Human NR5A1/SF-1 mutations show decreased activity on BDNF (brain-derived neurotrophic factor), an important regulator of energy balance: testing impact of novel SF-1 mutations beyond steroidogenesis.

PubMed

Malikova, Jana; Camats, Núria; Fernández-Cancio, Mónica; Heath, Karen; González, Isabel; Caimarí, María; del Campo, Miguel; Albisu, Marian; Kolouskova, Stanislava; Audí, Laura; Flück, Christa E

2014-01-01

Human NR5A1/SF-1 mutations cause 46,XY disorder of sex development (DSD) with broad phenotypic variability, and rarely cause adrenal insufficiency although SF-1 is an important transcription factor for many genes involved in steroidogenesis. In addition, the Sf-1 knockout mouse develops obesity with age. Obesity might be mediated through Sf-1 regulating activity of brain-derived neurotrophic factor (BDNF), an important regulator of energy balance in the ventromedial hypothalamus. To characterize novel SF-1 gene variants in 4 families, clinical, genetic and functional studies were performed with respect to steroidogenesis and energy balance. 5 patients with 46,XY DSD were found to harbor NR5A1/SF-1 mutations including 2 novel variations. One patient harboring a novel mutation also suffered from adrenal insufficiency. SF-1 mutations were studied in cell systems (HEK293, JEG3) for impact on transcription of genes involved in steroidogenesis (CYP11A1, CYP17A1, HSD3B2) and in energy balance (BDNF). BDNF regulation by SF-1 was studied by promoter assays (JEG3). Two novel NR5A1/SF-1 mutations (Glu7Stop, His408Profs*159) were confirmed. Glu7Stop is the 4th reported SF-1 mutation causing DSD and adrenal insufficiency. In vitro studies revealed that transcription of the BDNF gene is regulated by SF-1, and that mutant SF-1 decreased BDNF promoter activation (similar to steroid enzyme promoters). However, clinical data from 16 subjects carrying SF-1 mutations showed normal birth weight and BMI. Glu7Stop and His408Profs*159 are novel SF-1 mutations identified in patients with 46,XY DSD and adrenal insufficiency (Glu7Stop). In vitro, SF-1 mutations affect not only steroidogenesis but also transcription of BDNF which is involved in energy balance. However, in contrast to mice, consequences on weight were not found in humans with SF-1 mutations.

Inhibitory Control in the Cortico-Basal Ganglia-Thalamocortical Loop: Complex Regulation and Interplay with Memory and Decision Processes.

PubMed

Wei, Wei; Wang, Xiao-Jing

2016-12-07

We developed a circuit model of spiking neurons that includes multiple pathways in the basal ganglia (BG) and is endowed with feedback mechanisms at three levels: cortical microcircuit, corticothalamic loop, and cortico-BG-thalamocortical system. We focused on executive control in a stop signal task, which is known to depend on BG across species. The model reproduces a range of experimental observations and shows that the newly discovered feedback projection from external globus pallidus to striatum is crucial for inhibitory control. Moreover, stopping process is enhanced by the cortico-subcortical reverberatory dynamics underlying persistent activity, establishing interdependence between working memory and inhibitory control. Surprisingly, the stop signal reaction time (SSRT) can be adjusted by weights of certain connections but is insensitive to other connections in this complex circuit, suggesting novel circuit-based intervention for inhibitory control deficits associated with mental illness. Our model provides a unified framework for inhibitory control, decision making, and working memory. Copyright © 2016 Elsevier Inc. All rights reserved.

7 CFR 301.91 - Quarantine and regulations; restrictions on interstate movement of regulated articles. 1

Code of Federal Regulations, 2012 CFR

2012-01-01

... 7 Agriculture 5 2012-01-01 2012-01-01 false Quarantine and regulations; restrictions on interstate... QUARANTINE NOTICES European Larch Canker Quarantine and Regulations § 301.91 Quarantine and regulations... to stop and inspect persons and means of conveyance, and to seize, quarantine, treat, apply other...

7 CFR 301.91 - Quarantine and regulations; restrictions on interstate movement of regulated articles. 1

Code of Federal Regulations, 2010 CFR

2010-01-01

... 7 Agriculture 5 2010-01-01 2010-01-01 false Quarantine and regulations; restrictions on interstate... QUARANTINE NOTICES European Larch Canker Quarantine and Regulations § 301.91 Quarantine and regulations... to stop and inspect persons and means of conveyance, and to seize, quarantine, treat, apply other...

7 CFR 301.91 - Quarantine and regulations; restrictions on interstate movement of regulated articles. 1

Code of Federal Regulations, 2014 CFR

2014-01-01

... 7 Agriculture 5 2014-01-01 2014-01-01 false Quarantine and regulations; restrictions on interstate... QUARANTINE NOTICES European Larch Canker Quarantine and Regulations § 301.91 Quarantine and regulations... to stop and inspect persons and means of conveyance, and to seize, quarantine, treat, apply other...

7 CFR 301.91 - Quarantine and regulations; restrictions on interstate movement of regulated articles. 1

Code of Federal Regulations, 2011 CFR

2011-01-01

... 7 Agriculture 5 2011-01-01 2011-01-01 false Quarantine and regulations; restrictions on interstate... QUARANTINE NOTICES European Larch Canker Quarantine and Regulations § 301.91 Quarantine and regulations... to stop and inspect persons and means of conveyance, and to seize, quarantine, treat, apply other...

7 CFR 301.91 - Quarantine and regulations; restrictions on interstate movement of regulated articles. 1

Code of Federal Regulations, 2013 CFR

2013-01-01

... 7 Agriculture 5 2013-01-01 2013-01-01 false Quarantine and regulations; restrictions on interstate... QUARANTINE NOTICES European Larch Canker Quarantine and Regulations § 301.91 Quarantine and regulations... to stop and inspect persons and means of conveyance, and to seize, quarantine, treat, apply other...

7 CFR 301.91-4 - Conditions governing the interstate movement of regulated articles from regulated areas in...

Code of Federal Regulations, 2011 CFR

2011-01-01

... Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE... without stopping except under normal traffic conditions such as traffic lights or stop signs) any...

7 CFR 301.91-4 - Conditions governing the interstate movement of regulated articles from regulated areas in...

Code of Federal Regulations, 2010 CFR

2010-01-01

... Regulations of the Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE... without stopping except under normal traffic conditions such as traffic lights or stop signs) any...

49 CFR Appendix A to Part 180 - Internal Self-closing Stop Valve Emergency Closure Test for Liquefied Compressed Gases

Code of Federal Regulations, 2010 CFR

2010-10-01

... Test for Liquefied Compressed Gases A Appendix A to Part 180 Transportation Other Regulations Relating... Compressed Gases 1. In performing this test, all internal self-closing stop valves must be opened. Each.... 2. On pump-actuated pressure differential internal valves, the three-way toggle valve handle or its...

Damping of monocular pendular nystagmus with vibration in a patient with multiple sclerosis.

PubMed

Beh, Shin C; Tehrani, Ali Saber; Kheradmand, Amir; Zee, David S

2014-04-15

Acquired pendular nystagmus (PN) occurs commonly in multiple sclerosis (MS) and results in a highly disabling oscillopsia that impairs vision. It usually consists of pseudo-sinusoidal oscillations at a single frequency (3-5 Hz) that often briefly stop for a few hundred milliseconds after saccades and blinks. The oscillations are thought to arise from instability in the gaze-holding networks ("neural integrator") in the brainstem and cerebellum.(1,2) Here we describe a patient with monocular PN in whom vibration on the skull from a handheld muscle massager strikingly diminished or stopped her nystagmus.

Polypyrimidine tract binding protein 1 protects mRNAs from recognition by the nonsense-mediated mRNA decay pathway

PubMed Central

Ge, Zhiyun; Quek, Bao Lin; Beemon, Karen L; Hogg, J Robert

2016-01-01

The nonsense-mediated mRNA decay (NMD) pathway degrades mRNAs containing long 3'UTRs to perform dual roles in mRNA quality control and gene expression regulation. However, expansion of vertebrate 3'UTR functions has required a physical expansion of 3'UTR lengths, complicating the process of detecting nonsense mutations. We show that the polypyrimidine tract binding protein 1 (PTBP1) shields specific retroviral and cellular transcripts from NMD. When bound near a stop codon, PTBP1 blocks the NMD protein UPF1 from binding 3'UTRs. PTBP1 can thus mark specific stop codons as genuine, preserving both the ability of NMD to accurately detect aberrant mRNAs and the capacity of long 3'UTRs to regulate gene expression. Illustrating the wide scope of this mechanism, we use RNA-seq and transcriptome-wide analysis of PTBP1 binding sites to show that many human mRNAs are protected by PTBP1 and that PTBP1 enrichment near stop codons correlates with 3'UTR length and resistance to NMD. DOI: http://dx.doi.org/10.7554/eLife.11155.001 PMID:26744779

Air Pressure Responses to Sudden Vocal Tract Pressure Bleeds during Production of Stop Consonants: New Evidence of Aeromechanical Regulation.

ERIC Educational Resources Information Center

Zajac, David J.; Weissler, Mark C.

2004-01-01

Two studies were conducted to evaluate short-latency vocal tract air pressure responses to sudden pressure bleeds during production of voiceless bilabial stop consonants. It was hypothesized that the occurrence of respiratory reflexes would be indicated by distinct patterns of responses as a function of bleed magnitude. In Study 1, 19 adults…

FlpStop, a tool for conditional gene control in Drosophila

PubMed Central

Fisher, Yvette E; Yang, Helen H; Isaacman-Beck, Jesse; Xie, Marjorie; Gohl, Daryl M; Clandinin, Thomas R

2017-01-01

Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cell division. Here we describe FlpStop, a generalizable tool for conditional gene disruption and rescue in post-mitotic cells. In proof-of-principle experiments, we manipulated apterous, a regulator of wing development. Next, we produced conditional null alleles of Glutamic acid decarboxylase 1 (Gad1) and Resistant to dieldrin (Rdl), genes vital for GABAergic neurotransmission, as well as cacophony (cac) and paralytic (para), voltage-gated ion channels central to neuronal excitability. To demonstrate the utility of this approach, we manipulated cac in a specific visual interneuron type and discovered differential regulation of calcium signals across subcellular compartments. Thus, FlpStop will facilitate investigations into the interactions between genes, circuits, and computation. DOI: http://dx.doi.org/10.7554/eLife.22279.001 PMID:28211790

Safety and driver behavior studies at multiple lane approaches to stop-controlled intersections.

DOT National Transportation Integrated Search

2010-05-01

Multiple-lane approaches (MLAs) controlled by stop signs are becoming increasingly common in Nebraska. Installation of MLAs occurs when a single approach lane can no longer adequately serve the minor road traffic volume, and a signal is unwarranted b...

Evaluation of undergraduate geologists' problem solving and cognition during field exams using a mixed methods approach

NASA Astrophysics Data System (ADS)

Balliet, Russell N.

Understanding how geologists conduct fieldwork through analysis of problem solving has significant potential impact on field instruction methods. Recent progress has been made in this area but the problem solving behaviors displayed by geologists during fieldwork and the associated underlying cognition remains poorly understood. We present research showing how geology students initiate and develop geologic models as part of the problem solving process. We qualitatively analyzed field notes and interview data from 36 undergraduate geoscientists engaged in field exams while enrolled in a six-week advanced field camp. Eight cognitive frameworks grouped in two broad categories emerged from the data that show how students develop geologic models. Students employ both single and multiple model approaches with varying degrees of success and frequency. The success of any given approach is dependent on the level of students' geologic situational awareness. The development of multiple geologic models leads to a higher rate of success in general, because of the inherent flexibility to accommodate newly collected data. Instructors should continue to teach a multiple model approach until students have the proper geologic skills to ensure a high level of situational awareness and exhibit expert characteristics in the field. In addition, we collected GPS navigation data from students during these field exams in order to understand the relationship between navigation, cognition, and performance. From the analysis of this data we found that over half of all stops are 1-4 minutes long, while very few of students' stops are longer than 9 minutes as the frequency of stops decreases as the duration increases. Regardless of performance or framework, there is an increase in shorter stops and decrease in longer stops from exam one to three, indicating that students changed the way they investigated as the field course progressed. Temporal signatures categorized by performance only show slight differences, but do indicate that there is an increase in very short and longer stops with declining performance. In contrast, higher performance is linked to an increase in short and medium length stops, suggesting that stops 4-14 minutes long are a "sweet spot" for investigation. We speculate that a high percentage of very short stops involve basic field tasks such as locating or data collection and that the decreasing frequency of long stops indicates that there is a relationship between the length of the stop and the complexity of the activities performed during that stop. Students increased experience leads to more efficient stops as they become more competent with field tasks and more versed in the regional geology. The GPS data we collected from these students while they took these notes allowing us to connect the duration of a stop to the types of notes produced during that stop. Note taking species occurred in various frequencies with the most common type being those that focused on lithologic, or lithologic & structural data collection. Stops that produced geologic models, specifically structural models, were much less frequent. The more frequent data collection stops are very short in length (typically 1-4 minutes), while the more complex stops tend to be longer in duration as the note taking gets more complex. Poor performing students had a high proportion of stops where they only collect lithologic data or stops where they don't generate any hypotheses. In contrast, successful students have more structural data and hypothesis generation in their notes. From this analysis we conclude that too much effort spent on stops with only basic data collection leaves less time for the cognitive effort required for model development, eventually leading to poor exam performance. Specifically, a higher frequency of lithologic data stops and lack of structural data leads to the development of incomplete geologic models or lack of comprehensive models altogether. Field instructors often educate their students on good note taking practices and critique the content of their students' field notebooks, and these findings can inform the content of that critique. Students' utilize many different problem solving approaches in the field, but we suggest that instructors continue to advocate a multiple model approach until students are capable of using a single model approach. In this approach students should decrease the number of geologic models they are using as the day progresses to avoid overwhelming themselves with data and hypothesis. Furthermore, field instructors need to work with students on developing their geologic investigation skills further and improving their efficiency. Specifically students need to collect a higher proportion of structural data and develop complete geologic models earlier in the day. (Abstract shortened by UMI.)

Drosophila Short stop as a paradigm for the role and regulation of spectraplakins.

PubMed

Voelzmann, André; Liew, Yu-Ting; Qu, Yue; Hahn, Ines; Melero, Cristina; Sánchez-Soriano, Natalia; Prokop, Andreas

2017-09-01

Spectraplakins are evolutionarily well conserved cytoskeletal linker molecules that are true members of three protein families: plakins, spectrins and Gas2-like proteins. Spectraplakin genes encode at least 7 characteristic functional domains which are combined in a modular fashion into multiple isoforms, and which are responsible for an enormous breadth of cellular functions. These functions are related to the regulation of actin, microtubules, intermediate filaments, intracellular organelles, cell adhesions and signalling processes during the development and maintenance of a wide variety of tissues. To gain a deeper understanding of this enormous functional diversity, invertebrate genetic model organisms, such as the fruit fly Drosophila, can be used to develop concepts and mechanistic paradigms that can inform the investigation in higher animals or humans. Here we provide a comprehensive overview of our current knowledge of the Drosophila spectraplakin Short stop (Shot). We describe its functional domains and isoforms and compare them with those of the mammalian spectraplakins dystonin and MACF1. We then summarise its roles during the development and maintenance of the nervous system, epithelia, oocytes and muscles, taking care to compare and contrast mechanistic insights across these functions in the fly, but especially also with related functions of dystonin and MACF1 in mostly mammalian contexts. We hope that this review will improve the wider appreciation of how work on Drosophila Shot can be used as an efficient strategy to promote the fundamental concepts and mechanisms that underpin spectraplakin functions, with important implications for biomedical research into human disease. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Conforming STOP Violence Against Women Formula Grant Program Regulations to Statutory Change; Definitions and Confidentiality Requirements Applicable to All OVW Grant Programs. Final rule.

PubMed

2016-11-29

This rule amends the regulations for the STOP (ServicesTrainingOfficersProsecutors) Violence Against Women Formula Grant Program (STOP Program) and the general provisions governing Office on Violence Against Women (OVW) programs to comply with statutory changes and reduce repetition of statutory language. Also, this rule implements statutory requirements for nondisclosure of confidential or private information relating to all OVW grant programs.

29 CFR 1926.1418 - Authority to stop operation.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 29 Labor 8 2011-07-01 2011-07-01 false Authority to stop operation. 1926.1418 Section 1926.1418 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Cranes and Derricks in...

48 CFR 52.242-15 - Stop-Work Order.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 2 2010-10-01 2010-10-01 false Stop-Work Order. 52.242-15... Stop-Work Order. As prescribed in 42.1305(b), insert the following clause. The 90-day period stated in the clause may be reduced to less than 90 days. Stop-Work Order (AUG 1989) (a) The Contracting Officer...

48 CFR 52.242-15 - Stop-Work Order.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 2 2011-10-01 2011-10-01 false Stop-Work Order. 52.242-15... Stop-Work Order. As prescribed in 42.1305(b), insert the following clause. The 90-day period stated in the clause may be reduced to less than 90 days. Stop-Work Order (AUG 1989) (a) The Contracting Officer...

Target-responsive DNA hydrogel mediated "stop-flow" microfluidic paper-based analytic device for rapid, portable and visual detection of multiple targets.

PubMed

Wei, Xiaofeng; Tian, Tian; Jia, Shasha; Zhu, Zhi; Ma, Yanli; Sun, Jianjun; Lin, Zhenyu; Yang, Chaoyong James

2015-04-21

A versatile point-of-care assay platform was developed for simultaneous detection of multiple targets based on a microfluidic paper-based analytic device (μPAD) using a target-responsive hydrogel to mediate fluidic flow and signal readout. An aptamer-cross-linked hydrogel was used as a target-responsive flow regulator in the μPAD. In the absence of a target, the hydrogel is formed in the flow channel, stopping the flow in the μPAD and preventing the colored indicator from traveling to the final observation spot, thus yielding a "signal off" readout. In contrast, in the presence of a target, no hydrogel is formed because of the preferential interaction of target and aptamer. This allows free fluidic flow in the μPAD, carrying the indicator to the observation spot and producing a "signal on" readout. The device is inexpensive to fabricate, easy to use, and disposable after detection. Testing results can be obtained within 6 min by the naked eye via a simple loading operation without the need for any auxiliary equipment. Multiple targets, including cocaine, adenosine, and Pb(2+), can be detected simultaneously, even in complex biological matrices such as urine. The reported method offers simple, low cost, rapid, user-friendly, point-of-care testing, which will be useful in many applications.

Contraction Options and Optimal Multiple-Stopping in Spectrally Negative Lévy Models

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

Yamazaki, Kazutoshi, E-mail: kyamazak@kansai-u.ac.jp

This paper studies the optimal multiple-stopping problem arising in the context of the timing option to withdraw from a project in stages. The profits are driven by a general spectrally negative Lévy process. This allows the model to incorporate sudden declines of the project values, generalizing greatly the classical geometric Brownian motion model. We solve the one-stage case as well as the extension to the multiple-stage case. The optimal stopping times are of threshold-type and the value function admits an expression in terms of the scale function. A series of numerical experiments are conducted to verify the optimality and tomore » evaluate the efficiency of the algorithm.« less

Measured values of coal mine stopping resistance

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

Oswald, N.; Prosser, B.; Ruckman, R.

2008-12-15

As coal mines become larger, the number of stoppings in the ventilation system increases. Each stopping represents a potential leakage path which must be adequately represented in the ventilation model. Stopping resistance can be calculated using two methods, the USBM method, used to determine a resistance for a single stopping, and the MVS technique, in which an average resistance is calculated for multiple stoppings. Through MVS data collected from ventilation surveys of different subsurface coal mines, average resistances for stoppings were determined for stopping in poor, average, good, and excellent conditions. The calculated average stoppings resistance were determined for concretemore » block and Kennedy stopping. Using the average stopping resistance, measured and calculated using the MVS method, provides a ventilation modeling tool which can be used to construct more accurate and useful ventilation models. 3 refs., 3 figs.« less

An insulin resistance associated neural correlate of impulsivity in type 2 diabetes mellitus

PubMed Central

Eckstrand, Kristen L.; Mummareddy, Nishit; Kang, Hakmook; Cowan, Ronald; Zhou, Minchun; Zald, David; Silver, Heidi J.; Niswender, Kevin D.; Avison, Malcolm J.

2017-01-01

Central insulin resistance (IR) influences striatal dopamine (DA) tone, an important determinant of behavioral self-regulation. We hypothesized that an association exists between the degree of peripheral IR and impulse control, mediated by the impact of IR on brain circuits controlling the speed of executing “go” and/or “stop” responses. We measured brain activation and associated performance on a stop signal task (SST) in obese adults with type 2 diabetes (age, 48.1 ± 6.9 yrs (mean ± SD); BMI, 36.5 ± 4.0 kg/m2; HOMA-IR, 7.2 ± 4.1; 12 male, 18 female). Increasing IR, but not BMI, was a predictor of shorter critical stop signal delay (cSSD), a measure of the time window during which a go response can be successfully countermanded (R2 = 0.12). This decline was explained by an IR-associated increase in go speed (R2 = 0.13) with little impact of IR or BMI on stop speed. Greater striatal fMRI activation contrast in stop error (SE) compared with stop success (SS) trials (CONSE>SS) was a significant predictor of faster go speeds (R2 = 0.33, p = 0.002), and was itself predicted by greater IR (CONSE>SS vs HOMA-IR: R2 = 0.10, p = 0.04). Furthermore, this impact of IR on striatal activation was a significant mediator of the faster go speeds and greater impulsivity observed with greater IR. These findings suggest a neural mechanism by which IR may increase impulsivity and degrade behavioral self-regulation. PMID:29228027

Determinants of aggressive behavior: Interactive effects of emotional regulation and inhibitory control.

PubMed

Hsieh, I-Ju; Chen, Yung Y

2017-01-01

Aggressive behavior can be defined as any behavior intended to hurt another person, and it is associated with many individual and social factors. This study examined the relationship between emotional regulation and inhibitory control in predicting aggressive behavior. Seventy-eight participants (40 males) completed self-report measures (Negative Mood Regulation Scale and Buss-Perry Aggression Questionnaire), a stop signal task, and engaged in a modified version of Taylor Aggression Paradigm (TAP) exercise, in which the outcome was used as a measure of direct physical aggression. We used a hierarchical, mixed-model multiple regression analysis test to examine the effects of emotion regulation and inhibitory control on physical reactive aggression. Results indicated an interaction between emotion regulation and inhibitory control on aggression. For participants with low inhibitory control only, there was a significant difference between high and low emotion regulation on aggression, such that low emotion regulation participants registered higher aggression than high emotion regulation participants. This difference was not found among participants with high inhibitory control. These results have implications for refining and targeting training and rehabilitation programs aimed at reducing aggressive behavior.

Dominant-negative TLR5 polymorphism reduces adaptive immune response to flagellin and negatively associates with Crohn's disease.

PubMed

Gewirtz, Andrew T; Vijay-Kumar, Matam; Brant, Steven R; Duerr, Richard H; Nicolae, Dan L; Cho, Judy H

2006-06-01

Crohn's disease (CD) is associated with elevated adaptive immunity to commensal microbes, with flagellin being a dominant antigen. In light of heightened awareness of the importance of innate immunity in regulating adaptive immunity and ambiguity as to the role of CD-associated immune responses in CD pathophysiology, we sought to determine whether natural acquisition of immune responses to flagellin were regulated by the innate immune flagellin receptor toll-like receptor 5 (TLR5) and determine whether persons carrying a recently defined common dominant-negative TLR5 polymorphism (TLR5-stop) might be protected from developing CD. Carriage rates of a recently defined dominant-negative TLR5 polymorphism (TLR5-stop) and levels of serum immunoreactivity to bacterial products were measured in inflammatory bowel disease patients, first-degree relatives, and unrelated controls. We observed that, in healthy subjects, persons carrying TLR5-stop had significantly lower levels of flagellin-specific IgG and IgA but had similar levels of total and LPS-specific Ig. Moreover, we observed that, among Jewish subjects, the carriage rate of TLR5-stop (in heterozygous state) was significantly less in CD patients, but not ulcerative colitis (UC) patients, compared with unaffected relatives and unrelated controls (5.4, 0.9, 6.0, and 6.5% for unaffected relatives, CD, UC, and unrelated Jewish controls, respectively, n = 296, 215, 185, and 416, respectively; P = 0.037 by likelihood calculation for CD vs. controls), indicating that TLR5-stop can protect persons of Jewish ethnicity against CD. We did not observe a significant association of TLR5-stop with CD in a non-Jewish cohort (11.1, 10.4, and 11.7% for unaffected relatives, CD, and UC, respectively; n = 841, 543, and 300 for unaffected relatives, respectively). These results demonstrate that natural acquisition of immune responses to flagellin are regulated by TLR5 and suggest that immune responses to flagellin are not merely associated with CD but rather promote the pathogenic response.

Ribosome profiling reveals pervasive and regulated stop codon readthrough in Drosophila melanogaster

PubMed Central

Dunn, Joshua G; Foo, Catherine K; Belletier, Nicolette G; Gavis, Elizabeth R; Weissman, Jonathan S

2013-01-01

Ribosomes can read through stop codons in a regulated manner, elongating rather than terminating the nascent peptide. Stop codon readthrough is essential to diverse viruses, and phylogenetically predicted to occur in a few hundred genes in Drosophila melanogaster, but the importance of regulated readthrough in eukaryotes remains largely unexplored. Here, we present a ribosome profiling assay (deep sequencing of ribosome-protected mRNA fragments) for Drosophila melanogaster, and provide the first genome-wide experimental analysis of readthrough. Readthrough is far more pervasive than expected: the vast majority of readthrough events evolved within D. melanogaster and were not predicted phylogenetically. The resulting C-terminal protein extensions show evidence of selection, contain functional subcellular localization signals, and their readthrough is regulated, arguing for their importance. We further demonstrate that readthrough occurs in yeast and humans. Readthrough thus provides general mechanisms both to regulate gene expression and function, and to add plasticity to the proteome during evolution. DOI: http://dx.doi.org/10.7554/eLife.01179.001 PMID:24302569

Semantic integration of data on transcriptional regulation

PubMed Central

Baitaluk, Michael; Ponomarenko, Julia

2010-01-01

Motivation: Experimental and predicted data concerning gene transcriptional regulation are distributed among many heterogeneous sources. However, there are no resources to integrate these data automatically or to provide a ‘one-stop shop’ experience for users seeking information essential for deciphering and modeling gene regulatory networks. Results: IntegromeDB, a semantic graph-based ‘deep-web’ data integration system that automatically captures, integrates and manages publicly available data concerning transcriptional regulation, as well as other relevant biological information, is proposed in this article. The problems associated with data integration are addressed by ontology-driven data mapping, multiple data annotation and heterogeneous data querying, also enabling integration of the user's data. IntegromeDB integrates over 100 experimental and computational data sources relating to genomics, transcriptomics, genetics, and functional and interaction data concerning gene transcriptional regulation in eukaryotes and prokaryotes. Availability: IntegromeDB is accessible through the integrated research environment BiologicalNetworks at http://www.BiologicalNetworks.org Contact: baitaluk@sdsc.edu Supplementary information: Supplementary data are available at Bioinformatics online. PMID:20427517

Semantic integration of data on transcriptional regulation.

PubMed

Baitaluk, Michael; Ponomarenko, Julia

2010-07-01

Experimental and predicted data concerning gene transcriptional regulation are distributed among many heterogeneous sources. However, there are no resources to integrate these data automatically or to provide a 'one-stop shop' experience for users seeking information essential for deciphering and modeling gene regulatory networks. IntegromeDB, a semantic graph-based 'deep-web' data integration system that automatically captures, integrates and manages publicly available data concerning transcriptional regulation, as well as other relevant biological information, is proposed in this article. The problems associated with data integration are addressed by ontology-driven data mapping, multiple data annotation and heterogeneous data querying, also enabling integration of the user's data. IntegromeDB integrates over 100 experimental and computational data sources relating to genomics, transcriptomics, genetics, and functional and interaction data concerning gene transcriptional regulation in eukaryotes and prokaryotes. IntegromeDB is accessible through the integrated research environment BiologicalNetworks at http://www.BiologicalNetworks.org baitaluk@sdsc.edu Supplementary data are available at Bioinformatics online.

Familial cancer associated with a polymorphism in ARLTS1.

PubMed

Calin, George Adrian; Trapasso, Francesco; Shimizu, Masayoshi; Dumitru, Calin Dan; Yendamuri, Sai; Godwin, Andrew K; Ferracin, Manuela; Bernardi, Guido; Chatterjee, Devjani; Baldassarre, Gustavo; Rattan, Shashi; Alder, Hansjuerg; Mabuchi, Hideaki; Shiraishi, Takeshi; Hansen, Lise Lotte; Overgaard, Jens; Herlea, Vlad; Mauro, Francesca Romana; Dighiero, Guillaume; Movsas, Benjamin; Rassenti, Laura; Kipps, Thomas; Baffa, Raffaele; Fusco, Alfredo; Mori, Masaki; Russo, Giandomenico; Liu, Chang-Gong; Neuberg, Donna; Bullrich, Florencia; Negrini, Massimo; Croce, Carlo M

2005-04-21

The finding of hemizygous or homozygous deletions at band 14 on chromosome 13 in a variety of neoplasms suggests the presence of a tumor-suppressor locus telomeric to the RB1 gene. We studied samples from 216 patients with various types of sporadic tumors or idiopathic pancytopenia, peripheral-blood samples from 109 patients with familial cancer or multiple cancers, and control blood samples from 475 healthy people or patients with diseases other than cancer. We performed functional studies of cell lines lacking ARLTS1 expression with the use of both the full-length ARLTS1 gene and a truncated variant. We found a gene at 13q14, ARLTS1, a member of the ADP-ribosylation factor family, with properties of a tumor-suppressor gene. We analyzed 800 DNA samples from tumors and blood cells from patients with sporadic or familial cancer and controls and found that the frequency of a nonsense polymorphism, G446A (Trp149Stop), was similar in controls and patients with sporadic tumors but was significantly more common among patients with familial cancer than among those in the other two groups (P=0.02; odds ratio, 5.7; 95 percent confidence interval, 1.3 to 24.8). ARLTS1 was down-regulated by promoter methylation in 25 percent of the primary tumors we analyzed. Transfection of wild-type ARLTS1 into A549 lung-cancer cells suppressed tumor formation in immunodeficient mice and induced apoptosis, whereas transfection of truncated ARLTS1 had a limited effect on apoptosis and tumor suppression. Microarray analysis revealed that the wild-type and Trp149Stop-transfected clones had different expression profiles. A genetic variant of ARLTS1 predisposes patients to familial cancer. Copyright 2005 Massachusetts Medical Society.

76 FR 8365 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Comment...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-14

... ID number EPA-HQ- OECA-2010-0357, to (1) EPA online using www.regulations.gov (our preferred method... leaking equipment, repair methods used to stop the leaks, and dates of repair. The time period for this... correction of a mathematical error. There are no annual capital and O&M costs to the regulated entities...

49 CFR 236.511 - Cab signals controlled in accordance with block conditions stopping distance in advance.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Cab signals controlled in accordance with block conditions stopping distance in advance. 236.511 Section 236.511 Transportation Other Regulations Relating to... § 236.511 Cab signals controlled in accordance with block conditions stopping distance in advance. The...

Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma

ERIC Educational Resources Information Center

Prevost, Luanna B.; Smith, Michelle K.; Knight, Jennifer K.

2016-01-01

Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon…

One Stop Post Op cardiac surgery recovery--a proven success.

PubMed

Joyce, L; Pandolph, P

2001-01-01

The One Stop Post Op model for open heart surgery recovery is an innovative approach to post op care utilized in only a few facilities in the country. This model calls for an integration of acute ICU and step-down phases of care, thus changing the paradigm for nursing care of the open heart surgery patient. Typically, hospitals incur inefficiencies transferring the patient through multiple levels of care, thus resulting in a "disconnect" as new caregivers relearn the patient's care requirements and special needs. The construction of a "one stop" unit allows the patient to remain stationary while the service level changes to accommodate changing care needs. The cardiac "one stop" model is similar to the LDRP concept for obstetrical care. The One Stop Post Op patient rooms are designed to accommodate every level of patient acuity. All rooms meet the regulations for critical care room design, however this is where the aesthetic similarity ends. The patient environment looks more like hotel rooms rather than the traditional ICU setting. Cabinets designed to cover medical gases, in the room's private bathrooms and comfortable furnishings help to create a patient focused environment conducive to recovery. This model has been utilized by several facilities and has demonstrated clear clinical and economic advantages for patients, families, and health care providers. Implementing an open heart surgery (OHS) program presents the opportunity for several community based hospitals to challenge the way they have been providing patient care and establish an innovative approach to post surgery patient care. The One Stop Post Op cardiovascular recovery unit is designed to receive the OHS patient directly from the operating room and to be the "care unit" for the patient's entire stay. Patient flow, quality monitoring and caregiver acceptance in this unit requires new paradigms from the traditional two or three step post OHS care delivery process. The One Stop Post Op model focuses the delivery of care on the patient. With proven success in clinical outcomes, patient, physician and caregiver satisfaction, it is anticipated that this innovative approach will drive hospitals to integrate clinical process with physical planning in the future.

Keep at bay!--Abnormal personal space regulation as marker of paranoia in schizophrenia.

PubMed

Schoretsanitis, G; Kutynia, A; Stegmayer, K; Strik, W; Walther, S

2016-01-01

During threat, interpersonal distance is deliberately increased. Personal space regulation is related to amygdala function and altered in schizophrenia, but it remains unknown whether it is particularly associated with paranoid threat. We compared performance in two tests on personal space between 64 patients with schizophrenia spectrum disorders and 24 matched controls. Patients were stratified in those with paranoid threat, neutral affect or paranoid experience of power. In the stop-distance paradigm, participants indicated the minimum tolerable interpersonal distance. In the fixed-distance paradigm, they indicated the level of comfort at fixed interpersonal distances. Paranoid threat increased interpersonal distance two-fold in the stop-distance paradigm, and reduced comfort ratings in the fixed-distance paradigm. In contrast, patients experiencing paranoid power had high comfort ratings at any distance. Patients with neutral affect did not differ from controls in the stop-distance paradigm. Differences between groups remained when controlling for gender and positive symptom severity. Among schizophrenia patients, the stop-distance paradigm detected paranoid threat with 93% sensitivity and 83% specificity. Personal space regulation is not generally altered in schizophrenia. However, state paranoid experience has distinct contributions to personal space regulation. Subjects experiencing current paranoid threat share increased safety-seeking behavior. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

More cops more stops: evaluation of a combined HVE program in Oklahoma and Tennessee.

DOT National Transportation Integrated Search

2016-10-01

The More Cops More Stops (MCMS) high-visibility enforcement program was designed to address multiple traffic safety : issues with one message and program effort. Impaired driving, seat belt, and speeding enforcement were conducted and : advertised us...

Safety, operational, and energy impacts of in-vehicle adaptive stop displays using connected vehicle technology.

DOT National Transportation Integrated Search

2015-07-01

Un-signalized intersections create multiple opportunities for missed or misunderstood information. : Stop sign-controlled intersections have also been shown to be a source of delay and emissions due : to their frequent, often inappropriate use. By us...

More cops more stops: evaluation of a combined HVE program in Oklahoma and Tennessee : traffic tech.

DOT National Transportation Integrated Search

2016-10-01

More Cops More Stops (MCMS) was a high-visibility enforcement : (HVE) program designed to address multiple traffic : safety issues with one message and programmatic : effort. Law enforcement agencies (LEAs) in Oklahoma and : Tennessee conducted heigh...

The actin-microtubule cross-linking activity of Drosophila Short stop is regulated by intramolecular inhibition

PubMed Central

Applewhite, Derek A.; Grode, Kyle D.; Duncan, Mara C.; Rogers, Stephen L.

2013-01-01

Actin and microtubule dynamics must be precisely coordinated during cell migration, mitosis, and morphogenesis—much of this coordination is mediated by proteins that physically bridge the two cytoskeletal networks. We have investigated the regulation of the Drosophila actin-microtubule cross-linker Short stop (Shot), a member of the spectraplakin family. Our data suggest that Shot's cytoskeletal cross-linking activity is regulated by an intramolecular inhibitory mechanism. In its inactive conformation, Shot adopts a “closed” conformation through interactions between its NH2-terminal actin-binding domain and COOH-terminal EF-hand-GAS2 domain. This inactive conformation is targeted to the growing microtubule plus end by EB1. On activation, Shot binds along the microtubule through its COOH-terminal GAS2 domain and binds to actin with its NH2-terminal tandem CH domains. We propose that this mechanism allows Shot to rapidly cross-link dynamic microtubules in response to localized activating signals at the cell cortex. PMID:23885120

Inverse agonist abolishes desensitization of a constitutively active mutant of thyrotropin-releasing hormone receptor: role of cellular calcium and protein kinase C

PubMed Central

Grimberg, Hagit; Zaltsman, Ilona; Lupu-Meiri, Monica; Gershengorn, Marvin C; Oron, Yoram

1999-01-01

C335Stop is a constitutively active mutant of the TRH receptor (TRH-R). To investigate the mechanism of the decreased responsiveness of C335Stop TRH-R, we studied cellular Ca2+ concentrations ([Ca2+]i) in AtT20 cells stably transfected with C335Stop TRH-R cDNA, or Ca2+-activated chloride currents in Xenopus laevis oocytes expressing this mutant receptor after injection of cRNA. The competitive TRH-R binding antagonist, chlorodiazepoxide (CDE), was used as an inverse agonist to study the contribution of constitutive activity to desensitization. Acute treatment with CDE resulted in a rapid (within minutes) decrease in [Ca2+]i and an increase in the response amplitude to TRH with no measurable change in receptor density. Conversely, removal of chronically administered CDE caused a rapid increase in [Ca2+]i and a decrease in TRH response amplitude. CDE abolished heterologous desensitization induced by C335Stop TRH-R on muscarinic m1-receptor (m1-R) co-expressed in Xenopus oocytes. Chelation of extracellular calcium with EGTA caused a rapid decrease in [Ca2+]i and a concomitant increase in the response to TRH in AtT20 cells expressing C335Stop TRH-Rs. Chelerythrine, a specific inhibitor of protein kinase C (PKC), reversed the heterologous desensitization of the response to acetylcholine (ACh). The phosphoserine/phosphothreonine phosphatase inhibitor, okadaic acid, abolished the effect of chelerythrine. Down-regulation of PKC by chronic exposure to phorbol 12-myristate 13-acetate (PMA) or acute inhibition with chelerythrine caused a partial resensitization of the response to TRH. Western analysis indicated that the α subtype of protein kinase C was down-regulated in cells expressing C335Stop TRH-Rs. Following a 5 min exposure to PMA, the residual αPKC translocated to the particular fraction. We propose that cells expressing the constitutively active mutant TRH-R rapidly desensitize their response, utilizing a mechanism mediated by an increase in [Ca2+]i and PKC. PMID:10204996

Particle Identification in Nuclear Emulsion by Measuring Multiple Coulomb Scattering

NASA Astrophysics Data System (ADS)

Than Tint, Khin; Nakazawa, Kazuma; Yoshida, Junya; Kyaw Soe, Myint; Mishina, Akihiro; Kinbara, Shinji; Itoh, Hiroki; Endo, Yoko; Kobayashi, Hidetaka; E07 Collaboration

2014-09-01

We are developing particle identification techniques for single charged particles such as Xi, proton, K and π by measuring multiple Coulomb scattering in nuclear emulsion. Nuclear emulsion is the best three dimensional detector for double strangeness (S = -2) nuclear system. We expect to accumulate about 10000 Xi-minus stop events which produce double lambda hypernucleus in J-PARC E07 emulsion counter hybrid experiment. The purpose of this particle identification (PID) in nuclear emulsion is to purify Xi-minus stop events which gives information about production probability of double hypernucleus and branching ratio of decay mode. Amount of scattering parameterized as angular distribution and second difference is inversely proportional to the momentum of particle. We produced several thousands of various charged particle tracks in nuclear emulsion stack via Geant4 simulation. In this talk, PID with some measuring methods for multiple scattering will be discussed by comparing with simulation data and real Xi-minus stop events in KEK-E373 experiment.

We know how to prescribe natalizumab for multiple sclerosis, but do we know how to withdraw it?

PubMed

Fragoso, Yara D; Arruda, Niedja M; Arruda, Walter O; Brooks, Joseph B B; Correa, Eber C; Damasceno, Alfredo; Damasceno, Carlos A; Ferreira, Maria L B; Giacomo, Maria C B; Gomes, Sidney; Gonçalves, Marcus V M; Grzesiuk, Anderson K; Kaimen-Maciel, Damacio R; Lopes, Josiane; Machado, Suzana C N; Oliveira, Celso L S; Stella, Carla R A V

2014-02-01

Natalizumab is a potent immunosuppressive monoclonal antibody used for the treatment of multiple sclerosis (MS). While definite guidelines for the safety of natalizumab prescriptions are available in all countries, there are no specific recommendations on how to withdraw the drug if the need arises. There are reports describing MS complications after natalizumab infusions were stopped. Most neurologists seem to stop natalizumab treatment according to their idea on how to best carry out the withdrawal. The present study shows the very different manners in which expert neurologists from 14 MS units in Brazil stopped natalizumab in their patients. The authors concluded that pharmacovigilance on natalizumab must persist after the drug is withdrawn in order to have enough data for adequate recommendations.

Design and Analysis of a Triple Stop-band Filter Using Ratioed Periodical Defected Microstrip Structure

NASA Astrophysics Data System (ADS)

Jiang, Tao; Wang, Yanyan; Li, Yingsong

2017-07-01

In this paper, a triple stop-band filter with a ratioed periodical defected microstrip structure is proposed for wireless communication applications. The proposed ratioed periodical defected microstrip structures are spiral slots, which are embedded into a 50 Ω microstrip line to obtain multiple stop-bands. The performance of the proposed triple stop-band filter is investigated numerically and experimentally. Moreover, the equivalent circuit model of the proposed filter is also established and discussed. The results are given to verify that the proposed triple stop-band filter has three stop bands at 3.3 GHz, 5.2 GHz, 6.8 GHz to reject the unwanted signals, which is promising for integrating into UWB communication systems to efficiently prevent the potential interferences from unexpected narrowband signals such as WiMAX, WLAN and RFID communication systems.

Negative and Translation Termination-Dependent Positive Control of FLI-1 Protein Synthesis by Conserved Overlapping 5′ Upstream Open Reading Frames in Fli-1 mRNA

PubMed Central

Sarrazin, Sandrine; Starck, Joëlle; Gonnet, Colette; Doubeikovski, Alexandre; Melet, Fabrice; Morle, François

2000-01-01

The proto-oncogene Fli-1 encodes a transcription factor of the ets family whose overexpression is associated with multiple virally induced leukemias in mouse, inhibits murine and avian erythroid cell differentiation, and induces drastic perturbations of early development in Xenopus. This study demonstrates the surprisingly sophisticated regulation of Fli-1 mRNA translation. We establish that two FLI-1 protein isoforms (of 51 and 48 kDa) detected by Western blotting in vivo are synthesized by alternative translation initiation through the use of two highly conserved in-frame initiation codons, AUG +1 and AUG +100. Furthermore, we show that the synthesis of these two FLI-1 isoforms is regulated by two short overlapping 5′ upstream open reading frames (uORF) beginning at two highly conserved upstream initiation codons, AUG −41 and GUG −37, and terminating at two highly conserved stop codons, UGA +35 and UAA +15. The mutational analysis of these two 5′ uORF revealed that each of them negatively regulates FLI-1 protein synthesis by precluding cap-dependent scanning to the 48- and 51-kDa AUG codons. Simultaneously, the translation termination of the two 5′ uORF appears to enhance 48-kDa protein synthesis, by allowing downstream reinitiation at the 48-kDa AUG codon, and 51-kDa protein synthesis, by allowing scanning ribosomes to pile up and consequently allowing upstream initiation at the 51-kDa AUG codon. To our knowledge, this is the first example of a cellular mRNA displaying overlapping 5′ uORF whose translation termination appears to be involved in the positive control of translation initiation at both downstream and upstream initiation codons. PMID:10757781

40 CFR 205.174 - Remedial orders.

Code of Federal Regulations, 2012 CFR

2012-07-01

... not in compliance with the regulations of this subpart. Potential orders are stop sale orders, orders... Noise Emission Test Procedures Appendix I-1 to Subparts D and E—Test Procedure for Street and off-road Motorcycles (a) Instrumentation. Proper usage of all test instrumentation is essential to obtain valid...

40 CFR 205.174 - Remedial orders.

Code of Federal Regulations, 2011 CFR

2011-07-01

... not in compliance with the regulations of this subpart. Potential orders are stop sale orders, orders... Noise Emission Test Procedures Appendix I-1 to Subparts D and E—Test Procedure for Street and off-road Motorcycles (a) Instrumentation. Proper usage of all test instrumentation is essential to obtain valid...

40 CFR 205.174 - Remedial orders.

Code of Federal Regulations, 2013 CFR

2013-07-01

... not in compliance with the regulations of this subpart. Potential orders are stop sale orders, orders... Noise Emission Test Procedures Appendix I-1 to Subparts D and E—Test Procedure for Street and off-road Motorcycles (a) Instrumentation. Proper usage of all test instrumentation is essential to obtain valid...

New signatures and limits on R-parity violation from resonant squark production

DOE PAGES

Monteux, Angelo

2016-03-31

Here, we discuss resonant squark production at the LHC via baryonic R-parity violating interactions. The cross section easily exceeds pair-production and a new set of signatures can be used to probe squarks, particularly stops. These include dijet resonances, same-sign top quarks and four-jet resonances with large b-jet multiplicities, as well as the possibility of displaced neutralino decays. We use publicly available searches at √s = 8 TeV and first results from collisions at √s = 13 TeV to set upper limits on R-parity violating couplings, with particular focus on simplified models with light stops and neutralinos. The exclusion reach ofmore » these signatures is comparable to R-parity-conserving searches, m t ~ ≃ 500–700 GeV. In addition, we find that O(1) couplings involving the stop can be excluded well into the multi-TeV range, and stress that new searches for single- and pair-produced four-jet resonances will be necessary to exclude sub-TeV stops for a natural SUSY spectrum with light higgsinos.« less

A Stem-Loop Structure in Potato Leafroll Virus Open Reading Frame 5 (ORF5) Is Essential for Readthrough Translation of the Coat Protein ORF Stop Codon 700 Bases Upstream.

PubMed

Xu, Yi; Ju, Ho-Jong; DeBlasio, Stacy; Carino, Elizabeth J; Johnson, Richard; MacCoss, Michael J; Heck, Michelle; Miller, W Allen; Gray, Stewart M

2018-06-01

Translational readthrough of the stop codon of the capsid protein (CP) open reading frame (ORF) is used by members of the Luteoviridae to produce their minor capsid protein as a readthrough protein (RTP). The elements regulating RTP expression are not well understood, but they involve long-distance interactions between RNA domains. Using high-resolution mass spectrometry, glutamine and tyrosine were identified as the primary amino acids inserted at the stop codon of Potato leafroll virus (PLRV) CP ORF. We characterized the contributions of a cytidine-rich domain immediately downstream and a branched stem-loop structure 600 to 700 nucleotides downstream of the CP stop codon. Mutations predicted to disrupt and restore the base of the distal stem-loop structure prevented and restored stop codon readthrough. Motifs in the downstream readthrough element (DRTE) are predicted to base pair to a site within 27 nucleotides (nt) of the CP ORF stop codon. Consistent with a requirement for this base pairing, the DRTE of Cereal yellow dwarf virus was not compatible with the stop codon-proximal element of PLRV in facilitating readthrough. Moreover, deletion of the complementary tract of bases from the stop codon-proximal region or the DRTE of PLRV prevented readthrough. In contrast, the distance and sequence composition between the two domains was flexible. Mutants deficient in RTP translation moved long distances in plants, but fewer infection foci developed in systemically infected leaves. Selective 2'-hydroxyl acylation and primer extension (SHAPE) probing to determine the secondary structure of the mutant DRTEs revealed that the functional mutants were more likely to have bases accessible for long-distance base pairing than the nonfunctional mutants. This study reveals a heretofore unknown combination of RNA structure and sequence that reduces stop codon efficiency, allowing translation of a key viral protein. IMPORTANCE Programmed stop codon readthrough is used by many animal and plant viruses to produce key viral proteins. Moreover, such "leaky" stop codons are used in host mRNAs or can arise from mutations that cause genetic disease. Thus, it is important to understand the mechanism(s) of stop codon readthrough. Here, we shed light on the mechanism of readthrough of the stop codon of the coat protein ORFs of viruses in the Luteoviridae by identifying the amino acids inserted at the stop codon and RNA structures that facilitate this "leakiness" of the stop codon. Members of the Luteoviridae encode a C-terminal extension to the capsid protein known as the readthrough protein (RTP). We characterized two RNA domains in Potato leafroll virus (PLRV), located 600 to 700 nucleotides apart, that are essential for efficient RTP translation. We further determined that the PLRV readthrough process involves both local structures and long-range RNA-RNA interactions. Genetic manipulation of the RNA structure altered the ability of PLRV to translate RTP and systemically infect the plant. This demonstrates that plant virus RNA contains multiple layers of information beyond the primary sequence and extends our understanding of stop codon readthrough. Strategic targets that can be exploited to disrupt the virus life cycle and reduce its ability to move within and between plant hosts were revealed. Copyright © 2018 American Society for Microbiology.

Dual-scale topology optoelectronic processor.

PubMed

Marsden, G C; Krishnamoorthy, A V; Esener, S C; Lee, S H

1991-12-15

The dual-scale topology optoelectronic processor (D-STOP) is a parallel optoelectronic architecture for matrix algebraic processing. The architecture can be used for matrix-vector multiplication and two types of vector outer product. The computations are performed electronically, which allows multiplication and summation concepts in linear algebra to be generalized to various nonlinear or symbolic operations. This generalization permits the application of D-STOP to many computational problems. The architecture uses a minimum number of optical transmitters, which thereby reduces fabrication requirements while maintaining area-efficient electronics. The necessary optical interconnections are space invariant, minimizing space-bandwidth requirements.

Multiple-vehicle collision induced by a sudden stop in traffic flow

NASA Astrophysics Data System (ADS)

Sugiyama, Naoki; Nagatani, Takashi

2012-04-01

We study the dynamic process of the multiple-vehicle collision when a vehicle stops suddenly in a traffic flow. We apply the optimal-velocity model to the vehicular motion. If a vehicle does not decelerate successfully, it crashes into the vehicle ahead with a residual speed. The collision criterion is presented by vi(t)/Δxi(t)→∞ if Δxi(t)→0 where vi(t) and Δxi(t) are the speed and headway of vehicle i at time t. The number of crumpled vehicles depends on the initial velocity, the sensitivity, and the initial headway. We derive the region map (or phase diagram) for the multiple-vehicle collision.

Fingolimod

MedlinePlus

... symptoms flare up from time to time) of multiple sclerosis (MS; a disease in which the nerves do ... take your first dose.Fingolimod may help control multiple sclerosis but will not cure it. Do not stop ...

The frequentist implications of optional stopping on Bayesian hypothesis tests.

PubMed

Sanborn, Adam N; Hills, Thomas T

2014-04-01

Null hypothesis significance testing (NHST) is the most commonly used statistical methodology in psychology. The probability of achieving a value as extreme or more extreme than the statistic obtained from the data is evaluated, and if it is low enough, the null hypothesis is rejected. However, because common experimental practice often clashes with the assumptions underlying NHST, these calculated probabilities are often incorrect. Most commonly, experimenters use tests that assume that sample sizes are fixed in advance of data collection but then use the data to determine when to stop; in the limit, experimenters can use data monitoring to guarantee that the null hypothesis will be rejected. Bayesian hypothesis testing (BHT) provides a solution to these ills because the stopping rule used is irrelevant to the calculation of a Bayes factor. In addition, there are strong mathematical guarantees on the frequentist properties of BHT that are comforting for researchers concerned that stopping rules could influence the Bayes factors produced. Here, we show that these guaranteed bounds have limited scope and often do not apply in psychological research. Specifically, we quantitatively demonstrate the impact of optional stopping on the resulting Bayes factors in two common situations: (1) when the truth is a combination of the hypotheses, such as in a heterogeneous population, and (2) when a hypothesis is composite-taking multiple parameter values-such as the alternative hypothesis in a t-test. We found that, for these situations, while the Bayesian interpretation remains correct regardless of the stopping rule used, the choice of stopping rule can, in some situations, greatly increase the chance of experimenters finding evidence in the direction they desire. We suggest ways to control these frequentist implications of stopping rules on BHT.

49 CFR 392.10 - Railroad grade crossings; stopping required.

Code of Federal Regulations, 2010 CFR

2010-10-01

... controlled by a functioning highway traffic signal transmitting a green indication which, under local law... REGULATIONS DRIVING OF COMMERCIAL MOTOR VEHICLES Driving of Commercial Motor Vehicles § 392.10 Railroad grade... commercial motor vehicle specified in paragraphs (a) (1) through (6) of this section shall not cross a...

48 CFR 42.1304 - Government delay of work.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Government delay of work... CONTRACT MANAGEMENT CONTRACT ADMINISTRATION AND AUDIT SERVICES Suspension of Work, Stop-Work Orders, and Government Delay of Work 42.1304 Government delay of work. (a) The clause at 52.242-17, Government Delay of...

Studies on the flight medical aspects of the German Lufthansa non-stop route from Frankfurt to Rio de Janeiro, part 1

NASA Technical Reports Server (NTRS)

Wegmann, H. M.; Klein, K. E.; Goeters, K. M.; Samel, A.

1982-01-01

The problem of crew size for regularly scheduled flights between Frankfurt and Rio de Janeiro is discussed. Factors affecting crew performance are examined, comparisons are drawn to regulations of other countries and crew questionnaires and tests are presented.

Personal Space Regulation in Williams Syndrome: The Effect of Familiarity.

PubMed

Lough, Emma; Flynn, Emma; Riby, Deborah M

2016-10-01

Personal space refers to a protective barrier that we strive to maintain around our body. We examined personal space regulation in young people with Williams syndrome (WS) and their typically developing, chronological age-matched peers using a parent report questionnaire and a stop-distance paradigm. Individuals with WS were reported by their parents to be more likely to violate the personal space of others, and indeed they maintained a shorter interpersonal distance in the stop-distance paradigm. Interestingly, WS individuals failed to regulate their personal space based on the familiarity of the person they were interacting with. Findings are discussed in relation to the wider social profile associated with WS, and the possible impact of atypical personal space regulation on social vulnerability.

Continuing or Temporarily Stopping Prestroke Antihypertensive Medication in Acute Stroke: An Individual Patient Data Meta-Analysis.

PubMed

Woodhouse, Lisa J; Manning, Lisa; Potter, John F; Berge, Eivind; Sprigg, Nikola; Wardlaw, Joanna; Lees, Kennedy R; Bath, Philip M; Robinson, Thompson G

2017-05-01

Over 50% of patients are already taking blood pressure-lowering therapy on hospital admission for acute stroke. An individual patient data meta-analysis from randomized controlled trials was undertaken to determine the effect of continuation versus temporarily stopping preexisting antihypertensive medication in acute stroke. Key databases were searched for trials against the following inclusion criteria: randomized design; stroke onset ≤48 hours; investigating the effect of continuation versus stopping prestroke antihypertensive medication; and follow-up of ≥2 weeks. Two randomized controlled trials were identified and included in this meta-analysis of individual patient data from 2860 patients with ≤48 hours of acute stroke. Risk of bias in each study was low. In adjusted logistic regression and multiple regression analyses (using random effects), we found no significant association between continuation of prestroke antihypertensive therapy (versus stopping) and risk of death or dependency at final follow-up: odds ratio 0.96 (95% confidence interval, 0.80-1.14). No significant associations were found between continuation (versus stopping) of therapy and secondary outcomes at final follow-up. Analyses for death and dependency in prespecified subgroups revealed no significant associations with continuation versus temporarily stopping therapy, with the exception of patients randomized ≤12 hours, in whom a difference favoring stopping treatment met statistical significance. We found no significant benefit with continuation of antihypertensive treatment in the acute stroke period. Therefore, there is no urgency to administer preexisting antihypertensive therapy in the first few hours or days after stroke, unless indicated for other comorbid conditions. © 2017 American Heart Association, Inc.

The Influence of Depression on Cognitive Control: Disambiguating Approach and Avoidance Tendencies.

PubMed

Huang, He; Movellan, Javier; Paulus, Martin P; Harlé, Katia M

2015-01-01

Dysfunctions of approach and avoidance motivation play an important role in depression, which in turn may affect cognitive control, i.e., the ability to regulate thoughts and action to achieve internal goals. We use a novel experimental paradigm, i.e. a computer simulated driving-task, to study the impact of depression on cognitive control by measuring approach and avoidance actions in continuous time. In this task, 39 subjects with minimal to severe depression symptoms were instructed to use a joystick to move a virtual car as quickly as possible to a target point without crossing a stop-sign or crashing into a wall. We recorded their continuous actions on a joystick and found that depression 1) leads to further stopping distance to task target; and 2) increases the magnitude of late deceleration (avoidance) but not early acceleration (approach), which was only observed in the stop-sign condition. Taken together, these results are consistent with the hypothesis that depressed individuals have greater avoidance motivation near stopping target, but are minimally affected by approach motivation.

Note on measuring electronic stopping of slow ions

NASA Astrophysics Data System (ADS)

Sigmund, P.; Schinner, A.

2017-11-01

Extracting stopping cross sections from energy-loss measurements requires careful consideration of the experimental geometry. Standard procedures for separating nuclear from electronic stopping treat electronic energy loss as a friction force, ignoring its dependence on impact parameter. In the present study we find that incorporating this dependence has a major effect on measured stopping cross sections, in particular for light ions at low beam energies. Calculations have been made for transmission geometry, nuclear interactions being quantified by Bohr-Williams theory of multiple scattering on the basis of a Thomas-Fermi-Molière potential, whereas electronic interactions are characterized by Firsov theory or PASS code. Differences between the full and the restricted stopping cross section depend on target thickness and opening angle of the detector and need to be taken into account in comparisons with theory as well as in applications of stopping data. It follows that the reciprocity principle can be violated when checked on restricted instead of full electronic stopping cross sections. Finally, we assert that a seeming gas-solid difference in stopping of low-energy ions is actually a metal-insulator difference. In comparisons with experimental results we mostly consider proton data, where nuclear stopping is only a minor perturbation.

34 CFR 361.4 - Applicable regulations.

Code of Federal Regulations, 2014 CFR

2014-07-01

...-Stop Service Delivery System under Title I of the Workforce Investment Act of 1998). (d) 29 CFR part 37, to the extent programs and activities are being conducted as part of the One-Stop service delivery... (Nonprocurement) and Governmentwide Requirements for Drug-Free Workplace (Grants)). (9) 34 CFR part 86 (Drug and...

34 CFR 361.4 - Applicable regulations.

Code of Federal Regulations, 2013 CFR

2013-07-01

...-Stop Service Delivery System under Title I of the Workforce Investment Act of 1998). (d) 29 CFR part 37, to the extent programs and activities are being conducted as part of the One-Stop service delivery... (Nonprocurement) and Governmentwide Requirements for Drug-Free Workplace (Grants)). (9) 34 CFR part 86 (Drug and...

34 CFR 361.4 - Applicable regulations.

Code of Federal Regulations, 2012 CFR

2012-07-01

...-Stop Service Delivery System under Title I of the Workforce Investment Act of 1998). (d) 29 CFR part 37, to the extent programs and activities are being conducted as part of the One-Stop service delivery... (Nonprocurement) and Governmentwide Requirements for Drug-Free Workplace (Grants)). (9) 34 CFR part 86 (Drug and...

PTHrP and Indian hedgehog control differentiation of growth plate chondrocytes at multiple steps.

PubMed

Kobayashi, Tatsuya; Chung, Ung-Il; Schipani, Ernestina; Starbuck, Michael; Karsenty, Gerard; Katagiri, Takenobu; Goad, Dale L; Lanske, Beate; Kronenberg, Henry M

2002-06-01

In developing murine growth plates, chondrocytes near the articular surface (periarticular chondrocytes) proliferate, differentiate into flat column-forming proliferating cells (columnar chondrocytes), stop dividing and finally differentiate into hypertrophic cells. Indian hedgehog (Ihh), which is predominantly expressed in prehypertrophic cells, stimulates expression of parathyroid hormone (PTH)-related peptide (PTHrP) which negatively regulates terminal chondrocyte differentiation through the PTH/PTHrP receptor (PPR). However, the roles of PTHrP and Ihh in regulating earlier steps in chondrocyte differentiation are unclear. We present novel mouse models with PPR abnormalities that help clarify these roles. In mice with chondrocyte-specific PPR ablation and mice with reduced PPR expression, chondrocyte differentiation was accelerated not only at the terminal step but also at an earlier step: periarticular to columnar differentiation. In these models, upregulation of Ihh action in the periarticular region was also observed. In the third model in which the PPR was disrupted in about 30% of columnar chondrocytes, Ihh action in the periarticular chondrocytes was upregulated because of ectopically differentiated hypertrophic chondrocytes that had lost PPR. Acceleration of periarticular to columnar differentiation was also noted in this mouse, while most of periarticular chondrocytes retained PPR signaling. These data suggest that Ihh positively controls differentiation of periarticular chondrocytes independently of PTHrP. Thus, chondrocyte differentiation is controlled at multiple steps by PTHrP and Ihh through the mutual regulation of their activities.

Inspector General Regulation 1020.1: Processing Complaints of Discrimination

DTIC Science & Technology

1995-08-18

harassment in the workplace . The EEOC and DoD guidelines, as well as court decisions, have made it clear that employers are liable and responsible for...matter. Any supervisor within the OIG who permits prohibited harassment to occur without taking steps to stop it may be found to have tolerated sexual

49 CFR 393.22 - Combination of lighting devices and reflectors.

Code of Federal Regulations, 2010 CFR

2010-10-01

... REGULATIONS PARTS AND ACCESSORIES NECESSARY FOR SAFE OPERATION Lamps, Reflective Devices, and Electrical...) Prohibited combinations. (1) A turn signal lamp must not be combined optically with either a head lamp or... the turn signal lamp. (2) A turn signal lamp must not be combined optically with a stop lamp unless...

The Coexistence Claim and Its Possible Implications for Success in Teaching for Conceptual "Change"

ERIC Educational Resources Information Center

Potvin, Patrice

2017-01-01

This article presents recent research results in mental chronometry and neuroimaging that support the coexistence of multiple conceptions. It then presents and elaborates on six possible implications for an adherence to the coexistence claim within the context of scientific conceptual learning: (1) stop the war on misconceptions; (2) use a…

Overexpression of Shox2 Leads to Congenital Dysplasia of the Temporomandibular Joint in Mice

PubMed Central

Li, Xihai; Liang, Wenna; Ye, Hongzhi; Weng, Xiaping; Liu, Fayuan; Liu, Xianxiang

2014-01-01

Our previous study reported that inactivation of Shox2 led to dysplasia and ankylosis of the temporomandibular joint (TMJ), and that replacing Shox2 with human Shox partially rescued the phenotype with a prematurely worn out articular disc. However, the mechanisms of Shox2 activity in TMJ development remain to be elucidated. In this study, we investigated the molecular and cellular basis for the congenital dysplasia of TMJ in Wnt1-Cre; pMes-stop Shox2 mice. We found that condyle and glenoid fossa dysplasia occurs primarily in the second week after the birth. The dysplastic TMJ of Wnt1-Cre; pMes-stop Shox2 mice exhibits a loss of Collagen type I, Collagen type II, Ihh and Gli2. In situ zymography and immunohistochemistry further demonstrate an up-regulation of matrix metalloproteinases (MMPs), MMP9 and MMP13, accompanied by a significantly increased cell apoptosis. In addition, the cell proliferation and expressions of Sox9, Runx2 and Ihh are no different in the embryonic TMJ between the wild type and mutant mice. Our results show that overexpression of Shox2 leads to the loss of extracellular matrix and the increase of cell apoptosis in TMJ dysplasia by up-regulating MMPs and down-regulating the Ihh signaling pathway. PMID:25062348

Descriptive study of prescriptions for opioids from a suburban academic emergency department before New York's I-STOP Act.

PubMed

Ung, Lyncean; Dvorkin, Ronald; Sattler, Steven; Yens, David

2015-01-01

Controlled prescription opioid use is perceived as a national problem attributed to all specialties. Our objective was to provide a descriptive analysis of prescriptions written for controlled opioids from a database of emergency department (ED) visits prior to the enactment of the I-STOP law, which requires New York prescribers to consult the Prescription Monitoring Program (PMP) prior to prescribing Schedule II, III, and IV controlled substances for prescriptions of greater than five days duration. We conducted a retrospective medical record review of patients 21 years of age and older, who presented to the ED between July 1, 2011 - June 30, 2012 and were given a prescription for a controlled opioid. Our primary purpose was to characterize each prescription as to the type of controlled substance, the quantity dispensed, and the duration of the prescription. We also looked at outliers, those patients who received prescriptions for longer than five days. A total of 9,502 prescriptions were written for opioids out of a total 63,143 prescriptions for 69,500 adult patients. Twenty-six (0.27%) of the prescriptions for controlled opioids were written for greater than five days. Most prescriptions were for five days or less (99.7%, 95% CI [99.6 to 99.8%]). The vast majority of opioid prescriptions in our ED prior to the I-STOP legislature were limited to a five-day or less supply. These new regulations were meant to reduce the ED's contribution to the rise of opioid related morbidity. This study suggests that the emergency physicians' usual prescribing practices were negligibly limited by the new restrictive regulations. The ED may not be primarily contributing to the increase in opioid-related overdoses and death. The effect of the I-STOP regulation on future prescribing patterns in the ED remains to be determined.

7 CFR 301.92-4 - Conditions governing the interstate movement of regulated, restricted, and associated articles...

Code of Federal Regulations, 2011 CFR

2011-01-01

...) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE DOMESTIC QUARANTINE NOTICES... for refueling, rest stops, emergency repairs, and for traffic conditions, such as traffic lights or... as traffic lights or stop signs, and the article is not unpacked or unloaded in the quarantined area...

15 CFR 922.61 - Prohibited or otherwise regulated activities.

Code of Federal Regulations, 2010 CFR

2010-01-01

... COASTAL RESOURCE MANAGEMENT NATIONAL MARINE SANCTUARY PROGRAM REGULATIONS Monitor National Marine Sanctuary § 922.61 Prohibited or otherwise regulated activities. Except as may be permitted by the Director... be conducted within the Sanctuary: (a) Anchoring in any manner, stopping, remaining, or drifting...

An incremental analysis of a deep drawing steel’s material behaviour undergoing the predeformation using drawbeads

NASA Astrophysics Data System (ADS)

Schmid, H.; Suttner, S.; Merklein, M.

2017-09-01

Nowadays lightweight design in metal forming processes leads to complex deep drawing geometries, which can cause multiple damages. Therefore, drawbeads are one way to regulate and control material flow during the forming process. Not only in research, but also in industrial practice, it could be determined that material is work hardened passing drawbead geometries. It particularly means when material is pre-deformed with tensile and alternating bending loads. This incident also gives the opportunity to utilize it in a reasonable way if examined properly. To investigate these findings, a process oriented and comprehensive analysis of the material behaviour during these forming operations is needed. In this paper, sheet metal strips are linearly drawn through a drawbead and stopped after passing the drawbead. Within this forming operation, the material undergoes non-linear straining before reaching the in-plane position again. Here, the process will be stopped to investigate a permanent strengthening local along the sheet thickness. Therefore, microhardness measurements are realized before and after passing the drawbead. Because of its common use and its wide known material data, a deep drawing steel DC will be used for these studies. Additionally, the strategy is applied to advanced high strength steel.

NGEE Arctic Tram: Photographs over Low- and High-Centered Polygon Vegetation Communities, Barrow, Alaska, 2014-2017

DOE Data Explorer

J. Bryan Curtis; Margaret Torn

2017-10-05

This dataset provides a digital image of each measurement position stop for every run of the Tram. There are 137 stops per run and there were sometimes multiple runs per day. This first version provides 12,714 images (*.jpg) collected over 28 days in 2015. Images for the other years will be added.

Canceling actions involves a race between basal ganglia pathways

PubMed Central

Schmidt, Robert; Leventhal, Daniel K.; Mallet, Nicolas; Chen, Fujun; Berke, Joshua D.

2013-01-01

Salient cues can prompt the rapid interruption of planned actions. It has been proposed that fast, reactive behavioral inhibition involves specific basal ganglia pathways, and we tested this by comparing activity in multiple rat basal ganglia structures during performance of a stop-signal task. Subthalamic nucleus (STN) neurons showed low-latency responses to Stop cues, irrespective of whether actions were successfully canceled or not. By contrast, neurons downstream in the substantia nigra pars reticulata (SNr) responded to Stop cues only in trials with successful cancellation. Recordings and simulations together indicate that this sensorimotor gating arises from the relative timing of two distinct inputs to neurons in the SNr dorsolateral “core” subregion: cue-related excitation from STN and movement-related inhibition from striatum. Our results support race models of action cancellation, with successful stopping requiring Stop cue information to be transmitted from STN to SNr before increased striatal input creates a point of no return. PMID:23852117

49 CFR 398.6 - Hours of service of drivers; maximum driving time.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 5 2011-10-01 2011-10-01 false Hours of service of drivers; maximum driving time... REGULATIONS TRANSPORTATION OF MIGRANT WORKERS § 398.6 Hours of service of drivers; maximum driving time. No... or operate for more than 10 hours in the aggregate (excluding rest stops and stops for meals) in any...

49 CFR 398.6 - Hours of service of drivers; maximum driving time.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 5 2010-10-01 2010-10-01 false Hours of service of drivers; maximum driving time... REGULATIONS TRANSPORTATION OF MIGRANT WORKERS § 398.6 Hours of service of drivers; maximum driving time. No... or operate for more than 10 hours in the aggregate (excluding rest stops and stops for meals) in any...

30 CFR 280.25 - When may MMS require me to stop activities under this part?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 2 2011-07-01 2011-07-01 false When may MMS require me to stop activities under this part? 280.25 Section 280.25 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION... life), property, and any minerals (in areas leased or not leased), to the marine, coastal, or human...

Application of Frequent Itemsets Mining to Analyze Patterns of One-Stop Visits in Taiwan

PubMed Central

Tu, Chun-Yi; Chen, Tzeng-Ji; Chou, Li-Fang

2011-01-01

Background The free choice of health care facilities without limitations on frequency of visits within the National Health Insurance in Taiwan gives rise to not only a high number of annual ambulatory visits per capita but also a unique “one-stop shopping”phenomenon, which refers to a patient' visits to several specialties of the same healthcare facility in one day. The visits to multiple physicians would increase the potential risk of polypharmacy. The aim of this study was to analyze the frequency and patterns of one-stop visits in Taiwan. Methodology/Principal Findings The claims datasets of 1 million nationally representative people within Taiwan's National Health Insurance in 2005 were used to calculate the number of patients with one-stop visits. The frequent itemsets mining was applied to compute the combination patterns of specialties in the one-stop visits. Among the total 13,682,469 ambulatory care visits in 2005, one-stop visits occurred 144,132 times and involved 296,822 visits (2.2% of all visits) by 66,294 (6.6%) persons. People tended to have this behavior with age and the percentage reached 27.5% (5,662 in 20,579) in the age group ≥80 years. In general, women were more likely to have one-stop visits than men (7.2% vs. 6.0%). Internal medicine plus ophthalmology was the most frequent combination with a visited frequency of 3,552 times (2.5%), followed by cardiology plus neurology with 3,183 times (2.2%). The most frequent three-specialty combination, cardiology plus neurology and gastroenterology, occurred only 111 times. Conclusions/Significance Without the novel computational technique, it would be hardly possible to analyze the extremely diverse combination patterns of specialties in one-stop visits. The results of the study could provide useful information either for the hospital manager to set up integrated services or for the policymaker to rebuild the health care system. PMID:21747926

78 FR 40959 - Removing Unnecessary Office on Violence Against Women Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-09

.... VAWA was designed to improve criminal justice system responses to domestic violence, sexual assault... Office on Violence Against Women Regulations AGENCY: Office on Violence Against Women, Justice. ACTION: Final rule. SUMMARY: This rule removes the regulations for the STOP Violence Against Indian Women...

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions

PubMed Central

Hendrickx, Debbie A. E.; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G.; van Eden, Corbert G.; Hol, Elly M.; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1, and ANO4. Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16, and OLR1, and lipid uptake, such as CHIT1, GPNMB, and CCL18. Except CCL18, these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion. PMID:29312322

Gene Expression Profiling of Multiple Sclerosis Pathology Identifies Early Patterns of Demyelination Surrounding Chronic Active Lesions.

PubMed

Hendrickx, Debbie A E; van Scheppingen, Jackelien; van der Poel, Marlijn; Bossers, Koen; Schuurman, Karianne G; van Eden, Corbert G; Hol, Elly M; Hamann, Jörg; Huitinga, Inge

2017-01-01

In multiple sclerosis (MS), activated microglia and infiltrating macrophages phagocytose myelin focally in (chronic) active lesions. These demyelinating sites expand in time, but at some point turn inactive into a sclerotic scar. To identify molecular mechanisms underlying lesion activity and halt, we analyzed genome-wide gene expression in rim and peri-lesional regions of chronic active and inactive MS lesions, as well as in control tissue. Gene clustering revealed patterns of gene expression specifically associated with MS and with the presumed, subsequent stages of lesion development. Next to genes involved in immune functions, we found regulation of novel genes in and around the rim of chronic active lesions, such as NPY, KANK4, NCAN, TKTL1 , and ANO4 . Of note, the presence of many foamy macrophages in active rims was accompanied by a congruent upregulation of genes related to lipid binding, such as MSR1, CD68, CXCL16 , and OLR1 , and lipid uptake, such as CHIT1, GPNMB , and CCL18 . Except CCL18 , these genes were already upregulated in regions around active MS lesions, showing that such lesions are indeed expanding. In vitro downregulation of the scavenger receptors MSR1 and CXCL16 reduced myelin uptake. In conclusion, this study provides the gene expression profile of different aspects of MS pathology and indicates that early demyelination, mediated by scavenger receptors, is already present in regions around active MS lesions. Genes involved in early demyelination events in regions surrounding chronic active MS lesions might be promising therapeutic targets to stop lesion expansion.

Multiple Effects of Messages with Multiple Goals: Some Perceived Outcomes of Responses to Sexual Harassment.

ERIC Educational Resources Information Center

Bingham, Shereen G.; Burleson, Brant R.

1989-01-01

Tests the perceived effectiveness of different messages responding to sexual harassment in the organizational environment. Finds that none of the messages were perceived as being particularly effective at stopping the harasser's offensive conduct. (MM)

Effectiveness of transverse grooves in rigid pavement

NASA Astrophysics Data System (ADS)

Gurney, G. F.; Bryden, J. E.

1982-10-01

Transverse grooves were installed at 11 intersection approaches on worn rigid pavement to reduce a high rate of wet road accidents. In most cases, accident reductions were experienced only at intersections with multiple negative operational characteristics, including higher approach speeds, limited sight distances, and frequent vehicle stopping for turns or stop signs. Intersections with no more than one negative characteristic generally did not benefit from grooving.

77 FR 29579 - Removing Unnecessary Office on Violence Against Women Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-18

... Office on Violence Against Women Regulations AGENCY: Office on Violence Against Women, Justice. ACTION: Proposed rule. SUMMARY: This rule proposes to remove the regulations for the STOP Violence Against Indian... through regular or express mail, they should be sent to Kathi Grasso, Office on Violence Against Women...

Satiety and the self-regulation of food intake in children: A potential for gene-environment interplay

USDA-ARS?s Scientific Manuscript database

Child eating self-regulation refers to behaviors that enable children to start and stop eating in a manner consistent with maintaining energy balance. Perturbations in these behaviors, manifesting as poorer child eating self-regulation, are associated with higher child weight status. Initial researc...

17 CFR 242.611 - Order protection rule.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) REGULATIONS M, SHO, ATS, AC, AND NMS AND CUSTOMER MARGIN REQUIREMENTS FOR SECURITY FUTURES Regulation Nms... transaction was, for a stopped buy order, lower than the national best bid in the NMS stock at the time of...

Multi-arm group sequential designs with a simultaneous stopping rule.

PubMed

Urach, S; Posch, M

2016-12-30

Multi-arm group sequential clinical trials are efficient designs to compare multiple treatments to a control. They allow one to test for treatment effects already in interim analyses and can have a lower average sample number than fixed sample designs. Their operating characteristics depend on the stopping rule: We consider simultaneous stopping, where the whole trial is stopped as soon as for any of the arms the null hypothesis of no treatment effect can be rejected, and separate stopping, where only recruitment to arms for which a significant treatment effect could be demonstrated is stopped, but the other arms are continued. For both stopping rules, the family-wise error rate can be controlled by the closed testing procedure applied to group sequential tests of intersection and elementary hypotheses. The group sequential boundaries for the separate stopping rule also control the family-wise error rate if the simultaneous stopping rule is applied. However, we show that for the simultaneous stopping rule, one can apply improved, less conservative stopping boundaries for local tests of elementary hypotheses. We derive corresponding improved Pocock and O'Brien type boundaries as well as optimized boundaries to maximize the power or average sample number and investigate the operating characteristics and small sample properties of the resulting designs. To control the power to reject at least one null hypothesis, the simultaneous stopping rule requires a lower average sample number than the separate stopping rule. This comes at the cost of a lower power to reject all null hypotheses. Some of this loss in power can be regained by applying the improved stopping boundaries for the simultaneous stopping rule. The procedures are illustrated with clinical trials in systemic sclerosis and narcolepsy. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

78 FR 17432 - Kiewit Power Constructors Co. et al.; Application for a Permanent Variance and Request for Comments

Federal Register 2010, 2011, 2012, 2013, 2014

2013-03-21

... under Section 6(d) of the Occupational Safety and Health Act of 1970 (29 U.S.C. 655) and 29 CFR 1905.11... that regulate hoist towers. These paragraphs specify the following requirements: (c)(1)--Construction...)--Electrically interlocking entrance doors or gates to the hoistway and cars; (c)(13)--Emergency stop switch...

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

Huang, Er-Wen; Department of Forensic Pathology, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou; Xue, Sheng-Jiang

Highlights: • Levels of EEN expression paralleled with the rate of cell proliferation. • EEN was involved in the proliferation and survival of multiple myeloma (MM) cells. • EEN regulated the activity of IGF-1-Akt/mTOR pathway. • EEN regulated proliferation and survival of MM cells by enhancing IGF-1 secretion. - Abstract: The molecular mechanisms of multiple myeloma are not well defined. EEN is an endocytosis-regulating molecule. Here we report that EEN regulates the proliferation and survival of multiple myeloma cells, by regulating IGF-1 secretion. In the present study, we observed that EEN expression paralleled with cell proliferation, EEN accelerated cell proliferation,more » facilitated cell cycle transition from G1 to S phase by regulating cyclin-dependent kinases (CDKs) pathway, and delayed cell apoptosis via Bcl2/Bax-mitochondrial pathway. Mechanistically, we found that EEN was indispensable for insulin-like growth factor-1 (IGF-1) secretion and the activation of protein kinase B-mammalian target of rapamycin (Akt-mTOR) pathway. Exogenous IGF-1 overcame the phenotype of EEN depletion, while IGF-1 neutralization overcame that of EEN over-expression. Collectively, these data suggest that EEN may play a pivotal role in excessive cell proliferation and insufficient cell apoptosis of bone marrow plasma cells in multiple myeloma. Therefore, EEN may represent a potential diagnostic marker or therapeutic target for multiple myeloma.« less

Rules of UGA-N decoding by near-cognate tRNAs and analysis of readthrough on short uORFs in yeast.

PubMed

Beznosková, Petra; Gunišová, Stanislava; Valášek, Leoš Shivaya

2016-03-01

The molecular mechanism of stop codon recognition by the release factor eRF1 in complex with eRF3 has been described in great detail; however, our understanding of what determines the difference in termination efficiencies among various stop codon tetranucleotides and how near-cognate (nc) tRNAs recode stop codons during programmed readthrough in Saccharomyces cerevisiae is still poor. Here, we show that UGA-C as the only tetranucleotide of all four possible combinations dramatically exacerbated the readthrough phenotype of the stop codon recognition-deficient mutants in eRF1. Since the same is true also for UAA-C and UAG-C, we propose that the exceptionally high readthrough levels that all three stop codons display when followed by cytosine are partially caused by the compromised sampling ability of eRF1, which specifically senses cytosine at the +4 position. The difference in termination efficiencies among the remaining three UGA-N tetranucleotides is then given by their varying preferences for nc-tRNAs. In particular, UGA-A allows increased incorporation of Trp-tRNA whereas UGA-G and UGA-C favor Cys-tRNA. Our findings thus expand the repertoire of general decoding rules by showing that the +4 base determines the preferred selection of nc-tRNAs and, in the case of cytosine, it also genetically interacts with eRF1. Finally, using an example of the GCN4 translational control governed by four short uORFs, we also show how the evolution of this mechanism dealt with undesirable readthrough on those uORFs that serve as the key translation reinitiation promoting features of the GCN4 regulation, as both of these otherwise counteracting activities, readthrough versus reinitiation, are mediated by eIF3. © 2016 Beznosková et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Multiple scattering and stop band characteristics of flexural waves on a thin plate with circular holes

NASA Astrophysics Data System (ADS)

Wang, Zuowei; Biwa, Shiro

2018-03-01

A numerical procedure is proposed for the multiple scattering analysis of flexural waves on a thin plate with circular holes based on the Kirchhoff plate theory. The numerical procedure utilizes the wave function expansion of the exciting as well as scattered fields, and the boundary conditions at the periphery of holes are incorporated as the relations between the expansion coefficients of exciting and scattered fields. A set of linear algebraic equations with respect to the wave expansion coefficients of the exciting field alone is established by the numerical collocation method. To demonstrate the applicability of the procedure, the stop band characteristics of flexural waves are analyzed for different arrangements and concentrations of circular holes on a steel plate. The energy transmission spectra of flexural waves are shown to capture the detailed features of the stop band formation of regular and random arrangements of holes. The increase of the concentration of holes is found to shift the dips of the energy transmission spectra toward higher frequencies as well as deepen them. The hexagonal hole arrangement can form a much broader stop band than the square hole arrangement for flexural wave transmission. It is also demonstrated that random arrangements of holes make the transmission spectrum more complicated.

Combined pressure regulator and shutoff valve

NASA Technical Reports Server (NTRS)

Koch, E. F. (Inventor)

1974-01-01

A remotely operable pressure regulator and shutoff valve particularly suited for achieving high resolution and flow control, and positive shutoff is described. The valve is characterized by a spring-loaded ball coaxially aligned with a fluid port to be sealed, a spring-loaded pintle extended through the port into engagement with the ball, for controlling the position, a spring-loaded diaphragm for controlling the position of the pintle, and an axially displaceable spring supported by a movable stop which, in turn, is repositioned by a selectively operable stepper motor. Thus, the pressure-response characteristics for the valve can be varied through a selective repositioning of the stop.

Sensorimotor-Independent Prefrontal Activity During Response Inhibition

PubMed Central

Cai, Weidong; Cannistraci, Christopher J.; Gore, John C.; Leung, Hoi-Chung

2015-01-01

A network of brain regions involving the ventral inferior frontal gyrus/anterior insula (vIFG/AI), presupplementary motor area (pre-SMA) and basal ganglia has been implicated in stopping impulsive, unwanted responses. However, whether this network plays an equal role in response inhibition under different sensorimotor contexts has not been tested systematically. Here, we conducted an fMRI experiment using the stop signal task, a sensorimotor task requiring occasional withholding of the planned response upon the presentation of a stop signal. We manipulated both the sensory modality of the stop signal (visual versus auditory) and the motor response modality (hand versus eye). Results showed that the vIFG/AI and the preSMA along with the right middle frontal gyrus were commonly activated in response inhibition across the various sensorimotor conditions. Our findings provide direct evidence for a common role of these frontal areas, but not striatal areas in response inhibition independent of the sensorimotor contexts. Nevertheless, these three frontal regions exhibited different activation patterns during successful and unsuccessful stopping. Together with the existing evidence, we suggest that the vIFG/AI is involved in the early stages of stopping such as triggering the stop process while the preSMA may play a role in regulating other cortical and subcortical regions involved in stopping. PMID:23798325

7 CFR 301.86-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... traffic conditions such as traffic lights and stop signs); and (C) The regulated article is not unpacked...

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

Alderfer, R.R.; Futa, P.W.

This patent describes a fuel system for an engine having a filter through which fuel from a pump passes to a regulator in response to an operator input. The regulator controls the flow of fuel presented to a combustion chamber in the engine, the regulator having a feedback apparatus to provide an operator with a signal indicative of the fuel supplied to the combustion chamber. It comprises: bypass means having a housing with a chamber therein, the chamber having an entrance port connected to the pump and an exit port connected to the regulator; piston means located in the chambermore » for separating the entrance port from the exit port, the piston having a face with a projection extending therefrom; stop means located in the chamber; resilient means located is the chamber for urging the piston means toward the stop means to prevent the flow of fuel from the pump through the housing to the regulator; and indicator means having a body retained in the housing with a first end which extends through the housing into the from a full-open position at which the closed circuit is fully opened to a full-closed position at which the closed circuit is fully blocked; ratio detecting means which detects the speed reduction ratio to find if the speed reduction ratio becomes substantially 1; and valve position detecting means which detects position of the direct clutch valve to find if the direct clutch valve is moved to a slight-open position at which the closed circuit is slightly opened.« less

Hydraulic Fracture Induced Seismicity During A Multi-Stage Pad Completion in Western Canada: Evidence of Activation of Multiple, Parallel Faults

NASA Astrophysics Data System (ADS)

Maxwell, S.; Garrett, D.; Huang, J.; Usher, P.; Mamer, P.

2017-12-01

Following reports of injection induced seismicity in the Western Canadian Sedimentary Basin, regulators have imposed seismic monitoring and traffic light protocols for fracturing operations in specific areas. Here we describe a case study in one of these reservoirs, the Montney Shale in NE British Columbia, where induced seismicity was monitored with a local array during multi-stage hydraulic fracture stimulations on several wells from a single drilling pad. Seismicity primarily occurred during the injection time periods, and correlated with periods of high injection rates and wellhead pressures above fracturing pressures. Sequential hydraulic fracture stages were found to progressively activate several parallel, critically-stressed faults, as illuminated by multiple linear hypocenter patterns in the range between Mw 1 and 3. Moment tensor inversion of larger events indicated a double-couple mechanism consistent with the regional strike-slip stress state and the hypocenter lineations. The critically-stressed faults obliquely cross the well paths which were purposely drilled parallel to the minimum principal stress direction. Seismicity on specific faults started and stopped when fracture initiation points of individual injection stages were proximal to the intersection of the fault and well. The distance ranges when the seismicity occurs is consistent with expected hydraulic fracture dimensions, suggesting that the induced fault slip only occurs when a hydraulic fracture grows directly into the fault and the faults are temporarily exposed to significantly elevated fracture pressures during the injection. Some faults crossed multiple wells and the seismicity was found to restart during injection of proximal stages on adjacent wells, progressively expanding the seismogenic zone of the fault. Progressive fault slip is therefore inferred from the seismicity migrating further along the faults during successive injection stages. An accelerometer was also deployed close to the pad operations providing information about the local ground motion at near offsets, although no ground motion was recorded that exceeds the minimum levels requiring mandatory reporting to the regulator.

Brain-derived neurotrophic factor (BDNF)-induced mitochondrial motility arrest and presynaptic docking contribute to BDNF-enhanced synaptic transmission.

PubMed

Su, Bo; Ji, Yun-Song; Sun, Xu-lu; Liu, Xiang-Hua; Chen, Zhe-Yu

2014-01-17

Appropriate mitochondrial transport and distribution are essential for neurons because of the high energy and Ca(2+) buffering requirements at synapses. Brain-derived neurotrophic factor (BDNF) plays an essential role in regulating synaptic transmission and plasticity. However, whether and how BDNF can regulate mitochondrial transport and distribution are still unclear. Here, we find that in cultured hippocampal neurons, application of BDNF for 15 min decreased the percentage of moving mitochondria in axons, a process dependent on the activation of the TrkB receptor and its downstream PI3K and phospholipase-Cγ signaling pathways. Moreover, the BDNF-induced mitochondrial stopping requires the activation of transient receptor potential canonical 3 and 6 (TRPC3 and TRPC6) channels and elevated intracellular Ca(2+) levels. The Ca(2+) sensor Miro1 plays an important role in this process. Finally, the BDNF-induced mitochondrial stopping leads to the accumulation of more mitochondria at presynaptic sites. Mutant Miro1 lacking the ability to bind Ca(2+) prevents BDNF-induced mitochondrial presynaptic accumulation and synaptic transmission, suggesting that Miro1-mediated mitochondrial motility is involved in BDNF-induced mitochondrial presynaptic docking and neurotransmission. Together, these data suggest that mitochondrial transport and distribution play essential roles in BDNF-mediated synaptic transmission.

First experimental results of a cryogenic stopping cell with short-lived, heavy uranium fragments produced at 1000 MeV/u

NASA Astrophysics Data System (ADS)

Purushothaman, S.; Reiter, M. P.; Haettner, E.; Dendooven, P.; Dickel, T.; Geissel, H.; Ebert, J.; Jesch, C.; Plass, W. R.; Ranjan, M.; Weick, H.; Amjad, F.; Ayet, S.; Diwisch, M.; Estrade, A.; Farinon, F.; Greiner, F.; Kalantar-Nayestanaki, N.; Knöbel, R.; Kurcewicz, J.; Lang, J.; Moore, I. D.; Mukha, I.; Nociforo, C.; Petrick, M.; Pfützner, M.; Pietri, S.; Prochazka, A.; Rink, A.-K.; Rinta-Antila, S.; Scheidenberger, C.; Takechi, M.; Tanaka, Y. K.; Winfield, J. S.; Yavor, M. I.

2013-11-01

A cryogenic stopping cell (CSC) has been commissioned with 238U projectile fragments produced at 1000 MeV/u. The spatial isotopic separation in flight was performed with the FRS applying a monoenergetic degrader. For the first time, a stopping cell was operated with exotic nuclei at cryogenic temperatures (70 to 100 K). A helium stopping gas density of up to 0.05\\ \\text{mg/cm}^3 was used, about two times higher than reached before for a stopping cell with RF ion repelling structures. An overall efficiency of up to 15%, a combined ion survival and extraction efficiency of about 50%, and extraction times of 24 ms were achieved for heavy α-decaying uranium fragments. Mass spectrometry with a multiple-reflection time-of-flight mass spectrometer has demonstrated the excellent cleanliness of the CSC. This setup has opened a new field for the spectroscopy of short-lived nuclei.

Comparison of sEMG processing methods during whole-body vibration exercise.

PubMed

Lienhard, Karin; Cabasson, Aline; Meste, Olivier; Colson, Serge S

2015-12-01

The objective was to investigate the influence of surface electromyography (sEMG) processing methods on the quantification of muscle activity during whole-body vibration (WBV) exercises. sEMG activity was recorded while the participants performed squats on the platform with and without WBV. The spikes observed in the sEMG spectrum at the vibration frequency and its harmonics were deleted using state-of-the-art methods, i.e. (1) a band-stop filter, (2) a band-pass filter, and (3) spectral linear interpolation. The same filtering methods were applied on the sEMG during the no-vibration trial. The linear interpolation method showed the highest intraclass correlation coefficients (no vibration: 0.999, WBV: 0.757-0.979) with the comparison measure (unfiltered sEMG during the no-vibration trial), followed by the band-stop filter (no vibration: 0.929-0.975, WBV: 0.661-0.938). While both methods introduced a systematic bias (P < 0.001), the error increased with increasing mean values to a higher degree for the band-stop filter. After adjusting the sEMG(RMS) during WBV for the bias, the performance of the interpolation method and the band-stop filter was comparable. The band-pass filter was in poor agreement with the other methods (ICC: 0.207-0.697), unless the sEMG(RMS) was corrected for the bias (ICC ⩾ 0.931, %LOA ⩽ 32.3). In conclusion, spectral linear interpolation or a band-stop filter centered at the vibration frequency and its multiple harmonics should be applied to delete the artifacts in the sEMG signals during WBV. With the use of a band-stop filter it is recommended to correct the sEMG(RMS) for the bias as this procedure improved its performance. Copyright © 2015 Elsevier Ltd. All rights reserved.

Seizure Termination by Acidosis Depends on ASIC1a

PubMed Central

Ziemann, Adam E.; Schnizler, Mikael K.; Albert, Gregory W.; Severson, Meryl A.; Howard, Matthew A.; Welsh, Michael J.; Wemmie, John A.

2008-01-01

SUMMARY Most seizures stop spontaneously. However, the molecular mechanisms remain unknown. Earlier observations that seizures reduce brain pH and that acidosis inhibits seizures indicated that acidosis halts epileptic activity. Because acid–sensing ion channel–1a (ASIC1a) shows exquisite sensitivity to extracellular pH and regulates neuron excitability, we hypothesized that acidosis might activate ASIC1a to terminate seizures. Disrupting mouse ASIC1a increased the severity of chemoconvulsant–induced seizures, whereas overexpressing ASIC1a had the opposite effect. ASIC1a did not affect seizure threshold or onset, but shortened seizure duration and prevented progression. CO2 inhalation, long known to lower brain pH and inhibit seizures, also required ASIC1a to interrupt tonic–clonic seizures. Acidosis activated inhibitory interneurons through ASIC1a, suggesting that ASIC1a might limit seizures by increasing inhibitory tone. These findings identify ASIC1a as a key element in seizure termination when brain pH falls. The results suggest a molecular mechanism for how the brain stops seizures and suggest new therapeutic strategies. PMID:18536711

The influence of cognitive impairment with no dementia on driving restriction and cessation in older adults.

PubMed

Kowalski, Kristina; Love, Janet; Tuokko, Holly; MacDonald, Stuart; Hultsch, David; Strauss, Esther

2012-11-01

Cognitively impaired older adults may be at increased risk of unsafe driving. Individuals with insight into their own impairments may minimize their risk by restricting or stopping driving. The purpose of this study was to examine the influence of cognitive impairment on driving status and driving habits and intentions. Participants were classified as cognitively impaired, no dementia single (CIND-single), CIND-multiple, or not cognitively impaired (NCI) and compared on their self-reported driving status, habits, and intentions to restrict or quit driving in the future. The groups differed significantly in driving status, but not in whether they restricted their driving or reduced their driving frequency. CIND-multiple group also had significantly higher intention to restrict/stop driving than the NCI group. Reasons for restricting and quitting driving were varied and many individuals reported multiple reasons, both external and internal, for their driving habits and intentions. Regardless of cognitive status, none of the current drivers were seriously thinking of restricting or quitting driving in the next 6 months. It will be important to determine, in future research, how driving practices change over time and what factors influence decisions to restrict or stop driving for people with cognitive impairment. Copyright © 2011. Published by Elsevier Ltd.

Long-haul truck drivers want healthful meal options at truck-stop restaurants.

PubMed

Whitfield Jacobson, Pamela J; Prawitz, Aimee D; Lukaszuk, Judith M

2007-12-01

Long-haul truckers are confined, by parking regulations and other constraints, to dining at truck-stop restaurants. Objectives were to (a) compare truckers' anthropometrics with recommended guidelines; and (b) assess eating/exercise habits, importance of healthful food choices, and attitudes about restaurants' provision of healthful options. Hypotheses were: (a) overweight/obese drivers will place less importance on healthful food choices than will drivers of optimal weight; (b) importance of healthful food choices and attitudes about their provision will be positively correlated. Questionnaires included Food Choices Index, Nutrition Attitude Survey, and demographic information; bioelectrical impedance assessed weight, body fat, and body mass index. Subjects (n=92) were truckers at a Midwestern truck-stop restaurant; 79 were overweight, 52 were obese. Mean rating of importance of healthful choices was above average. There was no difference in importance of healthful food choices for overweight/obese and optimal weight drivers, t(89)=-1.312; P=0.19. Drivers placing more importance on healthful food choices had more positive attitudes about restaurants' provision of such options, r(90)=0.74, P<0.001. Overall, drivers indicated they would choose healthful foods if available and appetizing. Registered dietitian-directed wellness programs that include education, support, and cooperation of truck-stop restaurants are critical to reduce obesity and risk of disease in this population.

SZGR 2.0: a one-stop shop of schizophrenia candidate genes

PubMed Central

Jia, Peilin; Han, Guangchun; Zhao, Junfei; Lu, Pinyi; Zhao, Zhongming

2017-01-01

SZGR 2.0 is a comprehensive resource of candidate variants and genes for schizophrenia, covering genetic, epigenetic, transcriptomic, translational and many other types of evidence. By systematic review and curation of multiple lines of evidence, we included almost all variants and genes that have ever been reported to be associated with schizophrenia. In particular, we collected ∼4200 common variants reported in genome-wide association studies, ∼1000 de novo mutations discovered by large-scale sequencing of family samples, 215 genes spanning rare and replication copy number variations, 99 genes overlapping with linkage regions, 240 differentially expressed genes, 4651 differentially methylated genes and 49 genes as antipsychotic drug targets. To facilitate interpretation, we included various functional annotation data, especially brain eQTL, methylation QTL, brain expression featured in deep categorization of brain areas and developmental stages and brain-specific promoter and enhancer annotations. Furthermore, we conducted cross-study, cross-data type and integrative analyses of the multidimensional data deposited in SZGR 2.0, and made the data and results available through a user-friendly interface. In summary, SZGR 2.0 provides a one-stop shop of schizophrenia variants and genes and their function and regulation, providing an important resource in the schizophrenia and other mental disease community. SZGR 2.0 is available at https://bioinfo.uth.edu/SZGR/. PMID:27733502

Intracranial EEG reveals a time- and frequency-specific role for the right inferior frontal gyrus and primary motor cortex in stopping initiated responses.

PubMed

Swann, Nicole; Tandon, Nitin; Canolty, Ryan; Ellmore, Timothy M; McEvoy, Linda K; Dreyer, Stephen; DiSano, Michael; Aron, Adam R

2009-10-07

Inappropriate response tendencies may be stopped via a specific fronto/basal ganglia/primary motor cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from subdural electrodes in four patients while they performed a stop-signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band ( approximately 16 Hz) for successful versus unsuccessful stop trials. This finding adds to evidence for a functional network for stopping because changes in beta frequency activity have also been observed in the basal ganglia in association with behavioral stopping. In addition, the right IFG response occurred 100-250 ms after the stop signal, a time range consistent with a putative inhibitory control process rather than with stop-signal processing or feedback regarding success. A downstream target of inhibitory control is M1. In each patient, there was alpha/beta band desynchronization in M1 for stop trials. However, the degree of desynchronization in M1 was less for successfully than unsuccessfully stopped trials. This reduced desynchronization on successful stop trials could relate to increased GABA inhibition in M1. Together with other findings, the results suggest that behavioral stopping is implemented via synchronized activity in the beta frequency band in a right IFG/basal ganglia network, with downstream effects on M1.

Intracranial EEG reveals a time– and frequency–specific role for the right inferior frontal gyrus and primary motor cortex in stopping initiated responses

PubMed Central

Swann, Nicole; Tandon, Nitin; Canolty, Ryan; Ellmore, Timothy M; McEvoy, Linda K; Dreyer, Stephen; DiSano, Michael; Aron, Adam R

2009-01-01

Inappropriate response tendencies may be stopped via a specific fronto/basal-ganglia/primary-motor-cortical network. We sought to characterize the functional role of two regions in this putative stopping network, the right inferior frontal gyrus (IFG) and the primary motor cortex (M1), using electocorticography from sub-dural electrodes in four patients while they performed a stop signal task. On each trial, a motor response was initiated, and on a minority of trials a stop signal instructed the patient to try to stop the response. For each patient, there was a greater right IFG response in the beta frequency band (∼16 Hz) for successful vs. unsuccessful stop trials. This finding adds to evidence for a functional network for stopping because changes in beta frequency activity have also been observed in the basal ganglia in association with behavioral stopping. In addition, the right IFG response occurred 100 - 250 ms after the stop signal – a time range consistent with a putative inhibitory control process, rather than stop signal processing or feedback regarding success. A downstream target of inhibitory control is M1. In each patient, there was alpha/beta-band desynchronization in M1 for stop trials. However, the degree of desynchronization in M1 was less for successfully than unsuccessfully stopped trials. This reduced desynchronization on successful stop trials could relate to increased gamma-aminobutyric acid inhibition in M1. Taken together with other findings, the results suggest that behavioral stopping is implemented via synchronized activity in the beta-frequency band in a right IFG/basal-ganglia network, with downstream effects on M1. PMID:19812342

Resolvent-Techniques for Multiple Exercise Problems

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

Christensen, Sören, E-mail: christensen@math.uni-kiel.de; Lempa, Jukka, E-mail: jukka.lempa@hioa.no

2015-02-15

We study optimal multiple stopping of strong Markov processes with random refraction periods. The refraction periods are assumed to be exponentially distributed with a common rate and independent of the underlying dynamics. Our main tool is using the resolvent operator. In the first part, we reduce infinite stopping problems to ordinary ones in a general strong Markov setting. This leads to explicit solutions for wide classes of such problems. Starting from this result, we analyze problems with finitely many exercise rights and explain solution methods for some classes of problems with underlying Lévy and diffusion processes, where the optimal characteristicsmore » of the problems can be identified more explicitly. We illustrate the main results with explicit examples.« less

Multiple cell radiation detector system, and method, and submersible sonde

DOEpatents

Johnson, Larry O.; McIsaac, Charles V.; Lawrence, Robert S.; Grafwallner, Ervin G.

2002-01-01

A multiple cell radiation detector includes a central cell having a first cylindrical wall providing a stopping power less than an upper threshold; an anode wire suspended along a cylindrical axis of the central cell; a second cell having a second cylindrical wall providing a stopping power greater than a lower threshold, the second cylindrical wall being mounted coaxially outside of the first cylindrical wall; a first end cap forming a gas-tight seal at first ends of the first and second cylindrical walls; a second end cap forming a gas-tight seal at second ends of the first and second cylindrical walls; and a first group of anode wires suspended between the first and second cylindrical walls.

Relativity theory and time perception: single or multiple clocks?

PubMed

Buhusi, Catalin V; Meck, Warren H

2009-07-22

Current theories of interval timing assume that humans and other animals time as if using a single, absolute stopwatch that can be stopped or reset on command. Here we evaluate the alternative view that psychological time is represented by multiple clocks, and that these clocks create separate temporal contexts by which duration is judged in a relative manner. Two predictions of the multiple-clock hypothesis were tested. First, that the multiple clocks can be manipulated (stopped and/or reset) independently. Second, that an event of a given physical duration would be perceived as having different durations in different temporal contexts, i.e., would be judged differently by each clock. Rats were trained to time three durations (e.g., 10, 30, and 90 s). When timing was interrupted by an unexpected gap in the signal, rats reset the clock used to time the "short" duration, stopped the "medium" duration clock, and continued to run the "long" duration clock. When the duration of the gap was manipulated, the rats reset these clocks in a hierarchical order, first the "short", then the "medium", and finally the "long" clock. Quantitative modeling assuming re-allocation of cognitive resources in proportion to the relative duration of the gap to the multiple, simultaneously timed event durations was used to account for the results. These results indicate that the three event durations were effectively timed by separate clocks operated independently, and that the same gap duration was judged relative to these three temporal contexts. Results suggest that the brain processes the duration of an event in a manner similar to Einstein's special relativity theory: A given time interval is registered differently by independent clocks dependent upon the context.

29 CFR 530.103 - Employer assurances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... homeworkers shall be established using stop watch time studies or other work measurement methods. (h) All... Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS EMPLOYMENT... section 12. All homeworkers will be instructed not to permit minors to work in violation of such...

29 CFR 530.103 - Employer assurances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... homeworkers shall be established using stop watch time studies or other work measurement methods. (h) All... Regulations Relating to Labor (Continued) WAGE AND HOUR DIVISION, DEPARTMENT OF LABOR REGULATIONS EMPLOYMENT... section 12. All homeworkers will be instructed not to permit minors to work in violation of such...

Stress, social support, and stopping smoking after myocardial infarction in England.

PubMed Central

Greenwood, D C; Muir, K R; Packham, C J; Madeley, R J

1995-01-01

STUDY OBJECTIVE--To examine the effect on mortality of stopping smoking after myocardial infarction and the psychosocial factors that influence the decision to stop. DESIGN--Analysis of smokers in a large prospective study. Self completed questionnaires provided information on psychosocial factors. SETTING--Coronary care units at six English hospitals participating in a multicentre clinical trial. SUBJECTS--These comprised consenting myocardial infarction survivors who had been identified as smokers and who completed questionnaires within seven days of infarct at six hospitals participating in the Anglo-Scandinavian study of early thrombolysis. The 532 patients identified have been followed for over five and a half years. The main outcome measure was five year all cause mortality. MAIN RESULTS--Smokers who stopped within one month showed significantly reduced mortality compared with those who persisted, adjusting for other prognostic indicators (odds ratio 0.56, 95% confidence interval 0.33, 0.98). Overall, 74% stopped smoking. Being married, low life stress levels before infarct, and higher social class were associated with stopping smoking but the differentials were small. Of the clinical variables, a final diagnosis of definite myocardial infarction was associated with stopping smoking. All associations remained after multiple logistic regression. CONCLUSION--Smoking cessation can halve the smokers' odds of dying after myocardial infarction and psychosocial factors play a small but important role in the important decision to stop smoking. Health professionals should continue to stress the importance of stopping smoking to all patients as there is little evidence to support specific directing of advice to relatively "stress or "socially isolated" groups. PMID:8596092

A NIN-LIKE PROTEIN mediates nitrate-induced control of root nodule symbiosis in Lotus japonicus.

PubMed

Nishida, Hanna; Tanaka, Sachiko; Handa, Yoshihiro; Ito, Momoyo; Sakamoto, Yuki; Matsunaga, Sachihiro; Betsuyaku, Shigeyuki; Miura, Kenji; Soyano, Takashi; Kawaguchi, Masayoshi; Suzaki, Takuya

2018-02-05

Legumes and rhizobia establish symbiosis in root nodules. To balance the gains and costs associated with the symbiosis, plants have developed two strategies for adapting to nitrogen availability in the soil: plants can regulate nodule number and/or stop the development or function of nodules. Although the former is accounted for by autoregulation of nodulation, a form of systemic long-range signaling, the latter strategy remains largely enigmatic. Here, we show that the Lotus japonicus NITRATE UNRESPONSIVE SYMBIOSIS 1 (NRSYM1) gene encoding a NIN-LIKE PROTEIN transcription factor acts as a key regulator in the nitrate-induced pleiotropic control of root nodule symbiosis. NRSYM1 accumulates in the nucleus in response to nitrate and directly regulates the production of CLE-RS2, a root-derived mobile peptide that acts as a negative regulator of nodule number. Our data provide the genetic basis for how plants respond to the nitrogen environment and control symbiosis to achieve proper plant growth.

Who stops selling? A systematic analysis of ex-tobacco retailers.

PubMed

Feletto, Eleonora; Burton, Suzan; Williams, Kelly; Fry, Rae; Sutton, Clare; Bagus, Lachlan; Egger, Sam

2016-03-09

There is evidence that wide distribution of cigarettes contributes to smoking, and multiple commentators have called for a review of tobacco retailing. This study analyses retailers who stop selling cigarettes, why they do so, and discusses the implications for tobacco control. An audit of tobacco retailers in the Australian state of NSW was used to identify retailers who had stopped selling tobacco, and they were then compared with current retailers to determine how many, and what types of outlets stop selling tobacco. Attempts were made to contact and interview all former tobacco retailers identified in three audited regions. In-depth interviews were conducted with 13 ex-tobacco retailers, or 31% of the subset of ex-tobacco retailers. Low-volume outlet types were over-represented as a proportion of retailers exiting the market, and some had resumed selling within 18 months of the audit. Low profits were often cited as a contributor to stopping; however, in all but one case, the decision to stop selling was also influenced by a significant change in business circumstances-either legislative or other business changes. Few retailers stop selling tobacco while continuing in the same business, and those who stop disproportionately represent retailer types with low sales volume. The results suggest that legislative changes provide a window where retailers could be prompted to exit the market. 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/

The 5-HT1A/1B-receptor agonist eltoprazine increases both catecholamine release in the prefrontal cortex and dopamine release in the nucleus accumbens and decreases motivation for reward and "waiting" impulsivity, but increases "stopping" impulsivity.

PubMed

Korte, S Mechiel; Prins, Jolanda; Van den Bergh, Filip S; Oosting, Ronald S; Dupree, Rudy; Korte-Bouws, Gerdien A H; Westphal, Koen G C; Olivier, Berend; Denys, Damiaan A; Garland, Alexis; Güntürkün, Onur

2017-01-05

The 5-HT 1A/1B -receptor agonist eltoprazine has a behavioral drug signature that resembles that of a variety of psychostimulant drugs, despite the differences in receptor binding profile. These psychostimulants are effective in treating impulsivity disorders, most likely because they increase norepinephrine (NE) and dopamine (DA) levels in the prefrontal cortex. Both amphetamine and methylphenidate, however, also increase dopamine levels in the nucleus accumbens (NAc), which has a significant role in motivation, pleasure, and reward. How eltoprazine affects monoamine release in the medial prefrontal cortex (mPFC), the orbitofrontal cortex (OFC), and the NAc is unknown. It is also unknown whether eltoprazine affects different forms of impulsivity and brain reward mechanisms. Therefore, in the present study, we investigate the effects of eltoprazine in rats in the following sequence: 1) the activity of the monoaminergic systems using in vivo microdialysis, 2) motivation for reward measured using the intracranial self-stimulation (ICSS) procedure, and finally, 3) "waiting" impulsivity in the delay-aversion task, and the "stopping" impulsivity in the stop-signal task. The microdialysis studies clearly showed that eltoprazine increased DA and NE release in both the mPFC and OFC, but only increased DA concentration in the NAc. In contrast, eltoprazine decreased 5-HT release in the mPFC and NAc (undetectable in the OFC). Remarkably, eltoprazine decreased impulsive choice, but increased impulsive action. Furthermore, brain stimulation was less rewarding following eltoprazine treatment. These results further support the long-standing hypothesis that "waiting" and "stopping" impulsivity are regulated by distinct neural circuits, because 5-HT 1A/1B -receptor activation decreases impulsive choice, but increases impulsive action. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of awareness in head-neck acceleration in low velocity rear-end impacts.

PubMed

Kumar, S; Narayan, Y; Amell, T

2000-03-01

Fourteen normal healthy seated and restrained young adults were delivered rear-end impacts of four intensities of acceleration. The chair was delivered a regulated and controlled pneumatic blow using a 30 cm cylinder to cause an acceleration of 0.5, 0.9, 1.1 and 1.4g. The accelerated chair was stopped suddenly by impacting the stopper at the other end of the 2 m long friction reduced track. In one set of trials, subjects were informed about the impending impact and in the other they were blindfolded and provided with loud auditory input to eliminate cues of the impact. The accelerations of the chair, shoulder and head of the participating subjects were measured triaxially and compared between levels of acceleration and expectation. The multiple analyses of variance revealed that the peak acceleration was significantly affected by the gender (P < 0.01), intensity of impact (P < 0.001), and expectation (P < 0.0001). The accelerations were significantly different in different axes (P < 0.001). A significant two-way interaction between acceleration and expectation (P < 0.03), and expectation and axes of acceleration (P < 0.02) would imply that awareness of the impending impact serves to significantly reduce the level of accelerations of head and neck.

Test-Retest Reliability of Measures Commonly Used to Measure Striatal Dysfunction across Multiple Testing Sessions: A Longitudinal Study.

PubMed

Palmer, Clare E; Langbehn, Douglas; Tabrizi, Sarah J; Papoutsi, Marina

2017-01-01

Cognitive impairment is common amongst many neurodegenerative movement disorders such as Huntington's disease (HD) and Parkinson's disease (PD) across multiple domains. There are many tasks available to assess different aspects of this dysfunction, however, it is imperative that these show high test-retest reliability if they are to be used to track disease progression or response to treatment in patient populations. Moreover, in order to ensure effects of practice across testing sessions are not misconstrued as clinical improvement in clinical trials, tasks which are particularly vulnerable to practice effects need to be highlighted. In this study we evaluated test-retest reliability in mean performance across three testing sessions of four tasks that are commonly used to measure cognitive dysfunction associated with striatal impairment: a combined Simon Stop-Signal Task; a modified emotion recognition task; a circle tracing task; and the trail making task. Practice effects were seen between sessions 1 and 2 across all tasks for the majority of dependent variables, particularly reaction time variables; some, but not all, diminished in the third session. Good test-retest reliability across all sessions was seen for the emotion recognition, circle tracing, and trail making test. The Simon interference effect and stop-signal reaction time (SSRT) from the combined-Simon-Stop-Signal task showed moderate test-retest reliability, however, the combined SSRT interference effect showed poor test-retest reliability. Our results emphasize the need to use control groups when tracking clinical progression or use pre-baseline training on tasks susceptible to practice effects.

48 CFR 22.503 - Policy.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Policy. 22.503 Section 22.503 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SOCIOECONOMIC PROGRAMS... require multiple construction contractors and/or subcontractors employing workers in multiple crafts or...

Identification of Novel Growth Regulators in Plant Populations Expressing Random Peptides1[OPEN

PubMed Central

Bao, Zhilong; Clancy, Maureen A.

2017-01-01

The use of chemical genomics approaches allows the identification of small molecules that integrate into biological systems, thereby changing discrete processes that influence growth, development, or metabolism. Libraries of chemicals are applied to living systems, and changes in phenotype are observed, potentially leading to the identification of new growth regulators. This work describes an approach that is the nexus of chemical genomics and synthetic biology. Here, each plant in an extensive population synthesizes a unique small peptide arising from a transgene composed of a randomized nucleic acid sequence core flanked by translational start, stop, and cysteine-encoding (for disulfide cyclization) sequences. Ten and 16 amino acid sequences, bearing a core of six and 12 random amino acids, have been synthesized in Arabidopsis (Arabidopsis thaliana) plants. Populations were screened for phenotypes from the seedling stage through senescence. Dozens of phenotypes were observed in over 2,000 plants analyzed. Ten conspicuous phenotypes were verified through separate transformation and analysis of multiple independent lines. The results indicate that these populations contain sequences that often influence discrete aspects of plant biology. Novel peptides that affect photosynthesis, flowering, and red light response are described. The challenge now is to identify the mechanistic integrations of these peptides into biochemical processes. These populations serve as a new tool to identify small molecules that modulate discrete plant functions that could be produced later in transgenic plants or potentially applied exogenously to impart their effects. These findings could usher in a new generation of agricultural growth regulators, herbicides, or defense compounds. PMID:28807931

Polyarteritis nodosa: MDCT as a 'One-Stop Shop' Modality for Whole-Body Arterial Evaluation

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

Tsai, W.-L.; Tsai, I-C.; Lee Tain, E-mail: s841082@ym.edu.t

Polyarteritis nodosa is a rare disease, which is characterized by aneurysm formation and occlusion in the arteries of multiple systems. Due to its extensive involvement, whole-body evaluation is necessary for diagnosis and treatment monitoring. We report a case of polyarteritis nodosa using multidetector-row computed tomography (MDCT) as a 'one-stop shop' modality for whole-body arterial evaluation. With precise protocol design, MDCT can be used as a reliable noninvasive modality providing comprehensive whole-body arterial evaluation.

77 FR 12514 - Drawbridge Operation Regulation; Hood Canal, WA

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-01

... of 45 minutes during and after openings of the draw span. The stopped road traffic on this two-lane... hundred feet unless the maximum opening of 600 feet is requested. The current regulations remain in effect... three navigational openings for vessel passage, the movable floating span, subject to this proposed...

75 FR 17120 - Notice of Request for an Extension of a Currently Approved Information Collection

Federal Register 2010, 2011, 2012, 2013, 2014

2010-04-05

... approved information collection in support of the Regulations for Voluntary Grading of Poultry Products and....regulations.gov or to David Bowden, Jr., Chief, Standards, Promotion, & Technology Branch; Poultry Programs... Branch; Poultry Programs, AMS, U.S. Department of Agriculture; 1400 Independence Avenue, SW., Stop 0259...

29 CFR 1926.856 - Removal of walls, floors, and material with equipment.

Code of Federal Regulations, 2010 CFR

2010-07-01

....856 Section 1926.856 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Demolition § 1926... the imposed load. (b) Floor openings shall have curbs or stop-logs to prevent equipment from running...

29 CFR 1926.856 - Removal of walls, floors, and material with equipment.

Code of Federal Regulations, 2011 CFR

2011-07-01

....856 Section 1926.856 Labor Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Demolition § 1926... the imposed load. (b) Floor openings shall have curbs or stop-logs to prevent equipment from running...

The challenge of rapid diagnosis in oncology: Diagnostic accuracy and cost analysis of a large-scale one-stop breast clinic.

PubMed

Delaloge, Suzette; Bonastre, Julia; Borget, Isabelle; Garbay, Jean-Rémi; Fontenay, Rachel; Boinon, Diane; Saghatchian, Mahasti; Mathieu, Marie-Christine; Mazouni, Chafika; Rivera, Sofia; Uzan, Catherine; André, Fabrice; Dromain, Clarisse; Boyer, Bruno; Pistilli, Barbara; Azoulay, Sandy; Rimareix, Françoise; Bayou, El-Hadi; Sarfati, Benjamin; Caron, Hélène; Ghouadni, Amal; Leymarie, Nicolas; Canale, Sandra; Mons, Muriel; Arfi-Rouche, Julia; Arnedos, Monica; Suciu, Voichita; Vielh, Philippe; Balleyguier, Corinne

2016-10-01

Rapid diagnosis is a key issue in modern oncology, for which one-stop breast clinics are a model. We aimed to assess the diagnosis accuracy and procedure costs of a large-scale one-stop breast clinic. A total of 10,602 individuals with suspect breast lesions attended the Gustave Roussy's regional one-stop breast clinic between 2004 and 2012. The multidisciplinary clinic uses multimodal imaging together with ultrasonography-guided fine needle aspiration for masses and ultrasonography-guided and stereotactic biopsies as needed. Diagnostic accuracy was assessed by comparing one-stop diagnosis to the consolidated diagnosis obtained after surgery or biopsy or long-term monitoring. The medical cost per patient of the care pathway was assessed from patient-level data collected prospectively. Sixty-nine percent of the patients had masses, while 31% had micro-calcifications or other non-mass lesions. In 75% of the cases (87% of masses), an exact diagnosis could be given on the same day. In the base-case analysis (i.e. considering only benign and malignant lesions at one-stop and at consolidated diagnoses), the sensitivity of the one-stop clinic was 98.4%, specificity 99.8%, positive and negative predictive values 99.7% and 99.0%. In the sensitivity analysis (reclassification of suspect, atypical and undetermined lesions), diagnostic sensitivity varied from 90.3% to 98.5% and specificity varied from 94.3% to 99.8%. The mean medical cost per patient of one-stop diagnostic procedure was €420. One-stop breast clinic can provide timely and cost-efficient delivery of highly accurate diagnoses and serve as models of care for multiple settings, including rapid screening-linked diagnosis. Copyright © 2016 Elsevier Ltd. All rights reserved.

Incorporating body-type (apple vs. pear) in STOP-BANG questionnaire improves its validity to detect OSA.

PubMed

Sangkum, Lisa; Klair, Ikrita; Limsuwat, Chok; Bent, Sabrina; Myers, Leann; Thammasitboon, Supat

2017-09-01

The aim of this study is to evaluate whether adding the item of "apple body type" to the STOP-BANG questionnaire enhances diagnostic performance of the questionnaire for detecting obstructive sleep apnea (OSA). Cross-sectional study. Sleep center setting. Two hundred and eight subjects who were referred for an evaluation of possible OSA at Tulane Comprehensive Sleep Center. The exclusion criteria were age<18years old, incomplete or absent questionnaire, incomplete body type identification, polysomnography (PSG) refusal, and pregnant women. STOP-BANG items and body type data were collected on the initial clinic visit. An overnight PSG was performed on every participant. Descriptive analyses of the demographic data and PSG variables were performed. The predictive parameters of STOP and STOP-BANG without and with body type score (STOP-Apple and STOPBANG-Apple) were compared. The STOP questionnaire's sensitivity/specificity/positive likelihood ratio (+LR) (cut-off=2) was 96%/11%/1.1, respectively whereas the STOP-Apple questionnaire (cut-off=3) was 88%/39%/1.5. The STOP-BANG's sensitivity/specificity/+LR (cut-off=3) was 96%/19%/1.2, respectively whereas the STOP-BANG-Apple questionnaire (cut-off=4) was 90%/39%/1.5. The area under the Receiver Operating Characteristic (ROC) curve of STOP-Apple was comparable to the STOP-BANG (P=0.25). The addition of the apple body type item to the STOP-BANG questionnaire in participants with a score≥3 led to increased specificity (67.4%), increased the odds ratio of having OSA of 2.5 (95% CI, 1.2-5.3) and odds ratio of having moderate-severe OSA of 4.7 (95% CI, 2.5-8.7). In the sleep center setting, adding the body type item to the STOP-BANG questionnaire improves not only clinical prediction for PSG confirmed OSA but also predicts moderate to severe of OSA. Published by Elsevier Inc.

Development of a New Method for Platelet Function Test and Its Shearing Condition in Microfludic System

NASA Astrophysics Data System (ADS)

Lee, Hoyoon; Kim, Gyehyu; Choi, Seawhan; Shin, Sehyun; Korea University Department of Mechanical Engineering Team

2015-11-01

Platelet is a crucial blood cell on hemostasis. As platelet exposed to high shear stress, it can be activated showing morphological and functional changes to stop bleeding. When platelet is abnormal, there is high risk of cardiovascular diseases. Thus, quick and precise assay for platelet function is important in clinical treatment. In this study, we design a microfluidic system, which can test platelet function exposed with the stimulation of shear and agonists. The microfluidic system consists of three parts: 1) a shear mechanism with rotating stirrer; 2) multiple microchannels to flow samples and to stop; 3) camera-interfaced migration distance(MD) analyzing system. When sheared blood is driven by pressure through the microchannel, shear-activated platelets adhere to a collagen-coated surface, causing blood flow to significantly slow and eventually stop. As the micro-stirrer speed increases, MD decreases exponentially at first, but it increases beyond a critical rpm after all. These results are coincident with data measured by FACS flowcytometry. These results imply that the present system could quantitatively measure the degree of activation, aggregation and adhesion of platelets and that blood MD is potent index for measuring the shear-dependence of platelet function.

Interaction of dihydrofolate reductase with methotrexate: Ensemble and single-molecule kinetics

NASA Astrophysics Data System (ADS)

Rajagopalan, P. T. Ravi; Zhang, Zhiquan; McCourt, Lynn; Dwyer, Mary; Benkovic, Stephen J.; Hammes, Gordon G.

2002-10-01

The thermodynamics and kinetics of the interaction of dihydrofolate reductase (DHFR) with methotrexate have been studied by using fluorescence, stopped-flow, and single-molecule methods. DHFR was modified to permit the covalent addition of a fluorescent molecule, Alexa 488, and a biotin at the N terminus of the molecule. The fluorescent molecule was placed on a protein loop that closes over methotrexate when binding occurs, thus causing a quenching of the fluorescence. The biotin was used to attach the enzyme in an active form to a glass surface for single-molecule studies. The equilibrium dissociation constant for the binding of methotrexate to the enzyme is 9.5 nM. The stopped-flow studies revealed that methotrexate binds to two different conformations of the enzyme, and the association and dissociation rate constants were determined. The single-molecule investigation revealed a conformational change in the enzyme-methotrexate complex that was not observed in the stopped-flow studies. The ensemble averaged rate constants for this conformation change in both directions is about 2-4 s1 and is attributed to the opening and closing of the enzyme loop over the bound methotrexate. Thus the mechanism of methotrexate binding to DHFR involves multiple steps and protein conformational changes.

Automatic controls and regulators: A compilation

NASA Technical Reports Server (NTRS)

1974-01-01

Devices, methods, and techniques for control and regulation of the mechanical/physical functions involved in implementing the space program are discussed. Section one deals with automatic controls considered to be, essentially, start-stop operations or those holding the activity in a desired constraint. Devices that may be used to regulate activities within desired ranges or subject them to predetermined changes are dealt with in section two.

College Departure: Exploring Student Aid Effects on Multiple Mobility Patterns from Four-Year Institutions

ERIC Educational Resources Information Center

Kim, Dongbin; Saatcioglu, Argun; Neufeld, Amy

2012-01-01

College departure involves multiple mobility patterns that include lateral transfer (from a four-year to another four-year institution), reverse transfer (from a four-year to a two-year institution), and stop out (taking time out of higher education altogether). This study addresses how financial aid influences the likelihood of such mobility…

Defense Transportation Regulation Part 2, Cargo Movement.

DTIC Science & Technology

1998-08-01

Stop-Off Unloading Point (DD Form 1371) 202-18 202-7 Route Order Amendment (DD Form 2017 ) 202-19 204-1 Hazardous Materials Classification...DRO/IRO/SRO amendments will be submitted to the appropriate MTMC routing authority or theater CINC using DD Form 2017 , Route Order Amendment...Figure 202-5. 7. An example of a DD Form 2017 , Route Order Amendment, is provided in Figure 202.7. D. EXCEPTION Exceptions to assignment of routing

Increasing motorist compliance and caution at stop signs.

PubMed Central

Van Houten, R; Retting, R A

2001-01-01

This study evaluated strategies to improve motorist compliance and caution at three stop-sign-controlled intersections with a history of motor vehicle crashes. The primary intervention was a light-emitting diode (LED) sign that featured animated eyes scanning left and right to prompt drivers to look left and right for approaching traffic. Data were scored from videotape on the percentage of drivers coming to a complete stop and the percentage of drivers looking right before entering the intersection. Observational data were collected on the percentage of right-angle conflicts (defined as braking suddenly or swerving from the path to avoid an intersection crash). The introduction of the LED sign according to a multiple baseline across the three intersections was associated with an increase in the percentage of vehicles coming to a complete stop at all three intersections and a small increase in the percentage of drivers looking right before entering the intersections. Conflicts between vehicles on the major and minor road were also reduced following the introduction of the animated eyes prompt. PMID:11421311

Adiabatic perturbation theory of electronic stopping in insulators

DOE PAGES

Horsfield, Andrew P.; Lim, Anthony; Foulkes, W. M. C.; ...

2016-06-02

A model able to explain the complicated structure of electronic stopping at low velocities in insulating materials is presented. It is shown to be in good agreement with results obtained from time-dependent density-functional theory for the stopping of a channeling Si atom in a Si crystal. If we define the repeat frequency f=v/λ, where λ is the periodic repeat length of the crystal along the direction the channeling atom is traveling, and v is the velocity of the channeling atom, we find that electrons experience a perturbing force that varies in time at integer multiples l of f. This enablesmore » electronic excitations at low atom velocity, but their contributions diminish rapidly with increasing values of l. The expressions for stopping power are derived using adiabatic perturbation theory for many-electron systems, and they are then specialized to the case of independent electrons. Lastly, a simple model for the nonadiabatic matrix elements is described, along with the procedure for determining its parameters.« less

Fresh WNT into the regulation of mitosis.

PubMed

Stolz, Ailine; Bastians, Holger

2015-01-01

Canonical Wnt signaling triggering β-catenin-dependent gene expression contributes to cell cycle progression, in particular at the G1/S transition. Recently, however, it became clear that the cell cycle can also feed back on Wnt signaling at the G2/M transition. This is illustrated by the fact that mitosis-specific cyclin-dependent kinases can phosphorylate the Wnt co-receptor LRP6 to prime the pathway for incoming Wnt signals when cells enter mitosis. In addition, there is accumulating evidence that various Wnt pathway components might exert additional, Wnt-independent functions that are important for proper regulation of mitosis. The importance of Wnt pathways during mitosis was most recently enforced by the discovery of Wnt signaling contributing to the stabilization of proteins other than β-catenin, specifically at G2/M and during mitosis. This Wnt-mediated stabilization of proteins, now referred to as Wnt/STOP, might on one hand contribute to maintaining a critical cell size required for cell division and, on the other hand, for the faithful execution of mitosis itself. In fact, most recently we have shown that Wnt/STOP is required for ensuring proper microtubule dynamics within mitotic spindles, which is pivotal for accurate chromosome segregation and for the maintenance of euploidy.

SZGR 2.0: a one-stop shop of schizophrenia candidate genes.

PubMed

Jia, Peilin; Han, Guangchun; Zhao, Junfei; Lu, Pinyi; Zhao, Zhongming

2017-01-04

SZGR 2.0 is a comprehensive resource of candidate variants and genes for schizophrenia, covering genetic, epigenetic, transcriptomic, translational and many other types of evidence. By systematic review and curation of multiple lines of evidence, we included almost all variants and genes that have ever been reported to be associated with schizophrenia. In particular, we collected ∼4200 common variants reported in genome-wide association studies, ∼1000 de novo mutations discovered by large-scale sequencing of family samples, 215 genes spanning rare and replication copy number variations, 99 genes overlapping with linkage regions, 240 differentially expressed genes, 4651 differentially methylated genes and 49 genes as antipsychotic drug targets. To facilitate interpretation, we included various functional annotation data, especially brain eQTL, methylation QTL, brain expression featured in deep categorization of brain areas and developmental stages and brain-specific promoter and enhancer annotations. Furthermore, we conducted cross-study, cross-data type and integrative analyses of the multidimensional data deposited in SZGR 2.0, and made the data and results available through a user-friendly interface. In summary, SZGR 2.0 provides a one-stop shop of schizophrenia variants and genes and their function and regulation, providing an important resource in the schizophrenia and other mental disease community. SZGR 2.0 is available at https://bioinfo.uth.edu/SZGR/. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Personal Space Regulation in Williams Syndrome: The Effect of Familiarity

ERIC Educational Resources Information Center

Lough, Emma; Flynn, Emma; Riby, Deborah M.

2016-01-01

Personal space refers to a protective barrier that we strive to maintain around our body. We examined personal space regulation in young people with Williams syndrome (WS) and their typically developing, chronological age-matched peers using a parent report questionnaire and a stop-distance paradigm. Individuals with WS were reported by their…

How to Stop and Change a Response: The Role of Goal Activation in Multitasking

ERIC Educational Resources Information Center

Verbruggen, Frederick; Schneider, Darryl W.; Logan, Gordon D.

2008-01-01

Multitasking was studied in the stop-change paradigm, in which the response for a primary GO1 task had to be stopped and replaced by a response for a secondary GO2 task on some trials. In 2 experiments, the delay between the stop signal and the change signal was manipulated to determine which task goals (GO1, GO2, or STOP) were involved in…

Succinate Dehydrogenase (SDH) D Subunit (SDHD) Inactivation in a Growth-Hormone-Producing Pituitary Tumor: A New Association for SDH?

PubMed Central

Xekouki, Paraskevi; Pacak, Karel; Almeida, Madson; Wassif, Christopher A.; Rustin, Pierre; Nesterova, Maria; de la Luz Sierra, Maria; Matro, Joey; Ball, Evan; Azevedo, Monalisa; Horvath, Anelia; Lyssikatos, Charalampos; Quezado, Martha; Patronas, Nicholas; Ferrando, Barbara; Pasini, Barbara; Lytras, Aristides; Tolis, George

2012-01-01

Background: Mutations in the subunits B, C, and D of succinate dehydrogenase (SDH) mitochondrial complex II have been associated with the development of paragangliomas (PGL), gastrointestinal stromal tumors, papillary thyroid and renal carcinoma (SDHB), and testicular seminoma (SDHD). Aim: Our aim was to examine the possible causative link between SDHD inactivation and somatotropinoma. Patients and Methods: A 37-yr-old male presented with acromegaly and hypertension. Other family members were found with PGL. Elevated plasma and urinary levels of catecholamines led to the identification of multiple PGL in the proband in the neck, thorax, and abdomen. Adrenalectomy was performed for bilateral pheochromocytomas (PHEO). A GH-secreting macroadenoma was also found and partially removed via transsphenoidal surgery (TTS). Genetic analysis revealed a novel SDHD mutation (c.298_301delACTC), leading to a frame shift and a premature stop codon at position 133 of the protein. Loss of heterozygosity for the SDHD genetic locus was shown in the GH-secreting adenoma. Down-regulation of SDHD protein in the GH-secreting adenoma by immunoblotting and immunohistochemistry was found. A literature search identified other cases of multiple PGL and/or PHEO in association with pituitary tumors. Conclusion: We describe the first kindred with a germline SDHD pathogenic mutation, inherited PGL, and acromegaly due to a GH-producing pituitary adenoma. SDHD loss of heterozygosity, down-regulation of protein in the GH-secreting adenoma, and decreased SDH enzymatic activity supports SDHD's involvement in the pituitary tumor formation in this patient. Older cases of multiple PGL and PHEO and pituitary tumors in the literature support a possible association between SDH defects and pituitary tumorigenesis. PMID:22170724

Collective Deceleration: Toward a Compact Beam Dump

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

Wu, H.-C.; /Munich, Max Planck Inst. Quantenopt.; Tajima, T.

With the increasing development of laser accelerators, the electron energy is already beyond GeV and even higher in near future. Conventional beam dump based on ionization or radiation loss mechanism is cumbersome and costly, also has radiological hazards. We revisit the stopping power of high-energy charged particles in matter and discuss the associated problem of beam dump from the point of view of collective deceleration. The collective stopping length in an ionized gas can be several orders of magnitude shorter than the Bethe-Bloch and multiple electromagnetic cascades stopping length in solid. At the mean time, the tenuous density of themore » gas makes the radioactivation negligible. Such a compact and non-radioactivating beam dump works well for short and dense bunches, which is typically generated from laser wakefield accelerator.« less

Circumvention of Mcl-1-dependent drug resistance by simultaneous Chk1 and MEK1/2 inhibition in human multiple myeloma cells.

PubMed

Pei, Xin-Yan; Dai, Yun; Felthousen, Jessica; Chen, Shuang; Takabatake, Yukie; Zhou, Liang; Youssefian, Leena E; Sanderson, Michael W; Bodie, Wesley W; Kramer, Lora B; Orlowski, Robert Z; Grant, Steven

2014-01-01

The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM.

Circumvention of Mcl-1-Dependent Drug Resistance by Simultaneous Chk1 and MEK1/2 Inhibition in Human Multiple Myeloma Cells

PubMed Central

Pei, Xin-Yan; Dai, Yun; Felthousen, Jessica; Chen, Shuang; Takabatake, Yukie; Zhou, Liang; Youssefian, Leena E.; Sanderson, Michael W.; Bodie, Wesley W.; Kramer, Lora B.; Orlowski, Robert Z.; Grant, Steven

2014-01-01

The anti-apoptotic protein Mcl-1 plays a major role in multiple myeloma (MM) cell survival as well as bortezomib- and microenvironmental forms of drug resistance in this disease. Consequently, there is a critical need for strategies capable of targeting Mcl-1-dependent drug resistance in MM. The present results indicate that a regimen combining Chk1 with MEK1/2 inhibitors effectively kills cells displaying multiple forms of drug resistance stemming from Mcl-1 up-regulation in association with direct transcriptional Mcl-1 down-regulation and indirect disabling of Mcl-1 anti-apoptotic function through Bim up-regulation and increased Bim/Mcl-1 binding. These actions release Bak from Mcl-1, accompanied by Bak/Bax activation. Analogous events were observed in both drug-naïve and acquired bortezomib-resistant MM cells displaying increased Mcl-1 but diminished Bim expression, or cells ectopically expressing Mcl-1. Moreover, concomitant Chk1 and MEK1/2 inhibition blocked Mcl-1 up-regulation induced by IL-6/IGF-1 or co-culture with stromal cells, effectively overcoming microenvironment-related drug resistance. Finally, this regimen down-regulated Mcl-1 and robustly killed primary CD138+ MM cells, but not normal hematopoietic cells. Together, these findings provide novel evidence that this targeted combination strategy could be effective in the setting of multiple forms of Mcl-1-related drug resistance in MM. PMID:24594907

29 CFR 1926.1428 - Signal person qualifications.

Code of Federal Regulations, 2011 CFR

2011-07-01

..., DEPARTMENT OF LABOR (CONTINUED) SAFETY AND HEALTH REGULATIONS FOR CONSTRUCTION Cranes and Derricks in... operation and limitations, including the crane dynamics involved in swinging and stopping loads and boom...

Nucleo-cytoplasmic shuttling dynamics of the transcriptional regulators XYR1 and CRE1 under conditions of cellulase and xylanase gene expression in Trichoderma reesei

PubMed Central

Lichius, Alexander; Seidl-Seiboth, Verena; Seiboth, Bernhard; Kubicek, Christian P

2014-01-01

Trichoderma reesei is a model for investigating the regulation of (hemi-)cellulase gene expression. Cellulases are formed adaptively, and the transcriptional activator XYR1 and the carbon catabolite repressor CRE1 are main regulators of their expression. We quantified the nucleo-cytoplasmic shuttling dynamics of GFP-fusion proteins of both transcription factors under cellulase and xylanase inducing conditions, and correlated their nuclear presence/absence with transcriptional changes. We also compared their subcellular localization in conidial germlings and mature hyphae. We show that cellulase gene expression requires de novo biosynthesis of XYR1 and its simultaneous nuclear import, whereas carbon catabolite repression is regulated through preformed CRE1 imported from the cytoplasmic pool. Termination of induction immediately stopped cellulase gene transcription and was accompanied by rapid nuclear degradation of XYR1. In contrast, nuclear CRE1 rapidly decreased upon glucose depletion, and became recycled into the cytoplasm. In mature hyphae, nuclei containing activated XYR1 were concentrated in the colony center, indicating that this is the main region of XYR1 synthesis and cellulase transcription. CRE1 was found to be evenly distributed throughout the entire mycelium. Taken together, our data revealed novel aspects of the dynamic shuttling and spatial bias of the major regulator of (hemi-)cellulase gene expression, XYR1, in T. reesei. PMID:25302561

Dissociable Roles of Right Inferior Frontal Cortex and Anterior Insula in Inhibitory Control: Evidence from Intrinsic and Task-Related Functional Parcellation, Connectivity, and Response Profile Analyses across Multiple Datasets

PubMed Central

Ryali, Srikanth; Chen, Tianwen; Li, Chiang-Shan R.

2014-01-01

The right inferior frontal cortex (rIFC) and the right anterior insula (rAI) have been implicated consistently in inhibitory control, but their differential roles are poorly understood. Here we use multiple quantitative techniques to dissociate the functional organization and roles of the rAI and rIFC. We first conducted a meta-analysis of 70 published inhibitory control studies to generate a commonly activated right fronto-opercular cortex volume of interest (VOI). We then segmented this VOI using two types of features: (1) intrinsic brain activity; and (2) stop-signal task-evoked hemodynamic response profiles. In both cases, segmentation algorithms identified two stable and distinct clusters encompassing the rAI and rIFC. The rAI and rIFC clusters exhibited several distinct functional characteristics. First, the rAI showed stronger intrinsic and task-evoked functional connectivity with the anterior cingulate cortex, whereas the rIFC had stronger intrinsic and task-evoked functional connectivity with dorsomedial prefrontal and lateral fronto-parietal cortices. Second, the rAI showed greater activation than the rIFC during Unsuccessful, but not Successful, Stop trials, and multivoxel response profiles in the rAI, but not the rIFC, accurately differentiated between Successful and Unsuccessful Stop trials. Third, activation in the rIFC, but not rAI, predicted individual differences in inhibitory control abilities. Crucially, these findings were replicated in two independent cohorts of human participants. Together, our findings provide novel quantitative evidence for the dissociable roles of the rAI and rIFC in inhibitory control. We suggest that the rAI is particularly important for detecting behaviorally salient events, whereas the rIFC is more involved in implementing inhibitory control. PMID:25355218

Corpus Callosum Function in Verbal Dichotic Listening: Inferences from a Longitudinal Follow-Up of Relapsing-Remitting Multiple Sclerosis Patients

ERIC Educational Resources Information Center

Gadea, Marien; Marti-Bonmati, Luis; Arana, Estanislao; Espert, Raul; Salvador, Alicia; Casanova, Bonaventura

2009-01-01

This study conducted a follow-up of 13 early-onset slightly disabled Relapsing-Remitting Multiple Sclerosis (RRMS) patients within an year, evaluating both CC area measurements in a midsagittal Magnetic Resonance (MR) image, and Dichotic Listening (DL) testing with stop consonant vowel (C-V) syllables. Patients showed a significant progressive…

Adipose, Bone and Myeloma: Contributions from the Microenvironment

PubMed Central

McDonald, Michelle; Fairfield, Heather; Falank, Carolyne; Reagan, Michaela R.

2017-01-01

Researchers globally are working towards finding a cure for multiple myeloma (MM), a destructive blood cancer diagnosed yearly in ~750,000 people worldwide [1]. Although MM targets multiple organ systems, it is the devastating skeletal destruction experienced by over 90% of patients that often most severely impacts patient morbidity, pain, and quality of life. Preventing bone disease is therefore a priority in MM treatment, and understanding how and why myeloma cells target the bone marrow (BM) is fundamental to this process. This review focuses on a key area of MM research: the contributions of the bone microenvironment to disease origins, progression, and drug resistance. We describe some of the key cell types in the BM niche: osteoclasts, osteoblasts, osteocytes, adipocytes and mesenchymal stem cells. We then focus on how these key cellular players are, or could be, regulating a range of disease-related processes spanning MM growth, drug resistance, and bone disease (including osteolysis, fracture, and hypercalcemia). We summarize the literature regarding MM-bone cell and MM-adipocyte relationships and subsequent phenotypic changes or adaptations in MM cells, with the aim of providing a deeper understanding of how myeloma cells grow in the skeleton to cause bone destruction. We identify avenues and therapies that intervene in these networks to stop tumor growth and/or induce bone regeneration. Overall, we aim to illustrate how novel therapeutic target molecules, proteins, and cellular mediators may offer new avenues to attack this disease while reviewing currently utilized therapies. PMID:27343063

How Do People Stop Non-Suicidal Self-Injury? A Systematic Review.

PubMed

Mummé, Tess Alexandra; Mildred, Helen; Knight, Tess

2017-07-03

The current paper reviews extant quantitative and qualitative literature into how Non-Suicidal Self-Injury cessation occurs, and individuals' experiences of stopping. Specific search criteria utilizing a PRISMA format were used across 5 databases, which resulted in 454 papers being identified. After utilizing exclusion criteria and then review, nine of the 454 papers identified were retained for extensive synthesis and critique. Results from 8 of the identified papers indicated that both intra and inter personal factors can influence self-injury cessation. These include: family support, self-esteem, emotional regulation, and professional help. Only 1 paper articulated a cessation process, describing it as a procedural event of developing interpersonal strength, then implementing alternative coping strategies. Limitations and implications of the studies are reported, concluding that further research is warranted to inform effective prevention and treatment strategies to ameliorate this growing public health concern.

Multiple conversion between the genes encoding bacterial class-I release factors

PubMed Central

Ishikawa, Sohta A.; Kamikawa, Ryoma; Inagaki, Yuji

2015-01-01

Bacteria require two class-I release factors, RF1 and RF2, that recognize stop codons and promote peptide release from the ribosome. RF1 and RF2 were most likely established through gene duplication followed by altering their stop codon specificities in the common ancestor of extant bacteria. This scenario expects that the two RF gene families have taken independent evolutionary trajectories after the ancestral gene duplication event. However, we here report two independent cases of conversion between RF1 and RF2 genes (RF1-RF2 gene conversion), which were severely examined by procedures incorporating the maximum-likelihood phylogenetic method. In both cases, RF1-RF2 gene conversion was predicted to occur in the region encoding nearly entire domain 3, of which functions are common between RF paralogues. Nevertheless, the ‘direction’ of gene conversion appeared to be opposite from one another—from RF2 gene to RF1 gene in one case, while from RF1 gene to RF2 gene in the other. The two cases of RF1-RF2 gene conversion prompt us to propose two novel aspects in the evolution of bacterial class-I release factors: (i) domain 3 is interchangeable between RF paralogues, and (ii) RF1-RF2 gene conversion have occurred frequently in bacterial genome evolution. PMID:26257102

Small firm self-insurance under the Affordable Care Act.

PubMed

Buettgens, Matthew; Blumberg, Linda J

2012-11-01

The Affordable Care Act changes the small-group insurance market substan­tially beginning in 2014, but most changes do not apply to self-insured plans. This exemp­tion provides an opening for small employers with healthier workers to avoid broader sharing of health care risk, isolating higher-cost groups in the fully insured market. Private stop-loss or reinsurance plans can mediate the risk of self-insurance for small employ­ers, facilitating the decision to self-insure. We simulate small-employer coverage decisions under the law and find that low-risk stop-loss policies lead to higher premiums in the fully insured small-group market. Average single premiums would be up to 25 percent higher, if stop-loss insurance with no additional risk to employers than fully insuring is allowed--an option available in most states absent further government action. Regulation of stop-loss at the federal or state level can, however, prevent such adverse selection and increase stabil­ity in small-group insurance coverage.

In line monitoring of the preparation of water-in-oil-in-water (W/O/W) type multiple emulsions via dielectric spectroscopy.

PubMed

Beer, Sebastian; Dobler, Dorota; Gross, Alexander; Ost, Martin; Elseberg, Christiane; Maeder, Ulf; Schmidts, Thomas Michael; Keusgen, Michael; Fiebich, Martin; Runkel, Frank

2013-01-30

Multiple emulsions offer various applications in a wide range of fields such as pharmaceutical, cosmetics and food technology. Two features are known to yield a great influence on multiple emulsion quality and utility as encapsulation efficiency and prolonged stability. To achieve a prolonged stability, the production of the emulsions has to be observed and controlled, preferably in line. In line measurements provide available parameters in a short time frame without the need for the sample to be removed from the process stream, thereby enabling continuous process control. In this study, information about the physical state of multiple emulsions obtained from dielectric spectroscopy (DS) is evaluated for this purpose. Results from dielectric measurements performed in line during the production cycle are compared to theoretically expected results and to well established off line measurements. Thus, a first step to include the production of multiple emulsions into the process analytical technology (PAT) guidelines of the Food and Drug Administration (FDA) is achieved. DS proved to be beneficial in determining the crucial stopping criterion, which is essential in the production of multiple emulsions. The stopping of the process at a less-than-ideal point can severely lower the encapsulation efficiency and the stability, thereby lowering the quality of the emulsion. DS is also expected to provide further information about the multiple emulsion like encapsulation efficiency. Copyright © 2012 Elsevier B.V. All rights reserved.

Cell cycle G2/M arrest through an S phase-dependent mechanism by HIV-1 viral protein R.

PubMed

Li, Ge; Park, Hyeon U; Liang, Dong; Zhao, Richard Y

2010-07-07

Cell cycle G2 arrest induced by HIV-1 Vpr is thought to benefit viral proliferation by providing an optimized cellular environment for viral replication and by skipping host immune responses. Even though Vpr-induced G2 arrest has been studied extensively, how Vpr triggers G2 arrest remains elusive. To examine this initiation event, we measured the Vpr effect over a single cell cycle. We found that even though Vpr stops the cell cycle at the G2/M phase, but the initiation event actually occurs in the S phase of the cell cycle. Specifically, Vpr triggers activation of Chk1 through Ser345 phosphorylation in an S phase-dependent manner. The S phase-dependent requirement of Chk1-Ser345 phosphorylation by Vpr was confirmed by siRNA gene silencing and site-directed mutagenesis. Moreover, downregulation of DNA replication licensing factors Cdt1 by siRNA significantly reduced Vpr-induced Chk1-Ser345 phosphorylation and G2 arrest. Even though hydroxyurea (HU) and ultraviolet light (UV) also induce Chk1-Ser345 phosphorylation in S phase under the same conditions, neither HU nor UV-treated cells were able to pass through S phase, whereas vpr-expressing cells completed S phase and stopped at the G2/M boundary. Furthermore, unlike HU/UV, Vpr promotes Chk1- and proteasome-mediated protein degradations of Cdc25B/C for G2 induction; in contrast, Vpr had little or no effect on Cdc25A protein degradation normally mediated by HU/UV. These data suggest that Vpr induces cell cycle G2 arrest through a unique molecular mechanism that regulates host cell cycle regulation in an S-phase dependent fashion.

Initial Stop Voicing in Bilingual Children With Cochlear Implants and Their Typically Developing Peers With Normal Hearing.

PubMed

Bunta, Ferenc; Goodin-Mayeda, C Elizabeth; Procter, Amanda; Hernandez, Arturo

2016-08-01

This study focuses on stop voicing differentiation in bilingual children with normal hearing (NH) and their bilingual peers with hearing loss who use cochlear implants (CIs). Twenty-two bilingual children participated in our study (11 with NH, M age = 5;1 [years;months], and 11 with CIs, M hearing age = 5;1). The groups were matched on hearing age and a range of demographic variables. Single-word picture elicitation was used with word-initial singleton stop consonants. Repeated measures analyses of variance with three within-subject factors (language, stop voicing, and stop place of articulation) and one between-subjects factor (NH vs. CI user) were conducted with voice onset time and percentage of prevoiced stops as dependent variables. Main effects were statistically significant for language, stop voicing, and stop place of articulation on both voice onset time and prevoicing. There were no significant main effects for NH versus CI groups. Both children with NH and with CIs differentiated stop voicing in their languages and by stop place of articulation. Stop voicing differentiation was commensurate across the groups of children with NH versus CIs. Stop voicing differentiation is accomplished in a similar fashion by bilingual children with NH and CIs, and both groups differentiate stop voicing in a language-specific fashion.

Food-induced brain responses and eating behaviour.

PubMed

Smeets, Paul A M; Charbonnier, Lisette; van Meer, Floor; van der Laan, Laura N; Spetter, Maartje S

2012-11-01

The brain governs food intake behaviour by integrating many different internal and external state and trait-related signals. Understanding how the decisions to start and to stop eating are made is crucial to our understanding of (maladaptive patterns of) eating behaviour. Here, we aim to (1) review the current state of the field of 'nutritional neuroscience' with a focus on the interplay between food-induced brain responses and eating behaviour and (2) highlight research needs and techniques that could be used to address these. The brain responses associated with sensory stimulation (sight, olfaction and taste), gastric distension, gut hormone administration and food consumption are the subject of increasing investigation. Nevertheless, only few studies have examined relations between brain responses and eating behaviour. However, the neural circuits underlying eating behaviour are to a large extent generic, including reward, self-control, learning and decision-making circuitry. These limbic and prefrontal circuits interact with the hypothalamus, a key homeostatic area. Target areas for further elucidating the regulation of food intake are: (eating) habit and food preference formation and modification, the neural correlates of self-control, nutrient sensing and dietary learning, and the regulation of body adiposity. Moreover, to foster significant progress, data from multiple studies need to be integrated. This requires standardisation of (neuroimaging) measures, data sharing and the application and development of existing advanced analysis and modelling techniques to nutritional neuroscience data. In the next 20 years, nutritional neuroscience will have to prove its potential for providing insights that can be used to tackle detrimental eating behaviour.

Multiple origins of the phenol reaction negative phenotype in foxtail millet, Setaria italica (L.) P. Beauv., were caused by independent loss-of-function mutations of the polyphenol oxidase (Si7PPO) gene during domestication.

PubMed

Inoue, Takahiko; Yuo, Takahisa; Ohta, Takeshi; Hitomi, Eriko; Ichitani, Katsuyuki; Kawase, Makoto; Taketa, Shin; Fukunaga, Kenji

2015-08-01

Foxtail millet shows variation in positive phenol color reaction (Phr) and negative Phr in grains, but predominant accessions of this crop are negative reaction type, and the molecular genetic basis of the Phr reaction remains unresolved. In this article, we isolated polyphenol oxidase (PPO) gene responsible for Phr using genome sequence information and investigated molecular genetic basis of negative Phr and crop evolution of foxtail millet. First of all, we searched for PPO gene homologs in a foxtail millet genome database using a rice PPO gene as a query and successfully found three copies of the PPO gene. One of the PPO gene homologs on chromosome 7 showed the highest similarity with PPO genes expressed in hulls (grains) of other cereal species including rice, wheat, and barley and was designated as Si7PPO. Phr phenotypes and Si7PPO genotypes completely co-segregated in a segregating population. We also analyzed the genetic variation conferring negative Phr reaction. Of 480 accessions of the landraces investigated, 87 (18.1 %) showed positive Phr and 393 (81.9 %) showed negative Phr. In the 393 Phr negative accessions, three types of loss-of-function Si7PPO gene were predominant and independently found in various locations. One of them has an SNP in exon 1 resulting in a premature stop codon and was designated as stop codon type, another has an insertion of a transposon (Si7PPO-TE1) in intron 2 and was designated as TE1-insertion type, and the other has a 6-bp duplication in exon 3 resulting in the duplication of 2 amino acids and was designated as 6-bp duplication type. As a rare variant of the stop codon type, one accession additionally has an insertion of a transposon, Si7PPO-TE2, in intron 2 and was designated as "stop codon +TE2 insertion type". The geographical distribution of accessions with positive Phr and those with three major types of negative Phr was also investigated. Accessions with positive Phr were found in subtropical and tropical regions at frequencies of ca. 25-67 % and those with negative Phr were broadly found in Europe and Asia. The stop codon type was found in 285 accessions and was broadly distributed in Europe and Asia, whereas the TE-1 insertion type was found in 99 accessions from Europe and Asia but was not found in India. The 6-bp duplication type was found in only 8 accessions from Nansei Islands (Okinawa Prefecture) of Japan. We also analyzed Phr in the wild ancestor and concluded that the negative Phr type was likely to have originated after domestication of foxtail millet. It was also implied that negative Phr of foxtail millet arose by multiple independent loss of function of PPO gene through dispersal because of some advantages under some environmental conditions and human selection as in rice and barley.

Variable Conductance Heat Pipe Cooling of Stirling Convertor and General Purpose Heat Source

NASA Technical Reports Server (NTRS)

Tarau, Calin; Schwendeman, Carl; Anderson William G.; Cornell, Peggy A.; Schifer, Nicholas A.

2013-01-01

In a Stirling Radioisotope Power System (RPS), heat must be continuously removed from the General Purpose Heat Source (GPHS) modules to maintain the modules and surrounding insulation at acceptable temperatures. The Stirling convertor normally provides this cooling. If the Stirling convertor stops in the current system, the insulation is designed to spoil, preventing damage to the GPHS at the cost of an early termination of the mission. An alkali-metal Variable Conductance Heat Pipe (VCHP) can be used to passively allow multiple stops and restarts of the Stirling convertor. In a previous NASA SBIR Program, Advanced Cooling Technologies, Inc. (ACT) developed a series of sodium VCHPs as backup cooling systems for Stirling RPS. The operation of these VCHPs was demonstrated using Stirling heater head simulators and GPHS simulators. In the most recent effort, a sodium VCHP with a stainless steel envelope was designed, fabricated and tested at NASA Glenn Research Center (GRC) with a Stirling convertor for two concepts; one for the Advanced Stirling Radioisotope Generator (ASRG) back up cooling system and one for the Long-lived Venus Lander thermal management system. The VCHP is designed to activate and remove heat from the stopped convertor at a 19 degC temperature increase from the nominal vapor temperature. The 19 degC temperature increase from nominal is low enough to avoid risking standard ASRG operation and spoiling of the Multi-Layer Insulation (MLI). In addition, the same backup cooling system can be applied to the Stirling convertor used for the refrigeration system of the Long-lived Venus Lander. The VCHP will allow the refrigeration system to: 1) rest during transit at a lower temperature than nominal; 2) pre-cool the modules to an even lower temperature before the entry in Venus atmosphere; 3) work at nominal temperature on Venus surface; 4) briefly stop multiple times on the Venus surface to allow scientific measurements. This paper presents the experimental results from integrating the VCHP with an operating Stirling convertor and describes the methodology used to achieve their successful combined operation.

Alkali Metal Backup Cooling for Stirling Systems - Experimental Results

NASA Technical Reports Server (NTRS)

Schwendeman, Carl; Tarau, Calin; Anderson, William G.; Cornell, Peggy A.

2013-01-01

In a Stirling Radioisotope Power System (RPS), heat must be continuously removed from the General Purpose Heat Source (GPHS) modules to maintain the modules and surrounding insulation at acceptable temperatures. The Stirling convertor normally provides this cooling. If the Stirling convertor stops in the current system, the insulation is designed to spoil, preventing damage to the GPHS at the cost of an early termination of the mission. An alkali-metal Variable Conductance Heat Pipe (VCHP) can be used to passively allow multiple stops and restarts of the Stirling convertor. In a previous NASA SBIR Program, Advanced Cooling Technologies, Inc. (ACT) developed a series of sodium VCHPs as backup cooling systems for Stirling RPS. The operation of these VCHPs was demonstrated using Stirling heater head simulators and GPHS simulators. In the most recent effort, a sodium VCHP with a stainless steel envelope was designed, fabricated and tested at NASA Glenn Research Center (GRC) with a Stirling convertor for two concepts; one for the Advanced Stirling Radioisotope Generator (ASRG) back up cooling system and one for the Long-lived Venus Lander thermal management system. The VCHP is designed to activate and remove heat from the stopped convertor at a 19 C temperature increase from the nominal vapor temperature. The 19 C temperature increase from nominal is low enough to avoid risking standard ASRG operation and spoiling of the Multi-Layer Insulation (MLI). In addition, the same backup cooling system can be applied to the Stirling convertor used for the refrigeration system of the Long-lived Venus Lander. The VCHP will allow the refrigeration system to: 1) rest during transit at a lower temperature than nominal; 2) pre-cool the modules to an even lower temperature before the entry in Venus atmosphere; 3) work at nominal temperature on Venus surface; 4) briefly stop multiple times on the Venus surface to allow scientific measurements. This paper presents the experimental results from integrating the VCHP with an operating Stirling convertor and describes the methodology used to achieve their successful combined operation.

Alkali Metal Backup Cooling for Stirling Systems - Experimental Results

NASA Technical Reports Server (NTRS)

Schwendeman, Carl; Tarau, Calin; Anderson, William G.; Cornell, Peggy A.

2013-01-01

In a Stirling Radioisotope Power System (RPS), heat must be continuously removed from the General Purpose Heat Source (GPHS) modules to maintain the modules and surrounding insulation at acceptable temperatures. The Stirling convertor normally provides this cooling. If the Stirling convertor stops in the current system, the insulation is designed to spoil, preventing damage to the GPHS at the cost of an early termination of the mission. An alkali-metal Variable Conductance Heat Pipe (VCHP) can be used to passively allow multiple stops and restarts of the Stirling convertor. In a previous NASA SBIR Program, Advanced Cooling Technologies, Inc. (ACT) developed a series of sodium VCHPs as backup cooling systems for Stirling RPS. The operation of these VCHPs was demonstrated using Stirling heater head simulators and GPHS simulators. In the most recent effort, a sodium VCHP with a stainless steel envelope was designed, fabricated and tested at NASA Glenn Research Center (GRC) with a Stirling convertor for two concepts; one for the Advanced Stirling Radioisotope Generator (ASRG) back up cooling system and one for the Long-lived Venus Lander thermal management system. The VCHP is designed to activate and remove heat from the stopped convertor at a 19 degC temperature increase from the nominal vapor temperature. The 19 degC temperature increase from nominal is low enough to avoid risking standard ASRG operation and spoiling of the Multi-Layer Insulation (MLI). In addition, the same backup cooling system can be applied to the Stirling convertor used for the refrigeration system of the Long-lived Venus Lander. The VCHP will allow the refrigeration system to: 1) rest during transit at a lower temperature than nominal; 2) pre-cool the modules to an even lower temperature before the entry in Venus atmosphere; 3) work at nominal temperature on Venus surface; 4) briefly stop multiple times on the Venus surface to allow scientific measurements. This paper presents the experimental results from integrating the VCHP with an operating Stirling convertor and describes the methodology used to achieve their successful combined operation.

Bus Stops and Pedestrian-Motor Vehicle Collisions in Lima, Peru: A Matched Case-Control Study

PubMed Central

Quistberg, D. Alex; Koepsell, Thomas D.; Johnston, Brian D.; Boyle, Linda Ng; Miranda, J. Jaime; Ebel, Beth E.

2015-01-01

Objective To evaluate the relationship between bus stop characteristics and pedestrian-motor vehicle collisions. Design Matched case-control study where the units of study were pedestrian crossing. Setting Random sample of 11 police commissaries in Lima, Peru. Data collection occurred from February, 2011 to September, 2011. Participants 97 intersection cases representing 1,134 collisions and 40 mid-block cases representing 469 collisions that occurred between October, 2010 and January, 2011 and their matched controls. Main Exposures Presence of a bus stop and specific bus stop characteristics. Main Outcome Occurrence of a pedestrian-motor vehicle collision. Results Intersections with bus stops were three times more likely to have a pedestrian-vehicle collision (OR 3.28, 95% CI 1.53-7.03), relative to intersections without bus stops. Both formal and informal bus stops were associated with a higher odds of a collision at intersections (OR 6.23, 95% CI 1.76-22.0 and OR 2.98, 1.37-6.49). At mid-block sites, bus stops on a bus-dedicated transit lane were also associated with collision risk (OR 2.36, 95% CI 1.02-5.42). All bus stops were located prior to the intersection, contrary to practices in most high income countries. Conclusions In urban Lima, the presence of a bus stop was associated with a three-fold increase in risk of a pedestrian collision. The highly competitive environment among bus companies may provide an economic incentive for risky practices such as dropping off passengers in the middle of traffic and jockeying for position with other buses. Bus stop placement should be considered to improve pedestrian safety. PMID:24357516

Small-Portion Water Dispenser

NASA Technical Reports Server (NTRS)

Joerns, J. C.

1986-01-01

Pressure regulated and flow timed to control amount dispensed. Dispenser provides measured amount of water for reconstituting dehydrated foods and beverages. Dispenser holds food or beverage package while being filled with either cold or room-temperature water. Other uses might include dispensing of fluids or medicine. Pressure regulator in dispenser reduces varying pressure of water supply to constant pressure. Electronic timer stops flow after predetermined length of time. Timed flow at regulated pressure ensures controlled volume of water dispensed.

Higgs and Z assisted stop searches at hadron colliders

NASA Astrophysics Data System (ADS)

Su, Shufang; Zhang, Huanian

2018-05-01

Current searches for the light top squark (stop) mostly focus on the decay channels of \\tilde{t}\\to t{χ}_1^0 or \\tilde{t}\\to b{χ}_1^{±}\\to bW{χ}_1^0 , leading to [InlineMediaObject not available: see fulltext.] final states for stop pair productions at the LHC. However, in supersymmetric scenarios with light neutralinos and charginos other than the neutralino lightest supersymmetric particle (LSP), more than one decay mode of the stop could be dominant. While those new decay modes could significantly weaken the current stop search limits at the LHC, they also offer alternative discovery channels for stop searches. In this paper, we studied the scenario with light Higgsino next-to-LSPs (NLSPs) and Bino LSP. The light stop decays primarily via {\\tilde{t}}_1\\to t{χ}_2^0/{χ}_3^0 , with the neutralinos subsequent decaying to a Z boson or a Higgs boson: χ 2 0 / χ 3 0 → χ 1 0 h/ Z. Pair production of light stops at the LHC leads to final states of [InlineMediaObject not available: see fulltext.] or [InlineMediaObject not available: see fulltext.] . We consider three signal regions: one charged lepton (1 ℓ), two opposite sign charged leptons (2 OS ℓ) and at least three charged leptons (≥3 ℓ). We found that the 1 ℓ signal region of channel [InlineMediaObject not available: see fulltext.] has the best reach sensitivity for light stop searches. For 14 TeV LHC with 300 fb-1 integrated luminosity, a stop mass up to 900 GeV can be discovered at 5 σ significance, or up to 1050 GeV can be excluded at 95% C.L. Combining all three decay channels for 1 ℓ signal region extends the reach for about 100-150 GeV. We also studied the stop reach at the 100 TeV pp collider with 3 ab-1 luminosity, with discovery and exclusion reach being 6 TeV and 7 TeV, respectively.

Alternative Fuels Data Center

Science.gov Websites

Autonomous Vehicle (AV) Safe Testing Regulations Arizona state agencies must support the testing fails, the vehicle must be brought to a complete stop or safe state. The Arizona Department of Public

Unplanned gait termination in individuals with multiple sclerosis.

PubMed

Roeing, Kathleen L; Moon, Yaejin; Sosnoff, Jacob J

2017-03-01

Despite the pervasive nature of gait impairment in multiple sclerosis (MS), there is limited information concerning the control of gait termination in individuals with MS. The purpose of this investigation was to examine unplanned gait termination with and without cognitive distractors in individuals with MS compared to healthy controls. Thirty-one individuals with MS and 14 healthy controls completed a series of unplanned gait termination tasks over a pressure sensitive walkway under distracting and non-distracting conditions. Individuals with MS were further broken down into groups based on assistive device use: (no assistive device (MS noAD ) n=18; and assistive device (MS AD ) n=13). Individuals with MS who walked with an assistive device (MS AD : 67.8±15.1cm/s) walked slower than individuals without an assistive device (MS noAD : 110.4±32.3cm/s, p<0.01) and controls (120.0±30.0cm/s; p<0.01). There was a significant reduction in velocity in the cognitively distracting condition (93.4±32.1cm/s) compared to the normal condition [108.8±36.2cm/s; F(1,43)=3.4, p=0.04]. All participants took longer to stop during the distracting condition (1.7±0.6s) than the non-distracting condition (1.4±0.4s; U=673.0 p<0.01). After controlling for gait velocity, post-hoc analysis revealed the MS AD group took significantly longer to stop compared to the control group (p=0.05). Further research investigating the control of unplanned gait termination in MS is warranted. Copyright © 2017 Elsevier B.V. All rights reserved.

Ethics in Scientific Publishing

NASA Astrophysics Data System (ADS)

Sage, Leslie J.

2012-08-01

We all learn in elementary school not turn in other people's writing as if it were our own (plagiarism), and in high school science labs not to fake our data. But there are many other practices in scientific publishing that are depressingly common and almost as unethical. At about the 20 percent level authors are deliberately hiding recent work -- by themselves as well as by others -- so as to enhance the apparent novelty of their most recent paper. Some people lie about the dates the data were obtained, to cover up conflicts of interest, or inappropriate use of privileged information. Others will publish the same conference proceeding in multiple volumes, or publish the same result in multiple journals with only trivial additions of data or analysis (self-plagiarism). These shady practices should be roundly condemned and stopped. I will discuss these and other unethical actions I have seen over the years, and steps editors are taking to stop them.

Disease activity return after natalizumab cessation in multiple sclerosis.

PubMed

Rasenack, Maria; Derfuss, Tobias

2016-05-01

Natalizumab (NAT) was the first monoclonal antibody to be approved for the treatment of relapsing-remitting multiple sclerosis. Its considerable and sustained efficacy has been demonstrated in two phase III studies. However, there are several reasons why its use is limited in clinical practice. The main argument for stopping use of the drug is the risk of the rare but serious progressive multifocal leukencephalopathy. Other reasons are neutralizing antibodies and pregnancy. There is compelling evidence from some clinical trials and many case series that disease activity returns upon suspension or cessation of NAT. Several therapeutic strategies that have been tested to prevent or reduce the recurrence of disease activity will be reviewed in this article. Considering these data, it is evident that the decision to stop NAT treatment has different implications and consequences. A subsequent therapy after cessation of NAT is needed to reduce the risk of disease recurrence.

Investigation of TRPV1 loss-of-function phenotypes in TRPV1 Leu206Stop mice generated by N-ethyl-N-nitrosourea mutagenesis.

PubMed

Christoph, Thomas; Kögel, Babette; Schiene, Klaus; Peters, Thomas; Schröder, Wolfgang

2018-06-02

N-ethyl-N-nitrosourea (ENU) random mutagenesis was used to generate a mouse model for the analysis of the transient receptor potential vanilloid 1 (TRPV1) cation channel. A transversion from T→A in exon 4 led to a Leu206Stop mutation generating a loss-of-function mutant. The TRPV1 agonist capsaicin was used to analyze functional and nociceptive parameters in vitro and in vivo in TRPV1 Leu206Stop mice and congenic C3HeB/FeJ controls. Capsaicin-induced [Ca 2+ ] i changes in small diameter DRG neurons were significantly diminished in TRPV1 Leu206Stop mice and administration of capsaicin induced neither hypothermia nor nocifensive behaviour in vivo. TRPV1 Leu206Stop mice were tested in the spinal nerve ligation of mononeuropathic pain and developed mechanical hypersensitivity two weeks after nerve injury. In the open field test, a significant increase in spontaneous locomotion was detected in TRPV1 Leu206Stop mice as compared to wildtype controls. TRPV1 knockout mice have been reported to carry a similar phenotype regarding capsaicin-evoked responses in vitro and in vivo. However, in contrast to TRPV1 Leu206Stop mice, TRPV1 knockout mice did not differ in spontaneous locomotion as compared to congenic C57BL/6 mice, suggesting subtle ENU-dependent or independent strain differences between TRPV1 Leu206Stop mice and their wildtype controls. In summary, these data revealed a target-related (i.e. capsaicin-evoked) phenotype of TRPV1 Leu206Stop mice closely resembling that of published TRPV1 knockout mice. However, since ENU-mutant mice are congenic with the mouse strain initially used in random mutagenesis, direct phenotypic comparison with the respective wildtype controls is possible, and the time-consuming backcrossing in lines with targeted mutations is avoided. Copyright © 2018 Elsevier Inc. All rights reserved.

Long-lived stops in MSSM scenarios with a neutralino LSP

NASA Astrophysics Data System (ADS)

Johansen, M.; Edsjö, J.; Hellman, S.; Milstead, D.

2010-08-01

This work investigates the possibility of a long-lived stop squark in supersymmetric models with the neutralino as the lightest supersymmetric particle (LSP). We study the implications of meta-stable stops on the sparticle mass spectra and the dark matter density. We find that in order to obtain a sufficiently long stop lifetime so as to be observable as a stable R-hadron at an LHC experiment, we need to fine tune the mass degeneracy between the stop and the LSP considerably. This increases the stop-neutralino co-anihilation cross section, leaving the neutralino relic density lower than what is expected from the WMAP results for stop masses ≲1.5 TeV/ c 2. However, if such scenarios are realised in nature we demonstrate that the long-lived stops will be produced at the LHC and that stop-based R-hadrons with masses up to 1 TeV/c2 can be detected after one year of running at design luminosity.

Supporting Affect Regulation in Children with Multiple Disabilities during Psychotherapy: A Multiple Case Design Study of Therapeutic Attachment

ERIC Educational Resources Information Center

Schuengel, C.; Sterkenburg, P. S.; Jeczynski, P.; Janssen, C. G. C.; Jongbloed, G.

2009-01-01

In a controlled multiple case design study, the development of a therapeutic relationship and its role in affect regulation were studied in 6 children with visual disabilities, severe intellectual disabilities, severe challenging behavior, and prolonged social deprivation. In the 1st phase, children had sessions with an experimental therapist…

Spatio-Temporal Pattern Mining on Trajectory Data Using Arm

NASA Astrophysics Data System (ADS)

Khoshahval, S.; Farnaghi, M.; Taleai, M.

2017-09-01

Preliminary mobile was considered to be a device to make human connections easier. But today the consumption of this device has been evolved to a platform for gaming, web surfing and GPS-enabled application capabilities. Embedding GPS in handheld devices, altered them to significant trajectory data gathering facilities. Raw GPS trajectory data is a series of points which contains hidden information. For revealing hidden information in traces, trajectory data analysis is needed. One of the most beneficial concealed information in trajectory data is user activity patterns. In each pattern, there are multiple stops and moves which identifies users visited places and tasks. This paper proposes an approach to discover user daily activity patterns from GPS trajectories using association rules. Finding user patterns needs extraction of user's visited places from stops and moves of GPS trajectories. In order to locate stops and moves, we have implemented a place recognition algorithm. After extraction of visited points an advanced association rule mining algorithm, called Apriori was used to extract user activity patterns. This study outlined that there are useful patterns in each trajectory that can be emerged from raw GPS data using association rule mining techniques in order to find out about multiple users' behaviour in a system and can be utilized in various location-based applications.

ATPase activity and light scattering of acto-heavy meromyosin: dependence on ATP concentration and on ionic strength.

PubMed

Dancker, P

1975-01-01

1. The dependence on ATP concentration of ATPase activity and light scattering decrease of acto-HMM could be described at very low ionic strength by one hyperbolic adsorption isotherm with a dissociation constant of 3 X 10(-6)M. Hence the increase of ATP ase activity was paralleled by a decrease in light scattering. At higher values of ionic strength ATPase activity stopped rising before HMM was completely saturated with ATP. Higher ionic strength prevented ATPase activity from further increasing when the rigor links (links between actin and nucleotide-free myosin), which have formerly protected the ATPase against the suppressing action of higher ionic strength have fallen below a certain amount. This protecting influence of rigor links did not require tropomyosin-troponin. 2. For complete activation of ATPase activity by actin less actin was needed when HMM was incompletely saturated with ATP than when it was completely saturated with ATP. 3. The apparent affinity of ATP to regulated acto-HMM (which contained tropomyosin-troponin) was lower than to unregulated acto-HMM (which was devoid of tropomyosin-troponin). In the presence of rigor complexes (indicated by an incomplete decrease of light scattering) the ATPase activity of regulated acto-HMM was higher than that of unregulated acto-HMM. At increasing ATP concentrations the ATPase activity of regulated acto-HMM stopped rising at a similar degree of saturation with ATP as the ATPase activity of unregulated acto-HMM at the same ionic strength.

circlncRNAnet: an integrated web-based resource for mapping functional networks of long or circular forms of noncoding RNAs.

PubMed

Wu, Shao-Min; Liu, Hsuan; Huang, Po-Jung; Chang, Ian Yi-Feng; Lee, Chi-Ching; Yang, Chia-Yu; Tsai, Wen-Sy; Tan, Bertrand Chin-Ming

2018-01-01

Despite their lack of protein-coding potential, long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) have emerged as key determinants in gene regulation, acting to fine-tune transcriptional and signaling output. These noncoding RNA transcripts are known to affect expression of messenger RNAs (mRNAs) via epigenetic and post-transcriptional regulation. Given their widespread target spectrum, as well as extensive modes of action, a complete understanding of their biological relevance will depend on integrative analyses of systems data at various levels. While a handful of publicly available databases have been reported, existing tools do not fully capture, from a network perspective, the functional implications of lncRNAs or circRNAs of interest. Through an integrated and streamlined design, circlncRNAnet aims to broaden the understanding of ncRNA candidates by testing in silico several hypotheses of ncRNA-based functions, on the basis of large-scale RNA-seq data. This web server is implemented with several features that represent advances in the bioinformatics of ncRNAs: (1) a flexible framework that accepts and processes user-defined next-generation sequencing-based expression data; (2) multiple analytic modules that assign and productively assess the regulatory networks of user-selected ncRNAs by cross-referencing extensively curated databases; (3) an all-purpose, information-rich workflow design that is tailored to all types of ncRNAs. Outputs on expression profiles, co-expression networks and pathways, and molecular interactomes, are dynamically and interactively displayed according to user-defined criteria. In short, users may apply circlncRNAnet to obtain, in real time, multiple lines of functionally relevant information on circRNAs/lncRNAs of their interest. In summary, circlncRNAnet provides a "one-stop" resource for in-depth analyses of ncRNA biology. circlncRNAnet is freely available at http://app.cgu.edu.tw/circlnc/. © The Authors 2017. Published by Oxford University Press.

STOP using just GO: a multi-ontology hypothesis generation tool for high throughput experimentation

PubMed Central

2013-01-01

Background Gene Ontology (GO) enrichment analysis remains one of the most common methods for hypothesis generation from high throughput datasets. However, we believe that researchers strive to test other hypotheses that fall outside of GO. Here, we developed and evaluated a tool for hypothesis generation from gene or protein lists using ontological concepts present in manually curated text that describes those genes and proteins. Results As a consequence we have developed the method Statistical Tracking of Ontological Phrases (STOP) that expands the realm of testable hypotheses in gene set enrichment analyses by integrating automated annotations of genes to terms from over 200 biomedical ontologies. While not as precise as manually curated terms, we find that the additional enriched concepts have value when coupled with traditional enrichment analyses using curated terms. Conclusion Multiple ontologies have been developed for gene and protein annotation, by using a dataset of both manually curated GO terms and automatically recognized concepts from curated text we can expand the realm of hypotheses that can be discovered. The web application STOP is available at http://mooneygroup.org/stop/. PMID:23409969

Does the Level of Graphical Detail of a Virtual Handball Thrower Influence a Goalkeeper’s Motor Response?

PubMed Central

Vignais, Nicolas; Bideau, Benoit; Craig, Cathy; Brault, Sébastien; Multon, Franck; Delamarche, Paul; Kulpa, Richard

2009-01-01

The authors investigated how different levels of detail (LODs) of a virtual throwing action can influence a handball goalkeeper’s motor response. Goalkeepers attempted to stop a virtual ball emanating from five different graphical LODs of the same virtual throwing action. The five levels of detail were: a textured reference level (L0), a non-textured level (L1), a wire-frame level (L2), a point-light-display (PLD) representation (L3) and a PLD level with reduced ball size (L4). For each motor response made by the goalkeeper we measured and analyzed the time to respond (TTR), the percentage of successful motor responses, the distance between the ball and the closest limb (when the stopping motion was incorrect) and the kinematics of the motion. Results showed that TTR, percentage of successful motor responses and distance with the closest limb were not significantly different for any of the five different graphical LODs. However the kinematics of the motion revealed that the trajectory of the stopping limb was significantly different when comparing the L1 and L3 levels, and when comparing the L1 and L4 levels. These differences in the control of the goalkeeper’s actions suggests that the different level of information available in the PLD representations (L3 and L4) are causing the goalkeeper to adopt different motor strategies to control the approach of their limb to stop the ball. Key points Virtual reality technology can be used to analyze sport performance because it enables standardization and reproduction of sport situations. Defining a minimal graphical level of detail of a virtual action could decrease the real time calculation of a virtual reality system. A Point Light Display graphical representation of a virtual throwing motion seems to influence the regulation of action of real handball goalkeepers. PMID:24149589

Search for Scalar Top Quark Pair-Production in Scenario with Violated R-parity in pp¯ Collisions at √s = 1.96 TeV

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

Ogawa, Takashi

A search for the pair production of supersymmetric partner of the top quark in scenario with R-parity violation is presented. The quantum number called R-parity distinguishes particles in standard model from supersymmetric particles. A scalar top quark (stop) is assumed to decay only via R p-violating supersymmetric coupling into tau lepton and b-quark. To collect events with multiple taus, a new special tau trigger (the lepton plus track trigger) is installed in Run II experiment of the Collider Detector at Fermilab (CDF). The goal of the lepton plus track trigger is to collect generic dilepton (ll, lτ, ττ) events withmore » lower p T threshold (8 GeV/c) and without prescale even at high luminosity. The Z → ττ event, where one τ-lepton decays leptonically and the other hadronically, is a good benchmark to calibrate the lepton plus track trigger and τ identification. The data sample of 72 pb -1, collected using the electron plus track trigger, contains clear a τ signal from Z → ττ events. The data used in stop search correspond to 200 pb -1. The lower stop mass bound of 134 GeV/c 2 at a 95% confidence level is obtained. This limit is also directly applicable to the case of the third generation scalar leptoquark (LQ 3) assuming a 100% branching for the LQ 3 → τb decay mode.« less

Automaticity of Cognitive Control: Goal Priming in Response-Inhibition Paradigms

ERIC Educational Resources Information Center

Verbruggen, Frederick; Logan, Gordon D.

2009-01-01

Response inhibition is a hallmark of cognitive control. An executive system inhibits responses by activating a stop goal when a stop signal is presented. The authors asked whether the stop goal could be primed by task-irrelevant information in stop-signal and go/no-go paradigms. In Experiment 1, the task-irrelevant primes "GO," ###, or "STOP" were…

Timing and technique impact the effectiveness of road-based, mobile acoustic surveys of bats.

PubMed

D'Acunto, Laura E; Pauli, Benjamin P; Moy, Mikko; Johnson, Kiara; Abu-Omar, Jasmine; Zollner, Patrick A

2018-03-01

Mobile acoustic surveys are a common method of surveying bat communities. However, there is a paucity of empirical studies exploring different methods for conducting mobile road surveys of bats. During 2013, we conducted acoustic mobile surveys on three routes in north-central Indiana, U.S.A., using (1) a standard road survey, (2) a road survey where the vehicle stopped for 1 min at every half mile of the survey route (called a "start-stop method"), and (3) a road survey with an individual using a bicycle. Linear mixed models with multiple comparison procedures revealed that when all bat passes were analyzed, using a bike to conduct mobile surveys detected significantly more bat passes per unit time compared to other methods. However, incorporating genus-level comparisons revealed no advantage to using a bike over vehicle-based methods. We also found that survey method had a significant effect when analyses were limited to those bat passes that could be identified to genus, with the start-stop method generally detecting more identifiable passes than the standard protocol or bike survey. Additionally, we found that significantly more identifiable bat passes (particularly those of the Eptesicus and Lasiurus genera) were detected in surveys conducted immediately following sunset. As governing agencies, particularly in North America, implement vehicle-based bat monitoring programs, it is important for researchers to understand how variations on protocols influence the inference that can be gained from different monitoring schemes.

North Cascades Stehekin Valley Vehicle Decision Document.

DOT National Transportation Integrated Search

2007-08-31

This document serves as technical substantiation in support of a procurement for a fleet of vehicles to be used to operate a scheduled shuttle operation with multiple stops at North Cascades National Park Service Complex (NOCA), in the Stehekin Valle...

Neural and behavioral correlates of selective stopping: Evidence for a different strategy adoption.

PubMed

Sánchez-Carmona, Alberto J; Albert, Jacobo; Hinojosa, José A

2016-10-01

The present study examined the neural and behavioral correlates of selective stopping, a form of inhibition that has scarcely been investigated. The selectivity of the inhibitory process is needed when individuals have to deal with an environment filled with multiple stimuli, some of which require inhibition and some of which do not. The stimulus-selective stop-signal task has been used to explore this issue assuming that all participants interrupt their ongoing responses selectively to stop but not to ignore signals. However, recent behavioral evidence suggests that some individuals do not carry out the task as experimenters expect, since they seemed to interrupt their response non-selectively to both signals. In the present study, we detected and controlled the cognitive strategy adopted by participants (n=57) when they performed a stimulus-selective stop-signal task before comparing brain activation between conditions. In order to determine both the onset and the end of the response cancellation process underlying each strategy and to fully take advantage of the precise temporal resolution of event-related potentials, we used a mass univariate approach. Source localization techniques were also employed to estimate the neural underpinnings of the effects observed at the scalp level. Our results from scalp and source level analysis support the behavioral-based strategy classification. Specific effects were observed depending on the strategy adopted by participants. Thus, when contrasting successful stop versus ignore conditions, increased activation was only evident for subjects who were classified as using a strategy whereby the response interruption process was selective to stop trials. This increased activity was observed during the P3 time window in several left-lateralized brain regions, including middle and inferior frontal gyri, as well as parietal and insular cortices. By contrast, in those participants who used a strategy characterized by stopping non-selectively, no activation differences between successful stop and ignore conditions were observed at the estimated time at which response interruption process occurs. Overall, results from the current study highlight the importance of controlling for the different strategies adopted by participants to perform selective stopping tasks before analyzing brain activation patterns. Copyright © 2016 Elsevier Inc. All rights reserved.

Breastfeeding education and support for women with twins or higher order multiples.

PubMed

Whitford, Heather M; Wallis, Selina K; Dowswell, Therese; West, Helen M; Renfrew, Mary J

2017-02-28

There are rising rates of multiple births worldwide with associated higher rates of complications and more hospital care, often due to prematurity. While there is strong evidence about the risks of not breastfeeding, rates of breastfeeding in women who have given birth to more than one infant are lower than with singleton births. Breastfeeding more than one infant can be more challenging because of difficulties associated with the birth or prematurity. The extra demands on the mother of frequent suckling, coordinating the needs of more than one infant or admission to the neonatal intensive care unit can lead to delayed initiation or early cessation. Additional options such as breast milk expression, the use of donor milk or different methods of supplementary feeding may be considered. Support and education about breastfeeding has been found to improve the duration of any breastfeeding for healthy term infants and their mothers, however evidence is lacking about interventions that are effective to support women with twins or higher order multiples. To assess effectiveness of breastfeeding education and support for women with twins or higher order multiples. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2016), ClinicalTrials.gov (30 June 2016), the WHO International Clinical Trials Registry Platform (ICTRP) (1 July 2016), the excluded studies list from the equivalent Cochrane review of singletons, and reference lists of retrieved studies. Randomised or quasi-randomised trials comparing extra education or support for women with twins or higher order multiples were included. Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. We planned to assess the quality of evidence using the GRADE approach, but were unable to analyse any data. We found 10 trials (23 reports) of education and support for breastfeeding that included women with twins or higher order multiples. The quality of evidence was mixed, and the risk of bias was mostly high or unclear. It is difficult to blind women or staff to group allocation for this intervention, so in all studies there was high risk of performance and high or unclear risk of detection bias. Trials recruited 5787 women (this included 512 women interviewed as part of a cluster randomised trial); of these, data were available from two studies for 42 women with twins or higher order multiples. None of the interventions were specifically designed for women with more than one infant, and the outcomes for multiples were not reported separately for each infant. Due to the scarcity of evidence and the format in which data were reported, a narrative description of the data is presented, no analyses are presented in this review, and we were unable to GRADE the evidence.The two trials with data for women with multiple births compared home nurse visits versus usual care (15 women), and telephone peer counselling versus usual care (27 women). The number of women who initiated breastfeeding was reported (all 15 women in one study, 25 out of 27 women in one study). Stopping any breastfeeding before four to six weeks postpartum, stopping exclusive breastfeeding before four to six weeks postpartum, stopping any breastfeeding before six months postpartum andstopping exclusive breastfeeding before six months postpartum were not explicitly reported, and there were insufficient data to draw any meaningful conclusions from survival data. Stopping breast milk expression before four to six weeks postpartum, andstopping breast milk expression before six months postpartum were not reported. Measures ofmaternal satisfaction were reported in one study of 15 women, but there were insufficient data to draw any conclusions; no other secondary outcomes were reported for women with multiple births in either study. No adverse events were reported. We found no evidence from randomised controlled trials about the effectiveness of breastfeeding education and support for women with twins or higher order multiples, or the most effective way to provide education and support . There was no evidence about the best way to deliver the intervention, the timing of care, or the best person to deliver the care. There is a need for well-designed, adequately powered studies of interventions designed for women with twins or higher order multiples to find out what types of education and support are effective in helping these mothers to breastfeed their babies.

Role of the human endogenous retrovirus HERV-K18 in autoimmune disease susceptibility: study in the Spanish population and meta-analysis.

PubMed

de la Hera, Belén; Varadé, Jezabel; García-Montojo, Marta; Lamas, José Ramón; de la Encarnación, Ana; Arroyo, Rafael; Fernández-Gutiérrez, Benjamín; Alvarez-Lafuente, Roberto; Urcelay, Elena

2013-01-01

Human endogenous retroviruses (HERVs) are genomic sequences that resulted from ancestral germ-line infections by exogenous retroviruses and therefore are transmitted in a Mendelian fashion. Increased HERV expression and antibodies to HERV antigens have been found in various autoimmune diseases. HERV-K18 in chromosome 1 was previously associated with type one diabetes and multiple sclerosis (MS). The etiology of these complex conditions has not been completely elucidated even after the powerful genome wide association studies (GWAS) performed. Nonetheless, this approach does not scrutinize the repetitive sequences within the genome, and part of the missing heritability could lie behind these sequences. We aimed at evaluating the role of HERV-K18 in chromosome 1 on autoimmune disease susceptibility. Two HERV-K18 SNPs (97Y/C and 154W/Stop substitutions) conforming three haplotypes were genotyped in Spanish cohorts of multiple sclerosis (n = 942), rheumatoid arthritis (n = 462) and ethnically matched controls (n = 601). Our findings were pooled in a meta-analysis including 5312 autoimmune patients and 4032 controls. Significant associations of both HERV-K18 polymorphisms in chromosome 1 with MS patients stratified by HLA-DRB1*15:01 were observed [97Y/C p = 0.02; OR (95% CI) = 1.5 (1.04-2.17) and 154W/Stop: p = 0.001; OR (95% CI) = 1.6 (1.19-2.16)]. Combined meta-analysis of the previously published association studies of HERV-K18 with different autoimmune diseases, together with data derived from Spanish cohorts, yielded a significant association of the HERV-K18.3 haplotype [97Y-154W: p(M-H) = 0.0008; OR(M-H) (95% CI) = 1.22 (1.09-1.38)]. Association of the HERV-K18.3 haplotype in chromosome 1 with autoimmune-disease susceptibility was confirmed through meta-analysis.

Multiple Risks, Emotion Regulation Skill, and Cortisol in Low-Income African American Youth: A Prospective Study

ERIC Educational Resources Information Center

Kliewer, Wendy; Reid-Quinones, Kathryn; Shields, Brian J.; Foutz, Lauren

2009-01-01

Associations between multiple risks, emotion regulation skill, and basal cortisol levels were examined in a community sample of 69 African American youth (mean age = 11.30 years; 49% male) living in an urban setting. Multiple risks were assessed at Time 1 and consisted of 10 demographic and psychosocial risk factors including parent, child, and…

Multiple division cycles and long-term survival of hepatocytes are distinctly regulated by extracellular signal-regulated kinases ERK1 and ERK2.

PubMed

Frémin, Christophe; Bessard, Anne; Ezan, Frédéric; Gailhouste, Luc; Régeard, Morgane; Le Seyec, Jacques; Gilot, David; Pagès, Gilles; Pouysségur, Jacques; Langouët, Sophie; Baffet, Georges

2009-03-01

We investigated the specific role of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1 (ERK1)/ERK2 pathway in the regulation of multiple cell cycles and long-term survival of normal hepatocytes. An early and sustained epidermal growth factor (EGF)-dependent MAPK activation greatly improved the potential of cell proliferation. In this condition, almost 100% of the hepatocytes proliferated, and targeting ERK1 or ERK2 via RNA interference revealed the specific involvement of ERK2 in this regulation. However, once their first cell cycle was performed, hepatocytes failed to undergo a second round of replication and stayed blocked in G1 phase. We demonstrated that sustained EGF-dependent activation of the MAPK/ERK kinase (MEK)/ERK pathway was involved in this blockage as specific transient inhibition of the cascade repotentiated hepatocytes to perform a new wave of replication and multiple cell cycles. We identified this mechanism by showing that this blockage was in part supported by ERK2-dependent p21 expression. Moreover, continuous MEK inhibition was associated with a lower apoptotic engagement, leading to an improvement of survival up to 3 weeks. Using RNA interference and ERK1 knockout mice, we extended these results by showing that this improved survival was due to the specific inhibition of ERK1 expression/phosphorylation and did not involve ERK2. Our results emphasize that transient MAPK inhibition allows multiple cell cycles in primary cultures of hepatocytes and that ERK2 has a key role in the regulation of S phase entry. Moreover, we revealed a major and distinct role of ERK1 in the regulation of hepatocyte survival. Taken together, our results represent an important advance in understanding long-term survival and cell cycle regulation of hepatocytes.

PDRG1, a novel tumor marker for multiple malignancies that is selectively regulated by genotoxic stress

PubMed Central

Jiang, Lingyan; Luo, Xiuquan; Shi, Jingxue; Sun, Hong; Sun, Qing; Sheikh, M Saeed

2011-01-01

We have previously cloned and characterized a novel p53 and DNA damage-regulated gene named PDRG1. PDRG1 was found to be differentially regulated by ultraviolet (UV) radiation and p53. In this study, we further investigated stress regulation of PDRG1 and found it to be selectively regulated by agents that induce genotoxic stress (DNA damage). Using cancer profiling arrays, we also investigated PDRG1 expression in matching normal and tumor samples representing various malignancies and found its expression to be upregulated in multiple malignancies including cancers of the colon, rectum, ovary, lung, stomach, breast and uterus when compared to their respective matched normal tissues. Western blot and immunohistochemical analyses were also performed on select specimen sets of colon cancers and matching normal tissues and the results also indicated PDRG1 overexpression in tumors relative to normal tissues. To gain insight into the function of PDRG1, we performed PDRG1 knockdown in human colon cancer cells and found its depletion to result in marked slowdown of tumor cell growth. These results suggest that PDRG1 may be linked to cell growth regulation. Yeast two-hybrid screening also led to the identification of PDCD7, CIZ1 and MAP1S as PDRG1-interacting proteins that are involved in apoptosis and cell cycle regulation which further implicate PDRG1 in controlling cell growth regulation. Taken together, our results indicate that PDRG1 expression is increased in multiple human malignancies suggesting it to be a high-value novel tumor marker that could play a role in cancer development and/or progression. PMID:21193842

Prefrontal neurons encode context-based response execution and inhibition in reward seeking and extinction

PubMed Central

Moorman, David E.; Aston-Jones, Gary

2015-01-01

The prefrontal cortex (PFC) guides execution and inhibition of behavior based on contextual demands. In rodents, the dorsal/prelimbic (PL) medial PFC (mPFC) is frequently considered essential for execution of goal-directed behavior (“go”) whereas ventral/infralimbic (IL) mPFC is thought to control behavioral suppression (“stop”). This dichotomy is commonly seen for fear-related behaviors, and for some behaviors related to cocaine seeking. Overall, however, data for reward-directed behaviors are ambiguous, and few recordings of PL/IL activity have been performed to demonstrate single-neuron correlates. We recorded neuronal activity in PL and IL during discriminative stimulus driven sucrose seeking followed by multiple days of extinction of the reward-predicting stimulus. Contrary to a generalized PL-go/IL-stop hypothesis, we found cue-evoked activity in PL and IL during reward seeking and extinction. Upon analyzing this activity based on resultant behavior (lever press or withhold), we found that neurons in both areas encoded contextually appropriate behavioral initiation (during reward seeking) and withholding (during extinction), where context was dictated by response–outcome contingencies. Our results demonstrate that PL and IL signal contextual information for regulation of behavior, irrespective of whether that involves initiation or suppression of behavioral responses, rather than topographically encoding go vs. stop behaviors. The use of context to optimize behavior likely plays an important role in maximizing utility-promoting exertion of activity when behaviors are rewarded and conservation of energy when not. PMID:26170333

Using Student Writing and Lexical Analysis to Reveal Student Thinking about the Role of Stop Codons in the Central Dogma

PubMed Central

Prevost, Luanna B.; Smith, Michelle K.; Knight, Jennifer K.

2016-01-01

Previous work has shown that students have persistent difficulties in understanding how central dogma processes can be affected by a stop codon mutation. To explore these difficulties, we modified two multiple-choice questions from the Genetics Concept Assessment into three open-ended questions that asked students to write about how a stop codon mutation potentially impacts replication, transcription, and translation. We then used computer-assisted lexical analysis combined with human scoring to categorize student responses. The lexical analysis models showed high agreement with human scoring, demonstrating that this approach can be successfully used to analyze large numbers of student written responses. The results of this analysis show that students’ ideas about one process in the central dogma can affect their thinking about subsequent and previous processes, leading to mixed models of conceptual understanding. PMID:27909016

Low-velocity ion stopping in a dense and low-temperature plasma target

NASA Astrophysics Data System (ADS)

Deutsch, Claude; Popoff, Romain

2007-07-01

We investigate the stopping specificities involved in the heating of thin foils irradiated by intense ion beams in the 0.3-3 MeV/amu energy range and in close vicinity of the Bragg peak. Considering a swiftly ionized target to eV temperatures before expansion while retaining solid-state density, a typical warm dense matter (WDM) situation thus arises. We stress low Vp stopping through ion diffusion in the given target plasma. This allows to include the case of a strongly magnetized target in a guiding center approximation. We also demonstrate that the ion projectile penetration depth in target is significantly affected by multiple scattering on target electrons. The given plasma target is taken weakly coupled with Maxwell electron either with no magnetic field ( B=0) or strongly magnetized ( B≠0). Dynamical coupling between ion projectiles energy losses and projectiles charge state will also be addressed.

Risk of relapse after natalizumab withdrawal

PubMed Central

Vukusic, Sandra; Casey, Romain; Debard, Nadine; Stankoff, Bruno; Mrejen, Serge; Uhry, Zoe; Van Ganse, Eric; Castot, Anne; Clanet, Michel; Lubetzki, Catherine; Confavreux, Christian

2016-01-01

Objective: To assess disease activity within 12 months after natalizumab (NZ) discontinuation in a large French postmarketing cohort. Methods: In France, patients exposed at least once to NZ were included in the TYSEDMUS observational and multicenter cohort, part of the French NZ Risk Management Plan. Clinical disease activity during the year following NZ discontinuation was assessed in this cohort. Time to first relapse after NZ stop was analyzed using Kaplan-Meier method and potentially associated factors were studied using a multivariate Cox model. Results: Out of the 4,055 patients with multiple sclerosis (MS) included in TYSEDMUS, 1,253 discontinued NZ and 715 of them had relevant data for our study. The probability of relapse within the year after NZ stop was estimated at 45% (95% confidence interval 0.41–0.49). Conclusions: This large and systematic survey of patients with MS after NZ withdrawal allows quantifying the risk of increased disease activity following treatment discontinuation. This study provides large-scale, multicenter, systematic data after NZ cessation in real-life settings. PMID:27844037

Experimental evidence for simultaneous relaxation processes in super spin glass γ-Fe2O3 nanoparticle system

NASA Astrophysics Data System (ADS)

Nikolic, V.; Perovic, M.; Kusigerski, V.; Boskovic, M.; Mrakovic, A.; Blanusa, J.; Spasojevic, V.

2015-03-01

Spherical γ-Fe2O3 nanoparticles with the narrow size distribution of (5 ± 1) nm were synthesized by the method of thermal decomposition from iron acetyl acetonate precursor. The existence of super spin-glass state at low temperatures and in low applied magnetic fields was confirmed by DC magnetization measurements on a SQUID magnetometer. The comprehensive investigation of magnetic relaxation dynamics in low-temperature region was conducted through the measurements of single-stop and multiple stop ZFC memory effects, ZFC magnetization relaxation, and AC susceptibility measurements. The experimental findings revealed the peculiar change of magnetic relaxation dynamics at T ≈ 10 K, which arose as a consequence of simultaneous existence of different relaxation processes in Fe2O3 nanoparticle system. Complementarity of the applied measurements was utilized in order to single out distinct relaxation processes as well as to elucidate complex relaxation mechanisms in the investigated interacting nanoparticle system.

The spectraplakin Short stop is an essential microtubule regulator involved in epithelial closure in Drosophila

PubMed Central

Takács, Zsanett; Vilmos, Péter; Lénárt, Péter; Röper, Katja; Erdélyi, Miklós

2017-01-01

ABSTRACT Dorsal closure of the Drosophila embryonic epithelium provides an excellent model system for the in vivo analysis of molecular mechanisms regulating cytoskeletal rearrangements. In this study, we investigated the function of the Drosophila spectraplakin Short stop (Shot), a conserved cytoskeletal structural protein, during closure of the dorsal embryonic epithelium. We show that Shot is essential for the efficient final zippering of the opposing epithelial margins. By using isoform-specific mutant alleles and genetic rescue experiments with truncated Shot variants, we demonstrate that Shot functions as an actin–microtubule cross-linker in mediating zippering. At the leading edge of epithelial cells, Shot regulates protrusion dynamics by promoting filopodia formation. Fluorescence recovery after photobleaching (FRAP) analysis and in vivo imaging of microtubule growth revealed that Shot stabilizes dynamic microtubules. The actin- and microtubule-binding activities of Shot are simultaneously required in the same molecule, indicating that Shot is engaged as a physical crosslinker in this process. We propose that Shot-mediated interactions between microtubules and actin filaments facilitate filopodia formation, which promotes zippering by initiating contact between opposing epithelial cells. PMID:28062848

USABC Development of 12 Volt Battery for Start-Stop Application: Preprint

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

Tataria, H.; Gross, O.; Bae, C.

Global automakers are accelerating the development of fuel efficient vehicles, as a part of meeting regional regulatory CO2 emissions requirements. The micro hybrid vehicles with auto start-stop functionality are considered economical solutions for the stringent European regulations. Flooded lead acid batteries were initially considered the most economical solution for idle-stop systems. However, the dynamic charge acceptance (DCA) at lower state-of-charge (SOC) was limiting the life of the batteries. While improved lead-acid batteries with AGM and VRLA features have improved battery longevity, they do not last the life of the vehicle. The United States Advanced Battery Consortium (or USABC, a consortiummore » of GM, Ford, and Chrysler) analyzed energy storage needs for a micro hybrid automobile with start-stop capability, and with a single power source. USABC has analyzed the start-stop behaviors of many drivers and has developed the requirements for the start-stop batteries (Table 3). The testing procedures to validate the performance and longevity were standardized and published. The guideline for the cost estimates calculations have also been provided, in order to determine the value of the newly developed modules. The analysis effort resulted in a set of requirements which will help the battery manufacturers to develop a module to meet the automotive Original Equipment Manufacturers (OEM) micro hybrid vehicle requirements. Battery developers were invited to submit development proposals and two proposals were selected for 50% cost share with USABC/DOE.« less

Stopping power for 4.8-6.8 MeV C ions along [1 1 0] and [1 1 1] directions in Si

NASA Astrophysics Data System (ADS)

Yoneda, Tomoaki; Horikawa, Junsei; Saijo, Satoshi; Arakawa, Masakazu; Yamamoto, Yukio; Yamamoto, Yasukazu

2018-06-01

The stopping power for C ions with energies in the range of 4.8-6.8 MeV were investigated in a SIMOX (Separation by IMplanted OXygen into silicon) structure of Si(1 0 0)/SiO2/Si(1 0 0). Backscattering spectra were measured for random and channeling incidence along the [1 1 0] and [1 1 1] axes. The scattering angle was set to 90° to avoid an excessive decrease of the kinematic factor. The ratios of [1 1 0] and [1 1 1] channeling to the random stopping power were determined to be around 0.65 and 0.77 for 4.8-6.8 MeV ions, respectively. The validity of the impact parameter dependent stopping power calculated using Grande and Schiwietz's CasP (convolution approximation for swift particles) code was confirmed. The C ion trajectories and flux distributions in crystalline silicon were calculated by Monte Carlo simulation. The stopping power calculated with the CasP code is almost in agreement with the experimental results within the accuracy of measurement.

Second stop and sbottom searches with a stealth stop

NASA Astrophysics Data System (ADS)

Cheng, Hsin-Chia; Li, Lingfeng; Qin, Qin

2016-11-01

The top squarks (stops) may be the most wanted particles after the Higgs boson discovery. The searches for the lightest stop have put strong constraints on its mass. However, there is still a search gap in the low mass region if the spectrum of the stop and the lightest neutralino is compressed. In that case, it may be easier to look for the second stop since naturalness requires both stops to be close to the weak scale. The current experimental searches for the second stop are based on the simplified model approach with the decay modes {overset{˜ }{t}}_2to {overset{˜ }{t}}_1Z and {overset{˜ }{t}}_2to {overset{˜ }{t}}_1h . However, in a realistic supersymmetric spectrum there is always a sbottom lighter than the second stop, hence the decay patterns are usually more complicated than the simplified model assumptions. In particular, there are often large branching ratios of the decays {overset{˜ }{t}}_2to {overset{˜ }{b}}_1W and {overset{˜ }{b}}_1to {overset{˜ }{t}}_1W as long as they are open. The decay chains can be even more complex if there are intermediate states of additional charginos and neutralinos in the decays. By studying several MSSM benchmark models at the 14 TeV LHC, we point out the importance of the multi- W final states in the second stop and the sbottom searches, such as the same-sign dilepton and multilepton signals, aside from the traditional search modes. The observed same-sign dilepton excesses at LHC Run 1 and Run 2 may be explained by some of our benchmark models. We also suggest that the vector boson tagging and a new kinematic variable may help to suppress the backgrounds and increase the signal significance for some search channels. Due to the complex decay patterns and lack of the dominant decay channels, the best reaches likely require a combination of various search channels at the LHC for the second stop and the lightest sbottom.

Perceptions towards electronic cigarettes for smoking cessation among Stop Smoking Service users.

PubMed

Sherratt, Frances C; Newson, Lisa; Marcus, Michael W; Field, John K; Robinson, Jude

2016-05-01

Electronic cigarettes (e-cigarettes) are promoted as smoking cessation tools, yet they remain unavailable from Stop Smoking Services in England; the debate over their safety and efficacy is ongoing. This study was designed to explore perceptions and reasons for use or non-use of electronic cigarettes as smoking cessation tools, among individuals engaged in Stop Smoking Services. Semi-structured telephone interviews were undertaken with twenty participants engaged in Stop Smoking Services in the north-west of England. Participants comprised of both individuals who had tried e-cigarettes (n = 6) and those who had not (n = 14). Interviews were digitally recorded and transcribed verbatim. The transcripts were subject to thematic analysis, which explored participants' beliefs and experiences of e-cigarettes. A thematic analysis of transcripts suggested that the following three superordinate themes were prominent: (1) self-efficacy and beliefs in e-cigarettes; (2) e-cigarettes as a smoking cessation aid; and (3) cues for e-cigarette use. Participants, particularly never users, were especially concerned regarding e-cigarette efficacy and safety. Overall, participants largely expressed uncertainty regarding e-cigarette safety and efficacy, with some evidence of misunderstanding. Evidence of uncertainty and misunderstanding regarding information on e-cigarettes highlights the importance of providing smokers with concise, up-to-date information regarding e-cigarettes, enabling smokers to make informed treatment decisions. Furthermore, identification of potential predictors of e-cigarette use can be used to inform Stop Smoking Services provision and future research. What is already known on this subject? Research suggests that e-cigarettes may help smokers quit smoking, but further studies are needed. Electronic cigarette use in Stop Smoking Services has increased substantially in recent years, although e-cigarettes are currently not regulated. There is debate within the academic community regarding e-cigarette efficacy and safety. What does this study add? Service users interviewed in the current study felt uncertain regarding e-cigarette efficacy and safety. E-cigarette ever users viewed e-cigarettes as effective and safe, more often than never users. Accurate and up-to-date education will enable service users to make informed treatment decisions. © 2015 The British Psychological Society.

Self-regulating galaxy formation. Part 1: HII disk and Lyman alpha pressure

NASA Technical Reports Server (NTRS)

Cox, D. P.

1983-01-01

Assuming a simple but physically based prototype for behavior of interstellar material during formation of a disk galaxy, coupled with the lowest order description of infall, a scenario is developed for self-regulated disk galaxy formation. Radiation pressure, particularly that of Lyman depha (from fluorescence conversion Lyman continuum), is an essential component, maintaining an inflated disk and stopping infall when only a small fraction of the overall perturbation has joined the disk. The resulting galaxies consist of a two dimensional family whose typical scales and surface density are expressable in terms of fundamental constants. The model leads naturally to galaxies with a rich circumgalactic environment and flat rotation curves (but is weak in its analysis of the subsequent evolution of halo material).

Stopping a response has global or nonglobal effects on the motor system depending on preparation

PubMed Central

Greenhouse, Ian; Oldenkamp, Caitlin L.

2012-01-01

Much research has focused on how people stop initiated response tendencies when instructed by a signal. Stopping of this kind appears to have global effects on the motor system. For example, by delivering transcranial magnetic stimulation (TMS) over the leg area of the primary motor cortex, it is possible to detect suppression in the leg when the hand is being stopped (Badry R et al. Suppression of human cortico-motoneuronal excitability during the stop-signal task. Clin Neurophysiol 120: 1717–1723, 2009). Here, we asked if such “global suppression” can be observed proactively, i.e., when people anticipate they might have to stop. We used a conditional stop signal task, which allows the measurement of both an “anticipation phase” (i.e., where proactive control is applied) and a “stopping” phase. TMS was delivered during the anticipation phase (experiment 1) and also during the stopping phase (experiments 1 and 2) to measure leg excitability. During the anticipation phase, we did not observe leg suppression, but we did during the stopping phase, consistent with Badry et al. (2009). Moreover, when we split the subject groups into those who slowed down behaviorally (i.e., exercised proactive control) and those who did not, we found that subjects who slowed did not show leg suppression when they stopped, whereas those who did not slow did show leg suppression when they stopped. These results suggest that if subjects prepare to stop, then they do so without global effects on the motor system. Thus, preparation allows them to stop more selectively. PMID:22013239

Deciding where to Stop Speaking

ERIC Educational Resources Information Center

Tydgat, Ilse; Stevens, Michael; Hartsuiker, Robert J.; Pickering, Martin J.

2011-01-01

This study investigated whether speakers strategically decide where to interrupt their speech once they need to stop. We conducted four naming experiments in which pictures of colored shapes occasionally changed in color or shape. Participants then merely had to stop (Experiment 1); or they had to stop and resume speech (Experiments 2-4). They…

48 CFR 16.402-4 - Structuring multiple-incentive contracts.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Structuring multiple-incentive contracts. 16.402-4 Section 16.402-4 Federal Acquisition Regulations System FEDERAL ACQUISITION... include a cost incentive (or constraint) that operates to preclude rewarding a contractor for superior...

AN INDIRECT SEARCH FOR WEAKLY INTERACTING MASSIVE PARTICLES IN THE SUN USING 3109.6 DAYS OF UPWARD-GOING MUONS IN SUPER-KAMIOKANDE

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

Tanaka, T.; Abe, K.; Hayato, Y.

2011-12-01

We present the result of an indirect search for high energy neutrinos from Weakly Interacting Massive Particle (WIMP) annihilation in the Sun using upward-going muon (upmu) events at Super-Kamiokande. Data sets from SKI-SKIII (3109.6 days) were used for the analysis. We looked for an excess of neutrino signal from the Sun as compared with the expected atmospheric neutrino background in three upmu categories: stopping, non-showering, and showering. No significant excess was observed. The 90% C.L. upper limits of upmu flux induced by WIMPs of 100 GeV c{sup -2} were 6.4 Multiplication-Sign 10{sup -15} cm{sup -2} s{sup -1} and 4.0 Multiplication-Signmore » 10{sup -15} cm{sup -2} s{sup -1} for the soft and hard annihilation channels, respectively. These limits correspond to upper limits of 4.5 Multiplication-Sign 10{sup -39} cm{sup -2} and 2.7 Multiplication-Sign 10{sup -40} cm{sup -2} for spin-dependent WIMP-nucleon scattering cross sections in the soft and hard annihilation channels, respectively.« less

Uncover compressed supersymmetry via boosted bosons from the heavier stop/sbottom

NASA Astrophysics Data System (ADS)

Kang, Zhaofeng; Li, Jinmian; Zhang, Mengchao

2017-06-01

A light stop around the weak scale is a hopeful messenger of natural supersymmetry (SUSY), but it has not shown up at the current stage of LHC. Such a situation raises the question of the fate of natural SUSY. Actually, a relatively light stop can easily be hidden in a compressed spectra such as mild mass degeneracy between stop and neutralino plus top quark. Searching for such a stop at the LHC is a challenge. On the other hand, in terms of the argument of natural SUSY, other members in the stop sector, including a heavier stop \\tilde{t}_2 and lighter sbottom \\tilde{b}_1 (both assumed to be left-handed-like), are also supposed to be relatively light and therefore searching for them would provide an alternative method to probe natural SUSY with a compressed spectra. In this paper we consider quasi-natural SUSY which tolerates relatively heavy colored partners near the TeV scale, with a moderately large mass gap between the heavier members and the lightest stop. Then W / Z / h as companions of \\tilde{t}_2 and \\tilde{b}_1 decaying into \\tilde{t}_1 generically are well boosted, and they, along with other visible particles from \\tilde{t}_1 decay, are a good probe to study compressed SUSY. We find that the resulting search strategy with boosted bosons can have better sensitivity than those utilizing multi-leptons.

Post-transcriptional regulation of Pabpn1 by the RNA binding protein HuR.

PubMed

Phillips, Brittany L; Banerjee, Ayan; Sanchez, Brenda J; Di Marco, Sergio; Gallouzi, Imed-Eddine; Pavlath, Grace K; Corbett, Anita H

2018-06-25

RNA processing is critical for proper spatial and temporal control of gene expression. The ubiquitous nuclear polyadenosine RNA binding protein, PABPN1, post-transcriptionally regulates multiple steps of gene expression. Mutations in the PABPN1 gene expanding an N-terminal alanine tract in the PABPN1 protein from 10 alanines to 11-18 alanines cause the muscle-specific disease oculopharyngeal muscular dystrophy (OPMD), which affects eyelid, pharynx, and proximal limb muscles. Previous work revealed that the Pabpn1 transcript is unstable, contributing to low steady-state Pabpn1 mRNA and protein levels in vivo, specifically in skeletal muscle, with even lower levels in muscles affected in OPMD. Thus, low levels of PABPN1 protein could predispose specific tissues to pathology in OPMD. However, no studies have defined the mechanisms that regulate Pabpn1 expression. Here, we define multiple cis-regulatory elements and a trans-acting factor, HuR, which regulate Pabpn1 expression specifically in mature muscle in vitro and in vivo. We exploit multiple models including C2C12 myotubes, primary muscle cells, and mice to determine that HuR decreases Pabpn1 expression. Overall, we have uncovered a mechanism in mature muscle that negatively regulates Pabpn1 expression in vitro and in vivo, which could provide insight to future studies investigating therapeutic strategies for OPMD treatment.

Cardiac arrhythmia induced by interferon beta-1a.

PubMed

Kastalli, Sarrah; El Aïdli, Sihem; Mourali, Sami; Zaïem, Ahmed; Daghfous, Riadh; Lakhal, Mohamed

2012-04-01

Cardiac adverse effects have never been reported with interferon (INF) beta. We report a case of left bundle branch block in a 35-year-old woman treated with INF beta-1a for multiple sclerosis. Five years after INF therapy, she presented loss of consciousness, retrosternal pains, short breath and lowered tolerance of effort. ECG and Holter 24-h ECG monitoring revealed permanent complete left bundle branch block. Nine months after stopping INF, no abnormalities were found at ECG and echocardiogram examination. © 2011 The Authors Fundamental and Clinical Pharmacology © 2011 Société Française de Pharmacologie et de Thérapeutique.

Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment.

PubMed

Chen, Xiaowei Sylvia; Reader, Rose H; Hoischen, Alexander; Veltman, Joris A; Simpson, Nuala H; Francks, Clyde; Newbury, Dianne F; Fisher, Simon E

2017-04-25

A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential "multiple-hit" cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation.

Next-generation DNA sequencing identifies novel gene variants and pathways involved in specific language impairment

PubMed Central

Chen, Xiaowei Sylvia; Reader, Rose H.; Hoischen, Alexander; Veltman, Joris A.; Simpson, Nuala H.; Francks, Clyde; Newbury, Dianne F.; Fisher, Simon E.

2017-01-01

A significant proportion of children have unexplained problems acquiring proficient linguistic skills despite adequate intelligence and opportunity. Developmental language disorders are highly heritable with substantial societal impact. Molecular studies have begun to identify candidate loci, but much of the underlying genetic architecture remains undetermined. We performed whole-exome sequencing of 43 unrelated probands affected by severe specific language impairment, followed by independent validations with Sanger sequencing, and analyses of segregation patterns in parents and siblings, to shed new light on aetiology. By first focusing on a pre-defined set of known candidates from the literature, we identified potentially pathogenic variants in genes already implicated in diverse language-related syndromes, including ERC1, GRIN2A, and SRPX2. Complementary analyses suggested novel putative candidates carrying validated variants which were predicted to have functional effects, such as OXR1, SCN9A and KMT2D. We also searched for potential “multiple-hit” cases; one proband carried a rare AUTS2 variant in combination with a rare inherited haplotype affecting STARD9, while another carried a novel nonsynonymous variant in SEMA6D together with a rare stop-gain in SYNPR. On broadening scope to all rare and novel variants throughout the exomes, we identified biological themes that were enriched for such variants, including microtubule transport and cytoskeletal regulation. PMID:28440294

The Mitochondrial Genome and Transcriptome of the Basal Dinoflagellate Hematodinium sp.: Character Evolution within the Highly Derived Mitochondrial Genomes of Dinoflagellates

PubMed Central

Gornik, S. G.; Waller, R. F.

2012-01-01

The sister phyla dinoflagellates and apicomplexans inherited a drastically reduced mitochondrial genome (mitochondrial DNA, mtDNA) containing only three protein-coding (cob, cox1, and cox3) genes and two ribosomal RNA (rRNA) genes. In apicomplexans, single copies of these genes are encoded on the smallest known mtDNA chromosome (6 kb). In dinoflagellates, however, the genome has undergone further substantial modifications, including massive genome amplification and recombination resulting in multiple copies of each gene and gene fragments linked in numerous combinations. Furthermore, protein-encoding genes have lost standard stop codons, trans-splicing of messenger RNAs (mRNAs) is required to generate complete cox3 transcripts, and extensive RNA editing recodes most genes. From taxa investigated to date, it is unclear when many of these unusual dinoflagellate mtDNA characters evolved. To address this question, we investigated the mitochondrial genome and transcriptome character states of the deep branching dinoflagellate Hematodinium sp. Genomic data show that like later-branching dinoflagellates Hematodinium sp. also contains an inflated, heavily recombined genome of multicopy genes and gene fragments. Although stop codons are also lacking for cox1 and cob, cox3 still encodes a conventional stop codon. Extensive editing of mRNAs also occurs in Hematodinium sp. The mtDNA of basal dinoflagellate Hematodinium sp. indicates that much of the mtDNA modification in dinoflagellates occurred early in this lineage, including genome amplification and recombination, and decreased use of standard stop codons. Trans-splicing, on the other hand, occurred after Hematodinium sp. diverged. Only RNA editing presents a nonlinear pattern of evolution in dinoflagellates as this process occurs in Hematodinium sp. but is absent in some later-branching taxa indicating that this process was either lost in some lineages or developed more than once during the evolution of the highly unusual dinoflagellate mtDNA. PMID:22113794

The mitochondrial genome and transcriptome of the basal dinoflagellate Hematodinium sp.: character evolution within the highly derived mitochondrial genomes of dinoflagellates.

PubMed

Jackson, C J; Gornik, S G; Waller, R F

2012-01-01

The sister phyla dinoflagellates and apicomplexans inherited a drastically reduced mitochondrial genome (mitochondrial DNA, mtDNA) containing only three protein-coding (cob, cox1, and cox3) genes and two ribosomal RNA (rRNA) genes. In apicomplexans, single copies of these genes are encoded on the smallest known mtDNA chromosome (6 kb). In dinoflagellates, however, the genome has undergone further substantial modifications, including massive genome amplification and recombination resulting in multiple copies of each gene and gene fragments linked in numerous combinations. Furthermore, protein-encoding genes have lost standard stop codons, trans-splicing of messenger RNAs (mRNAs) is required to generate complete cox3 transcripts, and extensive RNA editing recodes most genes. From taxa investigated to date, it is unclear when many of these unusual dinoflagellate mtDNA characters evolved. To address this question, we investigated the mitochondrial genome and transcriptome character states of the deep branching dinoflagellate Hematodinium sp. Genomic data show that like later-branching dinoflagellates Hematodinium sp. also contains an inflated, heavily recombined genome of multicopy genes and gene fragments. Although stop codons are also lacking for cox1 and cob, cox3 still encodes a conventional stop codon. Extensive editing of mRNAs also occurs in Hematodinium sp. The mtDNA of basal dinoflagellate Hematodinium sp. indicates that much of the mtDNA modification in dinoflagellates occurred early in this lineage, including genome amplification and recombination, and decreased use of standard stop codons. Trans-splicing, on the other hand, occurred after Hematodinium sp. diverged. Only RNA editing presents a nonlinear pattern of evolution in dinoflagellates as this process occurs in Hematodinium sp. but is absent in some later-branching taxa indicating that this process was either lost in some lineages or developed more than once during the evolution of the highly unusual dinoflagellate mtDNA.

41 CFR 301-11.9 - When does per diem or actual expense entitlement start/stop?

Code of Federal Regulations, 2010 CFR

2010-07-01

... Federal Travel Regulation System TEMPORARY DUTY (TDY) TRAVEL ALLOWANCES ALLOWABLE TRAVEL EXPENSES 11-PER... authorized point and ends on the day you return to your home, office or other authorized point. ...

Reduced lighting on freeways during periods of low traffic density

DOT National Transportation Integrated Search

1995-02-01

Geometry-related effects of changes in truck size and weight regulations include a diverse set of highway design elements related to virtually every aspect of vehicle design and operation. The turning, stopping, acceleration, hill-climbing, and other...

49 CFR 236.830 - Time, acknowledging.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Time, acknowledging. 236.830 Section 236.830 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Time, acknowledging. As applied to an intermittent automatic train stop system, a predetermined time...

7 CFR 301.50-4 - Conditions governing the interstate movement of regulated articles from quarantined areas.

Code of Federal Regulations, 2011 CFR

2011-01-01

... Department of Agriculture (Continued) ANIMAL AND PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE... conditions, such as traffic lights or stop signs) during October, November, or December, or when ambient air...

Variable criteria sequential stopping rule: Validity and power with repeated measures ANOVA, multiple correlation, MANOVA and relation to Chi-square distribution.

PubMed

Fitts, Douglas A

2017-09-21

The variable criteria sequential stopping rule (vcSSR) is an efficient way to add sample size to planned ANOVA tests while holding the observed rate of Type I errors, α o , constant. The only difference from regular null hypothesis testing is that criteria for stopping the experiment are obtained from a table based on the desired power, rate of Type I errors, and beginning sample size. The vcSSR was developed using between-subjects ANOVAs, but it should work with p values from any type of F test. In the present study, the α o remained constant at the nominal level when using the previously published table of criteria with repeated measures designs with various numbers of treatments per subject, Type I error rates, values of ρ, and four different sample size models. New power curves allow researchers to select the optimal sample size model for a repeated measures experiment. The criteria held α o constant either when used with a multiple correlation that varied the sample size model and the number of predictor variables, or when used with MANOVA with multiple groups and two levels of a within-subject variable at various levels of ρ. Although not recommended for use with χ 2 tests such as the Friedman rank ANOVA test, the vcSSR produces predictable results based on the relation between F and χ 2 . Together, the data confirm the view that the vcSSR can be used to control Type I errors during sequential sampling with any t- or F-statistic rather than being restricted to certain ANOVA designs.

The Association of Trip Distance With Walking To Reach Public Transit: Data from the California Household Travel Survey.

PubMed

Durand, Casey P; Tang, Xiaohui; Gabriel, Kelley P; Sener, Ipek N; Oluyomi, Abiodun O; Knell, Gregory; Porter, Anna K; Oelscher, Deanna M; Kohl, Harold W

2016-06-01

Use of public transit is cited as a way to help individuals incorporate regular physical activity into their day. As a novel research topic, however, there is much we do not know. The aim of this analysis was to identify the correlation between distance to a transit stop and the probability it will be accessed by walking. We also sought to understand if this relation was moderated by trip, personal or household factors. Data from the 2012 California Household Travel Survey was used for this cross-sectional analysis. 2,573 individuals were included, representing 6,949 transit trips. Generalized estimating equations modeled the probability of actively accessing public transit as a function of distance from origin to transit stop, and multiple trip, personal and household variables. Analyses were conducted in 2014 and 2015. For each mile increase in distance from the point of origin to the transit stop, the probability of active access decreased by 12%. With other factors held equal, at two miles from a transit stop there is a 50% chance someone will walk to a stop versus non-active means. The distance-walking relation was modified by month the trips were taken. Individuals appear to be willing to walk further to reach transit than existing guidelines indicate. This implies that for any given transit stop, the zone of potential riders who will walk to reach transit is relatively large. Future research should clarify who transit-related walkers are, and why some are more willing to walk longer distances to transit than others.

The Association of Trip Distance With Walking To Reach Public Transit: Data from the California Household Travel Survey

PubMed Central

Durand, Casey P.; Tang, Xiaohui; Gabriel, Kelley P.; Sener, Ipek N.; Oluyomi, Abiodun O.; Knell, Gregory; Porter, Anna K.; oelscher, Deanna M.; Kohl, Harold W.

2015-01-01

Introduction Use of public transit is cited as a way to help individuals incorporate regular physical activity into their day. As a novel research topic, however, there is much we do not know. The aim of this analysis was to identify the correlation between distance to a transit stop and the probability it will be accessed by walking. We also sought to understand if this relation was moderated by trip, personal or household factors. Methods Data from the 2012 California Household Travel Survey was used for this cross-sectional analysis. 2,573 individuals were included, representing 6,949 transit trips. Generalized estimating equations modeled the probability of actively accessing public transit as a function of distance from origin to transit stop, and multiple trip, personal and household variables. Analyses were conducted in 2014 and 2015. Results For each mile increase in distance from the point of origin to the transit stop, the probability of active access decreased by 12%. With other factors held equal, at two miles from a transit stop there is a 50% chance someone will walk to a stop versus non-active means. The distance-walking relation was modified by month the trips were taken. Conclusions Individuals appear to be willing to walk further to reach transit than existing guidelines indicate. This implies that for any given transit stop, the zone of potential riders who will walk to reach transit is relatively large. Future research should clarify who transit-related walkers are, and why some are more willing to walk longer distances to transit than others. PMID:27429905

Influencing Cancer Screening Participation Rates-Providing a Combined Cancer Screening Program (a 'One Stop' Shop) Could Be a Potential Answer.

PubMed

Bobridge, Amanda; Price, Kay; Gill, Tiffany K; Taylor, Anne W

2017-01-01

Participation in established cancer screening programs remains variable. Therefore, a renewed focus on how to increase screening uptake, including addressing structural barriers such as time, travel, and cost is needed. One approach could be the provision of combined cancer screening, where multiple screening tests are provided at the same time and location (essentially a 'One Stop' screening shop). This cohort study explored both cancer screening behavior and the acceptability of a combined screening approach. Participants of the North Western Adelaide Health Study (NWAHS), South Australia were invited to participate in a questionnaire about cancer screening behaviors and the acceptability of a proposed 'One Stop' cancer screening shop. Data were collected from 10th August 2015 to 18th January 2016, weighted for selection probability, age, and sex and analyzed using descriptive and multivariable logistic regression analysis. 1,562 people, 52% female (mean age 54.1 years ± 15.2) participated. Reported screening participation was low, the highest being for Pap Smear (34.4%). Common reasons for screening participation were preventing sickness (56.1%, CI 53.2-59.0%), maintaining health (51%, CI 48-53.9%), and free program provision (30.9%, CI 28.2-33.6%). Females were less likely to state that screening is not beneficial [OR 0.37 (CI 0.21-0.66), p  < 0.001] and to cite sickness prevention [OR 2.10 (CI 1.46-3.00), p  < 0.001] and free program [OR 1.75 (CI 1.22-2.51), p  < 0.003] as reasons for screening participation. Of those who did not participate, 34.6% (CI 30.3-39.1%) stated that there was nothing that discouraged them from participation, with 55- to 64-year olds [OR 0.24 (CI 0.07-0.74), p  < 0.04] being less likely to cite this reason. 21% (CI 17.2-24.8%) thought they did not need screening, while a smaller proportion stated not having time (6.9%, CI 4.9-9.7%) and the costs associated with screening (5.2%, CI 3.5-7.7%). The majority of participants (85.3%, CI 81.9-88.2%) supported multiple screening being offered at the same time and location. Identified screening behaviors in this study are similar to those reported in the literature. The high support for the concept of combined cancer screening demonstrates that this type of approach is acceptable to potential end users and warrants further investigation.

Exploring the nearly degenerate stop region with sbottom decays

DOE PAGES

An, Haipeng; Gu, Jiayin; Wang, Lian-Tao

2017-04-13

A light stop with mass almost degenerate with the lightest neutralino has important connections with both naturalness and dark matter relic abundance. This region is also very hard to probe at colliders. In this paper, we demonstrate the potential of searching for such stop particles at the LHC from sbottom decays, focusing on two channels with final states 2ℓ+EmissT2ℓ+ETmiss and 1b1ℓ+Emore » $$miss\\atop{T}$$1b1ℓ+E$$miss\\atop{T}$$. We also found that, if the lightest sbottom has mass around or below 1 TeV and has a significant branching ratio to decay to stop and W($$\\tilde{b}$$→$$\\tilde{t}$$W), a stop almost degenerate with neutralino can be excluded up to about 500-600 GeV at the 13 TeV LHC with 300 fb -1 data. The searches we propose are complementary to other SUSY searches at the LHC and could have the best sensitivity to the stop-bino coannihilation region. Finally, since they involve final states which have already been used in LHC searches, a reinterpretation of the search results already has sensitivity. Further optimization could deliver the full potential of these channels.« less

Additional band broadening of peptides in the first size-exclusion chromatographic dimension of an automated stop-flow two-dimensional high performance liquid chromatography.

PubMed

Xu, Jucai; Sun-Waterhouse, Dongxiao; Qiu, Chaoying; Zhao, Mouming; Sun, Baoguo; Lin, Lianzhu; Su, Guowan

2017-10-27

The need to improve the peak capacity of liquid chromatography motivates the development of two-dimensional analysis systems. This paper presented a fully automated stop-flow two-dimensional liquid chromatography system with size exclusion chromatography followed by reversed phase liquid chromatography (SEC×RPLC) to efficiently separate peptides. The effects of different stop-flow operational parameters (stop-flow time, peak parking position, number of stop-flow periods and column temperature) on band broadening in the first dimension (1 st D) SEC column were quantitatively evaluated by using commercial small proteins and peptides. Results showed that the effects of peak parking position and the number of stop-flow periods on band broadening were relatively small. Unlike stop-flow analysis of large molecules with a long running time, additional band broadening was evidently observed for small molecule analytes due to the relatively high effective diffusion coefficient (D eff ). Therefore, shorter analysis time and lower 1 st D column temperature were suggested for analyzing small molecules. The stop-flow two-dimensional liquid chromatography (2D-LC) system was further tested on peanut peptides and an evidently improved resolution was observed for both stop-flow heart-cutting and comprehensive 2D-LC analysis (in spite of additional band broadening in SEC). The stop-flow SEC×RPLC, especially heart-cutting analysis with shorter analysis time and higher 1 st D resolution for selected fractions, offers a promising approach for efficient analysis of complex samples. Copyright © 2017 Elsevier B.V. All rights reserved.

Stop/Start: Overview

Science.gov Websites

1 Stop/Start vehicles use a combination of regenerative and conventional friction braking to slow , The gasoline engine in a start-stop hybrid is much like those in conventional vehicles. Unlike other hybrids that use an electric motor to help power the vehicle, the engine in a start-stop hybrid is usually

Association of Subway Driver's Depressive Symptoms and Experience of Work-Related Problems.

PubMed

Jo, Sun-Jin; Yim, Hyeon Woo; Kim, Hyoung-Ryoul; Lee, Kang Sook; Park, Jong-Ik; Chang, Sung Man

2010-12-03

Subway drivers experience various types of work-related problems during their driving, and those experiences can act as risk factors for depressive symptoms. This study was conducted to investigate the association between work-related problems and subway driver's depressive symptoms. We recruited all of the 961 current subway drivers of a subway company located in Seoul, South Korea and conducted a survey of their socio-demographic and vocational characteristics, hospital visits as an outpatient or inpatient, and work-related problem experiences during the last year. Work-related problems included an accident resulting in death or injury, a conflict with a customer, a sudden stop from an emergency bell, or a near accident. Depressive symptoms were measured with the Center for Epidemiologic Studies-Depression (CES-D) instrument. The survey was performed using a self-report questionnaire from April 16 to July 13, 2007. The data of 827 drivers (86.2%) were analyzed. Experience of a conflict with a passenger (p=0.011), a sudden stop from an emergency bell (p=0.001), or a near accident (p=0.001) increased the prevalence of depressive symptoms among subway drivers. A multiple logistic regression analysis revealed that a sudden stop from an emergency bell increased the risk of depressive symptoms significantly (OR=2.59, p=0.026). Near accidents were marginally associated with a higher risk for depressive symptoms (OR=1.62, p=0.062). The experience of a sudden stop from an emergency bell increased subway driver's depressive symptoms, and near accidents may increase the risk of depressive symptoms. Therefore, interventions for the drivers who had experienced these work-related problems are needed.

Method and apparatus to debug an integrated circuit chip via synchronous clock stop and scan

DOEpatents

Bellofatto, Ralph E [Ridgefield, CT; Ellavsky, Matthew R [Rochester, MN; Gara, Alan G [Mount Kisco, NY; Giampapa, Mark E [Irvington, NY; Gooding, Thomas M [Rochester, MN; Haring, Rudolf A [Cortlandt Manor, NY; Hehenberger, Lance G [Leander, TX; Ohmacht, Martin [Yorktown Heights, NY

2012-03-20

An apparatus and method for evaluating a state of an electronic or integrated circuit (IC), each IC including one or more processor elements for controlling operations of IC sub-units, and each the IC supporting multiple frequency clock domains. The method comprises: generating a synchronized set of enable signals in correspondence with one or more IC sub-units for starting operation of one or more IC sub-units according to a determined timing configuration; counting, in response to one signal of the synchronized set of enable signals, a number of main processor IC clock cycles; and, upon attaining a desired clock cycle number, generating a stop signal for each unique frequency clock domain to synchronously stop a functional clock for each respective frequency clock domain; and, upon synchronously stopping all on-chip functional clocks on all frequency clock domains in a deterministic fashion, scanning out data values at a desired IC chip state. The apparatus and methodology enables construction of a cycle-by-cycle view of any part of the state of a running IC chip, using a combination of on-chip circuitry and software.

A Model for the Stop Planning and Timetables of Customized Buses

PubMed Central

Yang, Yang

2017-01-01

Customized buses (CBs) are a new mode of public transportation and an important part of diversified public transportation, providing advanced, attractive and user-led service. The operational activity of a CB is planned by aggregating space–time demand and similar passenger travel demands. Based on an analysis of domestic and international research and the current development of CBs in China and considering passenger travel data, this paper studies the problems associated with the operation of CBs, such as stop selection, line planning and timetables, and establishes a model for the stop planning and timetables of CBs. The improved immune genetic algorithm (IIGA) is used to solve the model with regard to the following: 1) multiple population design and transport operator design, 2) memory library design, 3) mutation probability design and crossover probability design, and 4) the fitness calculation of the gene segment. Finally, a real-world example in Beijing is calculated, and the model and solution results are verified and analyzed. The results illustrate that the IIGA solves the model and is superior to the basic genetic algorithm in terms of the number of passengers, travel time, average passenger travel time, average passenger arrival time ahead of schedule and total line revenue. This study covers the key issues involving operational systems of CBs, combines theoretical research and empirical analysis, and provides a theoretical foundation for the planning and operation of CBs. PMID:28056041

A Model for the Stop Planning and Timetables of Customized Buses.

PubMed

Ma, Jihui; Zhao, Yanqing; Yang, Yang; Liu, Tao; Guan, Wei; Wang, Jiao; Song, Cuiying

2017-01-01

Customized buses (CBs) are a new mode of public transportation and an important part of diversified public transportation, providing advanced, attractive and user-led service. The operational activity of a CB is planned by aggregating space-time demand and similar passenger travel demands. Based on an analysis of domestic and international research and the current development of CBs in China and considering passenger travel data, this paper studies the problems associated with the operation of CBs, such as stop selection, line planning and timetables, and establishes a model for the stop planning and timetables of CBs. The improved immune genetic algorithm (IIGA) is used to solve the model with regard to the following: 1) multiple population design and transport operator design, 2) memory library design, 3) mutation probability design and crossover probability design, and 4) the fitness calculation of the gene segment. Finally, a real-world example in Beijing is calculated, and the model and solution results are verified and analyzed. The results illustrate that the IIGA solves the model and is superior to the basic genetic algorithm in terms of the number of passengers, travel time, average passenger travel time, average passenger arrival time ahead of schedule and total line revenue. This study covers the key issues involving operational systems of CBs, combines theoretical research and empirical analysis, and provides a theoretical foundation for the planning and operation of CBs.

In vitro incorporation of nonnatural amino acids into protein using tRNACys-derived opal, ochre, and amber suppressor tRNAs

PubMed Central

Gubbens, Jacob; Kim, Soo Jung; Yang, Zhongying; Johnson, Arthur E.; Skach, William R.

2010-01-01

Amber suppressor tRNAs are widely used to incorporate nonnatural amino acids into proteins to serve as probes of structure, environment, and function. The utility of this approach would be greatly enhanced if multiple probes could be simultaneously incorporated at different locations in the same protein without other modifications. Toward this end, we have developed amber, opal, and ochre suppressor tRNAs derived from Escherichia coli, and yeast tRNACys that incorporate a chemically modified cysteine residue with high selectivity at the cognate UAG, UGA, and UAA stop codons in an in vitro translation system. These synthetic tRNAs were aminoacylated in vitro, and the labile aminoacyl bond was stabilized by covalently attaching a fluorescent dye to the cysteine sulfhydryl group. Readthrough efficiency (amber > opal > ochre) was substantially improved by eRF1/eRF3 inhibition with an RNA aptamer, thus overcoming an intrinsic hierarchy in stop codon selection that limits UGA and UAA termination suppression in higher eukaryotic translation systems. This approach now allows concurrent incorporation of two different modified amino acids at amber and opal codons with a combined apparent readthrough efficiency of up to 25% when compared with the parent protein lacking a stop codon. As such, it significantly expands the possibilities for incorporating nonnative amino acids for protein structure/function studies. PMID:20581130

YY1 Regulates Melanocyte Development and Function by Cooperating with MITF

PubMed Central

Bell, Robert J. A.; Tran, Thanh-Nga T.; Haq, Rizwan; Liu, Huifei; Love, Kevin T.; Langer, Robert; Anderson, Daniel G.; Larue, Lionel; Fisher, David E.

2012-01-01

Studies of coat color mutants have greatly contributed to the discovery of genes that regulate melanocyte development and function. Here, we generated Yy1 conditional knockout mice in the melanocyte-lineage and observed profound melanocyte deficiency and premature gray hair, similar to the loss of melanocytes in human piebaldism and Waardenburg syndrome. Although YY1 is a ubiquitous transcription factor, YY1 interacts with M-MITF, the Waardenburg Syndrome IIA gene and a master transcriptional regulator of melanocytes. YY1 cooperates with M-MITF in regulating the expression of piebaldism gene KIT and multiple additional pigmentation genes. Moreover, ChIP–seq identified genome-wide YY1 targets in the melanocyte lineage. These studies mechanistically link genes implicated in human conditions of melanocyte deficiency and reveal how a ubiquitous factor (YY1) gains lineage-specific functions by co-regulating gene expression with a lineage-restricted factor (M-MITF)—a general mechanism which may confer tissue-specific gene expression in multiple lineages. PMID:22570637

Cyclin D1 down-regulation is essential for DBC2's tumor suppressor function

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

Yoshihara, Takashi; Collado, Denise; Hamaguchi, Masaaki

2007-07-13

The expression of tumor suppressor gene DBC2 causes certain breast cancer cells to stop growing [M. Hamaguchi, J.L. Meth, C. Von Klitzing, W. Wei, D. Esposito, L. Rodgers, T. Walsh, P. Welcsh, M.C. King, M.H. Wigler, DBC2, a candidate for a tumor suppressor gene involved in breast cancer, Proc. Natl. Acad. Sci. USA 99 (2002) 13647-13652]. Recently, DBC2 was found to participate in diverse cellular functions such as protein transport, cytoskeleton regulation, apoptosis, and cell cycle control [V. Siripurapu, J.L. Meth, N. Kobayashi, M. Hamaguchi, DBC2 significantly influences cell cycle, apoptosis, cytoskeleton, and membrane trafficking pathways. J. Mol. Biol. 346more » (2005) 83-89]. Its tumor suppression mechanism, however, remains unclear. In this paper, we demonstrate that DBC2 suppresses breast cancer proliferation through down-regulation of Cyclin D1 (CCND1). Additionally, the constitutional overexpression of CCND1 prevented the negative impact of DBC2 expression on their growth. Under a CCND1 promoter, the expression of CCNE1 exhibited the same protective effect. Our results indicate that the down-regulation of CCND1 is an essential step for DBC2's growth suppression of cancer cells. We believe that this discovery contributes to a better understanding of DBC2's tumor suppressor function.« less

Reach of the high-energy LHC for gluinos and top squarks in SUSY models with light Higgsinos

NASA Astrophysics Data System (ADS)

Baer, Howard; Barger, Vernon; Gainer, James S.; Serce, Hasan; Tata, Xerxes

2017-12-01

We examine the top squark (stop) and gluino reach of the proposed 33 TeV energy upgrade of the Large Hadron Collider (LHC33) in the Minimal Supersymmetric Standard Model (MSSM) with light Higgsinos and relatively heavy electroweak gauginos. In our analysis, we assume that stops decay to Higgsinos via t˜1→t Z˜1, t˜1→t Z˜2, and t˜1→b W˜1 with branching fractions in the ratio 1 ∶1 ∶2 (expected if the decay occurs dominantly via the superpotential Yukawa coupling), while gluinos decay via g ˜→t t˜1 or via three-body decays to third-generation quarks plus Higgsinos. These decay patterns are motivated by models of natural supersymmetry where Higgsinos are expected to be close in mass to mZ, but gluinos may be as heavy as 5-6 TeV, and stops may have masses up to ˜3 TeV . We devise cuts to optimize the signals from stop and gluino pair production at LHC33. We find that experiments at LHC33 should be able to discover stops with >5 σ significance if mt˜1<2.3 (2.8) [3.2] TeV for an integrated luminosity of 0.3 (1) [3 ] ab-1 . The corresponding reach for gluinos extends to 5 (5.5) [6] TeV. These results imply that experiments at LHC33 should be able to discover at least one of the stop or gluino pair signals even with an integrated luminosity of 0.3 ab-1 for natural supersymmetry models with no worse than 3% electroweak fine-tuning and quite likely both gluinos and stops for an integrated luminosity of 3 ab-1 .

Kisspeptin: past, present, and prologue.

PubMed

Steiner, Robert A

2013-01-01

Research in the nineteenth and early twentieth century established that the brain awakens reproduction, governs reproductive activity in the adult of virtually all vertebrates. By 1950, nearly 100 years later, scientists realized that the hypothalamus and its neurosecretory products play a key role in regulating gonadal function in both males and females. Another 20 years would be required to reveal the chemical identity of GnRH and establish that neurons producing GnRH represent the final common pathway through which the brain regulates gonadotropin secretion. It had also become clear that GnRH neurons behave more like motor neurons-better perhaps at going than stopping-and are themselves regulated by a complex network of afferent inputs, which guide the tempo of sexual maturation, regulate estrous and menstrual cycles, control seasonal breeding, and stop reproduction under adversity. In 2003, the revelation that kisspeptin and its receptor are critical for reproduction opened a floodgate of research documenting the role of kisspeptin neurons as central processors of reproduction. Today, there is wide consensus that kisspeptin signaling in the brain is essential, providing the impetus to GnRH neurons to awaken at puberty and reigning the activity of these neurons when discretion is advised. We celebrate this watershed moment-with full knowledge that time and discovery will provide context and perspective to even these heady days.

The rapid access palliative radiotherapy program: blueprint for initiation of a one-stop multidisciplinary bone metastases clinic.

PubMed

Fairchild, A; Pituskin, E; Rose, B; Ghosh, S; Dutka, J; Driga, A; Tachynski, P; Borschneck, J; Gagnon, L; Macdonnell, S; Middleton, J; Thavone, K; Carstairs, S; Brent, D; Severin, D

2009-02-01

Radiotherapy (RT) for palliation of pain due to bone metastases (BM) is effective but underutilized likely due to the traditional practice of separate clinic visits for consultation, treatment planning, and RT delivery. However, recent evidence proves one RT treatment is as effective as multiple for analgesia, enabling investigation of an alternative model of RT delivery, the rapid access palliative radiotherapy program (RAPRP). Prior to the start of the program, needs assessment was performed to determine the composition of the optimal team. Screening tools were implemented to streamline holistic, multidisciplinary assessment. An advertising strategy, treatment and research protocols, and mechanisms for patient feedback were established. After RAPRP implementation, patient outcomes such as symptom relief were tracked. Eighty-six patients with painful BM were referred over the 25-week pilot. Median age was 69.9 years; 64% had prostate cancer, and median performance status was 70. Patient-rated pain was on average 6.1/10 at baseline, improving to 2.6/10 by week 4 post-RT. On average, 6.2 symptoms were reported (baseline) compared to 5.2 (week 4). Team members assessed 10-100% of patients and were successful in stabilizing or improving all symptoms in >75% contacted at week 4. One hundred percent of patients surveyed were satisfied with their experience. Early needs assessment was advantageous in determining the optimal team and methods of assessment for our 'one-stop' BM clinic. This approach was successful in improving pain and other symptoms, and the convenience of seeing multiple providers on 1 day was appreciated by the patients.

Survey of diagnostic and treatment practices for multiple sclerosis (MS) in Europe. Part 2: Progressive MS, paediatric MS, pregnancy and general management.

PubMed

Fernández, O; Delvecchio, M; Edan, G; Fredrikson, S; Giovannoni, G; Hartung, H-P; Havrdova, E; Kappos, L; Pozzilli, C; Soerensen, P S; Tackenberg, B; Vermersch, P; Comi, G

2018-05-01

The European Charcot Foundation supported the development of a set of surveys to understand current practice patterns for the diagnosis and management of multiple sclerosis (MS) in Europe. Part 2 of the report summarizes survey results related to secondary progressive MS (SPMS), primary progressive MS (PPMS), pregnancy, paediatric MS and overall patient management. A steering committee of MS neurologists developed case- and practice-based questions for two sequential surveys distributed to MS neurologists throughout Europe. Respondents generally favoured changing rather than stopping disease-modifying treatment (DMT) in patients transitioning from relapsing-remitting MS to SPMS, particularly with active disease. Respondents would not initiate DMT in patients with typical PPMS symptoms, although the presence of ≥1 spinal cord or brain gadolinium-enhancing lesion might affect that decision. For patients considering pregnancy, respondents were equally divided on whether to stop treatment before or after conception. Respondents strongly favoured starting DMT in paediatric MS with active disease; recommended treatments included interferon, glatiramer acetate and, in John Cunningham virus negative patients, natalizumab. Additional results regarding practice-based questions and management are summarized. Results of part 2 of the survey of diagnostic and treatment practices for MS in Europe largely mirror results for part 1, with neurologists in general agreement about the treatment and management of SPMS, PPMS, pregnancy and paediatric MS as well as the general management of MS. However, there are also many areas of disagreement, indicating the need for evidence-based recommendations and/or guidelines. © 2018 EAN.

Management of multiple sclerosis: the role of coping self-efficacy and self-esteem.

PubMed

Mikula, Pavol; Nagyova, Iveta; Vitkova, Marianna; Szilasiova, Jarmila

2018-02-07

Patients with multiple sclerosis (MS) engage in various coping behaviours in order to manage their disease. The aim of this study is to find out if the self-esteem of patients is associated with coping strategies - problem-focused (e.g. making a plan of action when confronted with a problem); emotion focused (e.g. get emotional support from community); and focused on stopping unpleasant emotions and thoughts (e.g. keeping oneself from feeling sad), and if it can enhance or hinder coping efforts in the disease management. We collected data from 155 consecutive MS patients who completed the Coping Self-Efficacy Scale (CSE) and the Rosenberg Self-esteem Scale (RSE). Explained variance for problem-focused coping, emotion-focused coping, and coping focused on stopping unpleasant emotions and thoughts was 33, 24, and 31%, respectively. Self-esteem seems to be associated with coping strategies indicating that feelings of self-worth are linked with the ability to handle difficult life situations and can be helpful in chronic disease management.

Route optimization as an instrument to improve animal welfare and economics in pre-slaughter logistics.

PubMed

Frisk, Mikael; Jonsson, Annie; Sellman, Stefan; Flisberg, Patrik; Rönnqvist, Mikael; Wennergren, Uno

2018-01-01

Each year, more than three million animals are transported from farms to abattoirs in Sweden. Animal transport is related to economic and environmental costs and a negative impact on animal welfare. Time and the number of pick-up stops between farms and abattoirs are two key parameters for animal welfare. Both are highly dependent on efficient and qualitative transportation planning, which may be difficult if done manually. We have examined the benefits of using route optimization in cattle transportation planning. To simulate the effects of various planning time windows and transportation time regulations and number of pick-up stops along each route, we have used data that represent one year of cattle transport. Our optimization model is a development of a model used in forestry transport that solves a general pick-up and delivery vehicle routing problem. The objective is to minimize transportation costs. We have shown that the length of the planning time window has a significant impact on the animal transport time, the total driving time and the total distance driven; these parameters that will not only affect animal welfare but also affect the economy and environment in the pre-slaughter logistic chain. In addition, we have shown that changes in animal transportation regulations, such as minimizing the number of allowed pick-up stops on each route or minimizing animal transportation time, will have positive effects on animal welfare measured in transportation hours and number of pick-up stops. However, this leads to an increase in working time and driven distances, leading to higher transportation costs for the transport and negative environmental impact.

Route optimization as an instrument to improve animal welfare and economics in pre-slaughter logistics

PubMed Central

2018-01-01

Each year, more than three million animals are transported from farms to abattoirs in Sweden. Animal transport is related to economic and environmental costs and a negative impact on animal welfare. Time and the number of pick-up stops between farms and abattoirs are two key parameters for animal welfare. Both are highly dependent on efficient and qualitative transportation planning, which may be difficult if done manually. We have examined the benefits of using route optimization in cattle transportation planning. To simulate the effects of various planning time windows and transportation time regulations and number of pick-up stops along each route, we have used data that represent one year of cattle transport. Our optimization model is a development of a model used in forestry transport that solves a general pick-up and delivery vehicle routing problem. The objective is to minimize transportation costs. We have shown that the length of the planning time window has a significant impact on the animal transport time, the total driving time and the total distance driven; these parameters that will not only affect animal welfare but also affect the economy and environment in the pre-slaughter logistic chain. In addition, we have shown that changes in animal transportation regulations, such as minimizing the number of allowed pick-up stops on each route or minimizing animal transportation time, will have positive effects on animal welfare measured in transportation hours and number of pick-up stops. However, this leads to an increase in working time and driven distances, leading to higher transportation costs for the transport and negative environmental impact. PMID:29513704

Structural insights into the interaction between a potent anti-inflammatory protein, viral CC chemokine inhibitor (vCCI), and the human CC chemokine, Eotaxin-1.

PubMed

Kuo, Nai-Wei; Gao, Yong-Guang; Schill, Megan S; Isern, Nancy; Dupureur, Cynthia M; Liwang, Patricia J

2014-03-07

Chemokines play important roles in the immune system, not only recruiting leukocytes to the site of infection and inflammation but also guiding cell homing and cell development. The soluble poxvirus-encoded protein viral CC chemokine inhibitor (vCCI), a CC chemokine inhibitor, can bind to human CC chemokines tightly to impair the host immune defense. This protein has no known homologs in eukaryotes and may represent a potent method to stop inflammation. Previously, our structure of the vCCI·MIP-1β (macrophage inflammatory protein-1β) complex indicated that vCCI uses negatively charged residues in β-sheet II to interact with positively charged residues in the MIP-1β N terminus, 20s region and 40s loop. However, the interactions between vCCI and other CC chemokines have not yet been fully explored. Here, we used NMR and fluorescence anisotropy to study the interaction between vCCI and eotaxin-1 (CCL11), a CC chemokine that is an important factor in the asthma response. NMR results reveal that the binding pattern is very similar to the vCCI·MIP-1β complex and suggest that electrostatic interactions provide a major contribution to binding. Fluorescence anisotropy results on variants of eotaxin-1 further confirm the critical roles of the charged residues in eotaxin-1. In addition, the binding affinity between vCCI and other wild type CC chemokines, MCP-1 (monocyte chemoattractant protein-1), MIP-1β, and RANTES (regulated on activation normal T cell expressed and secreted), were determined as 1.1, 1.2, and 0.22 nm, respectively. To our knowledge, this is the first work quantitatively measuring the binding affinity between vCCI and multiple CC chemokines.

Structural Insights into the Interaction between a Potent Anti-inflammatory Protein, Viral CC Chemokine Inhibitor (vCCI), and the Human CC Chemokine, Eotaxin-1*

PubMed Central

Kuo, Nai-Wei; Gao, Yong-Guang; Schill, Megan S.; Isern, Nancy; Dupureur, Cynthia M.; LiWang, Patricia J.

2014-01-01

Chemokines play important roles in the immune system, not only recruiting leukocytes to the site of infection and inflammation but also guiding cell homing and cell development. The soluble poxvirus-encoded protein viral CC chemokine inhibitor (vCCI), a CC chemokine inhibitor, can bind to human CC chemokines tightly to impair the host immune defense. This protein has no known homologs in eukaryotes and may represent a potent method to stop inflammation. Previously, our structure of the vCCI·MIP-1β (macrophage inflammatory protein-1β) complex indicated that vCCI uses negatively charged residues in β-sheet II to interact with positively charged residues in the MIP-1β N terminus, 20s region and 40s loop. However, the interactions between vCCI and other CC chemokines have not yet been fully explored. Here, we used NMR and fluorescence anisotropy to study the interaction between vCCI and eotaxin-1 (CCL11), a CC chemokine that is an important factor in the asthma response. NMR results reveal that the binding pattern is very similar to the vCCI·MIP-1β complex and suggest that electrostatic interactions provide a major contribution to binding. Fluorescence anisotropy results on variants of eotaxin-1 further confirm the critical roles of the charged residues in eotaxin-1. In addition, the binding affinity between vCCI and other wild type CC chemokines, MCP-1 (monocyte chemoattractant protein-1), MIP-1β, and RANTES (regulated on activation normal T cell expressed and secreted), were determined as 1.1, 1.2, and 0.22 nm, respectively. To our knowledge, this is the first work quantitatively measuring the binding affinity between vCCI and multiple CC chemokines. PMID:24482230

49 CFR 236.744 - Element, roadway.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 49 Transportation 4 2013-10-01 2013-10-01 false Element, roadway. 236.744 Section 236.744 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Element, roadway. That portion of the roadway apparatus of automatic train stop, train control, or cab...

49 CFR 236.744 - Element, roadway.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Element, roadway. 236.744 Section 236.744 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Element, roadway. That portion of the roadway apparatus of automatic train stop, train control, or cab...

49 CFR 236.744 - Element, roadway.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 49 Transportation 4 2014-10-01 2014-10-01 false Element, roadway. 236.744 Section 236.744 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Element, roadway. That portion of the roadway apparatus of automatic train stop, train control, or cab...

49 CFR 236.744 - Element, roadway.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 49 Transportation 4 2012-10-01 2012-10-01 false Element, roadway. 236.744 Section 236.744 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Element, roadway. That portion of the roadway apparatus of automatic train stop, train control, or cab...

50 CFR 218.33 - Mitigation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... take proper and effective action to avoid a collision with any marine animal and can be stopped within... and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS Taking...

A xenograft model reveals that PU.1 functions as a tumor suppressor for multiple myeloma in vivo

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

Nishimura, Nao; Endo, Shinya; Ueno, Shikiko

We previously demonstrated that PU.1 expression is down-regulated in the majority of myeloma cell lines and primary myeloma cells from patients. We introduced the tet-off system into the human myeloma cell lines U266 and KMS12PE that conditionally express PU.1 and demonstrated that PU.1 induces cell cycle arrest and apoptosis in myeloma cells in vitro. Here, we established a mouse xenograft model of myeloma using these cell lines to analyze the effects of PU.1 on the phenotype of myeloma cells in vivo. When doxycycline was added to the drinking water of mice engrafted with these myeloma cells, all mice had continuous growth ofmore » subcutaneous tumors and could not survived more than 65 days. In contrast, mice that were not exposed to doxycycline did not develop subcutaneous tumors and survived for at least 100 days. We next generated mice engrafted with subcutaneous tumors 5–10 mm in diameter that were induced by exposure to doxycycline. Half of the mice stopped taking doxycycline-containing water, whereas the other half kept taking the water. Although the tumors in the mice taking doxycycline continued to grow, tumor growth in the mice not taking doxycycline was significantly suppressed. The myeloma cells in the tumors of the mice not taking doxycycline expressed PU.1 and TRAIL and many of such cells were apoptotic. Moreover, the expression of a cell proliferation marker Ki67 was significantly decreased in tumors from the mice not taking doxycycline, compared with that of tumors from the mice continuously taking doxycycline. The present data strongly suggest that PU.1 functions as a tumor suppressor of myeloma cells in vivo. - Highlights: • PU.1 suppresses xenograft myeloma cell growth and prolongs survival periods of mice. • PU.1 induces TRAIL expression and apoptosis in myeloma cells in vivo. • PU.1 suppresses Ki67 expression in myeloma cells in vivo. • Up-regulation of PU.1 is a promising strategy for generating anti-myeloma agents.« less

The impact of sociodemographic, treatment, and work support on missed work after breast cancer diagnosis.

PubMed

Mujahid, Mahasin S; Janz, Nancy K; Hawley, Sarah T; Griggs, Jennifer J; Hamilton, Ann S; Katz, Steven J

2010-01-01

Work loss is a potential adverse consequence of cancer. There is limited research on patterns and correlates of paid work after diagnosis of breast cancer, especially among ethnic minorities. Women with non-metastatic breast cancer diagnosed from June 2005 to May 2006 who reported to the Los Angeles County SEER registry were identified and asked to complete the survey after initial treatment (median time from diagnosis = 8.9 months). Latina and African American women were over-sampled. Analyses were restricted to women working at the time of diagnosis, <65 years of age, and who had complete covariate information (N = 589). The outcome of the study was missed paid work (1 month, stopped all together). Approximately 44, 24, and 32% of women missed 1 month, or stopped working, respectively. African Americans and Latinas were more likely to stop working when compared with Whites [OR for stop working vs. missed

Mis-Spliced Lr34 Transcript Events in Winter Wheat.

PubMed

Fang, Tilin; Carver, Brett F; Hunger, Robert M; Yan, Liuling

2017-01-01

Lr34 in wheat is a non-race-specific gene that confers resistance against multiple fungal pathogens. The resistant allele Lr34 and the susceptible allele Lr34s can be distinguished by three polymorphisms that cause alternation of deduced amino acid sequences of Lr34 at the protein level. In seedlings of a cultivar carrying the resistant Lr34r allele, only a portion (35%) of its transcripts was correctly spliced and the majority (65%) of its transcripts were incorrectly spliced due to multiple mis-splicing events. Lr34 mis-splicing events were also observed at adult plant age when this gene exerts its function. All of the mis-spliced Lr34r cDNA transcripts observed in this study resulted in a premature stop codon due to a shift of the open reading frame; hence, the mis-spliced Lr34r cDNAs were deduced to encode incomplete proteins. Even if a cultivar has a functional Lr34 gene, its transcripts might not completely splice in a correct pattern. These findings suggested that the partial resistance conferred by a quantitative gene might be due to mis-splicing events in its transcripts; hence, the resistance of the gene could be increased by eliminating or mutating regulators that cause mis-splicing events in wheat.

Engagement of large-scale networks is related to individual differences in inhibitory control

PubMed Central

Congdon, Eliza; Mumford, Jeanette A.; Cohen, Jessica R.; Galvan, Adriana; Aron, Adam R.; Xue, Gui; Miller, Eric; Poldrack, Russell A.

2010-01-01

Understanding which brain regions regulate the execution, and suppression, of goal-directed behavior has implications for a number of areas of research. In particular, understanding which brain regions engaged during tasks requiring the execution and inhibition of a motor response provides insight into the mechanisms underlying individual differences in response inhibition ability. However, neuroimaging studies examing the relation between activation and stopping have been inconsistent regarding the direction of the relationship, and also regarding the anatomical location of regions that correlate with behavior. These limitations likely arise from the relatively low power of vox-elwise correlations with small sample sizes. Here, we pooled data over five separate fMRI studies of the Stop-signal task in order to obtain a sufficiently large sample size to robustly detect brain/behavior correlations. In addition, rather than performing mass univariate correlation analysis across all voxels, we increased statistical power by reducing the dimensionality of the data set using independent components analysis and then examined correlations between behavior and the resulting component scores. We found that components reflecting activity in regions thought to be involved in stopping were associated with better stopping ability, while activity in a default-mode network was associated with poorer stopping ability across individuals. These results clearly show a relationship between individual differences in stopping ability in specific activated networks, including regions known to be critical for the behavior. The results also highlight the usefulness of using dimensionality reduction to increase the power to detect brain/behavior correlations in individual differences research. PMID:20600962

Chemical Dosing and First-Order Kinetics

ERIC Educational Resources Information Center

Hladky, Paul W.

2011-01-01

College students encounter a variety of first-order phenomena in their mathematics and science courses. Introductory chemistry textbooks that discuss first-order processes, usually in conjunction with chemical kinetics or radioactive decay, stop at single, discrete dose events. Although single-dose situations are important, multiple-dose events,…

41 CFR 102-5.30 - What definitions apply to this part?

Code of Federal Regulations, 2010 CFR

2010-07-01

... business or would substantially increase a Federal agency's efficiency and economy. Emergency means... locations other than his/her regular place of work. (Multiple stops (itinerant-type travel) within the... locations that are only accessible by Government-provided transportation are examples of field work.) Home...

Prediction of Supersonic Store Separation Characteristics Including Fuselage and Stores of Noncircular Cross Section. Volume II. Users Manual for the Computer Program.

DTIC Science & Technology

1980-11-01

CMACH $ FMACH) 132 TRJTRY STOP normal termination (test: TIME > TIMEF-0.00001 or NDIFEQ = 1) BDCOEF message warning - NAFLD exceeds blank common...BDCOEF**, NTAP7- , IUB= , NAFLD = . (Test: NAFLD > NADIM) CRFWBD STOP 001 (Test: NER > 1; equation solution singular) INVER2 STOP **Matrix is singular

AnnoLnc: a web server for systematically annotating novel human lncRNAs.

PubMed

Hou, Mei; Tang, Xing; Tian, Feng; Shi, Fangyuan; Liu, Fenglin; Gao, Ge

2016-11-16

Long noncoding RNAs (lncRNAs) have been shown to play essential roles in almost every important biological process through multiple mechanisms. Although the repertoire of human lncRNAs has rapidly expanded, their biological function and regulation remain largely elusive, calling for a systematic and integrative annotation tool. Here we present AnnoLnc ( http://annolnc.cbi.pku.edu.cn ), a one-stop portal for systematically annotating novel human lncRNAs. Based on more than 700 data sources and various tool chains, AnnoLnc enables a systematic annotation covering genomic location, secondary structure, expression patterns, transcriptional regulation, miRNA interaction, protein interaction, genetic association and evolution. An intuitive web interface is available for interactive analysis through both desktops and mobile devices, and programmers can further integrate AnnoLnc into their pipeline through standard JSON-based Web Service APIs. To the best of our knowledge, AnnoLnc is the only web server to provide on-the-fly and systematic annotation for newly identified human lncRNAs. Compared with similar tools, the annotation generated by AnnoLnc covers a much wider spectrum with intuitive visualization. Case studies demonstrate the power of AnnoLnc in not only rediscovering known functions of human lncRNAs but also inspiring novel hypotheses.

Historical development and current status of organ procurement from death-row prisoners in China.

PubMed

Allison, Kirk C; Caplan, Arthur; Shapiro, Michael E; Els, Charl; Paul, Norbert W; Li, Huige

2015-12-03

In December 2014, China announced that only voluntarily donated organs from citizens would be used for transplantation after January 1, 2015. Many medical professionals worldwide believe that China has stopped using organs from death-row prisoners. In the present article, we briefly review the historical development of organ procurement from death-row prisoners in China and comprehensively analyze the social-political background and the legal basis of the announcement. The announcement was not accompanied by any change in organ sourcing legislations or regulations. As a fact, the use of prisoner organs remains legal in China. Even after January 2015, key Chinese transplant officials have repeatedly stated that death-row prisoners have the same right as regular citizens to "voluntarily donate" organs. This perpetuates an unethical organ procurement system in ongoing violation of international standards. Organ sourcing from death-row prisoners has not stopped in China. The 2014 announcement refers to the intention to stop the use of organs illegally harvested without the consent of the prisoners. Prisoner organs procured with "consent" are now simply labelled as "voluntarily donations from citizens". The semantic switch may whitewash sourcing from both death-row prisoners and prisoners of conscience. China can gain credibility only by enacting new legislation prohibiting use of prisoner organs and by making its organ sourcing system open to international inspections. Until international ethical standards are transparently met, sanctions should remain.

45 CFR 1310.20 - Trip routing.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START... for reasons of safety or because of physical barriers. (4) Stops must be located to minimize traffic...

45 CFR 1310.20 - Trip routing.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START... for reasons of safety or because of physical barriers. (4) Stops must be located to minimize traffic...

45 CFR 1310.20 - Trip routing.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Welfare Regulations Relating to Public Welfare (Continued) OFFICE OF HUMAN DEVELOPMENT SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES THE ADMINISTRATION FOR CHILDREN, YOUTH AND FAMILIES, HEAD START... for reasons of safety or because of physical barriers. (4) Stops must be located to minimize traffic...

49 CFR 236.831 - Time, delay.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Time, delay. 236.831 Section 236.831 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Time, delay. As applied to an automatic train stop or train control system, the time which elapses...

49 CFR 236.812 - Speed, restricted.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Speed, restricted. 236.812 Section 236.812 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Speed, restricted. A speed that will permit stopping within one-half the range of vision, but not...

49 CFR 236.812 - Speed, restricted.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Speed, restricted. 236.812 Section 236.812 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Speed, restricted. A speed that will permit stopping within one-half the range of vision, but not...

50 CFR 218.33 - Mitigation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... take proper and effective action to avoid a collision with any marine animal and can be stopped within... Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS Taking...

50 CFR 218.33 - Mitigation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... take proper and effective action to avoid a collision with any marine animal and can be stopped within... Wildlife and Fisheries NATIONAL MARINE FISHERIES SERVICE, NATIONAL OCEANIC AND ATMOSPHERIC ADMINISTRATION, DEPARTMENT OF COMMERCE MARINE MAMMALS REGULATIONS GOVERNING THE TAKING AND IMPORTING OF MARINE MAMMALS Taking...

Reasons Why Children and Adolescents With Attention-Deficit/Hyperactivity Disorder Stop and Restart Taking Medicine.

PubMed

Brinkman, William B; Simon, John O; Epstein, Jeffery N

2018-04-01

To describe the prevalence of reasons why children and adolescents stop and restart attention-deficit/hyperactivity disorder (ADHD) medicine and whether functional impairment is present after stopping medicine. We used the prospective longitudinal cohort from the Multimodal Treatment of Study of Children With ADHD. At the 12-year follow-up, when participants were a mean of 21.1 years old, 372 participants (76% male, 64% white) reported ever taking ADHD medicine. Participants reported the age when they last stopped and/or restarted ADHD medicine and also endorsed reasons for stopping and restarting. Seventy-seven percent (286 of 372) reported stopping medicine for a month or longer at some time during childhood or adolescence. Participants were a mean of 13.3 years old when they last stopped medicine. The most commonly endorsed reasons for stopping medication related to 1) medicine not needed/helping, 2) adverse effects, 3) logistical barriers of getting or taking medication, and 4) social concerns or stigma. Seventeen percent (64 of 372) reported restarting medicine after stopping for a month or longer. Commonly endorsed reasons for restarting related to medicine being needed or medicine helping; and resolution of logistical barriers to getting or taking medicine. For both stopping and restarting, the proportion endorsing some reasons differed by age range, with the overall pattern suggesting that parental involvement in decisions decreased with age. Nearly all participants had impairment at the assessment after stopping, regardless of whether medication was resumed. Different reasons for stopping and/or restarting medicine are relevant at different times for different teens. Tailored strategies may help engage adolescents as full partners in their treatment plan. Copyright © 2017 Academic Pediatric Association. Published by Elsevier Inc. All rights reserved.

DISC1 regulates new neuron development in the adult brain via modulation of AKT-mTOR signaling through KIAA1212.

PubMed

Kim, Ju Young; Duan, Xin; Liu, Cindy Y; Jang, Mi-Hyeon; Guo, Junjie U; Pow-anpongkul, Nattapol; Kang, Eunchai; Song, Hongjun; Ming, Guo-li

2009-09-24

Disrupted-in-schizophrenia 1 (DISC1), a susceptibility gene for major mental illnesses, regulates multiple aspects of embryonic and adult neurogenesis. Here, we show that DISC1 suppression in newborn neurons of the adult hippocampus leads to overactivated signaling of AKT, another schizophrenia susceptibility gene. Mechanistically, DISC1 directly interacts with KIAA1212, an AKT binding partner that enhances AKT signaling in the absence of DISC1, and DISC1 binding to KIAA1212 prevents AKT activation in vitro. Functionally, multiple genetic manipulations to enhance AKT signaling in adult-born neurons in vivo exhibit similar defects as DISC1 suppression in neuronal development that can be rescued by pharmacological inhibition of mammalian target of rapamycin (mTOR), an AKT downstream effector. Our study identifies the AKT-mTOR signaling pathway as a critical DISC1 target in regulating neuronal development and provides a framework for understanding how multiple susceptibility genes may functionally converge onto a common pathway in contributing to the etiology of certain psychiatric disorders.

Developing Effective Linkages between Job Corps and One-Stop Systems: A Technical Assistance Guide.

ERIC Educational Resources Information Center

Dickinson, Katherine; Soukamneuth, Sengsouvanh

This document is intended to help Job Corps centers and Office of Acquisition Policy contractors establish linkages with one-stop systems. Chapter 1 summarizes the requirements for linkages between Job Corps and one-stop systems that are specified in the Workforce Investment Act (WIA) of 1998 and compares one-stop delivery systems before and under…

49 CFR Appendix A to Part 180 - Internal Self-closing Stop Valve Emergency Closure Test for Liquefied Compressed Gases

Code of Federal Regulations, 2011 CFR

2011-10-01

... Part 180—Internal Self-closing Stop Valve Emergency Closure Test for Liquefied Compressed Gases 1. In performing this test, all internal self-closing stop valves must be opened. Each emergency discharge control... 49 Transportation 3 2011-10-01 2011-10-01 false Internal Self-closing Stop Valve Emergency Closure...

Final Environmental Assessment (EA) for the Revitalization of Military Family Housing Keesler AFB, MS

DTIC Science & Technology

2006-03-01

12,000 square feet each). An Olympic-size swimming pool (approximately 71 feet by 164 feet). Twelve covered bus stops. A skateboard park...11,644 Covered Bus Stop 100 12 1,200 Skateboard Park 10,890 1 10,890 Storage Unit 100 534 53,400 Total N/A N/A 125,134 Location to be determined...Olympic-size Swimming Pool 1 1 Covered Bus Stop 5 4 3 12 Skateboard Park 1 1 Storage Unit 0 294 160 80 534 2.6 ALTERNATIVE 1 (IMMEDIATE

Grooming a CAT: customizing CAT administration rules to increase response efficiency in specific research and clinical settings.

PubMed

Kallen, Michael A; Cook, Karon F; Amtmann, Dagmar; Knowlton, Elizabeth; Gershon, Richard C

2018-05-05

To evaluate the degree to which applying alternative stopping rules would reduce response burden while maintaining score precision in the context of computer adaptive testing (CAT). Analyses were conducted on secondary data comprised of CATs administered in a clinical setting at multiple time points (baseline and up to two follow ups) to 417 study participants who had back pain (51.3%) and/or depression (47.0%). Participant mean age was 51.3 years (SD = 17.2) and ranged from 18 to 86. Participants tended to be white (84.7%), relatively well educated (77% with at least some college), female (63.9%), and married or living in a committed relationship (57.4%). The unit of analysis was individual assessment histories (i.e., CAT item response histories) from the parent study. Data were first aggregated across all individuals, domains, and time points in an omnibus dataset of assessment histories and then were disaggregated by measure for domain-specific analyses. Finally, assessment histories within a "clinically relevant range" (score ≥ 1 SD from the mean in direction of poorer health) were analyzed separately to explore score level-specific findings. Two different sets of CAT administration rules were compared. The original CAT (CAT ORIG ) rules required at least four and no more than 12 items be administered. If the score standard error (SE) reached a value < 3 points (T score metric) before 12 items were administered, the CAT was stopped. We simulated applying alternative stopping rules (CAT ALT ), removing the requirement that a minimum four items be administered, and stopped a CAT if responses to the first two items were both associated with best health, if the SE was < 3, if SE change < 0.1 (T score metric), or if 12 items were administered. We then compared score fidelity and response burden, defined as number of items administered, between CAT ORIG and CAT ALT . CAT ORIG and CAT ALT scores varied little, especially within the clinically relevant range, and response burden was substantially lower under CAT ALT (e.g., 41.2% savings in omnibus dataset). Alternate stopping rules result in substantial reductions in response burden with minimal sacrifice in score precision.

Air Pressure Responses to Sudden Vocal Tract Pressure Bleeds During Production of Stop Consonants: New Evidence of Aeromechanical Regulation

PubMed Central

Zajac, David J.; Weissler, Mark C.

2011-01-01

Two studies were conducted to evaluate short-latency vocal tract air pressure responses to sudden pressure bleeds during production of voiceless bilabial stop consonants. It was hypothesized that the occurrence of respiratory reflexes would be indicated by distinct patterns of responses as a function of bleed magnitude. In Study 1, 19 adults produced syllable trains of /pΛ/ using a mouthpiece coupled to a computer-controlled perturbator. The device randomly created bleed apertures that ranged from 0 to 40 mm2 during production of the 2nd or 4th syllable of an utterance. Although peak oral air pressure dropped in a linear manner across bleed apertures, it averaged 2 to 3 cm H2O at the largest bleed. While slope of oral pressure also decreased in a linear trend, duration of the oral pressure pulse remained relatively constant. The patterns suggest that respiratory reflexes, if present, have little effect on oral air pressure levels. In Study 2, both oral and subglottal air pressure responses were monitored in 2 adults while bleed apertures of 20 and 40 mm2 were randomly created. For 1 participant, peak oral air pressure dropped across bleed apertures, as in Study 1. Subglottal air pressure and slope, however, remained relatively stable. These patterns provide some support for the occurrence of respiratory reflexes to regulate subglottal air pressure. Overall, the studies indicate that the inherent physiologic processes of the respiratory system, which may involve reflexes, and passive aeromechanical resistance of the upper airway are capable of developing oral air pressure in the face of substantial pressure bleeds. Implications for understanding speech production and the characteristics of individuals with velopharyngeal dysfunction are discussed. PMID:15324286

Ultraconserved elements are associated with homeostatic control of splicing regulators by alternative splicing and nonsense-mediated decay

PubMed Central

Ni, Julie Z.; Grate, Leslie; Donohue, John Paul; Preston, Christine; Nobida, Naomi; O’Brien, Georgeann; Shiue, Lily; Clark, Tyson A.; Blume, John E.; Ares, Manuel

2007-01-01

Many alternative splicing events create RNAs with premature stop codons, suggesting that alternative splicing coupled with nonsense-mediated decay (AS-NMD) may regulate gene expression post-transcriptionally. We tested this idea in mice by blocking NMD and measuring changes in isoform representation using splicing-sensitive microarrays. We found a striking class of highly conserved stop codon-containing exons whose inclusion renders the transcript sensitive to NMD. A genomic search for additional examples identified >50 such exons in genes with a variety of functions. These exons are unusually frequent in genes that encode splicing activators and are unexpectedly enriched in the so-called “ultraconserved” elements in the mammalian lineage. Further analysis show that NMD of mRNAs for splicing activators such as SR proteins is triggered by splicing activation events, whereas NMD of the mRNAs for negatively acting hnRNP proteins is triggered by splicing repression, a polarity consistent with widespread homeostatic control of splicing regulator gene expression. We suggest that the extreme genomic conservation surrounding these regulatory splicing events within splicing factor genes demonstrates the evolutionary importance of maintaining tightly tuned homeostasis of RNA-binding protein levels in the vertebrate cell. PMID:17369403

Evaluation of chromium oxide and molybdenum disulfide coatings in self-acting stops of an air-lubricated Rayleigh step thrust bearing

NASA Technical Reports Server (NTRS)

Nemeth, Z. N.

1974-01-01

Two coatings for a Rayleigh step thrust bearing were tested when coasting down and stopping under self-acting operation in air. The thrust bearing had an outside diameter of 8.9 cm (3.5 in.), an inside diameter of 5.4 cm (2.1 in.), and nine sectors. The load was 73 N (16.4 lbf). The load pressure was 19.1 kN/per square meter (2.77 lbf/per square inch) on the total thrust bearing area. The chromium oxide coating was good to 150 stops without bearing deterioration, and the molybdenum disulfide coating was good for only four stops before bearing deterioration. The molybdenum disulfide coated bearing failed after nine stops.

The impact of sociodemographic, treatment, and work support on missed work after breast cancer diagnosis

PubMed Central

Mujahid, Mahasin S.; Janz, Nancy K.; Hawley, Sarah T.; Griggs, Jennifer J.; Hamilton, Ann S.; Katz, Steven J.

2016-01-01

Work loss is a potential adverse consequence of cancer. There is limited research on patterns and correlates of paid work after diagnosis of breast cancer, especially among ethnic minorities. Women with non-metastatic breast cancer diagnosed from June 2005 to May 2006 who reported to the Los Angeles County SEER registry were identified and asked to complete the survey after initial treatment (median time from diagnosis = 8.9 months). Latina and African American women were over-sampled. Analyses were restricted to women working at the time of diagnosis, <65 years of age, and who had complete covariate information (N = 589). The outcome of the study was missed paid work (≤ month, >1 month, stopped all together). Approximately 44, 24, and 32% of women missed ≤1 month, >1 month, or stopped working, respectively. African Americans and Latinas were more likely to stop working when compared with Whites [OR for stop working vs. missed ≤1 month: 3.0, 3.4, (P < 0.001), respectively]. Women receiving mastectomy and those receiving chemotherapy were also more likely to stop working, independent of sociodemographic and treatment factors [ORs for stopped working vs. missed ≤1 month: 4.2, P < 0.001; 7.9, P < 0.001, respectively]. Not having a flexible work schedule available through work was detrimental to working [ORs for stopped working 18.9, P < 0.001 after adjusting for sociodemographic and treatment factors]. Many women stop working altogether after a diagnosis of breast cancer, particularly if they are racial/ethnic minorities, receive chemotherapy, or those who are employed in an unsupportive work settings. Health care providers need to be aware of these adverse consequences of breast cancer diagnosis and initial treatment. PMID:19360466

Models for Access to Maternal Smoking cessation Support (MAMSS): a study protocol of a quasi-experiment to increase the engagement of pregnant women who smoke in NHS Stop Smoking Services.

PubMed

Bennett, Lorna; Grant, Aimee; Jones, Siobhan; Bowley, Mererid; Heathcote-Elliott, Christian; Ford, Catrin; Jones, Angela; Lewis, Rachel; Munkley, Margaret; Owen, Carol; Petherick, Annie; Paranjothy, Shantini

2014-10-06

Maternal smoking is a key cause of poor outcomes for mothers, babies and children and Wales has higher rates of smoking in pregnancy than any other UK country. Despite various improvements within the NHS Stop Smoking Service to strengthen the intervention for pregnant women, referrals and successful quit attempts for this group have continued to remain extremely low. A key element of UK national guidance for smoking cessation during pregnancy is to provide a flexible and tailored service to help increase levels of engagement. This study aims to test the effectiveness of three different models of service delivery to address the gap in the evidence base about how to deliver a flexible, tailored smoking cessation service to pregnant women. This study will adopt a quasi-experimental design over a 12 month period. The setting is four of Wales' seven Health Boards using an integrated approach between maternity services, local public health teams and the NHS Stop Smoking Service. Core recommendations from UK public health guidance are being implemented across intervention and usual care sites. Stop smoking support for pregnant women in intervention sites is being delivered more flexibly than in usual care sites. Both qualitative and quantitative approaches will be adopted to capture important contextual information and consider multiple perspectives. A health economic analysis will be undertaken using a cost-consequences analysis approach. The primary outcome measure is engagement with stop smoking services (defined as having at least one face-to-face therapeutic contact with a clinician). Supporting pregnant women to stop smoking is a challenging area of public health. The proposed study will address several areas where there are key evidence gaps relating to smoking cessation interventions for pregnant women. Specifically, how best to encourage pregnant women to attend a specialist stop smoking support service, how to deliver the service and who should provide it.

Effects of Alcohol on Tests of Executive Functioning in Men and Women: A Dose Response Examination

PubMed Central

Guillot, Casey R.; Fanning, Jennifer R.; Bullock, Joshua S.; McCloskey, Michael S.; Berman, Mitchell E.

2014-01-01

Alcohol has been shown to affect performance on tasks associated with executive functioning. However, studies in this area have generally been limited to a single dose or gender or have used small sample sizes. The purpose of this study was to provide a more nuanced and systematic examination of alcohol's effects on commonly used tests of executive functioning at multiple dosages in both men and women. Research volunteers (91 women and 94 men) were randomly assigned to one of four drink conditions (alcohol doses associated with target blood alcohol concentrations of .000%, .050%, .075% and .100%). Participants then completed three tasks comprising two domains of executive functioning: two set shifting tasks, the Trail Making Test and a computerized version of the Wisconsin Card Sorting Task, and a response inhibition task, the GoStop Impulsivity Paradigm. Impaired performance on set shifting tasks was found at the .100% and .075% dosages, but alcohol intoxication did not impair performance on the GoStop. No gender effects emerged. Thus, alcohol negatively affects set shifting at moderately high levels of intoxication in both men and women, likely due to alcohol's interference with prefrontal cortex function. Although it is well-established that alcohol negatively affects response inhibition as measured by auditory stop-signal tasks, alcohol does not appear to exert a negative effect on response inhibition as measured by the GoStop, a visual stop-signal task. PMID:20939644

Stop Teaching and Let Students Learn Geometry

ERIC Educational Resources Information Center

Bosse, Michael J.; Adu-Gyamfi, Kwaku

2011-01-01

For many high school students as well as preservice teachers, geometry can be difficult to learn without experiences that allow them to build their own understanding. The authors' approach to geometry instruction--with its integration of content, multiple representations, real-world examples, reading and writing, communication and collaboration as…

36 CFR 1192.35 - Public information system.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 36 Parks, Forests, and Public Property 3 2010-07-01 2010-07-01 false Public information system... Buses, Vans and Systems § 1192.35 Public information system. (a) Vehicles in excess of 22 feet in length, used in multiple-stop, fixed-route service, shall be equipped with a public address system permitting...

49 CFR 236.722 - Circuit, cut-in.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 49 Transportation 4 2011-10-01 2011-10-01 false Circuit, cut-in. 236.722 Section 236.722 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Circuit, cut-in. A roadway circuit at the entrance to automatic train stop, train control or cab signal...

49 CFR 236.722 - Circuit, cut-in.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 4 2010-10-01 2010-10-01 false Circuit, cut-in. 236.722 Section 236.722 Transportation Other Regulations Relating to Transportation (Continued) FEDERAL RAILROAD ADMINISTRATION... Circuit, cut-in. A roadway circuit at the entrance to automatic train stop, train control or cab signal...

78 FR 36013 - Petition for Waiver of Compliance

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-14

... waiver of compliance from certain provisions of the Federal railroad safety regulations contained at 49..., and Repair of Signal and Train Control Systems, Devices, and Appliances. FRA assigned the petition... each train operating in train stop, train control or cab signal territory; equipped. Specifically...

30 CFR 75.333 - Ventilation controls.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Radiant Heat Energy Source.” This publication is incorporated by reference and may be inspected at any... partitions, permanent stoppings, and regulators include concrete, concrete block, brick, cinder block, tile..., “Standard Test Method for Surface Flammability of Materials Using A Radiant Heat Energy Source.” This...

30 CFR 75.333 - Ventilation controls.

Code of Federal Regulations, 2013 CFR

2013-07-01

... Radiant Heat Energy Source.” This publication is incorporated by reference and may be inspected at any... partitions, permanent stoppings, and regulators include concrete, concrete block, brick, cinder block, tile..., “Standard Test Method for Surface Flammability of Materials Using A Radiant Heat Energy Source.” This...

Truck parking : an emerging safety hazard to highway users : final report - draft.

DOT National Transportation Integrated Search

2017-07-01

It is recognized nationwide that commercial motor vehicle operators are often unable to find safe and adequate parking to meet hours-of-service (HOS) regulations. This holds true in Oregon, where high-use corridor rest areas and truck stops are exper...

30 CFR 57.22218 - Seals and stoppings (III, V-A, and V-B mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Seals and stoppings (III, V-A, and V-B mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22218 Seals and stoppings (III, V-A, and V-B mines). (a) All seals, and those stoppings that separate main intake from main...

30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

30 CFR 57.22218 - Seals and stoppings (III, V-A, and V-B mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Seals and stoppings (III, V-A, and V-B mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22218 Seals and stoppings (III, V-A, and V-B mines). (a) All seals, and those stoppings that separate main intake from main...

30 CFR 57.22217 - Seals and stoppings (I-A, I-B, and I-C mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Seals and stoppings (I-A, I-B, and I-C mines... NONMETAL MINES Safety Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22217 Seals and stoppings (I-A, I-B, and I-C mines). All seals, and those stoppings that separate main intake from main...

The day that the START triage system came to a STOP: observations from the World Trade Center disaster.

PubMed

Asaeda, Glenn

2002-03-01

The Fire Department of the City of New York--Emergency Medical Services (EMS) Operations is one of the largest EMS systems in the country. On a daily basis, this system responds to approximately 3,000 to 3,500 calls for ambulance requests. This equates to 1.2 to 1.5 million calls annually. As part of its response, EMS deals on a daily basis with multiple casualty and disaster-type situations. The magnitude of the attacks on the World Trade Center, however, was on a scale not previously seen by any system. This article is a case report of the September 11, 2001, incident.

Barratt Impulsivity and Neural Regulation of Physiological Arousal

PubMed Central

Zhang, Sheng; Hu, Sien; Hu, Jianping; Wu, Po-Lun; Chao, Herta H.; Li, Chiang-shan R.

2015-01-01

Background Theories of personality have posited an increased arousal response to external stimulation in impulsive individuals. However, there is a dearth of studies addressing the neural basis of this association. Methods We recorded skin conductance in 26 individuals who were assessed with Barratt Impulsivity Scale (BIS-11) and performed a stop signal task during functional magnetic resonance imaging. Imaging data were processed and modeled with Statistical Parametric Mapping. We used linear regressions to examine correlations between impulsivity and skin conductance response (SCR) to salient events, identify the neural substrates of arousal regulation, and examine the relationship between the regulatory mechanism and impulsivity. Results Across subjects, higher impulsivity is associated with greater SCR to stop trials. Activity of the ventromedial prefrontal cortex (vmPFC) negatively correlated to and Granger caused skin conductance time course. Furthermore, higher impulsivity is associated with a lesser strength of Granger causality of vmPFC activity on skin conductance, consistent with diminished control of physiological arousal to external stimulation. When men (n = 14) and women (n = 12) were examined separately, however, there was evidence suggesting association between impulsivity and vmPFC regulation of arousal only in women. Conclusions Together, these findings confirmed the link between Barratt impulsivity and heightened arousal to salient stimuli in both genders and suggested the neural bases of altered regulation of arousal in impulsive women. More research is needed to explore the neural processes of arousal regulation in impulsive individuals and in clinical conditions that implicate poor impulse control. PMID:26079873

Barratt Impulsivity and Neural Regulation of Physiological Arousal.

PubMed

Zhang, Sheng; Hu, Sien; Hu, Jianping; Wu, Po-Lun; Chao, Herta H; Li, Chiang-shan R

2015-01-01

Theories of personality have posited an increased arousal response to external stimulation in impulsive individuals. However, there is a dearth of studies addressing the neural basis of this association. We recorded skin conductance in 26 individuals who were assessed with Barratt Impulsivity Scale (BIS-11) and performed a stop signal task during functional magnetic resonance imaging. Imaging data were processed and modeled with Statistical Parametric Mapping. We used linear regressions to examine correlations between impulsivity and skin conductance response (SCR) to salient events, identify the neural substrates of arousal regulation, and examine the relationship between the regulatory mechanism and impulsivity. Across subjects, higher impulsivity is associated with greater SCR to stop trials. Activity of the ventromedial prefrontal cortex (vmPFC) negatively correlated to and Granger caused skin conductance time course. Furthermore, higher impulsivity is associated with a lesser strength of Granger causality of vmPFC activity on skin conductance, consistent with diminished control of physiological arousal to external stimulation. When men (n = 14) and women (n = 12) were examined separately, however, there was evidence suggesting association between impulsivity and vmPFC regulation of arousal only in women. Together, these findings confirmed the link between Barratt impulsivity and heightened arousal to salient stimuli in both genders and suggested the neural bases of altered regulation of arousal in impulsive women. More research is needed to explore the neural processes of arousal regulation in impulsive individuals and in clinical conditions that implicate poor impulse control.

Multiple elements regulate nuclear/cytoplasmic shuttling of FOXO1: characterization of phosphorylation- and 14-3-3-dependent and -independent mechanisms.

PubMed Central

Zhao, Xiangshan; Gan, Lixia; Pan, Haiyun; Kan, Donghui; Majeski, Michael; Adam, Stephen A; Unterman, Terry G

2004-01-01

FOXO1, a Forkhead transcription factor, is an important target of insulin and growth factor action. Phosphorylation of Thr-24, Ser-256 and Ser-319 promotes nuclear exclusion of FOXO1, yet the mechanisms regulating nuclear/cytoplasmic shuttling of FOXO1 are poorly understood. Previous studies have identified an NLS (nuclear localization signal) in the C-terminal basic region of the DBD (DNA-binding domain), and a leucine-rich, leptomycin-B sensitive NES (nuclear export signal) located further downstream. Here, we find that other elements in the DBD also contribute to nuclear localization, and that multiple mechanisms contribute to nuclear exclusion of FOXO1. Phosphorylation of Ser-319 and a cluster of nearby residues (Ser-322, Ser-325 and Ser-329) functions co-operatively with the nearby NES to promote nuclear exclusion. The N-terminal region of FOXO1 (amino acids 1-149) also is sufficient to promote nuclear exclusion, and does so through multiple mechanisms. Amino acids 1-50 are sufficient to promote nuclear exclusion of green fluorescent protein fusion proteins, and the phosphorylation of Thr-24 is required for this effect. A leucine-rich, leptomycin B-sensitive export signal is also present nearby. Phosphorylated FOXO1 binds 14-3-3 proteins, and co-precipitation studies with tagged proteins indicate that 14-3-3 binding involves co-operative interactions with both Thr-24 and Ser-256. Ser-256 is located in the C-terminal region of the DBD, where 14-3-3 proteins may interfere both with DNA-binding and with nuclear-localization functions. Together, these studies demonstrate that multiple elements contribute to nuclear/cytoplasmic shuttling of FOXO1, and that phosphorylation and 14-3-3 binding regulate the cellular distribution and function of FOXO1 through multiple mechanisms. The presence of these redundant mechanisms supports the concept that the regulation of FOXO1 function plays a critical role in insulin and growth factor action. PMID:14664696

The effect of facial makeup on the frequency of drivers stopping for hitchhikers.

PubMed

Guéguen, Nicolas; Lamy, Lubomir

2013-08-01

Judgments of photographs have shown that makeup enhances ratings of women's facial attractiveness. The present study assessed whether makeup affects the stopping behavior of drivers in response to a hitchhiker's signal. Four 20- to 22-year-old female confederates wore facial makeup, or not, while pretending to be hitchhiking. Frequency of stopping was compared in 1,600 male and female drivers. Facial makeup was associated with an increase in the number of male drivers who stopped to offer a ride. Makeup did not affect frequency of stopping by female drivers.

Transcriptomic Impacts of Rumen Epithelium Induced by Butyrate Infusion in Dairy Cattle in Dry Period

PubMed Central

Baldwin, Ransom L; Li, Robert W; Jia, Yankai; Li, Cong-Jun

2018-01-01

The purpose of this study was to evaluate the effects of butyrate infusion on rumen epithelial transcriptome. Next-generation sequencing (NGS) and bioinformatics are used to accelerate our understanding of regulation in rumen epithelial transcriptome of cattle in the dry period induced by butyrate infusion at the level of the whole transcriptome. Butyrate, as an essential element of nutrients, is a histone deacetylase (HDAC) inhibitor that can alter histone acetylation and methylation, and plays a prominent role in regulating genomic activities influencing rumen nutrition utilization and function. Ruminal infusion of butyrate was following 0-hour sampling (baseline controls) and continued for 168 hours at a rate of 5.0 L/day of a 2.5 M solution as a continuous infusion. Following the 168-hour infusion, the infusion was stopped, and cows were maintained on the basal lactation ration for an additional 168 hours for sampling. Rumen epithelial samples were serially collected via biopsy through rumen fistulae at 0-, 24-, 72-, and 168-hour (D1, D3, D7) and 168-hour post-infusion (D14). In comparison with pre-infusion at 0 hours, a total of 3513 genes were identified to be impacted in the rumen epithelium by butyrate infusion at least once at different sampling time points at a stringent cutoff of false discovery rate (FDR) < 0.01. The maximal effect of butyrate was observed at day 7. Among these impacted genes, 117 genes were responsive consistently from day 1 to day 14, and another 42 genes were lasting through day 7. Temporal effects induced by butyrate infusion indicate that the transcriptomic alterations are very dynamic. Gene ontology (GO) enrichment analysis revealed that in the early stage of rumen butyrate infusion (on day 1 and day 3 of butyrate infusion), the transcriptomic effects in the rumen epithelium were involved with mitotic cell cycle process, cell cycle process, and regulation of cell cycle. Bioinformatic analysis of cellular functions, canonical pathways, and upstream regulator of impacted genes underlie the potential mechanisms of butyrate-induced gene expression regulation in rumen epithelium. The introduction of transcriptomic and bioinformatic technologies to study nutrigenomics in the farm animal presented a new prospect to study multiple levels of biological information to better apprehend the whole animal response to nutrition, physiological state, and their interactions. The nutrigenomics approach may eventually lead to more precise management of utilization of feed resources in a more effective approach. PMID:29785087

Molecular genetics and targeted therapy of WNT-related human diseases (Review)

PubMed Central

Katoh, Masuko; Katoh, Masaru

2017-01-01

Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription. Germline mutations in WNT signaling molecules cause hereditary colorectal cancer, bone diseases, exudative vitreoretinopathy, intellectual disability syndrome and PCP-related diseases. APC or CTNNB1 mutations in colorectal, endometrial and prostate cancers activate the WNT/β-catenin signaling cascade. RNF43, ZNRF3, RSPO2 or RSPO3 alterations in breast, colorectal, gastric, pancreatic and other cancers activate the WNT/β-catenin, WNT/STOP and other WNT signaling cascades. ROR1 upregulation in B-cell leukemia and solid tumors and ROR2 upregulation in melanoma induce invasion, metastasis and therapeutic resistance through Rho-ROCK, Rac-JNK, PI3K-AKT and YAP signaling activation. WNT signaling in cancer, stromal and immune cells dynamically orchestrate immune evasion and antitumor immunity in a cell context-dependent manner. Porcupine (PORCN), RSPO3, WNT2B, FZD5, FZD10, ROR1, tankyrase and β-catenin are targets of anti-WNT signaling therapy, and ETC-159, LGK974, OMP-18R5 (vantictumab), OMP-54F28 (ipafricept), OMP-131R10 (rosmantuzumab), PRI-724 and UC-961 (cirmtuzumab) are in clinical trials for cancer patients. Different classes of anti-WNT signaling therapeutics are necessary for the treatment of APC/CTNNB1-, RNF43/ZNRF3/RSPO2/RSPO3- and ROR1-types of human cancers. By contrast, Dickkopf-related protein 1 (DKK1), SOST and glycogen synthase kinase 3β (GSK3β) are targets of pro-WNT signaling therapy, and anti-DKK1 (BHQ880 and DKN-01) and anti-SOST (blosozumab, BPS804 and romosozumab) monoclonal antibodies are being tested in clinical trials for cancer patients and osteoporotic post-menopausal women. WNT-targeting therapeutics have also been applied as reagents for in vitro stem-cell processing in the field of regenerative medicine. PMID:28731148

Evidence for enhanced multi-component behaviour in Tourette syndrome - an EEG study.

PubMed

Brandt, Valerie C; Stock, Ann-Kathrin; Münchau, Alexander; Beste, Christian

2017-08-10

Evidence suggests that Tourette syndrome is characterized by an increase in dopamine transmission and structural as well as functional changes in fronto-striatal circuits that might lead to enhanced multi-component behaviour integration. Behavioural and neurophysiological data regarding multi-component behaviour was collected from 15 patients with Tourette syndrome (mean age = 30.40 ± 11.10) and 15 healthy controls (27.07 ± 5.44), using the stop-change task. In this task, participants are asked to sometimes withhold responses to a Go stimulus (stop cue) and change hands to respond to an alternative Go stimulus (change cue). Different onset asynchronies between stop and change cues were implemented (0 and 300 ms) in order to vary task difficulty. Tourette patients responded more accurately than healthy controls when there was no delay between stop and change stimulus, while there was no difference in the 300 ms delay condition. This performance advantage was reflected in a smaller P3 event related potential. Enhanced multi-component behaviour in Tourette syndrome is likely based on an enhanced ability to integrate information from multiple sources and translate it into an appropriate response sequence. This may be a consequence of chronic tic control in these patients, or a known fronto-striatal networks hyperconnectivity in Tourette syndrome.

Multi-Layer Identification of Highly-Potent ABCA1 Up-Regulators Targeting LXRβ Using Multiple QSAR Modeling, Structural Similarity Analysis, and Molecular Docking.

PubMed

Chen, Meimei; Yang, Fafu; Kang, Jie; Yang, Xuemei; Lai, Xinmei; Gao, Yuxing

2016-11-29

In this study, in silico approaches, including multiple QSAR modeling, structural similarity analysis, and molecular docking, were applied to develop QSAR classification models as a fast screening tool for identifying highly-potent ABCA1 up-regulators targeting LXRβ based on a series of new flavonoids. Initially, four modeling approaches, including linear discriminant analysis, support vector machine, radial basis function neural network, and classification and regression trees, were applied to construct different QSAR classification models. The statistics results indicated that these four kinds of QSAR models were powerful tools for screening highly potent ABCA1 up-regulators. Then, a consensus QSAR model was developed by combining the predictions from these four models. To discover new ABCA1 up-regulators at maximum accuracy, the compounds in the ZINC database that fulfilled the requirement of structural similarity of 0.7 compared to known potent ABCA1 up-regulator were subjected to the consensus QSAR model, which led to the discovery of 50 compounds. Finally, they were docked into the LXRβ binding site to understand their role in up-regulating ABCA1 expression. The excellent binding modes and docking scores of 10 hit compounds suggested they were highly-potent ABCA1 up-regulators targeting LXRβ. Overall, this study provided an effective strategy to discover highly potent ABCA1 up-regulators.

Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators.

PubMed

Le Mercier, Isabelle; Lines, J Louise; Noelle, Randolph J

2015-01-01

In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy.

Beyond CTLA-4 and PD-1, the Generation Z of Negative Checkpoint Regulators

PubMed Central

Le Mercier, Isabelle; Lines, J. Louise; Noelle, Randolph J.

2015-01-01

In the last two years, clinical trials with blocking antibodies to the negative checkpoint regulators CTLA-4 and PD-1 have rekindled the hope for cancer immunotherapy. Multiple negative checkpoint regulators protect the host against autoimmune reactions but also restrict the ability of T cells to effectively attack tumors. Releasing these brakes has emerged as an exciting strategy for cancer treatment. Conversely, these pathways can be manipulated to achieve durable tolerance for treatment of autoimmune diseases and transplantation. In the future, treatment may involve combination therapy to target multiple cell types and stages of the adaptive immune responses. In this review, we describe the current knowledge on the recently discovered negative checkpoint regulators, future targets for immunotherapy. PMID:26347741

Aspirin-triggered lipoxin A4 and lipoxin A4 up-regulate transcriptional corepressor NAB1 in human neutrophils.

PubMed

Qiu, F H; Devchand, P R; Wada, K; Serhan, C N

2001-12-01

Aspirin-triggered 15-epi-lipoxin A4 (ATL) is an endogenous lipid mediator that mimics the actions of native lipoxin A4, a putative "stop signal" involved in regulating resolution of inflammation. A metabolically more stable analog of ATL, 15-epi-16-(para-fluoro)-phenoxy-lipoxin A4 analog (ATLa), inhibits neutrophil recruitment in vitro and in vivo and displays potent anti-inflammatory actions. ATLa binds with high affinity to the lipoxin A4 receptor, a G protein-coupled receptor on the surface of leukocytes. In this study, we used freshly isolated human neutrophils to examine ATLa's potential for initiating rapid nuclear responses. Using differential display reverse transcription polymerase chain reaction, we identified a subset of genes that was selectively up-regulated upon short exposure of polymorphonuclear leukocytes to ATLa but not to the chemoattractant leukotriene B4 or vehicle alone. We further investigated ATLa regulation of one of the genes, NAB1, a transcriptional corepressor identified previously as a glucocorticoid-responsive gene in hamster smooth muscle cells. Treatment of human neutrophils with pertussis toxin blocked ATLa up-regulation of NAB1. In addition, ATLa stimulated NAB1 gene expression in murine lung vascular smooth muscle in vivo. These findings provide evidence for rapid transcriptional induction of a cassette of genes via an ATLa-stimulated G protein-coupled receptor pathway that is potentially protective and overlaps with the anti-inflammatory glucocorticoid regulatory circuit.

Mouse ACF7 and drosophila short stop modulate filopodia formation and microtubule organisation during neuronal growth.

PubMed

Sanchez-Soriano, Natalia; Travis, Mark; Dajas-Bailador, Federico; Gonçalves-Pimentel, Catarina; Whitmarsh, Alan J; Prokop, Andreas

2009-07-15

Spectraplakins are large actin-microtubule linker molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. Expression data for the mammalian spectraplakin ACF7 and genetic analyses of the Drosophila spectraplakin Short stop (Shot) suggest an important role during neurogenesis. Using three parallel neuronal culture systems we demonstrate that, like Shot, ACF7 is essential for axon extension and describe, for the first time, their subcellular functions during axonal growth. Firstly, both ACF7 and Shot regulate the organisation of neuronal microtubules, a role dependent on both the F-actin- and microtubule-binding domains. This role in microtubule organisation is probably the key mechanism underlying the roles of Shot and ACF7 in growth cone advance. Secondly, we found a novel role for ACF7 and Shot in regulating the actin cytoskeleton through their ability to control the formation of filopodia. This function in F-actin regulation requires EF-hand motifs and interaction with the translational regulator Krasavietz/eIF5C, indicating that the underlying mechanisms are completely different from those used to control microtubules. Our data provide the basis for the first mechanistic explanation for the role of Shot and ACF7 in the developing nervous system and demonstrate their ability to coordinate the organisation of both actin and microtubule networks during axonal growth.

Mouse ACF7 and Drosophila Short stop modulate filopodia formation and microtubule organisation during neuronal growth

PubMed Central

Sanchez-Soriano, Natalia; Travis, Mark; Dajas-Bailador, Federico; Gonçalves-Pimentel, Catarina; Whitmarsh, Alan J.; Prokop, Andreas

2009-01-01

Summary Spectraplakins are large actin-microtubule linker molecules implicated in various processes, including gastrulation, wound healing, skin blistering and neuronal degeneration. Expression data for the mammalian spectraplakin ACF7 and genetic analyses of the Drosophila spectraplakin Short stop (Shot) suggest an important role during neurogenesis. Using three parallel neuronal culture systems we demonstrate that, like Shot, ACF7 is essential for axon extension and describe, for the first time, their subcellular functions during axonal growth. Firstly, both ACF7 and Shot regulate the organisation of neuronal microtubules, a role dependent on both the F-actin- and microtubule-binding domains. This role in microtubule organisation is probably the key mechanism underlying the roles of Shot and ACF7 in growth cone advance. Secondly, we found a novel role for ACF7 and Shot in regulating the actin cytoskeleton through their ability to control the formation of filopodia. This function in F-actin regulation requires EF-hand motifs and interaction with the translational regulator Krasavietz/eIF5C, indicating that the underlying mechanisms are completely different from those used to control microtubules. Our data provide the basis for the first mechanistic explanation for the role of Shot and ACF7 in the developing nervous system and demonstrate their ability to coordinate the organisation of both actin and microtubule networks during axonal growth. PMID:19571116

Stopped in its tracks: negative regulation of the dynein motor by the yeast protein She1

PubMed Central

Moore, Jeffrey K.

2013-01-01

Summary How do cells direct the microtubule motor protein dynein to move cellular components to the right place at the right time? Recent studies in budding yeast shed light on a new mechanism for directing dynein, involving the protein She1. She1 restricts where and when dynein moves the nucleus and mitotic spindle. Experiments with purified proteins show that She1 binds to microtubules and inhibits dynein by stalling the motor on its track. Here I describe what we have learned so far about She1, based on a combination of genetic, cell biology, and biophysical approaches. These findings set the stage for further interrogation of the She1 mechanism, and raise the question of whether similar mechanisms exist in other species. PMID:23666903

48 CFR 452.236-75 - Maximum Workweek-Construction Schedule.

Code of Federal Regulations, 2011 CFR

2011-10-01

... hours (including the daily starting and stopping times) and days of the week the Contractor proposes to... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Maximum Workweek...: Maximum Workweek—Construction Schedule (NOV 1996) Within __ calendar days after receipt of a written...

77 FR 5847 - Manufacturer of Controlled Substances; Notice of Application

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-06

... DEPARTMENT OF JUSTICE Drug Enforcement Administration Manufacturer of Controlled Substances; Notice of Application Pursuant to Sec. 1301.33(a) Title 21 of the Code of Federal Regulations (CFR), this is notice that on December 20, 2011, Siemens Healthcare Diagnostics Inc., 100 GBC Drive, Mail Stop...

48 CFR 852.236-87 - Accident prevention.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Accident prevention. 852... Accident prevention. As prescribed in 836.513, insert the following clause: Accident Prevention (SEP 1993....236-13, Accident Prevention. However, only the Contracting Officer may issue an order to stop all or...

48 CFR 852.236-87 - Accident prevention.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Accident prevention. 852... Accident prevention. As prescribed in 836.513, insert the following clause: Accident Prevention (SEP 1993....236-13, Accident Prevention. However, only the Contracting Officer may issue an order to stop all or...

49 CFR 350.111 - What constitutes traffic enforcement for the purpose of the MCSAP?

Code of Federal Regulations, 2010 CFR

2010-10-01

... (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS COMMERCIAL MOTOR CARRIER SAFETY ASSISTANCE PROGRAM General § 350.111 What constitutes... State or local officials, including the stopping of vehicles operating on highways, streets, or roads...

49 CFR 350.111 - What constitutes traffic enforcement for the purpose of the MCSAP?

Code of Federal Regulations, 2011 CFR

2011-10-01

... (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS COMMERCIAL MOTOR CARRIER SAFETY ASSISTANCE PROGRAM General § 350.111 What constitutes... State or local officials, including the stopping of vehicles operating on highways, streets, or roads...

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

PubMed Central

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

2013-01-01

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

Multiple degradation pathways regulate versatile CIP/KIP CDK inhibitors.

PubMed

Starostina, Natalia G; Kipreos, Edward T

2012-01-01

The mammalian CIP/KIP family of cyclin-dependent kinase (CDK) inhibitors (CKIs) comprises three proteins--p21(Cip1/WAF1), p27(Kip1), and p57(Kip2)--that bind and inhibit cyclin-CDK complexes, which are key regulators of the cell cycle. CIP/KIP CKIs have additional independent functions in regulating transcription, apoptosis and actin cytoskeletal dynamics. These divergent functions are performed in distinct cellular compartments and contribute to the seemingly contradictory observation that the CKIs can both suppress and promote cancer. Multiple ubiquitin ligases (E3s) direct the proteasome-mediated degradation of p21, p27 and p57. This review analyzes recent data highlighting our current understanding of how distinct E3 pathways regulate subpopulations of the CKIs to control their diverse functions. Copyright © 2011 Elsevier Ltd. All rights reserved.

Seismic stops for nuclear power plants

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

Cloud, R.L.; Leung, J.S.M.; Anderson, P.H.

1989-10-01

In the regulated world of nuclear power, the need to have analytical proof of performance in hypothetical design-basis events such as earth quakes has placed a premium on design configurations that are mathematically tractable and easily analyzed. This is particularly true for the piping design. Depending on how the piping analyses are organized and on how old the plant is, there may be from 200 to 1000 separate piping runs to be designed, analyzed, and qualified. In this situation, the development of snubbers seemed like the answer to a piping engineer's prayer. At any place where seismic support was requiredmore » but thermal motion had to be accommodated, a snubber could be specified. But, as experience has now shown, the program was solved only on paper. This article presents an alternative to conventional snubbers. These new devices, termed Seismic Stops are designed to replace snubbers directly and look like snubbers on the outside. But their design is based on a completely different principle. The original concept has adapted from early seismic-resistant pipe support designs used on fossil power plants in California. The fundamental idea is to provide a space envelope in which the pipe can expand freely between the hot and cold positions, but cannot move outside the envelope. Seismic Stops are designed to transmit any possible impact load, as would occur in an earthquake, away from the pipe itself to the Seismic Stop. The Seismic Stop pipe support is shown.« less

Time-Resolved Tandem Faraday Cup Development for High Energy TNSA Particles

NASA Astrophysics Data System (ADS)

Padalino, S.; Simone, A.; Turner, E.; Ginnane, M. K.; Glisic, M.; Kousar, B.; Smith, A.; Sangster, C.; Regan, S.

2015-11-01

MTW and OMEGA EP Lasers at LLE utilize ultra-intense laser light to produce high-energy ion pulses through Target Normal Sheath Acceleration (TNSA). A Time Resolved Tandem Faraday Cup (TRTF) was designed and built to collect and differentiate protons from heavy ions (HI) produced during TNSA. The TRTF includes a replaceable thickness absorber capable of stopping a range of user-selectable HI emitted from TNSA plasma. HI stop within the primary cup, while less massive particles continue through and deposit their remaining charge in the secondary cup, releasing secondary electrons in the process. The time-resolved beam current generated in each cup will be measured on a fast storage scope in multiple channels. A charge-exchange foil at the TRTF entrance modifies the charge state distribution of HI to a known distribution. Using this distribution and the time of flight of the HI, the total HI current can be determined. Initial tests of the TRTF have been made using a proton beam produced by SUNY Geneseo's 1.7 MV Pelletron accelerator. A substantial reduction in secondary electron production, from 70% of the proton beam current at 2MeV down to 0.7%, was achieved by installing a pair of dipole magnet deflectors which successfully returned the electrons to the cups in the TRTF. Ultimately the TRTF will be used to normalize a variety of nuclear physics cross sections and stopping power measurements. Based in part upon work supported by a DOE NNSA Award#DE-NA0001944.

Immunologic Endocrine Disorders

PubMed Central

Michels, Aaron W.; Eisenbarth, George S.

2010-01-01

Autoimmunity affects multiple glands in the endocrine system. Animal models and human studies highlight the importance of alleles in HLA (human leukocyte antigen)-like molecules determining tissue specific targeting that with the loss of tolerance leads to organ specific autoimmunity. Disorders such as type 1A diabetes, Grave's disease, Hashimoto's thyroiditis, Addison's disease, and many others result from autoimmune mediated tissue destruction. Each of these disorders can be divided into stages beginning with genetic susceptibility, environmental triggers, active autoimmunity, and finally metabolic derangements with overt symptoms of disease. With an increased understanding of the immunogenetics and immunopathogenesis of endocrine autoimmune disorders, immunotherapies are becoming prevalent, especially in type 1A diabetes. Immunotherapies are being used more in multiple subspecialty fields to halt disease progression. While therapies for autoimmune disorders stop the progress of an immune response, immunomodulatory therapies for cancer and chronic infections can also provoke an unwanted immune response. As a result, there are now iatrogenic autoimmune disorders arising from the treatment of chronic viral infections and malignancies. PMID:20176260

Multiple Competencies and Self-Regulated Learning: Implications for Multicultural Education. Research in Multicultural Education and International Perspectives.

ERIC Educational Resources Information Center

Chiu, Chi-yue, Ed.; Salili, Farideh, Ed.; Hong, Ying-yi, Ed.

This book presents 13 papers from a 1998 conference in Hong Kong that examined how to apply psychology to enhance learning and teaching quality and focused on multicultural education: (1) "The Role of Multiple Competencies and Self-Regulated Learning in Multicultural Education" (Chi-yue Chiu, Farideh Salili, and Ying-yi Hong); (2)…

Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study: Protocol and baseline characteristics of a randomized controlled trial.

PubMed

Diamantidis, Clarissa J; Bosworth, Hayden B; Oakes, Megan M; Davenport, Clemontina A; Pendergast, Jane F; Patel, Sejal; Moaddeb, Jivan; Barnhart, Huiman X; Merrill, Peter D; Baloch, Khaula; Crowley, Matthew J; Patel, Uptal D

2018-06-01

Diabetic kidney disease (DKD) is the leading cause of end-stage kidney disease (ESKD) in the United States. Multiple risk factors contribute to DKD development, yet few interventions target more than a single DKD risk factor at a time. This manuscript describes the study protocol, recruitment, and baseline participant characteristics for the Simultaneous Risk Factor Control Using Telehealth to slOw Progression of Diabetic Kidney Disease (STOP-DKD) study. The STOP-DKD study is a randomized controlled trial designed to evaluate the effectiveness of a multifactorial behavioral and medication management intervention to mitigate kidney function decline at 3 years compared to usual care. The intervention consists of up to 36 monthly educational modules delivered via telephone by a study pharmacist, home blood pressure monitoring, and medication management recommendations delivered electronically to primary care physicians. Patients seen at seven primary care clinics in North Carolina, with diabetes and [1] uncontrolled hypertension and [2] evidence of kidney dysfunction (albuminuria or reduced estimated glomerular filtration rate [eGFR]) were eligible to participate. Study recruitment completed in December 2014. Of the 281 participants randomized, mean age at baseline was 61.9; 52% were male, 56% were Black, and most were high school graduates (89%). Baseline co-morbidity was high- mean blood pressure was 134/76 mmHg, mean body mass index was 35.7 kg/m 2 , mean eGFR was 80.7 ml/min/1.73 m 2 , and mean glycated hemoglobin was 8.0%. Experiences of recruiting and implementing a comprehensive DKD program to individuals at high risk seen in the primary care setting are provided. NCT01829256. Copyright © 2018 Elsevier Inc. All rights reserved.

Design and pilot evaluation of an Internet spit tobacco cessation program.

PubMed

Gala, S; Pesek, F; Murray, J; Kavanagh, C; Graham, S; Walsh, M

2008-01-01

To develop an interactive Web site to help smokeless tobacco (ST) users to reduce or stop their ST use and pilot test it for feasibility, acceptability, and short-term outcomes. An interactive, multiple-contact Internet ST cessation program was developed, refined based on feedback from 17 ST users, and pilot-tested for feasibility, acceptability, and short-term effects on the ST-related behavior and attitudes among baseball athletes attending 3 colleges in California. Consenting ST users completed a baseline questionnaire and enrolled on the Web site for help with stopping ST use. One month later, outcomes were assessed. Although 18 ST-using baseball athletes enrolled on the Web site, follow-up data were obtained from 12 individuals. Loss to follow-up occurred when we were unable to contact participants by telephone or mailed surveys. At 1-month follow-up, over 80% (N=11) reported that the Web site was: "helpful in stopping or reducing my tobacco use"; easy to navigate; and "appealing." Moreover, 8% (n=1) self-reported abstinence from ST use. Among nonquitters, there was a 26% mean reduction in ST use per day compared to baseline values. In addition, among all enrollees, there was a 4-fold increase in motivation to quit (7% versus 31%) and a 21% increase in their confidence in being able to quit (67% versus. 85%) from baseline to follow-up. The interactive ST cessation Web site was feasible to implement, acceptable to ST users, and appeared to reduce ST use, enhance motivation to quit, and increase confidence about one's ability to quit. Further study with a larger sample size and a control group is needed to determine efficacy to promote cessation of ST use.

Beclin 1 Is Required for Neuron Viability and Regulates Endosome Pathways via the UVRAG-VPS34 Complex

PubMed Central

Wold, Mitchell S.; Gong, Shiaoching; Phillips, Greg R.; Dou, Zhixun; Zhao, Yanxiang; Heintz, Nathaniel; Zong, Wei-Xing; Yue, Zhenyu

2014-01-01

Deficiency of autophagy protein beclin 1 is implicated in tumorigenesis and neurodegenerative diseases, but the molecular mechanism remains elusive. Previous studies showed that Beclin 1 coordinates the assembly of multiple VPS34 complexes whose distinct phosphatidylinositol 3-kinase III (PI3K-III) lipid kinase activities regulate autophagy at different steps. Recent evidence suggests a function of beclin 1 in regulating multiple VPS34-mediated trafficking pathways beyond autophagy; however, the precise role of beclin 1 in autophagy-independent cellular functions remains poorly understood. Herein we report that beclin 1 regulates endocytosis, in addition to autophagy, and is required for neuron viability in vivo. We find that neuronal beclin 1 associates with endosomes and regulates EEA1/early endosome localization and late endosome formation. Beclin 1 maintains proper cellular phosphatidylinositol 3-phosphate (PI(3)P) distribution and total levels, and loss of beclin 1 causes a disruption of active Rab5 GTPase-associated endosome formation and impairment of endosome maturation, likely due to a failure of Rab5 to recruit VPS34. Furthermore, we find that Beclin 1 deficiency causes complete loss of the UVRAG-VPS34 complex and associated lipid kinase activity. Interestingly, beclin 1 deficiency impairs p40phox-linked endosome formation, which is rescued by overexpressed UVRAG or beclin 1, but not by a coiled-coil domain-truncated beclin 1 (a UVRAG-binding mutant), Atg14L or RUBICON. Thus, our study reveals the essential role for beclin 1 in neuron survival involving multiple membrane trafficking pathways including endocytosis and autophagy, and suggests that the UVRAG-beclin 1 interaction underlies beclin 1's function in endocytosis. PMID:25275521

Search for a scalar partner of the top quark in the jets+ ETmiss final state with the ATLAS detector

NASA Astrophysics Data System (ADS)

Wanotayaroj, Chaowaroj

This dissertation presents searches for direct pair production of a scalar partner of the top quark in events with only jets and missing transverse energy in proton-proton collisions recorded during LHC Run 1 and Run 2 with the ATLAS detector. In the supersymmetry scenario, the partner is called top squark or stop. The stop (t˜) is assumed to decay via t˜ → t X˜10, t˜ → b X˜1+/- → bW(*) X˜ 10, or t˜ → bW X˜ 10, where X˜ 10 (X˜1+/- ) denotes the lightest neutralino (chargino). Exclusion limits are reported in terms of the stop and neutralino masses. The LHC Run 1 analysis uses an integrated luminosity of 20.1 fb -1 at √s = 8 tev to exclude top squark masses in the range 270-645 GeV for X˜1 0 masses below 30 GeV, assuming a 100% t˜ → t X˜10 branching ratio (BR). For a BR of 50% to either t˜ → t X˜10 or t˜→ b X˜1+/-, and assuming mX1+/- = 2 mX˜10, stop masses in the range 250-550 GeV are excluded for X˜ 10 masses below 60 GeV. The LHC Run 2 analysis uses an integrated luminosity of 13.3 fb -1 at √s = 13 tev. Assuming a 100% t˜ → t X˜10 BR, stop masses in the range 310-820 GeV are excluded for X˜ 10 masses below 160 GeV. For m t˜ ˜ mt + mX˜0 scenario, the search excludes stop masses between 23-380 GeV. Additionally, scenarios where stops are produced indirectly through gluino decay but have very low pT signature due to a very small Delta(mt˜, mX˜0), have been considered. The result is interpreted as an upper limit for the cross section in terms of the gluino and stop masses. This excludes all models considered which include mg˜ up to 1600 GeV with mX˜0 < 560 GeV at 95% CL. Finally, the analysis strategy from the LHC Run 1 search is applied in the broader scope of supersymmetry called Phenomenological Minimum Supersymmetric Standard Model (pMSSM). This dissertation presents a summary of the results that related to the stop search.

Optimizing Intratheater Military Airlift in Iraq and Afghanistan

DTIC Science & Technology

2013-01-01

2013 Page 37 Data lenr number of stops on route r aðr ; sÞ airfield at stop number s on route r, where 1# s # lenr carryaiaj cr amount of cargo c on...comes after, and within maxloadhops of, stop s on route r: 1# s , s## lenr , s#2 s #maxloadhops Variables SELECTr integer number of times airplane...so , lenr ; c (4) X r; s#: 1, s## lenr ; aðr; s#Þ5aj SELECTr # landingaj "aj 2 A (5) The objective function (1) calculates the priority-weighted value

Anti-inflammatory genes associated with multiple sclerosis: a gene expression study.

PubMed

Perga, S; Montarolo, F; Martire, S; Berchialla, P; Malucchi, S; Bertolotto, A

2015-02-15

Multiple sclerosis (MS) is an autoimmune inflammatory disease of the central nervous system caused by a complex interaction between multiple genes and environmental factors. HLA region is the strongest susceptibility locus, but recent huge genome-wide association studies identified new susceptibility genes. Among these, BACH2, PTGER4, RGS1 and ZFP36L1 were highlighted. Here, a gene expression analysis revealed that three of them, namely BACH2, PTGER4 and ZFP36L1, are down-regulated in MS patients' blood cells compared to healthy subjects. Interestingly, all these genes are involved in the immune system regulation with predominant anti-inflammatory role and their reduction could predispose to MS development. Copyright © 2015 Elsevier B.V. All rights reserved.

Educated Parents, Educated Children: Toward a Multiple Life Cycles Education Policy

ERIC Educational Resources Information Center

Sticht, Thomas G.

2012-01-01

Philanthropists and policymakers sometimes opt to fund childhood education to "stop illiteracy at the source" at the expense of funding for adult literacy education. In 2000, "The New York Times" published an article about a gift of $100 million being given to schools in Mississippi to promote the teaching of reading to…

Leading for Literacy: Engaging Schools and Districts in Transforming Subject-Area Literacy

ERIC Educational Resources Information Center

Schoenbach, Ruth; Greenleaf, Cynthia

2017-01-01

Two-thirds of U.S. high school students today are unable to read and comprehend complex academic materials, think critically about texts, synthesize information from multiple sources, or effectively communicate what they have learned. And in response, many teachers simply stop assigning challenging texts, opting instead to "deliver…

External Validity in Policy Evaluations That Choose Sites Purposively

ERIC Educational Resources Information Center

Olsen, Robert B.; Orr, Larry L.; Bell, Stephen H.; Stuart, Elizabeth A.

2013-01-01

Evaluations of the impact of social programs are often carried out in multiple sites, such as school districts, housing authorities, local TANF offices, or One-Stop Career Centers. Most evaluations select sites purposively following a process that is nonrandom. Unfortunately, purposive site selection can produce a sample of sites that is not…

Dual energy scanning beam laminographic x-radiography

DOEpatents

Majewski, Stanislaw; Wojcik, Randolph F.

1998-01-01

A multiple x-ray energy level imaging system includes a scanning x-ray beam and two detector design having a first low x-ray energy sensitive detector and a second high x-ray energy sensitive detector. The low x-ray energy detector is placed next to or in front of the high x-ray energy detector. The low energy sensitive detector has small stopping power for x-rays. The lower energy x-rays are absorbed and converted into electrical signals while the majority of the higher energy x-rays pass through undetected. The high energy sensitive detector has a large stopping power for x-rays as well as it having a filter placed between it and the object to absorb the lower energy x-rays. In a second embodiment; a single energy sensitive detector is provided which provides an output signal proportional to the amount of energy in each individual x-ray it absorbed. It can then have an electronic threshold or thresholds set to select two or more energy ranges for the images. By having multiple detectors located at different positions, a dual energy laminography system is possible.

Dual energy scanning beam laminographic x-radiography

DOEpatents

Majewski, S.; Wojcik, R.F.

1998-04-21

A multiple x-ray energy level imaging system includes a scanning x-ray beam and two detector design having a first low x-ray energy sensitive detector and a second high x-ray energy sensitive detector. The low x-ray energy detector is placed next to or in front of the high x-ray energy detector. The low energy sensitive detector has small stopping power for x-rays. The lower energy x-rays are absorbed and converted into electrical signals while the majority of the higher energy x-rays pass through undetected. The high energy sensitive detector has a large stopping power for x-rays as well as it having a filter placed between it and the object to absorb the lower energy x-rays. In a second embodiment; a single energy sensitive detector is provided which provides an output signal proportional to the amount of energy in each individual x-ray it absorbed. It can then have an electronic threshold or thresholds set to select two or more energy ranges for the images. By having multiple detectors located at different positions, a dual energy laminography system is possible. 6 figs.

Inseparability of Go and Stop in Inhibitory Control: Go Stimulus Discriminability Affects Stopping Behavior.

PubMed

Ma, Ning; Yu, Angela J

2016-01-01

Inhibitory control, the ability to stop or modify preplanned actions under changing task conditions, is an important component of cognitive functions. Two lines of models of inhibitory control have previously been proposed for human response in the classical stop-signal task, in which subjects must inhibit a default go response upon presentation of an infrequent stop signal: (1) the race model, which posits two independent go and stop processes that race to determine the behavioral outcome, go or stop; and (2) an optimal decision-making model, which posits that observers decides whether and when to go based on continually (Bayesian) updated information about both the go and stop stimuli. In this work, we probe the relationship between go and stop processing by explicitly manipulating the discrimination difficulty of the go stimulus. While the race model assumes the go and stop processes are independent, and therefore go stimulus discriminability should not affect the stop stimulus processing, we simulate the optimal model to show that it predicts harder go discrimination should result in longer go reaction time (RT), lower stop error rate, as well as faster stop-signal RT. We then present novel behavioral data that validate these model predictions. The results thus favor a fundamentally inseparable account of go and stop processing, in a manner consistent with the optimal model, and contradicting the independence assumption of the race model. More broadly, our findings contribute to the growing evidence that the computations underlying inhibitory control are systematically modulated by cognitive influences in a Bayes-optimal manner, thus opening new avenues for interpreting neural responses underlying inhibitory control.

A field operational test on valve-regulated lead-acid absorbent-glass-mat batteries in micro-hybrid electric vehicles. Part I. Results based on kernel density estimation

NASA Astrophysics Data System (ADS)

Schaeck, S.; Karspeck, T.; Ott, C.; Weckler, M.; Stoermer, A. O.

2011-03-01

In March 2007 the BMW Group has launched the micro-hybrid functions brake energy regeneration (BER) and automatic start and stop function (ASSF). Valve-regulated lead-acid (VRLA) batteries in absorbent glass mat (AGM) technology are applied in vehicles with micro-hybrid power system (MHPS). In both part I and part II of this publication vehicles with MHPS and AGM batteries are subject to a field operational test (FOT). Test vehicles with conventional power system (CPS) and flooded batteries were used as a reference. In the FOT sample batteries were mounted several times and electrically tested in the laboratory intermediately. Vehicle- and battery-related diagnosis data were read out for each test run and were matched with laboratory data in a data base. The FOT data were analyzed by the use of two-dimensional, nonparametric kernel estimation for clear data presentation. The data show that capacity loss in the MHPS is comparable to the CPS. However, the influence of mileage performance, which cannot be separated, suggests that battery stress is enhanced in the MHPS although a battery refresh function is applied. Anyway, the FOT demonstrates the unsuitability of flooded batteries for the MHPS because of high early capacity loss due to acid stratification and because of vanishing cranking performance due to increasing internal resistance. Furthermore, the lack of dynamic charge acceptance for high energy regeneration efficiency is illustrated. Under the presented FOT conditions charge acceptance of lead-acid (LA) batteries decreases to less than one third for about half of the sample batteries compared to new battery condition. In part II of this publication FOT data are presented by multiple regression analysis (Schaeck et al., submitted for publication [1]).

30 CFR 75.372 - Mine ventilation map.

Code of Federal Regulations, 2010 CFR

2010-07-01

... at each opening. (8) The elevation at the top and bottom of each shaft and slope, and shaft and slope... of all ventilation controls, including permanent stoppings, overcasts, undercasts, regulators, seals... seals for each worked-out area. (19) The entry height, velocity and direction of the air current at or...

49 CFR 236.567 - Restrictions imposed when device fails and/or is cut out en route.

Code of Federal Regulations, 2013 CFR

2013-10-01

... cut out en route. 236.567 Section 236.567 Transportation Other Regulations Relating to Transportation... GOVERNING THE INSTALLATION, INSPECTION, MAINTENANCE, AND REPAIR OF SIGNAL AND TRAIN CONTROL SYSTEMS, DEVICES, AND APPLIANCES Automatic Train Stop, Train Control and Cab Signal Systems Rules and Instructions...

48 CFR 452.236-75 - Maximum Workweek-Construction Schedule.

Code of Federal Regulations, 2010 CFR

2010-10-01

... hours (including the daily starting and stopping times) and days of the week the Contractor proposes to carry out the work. The maximum workweek that will be approved is __*. (End of clause) * Contracting... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Maximum Workweek...

5 CFR 894.601 - When does my FEDVIP coverage stop?

Code of Federal Regulations, 2010 CFR

2010-01-01

... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Termination or Cancellation of...) If you are enrolled with a combination dental and vision carrier with a restricted service area, and... carrier and you change to a dental only or vision only carrier, your existing combination plan coverage...

5 CFR 894.601 - When does my FEDVIP coverage stop?

Code of Federal Regulations, 2011 CFR

2011-01-01

... REGULATIONS (CONTINUED) FEDERAL EMPLOYEES DENTAL AND VISION INSURANCE PROGRAM Termination or Cancellation of...) If you are enrolled with a combination dental and vision carrier with a restricted service area, and... carrier and you change to a dental only or vision only carrier, your existing combination plan coverage...

A different approach to multiplicity-edited heteronuclear single quantum correlation spectroscopy

NASA Astrophysics Data System (ADS)

Sakhaii, Peyman; Bermel, Wolfgang

2015-10-01

A new experiment for recording multiplicity-edited HSQC spectra is presented. In standard multiplicity-edited HSQC experiments, the amplitude of CH2 signals is negative compared to those of CH and CH3 groups. We propose to reverse the sign of 13C frequencies of CH2 groups in t1 as criteria for editing. Basically, a modified [BIRD]r,x element (Bilinear Rotation Pulses and Delays) is inserted in a standard HSQC pulse sequence with States-TPPI frequency detection in t1 for this purpose. The modified BIRD element was designed in such a way as to pass or stop the evolution of the heteronuclear 1JHC coupling. This is achieved by adding a 180° proton RF pulse in each of the 1/2J periods. Depending on their position the evolution is switched on or off. Usually, the BIRD- element is applied on real and imaginary increments of a HSQC experiment to achieve the editing between multiplicities. Here, we restrict the application of the modified BIRD element to either real or imaginary increments of the HSQC. With this new scheme for editing, changing the frequency and/or amplitude of the CH2 signals becomes available. Reversing the chemical shift axis for CH2 signals simplifies overcrowded frequency regions and thus avoids accidental signal cancellation in conventional edited HSQC experiments. The practical implementation is demonstrated on the protein Lysozyme. Advantages and limitations of the idea are discussed.

Termination and read-through proteins encoded by genome segment 9 of Colorado tick fever virus.

PubMed

Mohd Jaafar, Fauziah; Attoui, Houssam; De Micco, Philippe; De Lamballerie, Xavier

2004-08-01

Genome segment 9 (Seg-9) of Colorado tick fever virus (CTFV) is 1884 bp long and contains a large open reading frame (ORF; 1845 nt in length overall), although a single in-frame stop codon (at nt 1052-1054) reduces the ORF coding capacity by approximately 40 %. However, analyses of highly conserved RNA sequences in the vicinity of the stop codon indicate that it belongs to a class of 'leaky terminators'. The third nucleotide positions in codons situated both before and after the stop codon, shows the highest variability, suggesting that both regions are translated during virus replication. This also suggests that the stop signal is functionally leaky, allowing read-through translation to occur. Indeed, both the truncated 'termination' protein and the full-length 'read-through' protein (VP9 and VP9', respectively) were detected in CTFV-infected cells, in cells transfected with a plasmid expressing only Seg-9 protein products, and in the in vitro translation products from undenatured Seg-9 ssRNA. The ratios of full-length and truncated proteins generated suggest that read-through may be down-regulated by other viral proteins. Western blot analysis of infected cells and purified CTFV showed that VP9 is a structural component of the virion, while VP9' is a non-structural protein.

EGFR-mutant Non-small Cell Lung Cancer Accompanied by Transient Asymptomatic Pulmonary Opacities Successfully Treated with "Stop-And-Go" Osimertinib.

PubMed

Kobayashi, Keigo; Naoki, Katsuhiko; Kuroda, Aoi; Yasuda, Hiroyuki; Kawada, Ichiro; Soejima, Kenzo; Betsuyaku, Tomoko

2018-04-01

A 69-year-old man with post-operative recurrence of lung adenocarcinoma was treated with multiple chemotherapies, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. A second biopsy revealed an EGFR T790M mutation. As 10th-line chemotherapy, osimertinib was initiated. After 24 weeks, chest computed tomography (CT) revealed asymptomatic ground-glass opacities in both lobes. After four weeks of osimertinib discontinuation, imaging revealed rapid lung cancer progression. Osimertinib was resumed. After 11 weeks, CT revealed decreased lung nodules with no exacerbation of interstitial lung disease. We describe a patient who experienced transient asymptomatic pulmonary opacities during treatment with osimertinib, which was successfully managed by a "stop-and-go" approach.

[Prevalence of the attempts to stop pregnancy and associated factors in a marginal suburban community in Lima-Peru, 2006].

PubMed

Tarqui-Mamani, Carolina; Barreda, Alejandro; Barreda, Milagros; Sanabria-Rojas, Hernán

2010-03-01

To estimate the prevalence for the attempts to stop pregnancy among women with history of previous pregnancies, and to determine the factors associated. A cross-sectional study was performed during 2006. Samples included 1057 women with background of pregnancy, living in Pamplona Alta, selected by a systematic random sampling. We applied descriptive and inferential statistics, including a logistic regression model. The prevalence for the attempt to stop pregnancy was 13.9% (99% CI: 11.1-16.7). The factors associated identified by multivariate analysis were: Unwanted pregnancy (OR=5.7; CI: 1.9-16.7), lack of pre-natal care (OR=4.7; CI: 1.8-12.2), prostitution (OR=11.4; CI: 1.5-87.9), age below 20 years (OR=2.9; CI: 1.1-7.9), and having more than two partners (OR=3.3; CI: 1.1-10.2). The estimated prevalence for the attempt to stop pregnancy among women with history of previous pregnancies in a marginal suburban area from Lima was low when compared to the national estimated prevalence of abortion. The associated factors identified for the attempts to stop pregnancy are: unwanted pregnancy, prostitution, age below 20 years, having more than two partners and lack of pre-natal care.

Search for the supersymmetric partner of the top quark in ppbar collisions at sqrt(s) = 1.96 TeV

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

Aaltonen, T.; /Helsinki Inst. of Phys.; Alvarez Gonzalez, B.

We present a search for the lightest supersymmetric partner of the top quark in proton-antiproton collisions at a center-of-mass energy {radical}s = 1.96 TeV. This search was conducted within the framework of the R-parity conserving minimal supersymmetric extension of the standard model, assuming the stop decays dominantly to a lepton, a sneutrino, and a bottom quark. We searched for events with two oppositely-charged leptons, at least one jet, and missing transverse energy in a data sample corresponding to an integrated luminosity of 1 fb{sup -1} collected by the CDF experiment. No significant evidence of a stop quark signal was found.more » Exclusion limits at 95% confidence level in the stop quark versus sneutrino mass plane are set. Stop quark masses up to 180 GeV/c{sup 2} are excluded for sneutrino masses around 45 GeV/c{sup 2}, and sneutrino masses up to 116 GeV/c{sup 2} are excluded for stop quark masses around 150 GeV/c{sup 2}.« less

Aging and inhibitory control of action: cortico-subthalamic connection strength predicts stopping performance.

PubMed

Coxon, James P; Van Impe, Annouchka; Wenderoth, Nicole; Swinnen, Stephan P

2012-06-13

Diffusion weighted imaging (DWI) studies in humans have shown that seniors exhibit reduced white matter integrity compared with young adults, with the most pronounced change occurring in frontal white matter. It is generally assumed that this structural deterioration underlies inhibitory control deficits in old age, but specific evidence from a structural neuroscience perspective is lacking. Cognitive action control is thought to rely on an interconnected network consisting of right inferior frontal cortex (r-IFC), pre-supplementary motor area (preSMA), and the subthalamic nucleus (STN). Here we performed probabilistic DWI tractography to delineate this cognitive control network and had the same individuals (20 young, 20 older adults) perform a task probing both response inhibition and action reprogramming. We hypothesized that structural integrity (fractional anisotropy) and connection strength within this network would be predictive of individual and age-related differences in task performance. We show that the integrity of r-IFC white matter is an age-independent predictor of stop-signal reaction time (SSRT). We further provide evidence that the integrity of white matter projecting to STN predicts both outright stopping (SSRT) and transient braking of response initiation to buy time for action reprogramming (stopping interference effects). These associations remain even after controlling for Go task performance, demonstrating specificity to the Stop component of this task. Finally, a multiple regression analysis reveals bilateral preSMA-STN tract strength as a significant predictor of SSRT in older adults. Our data link age-related decline in inhibitory control with structural decline of STN projections.

49 CFR 37.201 - Intermediate and rest stops.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 49 Transportation 1 2010-10-01 2010-10-01 false Intermediate and rest stops. 37.201 Section 37.201 Transportation Office of the Secretary of Transportation TRANSPORTATION SERVICES FOR INDIVIDUALS WITH DISABILITIES (ADA) Over-the-Road Buses (OTRBs) § 37.201 Intermediate and rest stops. (a) Whenever an OTRB makes...

The Spleen Is an HIV-1 Sanctuary During Combined Antiretroviral Therapy.

PubMed

Nolan, David J; Rose, Rebecca; Rodriguez, Patricia H; Salemi, Marco; Singer, Elyse J; Lamers, Susanna L; McGrath, Michael S

2018-01-01

Combined antiretroviral therapy (cART) does not eradicate HIV, which persists for years and can re-establish replication if treatment is stopped. The current challenge is identifying those tissues harboring virus through cART. Here, we used HIV env-nef single genome sequencing and HIV gag droplet digital PCR (ddPCR) to survey 50 tissues from five subjects on cART with no detectable plasma viral load at death. The spleen most consistently contained multiple proviral and expressed sequences (4/5 participants). Spleen-derived HIV demonstrated two distinct phylogenetic patterns: multiple identical sequences, often from different tissues, as well as diverse viral sequences on long terminal branches. Our results suggested that ddPCR may overestimate the size of the tissue-based viral reservoir. The spleen, a lymphatic organ at the intersection of the immune and circulatory systems, may play a key role in viral persistence.

Anterior midline point stop device (AMPS) in the treatment of myogenous TMDs: comparison with the stabilization splint and control group.

PubMed

Al Quran, Firas A M; Kamal, Mudar S

2006-06-01

Two occlusal splints, the full-arch stabilization splint and the anterior midline point stop (AMPS) device, were evaluated for their efficiency in relieving myogenous temporomandibular disorders (TMD). One hundred and fourteen patients with myogenous TMD were distributed into 3 groups. The first group was treated with the AMPS device, the second with the stabilization splint, and the third group was the control group. Pain intensity was scored using the visual analogue scale before treatment and 1 month and 3 months after treatment. Statistical Package for the Social Sciences (SPSS, Chicago, Ill) and multiple comparisons tests were used to compare results before and after treatment and to compare the groups. The use of AMPS device in the first group resulted in a significant improvement after 1 month and 3 months (P < or = .001) and showed a 56.66% pain reduction. A significant improvement was also noticed in the second group (P = .001) with a 47.71% pain reduction. Although pain reduction percentage appeared more in the first group, this was not statistically significant. There was a highly significant difference between groups treated with both kinds of splints and the control group. It was concluded that both types of occlusal splints are beneficial to patients with myogenous TMD.

Individual differences in phonetic cue use in production and perception of a non-native sound contrast

PubMed Central

Schertz, Jessamyn; Cho, Taehong; Lotto, Andrew; Warner, Natasha

2015-01-01

The current work examines native Korean speakers’ perception and production of stop contrasts in their native language (L1, Korean) and second language (L2, English), focusing on three acoustic dimensions that are all used, albeit to different extents, in both languages: voice onset time (VOT), f0 at vowel onset, and closure duration. Participants used all three cues to distinguish the L1 Korean three-way stop distinction in both production and perception. Speakers’ productions of the L2 English contrasts were reliably distinguished using both VOT and f0 (even though f0 is only a very weak cue to the English contrast), and, to a lesser extent, closure duration. In contrast to the relative homogeneity of the L2 productions, group patterns on a forced-choice perception task were less clear-cut, due to considerable individual differences in perceptual categorization strategies, with listeners using either primarily VOT duration, primarily f0, or both dimensions equally to distinguish the L2 English contrast. Differences in perception, which were stable across experimental sessions, were not predicted by individual variation in production patterns. This work suggests that reliance on multiple cues in representation of a phonetic contrast can form the basis for distinct individual cue-weighting strategies in phonetic categorization. PMID:26644630

Regulation of PRPP and nucleoside tri and tetraphosphate pools in Escherichia coli under conditions of nitrogen starvation.

PubMed Central

Villadsen, I S; Michelsen, O

1977-01-01

The ribonucleoside triphosphate, deoxyribonucleoside triphosphate, 3' -diphosphate guanosine 5' -diphosphate (ppGpp), and 5-phosphoribosyl 1-pyrophosphate (PRPP) pools in Escherichia coli B were determined by thin-layer chromatography during changing conditions to ammonium starvation. The intracellular concentrations of all nucleotides were found to change in a well-defined order several minutes before andy observed change in the optical density of the culture. The levels of purine nucleoside triphosphates (adenosine 5' -triphosphate [CTP], dCTP) and uridine nucleotides (uridine 5' -triphosphate, deoxythymidine 5'-triphosphate). The deoxyribonucleotides thus behaved as the ribonucleotides. The levels of ppGpp increased 11-fold after the decrease in uridine nucleotides, when the accumulation of stable ribonucleic acid (RNA) stopped. The level of the nucleotide pool did not stabilize until 30 min after the change in optical density. The pool of dGTP dropped concomitantly with the pool of CTP. The nucleotide precursor PRPP exhibited a transient increase, wtih maximum value of four times the exponential levels at the onset of starvation. Apparently the cell adjusts early to starvation by reducing either the phosphorylating activity or the nucleotide biosynthetic activity. As in other downshift systems, the accumulation of stable RNA stopped before the break in optical density and before the stop in protein accumulation. Cell divisions were quite insensitive to the control mechanisms operating on RNA and protein accumulation under ammonium starvation, since the cells continued to divide for 21 min without any net accumulation of RNA. Images PMID:323222

The electronic stopping powers and angular energy-loss dependence of helium and lithium ions in the silicon crystal

NASA Astrophysics Data System (ADS)

Mikšová, R.; Macková, A.; Malinský, P.

2017-09-01

We have measured the electronic stopping powers of helium and lithium ions in the channelling direction of the Si〈1 0 0〉 crystal. The energy range used (2.0-8.0 MeV) was changed by 200 and 400-keV steps. The ratio α between the channelling and random stopping powers was determined as a function of the angle for 2, 3 and 4 MeV 4He+ ions and for 3 and 6 MeV 7Li+,2+ ions. The measurements were carried out using the Rutherford backscattering spectrometry in the channelling mode (RBS-C) in a silicon-on-insulator material. The experimental channelling stopping-power values measured in the channelling direction were then discussed in the frame of the random energy stopping predictions calculated using SRIM-2013 code and the theoretical unitary convolution approximation (UCA) model. The experimental channelling stopping-power values decrease with increasing ion energy. The stopping-power difference between channelled and randomly moving ions increases with the enhanced initial ion energy. The ratio between the channelling and random ion stopping powers α as a function of the ion beam incoming angle for 2, 3 and 4 MeV He+ ions and for 3 and 6 MeV Li+,2+ ions was observed in the range 0.5-1.

Platelet storage in Fresenius/NPBI polyolefin and BTHC-PVC bags: a direct comparison.

PubMed

Hornsey, V S; McColl, K; Drummond, O; Macgregor, I R; Prowse, C V

2008-08-01

New platelet storage systems, such as changes in the plastic of the storage bags, require validation. In this study, pooled buffy coat platelets stored in Fresenius/NPBI polyolefin bags were compared with those stored in Fresenius/NPBI butyryl-trihexyl citrate (BTHC) plasticized polyvinyl chloride (PVC). The CompoSelect thrombocyte polishing filter system (1000 mL polyolefin bag) and the CompoStop F730 system (1300 mL BTHC-PVC bag) were used to prepare paired, plasma-suspended, buffy coat platelet concentrates. Samples were taken up to day 7 for in vitro analysis. In a separate experiment, 12 units were prepared using the CompoStop F730 system and samples taken after leucofiltration for FXIIa assay. By day 7, platelet concentrates stored in BTHC-PVC demonstrated significantly higher pH levels (7.32 +/- 0.05 vs. 7.26 +/- 0.05) and a greater degree of cell lysis as shown by increased lactate dehydrogenase levels (497 +/- 107 vs. 392 +/- 81 U L(-1)). The supernatants contained higher concentrations of soluble P-selectin and the chemokine 'regulated on activation, normal T-cell expressed and presumably secreted', which are released from the alpha-granules during activation. The ATP concentrations were significantly lower in BTHC-PVC. Platelet counts, mean platelet volume and hypotonic shock response were similar for both bags. FXIIa antigen concentrations were 0.6 +/- 0.2 ng mL(-1) indicating that activation of the contact factor pathway had not occurred. Although the CompoStop F730 leucoreduction filter did not activate the contact system, platelets stored in 100% plasma in BTHC-PVC bags demonstrated different in vitro characteristics from those stored in polyolefin. Further work is required to demonstrate whether these differences will affect in vivo recovery and survival.

Cloning and Characterization of a Critical Regulator for Preharvest Sprouting in Wheat

PubMed Central

Liu, Shubing; Sehgal, Sunish K.; Li, Jiarui; Lin, Meng; Trick, Harold N.; Yu, Jianming; Gill, Bikram S.; Bai, Guihua

2013-01-01

Sprouting of grains in mature spikes before harvest is a major problem in wheat (Triticum aestivum) production worldwide. We cloned and characterized a gene underlying a wheat quantitative trait locus (QTL) on the short arm of chromosome 3A for preharvest sprouting (PHS) resistance in white wheat using comparative mapping and map-based cloning. This gene, designated TaPHS1, is a wheat homolog of a MOTHER OF FLOWERING TIME (TaMFT)-like gene. RNA interference-mediated knockdown of the gene confirmed that TaPHS1 positively regulates PHS resistance. We discovered two causal mutations in TaPHS1 that jointly altered PHS resistance in wheat. One GT-to-AT mutation generates a mis-splicing site, and the other A-to-T mutation creates a premature stop codon that results in a truncated nonfunctional transcript. Association analysis of a set of wheat cultivars validated the role of the two mutations on PHS resistance. The molecular characterization of TaPHS1 is significant for expediting breeding for PHS resistance to protect grain yield and quality in wheat production. PMID:23821595

Stopping force and straggling of 0.6-4.7 MeV H, He and Li ions in the polyhydroxybutyrate foil

NASA Astrophysics Data System (ADS)

Hsu, J. Y.; Yu, Y. C.; Chen, K. M.

2010-06-01

Stopping force and straggling of 0.6-3.5 MeV 1H ions, 2.0-4.7 MeV 4He ions and 1.4-4.4 MeV 7Li ions in the polyhydroxybutyrate (PHB) foil were measured by means of a transmission technique. The measured stopping forces are in well agreement with the SRIM 2008 calculation and the ICRU Report tables, except for the lower energy region. The obtained energy loss straggling deviates from the Bohr's value by as much as 23.6% for the energies under study. The validity of the Bragg's rule has also been demonstrated in the stopping force and straggling for 1H, 4He and 7Li ions in the PHB foil.

MMSET deregulation affects cell cycle progression and adhesion regulons in t(4;14) myeloma plasma cells

PubMed Central

Brito, Jose L.R.; Walker, Brian; Jenner, Matthew; Dickens, Nicholas J.; Brown, Nicola J.M.; Ross, Fiona M.; Avramidou, Athanasia; Irving, Julie A.E.; Gonzalez, David; Davies, Faith E.; Morgan, Gareth J.

2009-01-01

Background The recurrent immunoglobulin translocation, t(4;14)(p16;q32) occurs in 15% of multiple myeloma patients and is associated with poor prognosis, through an unknown mechanism. The t(4;14) up-regulates fibroblast growth factor receptor 3 (FGFR3) and multiple myeloma SET domain (MMSET) genes. The involvement of MMSET in the pathogenesis of t(4;14) multiple myeloma and the mechanism or genes deregulated by MMSET upregulation are still unclear. Design and Methods The expression of MMSET was analyzed using a novel antibody. The involvement of MMSET in t(4;14) myelomagenesis was assessed by small interfering RNA mediated knockdown combined with several biological assays. In addition, the differential gene expression of MMSET-induced knockdown was analyzed with expression microarrays. MMSET gene targets in primary patient material was analyzed by expression microarrays. Results We found that MMSET isoforms are expressed in multiple myeloma cell lines, being exclusively up-regulated in t(4;14)-positive cells. Suppression of MMSET expression affected cell proliferation by both decreasing cell viability and cell cycle progression of cells with the t(4;14) translocation. These findings were associated with reduced expression of genes involved in the regulation of cell cycle progression (e.g. CCND2, CCNG1, BRCA1, AURKA and CHEK1), apoptosis (CASP1, CASP4 and FOXO3A) and cell adhesion (ADAM9 and DSG2). Furthermore, we identified genes involved in the latter processes that were differentially expressed in t(4;14) multiple myeloma patient samples. Conclusions In conclusion, dysregulation of MMSET affects the expression of several genes involved in the regulation of cell cycle progression, cell adhesion and survival. PMID:19059936

Position-dependent termination and widespread obligatory frameshifting in Euplotes translation

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

Lobanov, Alexei V.; Heaphy, Stephen M.; Turanov, Anton A.

2016-11-21

The ribosome can change its reading frame during translation in a process known as programmed ribosomal frameshifting. These rare events are supported by complex mRNA signals. However, we found that the ciliates Euplotes crassus and Euplotes focardii exhibit widespread frameshifting at stop codons. 47 different codons preceding stop signals resulted in either +1 or +2 frameshifts, and +1 frameshifting at AAA was the most frequent. The frameshifts showed unusual plasticity and rapid evolution, and had little influence on translation rates. The proximity of a stop codon to the 3' mRNA end, rather than its occurrence or sequence context, appeared tomore » designate termination. Thus, a ‘stop codon’ is not a sufficient signal for translation termination, and the default function of stop codons in Euplotes is frameshifting, whereas termination is specific to certain mRNA positions and probably requires additional factors.« less

Task Assignment and Path Planning for Multiple Autonomous Underwater Vehicles Using 3D Dubins Curves †

PubMed Central

Zhang, Meiyan; Zheng, Yahong Rosa

2017-01-01

This paper investigates the task assignment and path planning problem for multiple AUVs in three dimensional (3D) underwater wireless sensor networks where nonholonomic motion constraints of underwater AUVs in 3D space are considered. The multi-target task assignment and path planning problem is modeled by the Multiple Traveling Sales Person (MTSP) problem and the Genetic Algorithm (GA) is used to solve the MTSP problem with Euclidean distance as the cost function and the Tour Hop Balance (THB) or Tour Length Balance (TLB) constraints as the stop criterion. The resulting tour sequences are mapped to 2D Dubins curves in the X−Y plane, and then interpolated linearly to obtain the Z coordinates. We demonstrate that the linear interpolation fails to achieve G1 continuity in the 3D Dubins path for multiple targets. Therefore, the interpolated 3D Dubins curves are checked against the AUV dynamics constraint and the ones satisfying the constraint are accepted to finalize the 3D Dubins curve selection. Simulation results demonstrate that the integration of the 3D Dubins curve with the MTSP model is successful and effective for solving the 3D target assignment and path planning problem. PMID:28696377

Task Assignment and Path Planning for Multiple Autonomous Underwater Vehicles Using 3D Dubins Curves †.

PubMed

Cai, Wenyu; Zhang, Meiyan; Zheng, Yahong Rosa

2017-07-11

This paper investigates the task assignment and path planning problem for multiple AUVs in three dimensional (3D) underwater wireless sensor networks where nonholonomic motion constraints of underwater AUVs in 3D space are considered. The multi-target task assignment and path planning problem is modeled by the Multiple Traveling Sales Person (MTSP) problem and the Genetic Algorithm (GA) is used to solve the MTSP problem with Euclidean distance as the cost function and the Tour Hop Balance (THB) or Tour Length Balance (TLB) constraints as the stop criterion. The resulting tour sequences are mapped to 2D Dubins curves in the X - Y plane, and then interpolated linearly to obtain the Z coordinates. We demonstrate that the linear interpolation fails to achieve G 1 continuity in the 3D Dubins path for multiple targets. Therefore, the interpolated 3D Dubins curves are checked against the AUV dynamics constraint and the ones satisfying the constraint are accepted to finalize the 3D Dubins curve selection. Simulation results demonstrate that the integration of the 3D Dubins curve with the MTSP model is successful and effective for solving the 3D target assignment and path planning problem.

SHIELDING CONSIDERATIONS FOR THE SMALL ANIMAL RADIATION RESEARCH PLATFORM (SARRP)

PubMed Central

Sayler, Elaine; Dolney, Derek; Avery, Stephen; Koch, Cameron

2014-01-01

The Small Animal Radiation Research Platform (SARRP) is a commercially available platform designed to deliver conformal, image-guided radiation to small animals using a dual-anode kV x-ray source. At the University of Pennsylvania, a free-standing 2 m3 enclosure was designed to shield the SARRP according to federal code regulating cabinet x-ray systems. The initial design consisted of 4.0-mm-thick lead for all secondary barriers and proved wholly inadequate. Radiation levels outside the enclosure were 15 times higher than expected. Additionally, the leakage appeared to be distributed broadly within the enclosure, so concern arose that a subject might receive significant doses outside the intended treatment field. Thus, a detailed analysis was undertaken to identify and block all sources of leakage. Leakage sources were identified by Kodak X-OmatV (XV) film placed throughout the enclosure. Radiation inside the enclosure was quantified using Gafchromic film. Outside the enclosure, radiation was measured using a survey meter. Sources of leakage included (1) an unnecessarily broad beam exiting the tube, (2) failure of the secondary collimator to confine the primary beam entirely, (3) scatter from the secondary collimator, (4) lack of beam-stop below the treatment volume, and (5) incomplete shielding of the x-ray tube. The exit window was restricted, and a new collimator was designed to address problems (1–3). A beam-stop and additional tube shielding were installed. These modifications reduced internal scatter by more than 100-fold. Radiation outside the enclosure was reduced to levels compliant with federal regulations, provided the SARRP is operated using tube potentials of 175 kV or less. In addition, these simple and relatively inexpensive modifications eliminate the possibility of exposing a larger animal (such as a rat) to significant doses outside the treatment field. PMID:23532076

Measurement and Reliability of Response Inhibition

PubMed Central

Congdon, Eliza; Mumford, Jeanette A.; Cohen, Jessica R.; Galvan, Adriana; Canli, Turhan; Poldrack, Russell A.

2012-01-01

Response inhibition plays a critical role in adaptive functioning and can be assessed with the Stop-signal task, which requires participants to suppress prepotent motor responses. Evidence suggests that this ability to inhibit a prepotent motor response (reflected as Stop-signal reaction time (SSRT)) is a quantitative and heritable measure of interindividual variation in brain function. Although attention has been given to the optimal method of SSRT estimation, and initial evidence exists in support of its reliability, there is still variability in how Stop-signal task data are treated across samples. In order to examine this issue, we pooled data across three separate studies and examined the influence of multiple SSRT calculation methods and outlier calling on reliability (using Intra-class correlation). Our results suggest that an approach which uses the average of all available sessions, all trials of each session, and excludes outliers based on predetermined lenient criteria yields reliable SSRT estimates, while not excluding too many participants. Our findings further support the reliability of SSRT, which is commonly used as an index of inhibitory control, and provide support for its continued use as a neurocognitive phenotype. PMID:22363308

Tunable graphene-based mid-infrared plasmonic multispectral and narrow band-stop filter

NASA Astrophysics Data System (ADS)

Wang, Xianjun; Meng, Hongyun; Liu, Shuai; Deng, Shuying; Jiao, Tao; Wei, Zhongchao; Wang, Faqiang; Tan, Chunhua; Huang, Xuguang

2018-04-01

In this paper, we numerically investigate the band-stop properties of single- or few-layers doped graphene ribbon arrays operating in the mid-infrared region by finite-difference time-domain method (FDTD). A perfect band-stop filter with extinction ratio (ER) ∼17 dB, 3 dB bandwidth ∼200 nm and the resonance notch located at 6.64 μm can be achieved. And desired working regions can be obtained by tuning the Fermi level (E f ) of the graphene ribbons and the geometrical parameters of the structure. Besides, by tuning the Fermi level of odd or even graphene ribbons with terminal gate voltage, we can achieve a dual-circuit switch with four states combinations of on-to-off. Furthermore, the multiple filter notches can be achieved by stacking few-layers structure, and the filter dips can be dynamically tuned to achieve the tunability and selective characteristics by tuning the Fermi-level of the graphene ribbons in the system. We believe that our proposal has the potential applications in selective filters and active plasmonic switching in the mid-infrared region.

Rituximab Restores IFN-γ-STAT1 Function and Ameliorates Disseminated Mycobacterium avium Infection in a Patient with Anti-Interferon-γ Autoantibody.

PubMed

Koizumi, Yusuke; Sakagami, Takuro; Nishiyama, Naoya; Hirai, Jun; Hayashi, Yuta; Asai, Nobuhiro; Yamagishi, Yuka; Kato, Hideo; Hagihara, Mao; Sakanashi, Daisuke; Suematsu, Hiroyuki; Ogawa, Kenji; Mikamo, Hiroshige

2017-10-01

A 67-year-old Japanese female with back pain and severe cachexia visited our hospital. The diagnosis was disseminated Mycobacterium avium complex infection (dMAC) with multiple bone involvement. Anti-mycobacterial chemotherapy was started, but fever persisted and dislocation of cervical vertebrae has made her bedridden. Because anti-interferon (IFN)-γ autoantibody was positive, four doses of rituximab 375 mg/m 2 , every 7 day, were administered. Soon after treatment, progression of osteolytic lesions and wasting has stopped. We proved that rituximab has recovered IFN-γ signaling as shown by IFN-γ-induced STAT1 phosphorylation. It can be a promising option for dMAC cases with anti-IFN-γ autoantibody.

Miro1 Regulates Activity-Driven Positioning of Mitochondria within Astrocytic Processes Apposed to Synapses to Regulate Intracellular Calcium Signaling

PubMed Central

Stephen, Terri-Leigh; Higgs, Nathalie F.; Sheehan, David F.; Al Awabdh, Sana; López-Doménech, Guillermo; Arancibia-Carcamo, I. Lorena

2015-01-01

It is fast emerging that maintaining mitochondrial function is important for regulating astrocyte function, although the specific mechanisms that govern astrocyte mitochondrial trafficking and positioning remain poorly understood. The mitochondrial Rho-GTPase 1 protein (Miro1) regulates mitochondrial trafficking and detachment from the microtubule transport network to control activity-dependent mitochondrial positioning in neurons. However, whether Miro proteins are important for regulating signaling-dependent mitochondrial dynamics in astrocytic processes remains unclear. Using live-cell confocal microscopy of rat organotypic hippocampal slices, we find that enhancing neuronal activity induces transient mitochondrial remodeling in astrocytes, with a concomitant, transient reduction in mitochondrial trafficking, mediated by elevations in intracellular Ca2+. Stimulating neuronal activity also induced mitochondrial confinement within astrocytic processes in close proximity to synapses. Furthermore, we show that the Ca2+-sensing EF-hand domains of Miro1 are important for regulating mitochondrial trafficking in astrocytes and required for activity-driven mitochondrial confinement near synapses. Additionally, activity-dependent mitochondrial positioning by Miro1 reciprocally regulates the levels of intracellular Ca2+ in astrocytic processes. Thus, the regulation of intracellular Ca2+ signaling, dependent on Miro1-mediated mitochondrial positioning, could have important consequences for astrocyte Ca2+ wave propagation, gliotransmission, and ultimately neuronal function. SIGNIFICANCE STATEMENT Mitochondria are key cellular organelles that play important roles in providing cellular energy and buffering intracellular calcium ions. The mechanisms that control mitochondrial distribution within the processes of glial cells called astrocytes and the impact this may have on calcium signaling remains unclear. We show that activation of glutamate receptors or increased neuronal activity leads to the altered transport of mitochondria and their positioning at synapses dependent on a key mitochondrial trafficking protein called Miro1. We also show that, the control of mitochondrial movement and stopping by Miro plays an important role in regulating astrocyte calcium responses. Thus the regulation of intracellular calcium signaling, by Miro-mediated mitochondrial positioning, could have important consequences for astrocyte signaling and neuron–glial interactions. PMID:26631479

30 CFR 57.22219 - Seals and stoppings (II-A mines).

Code of Federal Regulations, 2010 CFR

2010-07-01

... 30 Mineral Resources 1 2010-07-01 2010-07-01 false Seals and stoppings (II-A mines). 57.22219... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22219 Seals and stoppings (II-A mines... fire resistance. (b) Seals shall be of substantial construction. Exposed surfaces on the fresh air side...

30 CFR 57.22219 - Seals and stoppings (II-A mines).

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 1 2011-07-01 2011-07-01 false Seals and stoppings (II-A mines). 57.22219... Standards for Methane in Metal and Nonmetal Mines Ventilation § 57.22219 Seals and stoppings (II-A mines... fire resistance. (b) Seals shall be of substantial construction. Exposed surfaces on the fresh air side...

Analysis of rural intersection accidents caused by stop sign violation and failure to yield the right-of-way

DOT National Transportation Integrated Search

2000-09-01

The objectives of this study were to (1) identify the factors that contribute to accidents caused by failure to stop and failure to yield the right-of-way at rural two-way stop-controlled intersections on the state highway system, and (2) determine w...

Analytical model for ion stopping power and range in the therapeutic energy interval for beams of hydrogen and heavier ions

NASA Astrophysics Data System (ADS)

Donahue, William; Newhauser, Wayne D.; Ziegler, James F.

2016-09-01

Many different approaches exist to calculate stopping power and range of protons and heavy charged particles. These methods may be broadly categorized as physically complete theories (widely applicable and complex) or semi-empirical approaches (narrowly applicable and simple). However, little attention has been paid in the literature to approaches that are both widely applicable and simple. We developed simple analytical models of stopping power and range for ions of hydrogen, carbon, iron, and uranium that spanned intervals of ion energy from 351 keV u-1 to 450 MeV u-1 or wider. The analytical models typically reproduced the best-available evaluated stopping powers within 1% and ranges within 0.1 mm. The computational speed of the analytical stopping power model was 28% faster than a full-theoretical approach. The calculation of range using the analytic range model was 945 times faster than a widely-used numerical integration technique. The results of this study revealed that the new, simple analytical models are accurate, fast, and broadly applicable. The new models require just 6 parameters to calculate stopping power and range for a given ion and absorber. The proposed model may be useful as an alternative to traditional approaches, especially in applications that demand fast computation speed, small memory footprint, and simplicity.

An empirical approach to the stopping power of solids and gases for ions from 3Li to 18Ar

NASA Astrophysics Data System (ADS)

Paul, Helmut; Schinner, Andreas

2001-08-01

A large collection of stopping power data for projectiles from 3Li to 18Ar is investigated as a possible basis for producing a table of stopping powers. We divide the experimental stopping powers for a particular projectile (nuclear charge Z1) by those for alpha particles in the same element, as given in ICRU Report 49. With proper normalization, we then obtain experimental stopping power ratios Srel that lie approximately on a single curve, provided we treat solid and gaseous targets separately, and provided we exclude H 2 and He targets. For every projectile, this curve is then fitted by a 3-parameter sigmoid function Srel= Srel( a, b, c). We find that the three parameters a, b and c depend smoothly on Z1 and can themselves be fitted by suitable functions af, bf and cf of Z1, separately for solid and gaseous targets. The low energy limit (coefficient a) for solids agrees approximately with the prediction by Lindhard and Scharff. We find that agas< asol in almost all cases. Introducing the coefficients af , bf and cf in Srel, we can calculate the stopping power for any ion (3⩽ Z1⩽18), and for any element (except H 2 and He) and any mixture or compound contained in the ICRU table.

Analytical model for ion stopping power and range in the therapeutic energy interval for beams of hydrogen and heavier ions.

PubMed

Donahue, William; Newhauser, Wayne D; Ziegler, James F

2016-09-07

Many different approaches exist to calculate stopping power and range of protons and heavy charged particles. These methods may be broadly categorized as physically complete theories (widely applicable and complex) or semi-empirical approaches (narrowly applicable and simple). However, little attention has been paid in the literature to approaches that are both widely applicable and simple. We developed simple analytical models of stopping power and range for ions of hydrogen, carbon, iron, and uranium that spanned intervals of ion energy from 351 keV u(-1) to 450 MeV u(-1) or wider. The analytical models typically reproduced the best-available evaluated stopping powers within 1% and ranges within 0.1 mm. The computational speed of the analytical stopping power model was 28% faster than a full-theoretical approach. The calculation of range using the analytic range model was 945 times faster than a widely-used numerical integration technique. The results of this study revealed that the new, simple analytical models are accurate, fast, and broadly applicable. The new models require just 6 parameters to calculate stopping power and range for a given ion and absorber. The proposed model may be useful as an alternative to traditional approaches, especially in applications that demand fast computation speed, small memory footprint, and simplicity.

OsSLI1, a homeodomain containing transcription activator, involves abscisic acid related stress response in rice (Oryza sativa L.).

PubMed

Huang, Xi; Duan, Min; Liao, Jiakai; Yuan, Xi; Chen, Hui; Feng, Jiejie; Huang, Ji; Zhang, Hong-Sheng

2014-01-01

Homeodomain-leucine zipper type I (HD-Zip I) proteins are involved in the regulation of plant development and response to environmental stresses. In this study, OsSLI1 (Oryza sativa stress largely induced 1), encoding a member of the HD-Zip I subfamily, was isolated from rice. The expression of OsSLI1 was dramatically induced by multiple abiotic stresses and exogenous abscisic acid (ABA). In silico sequence analysis discovered several cis-acting elements including multiple ABREs (ABA-responsive element binding factors) in the upstream promoter region of OsSLI1. The OsSLI1-GFP fusion protein was localized in the nucleus of rice protoplast cells and the transcriptional activity of OsSLI1 was confirmed by the yeast hybrid system. Further, it was found that OsSLI1 expression was enhanced in an ABI5-Like1 (ABL1) deficiency rice mutant abl1 under stress conditions, suggesting that ABL1 probably negatively regulates OsSLI1 gene expression. Moreover, it was found that OsSLI1 was regulated in panicle development. Taken together, OsSLI1 may be a transcriptional activator regulating stress-responsive gene expression and panicle development in rice.

Self-rated driving and driving safety in older adults.

PubMed

Ross, Lesley A; Dodson, Joan E; Edwards, Jerri D; Ackerman, Michelle L; Ball, Karlene

2012-09-01

Many U.S. states rely on older adults to self-regulate their driving and determine when driving is no longer a safe option. However, the relationship of older adults' self-rated driving in terms of actual driving competency outcomes is unclear. The current study investigates self-rated driving in terms of (1) systematic differences between older adults with high (good/excellent) versus low (poor/fair/average) self-ratings, and (2) the predictive nature of self-rated driving to adverse driving outcomes in older adults (n=350; mean age 73.9, SD=5.25, range 65-91). Adverse driving outcomes included self-reported incidences of (1) being pulled over by the police, (2) receiving a citation, (3) receiving a recommendation to cease or limit driving, (4) crashes, and (5) state-reported crashes. Results found that older drivers with low self-ratings reported more medical conditions, less driving frequency, and had been given more suggestions to stop/limit their driving; there were no other significant differences between low and high self-raters. Logistic regression revealed older drivers were more likely to have a state-reported crash and receive a suggestion to stop or limit driving. Men were more likely to report all adverse driving outcomes except for receiving a suggestion to stop or limit driving. Regarding self-rated driving, older adults with high ratings were 66% less likely (OR=0.34, 95% CI=0.14-0.85) to have received suggestions to limit or stop driving after accounting for demographics, health and driving frequency. Self-ratings were not predictive of other driving outcomes (being pulled over by the police, receiving a citation, self-reported crashes, or state-reported crashes, ps>0.05). Most older drivers (85.14%) rated themselves as either good or excellent drivers regardless of their actual previous citation or crash rates. Self-rated driving is likely not related to actual driving proficiency as indicated by previous crash involvement in older adults. Suggestions from other individuals to limit or cease driving may be more influential on self-ratings. Copyright © 2012 Elsevier Ltd. All rights reserved.

Self-rated Driving and Driving Safety in Older Adults

PubMed Central

Ross, Lesley A.; Dodson, Joan; Edwards, Jerri D.; Ackerman, Michelle L.; Ball, Karlene

2012-01-01

Many U.S. states rely on older adults to self-regulate their driving and determine when driving is no longer a safe option. However, the relationship of older adults’ self-rated driving in terms of actual driving competency outcomes is unclear. The current study investigates self-rated driving in terms of (1) systematic differences between older adults with high (good/excellent) versus low (poor/fair/average) self-ratings, and (2) the predictive nature of self-rated driving to adverse driving outcomes in older drivers (n=350; mean age 73.9, SD=5.25, range 65–91). Adverse driving outcomes included self-reported incidences of (1) being pulled over by the police, (2) receiving a citation, (3) receiving a recommendation to cease or limit driving, (4) crashes, and (5) state-reported crashes. Results found that older drivers with low self-ratings reported more medical conditions, less driving frequency, and had been given more suggestions to stop/limit their driving; there were no other significant differences between low and high self-raters. Logistic regression revealed older drivers were more likely to have a state-reported crash and receive a suggestion to stop or limit driving. Men were more likely to report all adverse driving outcomes except for receiving a suggestion to stop or limit driving. Regarding self-rated driving, older adults with high ratings were 66% less likely (OR=0.34, 95% CI=0.14–0.85) to have received suggestions to limit or stop driving after accounting for demographics, health and driving frequency. Self-ratings were not predictive of other driving outcomes (being pulled over by the police, receiving a citation, self-reported crashes, or state-reported crashes, ps>.05). Most older drivers (85.14%) rated themselves as either good or excellent drivers regardless of their actual previous citation or crash rates. Self-rated driving is likely not related to actual driving proficiency as indicated by previous crash involvement in older adults. Suggestions from other individuals to limit or cease driving may be more influential on self-ratings. PMID:22664719

Evaluation of bus emissions generated near bus stops

NASA Astrophysics Data System (ADS)

Yu, Qian; Li, Tiezhu

2014-03-01

The purpose of this research is to demonstrate a methodology for quantification of bus emissions generated near bus stops based on the real-world on-road emissions data collected by the Portable Emission Measurement System (PEMS). Data collection was carried out on an urban diesel bus throughout a bus line under normal operation condition on four work days. Stop influence zone is defined as the area in which the normal bus driving is interrupted by bus stops. The second-by-second data were screened out within the stop influence zone. And the bus running state near a stop was classified into three driving modes, deceleration, idling, and acceleration. Then emission characteristics were analyzed for each mode. Under the idling condition, the emission rates (g s-1) were not constant all the time. The NOX emission rate decreased in the first 4-6 s while the corresponding emission rates of CO2, CO, NOX, and HC increased in the last 4 s of idling. Besides, the influence of bus stop characteristics on emissions was investigated using statistical methods. Platform type, length and location of bus stops showed significant effects on the length of the stop influence zone. However, there were no significant effects on distance-based emission factors.

Routine intraoperative completion angiography after coronary artery bypass grafting and 1-stop hybrid revascularization results from a fully integrated hybrid catheterization laboratory/operating room.

PubMed

Zhao, David X; Leacche, Marzia; Balaguer, Jorge M; Boudoulas, Konstantinos D; Damp, Julie A; Greelish, James P; Byrne, John G; Ahmad, Rashid M; Ball, Stephen K; Cleator, John H; Deegan, Robert J; Eagle, Susan S; Fong, Pete P; Fredi, Joseph L; Hoff, Steven J; Jennings, Henry S; McPherson, John A; Piana, Robert N; Pretorius, Mias; Robbins, Mark A; Slosky, David A; Thompson, Annemarie

2009-01-20

This study sought to report our experience with a routine completion angiogram after coronary artery bypass surgery (CABG) and simultaneous (1-stop) percutaneous coronary intervention (PCI) at the time of CABG performed in the hybrid catheterization laboratory/operating room. The value of a routine completion angiogram after CABG and 1-stop hybrid CABG/PCI remains unresolved. Between April 2005 and July 2007, 366 consecutive patients underwent CABG surgery, with (n = 112) or without (n = 254) concomitant 1-stop PCI (hybrid), all with completion angiography before chest closure. Among the 112 1-stop hybrid CABG/PCI patients, 67 (60%) underwent a planned hybrid procedure based on pre-operative assessment, whereas 45 (40%) underwent open-chest PCI (unplanned hybrid) based on intraoperative findings. Among the 796 CABG grafts (345 left internal mammary artery, 12 right internal mammary artery/radial, and 439 veins), 97 (12%) angiographic defects were identified. Defects were repaired with either a minor adjustment of the graft (n = 22, 2.8%), with intraoperative open-chest PCI (unplanned hybrid, n = 48, 6%) or with traditional surgical revision (n = 27, 3.4%). Hybrid patients had clinical outcomes similar to standard CABG patients. Routine completion angiography detected 12% of grafts with important angiographic defects. One-stop hybrid coronary revascularization is reasonable, safe, and feasible. Combining the tools of the catheterization laboratory and operating room greatly enhances the options available to the surgeon and cardiologist for patients with complex coronary artery disease.

Methamphetamine, d-amphetamine and p-chloroamphetamine induced neurotoxicity differentially effect impulsive responding on the stop-signal task in rats

PubMed Central

Furlong, Teri M.; Leavitt, Lee S.; Keefe, Kristen A.; Son, Jong-Hyun

2016-01-01

Abused amphetamines, such as d-amphetamine (AMPH) and methamphetamine (METH), are highly addictive and destructive to health and productive lifestyles. The abuse of these drugs is associated with impulsive behavior, which is likely to contribute to addiction. The amphetamines also differentially damage dopamine (DA) and serotonin (5-HT) systems, which regulate impulsive behavior; therefore, exposure to these drugs may differentially alter impulsive behavior to effect the progression of addiction. We examined the impact of neurotoxicity induced by three amphetamines on impulsive action using a stop-signal task in rats. Animals were rewarded with a food pellet after lever pressing (i.e. a go trial), unless an auditory cue was presented and withholding lever press gained reward (i.e. a stop trial). Animals were trained on the task and then exposed to a neurotoxic regimen of either AMPH, p-chloroamphetamine (PCA), or METH. These regimens preferentially reduced DA transporter levels in striatum, 5-HT transporter levels in prefrontal cortex, or both, respectively. Assessment of performance on the stop-signal task beginning one week after the treatment revealed that AMPH produced a deficit in go-trial performance, whereas PCA did not alter performance on either trial type. In contrast, METH produced a deficit in stop-trial performance (i.e. impulsive action) but not go-trial performance. These findings suggest that the different neurotoxic consequences of substituted amphetamines are associated with different effects on inhibitory control over behavior. Thus, the course of addiction and maladaptive behavior resulting from exposure to these substances is likely to differ. PMID:26846719

Restraint and Cancellation: Multiple Inhibition Deficits in Attention Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Schachar, Russell; Logan, Gordon D.; Robaey, Philippe; Chen, Shirley; Ickowicz, Abel; Barr, Cathy

2007-01-01

We used variations of the stop signal task to study two components of motor response inhibition--the ability to withhold a strong response tendency (restraint) and the ability to cancel an ongoing action (cancellation)--in children with a diagnosis of attention deficit hyperactivity disorder (ADHD) and in non-ADHD controls of similar age (ages…

77 FR 46789 - Agency Request for Renewal of a Previously Approved Collection: Disclosure of Change-of-Gauge...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-06

... change planes at an intermediate stop. In addition to one-flight-to-one-flight change-of-gauge services... changes planes, but in addition, the single flight to or from the exchange point itself has multiple... valuable consumer benefits, they can be confusing and misleading unless consumers are given reasonable and...

75 FR 32773 - Auction of 218-219 MHz Service and Phase II 220 MHz Service Licenses Scheduled for December 7...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-06-09

... licenses included in Auction 89 using the Commission's standard simultaneous multiple-round auction format... sequential bidding rounds. The initial bidding schedule will be announced in a public notice to be released.... For Auction 89, the Bureau proposes to employ a simultaneous stopping rule approach. A simultaneous...

StopApp: Using the Behaviour Change Wheel to Develop an App to Increase Uptake and Attendance at NHS Stop Smoking Services.

PubMed

Fulton, Emily Anne; Brown, Katherine E; Kwah, Kayleigh L; Wild, Sue

2016-06-08

Smokers who attend NHS Stop Smoking Services (SSS) are four times more likely to stop smoking; however, uptake has been in decline. We report the development of an intervention designed to increase uptake of SSS, from a more motivated self-selected sample of smokers. In Phase 1 we collected data to explore the barriers and facilitators to people using SSS. In Phase 2, data from extant literature and Phase 1 were subject to behavioural analysis, as outlined by the Behaviour Change Wheel (BCW) framework. Relevant Behaviour Change Techniques (BCTs) were identified in order to address these, informing the content of the StopApp intervention. In Phase 3 we assessed the acceptability of the StopApp. Smokers and ex-smokers identified a number of barriers to attending SSS, including a lack of knowledge about what happens at SSS (Capability); the belief that SSS is not easy to access (Opportunity); that there would be 'scare tactics' or 'nagging'; and not knowing anyone who had been and successfully quit (Motivation). The 'StopApp' is in development and will link in with the commissioned SSS booking system. Examples of the content and functionality of the app are outlined. The next phase will involve a full trial to test effectiveness.

Do wire fences stop ground fires?

Treesearch

James L. Murphy; Harry E. Schimke

1965-01-01

Five meshes (1/8 to 1 inch) of 16-gauge steel wire fences, 3 feet high, were tested as possible ground fire barriers in 4 fuel types. The 1/8-inch mesh stopped only 1 test fire but retarded others; 1/4-inch mesh retarded some. The results suggest that further trials may be worthwhile.

The BMI1 inhibitor PTC-209 is a potential compound to halt cellular growth in biliary tract cancer cells

PubMed Central

Mayr, Christian; Wagner, Andrej; Loeffelberger, Magdalena; Bruckner, Daniela; Jakab, Martin; Berr, Frieder; Di Fazio, Pietro; Ocker, Matthias; Neureiter, Daniel; Pichler, Martin; Kiesslich, Tobias

2016-01-01

BMI1 is a core component of the polycomb repressive complex 1 (PRC1) and is up-regulated in biliary tract cancer (BTC), contributing to aggressive clinical features. In this study we investigated the cytotoxic effects of PTC-209, a recently developed inhibitor of BMI1, in BTC cells. PTC-209 reduced overall viability in BTC cell lines in a dose-dependent fashion (0.04 - 20 μM). Treatment with PTC-209 led to slightly enhanced caspase activity and stop of cell proliferation. Cell cycle analysis revealed that PTC-209 caused cell cycle arrest at the G1/S checkpoint. A comprehensive investigation of expression changes of cell cycle-related genes showed that PTC-209 caused significant down-regulation of cell cycle-promoting genes as well as of genes that contribute to DNA synthesis initiation and DNA repair, respectively. This was accompanied by significantly elevated mRNA levels of cell cycle inhibitors. In addition, PTC-209 reduced sphere formation and, in a cell line-dependent manner, aldehyde dehydrogease-1 positive cells. We conclude that PTC-209 might be a promising drug for future in vitro and in vivo studies in BTC. PMID:26623561

Does chronic warfarin cause increased blood loss and transfusion during lumbar spinal surgery?

PubMed

Young, Ernest Y; Ahmadinia, Kasra; Bajwa, Navkirat; Ahn, Nicholas U

2013-10-01

The use of oral anticoagulation therapy such as warfarin is projected to increase significantly as the population ages and the prevalence of cardiovascular disease increases. Current recommendations state that warfarin be discontinued before surgery and the international normalized ratio (INR) normalized. To determine if stopping warfarin 7 days before surgery and correcting INR had any effect on intraoperative blood loss or the requirements for blood product transfusion. This was a retrospective cohort study in a high-volume tertiary care center. Sample comprised 263 consecutive patients who underwent elective lumbar spinal surgery. The outcome measures were intraoperative blood loss, intraoperative blood transfusion, postoperative blood transfusion, and the number of blood products transfused. The records of patients undergoing elective spinal surgery were analyzed for patient demographic data, comorbidities, coagulation panel laboratory findings, operative characteristics, blood loss, and blood transfusion requirements. These included patients undergoing full laminectomies with or without posterolateral fusion and instrumentation. Patients on warfarin were analyzed for the mean dosage of warfarin and underlying pathology that required anticoagulation. All patients on warfarin had their anticoagulation therapy stopped 7 days before surgery and their INR checked preoperatively to confirm normalization. Both univariate and multiple linear regression analyses were performed. The patients on warfarin had a mean intraoperative blood loss of 839 mL compared with 441 mL for patients not on warfarin (p<.01). Multiple regression analysis determined that warfarin and number of spinal levels decompressed/fused/instrumented were predictors for increased blood loss (R(2)=0.37). Patients on warfarin also had increased postoperative blood transfusions (23.1% compared with 7.4%, p=.04). There was no significant difference between groups in terms of intraoperative blood transfusion or number of units transfused. Patients on chronic anticoagulation therapy with warfarin who have their therapy stopped 7 days before surgery and have their INR normalized still demonstrated increased intraoperative blood loss and requirement for postoperative transfusion. Surgeons should be aware of the increased propensity of these patients to bleed despite adherence to protocols and should attempt to mitigate this risk. Copyright © 2013 Elsevier Inc. All rights reserved.

Visualization of Global Disease Burden for the Optimization of Patient Management and Treatment.

PubMed

Schlee, Winfried; Hall, Deborah A; Edvall, Niklas K; Langguth, Berthold; Canlon, Barbara; Cederroth, Christopher R

2017-01-01

The assessment and treatment of complex disorders is challenged by the multiple domains and instruments used to evaluate clinical outcome. With the large number of assessment tools typically used in complex disorders comes the challenge of obtaining an integrative view of disease status to further evaluate treatment outcome both at the individual level and at the group level. Radar plots appear as an attractive visual tool to display multivariate data on a two-dimensional graphical illustration. Here, we describe the use of radar plots for the visualization of disease characteristics applied in the context of tinnitus, a complex and heterogeneous condition, the treatment of which has shown mixed success. Data from two different cohorts, the Swedish Tinnitus Outreach Project (STOP) and the Tinnitus Research Initiative (TRI) database, were used. STOP is a population-based cohort where cross-sectional data from 1,223 non-tinnitus and 933 tinnitus subjects were analyzed. By contrast, the TRI contained data from 571 patients who underwent various treatments and whose Clinical Global Impression (CGI) score was accessible to infer treatment outcome. In the latter, 34,560 permutations were tested to evaluate whether a particular ordering of the instruments could reflect better the treatment outcome measured with the CGI. Radar plots confirmed that tinnitus subtypes such as occasional and chronic tinnitus from the STOP cohort could be strikingly different, and helped appreciate a gender bias in tinnitus severity. Radar plots with greater surface areas were consistent with greater burden, and enabled a rapid appreciation of the global distress associated with tinnitus in patients categorized according to tinnitus severity. Permutations in the arrangement of instruments allowed to identify a configuration with minimal variance and maximized surface difference between CGI groups from the TRI database, thus affording a means of optimally evaluating the outcomes in individual patients. We anticipate such a tool to become a starting point for more sophisticated measures in clinical outcomes, applicable not only in the context of tinnitus but also in other complex diseases where the integration of multiple variables is needed for a comprehensive evaluation of treatment response.

Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7.

PubMed

Rai, Ashutosh Kumar; Dubey, Ashutosh Prakash; Kumar, Santosh; Dutta, Debashis; Mishra, Mukti Nath; Singh, Bhupendra Narain; Tripathi, Anil Kumar

2016-11-01

Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the regulation of a gene encoding geranylgeranyl pyrophosphate synthase (crtE2) by RpoE1→RpoH2→CrtE2 and RpoE2→RpoH1→CrtE2 cascades in A. brasilense It also provides an insight into existence of an additional cascade or cascades regulating expression of another paralog of crtE. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Carotenoid Biosynthetic Pathways Are Regulated by a Network of Multiple Cascades of Alternative Sigma Factors in Azospirillum brasilense Sp7

PubMed Central

Rai, Ashutosh Kumar; Dubey, Ashutosh Prakash; Kumar, Santosh; Dutta, Debashis; Mishra, Mukti Nath; Singh, Bhupendra Narain

2016-01-01

ABSTRACT Carotenoids constitute an important component of the defense system against photooxidative stress in bacteria. In Azospirillum brasilense Sp7, a nonphotosynthetic rhizobacterium, carotenoid synthesis is controlled by a pair of extracytoplasmic function sigma factors (RpoEs) and their cognate zinc-binding anti-sigma factors (ChrRs). Its genome harbors two copies of the gene encoding geranylgeranyl pyrophosphate synthase (CrtE), the first critical step in the carotenoid biosynthetic pathway in bacteria. Inactivation of each of two crtE paralogs found in A. brasilense caused reduction in carotenoid content, suggesting their involvement in carotenoid synthesis. However, the effect of crtE1 deletion was more pronounced than that of crtE2 deletion. Out of the five paralogs of rpoH in A. brasilense, overexpression of rpoH1 and rpoH2 enhanced carotenoid synthesis. Promoters of crtE2 and rpoH2 were found to be dependent on RpoH2 and RpoE1, respectively. Using a two-plasmid system in Escherichia coli, we have shown that the crtE2 gene of A. brasilense Sp7 is regulated by two cascades of sigma factors: one consisting of RpoE1and RpoH2 and the other consisting of RpoE2 and RpoH1. In addition, expression of crtE1 was upregulated indirectly by RpoE1 and RpoE2. This study shows, for the first time in any carotenoid-producing bacterium, that the regulation of carotenoid biosynthetic pathway involves a network of multiple cascades of alternative sigma factors. IMPORTANCE Carotenoids play a very important role in coping with photooxidative stress in prokaryotes and eukaryotes. Although extracytoplasmic function (ECF) sigma factors are known to directly regulate the expression of carotenoid biosynthetic genes in bacteria, regulation of carotenoid biosynthesis by one or multiple cascades of sigma factors had not been reported. This study provides the first evidence of the involvement of multiple cascades of sigma factors in the regulation of carotenoid synthesis in any bacterium by showing the regulation of a gene encoding geranylgeranyl pyrophosphate synthase (crtE2) by RpoE1→RpoH2→CrtE2 and RpoE2→RpoH1→CrtE2 cascades in A. brasilense. It also provides an insight into existence of an additional cascade or cascades regulating expression of another paralog of crtE. PMID:27551017

SU-G-TeP1-02: Analytical Stopping Power and Range Parameterization for Therapeutic Energy Intervals

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

Donahue, W; Newhauser, W; Mary Bird Perkins Cancer Center, Baton Rouge, LA

Purpose: To develop a simple, analytic parameterization of stopping power and range, which covers a wide energy interval and is applicable to many species of projectile ions and target materials, with less than 15% disagreement in linear stopping power and 1 mm in range. Methods: The new parameterization was required to be analytically integrable from stopping power to range, and continuous across the range interval of 1 µm to 50 cm. The model parameters were determined from stopping power and range data for hydrogen, carbon, iron, and uranium ions incident on water, carbon, aluminum, lead and copper. Stopping power andmore » range data was taken from SRIM. A stochastic minimization algorithm was used to find model parameters, with 10 data points per energy decade. Additionally, fitting was performed with 2 and 26 data points per energy decade to test the model’s robustness to sparse Results: 6 free parameters were sufficient to cover the therapeutic energy range for each projectile ion species (e.g. 1 keV – 300 MeV for protons). The model agrees with stopping power and range data well, with less than 9% relative stopping power difference and 0.5 mm difference in range. As few as, 4 bins per decade were required to achieve comparable fitting results to the full data set. Conclusion: This study successfully demonstrated that a simple analytic function can be used to fit the entire energy interval of therapeutic ion beams of hydrogen and heavier elements. Advantages of this model were the small number (6) of free parameters, and that the model calculates both stopping power and range. Applications of this model include GPU-based dose calculation algorithms and Monte Carlo simulations, where available memory is limited. This work was supported in part by a research agreement between United States Naval Academy and Louisiana State University: Contract No N00189-13-P-0786. In addition, this work was accepted for presentation at the American Nuclear Society Annual Meeting 2016.« less

Transcription profiling suggests that mitochondrial topoisomerase IB acts as a topological barrier and regulator of mitochondrial DNA transcription.

PubMed

Dalla Rosa, Ilaria; Zhang, Hongliang; Khiati, Salim; Wu, Xiaolin; Pommier, Yves

2017-12-08

Mitochondrial DNA (mtDNA) is essential for cell viability because it encodes subunits of the respiratory chain complexes. Mitochondrial topoisomerase IB (TOP1MT) facilitates mtDNA replication by removing DNA topological tensions produced during mtDNA transcription, but it appears to be dispensable. To test whether cells lacking TOP1MT have aberrant mtDNA transcription, we performed mitochondrial transcriptome profiling. To that end, we designed and implemented a customized tiling array, which enabled genome-wide, strand-specific, and simultaneous detection of all mitochondrial transcripts. Our technique revealed that Top1mt KO mouse cells process the mitochondrial transcripts normally but that protein-coding mitochondrial transcripts are elevated. Moreover, we found discrete long noncoding RNAs produced by H-strand transcription and encompassing the noncoding regulatory region of mtDNA in human and murine cells and tissues. Of note, these noncoding RNAs were strongly up-regulated in the absence of TOP1MT. In contrast, 7S DNA, produced by mtDNA replication, was reduced in the Top1mt KO cells. We propose that the long noncoding RNA species in the D-loop region are generated by the extension of H-strand transcripts beyond their canonical stop site and that TOP1MT acts as a topological barrier and regulator for mtDNA transcription and D-loop formation.

Mutants of the Paf1 Complex Alter Phenotypic Expression of the Yeast Prion [PSI+

PubMed Central

Strawn, Lisa A.; Lin, Changyi A.; Tank, Elizabeth M.H.; Osman, Morwan M.; Simpson, Sarah A.

2009-01-01

The yeast [PSI+] prion is an epigenetic modifier of translation termination fidelity that causes nonsense suppression. The prion [PSI+] forms when the translation termination factor Sup35p adopts a self-propagating conformation. The presence of the [PSI+] prion modulates survivability in a variety of growth conditions. Nonsense suppression is essential for many [PSI+]-mediated phenotypes, but many do not appear to be due to read-through of a single stop codon, but instead are multigenic traits. We hypothesized that other global mechanisms act in concert with [PSI+] to influence [PSI+]-mediated phenotypes. We have identified one such global regulator, the Paf1 complex (Paf1C). Paf1C is conserved in eukaryotes and has been implicated in several aspects of transcriptional and posttranscriptional regulation. Mutations in Ctr9p and other Paf1C components reduced [PSI+]-mediated nonsense suppression. The CTR9 deletion also alters nonsense suppression afforded by other genetic mutations but not always to the same extent as the effects on [PSI+]-mediated read-through. Our data suggest that the Paf1 complex influences mRNA translatability but not solely through changes in transcript stability or abundance. Finally, we demonstrate that the CTR9 deletion alters several [PSI+]-dependent phenotypes. This provides one example of how [PSI+] and genetic modifiers can interact to uncover and regulate phenotypic variability. PMID:19225160

Analysis of Internet information on the controversial X-Stop device.

PubMed

Anderson, Joshua T; Sullivan, T Barrett; Ahn, Uri M; Ahn, Nicholas U

2014-10-01

The Internet is frequently used by patients to aid in medical decision making. Multiple studies display the Internet's ineffectiveness in presenting high-quality information regarding surgical procedures and devices. With recent reports of unacceptably high complication rates and poor outcomes with the X-Stop device, it is important that online information is comprehensive and accurate. This study is the first to examine Internet information on the controversial X-Stop. To determine how accurately public information over the Internet portrays the existing primary literature on the X-Stop, how extensively the X-Stop is characterized online, and how patient decision making could foreseeably be affected. This cross-sectional study analyzed publicly available Internet information, including videos on the web site YouTube regarding the X-Stop device. No patients were involved in this study. No specific outcome measures were used. Search engines Google, Yahoo, and Bing were used to identify 105 web sites providing information on the X-Stop. Videos on the web site YouTube were included. Web sites were categorized based on the authorship. Each site was analyzed for the provision of appropriate patient inclusion and exclusion criteria, surgical and nonsurgical treatment alternatives, purported benefits, common complications, peer-reviewed literature citations, and descriptions/diagrams of the procedure. Data were evaluated for each authorship subgroup and the entire group of sites. Forty-three percent of sites were authored by a private medical group, 4% by an academic medical group, 16% by an insurance company, 9% by a biomedical industry, 10% by news sources, and 19% by other. Thirty-one percent of web sites and 11% of sites authored by private medical groups contained references to peer-reviewed literature. Fifty-six percent of web sites reported patient inclusion criteria, whereas 33% reported exclusion criteria. Benefits and complications were reported within 91% and 23% of sites, respectively. Surgical and nonsurgical treatment options were mentioned within 59% and 61% of web sites, respectively. Our study demonstrates the Internet's ineffectiveness in reporting quality information on the X-Stop. Information was often incomplete and potentially misleading. Significant controversy exists within primary literature regarding the safety and efficacy of the X-Stop. Yet, publicly available Internet information largely provided misinformation and did not reflect any such controversy. This raises the concern that such information lends itself more toward patient recruitment than patient education. Medical professionals need to know how this may affect their patients' decision making. Copyright © 2014 Elsevier Inc. All rights reserved.

Comprehensive single cell-resolution analysis of the role of chromatin regulators in early C. elegans embryogenesis.

PubMed

Krüger, Angela V; Jelier, Rob; Dzyubachyk, Oleh; Zimmerman, Timo; Meijering, Erik; Lehner, Ben

2015-02-15

Chromatin regulators are widely expressed proteins with diverse roles in gene expression, nuclear organization, cell cycle regulation, pluripotency, physiology and development, and are frequently mutated in human diseases such as cancer. Their inhibition often results in pleiotropic effects that are difficult to study using conventional approaches. We have developed a semi-automated nuclear tracking algorithm to quantify the divisions, movements and positions of all nuclei during the early development of Caenorhabditis elegans and have used it to systematically study the effects of inhibiting chromatin regulators. The resulting high dimensional datasets revealed that inhibition of multiple regulators, including F55A3.3 (encoding FACT subunit SUPT16H), lin-53 (RBBP4/7), rba-1 (RBBP4/7), set-16 (MLL2/3), hda-1 (HDAC1/2), swsn-7 (ARID2), and let-526 (ARID1A/1B) affected cell cycle progression and caused chromosome segregation defects. In contrast, inhibition of cir-1 (CIR1) accelerated cell division timing in specific cells of the AB lineage. The inhibition of RNA polymerase II also accelerated these division timings, suggesting that normal gene expression is required to delay cell cycle progression in multiple lineages in the early embryo. Quantitative analyses of the dataset suggested the existence of at least two functionally distinct SWI/SNF chromatin remodeling complex activities in the early embryo, and identified a redundant requirement for the egl-27 and lin-40 MTA orthologs in the development of endoderm and mesoderm lineages. Moreover, our dataset also revealed a characteristic rearrangement of chromatin to the nuclear periphery upon the inhibition of multiple general regulators of gene expression. Our systematic, comprehensive and quantitative datasets illustrate the power of single cell-resolution quantitative tracking and high dimensional phenotyping to investigate gene function. Furthermore, the results provide an overview of the functions of essential chromatin regulators during the early development of an animal. Copyright © 2014 Elsevier Inc. All rights reserved.

77 FR 16795 - Approval and Promulgation of Implementation Plans and Operating Permits Program; Commonwealth of...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-22

.... SUMMARY: EPA is proposing to approve revisions to the Puerto Rico Regulations for the Control of Atmospheric Pollution, submitted to EPA by the Puerto Rico Environmental Quality Board (PREQB) on July 13... de Leon Avenue, Stop 22, Santurce, Puerto Rico 00909. FOR FURTHER INFORMATION CONTACT: Kirk J. Wieber...

78 FR 44878 - Turtles Intrastate and Interstate Requirements

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-25

... turtle eggs and live turtles with a carapace length of less than 4 inches to remove procedures for... eggs and turtles with a carapace length of less than 4 inches to stop the spread of turtle-associated salmonellosis in humans, especially in young children. The regulations provide that viable turtle eggs and live...

The Potato leafroll virus structural proteins manipulate overlapping, yet distinct protein interaction networks during infection

USDA-ARS?s Scientific Manuscript database

Potato leafroll virus (PLRV) produces a readthrough protein (RTP) via translational readthrough of the coat protein amber stop codon. The RTP functions as a structural component of the virion and as a non-incorporated protein in concert with numerous insect and plant proteins to regulate virus movem...

49 CFR 392.10 - Railroad grade crossings; stopping required.

Code of Federal Regulations, 2013 CFR

2013-10-01

... REGULATIONS DRIVING OF COMMERCIAL MOTOR VEHICLES Driving of Commercial Motor Vehicles § 392.10 Railroad grade..., the driver may drive the commercial motor vehicle across the tracks in a gear that permits the... purposes, within a business district, as defined in § 390.5 of this chapter. (2) A railroad grade crossing...

49 CFR 392.10 - Railroad grade crossings; stopping required.

Code of Federal Regulations, 2012 CFR

2012-10-01

... REGULATIONS DRIVING OF COMMERCIAL MOTOR VEHICLES Driving of Commercial Motor Vehicles § 392.10 Railroad grade..., the driver may drive the commercial motor vehicle across the tracks in a gear that permits the... purposes, within a business district, as defined in § 390.5 of this chapter. (2) A railroad grade crossing...

78 FR 72817 - Drawbridge Operation Regulation; Gulf Intracoastal Waterway, Near Moss Lake, LA

Federal Register 2010, 2011, 2012, 2013, 2014

2013-12-04

... temporarily closed to navigation during daylight for ten consecutive hours, Monday through Thursday for three weeks. DATES: This deviation is effective without actual notice from December 4, 2013 until December 19... in accordance with this subpart. The draw bridge must return to operation when the work has stopped...

78 FR 22043 - Rural Energy for America Program-Grants and Guaranteed Loans

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-12

... Chief, Regulations and Paperwork Management Branch, U.S. Department of Agriculture, STOP 0742, 1400... Paperwork Management Branch, U.S. Department of Agriculture, 300 7th Street SW., 7th Floor, Washington, DC... has been determined to be economically significant by the Office of Management and Budget. The EO...

77 FR 25366 - Underground Storage Tank Program: Approved State Program for the State of Oregon

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-30

... the online instructions for submitting comments. Email: griffith[email protected] . Mail: Katherine Griffith, U. S. Environmental Protection Agency, Region 10, 1200 Sixth Avenue, Suite 900, Mail Stop: OCE... electronically in http://www.regulations.gov or in hard copy. FOR FURTHER INFORMATION CONTACT: Katherine Griffith...

40 CFR 80.1340 - How does a refiner obtain approval as a small refiner?

Code of Federal Regulations, 2014 CFR

2014-07-01

... (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Small Refiner... for small refiner status must be sent to: Attn: MSAT2 Benzene, Mail Stop 6406J, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. For commercial delivery: MSAT2 Benzene...

40 CFR 80.1340 - How does a refiner obtain approval as a small refiner?

Code of Federal Regulations, 2011 CFR

2011-07-01

... (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Small Refiner... for small refiner status must be sent to: Attn: MSAT2 Benzene, Mail Stop 6406J, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. For commercial delivery: MSAT2 Benzene...

40 CFR 80.1340 - How does a refiner obtain approval as a small refiner?

Code of Federal Regulations, 2013 CFR

2013-07-01

... (CONTINUED) AIR PROGRAMS (CONTINUED) REGULATION OF FUELS AND FUEL ADDITIVES Gasoline Benzene Small Refiner... for small refiner status must be sent to: Attn: MSAT2 Benzene, Mail Stop 6406J, U.S. Environmental Protection Agency, 1200 Pennsylvania Ave., NW., Washington, DC 20460. For commercial delivery: MSAT2 Benzene...

A banana NAC transcription factor (MusaSNAC1) impart drought tolerance by modulating stomatal closure and H2O2 content.

PubMed

Negi, Sanjana; Tak, Himanshu; Ganapathi, T R

2018-03-01

MusaSNAC1 function in H 2 O 2 mediated stomatal closure and promote drought tolerance by directly binding to CGT[A/G] motif in regulatory region of multiple stress-related genes. Drought is a abiotic stress-condition, causing reduced plant growth and diminished crop yield. Guard cells of the stomata control photosynthesis and transpiration by regulating CO 2 exchange and water loss, thus affecting growth and crop yield. Roles of NAC (NAM, ATAF1/2 and CUC2) protein in regulation of stress-conditions has been well documented however, their control over stomatal aperture is largely unknown. In this study we report a banana NAC protein, MusaSNAC1 which induced stomatal closure by elevating H 2 O 2 content in guard cells during drought stress. Overexpression of MusaSNAC1 in banana resulted in higher number of stomata closure causing reduced water loss and thus elevated drought-tolerance. During drought, expression of GUS (β-glucuronidase) under P MusaSNAC1 was remarkably elevated in guard cells of stomata which correlated with its function as a transcription factor regulating stomatal aperture closing. MusaSNAC1 is a transcriptional activator belonging to SNAC subgroup and its 5'-upstream region contain multiple Dof1 elements as well as stress-associated cis-elements. Moreover, MusaSNAC1 also regulate multiple stress-related genes by binding to core site of NAC-proteins CGT[A/G] in their 5'-upstream region. Results indicated an interesting mechanism of drought tolerance through stomatal closure by H 2 O 2 generation in guard cells, regulated by a NAC-protein in banana.

Spurious claims for health-care products: an experimental approach to evaluating current UK legislation and its implementation.

PubMed

Rose, Leslie B; Posadzki, Paul; Ernst, Edzard

2012-01-01

The lay media, and especially the Internet, contain many misleading claims for health products which have previously been inadequately regulated by consumer law. This was an experimental interventional survey within a consumer health-care setting. Three health products were chosen on the basis of being widely available on the UK market and having no available evidence of effectiveness. Twelve volunteers submitted 39 complaints to Consumer Direct (UK portal for the regulator Trading Standards) regarding false health claims, and 36 complaints were followed up for a maximum of 4.8 months. The mean time from submission of complaints to Consumer Direct to acknowledgement by the relevant Trading Standards office was 13 days. There were no responses from Trading Standards for 22% of complaints. At the end of the study one supplier had amended their website following Trading Standards advice, but did not stop all health claims. Another stopped advertising their product on the Internet and the third continued the health claims unchanged. EU directive 2005/29/EC is largely ineffective in preventing misleading health claims for consumer products in the UK.

The control of translational accuracy is a determinant of healthy ageing in yeast

PubMed Central

Leadsham, Jane E.; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S.; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F.; Gourlay, Campbell W.

2017-01-01

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing. PMID:28100667

The control of translational accuracy is a determinant of healthy ageing in yeast.

PubMed

von der Haar, Tobias; Leadsham, Jane E; Sauvadet, Aimie; Tarrant, Daniel; Adam, Ilectra S; Saromi, Kofo; Laun, Peter; Rinnerthaler, Mark; Breitenbach-Koller, Hannelore; Breitenbach, Michael; Tuite, Mick F; Gourlay, Campbell W

2017-01-01

Life requires the maintenance of molecular function in the face of stochastic processes that tend to adversely affect macromolecular integrity. This is particularly relevant during ageing, as many cellular functions decline with age, including growth, mitochondrial function and energy metabolism. Protein synthesis must deliver functional proteins at all times, implying that the effects of protein synthesis errors like amino acid misincorporation and stop-codon read-through must be minimized during ageing. Here we show that loss of translational accuracy accelerates the loss of viability in stationary phase yeast. Since reduced translational accuracy also reduces the folding competence of at least some proteins, we hypothesize that negative interactions between translational errors and age-related protein damage together overwhelm the cellular chaperone network. We further show that multiple cellular signalling networks control basal error rates in yeast cells, including a ROS signal controlled by mitochondrial activity, and the Ras pathway. Together, our findings indicate that signalling pathways regulating growth, protein homeostasis and energy metabolism may jointly safeguard accurate protein synthesis during healthy ageing. © 2017 The Authors.

A recognizable type of syndromic short stature with arthrogryposis caused by bi-allelic SEMA3A loss-of-function variants.

PubMed

Baumann, M; Steichen-Gersdorf, E; Krabichler, B; Müller, T; Janecke, A R

2017-07-01

The semaphorins constitute a large family of secreted and membrane-associated proteins that regulate many developmental processes, including neural circuit assembly, bone formation and angiogenesis. Recently, bi-allelic loss-of-function variants in SEMA3A (semaphorin 3A) were identified in a single patient with a particular pattern of multiple congenital anomalies (MCA). Using homozygosity mapping combined with exome sequencing, we identified a homozygous SEMA3A variant causing a premature stop codon in an 8 year old boy with the same pattern of MCA. The phenotype of these patients is characterized by postnatal short stature, skeletal anomalies of the thorax, a minor congenital heart or vascular defect, camptodactyly, micropenis, and variable additional anomalies. Motor development is delayed in both patients, and intellectual development is delayed in one patient. Our observation of a second case supports the notion that bi-allelic mutations in SEMA3A cause an autosomal recessive type of syndromic short stature. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Internet-based intervention for smoking cessation (StopAdvisor) in people with low and high socioeconomic status: a randomised controlled trial.

PubMed

Brown, Jamie; Michie, Susan; Geraghty, Adam W A; Yardley, Lucy; Gardner, Benjamin; Shahab, Lion; Stapleton, John A; West, Robert

2014-12-01

Internet-based interventions for smoking cessation could help millions of people stop smoking at very low unit costs; however, long-term biochemically verified evidence is scarce and such interventions might be less effective for smokers with low socioeconomic status than for those with high status because of lower online literacy to engage with websites. We aimed to assess a new interactive internet-based intervention (StopAdvisor) for smoking cessation that was designed with particular attention directed to people with low socioeconomic status. We did this online randomised controlled trial between Dec 6, 2011, and Oct 11, 2013, in the UK. Participants aged 18 years and older who smoked every day were randomly assigned (1:1) to receive treatment with StopAdvisor or an information-only website. Randomisation was automated with an unseen random number function embedded in the website to establish which treatment was revealed after the online baseline assessment. Recruitment continued until the required sample size had been achieved from both high and low socioeconomic status subpopulations. Participants, and researchers who obtained data and did laboratory analyses, were masked to treatment allocation. The primary outcome was 6 month sustained, biochemically verified abstinence. The main secondary outcome was 6 month, 7 day biochemically verified point prevalence. Analysis was by intention to treat. Homogeneity of intervention effect across the socioeconomic subsamples was first assessed to establish whether overall or separate subsample analyses were appropriate. The study is registered as an International Standard Randomised Controlled Trial, number ISRCTN99820519. We randomly assigned 4613 participants to the StopAdvisor group (n=2321) or the control group (n=2292); 2142 participants were of low socioeconomic status and 2471 participants were of high status. The overall rate of smoking cessation was similar between participants in the StopAdvisor and control groups for the primary (237 [10%] vs 220 [10%] participants; relative risk [RR] 1·06, 95% CI 0·89-1·27; p=0·49) and the secondary (358 [15%] vs 332 [15%] participants; 1·06, 0·93-1·22; p=0·37) outcomes; however, the intervention effect differed across socioeconomic status subsamples (1·44, 0·99-2·09; p=0·0562 and 1·37, 1·02-1·84; p=0·0360, respectively). StopAdvisor helped participants with low socioeconomic status stop smoking compared with the information-only website (primary outcome: 90 [8%] of 1088 vs 64 [6%] of 1054 participants; RR 1·36, 95% CI 1·00-1·86; p=0·0499; secondary outcome: 136 [13%] vs 100 [10%] participants; 1·32, 1·03-1·68, p=0·0267), but did not improve cessation rates in those with high socioeconomic status (147 [12%] of 1233 vs 156 [13%] of 1238 participants; 0·95, 0·77-1·17; p=0·61 and 222 [18%] vs 232 [19%] participants; 0·96, 0·81-1·13, p=0·64, respectively). StopAdvisor was more effective than an information-only website in smokers of low, but not high, socioeconomic status. StopAdvisor could be implemented easily and made freely available, which would probably improve the success rates of smokers with low socioeconomic status who are seeking online support. National Prevention Research Initiative. Copyright © 2014 Brown et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.

Emerging roles of protein kinase CK2 in abscisic acid signaling.

PubMed

Vilela, Belmiro; Pagès, Montserrat; Riera, Marta

2015-01-01

The phytohormone abscisic acid (ABA) regulates many aspects of plant growth and development as well as responses to multiple stresses. Post-translational modifications such as phosphorylation or ubiquitination have pivotal roles in the regulation of ABA signaling. In addition to the positive regulator sucrose non-fermenting-1 related protein kinase 2 (SnRK2), the relevance of the role of other protein kinases, such as CK2, has been recently highlighted. We have recently established that CK2 phosphorylates the maize ortholog of open stomata 1 OST1, ZmOST1, suggesting a role of CK2 phosphorylation in the control of ZmOST1 protein degradation (Vilela et al., 2015). CK2 is a pleiotropic enzyme involved in multiple developmental and stress-responsive pathways. This review summarizes recent advances that taken together suggest a prominent role of protein kinase CK2 in ABA signaling and related processes.

Physiological markers of motor inhibition during human behavior

PubMed Central

Duque, Julie; Greenhouse, Ian; Labruna, Ludovica; Ivry, Richard B.

2017-01-01

Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another. PMID:28341235

Malignant insulinoma with hepatic and pulmonary metastases associated with primary hyperparathyroidism. Case report and review of the literature

PubMed Central

A., Albu; A., Zirnea; O., Georgescu; D., Terzea; D., Jinga; S., Fica

2008-01-01

Malignant insulinomas are rare tumors (10% of insulinomas) that often present as multicentric macro nodules with multiple liver metastases before diagnosis. We report the case of a 55 year old female with a medical history of severe hypoglycemic attacks for two months. Blood tests showed a decreased value of glycemia (30mg/dl) associated with increased insulin level (16μU/ml) and an increased glycemia/insulinemia ratio of 1.87 supporting the diagnosis of insulinoma. Abdominal CT showed a 1.5 cm mass localized in the head of the pancreas with disseminated hepatic tumors, confirmed as neuroendocrine metastases by biopsy (which proved the presence of a malignant insulinoma). Primary hyperparathyroidism was diagnosed based on mild elevation of calcium (10.4 mg/dl) associated with a high level of PTH (71,2 pg/ml). The coexistence of the two endocrinopathies suggested the presence of type 1 multiple endocrine neoplasia (MEN 1). Because of multiple hepatic masses and liver function impairment, surgery and hepatic artery embolization were not performed. Somatostatin analog therapy was started with symptomatic control in the beginning, but rapid loss of beneficial effect. Finally, systemic chemotherapy with doxorubicin was administered, but the disease was progressive and after three months we decided to stop it. The patient died at home after one month, probably in hypoglycemic coma. PMID:20108468

Children's probability intuitions: understanding the expected value of complex gambles.

PubMed

Schlottmann, A

2001-01-01

Two experiments used Information Integration Theory to study how children judge expected value of complex gambles in which alternative outcomes have different prizes. Six-year-olds, 9-year-olds and adults (N = 73 in Study 1, N = 28 in Study 2) saw chance games that involved shaking a marble in a bicolored tube. One prize was won if the marble stopped on blue, another if it stopped on yellow. Children judged how happy a puppet playing the game would be, with the prizes and probability of the blue and yellow outcomes varied factorially. Three main results appeared in both studies: First, participants in all age groups used the normatively prescribed multiplication rule for integrating probability and value of each individual outcome--a striking finding because multiplicative reasoning does not usually appear before 8 years of age in other domains. Second, all age groups based judgment of overall expected value meaningfully on both alternative outcomes, but there were individual differences--many participants deviated from the normative addition rule, showing risk seeking and risk averse patterns of judgment similar to the risk attitudes often found with adults. Third, even the youngest children took probability to be an abstract rather than physical property of the game. Overall, in contrast to the traditional view, the present results demonstrate functional understanding of probability and expected value in children as young as 5 or 6. These results contribute to the growing evidence on children's intuitive reasoning competence. This intuition can, on the one hand, support surprisingly precocious performance in young children, but it may also contribute to the biases evident in adults' judgment and decision.

Neutron multiplicity counting: Confidence intervals for reconstruction parameters

DOE PAGES

Verbeke, Jerome M.

2016-03-09

From nuclear materials accountability to homeland security, the need for improved nuclear material detection, assay, and authentication has grown over the past decades. Starting in the 1940s, neutron multiplicity counting techniques have enabled quantitative evaluation of masses and multiplications of fissile materials. In this paper, we propose a new method to compute uncertainties on these parameters using a model-based sequential Bayesian processor, resulting in credible regions in the fissile material mass and multiplication space. These uncertainties will enable us to evaluate quantitatively proposed improvements to the theoretical fission chain model. Additionally, because the processor can calculate uncertainties in real time,more » it is a useful tool in applications such as portal monitoring: monitoring can stop as soon as a preset confidence of non-threat is reached.« less

46 CFR 32.56-45 - Draft stops-T/ALL.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 1 2013-10-01 2013-10-01 false Draft stops-T/ALL. 32.56-45 Section 32.56-45 Shipping....56-45 Draft stops—T/ALL. (a) Where ceilings or linings are fitted in accommodation, service, or... if draft stops of “B” Class construction are fitted between the ceiling or lining and the deck or...

46 CFR 32.56-45 - Draft stops-T/ALL.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 1 2014-10-01 2014-10-01 false Draft stops-T/ALL. 32.56-45 Section 32.56-45 Shipping....56-45 Draft stops—T/ALL. (a) Where ceilings or linings are fitted in accommodation, service, or... if draft stops of “B” Class construction are fitted between the ceiling or lining and the deck or...

46 CFR 32.56-45 - Draft stops-T/ALL.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 1 2012-10-01 2012-10-01 false Draft stops-T/ALL. 32.56-45 Section 32.56-45 Shipping....56-45 Draft stops—T/ALL. (a) Where ceilings or linings are fitted in accommodation, service, or... if draft stops of “B” Class construction are fitted between the ceiling or lining and the deck or...

Electron and Positron Stopping Powers of Materials

National Institute of Standards and Technology Data Gateway

SRD 7 NIST Electron and Positron Stopping Powers of Materials (PC database for purchase)   The EPSTAR database provides rapid calculations of stopping powers (collisional, radiative, and total), CSDA ranges, radiation yields and density effect corrections for incident electrons or positrons with kinetic energies from 1 keV to 10 GeV, and for any chemically defined target material.

Monotop signature from the supersymmetric t t¯ H channel

NASA Astrophysics Data System (ADS)

Gonçalves, Dorival; Sakurai, Kazuki; Takeuchi, Michihisa

2016-10-01

We point out that a distinctive monotop signature is present in natural supersymmetry scenarios when a scalar top quark and Higgsinos are almost mass degenerate. This signature originates from a supersymmetric counterpart of the t t ¯H process, i.e. p p →t ˜t h ˜. Unlike monojet signatures exploiting initial state radiation, this channel can be regarded as a clear signature of a light stop and Higgsinos, allowing a direct probe of the stop and neutralino sectors. The production rate of this channel largely depends on the up-type Higgsino components in the neutralinos while the stop sector is sensitive to angular distributions of the top-quark's decay products. We develop an optimal search strategy to capture the supersymmetric t t ¯ H process and find that a high luminosity LHC can probe the stop and Higgsino sectors with mt˜1≲380 GeV and mt˜1-mχ˜1 0≲mW . Additionally, we propose a kinematic variable with which one can measure the stop mixing in this channel.

Evidence That Up-Regulation of MicroRNA-29 Contributes to Postnatal Body Growth Deceleration

PubMed Central

Kamran, Fariha; Andrade, Anenisia C.; Nella, Aikaterini A.; Clokie, Samuel J.; Rezvani, Geoffrey; Nilsson, Ola; Baron, Jeffrey

2015-01-01

Body growth is rapid in infancy but subsequently slows and eventually ceases due to a progressive decline in cell proliferation that occurs simultaneously in multiple organs. We previously showed that this decline in proliferation is driven in part by postnatal down-regulation of a large set of growth-promoting genes in multiple organs. We hypothesized that this growth-limiting genetic program is orchestrated by microRNAs (miRNAs). Bioinformatic analysis identified target sequences of the miR-29 family of miRNAs to be overrepresented in age–down-regulated genes. Concomitantly, expression microarray analysis in mouse kidney and lung showed that all members of the miR-29 family, miR-29a, -b, and -c, were strongly up-regulated from 1 to 6 weeks of age. Real-time PCR confirmed that miR-29a, -b, and -c were up-regulated with age in liver, kidney, lung, and heart, and their expression levels were higher in hepatocytes isolated from 5-week-old mice than in hepatocytes from embryonic mouse liver at embryonic day 16.5. We next focused on 3 predicted miR-29 target genes (Igf1, Imp1, and Mest), all of which are growth-promoting. A 3′-untranslated region containing the predicted target sequences from each gene was placed individually in a luciferase reporter construct. Transfection of miR-29 mimics suppressed luciferase gene activity for all 3 genes, and this suppression was diminished by mutating the target sequences, suggesting that these genes are indeed regulated by miR-29. Taken together, the findings suggest that up-regulation of miR-29 during juvenile life drives the down-regulation of multiple growth-promoting genes, thus contributing to physiological slowing and eventual cessation of body growth. PMID:25866874

Evidence That Up-Regulation of MicroRNA-29 Contributes to Postnatal Body Growth Deceleration.

PubMed

Kamran, Fariha; Andrade, Anenisia C; Nella, Aikaterini A; Clokie, Samuel J; Rezvani, Geoffrey; Nilsson, Ola; Baron, Jeffrey; Lui, Julian C

2015-06-01

Body growth is rapid in infancy but subsequently slows and eventually ceases due to a progressive decline in cell proliferation that occurs simultaneously in multiple organs. We previously showed that this decline in proliferation is driven in part by postnatal down-regulation of a large set of growth-promoting genes in multiple organs. We hypothesized that this growth-limiting genetic program is orchestrated by microRNAs (miRNAs). Bioinformatic analysis identified target sequences of the miR-29 family of miRNAs to be overrepresented in age-down-regulated genes. Concomitantly, expression microarray analysis in mouse kidney and lung showed that all members of the miR-29 family, miR-29a, -b, and -c, were strongly up-regulated from 1 to 6 weeks of age. Real-time PCR confirmed that miR-29a, -b, and -c were up-regulated with age in liver, kidney, lung, and heart, and their expression levels were higher in hepatocytes isolated from 5-week-old mice than in hepatocytes from embryonic mouse liver at embryonic day 16.5. We next focused on 3 predicted miR-29 target genes (Igf1, Imp1, and Mest), all of which are growth-promoting. A 3'-untranslated region containing the predicted target sequences from each gene was placed individually in a luciferase reporter construct. Transfection of miR-29 mimics suppressed luciferase gene activity for all 3 genes, and this suppression was diminished by mutating the target sequences, suggesting that these genes are indeed regulated by miR-29. Taken together, the findings suggest that up-regulation of miR-29 during juvenile life drives the down-regulation of multiple growth-promoting genes, thus contributing to physiological slowing and eventual cessation of body growth.

Aurora-B Regulates RNA Methyltransferase NSUN2

PubMed Central

Sakita-Suto, Shiho; Kanda, Akifumi; Suzuki, Fumio; Sato, Sunao; Takata, Takashi

2007-01-01

Disassembly of the nucleolus during mitosis is driven by phosphorylation of nucleolar proteins. RNA processing stops until completion of nucleolar reformation in G1 phase. Here, we describe the RNA methyltransferase NSUN2, a novel substrate of Aurora-B that contains an NOL1/NOP2/sun domain. NSUN2 was concentrated in the nucleolus during interphase and was distributed in the perichromosome and cytoplasm during mitosis. Aurora-B phosphorylated NSUN2 at Ser139. Nucleolar proteins NPM1/nucleophosmin/B23 and nucleolin/C23 were associated with NSUN2 during interphase. In mitotic cells, association between NPM1 and NSUN2 was inhibited, but NSUN2-S139A was constitutively associated with NPM1. The Aurora inhibitor Hesperadin induced association of NSUN2 with NPM1 even in mitosis, despite the silver staining nucleolar organizer region disassembly. In vitro methylation experiments revealed that the Aurora-B-phosphorylation and the phosphorylation-mimic mutation (S139E) suppressed methyltransferase activities of NSUN2. These results indicate that Aurora-B participates to regulate the assembly of nucleolar RNA-processing machinery and the RNA methyltransferase activity of NSUN2 via phosphorylation at Ser139 during mitosis. PMID:17215513

Two Chimeric Regulators of G-protein Signaling (RGS) Proteins Differentially Modulate Soybean Heterotrimeric G-protein Cycle*

PubMed Central

Roy Choudhury, Swarup; Westfall, Corey S.; Laborde, John P.; Bisht, Naveen C.; Jez, Joseph M.; Pandey, Sona

2012-01-01

Heterotrimeric G-proteins and the regulator of G-protein signaling (RGS) proteins, which accelerate the inherent GTPase activity of Gα proteins, are common in animals and encoded by large gene families; however, in plants G-protein signaling is thought to be more limited in scope. For example, Arabidopsis thaliana contains one Gα, one Gβ, three Gγ, and one RGS protein. Recent examination of the Glycine max (soybean) genome reveals a larger set of G-protein-related genes and raises the possibility of more intricate G-protein networks than previously observed in plants. Stopped-flow analysis of GTP-binding and GDP/GTP exchange for the four soybean Gα proteins (GmGα1–4) reveals differences in their kinetic properties. The soybean genome encodes two chimeric RGS proteins with an N-terminal seven transmembrane domain and a C-terminal RGS box. Both GmRGS interact with each of the four GmGα and regulate their GTPase activity. The GTPase-accelerating activities of GmRGS1 and -2 differ for each GmGα, suggesting more than one possible rate of the G-protein cycle initiated by each of the Gα proteins. The differential effects of GmRGS1 and GmRGS2 on GmGα1–4 result from a single valine versus alanine difference. The emerging picture suggests complex regulation of the G-protein cycle in soybean and in other plants with expanded G-protein networks. PMID:22474294

Circular RNA profiling reveals that circular RNAs from ANXA2 can be used as new biomarkers for multiple sclerosis.

PubMed

Iparraguirre, Leire; Muñoz-Culla, Maider; Prada-Luengo, Iñigo; Castillo-Triviño, Tamara; Olascoaga, Javier; Otaegui, David

2017-09-15

Multiple sclerosis is an autoimmune disease, with higher prevalence in women, in whom the immune system is dysregulated. This dysregulation has been shown to correlate with changes in transcriptome expression as well as in gene-expression regulators, such as non-coding RNAs (e.g. microRNAs). Indeed, some of these have been suggested as biomarkers for multiple sclerosis even though few biomarkers have reached the clinical practice. Recently, a novel family of non-coding RNAs, circular RNAs, has emerged as a new player in the complex network of gene-expression regulation. MicroRNA regulation function through a 'sponge system' and a RNA splicing regulation function have been proposed for the circular RNAs. This regulating role together with their high stability in biofluids makes them seemingly good candidates as biomarkers. Given the dysregulation of both protein-coding and non-coding transcriptome that have been reported in multiple sclerosis patients, we hypothesised that circular RNA expression may also be altered. Therefore, we carried out expression profiling of 13.617 circular RNAs in peripheral blood leucocytes from multiple sclerosis patients and healthy controls finding 406 differentially expressed (P-value < 0.05, Fold change > 1.5) and demonstrate after validation that, circ_0005402 and circ_0035560 are underexpressed in multiple sclerosis patients and could be used as biomarkers of the disease. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

WE-F-16A-03: 3D Printer Application in Proton Therapy: A Novel Method to Deliver Passive-Scattering Proton Beams with a Fixed Range and Modulation for SRS and SRT

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

Ding, X; Witztum, A; Liang, X

2014-06-15

Purpose: To present a novel technique to deliver passive-scattering proton beam with fixed range and modulation using a 3D printed patient-specific bolus for proton stereotactic radiosurgery and radiotherapy. Methods: A CIRS head phantom was used to simulate a patient with a small brain lesion. A custom bolus was created in the Eclipse Treatment Planning System (TPS) to compensate for the different water equivalent depths from the patient surface to the target from multiple beam directions. To simulate arc therapy, a plan was created on the initial CT using three passive-scattering proton beams with a fixed range and modulations irradiating frommore » different angles. The DICOM-RT structure file of the bolus was exported from the TPS and converted to STL format for 3D printing. The phantom was rescanned with the printed custom bolus and head cup to verify the dose distribution comparing to the initial plan. EBT3 films were placed in the sagital plane of the target to verify the delivered dose distribution. The relative stopping power of the printing material(ABSplus-P430) was measured using the Zebra multi-plate ion chamber. Results: The relative stopping power of the 3D printing material, ABSplus-P430 was 1.05 which is almost water equivalent. The dose difference between verification CT and Initial CT is almost negligible. Film measurement also confirmed the accuracy for this new proton delivery technique. Conclusion: Our method using 3D printed range modifiers simplify the treatment delivery of multiple passive-scattering beams in treatment of small lesion in brain. This technique makes delivery of multiple beam more efficient and can be extended to allow arc therapy with proton beams. The ability to create and construct complex patient specific bolus structures provides a new dimension in creating optimized quality treatment plans not only for proton therapy but also for electron and photon therapy.« less

EGFR-mutant Non-small Cell Lung Cancer Accompanied by Transient Asymptomatic Pulmonary Opacities Successfully Treated with “Stop-And-Go” Osimertinib

PubMed Central

Kobayashi, Keigo; Naoki, Katsuhiko; Kuroda, Aoi; Yasuda, Hiroyuki; Kawada, Ichiro; Soejima, Kenzo; Betsuyaku, Tomoko

2017-01-01

A 69-year-old man with post-operative recurrence of lung adenocarcinoma was treated with multiple chemotherapies, including epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors. A second biopsy revealed an EGFR T790M mutation. As 10th-line chemotherapy, osimertinib was initiated. After 24 weeks, chest computed tomography (CT) revealed asymptomatic ground-glass opacities in both lobes. After four weeks of osimertinib discontinuation, imaging revealed rapid lung cancer progression. Osimertinib was resumed. After 11 weeks, CT revealed decreased lung nodules with no exacerbation of interstitial lung disease. We describe a patient who experienced transient asymptomatic pulmonary opacities during treatment with osimertinib, which was successfully managed by a “stop-and-go” approach. PMID:29269665

Computational Analysis and Low-Scale Constitutive Expression of Laccases Synthetic Genes GlLCC1 from Ganoderma lucidum and POXA 1B from Pleurotus ostreatus in Pichia pastoris

PubMed Central

Reyes-Guzmán, Edwin Alfredo; Poutou-Piñales, Raúl A.; Reyes-Montaño, Edgar Antonio; Pedroza-Rodríguez, Aura Marina; Rodríguez-Vázquez, Refugio; Cardozo-Bernal, Ángela M.

2015-01-01

Lacasses are multicopper oxidases that can catalyze aromatic and non-aromatic compounds concomitantly with reduction of molecular oxygen to water. Fungal laccases have generated a growing interest due to their biotechnological potential applications, such as lignocellulosic material delignification, biopulping and biobleaching, wastewater treatment, and transformation of toxic organic pollutants. In this work we selected fungal genes encoding for laccase enzymes GlLCC1 in Ganoderma lucidum and POXA 1B in Pleurotus ostreatus. These genes were optimized for codon use, GC content, and regions generating secondary structures. Laccase proposed computational models, and their interaction with ABTS [2, 2′-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)] substrate was evaluated by molecular docking. Synthetic genes were cloned under the control of Pichia pastoris glyceraldehyde-3-phosphate dehydrogenase (GAP) constitutive promoter. P. pastoris X-33 was transformed with pGAPZαA-LaccGluc-Stop and pGAPZαA-LaccPost-Stop constructs. Optimization reduced GC content by 47 and 49% for LaccGluc-Stop and LaccPost-Stop genes, respectively. A codon adaptation index of 0.84 was obtained for both genes. 3D structure analysis using SuperPose revealed LaccGluc-Stop is similar to the laccase crystallographic structure 1GYC of Trametes versicolor. Interaction analysis of the 3D models validated through ABTS, demonstrated higher substrate affinity for LaccPost-Stop, in agreement with our experimental results with enzymatic activities of 451.08 ± 6.46 UL-1 compared to activities of 0.13 ± 0.028 UL-1 for LaccGluc-Stop. This study demonstrated that G. lucidum GlLCC1 and P. ostreatus POXA 1B gene optimization resulted in constitutive gene expression under GAP promoter and α-factor leader in P. pastoris. These are important findings in light of recombinant enzyme expression system utility for environmentally friendly designed expression systems, because of the wide range of substrates that laccases can transform. This contributes to a great gamut of products in diverse settings: industry, clinical and chemical use, and environmental applications. PMID:25611746

Computational analysis and low-scale constitutive expression of laccases synthetic genes GlLCC1 from Ganoderma lucidum and POXA 1B from Pleurotus ostreatus in Pichia pastoris.

PubMed

Rivera-Hoyos, Claudia M; Morales-Álvarez, Edwin David; Poveda-Cuevas, Sergio Alejandro; Reyes-Guzmán, Edwin Alfredo; Poutou-Piñales, Raúl A; Reyes-Montaño, Edgar Antonio; Pedroza-Rodríguez, Aura Marina; Rodríguez-Vázquez, Refugio; Cardozo-Bernal, Ángela M

2015-01-01

Lacasses are multicopper oxidases that can catalyze aromatic and non-aromatic compounds concomitantly with reduction of molecular oxygen to water. Fungal laccases have generated a growing interest due to their biotechnological potential applications, such as lignocellulosic material delignification, biopulping and biobleaching, wastewater treatment, and transformation of toxic organic pollutants. In this work we selected fungal genes encoding for laccase enzymes GlLCC1 in Ganoderma lucidum and POXA 1B in Pleurotus ostreatus. These genes were optimized for codon use, GC content, and regions generating secondary structures. Laccase proposed computational models, and their interaction with ABTS [2, 2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid)] substrate was evaluated by molecular docking. Synthetic genes were cloned under the control of Pichia pastoris glyceraldehyde-3-phosphate dehydrogenase (GAP) constitutive promoter. P. pastoris X-33 was transformed with pGAPZαA-LaccGluc-Stop and pGAPZαA-LaccPost-Stop constructs. Optimization reduced GC content by 47 and 49% for LaccGluc-Stop and LaccPost-Stop genes, respectively. A codon adaptation index of 0.84 was obtained for both genes. 3D structure analysis using SuperPose revealed LaccGluc-Stop is similar to the laccase crystallographic structure 1GYC of Trametes versicolor. Interaction analysis of the 3D models validated through ABTS, demonstrated higher substrate affinity for LaccPost-Stop, in agreement with our experimental results with enzymatic activities of 451.08 ± 6.46 UL-1 compared to activities of 0.13 ± 0.028 UL-1 for LaccGluc-Stop. This study demonstrated that G. lucidum GlLCC1 and P. ostreatus POXA 1B gene optimization resulted in constitutive gene expression under GAP promoter and α-factor leader in P. pastoris. These are important findings in light of recombinant enzyme expression system utility for environmentally friendly designed expression systems, because of the wide range of substrates that laccases can transform. This contributes to a great gamut of products in diverse settings: industry, clinical and chemical use, and environmental applications.

Reliability Based Geometric Design of Horizontal Circular Curves

NASA Astrophysics Data System (ADS)

Rajbongshi, Pabitra; Kalita, Kuldeep

2018-06-01

Geometric design of horizontal circular curve primarily involves with radius of the curve and stopping sight distance at the curve section. Minimum radius is decided based on lateral thrust exerted on the vehicles and the minimum stopping sight distance is provided to maintain the safety in longitudinal direction of vehicles. Available sight distance at site can be regulated by changing the radius and middle ordinate at the curve section. Both radius and sight distance depend on design speed. Speed of vehicles at any road section is a variable parameter and therefore, normally the 98th percentile speed is taken as the design speed. This work presents a probabilistic approach for evaluating stopping sight distance, considering the variability of all input parameters of sight distance. It is observed that the 98th percentile sight distance value is much lower than the sight distance corresponding to 98th percentile speed. The distribution of sight distance parameter is also studied and found to follow a lognormal distribution. Finally, the reliability based design charts are presented for both plain and hill regions, and considering the effect of lateral thrust.

Dependence and motivation to stop smoking as predictors of success of a quit attempt among smokers seeking help to quit.

PubMed

Ussher, Michael; Kakar, Geetanjali; Hajek, Peter; West, Robert

2016-02-01

It is not known how well motivation to stop smoking predicts abstinence in a clinical sample relative to the most widely used measure of cigarette dependence. A secondary analysis was conducted from a trial with 864 smokers making quit attempt. Fagerström Test of Cigarette Dependence (FTCD), Heaviness of Smoking Index (HSI), and motivation to stop smoking (composite of determination to quit and importance of quitting) were measured at baseline. Continuous smoking abstinence, validated by expired-air carbon monoxide, was assessed at 4weeks, 6months and 12months post-quit date. FTCD, HSI, non-HSI items in FTCD, and motivation were assessed as predictors of abstinence. In multiple-logistic regressions, controlling for age, gender and medication use, lower scores for FTCD, HSI and non-HSI all significantly predicted abstinence at all follow-ups, while motivation did not predict abstinence at any time. Likelihood ratio tests showed that the FTCD contributed most to the model at 4weeks and 6months; at 12months FTCD and non-HSI equally contributed most to the model. At 4weeks and 6months, predictions were improved by combining HSI and non-HSI components, compared with using these components alone. Cigarette dependence, measured by the FTCD, or by its HSI or non-HSI components, predicts both short-term and medium-term outcomes of attempts to stop smoking in treatment-seeking smokers involved in a clinical trial, whereas strength of motivation to stop predicts neither. Both the HSI and non-HSI components may be considered as briefer alternatives to the full FTCD. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Increasing BCI Communication Rates with Dynamic Stopping Towards More Practical Use: An ALS Study

PubMed Central

Mainsah, B. O.; Collins, L. M.; Colwell, K. A.; Sellers, E. W.; Ryan, D. B.; Caves, K.; Throckmorton, C. S.

2015-01-01

Objective The P300 speller is a brain-computer interface (BCI) that can possibly restore communication abilities to individuals with severe neuromuscular disabilities, such as amyotrophic lateral sclerosis (ALS), by exploiting elicited brain signals in electroencephalography data. However, accurate spelling with BCIs is slow due to the need to average data over multiple trials to increase the signal-to-noise ratio of the elicited brain signals. Probabilistic approaches to dynamically control data collection have shown improved performance in non-disabled populations; however, validation of these approaches in a target BCI user population has not occurred. Approach We have developed a data-driven algorithm for the P300 speller based on Bayesian inference that improves spelling time by adaptively selecting the number of trials based on the acute signal-to-noise ratio of a user’s electroencephalography data. We further enhanced the algorithm by incorporating information about the user’s language. In this current study, we test and validate the algorithms online in a target BCI user population, by comparing the performance of the dynamic stopping (or early stopping) algorithms against the current state-of-the-art method, static data collection, where the amount of data collected is fixed prior to online operation. Main Results Results from online testing of the dynamic stopping algorithms in participants with ALS demonstrate a significant increase in communication rate as measured in bits/sec (100-300%), and theoretical bit rate (100-550%), while maintaining selection accuracy. Participants also overwhelmingly preferred the dynamic stopping algorithms. Significance We have developed a viable BCI algorithm that has been tested in a target BCI population which has the potential for translation to improve BCI speller performance towards more practical use for communication. PMID:25588137

Large-scale oscillatory calcium waves in the immature cortex.

PubMed

Garaschuk, O; Linn, J; Eilers, J; Konnerth, A

2000-05-01

Two-photon imaging of large neuronal networks in cortical slices of newborn rats revealed synchronized oscillations in intracellular Ca2+ concentration. These spontaneous Ca2+ waves usually started in the posterior cortex and propagated slowly (2.1 mm per second) toward its anterior end. Ca2+ waves were associated with field-potential changes and required activation of AMPA and NMDA receptors. Although GABAA receptors were not involved in wave initiation, the developmental transition of GABAergic transmission from depolarizing to hyperpolarizing (around postnatal day 7) stopped the oscillatory activity. Thus we identified a type of large-scale Ca2+ wave that may regulate long-distance wiring in the immature cortex.

Mutations in eukaryotic release factors 1 and 3 act as general nonsense suppressors in Drosophila.

PubMed Central

Chao, Anna T; Dierick, Herman A; Addy, Tracie M; Bejsovec, Amy

2003-01-01

In a screen for suppressors of the Drosophila wingless(PE4) nonsense allele, we isolated mutations in the two components that form eukaryotic release factor. eRF1 and eRF3 comprise the translation termination complex that recognizes stop codons and catalyzes the release of nascent polypeptide chains from ribosomes. Mutations disrupting the Drosophila eRF1 and eRF3 show a strong maternal-effect nonsense suppression due to readthrough of stop codons and are zygotically lethal during larval stages. We tested nonsense mutations in wg and in other embryonically acting genes and found that different stop codons can be suppressed but only a subset of nonsense alleles are subject to suppression. We suspect that the context of the stop codon is significant: nonsense alleles sensitive to suppression by eRF1 and eRF3 encode stop codons that are immediately followed by a cytidine. Such suppressible alleles appear to be intrinsically weak, with a low level of readthrough that is enhanced when translation termination is disrupted. Thus the eRF1 and eRF3 mutations provide a tool for identifying nonsense alleles that are leaky. Our findings have important implications for assigning null mutant phenotypes and for selecting appropriate alleles to use in suppressor screens. PMID:14573473

Heavy and Overweight Vehicle Brake Testing: Five-Axle Combination Tractor-Flatbed Final Report

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

Lascurain, Mary Beth; Capps, Gary J; Franzese, Oscar

The Federal Motor Carrier Safety Administration, in coordination with the Federal Highway Administration, sponsored the Heavy and Overweight Vehicle Brake Testing (HOVBT) program in order to provide information about the effect of gross vehicle weight (GVW) on braking performance. Because the Federal Motor Carrier Safety Regulations limit the number of braking system defects that may exist for a vehicle to be allowed to operate on the roadways, the examination of the effect of brake defects on brake performance for increased loads is also relevant. The HOVBT program seeks to provide relevant information to policy makers responsible for establishing load limits,more » beginning with providing test data for a combination tractor/trailer. This testing was conducted on a five-axle combination vehicle with tractor brakes meeting the Reduced Stopping Distance requirement rulemaking. This report provides a summary of the testing activities, the results of various analyses of the data, and recommendations for future research. Following a complete brake rebuild, instrumentation, and brake burnish, stopping tests were performed from 20 and 40 mph with various brake application pressures (15 psi, 25 psi, 35 psi, 45 psi, 55 psi, and full system pressure). These tests were conducted for various brake conditions at the following GVWs: 60,000, 80,000, 91,000, 97,000, 106,000, and 116,000 lb. The 80,000-lb GVWs included both balanced and unbalanced loads. The condition of the braking system was also varied. To introduce these defects, brakes (none, forward drive axle, or rear trailer axle) were made inoperative. In addition to the stopping tests, performance-based brake tests were conducted for the various loading and brake conditions. Analysis of the stopping test data showed the stopping distance to increase with load (as expected) and also showed that more braking force was generated by the drive axle brakes than the trailer axle brakes. The constant-pressure stopping test data revealed a linear relationship between brake application pressure and was used to develop an algorithm to normalize stopping data for weight and initial speed.« less

Germline mutations of regulator of telomere elongation helicase 1, RTEL1, in Dyskeratosis congenita.

PubMed

Ballew, Bari J; Yeager, Meredith; Jacobs, Kevin; Giri, Neelam; Boland, Joseph; Burdett, Laurie; Alter, Blanche P; Savage, Sharon A

2013-04-01

Dyskeratosis congenita (DC) is an inherited bone marrow failure and cancer predisposition syndrome caused by aberrant telomere biology. The classic triad of dysplastic nails, abnormal skin pigmentation, and oral leukoplakia is diagnostic of DC, but substantial clinical heterogeneity exists; the clinically severe variant Hoyeraal Hreidarsson syndrome (HH) also includes cerebellar hypoplasia, severe immunodeficiency, enteropathy, and intrauterine growth retardation. Germline mutations in telomere biology genes account for approximately one-half of known DC families. Using exome sequencing, we identified mutations in RTEL1, a helicase with critical telomeric functions, in two families with HH. In the first family, two siblings with HH and very short telomeres inherited a premature stop codon from their mother who has short telomeres. The proband from the second family has HH and inherited a premature stop codon in RTEL1 from his father and a missense mutation from his mother, who also has short telomeres. In addition, inheritance of only the missense mutation led to very short telomeres in the proband's brother. Targeted sequencing identified a different RTEL1 missense mutation in one additional DC proband who has bone marrow failure and short telomeres. Both missense mutations affect the helicase domain of RTEL1, and three in silico prediction algorithms suggest that they are likely deleterious. The nonsense mutations both cause truncation of the RTEL1 protein, resulting in loss of the PIP box; this may abrogate an important protein-protein interaction. These findings implicate a new telomere biology gene, RTEL1, in the etiology of DC.

Germline Mutations of Regulator of Telomere Elongation Helicase 1, RTEL1, In Dyskeratosis Congenita

PubMed Central

Ballew, Bari J.; Yeager, Meredith; Jacobs, Kevin; Giri, Neelam; Boland, Joseph; Burdett, Laurie; Alter, Blanche P.; Savage, Sharon A.

2013-01-01

Dyskeratosis congenita (DC) is an inherited bone marrow failure and cancer predisposition syndrome caused by aberrant telomere biology. The classic triad of dysplastic nails, abnormal skin pigmentation, and oral leukoplakia is diagnostic of DC, but substantial clinical heterogeneity exists; the clinically severe variant Hoyeraal Hreidarsson syndrome (HH) also includes cerebellar hypoplasia, severe immunodeficiency, enteropathy, and intrauterine growth retardation. Germline mutations in telomere biology genes account for approximately one-half of known DC families. Using exome sequencing, we identified mutations in RTEL1, a helicase with critical telomeric functions, in two families with HH. In the first family, two siblings with HH and very short telomeres inherited a premature stop codon from their mother who has short telomeres. The proband from the second family has HH and inherited a premature stop codon in RTEL1 from his father and a missense mutation from his mother, who also has short telomeres. Additionally, inheritance of only the missense mutation led to very short telomeres in the proband’s brother. Targeted sequencing identified a different RTEL1 missense mutation in one additional DC proband who has bone marrow failure and short telomeres. Both missense mutations affect the helicase domain of RTEL1, and three in silico prediction algorithms suggest that they are likely deleterious. The nonsense mutations both cause truncation of the RTEL1 protein, resulting in loss of the PIP box; this may abrogate an important protein-protein interaction. These findings implicate a new telomere biology gene, RTEL1, in the etiology of DC. PMID:23329068

Measurements of hydrogen gas stopping efficiency for tin ions from laser-produced plasma

NASA Astrophysics Data System (ADS)

Abramenko, D. B.; Spiridonov, M. V.; Krainov, P. V.; Krivtsun, V. M.; Astakhov, D. I.; Medvedev, V. V.; van Kampen, M.; Smeets, D.; Koshelev, K. N.

2018-04-01

Experimental studies of stopping of ion fluxes from laser-produced plasma by a low-pressure gas atmosphere are presented. A modification of the time-of-flight spectroscopy technique is proposed for the stopping cross-sectional measurements in the ion energy range of 0.1-10 keV. The application of the proposed technique is demonstrated for Sn ion stopping by H2 gas. This combination of elements is of particular importance for the development of plasma-based sources of extreme ultraviolet radiation for lithographic applications.

Feasibility and user perception of a fully automated push-based multiple-session alcohol intervention for university students: randomized controlled trial.

PubMed

Bendtsen, Marcus; Bendtsen, Preben

2014-06-23

In recent years, many electronic health behavior interventions have been developed in order to reach individuals with unhealthy behaviors, such as risky drinking. This is especially relevant for university students, many of whom are risky drinkers. This study explored the acceptability and feasibility in a nontreatment-seeking group of university students (including both risk and nonrisk drinkers), of a fully automated, push-based, multiple-session, alcohol intervention, comparing two modes of delivery by randomizing participants to receive the intervention either by SMS text messaging (short message service, SMS) or by email. A total of 5499 students at Luleå University in northern Sweden were invited to participate in a single-session alcohol assessment and feedback intervention; 28.04% (1542/5499) students completed this part of the study. In total, 29.44% (454/1542) of those participating in the single-session intervention accepted to participate further in the extended multiple-session intervention lasting for 4 weeks. The students were randomized to receive the intervention messages via SMS or email. A follow-up questionnaire was sent immediately after the intervention and 52.9% (240/454) responded. No difference was seen regarding satisfaction with the length and frequency of the intervention, regardless of the mode of delivery. Approximately 15% in both the SMS (19/136) and email groups (15/104) would have preferred the other mode of delivery. On the other hand, more students in the SMS group (46/229, 20.1%) stopped participating in the intervention during the 4-week period compared with the email group (10/193, 5.2%). Most students in both groups expressed satisfaction with the content of the messages and would recommend the intervention to a fellow student in need of reducing drinking. A striking difference was seen regarding when a message was read; 88.2% (120/136) of the SMS group read the messages within 1 hour in contrast to 45.2% (47/104) in the email group. In addition, 83.1% (113/136) in the SMS group stated that they read all or almost all the messages, compared with only 63.5% (66/104) in the email group. Based on the feedback from the students, an extended, multiple-session, push-based intervention seems to be a feasible option for students interested in additional support after a single-session alcohol intervention. SMS as a mode of delivery seems to have some advantages over email regarding when a message is read and the proportion of messages read. However, more students in the SMS group stopped the intervention than in the email group. Based on these promising findings, further studies comparing the effectiveness of single-session interventions with extended multiple-session interventions delivered separately or in combination are warranted.

Mx1 and Mx2 key antiviral proteins are surprisingly lost in toothed whales

PubMed Central

Braun, Benjamin A.; Marcovitz, Amir; Camp, J. Gray; Jia, Robin; Bejerano, Gill

2015-01-01

Viral outbreaks in dolphins and other Delphinoidea family members warrant investigation into the integrity of the cetacean immune system. The dynamin-like GTPase genes Myxovirus 1 (Mx1) and Mx2 defend mammals against a broad range of viral infections. Loss of Mx1 function in human and mice enhances infectivity by multiple RNA and DNA viruses, including orthomyxoviruses (influenza A), paramyxoviruses (measles), and hepadnaviruses (hepatitis B), whereas loss of Mx2 function leads to decreased resistance to HIV-1 and other viruses. Here we show that both Mx1 and Mx2 have been rendered nonfunctional in Odontoceti cetaceans (toothed whales, including dolphins and orcas). We discovered multiple exon deletions, frameshift mutations, premature stop codons, and transcriptional evidence of decay in the coding sequence of both Mx1 and Mx2 in four species of Odontocetes. We trace the likely loss event for both proteins to soon after the divergence of Odontocetes and Mystocetes (baleen whales) ∼33–37 Mya. Our data raise intriguing questions as to what drove the loss of both Mx1 and Mx2 genes in the Odontoceti lineage, a double loss seen in none of 56 other mammalian genomes, and suggests a hitherto unappreciated fundamental genetic difference in the way these magnificent mammals respond to viral infections. PMID:26080416

Mx1 and Mx2 key antiviral proteins are surprisingly lost in toothed whales.

PubMed

Braun, Benjamin A; Marcovitz, Amir; Camp, J Gray; Jia, Robin; Bejerano, Gill

2015-06-30

Viral outbreaks in dolphins and other Delphinoidea family members warrant investigation into the integrity of the cetacean immune system. The dynamin-like GTPase genes Myxovirus 1 (Mx1) and Mx2 defend mammals against a broad range of viral infections. Loss of Mx1 function in human and mice enhances infectivity by multiple RNA and DNA viruses, including orthomyxoviruses (influenza A), paramyxoviruses (measles), and hepadnaviruses (hepatitis B), whereas loss of Mx2 function leads to decreased resistance to HIV-1 and other viruses. Here we show that both Mx1 and Mx2 have been rendered nonfunctional in Odontoceti cetaceans (toothed whales, including dolphins and orcas). We discovered multiple exon deletions, frameshift mutations, premature stop codons, and transcriptional evidence of decay in the coding sequence of both Mx1 and Mx2 in four species of Odontocetes. We trace the likely loss event for both proteins to soon after the divergence of Odontocetes and Mystocetes (baleen whales) ∼33-37 Mya. Our data raise intriguing questions as to what drove the loss of both Mx1 and Mx2 genes in the Odontoceti lineage, a double loss seen in none of 56 other mammalian genomes, and suggests a hitherto unappreciated fundamental genetic difference in the way these magnificent mammals respond to viral infections.

Light stops and observation of supersymmetry at LHC run II

NASA Astrophysics Data System (ADS)

Kaufman, Bryan; Nath, Pran; Nelson, Brent D.; Spisak, Andrew B.

2015-11-01

Light stops consistent with the Higgs boson mass of ˜126 GeV are investigated within the framework of minimal supergravity. It is shown that models with light stops which are also consistent with the thermal relic density constraints require stop coannihilation with the neutralino LSP. The analysis shows that the residual set of parameter points with light stops satisfying both the Higgs mass and the relic density constraints lie within a series of thin strips in the m0-m1 /2 plane for different values of A0/m0. Consequently, this region of minimal supergravity parameter space makes a number of very precise predictions. It is found that light stops of mass down to 400 GeV or lower can exist consistent with all constraints. A signal analysis for this class of models at LHC run II is carried out and the dominant signals for their detection identified. Also computed is the minimum integrated luminosity for 5 σ discovery of the models analyzed. If supersymmetry is realized in this manner, the stop masses can be as low as 400 GeV or lower, and the mass gap between the lightest neutralino and lightest stop will be approximately 30-40 GeV. We have optimized the ATLAS signal regions specifically for stop searches in the parameter space and find that a stop with mass ˜375 GeV can be discovered with as little as ˜60 fb-1 of integrated luminosity at run II of the LHC; the integrated luminosity needed for discovery could be further reduced with more efficient signature analyses. The direct detection of dark matter in this class of models is also discussed. It is found that dark matter cross sections lie close to, but above, coherent neutrino scattering and would require multiton detectors such as LZ to see a signal of dark matter for this class of models.

Stop identity cue as a cue to language identity

NASA Astrophysics Data System (ADS)

Castonguay, Paula Lisa

The purpose of the present study was to determine whether language membership could potentially be cued by the acoustic-phonetic detail of word-initial stops and retained all the way through the process of lexical access to aid in language identification. Of particular interest were language-specific differences in CE and CF word-initial stops. Experiment 1 consisted of an interlingual homophone production task. The purpose of this study was to examine how word-initial stop consonants differ in terms of acoustic properties in Canadian English (CE) and Canadian French (CF) interlingual homophones. The analyses from the bilingual speakers in Experiment 1 indicate that bilinguals do produce language-specific differences in CE and CF word-initial stops, and that closure duration, voice onset time, and burst spectral SD may provide cues to language identity in CE and CF stops. Experiment 2 consisted of a Phoneme and Language Categorization task. The purpose of this study was to examine how stop identity cues, such as VOT and closure duration, influence a listener to identify word-initial stop consonants as belonging to Canadian English (CE) or Canadian French (CF). The RTs from the bilingual listeners in this study indicate that bilinguals do perceive language-specific differences in CE and CF word-initial stops, and that voice onset time may provide cues to phoneme and language membership in CE and CF stops. Experiment 3 consisted of a Phonological-Semantic priming task. The purpose of this study was to examine how subphonetic variations, such as changes in the VOT, affect lexical access. The results of Experiment 3 suggest that language-specific cues, such as VOT, affects the composition of the bilingual cohort and that the extent to which English and/or French words are activated is dependent on the language-specific cues present in a word. The findings of this study enhanced our theoretical understanding of lexical structure and lexical access in bilingual speakers. In addition, this study provides further insight on cross-language effects at the subphonetic level.

Quaternary stratigraphy and tectonics, and late prehistoric agriculture of the Safford Basin (Gila and San Simon river valleys), Graham County, Arizona

USGS Publications Warehouse

Houser, Brenda B.; Pearthree, Phillip A.; Homburg, Jeffry A.; Thrasher, Lawrence C.

2004-01-01

This guidebook accompanied the 46th annual meeting of the Rocky Mountain Cell of the Friends of the Pleistocene (FOP) and the 2002 Fall Field Trip of the Arizona Geological Society. The meeting and field trip were held in the Safford Basin, southeastern Arizona. The Friends of the Pleistocene is an informal gathering of Quaternary geologists, geomorphologists, and pedologists who meet annually for a field conference. The first part of the guidebook consists of road logs with descriptions of stops covering the three days of the field trip. An overview of the geology of the Safford Basin is given in Stop 1-1. The second part of the guidebook consists of four short papers that discuss adjacent areas or that expand upon the road log descriptions of the field trip stops. The first paper by Reid and Buffler is a summary of upper Cenozoic depositional facies in the Duncan Basin, the first basin to the east of the Safford Basin. The next three papers expand upon (1) the soil study of the gridded field agricultural complex (Stop 2-3, Homburg and Sandor), (2) the vertebrate fossils of the San Simon Valley in the southeastern part of the Safford Basin (Stop 3-1, Thrasher), and (3) paleoIndian irrigation systems and settlements in Lefthand Canyon at the foot of the Pinaleno Mountains (Stop 3-2, Neely and Homburg).

Electronic cigarette: a longitudinal study of regular vapers.

PubMed

Etter, Jean-François

2017-06-07

It is unclear how vaping behaviour changes over time in regular vapers, and what occurs when vapers relapse to smoking or when they stop vaping. We assessed change in vaping and smoking behaviours over 12 months in regular vapers. A longitudinal study of 3868 regular vapers enrolled on the Internet in 2012-2015 ("baseline"), followed after one (n=1631, 42%), three (n=1337, 35%), six (n=1148, 30%) and 12 months (n=893, 23%). Participants had been vaping for a median of five months at baseline. Most (77%) were former smokers, who had not smoked for a median of three months at baseline. Over 12 months, enjoyment gradually became the most frequently cited reason to vape (93%), and vaping to deal with craving for tobacco gradually decreased (from 87% to 56%). In exclusive vapers (ex-smokers), nicotine concentration in e-liquids decreased over time (from 12 to 9 mg/mL), but puffs/day remained stable (200 puffs/day). After 12 months, 9% of 687 former smokers relapsed to smoking and 28% of 64 daily smokers (dual users) stopped smoking. After 12 months, when participants stopped vaping, they tended to relapse to smoking (+18% daily smokers among those who stopped vaping versus -2% in permanent vapers, p<.001). When ex-smokers relapsed to smoking, they tended to stop vaping. After 12 months, enjoyment and relapse prevention were the most important reasons to vape. Rates of relapse to smoking were low in former smokers and quit rates were high in current smokers. Stopping vaping was associated with relapsing to smoking. Even in established vapers, vaping behaviour and reasons to vape change over time. This should be taken into account by clinicians, manufacturers and regulators. Results from this non-representative sample can help generate hypotheses that can later be tested in representative samples of vapers. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Evaluation of an accelerated 3D SPACE sequence with compressed sensing and free-stop scan mode for imaging of the knee.

PubMed

Henninger, B; Raithel, E; Kranewitter, C; Steurer, M; Jaschke, W; Kremser, C

2018-05-01

To prospectively evaluate a prototypical 3D turbo-spin-echo proton-density-weighted sequence with compressed sensing and free-stop scan mode for preventing motion artefacts (3D-PD-CS-SPACE free-stop) for knee imaging in a clinical setting. 80 patients underwent 3T magnetic resonance imaging (MRI) of the knee with our 2D routine protocol and with 3D-PD-CS-SPACE free-stop. In case of a scan-stop caused by motion (images are calculated nevertheless) the sequence was repeated without free-stop mode. All scans were evaluated by 2 radiologists concerning image quality of the 3D-PD-CS-SPACE (with and without free-stop). Important knee structures were further assessed in a lesion based analysis and compared to our reference 2D-PD-fs sequences. Image quality of the 3D-PD-CS-SPACE free-stop was found optimal in 47/80, slightly compromised in 21/80, moderately in 10/80 and severely in 2/80. In 29/80, the free-stop scan mode stopped the 3D-PD-CS-SPACE due to subject motion with a slight increase of image quality at longer effective acquisition times. Compared to the 3D-PD-CS-SPACE with free-stop, the image quality of the acquired 3D-PD-CS-SPACE without free-stop was found equal in 6/29, slightly improved in 13/29, improved with equal contours in 8/29, and improved with sharper contours in 2/29. The lesion based analysis showed a high agreement between the results from the 3D-PD-CS-SPACE free-stop and our 2D-PD-fs routine protocol (overall agreement 96.25%-100%, Cohen's Kappa 0.883-1, p < 0.001). 3D-PD-CS-SPACE free-stop is a reliable alternative for standard 2D-PD-fs protocols with acceptable acquisition times. Copyright © 2018 Elsevier B.V. All rights reserved.

The Role of Prosodic Structure in the L2 Acquisition of Spanish Stop Lenition

ERIC Educational Resources Information Center

Cabrelli Amaro, Jennifer

2017-01-01

This study tests the hypothesis that late first-language English / second-language Spanish learners (L1 English / L2 Spanish learners) acquire spirantization in stages according to the prosodic hierarchy (Zampini, 1997, 1998). In Spanish, voiced stops [b d g] surface after a pause or nasal stop, and continuants [ß? ð? ??] surface postvocalically,…

49 CFR 571.108, Nt. - Standard No. 108; Lamps, reflective devices, and associated equipment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... or less, manufactured on or after September 1, 1993, shall be equipped with a high-mounted stop lamp... Practice J186a, Supplemental High-Mounted Stop and Rear Turn Signal Lamps, September 1977, if it is mounted... doors, which lacks sufficient space to install a single high-mounted stop lamp on the centerline above...

Use of blade pitch control to provide power train damping for the Mod-2, 2.5-mW wind turbine

NASA Technical Reports Server (NTRS)

Blissell, W. A., Jr.

1995-01-01

The Control System for the Mod-2 wind turbine system is required to provide not only for startup, RPM regulation, maximizing or regulating power, and stopping the rotor, but also for load limiting, especially in the power train. Early operations with above-rated winds revealed an instability which was caused primarily by coupling between the quill shaft and the rotor air loads. This instability caused the first of several major Mod-2 Control System changes which are reviewed in the paper.

Molecular genetics and targeted therapy of WNT-related human diseases (Review).

PubMed

Katoh, Masuko; Katoh, Masaru

2017-09-01

Canonical WNT signaling through Frizzled and LRP5/6 receptors is transduced to the WNT/β-catenin and WNT/stabilization of proteins (STOP) signaling cascades to regulate cell fate and proliferation, whereas non-canonical WNT signaling through Frizzled or ROR receptors is transduced to the WNT/planar cell polarity (PCP), WNT/G protein-coupled receptor (GPCR) and WNT/receptor tyrosine kinase (RTK) signaling cascades to regulate cytoskeletal dynamics and directional cell movement. WNT/β-catenin signaling cascade crosstalks with RTK/SRK and GPCR-cAMP-PKA signaling cascades to regulate β-catenin phosphorylation and β-catenin-dependent transcription. Germline mutations in WNT signaling molecules cause hereditary colorectal cancer, bone diseases, exudative vitreoretinopathy, intellectual disability syndrome and PCP-related diseases. APC or CTNNB1 mutations in colorectal, endometrial and prostate cancers activate the WNT/β-catenin signaling cascade. RNF43, ZNRF3, RSPO2 or RSPO3 alterations in breast, colorectal, gastric, pancreatic and other cancers activate the WNT/β-catenin, WNT/STOP and other WNT signaling cascades. ROR1 upregulation in B-cell leukemia and solid tumors and ROR2 upregulation in melanoma induce invasion, metastasis and therapeutic resistance through Rho-ROCK, Rac-JNK, PI3K-AKT and YAP signaling activation. WNT signaling in cancer, stromal and immune cells dynamically orchestrate immune evasion and antitumor immunity in a cell context-dependent manner. Porcupine (PORCN), RSPO3, WNT2B, FZD5, FZD10, ROR1, tankyrase and β-catenin are targets of anti-WNT signaling therapy, and ETC-159, LGK974, OMP-18R5 (vantictumab), OMP-54F28 (ipafricept), OMP-131R10 (rosmantuzumab), PRI-724 and UC-961 (cirmtuzumab) are in clinical trials for cancer patients. Different classes of anti-WNT signaling therapeutics are necessary for the treatment of APC/CTNNB1-, RNF43/ZNRF3/RSPO2/RSPO3- and ROR1-types of human cancers. By contrast, Dickkopf-related protein 1 (DKK1), SOST and glycogen synthase kinase 3β (GSK3β) are targets of pro-WNT signaling therapy, and anti-DKK1 (BHQ880 and DKN-01) and anti-SOST (blosozumab, BPS804 and romosozumab) monoclonal antibodies are being tested in clinical trials for cancer patients and osteoporotic post-menopausal women. WNT-targeting therapeutics have also been applied as reagents for in vitro stem-cell processing in the field of regenerative medicine.

Predictors of self-injury cessation and subsequent psychological growth: results of a probability sample survey of students in eight universities and colleges.

PubMed

Whitlock, Janis; Prussien, Kemar; Pietrusza, Celeste

2015-01-01

Factors affecting non-suicidal self-injury cessation are poorly understood. The aim of this study was to identify differences between individuals with current and past non-suicidal self-injury (NSSI) in a large probability sample of university students using quantitative and qualitative methods. Predictors of psychological growth related following NSSI cessation were also examined. The sample included 836 students who participated in a larger online study of well-being at eight U.S. colleges and who reported current or past history of repeated NSSI. The average age of respondents used in analysis was 21.3 years. They were 78.3 % female and 21.7 % male and were 70.7 % Caucasian, 1.4 % African American/Black, 5.5 % Hispanic, 7.8 % Asian/Asian American and 14.7 % other. Analyses tested differences in demographics, NSSI characteristics (e.g. lifetime frequency, number of NSSI functions, NSSI disclosure), formal help-seeking, psychosocial factors, and mental health and trauma histories. Individuals with current NSSI status were more likely to be female and slightly younger, to report higher NSSI lifetime frequency, more NSSI forms and functions, thinking of themselves as a "self-injurer", and current psychological distress. Individuals with current NSSI status were less likely to report that self-injury interfered with life, that therapy was useful in stopping, perceiving social support, having a sense of meaning in life, access to more emotion regulation strategies, and life satisfaction. Qualitative data suggested that cessation may be attributable to changes in ability to regulate emotion (62.6 %), self-awareness (38.7 %), and important relationships to others (36.0 %). Psychological growth after stopping NSSI was predicted by more severe NSSI (form and perceived NSSI dependence), having talked about NSSI with others and higher numbers of confidantes, perceived life satisfaction, and a history of suicide action. These findings add to the still nascent body of literature examining processes related to NSSI cessation. Our results point to the importance of help-seeking and social support, as well as psychosocial processes in stopping NSSI.

Computer-Based Video Instruction to Teach Students with Intellectual Disabilities to Use Public Bus Transportation

ERIC Educational Resources Information Center

Mechling, Linda; O'Brien, Eileen

2010-01-01

This study investigated the effectiveness of computer-based video instruction (CBVI) to teach three young adults with moderate intellectual disabilities to push a "request to stop bus signal" and exit a city bus in response to target landmarks. A multiple probe design across three students and one bus route was used to evaluate effectiveness of…

[How dangerous is the pill?].

PubMed

1975-09-20

Neurologic complications of oral contraception in 3 women aged 36, 22, and 36, respectively, are reported. Neurologic symptomatology was diagnosed as myasthenia gravis pseudoparalytica, thrombosis of the right internal occipital artery, and multiple sclerosis. In 2 cases, neurologic symptoms disappeared after oral contraception was stopped. In all 3 cases immune deficiency symptoms were found. The possible relationship between immunologic deficiency syndromes and hormone status are discussed.

System and method for detecting components of a mixture including tooth elements for alignment

DOEpatents

Sommer, Gregory Jon; Schaff, Ulrich Y.

2016-11-22

Examples are described including assay platforms having tooth elements. An impinging element may sequentially engage tooth elements on the assay platform to sequentially align corresponding detection regions with a detection unit. In this manner, multiple measurements may be made of detection regions on the assay platform without necessarily requiring the starting and stopping of a motor.

Addressing wild turkey population declines using structured decision making

USGS Publications Warehouse

Robinson, Kelly F.; Fuller, Angela K.; Schiavone, Michael V.; Swift, Bryan L.; Diefenbach, Duane R.; Siemer, William F.; Decker, Daniel J.

2017-01-01

We present a case study from New York, USA, of the use of structured decision making (SDM) to identify fall turkey harvest regulations that best meet stakeholder objectives, in light of recent apparent declines in abundance of wild turkeys in the northeastern United States. We used the SDM framework to incorporate the multiple objectives associated with turkey hunting, stakeholder desires, and region-specific ecological and environmental factors that could influence fall harvest. We identified a set of 4 fall harvest regulations, composed of different season lengths and bag limits, and evaluated their relative achievement of the objectives. We used a stochastic turkey population model, statistical modeling, and expert elicitation to evaluate the consequences of each harvest regulation on each of the objectives. We conducted a statewide mail survey of fall turkey hunters in New York to gather the necessary information to evaluate tradeoffs among multiple objectives associated with hunter satisfaction. The optimal fall harvest regulation was a 2-week season and allowed for the harvest of 1 bird/hunter. This regulation was the most conservative of those evaluated, reflecting the concerns about recent declines in turkey abundance among agency wildlife biologists and the hunting public. Depending on the region of the state, the 2-week, 1-bird regulation was predicted to result in 7–32% more turkeys on the landscape after 5 years. The SDM process provided a transparent framework for setting fall turkey harvest regulations and reduced potential stakeholder conflict by explicitly taking the multiple objectives of different stakeholder groups into account.

Low-bias flat band-stop filter based on velocity modulated gaussian graphene superlattice

NASA Astrophysics Data System (ADS)

Sattari-Esfahlan, S. M.; Shojaei, S.

2018-05-01

Transport properties of biased planar Gaussian graphene superlattice (PGGSL) with Fermi velocity barrier is investigated by transfer matrix method (TMM). It is observed that enlargement of bias voltage over miniband width breaks the miniband to WSLs leads to suppressing resonant tunneling. Transmission spectrum shows flat wide stop-band property controllable by external bias voltage with stop-band width of near 200 meV. The simulations demonstrate that strong velocity barriers prevent tunneling of Dirac electrons leading to controllable enhancement of stop-band width. By increasing ratio of Fermi velocity in barriers to wells υc stop-band width increase. As wide transmission stop-band width (BWT) of filter is tunable from 40 meV to 340 meV is obtained by enhancing ratio of υc from 0.2 to 1.5, respectively. Proposed structure suggests easy tunable wide band-stop electronic filter with a modulated flat stop-band characteristic by height of electrostatic barrier and structural parameters. Robust sensitivity of band width to velocity barrier intensity in certain bias voltages and flat band feature of proposed filter may be opens novel venue in GSL based flat band low noise filters and velocity modulation devices.

Evidence for interaction between the stop signal and the Stroop task conflict.

PubMed

Kalanthroff, Eyal; Goldfarb, Liat; Henik, Avishai

2013-04-01

Performance of the Stroop task reflects two conflicts--informational (between the incongruent word and ink color) and task (between relevant color naming and irrelevant word reading). The task conflict is usually not visible, and is only seen when task control is damaged. Using the stop-signal paradigm, a few studies demonstrated longer stop-signal reaction times for incongruent trials than for congruent trials. This indicates interaction between stopping and the informational conflict. Here we suggest that "zooming in" on task-control failure trials will reveal another interaction--between stopping and task conflict. To examine this suggestion, we combined stop-signal and Stroop tasks in the same experiment. When participants' control failed and erroneous responses to a stop signal occurred, a reverse facilitation emerged in the Stroop task (Experiment 1) and this was eliminated using methods that manipulated the emergence of the reverse facilitation (Experiment 2). Results from both experiments were replicated when all stimuli were used in the same task (Experiment 3). In erroneous response trials, only the task conflict increased, not the informational conflict. These results indicate that task conflict and stop-signal inhibition share a common control mechanism that is dissociable from the control mechanism activated by the informational conflict.

Stopping-power ratios for clinical electron beams from a scatter-foil linear accelerator.

PubMed

Kapur, A; Ma, C M

1999-09-01

Restricted mass collision stopping-power ratios for electron beams from a scatter-foil medical linear accelerator (Varian Clinac 2100C) were calculated for various combinations of beams, phantoms and detector materials using the Monte Carlo method. The beams were of nominal energy 6, 12 or 20 MeV, with square dimensions 1 x 1 cm2 to 10 x 10 cm2. They were incident at nominal SSDs of 100 or 120 cm and inclined at 90 degrees or 30 degrees to the surface of homogeneous water phantoms or water phantoms interspersed with layered lung or bone-like materials. The broad beam water-to-air stopping-power ratios were within 1.3% of the AAPM TG21 protocol values and consistent with the results of Ding et al to within 0.2%. On the central axis the stopping-power ratio variations for narrow beams compared with normally incident broad beams were 0.1% or less for water-to-LiF-100, graphite, ferrous sulfate dosimeter solution, polystyrene and PMMA, 0.5% for water-to-silicon and 1% for water-to-air and water-to-photographic-film materials. The transverse variations of the stopping-power ratios were up to 4% for water-to-silicon, 7% for water-to-photographic-film materials and 10% for water-to-air in the penumbral regions (where the dose was 10% of the global dose maximum) at shallow depths compared with the values at the same depths on the central axis. In the inhomogeneous phantoms studied, the stopping-power ratio correction factors varied more significantly for air, followed by photographic materials and silicon, at various depths on the central axis in the heterogeneous regions. For the simple layered phantoms studied, the estimation of the stopping-power ratio correction factors based on the relative electron-density derived effective depth approach yielded results that were within 0.5% of the Monte Carlo derived values for all the detector materials studied.

76 FR 4416 - Notice of Application for Approval of Discontinuance or Modification of a Railroad Signal System

Federal Register 2010, 2011, 2012, 2013, 2014

2011-01-25

... Discontinuance or Modification of a Railroad Signal System Pursuant to Title 49 Code of Federal Regulations (CFR... Administration (FRA) seeking approval for the discontinuance or modification of the signal system. [Docket Number...--Signal/Comm./TCO, 1400 Douglas Street, Mail Stop 0910, Omaha, Nebraska 68179. The Union Pacific Railroad...

Mammary gland involution is associated with rapid down regulation of major mammary Ca**2+-ATPases

USDA-ARS?s Scientific Manuscript database

Sixty percent of calcium in milk is transported across the mammary cells apical membrane by the plasma membrane Ca**2+-ATPase 2 (PMCA2). The effect of abrupt cessation of milk production on the Ca**2+-ATPases and mammary calcium transport is unknown. We found that 24 hours after stopping milk prod...

29 CFR 1471.325 - What happens if I do business with an excluded person in a covered transaction?

Code of Federal Regulations, 2010 CFR

2010-07-01

... business with an excluded person, we may disallow costs, annul or terminate the transaction, issue a stop... covered transaction? 1471.325 Section 1471.325 Labor Regulations Relating to Labor (Continued) FEDERAL... of Participants Regarding Transactions Doing Business with Other Persons § 1471.325 What happens if I...

20 CFR 404.302 - Other regulations related to this subpart.

Code of Federal Regulations, 2013 CFR

2013-04-01

... to several others. Subpart H sets out what evidence you need to prove you qualify for benefits. Subpart P describes what is needed to prove you are disabled. Subpart E describes when your benefits may be reduced or stopped for a time. Subpart G describes the need for and the effect of an application...

20 CFR 404.302 - Other regulations related to this subpart.

Code of Federal Regulations, 2011 CFR

2011-04-01

... to several others. Subpart H sets out what evidence you need to prove you qualify for benefits. Subpart P describes what is needed to prove you are disabled. Subpart E describes when your benefits may be reduced or stopped for a time. Subpart G describes the need for and the effect of an application...

20 CFR 404.302 - Other regulations related to this subpart.

Code of Federal Regulations, 2014 CFR

2014-04-01

... to several others. Subpart H sets out what evidence you need to prove you qualify for benefits. Subpart P describes what is needed to prove you are disabled. Subpart E describes when your benefits may be reduced or stopped for a time. Subpart G describes the need for and the effect of an application...

20 CFR 404.302 - Other regulations related to this subpart.

Code of Federal Regulations, 2012 CFR

2012-04-01

... to several others. Subpart H sets out what evidence you need to prove you qualify for benefits. Subpart P describes what is needed to prove you are disabled. Subpart E describes when your benefits may be reduced or stopped for a time. Subpart G describes the need for and the effect of an application...

20 CFR 404.302 - Other regulations related to this subpart.

Code of Federal Regulations, 2010 CFR

2010-04-01

... to several others. Subpart H sets out what evidence you need to prove you qualify for benefits. Subpart P describes what is needed to prove you are disabled. Subpart E describes when your benefits may be reduced or stopped for a time. Subpart G describes the need for and the effect of an application...

A speed guidance strategy for multiple signalized intersections based on car-following model

NASA Astrophysics Data System (ADS)

Tang, Tie-Qiao; Yi, Zhi-Yan; Zhang, Jian; Wang, Tao; Leng, Jun-Qiang

2018-04-01

Signalized intersection has great roles in urban traffic system. The signal infrastructure and the driving behavior near the intersection are paramount factors that have significant impacts on traffic flow and energy consumption. In this paper, a speed guidance strategy is introduced into a car-following model to study the driving behavior and the fuel consumption in a single-lane road with multiple signalized intersections. The numerical results indicate that the proposed model can reduce the fuel consumption and the average stop times. The findings provide insightful guidance for the eco-driving strategies near the signalized intersections.

The Arabidopsis USL1 controls multiple aspects of development by affecting late endosome morphology.

PubMed

Yuan, Rongrong; Lan, Jingqiu; Fang, Yuxing; Yu, Hao; Zhang, Jinzhe; Huang, Jiaying; Qin, Genji

2018-06-13

The polar transport of auxin controls many aspects of plant development. However, the molecular mechanisms underlying auxin tranport regulation remain to be further elucidated. We identified a mutant named as usl1 (unflattened and small leaves) in a genetic screen in Arabidopsis thaliana. The usl1 displayed multiple aspects of developmental defects in leaves, embryogenesis, cotyledons, silique phyllotaxy and lateral roots in addition to abnormal leaves. USL1 encodes a protein orthologous to the yeast vacuolar protein sorting (Vps) 38p and human UV RADIATION RESISTANCE-ASSOCIATED GENE (UVRAG). Cell biology, Co-IP/MS and yeast two-hybrid were used to identify the function of USL1. USL1 colocalizes at the subcellular level with VPS29, a key factor of the retromer complex that controls auxin transport. The morphology of the VPS29-associated late endosomes (LE) is altered from small dots in the wild-type to aberrant enlarged circles in the usl1 mutants. The usl1 mutant synergistically interacts with vps29. We also found that USL1 forms a complex with AtVPS30 and AtVPS34. We propose that USL1 controls multiple aspects of plant development by affecting late endosome morphology and by regulating the PIN1 polarity. Our findings provide a new layer of the understanding on the mechanisms of plant development regulation. © 2018 The Authors. New Phytologist © 2018 New Phytologist Trust.

Any way you look at it, successful obstacle negotiation needs visually guided on-line foot placement regulation during the approach phase.

PubMed

Patla, Aftab E; Greig, Michael

In the two experiments discussed in this paper we quantified obstacle avoidance performance characteristics carried out open loop (without vision) but with different initial visual sampling conditions and compared it to the full vision condition. The initial visual sampling conditions included: static vision (SV), vision during forward walking for three steps and stopping (FW), vision during forward walking for three steps and not stopping (FW-NS), and vision during backward walking for three steps and stopping (BW). In experiment 1, we compared performance during SV, FW and BW with full vision condition, while in the second experiment we compared performance during FW and FW-NS conditions. The questions we wanted to address are: Is ecologically valid dynamic visual sampling of the environment superior to static visual sampling for open loop obstacle avoidance task? What are the reasons for failure in performing open loop obstacle avoidance task? The results showed that irrespective of the initial visual sampling condition when open loop control is initiated from a standing posture, the success rate was only approximately 50%. The main reason for the high failure rates was not inappropriate limb elevation, but incorrect foot placement before the obstacle. The second experiment showed that it is not the nature of visual sampling per se that influences success rate, but the fact that the open loop obstacle avoidance task is initiated from a standing posture. The results of these two experiments clearly demonstrate the importance of on-line visual information for adaptive human locomotion.

The Role of Multiple Neuromodulators in Reinforcement Learning That Is Based on Competition between Eligibility Traces.

PubMed

Huertas, Marco A; Schwettmann, Sarah E; Shouval, Harel Z

2016-01-01

The ability to maximize reward and avoid punishment is essential for animal survival. Reinforcement learning (RL) refers to the algorithms used by biological or artificial systems to learn how to maximize reward or avoid negative outcomes based on past experiences. While RL is also important in machine learning, the types of mechanistic constraints encountered by biological machinery might be different than those for artificial systems. Two major problems encountered by RL are how to relate a stimulus with a reinforcing signal that is delayed in time (temporal credit assignment), and how to stop learning once the target behaviors are attained (stopping rule). To address the first problem synaptic eligibility traces were introduced, bridging the temporal gap between a stimulus and its reward. Although, these were mere theoretical constructs, recent experiments have provided evidence of their existence. These experiments also reveal that the presence of specific neuromodulators converts the traces into changes in synaptic efficacy. A mechanistic implementation of the stopping rule usually assumes the inhibition of the reward nucleus; however, recent experimental results have shown that learning terminates at the appropriate network state even in setups where the reward nucleus cannot be inhibited. In an effort to describe a learning rule that solves the temporal credit assignment problem and implements a biologically plausible stopping rule, we proposed a model based on two separate synaptic eligibility traces, one for long-term potentiation (LTP) and one for long-term depression (LTD), each obeying different dynamics and having different effective magnitudes. The model has been shown to successfully generate stable learning in recurrent networks. Although, the model assumes the presence of a single neuromodulator, evidence indicates that there are different neuromodulators for expressing the different traces. What could be the role of different neuromodulators for expressing the LTP and LTD traces? Here we expand on our previous model to include several neuromodulators, and illustrate through various examples how different these contribute to learning reward-timing within a wide set of training paradigms and propose further roles that multiple neuromodulators can play in encoding additional information of the rewarding signal.

Patient Condition Occurrence Frequency (PCOF) Tool Version 1.0.0.0 User Guide

DTIC Science & Technology

2013-06-19

4) and USS Kearsarge (LHD 3). Boxer made stops in Peru , El Salvador, and Guatemala and Kearsarge made stops in Columbia, Dominican Republic, Guyana...from Haiti surveillance data 20.1% 11.0% Metabolism disorders Non-zero and greater than .5 because diabetes is common worldwide 0.0% 1.0

Control of trunk motion following sudden stop perturbations during cart pushing.

PubMed

Lee, Yun-Ju; Hoozemans, Marco J M; van Dieën, Jaap H

2011-01-04

External perturbations during pushing tasks have been suggested to be a risk factor for low-back symptoms. An experiment was designed to investigate whether self-induced and externally induced sudden stops while pushing a high inertia cart influence trunk motions, and how flexor and extensor muscles counteract these perturbations. Twelve healthy male participants pushed a 200 kg cart at shoulder height and hip height. Pushing while walking was compared to situations in which participants had to stop the cart suddenly (self-induced stop) or in which the wheels of the cart were unexpectedly blocked (externally induced stop). For the perturbed conditions, the peak values and the maximum changes from the reference condition (pushing while walking) of the external moment at L5/S1, trunk inclination and electromyographic amplitudes of trunk muscles were determined. In the self-induced stop, a voluntary trunk extension occurred. Initial responses in both stops consisted of flexor and extensor muscle cocontraction. In self-induced stops this was followed by sustained extensor activity. In the externally induced stops, an external extension moment caused a decrease in trunk inclination. The opposite directions of the internal moment and trunk motion in the externally induced stop while pushing at shoulder height may indicate insufficient active control of trunk posture. Consequently, sudden blocking of the wheels in pushing at shoulder height may put the low back at risk of mechanical injury. Copyright © 2010 Elsevier Ltd. All rights reserved.

A Road Paved with Safe Intentions: Increasing Intentions to Use Alcohol Protective Behavioral Strategies via Deviance Regulation Theory

PubMed Central

Dvorak, Robert D.; Pearson, Matthew R.; Neighbors, Clayton; Martens, Matthew P.; Stevenson, Brittany L.; Kuvaas, Nicholas J.

2015-01-01

OBJECTIVE Drinking remains a problem across college campuses. Changing this behavior requires interventions that can be easily and widely dispersed. Several theories place intentions as a proximal predictor of behavior change. The current study examines the effects of a web-based Deviance Regulation Theory (DRT) intervention on (1) intentions to use alcohol protective behavior strategies (PBS) and (2) associations between these intentions and actual behavior. METHODS Participants (n = 76) completed a six-week, web-based, study examining drinking behaviors. Participants were randomly assigned to receive a positive frame about individuals who use PBS or a negative frame about individuals who do not. They also reported normative perceptions of PBS use among college students. They subsequently logged onto a secure server each week to report on alcohol involvement, use of three types of PBS (Manner of Drinking, Stopping/Limiting, and Serious Harm Reduction), and intentions to use these PBS the following week. RESULTS Consistent with DRT, negative frames resulted in higher PBS use intentions if individuals held high normative beliefs about PBS use. Positive frames resulted in higher Manner of Drinking PBS use intentions if individuals held low normative beliefs about PBS use, but only if individuals endorsed a high belief in the frame. In addition, there was a DRT consistent increase in intention-action associations, but only for Stopping/Limiting PBS. DISCUSSION A brief web-based DRT intervention was effective at increasing PBS intentions and increasing PBS intention-action associations. DRT may provide a mechanism to additively or synergistically improve other web-based interventions for college drinking. PMID:26914646

A novel G-quadruplex motif in the Human MET promoter region.

PubMed

Yan, Jing; Zhao, Deming; Dong, Liping; Pan, Shuang; Hao, Fengjin; Guan, Yifu

2017-12-22

It is known that the guanine-rich strands in proto-oncogene promoters can fold into G-quadruplex structures to regulate gene expression. An intramolecular parallel G-quadruplex has been identified in MET promoter. It acts as a repressor in regulating MET expression. However, the full guanine-rich region in MET promoter forms a hybrid parallel/antiparallel G-quadruplex structure under physiological conditions, which means there are some antiparallel and hybrid parallel/antiparallel G-quadruplex structures in this region. In the present study, our data indicate that g3-5 truncation adopts an intramolecular hybrid parallel/antiparallel G-quadruplex under physiological conditions in vitro The g3-5 G-quadruplex structure significantly stops polymerization by Klenow fragment in K + buffer. Furthermore, the results of circular dichroism (CD) spectra and polymerase stop assay directly demonstrate that the G-quadruplex structure in g3-5 fragment can be stabilized by the G-quadruplex ligand TMPyP4 (5,10,15,20-tetra-(N-methyl-4-pyridyl) porphine). But the dual luciferase assay indicates TMPyP4 has no effect on the formation of g3-5 G-quadruplex in HepG2 cells. The findings in the present study will enrich our understanding of the G-quadruplex formation in proto-oncogene promoters and the mechanisms of gene expression regulation. © 2017 The Author(s).

Rapid Y degeneration and dosage compensation in plant sex chromosomes

PubMed Central

Papadopulos, Alexander S. T.; Chester, Michael; Ridout, Kate; Filatov, Dmitry A.

2015-01-01

The nonrecombining regions of animal Y chromosomes are known to undergo genetic degeneration, but previous work has failed to reveal large-scale gene degeneration on plant Y chromosomes. Here, we uncover rapid and extensive degeneration of Y-linked genes in a plant species, Silene latifolia, that evolved sex chromosomes de novo in the last 10 million years. Previous transcriptome-based studies of this species missed unexpressed, degenerate Y-linked genes. To identify sex-linked genes, regardless of their expression, we sequenced male and female genomes of S. latifolia and integrated the genomic contigs with a high-density genetic map. This revealed that 45% of Y-linked genes are not expressed, and 23% are interrupted by premature stop codons. This contrasts with X-linked genes, in which only 1.3% of genes contained stop codons and 4.3% of genes were not expressed in males. Loss of functional Y-linked genes is partly compensated for by gene-specific up-regulation of X-linked genes. Our results demonstrate that the rate of genetic degeneration of Y-linked genes in S. latifolia is as fast as in animals, and that the evolutionary trajectories of sex chromosomes are similar in the two kingdoms. PMID:26438872

Multicenter accuracy and interobserver agreement of spot sign identification in acute intracerebral hemorrhage.

PubMed

Huynh, Thien J; Flaherty, Matthew L; Gladstone, David J; Broderick, Joseph P; Demchuk, Andrew M; Dowlatshahi, Dar; Meretoja, Atte; Davis, Stephen M; Mitchell, Peter J; Tomlinson, George A; Chenkin, Jordan; Chia, Tze L; Symons, Sean P; Aviv, Richard I

2014-01-01

Rapid, accurate, and reliable identification of the computed tomography angiography spot sign is required to identify patients with intracerebral hemorrhage for trials of acute hemostatic therapy. We sought to assess the accuracy and interobserver agreement for spot sign identification. A total of 131 neurology, emergency medicine, and neuroradiology staff and fellows underwent imaging certification for spot sign identification before enrolling patients in 3 trials targeting spot-positive intracerebral hemorrhage for hemostatic intervention (STOP-IT, SPOTLIGHT, STOP-AUST). Ten intracerebral hemorrhage cases (spot-positive/negative ratio, 1:1) were presented for evaluation of spot sign presence, number, and mimics. True spot positivity was determined by consensus of 2 experienced neuroradiologists. Diagnostic performance, agreement, and differences by training level were analyzed. Mean accuracy, sensitivity, and specificity for spot sign identification were 87%, 78%, and 96%, respectively. Overall sensitivity was lower than specificity (P<0.001) because of true spot signs incorrectly perceived as spot mimics. Interobserver agreement for spot sign presence was moderate (k=0.60). When true spots were correctly identified, 81% correctly identified the presence of single or multiple spots. Median time needed to evaluate the presence of a spot sign was 1.9 minutes (interquartile range, 1.2-3.1 minutes). Diagnostic performance, interobserver agreement, and time needed for spot sign evaluation were similar among staff physicians and fellows. Accuracy for spot identification is high with opportunity for improvement in spot interpretation sensitivity and interobserver agreement particularly through greater reliance on computed tomography angiography source data and awareness of limitations of multiplanar images. Further prospective study is needed.

SENP1 inhibition induces apoptosis and growth arrest of multiple myeloma cells through modulation of NF-κB signaling

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

Xu, Jun; Department of Experimental Hematology, Beijing Institute of Radiation Medicine, Beijing 100850; Sun, Hui-Yan

2015-05-01

SUMO/sentrin specific protease 1 (Senp1) is an important regulation protease in the protein sumoylation, which affects the cell cycle, proliferation and differentiation. The role of Senp1 mediated protein desumoylation in pathophysiological progression of multiple myeloma is unknown. In this study, we demonstrated that Senp1 is overexpressed and induced by IL-6 in multiple myeloma cells. Lentivirus-mediated Senp1 knockdown triggers apoptosis and reduces viability, proliferation and colony forming ability of MM cells. The NF-κB family members including P65 and inhibitor protein IkBα play important roles in regulation of MM cell survival and proliferation. We further demonstrated that Senp1 inhibition decreased IL-6-induced P65more » and IkBα phosphorylation, leading to inactivation of NF-kB signaling in MM cells. These results delineate a key role for Senp1in IL-6 induced proliferation and survival of MM cells, suggesting it may be a potential new therapeutic target in MM. - Highlights: • Senp1 is overexpressed and induced by IL-6 in multiple myeloma cells. • Senp1 knockdown triggers apoptosis and reduces proliferation of MM cells. • Senp1 inhibition decreased IL-6-induced P65 and IkBα phosphorylation.« less

Inflammasome and Autophagy Regulation: A Two-way Street

PubMed Central

Qian, Sun; Fan, Jie; Billiar, Timothy R; Scott, Melanie J

2017-01-01

Inflammation plays a significant role in protecting hosts against pathogens. Inflammation induced by noninfectious endogenous agents can be detrimental and, if excessive, can result in organ and tissue damage. The inflammasome is a major innate immune pathway that can be activated via both exogenous pathogen-associated molecular patterns (PAMPs) and endogenous damage-associated molecular patterns (DAMPs). Inflammasome activation involves formation and oligomerization of a protein complex including a nucleotide oligomerization domain (NOD)-like receptor (NLR), an adaptor protein and pro-caspase-1. This then allows cleavage and activation of caspase-1, followed by downstream cleavage and release of proinflammatory cytokines interleukin (IL)-1β and IL-18 from innate immune cells. Hyperinflammation caused by unrestrained inflammasome activation is linked with multiple inflammatory diseases, including inflammatory bowel disease, Alzheimer’s disease and multiple sclerosis. So there is an understandable rush to understand mechanisms that regulate such potent inflammatory pathways. Autophagy has now been identified as a main regulator of inflammasomes. Autophagy is a vital intracellular process involved in cellular homeostasis, recycling and removal of damaged organelles (eg, mitochondria) and intracellular pathogens. Autophagy is regulated by proteins that are important in endosomal/phagosomal pathways, as well as by specific autophagy proteins coded for by autophagy-related genes. Cytosolic components are surrounded and contained by a double-membraned vesicle, which then fuses with lysosomes to enable degradation of the contents. Autophagic removal of intracellular DAMPs, inflammasome components or cytokines can reduce inflammasome activation. Similarly, inflammasomes can regulate the autophagic process, allowing for a two-way mutual regulation of inflammation that may hold the key for treatment of multiple diseases. PMID:28741645

Poisoning deaths involving opioid analgesics - New York State, 2003-2012.

PubMed

Sharp, Mark J; Melnik, Thomas A

2015-04-17

Deaths involving opioid analgesics have increased dramatically in the United States. Approximately 4,000 such deaths were documented in 1999, increasing to 16,235 in 2013, reflecting a nearly quadrupled death rate from 1.4 to 5.1 deaths per 100,000. To investigate this increase in New York state, trends in poisoning deaths involving opioid analgesics from 2003 to 2012 were examined. Data sources used were New York state vital statistics multiple-cause-of-death data, consisting of data from both the New York City (NYC)* and non-NYC reporting jurisdictions, as well as statewide Medicaid enrollment data. Deaths involving opioid analgesics increased both in number and as a percentage of all drug poisoning deaths, and rates were highest among men, whites, persons aged 45-64 years, persons residing outside of NYC, and Medicaid enrollees. The analysis found that, in 2012, 70.7% of deaths involving opioid analgesics also involved at least one other drug, most frequently a benzodiazepine. These results underscore the potential to mitigate the trend of increasing opioid analgesic-related mortality through initiatives such as New York state's Internet System for Tracking Over-Prescribing (I-STOP) law,† which took effect on August 27, 2013. Provisions under I-STOP include the requirements that providers consult the Prescription Monitoring Program (PMP) Registry when writing prescriptions for controlled substances, and that they use electronic prescribing.

Physiological Markers of Motor Inhibition during Human Behavior.

PubMed

Duque, Julie; Greenhouse, Ian; Labruna, Ludovica; Ivry, Richard B

2017-04-01

Transcranial magnetic stimulation (TMS) studies in humans have shown that many behaviors engage processes that suppress excitability within the corticospinal tract. Inhibition of the motor output pathway has been extensively studied in the context of action stopping, where a planned movement needs to be abruptly aborted. Recent TMS work has also revealed markers of motor inhibition during the preparation of movement. Here, we review the evidence for motor inhibition during action stopping and action preparation, focusing on studies that have used TMS to monitor changes in the excitability of the corticospinal pathway. We discuss how these physiological results have motivated theoretical models of how the brain selects actions, regulates movement initiation and execution, and switches from one state to another. Copyright © 2017 Elsevier Ltd. All rights reserved.

Desacyl Ghrelin Decreases Anxiety-like Behavior in Male Mice.

PubMed

Mahbod, Parinaz; Smith, Eric P; Fitzgerald, Maureen E; Morano, Rachel L; Packard, Benjamin A; Ghosal, Sriparna; Scheimann, Jessie R; Perez-Tilve, Diego; Herman, James P; Tong, Jenny

2018-01-01

Ghrelin is a 28-amino acid polypeptide that regulates feeding, glucose metabolism, and emotionality (stress, anxiety, and depression). Plasma ghrelin circulates as desacyl ghrelin (DAG) or, in an acylated form, acyl ghrelin (AG), through the actions of ghrelin O-acyltransferase (GOAT), exhibiting low or high affinity, respectively, for the growth hormone secretagogue receptor (GHSR) 1a. We investigated the role of endogenous AG, DAG, and GHSR1a signaling on anxiety and stress responses using ghrelin knockout (Ghr KO), GOAT KO, and Ghsr stop-floxed (Ghsr null) mice. Behavioral and hormonal responses were tested in the elevated plus maze and light/dark (LD) box. Mice lacking both AG and DAG (Ghr KO) increased anxiety-like behaviors across tests, whereas anxiety reactions were attenuated in DAG-treated Ghr KO mice and in mice lacking AG (GOAT KO). Notably, loss of GHSR1a (Ghsr null) did not affect anxiety-like behavior in any test. Administration of AG and DAG to Ghr KO mice with lifelong ghrelin deficiency reduced anxiety-like behavior and decreased phospho-extracellular signal-regulated kinase phosphorylation in the Edinger-Westphal nucleus in wild-type mice, a site normally expressing GHSR1a and involved in stress- and anxiety-related behavior. Collectively, our data demonstrate distinct roles for endogenous AG and DAG in regulation of anxiety responses and suggest that the behavioral impact of ghrelin may be context dependent. Copyright © 2018 Endocrine Society.

Selection of HIV resistance associated with antiretroviral therapy initiated due to pregnancy and suspended postpartum.

PubMed

Ellis, Giovanina M; Huang, Sharon; Hitti, Jane; Frenkel, Lisa M

2011-11-01

Compare the risk of HIV drug resistance in women stopping suppressive nelfinavir (NFV)-based or Nevirapine (NVP)-based antiretroviral therapy (ART) after pregnancy. Specimens collected after stopping ART were tested for drug resistance by an oligonucleotide ligation assay and consensus sequencing. When postpartum drug resistance was detected, specimens obtained at study entry and during ART were evaluated. Sixteen of 38 women with ART-induced suppression of viral replication suspended ART postpartum. Resistance mutations were detected in 75% who stopped NFV-ART and in 50% who stopped NVP-ART. M184V, associated with Lamivudine resistance, was more frequent among those randomized to NFV-ART compared with NVP-ART (6 of 8 versus 1 of 8; P = 0.04), and nonnucleoside reverse transcriptase inhibitor resistance was detected in 4 of 8 stopping NVP-ART. HIV drug resistance was frequently observed among women who stopped suppressive NVP-ART or NFV-ART postpartum. This suggests that NFV-ART may have suboptimal potency, that staggering discontinuation of NVP-ART may be warranted, and/or ART adherence may be lax in women who choose to stop ART postpartum.

Effects of first formant onset frequency on [-voice] judgments result from auditory processes not specific to humans.

PubMed

Kluender, K R; Lotto, A J

1994-02-01

When F1-onset frequency is lower, longer F1 cut-back (VOT) is required for human listeners to perceive synthesized stop consonants as voiceless. K. R. Kluender [J. Acoust. Soc. Am. 90, 83-96 (1991)] found comparable effects of F1-onset frequency on the "labeling" of stop consonants by Japanese quail (coturnix coturnix japonica) trained to distinguish stop consonants varying in F1 cut-back. In that study, CVs were synthesized with natural-like rising F1 transitions, and endpoint training stimuli differed in the onset frequency of F1 because a longer cut-back resulted in a higher F1 onset. In order to assess whether earlier results were due to auditory predispositions or due to animals having learned the natural covariance between F1 cut-back and F1-onset frequency, the present experiment was conducted with synthetic continua having either a relatively low (375 Hz) or high (750 Hz) constant-frequency F1. Six birds were trained to respond differentially to endpoint stimuli from three series of synthesized /CV/s varying in duration of F1 cut-back. Second and third formant transitions were appropriate for labial, alveolar, or velar stops. Despite the fact that there was no opportunity for animal subjects to use experienced covariation of F1-onset frequency and F1 cut-back, quail typically exhibited shorter labeling boundaries (more voiceless stops) for intermediate stimuli of the continua when F1 frequency was higher. Responses by human subjects listening to the same stimuli were also collected. Results lend support to the earlier conclusion that part or all of the effect of F1 onset frequency on perception of voicing may be adequately explained by general auditory processes.(ABSTRACT TRUNCATED AT 250 WORDS)

49 CFR 391.63 - Multiple-employer drivers.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Transportation Other Regulations Relating to Transportation (Continued) FEDERAL MOTOR CARRIER SAFETY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION FEDERAL MOTOR CARRIER SAFETY REGULATIONS QUALIFICATIONS OF DRIVERS... motor carrier need not— (1) Require the person to furnish an application for employment in accordance...

Maternal obesity is associated with ovarian inflammation and up-regulation of early growth response factor 1

USDA-ARS?s Scientific Manuscript database

Obesity impairs reproductive functions through multiple mechanisms, possibly through disruption of ovarian function. We hypothesized that increased adiposity will lead to a pro-inflammatory gene signature and up-regulation of Egr-1 protein in ovaries from obese (OB, n=7) compared to lean (LN, n=10) ...

Na[superscript +] binding to meizothrombin desF1

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

Papaconstantinou, M.E.; Gandhi, P.S.; Chen, Z.

2009-06-10

Meizothrombin is the physiologically active intermediate generated by a single cleavage of prothrombin at R320 to separate the A and B chains. Recent evidence has suggested that meizothrombin, like thrombin, is a Na{sup +}-activated enzyme. In this study we present the first X-ray crystal structure of human meizothrombin desF1 solved in the presence of the active site inhibitor PPACK at 2.1 {angstrom} resolution. The structure reveals a Na{sup +} binding site whose architecture is practically identical to that of human thrombin. Stopped-flow measurements of Na{sup +} binding to meizothrombin desF1 document a slow phase of fluorescence change with a kmore » obs decreasing hyperbolically with increasing [Na{sup +}], consistent with the existence of three conformations in equilibrium, E*, E and E:Na{sup +}, as for human thrombin. Evidence that meizothrombin exists in multiple conformations provides valuable new information for studies of the mechanism of prothrombin activation.« less

Stopping power and range calculations in human tissues by using the Hartree-Fock-Roothaan wave functions

NASA Astrophysics Data System (ADS)

Usta, Metin; Tufan, Mustafa Çağatay

2017-11-01

The object of this work is to present the consequences for the stopping power and range values of some human tissues at energies ranging from 1 MeV to 1 GeV and 1-500 MeV, respectively. The considered human tissues are lung, intestine, skin, larynx, breast, bladder, prostate and ovary. In this work, the stopping power is calculated by considering the number of velocity-dependent effective charge and effective mean excitation energies of the target material. We used the Hartree-Fock-Roothaan (HFR) atomic wave function to determine the charge density and the continuous slowing down approximation (CSDA) method for the calculation of the proton range. Electronic stopping power values of tissues results have been compared with the ICRU 44, 46 reports, SRIM, Janni and CasP data over the percent error rate. Range values relate to tissues have compared the range results with the SRIM, FLUKA and Geant4 data. For electronic stopping power results, ICRU, SRIM and Janni's data indicated the best fit with our values at 1-50, 50-250 MeV and 250 MeV-1 GeV, respectively. For range results, the best accordance with the calculated values have been found the SRIM data and the error level is less than 10% in proton therapy. However, greater 30% errors were observed in the 250 MeV and over energies.

Acoustical study of the development of stop consonants in children

NASA Astrophysics Data System (ADS)

Imbrie, Annika K.

2003-10-01

This study focuses on the acoustic patterns of stop consonants and adjacent vowels as they develop in young children (ages 26-33) over a six month period. The acoustic properties that are being measured for stop consonants include spectra of bursts, frication noise and aspiration noise, and formant movements. Additionally, acoustic landmarks are labeled for measurements of durations of events determined by these landmarks. These acoustic measurements are being interpreted in terms of the supraglottal, laryngeal, and respiratory actions that give rise to them. Preliminary data show that some details of the child's gestures are still far from achieving the adult pattern. The burst of frication noise at the release tends to be shorter than adult values, and often consists of multiple bursts. From the burst spectrum, the place of articulation appears to be normal. Finally, coordination of closure of the glottis and release of the primary articulator is still quite variable, as is apparent from a large standard deviation in VOT. Analysis of longitudinal data on young children will result in better models of the development of the coordination of articulation, phonation, and respiration for motor speech production. [Work supported by NIH Grants Nos. DC00038 and DC00075.

Acoustical study of the development of stop consonants in children

NASA Astrophysics Data System (ADS)

Imbrie, Annika K.

2004-05-01

This study focuses on the acoustic patterns of stop consonants and adjacent vowels as they develop in young children (ages 2.6-3.3) over a 6-month period. The acoustic properties that are being measured for stop consonants include spectra of bursts, frication noise and aspiration noise, and formant movements. Additionally, acoustic landmarks are labeled for measurements of durations of events determined by these landmarks. These acoustic measurements are being interpreted in terms of the supraglottal, laryngeal, and respiratory actions that give rise to them. Preliminary data show that some details of the child's gestures are still far from achieving the adult pattern. The burst of frication noise at the release tends to be shorter than adult values, and often consists of multiple bursts, possibly due to greater compliance of the active articulator. From the burst spectrum, the place of articulation appears to be normal. Finally, coordination of closure of the glottis and release of the primary articulator is still quite variable, as is apparent from a large standard deviation in VOT. Analysis of longitudinal data on young children will result in better models of the development of motor speech production. [Work supported by NIH Grants DC00038 and DC00075.

Unraveling resistive versus collisional contributions to relativistic electron beam stopping power in cold-solid and in warm-dense plasmas

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

Vauzour, B.; Laboratoire d'Optique Appliquée, ENSTA-CNRS-Ecole Polytechnique, UMR 7639, 91761 Palaiseau; Debayle, A.

2014-03-15

We present results on laser-driven relativistic electron beam propagation through aluminum samples, which are either solid and cold or compressed and heated by laser-induced shock. A full numerical description of fast electron generation and transport is found to reproduce the experimental absolute K{sub α} yield and spot size measurements for varying target thicknesses, and to sequentially quantify the collisional and resistive electron stopping powers. The results demonstrate that both stopping mechanisms are enhanced in compressed Al samples and are attributed to the increase in the medium density and resistivity, respectively. For the achieved time- and space-averaged electronic current density, 〈j{submore » h}〉∼8×10{sup 10} A/cm{sup 2} in the samples, the collisional and resistive stopping powers in warm and compressed Al are estimated to be 1.5 keV/μm and 0.8 keV/μm, respectively. By contrast, for cold and solid Al, the corresponding estimated values are 1.1 keV/μm and 0.6 keV/μm. Prospective numerical simulations involving higher j{sub h} show that the resistive stopping power can reach the same level as the collisional one. In addition to the effects of compression, the effect of the transient behavior of the resistivity of Al during relativistic electron beam transport becomes progressively more dominant, and for a significantly high current density, j{sub h}∼10{sup 12} A/cm{sup 2}, cancels the difference in the electron resistive stopping power (or the total stopping power in units of areal density) between solid and compressed samples. Analytical calculations extend the analysis up to j{sub h}=10{sup 14} A/cm{sup 2} (representative of the full-scale fast ignition scenario of inertial confinement fusion), where a very rapid transition to the Spitzer resistivity regime saturates the resistive stopping power, averaged over the electron beam duration, to values of ∼1 keV/μm.« less

Work behaviour during pregnancy in rural China in 2009.

PubMed

Neupane, Subas; Nwaru, Bright I; Wu, Zhuochun; Hemminki, Elina

2014-02-01

To describe the pattern and determinants of working during pregnancy in rural China. A cross-sectional survey was carried out in 2009 in three provinces (Anhui, Chongqing and Shaanxi) in rural China among 3966 mothers who had recently given birth. Multilevel logistic regression was used to examine the determinants of work behaviour during pregnancy. Overall, 39% of the women stopped working during early pregnancy, 32% worked the same throughout pregnancy and the rest decreased their work or stopped later in pregnancy. Women from Anhui (53%) and Chongqing (54%) provinces were more likely to stop work in early pregnancy than women from Shaanxi province (20%). Older women [odds ratio (OR) 0.74, 95% confidence interval (CI) 0.56-0.99], those having two or more children (OR 0.55, 95% CI 0.43-0.69) and non-farmers (OR 0.50, 95% CI 0.65-0.99) were less likely to stop working on the first trimester, but those with higher education (high school OR 1.43, 95% CI 1.05-1.94) were more likely to stop working. Stopping work early was not related to household income and adequacy of prenatal care. Women with two or more children, non-farmers and those from Shaanxi province were more likely to continue to work to the same extent during pregnancy. But those with higher household income and middle and high school were less likely to work the same. Women's working patterns during pregnancy in rural China were polarized: many women stopped working already in early pregnancy, but others continued to work as before. The key determinant of the working patterns was the province of residence.

A numerical simulation approach to studying anterior cruciate ligament strains and internal forces among young recreational women performing valgus inducing stop-jump activities.

PubMed

Kar, Julia; Quesada, Peter M

2012-08-01

Anterior cruciate ligament (ACL) injuries are commonly incurred by recreational and professional women athletes during non-contact jumping maneuvers in sports like basketball and volleyball, where incidences of ACL injury is more frequent to females compared to males. What remains a numerical challenge is in vivo calculation of ACL strain and internal force. This study investigated effects of increasing stop-jump height on neuromuscular and bio-mechanical properties of knee and ACL, when performed by young female recreational athletes. The underlying hypothesis is increasing stop-jump (platform) height increases knee valgus angles and external moments which also increases ACL strain and internal force. Using numerical analysis tools comprised of Inverse Kinematics, Computed Muscle Control and Forward Dynamics, a novel approach is presented for computing ACL strain and internal force based on (1) knee joint kinematics and (2) optimization of muscle activation, with ACL insertion into musculoskeletal model. Results showed increases in knee valgus external moments and angles with increasing stop-jump height. Increase in stop-jump height from 30 to 50 cm lead to increase in average peak valgus external moment from 40.5 ± 3.2 to 43.2 ± 3.7 Nm which was co-incidental with increase in average peak ACL strain, from 9.3 ± 3.1 to 13.7 ± 1.1%, and average peak ACL internal force, from 1056.1 ± 71.4 to 1165.4 ± 123.8 N for the right side with comparable increases in the left. In effect this study demonstrates a technique for estimating dynamic changes to knee and ACL variables by conducting musculoskeletal simulation on motion analysis data, collected from actual stop-jump tasks performed by young recreational women athletes.

Salience network integrity predicts default mode network function after traumatic brain injury

PubMed Central

Bonnelle, Valerie; Ham, Timothy E.; Leech, Robert; Kinnunen, Kirsi M.; Mehta, Mitul A.; Greenwood, Richard J.; Sharp, David J.

2012-01-01

Efficient behavior involves the coordinated activity of large-scale brain networks, but the way in which these networks interact is uncertain. One theory is that the salience network (SN)—which includes the anterior cingulate cortex, presupplementary motor area, and anterior insulae—regulates dynamic changes in other networks. If this is the case, then damage to the structural connectivity of the SN should disrupt the regulation of associated networks. To investigate this hypothesis, we studied a group of 57 patients with cognitive impairments following traumatic brain injury (TBI) and 25 control subjects using the stop-signal task. The pattern of brain activity associated with stop-signal task performance was studied by using functional MRI, and the structural integrity of network connections was quantified by using diffusion tensor imaging. Efficient inhibitory control was associated with rapid deactivation within parts of the default mode network (DMN), including the precuneus and posterior cingulate cortex. TBI patients showed a failure of DMN deactivation, which was associated with an impairment of inhibitory control. TBI frequently results in traumatic axonal injury, which can disconnect brain networks by damaging white matter tracts. The abnormality of DMN function was specifically predicted by the amount of white matter damage in the SN tract connecting the right anterior insulae to the presupplementary motor area and dorsal anterior cingulate cortex. The results provide evidence that structural integrity of the SN is necessary for the efficient regulation of activity in the DMN, and that a failure of this regulation leads to inefficient cognitive control. PMID:22393019

A novel mechanism of myostatin regulation by its alternative splicing variant during myogenesis in avian species.

PubMed

Shin, Sangsu; Song, Yan; Ahn, Jinsoo; Kim, Eunsoo; Chen, Paula; Yang, Shujin; Suh, Yeunsu; Lee, Kichoon

2015-11-15

Myostatin (MSTN) is a key negative regulator of muscle growth and development, and an increase of muscle mass is achieved by inhibiting MSTN signaling. In the current study, five alternative splicing isoforms of MSTN mRNAs in avian species were identified in various tissues. Among these five, three truncated forms of myostatin, MSTN-B, -C, and -E created premature stop codons and produced partial MSTN prodomains encoded from exon 1. MSTN-B is the second dominant isoform following full-length MSTN-A, and their expression was dynamically regulated during muscle development of chicken, turkey, and quail in vivo and in vitro. To clarify the function of MSTN-B, two stable cell lines of quail myoblasts (QM7) were generated to overexpress MSTN-A or MSTN-B. Interestingly, MSTN-B promoted both cell proliferation and differentiation similar to the function of the MSTN prodomain to counteract the negative role of MSTN on myogenesis. The coimmunoprecipitation assay revealed that MSTN-B binds to MSTN-A and reduces the generation of mature MSTN. Furthermore, the current study demonstrated that the partial prodomain encoded from exon 1 is critical for binding of MSTN-B to MSTN-A. Altogether, these data imply that alternative splicing isoforms of MSTN could negatively regulate pro-myostatin processing in muscle cells and prevent MSTN-mediated inhibition of myogenesis in avian species. Copyright © 2015 the American Physiological Society.

Regulation of the syncytin-1 promoter in human astrocytes by multiple sclerosis-related cytokines

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

Mameli, Giuseppe; Astone, Vito; Khalili, Kamel

Syncytin-1 has a physiological role during early pregnancy, as mediator of trophoblast fusion into the syncytiotrophoblast layer, hence allowing embryo implantation. In addition, its expression in nerve tissue has been proposed to contribute to the pathogenesis of multiple sclerosis (MS). Syncytin-1 is the env glycoprotein of the ERVWE1 component of the W family of human endogenous retroviruses (HERV), located on chromosome 7q21-22, in a candidate region for genetic susceptibility to MS. The mechanisms of ERVWE1 regulation in nerve tissue remain to be identified. Since there are correlations between some cytokines and MS outcome, we examined the regulation of the syncytin-1more » promoter by MS-related cytokines in human U-87MG astrocytic cells. Using transient transfection assays, we observed that the MS-detrimental cytokines TNF{alpha}, interferon-{gamma}, interleukin-6, and interleukin-1 activate the ERVWE1 promoter, while the MS-protective interferon-{beta} is inhibitory. The effects of cytokines are reduced by the deletion of the cellular enhancer domain of the promoter that contains binding sites for several transcription factors. In particular, we found that TNF{alpha} had the ability to activate the ERVWE1 promoter through an NF-{kappa}B-responsive element located within the enhancer domain of the promoter. Electrophoretic mobility shift and ChIP assays showed that TNF{alpha} enhances the binding of the p65 subunit of NF-{kappa}B, to its cognate site within the promoter. The effect of TNF{alpha} is abolished by siRNA directed against p65. Taken together, these results illustrate a role for p65 in regulating the ERVWE1 promoter and in TNF{alpha}-mediated induction of syncytin-1 in multiple sclerosis.« less

Ray Tracing Techniques - Derivation and Application to Atmospheric Sound Propagation.

DTIC Science & Technology

1980-01-01

NVFTNTF,NWV,NRFT,IVEL,ITEMP,IWV, IRHM IF (CIVEL+ITEMP).EQ.O) STOP C IF SVP DATA IS 10 BE INTERNALLY GENERATED, REPLACE ’STOP’ BY C APPROPRIATE ’GO TO...NRFT - range given inj 1 feet 0 calculated 6 IVEL - sound velocity 1 given 80 not given7 ITEMP - temperaturegie 1 givenonot given IRHM relative

Abbreviated right-sided heart echocardiogram and the STOP-Bang questionnaire-a useful relationship for preoperative patient evaluation?

PubMed

Evans, Rebecca E; Zimmerman, Joshua; Shishido, Sonia; Heath, Elise; Bledsoe, Amber; Johnson, Ken

2016-05-01

The aims of this study were to (1) explore the incidence of right-sided heart dysfunction (RHD) and STOP-Bang questionnaire responses consistent with obstructive sleep apnea (OSA) and (2) assess the relationship between patients with STOP-Bang questionnaire responses consistent with OSA and echocardiographic findings suggestive of RHD. Observational study. Tertiary academic center preoperative clinic. Two hundred patients presenting for elective surgery to the University of Utah preoperative clinic. Abbreviated transthoracic right-sided echocardiogram and STOP-Bang questionnaire. Tricuspid annular plane systolic excursion, tissue Doppler-derived tricuspid lateral annular systolic velocity (S'), and the tricuspid inflow E wave to tricuspid annular tissue Doppler e' wave ratio (E/e') for the presence of RHD, as well as responses to STOP-Bang questionnaire. A total of 140 echocardiograms were analyzed after exclusion of participants with incomplete STOP-Bang questionnaires and inadequate images. Thirty-five patients (25%) reported 5 or more positive responses to the STOP-Bang questionnaire. Forty-six patients (35%) had abnormal right-sided heart measurements. Of the 35 patients with STOP-Bang scores 5 or greater, 11 (31%) had evidence of RHD. No correlation was observed between STOP-Bang scores and the echocardiography metrics of RHD. This preliminary study suggests that there are numerous sources of RHD, among one of which is sleep apnea, and/or the STOP-Bang questionnaire is not a sensitive tool for predicting RHD. We conclude that although the STOP-Bang questionnaire is easy to implement in a preoperative clinical setting, it is not useful in identifying patients at risk for RHD. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of anti-siphon devices-how do they affect CSF dynamics in supine and upright posture?

PubMed

Gehlen, Manuel; Eklund, Anders; Kurtcuoglu, Vartan; Malm, Jan; Schmid Daners, Marianne

2017-08-01

Three different types of anti-siphon devices (ASDs) have been developed to counteract siphoning-induced overdrainage in upright posture. However, it is not known how the different ASDs affect CSF dynamics under the complex pressure environment seen in clinic due to postural changes. We investigated which ASDs can avoid overdrainage in upright posture best without leading to CSF accumulation. Three shunts each of the types Codman Hakim with SiphonGuard (flow-regulated), Miethke miniNAV with proSA (gravitational), and Medtronic Delta (membrane controlled) were tested. The shunts were compared on a novel in vitro setup that actively emulates the physiology of a shunted patient. This testing method allows determining the CSF drainage rates, resulting CSF volume, and intracranial pressure in the supine, sitting, and standing posture. The flow-regulated ASDs avoided increased drainage by closing their primary flow path when drainage exceeded 1.39 ± 0.42 mL/min. However, with intraperitoneal pressure increased in standing posture, we observed reopening of the ASD in 3 out of 18 experiment repetitions. The adjustable gravitational ASDs allow independent opening pressures in horizontal and vertical orientation, but they did not provide constant drainage in upright posture (0.37 ± 0.03 mL/min and 0.26 ± 0.03 mL/min in sitting and standing posture, respectively). Consequently, adaptation to the individual patient is critical. The membrane-controlled ASDs stopped drainage in upright posture. This eliminates the risk of overdrainage, but leads to CSF accumulation up to the volume observed without shunting when the patient is upright. While all tested ASDs reduced overdrainage, their actual performance will depend on a patient's specific needs because of the large variation in the way the ASDs influence CSF dynamics: while the flow-regulated shunts provide continuous drainage in upright posture, the gravitational ASDs allow and require additional adaptation, and the membrane-controlled ASDs show robust siphon prevention by a total stop of drainage.

Light stops and fine-tuning in MSSM

NASA Astrophysics Data System (ADS)

Çiçi, Ali; Kırca, Zerrin; Ün, Cem Salih

2018-01-01

We discuss the fine-tuning issue within the MSSM framework. Following the idea that the fine-tuning can measure effects of some missing mechanism, we impose non-universal gaugino masses at the GUT scale, and explore the low scale implications. We realize that the fine-tuning parametrized with Δ _{EW} can be as low as zero. We consider the stop mass with a special importance and focus on the mass scales as m_{\\tilde{t}} ≤ 700 GeV, which are excluded by the current experiments when the stop decays into a neutralino along with a top quark or a chargino along with a bottom quark. We find that the stop mass can be as low as about 250 GeV with Δ _{EW} ˜ 50. We find that the solutions in this region can be exluded only up to 60% when stop decays into a neutralino-top quark, and 50% when it decays into a chargino-b quark. Setting 65% CL to be potential exclusion and 95% to be pure exclusion limit such solutions will be tested in near future experiments, which are conducted with higher luminosity. In addition to stop, the region with low fine-tuning and light stops predicts masses for the other supersymmetric particles such as m_{\\tilde{b}} ≳ 700 GeV, m_{\\tilde{τ }} ≳ 1 TeV, m_{\\tilde{χ }1^{± }} ≳ 120 GeV. The details for the mass scales and decay rates are also provided by tables of benchmark points.

Performance of life support breathing apparatus for under-ice diving operations.

PubMed

Lang, Michael A; Clarke, John R

2017-01-01

Single-hose scuba regulators dived in very cold water may suffer first- or second-stage malfunction, yielding complete occlusion of air flow or massive freeflow that rapidly expends a diver's air supply. This study, conducted in Antarctica, evaluated the under-ice performance of a sampling of commercially available regulators. Seventeen science divers logged a total of 305 dives in -1.86°C seawater under 6-meter-thick Antarctic fast-ice over two field seasons in 2008 and 2009. Dive profiles had an average depth of 30 msw and dive time of 29 minutes, including a mandatory three-minute safety stop at 6 msw. Sixty-nine unmodified regulator units (17 models) from 12 different manufacturers underwent standardized pre-dive regulator care and were randomly assigned to divers. Depths and times of onset of second-stage regulator freeflow were recorded. In 305 dives, there were 65 freeflows. The freeflows were not evenly distributed across the regulator brands. Regulator failure rates fell into two categories (⟨ 11% and ⟩ 26%). The regulators classified for the purpose of the test as "acceptable" (⟨ 11% failure rate: Dive-Rite Jetstream, Sherwood Maximus SRB3600, Poseidon Xstream Deep, Poseidon Jetstream, Sherwood Maximus SRB7600, Poseidon Cyklon, Mares USN22 Abyss) experienced only nine freeflows out of 146 exposures for a 6% overall freeflow incidence. Those classified as "unacceptable" (⟨ 26% failure rate) suffered 56 freeflows out of 159 exposures (35% freeflow incidence.). Contrary to expectations, the pooled incidences for the seven best performing regulators was significantly different by Chi-square test from the 10 remaining regulators (P ⟨ 0.001).