of requests for the purpose of... reasonable is the time period over which the requests have occurred. ...

  6. 49 CFR 802.7 - Requests: How, where, and when presented; verification of identity of individuals making requests...

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...; verification of identity of individuals making requests; accompanying persons; and procedures for... individuals making requests; accompanying persons; and procedures for acknowledgment of requests. (a) Requests... Request,” “Privacy Act Statement of Disagreement,” “Privacy Act Disclosure Accounting Request,” “Appeal...

  7. Task conflict effect in task switching.

    PubMed

    Braverman, Ami; Meiran, Nachshon

    2010-11-01

    A part of action preparation is deciding what the relevant task is. This task-decision process is conceptually separate from response selection. To show this, the authors manipulated task conflict in a spatial task-switching paradigm, using conflict stimuli that appeared during trials with univalent targets (affording 1 task). The conflict stimuli afforded task identity because they were used as task cues with bivalent targets (affording 2 tasks) that were intermixed with the univalent targets. Thus, for univalent targets, irrelevant stimuli either caused low task conflict or high task conflict. In three experiments, the authors found poorer performance in high task conflict trials than in low task conflict trials. Task conflict was introduced during target appearance (Experiment 1) or task preparation (Experiments 2 and 3). In the latter case, the task conflict effect decreased with increasing task preparation time showing that task preparation involves task decision.

  8. A multi-site cognitive task analysis for biomedical query mediation.

    PubMed

    Hruby, Gregory W; Rasmussen, Luke V; Hanauer, David; Patel, Vimla L; Cimino, James J; Weng, Chunhua

    2016-09-01

    To apply cognitive task analyses of the Biomedical query mediation (BQM) processes for EHR data retrieval at multiple sites towards the development of a generic BQM process model. We conducted semi-structured interviews with eleven data analysts from five academic institutions and one government agency, and performed cognitive task analyses on their BQM processes. A coding schema was developed through iterative refinement and used to annotate the interview transcripts. The annotated dataset was used to reconstruct and verify each BQM process and to develop a harmonized BQM process model. A survey was conducted to evaluate the face and content validity of this harmonized model. The harmonized process model is hierarchical, encompassing tasks, activities, and steps. The face validity evaluation concluded the model to be representative of the BQM process. In the content validity evaluation, out of the 27 tasks for BQM, 19 meet the threshold for semi-valid, including 3 fully valid: "Identify potential index phenotype," "If needed, request EHR database access rights," and "Perform query and present output to medical researcher", and 8 are invalid. We aligned the goals of the tasks within the BQM model with the five components of the reference interview. The similarity between the process of BQM and the reference interview is promising and suggests the BQM tasks are powerful for eliciting implicit information needs. We contribute a BQM process model based on a multi-site study. This model promises to inform the standardization of the BQM process towards improved communication efficiency and accuracy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. A Multi-Site Cognitive Task Analysis for Biomedical Query Mediation

    PubMed Central

    Hruby, Gregory W.; Rasmussen, Luke V.; Hanauer, David; Patel, Vimla; Cimino, James J.; Weng, Chunhua

    2016-01-01

    Objective To apply cognitive task analyses of the Biomedical query mediation (BQM) processes for EHR data retrieval at multiple sites towards the development of a generic BQM process model. Materials and Methods We conducted semi-structured interviews with eleven data analysts from five academic institutions and one government agency, and performed cognitive task analyses on their BQM processes. A coding schema was developed through iterative refinement and used to annotate the interview transcripts. The annotated dataset was used to reconstruct and verify each BQM process and to develop a harmonized BQM process model. A survey was conducted to evaluate the face and content validity of this harmonized model. Results The harmonized process model is hierarchical, encompassing tasks, activities, and steps. The face validity evaluation concluded the model to be representative of the BQM process. In the content validity evaluation, out of the 27 tasks for BQM, 19 meet the threshold for semi-valid, including 3 fully valid: “Identify potential index phenotype,” “If needed, request EHR database access rights,” and “Perform query and present output to medical researcher”, and 8 are invalid. Discussion We aligned the goals of the tasks within the BQM model with the five components of the reference interview. The similarity between the process of BQM and the reference interview is promising and suggests the BQM tasks are powerful for eliciting implicit information needs. Conclusions We contribute a BQM process model based on a multi-site study. This model promises to inform the standardization of the BQM process towards improved communication efficiency and accuracy. PMID:27435950

  10. 78 FR 75575 - Agency Information Collection Activities: Submission for OMB Review; Comment Request; Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ... Request; Request for the Site Inspection, Landowners Authorization/Ingress/Egress Agreement. AGENCY... . SUPPLEMENTARY INFORMATION: Collection of Information Title: Request for the Site Inspection, Landowners...-09, Request for the Site Inspection; FEMA Form 010-0-10, Landowner's Authorization Ingress- Egress...

  11. Estimation of the impact of warfarin's time-in-therapeutic range on stroke and major bleeding rates and its influence on the medical cost avoidance associated with novel oral anticoagulant use-learnings from ARISTOTLE, ROCKET-AF, and RE-LY trials.

    PubMed

    Amin, Alpesh; Deitelzweig, Steve; Jing, Yonghua; Makenbaeva, Dinara; Wiederkehr, Daniel; Lin, Jay; Graham, John

    2014-01-01

    Warfarin's time-in-therapeutic range (TTR) is highly variable among patients with nonvalvular atrial fibrillation (NVAF). The objective of this study was to estimate the impact of variations in wafarin's TTR on rates of stroke/systemic embolism (SSE) and major bleedings among NVAF patients in the ARISTOTLE, ROCKET-AF, and RE-LY trials. Additionally, differences in medical costs for clinical endpoints when novel oral anticoagulants (NOACs) were used instead of warfarin at different TTR values were estimated. Quartile ranges of TTR values and corresponding event rates (%/patient - year = %/py) of SSE and major bleedings among NVAF patients treated with warfarin were estimated from published literature and FDA documents. The associations of SSE and major bleeding rates with TTR values were evaluated by regression analysis and then the calculated regression coefficients were used in analysis of medical cost differences associated with use of each NOAC versus warfarin (2010 costs; US payer perspective) at different TTRs. Each 10 % increase in warfarin's TTR correlated with a -0.32%/py decrease in SSE rate (R(2) = 0.61; p < 0.001). Although, the rate of major bleedings decreased as TTR increased, it was not significant (-0.035%/py, p = 0.63). As warfarin's TTR increased from 30 to 90% the estimated medical cost decreased from -$902 to -$83 for apixaban, from -$506 to +$314 for rivaroxaban, and from -$596 to +$223 for dabigatran. Among NVAF patients there is a significant negative correlation between warfarin's TTR and SSE rate, but not major bleedings. The variations in warfarin's TTR impacted the economic comparison of use of individual NOACs versus warfarin.

  12. Why is Leu55→Pro55 transthyretin variant the most amyloidogenic: Insights from molecular dynamics simulations of transthyretin monomers

    PubMed Central

    Yang, Mingfeng; Lei, Ming; Huo, Shuanghong

    2003-01-01

    Transthyretin (TTR) is one of the known human amyloidogenic proteins. Its native state is a homotetramer with each monomer having a β-sandwich structure. Strong experimental evidence suggests that TTR dissociates into monomeric intermediates and that the monomers subsequently self-assemble to form amyloid deposits and insoluble fibrils. However, details on the early steps along the pathway of TTR amyloid formation are unclear, although various experimental approaches with resolutions at the molecular or residue level have provided some clues. It is highly likely that the stability and flexibility of monomeric TTR play crucial roles in the early steps of amyloid formation; thereby, it is essential to characterize initial conformational changes of TTR monomers. In this article we probe the possibility that the differences in the monomeric forms of wild-type (WT) TTR and its variants are responsible for differential amyloidogenesis. We begin with the simulations of WT, Val30→Met (V30M), and Leu55→Pro (L55P) TTR monomers. Nanosecond time scale molecular dynamics simulations at 300 K were performed using AMBER. The results indicate that the L55P-TTR monomer undergoes substantial structural changes relative to fluctuations observed in the WT and V30M TTR monomers. The observation supports earlier speculation that the L55P mutation may lead to disruption of the β-sheet structure through the disorder of the “edge strands” that might facilitate amyloidogenesis. PMID:12761393

  13. A New Folding Kinetic Mechanism for Human Transthyretin and the Influence of the Amyloidogenic V30M Mutation.

    PubMed

    Jesus, Catarina S H; Almeida, Zaida L; Vaz, Daniela C; Faria, Tiago Q; Brito, Rui M M

    2016-08-31

    Protein aggregation into insoluble amyloid fibrils is the hallmark of several neurodegenerative diseases, chief among them Alzheimer's and Parkinson's. Although caused by different proteins, these pathologies share some basic molecular mechanisms with familial amyloidotic polyneuropathy (FAP), a rare hereditary neuropathy caused by amyloid formation and deposition by transthyretin (TTR) in the peripheral and autonomic nervous systems. Among the amyloidogenic TTR mutations known, V30M-TTR is the most common in FAP. TTR amyloidogenesis (ATTR) is triggered by tetramer dissociation, followed by partial unfolding and aggregation of the low conformational stability monomers formed. Thus, tetramer dissociation kinetics, monomer conformational stability and competition between refolding and aggregation pathways do play a critical role in ATTR. Here, we propose a new model to analyze the refolding kinetics of WT-TTR and V30M-TTR, showing that at pH and protein concentrations close to physiological, a two-step mechanism with a unimolecular first step followed by a second-order second step adjusts well to the experimental data. Interestingly, although sharing the same kinetic mechanism, V30M-TTR refolds at a much slower rate than WT-TTR, a feature that may favor the formation of transient species leading to kinetic partition into amyloidogenic pathways and, thus, significantly increasing the probability of amyloid formation in vivo.

  14. The trading time risks of stock investment in stock price drop

    NASA Astrophysics Data System (ADS)

    Li, Jiang-Cheng; Tang, Nian-Sheng; Mei, Dong-Cheng; Li, Yun-Xian; Zhang, Wan

    2016-11-01

    This article investigates the trading time risk (TTR) of stock investment in the case of stock price drop of Dow Jones Industrial Average (ˆDJI) and Hushen300 data (CSI300), respectively. The escape time of stock price from the maximum to minimum in a data window length (DWL) is employed to measure the absolute TTR, the ratio of the escape time to data window length is defined as the relative TTR. Empirical probability density functions of the absolute and relative TTRs for the ˆDJI and CSI300 data evidence that (i) whenever the DWL increases, the absolute TTR increases, the relative TTR decreases otherwise; (ii) there is the monotonicity (or non-monotonicity) for the stability of the absolute (or relative) TTR; (iii) there is a peak distribution for shorter trading days and a two-peak distribution for longer trading days for the PDF of ratio; (iv) the trading days play an opposite role on the absolute (or relative) TTR and its stability between ˆDJI and CSI300 data.

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

    Saelices, Lorena; Johnson, Lisa M.; Liang, Wilson Y.

    The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of transthyretin has been reported as the cause of the life-threatening transthyretin amyloidosis. The standard treatment of familial cases of TTR amyloidosis has been liver transplantation. Although aggregation-preventing strategies involving ligands are known, understanding the mechanism of TTR aggregation can lead to additional inhibition approaches. Several models of TTR amyloid fibrils have been proposed, but the segments that drive aggregation of the protein have remained unknown. Here we identify β-strands F and H as necessary for TTR aggregation. Based on the crystal structuresmore » of these segments, we designed two non-natural peptide inhibitors that block aggregation. Lastly, this work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.« less

  16. Uncovering the mechanism of aggregation of human transthyretin

    DOE PAGES

    Saelices, Lorena; Johnson, Lisa M.; Liang, Wilson Y.; ...

    2015-10-12

    The tetrameric thyroxine transport protein transthyretin (TTR) forms amyloid fibrils upon dissociation and monomer unfolding. The aggregation of transthyretin has been reported as the cause of the life-threatening transthyretin amyloidosis. The standard treatment of familial cases of TTR amyloidosis has been liver transplantation. Although aggregation-preventing strategies involving ligands are known, understanding the mechanism of TTR aggregation can lead to additional inhibition approaches. Several models of TTR amyloid fibrils have been proposed, but the segments that drive aggregation of the protein have remained unknown. Here we identify β-strands F and H as necessary for TTR aggregation. Based on the crystal structuresmore » of these segments, we designed two non-natural peptide inhibitors that block aggregation. Lastly, this work provides the first characterization of peptide inhibitors for TTR aggregation, establishing a novel therapeutic strategy.« less

  17. 78 FR 41926 - Proposed Information Collection Request; Comment Request; Performance Evaluation Studies on...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-12

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OECA-2013-0413; FRL--9832-8] Proposed Information Collection Request; Comment Request; Performance Evaluation Studies on Wastewater Laboratories (Renewal); EPA... request (ICR), ``Performance Evaluation Studies on Wastewater Laboratories'' (EPA ICR No. 0234.11, OMB...

  18. Maternal responses to child frustration and requests for help in dyads with fragile X syndrome.

    PubMed

    Wheeler, A C; Hatton, D; Holloway, V T; Sideris, J; Neebe, E C; Roberts, J E; Reznick, J S

    2010-06-01

    Variability in behaviour displayed by children with fragile X syndrome (FXS) may be partially attributable to environmental factors such as maternal responsivity. The purpose of this study was to explore variables associated with maternal behaviour during a task designed to elicit frustration in their children with FXS. Forty-six mother-child dyads, in which the child had full-mutation FXS, were observed in their homes during a task designed to elicit frustration in the child. Each child was given a wrong set of keys and asked to open a box to retrieve a desired toy. Mothers were provided with the correct set of keys and instructed to intervene when they perceived their child was getting too frustrated. Child-expressed frustration and requests for help and maternal behaviours (comforting, negative control, and encouraging/directing) were observed and coded. Maternal variables (e.g. depression, stress, education levels), child variables (e.g. autistic behaviours, age, medication use) and child behaviours (frustration, requests for help) were explored as predictors of maternal behaviour. Almost all mothers intervened to help their children and most used encouraging/directing behaviours, whereas very few used comforting or negative control. Child age and child behaviours during the frustrating event were significant predictors of encouraging/directing behaviours in the mothers. Children whose mothers reported higher depressive symptomology used fewer requests for help, and mothers of children with more autistic behaviours used more negative control. The results of this study suggest that child age and immediate behaviours are more strongly related to maternal responsivity than maternal traits such as depression and stress.

  19. Task Management for Firefighters: A Practical Approach to Task Management.

    ERIC Educational Resources Information Center

    Roberts, Stephen S.

    1979-01-01

    A project management system for organizing requests from multiple departments and controlling the workload of the development/maintenance computer staff is described. Practical solutions to deciding project priorities, determining time estimates, creating positive peer pressure among programing staff, and formalizing information requests are…

  20. Timing of Gazes in Child Dialogues: A Time-Course Analysis of Requests and Back Channelling in Referential Communication

    ERIC Educational Resources Information Center

    Sandgren, Olof; Andersson, Richard; van de Weijer, Joost; Hansson, Kristina; Sahlen, Birgitta

    2012-01-01

    Background: This study investigates gaze behaviour in child dialogues. In earlier studies the authors have investigated the use of requests for clarification and responses in order to study the co-creation of understanding in a referential communication task. By adding eye tracking, this line of research is now expanded to include non-verbal…

  1. Efficacy and safety of dabigatran compared with warfarin at different levels of international normalised ratio control for stroke prevention in atrial fibrillation: an analysis of the RE-LY trial.

    PubMed

    Wallentin, Lars; Yusuf, Salim; Ezekowitz, Michael D; Alings, Marco; Flather, Marcus; Franzosi, Maria Grazia; Pais, Prem; Dans, Antonio; Eikelboom, John; Oldgren, Jonas; Pogue, Janice; Reilly, Paul A; Yang, Sean; Connolly, Stuart J

    2010-09-18

    Effectiveness and safety of warfarin is associated with the time in therapeutic range (TTR) with an international normalised ratio (INR) of 2·0-3·0. In the Randomised Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, dabigatran versus warfarin reduced both stroke and haemorrhage. We aimed to investigate the primary and secondary outcomes of the RE-LY trial in relation to each centre's mean TTR (cTTR) in the warfarin population. In the RE-LY trial, 18 113 patients at 951 sites were randomly assigned to 110 mg or 150 mg dabigatran twice daily versus warfarin dose adjusted to INR 2·0-3·0. Median follow-up was 2·0 years. For 18 024 patients at 906 sites, the cTTR was estimated by averaging TTR for individual warfarin-treated patients calculated by the Rosendaal method. We compared the outcomes of RE-LY across the three treatment groups within four groups defined by the quartiles of cTTR. RE-LY is registered with ClinicalTrials.gov, number NCT00262600. The quartiles of cTTR for patients in the warfarin group were: less than 57·1%, 57·1-65·5%, 65·5-72·6%, and greater than 72·6%. There were no significant interactions between cTTR and prevention of stroke and systemic embolism with either 110 mg dabigatran (interaction p=0·89) or 150 mg dabigatran (interaction p=0·20) versus warfarin. Neither were any significant interactions recorded with cTTR with regards to intracranial bleeding with 110 mg dabigatran (interaction p=0·71) or 150 mg dabigatran (interaction p=0·89) versus warfarin. There was a significant interaction between cTTR and major bleeding when comparing 150 mg dabigatran with warfarin (interaction p=0·03), with less bleeding events at lower cTTR but similar events at higher cTTR, whereas rates of major bleeding were lower with 110 mg dabigatran than with warfarin irrespective of cTTR. There were significant interactions between cTTR and effects of both 110 mg and 150 mg dabigatran versus warfarin on the composite of all

  2. Using task analysis in healthcare design to improve clinical efficiency.

    PubMed

    Lu, Jun; Hignett, Sue

    2009-01-01

    To review the functionality of the proposed soiled workroom design for efficient and safe clinical activities. As part of a hospital refurbishment program, the planning team of a United Kingdom National Health Service hospital requested a review of a proposed standardized room design. A 7-day observational study was conducted in five clinical departments at three hospitals. Link analysis was used to record and analyze the movements among components, i.e., nursing staff, equipment/devices, and furniture. Fifty-four observations were recorded for 18 clinical tasks. The most frequent tasks were the disposal of urine and used urine bottles, and returning used commode chairs. Minor recommendations were made to improve the proposed design, and major revisions were suggested to address functionality problems. It was found that the proposed design did not offer the optimal layout for efficient and safe clinical activities. Link analysis was found to be effective for plotting the movements of the staff and accounting for the complexity of tasks. This ergonomic method, in combination with observational field studies, provided a simple and effective way to determine functional space requirements for clinical activities and should be used in all healthcare building design projects.

  3. "I Just Need More Time": A Study of Native and Non-Native Students' Requests to Faculty for an Extension

    ERIC Educational Resources Information Center

    Woodfield, Helen; Economidou-Kogetsidis, Maria

    2010-01-01

    This paper examines the status-unequal requests of 89 advanced mixed-L1 learners and 87 British English native speakers elicited by a written discourse completion task. Significant differences were observed in all three dimensions analysed: internal and external modification, and perspective. The data demonstrate learners' overuse of zero marking…

  4. Synergy of combined Doxycycline/TUDCA treatment in lowering Transthyretin deposition and associated biomarkers: studies in FAP mouse models

    PubMed Central

    2010-01-01

    Familial Amyloidotic Polyneuropathy (FAP) is a disorder characterized by the extracellular deposition of fibrillar Transthyretin (TTR) amyloid, with a special involvement of the peripheral nerve. We had previously shown that doxycycline administered for 3 months at 40 mg/Kg/ml in the drinking water, was capable of removing TTR amyloid deposits present in stomachs of old TTR-V30M transgenic mice; the removal was accompanied by a decrease in extracellular matrix remodeling proteins that accompany fibrillar deposition, but not of non-fibrillar TTR deposition and/or markers associated with pre-fibrillar deposits. On the other hand, Tauroursodeoxycholic acid (TUDCA), a biliary acid, administrated to the same mouse model was shown to be effective at lowering deposited non-fibrillar TTR, as well as the levels of markers associated with pre-fibrillar TTR, but only at young ages. In the present work we evaluated different doxycycline administration schemes, including different periods of treatment, different dosages and different FAP TTR V30M animal models. Evaluation included CR staining, immunohistochemistry for TTR, metalloproteinase 9 (MMP-9) and serum amyloid P component (SAP). We determined that a minimum period of 15 days of treatment with a 8 mg/Kg/day dosage resulted in fibril removal. The possibility of intermittent treatments was also assessed and a maximum period of 15 days of suspension was determined to maintain tissues amyloid-free. Combined cycled doxycycline and TUDCA administration to mice with amyloid deposition, using two different concentrations of both drugs, was more effective than either individual doxycycline or TUDCA, in significantly lowering TTR deposition and associated tissue markers. The observed synergistic effect of doxycycline/TUDCA in the range of human tolerable quantities, in the transgenic TTR mice models prompts their application in FAP, particularly in the early stages of disease. PMID:20673327

  5. Non-vitamin K antagonist oral anticoagulants compared with warfarin at different levels of INR control in atrial fibrillation: A meta-analysis of randomized trials.

    PubMed

    Carmo, João; Ferreira, Jorge; Costa, Francisco; Carmo, Pedro; Cavaco, Diogo; Carvalho, Salomé; Morgado, Francisco; Adragão, Pedro; Mendes, Miguel

    2017-10-01

    The efficacy and safety of warfarin for stroke prevention in atrial fibrillation (AF) depend on the time in the therapeutic range (TTR) with an international normalised ratio (INR) of 2.0-3.0. This meta-analysis focused the relative efficacy and safety of non-VKA oral anticoagulants (NOAC) compared with warfarin at different thresholds of centre's TTR (cTTR). We searched PubMed, Embase, CENTRAL and websites of regulatory agencies, limiting searches to randomized phase 3 trials. Primary outcomes were stroke or systemic embolism (SSE) and major or non-major clinically relevant (NMCR) bleeding. We used a random-effects model to pool effect on outcomes according to different thresholds of cTTR. Four TTR sub-studies with a total of 71,222 patients were included. The benefit of NOAC in reducing SSE compared with warfarin was significantly higher in patients at cTTR<60% (HR 0.79, 95% CI 0.68-0.90) and at 60% to <70% (0.82, 0.71-0.95) but not at ≥70% (1.00, 0.82-1.23) with a significant interaction for cTTR<70% or ≥70% (p=0.042). The risk of major or NMCR bleeding was significantly lower with NOAC as compared with warfarin in patients at all sub-groups (0.67, 0.54-0.83 for patients at cTTR<60% and 0.75, 0.63-0.89 at 60% to <70%) except for cTTR≥70% (HR 0.84, 0.64-1.11), but the interaction for cTTR<70% or ≥70% was not statistically significant (p=0.271). The superiority in efficacy of NOAC compared with warfarin for stroke prevention is lost above a cTTR threshold of approximately 70%, but the relative safety appears to be less modified by the centre-based quality of INR control. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. Inadequate anticoagulation by Vitamin K Antagonists is associated with Major Adverse Cardiovascular Events in patients with atrial fibrillation.

    PubMed

    Pastori, Daniele; Pignatelli, Pasquale; Saliola, Mirella; Carnevale, Roberto; Vicario, Tommasa; Del Ben, Maria; Cangemi, Roberto; Barillà, Francesco; Lip, Gregory Y H; Violi, Francesco

    2015-12-15

    Time in therapeutic range (TTR) reflects the quality of anticoagulation and is inversely correlated with ischemic stroke in atrial fibrillation (AF) patients. Few data on the relationship between TTR and myocardial infarction (MI) are available. We investigated the association between TTR and Major Adverse Cardiovascular Events (MACE) in a cohort of anticoagulated AF patients. We calculated TTR for 627 AF patients on vitamin K antagonists, who were followed for a median of 30.8 months (1755 patients/year). The primary outcome was a combined endpoint of MACE including fatal/nonfatal MI and cardiovascular death. Mean age was 73.3 (±8.2) years, and 40.2% were women. During follow-up, we recorded 67 events: 19 stroke/TIA (1.1%/year) and 48 MACE (2.9%/year): 24 MI and 24 cardiovascular deaths. The cohort was categorized according to tertiles of TTR values: TTR 13-58%, 59-74%, and 75-100%. There was a significant increased rate of MACE across tertiles of TTR (Log-Rank test: p<0.001). On Cox proportion hazard analysis, the 2nd vs. 1st tertile of TTR (p=0.002, hazard ratio [HR] 0.347, confidence interval [CI] 95% 0.177-0.680), 3rd vs. 1st tertile of TTR (p<0.001, HR 0.164, CI 95% 0.067-0.402), age (p<0.001, HR 1.094, CI 95% 1.042-1.148), history of stroke/TIA (p=0.015, HR 2.294, CI 95% 1.172-4.490) and smoking (p=0.003, HR 3.450, CI 95% 1.532-7.769) predicted MACE. TTR was an independent predictor of MACE in our cohort of AF patients. Our findings suggest that a good anticoagulation control is necessary to reduce not only the risk of stroke but also that of MACE. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Post-translational modifications of transthyretin affect the triiodonine-binding potential

    PubMed Central

    Henze, Andrea; Homann, Thomas; Serteser, Mustafa; Can, Ozge; Sezgin, Ozlem; Coskun, Abdurrahman; Unsal, Ibrahim; Schweigert, Florian J; Ozpinar, Aysel

    2015-01-01

    Transthyretin (TTR) is a visceral protein, which facilitates the transport of thyroid hormones in blood and cerebrospinal fluid. The homotetrameric structure of TTR enables the simultaneous binding of two thyroid hormones per molecule. Each TTR subunit provides a single cysteine residue (Cys10), which is frequently affected by oxidative post-translational modifications. As Cys10 is part of the thyroid hormone-binding channel within the TTR molecule, PTM of Cys10 may influence the binding of thyroid hormones. Therefore, we analysed the effects of Cys10 modification with sulphonic acid, cysteine, cysteinylglycine and glutathione on binding of triiodothyronine (T3) by molecular modelling. Furthermore, we determined the PTM pattern of TTR in serum of patients with thyroid disease by immunoprecipitation and mass spectrometry to evaluate this association in vivo. The in silico assays demonstrated that oxidative PTM of TTR resulted in substantial reorganization of the intramolecular interactions and also affected the binding of T3 in a chemotype- and site-specific manner with S-glutathionylation as the most potent modulator of T3 binding. These findings were supported by the in vivo results, which indicated thyroid function-specific patterns of TTR with a substantial decrease in S-sulphonated, S-cysteinylglycinated and S-glutathionylated TTR in hypothyroid patients. In conclusion, this study provides evidence that oxidative modifications of Cys10 seem to affect binding of T3 to TTR probably because of the introduction of a sterical hindrance and induction of conformational changes. As oxidative modifications can be dynamically regulated, this may represent a sensitive mechanism to adjust thyroid hormone availability. PMID:25311081

  8. A New Folding Kinetic Mechanism for Human Transthyretin and the Influence of the Amyloidogenic V30M Mutation

    PubMed Central

    Jesus, Catarina S. H.; Almeida, Zaida L.; Vaz, Daniela C.; Faria, Tiago Q.; Brito, Rui M. M.

    2016-01-01

    Protein aggregation into insoluble amyloid fibrils is the hallmark of several neurodegenerative diseases, chief among them Alzheimer’s and Parkinson’s. Although caused by different proteins, these pathologies share some basic molecular mechanisms with familial amyloidotic polyneuropathy (FAP), a rare hereditary neuropathy caused by amyloid formation and deposition by transthyretin (TTR) in the peripheral and autonomic nervous systems. Among the amyloidogenic TTR mutations known, V30M-TTR is the most common in FAP. TTR amyloidogenesis (ATTR) is triggered by tetramer dissociation, followed by partial unfolding and aggregation of the low conformational stability monomers formed. Thus, tetramer dissociation kinetics, monomer conformational stability and competition between refolding and aggregation pathways do play a critical role in ATTR. Here, we propose a new model to analyze the refolding kinetics of WT-TTR and V30M-TTR, showing that at pH and protein concentrations close to physiological, a two-step mechanism with a unimolecular first step followed by a second-order second step adjusts well to the experimental data. Interestingly, although sharing the same kinetic mechanism, V30M-TTR refolds at a much slower rate than WT-TTR, a feature that may favor the formation of transient species leading to kinetic partition into amyloidogenic pathways and, thus, significantly increasing the probability of amyloid formation in vivo. PMID:27589730

  9. Dealing with requests for euthanasia: a qualitative study investigating the experience of general practitioners.

    PubMed

    Georges, J-J; The, A M; Onwuteaka-Philipsen, B D; van der Wal, G

    2008-03-01

    Caring for terminally ill patients is a meaningful task, however the patient's suffering can be a considerable burden and cause of frustration. The aim of this study is to describe the experiences of general practitioners (GPs) in The Netherlands in dealing with a request for euthanasia from a terminally ill patient. The data, collected through in-depth interviews, were analysed according to the constant comparative method. Having to face a request for euthanasia when attempting to relieve a patient's suffering was described as a very demanding experience that GPs generally would like to avoid. Nearly half of the GPs (14/30) strive to avoid euthanasia or physician assisted suicide because it was against their own personal values or because it was emotional burdening to be confronted with this issue. They explained that by being directed on promoting a peaceful dying process, or the quality of end-of-life of a patient by caring and supporting the patient and the relatives it was mainly possible to shorten patient's suffering without "intentionally hastening a patient's death on his request". The other GPs (16/30) explained that as sometimes the suffering of a patient could not be lessened they were open to consider a patient's request for euthanasia or physician assisted suicide. They underlined the importance of a careful decision-making process, based on finding a balance between the necessity to shorten the patient's suffering through euthanasia and their personal values. Dealing with requests for euthanasia is very challenging for GPs, although they feel committed to alleviate a patient's suffering and to promote a peaceful death.

  10. 18 CFR 385.2013 - Notification of requests for Federal authorizations and requests for further information (Rule...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... requests for Federal authorizations and requests for further information (Rule 2013). 385.2013 Section 385.2013 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... Before the Commission § 385.2013 Notification of requests for Federal authorizations and requests for...

  11. 18 CFR 385.2013 - Notification of requests for Federal authorizations and requests for further information (Rule...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... requests for Federal authorizations and requests for further information (Rule 2013). 385.2013 Section 385.2013 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF... Before the Commission § 385.2013 Notification of requests for Federal authorizations and requests for...

  12. 77 FR 18849 - Notice of Proposed Information Collection: Comment Request: Insurance Termination Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-03-28

    ... Information Collection: Comment Request: Insurance Termination Request for Multifamily Mortgage AGENCY: Office... also lists the following information: Title of Proposal: Insurance Termination Request for Multifamily... mortgagee mutually agree to terminate the HUD multifamily mortgage insurance. Agency form numbers, if...

  13. [Transthyretin: it's miracle function and pathogenesis].

    PubMed

    Ando, Yukio

    2009-03-01

    Transthyretin (TTR) was previously called prealbumin because the band it formed on agarose gel electrophoresis at pH 8.6 was at the prealbumin position. However, it has been well documented that TTR of rodents does not show a prealbumin position on electrophoresis. Now, its name describes its function, binding to retinol binding protein (RBP) and T4. The serum concentration of the protein is 20-40 mg/dl, and TTR forms a tetramer. The plasma half life of the protein is 1.9 days. TTR is synthesized by the liver, retina, pancreas, and choroid plexus. In cerebro-spinal fluid (CSF), it is the second most abundant protein, and is considered as an important protein in the pathogenesis of Alzheimer's disease, depression, and lead intoxication. In addition, TTR is a tryptophan-rich protein, it is used as one of the nutrition assessment proteins, it acts as an anti acute phase protein, and its plasma concentration decreases during inflammation and bacterial infection. Since TTR is a highly amyloidogenic protein because it contains a beta-sheet structure, it becomes a precursor protein in familial amyloidotic polyneuropathy(FAP). Moreover, TTR plays important roles in various CNS disorders, diabetes melitus, and lipid metabolism.

  14. Knowledge of Previous Tasks: Task Similarity Influences Bias in Task Duration Predictions

    PubMed Central

    Thomas, Kevin E.; König, Cornelius J.

    2018-01-01

    Bias in predictions of task duration has been attributed to misremembering previous task duration and using previous task duration as a basis for predictions. This research sought to further examine how previous task information affects prediction bias by manipulating task similarity and assessing the role of previous task duration feedback. Task similarity was examined through participants performing two tasks 1 week apart that were the same or different. Duration feedback was provided to all participants (Experiment 1), its recall was manipulated (Experiment 2), and its provision was manipulated (Experiment 3). In all experiments, task similarity influenced bias on the second task, with predictions being less biased when the first task was the same task. However, duration feedback did not influence bias. The findings highlight the pivotal role of knowledge about previous tasks in task duration prediction and are discussed in relation to the theoretical accounts of task duration prediction bias. PMID:29881362

  15. A study of the influence of task familiarity on user behaviors and performance with a MeSH term suggestion interface for PubMed bibliographic search.

    PubMed

    Tang, Muh-Chyun; Liu, Ying-Hsang; Wu, Wan-Ching

    2013-09-01

    Previous research has shown that information seekers in biomedical domain need more support in formulating their queries. A user study was conducted to evaluate the effectiveness of a metadata based query suggestion interface for PubMed bibliographic search. The study also investigated the impact of search task familiarity on search behaviors and the effectiveness of the interface. A real user, user search request and real system approach was used for the study. Unlike tradition IR evaluation, where assigned tasks were used, the participants were asked to search requests of their own. Forty-four researchers in Health Sciences participated in the evaluation - each conducted two research requests of their own, alternately with the proposed interface and the PubMed baseline. Several performance criteria were measured to assess the potential benefits of the experimental interface, including users' assessment of their original and eventual queries, the perceived usefulness of the interfaces, satisfaction with the search results, and the average relevance score of the saved records. The results show that, when searching for an unfamiliar topic, users were more likely to change their queries, indicating the effect of familiarity on search behaviors. The results also show that the interface scored higher on several of the performance criteria, such as the "goodness" of the queries, perceived usefulness, and user satisfaction. Furthermore, in line with our hypothesis, the proposed interface was relatively more effective when less familiar search requests were attempted. Results indicate that there is a selective compatibility between search familiarity and search interface. One implication of the research for system evaluation is the importance of taking into consideration task familiarity when assessing the effectiveness of interactive IR systems. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. 78 FR 62603 - Notice of Proposed Collection Requests; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... DEPARTMENT OF EDUCATION Notice of Proposed Collection Requests; Comment Request AGENCY: Department of Education. ACTION: Correction Notice. SUMMARY: On October 3, 2013, the U.S. Department of Education published a 30-day comment period notice in the Federal Register (Page 61348, Column 1) seeking...

  17. 18 CFR 388.108 - Requests for Commission records not available through the Public Reference Room (FOIA requests).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... RULES INFORMATION AND REQUESTS § 388.108 Requests for Commission records not available through the... “Freedom of Information Act Request.” (ii) The request must include: (A) A statement by the requester of a... paragraph (a)(5) of this section. (5) Except for the purpose of making a determination regarding expedited...

  18. What's Happening in Freshman Composition in the California Two-Year College: A Collection of Writing Tasks. "A Working Book."

    ERIC Educational Resources Information Center

    Hale, Helena, Comp.

    Designed as a looseleaf resource, a supplement to established teaching plans, and an aid to meeting individual needs, this compilation of writing exercises represents the responses of 157 teachers from 87 two-year colleges to the request, "Describe a successful writing task -- what it is, how you teach it, and why." The compilation includes tasks…

  19. Comparing spatially static and dynamic vibrotactile take-over requests in the driver seat.

    PubMed

    Petermeijer, S M; Cieler, S; de Winter, J C F

    2017-02-01

    Vibrotactile stimuli can be effective as warning signals, but their effectiveness as directional take-over requests in automated driving is yet unknown. This study aimed to investigate the correct response rate, reaction times, and eye and head orientation for static versus dynamic directional take-over requests presented via vibrating motors in the driver seat. In a driving simulator, eighteen participants performed three sessions: 1) a session involving no driving (Baseline), 2) driving a highly automated car without additional task (HAD), and 3) driving a highly automated car while performing a mentally demanding task (N-Back). Per session, participants received four directional static (in the left or right part of the seat) and four dynamic (moving from one side towards the opposite left or right of the seat) take-over requests via two 6×4 motor matrices embedded in the seat back and bottom. In the Baseline condition, participants reported whether the cue was left or right, and in the HAD and N-Back conditions participants had to change lanes to the left or to the right according to the directional cue. The correct response rate was operationalized as the accuracy of the self-reported direction (Baseline session) and the accuracy of the lane change direction (HAD & N-Back sessions). The results showed that the correct response rate ranged between 94% for static patterns in the Baseline session and 74% for dynamic patterns in the N-Back session, although these effects were not statistically significant. Steering wheel touch and steering input reaction times were approximately 200ms faster for static patterns than for dynamic ones. Eye tracking results revealed a correspondence between head/eye-gaze direction and lane change direction, and showed that head and eye-gaze movements where initiated faster for static vibrations than for dynamic ones. In conclusion, vibrotactile stimuli presented via the driver seat are effective as warnings, but their effectiveness

  20. Part-task vs. whole-task training on a supervisory control task

    NASA Technical Reports Server (NTRS)

    Battiste, Vernol

    1987-01-01

    The efficacy of a part-task training for the psychomotor portion of a supervisory control simulation was compared to that of the whole-task training, using six subjects in each group, who were asked to perform a task as quickly as possible. Part-task training was provided with the cursor-control device prior to transition to the whole-task. The analysis of both the training and experimental trials demonstrated a significant performance advantage for the part-task group: the tasks were performed better and at higher speed. Although the subjects finally achieved the same level of performance in terms of score, the part-task method was preferable for economic reasons, since simple pretraining systems are significantly less expensive than the whole-task training systems.

  1. 76 FR 55999 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-09

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information [email protected] . [[Page 56000

  2. 78 FR 57153 - Proposed Information Collection Request; Comment Request; NOX

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-17

    ... to reduce emissions of nitrogen oxides (NO X ) from power plants and other large combustion sources...), a pervasive air pollution problem in many areas of the eastern United States. The NO X Budget... Collection Request; Comment Request; NOX Budget Trading Program To Reduce the Regional Transport of Ozone...

  3. Examination of Learner and Situation Level Variables: Choice of Speech Act and Request Strategy by Spanish L2 Learners

    ERIC Educational Resources Information Center

    Kuriscak, Lisa

    2015-01-01

    This study focuses on variation within a group of learners of Spanish (N = 253) who produced requests and complaints via a written discourse completion task. It examines the effects of learner and situational variables on production--the effect of proficiency and addressee-gender on speech-act choice and the effect of perception of imposition on…

  4. 38 CFR 20.1304 - Rule 1304. Request for change in representation, request for personal hearing, or submission of...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... change in representation, request for personal hearing, or submission of additional evidence following... Miscellaneous § 20.1304 Rule 1304. Request for change in representation, request for personal hearing, or...) Request for a change in representation, request for a personal hearing, or submission of additional...

  5. 45 CFR 612.6 - Processing requests.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 3 2012-10-01 2012-10-01 false Processing requests. 612.6 Section 612.6 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION AVAILABILITY OF RECORDS AND INFORMATION § 612.6 Processing requests. (a) Acknowledgment of requests. Each request is...

  6. 45 CFR 612.6 - Processing requests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 3 2011-10-01 2011-10-01 false Processing requests. 612.6 Section 612.6 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION AVAILABILITY OF RECORDS AND INFORMATION § 612.6 Processing requests. (a) Acknowledgment of requests. Each request is...

  7. 45 CFR 612.6 - Processing requests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 3 2010-10-01 2010-10-01 false Processing requests. 612.6 Section 612.6 Public Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION AVAILABILITY OF RECORDS AND INFORMATION § 612.6 Processing requests. (a) Acknowledgment of requests. Each request is...

  8. 49 CFR 802.7 - Requests: How, where, and when presented; verification of identity of individuals making requests...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...; verification of identity of individuals making requests; accompanying persons; and procedures for... Procedures and Requirements § 802.7 Requests: How, where, and when presented; verification of identity of... which the record is contained. (d) Verification of identity of requester. (1) For written requests, the...

  9. 49 CFR 802.7 - Requests: How, where, and when presented; verification of identity of individuals making requests...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...; verification of identity of individuals making requests; accompanying persons; and procedures for... Procedures and Requirements § 802.7 Requests: How, where, and when presented; verification of identity of... which the record is contained. (d) Verification of identity of requester. (1) For written requests, the...

  10. Identification of Transthyretin Fibril Formation Inhibitors Using Structure-Based Virtual Screening.

    PubMed

    Ortore, Gabriella; Martinelli, Adriano

    2017-08-22

    Transthyretin (TTR) is the primary carrier for thyroxine (T 4 ) in cerebrospinal fluid and a secondary carrier in blood. TTR is a stable homotetramer, but certain factors, genetic or environmental, could promote its degradation to form amyloid fibrils. A docking study using crystal structures of wild-type TTR was planned; our aim was to design new ligands that are able to inhibit TTR fibril formation. The computational protocol was thought to overcome the multiple binding modes of the ligands induced by the peculiarity of the TTR binding site and by the pseudosymmetry of the site pockets, which generally weaken such structure-based studies. Two docking steps, one that is very fast and a subsequent step that is more accurate, were used to screen the Aldrich Market Select database. Five compounds were selected, and their activity toward inhibiting TTR fibril formation was assessed. Three compounds were observed to be actives, two of which have the same potency as the positive control, and the other was found to be a promising lead compound. These results validate a computational protocol that is able to archive information on the key interactions between database compounds and TTR, which is valuable for supporting further studies. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Sex-based comparison of limb segmentation in ostriches aged 14 months with and without tibiotarsal rotation.

    PubMed

    Cooper, R G; Naranowicz, H; Maliszewska, E; Tennett, A; Horbańczuk, J O

    2008-09-01

    The aim of this study was to propose equations to predict changes that occur over time in the angular position of the bones during motion and the angular velocity of the bones in forward motion as a consequence of tibiotarsal rotation (TTR) in ostriches aged 14 months. Twenty-four normal 14-month-old ostriches (12 cocks and 12 hens) and 20 birds with TTR (9 cocks and 11 hens) were used in the study. Daily readings of temperature, relative humidity and rainfall, the lengths of the different segments of the legs and wings, the perpendicular height from the top of the torso to ground level and the length of the erect neck were recorded. Measurements of the degree of valgus deformity in the left foot were made where applicable. TTR hens and cocks were smaller in stature than normal birds. Comparing TTR hens and cocks, the toe, claw, humerus, perpendicular height and angle of rotation were larger in cocks, indicating a larger body in cocks. Hens were more severely affected by TTR. We suggest that the equations used in this study will assist in measuring movement of ostriches and how movement is compromised by overcrowding and TTR. Birds suffering from TTR may experience an increased degree of stress due to movement restrictions in confinement.

  12. 78 FR 77119 - Proposed Information Collection Request; Comment Request; Regulation of Fuels and Fuel Additives...

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  13. 78 FR 35631 - Proposed Information Collection Request; Comment Request; 40 CFR Part 64 Compliance Assurance...

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  14. 7 CFR 1.6 - Aggregating requests.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 1 2013-01-01 2013-01-01 false Aggregating requests. 1.6 Section 1.6 Agriculture Office of the Secretary of Agriculture ADMINISTRATIVE REGULATIONS Official Records § 1.6 Aggregating requests. When an agency reasonably believes that a requester, or a group of requesters acting in concert...

  15. 22 CFR 1002.4 - Written requests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 22 Foreign Relations 2 2010-04-01 2010-04-01 true Written requests. 1002.4 Section 1002.4 Foreign Relations INTER-AMERICAN FOUNDATION AVAILABILITY OF RECORDS § 1002.4 Written requests. In order to facilitate the processing of written requests, every petitioner should: (a) Address his request to: General...

  16. Nitrofen interferes with trophoblastic expression of retinol-binding protein and transthyretin during lung morphogenesis in the nitrofen-induced congenital diaphragmatic hernia model.

    PubMed

    Kutasy, Balazs; Gosemann, Jan H; Doi, Takashi; Fujiwara, Naho; Friedmacher, Florian; Puri, Prem

    2012-02-01

    Retinoids play a key role in lung development. Retinoid signaling pathway has been shown to be disrupted in the nitrofen model of congenital diaphragmatic hernia (CDH) but the exact mechanism is not clearly understood. Retinol-binding protein (RBP) and transthyretin (TTR) are transport proteins for delivery of retinol to the tissues via circulation. Previous studies have shown that pulmonary retinol levels are decreased during lung morphogenesis in the nitrofen CDH model. In human newborns with CDH, both retinol and RBP levels are decreased. It has been reported that maternal RBP does not cross the placenta and the fetus produces its own RBP by trophoblast. RBP and TTR synthesized in the fetus are essential for retinol transport to the developing organs including lung morphogenesis. We hypothesized that nitrofen interferes with the trophoblastic expression of RBP and TTR during lung morphogenesis and designed this study to examine the trophoblastic expression of RBP and TTR, and the total level of RBP and TTR in the lung in the nitrofen model of CDH. Pregnant rats were exposed to either olive oil or nitrofen on day 9 of gestation (D9). Fetal lungs and placenta harvested on D21 and divided into two groups: control (n = 8) and nitrofen with CDH (n = 8). Total lung RBP and TTR levels using protein extraction were compared with enzyme linked immunoassay (ELISA). Immunohistochemistry was performed to evaluate trophoblastic RBP and TTR expression. Total protein levels of lung RBP and TTR were significantly lower in CDH (0.26 ± 0.003 and 6.4 ± 0.5 μg/mL) compared with controls (0.4 ± 0.001 and 9.9 ± 1.6 μg/mL, p < 0.05). In the control group, immunohistochemical staining showed strong immunoreactivity of RBP and TTR in the trophoblast compared to CDH group. Decreased trophoblast expression of retinol transport proteins suggest that nitrofen may interfere with the fetal retinol transport resulting in reduced pulmonary RBP and TTR levels and causing pulmonary

  17. 22 CFR 1502.4 - Written requests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

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  18. 76 FR 41320 - Agency Information Collection Activities; Proposed Request and Comment Request

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  19. 19 CFR 201.12 - Requests.

    Code of Federal Regulations, 2013 CFR

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  20. 19 CFR 201.12 - Requests.

    Code of Federal Regulations, 2014 CFR

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  1. 78 FR 39054 - Agency Information Collection Activities: Proposed Request and Comment Request

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  10. 8 CFR 103.40 - Genealogical Research Requests.

    Code of Federal Regulations, 2014 CFR

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  11. 8 CFR 103.40 - Genealogical Research Requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    .... Genealogy requests are requests for searches and/or copies of historical records relating to a deceased person, usually for genealogy and family history research purposes. (b) Manner of requesting genealogical searches and records. Requests must be submitted on Form G-1041, Genealogy Index Search Request, or Form G...

  12. Impact of co-morbidities and patient characteristics on international normalized ratio control over time in patients with nonvalvular atrial fibrillation.

    PubMed

    Nelson, Winnie W; Choi, Jiyoon C; Vanderpoel, Julie; Damaraju, Chandrasekharra V; Wildgoose, Peter; Fields, Larry E; Schein, Jeffrey R

    2013-08-15

    This study determined the association between co-morbidities, including heart failure (HF) and time in therapeutic range (TTR), in patients with nonvalvular atrial fibrillation. Longitudinal patient-level anticoagulation management records collected from 2006 to 2010 were analyzed. Adult patients with nonvalvular atrial fibrillation who used warfarin for a 12-month period with no gap of >60 days between visits were identified. TTR <55% was defined as "lower" TTR. CHADS₂ score of ≥2 was defined as "higher" CHADS₂. Logistic regression analyses were conducted to determine the association between co-morbidities and TTR. A total of 23,425 patients met the study criteria. The mean age ± SD was 74.8 ± 9.7 years, with 84.8% aged ≥65 years. The most common co-morbidities were hypertension (41.7%), diabetes (24.1%), HF (11.7%), and previous stroke (11.1%). The mean TTR ± SD was 67.3 ± 14.4%, with 18.6% of patients in the lower TTR range. In multivariate analyses using age, gender, hypertension, diabetes, stroke, and region as covariates, HF (adjusted odds ratio [OR] 1.41, 95% confidence interval [CI] 1.28 to 1.56; p <0.001), diabetes (OR 1.28, 95% CI 1.19 to 1.38; p <0.001), and previous stroke (OR 1.15, 95% CI 1.04 to 1.27; p <0.001) were associated with lower TTR. In a second set of multivariate analyses using gender and region as covariates, a higher CHADS₂ score was associated with lower TTR (OR 1.11, 95% CI 1.04 to 1.18; p <0.001). In conclusion, HF was associated with the greatest likelihood of a lower TTR, followed by diabetes, then stroke. Anticoagulation control may be more challenging for patients with these conditions. Copyright © 2013 The Authors. Published by Elsevier Inc. All rights reserved.

  13. The effect of the amiodarone-warfarin interaction on anticoagulation quality in a single, high-quality anticoagulation center.

    PubMed

    White, Ryan D; Riggs, Kyle W; Ege, Ed J; Petroski, Gregory F; Koerber, Scott M; Flaker, Greg

    2016-03-01

    Clinical trials have reported a low time in therapeutic range (TTR) in patients with atrial fibrillation treated with both warfarin andamiodarone. These trials included centers and countries with both high and low TTRs. What is the impact of amiodarone on the TTR in a single, high-quality anticoagulation clinic? TTR was assessed in amiodarone and nonamiodarone-treated patients from a University anticoagulation clinic. Baseline characteristics between patients ever-taking or never-taking amiodarone were similar, except more amiodarone patients were smokers (19.5 vs. 6.1%, P = 0.0031). The TTR calculated from 8901international normalized ratios (INRs) in 249 nonamiodarone patients with a mean follow-up of 34 ± 20 months (mean INR 36 ± 18) was 66 ± 16.6% compared with 61.3 ± 16.2% (P = 0.111) from 1455 INRs in 41 amiodarone-treated patients with a mean follow-up of 28 ± 20 months (mean INR 35 ± 22). Factors associated with a low TTR were male sex (P = 0.0013), smoker (P = 0.0048), and amiodarone use (P = 0.0374). A second on-treatment analysis, in which the TTR was calculated only during amiodarone therapy, resulted in similar findings; however, amiodarone did not emerge as a predictor of a low TTR. In 11 patients, the TTR prior to amiodarone (54.5 ± 22.2%) was not significantly different in the first 3 months (54.6 ± 33.4%) or after 3 months (67.2 ± 33.7%) of amiodarone. In a single high-quality anticoagulation center, anticoagulation quality, as measured by the TTR, can be comparable in amiodarone and nonamiodarone-treated patients.

  14. Quality of Anticoagulation Control in Preventing Adverse Events in Heart Failure Patients in Sinus Rhythm: A Warfarin Aspirin Reduced Cardiac Ejection Fraction Trial (WARCEF) Substudy

    PubMed Central

    Homma, Shunichi; Thompson, John L.P.; Qian, Min; Ye, Siqin; Di Tullio, Marco R.; Lip, Gregory Y.H.; Mann, Douglas L.; Sacco, Ralph L.; Levin, Bruce; Pullicino, Patrick M.; Freudenberger, Ronald S.; Teerlink, John R.; Graham, Susan; Mohr, J.P.; Labovitz, Arthur J.; Buchsbaum, Richard; Estol, Conrado J.; Lok, Dirk J.; Ponikowski, Piotr; Anker, Stefan D.

    2015-01-01

    Background The aim of this study is to examine the relationship between time in therapeutic range (TTR) and clinical outcomes in heart failure (HF) patients in sinus rhythm (SR) treated with warfarin. Methods and Results We used data from the Warfarin vs. Aspirin in Reduced Cardiac Ejection Fraction Trial (WARCEF) to assess the relationship of TTR with the WARCEF primary outcome (ischemic stroke, intracerebral hemorrhage, or death); with death alone; ischemic stroke alone; major hemorrhage alone; and net clinical benefit (primary outcome and major hemorrhage combined). Multivariable Cox models were used to examine how the event risk changed with TTR and to compare the high TTR, low TTR, and aspirin patients, with TTR being treated as a time-dependent covariate. 2,217 patients were included in the analyses, among whom 1,067 were randomized to warfarin and 1,150 were randomized to aspirin. The median (IQR) follow-up duration was 3.6 (2.0–5.0) years. Mean (±SD) age was 61±11.3 years, with 80% being men. The mean (±SD) TTR was 57% (±28.5%). Increasing TTR was significantly associated with reduction in primary outcome (adjusted p<0.001), death alone (adjusted p=0.001), and improved net clinical benefit (adjusted p<0.001). A similar trend was observed for the other two outcomes but significance was not reached (adjusted p=0.082 for ischemic stroke, adjusted p=0.109 for major hemorrhage). Conclusions In HF patients in SR, increasing TTR is associated with better outcome and improved net clinical benefit. Patients in whom good quality anticoagulation can be achieved may benefit from the use of anticoagulants. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00041938. PMID:25850425

  15. Alternative calculations of individual patient time in therapeutic range while taking warfarin: results from the ROCKET AF trial.

    PubMed

    Singer, Daniel E; Hellkamp, Anne S; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R; Piccini, Jonathan P; Hankey, Graeme J; Breithardt, Günter; Halperin, Jonathan L; Becker, Richard C; Hacke, Werner; Nessel, Christopher C; Mahaffey, Kenneth W; Fox, Keith A A; Califf, Robert M

    2015-03-03

    In the ROCKET AF (Rivaroxaban-Once-daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter-INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow-up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change-based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in-range INRs ("corrections") versus INRs that were out of range in the opposite direction ("overshoots"). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change-based approach, depending on assumptions. However, large inter-regional differences in anticoagulation control persisted. TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow-up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change-based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter-regional differences previously reported. URL: ClinicalTrials.gov. Unique identifier: NCT00403767. © 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  16. Alternative Calculations of Individual Patient Time in Therapeutic Range While Taking Warfarin: Results From the ROCKET AF Trial

    PubMed Central

    Singer, Daniel E.; Hellkamp, Anne S.; Yuan, Zhong; Lokhnygina, Yuliya; Patel, Manesh R.; Piccini, Jonathan P.; Hankey, Graeme J.; Breithardt, Günter; Halperin, Jonathan L.; Becker, Richard C.; Hacke, Werner; Nessel, Christopher C.; Mahaffey, Kenneth W.; Fox, Keith A. A.; Califf, Robert M.

    2015-01-01

    Background In the ROCKET AF (Rivaroxaban–Once‐daily, oral, direct Factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation) trial, marked regional differences in control of warfarin anticoagulation, measured as the average individual patient time in the therapeutic range (iTTR) of the international normalized ratio (INR), were associated with longer inter‐INR test intervals. The standard Rosendaal approach can produce biased low estimates of TTR after an appropriate dose change if the follow‐up INR test interval is prolonged. We explored the effect of alternative calculations of TTR that more immediately account for dose changes on regional differences in mean iTTR in the ROCKET AF trial. Methods and Results We used an INR imputation method that accounts for dose change. We compared group mean iTTR values between our dose change–based method with the standard Rosendaal method and determined that the differences between approaches depended on the balance of dose changes that produced in‐range INRs (“corrections”) versus INRs that were out of range in the opposite direction (“overshoots”). In ROCKET AF, the overall mean iTTR of 55.2% (Rosendaal) increased up to 3.1% by using the dose change–based approach, depending on assumptions. However, large inter‐regional differences in anticoagulation control persisted. Conclusions TTR, the standard measure of control of warfarin anticoagulation, depends on imputing daily INR values for the vast majority of follow‐up days. Our TTR calculation method may better reflect the impact of warfarin dose changes than the Rosendaal approach. In the ROCKET AF trial, this dose change–based approach led to a modest increase in overall mean iTTR but did not materially affect the large inter‐regional differences previously reported. Clinical Trial Registration URL: ClinicalTrials.gov. Unique identifier: NCT00403767. PMID:25736441

  17. 78 FR 15377 - Agency Information Collection Activities; Submission for OMB Review; Comment Request; Requests To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-11

    ... for OMB Review; Comment Request; Requests To Approve Conformed Wage Classifications and Unconventional... Classifications and Unconventional Fringe Benefit Plans Under the Davis-Bacon and Related Acts and Contract Work... collection consist of: (A) Reports of conformed classifications and wage rates and (B) requests for approval...

  18. 76 FR 23640 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-27

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202-395-6974, E-mail address: [email protected] . (SSA), Social Security Administration...

  19. 78 FR 33142 - Agency Information Collection Activities; Proposed Request and Comment Request

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    2013-06-03

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities; Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202-395-6974, Email address: [email protected] . (SSA) Social Security Administration, DCRDP...

  20. 78 FR 79723 - Agency Information Collection Activities: Proposed Request and Comment Request

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    2013-12-31

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202-395-6974, Email address: [email protected] . (SSA) Social Security Administration, OLCA...

  1. 78 FR 72744 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-03

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202-395-6974, Email address: [email protected] . (SSA) Social Security Administration, OLCA...

  2. 75 FR 35512 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-22

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202-395-6974, E-mail address: [email protected] . (SSA), Social Security Administration...

  3. 78 FR 70391 - Agency Information Collection Activities: Proposed Request and Comment Request

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    2013-11-25

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202-395-6974, Email address: [email protected] . (SSA), Social Security Administration, OLCA...

  4. 75 FR 59318 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-27

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202- 395-6974, E-mail address: [email protected] . (SSA) Social Security Administration...

  5. 76 FR 18290 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-04-01

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202-395-6974, E-mail address: [email protected] ; (SSA), Social Security Administration...

  6. 76 FR 19175 - Agency Information Collection Activities: Proposed Request and Comment Request

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    2011-04-06

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202-395-6974, E-mail address: [email protected] . (SSA), Social Security Administration...

  7. 76 FR 48200 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-08

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202-395-6974, E-mail address: [email protected] . (SSA), Social Security Administration...

  8. 76 FR 17977 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-31

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202- 395-6974, E-mail address: [email protected] . (SSA) Social Security Administration...

  9. 76 FR 5233 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-28

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: 202-395-6974. E-mail address: [email protected] . (SSA) Social Security Administration...

  10. Goal orientation, perceived task outcome and task demands in mathematics tasks: effects on students' attitude in actual task settings.

    PubMed

    Seegers, Gerard; van Putten, Cornelis M; de Brabander, Cornelis J

    2002-09-01

    In earlier studies, it has been found that students' domain-specific cognitions and personal learning goals (goal orientation) influence task-specific appraisals of actual learning tasks. The relations between domain-specific and task-specific variables have been specified in the model of adaptive learning. In this study, additional influences, i.e., perceived task outcome on a former occasion and variations in task demands, were investigated. The purpose of this study was to identify personality and situational variables that mediate students' attitude when confronted with a mathematics task. Students worked on a mathematics task in two subsequent sessions. Effects of perceived task outcome at the first session on students' attitude at the second session were investigated. In addition, we investigated how differences in task demands influenced students' attitude. Variations in task demands were provoked by different conditions in task-instruction. In one condition, students were told that the result on the test would add to their mark on mathematics. This outcome orienting condition was contrasted with a task-orienting condition where students were told that the results on the test would not be used to give individual grades. Participants were sixth grade students (N = 345; aged 11-12 years) from 14 primary schools. Multivariate and univariate analyses of (co)variance were applied to the data. Independent variables were goal orientation, task demands, and perceived task outcome, with task-specific variables (estimated competence for the task, task attraction, task relevance, and willingness to invest effort) as the dependent variables. The results showed that previous perceived task outcome had a substantial impact on students' attitude. Additional but smaller effects were found for variation in task demands. Furthermore, effects of previous perceived task outcome and task demands were related to goal orientation. The resulting pattern confirmed that, in general

  11. 78 FR 54889 - Proposed Information Collection Request; Comment Request; Confidentiality Rules (Renewal)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-06

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OEI-2013-0565; FRL -9535-9] Proposed Information Collection Request; Comment Request; Confidentiality Rules (Renewal) AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The Environmental Protection Agency is planning to submit an...

  12. 78 FR 62629 - Proposed Information Collection Request; Comment Request; Clean Water Act Section 404 State...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-22

    ... comments to OMB. Abstract: Section 404(g) of the Clean Water Act authorizes States [and Tribes] to assume... States/Tribes requesting assumption of the Clean Water Act section 404 permit program; States/ [[Page... Collection Request; Comment Request; Clean Water Act Section 404 State-Assumed Programs (Renewal) AGENCY...

  13. 78 FR 45283 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-26

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...: Desk Officer for SSA, Fax: 202-395-6974, Email address: [email protected] . (SSA) Social...

  14. 78 FR 67434 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-12

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection... Officer for SSA, Fax: 202-395-6974, Email address: [email protected] . (SSA) Social Security...

  15. 77 FR 29441 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-17

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection... Officer for SSA, Fax: 202-395-6974, Email address: [email protected] . (SSA), Social Security...

  16. 78 FR 21181 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-09

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection... Officer for SSA, Fax: 202-395-6974, Email address: [email protected] . (SSA) Social Security...

  17. 77 FR 6853 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-09

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection... Officer for SSA, Fax: 202-395-6974, Email address: [email protected] . (SSA), Social Security...

  18. 78 FR 9102 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-07

    ... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection... Officer for SSA, Fax: 202-395-6974, Email address: [email protected] . (SSA) Social Security...

  19. Interval to Testosterone Recovery After Hormonal Therapy for Prostate Cancer and Risk of Death

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

    D'Amico, Anthony V.; Chen, M.-H.; Renshaw, Andrew A.

    Purpose: To assess whether the risk of death is associated with the time to testosterone recovery (TTR) after radiotherapy (RT) and hormonal therapy (HT) for prostate cancer (PCa). Patients and Methods: Between 1995 and 2001, 206 men with localized, unfavorable-risk PCa were randomized to receive RT or RT plus 6 months of HT. A multivariate postrandomization Cox regression analysis was used to assess whether the TTR in years was associated with the risk of death after adjusting for the known prognostic factors, age, Adult Comorbidity Evaluation-27 score, and the use of HT for recurrence. Results: Of the 102 men randomizedmore » to receive RT and HT, 57 (56%) had a TTR of >2 years, and none of these men had died of PCa after a median follow-up of 7.6 years. As the TTR increased, the risk of death decreased significantly (adjusted hazard ratio, 0.60; 95% confidence interval, 0.43-0.84; p = .003). A significant interaction was noted between the TTR and the comorbidity score (p = .002). The survival estimates were similar (p = 0.17) across the TTR values in men with moderate to severe comorbidity; however, these estimates increased significantly (p < .001) with decreasing PCa-specific mortality (p = .006) as the TTR increased in men with no or minimal comorbidity. Conclusion: The results of our study have shown that a longer TTR after RT plus 6 months of HT for unfavorable-risk PCa is associated with a lower risk of death in men with no or minimal comorbidity.« less

  20. The Importance of a Gatekeeper Residue on the Aggregation of Transthyretin

    PubMed Central

    Sant'Anna, Ricardo; Braga, Carolina; Varejão, Nathalia; Pimenta, Karinne M.; Graña-Montes, Ricardo; Alves, Aline; Cortines, Juliana; Cordeiro, Yraima; Ventura, Salvador; Foguel, Debora

    2014-01-01

    Protein aggregation into β-sheet-enriched amyloid fibrils is associated with an increasing number of human disorders. The adoption of such amyloid conformations seems to constitute a generic property of polypeptide chains. Therefore, during evolution, proteins have adopted negative design strategies to diminish their intrinsic propensity to aggregate, including enrichment of gatekeeper charged residues at the flanks of hydrophobic aggregation-prone segments. Wild type transthyretin (TTR) is responsible for senile systemic amyloidosis, and more than 100 mutations in the TTR gene are involved in familial amyloid polyneuropathy. The TTR 26–57 segment bears many of these aggressive amyloidogenic mutations as well as the binding site for heparin. We demonstrate here that Lys-35 acts as a gatekeeper residue in TTR, strongly decreasing its amyloidogenic potential. This protective effect is sequence-specific because Lys-48 does not affect TTR aggregation. Lys-35 is part of the TTR basic heparin-binding motif. This glycosaminoglycan blocks the protective effect of Lys-35, probably by neutralization of its side chain positive charge. A K35L mutation emulates this effect and results in the rapid self-assembly of the TTR 26–57 region into amyloid fibrils. This mutation does not affect the tetrameric protein stability, but it strongly increases its aggregation propensity. Overall, we illustrate how TTR is yet another amyloidogenic protein exploiting negative design to prevent its massive aggregation, and we show how blockage of conserved protective features by endogenous factors or mutations might result in increased disease susceptibility. PMID:25086037

  1. Flavonoid interactions with human transthyretin: combined structural and thermodynamic analysis.

    PubMed

    Trivella, Daniela B B; dos Reis, Caio V; Lima, Luís Maurício T R; Foguel, Débora; Polikarpov, Igor

    2012-10-01

    Transthyretin (TTR) is a carrier protein involved in human amyloidosis. The development of small molecules that may act as TTR amyloid inhibitors is a promising strategy to treat these pathologies. Here we selected and characterized the interaction of flavonoids with the wild type and the V30M amyloidogenic mutant TTR. TTR acid aggregation was evaluated in vitro in the presence of the different flavonoids. The best TTR aggregation inhibitors were studied by Isothermal Titration Calorimetry (ITC) in order to reveal their thermodynamic signature of binding to TTRwt. Crystal structures of TTRwt in complex with the top binders were also obtained, enabling us to in depth inspect TTR interactions with these flavonoids. The results indicate that changing the number and position of hydroxyl groups attached to the flavonoid core strongly influence flavonoid recognition by TTR, either by changing ligand affinity or its mechanism of interaction with the two sites of TTR. We also compared the results obtained for TTRwt with the V30M mutant structure in the apo form, allowing us to pinpoint structural features that may facilitate or hamper ligand binding to the V30M mutant. Our data show that the TTRwt binding site is labile and, in particular, the central region of the cavity is sensible for the small differences in the ligands tested and can be influenced by the Met30 amyloidogenic mutation, therefore playing important roles in flavonoid binding affinity, mechanism and mutant protein ligand binding specificities. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Transthyretin amyloid polyneuropathies mimicking a demyelinating polyneuropathy.

    PubMed

    Lozeron, Pierre; Mariani, Louise-Laure; Dodet, Pauline; Beaudonnet, Guillemette; Théaudin, Marie; Adam, Clovis; Arnulf, Bertrand; Adams, David

    2018-06-15

    To clearly define transthyretin familial amyloid polyneuropathies (TTR-FAPs) fulfilling definite clinical and electrophysiologic European Federation of Neurological Societies/Peripheral Nerve Society criteria for chronic inflammatory demyelinating polyneuropathy (CIDP). From a cohort of 194 patients with FAP, 13 of 84 patients (15%) of French ancestry had late-onset demyelinating TTR-FAP. We compared clinical presentation and electrophysiology to a cohort with CIDP and POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes) syndrome. We assessed nerve histology and the correlation between motor/sensory amplitudes/velocities. Predictors of demyelinating TTR-FAP were identified from clinical and electrophysiologic data. Pain, dysautonomia, small fiber sensory loss above the wrists, upper limb weakness, and absence of ataxia were predictors of demyelinating TTR-FAP ( p < 0.01). The most frequent demyelinating features were prolonged distal motor latency of the median nerve and reduced sensory conduction velocity of the median and ulnar nerves. Motor axonal loss was severe and frequent in the median, ulnar, and tibial nerves ( p < 0.05) in demyelinating FAP. Ulnar nerve motor amplitude <5.4 mV and sural nerve amplitude <3.95 μV were distinguishing characteristics of demyelinating TTR-FAP. Nerve biopsy showed severe axonal loss and occasional segmental demyelination-remyelination. Misleading features of TTR-FAP fulfilling criteria for CIDP are not uncommon in sporadic late-onset TTR-FAP, which highlights the limits of European Federation of Neurological Societies/Peripheral Nerve Society criteria. Specific clinical aspects and marked electrophysiologic axonal loss are red flag symptoms that should alert to this diagnosis and prompt TTR gene sequencing. © 2018 American Academy of Neurology.

  3. 77 FR 59664 - Agency Information Collection Activities: Extension Requested; Comments Requested, Monitoring...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-28

    ... DEPARTMENT OF JUSTICE [OMB Number 1103-0100] Agency Information Collection Activities: Extension Requested; Comments Requested, Monitoring Information Collections ACTION: 60-day notice. The Department of.... (2) Title of the Form/Collection: Monitoring Information Collections. (3) Agency form number, if any...

  4. 75 FR 15761 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-30

    ... technology. Mail, e-mail, or fax your comments and recommendations on the information collection(s) to the... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...

  5. 77 FR 8322 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-02-14

    ... Fund and Federal income tax revenues. Sections 1110 and 234 of the Social Security Act authorize this... SOCIAL SECURITY ADMINISTRATION Agency Information Collection Activities: Proposed Request and Comment Request The Social Security Administration (SSA) publishes a list of information collection...

  6. 14 CFR 1206.703 - Aggregation of requests.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... RECORDS TO MEMBERS OF THE PUBLIC Search, Review, and Duplication Fees § 1206.703 Aggregation of requests... group of requesters acting in concert, is attempting to break a request down into a series of requests...

  7. 14 CFR 1206.703 - Aggregation of requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... RECORDS TO MEMBERS OF THE PUBLIC Search, Review, and Duplication Fees § 1206.703 Aggregation of requests... group of requesters acting in concert, is attempting to break a request down into a series of requests...

  8. 14 CFR 1206.703 - Aggregation of requests.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... RECORDS TO MEMBERS OF THE PUBLIC Search, Review, and Duplication Fees § 1206.703 Aggregation of requests... group of requesters acting in concert, is attempting to break a request down into a series of requests...

  9. 25 CFR 517.4 - Requirements for making requests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... INFORMATION ACT PROCEDURES § 517.4 Requirements for making requests. (a) How to make a FOIA request. Requests... additional information. If the requester is making a request for records about another individual, the..., the requester will be notified of this decision and advised that fees associated with the processing...

  10. 45 CFR 2106.2 - Requests for access.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... WITH 5 U.S.C. 552a, THE PRIVACY ACT OF 1974 § 2106.2 Requests for access. (a) Requirement for written.... The request should state that the request is pursuant to the Privacy Act of 1974. In the absence of... system of records, the request will be presumed to be made under the Privacy Act of 1974. The requester...

  11. 45 CFR 2106.2 - Requests for access.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... WITH 5 U.S.C. 552a, THE PRIVACY ACT OF 1974 § 2106.2 Requests for access. (a) Requirement for written.... The request should state that the request is pursuant to the Privacy Act of 1974. In the absence of... system of records, the request will be presumed to be made under the Privacy Act of 1974. The requester...

  12. 78 FR 75342 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; NESHAP...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-11

    ... Request Submitted to OMB for Review and Approval; Comment Request; NESHAP for Lime Manufacturing (Renewal... Agency has submitted an information collection request (ICR), ``NESHAP for Lime Manufacturing (40 CFR... required semiannually. Form Numbers: None. Respondents/affected entities: Lime manufacturing plants...

  13. 77 FR 30306 - Notice of Proposed Information Collection: Comment Request; Request for Acceptance of Changes in...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-22

    ... Information Collection: Comment Request; Request for Acceptance of Changes in Approved Drawings and... also lists the following information: Title of Proposal: Changes in Approved Drawings and... proposed use: Builders who request changes to HUD's accepted drawings and specifications for proposed...

  14. 78 FR 10263 - Proposed Collection; Comment Request for ADA Accommodations Request Packet

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-13

    ... DEPARTMENT OF THE TREASURY Internal Revenue Service Proposed Collection; Comment Request for ADA... the ADA Accommodations Packet. DATES: Written comments should be received on or before April 15, 2013...: ADA Accommodations Request Packet. OMB Number: 1545-2027. Abstract: Information is collected so that...

  15. Relations of Anticoagulant Therapy with Cognitive Impairment among Patients with Atrial Fibrillation: A Meta-Analysis and Systematic Review.

    PubMed

    Cheng, Wenke; Liu, Weijun; Li, Bin; Li, Dongfang

    2018-03-02

    Currently, it is considered that atrial fibrillation (AF) is a risk factor for cognitive impairment and dementia, which is independent of stroke. However, the relationship between anticoagulant drugs and cognitive function in patients with atrial fibrillation is unknown. This study aimed to complete a meta-analysis, and investigate the association between Anticoagulant therapy and cognitive impairment in patients undergoing AF. Two investigators systematically searched the Cochrane Library, PubMed, Embase databases and Web of Science for all studies showing associations. Hazard ratios (HRs) were extracted and pooled. 8 studies included 471057 participants; TTR < 25% vs TTR> 75%; (HR 3.02, 95% CI 1.12-8.91; P=0.03); TTR 25-50% vs TTR> 75% (HR 2.44, 95% CI 0.95-6.22; P=0.06); TTR 50-75% vs TTR> 75% (HR 1.75, 95% CI 0.90-3.99; P=0.1); OAC vs No OAC (HR 0.71, 95% CI.69-0.74; P<0.00001) NOAC vs warfarin (HR0.51, 95% CI0.37-0.71; P<0.00001). Oral anticoagulants (OAC) significantly reduce the occurrence of cognitive impairment in patients with atrial fibrillation. Compared with warfarin, NOAC has an efficiently protective effect on cognition. In the range of INR2-3, with the increase of TTR, the incidence of cognitive impairment is lower.

  16. Task frequency influences stimulus-driven effects on task selection during voluntary task switching.

    PubMed

    Arrington, Catherine M; Reiman, Kaitlin M

    2015-08-01

    Task selection during voluntary task switching involves both top-down (goal-directed) and bottom-up (stimulus-driven) mechanisms. The factors that shift the balance between these two mechanisms are not well characterized. In the present research, we studied the role that task frequency plays in determining the extent of stimulus-driven task selection. In two experiments, we used the basic paradigm adapted from Arrington (Memory & Cognition, 38, 991-997, 2008), in which the effect of stimulus availability serves as a marker of stimulus-driven task selection. A number and letter appeared on each trial with varying stimulus onset asynchronies, and participants performed either a consonant/vowel or an even/odd judgment. In Experiment 1, participants were instructed as to the relative frequency with which each task was to be performed (i.e., 50/50, 60/40, or 75/25) and were further instructed to make their transitions between tasks unpredictable. In Experiment 2, participants were given no instructions about how to select tasks, resulting in naturally occurring variation in task frequency. With both instructed (Exp. 1) and naturally occurring (Exp. 2) relative task frequencies, the less frequently performed task showed a greater effect of stimulus availability on task selection, suggestive of a larger influence of stimulus-driven mechanisms during task performance for the less frequent task. When goal-directed mechanisms of task choice are engaged less frequently, the relative influence of the stimulus environment increases.

  17. 14 CFR 1206.703 - Aggregation of requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... documents, solely in order to avoid payment of fees. When NASA has reason to believe that a requester or a group of requesters acting in concert, is attempting to break a request down into a series of requests...

  18. 78 FR 73524 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; NSPS...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-06

    ... Request Submitted to OMB for Review and Approval; Comment Request; NSPS for Rubber Tire Manufacturing... Protection Agency has submitted an information collection request (ICR), ``NSPS for Rubber Tire Manufacturing.../dockets . Abstract: Respondents are owners or operators of rubber tire manufacturing plants which include...

  19. 36 CFR 1007.4 - Preliminary processing of requests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... requests. 1007.4 Section 1007.4 Parks, Forests, and Public Property PRESIDIO TRUST REQUESTS UNDER THE FREEDOM OF INFORMATION ACT § 1007.4 Preliminary processing of requests. (a) Scope of requests. Unless a... request under § 1007.6, the requester shall be notified of the delay as provided in § 1007.6(f). (5...

  20. 12 CFR 602.16 - Combining requests.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ....16 Combining requests. You may not avoid paying fees by filing multiple requests at the same time. When FCA reasonably believes that you, alone or with others, are breaking down a request into a series...

  1. 12 CFR 602.16 - Combining requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ....16 Combining requests. You may not avoid paying fees by filing multiple requests at the same time. When FCA reasonably believes that you, alone or with others, are breaking down a request into a series...

  2. 12 CFR 602.16 - Combining requests.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ....16 Combining requests. You may not avoid paying fees by filing multiple requests at the same time. When FCA reasonably believes that you, alone or with others, are breaking down a request into a series...

  3. 75 FR 21294 - Agency Information Collection Request; 30-Day Public Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-04-23

    ... DEPARTMENT OF HEALTH AND HUMAN SERVICES [Document Identifier OS-0990-0344; 30-Day Notice] Agency Information Collection Request; 30-Day Public Comment Request AGENCY: Office of the Secretary, HHS. In... of the Secretary (OS), Department of Health and Human Services, is publishing the following summary...

  4. 76 FR 38449 - Agency Information Collection Activities; Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-30

    ... verifying the requester's identity, SSA uses the information from BEVE to provide the POI statement. SSA...: 2 minutes. Estimated Annual Burden: 1,067 hours. 3. Teacher Questionnaire and Request for...), SSA obtains information about the child's functioning from teachers, parents, and others who observe...

  5. 76 FR 16857 - Proposed Information Collection (Request for Contact Information); Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-25

    ... (Request for Contact Information); Comment Request AGENCY: Veterans Benefits Administration, Department of... response to the notice. This notice solicits comments on information needed to obtain contact information... viewed online through FDMS. FOR FURTHER INFORMATION CONTACT: Nancy J. Kessinger at (202) 461-9769 or FAX...

  6. Identifying Speech Acts in E-Mails: Toward Automated Scoring of the "TOEIC"® E-Mail Task. Research Report. ETS RR-12-16

    ERIC Educational Resources Information Center

    De Felice, Rachele; Deane, Paul

    2012-01-01

    This study proposes an approach to automatically score the "TOEIC"® Writing e-mail task. We focus on one component of the scoring rubric, which notes whether the test-takers have used particular speech acts such as requests, orders, or commitments. We developed a computational model for automated speech act identification and tested it…

  7. Aerial Refueling Clearance Initiation Request

    DTIC Science & Technology

    2016-07-14

    and receiver agencies. The AR Clearance Initiation Request document recognizes the requirement for definitive aerial refueling agreements between...and contractual tanker support requests from one organization or nation to another. The AR Clearance Initiation Request document is not intended to...proprietary, sensitive, classified or otherwise restricted information. ARSAG documents, as prepared, are not DOD, MOD or NATO standards, but provide

  8. The recombinant adeno-associated virus vector (rAAV2)-mediated apolipoprotein B mRNA-specific hammerhead ribozyme: a self-complementary AAV2 vector improves the gene expression

    PubMed Central

    Zhong, Shumei; Sun, Shihua; Teng, Ba-Bie

    2004-01-01

    Background In humans, overproduction of apolipoprotein B (apoB) is positively associated with premature coronary artery diseases. To reduce the levels of apoB mRNA, we have designed an apoB mRNA-specific hammerhead ribozyme targeted at nucleotide sequences GUA6679 (RB15) mediated by adenovirus, which efficiently cleaves and decreases apoB mRNA by 80% in mouse liver and attenuates the hyperlipidemic condition. In the current study, we used an adeno-associated virus vector, serotype 2 (AAV2) and a self-complementary AAV2 vector (scAAV2) to demonstrate the effect of long-term tissue-specific gene expression of RB15 on the regulation apoB mRNA in vivo. Methods We constructed a hammerhead ribozyme RB15 driven by a liver-specific transthyretin (TTR) promoter using an AAV2 vector (rAAV2-TTR-RB15). HepG2 cells and hyperlipidemic mice deficient in both the low density lipoprotein receptor and the apoB mRNA editing enzyme genes (LDLR-/-Apobec1-/-; LDb) were transduced with rAAV2-TTR-RB15 and a control vector rAAV-TTR-RB15-mutant (inactive ribozyme). The effects of ribozyme RB15 on apoB metabolism and atherosclerosis development were determined in LDb mice at 5-month after transduction. A self-complementary AAV2 vector expressing ribozyme RB15 (scAAV2-TTR-RB15) was also engineered and used to transduce HepG2 cells. Studies were designed to compare the gene expression efficiency between rAAV2-TTR-RB15 and scAAV2-TTR-RB15. Results The effect of ribozyme RB15 RNA on reducing apoB mRNA levels in HepG2 cells was observed only on day-7 after rAAV2-TTR-RB15 transduction. And, at 5-month after rAAV2-TTR-RB15 treatment, the apoB mRNA levels in LDb mice were significantly decreased by 43%, compared to LDb mice treated with control vector rAAV2-TTR-RB15-mutant. Moreover, both the rAAV2-TTR-RB15 viral DNA and ribozyme RB15 RNA were still detectable in mice livers at 5-month after treatment. However, this rAAV2-TTR-RB15 vector mediated a prolonged but low level of ribozyme RB15 gene

  9. 78 FR 24194 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; Solid...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-24

    ... Request Submitted to OMB for Review and Approval; Comment Request; Solid Waste Disposal Facility Criteria... Protection Agency has submitted an information collection request (ICR), Solid Waste Disposal Facility... 40 CFR Part 258 on a State level, owners/operators of municipal solid waste landfills have to comply...

  10. 77 FR 27829 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-11

    ... request special needs related to an ALJ hearing. All respondents will use the ASA system (via SSA's... Administration to Obtain Account Records from a Financial Institution and Request for Records (Medicare)--0960... applicants' accounts at financial institutions to determine if they are eligible for the [[Page 27830...

  11. 8 CFR 103.40 - Genealogical Research Requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 8 Aliens and Nationality 1 2010-01-01 2010-01-01 false Genealogical Research Requests. 103.40... DUTIES; AVAILABILITY OF RECORDS § 103.40 Genealogical Research Requests. (a) Nature of requests... person, usually for genealogy and family history research purposes. (b) Manner of requesting genealogical...

  12. 14 CFR 1206.701 - Categories of requesters.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... scientific institution) research. Requesters must reasonably describe the records sought. (c) Requesters who... RECORDS TO MEMBERS OF THE PUBLIC Search, Review, and Duplication Fees § 1206.701 Categories of requesters... scientific institutions; representatives of the news media; and all other requesters. The Act prescribes...

  13. 14 CFR 1206.701 - Categories of requesters.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... scientific institution) research. Requesters must reasonably describe the records sought. (c) Requesters who... RECORDS TO MEMBERS OF THE PUBLIC Search, Review, and Duplication Fees § 1206.701 Categories of requesters... scientific institutions; representatives of the news media; and all other requesters. The Act prescribes...

  14. 14 CFR 1206.701 - Categories of requesters.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... scientific institution) research. Requesters must reasonably describe the records sought. (c) Requesters who... RECORDS TO MEMBERS OF THE PUBLIC Search, Review, and Duplication Fees § 1206.701 Categories of requesters... scientific institutions; representatives of the news media; and all other requesters. The Act prescribes...

  15. 31 CFR 14.4 - Contents of request.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... § 14.4 Contents of request. The formal written request shall be in the form of a letter or memorandum... forth that official's name, title, business address and business phone number. The request shall also... order shall be attached to the formal written request. ...

  16. Post-Closure Inspection Report for the Tonopah Test Range, Nevada, for Calendar Year 2014

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

    Silvas, A. J.; Lantow, Tiffany A.

    This report provides the results of the annual post-closure inspections conducted at the closed Corrective Action Units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2014 and includes inspection and repair activities completed at the following CAUs; CAU 400: Bomblet Pit and Five Points Landfill (TTR); CAU 407: Roller Coaster RadSafe Area (TTR); CAU 424: Area 3 Landfill Complexes (TTR); CAU 453: Area 9 UXO Landfill (TTR); and CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved Closure Reports and subsequent correspondence with the Nevada Division ofmore » Environmental Protection. The post-closure inspection plans and subsequent correspondence modifying the requirements for each CAU are included in Appendix B. The inspection checklists are included in Appendix C. Photographs taken during inspections are included in Appendix D. The annual post-closure inspections were conducted on May 28, 2014. Maintenance was required at CAU 407. Animal burrows were backfilled and erosion repairs were performed. Vegetation monitoring was performed at CAU 407 in June 2014. The vegetation monitoring report is included in Appendix E.« less

  17. 76 FR 71035 - Agency Information Collection Request. 30-Day Public Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-11-16

    .... This data collection effort is crucial to HPP's decision-making process regarding the continued... visits by project and field officers (e.g. pre- populating some elements of the mid-year and end- of-year... Information Collection Request. 30-Day Public Comment Request AGENCY: Office of the Secretary, HHS. In...

  18. Autonomy, age and sterilisation requests.

    PubMed

    McQueen, Paddy

    2017-05-01

    Sterilisation requests made by young, child-free adults are frequently denied by doctors, despite sterilisation being legally available to individuals over the age of 18. A commonly given reason for denied requests is that the patient will later regret their decision. In this paper, I examine whether the possibility of future regret is a good reason for denying a sterilisation request. I argue that it is not and hence that decision-competent adults who have no desire to have children should have their requests approved. It is a condition of being recognised as autonomous that a person ought to be permitted to make decisions that they might later regret, provided that their decision is justified at the time that it is made. There is also evidence to suggest that sterilisation requests made by men are more likely to be approved than requests made by women, even when age and number of children are factored in. This may indicate that attitudes towards sterilisation are influenced by gender discourses that define women in terms of reproduction and mothering. If this is the case, then it is unjustified and should be addressed. There is no good reason to judge people's sterilisation requests differently in virtue of their gender. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  19. 32 CFR 1665.5 - Request for review.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROCEDURES § 1665.5 Request for review. (a) Individuals wishing to request a review of the decision by SSS... the information specified in § 1665.5(b). Individuals desiring assistance in the preparation of their... requester believes that access should be granted or the disputed information amended. The request for review...

  20. 29 CFR 1921.5 - Motions and requests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... motion or request shall state the particular order, ruling, or action desired, and the grounds therefor... 29 Labor 7 2011-07-01 2011-07-01 false Motions and requests. 1921.5 Section 1921.5 Labor... WORKERS' COMPENSATION ACT Prehearing Procedures § 1921.5 Motions and requests. Motions or requests shall...

  1. 29 CFR 1921.5 - Motions and requests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... motion or request shall state the particular order, ruling, or action desired, and the grounds therefor... 29 Labor 7 2010-07-01 2010-07-01 false Motions and requests. 1921.5 Section 1921.5 Labor... WORKERS' COMPENSATION ACT Prehearing Procedures § 1921.5 Motions and requests. Motions or requests shall...

  2. Comparative study on 2,2′,4,5,5′-pentachlorobiphenyl-mediated decrease in serum thyroxine level between C57BL/6 and its transthyretin-deficient mice

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

    Kato, Yoshihisa, E-mail: kato@kph.bunri-u.ac.jp; Tamaki, Sekihiro; Haraguchi, Koichi

    The relationships between the changes in the levels of serum total thyroxine (T{sub 4}), serum T{sub 4}-transthyretin (TTR) complex, and accumulation of T{sub 4} in tissues by 2,2′,4,5,5′-pentachlorobiphenyl (PentaCB) were examined using wild-type C57BL/6 (WT) and its TTR-deficient (TTR-null) mice. The constitutive level of serum total T{sub 4} was much higher in WT mice than in TTR-null mice. In WT mice 4 days after a single intraperitoneal injection with PentaCB (112 mg/kg), serum total T{sub 4} level was significantly decreased along with a decrease in serum T{sub 4}–TTR complex, and the levels of serum total T{sub 4} in the PentaCB-treatedmore » WT mice were almost the same to those in PentaCB-untreated (control) TTR-null mice. In addition, a slight decrease in serum total T{sub 4} by PentaCB treatment was observed in TTR-null mice. Furthermore, clearance of [{sup 125}I]T{sub 4} from the serum after [{sup 125}I]T{sub 4}-administration was promoted by the PentaCB-pretreatment in either strain of mice, especially WT mice. On the other hand, accumulation level of [{sup 125}I]T{sub 4} in the liver, but not in extrahepatic tissues, was strikingly enhanced in the PentaCB-pretreated WT and TTR-null mice. Furthermore, in both strains of mice, PentaCB-pretreatment led to significant increases in the steady-state distribution volume of [{sup 125}I]T{sub 4} and the concentration ratio of the liver to serum. The present findings demonstrate that PentaCB-mediated decrease in serum T{sub 4} level occurs mainly through increase in accumulation level of T{sub 4} in the liver and further indicate that the increased accumulation of T{sub 4} in the liver of WT mice is primarily dependent on the PentaCB-mediated inhibition of serum T{sub 4}–TTR complex formation.« less

  3. A Proposal for Program Assessment at Kean College of New Jersey. Final Report of the Presidential Task Force on Student Learning and Development.

    ERIC Educational Resources Information Center

    Kean Coll. of New Jersey, Union.

    In response to a request from its president, an institutional task force at Kean College of New Jersey studied approaches to program assessment used at other colleges, identified the measurement approaches being used at Kean College, and made policy recommendations for implementing an assessment program at the college. A major finding was that no…

  4. 22 CFR 303.8 - Requests for records.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., a requester should try to provide the following kinds of information, if known; (1) The specific... determination may be expected to be dispatched, and the requester's right to treat the delay as a denial and to... extension thereof, the requester may deem the request denied, and exercise a right of appeal in accordance...

  5. 22 CFR 303.8 - Requests for records.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., a requester should try to provide the following kinds of information, if known; (1) The specific... determination may be expected to be dispatched, and the requester's right to treat the delay as a denial and to... extension thereof, the requester may deem the request denied, and exercise a right of appeal in accordance...

  6. 22 CFR 303.8 - Requests for records.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., a requester should try to provide the following kinds of information, if known; (1) The specific... determination may be expected to be dispatched, and the requester's right to treat the delay as a denial and to... extension thereof, the requester may deem the request denied, and exercise a right of appeal in accordance...

  7. 22 CFR 303.8 - Requests for records.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., a requester should try to provide the following kinds of information, if known; (1) The specific... determination may be expected to be dispatched, and the requester's right to treat the delay as a denial and to... extension thereof, the requester may deem the request denied, and exercise a right of appeal in accordance...

  8. 10 CFR 1705.05 - Processing of requests.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Processing of requests. 1705.05 Section 1705.05 Energy DEFENSE NUCLEAR FACILITIES SAFETY BOARD PRIVACY ACT § 1705.05 Processing of requests. (a) Requests in writing. The Privacy Act Officer will acknowledge receipt of the request within five working days of its...

  9. 22 CFR 505.3 - Procedures for requests.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Foreign Relations BROADCASTING BOARD OF GOVERNORS PRIVACY ACT REGULATION § 505.3 Procedures for requests... to herself/himself as a request made under the Privacy Act of 1974, as amended (5 U.S.C. 552a) whether or not the individual specifically cites the Privacy Act when making the request. (b) All requests...

  10. 10 CFR 1705.05 - Processing of requests.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Processing of requests. 1705.05 Section 1705.05 Energy DEFENSE NUCLEAR FACILITIES SAFETY BOARD PRIVACY ACT § 1705.05 Processing of requests. (a) Requests in writing. The Privacy Act Officer will acknowledge receipt of the request within five working days of its...

  11. 10 CFR 1705.05 - Processing of requests.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Processing of requests. 1705.05 Section 1705.05 Energy DEFENSE NUCLEAR FACILITIES SAFETY BOARD PRIVACY ACT § 1705.05 Processing of requests. (a) Requests in writing. The Privacy Act Officer will acknowledge receipt of the request within five working days of its...

  12. 10 CFR 1705.05 - Processing of requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Processing of requests. 1705.05 Section 1705.05 Energy DEFENSE NUCLEAR FACILITIES SAFETY BOARD PRIVACY ACT § 1705.05 Processing of requests. (a) Requests in writing. The Privacy Act Officer will acknowledge receipt of the request within five working days of its...

  13. 10 CFR 1705.05 - Processing of requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Processing of requests. 1705.05 Section 1705.05 Energy DEFENSE NUCLEAR FACILITIES SAFETY BOARD PRIVACY ACT § 1705.05 Processing of requests. (a) Requests in writing. The Privacy Act Officer will acknowledge receipt of the request within five working days of its...

  14. 40 CFR 204.57-1 - Test request.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Test request. 204.57-1 Section 204.57... NOISE EMISSION STANDARDS FOR CONSTRUCTION EQUIPMENT Portable Air Compressors § 204.57-1 Test request. (a) The Administrator will request all testing under this subpart by means of a test request addressed to...

  15. 40 CFR 211.212-1 - Test request.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Test request. 211.212-1 Section 211... PRODUCT NOISE LABELING Hearing Protective Devices § 211.212-1 Test request. (a) The Administrator will request all testing under this section by means of a test request addressed to the -manufacturer. (b) The...

  16. 40 CFR 204.57-1 - Test request.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Test request. 204.57-1 Section 204.57... NOISE EMISSION STANDARDS FOR CONSTRUCTION EQUIPMENT Portable Air Compressors § 204.57-1 Test request. (a) The Administrator will request all testing under this subpart by means of a test request addressed to...

  17. Representational task formats and problem solving strategies in kinematics and work

    NASA Astrophysics Data System (ADS)

    Ibrahim, Bashirah; Rebello, N. Sanjay

    2012-06-01

    Previous studies have reported that students employed different problem solving approaches when presented with the same task structured with different representations. In this study, we explored and compared students’ strategies as they attempted tasks from two topical areas, kinematics and work. Our participants were 19 engineering students taking a calculus-based physics course. The tasks were presented in linguistic, graphical, and symbolic forms and requested either a qualitative solution or a value. The analysis was both qualitative and quantitative in nature focusing principally on the characteristics of the strategies employed as well as the underlying reasoning for their applications. A comparison was also made for the same student’s approach with the same kind of representation across the two topics. Additionally, the participants’ overall strategies across the different tasks, in each topic, were considered. On the whole, we found that the students prefer manipulating equations irrespective of the representational format of the task. They rarely recognized the applicability of a “qualitative” approach to solve the problem although they were aware of the concepts involved. Even when the students included visual representations in their solutions, they seldom used these representations in conjunction with the mathematical part of the problem. Additionally, the students were not consistent in their approach for interpreting and solving problems with the same kind of representation across the two topical areas. The representational format, level of prior knowledge, and familiarity with a topic appeared to influence their strategies, their written responses, and their ability to recognize qualitative ways to attempt a problem. The nature of the solution does not seem to impact the strategies employed to handle the problem.

  18. 32 CFR 300.7 - FOIA request processing procedures.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... (CONTINUED) FREEDOM OF INFORMATION ACT PROGRAM DEFENSE LOGISTICS AGENCY FREEDOM OF INFORMATION ACT PROGRAM... request is perfected. When a DLA FOIA Requester Service Center receives a request for records that clearly... Service Center has a telephone line to inform the requester of the status of their request (see Appendix A...

  19. Patient-initiated electronic health record amendment requests

    PubMed Central

    Hanauer, David A; Preib, Rebecca; Zheng, Kai; Choi, Sung W

    2014-01-01

    Background and objective Providing patients access to their medical records offers many potential benefits including identification and correction of errors. The process by which patients ask for changes to be made to their records is called an ‘amendment request’. Little is known about the nature of such amendment requests and whether they result in modifications to the chart. Methods We conducted a qualitative content analysis of all patient-initiated amendment requests that our institution received over a 7-year period. Recurring themes were identified along three analytic dimensions: (1) clinical/documentation area, (2) patient motivation for making the request, and (3) outcome of the request. Results The dataset consisted of 818 distinct requests submitted by 181 patients. The majority of these requests (n=636, 77.8%) were made to rectify incorrect information and 49.7% of all requests were ultimately approved. In 6.6% of the requests, patients wanted valid information removed from their record, 27.8% of which were approved. Among all of the patients requesting a copy of their chart, only a very small percentage (approximately 0.2%) submitted an amendment request. Conclusions The low number of amendment requests may be due to inadequate awareness by patients about how to make changes to their records. To make this approach effective, it will be important to inform patients of their right to view and amend records and about the process for doing so. Increasing patient access to medical records could encourage patient participation in improving the accuracy of medical records; however, caution should be used. PMID:24863430

  20. Structural aspects of inotropic bipyridine binding. Crystal structure determination to 1.9 A of the human serum transthyretin-milrinone complex.

    PubMed

    Wojtczak, A; Luft, J R; Cody, V

    1993-03-25

    The crystal structure of human transthyretin (TTR) complexed with milrinone (2-methyl-5-cyano-3,4'-bipyridin-6(1H)-one), a positive inotropic cardiac agent, has been refined to R = 17.4% for 8-1.9-A resolution data. This report provides the first detailed description of protein interactions for an inotropic bipyridine agent which is an effective thyroid hormone binding competitor to transthyretin. Milrinone is bound along the 2-fold axis in the binding site with its substituted pyridone ring located deep within the channel of the two identical binding domains of the TTR tetramer. In this orientation the 5-cyano group occupies the same site as the 3'-iodine in the TTR complex with 3,3'-diiodothyronine (Wojtczak, A., Luft, J., and Cody, V. (1992) J. Biol. Chem. 267, 353-357), which is 3.5 A deeper in the channel than thyroxine (Blake, C. C. F., and Oately, S. J., (1977) Nature 268, 115-120). These structural results confirm computer modeling studies of milrinone structural homology with thyroxine and its TTR binding interactions and explain the effectiveness of milrinone competition for thyroxine binding to TTR. To understand the weaker binding affinity of the parent inotropic drug, amrinone (5-amino-3,4'-bipyridin-6(1H)-one), modeling studies of its TTR binding were carried out which indicate that the 5-amino group cannot participate in strong interactions with TTR and the lack of the 2-methyl further weakens amrinone binding.

  1. 14 CFR 1212.300 - Requesting amendment.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 14 Aeronautics and Space 5 2012-01-01 2012-01-01 false Requesting amendment. 1212.300 Section 1212.300 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION PRIVACY ACT-NASA REGULATIONS Amendments to Privacy Act Records § 1212.300 Requesting amendment. Individuals may request that NASA amend...

  2. 7 CFR 1430.204 - Requesting benefits.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Requesting benefits. 1430.204 Section 1430.204... Program § 1430.204 Requesting benefits. (a) A request for benefits or contract application, under this... MILC benefits must certify the accuracy and truthfulness of the information in their contract...

  3. 7 CFR 1430.204 - Requesting benefits.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Requesting benefits. 1430.204 Section 1430.204... Program § 1430.204 Requesting benefits. (a) A request for benefits or contract application, under this... MILC benefits must certify the accuracy and truthfulness of the information in their contract...

  4. 7 CFR 1430.204 - Requesting benefits.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Requesting benefits. 1430.204 Section 1430.204... Program § 1430.204 Requesting benefits. (a) A request for benefits or contract application, under this... MILC benefits must certify the accuracy and truthfulness of the information in their contract...

  5. 7 CFR 1430.204 - Requesting benefits.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Requesting benefits. 1430.204 Section 1430.204... Program § 1430.204 Requesting benefits. (a) A request for benefits or contract application, under this... MILC benefits must certify the accuracy and truthfulness of the information in their contract...

  6. 7 CFR 1430.204 - Requesting benefits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Requesting benefits. 1430.204 Section 1430.204... Program § 1430.204 Requesting benefits. (a) A request for benefits or contract application, under this... MILC benefits must certify the accuracy and truthfulness of the information in their contract...

  7. 14 CFR 1212.300 - Requesting amendment.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 14 Aeronautics and Space 5 2011-01-01 2010-01-01 true Requesting amendment. 1212.300 Section 1212.300 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION PRIVACY ACT-NASA REGULATIONS Amendments to Privacy Act Records § 1212.300 Requesting amendment. Individuals may request that NASA amend...

  8. 14 CFR 1212.300 - Requesting amendment.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 5 2010-01-01 2010-01-01 false Requesting amendment. 1212.300 Section 1212.300 Aeronautics and Space NATIONAL AERONAUTICS AND SPACE ADMINISTRATION PRIVACY ACT-NASA REGULATIONS Amendments to Privacy Act Records § 1212.300 Requesting amendment. Individuals may request that NASA amend...

  9. 15 CFR 2005.6 - Request for review.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... person making the request in writing of the decision on the request for review within 30 days (excluding... wishing to request a review of the decision by STR with regard to an initial request to amend a record in... extent possible, include the information specified in § 2005.5(a). Individuals desiring assistance in the...

  10. 29 CFR 458.72 - Motions and requests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 29 Labor 2 2010-07-01 2010-07-01 false Motions and requests. 458.72 Section 458.72 Labor... STANDARDS OF CONDUCT Hearing and Related Matters § 458.72 Motions and requests. (a) Motions and requests... shall serve a copy of all motions and requests on all other parties. Motions during the course of the...

  11. 7 CFR 283.18 - Motions and requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... particular order, ruling, or action desired and the grounds therefor. (d) Response to motions and requests... 7 Agriculture 4 2011-01-01 2011-01-01 false Motions and requests. 283.18 Section 283.18... Claims of $50,000 or More § 283.18 Motions and requests. (a) Filing. All motions and requests shall be...

  12. 7 CFR 283.18 - Motions and requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... particular order, ruling, or action desired and the grounds therefor. (d) Response to motions and requests... 7 Agriculture 4 2010-01-01 2010-01-01 false Motions and requests. 283.18 Section 283.18... Claims of $50,000 or More § 283.18 Motions and requests. (a) Filing. All motions and requests shall be...

  13. 40 CFR 205.160-1 - Test request.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Test request. 205.160-1 Section 205... TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycles § 205.160-1 Test request. (a) The Administrator will request all testing under § 205.160 by means of a test request addressed to the manufacturer. (b) The test...

  14. 40 CFR 205.171-1 - Test request.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Test request. 205.171-1 Section 205... TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Motorcycle Exhaust Systems § 205.171-1 Test request. (a) The Administrator will request all testing under § 205.171 by means of a test request addressed to the manufacturer...

  15. An audit of the completion of radiology request forms and the request practice

    PubMed Central

    Akintomide, Akintunde O.; Ikpeme, Anthonia A.; Ngaji, Affiong I.; Ani, Nchiewe E.; Udofia, Appolline T.

    2015-01-01

    Objective: To assess the degree of utilization of the radiology request form (RRF), the extent of completion each form, the frequency of filling the fields in all the forms, and its effectiveness as a communication tool between the referring clinicians and radiologists. Materials and Methods: All the RRFs for conventional radiographic examinations were audited over a 3-month period. A database containing all the fields in the form, type of request paper used, and legibility of the physician's handwriting was created. A few resident radiologists in the plain film reporting unit were recruited to join in collecting the data daily. We used simple statistical methods to analyze the extent of completion of each form, frequency of completion of the fields in all the request forms, frequency of use of the appropriate form, and frequency of legibility of the physician's handwriting. The results are expressed in percentages. Results: Five hundred eighty (580) requests were analyzed, consisting of 180 for males and 400 for females. The most-completed request form was 86.67% filled, while the least-completed was 26.67%. The most frequently filled field was the requested examination (99.66%). Of the clinicians, 28% did not use the RRF for their referrals, while 7.37% had illegible handwriting. Conclusion: A significant number of the referring clinicians did not make the best use of the radiology department by not using the institution's approved RRF as an effective means of communication with the radiologists, mainly due to the inadequate completion of the forms. PMID:26288767

  16. Cognitive task analysis: harmonizing tasks to human capacities.

    PubMed

    Neerincx, M A; Griffioen, E

    1996-04-01

    This paper presents the development of a cognitive task analysis that assesses the task load of jobs and provides indicators for the redesign of jobs. General principles of human task performance were selected and, subsequently, integrated into current task modelling techniques. The resulting cognitive task analysis centres around four aspects of task load: the number of actions in a period, the ratio between knowledge- and rule-based actions, lengthy uninterrupted actions, and momentary overloading. The method consists of three stages: (1) construction of a hierarchical task model, (2) a time-line analysis and task load assessment, and (3), if necessary, adjustment of the task model. An application of the cognitive task analysis in railway traffic control showed its benefits over the 'old' task load analysis of the Netherlands Railways. It provided a provisional standard for traffic control jobs, conveyed two load risks -- momentary overloading and underloading -- and resulted in proposals to satisfy the standard and to diminish the two load risk.

  17. Primary care requests for anaemia chemistry tests in Spain: potential iron, transferrin and folate over-requesting.

    PubMed

    Salinas, Maria; López-Garrigós, Maite; Flores, Emilio; Leiva-Salinas, Carlos

    2017-09-01

    To study the regional variability of requests for anaemia chemistry tests in primary care in Spain and the associated economic costs of potential over-requesting. Requests for anaemia tests were examined in a cross-sectional study. Clinical laboratories from different autonomous communities (AACCs) were invited to report on primary care anaemia chemistry tests requested during 2014. Demand for iron, ferritin, vitamin B12 and folate tests per 1000 inhabitants and the ratios of the folate/vitamin B12 and transferrin/ferritin requests were compared between AACCs. We also calculated reagent costs and the number of iron, transferrin and folate tests and the economic saving if every AACC had obtained the results achieved by the AACC with best practice. 110 laboratories participated (59.8% of the Spanish population). More than 12 million tests were requested, resulting in reagent costs exceeding €16.5 million. The serum iron test was the most often requested, and the ferritin test was the most costly (over €7 million). Close to €4.5 million could potentially have been saved if iron, transferrin and folate had been appropriately requested (€6 million when extrapolated to the whole Spanish population). The demand for and expenditure on anaemia chemistry tests in primary care in Spain is high, with significant regional differences between different AACCs. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  18. 36 CFR 1007.3 - Requests for records.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 3 2012-07-01 2012-07-01 false Requests for records. 1007.3... INFORMATION ACT § 1007.3 Requests for records. (a) Submission of requests. A request to inspect or copy records shall be submitted to the Presidio Trust's FOIA Officer at P.O. Box 29052, San Francisco, CA 94129...

  19. 40 CFR 205.57-1 - Test request.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 40 Protection of Environment 26 2013-07-01 2013-07-01 false Test request. 205.57-1 Section 205.57... TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.57-1 Test request. (a) The Administrator will request all testing under § 205.57 by means of a test request addressed to the manufacturer...

  20. 40 CFR 205.57-1 - Test request.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Test request. 205.57-1 Section 205.57... TRANSPORTATION EQUIPMENT NOISE EMISSION CONTROLS Medium and Heavy Trucks § 205.57-1 Test request. (a) The Administrator will request all testing under § 205.57 by means of a test request addressed to the manufacturer...

  1. 32 CFR 807.5 - Processing requests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Processing requests. 807.5 Section 807.5 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION SALE TO THE PUBLIC § 807.5 Processing requests. Payment is required before shipping the requested material. Payment...

  2. 28 CFR 47.4 - Written request.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... official of the financial institution from which financial records are requested. The request shall be... business phone number. The request shall also contain the following: (1) The identity of the customer or customers to whom the records pertain; (2) A reasonable description of the records sought; and (3) Such...

  3. 28 CFR 47.4 - Written request.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... official of the financial institution from which financial records are requested. The request shall be... business phone number. The request shall also contain the following: (1) The identity of the customer or customers to whom the records pertain; (2) A reasonable description of the records sought; and (3) Such...

  4. 28 CFR 47.4 - Written request.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... official of the financial institution from which financial records are requested. The request shall be... business phone number. The request shall also contain the following: (1) The identity of the customer or customers to whom the records pertain; (2) A reasonable description of the records sought; and (3) Such...

  5. 28 CFR 47.4 - Written request.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... official of the financial institution from which financial records are requested. The request shall be... business phone number. The request shall also contain the following: (1) The identity of the customer or customers to whom the records pertain; (2) A reasonable description of the records sought; and (3) Such...

  6. 12 CFR 261.13 - Processing requests.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Information Office and that have already been cleared for public release may qualify for fast-track processing... will make the determination whether a request qualifies for fast-track processing. A requester may contact the Freedom of Information Office to learn whether a particular request has been assigned to fast...

  7. 12 CFR 261.13 - Processing requests.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Information Office and that have already been cleared for public release may qualify for fast-track processing... will make the determination whether a request qualifies for fast-track processing. A requester may contact the Freedom of Information Office to learn whether a particular request has been assigned to fast...

  8. 12 CFR 261.13 - Processing requests.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Information Office and that have already been cleared for public release may qualify for fast-track processing... will make the determination whether a request qualifies for fast-track processing. A requester may contact the Freedom of Information Office to learn whether a particular request has been assigned to fast...

  9. 12 CFR 261.13 - Processing requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Information Office and that have already been cleared for public release may qualify for fast-track processing... will make the determination whether a request qualifies for fast-track processing. A requester may contact the Freedom of Information Office to learn whether a particular request has been assigned to fast...

  10. 12 CFR 261.13 - Processing requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Information Office and that have already been cleared for public release may qualify for fast-track processing... will make the determination whether a request qualifies for fast-track processing. A requester may contact the Freedom of Information Office to learn whether a particular request has been assigned to fast...

  11. 75 FR 14150 - Agency Information Collection Activities; Proposed Collection; Comment Request; Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-03-24

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPPT-2009-0929; FRL-8806-1] Agency Information Collection Activities; Proposed Collection; Comment Request; Request for Contractor Access to TSCA CBI; EPA ICR No. 1250.09, OMB Control No. 2070-0075 AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY...

  12. 78 FR 57415 - Agency Information Collection Activities; Proposed Collection; Comments Requested: Request for...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ... DEPARTMENT OF JUSTICE Bureau of Alcohol, Tobacco, Firearms and Explosives [OMB Number 1140-NEW] Agency Information Collection Activities; Proposed Collection; Comments Requested: Request for ATF Background Investigation Information ACTION: 60-Day Notice. The Department of Justice (DOJ), Bureau of Alcohol, Tobacco, Firearms and Explosives (ATF),...

  13. 8 CFR 103.9 - Request for further action on an approved benefit request.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 8 Aliens and Nationality 1 2013-01-01 2013-01-01 false Request for further action on an approved benefit request. 103.9 Section 103.9 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS IMMIGRATION BENEFITS; BIOMETRIC REQUIREMENTS; AVAILABILITY OF RECORDS Applying for Benefits...

  14. 8 CFR 103.9 - Request for further action on an approved benefit request.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 8 Aliens and Nationality 1 2012-01-01 2012-01-01 false Request for further action on an approved benefit request. 103.9 Section 103.9 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS IMMIGRATION BENEFITS; BIOMETRIC REQUIREMENTS; AVAILABILITY OF RECORDS Applying for Benefits...

  15. 8 CFR 103.9 - Request for further action on an approved benefit request.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 8 Aliens and Nationality 1 2014-01-01 2014-01-01 false Request for further action on an approved benefit request. 103.9 Section 103.9 Aliens and Nationality DEPARTMENT OF HOMELAND SECURITY IMMIGRATION REGULATIONS IMMIGRATION BENEFITS; BIOMETRIC REQUIREMENTS; AVAILABILITY OF RECORDS Applying for Benefits...

  16. Cavity filling mutations at the thyroxine-binding site dramatically increase transthyretin stability and prevent its aggregation.

    PubMed

    Sant'Anna, Ricardo; Almeida, Maria Rosário; Varejāo, Nathalia; Gallego, Pablo; Esperante, Sebastian; Ferreira, Priscila; Pereira-Henriques, Alda; Palhano, Fernando L; de Carvalho, Mamede; Foguel, Debora; Reverter, David; Saraiva, Maria João; Ventura, Salvador

    2017-03-24

    More than a hundred different Transthyretin (TTR) mutations are associated with fatal systemic amyloidoses. They destabilize the protein tetrameric structure and promote the extracellular deposition of TTR as pathological amyloid fibrils. So far, only mutations R104H and T119M have been shown to stabilize significantly TTR, acting as disease suppressors. We describe a novel A108V non-pathogenic mutation found in a Portuguese subject. This variant is more stable than wild type TTR both in vitro and in human plasma, a feature that prevents its aggregation. The crystal structure of A108V reveals that this stabilization comes from novel intra and inter subunit contacts involving the thyroxine (T 4 ) binding site. Exploiting this observation, we engineered a A108I mutation that fills the T 4 binding cavity, as evidenced in the crystal structure. This synthetic protein becomes one of the most stable TTR variants described so far, with potential application in gene and protein replacement therapies.

  17. Management of asymptomatic gene carriers of transthyretin familial amyloid polyneuropathy.

    PubMed

    Schmidt, Hartmut H-J; Barroso, Fabio; González-Duarte, Alejandra; Conceição, Isabel; Obici, Laura; Keohane, Denis; Amass, Leslie

    2016-09-01

    Transthyretin familial amyloid polyneuropathy (TTR-FAP) is a rare, severe, and irreversible, adult-onset, hereditary disorder caused by autosomal-dominant mutations in the TTR gene that increase the intrinsic propensity of transthyretin protein to misfold and deposit systemically as insoluble amyloid fibrils in nerve tissues, the heart, and other organs. TTR-FAP is characterized by relentless, progressively debilitating polyneuropathy, and leads to death, on average, within 10 years of symptom onset without treatment. With increased availability of disease-modifying treatment options for a wider spectrum of patients with TTR-FAP, timely detection of the disease may offer substantial clinical benefits. This review discusses mutation-specific predictive genetic testing in first-degree relatives of index patients diagnosed with TTR-FAP and the structured clinical follow-up of asymptomatic gene carriers for prompt diagnosis and early therapeutic intervention before accumulation of substantial damage. Muscle Nerve 54: 353-360, 2016. © 2016 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.

  18. 17 CFR 200.304 - Disclosure of requested records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... making the request. (b) Grant of request for access. (1) If it is determined that a request for access to... individual shall pay the cost of making the requested copies, as set forth in § 200.310 of this subpart. (2... pertaining to individuals other than the person making the request or of other information that does not...

  19. Automated Computer Access Request System

    NASA Technical Reports Server (NTRS)

    Snook, Bryan E.

    2010-01-01

    The Automated Computer Access Request (AutoCAR) system is a Web-based account provisioning application that replaces the time-consuming paper-based computer-access request process at Johnson Space Center (JSC). Auto- CAR combines rules-based and role-based functionality in one application to provide a centralized system that is easily and widely accessible. The system features a work-flow engine that facilitates request routing, a user registration directory containing contact information and user metadata, an access request submission and tracking process, and a system administrator account management component. This provides full, end-to-end disposition approval chain accountability from the moment a request is submitted. By blending both rules-based and rolebased functionality, AutoCAR has the flexibility to route requests based on a user s nationality, JSC affiliation status, and other export-control requirements, while ensuring a user s request is addressed by either a primary or backup approver. All user accounts that are tracked in AutoCAR are recorded and mapped to the native operating system schema on the target platform where user accounts reside. This allows for future extensibility for supporting creation, deletion, and account management directly on the target platforms by way of AutoCAR. The system s directory-based lookup and day-today change analysis of directory information determines personnel moves, deletions, and additions, and automatically notifies a user via e-mail to revalidate his/her account access as a result of such changes. AutoCAR is a Microsoft classic active server page (ASP) application hosted on a Microsoft Internet Information Server (IIS).

  20. 31 CFR 103.84 - Withdrawing requests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Withdrawing requests. 103.84 Section 103.84 Money and Finance: Treasury Regulations Relating to Money and Finance FINANCIAL RECORDKEEPING... requests. A person may withdraw a request for an administrative ruling at any time before the ruling has...

  1. 42 CFR 435.948 - Requesting information.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Requesting information. 435.948 Section 435.948... Verification Requirements § 435.948 Requesting information. (a) Except as provided in paragraphs (d), (e), and (f) of this section, the agency must request information from the sources specified in this paragraph...

  2. 12 CFR 404.4 - Request requirements.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Request requirements. 404.4 Section 404.4 Banks and Banking EXPORT-IMPORT BANK OF THE UNITED STATES INFORMATION DISCLOSURE Procedures for Disclosure of Records Under the Freedom of Information Act. § 404.4 Request requirements. (a) Form. Requests...

  3. 31 CFR 103.81 - Submitting requests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Submitting requests. 103.81 Section 103.81 Money and Finance: Treasury Regulations Relating to Money and Finance FINANCIAL RECORDKEEPING... which the request is made. (b) A request filed by a corporation shall be signed by a corporate officer...

  4. 7 CFR 760.1303 - Requesting benefits.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 7 2013-01-01 2013-01-01 false Requesting benefits. 760.1303 Section 760.1303....1303 Requesting benefits. (a) If as a dairy operation or producer, your records are currently available... by FSA, you do not need to request benefits under this subpart to receive payments. FSA will make...

  5. 7 CFR 760.1303 - Requesting benefits.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Requesting benefits. 760.1303 Section 760.1303....1303 Requesting benefits. (a) If as a dairy operation or producer, your records are currently available... by FSA, you do not need to request benefits under this subpart to receive payments. FSA will make...

  6. 7 CFR 760.1303 - Requesting benefits.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 7 2012-01-01 2012-01-01 false Requesting benefits. 760.1303 Section 760.1303....1303 Requesting benefits. (a) If as a dairy operation or producer, your records are currently available... by FSA, you do not need to request benefits under this subpart to receive payments. FSA will make...

  7. 7 CFR 760.1303 - Requesting benefits.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 7 2014-01-01 2014-01-01 false Requesting benefits. 760.1303 Section 760.1303....1303 Requesting benefits. (a) If as a dairy operation or producer, your records are currently available... by FSA, you do not need to request benefits under this subpart to receive payments. FSA will make...

  8. 7 CFR 760.1303 - Requesting benefits.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 7 2010-01-01 2010-01-01 false Requesting benefits. 760.1303 Section 760.1303....1303 Requesting benefits. (a) If as a dairy operation or producer, your records are currently available... by FSA, you do not need to request benefits under this subpart to receive payments. FSA will make...

  9. 76 FR 3688 - Agency Information Collection Activities: Proposed Request and Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-20

    ... may request Appeals Council review by filing a written request using Form HA-520. SSA uses the... CFR 404.938 & 416.1438--0960-0671. SSA uses Forms HA-504 and HA-504-OP1 to inform claimants of a... exclusion of the video teleconferencing option on the HA-504-OP1. We exclude video teleconferencing when it...

  10. 33 CFR 133.11 - Request: Contents.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Request: Contents. 133.11 Section 133.11 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) MARINE POLLUTION FINANCIAL RESPONSIBILITY AND COMPENSATION OIL SPILL LIABILITY TRUST FUND; STATE ACCESS § 133.11 Request: Contents. In making a request...

  11. 28 CFR 47.4 - Written request.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Written request. 47.4 Section 47.4 Judicial Administration DEPARTMENT OF JUSTICE (CONTINUED) RIGHT TO FINANCIAL PRIVACY ACT § 47.4 Written request. (a) The formal written request shall be in the form of a letter or memorandum to an appropriate...

  12. Encoding and immediate retrieval tasks in patients with epilepsy: A functional MRI study of verbal and visual memory.

    PubMed

    Saddiki, Najat; Hennion, Sophie; Viard, Romain; Ramdane, Nassima; Lopes, Renaud; Baroncini, Marc; Szurhaj, William; Reyns, Nicolas; Pruvo, Jean Pierre; Delmaire, Christine

    2018-05-01

    Medial lobe temporal structures and more specifically the hippocampus play a decisive role in episodic memory. Most of the memory functional magnetic resonance imaging (fMRI) studies evaluate the encoding phase; the retrieval phase being performed outside the MRI. We aimed to determine the ability to reveal greater hippocampal fMRI activations during retrieval phase. Thirty-five epileptic patients underwent a two-step memory fMRI. During encoding phase, subjects were requested to identify the feminine or masculine gender of faces and words presented, in order to encourage stimulus encoding. One hour after, during retrieval phase, subjects had to recognize the word and face. We used an event-related design to identify hippocampal activations. There was no significant difference between patients with left temporal lobe epilepsy, patients with right temporal lobe epilepsy and patients with extratemporal lobe epilepsy on verbal and visual learning task. For words, patients demonstrated significantly more bilateral hippocampal activation for retrieval task than encoding task and when the tasks were associated than during encoding alone. Significant difference was seen between face-encoding alone and face retrieval alone. This study demonstrates the essential contribution of the retrieval task during a fMRI memory task but the number of patients with hippocampal activations was greater when the two tasks were taken into account. Copyright © 2018. Published by Elsevier Masson SAS.

  13. First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy

    PubMed Central

    Adams, David; Suhr, Ole B.; Hund, Ernst; Obici, Laura; Tournev, Ivailo; Campistol, Josep M.; Slama, Michel S.; Hazenberg, Bouke P.; Coelho, Teresa

    2016-01-01

    Purpose of review Early and accurate diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP) represents one of the major challenges faced by physicians when caring for patients with idiopathic progressive neuropathy. There is little consensus in diagnostic and management approaches across Europe. Recent findings The low prevalence of TTR-FAP across Europe and the high variation in both genotype and phenotypic expression of the disease means that recognizing symptoms can be difficult outside of a specialized diagnostic environment. The resulting delay in diagnosis and the possibility of misdiagnosis can misguide clinical decision-making and negatively impact subsequent treatment approaches and outcomes. Summary This review summarizes the findings from two meetings of the European Network for TTR-FAP (ATTReuNET). This is an emerging group comprising representatives from 10 European countries with expertise in the diagnosis and management of TTR-FAP, including nine National Reference Centres. The current review presents management strategies and a consensus on the gold standard for diagnosis of TTR-FAP as well as a structured approach to ongoing multidisciplinary care for the patient. Greater communication, not just between members of an individual patient's treatment team, but also between regional and national centres of expertise, is the key to the effective management of TTR-FAP. PMID:26734952

  14. [Therapeutic strategy for familial amyloid polyneuropathy (FAP)].

    PubMed

    Ikeda, Shu-ichi

    2009-11-01

    Familial amyloid polyneuropathy (FAP) was long considered to be an incurable disease, but a new therapeutic approach was developed 15 years ago. As the liver produces most of the transthyretin (TTR) in serum, it was assumed that the replacement of a liver expressing an abnormal TTR gene should stop the production of the variant TTR, the serum amyloid precursor in FAP. Until now about 1,500 FAP patients underwent liver transplantation, and the 10-year-survival rate is about 77%. After operation the progression of FAP symptoms certainly stopped, and patients who were in an early stage of the disease and underwent successful operations showed considerable improvement in their quality of life. Electrophysiological study of peripheral nerve function has demonstrated that liver transplantation can halt the progression of peripheral neuropathy in FAP patients, and histopathological regression of amyloid deposits was seen on the patients with long post-transplatation courses. Pharmacological therapies have been considered for FAP patients and among them, diflunisal, one of non-steroidal antiinflammatory drugs, is very promising. TTR tetramer dissociation is an initial step for the process of TTR-derived amyloid fibril formation associated with FAP and diflinisal can inhibit this process by stabilization of the TTR tetramer. Clinical trial of this drug for FAP patients is now going worldwide.

  15. 41 CFR 51-8.6 - Aggregating requests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ..., or a group of requesters acting in concert, is attempting to break a request down into a series of... include the time period in which the requests have occurred and the subject matter involved. ...

  16. 41 CFR 51-8.6 - Aggregating requests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ..., or a group of requesters acting in concert, is attempting to break a request down into a series of... include the time period in which the requests have occurred and the subject matter involved. ...

  17. 41 CFR 51-8.6 - Aggregating requests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ..., or a group of requesters acting in concert, is attempting to break a request down into a series of... include the time period in which the requests have occurred and the subject matter involved. ...

  18. 78 FR 69664 - Proposed Information Collection Request; Comment Request; Approval of State Coastal Nonpoint...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-20

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OW-2006-0394; FRL-9903-09-OW] Proposed Information Collection Request; Comment Request; Approval of State Coastal Nonpoint Pollution Control Programs AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The Environmental Protection Agency is planning...

  19. 5 CFR 2604.301 - Requests for records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... submit his request under the FOIA in writing. In the case of a written request, the envelope containing... requested records can be shown. (2) “Compelling need” means: (i) Circumstances in which failure to obtain...

  20. 78 FR 69140 - CSMI, LLC; Request for Action

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-18

    ... NUCLEAR REGULATORY COMMISSION [Docket No. NRC-2013-0250] CSMI, LLC; Request for Action AGENCY: Nuclear Regulatory Commission. ACTION: Request for action; receipt. SUMMARY: The U.S. Nuclear Regulatory... petitioner) has requested that the NRC take action with regard to CSMI. The petitioner's requests are...

  1. 78 FR 16498 - Proposed Information Collection Request; Comment Request; Registration of Fuels and Fuel...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-15

    ... fuel or additive, and certain technical, marketing, and health-effects information. The development of... Request; Comment Request; Registration of Fuels and Fuel Additives--Requirements for Manufacturers; EPA... Fuels and Fuel Additives--Requirements for Manufacturers'' (EPA ICR No. 0309.14, OMB Control No. 2060...

  2. Task Prioritization in Dual-Tasking: Instructions versus Preferences

    PubMed Central

    Jansen, Reinier J.; van Egmond, René; de Ridder, Huib

    2016-01-01

    The role of task prioritization in performance tradeoffs during multi-tasking has received widespread attention. However, little is known on whether people have preferences regarding tasks, and if so, whether these preferences conflict with priority instructions. Three experiments were conducted with a high-speed driving game and an auditory memory task. In Experiment 1, participants did not receive priority instructions. Participants performed different sequences of single-task and dual-task conditions. Task performance was evaluated according to participants’ retrospective accounts on preferences. These preferences were reformulated as priority instructions in Experiments 2 and 3. The results showed that people differ in their preferences regarding task prioritization in an experimental setting, which can be overruled by priority instructions, but only after increased dual-task exposure. Additional measures of mental effort showed that performance tradeoffs had an impact on mental effort. The interpretation of these findings was used to explore an extension of Threaded Cognition Theory with Hockey’s Compensatory Control Model. PMID:27391779

  3. Effects of noise and task loading on a communication task loading on a communication task

    NASA Astrophysics Data System (ADS)

    Orrell, Dean H., II

    Previous research had shown the effect of noise on a single communication task. This research has been criticized as not being representative of a real world situation since subjects allocated all of their attention to only one task. In the present study, the effect of adding a loading task to a standard noise-communication paradigm was investigated. Subjects performed both a communication task (Modified Rhyme Test; House et al. 1965) and a short term memory task (Sternberg, 1969) in simulated levels of aircraft noise (95, 105 and 115 dB overall sound pressure level (OASPL)). Task loading was varied with Sternberg's task by requiring subjects to memorize one, four, or six alphanumeric characters. Simulated aircraft noise was varied between levels of 95, 105 and 115 dB OASPL using a pink noise source. Results show that the addition of Sternberg's task and little effect on the intelligibility of the communication task while response time for the communication task increased.

  4. Who multi-tasks and why? Multi-tasking ability, perceived multi-tasking ability, impulsivity, and sensation seeking.

    PubMed

    Sanbonmatsu, David M; Strayer, David L; Medeiros-Ward, Nathan; Watson, Jason M

    2013-01-01

    The present study examined the relationship between personality and individual differences in multi-tasking ability. Participants enrolled at the University of Utah completed measures of multi-tasking activity, perceived multi-tasking ability, impulsivity, and sensation seeking. In addition, they performed the Operation Span in order to assess their executive control and actual multi-tasking ability. The findings indicate that the persons who are most capable of multi-tasking effectively are not the persons who are most likely to engage in multiple tasks simultaneously. To the contrary, multi-tasking activity as measured by the Media Multitasking Inventory and self-reported cell phone usage while driving were negatively correlated with actual multi-tasking ability. Multi-tasking was positively correlated with participants' perceived ability to multi-task ability which was found to be significantly inflated. Participants with a strong approach orientation and a weak avoidance orientation--high levels of impulsivity and sensation seeking--reported greater multi-tasking behavior. Finally, the findings suggest that people often engage in multi-tasking because they are less able to block out distractions and focus on a singular task. Participants with less executive control--low scorers on the Operation Span task and persons high in impulsivity--tended to report higher levels of multi-tasking activity.

  5. Interlanguage request modification: a case in vocational college

    NASA Astrophysics Data System (ADS)

    Widanta, I. M. R. J.; Sitawati, A. A. R.; Suciani, N. K.; Handayani, L. N. C.

    2018-01-01

    There has been much attention given by scholars to the investigation of inter-language pragmatics (ILP), and some of them have been concentrating on how ILP speakers modify their speech acts (SA) of request. This study was aimed at investigating request modification produced by Indonesian English speakers. A group of 23 college students majoring in tourism was involved as research participants. The participants were given two tests using two role play cards with two hotel-context request situations, i.e. low imposing request (R-Rq) and high imposing request (R+ Rq). Pretest was given prior to and post-test was given upon treatment. The situation was chosen based on[1] exemplar generation1 model. The data of request utterances was analyzed and compared with request taxonomies proposed by some scholars. Data analysis showed that the research participants were more competent pragmatically upon the treatment, indicated with the fact where they were able to produce 13 request modification patterns being compared to 11 patterns prior to the treatment.

  6. 38 CFR 1.554 - Requirements for making requests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... must contain an image of the requester's handwritten signature. To make a request for VA records, write... by another confidentiality statute, the e-mail transmission must contain an image of the requester's... assure prompt processing, e-mail FOIA requests must be sent to official VA FOIA mailboxes established for...

  7. 38 CFR 1.554 - Requirements for making requests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... must contain an image of the requester's handwritten signature. To make a request for VA records, write... by another confidentiality statute, the e-mail transmission must contain an image of the requester's... assure prompt processing, e-mail FOIA requests must be sent to official VA FOIA mailboxes established for...

  8. 38 CFR 1.554 - Requirements for making requests.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... must contain an image of the requester's handwritten signature. To make a request for VA records, write... by another confidentiality statute, the e-mail transmission must contain an image of the requester's... assure prompt processing, e-mail FOIA requests must be sent to official VA FOIA mailboxes established for...

  9. ROME (Request Object Management Environment)

    NASA Astrophysics Data System (ADS)

    Kong, M.; Good, J. C.; Berriman, G. B.

    2005-12-01

    Most current astronomical archive services are based on an HTML/ CGI architecture where users submit HTML forms via a browser and CGI programs operating under a web server process the requests. Most services return an HTML result page with URL links to the result files or, for longer jobs, return a message indicating that email will be sent when the job is done. This paradigm has a few serious shortcomings. First, it is all too common for something to go wrong and for the user to never hear about the job again. Second, for long and complicated jobs there is often important intermediate information that would allow the user to adjust the processing. Finally, unless some sort of custom queueing mechanism is used, background jobs are started immediately upon receiving the CGI request. When there are many such requests the server machine can easily be overloaded and either slow to a crawl or crash. Request Object Management Environment (ROME) is a collection of middleware components being developed under the National Virtual Observatory Project to provide mechanism for managing long jobs such as computationally intensive statistical analysis requests or the generation of large scale mosaic images. Written as EJB objects within the open-source JBoss applications server, ROME receives processing requests via a servelet interface, stores them in a DBMS using JDBC, distributes the processing (via queuing mechanisms) across multiple machines and environments (including Grid resources), manages realtime messages from the processing modules, and ensures proper user notification. The request processing modules are identical in structure to standard CGI-programs -- though they can optionally implement status messaging -- and can be written in any language. ROME will persist these jobs across failures of processing modules, network outages, and even downtime of ROME and the DBMS, restarting them as necessary.

  10. Children with Autism Understand Indirect Speech Acts: Evidence from a Semi-Structured Act-Out Task

    PubMed Central

    Kissine, Mikhail; Cano-Chervel, Julie; Carlier, Sophie; De Brabanter, Philippe; Ducenne, Lesley; Pairon, Marie-Charlotte; Deconinck, Nicolas; Delvenne, Véronique; Leybaert, Jacqueline

    2015-01-01

    Children with Autism Spectrum Disorder are often said to present a global pragmatic impairment. However, there is some observational evidence that context-based comprehension of indirect requests may be preserved in autism. In order to provide experimental confirmation to this hypothesis, indirect speech act comprehension was tested in a group of 15 children with autism between 7 and 12 years and a group of 20 typically developing children between 2:7 and 3:6 years. The aim of the study was to determine whether children with autism can display genuinely contextual understanding of indirect requests. The experiment consisted of a three-pronged semi-structured task involving Mr Potato Head. In the first phase a declarative sentence was uttered by one adult as an instruction to put a garment on a Mr Potato Head toy; in the second the same sentence was uttered as a comment on a picture by another speaker; in the third phase the same sentence was uttered as a comment on a picture by the first speaker. Children with autism complied with the indirect request in the first phase and demonstrated the capacity to inhibit the directive interpretation in phases 2 and 3. TD children had some difficulty in understanding the indirect instruction in phase 1. These results call for a more nuanced view of pragmatic dysfunction in autism. PMID:26551648

  11. 78 FR 79510 - Proposed Collection; Comment Request Upon Written Request Copies Available From: Securities and...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-30

    ... SECURITIES AND EXCHANGE COMMISSION Proposed Collection; Comment Request Upon Written Request Copies Available From: Securities and Exchange Commission, Office of Investor Education and Advocacy... seq.), the Securities and Exchange Commission (``Commission'') is soliciting comments on the...

  12. Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for beta-lactam acetylation.

    PubMed

    He, Hongzhen; Ding, Yi; Bartlam, Mark; Sun, Fei; Le, Yi; Qin, Xincheng; Tang, Hong; Zhang, Rongguang; Joachimiak, Andrzej; Liu, Jinyuan; Zhao, Nanming; Rao, Zihe

    2003-01-31

    Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55A resolution. The binary complex forms a characteristic "V" shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also report that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.

  13. Effect of a combined education and eHealth programme on the control of oral anticoagulation patients (PORTALS study): a parallel cohort design in Dutch primary care.

    PubMed

    Talboom-Kamp, Esther P W A; Verdijk, Noortje A; Kasteleyn, Marise J; Harmans, Lara M; Talboom, Irvin J S H; Numans, Mattijs E; Chavannes, Niels H

    2017-09-27

    To analyse the effect on therapeutic control and self-management skills of the implementation of self-management programmes, including eHealth by e-learning versus group training. Primary Care Thrombosis Service Center. Of the 247 oral anticoagulation therapy (OAT) patients, 63 started self-management by e-learning, 74 self-management by group training and 110 received usual care. Parallel cohort design with two randomised self-management groups (e-learning and group training) and a group receiving usual care. The effect of implementation of self-management on time in therapeutic range (TTR) was analysed with multilevel linear regression modelling. Usage of a supporting eHealth platform and the impact on self-efficacy (Generalised Self-Efficacy Scale (GSES)) and education level were analysed with linear regression analysis. After intervention, TTR was measured in three time periods of 6 months. (1) TTR, severe complications,(2) usage of an eHealth platform,(3) GSES, education level. Analysis showed no significant differences in TTR between the three time periods (p=0.520), the three groups (p=0.460) or the groups over time (p=0.263). Comparison of e-learning and group training showed no significant differences in TTR between the time periods (p=0.614), the groups (p=0.460) or the groups over time (p=0.263). No association was found between GSES and TTR (p=0.717) or education level and TTR (p=0.107). No significant difference was found between the self-management groups in usage of the platform (0-6 months p=0.571; 6-12 months p=0.866; 12-18 months p=0.260). The percentage of complications was low in all groups (3.2%; 1.4%; 0%). No differences were found between OAT patients trained by e-learning or by a group course regarding therapeutic control (TTR) and usage of a supporting eHealth platform. The TTR was similar in self-management and regular care patients. With adequate e-learning or group training, self-management seems safe and reliable for a selected

  14. 25 CFR 517.6 - Timing of responses to requests.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... FOIA Officer will respond. Unusual circumstances warranting extension are: (i) The need to search for... the office processing the request; (ii) The need to search for, collect, and appropriately examine a... conclude that a requester or group of requesters has divided a request into a series of requests on a...

  15. 25 CFR 517.6 - Timing of responses to requests.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... FOIA Officer will respond. Unusual circumstances warranting extension are: (i) The need to search for... the office processing the request; (ii) The need to search for, collect, and appropriately examine a... conclude that a requester or group of requesters has divided a request into a series of requests on a...

  16. 25 CFR 517.6 - Timing of responses to requests.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... FOIA Officer will respond. Unusual circumstances warranting extension are: (i) The need to search for... the office processing the request; (ii) The need to search for, collect, and appropriately examine a... conclude that a requester or group of requesters has divided a request into a series of requests on a...

  17. 14 CFR 1206.701 - Categories of requesters.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... scientific institutions; representatives of the news media; and all other requesters. The Act prescribes... reproduction of documents. (b) Education and noncommercial scientific institution requesters. NASA shall... are representatives of the news media. NASA shall provide documents to requesters in this category for...

  18. 77 FR 20355 - Proposed Information Collection; Comment Request; Award Amendment Requests and Project Service Maps

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-04

    ... higher education or a consortium of institutions of higher education; (4) public or private non-profit... DEPARTMENT OF COMMERCE Economic Development Administration Proposed Information Collection; Comment Request; Award Amendment Requests and Project Service Maps AGENCY: Economic Development...

  19. 10 CFR 1303.105 - Requests for Board records.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Requests for Board records. 1303.105 Section 1303.105 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PUBLIC INFORMATION AND REQUESTS § 1303.105 Requests for Board records. (a) A written FOIA request must be submitted. You may: (1) Write: NWTRB Designated FOIA Officer...

  20. 10 CFR 1303.105 - Requests for Board records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Requests for Board records. 1303.105 Section 1303.105 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PUBLIC INFORMATION AND REQUESTS § 1303.105 Requests for Board records. (a) A written FOIA request must be submitted. You may: (1) Write: NWTRB Designated FOIA Officer...

  1. 10 CFR 1303.105 - Requests for Board records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Requests for Board records. 1303.105 Section 1303.105 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PUBLIC INFORMATION AND REQUESTS § 1303.105 Requests for Board records. (a) A written FOIA request must be submitted. You may: (1) Write: NWTRB Designated FOIA Officer...

  2. 10 CFR 1303.105 - Requests for Board records.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Requests for Board records. 1303.105 Section 1303.105 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PUBLIC INFORMATION AND REQUESTS § 1303.105 Requests for Board records. (a) A written FOIA request must be submitted. You may: (1) Write: NWTRB Designated FOIA Officer...

  3. 10 CFR 1303.105 - Requests for Board records.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Requests for Board records. 1303.105 Section 1303.105 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PUBLIC INFORMATION AND REQUESTS § 1303.105 Requests for Board records. (a) A written FOIA request must be submitted. You may: (1) Write: NWTRB Designated FOIA Officer...

  4. 78 FR 52191 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-22

    ... Submitted to OMB for Review and Approval; Comment Request; Reformulated Gasoline Commingling Provisions... Protection Agency has submitted an information collection request (ICR), Reformulated Gasoline Commingling...: EPA would like to continue collecting notifications from gasoline retailers and wholesale purchaser...

  5. 78 FR 7778 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

    ... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OPP-2010-0793; FRL-9527-3] Information Collection Request... Annual Measures Reporting AGENCY: Environmental Protection Agency (EPA). ACTION: Notice. SUMMARY: The Environmental Protection Agency has submitted an information collection request (ICR), ``Pesticide Environmental...

  6. 45 CFR 612.4 - Responding to requests.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION AVAILABILITY OF RECORDS AND INFORMATION § 612.4 Responding to requests. (a) Monitoring of requests. The NSF Office of the... the part of the request that has been referred, unless such notification would disclose information...

  7. 45 CFR 612.4 - Responding to requests.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION AVAILABILITY OF RECORDS AND INFORMATION § 612.4 Responding to requests. (a) Monitoring of requests. The NSF Office of the... the part of the request that has been referred, unless such notification would disclose information...

  8. 45 CFR 612.6 - Responses to requests.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION AVAILABILITY OF RECORDS AND INFORMATION § 612.6 Responses to requests. (a) Acknowledgment of requests. The NSF or OIG will... the location of the information deleted where practicable. (c) Denials of requests. (1) Denials of...

  9. 45 CFR 612.4 - Responding to requests.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION AVAILABILITY OF RECORDS AND INFORMATION § 612.4 Responding to requests. (a) Monitoring of requests. The NSF Office of the... the part of the request that has been referred, unless such notification would disclose information...

  10. 45 CFR 612.6 - Responses to requests.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Welfare Regulations Relating to Public Welfare (Continued) NATIONAL SCIENCE FOUNDATION AVAILABILITY OF RECORDS AND INFORMATION § 612.6 Responses to requests. (a) Acknowledgment of requests. The NSF or OIG will... the location of the information deleted where practicable. (c) Denials of requests. (1) Denials of...

  11. 19 CFR 357.109 - Request for reconsideration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 19 Customs Duties 3 2010-04-01 2010-04-01 false Request for reconsideration. 357.109 Section 357.109 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE SHORT SUPPLY PROCEDURES § 357.109 Request for reconsideration. Interested parties may file a request for reconsideration with...

  12. 19 CFR 357.109 - Request for reconsideration.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 19 Customs Duties 3 2011-04-01 2011-04-01 false Request for reconsideration. 357.109 Section 357.109 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE SHORT SUPPLY PROCEDURES § 357.109 Request for reconsideration. Interested parties may file a request for reconsideration with...

  13. 19 CFR 357.109 - Request for reconsideration.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 19 Customs Duties 3 2012-04-01 2012-04-01 false Request for reconsideration. 357.109 Section 357.109 Customs Duties INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE SHORT SUPPLY PROCEDURES § 357.109 Request for reconsideration. Interested parties may file a request for reconsideration with...

  14. 7 CFR 2018.254 - Requests for records.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 15 2014-01-01 2014-01-01 false Requests for records. 2018.254 Section 2018.254 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) ADMINISTRATIVE REGULATIONS GENERAL Availability of Information § 2018.254 Requests for records. Requests for...

  15. 7 CFR 2018.254 - Requests for records.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 15 2012-01-01 2012-01-01 false Requests for records. 2018.254 Section 2018.254 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) ADMINISTRATIVE REGULATIONS GENERAL Availability of Information § 2018.254 Requests for records. Requests for...

  16. 7 CFR 2018.254 - Requests for records.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 15 2011-01-01 2011-01-01 false Requests for records. 2018.254 Section 2018.254 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) ADMINISTRATIVE REGULATIONS GENERAL Availability of Information § 2018.254 Requests for records. Requests for...

  17. 7 CFR 2018.254 - Requests for records.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 15 2013-01-01 2013-01-01 false Requests for records. 2018.254 Section 2018.254 Agriculture Regulations of the Department of Agriculture (Continued) RURAL HOUSING SERVICE, RURAL BUSINESS...) ADMINISTRATIVE REGULATIONS GENERAL Availability of Information § 2018.254 Requests for records. Requests for...

  18. Nonpreemptive run-time scheduling issues on a multitasked, multiprogrammed multiprocessor with dependencies, bidimensional tasks, folding and dynamic graphs

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

    Miller, Allan Ray

    1987-05-01

    Increases in high speed hardware have mandated studies in software techniques to exploit the parallel capabilities. This thesis examines the effects a run-time scheduler has on a multiprocessor. The model consists of directed, acyclic graphs, generated from serial FORTRAN benchmark programs by the parallel compiler Parafrase. A multitasked, multiprogrammed environment is created. Dependencies are generated by the compiler. Tasks are bidimensional, i.e., they may specify both time and processor requests. Processor requests may be folded into execution time by the scheduler. The graphs may arrive at arbitrary time intervals. The general case is NP-hard, thus, a variety of heuristics aremore » examined by a simulator. Multiprogramming demonstrates a greater need for a run-time scheduler than does monoprogramming for a variety of reasons, e.g., greater stress on the processors, a larger number of independent control paths, more variety in the task parameters, etc. The dynamic critical path series of algorithms perform well. Dynamic critical volume did not add much. Unfortunately, dynamic critical path maximizes turnaround time as well as throughput. Two schedulers are presented which balance throughput and turnaround time. The first requires classification of jobs by type; the second requires selection of a ratio value which is dependent upon system parameters. 45 refs., 19 figs., 20 tabs.« less

  19. Incidence of nonamyloidogenic mutations in the transthyretin gene in patients with autonomic and small fiber neuropathy.

    PubMed

    Levine, Todd D; Bland, Ruth J

    2018-01-01

    Mutations of the transthyretin (TTR) gene have been associated with polyneuropathy; the protein product has a tendency to form amyloid deposits in the peripheral nervous system. Patients with small fiber neuropathy (SFN) with or without autonomic symptoms were given skin biopsies to assess nerve fiber density. Any patient with autonomic symptoms was assessed for autonomic neuropathy (AN). If testing revealed no clear cause of neuropathy, the TTR gene was sequenced. Thirty-six percent of patients were found to harbor at least 1 mutation in the TTR gene sequence (variants of unknown significance [VUS]). Of 24 patients diagnosed with SFN, 8% of patients had a point mutation (c76G>A). Of those patients who were diagnosed with both SFN and AN, 68% of patients had a VUS within the TTR gene (c76G>A, c337-18G>C). The results suggest an association between presumed nonamyloidogenic mutations in the TTR gene and the development of AN and SFN. Muscle Nerve 57: 140-142, 2017. © 2017 Wiley Periodicals, Inc.

  20. 16 CFR § 1015.5 - Time limitation on responses to requests for records and requests for expedited processing.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... circumstances: (1) The need to search for and collect the requested records from field facilities or other establishments that are separate from the Office of the Secretary. (2) The need to search for, collect and... requester, or a group of requesters acting in concert, if the Secretary or delegate reasonably believes that...

  1. Autonomic nervous system correlates to readiness state and negative outcome during visual discrimination tasks.

    PubMed

    Salvia, Emilie; Guillot, Aymeric; Collet, Christian

    2012-05-01

    Decision-making in daily activities require different levels of mental load depending on both objective task requirements and self-perception of task constraints. Such factors elicit strain that could influence information processing, decision-making, and forthcoming performance. This experiment aimed at studying how task difficulty, errors and unfair feedback may impact strain. Participants were requested to compare two polygons and to decide as quickly and accurately as possible whether these were identical or different. Task difficulty depended upon the number of polygon sides (from 12 to 21 sides) and their degree of similarity (different by 1, 2 or 3 sides). Reaction time (RT) and response accuracy were the dependent variables as well as electrodermal activity (EDA) and Instantaneous Heart Rate (IHR). Physiological variables from the autonomic nervous system were expected to evolve as a function of strain. As expected, we found that RT increased along with task difficulty. Similarly, the amplitude of IHR responses was affected by task difficulty. We recorded bradycardia during the 5s pre-stimulation period associated with correct responses, while wrong responses were associated with tachycardia. Bradycardia was thus a predictive index of performance related to the readiness to act when the participants focused on external cues. Processing identical polygons elicited longer electrodermal responses than those for different polygons. Indeed, the comparison of two different polygons ended as early as the difference was found. When similar, the participants were still looking for a difference and the issue was uncertain until the performance was displayed. Unfair information, i.e. wrong feedback associated with a good response, as well as response errors elicited larger and longer electrodermal responses. Autonomic nervous system activity was thus task-specific, and correlated to both cognitive and emotional processes. Copyright © 2012 Elsevier B.V. All rights

  2. 4 CFR 201.5 - Requests for Board records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Requests for Board records. 201.5 Section 201.5 Accounts RECOVERY ACCOUNTABILITY AND TRANSPARENCY BOARD PUBLIC INFORMATION AND REQUESTS § 201.5 Requests for Board... of Information Act Request” on the letter and envelope or in the subject line of the e-mail request...

  3. 78 FR 69816 - Proposed Information Collection; Comment Request; Request for Duty-Free Entry of Scientific...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-21

    ... DEPARTMENT OF COMMERCE International Trade Administration Proposed Information Collection; Comment Request; Request for Duty-Free Entry of Scientific Instrument or Apparatus AGENCY: International Trade Administration, Commerce. ACTION: Notice. SUMMARY: The Department of Commerce, as part of its continuing effort...

  4. A Feasible Approach for an Early Manned Lunar Landing. Part II: Detailed Report of Ad Hoc Task Group

    NASA Technical Reports Server (NTRS)

    Fleming, William A.

    1961-01-01

    This report, in two parts, presents a program development plan for attempting a first manned lunar landing in 1967. The two parts consist of a Summary Report and a Detailed Report representing the coordinated output of the Ad Hoc Task Group assigned to the study. The study was started in response to the request for such a study by the Associate Administrator in his memorandum of May 2, 1961 establishing the Ad Hoc Task Group. The purpose of the study was to take a first cut at the tasks associated with the design, development and construction of the equipment and facilities as well as the development of the crews, and to show the time phasing 6f these tasks. Included are the space sciences, life science and advanced technology tasks whose data and results are needed for designing and developing the systems required in carrying out the mission. The plan presented in the two reports does not presume to be a firm plan. Its basic purpose is, by choosing one feasible method, to size up the scope, schedule and cost of the job, discover the main problems, pacing items and major decisions and provide a threshold from which a firm and detailed project development plan can be jointly formulated by the various elements of NASA.

  5. TANKS 18 AND 19-F EQUIPMENT GROUT FILL MATERIAL EVALUATION AND RECOMMENDATIONS

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

    Stefanko, D.; Langton, C.

    The United States Department of Energy (US DOE) intends to remove Tanks 18-F and 19-F at the Savannah River Site (SRS) from service. The high-level waste (HLW) tanks have been isolated from the F-area Tank Farm (FTF) facilities and will be filled with cementitious grout for the purpose of: (1) physically stabilizing the empty volumes in the tanks, (2) limiting/eliminating vertical pathways from the surface to residual waste on the bottom of the tanks, (3) providing an intruder barrier, and (4) providing an alkaline, chemical reducing environment within the closure boundary to limit solubility of residual radionuclides. Bulk waste andmore » heel waste removal equipment will remain in Tanks 18-F and 19-F when the tanks are closed. This equipment includes: mixer pumps, transfer pumps, transfer jets, equipment support masts, sampling masts and dip tube assemblies. The current Tank 18-F and 19-F closure strategy is to grout the internal void spaces in this equipment to eliminate fast vertical pathways and slow water infiltration to the residual material on the tank floor. This report documents the results of laboratory testing performed to identify a grout formulation for filling the abandoned equipment in Tanks 18-F and 19-F. The objective of this work was to formulate a flowable grout for filling internal voids of equipment that will remain in Tanks 18-F and 19-F during the final closures. This work was requested by V. A. Chander, Tank Farm Closure Engineering, in HLW-TTR-2011-008. The scope for this task is provided in the Task Technical and Quality Assurance Plan (TTQAP), SRNL-RP-2011-00587. The specific objectives of this task were to: (1) Prepare and evaluate the SRR cooling coil grout identified in WSRC-STI-2008-00298 per the TTR for this work. The cooling coil grout is a mixture of BASF MasterFlow{reg_sign} 816 cable grout (67.67 wt. %), Grade 100 ground granulated blast furnace slag (7.52 wt. %) and water (24.81 wt. %); (2) Identify equipment grout placement

  6. 45 CFR 1602.8 - Requests for records.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... in which the lack of expedited treatment could reasonably be expected to pose an imminent threat to... the Federal government's integrity which affect public confidence. (2) A request for expedited... and shall notify the requester of the decision. If a request for expedited treatment is granted, the...

  7. 10 CFR 1008.7 - Processing of requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Manager or Managers concerned shall transmit to the Privacy Act Officer the requested material. The... DEPARTMENT OF ENERGY (GENERAL PROVISIONS) RECORDS MAINTAINED ON INDIVIDUALS (PRIVACY ACT) Requests for Access....6 shall be promptly acknowledged by the Privacy Act Officer. (b) Each request shall be acted upon...

  8. 42 CFR 102.44 - Representatives of requesters.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

  9. 42 CFR 102.44 - Representatives of requesters.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

  10. 42 CFR 102.44 - Representatives of requesters.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

  11. 42 CFR 102.44 - Representatives of requesters.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

  12. 42 CFR 102.44 - Representatives of requesters.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Representatives of requesters. 102.44 Section 102.44 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES VACCINES SMALLPOX COMPENSATION PROGRAM Procedures for Filing Request Packages § 102.44 Representatives of requesters. (a) Persons...

  13. Task switching in a hierarchical task structure: evidence for the fragility of the task repetition benefit.

    PubMed

    Lien, Mei-Ching; Ruthruff, Eric

    2004-05-01

    This study examined how task switching is affected by hierarchical task organization. Traditional task-switching studies, which use a constant temporal and spatial distance between each task element (defined as a stimulus requiring a response), promote a flat task structure. Using this approach, Experiment 1 revealed a large switch cost of 238 ms. In Experiments 2-5, adjacent task elements were grouped temporally and/or spatially (forming an ensemble) to create a hierarchical task organization. Results indicate that the effect of switching at the ensemble level dominated the effect of switching at the element level. Experiments 6 and 7, using an ensemble of 3 task elements, revealed that the element-level switch cost was virtually absent between ensembles but was large within an ensemble. The authors conclude that the element-level task repetition benefit is fragile and can be eliminated in a hierarchical task organization.

  14. Task switching in a hierarchical task structure: evidence for the fragility of the task repetition benefit

    NASA Technical Reports Server (NTRS)

    Lien, Mei-Ching; Ruthruff, Eric

    2004-01-01

    This study examined how task switching is affected by hierarchical task organization. Traditional task-switching studies, which use a constant temporal and spatial distance between each task element (defined as a stimulus requiring a response), promote a flat task structure. Using this approach, Experiment 1 revealed a large switch cost of 238 ms. In Experiments 2-5, adjacent task elements were grouped temporally and/or spatially (forming an ensemble) to create a hierarchical task organization. Results indicate that the effect of switching at the ensemble level dominated the effect of switching at the element level. Experiments 6 and 7, using an ensemble of 3 task elements, revealed that the element-level switch cost was virtually absent between ensembles but was large within an ensemble. The authors conclude that the element-level task repetition benefit is fragile and can be eliminated in a hierarchical task organization.

  15. 78 FR 43879 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-22

    ... Submitted to OMB for Review and Approval; Comment Request; Standards for Pesticide Containers and... Protection Agency has submitted an information collection request (ICR), ``Standards for Pesticide Containers... covers the information collection activities associated with the container design and residue removal...

  16. 78 FR 57630 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-19

    ..., threats, information claimed to be Confidential Business Information (CBI) or other information whose... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OAR-2013-0048; FRL 9532-5] Information Collection Request Submitted to OMB for Review and Approval; Comment Request; Information Requirements for Importation of...

  17. 75 FR 55302 - Proposed Information Collection; Comment Request; Request for Duty-Free Entry of Scientific...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-10

    ... DEPARTMENT OF COMMERCE International Trade Administration Proposed Information Collection; Comment Request; Request for Duty-Free Entry of Scientific Instrument or Apparatus AGENCY: International Trade Administration. ACTION: Notice. SUMMARY: The Department of Commerce, as part of its continuing effort to reduce...

  18. 77 FR 29690 - Extension of a Currently Approved Collection; Comments Requested; COPS Extension Request Form

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-18

    ... DEPARTMENT OF JUSTICE Agency Information Collection Activities [OMB Number 1103-0093] Extension of a Currently Approved Collection; Comments Requested; COPS Extension Request Form ACTION: 30-Day Notice of Information Collection Under Review. The Department of Justice (DOJ) Office of Community...

  19. 36 CFR § 1007.3 - Requests for records.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 3 2013-07-01 2012-07-01 true Requests for records. § 1007... INFORMATION ACT § 1007.3 Requests for records. (a) Submission of requests. A request to inspect or copy records shall be submitted to the Presidio Trust's FOIA Officer at P.O. Box 29052, San Francisco, CA 94129...

  20. 12 CFR 1102.306 - Procedures for requesting records.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... a request for records. (1) The request shall be submitted in writing to the Executive Director: (i... period of: (A) Ten (10) working days as provided by written notice to the requester, setting forth the... ASC will advise the requester in writing: (A) If the denial is in part or in whole; (B) The name and...

  1. Different binding mechanisms of neutral and anionic poly-/perfluorinated chemicals to human transthyretin revealed by In silico models.

    PubMed

    Yang, Xianhai; Lyakurwa, Felichesmi; Xie, Hongbin; Chen, Jingwen; Li, Xuehua; Qiao, Xianliang; Cai, Xiyun

    2017-09-01

    Chemical forms-dependent binding interactions between phenolic compounds and human transthyretin (hTTR) have been elaborated previously. However, it is not known whether the binding interactions between ionizable halogenated alphatic compounds and hTTR also have the same manner. In this study, poly-/perfluorinated chemicals (PFCs) were selected as model compounds and molecular dynamic simulation was performed to investigate the binding mechanisms between PFCs and hTTR. Results show the binding interactions between the halogenated aliphatic compounds and hTTR are related to the chemical forms. The ionized groups of PFCs can form electrostatic interactions with the -NH + 3 groups of Lys 15 residues in hTTR and form hydrogen bonds with the residues of hTTR. By analyzing the molecular orbital energies of PFCs, we also found that the anionic groups (nucleophile) in PFCs could form electron donor - acceptor interactions with the -NH + 3 groups (electrophile) in Lys 15. The aforementioned orientational interactions make the ionized groups of the PFCs point toward the entry port of the binding site. The roles of fluorine atoms in the binding interactions were also explored. The fluorine atoms can influence the binding interactions via inductive effects. Appropriate molecular descriptors were selected to characterize these interactions, and two quantitative structure-activity relationship models were developed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Involvement of Macrophages in the Pathogenesis of Familial Amyloid Polyneuropathy and Efficacy of Human iPS Cell-Derived Macrophages in Its Treatment

    PubMed Central

    Komohara, Yoshihiro; Takamatsu, Koutaro; Kakuma, Tatsuyuki; Tasaki, Masayoshi; Misumi, Yohei; Ueda, Mitsuharu; Ito, Takaaki; Senju, Satoru; Ando, Yukio

    2016-01-01

    We hypothesized that tissue-resident macrophages in familial amyloid polyneuropathy (FAP) patients will exhibit qualitative or quantitative abnormalities, that may accelerate transthyretin (TTR)-derived amyloid deposition. To evaluate this, we examined the number and subset of tissue-resident macrophages in heart tissue from amyloid-deposited FAP and control patients. In both FAP and control patients, tissue-resident macrophages in heart tissue were all Iba+/CD163+/CD206+ macrophages. However, the number of macrophages was significantly decreased in FAP patients compared with control patients. Furthermore, the proportion of intracellular TTR in CD14+ monocytes was reduced in peripheral blood compared with healthy donors. Based on these results, we next examined degradation and endocytosis of TTR in human induced pluripotent stem (iPS) cell-derived myeloid lineage cells (MLs), which function like macrophages. iPS-MLs express CD163 and CD206, and belong to the inhibitory macrophage category. In addition, iPS-MLs degrade both native and aggregated TTR in a cell-dependent manner in vitro. Further, iPS-MLs endocytose aggregated, and especially polymerized, TTR. These results suggest that decreased tissue-localized macrophages disrupt clearance of TTR-derived amyloid deposits, leading to progression of a pathological condition in FAP patients. To improve this situation, clinical application of pluripotent stem cell-derived MLs may be useful as an approach for FAP therapy. PMID:27695122

  3. 76 FR 10364 - Agency Information Collection Request. 30-Day Public Comment Request, Grants.gov

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-02-24

    ...-Day Public Comment Request, Grants.gov AGENCY: Office of the Secretary, HHS. In compliance with the... your request, including your address, phone number, OMB number, to [email protected]gov , or call the... information collections within 30 days of this notice directly to the Grants.gov OMB Desk Officer; faxed to...

  4. 5 CFR 1302.5 - Request for review.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ....5 Request for review. (a) Individuals wishing to request a review of the decision by OMB with regard..., include the information specified in § 1302.5(b), below. Individuals desiring assistance in the... disputed information amended. The request for review should make reference to the information furnished by...

  5. 31 CFR 8.60 - Motions and requests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 1 2010-07-01 2010-07-01 false Motions and requests. 8.60 Section 8... ALCOHOL, TOBACCO AND FIREARMS Disciplinary Proceedings § 8.60 Motions and requests. Motions and requests may be filed with the Director of Practice or with the Administrative Law Judge. ...

  6. 31 CFR 8.60 - Motions and requests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 31 Money and Finance: Treasury 1 2011-07-01 2011-07-01 false Motions and requests. 8.60 Section 8... ALCOHOL, TOBACCO AND FIREARMS Disciplinary Proceedings § 8.60 Motions and requests. Motions and requests may be filed with the Director of Practice or with the Administrative Law Judge. ...

  7. 31 CFR 8.60 - Motions and requests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance: Treasury 1 2012-07-01 2012-07-01 false Motions and requests. 8.60 Section 8... ALCOHOL, TOBACCO AND FIREARMS Disciplinary Proceedings § 8.60 Motions and requests. Motions and requests may be filed with the Director of Practice or with the Administrative Law Judge. ...

  8. A chemometric approach for characterization of serum transthyretin in familial amyloidotic polyneuropathy type I (FAP-I) by electrospray ionization-ion mobility mass spectrometry.

    PubMed

    Pont, Laura; Sanz-Nebot, Victoria; Vilaseca, Marta; Jaumot, Joaquim; Tauler, Roma; Benavente, Fernando

    2018-05-01

    In this study, we describe a chemometric data analysis approach to assist in the interpretation of the complex datasets from the analysis of high-molecular mass oligomeric proteins by ion mobility mass spectrometry (IM-MS). The homotetrameric protein transthyretin (TTR) is involved in familial amyloidotic polyneuropathy type I (FAP-I). FAP-I is associated with a specific TTR mutant variant (TTR(Met30)) that can be easily detected analyzing the monomeric forms of the mutant protein. However, the mechanism of protein misfolding and aggregation onset, which could be triggered by structural changes in the native tetrameric protein, remains under investigation. Serum TTR from healthy controls and FAP-I patients was purified under non-denaturing conditions by conventional immunoprecipitation in solution and analyzed by IM-MS. IM-MS allowed separation and characterization of several tetrameric, trimeric and dimeric TTR gas ions due to their differential drift time. After an appropriate data pre-processing, multivariate curve resolution alternating least squares (MCR-ALS) was applied to the complex datasets. A group of seven independent components being characterized by their ion mobility profiles and mass spectra were resolved to explain the observed data variance in control and patient samples. Then, principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were considered for exploration and classification. Only four out of the seven resolved components were enough for an accurate differentiation. Furthermore, the specific TTR ions identified in the mass spectra of these components and the resolved ion mobility profiles provided a straightforward insight into the most relevant oligomeric TTR proteoforms for the disease. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Working Memory Training Improves Dual-Task Performance on Motor Tasks.

    PubMed

    Kimura, Takehide; Kaneko, Fuminari; Nagahata, Keita; Shibata, Eriko; Aoki, Nobuhiro

    2017-01-01

    The authors investigated whether working memory training improves motor-motor dual-task performance consisted of upper and lower limb tasks. The upper limb task was a simple reaction task and the lower limb task was an isometric knee extension task. 45 participants (age = 21.8 ± 1.6 years) were classified into a working memory training group (WM-TRG), dual-task training group, or control group. The training duration was 2 weeks (15 min, 4 times/week). Our results indicated that working memory capacity increased significantly only in the WM-TRG. Dual-task performance improved in the WM-TRG and dual-task training group. Our study provides the novel insight that working memory training improves dual-task performance without specific training on the target motor task.

  10. 78 FR 39282 - Proposed Information Collection Request; Comment Request; Willingness to Pay Survey for Salmon...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-01

    ... the survey, a choice experiment framework is used with statistically designed tradeoff questions... reason for the survey is public value research. All survey responses will be kept confidential. Form... Collection Request; Comment Request; Willingness to Pay Survey for Salmon Recovery in the Willamette...

  11. Serum transthyretin concentration is decreased in dogs with nonthyroidal illness.

    PubMed

    Piechotta, Marion; Jens, Raila; Rick, Markus; Beyerbach, Martin; Hoppen, Hans-Otto

    2012-03-01

    Hypothyroidism in dogs is often difficult to diagnose owing to nonspecific clinical signs and laboratory test results that can be mimicked by nonthyroidal illness (NTI). Thyroxine (T4) circulates in blood mainly bound to T4-binding globulin and, to a lesser degree, transthyretin (TTR) and albumin. The concentration of total T4 depends on the concentrations of these binding proteins. We hypothesized that dogs with NTI and decreased serum total T4 concentrations would have decreased serum TTR concentrations. The objective of the study was to measure and compare serum TTR concentrations in healthy dogs, in dogs with NTI and low serum T4 concentrations, and in dogs with hypothyroidism. Assignment of dogs to 3 groups was based on physical examination and serum concentrations of T4 and TSH (mean ± SD): for healthy dogs (n = 13), T4 was 24.8 ± 3.6 nmol/L and TSH was 0.15 ± 0.08 μg/L; for dogs with NTI and low T4 (n = 20), T4 was 3.2 ± 3.0 nmol/L and TSH was 0.18 ± 0.13 μg/L; and for hypothyroid dogs (n = 19), T4 was 5.3 ± 4.3 nmol/L and TSH was 2.33 ± 1.90 μg/L). TTR concentrations in serum were determined semiquantitatively using western blot analysis. Serum TTR concentration (mean ± SD) was decreased in the dogs with NTI (24.8 ± 7.9 mg/L) compared with that of hypothyroid dogs (41.1 ± 21.4 mg/L, P = .0035). Differences were not found between TTR concentrations in clinically healthy dogs (33.3 ± 10.1 mg/L) and hypothyroid dogs or dogs with NTI. Serum TTR concentrations were significantly decreased in dogs with NTI and low T4 compared with concentrations in hypothyroid dogs. Additional studies should be done to determine if TTR concentrations can discriminate between dogs with NTI and low T4 and dogs with primary hypothyroidism. © 2012 American Society for Veterinary Clinical Pathology.

  12. 21 CFR 203.35 - Standing requests.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... PRESCRIPTION DRUG MARKETING Samples § 203.35 Standing requests. Manufacturers or authorized distributors of... subsequent oral communication or electronic transmission, is not considered to be a standing request. ...

  13. Effects of a no-go Task 2 on Task 1 performance in dual - tasking: From benefits to costs.

    PubMed

    Janczyk, Markus; Huestegge, Lynn

    2017-04-01

    When two tasks are combined in a dual-task experiment, characteristics of Task 2 can influence Task 1 performance, a phenomenon termed the backward crosstalk effect (BCE). Besides instances depending on the (spatial) compatibility of both responses, a particularly interesting example was introduced by Miller (2006): If Task 2 was a no-go task (i.e., one not requiring any action at all), responses were slowed in Task 1. Subsequent work, however, also reported the opposite result-that is, faster Task 1 responses in cases of no-go Task 2 trials. We report three experiments aiming to more precisely identify the conditions under which a no-go Task 2 facilitates or impedes Task 1 performance. The results suggest that an adverse no-go BCE is only observed when the Task 2 response(s) are sufficiently prepared in advance, yielding strong inhibitory control demands for Task 2 that eventually hamper Task 1 processing as well (i.e., inhibitory costs). If this is not the case, encountering a no-go Task 2 trial facilitates Task 1 performance, suggesting that the underlying task representation is reduced to a single - task. These results are discussed in the context of other recent work on BCEs and of recently suggested accounts of the no-go BCE.

  14. 4 CFR 200.6 - Processing of requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4 Accounts 1 2010-01-01 2010-01-01 false Processing of requests. 200.6 Section 200.6 Accounts RECOVERY ACCOUNTABILITY AND TRANSPARENCY BOARD PRIVACY ACT OF 1974 § 200.6 Processing of requests. Upon receipt of a request for information, the Privacy Act Officer will ascertain whether the records...

  15. 32 CFR 1665.2 - Requests for access.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM PRIVACY ACT... description of such system of records. The request should state that the request is pursuant to the Privacy Act of 1974. In the absence of specifying solely the Privacy Act of 1974 and, if the request may be...

  16. 32 CFR 1665.2 - Requests for access.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... National Defense Other Regulations Relating to National Defense SELECTIVE SERVICE SYSTEM PRIVACY ACT... description of such system of records. The request should state that the request is pursuant to the Privacy Act of 1974. In the absence of specifying solely the Privacy Act of 1974 and, if the request may be...

  17. 32 CFR 701.8 - Processing FOIA requests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... queues as they wish, however, at a minimum three processing tracks shall be established, all based on a... simple requests, one track for complex requests, and one track for expedited processing. Determinations as to whether a request is simple or complex shall be made by each DON activity. (2) DON activities...

  18. 29 CFR 19.4 - Contents of request.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... from which financial records are requested. The request shall be signed by an issuing official of the..., business address and business phone number. The request shall also contain the following: (a) The identity of the customer or customers to whom the records pertain; (b) A reasonable description of the records...

  19. 29 CFR 19.4 - Contents of request.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... from which financial records are requested. The request shall be signed by an issuing official of the..., business address and business phone number. The request shall also contain the following: (a) The identity of the customer or customers to whom the records pertain; (b) A reasonable description of the records...

  20. 29 CFR 19.4 - Contents of request.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... from which financial records are requested. The request shall be signed by an issuing official of the..., business address and business phone number. The request shall also contain the following: (a) The identity of the customer or customers to whom the records pertain; (b) A reasonable description of the records...

  1. 29 CFR 19.4 - Contents of request.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... from which financial records are requested. The request shall be signed by an issuing official of the..., business address and business phone number. The request shall also contain the following: (a) The identity of the customer or customers to whom the records pertain; (b) A reasonable description of the records...

  2. 45 CFR 2106.6 - Request for review.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... request a review of the decision by CFA with regard to an initial request to amend a record in accordance... the extent possible, include the information specified in paragraph (a) of this section. Individuals... and also the reasons why the requester believes that the disputed information should be amended. The...

  3. 10 CFR 2.1325 - Motions and requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Motions and requests. 2.1325 Section 2.1325 Energy NUCLEAR REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING PROCEEDINGS AND ISSUANCE OF ORDERS Procedures for Hearings on License Transfer Applications § 2.1325 Motions and requests. (a) Motions and requests...

  4. 10 CFR 2.1325 - Motions and requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Motions and requests. 2.1325 Section 2.1325 Energy NUCLEAR REGULATORY COMMISSION RULES OF PRACTICE FOR DOMESTIC LICENSING PROCEEDINGS AND ISSUANCE OF ORDERS Procedures for Hearings on License Transfer Applications § 2.1325 Motions and requests. (a) Motions and requests...

  5. 32 CFR 701.8 - Processing FOIA requests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ...) Control FOIA Request. Each FOIA request should be date stamped upon receipt; given a case number; and entered into a formal control system to track the request from receipt to response. Coordinators may wish... in mind a test for reasonableness (i.e., file disposition requirements set forth in SECNAVINST 5212...

  6. 32 CFR 701.8 - Processing FOIA requests.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ...) Control FOIA Request. Each FOIA request should be date stamped upon receipt; given a case number; and entered into a formal control system to track the request from receipt to response. Coordinators may wish... in mind a test for reasonableness (i.e., file disposition requirements set forth in SECNAVINST 5212...

  7. 32 CFR 701.8 - Processing FOIA requests.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ...) Control FOIA Request. Each FOIA request should be date stamped upon receipt; given a case number; and entered into a formal control system to track the request from receipt to response. Coordinators may wish... in mind a test for reasonableness (i.e., file disposition requirements set forth in SECNAVINST 5212...

  8. 20 CFR 655.420 - Request for hearing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... FOREIGN WORKERS IN THE UNITED STATES Enforcement of H-1A Attestations § 655.420 Request for hearing. (a) Any interested party desiring to request an administrative hearing on a determination issued pursuant... address stated in the notice of determination. (b) An interested party may request a hearing in the...

  9. 7 CFR 1.143 - Motions and requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Contents. All written motions and requests shall state the particular order, ruling, or action desired and... 7 Agriculture 1 2010-01-01 2010-01-01 false Motions and requests. 1.143 Section 1.143 Agriculture... Adjudicatory Proceedings Instituted by the Secretary Under Various Statutes § 1.143 Motions and requests. (a...

  10. 7 CFR 1.143 - Motions and requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Contents. All written motions and requests shall state the particular order, ruling, or action desired and... 7 Agriculture 1 2011-01-01 2011-01-01 false Motions and requests. 1.143 Section 1.143 Agriculture... Adjudicatory Proceedings Instituted by the Secretary Under Various Statutes § 1.143 Motions and requests. (a...

  11. The Effect of Hierarchical Task Representations on Task Selection in Voluntary Task Switching

    ERIC Educational Resources Information Center

    Weaver, Starla M.; Arrington, Catherine M.

    2013-01-01

    The current study explored the potential for hierarchical representations to influence action selection during voluntary task switching. Participants switched between 4 individual task elements. In Experiment 1, participants were encouraged to represent the task elements as grouped within a hierarchy based on experimental manipulations of varying…

  12. Crystal structure of tabtoxin resistance protein complexed with acetyl coenzyme A reveals the mechanism for {beta}-lactam acetylation.

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

    He, H.; Ding, Y.; Bartlam, M.

    2003-01-31

    Tabtoxin resistance protein (TTR) is an enzyme that renders tabtoxin-producing pathogens, such as Pseudomonas syringae, tolerant to their own phytotoxins. Here, we report the crystal structure of TTR complexed with its natural cofactor, acetyl coenzyme A (AcCoA), to 1.55 {angstrom} resolution. The binary complex forms a characteristic 'V' shape for substrate binding and contains the four motifs conserved in the GCN5-related N-acetyltransferase (GNAT) superfamily, which also includes the histone acetyltransferases (HATs). A single-step mechanism is proposed to explain the function of three conserved residues, Glu92, Asp130 and Tyr141, in catalyzing the acetyl group transfer to its substrate. We also reportmore » that TTR possesses HAT activity and suggest an evolutionary relationship between TTR and other GNAT members.« less

  13. 78 FR 63181 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... Request Submitted to OMB for Review and Approval; Comment Request; Information Requirements for Boilers...), ``Information Requirements for Boilers and Industrial Furnaces (Renewal)'' (EPA ICR No. ICR No. 1361.16, OMB... http://www.epa.gov/dockets . Abstract: EPA regulates the burning of hazardous waste in boilers...

  14. 77 FR 70749 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-27

    ... released, combusted, or oxidized, industrial gas suppliers, and manufacturers of heavy-duty and off-road... Submitted to OMB for Review and Approval; Comment Request; Greenhouse Gas Reporting Program (Renewal) AGENCY... submitted an information collection request (ICR), Greenhouse Gas Reporting Program (Renewal) (EPA ICR No...

  15. 6 CFR 5.6 - Responses to requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 6 Domestic Security 1 2010-01-01 2010-01-01 false Responses to requests. 5.6 Section 5.6 Domestic Security DEPARTMENT OF HOMELAND SECURITY, OFFICE OF THE SECRETARY DISCLOSURE OF RECORDS AND INFORMATION Freedom of Information Act § 5.6 Responses to requests. (a) Acknowledgements of requests. On receipt of a...

  16. 45 CFR 1602.8 - Requests for records.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... should try to provide the following kinds of information, if known: (1) The specific event or action to... on which a determination may be expected to be dispatched, and the requester's right to treat the... thereof, the requester may deem the request denied, and exercise a right of appeal in accordance with...

  17. 45 CFR 1602.8 - Requests for records.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... should try to provide the following kinds of information, if known: (1) The specific event or action to... on which a determination may be expected to be dispatched, and the requester's right to treat the... thereof, the requester may deem the request denied, and exercise a right of appeal in accordance with...

  18. 45 CFR 1602.8 - Requests for records.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... should try to provide the following kinds of information, if known: (1) The specific event or action to... on which a determination may be expected to be dispatched, and the requester's right to treat the... thereof, the requester may deem the request denied, and exercise a right of appeal in accordance with...

  19. 45 CFR 1602.8 - Requests for records.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... should try to provide the following kinds of information, if known: (1) The specific event or action to... on which a determination may be expected to be dispatched, and the requester's right to treat the... thereof, the requester may deem the request denied, and exercise a right of appeal in accordance with...

  20. 9 CFR 124.40 - Request for hearing.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Diligence Hearing § 124.40 Request for hearing. (a) Any interested person may request, within 60 days beginning on the date of publication of a due diligence determination by APHIS in accordance with § 124.32, that APHIS conduct an informal hearing on the due diligence determination. (b) The request for a...

  1. 15 CFR 2007.4 - Publication regarding requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 3 2010-01-01 2010-01-01 false Publication regarding requests. 2007.4...)) § 2007.4 Publication regarding requests. (a) Whenever a request is received which conforms to these... publication of any Presidential action modifying the GSP, a summary of the decisions made will be published in...

  2. 36 CFR 1007.3 - Requests for records.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... waivers set out in § 1007.10 are met. (5) To expedite processing, both the envelope containing a request... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Requests for records. 1007.3 Section 1007.3 Parks, Forests, and Public Property PRESIDIO TRUST REQUESTS UNDER THE FREEDOM OF...

  3. 42 CFR 431.221 - Request for hearing.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Request for hearing. 431.221 Section 431.221 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Recipients Right to Hearing § 431.221 Request for hearing. (a) The agency may require that a request for a...

  4. 15 CFR 2007.4 - Publication regarding requests.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 3 2013-01-01 2013-01-01 false Publication regarding requests. 2007.4...)) § 2007.4 Publication regarding requests. (a) Whenever a request is received which conforms to these... publication of any Presidential action modifying the GSP, a summary of the decisions made will be published in...

  5. 15 CFR 2007.4 - Publication regarding requests.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 3 2014-01-01 2014-01-01 false Publication regarding requests. 2007.4...)) § 2007.4 Publication regarding requests. (a) Whenever a request is received which conforms to these... publication of any Presidential action modifying the GSP, a summary of the decisions made will be published in...

  6. 15 CFR 2007.4 - Publication regarding requests.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 3 2012-01-01 2012-01-01 false Publication regarding requests. 2007.4...)) § 2007.4 Publication regarding requests. (a) Whenever a request is received which conforms to these... publication of any Presidential action modifying the GSP, a summary of the decisions made will be published in...

  7. 40 CFR 1601.20 - Requests for records.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... request. Records to be obtained in person will be available for inspection or copying during business hours on a regular business day in the office of the CSB. (b) Description of records. Each request must... satisfying a request for records; (2) Provide records not yet in existence, even if such records may be...

  8. 29 CFR 19.4 - Contents of request.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Secretary of Labor RIGHT TO FINANCIAL PRIVACY ACT § 19.4 Contents of request. The formal written request shall be in the form of a letter or memorandum to an appropriate official of the financial institution..., business address and business phone number. The request shall also contain the following: (a) The identity...

  9. Task Switching in a Hierarchical Task Structure: Evidence for the Fragility of the Task Repetition Benefit

    ERIC Educational Resources Information Center

    Lien, Mei-Ching; Ruthruff, Eric

    2004-01-01

    This study examined how task switching is affected by hierarchical task organization. Traditional task-switching studies, which use a constant temporal and spatial distance between each task element (defined as a stimulus requiring a response), promote a flat task structure. Using this approach, Experiment 1 revealed a large switch cost of 238 ms.…

  10. 22 CFR 303.8 - Requests for records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... treatment could reasonably be expected to pose an imminent threat to the life or physical safety of an... affect public confidence. (2) A request for expedited processing may be made at the time of the initial... Officer shall decide whether to grant the request and shall notify the requester of the decision. If a...

  11. 6 CFR 1002.3 - Privacy Act requests.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 6 Domestic Security 1 2014-01-01 2014-01-01 false Privacy Act requests. 1002.3 Section 1002.3 Domestic Security PRIVACY AND CIVIL LIBERTIES OVERSIGHT BOARD IMPLEMENTATION OF THE PRIVACY ACT OF 1974 § 1002.3 Privacy Act requests. (a) Requests to determine if you are the subject of a record. You may...

  12. 21 CFR 60.40 - Request for hearing.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... RESTORATION Due Diligence Hearings § 60.40 Request for hearing. (a) Any person may request, not later than 60 days after the publication under § 60.34(a) of FDA's due diligence determination, that FDA conduct an informal hearing on the due diligence determination. (b) The request for a hearing under this section shall...

  13. 25 CFR 700.241 - Request for records.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... Records § 700.241 Request for records. (a) Submission of requests. A request to inspect or copy records shall be made to the installation where the records are located. If the records are located at more than one installation or if the specific location of the records is not known to the person wishing to...

  14. 7 CFR 1.172 - Motions and requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 1 2011-01-01 2011-01-01 false Motions and requests. 1.172 Section 1.172 Agriculture... Desist Proceedings Under Section 2 of the Capper-Volstead Act § 1.172 Motions and requests. (a) General. All motions and requests shall be filed with the Hearing Clerk, and shall be served upon the parties...

  15. 7 CFR 1.172 - Motions and requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 1 2010-01-01 2010-01-01 false Motions and requests. 1.172 Section 1.172 Agriculture... Desist Proceedings Under Section 2 of the Capper-Volstead Act § 1.172 Motions and requests. (a) General. All motions and requests shall be filed with the Hearing Clerk, and shall be served upon the parties...

  16. Subjective Estimation of Task Time and Task Difficulty of Simple Movement Tasks.

    PubMed

    Chan, Alan H S; Hoffmann, Errol R

    2017-01-01

    It has been demonstrated in previous work that the same neural structures are used for both imagined and real movements. To provide a strong test of the similarity of imagined and actual movement times, 4 simple movement tasks were used to determine the relationship between estimated task time and actual movement time. The tasks were single-component visually controlled movements, 2-component visually controlled, low index of difficulty (ID) moves and pin-to-hole transfer movements. For each task there was good correspondence between the mean estimated times and actual movement times. In all cases, the same factors determined the actual and estimated movement times: the amplitudes of movement and the IDs of the component movements, however the contribution of each of these variables differed for the imagined and real tasks. Generally, the standard deviations of the estimated times were linearly related to the estimated time values. Overall, the data provide strong evidence for the same neural structures being used for both imagined and actual movements.

  17. Property Accountability Task Force

    DTIC Science & Technology

    1978-06-30

    accountability. Many organizations have initiated innovative changes. I can as’,ure you that the pro, edures being put into effect will not be "auick...08184Z MAR 78 B. TRADOC MSG, DTG 031705Z APR 78, SAB 1. REF A REQUESTED THAT YOU PROVIDE DIRECTION TO ALL SERVICE SCHOOLS ON THE USE OF THE LOGISTICS...ABOVE. 3. REQUEST YOU INFORM DAPATF OF YOUR PLANS CONCERNING THE FOLLLOWING POINTS: A. ENSURING THAT ALL STUDENTS MASTER THE SUPPLY PROCEDURES

  18. Task-set inertia and memory-consolidation bottleneck in dual tasks.

    PubMed

    Koch, Iring; Rumiati, Raffaella I

    2006-11-01

    Three dual-task experiments examined the influence of processing a briefly presented visual object for deferred verbal report on performance in an unrelated auditory-manual reaction time (RT) task. RT was increased at short stimulus-onset asynchronies (SOAs) relative to long SOAs, showing that memory consolidation processes can produce a functional processing bottleneck in dual-task performance. In addition, the experiments manipulated the spatial compatibility of the orientation of the visual object and the side of the speeded manual response. This cross-task compatibility produced relative RT benefits only when the instruction for the visual task emphasized overlap at the level of response codes across the task sets (Experiment 1). However, once the effective task set was in place, it continued to produce cross-task compatibility effects even in single-task situations ("ignore" trials in Experiment 2) and when instructions for the visual task did not explicitly require spatial coding of object orientation (Experiment 3). Taken together, the data suggest a considerable degree of task-set inertia in dual-task performance, which is also reinforced by finding costs of switching task sequences (e.g., AC --> BC vs. BC --> BC) in Experiment 3.

  19. 10 CFR 1304.106 - Processing of requests.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 4 2014-01-01 2014-01-01 false Processing of requests. 1304.106 Section 1304.106 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.106 Processing of requests. Upon receipt...) Requests in writing, including those sent by e-mail, via the Web site, or by Fax. Within five working days...

  20. 10 CFR 1304.106 - Processing of requests.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 4 2012-01-01 2012-01-01 false Processing of requests. 1304.106 Section 1304.106 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.106 Processing of requests. Upon receipt...) Requests in writing, including those sent by e-mail, via the Web site, or by Fax. Within five working days...

  1. 10 CFR 1304.106 - Processing of requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Processing of requests. 1304.106 Section 1304.106 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.106 Processing of requests. Upon receipt...) Requests in writing, including those sent by e-mail, via the Web site, or by Fax. Within five working days...

  2. 10 CFR 1304.106 - Processing of requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Processing of requests. 1304.106 Section 1304.106 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.106 Processing of requests. Upon receipt...) Requests in writing, including those sent by e-mail, via the Web site, or by Fax. Within five working days...

  3. 10 CFR 1304.106 - Processing of requests.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 4 2013-01-01 2013-01-01 false Processing of requests. 1304.106 Section 1304.106 Energy NUCLEAR WASTE TECHNICAL REVIEW BOARD PRIVACY ACT OF 1974 § 1304.106 Processing of requests. Upon receipt...) Requests in writing, including those sent by e-mail, via the Web site, or by Fax. Within five working days...

  4. 7 CFR 1.424 - Motions and requests.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... written motions and requests shall state the particular order, ruling, or action desired and the grounds... 7 Agriculture 1 2011-01-01 2011-01-01 false Motions and requests. 1.424 Section 1.424 Agriculture... Conservation and Shortage Relief Act of 1990 (16 U.S.C. 620 et seq.) § 1.424 Motions and requests. (a) General...

  5. 7 CFR 1.424 - Motions and requests.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... written motions and requests shall state the particular order, ruling, or action desired and the grounds... 7 Agriculture 1 2010-01-01 2010-01-01 false Motions and requests. 1.424 Section 1.424 Agriculture... Conservation and Shortage Relief Act of 1990 (16 U.S.C. 620 et seq.) § 1.424 Motions and requests. (a) General...

  6. 78 FR 43880 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; Notice...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-22

    ... personal information provided, unless the comment includes profanity, threats, information claimed to be... ENVIRONMENTAL PROTECTION AGENCY [EPA-OPP-2012-0544; FRL-9534-8] Information Collection Request... Environmental Protection Agency has submitted an information collection request (ICR), ``Notice of Supplemental...

  7. 78 FR 15945 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; Tips...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-13

    ..., unless the comment includes profanity, threats, information claimed to be Confidential Business... ENVIRONMENTAL PROTECTION AGENCY [EPA-HQ-OECA-2009-0494; FRL 9527-7] Information Collection Request... Environmental Protection Agency has submitted an information collection request (ICR), ``Tips and Complaints...

  8. 78 FR 63183 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request; Mobile...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-10-23

    ... of air conditioning systems and recovery/recycling equipment. Form Numbers: None. Respondents... automotive repair shops, automotive repair shops not elsewhere classified, including air conditioning and... Request Submitted to OMB for Review and Approval; Comment Request; Mobile Air Conditioner Retrofitting...

  9. 78 FR 25091 - Submission for OMB Review; 30-Day Comment Request: Request for Human Embryonic Stem Cell Line To...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-29

    ...; 30-Day Comment Request: Request for Human Embryonic Stem Cell Line To Be Approved for Use in NIH... Embryonic Stem Cell Line to be Approved for Use in NIH-Funded Research, 0925-0601, Expiration Date 04/30... Information Collection: The form is used by applicants to request that human embryonic stem cell lines be...

  10. 28 CFR 513.60 - Freedom of Information Act requests.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 2 2010-07-01 2010-07-01 false Freedom of Information Act requests. 513... AND ADMINISTRATION ACCESS TO RECORDS Release of Information Freedom of Information Act Requests for Information § 513.60 Freedom of Information Act requests. Requests for any Bureau record (including Program...

  11. 10 CFR 501.131 - Filing a request for interpretation.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Filing a request for interpretation. 501.131 Section 501.131 Energy DEPARTMENT OF ENERGY (CONTINUED) ALTERNATE FUELS ADMINISTRATIVE PROCEDURES AND SANCTIONS Requests for Interpretation § 501.131 Filing a request for interpretation. A proceeding to request an...

  12. 77 FR 43822 - Proposed Information Collection Request; Comment Request; Valuing Improved Water Quality in the...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-26

    ... Request; Comment Request; Valuing Improved Water Quality in the Chesapeake Bay Using Stated Preference... efforts to improve water quality in the Chesapeake Bay. In 2009, Executive Order (E.O.) 13508 re... undertaking a benefits analysis of improvements in Bay water quality under the TMDLs, as well as of ancillary...

  13. 14 CFR § 1206.703 - Aggregation of requests.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... AGENCY RECORDS TO MEMBERS OF THE PUBLIC Search, Review, and Duplication Fees § 1206.703 Aggregation of... requester or a group of requesters acting in concert, is attempting to break a request down into a series of...

  14. 32 CFR 887.4 - Requesting CILs.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ...: Persons authorized CILs may be assisted in their request by the Customer Service Unit (DPMAC) in the... 180 (SF 180), Request Pertaining to Military Records, should be used by persons who had service as...

  15. 78 FR 25058 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-29

    ... tags: designation 10 minutes, requests for tags, 2 minutes; lobster area waiver, 20 minutes and request... also required to request gillnet and lobster tags through the Northeast region permit office when using gillnet gear or lobster traps. Lastly, vessel owners that own multiple vessels, but would like to request...

  16. 42 CFR 110.44 - Legal or personal representatives of requesters.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... jurisdiction, does not need a legal or personal representative to file a Request Form or Request Package on his... 42 Public Health 1 2011-10-01 2011-10-01 false Legal or personal representatives of requesters... or personal representatives of requesters. (a) Generally. Persons other than a requester (e.g., a...

  17. Recalling academic tasks

    NASA Astrophysics Data System (ADS)

    Draper, Franklin Gno

    This study was focused on what students remembered about five middle school science tasks when they were juniors and seniors in high school. Descriptions of the five tasks were reconstructed from available artifacts and teachers' records, notes and recollections. Three of the five tasks were "authentic" in the sense that students were asked to duplicate the decisions practitioners make in the adult world. The other two tasks were more typical school tasks involving note taking and preparation for a quiz. All five tasks, however, involved use of computers. Students were interviewed to examine what and how well they recalled the tasks and what forms or patterns of recall existed. Analysis of their responses indicated that different kinds of tasks produced different levels of recall. Authentically situated tasks were remembered much better than routine school tasks. Further, authentic tasks centered on design elements were recalled better than those for which design was not as pivotal. Patterns of recall indicated that participants most often recalled the decisions they made, the scenarios of the authentically situated tasks, the consequences of their tasks and the social contexts of the classroom. Task events, in other words, appeared to form a framework upon which students constructed stories of the tasks. The more salient the events, the richer the story, the deeper and more detailed the recall of the task. Thus, authentic tasks appeared to lend themselves to creating stories better than regular school tasks and therefore such tasks were recalled better. Implications of these patterns of recall are discussed with respect to issues of school learning and assessment.

  18. The importance of mean time in therapeutic range for complication rates in warfarin therapy of patients with atrial fibrillation: A systematic review and meta-regression analysis.

    PubMed

    Vestergaard, Anne Sig; Skjøth, Flemming; Larsen, Torben Bjerregaard; Ehlers, Lars Holger

    2017-01-01

    \\Anticoagulation is used for stroke prophylaxis in non-valvular atrial fibrillation, amongst other by use of the vitamin K antagonist, warfarin. Quality in warfarin therapy is often summarized by the time patients spend within the therapeutic range (percent time in therapeutic range, TTR). The correlation between TTR and the occurrence of complications during warfarin therapy has been established, but the influence of patient characteristics in that respect remains undetermined. The objective of the present papers was to examine the association between mean TTR and complication rates with adjustment for differences in relevant patient cohort characteristics. A systematic literature search was conducted in MEDLINE and Embase (2005-2015) to identify eligible studies reporting on use of warfarin therapy by patients with non-valvular atrial fibrillation and the occurrence of hemorrhage and thromboembolism. Both randomized controlled trials and observational cohort studies were included. The association between the reported mean TTR and major bleeding and stroke/systemic embolism was analyzed by random-effects meta-regression with and without adjustment for relevant clinical cohort characteristics. In the adjusted meta-regressions, the impact of mean TTR on the occurrence of hemorrhage was adjusted for the mean age and the proportion of populations with prior stroke or transient ischemic attack. In the adjusted analyses on thromboembolism, the proportion of females was, furthermore, included. Of 2169 papers, 35 papers met pre-specified inclusion criteria, holding relevant information on 31 patient cohorts. In univariable meta-regression, increasing mean TTR was significantly associated with a decreased rate of both major bleeding and stroke/systemic embolism. However, after adjustment mean TTR was no longer significantly associated with stroke/systemic embolism. The proportion of residual variance composed by between-study heterogeneity was substantial for all analyses

  19. 7 CFR 1.6 - Aggregating requests.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., is attempting to break a request down into a series of requests for the purpose of evading the... be considered in determining whether such a belief would be reasonable is the brevity of the time...

  20. 5 CFR 294.103 - Definitions of categories and assignment of requests and requesters to categories.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... scientific institutions, requests for non-commercial use made by representatives of the news media, and all... product or industry. (c) Request from a representative of the news media. “Representative of the news media” refers to any person actively gathering news for an entity that is organized and operated to...

  1. 5 CFR 294.103 - Definitions of categories and assignment of requests and requesters to categories.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... scientific institutions, requests for non-commercial use made by representatives of the news media, and all... product or industry. (c) Request from a representative of the news media. “Representative of the news media” refers to any person actively gathering news for an entity that is organized and operated to...

  2. 5 CFR 294.103 - Definitions of categories and assignment of requests and requesters to categories.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... scientific institutions, requests for non-commercial use made by representatives of the news media, and all... product or industry. (c) Request from a representative of the news media. “Representative of the news media” refers to any person actively gathering news for an entity that is organized and operated to...

  3. 78 FR 26773 - Proposed Information Collection Request; Comment Request; Willingness To Pay Survey for Santa...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-08

    ... lengths, are derived from natural science research. For the survey, a choice experiment framework is used... survey is public value research. The Santa Cruz River is a case study of a waterway highly impacted by... Request; Comment Request; Willingness To Pay Survey for Santa Cruz River Management Options in Southern...

  4. 78 FR 7777 - Information Collection Request Submitted to OMB for Review and Approval; Comment Request...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-04

    ... Submitted to OMB for Review and Approval; Comment Request; Notification of Chemical Exports--TSCA Section 12... forwarded to the Office of Management and Budget (OMB) for review and approval. This is a request to renew the current approval for the ICR entitled ``Notification of Chemical Exports--TSCA Section 12(b)'' and...

  5. 76 FR 27378 - Request for Service Corporation Activity

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-05-11

    ... DEPARTMENT OF THE TREASURY Office of Thrift Supervision Request for Service Corporation Activity AGENCY: Office of Thrift Supervision (OTS), Treasury. ACTION: Notice and request for comment. SUMMARY... on the following information collection. Title of Proposal: Request for Service Corporation Activity...

  6. Sulfated Metabolites of Polychlorinated Biphenyls Are High-Affinity Ligands for the Thyroid Hormone Transport Protein Transthyretin

    PubMed Central

    Grimm, Fabian A.; Lehmler, Hans-Joachim; He, Xianran; Robertson, Larry W.

    2013-01-01

    Background: The displacement of l-thyroxine (T4) from binding sites on transthyretin (TTR) is considered a significant contributing mechanism in polychlorinated biphenyl (PCB)-induced thyroid disruption. Previous research has discovered hydroxylated PCB metabolites (OH-PCBs) as high-affinity ligands for TTR, but the binding potential of conjugated PCB metabolites such as PCB sulfates has not been explored. Objectives: We evaluated the binding of five lower-chlorinated PCB sulfates to human TTR and compared their binding characteristics to those determined for their OH-PCB precursors and for T4. Methods: We used fluorescence probe displacement studies and molecular docking simulations to characterize the binding of PCB sulfates to TTR. The stability of PCB sulfates and the reversibility of these interactions were characterized by HPLC analysis of PCB sulfates after their binding to TTR. The ability of OH-PCBs to serve as substrates for human cytosolic sulfotransferase 1A1 (hSULT1A1) was assessed by OH-PCB–dependent formation of adenosine-3´,5´-diphosphate, an end product of the sulfation reaction. Results: All five PCB sulfates were able to bind to the high-affinity binding site of TTR with equilibrium dissociation constants (Kd values) in the low nanomolar range (4.8–16.8 nM), similar to that observed for T4 (4.7 nM). Docking simulations provided corroborating evidence for these binding interactions and indicated multiple high-affinity modes of binding. All OH-PCB precursors for these sulfates were found to be substrates for hSULT1A1. Conclusions: Our findings show that PCB sulfates are high-affinity ligands for human TTR and therefore indicate, for the first time, a potential relevance for these metabolites in PCB-induced thyroid disruption. PMID:23584369

  7. Is all hypoglycaemia treated as equal? An observational study of how the type of diabetes and treatment prescribed prior to admission influences quality of treatment of inpatient hypoglycaemia.

    PubMed

    Jones, Gregory C; Khan, Jansher; Sainsbury, Christopher A R

    2017-03-01

    Inpatient hypoglycaemia is common and associated with adverse outcomes. There is often increased vigilance of hypoglycaemia in inpatients with type 1 diabetes (T1DM) compared to type 2 diabetes (T2DM). We aimed to investigate this apparent discrepancy, utilising the time to repeat (TTR) capillary blood glucose (CBG) measurement as a surrogate for engagement with guidelines stating that CBG should be rechecked following intervention within 15 min of an initial CBG of <4 mmol/L. This is an observational study of inpatient CBG data from 8 hospitals over a 7-year period. A national diabetes registry allowed identification of individual's diagnosis and diabetes therapy. For each initial (index) CBG, the TTR for individuals with T2DM-on insulin or sulphonylurea-was compared with the TTR for individuals with T1DM, using a t test for significance performed on log(TTR). The median TTR was plotted for each group per index CBG. In total, 1480,335 CBG measurements were obtained. A total of 26,664 were <4 mmol/L. The TTR in T2DM individuals on sulphonylurea was significantly greater than in T1DM individuals where index CBG was ≥2.3 mmol/L (except index CBG 2.6 mmol/L). For T2DM patients receiving insulin significance exists for index CBGs of ≥3.2 mmol/L. This analysis suggests that quality of care of hypoglycaemia varies according to diagnosis and medication. The group with the highest TTR (T2DM sulphonylurea treated) are possibly the clinical group in whom hypoglycaemia is most concerning. These data therefore suggest a need for education and raising awareness within the inpatient nursing staff.

  8. Post-Closure Inspection Report for the Tonopah Test Range, Nevada. For Calendar Year 2015, Revision 0

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

    Matthews, Patrick; Petrello, Jaclyn

    This report provides the results of the annual post-closure inspections conducted at the closed corrective action units (CAUs) located on the Tonopah Test Range (TTR), Nevada. This report covers calendar year 2015 and includes inspection and repair activities completed at the following CAUs; CAU 400: Bomblet Pit and Five Points Landfill (TTR); CAU 407: Roller Coaster RadSafe Area (TTR); CAU 424: Area 3 Landfill Complexes (TTR); CAU 453: Area 9 UXO Landfill (TTR); and CAU 487: Thunderwell Site (TTR) Inspections were conducted according to the post-closure plans in the approved closure reports and subsequent correspondence with the Nevada Division ofmore » Environmental Protection. The post-closure inspection plans and subsequent correspondence modifying the requirements for each CAU are included in Appendix B. The inspection checklists are included in Appendix C. Field notes are included in Appendix D. The annual post-closure inspections were conducted on May 12, 2015. Maintenance was required at CAU 453. Cracking along the north trench was repaired. One monument is missing at CAU 424; it will be replaced in 2016. Postings at CAUs 407, 424, 453, and 487 contain contact information for TTR Security. It was noted that protocols may not be in place to ensure that the U.S. Department of Energy, National Nuclear Security Administration Nevada Field Office (NNSA/NFO) is notified if access is needed at these sites. NNSA/NFO is working with the U.S. Air Force and Sandia to determine whether more appropriate contact information or new protocols are warranted for each CAU. Based on these inspections, there has not been a significant change in vegetation, and vegetation monitoring was not recommended at CAU 400 or CAU 407 in 2015.« less

  9. Quality of warfarin therapy and risk of stroke, bleeding, and mortality among patients with atrial fibrillation: results from the nationwide FinWAF Registry.

    PubMed

    Lehto, Mika; Niiranen, Jussi; Korhonen, Pasi; Mehtälä, Juha; Khanfir, Houssem; Hoti, Fabian; Lassila, Riitta; Raatikainen, Pekka

    2017-06-01

    The most important management strategy in atrial fibrillation (AF) patients is preventing stroke with oral anticoagulants. Warfarin is still used as a first-line anticoagulant, although non-vitamin K antagonist oral anticoagulants are currently recommended to manage AF. Using a large, unselected national sample of AF patients, we evaluated the relationships between quality of warfarin therapy and the risks of thromboembolism, bleeding complications, and mortality. The nationwide FinWAF study included 54 568 AF patients taking warfarin. Time in the therapeutic range (TTR) was calculated on a continuous basis using the Rosendaal method and international normalized ratio values over the previous 60 days. Adjusted Cox proportional hazard models were prepared for different TTR levels and major clinical end points. The mean age of patients was 73.1 years (standard deviation 10.8), and 47% were female. The mean follow-up time was 3.2 ± 1.6 years (median 3.4). In the TTR groups of ≤40%, 60-70%, 70-80%, and >80%, the annual risk of stroke was 9.3%, 4.7%, 4.6%, and 3.1%; bleeding events 7.5%, 4.5%, 4.3%, and 2.6%; and overall mortality 20.9%, 8.5%, 6.4%, and 3.1%, respectively. All differences among the TTR groups were highly significant (p < 0.001). The quality of warfarin treatment was strongly associated with the risk of stroke and the prognosis of AF patients. Patient outcomes continued to improve with increasing TTR values up to a TTR ≥80%; therefore, the target for the TTR should exceed 80% instead of the traditional range of at least 60-70%. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  10. Biennial Operating Budget Request, FY 2007-2009

    ERIC Educational Resources Information Center

    Connecticut Department of Higher Education (NJ1), 2006

    2006-01-01

    The Connecticut public higher education community requests an overall general fund/operating fund budget of $1.95 billion for FY 2008 and $2.02 billion for FY 2009. In FY 2008, this includes general fund current service support of $717.7 million and other funding requests of $53.0 million. For FY 2009, the general fund current service request is…

  11. 29 CFR 18.6 - Motions and requests.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 1 2011-07-01 2011-07-01 false Motions and requests. 18.6 Section 18.6 Labor Office of the... ADMINISTRATIVE LAW JUDGES General § 18.6 Motions and requests. (a) Generally. Any application for an order or any other request shall be made by motion which, unless made during a hearing or trial, shall be made in...

  12. 49 CFR 701.7 - Timing of responses to requests.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... by a requester or by a group of requesters acting in concert constitute a single request that would... circumstances that may justify delay include: (i) The need to search for and collect the requested records from other facilities that are separate from Amtrak's headquarters offices. (ii) The need to search for...

  13. 40 CFR 1601.24 - Timing of responses to requests.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... by a group of requesters acting in concert, constitute a single request that would otherwise involve... means that there is a need to: (1) Search for and collect the requested records from facilities that are separate from the office processing the request; (2) Search for, collect, and appropriately examine a...

  14. BioCreative III interactive task: an overview

    PubMed Central

    2011-01-01

    Background The BioCreative challenge evaluation is a community-wide effort for evaluating text mining and information extraction systems applied to the biological domain. The biocurator community, as an active user of biomedical literature, provides a diverse and engaged end user group for text mining tools. Earlier BioCreative challenges involved many text mining teams in developing basic capabilities relevant to biological curation, but they did not address the issues of system usage, insertion into the workflow and adoption by curators. Thus in BioCreative III (BC-III), the InterActive Task (IAT) was introduced to address the utility and usability of text mining tools for real-life biocuration tasks. To support the aims of the IAT in BC-III, involvement of both developers and end users was solicited, and the development of a user interface to address the tasks interactively was requested. Results A User Advisory Group (UAG) actively participated in the IAT design and assessment. The task focused on gene normalization (identifying gene mentions in the article and linking these genes to standard database identifiers), gene ranking based on the overall importance of each gene mentioned in the article, and gene-oriented document retrieval (identifying full text papers relevant to a selected gene). Six systems participated and all processed and displayed the same set of articles. The articles were selected based on content known to be problematic for curation, such as ambiguity of gene names, coverage of multiple genes and species, or introduction of a new gene name. Members of the UAG curated three articles for training and assessment purposes, and each member was assigned a system to review. A questionnaire related to the interface usability and task performance (as measured by precision and recall) was answered after systems were used to curate articles. Although the limited number of articles analyzed and users involved in the IAT experiment precluded rigorous

  15. Factors influencing warfarin control in Australia and Singapore.

    PubMed

    Bernaitis, Nijole; Ching, Chi Keong; Teo, Siew Chong; Chen, Liping; Badrick, Tony; Davey, Andrew K; Crilly, Julia; Anoopkumar-Dukie, Shailendra

    2017-09-01

    Warfarin is widely used for patients with non-valvular atrial fibrillation (NVAF). Variations in warfarin control, as measured by time in therapeutic range (TTR), have been reported across different regions and ethnicities, particularly between Western and Asian countries. However, there is limited data on comparative factors influencing warfarin control in Caucasian and Asian patients. Therefore, the aim of this study was to determine warfarin control and potential factors influencing this in patients with NVAF in Australia and Singapore. Retrospective data was collected for patients receiving warfarin for January to June 2014 in Australia and Singapore. TTR was calculated for individuals with mean patient TTR used for analysis. Possible influential factors on TTR were analysed including age, gender, concurrent co-morbidities, and concurrent medication. The mean TTR was significantly higher in Australia (82%) than Singapore (58%). At both sites, chronic kidney disease significantly lowered this TTR. Further factors influencing control were anaemia and age<60years in Australia, and vascular disease, CHA 2 DS 2 -VASc score of 6, and concurrent platelet inhibitor therapy in Singapore. Warfarin control was significantly higher in Australia compared to Singapore, however chronic kidney disease reduced control at both sites. The different levels of control in these two countries, together with patient factors further reducing control may impact on anticoagulant choice in these countries with better outcomes from warfarin in Australia compared to Singapore. Copyright © 2017 Elsevier Ltd. All rights reserved.

  16. Calendar year 2002 annual site environmental report for Tonopah Test Range, Nevada and Kauai Test Facility, Hawaii.

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

    Wagner, Katrina; Sanchez, Rebecca V.; Mayeux, Lucie

    2003-09-01

    Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, oversees TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility.more » This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2002. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 5400.1, General Environmental Protection Program (DOE 1990) and DOE Order 231.1, Environment, Safety, and Health Reporting (DOE 1996).« less

  17. Calendar year 2003 : annual site enviromental report for Tonopah Test Range, Nevada and Kauai Test Facility, Hawaii.

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

    Wagner, Katrina; Sanchez, Rebecca V.; Mayeux, Lucie

    2004-09-01

    Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, manages TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility.more » This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2003. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2003) and DOE Order 231.1 Chg 2., Environment, Safety, and Health Reporting (DOE 1996).« less

  18. Comparison of international normalized ratio audit parameters in patients enrolled in GARFIELD-AF and treated with vitamin K antagonists.

    PubMed

    Fitzmaurice, David A; Accetta, Gabriele; Haas, Sylvia; Kayani, Gloria; Lucas Luciardi, Hector; Misselwitz, Frank; Pieper, Karen; Ten Cate, Hugo; Turpie, Alexander G G; Kakkar, Ajay K

    2016-08-01

    Vitamin K antagonist (VKA) therapy for stroke prevention in atrial fibrillation (AF) requires monitoring of the international normalized ratio (INR). We evaluated the agreement between two INR audit parameters, frequency in range (FIR) and proportion of time in the therapeutic range (TTR), using data from a global population of patients with newly diagnosed non-valvular AF, the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF). Among 17 168 patients with 1-year follow-up data available at the time of the analysis, 8445 received VKA therapy (±antiplatelet therapy) at enrolment, and of these patients, 5066 with ≥3 INR readings and for whom both FIR and TTR could be calculated were included in the analysis. In total, 70 905 INRs were analysed. At the patient level, TTR showed higher values than FIR (mean, 56·0% vs 49·8%; median, 59·7% vs 50·0%). Although patient-level FIR and TTR values were highly correlated (Pearson correlation coefficient [95% confidence interval; CI], 0·860 [0·852-0·867]), estimates from individuals showed widespread disagreement and variability (Lin's concordance coefficient [95% CI], 0·829 [0·821-0·837]). The difference between FIR and TTR explained 17·4% of the total variability of measurements. These results suggest that FIR and TTR are not equivalent and cannot be used interchangeably. © 2016 John Wiley & Sons Ltd.

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

    Griffith, Stacy Rene; Agogino, Karen; Li, Jun

    Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities managed and operated by Sandia Corporation (Sandia), a wholly owned subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Field Office (SFO), in Albuquerque, New Mexico, administers the contract and oversees contractor operations at TTR and KTF. Sandia manages and conducts operations at TTR in support of the DOE/NNSA’s Weapons Ordnance Program and has operated the site since 1957. Navarro Research and Engineering subcontracts to Sandia in administering most of the environmental programsmore » at TTR. Sandia operates KTF as a rocket preparation launching and tracking facility. This Annual Site Environmental Report summarizes data and the compliance status of the sustainability, environmental protection, and monitoring program at TTR and KTF through Calendar Year 2013. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, Environmental Restoration (ER) cleanup activities, and the National Environmental Policy Act. Sandia is responsible only for those environmental program activities related to its operations. The DOE/NNSA/Nevada Field Office retains responsibility for the cleanup and management of TTR ER sites. Environmental monitoring and surveillance programs are required by DOE Order 231.1B, Environment, Safety, and Health Reporting (DOE 2012).« less

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

    Montoya, Amber L.; Wagner, Katrina; Goering, Teresa Lynn

    Tonopah Test Range (TTR) in Nevada and Kauai Test Facility (KTF) in Hawaii are government-owned, contractor-operated facilities operated by Sandia Corporation, a subsidiary of Lockheed Martin Corporation. The U.S. Department of Energy (DOE), National Nuclear Security Administration (NNSA), through the Sandia Site Office (SSO), in Albuquerque, NM, manages TTR and KTF's operations. Sandia Corporation conducts operations at TTR in support of DOE/NNSA's Weapons Ordnance Program and has operated the site since 1957. Westinghouse Government Services subcontracts to Sandia Corporation in administering most of the environmental programs at TTR. Sandia Corporation operates KTF as a rocket preparation launching and tracking facility.more » This Annual Site Environmental Report (ASER) summarizes data and the compliance status of the environmental protection and monitoring program at TTR and KTF through Calendar Year (CY) 2004. The compliance status of environmental regulations applicable at these sites include state and federal regulations governing air emissions, wastewater effluent, waste management, terrestrial surveillance, and Environmental Restoration (ER) cleanup activities. Sandia Corporation is responsible only for those environmental program activities related to its operations. The DOE/NNSA, Nevada Site Office (NSO) retains responsibility for the cleanup and management of ER TTR sites. Currently, there are no ER Sites at KTF. Environmental monitoring and surveillance programs are required by DOE Order 450.1, Environmental Protection Program (DOE 2005) and DOE Order 231.1A, Environment, Safety, and Health Reporting (DOE 2004b).« less